CA2688812A1 - Highly charged microcapsules - Google Patents

Abstract

The invention encompasses compositions containing sol-gel microcapsules that are highly positively charged. The sol-gel capsules generally contain additives. The invention also encompasses methods for producing highly charged microcapsules using cationic additives which can include cationic polymers. The methods allow for the encapsulation of polar or non-polar active ingredients.

Description

HIGHLY CHARGED MICROCAPSULES

CROSS-REPRRENCE
[0001] This applieation claims the benefit U.S. Provisional Application No.
60/939,318 Sled May 21, 2007, which is inrnrporated herein by refereace in its en,tirety.

BACKGROUND OF THE INVENTION
lem1 Bxposuro to ultraviolet 1[ght, primarily through exposute to tlhe suds rays, producas a number of harmful effocts inctnding premetiue skin aging, loss of elasticity, wrinkling, drying, and an inereased risk of developing akin cancer. Currently a number of sunsoreen products are marketed to pmrtect ageinst tlsose ham-fal effeces. All of these peoduets contain agants known to fiher out some of tfie sun's haimful rays incorporated into creams, oittments, lotiens, solutions or suspensions. Such peoducts are generally applied just prior to anticipated sun exposure, provide short tetm protecti.on, and aro removed by bathing, washing or normal desquamation of skin.
Soap in the fomi of bodywash has for years been used to remove oil due to its surfactant composition and associated charges. A nortnal soap contains both charges of a positive and negative natare. AlWough attempts have been made to combine sunscreens with soaps (i.e., surfacmnt agents), none has provided an ideal combinetion of high sun protection factor (SPF) and long-lasting effeet in a composition that maintains its integrity.
[000.3[ OOter additives in addition to suntc[een are also peteatially uaofiil when applied in to surfacas either as a wash-on or as a leave-on formulation. Other additives in addition to sunscreens are also useful when applied to a surface as a erkne, gel, lotion, shampoo, conditioner, coating, apray, or as a bath bar. One appmacA to providing active ingredienls to surfaoes including topical preparations is to encapsulate the additive in order to ptntect the additive, oontrol the release of the additive, modify the function of the additive, and in some aases to prevert the additive &om hannting the sarfaoe, which in some caeas is skin_ In additicm to functional additives useful for the skin, the application of fanctional additives to the surfaces of plants and on other substrates suoh as textiles, walls, floors, cara, trucks, and boats is also important. Methods of encapsulation, such as sol-gel enespsulation aro known In the art, but there is a need for improved encapsulated additives that have stability and the ability to effectively bind and to mkase at the appropriate time when applied either to the body, or to other substratos. The prasent invention addresses these needs.

SUMMARY OF THE INVENTION
[0004] One aspect of the imention provides for highly ehsegcd aol-gel capsules that are usefal for applications on a variety of surfacas. In one aspect, the invention provides a sol-gel microcapsule with a zeta potential of at least about 40 mV. In some embodiments the zeta WO 2008/144734 PCT[US2008/064369 potential is at Icast about 50 mV. In some embodiments the zeta potential is at least about 55 mV. In some embodiments the zda potential is at least about 60 mV.
100051 One aspect of the invention is a plurality of sol-gel microcapsules capable of binding to a surface wberein an average of at leest about SOYo of the microcapsules remain bound to the surface for an average of greater than at leaat about 4 hours.
[0006] One aspect of the invention is a sol-gel microcapsule with a aft potential of at least about 40 mV wherein the microcapsule comprises a cationic agent In some embodiments the eationic agent comprises a cationic polymer. In some embod'mtems the cationic polymm comprisa polyquatemium-4, -7, -11, -22, -27, -44, 51, or -64. In some embodiments the cationic polymer oomprises polyquaternium-4.
[00071 ln some embodiments sol-gel microcapsule of claims 1-4, wherein the microcapsule is aseoaiated with an additive. In some embodiments is encapsulated in the miemcapsale. In some embodiments the additive is looeted substantially within the sol-gel microcapsule.
[000g] In some embodiments the additive is selec0ed from the group oonsisting of steroidal anti-inflammatory actives, analgasic actives, antifungals, antibacterials, antipara.cities, anti-virais, anti-allergenics, anti-cellulite additives, medicinal actives, skin rash, skin disease and dermatitis medications, inseM repollaM lotives, antioxidants, hair growth promoter, hair growth inhibitor, hair bleaching agents, deodorant compounds, suniess tanning actives, skin lightening sodves, anti-acne activos, anti-slan wrmkling actives, anti-skin aging activos, vitamina, nonsteroidal anti-inflammatory actives, anesthetic actives, anti-pruritic actives, anti-microbial activea, dental care agents, personal oare agents, nutraceuticels, phamscetiticeds, fraganees, antifouling agants, pesticides, lubrieaats, etchants, and mixtutes and combinations thereof.
[0009] The highly charged microaipsabs ctm be used fbr agrlcultural, textile, industrial, transpoAation, marine, phennaceutioal, or personal eare applications.
[0010] In some embodiments the additive is selectod fraro the group consishing of sunsotecns, skin lightening actives, anti-aging additives, fragrances, pharmaceuticals, antibacterials, moistorizers, and-acne actives, and inseot repeliants, In some embodiments the additive comprisos a sunscreen. In some embodiments the sunscreen is selected from the group consisting of aminobenzoic acid, avobenzono, einnoxate, dioKybenzone, homosalatq menthyl anthranilaoe, octocrylenc, octyl methoxyoinnamate, octyl salicylate, oxybenzone, padimate 0, phenylbenzimidaaob solfonic acid, solisobenaone, and trolmnine salieylate_ In some embodiments the sunscreen comprises a UVA-absotbing sunscreen, a UVB-absorbing sunscreen, and a physical blocker sunscreen. In some embodiments (i) the iJVB-absorber sunscreen is selectod from the group consisting of aminobenzoic acid, cinoxate, dioxybenzone, homosalate, octocrylene, octyl methoxycinnamate, ootyl salicylate, oxybenzone, psdimate 0, phenylbenzimidamle sulfonic acid, sulisobenzone, and trolamine salicylate;
(ii) the UVA-absorber sunscreen is selected from the group consisting of avobenzone and menthyl anthranilate;

WO 2008/144734 PCT[US2008/064369 and (iii) the physical blocker sunscreen is selected fiom the group consisting of titanium dioxide and tino oxide.
[0011] One aspect of the invention is composition comprising a highly charged microoapsule and further comprising a vehicle suitable for treatment of aurFaces in topical, agricultunil, tsxtile, industrial, traospastation, marurc, phumaoeutioal, or pasosal caie uses. In some embodiments the composition comprises a wash-on product. In some embodiments the oomposition wmprises a leave-on produot. In some embodiments the mierocapsulea in the composition experience an average of greater than about 50% breakage when applied to the surface. In some embodiments the brealcage substantially ooours on initial appiication to the surface. In some embodimenas the average of greater than 50% breakage occum over a period of about 1 hour. In some entboditnents the avarage of groater than 50% breakage ocours over a period of about 6 hours. In some embodiments the average of greater than 50% breakege occurs over a period of about 12 honrs. In some anbodimetts the avemga of groater tlun 50% breskage oceura over a period of about 24 hours.
[0012] In some embodiments the breakage occurs due to the conditions of surface application.
In soma embodirnants the oondition of surPaoo application is fiiction, pressure, iight, pH citanga, or enzymatic action.
[0013] One aspect of the invention is a method of applying an active compound to a surfeee comprising; providing a composition comprising an active compound encapsulated into a so[-gel microaepsuk having a zota poteatial of graRer than about 30 mV; and applying the compositioa to the surface. Ia same embodiments the zets potemial is groaDer than 30 mV.
In some embodiments the zeta potential is greater than 40 mV. In some embodiments the zeta potentist is greater than 55 mV. In some embodiments the zeta potential is greater than 60 mV.
[0014] In some embodimeats the capsules comprise a cationic polynur. In soma embod'unenta the cationic potymer eomprises a polyquaternium. In some embodiments the cationic polymer comprises polyquaterniutn-4, -7, -11, -22, -27, -44, 51, or -64, [0015] In some embodimenta the additive is selected front the group consisting of steroidal anti-iotlammatory actives, anelgesic actives, antifimgals, antibacterials, antipsrasitios, anti-virals, anti-allergenics, anti-cellulite additives, medicinal actives, skin rash, skin disease and dennatitis medications, insect repeliant actives, antioxidants, hair growth promoter, hair growlh inhibitor, hair bleaohing agents, deodorant compounds, suaiess tanning scdves, skin lightening actives, anti-acee actives, anti-slcitt wrinkling activea, anti-skin aging aotives, vitamins, nonsteroidal anti-inflammatory actives, anesthetic actives, anti-pnuitic actives, anti-microbial aetives, dental oare agents, personal care agents, nutracenticals, phermsceuticals, fragrances, antifouling agents, pesticides, lubricants, etchants, aud mix.dires and combinetions thereo (00161 In some embodimenU the additive is selected from the group consisting of sunscreens, skin lightening actives, anti-aging additives, fregrances, phamtaceuticals, antibaeterials, moisturizers, anti-acne actives, and insect repollsnts. In some embodiments the additive comprises a sunacreen. In some embodiments the sunscreen is selected from the group consisfing of atninobenzoic acid, avobemmne, cimnoxate, dioxybennone, homosalato, menthyl an<hranilate, octocrylene, oetyl methoxycinnamate, octyl salicylate, oxybenzone, padimate 0, phenylbenzimidazole sulfonic acid, sulisobenzone, and trolamine salicylate. In tme embodiments the sunscreen comprises a UVA-absorbing sunscreen, a UVB-absorbing sunscreen, and a physical blocker sunscreen. In some embodiments (i) the UVB-absorber sunscreen is selected from the group congsting of aminobeuzoic acid, cinoxate, dioxybenzone, homaealate, octoorylene, ootyl methoxycinnamate, octyl salicylate, oxybenzone, paditdate 0, phenylbenamidemle su[famic acid, sulisobenzone, and trolamine sdieylate; (ii) the UVA-absorber sunscroen is selected from the group consisting of avobenzone and menthyl anthrenilate;
and (iit) the pbysioal blocker sunscreen is selected from the gtoup consieting of titanium dioxide and zinc oxide.
100171 In soma embodiments the microcapsules in the composition experience an average of gmaw than about 50'Y. breakage when appliod to the surfeoa In some embod'anents the breakage substantially occurs on initial application to the surface. In some embodiments the break.ap occurs over a period of 1 hour. In some embodiments the broslar occurs over a period of 6 hours. In some embodiments the breaksge occurs over a period of 12 hours.
In some embodimems the breakege occurs over a period of 24 hours.
[00181 One aspect of the invention is a method of manufacturing a highly charged sol-gel microcapsule eanprising a non-polar active ingredient comprising: (a) combining the non-polar active ingnedient, optiona[ non-polar d7uent, and aqueous phese; (b) agitating the eombination formed in (a) to form an oil-in-water (O/W) emulsion wherein the non-polar active ingredient and optional non-polar diluent ooinprise the dispetaed phase; (c) adding one or more surfactants; (d) adding a cationic agent; (e) adding a gel precursor to the O/W emulsion; and (f) mixing the composition from step (e) vdnle the gel preoursor hydrolyaes aad sol-gel oapsules ate fafined which comprise the non-polar aetive ingredient.
[00191 In some embodiments the method fbr8ux eomprisas step (g) filtering the sol-gal microoapsules and soep (h) rinsing the sol-gel microcapsules.
10020J In some embodiments the method furlher comprises step (i) drying the mierocapsules.
[00211 In some embodiments the method of manufaduring produces a micmcapsule haviog nela potential of at least about 30 mV. In some embodiments the method of manufacturing produces a mioeocapsule having a aeta potentia[ of at least about 40 mV. In some embodiments the method of manufacturing produces a microcapsule zeta potential of at least about 55 mV. In sonw embod'unents the method of manufacturing produces a m{crooapsule having zeta potential of at least about 60 mV.
[00d2] In some embodiments the steps are carried out in the order lisbod. In some embodiments the cationic agent is added after the addition of the gel precursm. In some embod'mnents the cationic agent is added during step (f). In some embodiments the cationic agent is added after step (f). In some embodiments cationic agant is added during step (h) of rinsing the sol-gei microcapsules. In some embodiments the cationic agent is added after step (i) of drying the sol-gel mieroeapsules. In some embodiments the cationic agem oompriaes a cationic polymer. In some embodiments the cationic polymer comprises polyquaternium-4, -7, -11, -22, -27, -44, 51, or -64. In sonti embodiments the eationic polymer comprises polyquatemium-4.
In some embodiments the cationic agent comprises a proton donor.
[0023] In some embodiments step (t) is carried out at acidic pH. In some embodiments step (f) is cartied out at a pH 5om 3.6 to 4Ø In aome embodimenta the one or more surfactants oomprises a copolymer surfactent. In some embodiments the one or more sutfactenta have a oombined hydrophile-lipophile balance (HLB) of between 9 and 11.
[0024] One aspect of the invention is a method of manufacturing a highly charged sol gel microcapsule comprising a polar active ingiedient comprising: (a) combining the polar active ing[edient, water, optiond polar dilnenk and a non-polar (oil) phase; (b) agitating the combination formed in (a) to fomt an water-in-oil (W/O) emulsion wherein the polar active ingredient, wa4er, and optional polar diluent oomprisa the dispetsod phase;
(o) adding one or more surfadents; (d) adding a cationio agent; (e) adding a gel precursor to the W/O
emulsion; and (f) mixing the composition from step (e) while the gel precursor hydrolyzes and sol-gel capsules aro fonned whioh compriae the polar active ingredient.
[0025] In some embodiments the method fuRher comprises step (g) filtering the sol-gel miorocapsules and step (h) rinsing the sol-gel microcapaules.
[0026] In some embod'onents the methad fiuther comprises step (i) drying the microcapsules.
[0027] In some embodiments the method of manufacturing produces a microcapsule having zeta potential of at least 30 mV. In some embodiroents the method of manafsauring produces a microoapsule having a zeta potential of at least 40 mV. In some embodiments method of manufacturing produces a microcapsule zda potential of at least 55 mV. In some embodiments the metbod of nunmfacturmg produces a microcapsuk having wta potential of at k,a9t 60 mV.
[0028] In some emboduaents the steps are oarried out in the order listed. In some embodiments the cationio agent is added atier the addition of the gel psacutsa In some embodiments the ca4onic agent is addod during step (1). In some embodiments the oetionic agent is added a8er step (f). In some embodiments the cationic agent is added during step (h) of rinsing the sol-gel microcapsules. In some embodiments the cationic agent is added afber stop (i) of drying the sol-gel microcapsules.
[00291 In some embodiments the cationic agent compnsos a cationic polymer. In some embodiments the cationic polymer oomprises polyquaternium-4, -7, -11, -22, -27, -44, 51, or -64.
In some embodiments the cationio polymer oomprises polyquatarntum-4. In some embodiments the cationic agent comprises a proton donor.
[0030] In some embodiments step (f) is camed out at acidic pH. In some embodiments step (f) is carried out at a pH from 3.6 to 4Ø In some embodiments the one or more surfactants comprises a copolymer surfacfant. In some embodintanis the one or mote surfactants have a combined hydrophile-lipophile balance (HLB) of between 2 and 6.
[0031] One aspect of the invention is a method of forming a highly charged sol-gel microcapsule omprisinQ an active ingredient widtitt a template comprising: (a) fotming a dispersion of templates, wherein the templates comprise an active ingredient, in an aqueous continuous phase;
(b) adding a cationic agent; (c) adding a gel precursor to the aqueous continuous pbase; and (d) mixing the composition fran step (c) while the gel preamsor hydrolyaes and soi-gel capsules ace fotnted.
[0032] In some embodiments the method fluther oomprises step (e) filtering the sol-gol mierocapsules and step (f) rinsing the sol-gel miorocapsulea.
[0033] In some embodiments the method fiuther comprises step (g) drying the mierocapsubs.
[0034] In some embodiments the method of manufacturing produces a microcapsule having zeta potential of at least 30 mV. In some embodiments the method of manufaoturing produces a microcapsale having a zeta potential of at (east 40 mV. In some embodiments the method of manufacturing produoes a microcapsule wta potential of at least 55 mV. In some embodiments the method of manufacturing produces a microcapsule having zeta potential of at least 60 mV.
[00331 In some embodmtenas the steps aro carried out in the order listed. In some embodiments the cationic agent is added aRer the addition of the gel precursor. In some embodiments the cationic agent is added during step (c). In some embodiments the cationic agent is added after step (c). (n some embodiments the cationic agent is added during step (f) of rinsing the sol-gel mierocapeules. In some embodiments the oationic agent is added after step (g) of drying the sol-gel microcapsules.
[00361 In some embodiments the cetionic agont oomprises a catlonic polymer. In some embodiments the cationic polymer comprises polyqusternimn-4, -7, -11, -22, -27, -444, 51, or -64.
In some embodiments the cationic polymer comprises polyquaternium-4. In some embodiments the cationic agent comprises a proton donor.
100371 In some embodiments step (d) is cartied out at acidic pH. In some embodiments step (d) is carried out at a pH from 3.6 to 4,0. In some embodiments the template comprises a mierosphere. ln some embodiments the template comprises a polymer, liposome or miodle. In some embodiments the template oomprises a phospholipid.
INCORPORATION BY REFERENCE
[0038] All publicattons and palent applications mentioned in dds speci8cmion are herein incorpomted by reference to the same eatattt as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
DETAII.ED DESCItiMTON OF THE INVENTION
[0039] The present invention encompasses compositions containing one or more additives that can be active ingredients (also referred to herein as "actives") that may be added to the highly char od sot-gel tnicrocapsule containing composition, for example, to provide an active in eitha a leave-on or a wash-on formulation. A wash on formulation can include an active/bodywash combination. The invention also encompasses a bodywash containing such an active ingredient.
In some embodiments, the active ingredient is one or more sunscreens. In some embodiments, the highly charged microcapsules are used for agricultural, terztile, iodustrial, traa4portation, marine, pharmeceutical, or personal care applications. 17o highly chmged mierocapsules generally oomprise an active agent within the microcapsule. In some cases, the ac.tive agent can perform its function while contained within the microcapsule. In sonte cases, the active agent must leave the microcbpsole in oMer to perform its aotion. In some embodiments, the capsules are produced such that the capsules rupture in order to release the active ingredient. TLe cationic component can act to facilitate the controlled broakage of the capsules. In some csses, the surface onto which the oepaules are applied is pre-costod with an agem that rstas with the sol gel capsule in order to causa controlled breakage of the capsules and releaso of the active ittgredient.
In some cases the surface can be post treaeed with a substance that either enhances or reterds capsule breakage. The invention further encompasses methods of use and manufacture of the twmpositions, and business methods.
[Og4U] A used harein, a"wash-0n" fmmulation encompasses all ckmsing vehiclos applied to a surface. A wash-on formulation is generally applied to a surface in order to perform a cleaning function, and in addition to the cleaning aspect of the wash-on, a portion of the wash-on formulation remains on the surface to provide a finuboa beyond cleaning.
Exemplary fonns of eleansing vehicles include, but are not limited to, liquid, bar, gel, foam, aerosol or pump spray, cream, lotion, stick powder, or incorporated into a patch or a towelette. In addition, soapless cleansers may be used as well. The wash-on ean be made into any suitable product form.
[0041] As used herein, a "leave-on" formulation is applied directly to a surface. A leave-ott formulation may not perfonn a cleansing function. The leave-on can be, for example, a coeany lotion, gel, coating, paint, vamish, oil, spray, or powder. 'Phe leave-on fotmulations of the invention genarally have a fimction that is perfarmed or enhanced by the active that is deliveted to the suntaoe within the highly charged aol-gel capsulas.
[0042] As used herein, "bodywash is a type of wash-on formulation that encompasses all cleansing vehicles applied to the body. Exemplary fonns of cleansing vehicles include, but are not limibed to, liquid, bar, gel, foam, aerosol or pump spray, cteam, lotion, stick, powder, or htcorpotated Into a patch or a towektte. ln additim soapleas cleansers may be used as well. 17se bodywash can ba nutde into any suitable product form. Thus, as used herein, "bodywash"
includes, but is not limited to, a soap including liquid and bar soap; a shampoo; a hair conditioner; a shower gel; including an exfoliating shower gel; a foaming bath product (e.g. gel.
soap or lotion); a milk bath; a soapless cleanser, including a gel cleanser, a liquid cleanser and a cleansing bar; moist towelletes; a body lotion; a body spmy, mist or gel; bath eft'ervescent tablets (o.g., bubbla bath); a hand and nail cream; a bath/shower gel; a shower cream;
a depilatory cream;
.7.

a shaving product e.g. a shaving cream, gel, foam or soap, an atter-shave, a8er-shave moistiu'raer, and combinations thereof, and any other composition used for cleansing or post-cleansing application to the body, including the skin and hair. Especially ueefltl as bodywasbes in the invention are soaps, e.g., liquid soaps and bar soaps, and shatnpoos.
L Compoaitiom 100431 The highly charged microcapsules of the invention are used to produce compositions for agriculturnl, textile, industriai, transportation, marine, pharmaceutical, or personal care applications. 1he ootapositions oea be applied to a broad range of aurfaces.
'Ihe highly ohar ed microcapsules contain additives or active ingredients that porform a function when applied as part of the compositions of the present invention.
100411 In one aspect, the invmtion provldes additives containing active mgmdierrts, where the additive is designed to be added to a leave-on or wash-on product such s a bodywash (e.g., aoap or shampoo). In sonte embodintents, the invention provides sunscmen compositiona ("sunacreen additives") that may be added to a bodycvash preparation to impant sun proteclion. ln so=
embadiments, the invention provides a combination of a sunscreen additive and a bodywash preparation ("mmactaenlbodywash"). Thus, a sunsereen additive of the invmtion may be mixed with a waventional bodywash; altetnatively, the invention provides pro-mixed sunscroen/bodywash. In either case, the sunscreeo/bodywash composition is generally applied in the same manner as the bodywash alone and, typieally, rinwd, wit4 additive, o.g., sunscreen protection, being left oa the skin after rinsing. In some cases, e.g., soapless cteansers, the bodywash is applied without rinsing. For sunscreen additives as part of a sunscreerJbodywash, the sunsoreen proteotim aflar appGcatien and, typioeily, rinsing is, on average, greater than an SPF of 1, up to about SPF 50. As used herein in the context of SPF, "average SPF" is the SPF, determined as described herein, for about 5 to about 50 subjects, or about 5 to about 20 subjects, or about S to about 10 subjects, where the subjecls preferably have Type II
skin. In some embodiments, the average SPF provided by the sunscreen/bodywash after rinsing is about i to about 50, or about 2 to about 50, or about 2 to about 40, or about 2 to about 30, or about 2 to about 20, or about 2 to about 10, or about 2 to about 5, or about 5 to about 25, or about 5 to about 20, or about 5 to about 15, or about 5 to about 10. In some embodiments, the avorage SPF
provided by the sunscteenlbodywash, after rinsing, is above about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14,15, 16, 17,18, 19, or 20. In some embodiments, the average SPF after rmaing is above about 2. In some embodiments, the average SPF aftor rinsing is above about 5. In some embodinionts, the average SPF after rinsing is above about 10. In some embodiments, the average SPF after rineing is above about 15. In some embodiments, the average SPF provided by the sunscreen/bodywash of the invention remains above about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, for an average of at lesst about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, or more than about 10 hours after rinsing. In some embodiments the average SPF
provided by the -g-sunsaeagbodywash of the invention ina+oaves with caoh additioml washing aRer a fust wash, so that atber a second, third, fourth, or fiith wash, the SPF provided can be above about 2, 4, 6, 8, 10, 15õ 20, 25, 30, 40, 45, or mom than about 45, [0"5] SPF is a conmwnly used nteasure of photo protection of a sunscreen against eiy+ILema.
This number is derived from another parameter, the minimal erythemal dose (MED). MED is defined as the "least exposure dose at a specified wavelenglh that will elicit a delayed erythema respoase." The MED indicates the amowat of energy irrmdiating the,kin and the msponsiveness of the skin to the radiation. The SPF of a particular photo protector Is obtained by dividing the MED of protected skin by the MED of unprotected skin. The higher the SPF, the more effective the ageet in preventieg sunburn. The SPF value tells how many times longer a petson can stay in the sun before the person will experience 1 MED. For example, utilizing a sunscreen with an SPF
of 6 wi7l allow an individual to stay in the san six times longer befo[e roeeiving I MID. As the SPF value of a sunscreen inereases, the less chance exists for development of tanning of the skin.
Typically, commercially available sunscreening products have SPF values ranging from about 2 to 45.
[0046] Methods for measuring SPF are described in, e.g., FDA monograph 21 C.F.R 352. In order to detertnine SPF, the procedwos of the FDA monograph can be used.
Another usoful method for applying the sunscroan prior to measurement ia as follows: Wet 50 cm' sqwue aisa of testing site with 10 ml of water del'rvered with a syringe. Apply teat sample as per FDA
monograph to area. Work lather on the subjeot for 3 minutes to albw the product to absorb into the skin. Rmse area after 2 additional minutos with 20m1 of watea. Pat dry and allow 15 minutes before exposure to radiation as per FDA monograph.
[0047] The sol-gel capsules of the invention oan be formulated to oomtrol whether or not there is penetration into the skin or other surface and if there is penetration, to what depth. In some cases the control of penetration can be influenced by the conditions of the skin such as pH, presanee of film formers, and roughness. Where sunstmens are used, penetration into HtC
sitin is not generally desirable and the capsules can be formulated to miniinize or el'uninate skin penetration.
In some embodiments, such as where the active ingredient is a pigment or phamaamutical on the skin, some amount of skin penetration is desirod. In some embodiasents, after application of the bodywash containing the additive to the skin followed by rinsing, the additive peneuates to an average of at least about 5 microns beneath the skin surface. I'he capsules ean be formulated such that the active will penetrate only to a given layer of the skia. The skin can be seeo to haYe three primary layer , the epidermis, which provides waterproofmg and serves as a barrier to infeotion; the dertnis, which serves as a location for the appendages of skin;
and the hypodmmis (subcutaneous adipose layer). In sonme embodiments the active ingrodient panettates the epidermis. In some embodiments the active ingradient ponetratcs the dermis. In some embodiments the active ingrediont penetrMes the hypodennis. 7Le capsules can thus be produced such that the contents of the capsules, the active ingredients, are introduced into the blood stream.

In some embodiments, the additive penetrates to an average of at least about 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100,120, or 150 microns beneath the skin surface. In some embodiments, after application of the leave-on or bodywash containing the additive to the skin followed by rinsing, the additive penetrates to an average of no more than about 30 microns beneath the skin surface. In some embodiments, the additive penetrates to an averago of no more than about 50, 40, 30, 25, 20, 15, 10, or 5 microns beneath the skin surface. In some embodiments, after application of the bodywash containing the additive to the skin followed by rinsing, the additive penetrates to an average of about 5 to about 50, or about 5 to about 40, or about 5 to about 30, or about 10 to about 40, or about 15 to about 40, or about 20 to about 40, or about 5, 10, 15, 20, 25, 30, 25, 40,45, or 50 microns beneath the skin surfaee. Depth of penetration may be tested by tqm stripping methods, as are well-known in the art. In some embodiments, the highly charged material in the capsules can assist in disrupting cell membranes in order to actively deliver active agents into the tissue or the blood. In some embodiments the highly charged material will be inert to the skin and will not cause disruption and penetration.
[0048[ The sunscreen additives and sunscrean/bodywashes of the invention contain at least one sunscreen. In some embodiments, the sunscraen additives of the invention contain one, two, three, four, or more than four sunscneens. In some embodiments, the sunscreen additives of the invention include throe sunscreans. In other embodiments, the sunscreen additives of the invention include four sunscreens. The sunsoreens may be organic or inorganic.
The sunscreens may be a UVA absorber, a UVB absorber, a physical blocker, or any combination thereof. In some embodiments one or more of the sunscreens is encapsulated. A number of types of encapsulation may be employed as described herein.
100491 Compositions of the invention may include one or more actives that are not sunscreens, where the composition is designed to be an additive to a bodywash. In some compositions of the invention, the actives are provided in combination with one or more sunsoreens. In sonme compositions, the actives are provided without sunscroen.
100501 The compositions, e.g., sunscreen additives, and additive/bodywashes, e.g., sunscreen/bodywashes, of the invention may further include one or more components to provide a positive cherge to the system to assist with attachment to protein and other charged components of skin and/or hair, e.g., cationicpolymeric agents. The cationic polymer may be, for example, a quatemiuni, e.g., polyquatemium.
[0031] The additives, e.g., sunscreen additives, and additive/bodywashes, e.g., sunscreen/bodywashes, of the invention may further include a film former.
[00521 Other optional ingredients of the additives, e.g., sunscreen additives, and additive/bodywashes, e.g., sunscreen/bodywashes, ofthe invention include preservatives, antioxidants, chelating agents, liquid hydrocarbon (e.g., similar to pentane), foaming agents (e.g., a cationic foaming agent), gkin nourishing components, antibacterials, medieinals, and the like, as described below.

[OOd3i The additives, e.g., smisonxa additives, of the invention may be combined with any convontional bodywash. The bodywash composition with wbich the additive, e.g., sunscreen additive is combined may be any bodywash known in the aR or apparent to one of skiil in the ait, as deacribed above. In embodimenb where the additive is a tmn-mmsoroet active, the additive may be combined with any composition intended for topical application, In these embodiments, the additive is often encapsulated, e.g., in sol-gel microcapsuies.
[00541 In some embodiments the invention pr(vides an additive, e.g., sunscreen additive, in combination with a bodywash composition to provide an additive/bodywash, e.g.
sunscreen/bodywash, composition. In these embodiments, the additive, e.g., sunscreen additives, of the invention are provided in combination with one or mote surfaofants. The sorbmAwt(s) may be catimuc, anionic, nonionic, zwitterionic, amphoseric, or any combination ehereot In some embodiments, the sunscrean/bodywash compositions of the invention include at least one cationic surfactaat.

A. Snsucreens [0055] The sunscreen additives and sunscroen/bodywashes of the invention contain at least one suasmeen. The sunscreen may be orgettic or inorganic, or a combioatioa of both may be used.
Sunscreens of use in the invention include UV absorbera or bloekers (e.g., many inorganic sunscreens are W blockers). UV absorbers may be a UYB or UVA absorber (e.g., UVA I or UVA 11 absorber). In some embodiments, the sunscroee additives or sunspeedbodywashes of the invention include an organic and an inorganic sunscreen. In some embodiments, the sunsoreen additives or sunscroonlbodywashes of the invention include more than one organic sunscxeen (e.g., at least one UVB absorber and at least one UVA absorber) and at least one inorganie sunscreen. In some embodimaits, the sunsveen additives of the invention inehtde only a physival blocker sumscreen, e.g., titanium dioxide. These embodiments may further contain a cationic polymer and/or a fihn former, as well as any other eomponents described herein for sunsoteen additives.
[00561 Additionat ingredients may include film formers, eetionic polymers, antioxidants, preservatives, and the like, as described herein. In some embodiments, the sunscreen additives or sunsamen/bodywashes of the invention include an organic and an inorganic sunscreen. In some embodiments, the sunscreen additives or sunscreen/bodywashes of the invention include more than one organic sunscreen (e.g., at least one AVB absorber and at least one UVA absorber) and at least one inotgmic sunscreen.
[OYS7J In some embodiments, one or more of the sunscreens usod in the invention are encapsulated.
[OOSS] Any sunscreon known in the att or apparent to the skilled artisatt may be used in the invendon. Tbe term "sunscreen" or aunsoroen agent" as used herein det-mes ultraviolet ray=
blocking compounds exhibiting absorption or blockage within the wavelength region between about 290 and 420 nm. Sunscreens may be classified into five groups based upon their chemical structure: para-amino benzoates; salicylates; cinnamates; benzophenones; and miseeIIaneous chemicals including menthyl aMhralinate and digalloyl trioleate. Inorganic sunscreens may also be used including titanium dioxide, zinc oxide, iron oxide and polymer particles such as those of polyethylene end polyamides.
100591 Specifie suitable sunscreens include, for example: p-aminobenzoic acid, its salts and its derivatives (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid);
Anthranilates (i.e., o-aminobenzoates; metbyl, menthyl, phonyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl estors); Salicylates (amyl, phenyl, bettzyi, menthyl, glyceryl, and dipropylene glycol esters); Cinnamic acid derivatives (methyl and benzyl esters, alpha-phenyl cinnamonitrile;
butyl cinnamoyl pyruvate); Dihydroxycinnarnic acid derivatives (umbelliferone, methylumbelliferone, methylaeeto-umbelliferone); Trd-ydroxycinnamic acid derivatives (esculetin, methylesculetin, daphnetin, and the glucosides, esculin and daphnin); Hydrocarbons (diphenylbutadiene, stilbene); Diben7alacetone and benzalacetopbenone;
Naphtholsulfonates (sodium salts of 2-naphthol-3,3-disulfonic and of 2-naphthol-6,8-disulfonic acids);
Dihydroxynaphthoic acid and its salts; o- and p-Hydroxybipbenyidisulfonates;
Coumarin derivatives (7-hydroxy, 7-methyl, 3-phenlyll); Diazoles (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl naphthoxalole, various ary) benzothiazoles); Quinine saks (bisulfate, sulfate, chloride, oloato, and tannate); quinoline derivatives (8-hydroxyquinoline salts, 2-phenylquinoline); Hydroxy-or methoxy substituted benzophenones; Uric and vilouric acids;
Tannnic acid and its derivatives (e.g., hexavthylether); (Butyl carbityl) (6-propyl piperonyl) ether;
Hydroquinone; Benzophenones (Oxybenzene, Sulisobenzone, Dioxybenzone, Benzomsorcinol, 2,2',4,4'-Tetrahydroxybenzophenone, 2,2'-Dihydroxy4,4'-dimethoxybenzophenone, Octabenzone;
4-Isopropyhldibenzoylmethane; Butylmethoxydibanzoylmothane; Etocrylene; and 4-isopropyl-di-benzoylmethane; titanium dioxide, iron oxide, zinc oxide, and mixtures thereof. Other cosmetically-acceptable sunscreens and concentrations (percent by weight of the total cosmetic sunsoroen composition) include diethanolamine methoxycinnamate (10% or less), ethyl-[bis(hydroxypropyl)]aminobenzoate (5% or less), glyceryl aminoben7oate (3% or less), 4-isopropyl d'benzoyhnethane (5% or less), 4-methylbenzylidene camphor (6% or less), terephthalylidene dicamphor sulfonic acid (10% or less), and sulisobenzone (also called benzopbenone-4, 10% or less).
(00601 In some embodiments, sunscreens are FDA-approved or approved for use in the European Union. For example, FDA-approved sunsoreens may be used, singly, or in combination. See, e.g., U.S. Patent Nos. 5,169,624; 5,543,136; 5,849,273;
5,904,917; 6,224,852;
6,217,852; and Segarin et al., chapter Vil, pages 189 of Cosmetics Science and Technology, and Final Over-the-Counter Drug Products Monograph on Sunscreens (Federal Register, 1999:64:27666-27963), all of which are incorporated herein by referonce.

[00611 For example, for a product marketed in the United 3tates, preferred cosmetically-acceptable sunscreens and coneentrations (reported as a percentage by weight of the total cosmetic sunscreen composition, and referring to the final percentage of the sunsoreen after addition to the bodywash) include: aminobenzoic acid (also called para-aminobenzoic acid and PABA; 15% or less; a UVB absorbing organic sunscreen), avobenzone (also called butyl methoxy dibenzoylmethane; 3% or less, a UVA I absorbing organic sunscreen), cinoxate (also called 2-ethoxyethyl p-methoxycinnamabe; 3% or less, a UVB absorbing organic sunscreen), dioxybenzone (also called benzophenone-8; 3% or less, a UVB and UVA 11 absorbing organic sunscreen), homosalaUe (15% or less, a UVB absorbing organic sunscreen), menthyl anthranilate (also called menthyl2-aminobenzoate; 5% or less, a UVA II absorbing organic sunscreen), octocrylene (also called 2-ethylhexyl-2-cyano-3,3 diphenylacrylete; 10% or less, a UVB
absorbing organic sunscreen), octyl methoxycinnamate (7.5% or less, a UVB
absorbing organic sunscreen), octyl salicylate (also called 2-ethylhexyl salicylate; 5% or less, a UVB absorbing organic sunscreen), oxybenzone (also called benzophenone-3; 6% or less, a UVB
and UVA ll absorbing organic sunscreen), padimate O(also called octyl dimethyl PABA; 8%
or less, a UVB
absorbing organic sunscreen), phenylbenzimidazole sulfonic acid (water soluble; 4% or less, a UVB absorbing organic sunscreen), sulisobenzone (also called benzophenone-0;
10'/0 or less, a UVB and UVA II absorbing orgaaic sunscreen), titanium dioxide (25% or less, an inorganic physical blocker of UVA and UVB), trolamine salicylate (also called triethanolamine salicylate;
12% or less, a UVB absorbing organic sunscreen), and zinc oxide (25% or less, an inorganic physical blocker of UVA and UVB).
[11062[ For a product marketed in the European Union, preferred cosmetically-acceptable photoactive compounds and concentrations (reported as a parcentage by weight of the total cosmetic sunscreen composition, and referring to the final percentage of the sunscreen after addition to the bodywash) include: PABA (5% or less), camphor benzalkonium methosulfate (6%
or less), homosalate (10% or less), benzophenone-3 (10'/o or less), phenylbenzimidazole sulfonic acid (8% or less, expressed as acid), terephthalidene dicamphor sulfonic acid (10% or less, expressed as acid), butyl methoxydibenzoylmethane (5% or less), benzylidena cemphor sulfonic acid (6% or less, exprossed as acid), octocrylene (10% or less, expnessed as aeid), polyacrylamidomethyl benzylidene camphor (6% or less), octyl methoxycinnamate (10 Yo or less), PEG-25 PABA (10'/a or less), isoamyl p-methoxycinnamate (10'/a or less), ethylhexyl triazone (5% or less), drometrizole trielloxane (15% or less), diethylhexyl butantido triazone (10'/0 or less), 4-methylbenzylidene cantphor (4=k or less), 3-benzylidene camphor (2%
or less), ethylhexyl salicylate (5% or less), ethylhexyl diniethyl PABA (8% or less), benzophenone-4 (5%, expressed as acid), methylene bis-benztriazolyl tehamethylbutylphenol (1fY/o or less), disodium phenyl dibenzimidazole tetrasulfonate (10'/0 or less, expressed as acid), bis-ethylhexyloxyphenol methoxyphenol triazine (10% or less), methylene bisbenzotriazolyl tetramethylbutylphenol (10%

or less, also called TINOSORB M), and bisethylhexyloxyphenol methoxyphenyl triazine.(l0"/. or less, also called TINOSORB S).
100631 In some embodiments, the sunscreen additives or sunscreen/bodywashes of the invention include a silicone long-chain molecule with chnomophores, e.g., PARASOL SLX
(DSM
Nutritional Products), which contains benzyl malonate chromophores attached to specific points on a polysiloxane chain. Thus, in some embodiments, the invention provides a sunscreen additive or stmscreen/bodywash composition that contains sunscreen that comprises a silicone long-chain molecule with chromophores. For example, compositions of the invention include a composition containing oatyl methoxycinnamate, octocrylene, avobenzone, titanium dioxide, and a silicone long-chain molecule with chromophores. The silicon long-chain molecule may be used in sunsoreen additives at about 0.5 to about 5%, or in sunscteen/bodywashes at about 0.2 to about 2%.
100641 Inorganic physical blockers of UVA and UVB useful in the invention further include iron oxide and polymer particles suah as those of polyethylene and polyamides.
100651 In some embodiments, the sunscreen additives and sunscreen/bodywashes contain at least one sunscreen aative that is einnamate (e.g., Octylmethoxycinnamato (ethyl hexyl methoxycinnamate), (available under the tradename PARSOL MCX), oxybenzone (e.g., benzophenone-3 (2-Hydroxy4-Methoxybenzophenone), avobanzone (4tert-Butyl-4'-methoxydibenzoylmethane or PARSOL 1789), octyl salicylate (2-Ethylhexyl Salicylate), octocrylene (2-Ethylhexyl2-Cyano-3,3-Diphenylacrylate), methyl anthranilate, and/or titanium dioxide, or combinations thereof.
10066) The sunscreen additives include and a physical blocker sunscreen such as an inorganic or organic compound which may reflect, scatter or absorb light.
100671 Sunscreen additives and sunscroenlbodywashes of the invention may, in some embodiments, contain as a sunscreen component only titanium dioxide. When titanium dioxide is used in compositions of the invention, either alone or in combination with other sunscreens, the titanium dioxide can have an anatase, rutile, or amorphous structure. The titanium dioxide particles can be uncoated or can be coated with a variety of materials including, but not limited to, aluminum compounds such as aluminum oxide, aluminum stearate, aluminum laurate and the like; phospholipids such as lecithin; silicone compounds; and mixtures thereof. Various grades and forms of titanium dioxide are described in CTFA Cosmetic Ingredient Dictionary, l lm Edition (1982), pp. 318-319; U.S. Pat. No. 4,820,508 to Wortzman, issued Apr.11, 1989; and World Patent No. WO 90/11067 to Elsom et al, published Oct. 4, 1990; these three referenees are incorporated by reference heroin in their entirety. Suitable grades of titanium dioxide for use in the compositions of the present invention are available commercially such as the MT micronized series from Tri-K Industries (Emerson, NJ). These micronized titanium dioxides generally have a mean primary particle size ranging from about 10 nm to about 50 nm. For example, titanium dioxide having a mean primary particle size of about 15 nm is available under the trade designations MT-150W (uncoated) and MT-100T (coated with stearic acid and aluminum compounds). Uncoated titanium dioxides having mean primary particle sizea of around 35 nm and around 50 nm are available under the trade designations MT-SOOB and MT-600B, respectively. Other coated titanium dioxides having a mean primary particle size around 15 nm include MT-100F (modified with stearie acid and iron hydroxide) and MT-100S
(treated with lauric acid and aluminum hydroxide). Mixtures of two or more types and particle size variations of titanium dioxide can be used in the present invention.
[0068] One form of titanium dioxide is silica-coated TiOz. Such a silica-coated TiO2 is available under the tradename T-AVO (Eusolex).
[0969] If a zinc compound is chosen as the inorganic sunscreen, some zinc-based compositions (e.g., Z-CoteTM BP1 [registered tradetnark, SkinCeuticals]) provide micro-fine zinc oxide coated with a form of dimethicone. As expressed by the manufactueer, the dimethicone coating transforms the frequently granular and pasty particles of zinc oxide to a smooth formulation which is trensparent. The micronizing of these particles achieves the important advantage of providing effective sunscreening without giving the appearance of skin coated with white paim.
(0070] Also to be noted in reiation to inorganic blockers are Tioveil and Spectcaveil (both of the Tioxide Group). Tioveil include products which are 40% dispersions of surface-treated titanium dioxide in a range of cosmetic vehicles. Spectraveil include products which arc 60% dispersions of zinc oxide in a range of cosmefic vehicles. In certain variations, these products may be film-formers and may have advantageous uses here.
[0071) In sunscreen additives, the total sunscreens comprise about 0.1-50%, or about 1-30%, or about 1-25%, or about 3-25%, or about 5-25%, or about 10-25% or about 15-25%, or about 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50% of the composition (all percentages herein are weight peroent unless otherwise specified). In sunscreen/bodywash compositions, the total sunscreens can comprise 0.05-30%, or about 0.5-15%, or about 0.5-12%, or about 1.5-12%, or about 2.5-12%, or about 5-12% or about 7-12%, or about 2.5, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 33, 35, 40,45, 50, or more than 50 Yo of the composition.
[0072] In some embodiments, a sunscreen additive ofthe invention includes octyl methoxycinnamate at about 4.5-9%, Octocrylene at about 0.5-15%, Avobenzone (e.g., PARSOL
1789) at about 2-4%, and titanium dioxide at about 3-9%. hi some embodiments, the octyl methoxy cinnamate is encapsulated, e.g., in amorphous silica. Such encapsulated octyl methoxy cinnamate is commercially available under the trade name UV PEARLS; about 20-400/o UV
PEARLS supplies about 4.5-98/o octyl methoxy cinnamate. In some embodiments, a sunscreen additive of the invention includes octyl methoxycinnamate at about 7.6% (in some embodiments, encapsulated as described, e.g., in UV PEARLS wherein the UV PEARLS are provided at about 33.3%), Octocrylene at about 113 %, Avobenzone (PARSOL 1789) at about 2.8%, and titanium dioxide at about 6.4%. The sunscreen additives may further include a polyquaterniutn, e.g., polyquaternium-4. In some embodiments, the polyquatemium-0 is prosent at about 0.5% to about 51A in some embodimarts, the polyquatemium-4 is present at about 2.8%. Tha sansanen additives may fluther include a film-fonner, which may compriso dimetbioone andlor petrolatpm, andlor a preservative, such as BHT. This sunsoreen additive may be added to a conventional bodywash farmulation (e.g., SUAVE Bodywash) in a ratio of about one patt sunsaeen additive to two parts bodywash (w/w). Other ratios atn edcanpaaced by the invention, e.g., about one pad sunscreen additive to about 0.2, 0.5, 0.7 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.2, 3.5, 3.7, 4.0, 4.2, 4.5, 4.7, 5.0, 6.0, 7.0, 8.0, 9.0, 10,12, 15, or 20 parta bodywash (w/w).
[0073[ lt will be appreciated by those of skill in the art that the various iagrodients of the sunscreen additive may be added to the bodywash all at once, or in groups, or separately. In some embodiments, the sunscreen additive comprises at least two components.
For examplq the 6rst component may comprie afl the ingredients exaopt an inorganie or physieal blocker sunsa+eay and the seoond oomponent may oomprise the inargenic or phyaioal blocker sunscreen.
The first component is added to the bodywash with thorough mixing, then the seeond component is added. For example, in some embodiments, all ingredients except the titanium dioxide are mbced, then added bo the bodywasb, and then the titanium dioxido is added (see Examples).
[00741 In some embodiments, the sunseteen additives of the invention include about 0.1 to 7.5 weight percent of oetylmethoxy cinnamate, about 0.1 to 6 parts weight percent of octyl salicylate, about 0. l to 5 parts weight percent of oxybenzone, about i to 10 weight percent of eationic surfactartt, and about 0.01 to I weight pa+certt of a quaternized compound. These composition may fitrflter include a SLn former. These compositions may further include 0.01 to I weight peroent of a preservative.
[A0751 This UV component additives are not be limited to the commonly categorized sunscreens but to all suitable oompounda including polymers or other compositions that exhibit sunscreen properties described above.

B. Noa-sansereen addifivea aod actives [0076) In one aspect, the invention provides additives containing non-sunscreen active ingredients, where the additive is designed to be added to a composition for applications to a variety of surfaces in, for example, agricultural, textile, industrial, transportadon, marine, phermaceutieal, or personal oare appllcations. One aspect oomprises a topieal applioation, e.g., a bodywash. These actives may be used in combination with the sunscreens described above in a sunsoreen additive or sunsotten/bodywash, or may be used in separate, non-sunserean compositions. In some eanbodiments, at least oaa of the additives is encapsulated In aaothw aspect, the inventimt provides a composition for topical application, eg., a bodywash, containiug one or more such additives. These actives may be used in combination with the sunscreens WO 2008/144734 PCT/iJS2008/064369 described above in a sunsareen additive or suoscreenlbodywash, or may be used in separate, neas-sunscrean oompositions.
[00771 Non-limiting examples of non-sunsareen actives useful in compositions of the invention include sunless tamling actives, skin lightening actives, anti-aone actives, anti-slrin wrinkling and anti-skin aging actives, vitamins, anti-inflammatory actives, anesthetic aetives, analgesic actives, anti-pruritic actives, anti-microbial actives (e.g.
antifungals, antibaoterials, and antiparasitics), anti-virals, anti-allergenics, medicinal aetives (e.g., skin rash, s[dn disease and dermatitis medications), anti-cxllulite additives, insect repellant actives, antioxidants, hair growth promoters, hair growth inhibitors, hair bleaching agents, deodorant oompounds, fragrances, pharmaceuticals, moisturizers, dental care agents, personal care agents, nuttaceutieals, and mixtures and combinations thereot [0078] In some embodiments, the actives can also include constituents for gene therepy including vectors such including viral and non-viral vectors. Viral vectors inolude, for example, adenovimses, adeno-associated viruaes, and retrovimse). Tbe gene therapy conslitaenb can include twcleic acids such as DNA or RNA in the form of pla.wnid DNA, and single or double stranded oligonucleoddes. The nucleic acids can be included, for example, within liposomes, virosomes, and dendrimers.
[M791 Ibe non-sonacreen additives can be useful for the lextiles, compsising, for eample.
smooffimg agents and soflenws, an6-setting treatment of wool, antistatic agents, binders and auxiliaries for pigment dyeing, catalysts, crosalinking agents, 6lHng and stiffening agents, hydrophilizing agents, non-felt finish on wool, watar-repellonts, wetting and antifoaniing agents, siaes, textile waxes, activators for peioxido bbaohing, complexiag agents, extraaing agents, peroxide killer, pretreatment agents for printing on wool, rodnction bleaching agents , and special extiacting agonts [0980] The additives can be usad to improve lubricity or fciction, wetability, water absorption, water release, flnid rolesse, surAsce energy, suffbce area, visibility, iwmpatibility, leaching, intended release of a substenoes, biostatic behavior, chemioa[ roactivity, interaction with proteins and other molecules, adhesion or repellenee of microorganistns or marine life, incros[ation, sedimentakion, esJcification, antigenicity aad biocompatibility.
[OOgll The additives can include antifouling agents including marine antifouling agents suoh as algaecides and molluseicides. The aotives can provide marine antifouling activity including both the elimination of and inhibition of growth of marine organisms. Marine organisms controlled by marine antifouling agents suitable for use in this invention inolude both hard and soft fouling organisms. (3enerally speaking, the term "soft fouling organisms" refas to pleuNs and invertebrates, such as slime, algae, kelp, soft corals, tunicates, hydroids, sponges, and anemones, while the tenn "hard fouling organisms" refers to invertebiates having some type of hard outer shell, such as bamacles, tubeworms, and molluscs.
[00821 The additives can be used for agrioultuual applications including agents to improve plant growth, nutrients, fertilizers, hygroscopio agents, and pesticides.
Agricuhural pesticides include agricultursl fangicides, herbieides, insocticides and miticidea. An agricultnral fimgioide generaliy refers to a wtepound capable of inhibiting the growth of or controlling the growth of fungi in an agdcuhural application, such as treatment of plants and soil; "h"icide" refets to a compound capable of inhibiting the growth of or oontrolling the gnowth of cattaia plants; "iasecticide" refars to a compound capable of controlling insects; and "miticide" refeaa to a compound capable of oontrolling mitos. Additives for agricultural applications include either topical appiications such as leaf, stent, root, or trunk of trees and or applications surrounding plants or trees for uptake.
Applications can also include addition to aigae, fungi, bacteria, viruses or parasites on any substrate or in any environmeat these orgaaisms are found.
(0083J Sunless tanning actives inolude dt'bydroxyacetone (DHA); glyceryl aldehyde; tyrosine and tyrvsine derivat'rves such as amlyltyrosiae, tyrosine glucosinate, aod ethyl tyrosine; phospho-DOPA, indoles and derivatives; and mixtures thereof (06g4) Non-limiting examphs of skin lightening actives include EMBLICA (also an antioxidant), manobenaone (a depigmontiag agent), kojic acid, arbutin, ascorbic acid and derivatives thereof (e.g., magnesiu¾n ascorbyl phosphate or sodium ascorbyl phosphate), and exhacts (e.g=, mulbeny extract, placental exlract). Non-limiting examples of skin lightening agents suitable for use herein also include those desoribed in WO 95/34280, WO
95/07432, and WO 95/23780.
[OYg3J Vitamins may be inchxled in the compositiona of fhe presait inventioa.
Exampbs include Vitamin A and derivatives thereof(including, for example, retinol, see anti-wrinkling actives), ascorbic acid (Vitamin C and derivatives), Vitamin B (e.g., ri'boflavin, vitamin BA biotin, Vitamin D (all fovms), Vitamin E and derivatives theroof such as tocopheryi acetate, beta-carotene, paathothenio ecid and mixtures thoreof.
[OOB6J Anti.acne actives ieclade benzoyl peroxide, eaythromyein, clmdamyoin phosphate, 5,7-dichloro-8-hydroxyquinoline, resonoinol, resorcinol acetate, salicylic acid, affiloic acid, long ahain dicarboxylic acids, sulfur, zinc, various naturai agents such as those derived fc-om green tea, and mbstures thoroof. Other non-limiting examples of suitable anti-ecne actives for use herein are desoribed in U.S. Pat. No. 5,607,980, which description is incorporated herein by reference.
IOie71 Anti-Wan vvriakling actives inolude a veriety of agents, often in combination, that prevent or treat wrinkling through a variety of actions. Many approaches are taken to reduce the appearance of facial wrinkles based on the undersfanding of the molecular basis of wrinkle formation. Such treatments inchide cosmetic products, drug therapy and surgical procedures. For example, many oosmetio products contain hydroxy acids, which may stimulate cwllagen synthesis. Another common trosunent ntilizas tetinol, retinoic, retinol pahnitate, a derivative of vitamin A, (or its stronger, prescribed version Retin=A and Renova) which helps collagen production. Bicyclic ammatic compounds with retinoid-type wtivity, which are useful in particular in pmventing or aresr.ing various keratiniatation disordem, are descr9bed in EP 679 630.
These compounds are particularly aotive for repairing or combating chronologieal or actinic ageing of the skin, for exemple such as in ant[-wrinkle prodmb. Antioxidants such as vitamin C
and B and ooenzyme Q-10 are believed to counteraat free radicals, which demage cells and cause ag[ng and have been used in treatmente of wrinldes. For inema, the FDA hss approved oosmetic use of Botox (an extretnely diluted form of botulinum toxin) to treot glabolla frown lines. Thus non-sunscraw a atlves of the invention that are anti-skin aging or anti-wrinkling actives may contain, alone or in combination, the bicyclic aromatic compounds defined above, other compounds which have retinoid-type activity, free-ndical scavengers, hydroxy or keto acids or derivatives thereof. The term "froo-nidical scavenger" tefers to, for example, a-tocopherol, superoxide dismutese, ubiquinol or certain metal-ehelating agents. Hydroxy acids include, e.g., alpha-hydroxy acids such as lactic acid md glycolic acid or beta-hydroxy acids sud- as salicylic acid and salicylic acid derivatives such as the octanoyl derivative; other hydroxy aoids and keto acids inchde malk, citrie, mandelic, tartaric or glyceric acids or the salkv, amides or estas thereof.
[0888] Other anti-wrlnkling agents and anti-skin agiag agents useful in the invention inchWie sulfur-containing D and L amino acids and their derivatives and salts, particularly the N-acetyl derivatives, an example of which is N-acetyl-L-cysteine; thiols, e.g. ethaae thiol; fat-soluble vitamins, ascorbyl palmitate, ceramides, pseudoceramides (e.g., psandocaamides deseribed in U.S. Pat. Nos. 5,199,2 10; 4,778,823; 4,985,547; 5,175,321, all of which are incorporated by rcfarenoe herein), phospholipids (e g., distearoyl lecilbin phospholipid), fatty acids, fatly aleoholss, cholesterol, plant sterols, phytic acid, lipoic acid; lysophosphatidic acid, and skin peel agenta (e.g, phenol and ehe like), and nrixtares thereof. In some embodiments, the fatty acids or alcohols sre those that have straight or branched alkyl chains containing 12-20 carbon atoms. In one embodiment, the fatty acid is linoleic aeid since linoleic aoid assiste in the absorption of ultraviolet ligbt and furthermore is a vital oomponent of the natural sldn lipids. Other non-limiting examples of suitable anti-wrinkle actives for use herein are described in U.S. Pat. No.
6,217,888, which descriptioo is incorpmabed herein by reforence.
[0089] Anti-inflammatory actives include steroidal, non-steroidal, and other compounds.
[0990] Non-limiting eaamples of steroidal anti-inflammatory agents suitable for use herein include corticosteroids such as hydrocortisone, hydroxyltrismcinolone, alpha-methyl dexamethasone, dexemeH-asone-phosphsbo, beclomethssone dipropionates, cbbetasotvalerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichbrisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, tluciorolone acetonide, fludroeortisono, flunretltasoee pivalate, fluosinolone acetonide, fiuocinonide, flucortine butylesters, fluooortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone aoetonide, cortisone, cwrtodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone, fludrocortisone, diflurosone diacetate, fluradrenolone acetonide, nudrysone, amcinafel, atncinafide, betamethasone and the balance of its esters, cbloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, diflurprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, flupnednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortatnate, meprednisone, parametbasone, prednisolone, prednisone, beclomethasone dipropionate, triamcinolone, and mixtures thereof may be used.
One steroidal anti-inflammatory for use is hydrocortisone.
[00911 Nonsteroidal anti-inflammatory agents are also suitable for use herein as skin active agents in the compositions of the invention. Non-limiting examples of non-steroidal anti-inflammatory agents suitable for use herein include oxicams (e.g., piroxicam, isoxicam, tenoxicam, sudoxicam, CP-14,304); salicylates (e.g., aspirin, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, fendosal); acetic acid derivatives (e.g., diclofenao, fenclofenac, indoroethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zamepirac, clindanac, oxepinac, felbinac, ketorolac); fenamates (e.g., mefenamic, meclofenantic, flufenamic, niflumic, tolfenamic acids); propionic acid derivatives (e,g., ibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufan, indopropfen, pirprofen, carpoofen, oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, tiaprofenic); pyrazoles (e.g., phenylbutazone, oxyphenbutazone, feprazone, azepropazone, trimethazbne); and combinations tbereof as well as any dermatologically acceptable salts or esters of thereof. COX-2 inhibitors are also suitable for use herein, and include, but are not limited to, AZD 3582 (ASTRAZENECA and NicOx), Celecoxib (PHARMACIA Corp.) (4-[5{4-methylphenyl}3-(trifluorome6yl)-1H-pyrazol-l-yl] benzonesulfonamide), Meloxicam (BOEHRINGER WGELHEIM Pharmaceuticals) (4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2GW-406381 (GLAXOSMITIIICLINE), Etoricoxib (MERCK & Co.), Rofecoxib (MERCK
& Co.) (4-[4-(methylsulfonyl) phenyl]-3-phenyl-2(5H)-furanone), Lumiracoxib (NOVARTIS
Pharma AG), Valdecoxib (PHARMACIA Corp.) (4-(5-methyl-3-phenyl-4-isox-azolyl) bennenesulfonamide), and Etodolac (WYETH Ayerst Laboratories) ((±) 1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]acid).
[00921 Other non-limiting examples of suitable anti-inflammatory or similar other skin active agents include candelilla wax, bisabolol (e.g., alpha bisabolol), aloe vera, plant sterols (e.g., phytosterol), Manjistha (extracted from plants in the genus Rubia, particularly Rubia Cordifolia), and Guggal (extracted from plants in the genus Commiphora, particularly Commiphora Mukul), kola extract, chamomile, red clover extract, sea whip extraet, aniso oil, garlic oil, ginger extract, vasoconstrictors such as phenylephrine hydrochloride, and combinations therooE
[0093] Further non-limiting examples of suitable anti-inflammatory or similar other skin active agents include compounds of the Licorice (the plant genus/species Glycyrrhiva glabra) family, including glycyrrhetic acid, glycyrrhizic acid, and derivatives thenxf (e.g., salts and esters).
Suitable salts of the foregoing compounds include ntetal and ammonium salts.
Suitable esters include C~-Cz4 saturated or unsaturated esters of the acids, Cio-C24, or C16-C24. Specific non-limiting examples of the foregoing include oil soluble licorice extract, the glycyrrhizic and glycyrrhetic acids themselves, monoammonium glycytrhizinate, monopotassium glycyrrhizinate, dipotassium glycytrhizmate, 1-beta-glycyrrhetic acid,stearyl glycyrrhetinate, and 3-stearyloxy-glycyrrhetinic acid, disodium 3-succinyloxy-beta-glyeyrchetinate,and combinations themf.
[8094] Anesthetic actives include butamben pietate, lidocaine, xylocaine, benzooaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine,tetracnine, dyclonine, hexylcaine, ptocaine, cooaine, ketamine, pramoxine, phenol, and phartnaeoutically acceptable salts thereof.
100951 Analgesic actives include dyclonine hydrochloride, aloe vera, fentanyl, capsaicin, and the like.
[0096] Anti-pruritic actives include alclometasone dipropionate, betamethasone valerate, and isopropyl myristate MSD.
[0097] Anti-microbial actives inchide antifungal, antibaeterial, and antiseptic compounds.
Antifungal compounds include, but ara not limited to, compounds such as imidazole antifungals.
Specific antifungals include butocouazole nitrate, miconazole, econazole, ketoconazole, oxiconizole, haloprogin, clotrimazole, and butenafine HCI, naRifine, terbinafine, ciclopirox, and tolna8ate. Antibacterial and antiseptic compounds include phenol-TEA complex, mupirocin, triolosan, chlorocresol, chlorbutol, iodine, olindamycin, CA6 (Anjinomoto Co., Inc., containing DL-pyrrolidone Carboxyiic acid sah of L-Cocoyl Arginine Ethyl Ester), povidono-iodine, polymyxin b sulfate-bacitracin, zinc-neomycin sulfate-hydrocortisone, chloramphenicol, methylbenzethonium chloride, and erythromycin and antiseptics (e.g., benzalkonium chloride, benzetltonium chloride, chlorhexidine gluconate, mafenide acetate, nitrofurazone, nitromersol and the like may be Included in compositions of the invention. Many deodorant compounds are also antimicrobial (see below). Antiparasitics, such as lindane may also be included.
[0098] Further examples of antimicrobial and antifnngal actives useful in the compositions of the present invention include, but are not limited to, 13-lactam drugs, quinolone drugs, ciprofloxacin, norfloxaein, tetracycline, amikacin, 2,4,4'-trichloro-2'-hydroxy diphenyl ether, 3,4,4'-trichlorocarbanilide, phenoxyethanol, phenoxy propanol, phenoxyisopropanol, doxycycline, capraomycin, chlorhoxidine, chlortetracycline, oxytetracycline, ethambutol, hexamidine isethionate, metronidazole, pentamidine, gentamicin, kanamycin, lineomycin, methacycline, methenamine, minocycline, neomycin, netilmicin, paromomycin, streptoinycin, tobramycin, niiconazole, tetracycline hydrochloride, erythromycin, zinc erythromycin, erythromycin estolate, orythtomycin stearate, amikacin sulfate, doxycycline hydrochloride, capreomycin sulfate, chlothexidine gluconate, chlorhexidine hydrochloride, chlortetracycline hydrochloride, oxytetracycline hydrochloride, clindamycin hydrochloride, ethambutol hydrochloride, metronidezole hydrochloride, pentamidine hydrochloride, gentamicin sulfate, kan nycin sulfate, lineomycin hydtoobloride, melhacycline hydrochloride, methenamine hippurate, methenamine mandelate, minocycline hydrochloride, neonrycin sulfate, netihnicin sulfate, paromomycin sulfate, streptomycin sulfate, tobramycin sulfate, mioonazole hydrochloride, amanfadine hydrochloride, amanfadine sulfaUe, octopirox, psmchlorometa xylenol, nystatin, toina8ate, zinc pyrithione and clotrimazole [0099] Compositions of the invention may include antiviral agents. Suitable anti-viral agents include, but ara not limited to, motal sahs (e.g., silver nitrate, copper sulfate, iron olilotide, eic.) and organic acids (e.g., malic acid, salicylic acid, suooinic acid, benzoic acid, etc.). In particular oompositioas which contain add'kionat suitable anti-viral agents include those described 'm copending U.S. patent applications Ser. Nos. 09/421,084 (Beerse at al.);
09/421,131 (Biedermann et al.); 09/420,646 (Morgan et al.); and 09/421,179 (Page et aL), which were each filed on Oet.
19,1999 [00100] Anti-allergenics include antihistamines. Antihistamines can be of H, or H2 antagonists or othar types of histamine release inhibitors. The H, antegonisls can be sedating or non-sedating.
Examples of H, -sedating antiMstamines include diphenbydramine (Benadryl), chlorpheniramine, tripelennamine, promethazine, clentastine, doxylamine, benadryl etc. Exanrples of Hi -non-sodating antihistamines inelude astemizole, terfenadine, lornadine etc.
Examples of Hl antagonists include cimetadine, famotidine, nizatidine, and ranitidine.
Examplos of histamine-release-inhibitors include cromolyn.
[00101] A further aetive aseful in tbo invention may be a medicinal for tmatmant of detmatologieal conditions such as psoriasis, acne, eczema, and otha skin conditions due to disease, pathology, aeeident, and the fike. Medicinels include burn relief ointments, such as o-amino-p-toluenesulfonamide monoecetate; dermatitis relief agents, such as the active steroid amcinonide, diflorasone diacetate, and hydrocortisone; diaper rash relief agents, such as methylbonxcthonium chlaride and the lOce; heqes iratment drugs, such as 0-[(2-hydroxyethoxy)methyl]guanine; psoriasis, seborrhea and scabicide agents, such as shale oil and derivatives thereot elubiol, ketoconazole, ooel tar and petroleum dietillates, salicylic acid, zinc pyrithione, selenium sulfide, hydrocortisone, aulfur, menthol, psoralen, pramoxine hydrochloride anfhralin, and methoxsalen; steroids, such as 2{acetyloxy)-9-fluoro-l',2',3',4'-tetrahydro-ll-Aydroxypregna-1,"eno[16,17-b]aaphthalene-3,20-dioes and 21-ahloro-9-fluoro-l',2',3',4'-teltahydro-llb-hydroxypregna-1,44eno[16z, 17-b]naphthalene3,20-dione,and otheraincluding those that are antiinflammatories. Other medicinale include those useful in the treatrnent of expoawm to poison oak, poison ivy. poison sumac, end the like. 7hese Inolude camphot; menthol, beemcaine, butamben picrate, dibucaine, dibucaine hydrochloride, dimethisoquin hydroehloride, dyclonine hydrocLloride, lidocaine, metacresol, lidoceine hydrochloride, prarnoxine hydrochloride, tetraeaina, tottHCaine hydrochloride, benzyl alcohol, camphorated metacresol, juniper tar, phenol, phenolate sodium, resorcinol, diphenhydramine hydrochloride, tripelennamine hydroohloride, hydrocortisone, a coriieosteroid, and hydrocortisone aoetate. Any other medication capable of topical administration also can be incorporated in a composition of the present invention in an amount sufficient to perform its intended function.
1001021 Antioellulite actives include isobutylmethyhumthine, caffeine, theophylline, theobromine, aminophylline,yohimbine, and mixtures thereof.
1001031 Examples of actives suitable for treating hair loss include, but are not limited to potassium channel openers or peripheral vasodilators such as minoxidil, diazoxide, and oompounds such as N*-cyano-N-(tert-pentyl)-N'-3-pyridinyl-guanidine ("P-1075") as disclosed in U.S. Pat. No.: 5,244,664, which is incorporated herein by reference; vitamins, such as vitamin E
and vitamin C, and derivafives thereof such as vitamin E acetate and vitamin C
pahnitate;
hormones, such as erythnopoietin, prostaglandins, such as prostaglandin El and prostaglandin F2-alpha; fatty a¾ids, such as oleic acid; diuretics such as spironolacta-e; heat shock proteins ("HSP"), such as HSP 27 and HSP 72; calcium channel blockers, such as verapamil HCL, nifedipine, and diltiazemamiloride; immunosuppressant drugs, such as cyclosporin and Fk-506; 5 alpha-reductase inhibitors such as fmasteride; growth factors such as, EGF, IGF and FGF;
transforming growth factor beta; tumor necrosis factor; non-storoidal anti-inflammatory agents such as benoxaprofon; retinoids such as tretinoin; cytokines, such as II,-6, IL-1 alpha, and II.-1 beta; cell adhesion molecules such as ICAM; glueorcorticoids such as betametasane; botanical extracts such as aloe, clove, ginseng, rehmannia, swertia, sweet orsnge, zattthoxylum, Serenoa repens (saw palmetto), Hypoxis rooperi, stinging nettle, pumpkin seeds, and rye pollen; other botanical extracts including sandlewood, red beet root, chrysanthemum, rosemary, burdock root and other hair growth pronmter activators which are disclosed in DE 4330597 which is incorporated by roference in its entirety herein; homeopathic agents such as ICalium Phosphoricum D2, Azadirachta indica D2, and Joborandi Dl~ genes for cytokines, growth factors, and male-pattered baldness; antifungals such as ketoconazole and elubiol;
antibiotics such as streptonrycin; proteins inhibitors such as cycloheximide; acetaz.olamide;
benoxaprofen; cortisone;
diltiazem; hexaehlorobenzene; hydantoin; nifedipine; penicillamine;
phenothaiazines; pinaeidil;
psonsiens, verepamil; zidovudine; alpha-glucosylated rutin having at least one of the following rutins: quercetin, isoquercitrin, hcspeddin, naringin, and methylbesperidin, and flavonoids and tnsnsglycosidated derivatives thereof which are all disclosed in JP 7002677, which is incorporated by refenence in its entirety herein; and mixtures thereof. In some embodiments, the hair loss treatment agents include minoxidil, 6-(I-piperdinyl)-2,4-pyrimidinediamine-3-oxide, N'-cyano-N-(tert-pentyl)-N'-3-pyridinyl-guanidine, finasteride, retinoids and derivatives thereof, ketoconazole, elubiol or mixtures theraof.
[00104] Examples of actives suitable for use in inhibiting hair growth include: serine proteases such as trypsin; vitamins such as alpha-tocophenol (vitamin E) and derivatives thereof such as tocophenol acetate and tooophenol palmitate; antineoplastic agents, such as doxorubicin, cyclophosphamide, chlormethine, methotrexate, fluorouracil, vincristine, daunorubicin, bleamycin and hydroxycarbamide; anticoagulants, such as heparin, heparinoids, coumaerins, detran and indandiones; antithyroid drugs, such as iodine, thiouracils and carbimazole; lithium and lithium carbonate; interferons, such as interferon alpha, intorferon alpha-2a and interferon alpha-2b; retinoids, such as retinol (vitamin A), isotretinoin:
glucocorticoids such as betamethasone, and dexamethosone; antilryperlipidaemic drugs, such as triparanol and clofibrate;
thallium; mercury; albendazole; allopurinol; amiodarone; amphetamines;
androgens;
bromocriptine; butyrophenones; carbamazepine; cholestyrantine; cimetidine;
clofibrate; danazol;
desipramine; dixyrazine; ethambutol; etionamide; fluoxetine; gentamicin, gold salts; hydantoins;
ibuprofen; impramine; immunoglobulins; indandiones; indomethacin;
intraconazole; levadopa;
maprotiline; methysorgide; metoprolol; metyrapone; nadolol; nicotinic acid;
potassium thiocyanate; propranolol; pyridostimine; salicylates; sulfasalazine;
terfenadine; thiamphenicol;
thiouracils; trimethadione; troperenol; valproic acid; and mixtures thereof.
In some embodiments, the hair growth inhibitory agents include serine protoases, retinol, isotretinoin, betamethoisone, alpha-tocophenol and derivatives thereof, or mixtures t6ereo [001051 Examples of ha'v bleaching agents include perborate or persulfate salts.
[00106) Deodorant oompounds include astringent salts and bioactive compounds.
The astringent salts include organic and inorganic sahs of aluminum, zirconium, zinc, and mixtures thereof. The anion of the astringent salt can be, for example, sulfate, chloride, chlorohydroxide, ahun, formate, lactate, benzyl sulfonate or phenyl sulfooate. Exemplary classes of antiperspirant astringent salts include aluminum halides, aluminum hydroxyhalides, zirconyl oxyhalides, zirconyl hydroxyhalides, and mixturos theneoE Exemplary aluminum sahs include aluminum chloride and the aluminum hydroxyhalides having the general formula Als (OH),QyXH20, wherein Q is chlorine, bromine or iodine; x is about 2 to about 5; x+y is about 6, wherein x and y are not necessarily integots; and X is about 1 to about 6. Exemplary zirconium compounds include zirconium oxy salts and zirconium hydroxy salts, aLso refemed to as zirconyl sahs and zirconyl hydroxy salts, and represented by the general empirieal formula ZrO(OH)1-nz L~
wherein z varies from about 0.9 to about 2 and is not necesserily an intager; n is the valence of L; 2-nz is greater than or equal to 0; and L is selecxed from the group consisting of halidos, nitrate, sulfamate, sulfate, and mixtures thereof. In some cases, the active ingredients constitute reodorant compounds.
[00107] Exemplary deodorant compounds therefore include, but are not limited to, aluminum bromohydrate, potassium alum, sodium aluminum chlorohydroxy lactate, aluminum sulfate, aluminum chlorohydrate, aluntinum-zirconium tefrachlorohydrate, an aluminum-ziroonium polychlorohydrate complexed with glycine, aluminum-zirconium trichlorohydrate, aluminum-zirconium octachlorohydrate, aluminum sesqirichlorohydrate, aluminum sesquichlorohydrex PG, aluminum chlorohydrex PEG, aluminum zirconium octachlorohydrex glycine complex, aluminum zirconium pentachlorohydrax glycine complex, aluminum ziroonium tetrachlorohydrex glycine complex, aluminum zirconium trichlorohydrex glycine complex, aluminum chlorohydrex PG, zirconium chlorohydrate, aluminum dichlorohydrate, aluminum dichlorohydrex PEG, aluminum dichlorohydrex PG, aluminum sesquichkttohydrex PG, aluminum chloride, aluminum zirconium pentachlorohydrate, numerous other useful antipmpirant compounds listed in the CTFA Handbook at p. 56, incorpornted herein by referenc:e, and mixtures thereof.
[00108] In addition to the astringent sahs, the deodorant compound can be a bacteriostatic quatemary ammonium compound, such as, for example, cetyl trimethyl ammonium bromide, eetyl pyridinium chloride, benzethonium chloride, diisobutylbenzoxyethoxyethyld'unethylbenzyl ammonium chloride, sodium N-lauryl sarcosine, sodium N-polymethyl sarcosine, lauroyl sercosine, N-myristolyl glycine, potassium N-lauroyl saroosine, and stearyl trimethyl ammonium chloride; or a bioactive compound; or a carbonate or bicabonate salt, such as, for example, the alkali metal carbonates and bicarbonates, and the ammonium and tetralkylammonium carbonaoes and bicarbonates. Other useful deodorant compounds include chlorophyllin copper complex, aluminum chloride, aluminum chloride hexahydrate, and methylbenzethonium chloride.
[00109] Antioxidants are also useful in formulations of the invention. Typical suitable antioxidants include propyl, octyl and dodecyl esters of gallic acid, butylated hydroxyanisole (BHA, usually purchased as a mixture of ortho and meta isomers), butylated hydroxytoluene (BHT), nordihydraguaiaretic acid, Vitamin A. ascorbic aoid and its salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherol, tocopherol acetate, other esters of tocopherol, tocotrienols and their esters, and 6-hydroxy-2,5,7,8-tet=ethylchroman-2-carboxylic acid (commercially available under the tradename TROLOX). Other suitable antioxidants include uric acid and its sahg and alkyl esters, sorbic acid and its salts, lipoic acid, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine), sulthydryl compounds (e.g., glutathione, N,acetyl oysteine), dihydroxy fumaric acid and its salts, lycine pidolae, arginine pilolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, methionine, proline, superoxide dismutase, silymarin, tea extracts, grape skin/seed eatracts, melanin, and rosemary extracts may be used. It is oSen desried ahat the antioxidants be photostable antioxidants. An exemplary photostable antioxidant is marketed under the tredename EMBLICA by EMD Chemicals. See, e.g., U.S. Patent No.
6,831,191.
Antioxidants (e.g., EMBLICA), may be included in sunscreen additives at about 0.05 to about 5%, or about 0.05 to about 20/% or about 0.1'/0, 0.25'0, 0.3%, or 0.4%, or in sunscreeo/bodywashes at about 0.02 to about 2 Yo, or about 0.02 to about 1%, or about 0.04%, 0.06%, 0.08%, 0.1%, 0.29/u, or 0.3%.
[00110] Insect repellants include the most widely used active agent for personal care products, N,N-Diethyl-m-toluamide, frequently called "DEET" and available in the form of a concentrate containing at least about 95 percent DEET. Other synthetic chemical repellents include dimethyl phthalate, ethyl hexanediol, indalone, di-n-propylisocinchoronat- e, bicycloheptene, dicerboximide and tetrahydrofuraldehyde. Certain plant-derived materials also bave inseot repellent activity, including citronella oil and other sources of citronella (including lemon grass oil), limonene, rosenuuy oil and eucalyptus oil. Choice of an insect repellent for incorporation into compositions of the invention will frequently be influenced by the odor of the repellent. The amount of repellent agent used will depend upon the choice of agent; DEET is useful at high concentrations, such as up to about 15 percent or more, while some of the plant-derived substances are typically used in much lower amounts, such as 0.1 percent or less. Fragrances include essential oils, natural derivatives, and water soluble &angraces. J.
Lawless, The Blustrated Encyclopedia of Essential Oils (1995), Element Books, USA, pp. 36-41, 50-55, 57-58, 62, 106, 156-157,160, 194195, 204, 214, and 234. Non-limiting examples of essential oils are eedarwood oil, eucalyptas oil, patchouli oil, sandalwood oil, vetiver oil, guaiacwood oil, bay oil, clove oil, chamomile oil, ginger oil, cumin oil, pepper oil, rosemery oil, hinoki oil, hiba oil, pimentoberry resinoid and myrrh resinoid.
[00111] A nutraoeutical is a substance that is a food or a part of a food and provides medical or health benefits, including the prevention and treatment of disease. Such substances may be isolated nutrients, dietary supplements, genetically engineered designer foods, herbal products.
[001121 A phamu-ceutical as used herein is a compound that has medicinal or healing properties.
The pharmaaeuticals useful as actives of the present invention include the topically active compounds such as anti-inflammatory agents, anti-acne agents, and medicinals are pharmaceutical compounds described above, and also include compounds with medicinal or healing properties that are not topically active.
[00113] The compositions of the present invention may contain a wide range of additional active components. The CTFA Cosmetic InBredient Handbook, Seventh Edition, 1997 and the Eighth Edition, 2000, which are incorporated by reference herein in its entirety, describes a wide variety of active ingredients commonly used in skin care compositions, which are suitable for use in the compositions of the present invention. Other topically-active compounds are listed in Remington's Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Witkins, Baltimore, MD
(2000) (hereinafter Remington's), U.S. Phannacopeia and National Formulary, The United States Pharmacopeial Convention, Inc., Rockville, Md. and Physician's Desk Referonoe, Medical Economics Co., Inc., Oradell, N.J.incorporated herein by raference.
[00114] The non-sunscreen active may be provided as is or in encapsulated fonn. Besides the encapsulated active, in some embodiments an additive or oomposition for topical application containing the active further includes a cationic polymer, as described herein, as well as, optionally, a film former, a preservative, and/or an antioxidant that is stable upon exposure to sunlight. Other components may be as described herein. In some embodiments the additive or composition for topical application may comprise two, three, four, five, six, seven, eight, nine, ten, or more than ten actives, eaoh of which may be encapsulated or non-encapsulated, in any combination.

C. Encapsulatlon [00115) The actives used in the invention may be encapsulated. Any means of encapsulation known in the art, including but not limited to liposomes, malbodextrin capsules, silica gels, siloxanes, and the like, may be used in the compositions of the invention. The actives of the invention can, for example, be eneapsulated within microcapsules.
Microcapsules can be viewed as having two parts, the core and the shell. The core contains the active ingredient, while the shell surrounds and protects the core. The core materials used in the invention can be solid or liquid, and if liquid, can be, for example, in the form of a pure compound, solution, dispersion or emulsion. The shell material can be a natural or synthetic polymer material or cen be an inorganic material, such as a silica-based shell. The shell can be made permeable, semi-penaeable or impermeable. Permeable and semi-permeable shells can be used for release applications. Semi-permeable capsules can be made to be imperateable to the eore material but permeable to low molecular-weight liquids and can be used to absorb substances from the enviromnent and to release them again when brought into another medium. The impermeable shell encloses the core material. To release the content of the core material the shell must be tupturod. Microencapsulation useful in the present invention is described, for exatnple, in Ghosh, K., Functional Coatings and Microeneapsulation: A General Perspective, Wiley-VCH, Weinheim, 2006, Benita, S., Microencapsulation: Methods and Industrial applications, Marcel Dekker, Inc., NY, 1996., and Arshady, R., Microspheres, Microcapsules and Liposomes, Citrus Books, Latdon, 1999.
1001161 The present invention can also incorporate mesopourous shell.s. The synthesis of mesoporous hollow spheres is described in Yeh et al., Langmuir, 2006, 22, 6, and in U.S. Patent 6,913,825.
[00117] The encapsulated actives of the present invention can be made by chemical, phisico-chemical, and physico-mechanical methods such as suspension, dispersion and emulsion, coacervation, layer-by-layer polymerization (L-B-L) assembly, sol-gel encapsulation, supercritical C02-assisted microencapsulation, spray-drying, multiple nozzle spraying, fluid-bed coating, polycondensation, centrifugal techniques, vacuum encapsulation, and electrostatic encapsulation.
[00118] In some emboditnents, the active is encapsulated sol-gel micracapsules, such as silica sol-gel microcapsules. Such microeapsules are described in U.S. Patent Nos.
6,238,650;
6,436,375, 6,303,149; 6,468,509, and in U.S. Patent Application No. 2005/0 1 236 1 1. Thus, in some embodiments the invention provides an additive for addition to a composition for topical application, where the additive eomprises an encapsulated sunscreen active, and optionally further comprises a cationic polymer. In other embodiments the invention provides a composition for topical application that contains an additive, where the additive comprises an encapsulated non-sunscreen active, and optionally further comprises a cationic polymer. Further ingredients include film formers, antioxidants, proservatives, and other ingredients as listed herein. The composition for topical application may be, e.g., a bodywash.
(00119) The sol-gel process can produce particles with a ceramic shell. The shells are prepared by a sol-gel based process in which partly hydrolyzed oxides of suitable metals are prepared in the presence of an active material by hydrolysis of the gel precursor followed by condensation (alteniatively referred to as polycondensation). The gel precursor may be, for example, a metal oxide gel precursor including silicon oxide gel precursor or a transition metal oxide precursor.
The type of gel precursor used will depend on the intended use of the ceratnie particles. The gel proenrsor is typically a silioa-based gel preoursor, an alumina-besod gel prooursor, a titanium dioxide-based gel precursor, an iron oxide based gel pracursor, a zirconium dioxide-based gel precursor or any combination thereof. A fanctionaliaed, derivatized or partially hydrolyzed gel pnecursor may also be used.
[00120] There are many silicon precursors which can used in the present invention. For convenience, they can be divided into 4 categories, the silicates (silicon acetate, silicic acid or salts theraof) the silsequioxanes and poly-silsequioxanes, the silicon alkoxides (e.g. from silicon methoxide to silicon octadecyloxide), and functionalised alkoxides for ORMOCER
(Organically Modified Ceramics) production (such as ethyltrimethoxysilane, aminopropylariethoxysilane, vinyltrimethoxysilane, diethyldiethoxysilane, diphenyldiethoxysilane, ellc).
Further specific examples of silica-based gel precursors include tetramethoxysilane (TMOS), tetraethoxysilane (TEOS), tetrabutoxysilenc (TBOS), tetrapropoxysilane (TPOS), polydiethoxysilane, methyltrimethoxysilane, methyltriethoxysilane, ethyltriethoxysilane, octylpolysilsesquioxane and hexylpolysilsesquioxane. In some embodiments, the silica based precursors of the present invention are TEOS and TMOS.
[00121] Non-limiting examples of alumina-based gel pracursors include aluminium ethoxide, aluminium n- or iso-propoxide, aluminium n- or sea or tert-butoxide. Tha alkoxide can also be modified using eerboxy6c acids (for example, acetic, methacrylic, 2-odiylhexanoic acid) or beta di-ketones such as acetylacetone, ethyl-acetylacetone, benzoylacetone, or other complexing agent.
[00122] Non-limiting examples of titanium or zirconium gel precursors include the alkoxides (e.g.
elboxide, propoxide, butoxide), the metal salts (e.g. chloride, oxychloride, sulfate, nitrata) and the acid and beta diketone complexes.
(00123] The silica gel precursor or the metal oxide gel precursor may include, for example, from one to four alkoxide groups each having &om I or more oxygen atoms, and from I
to 18 carbon atoms, more typically from I to 5 carbon atoms. The alkoxide groups may be replaced by one or more suitable modifying groups or fuoctionalized or derivatized by one or more suitable derivatizing groups (see K. Tsum et al., J. Material Sci. Mater. Medicino, 1997, 8).
(00124] Typically, the silica gel precursor is a silicon alkoxide or a silicon alkyl alkoxide.

[00125] Particular examples of suitable silicon alkoxide precursors include such as methoxide, etboxide, iso-propoxide, butoxide and pentyl oxide. Particular examples of suitable silicon or metal alkyl (or phenyl) alkoxide precursors include methyl trimethoxysilane, di-methyldimethoxysilane, ethyltriethoxysilane, diethyldiethoxysilane, triethyl-methoxysilane, phenyltriethoxysilane, diphenyldiethoxysilane, vinyltriethoxysilane, etc.
Alternatively, the silica gel precursor may be a silicon earboxylate. For example, an acetate, tartrate, oxalate, lactate, propylate, formate, or citrate. Examples of other fnnetional groups attached to silica gel precursors include esters, alkylamines and amides.
[00126] Typically, the metal oxide gel precursor is a metal alkoxide which may be derivatised or functionalised Examples of suitable metal oxide precrosors include alkoxides such as methoxide, ethoxide, iso-propoxide, butyloxide and pentyl oxide. Alternatively, metal oxide gel precursor may be a metal carboxylate or a metal betadiket.onate, for exemple, an acetate, tartrate, oxalate, lactate, propylabe, formate, citrate, or acetylacetonate. Examples of other functional groups attached to metal oxide precursors include esters, alkylamines and amides.
More than one type of metal ion may be present.
[00127] Sol-gel processing is based on the hydrolysis and condensation of appropriate precursors.
Water is thus typieally used as th.e condensing agent.
[00128] The sol-gel process is carried out in the presence of a surfactant.
Suitable surfactsnts may have a hydrophilic head group and a hydrophyllic tail group. Non-limiting examples of hydrophyllic head groups are sorbitan, polyether, polyoxyethykne, sulfosuccinate, phosphate, carboxylate, sulfate, amino or aoetylacotonate and a hydophobic tail group.
The tail group may be, for example, straight or branched chain hydrocarbons with from about 8 to 24 carbon atoms, or from about 12 to 18 carbon atoms. The tail group may contain aromatic moieties such as for example iso-ociylphenyl. The surfactants can be nonionic, cationic, or anionic. Ionic surfactants sucha as oationio surfactants can be used to impart a chargo to the sol-gel capsules alone or in cornbination with cationic polymers to produce highly charged sol-gol microcapsules. Other suitable surfactants are described in detail below.
[09129] One or more of the sunscreens used in a composition may be encapsulated; in some embodiments, all sunscreens used are ene.apsulated. Sunscreen actives may be encapsulated together, or may be encapsulated separately, in any combination, in the same or in difPerent types of encapsulations. Generally, encapsulation involves trapping the sunscreen in, e.g., a vesicle.
Depending on the vesicle of choice, the vesicle may break open when applied.
Without being limited by theory, it is thought that the vesicle breaks open in various types of encapsulation due to friction, tompemture, or pH from the skin or hair, or some combination of these. By choosing the appropriate capsule and additives for the system, the stability, durability, and/or SPF provided by the sunscreen additives and sunscreen/bodywashos of the invention can be increased.
[00130] Commercial embodiments of encapsulated sunscreens or vehicles suitable for encapsulating sunscreens include CATEZOMES (Engolbard Corp.), EUSOLEX UV
PEARLS

(EMD Biosciences), and others Imown in the art. Methods of encapsulation suitable for delivering benefit agents that are mixed with a bodywash composition are well-known in the art.
See, e.g., U.S. PatentNos. 6,825,161; 6,436,375; 6,238,650; 6,468,509, 6,362,146; 6,074,630;
5,455,048;5,770,556;5,955,409;5,876,755;4,803,195;5,508,259;4,749,501 ;
6,248,703 ;
5,476,660; and 4,904,524 and EP Pat. Nos. 0,254,447; 0,025,379; end 0,399,911.
100131] One embodiment of a method of encapsulation of sunscreens is sol-gel encapsulation.
This technique is described in, e.g., U.S. Patent Nos. 6,238,650; 6,436,375, 6,303,149; and 6,468,509 and futher heroin. Any or all of the sunscreens and/or other active ingredients of the compositions of the invention may be enc.apsulated by such sol-gel encapsulation. The sol-gel capsules may be prepared so as to have a surface charge, e.g., a cationic charge. This is advantageous in that otherwise water-insoluble components may be encapsulated within the microcapsules, which are then 5eely miscible in water, e.g., without the need for an emulsifying agent. For example, in some embodiments, a UVA absorber, a UVB absorber (e.g., octyl methoxycinnamate) and/or a physical blocker, e.g., titanium dioxide, is provided as a silica sol-gel encapsulate, optionally with futtlter ingredients including PVP, Chlorphenesin, and an antioxidant such as BHT. A commeroial embodiment of such an encapsulation containing octyl methoxycinnamate, PVP, chlorphenesin, and BHT, is available under the trade name EUSOLEX
UV PEARLS (EMD Bioscienoes). Such a silica sol-gel encapsulated UVB absorber, e.g., octyl methoxycinnamate, may be used in a sunscreen additive at a oonoentration that results in a final concentcation of the UVB absorber of about 1% to about 409'0, or about 2% to about 20%, or about 2% to about 10%, or about 5% to about 10%, or about 6%, 7%, 7.4%, 7.5%, 7.6%, 8%, or 9%. In somembodiments, the final concentration is about 7.6%. In other embodiments, more than one sunscreen is encapsulated as silica sol-gol encapsulate. In these embodiments, the final concent.ration of each of the sunscreens, independently, in the final sunsareen additive, is about 1% to about 40%, or about 2% to about 20%, or about 20/a to about 10%, or about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 7.5%, 8%, 9%, or 10%. The sunscreens may be encapsulated together or sepatately, or any oombination thereoE In some embodiments, the invention provides an additive for addition to a bodywash that includes a sunscreen encapsulated in a sol-gel microcapsule and a cationic polymer (described below). Further ingredients in these embodiments may include a film former, antioxidant, preservative, chelating agent, thickener, emollient, and/or other active and inaetive ingredients as described herein.
1001321 Other fotms of immobilization or entrapment of sunscreen and other active oomponents are also useful. For example, as a furthor variant of the use of chemical sunscreen agents, compositions of the invention may employ an organic sunsareen such as octyl methoxycinnamate trapped within a matrix. A contmercial example of such a eomposition is found in SunCapsTM) (trademark, SkinCeuticals) in which the organic sunscreen molecules are evenly distributed throughout the particle.

[00133] In some embodiments the invention provides microcapsules, e.g., sol-gel mierocapsules (e.g., as described in U.S. Patents No. 6,238,650; 6,436,375, 6,303,149; and 6,468,509) that act as a protedive barrier on the skin when used either alone, or as an additive in a bodywash. In these embodiments, the sol-gel microcapsules may be used without any additional active ingredients (i.e., empty), providing a physical barrier, or they may be used with additional encapsulated active ingredients that enhance their barrier function. For example, the miotocapsules may contain substances that act to screen toxic agents (e.g., biological or chemical warfare agents) or radiation (e.g., alpha, beta, or gamma radiation) partially or completely from penetmting the user's skin. In some embodiments, the microcapsules may contain one or more agents that absorb radiation, such as graphite, lead, tungsten, and others known in the art, or agents that reflect njdiation such as ceramic beads. As the microcapsules may be designed so as to experience minimal or no breakage when applied to the skin, as well as to experienoe minimal penetretion of the skie, it is possible to use even toxic substances (e.g., lead) that provide a screening effect, since these substances will not be released or will be released in only minimal amounts. The microcapsules are eventually removed from the skin through repeated washing and/or normal sloughing of the exteroal skin cell layers. Especially for agents used for one-time or very few exposures, such as can occur for personnel engaged in combating or containing terrorist attacks or in wanPare, the invention provides a means to deliver a last line of defense on the skin of personnel where the act'rve used in the microcapsu[es may be one that is not appropriate for long-term use, but that is appropriate for a limited number of applications in order to protect the wearer fiom a greater risk (e.g., microcapsules encapsulating lead to pnobect against a radiation attack). Additives for protecting the user include agents that protect a user from the environment, including additives that protect fire fighters from the toxic agents generated in a fire, for protection of workers in factory environments that eontain toxins, and for protection of individuals from hararful atmospheric compounds such as pi otection from acid rain.
[00134] In some embodiments, the active is encapsulated sol-gel microcapsules, such as silica sol-gel microcapsules. Such microcapsules are described in U.S. Patent Nos.
6,238,650;
6,436,375, 6,303,149; and 6,468,509. Thus, in some embodiments the invention provides an additive for addition to a composition for topical application, where the additive comprises an encapsulated non-sunscreen aotive, and optionally further comprises a cationic polymer. In other embodiments the invention provides a composition for topical application that contains an additive, where the additive comprises an encapsulated non-sunscreen active, and optionally further comprises a cationic polymer. Further ingredients include film formers, antioxidants, preservatives, and other ingredients as listed herein. The composition for topical application may be, e.g., a bodywash.
[061351 Microoapsules of the present invention can have a positive charge density. The microcapsules of the present invention can have a positive charge. 'Itie positive charge can, for example, can impart improved emulsion stability and improve adhesion to the sk7n. While not being bound by theory, one framework commonly employed in the area of colloid sciences is the DLVO theory, which states that the stability of a particle in solution is dependent upon its total potential energy function, V. The theory recogniDes that VT is the balance of several competing contributions: the potential energy due to solvent, Vs, the potential energy due to attraction, Vk, and the potential energy due to repulsion, VR. The potential energy due to repulsion, VR, is an important contributor to the stability of the colloid. One aspect of Va is the electrostatic repulsion, which is rehued to the square of the zeta potential. The zeta potential can be described in the following manner. Each particle has a liquid layer around it that can be viewed as existing as two parts; an inner region (Stern layer) where the ions are strongly bound and an outer (diffuse) n:gion where they are less firmly associated. This system is referred to as the double layer. Within the diffuse layer there is a notional boundary inside which the ions and particles form a stable entity. When a particle moves, ions within the boundary move it.
Those ions beyond the boundary stay with the bulk dispersant. The potential at this boundary (surface of hydrodynamic shear) is the zeta potential. Beoause the electrostatic repulsion of the repulsion potential, VR is related to the square of the zeta potential, as the square of the zeta potential rises, the eleotrostatic repulsion rises, and the stability of the colloid rises. The positively charged microcapsules of the present invention thus exhibit gtability in solution, while at the same tinie, potentially providing enhanced binding to the skin and bair.
[00136] Zeta potential can be calculated using theoretical models and an experimentally-determined electrophoretic mobility or dynamic ebetrophoretic mobility.
Eleclrokinetic phenomena and electroacoustic phenomena are the usual sources of data for calculation of zeta potential. For example, electrophoresis ie used for estimating zeta potential of particulates.
Electrophorotic velocity is genemiUy proportional to electrophoretic mobility, which is the measurable parameter. There are several theorles that link oleotrophoretic mobility with zeta potential (see, for example, Lykiema, J. "Fundamentals of Interface and Colloid Science", vol.2, page.3.208, 1995; and Hunter, R.J. "Foundations of Colloid Science", Oxford University Press, 1989). Zeta potential can be determined, for example using microelectrophoiesis or elech+ophoretic light scattering. With microelectrophoresis, images of the moving particles are used. In some cases, this method can be eomplicated by eleetro-osmosis at the walls of the sample cell.
[00137] Electrophoretic light scattering is based on dynamic light scattering.
It allows measurement in an open cell, which eliminates the problem of electro-osmotic flow. Both these measuring techniques generally require dilution of the semple. Dilution is usually performed using equilibrium supernatant solution to minimize the effeot of dilution on the zeta potential. In some cases, zeta potential can be measured electroacoustically. For example, the techniques of Colloid Vibration Ciment and Eleotric Sonic Amplitude can be used, (Dukhin, A.S. and Goetz, P.J. "Ultrasound for characterizing colloids", Elsevier, 2002. reference). In some cases, the measurement of zota potential provides a distribution of zeta potentials for the particles in the sample. In other cases, the methods provide a single zeta potential for the sample. l.Jenerally herein, where a reference to a zeta potential for a sample is described, it represents either the single measurement for the sample, or the mean, median or avemge of the distribution. In some cases the median value of the distribution of zeta potentials is used.
[001381 The zete potential can be meaaured for instance on a 7etasizer instrument from Malvern Instruments, Malvern, UK, or on a ZetaPlus or ZetaPALS instnunent from Brookhaven Instroments, Holtsville, NY.
[001391 In some embodiments, the microcapsules of the present invention have a zeta potential of at least about 5, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90 or 100 mV. In some embodiments, the microcapsules of the present invention have a zeta potential of no more than about 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 150, 200, 300, 400 or 500 mV. In some embodiments the zeta potential is between 10 and 70 mV, between 20 and 65 mV, between 25 and 65 mV, betwean 30 and 60 mV, between 30 and 100 mV, between 40 and 80 mV, between 70 and 100 mV or between 40 and 55 mV. In some embodiments, the microcapsules have a zeta potential of at least about 70 mV, in some embodiniants, the microcapsules have a zeta potential of at least about 60 mV, in some embodiments, the microoapsules have a zeta potential of at least about 50 mV, in some embodiments, the microoapsules have a zota potential of at lesst about 45 mV, in some embodiments, the microcapsules have a zeta potential of at least about 35 mV, in some embodiments, the microcapsules have a zeta potential of at least about 25 mV in some embodiments, the microcapsules have a zeta potential of at least about 15 mV.
[001401 The microcapsules of the present invention are usually dispersed in water or in an aqueous medium. The aqueous medium may contain salts, surfactants, viscosity modifiers, film fonners, and other additives that may affect the zeta potential of the perticles. It is known, for example that the zeta potential of a particle can be affected by the pH of the medium. The pH of the medium will have a particularly large effect on the zeta potential of a microcapsuk when the microcapsule has ionizable, e.g. acidic or basic groups on its surface. For instance, where the microcapsule has a neutral acidic group, such as a carboxylic acid, that gives up a positively charged proton to the solution, the loss of the positively charged proton to the solution can give rise to one negative charge on the microcapsule surface. Conversely, a mierocapsule surface with a neutral basic entity such as a trialkylamine, can beconie protonated in acidic solution, thus causing the microeapsule to take on a positive charge for each proton added.
In both cases, the magnitude of the surface charge depends on the acidic or basic strengths of the surface groups and on the pH of the solution. In aqueous media, where the microcapsule has ionizable groups, the pH of the solution can have a dramatic affect on its zeta potential. For example, a microcapsule with ionizable carboxylic acid groups on the surface will have a negative zeta potential at high pH (basic conditions). If acid is added to this suspension then solution becomes more acidic, and the microcapsules tend to lose their negative charge. If enough acid is added to this suspension then a point wi11 be reached where the charge will be neutralized. Where all of the charge is neutralized, there can be a point where microcapsules have zero zeta potential. This point is called the isoelectric point. The isoeleotric point is normally the point where the colloidal system is least stable. Further addition of acid may cause a build up of positive charge on the microcapsules. Therefore a zeta potential versus pH curve will generally be positive at low pH
and lower or negative at high pH
[00141] One aspect of the present invention is encapsulated actives wherein the capsules are positively charged at the pH at which the encapsulated additives are stored and applied. It will be understood by those skilled in the art that for tepical applications, the compositions of the present invention will generally not be extremely acidic or extremely basic, because such solutions could be damaging to biological tissue such as skin and hair. Such solutions generally have a pH of 2-7. It will also be understood that whero the applioation is not to a body, it may be desirable to have extremely high or low pH. For instance, in some cases, it will be useful to have an active agent with the capability of etching a surface such as a glass or a metal, where an very high or low pH is useful. Thus, the compositions of the present invention are formulated to have capsules of the desired zeta potential in the pH range of use.
[00142] The compounds of the prasont invention can also use buffered systems.
Buffered systems use combinations of acidic and basic species in order to create a solution that has a pH
which is less sensitive to the loss or addition of acidic or basic species.
The buffered systems are used to stabilize the pH of the composition.
[001431 The capsules of the present invention will often have more than one acidic or basic group associated with the surfaca of the psrticle. For instance the particle may have a sol-gel eoating, surfactants, and cationic components, each of which may have ionizable, acidic, or basic groups.
The acidity of a group is can be represented by the pKa of the group. Under ideal conditions, the pKa is the pH at which the functional group is equally in its protonated and non-protonated forms. At a pH above the pKa most groups will be non-protonated. At a pH below the pKa, most of the groups will be protonated. Thus, where there are a variety of functional groups, each of these groups on the surface of the microcapsule that had a differont pKa would give rise to a different zeta potential versus different pH response. The zeta potential on the capsule will be a composite of the zeta potentials that would be provided by each of these groups individually at any given pH. It would be understood by one skilled in the art to use compositions and processes in order to provide the relative amount of each of these groups to provide the desired zeta potential at the desired pH range of the composition.
[001441 The zeta potential can also be affected by the level of other salts in solution, also referred to as the ionic strength. In genetal, the higher the ionic strength, the more compressed is the double layer. The type of ion in solution can also affect the zeta potential.
For example, multivalent ions will notmally compress the double layer more than monovalent ions. As would be appreciated by one of skill in the art, the number and type of ion in the compositions of the present invention can be modified in order to produce the highly charged sol-gel microcapsules of the present invention.
[00145] One aspect of the invention is the use of non-ionizable cationic agents to create a positively ebarged microcapsnle. For example, a quatornery ammonium functional group, such as that present in the polyquaterniums has nitrogen molecules which have 4 alkyl groups covalently attached. The positively charged nitrogen atoms have no protons to donate and no lone pairs are present to accept protons. This resuhs in a positive charge on these molecules over a wide pH range. These groups are charged, but are thus considered neither acidic nor basic in the pH ranges useful in topical applications. Since the groups are neither acidic nor basic, they tend to provide microcapsules with a zeta potential which is less sensitive to changes in pH than for a microcapsule with a positively charged ionizable group. Having a zeta potential which is less sensitive to pH can be useful in providing freedom to fonnulata the compound containing the microcapsules, and for maintaining stability when the compound is exposed to conditions which might affect its pH.
[00146] While it is usually desired to have a high positive zeta potential on the microcapsules of the invention, there are cases, where it a negative zeta potential is desired.
A negative zeta potentlal may be desired, for example for a wash off product, where there is less of a need for the capsules to adhere to skin and hair.
[00147] Methods of deteoting the quantity of additives functionally remaining on the skin or hair are known in the art. One nonexchusive method is to measure the functionafity of the add"-tive on the skin or hair. This can be accomplished by applying an additive encapsulated in a microcapsule to the skin, and measuring the activity level of the additive.
Another teehnique to measuro thc amount of additive functionally ramaining on the skin is tape stripping, which is well known in the art A microcapsule encapsulating an additive and dye compound is applied to the skin or hair. An adhesive material is applied to the skin and removed. The nemoved tape can then be analyzed. The level of the dye can be measured, which can thea be correlated with the quantity of microoapsules bound to the skin. An electron microscope can also be used to detect whether the microcapsules are broken open, and to deterntine how many microcapsules are present per unit area. Multiple tape strippings can be performed sequentially.
Each tape strip cevoals a different level of the skin, so can be used to determine how deep the microcapsules penetrate.
[00148] In some embodiments wherein encapsulation, e.g., sol-gel microencapsulation, is utilized, the composition of the microcapsule, e.g., sol-gel microcapsule, may be varied so as to allow for varying amounts of the active within the microcapsule to be released. The microcapsules, e.g., sol-gel microcapsules, can be prepared so as to experience minimal or no breakage when applied to the skin and when left on the skin. Alternatively, the microcapsules, e.g., sol-gel microcapsules, can be prepared so as to experience various degrces of breakage, on average, when applied to the skin and when left on the skin. Thus, the micrncapsules, e.g., sol-gel WO 2008/144734 PCT[US2008/064369 microcapsules, may be prepared so as to experience about 0% breakage, or breakage in a range from ebout 0.1, 0.5,1, 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, or 90% to about 0.5, 1, 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, or 90%, after application (or application and rinsing in the case of a or bodywash containing the microcapsules). Furthermore, the microcapsules may be formulated so as to break open in response to conditions that occur on the skin, so that after application the microcapsules aot to release their contents in a time-release or controlled manner. Non-limiting exemplary skin or hair conditions that can vary with the user's environment, the variation of which can trigger breakage of microcapsules, include pH, temperature, friction, exposure to light or air, pressure, enzymes, and the like.
[00149] In some cases the capsules ane designed to break open and release their contents within a short period of time of contacting the skin or hair. For example, where a free-radical scavenger such as Vitamin E acetate is encapsulated, the capsules are formulated to break readily upon topical treatment, such that more than 501'= of the capsules break open within 10,15, 25, 35, or 50 minutes of topical application. In other cases, for example, where a skin lightener is encapsulatod, the capsules can be formulated such that the active is released over a long period of time, for example, where 50% of the active is released after 4, 8, 12, 24, or 48 hours.
[00150]One way of controlling whether the microcapsules will tend to break is by controlling the conditions of manufacture including the tempemture and the shear during mixing. In some cases, polymer wrapped or poiymer coated niicrocapsules such as silica microcepsules will be able to stand higher salt concentrations and alkaline pH. The polymeric coatings are believed to assist in controlling breaking both by acting as a chemical barrier between the silica and the enviroument and also by providing more mechanical strength and elasticity.
[00151] The tendenoy of a mierocapsule to break under shear can be moasured by exposing the compound containing microcapsules to a set of conditions of shear (e.g. by controlling the RPM of stirring), temperature, and time, and analyzing the resulting mixtun; or aliquot of the mixture. The mixture can be analyzed, for example, by analyzing the solution in which the microcapsules are dispersed by high perfonnattce liquid chromatography (HPLC), which can be used to determine the amount of active or other oomponent that has gone into the solution.

D. Catiouic componeat [00152] One aspect of the invention is a composition with containing a cationic agent. In some embodiments the cationic agent is added to the sunscreen or non-sunsoreen additive, imparting beneficial properties such as promoting attachment of the additive to skin or hair. In other embodiments the cationic agent is associated with the microcapsule, providing positive charge to the microcapsule. In some embodiments the additives, e.g., sunscreen additives and sunscreen/bodywashes of the invention include a cationic component. Without being bound by theory, it is thought that this component serves as a protein binder, to provide a positive charge to promote attachment of the composition to proteins of the skin and hair, thus increasing retention of the components, e.g., sunscreen, after rinse and during normal activities.
This positive charge can create a strong aB-uiity for the protem in the hair or skin. As described above, the cationic component can also create a positive charge on the surface of a microcapsule so as to stabilize the composition. Any means of imparting a positive cberge to the mierocapsule may be used.
[001531 In sonie embodiments any suitable cationic compound that may be useful to impart a positive charge on the microcapsule may be used.
[0015411n some embodiments, one or more cationic polymers are included in the composition. The term polymer means many "mers" or units. As used herein, the term polymer means a molecule having two or more tepeating units. Various cationic polymers may be used.
Examples of cationic polymers are desoribed in U.S. Pat. Nos. 6,224,852; 3,816,616;
4,272,515; 4,298,494;
4,080,310; 4,048,301; 4,009,256; and 3,186,911. Cationic polymers are available commercially, e.g., from Union Carbide Corp. under the trademark POLYMER JR., from Celanese-Stein Hall under the trademark JAGUAR, from GAF Corporation under the tradename Gafquatm and from Merck & Co., Inc under the trademark MERQUAT by. Roptesantat'tve one are Marquat 100, a highly charged cationic dimetbyldiallylammonium chloride homopolymer, and Merquat"m 550, a highly charged cationic copolymer prepared with dimethyidiallylammonium chloride and acrylamide. These materials are designated in the CTFA dictionary as Quaternium40 and Quaternium-4l, respectively.
1001551 Suitable cationic polymers include Polyquaternium-4 (Celquat H-100;
L200-supplier National Starch); Polyquaternium-7; Polyquaternium-10 (Celquat SC-240C; SC-230 M-supplier National Statch); (UCARE polymer series-JR-125, JR-400, LR-400, LR-30M, LK, supplier Anterohol); Polyquaternium-11(Gafquat 734; 755N--supplier ISP); Polyquaternium-16 (Luviquat FC 370; FC550; FC905; HM-552 supplier by BASF); Polyquatemium-22, Polyquaternium-37, Polyquaternium-44, Polyquaternium-51, and Polyquaternium-64.
PVP/Dimethylaminoethyhnetbacrylate (Copolymer 845; 937; 958--ISP supplier);
Vinyl Caprolactam/PVP/Dimethylaminoethyl Methacrylate copolymer (Gaffix VC-713;

supplier ISP); Chitosan (Kytamer L; Kytamer PC-supplier Amerohol);
Polyquatemium-7 (Merquat 550-supplier Calgon); Polyquatemium-18 (Mirapol A2r1 supplied by Rhone-Poulenc);
Polyquaternium-24 (Quatrisoft Polymer LM-200--supplier Amerchol);
Polyquatemium-28 (Gafquat HS-100--supplier ISP); Polyquaternium-46 (Luviquat Hold-supplier BASF); and Chitosan Glycolate (Hydagen CMF; CMFP-supplier Henkel); Hydroxyethyl Cetyldimonium Phosphate (Luviquat Mono CP--supplier BASF); and Guar Hydroxylpropyl Trimonium Chloride (Jaguar C series -13S, -14S, -17, 162,-2000, Hi-CARE 1000--supplier Rhone-Poulenc).
1001561 Suitable cationic polymers also include Chitosan (Chitosan); Guar Hydroxypropyltrimonium Chloride (Guar Hydroxypropyltrimonium Chloride);
Hydroxypropyl Guar Hydroxypropyltrimonium Chloride; Poly(Ethylenimine) (PEI-7 PEI-I O PEI-1500 ... PEI-7500 PEI-14M); Poly(Methacrylamidopropyltrimonium ChlorideJMethosulfato) (Polymethacrylamidopropyltrimonium Chloride); (Polyquatemium-2);

Co(Hydroxyethyloellulose-g-Diallyldimethyl Ammonium Chloride) (Polyquaternium-4);
Poly(Diallylditnethyl Ammonium Chloride) (Polyquatemium-6); Co(Diallyldimethyl Ammonium Chloride-Aciylamide) (Polyquaternium-7); Hydroxypropyltrinwnium Hydroxyethylcellulose Chloride (Polyquaternium-10); Quatemized Co(Vinyl Pyrrolidone-Dimethylaminoethyl Methacrylate) (Polyquatemium-11); Co(Diallyiditnethyl Ammonium Chloride-Acrylic Acid) (Polyquaternium-22); Hydroxypropyllauryldimonium Hydroxyethylcellulose Chloride (Polyquaternium-24); Co(Vinyl Pyrrolidone-Methacrylamidopropyl Trimethylammonium Chloride) (Polyquatemium-28); Co(Diallyldimethyl Ammonium Chloride-Acrylic Acid-Acrylamide) (Polyquaternium-39); Co(Vinyl Caprolactam-Vinyl Pyrrolidone-N-Vinyl-N-Methyl Imidazolinium Methosulfate) (Polyquateroium-46); Co(Vinyl Pyrrolidono-Dimethylaminopropylmethacrylamido-Lauryl Dimethyl Methacrylamidopropyl Ammonium Chloride) (Polyquaternium-55); Co(Vinylpynrolidone-Dimethylaminoethylmethacrylate)/Polycarbamyl Polyglycol Ester (PVP/Dimethylaminoethylmethacrylate)Polycarbamyl Polyglycol Estar); Co(Vinyl Pyrrolidone-Dimethylaminopropyl Methacrylamide) (PVP/DMAPA Copolymer); Co(Vinyl Pyrrolidone-Dimethylatninoethyl Methacrylate) (Vinyl Pyrrolidone/Dimethylamincethylmethacrylate Copolymer); Co(Vinyl Pyrrolidone-Vinyl Caprolactam-Dimethylamin)ethylmethacrylate) (Vinyl Pyrrolidonc/Vinyl Caprolaetam/ Dimethylaminoethylmethecrylate Terpolymer);
Co(Vinyl Pyrrolidone-Vinyl Caprolactam-Dimethylaminopropylmethacrylamide (Vinyl PyrrolidonelVinyl Caprolactam/ Dimethylaminopropylmethacrylamide Terpolymer); Co(Vinyl Pyrmlidone-Vinyl Imidazole) (Vinyl Pytrolidone/Vinyl Imidazole Copolymer); and Co(Vinyl Pynrolidone-3-methyl-l-Vinyl'unidazolinium methyl sulfate) (Vinyl Pyffolidone/Vinylimidazolinium Methylsulfate Copolymer).
100157J Some embodiments employ polyquaterniums. Quaternized material in powder fonn, not limited to the polyquaterniums, may also be used. Exemplary polyquaterniums of usa in the invention include Polyquaternium-0, -7, -11, -22, -37, -44, -51, and -64.
Without being limited by theory, it is believed that with the trapping of the encapsulate (e.g., sunscreen active inside the capsule) by the cationic component increasas adhesion to the skin, making rinse off difficult and facilitating rendering the active substance, for instance, to the protein in the skin and hair. In other embodiments, other polyqua6omiums may be useful for imparting a positive charge on the microcapsules.
Mixtures of the earionic components can be used. Uses of mixtures of cationic components can be made to increase solubility, improve processing, and to improve the properties of the compound, for example, enhancing adhesion to the skin and hair. Mixturas of different polyquatemiums can be used, for example, polyquaterniums with differont molecular weight ranges, and mixtures of polyquaterniums and non-polyquaterniums can be used.
100158) In some embodiments cationic surfactants can be used to impart a positive charge on the mierocapsules. Cationic surfaetants useful in the invention are described below. While the eationie component should be catioinic over all, the cationic eomponent may also contain some anionic groups as well, and may be, for example amphoteric.
1001591 Useful in some embodiments of the invention is a dry cationic component, such as sold under the tradename CAE (Anjinomoto Co., Inc.), containing DL-pyrrolidone Carboxylic acid salt of L-Cocoyl Arginine Ethyl Ester, which is a cationic agent useful for binding to proteins and providing an antimicrobial affect.
[00160J In some embodiments, as an additive, the cationic component comprises about 0.1 to about 20'/o, or about 0.1 to about 10%, or about 0.5 to about 100/9, or about 1 to about 10%, or about 0.5 to about 5%, or about 0.5 to about 3% or about I to about 5"/0, or about I to about 3%, or about 1% of the total eomposition. In some embodiments, the cationic component includes polyquaternium-4; in some embodiments the polyquaternium-4 is present at about 1%.
[001611 In some embodiments of active/bodywashes, e.g., sunsareen/bodywashes, the cationic component (e.g., cationic polymer) comprises about 0.03 to about 7%, or about 0.03 to about 4%, or about 0.2 to about 4%, or about 0.3 to about 4%, or about 0.2 to about 2%, or about 0.3 to about 4%, or about 0.3 to about l%õ or about 0.3 or 0.4% of the total composition. In some embodiments, the cationic component is polyquaternium-4; in some embodiments the polyqueternium4 is present at about 0.33%.
[00162] In some embodiments, the cationic compound may be associated with the microcapsule in any suitable tnamter. In some embodiments the cationic compound is associatod with the outside of the highly charged miorocapsule. The cationic compound may be covalently bound to the microcapsule, may be bound non-oovalently, or may exhibit a mixture of covalent and non-covalent binding. Non-limiting Examples of types non-covalent intemctions between the cstionic compound and the microcapsule are those due to electrostatic, hydrogen bonds, hydrophobic, or Van Der Waals forces.
[001631 In some embodiments it is desired to have an active contained within a microcapsule, while at the same time, providing another active outside the capsule, in the continuous phase of the composition. In one non-limiting example, it may be desired to have a moisturizer outside of the capsule for immediate access to the skin, while at the same time having a fiagrance encapsulated within a capsule, for a longer, more controlled release of the fragrance.
Another example of providing one active inside the capsule and another outside the capsule is in the area of tanning.
In some cases a tanning active is used that is activated by another compound, for example by an amino acid. In such cases, the tanning active may be encapsulated within the microcapsule, while the activating compound is provided in the topical formulation, but outside of the mierocapsules, and prevented &om interacting with the tanning active on storage. Upon topical application, the sol-gel microcapsuies are broken, for example, by friction, pressure, pH
change, light, or enzymatic action, allowing release of the encapsulated active and allowing interaction of the activator with the tanning agent. This composition of one active encapsulated inside the microcapsule and one active outside the mierocapsule allows for greater control of the tanning process and for improved storage life ofthe composition.
E Film formers 1001641 In some embodiments, compositions of the invention fvrl[her include a component that provide a film barrier system, typically a hydrophobic layer that serves to maintain the residual sunscreen after rinse. Film barrier systems are well-known in the art and include, without limitation, petrolatum, silicon derivatives, and oambinations thereof. Also useful are polymers with carboxylic ends which render themselves insoluble until neutralized.
After being neutralized they can act as film formers. Film formers also include emollient esters, lanolin derivatives (e.g., acetylated lanolins), and superfatted oils. Film formers are available commercially, e.g., one exemplary film former is MOIST(JREGUARDr*% which contains petrolstum, dimethicone, stearamidopropyl dimethylamine stearate, and tocopheryl acetate, available from Engethard.
[00165] It may also be desirable to add acrylic eo-polymers to the formulations of the invention as fihn fonmers. An exemplary liquid acrylic copolymer formulation is DERMACRYL, marketed by National Starch and Chemical. Acrylic co-polymers may be included in sunscreen additives at about 0.1 to about 5%, or about 0.2 to about 3%, or about 0.2%, 0.3%, 0.4"/0, or 0.5%, or in sunscreen/bodywashes at about 0.05 to about 2%, or about 0.1 to about 1%, or about 0.05%, 0.1%, 02%, 0.3%, 0.4%, or 0.5%.
[00166] A secondary film former may also be used, e.g., keratin or other protein derivative in an amino acid complex such as cysteine.
(00167] The film former may be present in the sunscreen additive in the range of about 0.1 to about 25%, or about 1 to about 10%; or about 2 to about 6%; or about 3, 4, or 5%. In some embodiments, the fibn former MoistureGuard is used at a concentration of about 4.2%.
Equivalent fibn formers, at equivalent concentrations, may also be used.
[0016g] As noted, some preparations may perform more than one function, for example, inorganic blockers such as Tioveil and Speetravoil (both of the Tioxide Oroup), in certain variations, may be film-formers and may have advantageous uses here.
[00169] .In addition, many emollients may also perform a film foimer function in that they provide a barrier on the skin. Thus, oompositions of the invention may include water-insoluble emollients that include fatty acids such as oleic and stearic; fatty alcohols such as cetyl, and hexadecyl (ENJAY); esters such as diisopropyl adipate, benzoic acid esters of C9 -C15 ak.ohols, and isononyl iso-nonanoate; alkanes such as mineral oil; silicones; such as dimethyl polysiloxane and ethers such as polyoxypropylene butyl ethers and polyoxypropylene cetyl ethers. If a water-insoluble emoiflent is used it may be in an amount from about 2% to about 15%
by weight, or from about 4% to about 10%.
[00170] Other useful film formers include polythylenes, such as those available from New Phase Technologies as PERFORMALENE 400, a polyethylene having a molecular weight of 400.

Another suitable water-proofiag agent is polyethylene 2000 (molecular weight of 2000), which is available from New Phase Technologies as PERFORMALENE 2000.
1001711 Yet another suitable fihn former/waterproofmg agent is synthetic wax, also available from New Phase Technologies as PERFORMA V-825. Still yet another suitable film fonner/waterproofmg agent is octadeeeneJMA copolymer 1001721 Additional film formers which also may be used within the framework of the invention include any fibn fonner chemistry known in the art. Thus, suitable additional film fonmers inciude acacia gum, cellulose derivatives, guar derivatives and all those set forth on pages 68-69 of the C.T.F.A. Cosmetic Ingredient Handbook, First Edition, 1988, which is hereby incorporated by reference. Such film formers include acrylamides copolymer, acrylamide/sodium aciylate copolymer, acrylate/acrylamide copolymer, acrylate/ammonium melhacrylate copolymer, acrylates copolymer, acrylates/diacetoneacrylamide copolymer, acryliclacrylate copolynwr, adipic acid/dimethylaminohydrosypropyl diethlenetnsmine copolymer, adipic acid/epoxypropyl/diethlenetriamine copolymer, albumen, allyl steerate/VA
cqpolymer, aminoethylaarylate phosphate/acrylate eopolymer, ammonium acrylates copolymer, smmonium alginate, ammonium vinyl acetate/acrylates copolymer, AMP
acrylates/diaoetoneacrylamide copolyiner, balsam canada, balsem orogon, balsam peru, balsam tolu, benzoi acid/phthalic anhydride/pentaerythritoVneopentyl glycol/palmitic acid copolymer, benzoin extraot, butadiene/acrylonitrile copolymer, butylated uroa-formaldehyde resin, butyl benzoic acid/phthalic anhydride trimethylolethane copolymer, butyl ester of ethylene maleic anhydride copolyiner, butyl ester of PVM/MA copolymer, calcium carrageenean, calcium/sodium PVM/MA
copolymer, carboxymethyl hydroxyethyl collulose, cellulose gum, collodion, copal, cora starch/aciylainide/sodium acrylata copolymer, damar, diethylene glycolamine%pichiorohydrin/piperazine copolymer, DMJ-IF, dodeoanedoic acid/cetearyl alcoholglycol copolymer, ethylcellulose, ethylene/acrylate copolymer, ethylene/maleic anhydride copolymer, ethylene/vinyl acotate copolymer, ethyl ester of PVM/fvlA
copolymer, flexible collodian, gunt benzoin, gutta percha, hydroxybutyl methylceflulose, bydroxyethylcellulose, hydroxyethyl cthyl cellulose, hydroxypropylceilulose, hydroxypropyl guar, hydroxypropyl methylcellulose, isopropyl ester of PVM/MA copolymer, maltodextrin, melamine/formaldehyde resin, methacryloyl ethyl betainelmethacrylates copolyrner, nitrocellulose, octylacrylamide/acrylates/butylaminoethylmethaciylate copolymer, octylacrylamide/acrylates copolymer, phthatic anhydride/glycerin/gycidyl decanoate copolymer, phthaGc/trimellitic/glycols copolymer, polyacrylamide, polyaciyhunidomethylpropane sulfone aeid, polyacrylic acid, polybutylene terephthalate, polychlorotrifluoroethylene, polyethylacrylate, polyethylene, polyethylene terophthalate, polyisobutene, Polyquaternium-1, Polyquaternium-2, Polyquaternium-4, Polyquaternium-5, Polyquatcmium-6, Polyquatemium-7, Polyquaten-ium-8, Polyquaternium-9, Polyquaternium-10, Polyquatemium-1 1, Polyquatemiuni-12, Polyquaternium-13, Polyquaternium-14, Polyquaternium-15, polyatyrene, polyvinyl acetate, polyvinyl alcohol, polyvinyl butyral, polyvinyl iinidazolinium acetate, polyvinyl huuate, polyvinyl methyl ether, potassium carrageenan, PVM/MA copolymer, PVP, PVP/dimethylaminoethymethacrylate copolymer, PVP/eicosene copolytner, PVP/ethyl melhacrylate/methacrylic acid copolyerm, PVP/hexadecene copolymer, PVPNA copolymer, PVP/vinyl acetate/itaconic acid copolyrner, rosin, serum albumin, shellac, sodium acrylateJvinyl alcohol, copolymer, sodium carrageen, sodium polymethacrylate, sodium polystyrene sulfonate, starchlacrylates/acrylamide copolymer, starch diethylaminoethyl ether, steaxyvinyl ether/maleic anhydride copolymer, styrene/acrylate/acrylonitrile copolymer, styrene/aorylate/ammonium methaorylate copolymer, styrenelmaleic anhydride copolymer, styrene/PVP copolymer, sucrose benzoate/sucrose acetate isobutyrate/butyl benzyl phthalate copolymer, suoroe benzoate/sucrose acetate isobutymte/butyl benzyl phthalate/methyl methaciylate copolymer, sucrosa benzoatelsucrose ac.etate isobutyrate copolymer, toluenesulfonamide/formaldehyde resin, tragacath gum, vinyl acetate%rotonates copolymer, vinyl aeetate%rotonic acid copolymer, vinyl acetate%rotonic acid/methacryloxybenzophenon-l copolymer, vinyl acetate/crotonic aid/vinyl neodecanoate copolymer, and zein [00173] Additional film formers include those set forth in U.S. Pat. Nos.
6,838,419; 6,838,088;
6,780,422,; 6,531,118; and 5,916,541, all of which are incorporated herein by reference F. Other components (001741 A wide variety of additional eomponents may be added to the compositions of the present invention, as long as the components are selected so as to avoid any undesirable reaction with the primary oomponents (e.g., one or more of the sunscreen agents) of the composition. The CTFA
Cosmetic Ingredient Handbook, Seventh Edition, 1997 and the Eighth Edition, (incorporated by reference herein), provide a broad source of possible cosmetic and pharmaceutical ingredients typically used in skin eare compositions. Examples of such additional components include one or more of the following: Absorbents, abrasives, anticaking agents, antifoaming agents, binders, biological additives, buffering agents, bulking agents, chelating agents/sequestrants (e.g., disodium EDTA), chemioal additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, emollients (including glycerin alovera, and Vitamins A, C, and D[hydrating agents and skin protectnnts]), foam boosters, fragrance components, gums, humectants/moisturizers (including urea, guanidine, glycolic acid, polyhydroxy alcohols such as sorbitol, glycerin, hexanetriol, propylene glycol, hexylene glycol and the like, polyethylene glycol, sugars and starches, sugar and starch derivatives, D-panthenol, hyaluronic acid, lactamide monoethanolamine, acotamide monoethanolamine, and mixtures thereof), hydrotropes, neutralizing agents, opacifying agents and pigments, pH
adjusters, plasticizers, preservatives, propellants, reducing agents, skin bk.aching agents, skin protectants, solubilizing agents, and suspending agents (e.g., Carbomer 1382).

[00175] In some embodiments, anionic polymers are used. Suitable anionic polymers include Crosslinkad, Hydrophobically Modified Poly(Acrylie Acid) (Acrylates/C 10-30 Alkyl Aeiylate Crosspolymer ); Co(Alkyl Acrylate-Alkyl Methacrylate-Acrylic Acid-Methacrylic Acid) (Acrylates Copolymer ); Co(Aerylio Acid-Metbacrylic Acid-Alkyl Acrylates), Crosslinked (Acrylates Copolymer ); Crosslinked, Co(Alkyl Acrylato-Methacrylic Acid) (Acrylates Copolymer ); Co(Alkyl Acrylate-Methacrylic Acid-Acrylic Acid-Beheneth-25 Methacrylate) (Acrylates/Methacrylates/ Beheneth-25 Methacrylate Copolymer ); Co(Alkyl Acrylata Methacrylic Acid-Steareth-20 Methecrylate) (Acrylates/Stearoth-20 Methacrylate Copolymer);
Co(Methacrylic Acid-Atkylene Succinic Acid-Alkyl Acrylate-Hydroxyalkyl Acrylate) Tetrapolymer (Acrylates/[C1-2 Succinates]/Hydroxyacrylates Copolymer );
Alginic Acid (Alginic Acid or Algin for Sodium Alginate); Crosslinked Poly(Acrylic Acid) (Carbomer );
Sodium Carboxymetbylceiiulose (Cellulose Gum); Co(Polyethybne Glycol-1,4 Cyclohexanedimethanol-Isophtalic Acid-Sulphonated Isophtalic Acid) (Diglycol/CHDM/Isophtalates/SIP Copolymer); Co(Methyl Vinyl Ether/Maleie Acid) (Methyl Vinyl Ether/Maleic Acid Copolymer ); Co(Methyl Vinyl Ether/Maleic Acid-l,9-Decadicne) (PVM/MA Decadiene Crosspolymer ); Monoalkyl Ester of Poly(Methyl Vinyl Ether/Maleic Acid) (Monoalkyl Ester of PVM/MA Copolymer); Co(Octylacrylamide-Acrylates-Butylaminoethyl Methaorylate) Terpolymer (Oetylaerylamide-Acrylates-Butylaminoethyl Methacrylate Coolymer ); Poly(Styrene Sulpfonate), Sodium Salt (Sodium Polystyrene Sulfonate ); Co(Acrylic Acid-Methacrylic Acid-Alkyl Acrylates - Steareth-10 Allyl Ether) (Stcareth-10 Allyl Ether/Acrylates Copolymer ); Co(Vinyl Acetate-Crotonic Acid) (VA/Crotonates Copolymer ); Co(Vinyl Acetate-Crotonic Acid-Vinyl Neodecanoate) Torpolymer (VA/CrotonatesNinyl Neodecanoate Copolymer ); and Xanthan Gum.
1001761 In some embodiments, the additives and bodywashes of the invention, e.g., sunscreen additives or sunscreen/hodywashes include a presorvative. Exemplary praservatives useful in the invention include citric acid, tartaric acid, phosphoric acid, iminodiacetic acid, nitrilotriacetic acid, hydroxyethyleneaminodiaceNe acid and ethylenediaminetetraacetic acid and salts thereof;
para-hydroxybenzoates such as butyl paraben, methyl paraben and propyl paraben; imidazolines (e.g., imidiazolinyhurA), triclosan, hydantoins (e.g., dimethyloldimethylhydaatoin), isothiazolidinone compounds and mixtures thoreof. Commercially available preservatives include KATHON CO and KATHON COIl, which contain methylchloroisothiazolinone and methylisothiazol'mone (Rohm and Haas). When present, the quantity of preservative is in the range from 0.00 1 to 2%, or from 0.01 to 0.2 h.
[0 177] In certain embodiments the compositions of the invention include a chelating agent.
Chelating agents are substances used to chelate or bind metallic ions, suoh as with a heterocyclic ring strueture so that the ion is held by chemical bonds from each of the participating rings.
Suitable chelating agents include ethylene diaminetetraaoetic acid (EDTA), EDTA disodium, calcium disodium edetate, EDTA trisodium, EDTA tetrasodium and EDTA
dipotassium. One or more chelating agents can optionally be included in the additives or additiveJbodywashes in amounts ranging from about 0.001 to about 0.2 weight percmt, or about 0.01 %
weight petr.ent.
(00178] Thickening agents or gellants may be added as desired to adjust the texture and viscosity of the composition. Exemplary agents or gallants may be selected rom CarbopolT"' nesins [e.g., 934, 971, 974, 980, 981] and PemulenTm [TR-1 and TR 2][both Carbopol "'and Pemulenn' are registared trademarks of BF, Goodrich], Noveon AA-1, ETD resins, and UhrezTM
resins [registered trademark, BF Goodrich]. In addition, carbomers might be useful for this purpose.
[00179] It may be desired to include a non-polar wax. Examples of such useful waxes include ester waxes, diester waxes, hydrocarbon waxes, silicone waxes and triglyceride waxes and mixtures thereof.
[00180] Other components may include a liquid hydrocarbon (similar to pentane), and/or a cationic foaming agont derived firom arginine and or cysteine.
[00181] Further optional ingredients which can be present in the composition include fiagranoe, dyes, antimicrobial materials such as triclooarban, triclosan, iodophors, iodine formulations, phenolic compounds, e.g. hexachlorophene, and bisbiguanides, e.g. chloii-exidene gluconate, and the like. See, e.g., U.S. Patent Nos. 6,827,795; 6,517,854; 6,010,817;
5,173,216; 5,719,113;
5,259,984; 5,562,912; 5,629,006; 5,728,662; 5,767,163; 5,750,579; 5,591,442;
5,650,143;
5,772,640; and 4,478,821.
[00182) The components of the eomposition are generally mixed in water.
G. Surfactants and bodywasbes [00183] Compositions of the invention may be formulated as products for use as a wash-on formulation, for providing a cleaning function with respect to a surfeoe. In some casese, the compositions are formulated for washing the skin, for example, bath or shower gels, hand washing compositions or facial washing liquids; pre- and post-shaving products; rinse-off, wipo-offand leave-0n skin care products; products for washing the hair and for dental use. Shower gels are particularly exemplary product forms.
[00184] If it is desired to prepare a sunscreen/bodywash composition, the sunscreen additives of the invention may be combined with other ingredients to produce a bodywash (e.g., a Gquid or solid formulation). The sunscreen/bodywash may include one or more surfactants. 7le use of surfactants in bodywashes is well-known in the art. Any surfactant known in the art and appropriate for a bodywash composition may be used. See, McCutcheon's Aetergents &
Enuds{ffers, M.C. Publishing Co. (North American edition 1989); Schwartz, et al., Surface Acttve Agents, Thefr Chemistry and Technology, New York, Interscience Publishers, 1949, and U.S.
Patent Nos. 6,096,697; 4,741,855; 4,788,066; 5,104,646; 5,106,609; 2,658,072;
2,438,091;
2,528,378; 2,486,921; 2,486,922; 2,396,278; 2,979,465; 3,179,599; 5,322,643;
5,084,212;
3,332,880; 4,122,029; 4,265,878; 4,421,769; 3,929,678; 3,959,461; 4,387,090;
4,303,543; and 6,224,852; and in British Patent Nos. 848,224 and 791,415. Also see CTFA
Cosmetic Ingredient Dictionary, 4m Edition 1991, pages 509-514 for various long chain alkyl cationic surfaotents; and Richmond, James M., Cationic Sar, jactmls, Marcel Dekker, Inc., New York and Basel,1990.
[00185] The surfactant(s) may be cationic, anionic, nonionic, zwitterionic, amphoteric, or any combination thereof.
[00186] Specific examples of anionic surfactants include those selected from the group consisting of alkyl and alkyl ether sulfates, sulfated monoglycerides, sulfonated okfuu, alkyl aryl sulfonates, primary or secondary alkane sulfonates, alkyl sulfosueoinates, acyl taurates, acyl isethionates, alkyl glycerylether sulfonate, sulfonated methyl esters, sulfonated fatty acids, alkyl phosphates, ethoxylated alkyl phosphates, acyl glutamates, acyl sarcosinates, alkyl sulfoaeetates, acylated peptides, alkyl ether carboxylates, acyl lactylates, anionic fluorosurfactants, and combinations thereof. Combinations of anionic surfactants ean be used effectively in the present invention. Specific examplea of alkyl sulfates that may be used are sodium, ammoniuni, potassium, magnesium, or TEA salts of lauryl or myristyl sulfate. Examples of alkyl ether sulfates that may be used include ammonium, sodium, magnesium, or TEA laureth-3 sulfate.
[00187] Another suitable class of anionic surfactants are the sulfated monoglycerides of the form R1 CO-O--CHZ-C(OH)H-CH=-O-SO3M, wherein RI is a saturated or unsaturated, branched or unbranahad alkyl group from about 8 to about 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolantine and monoethanolamine. An example of a sulfated monoglyceride is sodium eocomonoglyceride sulfate.
[001881 Other suitable anionic surfactants include olefin sulfonatea of the form R1 SO3M, wherein Rl is a mono-olefin having from about 12 to about 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine. An example of a sulfonated olefin is sodium C14/06 alpha olefin sulfonate.
[00189] Other suitable anionic surfactants are the linear slkylbenzene sulfonates of the form Rl-C414-SO3M, wherein RI is a saturated or unsaturated, branched or unbranahed alkyl group from about 8 to about 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine. An example of this anionic surfactant is sodium dodecylbenzene sulfonate.
[00190] Still other anionic surfactants suitable for the compositions of the present invention include the primary or secondary alkane sulfonates of the form Rl SO3M, whercin Rl is a saturated or unsaturated, branched or unbranched alkyl chain from about 8 to about 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine. An example of an alkane sulfonate useful herein is alkali metal or ammonium C 13-C17 paraffm sulfonates.
[00191] Still other suitable anionic surfactants are the alkyl sulfosuccinates, which include disodium N-octadecylsulfosucainamate; diammonium lauryl sulfosuacinate;
tettssodium N-(1,2-dicarboxyethyl)-N-octadecylsulfosuccinate; diamyl ester of sodium sulfosuooinic acid; dihexyl ester of sodium sulfosuccinic acid; and dioctyl esters of sodium sulfosuocinic acid.
1001921 Also useful are tauretes dW are based on taurine. Examples of taurates include N-alkyltaurines such as the one preparod by reacting dodecylamine with sodium isethionate as detailed in U.S. Pat. No. 2,658,072.
[00193] Another class of suitable anionic surfactants is the acyl isethionates. Nonlimiting examples of these acyl isethionates include ammonium cocoyl isetbionate, sodium cocoyl isethionate, sodium lauroyl isethionate, and mbRures thereof.
1001941 Still other suitable anionic surfactattts are the alkylglyceryl ether sulfonates of the form Rl-OCH2-C(OH)H--CH2-SO3M, wherein R1 is a satvrated or unsaturated, branohed or unbranched alky) group from about 8 to about 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodimn, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine. One example is sodium oocoglyceryl ether sulfonate.
100195] Other suitable anionic surfactants include: Sulfonated fatty acids of the form Rl-CH(SO4)-COOH and sulfonated methyl esters of the from Rl-CH(SO4)-CO--O-CH3i where RI
is a saturated or unsat-uated, branched or unbranched alkyl group from about 8 to about 24 carbon atoms (e.g., alpha sulphonated coconut fatty acid and lauryl methyl ester); phosphates such as monoallryl, dialkyl, and triallcyiphosphate salts formed by the reaction of phosphorous pentoxide with monohydric bmnched or unbranched alcohols having from about 8 to about 24 carbon atoms (e.g., sodium mono or dilaurylphosphate, ethoxylated monoalkyl phosphates, etc.);
acyl glutamates corresponding to the formula RICO-N(COOH)-CH2CH2-CO2M wherein Ri is a saturated or unsatw'ated, branched or unbranched alkyl or alkenyl group of about 8 to about 24 carbon atoms, and M is a water-soluble cation (e.g., sodium lauroyl glutamate and sodium cocoyl glutamate); alkanoyl sarcosinates corresponding to the formula R1CON(CH+CHZCHZ-wherein Rl is a saturated or unsaturated, branched or unbnmched alkyl or alkenyl group of about 10 to about 20 carbon atoms, and M is a water-soluble cation (e.g., sodium lauroyl sarcosinate, sodium cocoyl sarcosinate, and ammonium lauroyl sarcosinate); alkyl ether carboxylates corresponding to the fonnula Rl {OCH=CH2)x-OCH2-CO2M wherein RI is a saturated or unsaturated, branehed or unbranched alkyl or alkenyl group of about 8 to about 24 carbon atoms, x is 1 to 10, and M is a water-soluble cation (e.g., sodium laureth carboxylate); acyl lactylates corresponding to the formula R1CO-[O--CH(CH3)-CO]x-COZM wheroin Rl is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of about 8 to about 24 carbon atoms, x is 3, and M is a water-soluble cation (e.g., sodium coooyl lactylate);
carboxylates, nonlimiting examples of which include sodium lauroyl carboxylate, sodium cocoyl eerboxylate, and ammonium lauroyl carboxylate; anionic flourosurfaotants; and natural soaps derived from the saponification of vegetable and/or animal fats & oils examples of which include sodium laurate, sodium myristate, palmitate, stearate, tallowate, cocoate.

[09196] Any counter cation, M, can be used on the anionic surfactant. The counter cation may be, for example, selected from the group consisting of sodium, potassium, ammonium, monoethanolamine, diethanolamine, and trietlwnolamine.
[00197] Nonlimiting examples of nonionic surfaetants that may be included in the compositions of the present invention include those selected from the group consisting of alkyl glucosides, alkyl polyglucosides, polyhydroxy fatty acid amides, alkoxylated fatty acid esters, sucrose esters, amine oxides, and mixtures thereof.
[00198] Alkyl glucosides and alkyl polyglucosides are useful herein, and can be broadly defined as condensation products of long chain aloohols, e.g., C8-30 alcohols, with sugars or starches or sugar or starch polymers, i.e_, glycosides or polyglycosides. These compounds can be represented by the formula (S)^ --O--R wherein S is a sugar moiety such as glucose, fivctose, mannose, and galactose; n is an integer of from about Ito about 1000, and R is a C8-30 alkyl group. Examples of long chain alcohols from which the alkyl group can be derivod include decyl alcohol, cetyl alcohol, steary] alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol, and the like. Some examples of these surfactants include those wherein S is a gluoose moiety, R
is a C8-20 alkyl group, and n is an integer of fiom about I to about 9. Commercially available examples of these surfactants include deoyl polyglucoside (available as APG 325 CS from Henkel) and lauryl polyglucoside (available as APG 600CS and 625 CS from Henkel). Also useful are sucrose ester surfactants such as sucrose cocoate and sucrose laurate.
[00199] Other useful nonionic surfactants include polyhydroxy fatty acid amide surfactants, more specific examples of which include glucosamides Processes for making compositions containing polyhydroxy fatty acid amides are disclosed, for example, in G.B. Pat.
Specification 809,060, published Feb. 18, 1959, by Thomas Hedley & Co., Ltd.; U.S. PaL No. 2,965,576, to E. R.
Wilson, issued Dec. 20, 1960; U.S. Pat. No. 2,703,798, to A. M. Schwartz, issued Mar. 8, 1955;
and U.S. Pat. No. 1,985,424, to Piggott, issued Dec.25, 1934.
1002001 Other examples of nonionic surfactants include amine oxides. Amine oxides correspond to the general formula R, R2 R3 N-O, wherein R, contains an alkyl, alkenyl or monohydroxy alkyl radical of from about 8 to about 18 carbon atoms, from 0 to about 10 ethylene oxide moieties, and from 0 to about 1 glycoryl moiety, and R= and R3 contain from about 1 to about 3 carbon atoms and from 0 to about 1 hydroxy group, e.g., methyl, ethyl, propyl, hydroxyethyl, or hydroxypropyl radicals. The arrow in the formula is a conventional representation of a somipolar bond. Examples of amino oxides suitable for use in this invention include dimethyl-dodecylamine oxide, oleyldi(2-hydroxyethyl) amine oxide, dimethyloctylamine oxide, dimethyl-decylamine oxide, dimethyl-tetradecylamine oxide, 3,6,9-trioxaheptadecyldiethylamine oxide, di(2-hydroxyethyl)-tetrackcylamine oxide, 2-dodecoxyethyldimethylamine oxide, 3-dodecosy-2-hydroxypropyldi(3-hydroxypropyl)amine oxide, dimethylhexadecylamine oxide.

[00201] The tann "amphoteric surfaotant," as used herein, is also intended to oncompass zwitterionic surfactants, which aro well known to formulators skilled in the art as a subset of amphoteric surfactants.
[00202] A wide variety of amphoteric lathering surfactants can be used in the compositions of the present invention. Particularly useful are those which are bmadly described as derivatives of aliphatic secondary and tettiary amines, in some cases, the nitrogen is in a cationic state, in which the aliphatic radicals can be straight or branched chain and wherein one of the radicals contains an ionizable water solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
[00203] Nonlimiting examples of amphoteric or zwitterionic surfactants are those selectsd from the group consisting of betaines, sultaines, hydroxysultaines, alkyliminoacetatas, iminodialkanoates, aminoalkanoates, and mixtures thereof.
[002041 Examples of betaines include the higher alkyl betaines, such as cooo dimethyl carboxymethyl betaine, lauryl dimethyl carboxymethyl betaine, lawyl dimethyl alphaearboxyethyl botaine, cetyl dimethyl carboxymethyl betaine, cetyl dimethyl betaine (available as Lonzaine 16SP from Lonza Corp.), lauryl bis-(2-hydroxyethyl) cafioxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, lautyl bis-(2-hydroxypropyl)alpha carboxyethyl betaine, coco dimethyl sulfopropyl betaine, lauryl dimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl) sulfopropyl betaine, amidobetaines and amidosulfobetaines (wherein the RCONH(CH₂)₃ radical is attached to the ditrogen atom of the betaine), oleyl betaine (available as amphoteFic Velvetex OLB-50 from Henkel), and cocamidopropyl betaine (available as Velvetex BK-35 and BA-35 from Henkel).
[00205] Examples of sultaines and hydroxysultainea include maberials such as cocamidopropyl hydroxysultaine (available as Mirataine CBS from Rhone=Poulenc).
[00206] Examples of amphoteric surfactants of the praqent invention include the fotlowing compounds: Cetyl d'unethyl betaine (this material also has the CTFA
designation cetyl betaine);
Coeamidopropylbotaine; Cocamidopropyl hydroxy sultaine. Examples of other useful amphoteric surfaotants are alkyliminoacetates, and iminodialkerwates and aminoalkanoates of the formulas RN[(CH2) M M] 2 and RNH(CH2).m CO2 M wherein m is from i to 4, R is a Cs -Cu alkyl or alkenyl, and M is H, alkali metal, alkaline earth metal ammonium, or alkanolammonium.
Also included are imidazolinium and ammonium derivatives. Specific examplas of suitable amphoteric surfactants include sodium 3-dodecyl-aminopropionate, sodium 3-dodecylaminopropane sulfonate, N-higber alkyl aspartic acids such as those produced according to the teaching of U.S. Pat. 2,438,091; and the products sold under the trade name "Miranol" and described in U.S. Pat. 2,528,378. Other exatnples of useful amphoterics include amphoteric phosphates, such as coamidopropyl PG-dimonium chloride phosphate (commercially available as Monaquat PTC, from Mona Corp.). Also useful are amphoacetates such as disodium lauroamphodiacetate, sodium lauroamphoacetate, and mixtures thereof.

WO 2008/144734 PCT[US2008/064369 [00207] In some embodiments, the sunsereen/bodywashes of the invention include at least one cationic surfaetant. As described above, cationic surfactants can be used to pat.ially or fully provide a positive charge to the microcapsules of the invention. Many cationic surfactants are known to the art. Suitable cat'anic sutfactants include, but are not limited to, fatty amines, di-fatty quatemary amines, tri-fatty qua0arnmy antines, imidawlinium quatemary amines, and combinations thereof. Suitable fatty amines include monalkyl quaternary amines such as cetyltrimethylammonium bromide. A suitable quaternary amine is dialklamidaethyl hydroxyethylmonium methosulfate. By way of example, the following may be mentioned:
stearyidimenthylbenzyl ammonium chloride; dodecyltrimethylamtnonium chloride;
nonylbenzylethyldimethyl anunonium nitrate; tetradecylpyridinium bromide;
laurylpyridinium chloride; cetylpyridinium chloride; laurylpyridinium chloride;
leurylisoquinolium bromide;
ditallow(Hydrogenated)dimethyl ammonium chloride; dilauryldimethyl ammonium chloride; and stearalkonium chloride.
Additional cationic surfactants are disclosed in U.S. Pat. No. 4,303,543 seo column 4, lines 58 and column 5, lines 1-42, incorporated herein by references. Also see CTFA
Cosmetic Ingredient Dictionary, 4th Edition 1991, pages 509-514 for various long chain alkyl cationic surfactants;
incorporated herein by reference.
[00208] The total surfactants, e.g., cationic surfectant, may be present in the sunsctbon/bodywash at about 0.1 to about 20%, or about 0.1 to about I0 /., or about 0.1 to about 5%, orabout 0.5 to about 5%, or about 1 to about 10'/o, or about 1 to about 5%, or about 0.1 to about 2%, or about I
to about 2%. In some embodiments, a sunscreen/bodywash composition of the invention contains a surfactant, e.g., a cationic surfactant, at about 1%.
[00209] In addition to surfactants, other ingredients, as described above for additives, may be included in the additive/bodywash. Any component known in the art or useful in bodywashes may be used.
[002101 In some embodiments, soapless cleansers may be used in addition to, or instead of, soaps/surfactants. For example, Oilatumm AD (registered trademark, Stiefel Laboratories), Aquanil'"' (registered tredemark, Person & Covey, Inc.), Cetaphil'I"
(trademark, Galderma Laboratories, Inc.) or SpectroDerm"m (regisWred trademark, Draxis Pharmaoeutical Inc.), or their equivalents, may be utilized as a soapless component in the present invention.
[002111 As noted above, the sunscreen additives of the invention may also be combined with conventional bodywash compositions, as well as with shampoos for hair, and post-wash skinoane compositions. Proportions for addition and mixing are given above as well as in more detail hereafter. An exemplary bodywash tiiat may be used with additives of the invention is exemplified by SUAVE Body Wash. Ingredients of a typical SUAVE bodywash include: Water, Ammonium Lauryl Sulfate, Ammonium Laureth Sulfate, Cocamidopropyl Betaine, Fragrance, Glycerin, Hydrolyzed Milk Protein & Honey Extract, PEG-10 Sunflower t3lycerides, Cocamide MEA, Guar Hydroxypropylrimonium Chloride, Acrylates Copolymer, PEG-5 Cocamide, Helianthus Annuus (Sunflower) Seed Oil or Glycine Soja (Soybean) Oil, Tetrasoidum EDTA, Propylene Glycol, Ammonium Chloride, Sodium Hydroxide, Methylchloroisothiaxolinone, Methylisothiazolinone, Titanium Dioxide (CI 77891) II. Methods A. Preparation [00212] The compositions ofihe invention may be prepared by any suitable method.
[00213] The encapsulated actives of the present invention can be made by chemieal, physico-chemical, and physico-mechanical methods such as suspension, dispersion and emulsion, coacervation, layer-by-layer polymerization (L-B-L) assembly, sol-gel encapsulation, supercritieal C02-assisted mioroencapsulation, spray-drying, multiple nozzle sMying, fluid-bed coating, po(yoondensation, centrifugal toohniques, vacuum encapsulation, and electrostatic encapsulation.
[00214] Microene.apsulation methods useful in the present invention is described, for example, in Ghosh, K., Functional Coatings and Microencapsulation: A General Perspective, Wiley-VCH, Weinheim, 2006, Benita, S., Microencapsulation: Methods and Industrial applications, Marcel Dekker, Inc., NY, 1996., Arshady, R, Microsphetes, Mierocapsules and Liposomes, Citrus Books, London, 1999, and Boissiere et al. J. Mater. Chem., 2006, 16, 1178.
[002151 The sol-gol microcapsules of the invention can be formed, for example, by using techniques described in U.S. Patent Nos. 6,238,650; 6,436,375, 6,303,149;
6,468,509, and U.S.
Patem Application No. 2005/0123611. In order to form highly charged microcapsules, a cationic agent may be incorporated into the microcapsule or become associated with the microcapsule.
The cationic agent can, for example, be a cationic surfactant, a cationic polymer, or a both a cationic surfactant and a cationic polymer. The process for forming the microcapsules of the present invention genetally involves mixing a gel precursor, an active ingredient, and a surfactant to form a mixture, emulsifying the mixture in an aqueous medium such that the gel precursor hydrolyzes to form a sol-gel eeramie microcapsule, resulting in at least a portion of the additive encapsulated within the microcapsule, and adding a cationic agent to impart a high zeta potential to the microcapsules. At least some of the cationic agent can be added prior to the formation of microcapsules. For instance, a cationic surfactant can be used in the initial formation stage in order to impart some charge. The cationic agent can also be incorporated after the formation of the microcapsules. For instance, a cationic polymer can be added to the solution containing the formed microcapsules containing the active ingredient. The cationic polymer, such as polyquaternium-4 can bind to the microcapsules, and/or become partially incorporated into the microcapsuls, inereasing the charge on the microcapsules.
[00216] One aspect of the invention comprises methods for preparation of highly charged sol-gel microcapsules comprising active ingredients. The methods include formmg oapsules using oil-in-water (O/W) emulsions, water-in-oil (W/O) emulsions, liposomes, micelles, and polymeric microspheres. The various methods allow for the encapsulation of any type of suitable ingredient, for example, those described herein. For example, an oil-in-water emulsion can be used for incorporating a non-polar active ingredient, where the non-polar active ingredient either comprises substantially all of the oil phase, or the non-polar active ingrodient is mixed with other non-polar components, either active or ineR. The non-polar components comprise the "oil" phase of the water-in-oil emulsion. '1]ie oil phase constitutes generally spheroidal liquid particles or droplets dispersed in the continuous aqueous phase. Hydrolysis of the gel precursor material produces a sol-el capsule which is formed around the non-polar oomponents. The highly charged capsules are formed by incorporating a cationic agent into the capsules. In some embodiments, the cationic agent is added prior to formation of the sol-gel oapsules. In some embodiments, the cationic agent is added during the formation of the aol-gel capsules. In some embodiments, the cationic agent is added a8er the formation of ahe sol-gel capsules.
[00217] One aspect of the invention comprises a method of manufacturing a highly charged sol-gel microcapsule comprising a non-polar active ingredient comprising: (a) combining the non-polar active ingredient, optional non-polar diluent, and aqueous phase; (b) agitating the canbination formed in (a) to fotm an oil-in-water (O/W) emulsion wherein the non-polar active ingredient and optional non-polar diluent comprise the dispersed phase; (c) adding one or more surfactants; (d) adding a cationic agent; (e) adding a gel precursor to the O/W emulsion; and (f) mixing the composition from step (e) while the gel precursor hydrolyzes and sol-gel capsules ane formed which comprise the non-polar active ingredient.
[002181 A water-in-oil emulsion provides for the encapsulation of polar and aqueous soluble active ingredients. In the water-in-oil method, the active ingredient or ingredients and optional polar diluent are dissolvod or dispersed in an aqueous phase. A water-in-oil emulsion is fonned, wherein the aqueous liquid particles or droplets are dispersed within a non-polar, aquoous immiscible "oil" phase. Hydrolysis of the gel precursor material produces a sol-ge1 capsule which is formed around the non-polar component. In some embodiments, the cationic agent is added prior to formation of the sol-gel capsules. In some embodiments, the cationic agent is addad during the formation of the sol-gel capsules. In some embodiments, the cationic agent is added after the formation of the sol-gel capsules.
[002191 One aspect of the invention is a method of manufacturing a highly charged sol gel microeapsule comprising a polar active ingredient comprising: (a) combining the polar active ingradient, water, optional polar diluent, and a non-polar (oil) phase; (b) agitating the combination formed in (a) to form an water-in-oil (W/O) emulsion wherein the polar active ingredient, water, and optional polar diluent comprise the dispersed phase;
(c) adding one or more surfactants; (d) adding a cationic agent; (e) adding a gel precursor to the W/O emulsion; and (f) mixing the composition from step (e) while the gel precursor hydrolyzes and sol-gel capsules are formed which comprise the polar active ingredient.

[00220] While we describe the invention with respect to the binery O/W or W/O, the methods of the invention can also be used in ternary, quatemary or higher emulsions such as W/OJW, O/W/O, W/O/W/0, etc.
1002211 The invention also provides for methods of forming highly charged sol-gel microcapsules using template within a solution, usually an aqueous solution. The template is generally structure dispersed within a continuous solution that comprises the active ingredient.
The template is generally spheroidal, neod not be a spheroid, and can have an elongated or irrogular shape or distribution of shapes. The template can be a polymer microsphere, liposome, or micelle.
Hydrolysis of the gel puecursor material produces a sol-gel capsule which is fonned around the template. The highly charged capsules are formed by incorporating a cetionic agent into the capsules. In some embodiments, the cationic agent is added prior to formation of the sol-gel capsules. In some embodiments, the cationic agent is added during the formation of the sol-gel capsules. In some embodiments, the cationic agent is added after the formation of the sol-gel capsules.
[U0222] One aspact of the invention is a method of forming a highly charged sol-gel microcapsule camprising an active ingredient within a template comprising: (a) fomting a dispersion of templates, wherein the templates comprise an active ingredient, in an aqueous continuous phase;
(b) adding a cationic agent; (c) adding a gel precuisor to the aqueous continuous phase; and (d) mixing the composition from stop (c) while the gel precursor hydrolyzes and sol-gel capsules ato formed.
[00223] A non-polar active ingredient is generally an ingredient that is insoluble or sparingly soluble in water or in aqueous solution. The non-polar ingredient may be soluble in an oil such as mineral oil, palm oil, or silicone oil. It is understood in the art how to determine solubility in order to determine if a non-polar ingredient is suitable. In some embodiments, such as with the O/W method, the active ingredient or ingredients comprise the whole of the non-polar "oil"
phase. In some embodiments of the O/W method, the non-polar active ingredient9 ere dissolved or dispersed into an optional non-polar diluent. The non-polar diluent can be any suitable oil, wax, or solvent.
[09224] The non-polar phase can be dispersed within the aqueous phase by any suitable means.
The dispersion of the non-polar phase in the aqueous phase is generally referred to as an emulsion. The formation of emulsions is known in the art. In some cases, a mixer, suoh as a mixer with a rotor-stator is used. Emulsions of the invention can also be formed using liquid gets, vibrating nozzles or other methods. The aqueous phase generally comprises at least 50% water.
In some eases, the aqueous phase is substantially all water. In some cases, the aqueous phase comprises othar co-solvents or other water soluble agents. Co-solvents, can be any water miscible solvent including, for example, methanol, ethanol, or ethylene glycol. The aqueous phase can also comprise othor additives such as thickening agents, sugars, watet soluble polymers, etc-[092251 The oil-in-water emulsion or water-in-oil emulsion is generally xtabilized using one or more surfactants. Suitable surfactants are described herein and known in the art.
[00226] In order to form the oil-in-water emulsion of the invention, surfaotants with an HLB
value above about 8 are generally used. In some cases, multiple surfactants are used. Where there are multiple surfactants, the combined HLB of the surfactants is generally used. The HLB
of the surfactsnt or surfactants is between, for example, 7 and 13, 8 and 12, 9 and 11, 9.5 and 10.5. In some embodiments, the HLB of the surfactants is 8, 8.5, 9, 93, 10, 10.5, 11, 11.5 or 12.
1002271 In order to form the water-in-oil emulsion of the invention, surfactants with an 1-1LB
value below about 8 are generally used. In some oases, muhiple surfactants are used. Where there are multiple surfactants, the combined HLB of the surfactants is generally used. The HLB
of the surfactant or surfaataats is between, for example, 2 and 7, 3 and 6, 4 and 5, or 3.5 and 4.5.
In some embodiments, the HLB of the surfactants is 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 or 6.
[002281 Suitable surfactants for forming the oil-in-watar emulsion, water-in-oil emulsion, or template micelle include, for example, anionic, cationic, zwittenionic, semipolar, PEGylated, amine oxide and aminolipids. Suitable surfactants include: anionic-sodium oleate, sodium dodecyl sulfate, sodium diethylhexyl sulfosuccinate, sodium dimethylhexyl sulfosueeinate, sodium di-2-othylacetaroe, sodium 2-ethylhexyl sulfate, sodium undecane-3-sulfate, sodium ethylphenyiundeoanoate, carboxylate soaps; cationic--dimethylammonium and trimethylammonium surfactants of chain length from 8 to 20 and with chloride, bromide or sulfate counterion, myristyl-gammapicolinium chloride and relatives with alkyl chain lengths from 8 to 18, benzalkonium benzoate, double-tailed quaternary ammonium surfactants with chain lengths between 8 and 18 carbons and bromide, chloride or sulfate counterions;
nonionic:
PEGylated surfactants of the forcn C,6õ where the alkane chain length n is from 6 to 20 carbons and the average number of ethylene oxide groups m is from 2 tIO 80, ethoxylated cholesterol;
zwitterionics and semipolars--N,N,N-trimethylaminodecanoimide, amine oxide surfactants with alkyl chain length from 8 to 18 carbons; dodecyldimethylammoniopropane-l-sulfate, dodecyldimethylammoniobutyrate, dodecyltrimethylecu di(ammonium chloride);
decylmethylsulfonediimine; dimethyleicosylammoniohexanoate and roladves of these zwitterionics and semipolars with alkyl chain lengths from 8 to 20.
1002291 The cationic agent or oationic component used in the method to impart the high chargo can be any suitable cationic agent described herein or known in the art including a cationic surfactant, a cationic polymer, or a both a cationic surfactant and a cationic polymer. The cationic polymer can comprise a polyquaternium, such as polyquaternium-4, -7, -11, -22, -27, -44, 51, or -64. In one exemplary embodiment, the cetionic polymer is polyquatemium-4. In some embodiments, the cationic agent can also comprise a proton donor or lewis acid.
[00230] The point in the process where the cationic agent is introduced into the reaction mixture can be irnportant with respect to the production of highly charged sol-gel capsules. The point of addition will depend, for example, on the type of reaction conditions and the type of cationic agent or agents employed. In some embodiments, the cationic agent is added prior to the hydrolysis of the get precursor. In these cases, the cationic agent will often be added just before, during, or just after the addition of the gel precursor.
[00231] In some eases, the cationic agent is added during the hydrolysis of the gel precursor and fommtion of the sol-gel capaule. While not being bound by theory, it is believed that the presence of the cationic agent or addition of the cationic agent during formation of the capsule can result in incorporation of the cationic agent into the wall of the capsule. It is believed that in some cases, this type of addition can result in improved stability of the cationic charge.
[00232) In some ceses, the oationic agent is added subsequent to the formation of the capsule, thus providing a coating of the cationic agent onto the outside of the capsule. While not being bound by theory, it is believed that treatnunt of the capsules with the cationic agent subsequent to the formstion of the sol-gel capsule can result in the cationic agent being concentrated on the outermost portion of the sol-gel capsule, which can provide a high amount of charge for a given amount of cationic agent.
] 5 [00233) The cationic agent can be added at more than one point in the prooess. In some cases, more than one cationic agent is used, each of which is added at a different point in the process.
For example, in one embodiment a first cationic agent comprising, for example, a cationic surfactant is added before addition of the gel precursor, and during or subsequent to formation of the so]-gel capsules a second cationic agent, for example, a polymeric cationic agent such as a polyquaternium is added. In this manner the oombination of cationic agents can act together to create the highly charged sol-gel capsules of the invention.
[00234) The gel precureor can be any suitable sol-gel forming material desonbed herein or known in the art. The gel precursor can be, for example, a silica-based gel precursors include tetramethoxysilane (TMOS), tetraetboxysilane (TEOS), tetrabutoxysilane (TBOS), tetrapropoxysilane (TPOS), polydiethoxysilane, methyltrimethoxysilane, methyltriethoxysilane, ethyltriethoxysilane, oetylpolysilsosquioxane and hexylpolysilsesquioxane. The gel precursor is added to the oil-in-water emulsion, and the pH is adjusted in order to cause the gel-precursor to hydrolyze and form the sol-gel capsule. 1he reaction is earried out with mixing at a rate such that the sol-gel reaction occurs at the interfaca between the oil and water, creating the sol-gel capsule.
In some embodiments the pH is raised (made basic) in order to form the sol-gel capsule. In some embodiments, the pH is lowerod (made acidic) in order to form the sol-gel capsule. In somo embodiments, the pH is lowered to between 2 and 6, 3 and 5, 3 and 4, or 3.2 and 3.6. In some embodiments the pH is lowered to 2, 2.5, 3, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 42, 4.4, 4.6, 4.8, 5, 5.5, or 6. The hydrolysis of the gel precursor generally requires the presence of water. In the case of the oil-in-water emulsion, the water for hydrolysis can be provided from the continuous aqueous phase of the emulsion. In the c,aso of the water-in-oil emulsion, the water can be provided as part of the polar dispersed phase, and/or water can be added to the reaction mixture after formation of the emulsion in order to facilitate hydrolysis.

[002351 The size of the so] gel capsules formed is detemnined, at least in part, by the conditions of the reaction including the size of the original emulsion, and the conditions used for formation of the sot-gel capsules. A distribution of capsule sizes is generally obtainod.
The sol-gel capsules can also be fcactionated into a desired size range a@er capsule formetion.
Fractionation can be carried out by methods known in the art such as selective precipitation, or by using filbers or sieves in order to pass a selected size range and retain the rest. The size of the sol-gel capsules can be modified in order to suit a particular application. In some embodiments, the mean, median, or average size of the capsules is between 10 nm and 1 mm, between 10 nm and I m, between I m and 100 m, 10 m and 50 m, 50 m and 200 m, or between 200 m and 500 pm. In some embodiments, the mean, median, or average size of the capsules is between 1 nm and 10 nm, 10 nm and 100 nm, 100 nm and 1 pm, 1 m and 10 pm, 10 m and 100 p.m, 100 m and 1 mm, I nun -10 mm, or larger. In some embodiments, the mean, median, or average size of the capsulos is within plus or minus 10% of 1 nm, 10 nm, 25 am, 50 nm, 75 nm, 90 nm, 100 nm, 250 nm, 500 nm, 750 mn, 900 nm, 1 m, 10 m, 25 m, 50 pm, 75 pm, 90 pm, 100 ny 250 pm, 500 pm, 750 pm, 900 pm, I mm or larger.
[002361 The sol gel capsules can be isolated from the reaction mixture, for example by filtration or precipitation. In addition to isolation of the capsules fiom the sohrtion, these processes can affect the size distribution of the sot-gel capsules. The capsules can be fitteted using standard filtration equipment. In some cases a vacuum or pressure is used to facilitate the filtration process. The capsules can then be rinsed to remove impurities from the reaction mixGm including residual ethanol and/or unreacted gel precursor. The capsules can be rinsed with any suitable solvent. In some embodiments, the capsules are rinsed with water. The rinsing steps can also be used to add other components to the capsules. For example, a rinse using a solvent comprising a cationic component can result in increasing the charge on the microcapsules.
[00237] The sol-gel capsules of the present invention can be dried. In some cases, the dried sol-gel capsules have better shelf life stability than the wet capsules. In some cases, the dried capsules are more suitable for incorporation into a formulation, for example a non-polar fornmlation for products such as wash-on or leave-on products. Drying can be accomplished by any suitable means including passive exposuro to heat and dry air or with spray-dry maohinery.
In some cases the capsules are dried at room temperatwo, in some cases the capsules are dried at between room temperature and 50 C
[002381 The methods of the invention can produce highly charged microcapsules.
One method for measuring the charge on the microcapsule is with zeta potential. The methods produce capsules having a zeta potential of at least 5, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80,90 or 100 mV_ In some embodiments, the microoapsules ofthe present invention have a zeta potential of no more than 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, 150, 200, 300, 400 or 500 mV. In some embodiments the zeta potential is between 10 and 70 mV, between 20 and 65 mV, between 25 and 65 mV, between 30 and 60 mV, between 30 and 100 mV, between 40 and 80 mV, between 70 and 100 mV or between 40 and 55 mV. In some embodiments, the microcapsules have a zeta potential of at least 70 mV, in some embodiments, the microcapsules have a zeta potential of at least 65 mV, in some embodiments, the microeapsules have a zeta potential of at kast 60 mV, in some embodiments, the microcapsules have a zeta potential of at least 55 mV, in some embodiments, the mierocapsules have a zeta potential of at least 50 mV, in some embodiments, the microcapsules have a zeta potential of at least 45 mV, in some embodiments, the microcapsules have a zeta potential of at least 35 mV, in some embodiments, the microcapsulos have a zota potential of at least 25 mV in some embodiments, the mierocapsules have a zeta potential of at least 15 mV.
[00239] In one aspect of the invention, the methods of the invention produce oapsules with a zeta potential that is higher than the zeta potential without the cationic agent.
In some embodments, the zeta potential of the capsule is 5%,10%, 20 /., 300/e, 40%, 50%, 60%, 700*
80%, 90%, or ltimes, 2 times, 3 times, 4 times, 5 times, 10 times, 20 tintes, 50 thnes,100 times or more than the zeta potential of the capsule without the cationic agant. In some embodiments the zeta potential of the capsule is 5% to 10%, 10o to 20%, 20% to 50%, 50% to 90%, 1 to 2 times, 2 to 5 times, 5 to 10 times, 10 to 100 tunes or more than the zeta potential of the capsule without the cationic agent.
[002401 For the methods of the invention, in some cases, the steps are carried out in the order that they are listed. ln some cases, where appropriate, the order of the steps can be different than the order listed [00241] In the methods which utilize a template for the formation of a highly charged sol-gol miorocapsule, the template is generally a microsphere, liposome or micelle.
Where the template is a microsphere, it is genernlly a polymeric microsphere.
[00242] Polymeric microspheres of the present invention are generally microspheres formed (at least in part) from a crosslinkable polymer. The highly charged sol-gel microspheres may be employed, for example, as drug delivery agents, tissue bulking agents, tissue engineering agents, and embolization agents. There are numeraus methods known for preparing polymeric microspheres. These methods include dispersion polymerization of the monomer, potentiometric dispersion of a dissolved crosslinkable polymer within an emulsifying solution followed by solvent evaporation, electrostatically controlled exttusion, and injection of a dissolved crosslinkable polymer into an emulsifying solution through a porous membrane followed by solvent evaporation.
[00243] In some oases, the polymeric microsphere template is porous. Suitable porous template polymers inchule, for example, alginates, polysaocherides, carrageenans, chitosan, hyaluronic acid, or other ionically crosslinkable polymers (also known as "shape-forming agents"), such as the classes of carboxylic-, sulfate-, or amine-functionalized polymers. The template polymer can also be generated from a blend of one or more of the above synthetic or naturally occurring materials, or derivatives thereof. In one preforred embodiment of the invention, the template polymer is an alginate, which is ionically orosslinlcable. Polymeric microspheres oan also be made from wide variety of generally chemically crosslinkable polymers such as, for example, vinyl polymas, polyscrylamides, polsrothy-ene gly-l, polyamides, polyu.ee9, polyuretbranes, polyvinyl aloohols, and derivatives thereo For some (e.g., embolic) applications, a hydrophilie polymer, such as polyvinyl alcohol, will be preferred.
[002441 Other polymers suitable for the production of polymeric microspheres ate ethylene/acrylic acid copolymer, FID]Vtrimethylol hexyllactone oopolymer and silica, polymethyl methsoryhte, methyl methacrylate eopolymer, nylon 6, nylon 12, polyethylene, polymeWytsilsesquioxano, and polystyrene [002451 Suitable microsphere to serve as templates for the present invention include microspheres commercially available from Kobo Products, Inc. including EA-209, BPD-500W, BPD-500, BPD-500T, BPA-500, MP 2200, SunPMMA-S, BPA-500X, MSP-825, MSP-930, SunPMMA-P, TR-1, POMP6I0, SP-500, SP-10, SP-IOL, CL-1080, CL-2080, TOSPEARL 120A, TOSPEARI. 145A, TOSPEARL 2000B, TOSPEARLZ 3000A, TOSPEARL 150K, TOSPEARIO I 110A.
[002461 In somee eases, microspheres having an active inp~ediant tMt can be used as templates for forming highly charged sol-gel capsules are eommercially available, such as those from Salvons L.L.C., New Jersey including: 7010 HydroSalTm LiB, 7014 HydroSalTN NanoFrosh, HydroSalTM Neutralizer, 7020-SS HydroSalT"' Sal Sillc, 202 Sebum Control, 2002 MultiSallM
Flavor/Cooling (Lip Care), 2101 MultiSal*M Vitamin C+E, 2104 Multi3alf SalCoolr"r, 2105 MuhiSal- Saticylic Acid 10, 2106 MuhiSalTM Salicylic Acid 30, 2106-BW
IvlultiSalM Salicylic Acid 20,2107 MultiSalTM AL (Anti-Inflammatory), 2110 MultiSa1' " LipVantage, MultiSalTm Silicone, 2115 MultiSalT*s Collagen Tripeptide, 2401 MultiSalTm Fragrance, 2403 MultiSal'n+ Menthol, 2801 Mu1liSalTM Flavor/Cooling (Oral Care), 105 SalSphere'r*r Moisture Key, 4201 SalSphereTm Anti Frizz, 4221-1, SalSphemTM Vita Hair, 4222 SalSphereTM Color Guard, 4308 SalSphereTU Resveratrol.
[002471 The template for forming the highly charged mierocapsule of the present invention can be a liposome. A liposome is generally a substantially spherical vesicle or capsule generally comprised of amphipathic molemdes (e.g., having both a hydrophobic (nonpolar) portian and a hydrophilic (polar) portion). Typically, the liposome can be produced as a single (unilamellar) closed bilayer or a multicompartment (multilamellar) closed bilayer. The liposome can be formed by natural lipids, synthetic lipids, or a combinatan thereoE In some embodiments, the 6posome comprises one or more phospholipids. In a sasne embodiments, the 1'ryosome eomprises one or more additives, for example, a membrane stabilizer, an isotonic agent (e.g., sugars, sodium chloride, polyalcohols such as mannitol, sorbitol, and the like, a pH
adjusting agent (e.g., a base, a basic amino acid, an acidic amino acid, sodium phosphate, sodium carbonate, and the like, present in an amount to adjust the lipo aue to a desired pH)s an aggregation minimizer (e.g., a surfactant (e.g., polysorbates, poloxamers), polysaccharide, liposomal surface carboxyl groups, and the like), or a combination thereof. Lipids for use in the present invention include, but are not limited to, lecithin (soy or egg; phosphatidylcholine), dipalmitoylphosphatidylcbolino, dimyristoylphosphatidylcholine, distearoylphosphatidylcholine, dicetylphosphate, phosphatidylglyoerol, hydrroganated phosphatidylcholine, phosphatidic acid, a phospholipid, cholesterol, phosphatidylinositol, a glycolipid, phospbatidylethanolamine, phosphatidylsetine, a maleimidykierivatized phospholipid (e.g., N-[4(p-malei-midophenyl)buty7y]]phosphatidylethanolamine), dioleylphosphatidylcholine, dipalmitoylphosphatldylglycerol, dimyristoylphosphatidic acid, or a combination thereof. The Iiposome genereally comprises a polar (aqueous) interior which can be used for the fomiation of highly charged sol-gel microspheres comprising polar active ingredients.
1002481 In one method, a "Phase I," which is a"wata phase," is prepered by mixing the more water-soluble components of the composition. For example, Polyquaternium-4, a film former (e.g., in MOISTUREGUARD), and encapsulated sunsereen (e.g., in UV PEARLS), may be mixed until uniform. A"Phase II," which is an "oil phase," is prepared by mixing the more hydrophobic components of the composition. For example, Avobenwne (e.g., PARSOL 1789) may be mixed with Octocrylene, with heating, until dissolved. Tben Phase I and Phase II are combined with gentle agitaflon, until a uniform composition is obtained (Phase Ill). Phase III
may be further combined with a bodywash composition (e.g., SUAVE bodywash) and mixed until uniform. A further sunscreen, such as titanium dioxide, may be added to the Phase III/bodywash composition and mixed until uniform. Altematively, the sunscreen may be added before addition to the bodywash or soap to provide an additive ready for formulation with a bodywash or soap.
[00249] In some embodiments of the invention, the highly charged microcapsules of the invention may be prepared by mixing the microcapsule with a cationic compound to impart the high positive charge density onto the microcapsule. In some embodiments, the cationic compound added to the microcapsule is a cationic polymer. The cationic polymer may be, for example, a polyquatternium. The polyquatemium may be, for example, polyquaternium-4.
[00250] In one embodiment, the cationic compound is associated with the outside of the highly charged microcapsule . In a further embodiment, the cationic compound is covalently bound to the microcapsule. In another embodiment, the cationic compound is noncovalently bound to the microcapsule. The interaction betwean bo cationic compound and the microcapsule may be, for example, an electrostatic, ionic, or a Van Der Waals attraction.

B. Use [00251] The highly charged sol-gel capsules containing active agents are useful in many applications. The highly charged microcapsules are used for example for agricultural, textile, industrial, transportation, marine, pharmaceutical, or personal care applications. The sol-gel capsules of the invention can be used as wash-on or as leave-on formulations.

1002521 Additives, e.g., sunscreen additives of the invention which are inoorporated into highly charged sol-gel capsulse can be designed to be used in combination with a bodywash. Thus, the compositions of the invention can be designed to be applied while washing.
This cbaracteristic facilitates ease of use and may have the added benefit of being cumulative.
Compositions of the present invention are readily applied during washing in a suitable or effective amount and may be generally applied all over the body. Shampoos may be applied specifically to the hair. A
selected amount of a composition may be applied directly to the skin or may be used through intennediate application to a washcloth, pad, sponge, or other applicator.
After lathering, dirt and sloughed-off skin may be washed away by rinsing with water leaving behind one or more of the additives, e.g., sunscreet components. Additives of the invention, e.g., sunscreen additives of the invention are also useful in hair shampoos and conditioners, and in after-wash lotions.
[002531 '1'hus, methods of the invention include methods for protedion of skin &om sunlight, comprising applying a bodywash comprising a sunscreen to the skin, wherein after applioation of the bodywash to skin and rinsing, the skin is protected from sunligbt with an averago SPF of at least about 2, 3, 4, 5, 6, 7, 9,9,10,11,12,13,14,15,16,17,18,19,20, or more than 20. In soma embodiments, the skin is protected from sunlight with an average SPF of at least about 2.
In some embodiments, the skin is protected from sunlight with an average SPF
of at least about 5.
In some embodiments, tho skin is protected from sunlight with an average SPF
of at least about 10. In some embodiments, the skin is protected from sunlight with an aversge SPF of at least about 15. In some embodiments, the bodywash is applied more than once; in these cases, the SPF
may be cumulative and can increase with the second wash to, e.g., an average of more than 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, or more than about 45. In some embodiments the bodywash is applied once per day. In some embodiments, the bodywash is applied more than once per day, for example, 2, 3, 4, or more than 4 times per day. [n sonu embodiments, the bodywash is applied about every other day. In some embodiments, the body wash is applied about 10, 8, 7, 6, 5, 4, 3, 2 or 1 time per week.
100254] In these methods, the active additive, e.g., sunscreen, often does not penetrate beyond a eertain level in the skin, typically due to encapsulation. Thus, in some embodiments of the methods of the invention, the active additive, e.g., sunscreen, does not penetrate more than about 10, 20, 25, 30, 35, 40, 45, or 50 microas into the skin with one washing with a bodywash containing the additive. In some embodiments, the active additive, e.g., sunscreen, does not penetrate more than about 10, 20, 25, 30, 35, 40,45, 50, 60, 70, 80, 90, 100, 120, or 150 microns into the skin, even with repeated washings.
[00236] In other embodiments the additive is designed to penetrate into the skin, thus, in these embodiments, the active additive penetrates to at least about 10, 20, 25, 30, 35, 40, 45, or 50 microns into the skin with one washing with a bodywash containing the additive. In some embodiments, the active additive penetmtes more than about 10, 20,25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 120, or 150 microns into the skin. In some embodiments this penetration occurs with a single washing and rinsing. In some embodiments this penetration occurs with repeated washings and rinsings.
[002561 Methods of the invention also include methods for protection of skin from sunlight, comprising applying a leave-on formulation comprising applying a sunscreen encapsulated in a highly charged so]-gel capsule to the skin, wherein after application of the leave-on fbrmulation, the skin is protected from sunlight with an average SPF of at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more than 20. In some embodiments, the skin is protected from sunlight with an average SPF of at least about 2. In some embodiments, the skin is protected from sunligbt with an average SPF of at least about 5. In some embod'nnents, the skin is protected from sunGght with an average SPF of at least about 10. In some embodiments, the skin is protected from sunlight with an average SPF of at least about 15.
In sonme embodiments, the leave-on formulation is applied more than once; in these cases, the SPF may be cumulative and can increase with the sacond wash to, e.g., an average of more than 2, 5, 6, 7, 8, 9, 10, 1 l, 12, 13, 15, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, or more than about 45. In some embodiments the leave-on formulation is applied once per day. In some embodiments, the leave-on formulation is applied more than once per day, for example, 2, 3, 4, or more than 4 times per day. ]n some embodiments, the leave-on formulation is applied about every other day. In some embodiments, the body wash is applied about 10, 8, 7, 6, 5, 4, 3, 2 or 1 time per week.
[06257] In these methods, the active additive, e.g., sunscreen, o8en does not penetrato beyond a certain level in the skin, typically due to eneapsulation. Thus, in some embodiments of the methods of the invention, the active additive, e.g., sunscreen, does not penetrate more than about 10, 20, 25, 30, 35, 40, 45, or 50 microns into the skin with one application with a leave-on formulation containing the additive. In some embodiments, the active additive, e.g., sunscreen, does not penetrate mora than about 10, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 120, or 150 microns into the skin, even with repeated applications.
[002581 ]n other embodimants the additive, is designed to penetrate into the skin, thus, in these embodiments, the active additive penetmtes to at lesst about 10, 20, 25, 30, 35, 40, 45, or 50 microns into the skin with one washing with a leave-on formulation containing the additive. In some embodiments, the active additive penetrates more than about 10, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 120, or 150 microns into the skin. In some embodiments this penetration occurs with a single application. In some embodiments this penetration occurs with repeated applications.
[092591 Any additive described herein, e.g., sunscreen additives, generslly as a component of a bodywash or a leave on formulation, may be used in the methods of the invention. In some embodiments, the additive is a non-sunscreen additive and is encapsulated, e.g., in the form of sol-gel microcapsules. In these embodiments, the additive may be used in combination with a bodywash or a non- bodywash vehicle, such as a skin lotion, gel, oream, and the like, as are well-known in the art.
[002601 While it is ordinarily preferred to use the bodywash compositions of the present invention in a manner similar to ordinary soap (i.e., wetting, appGeation of composition, rinsing), it is also anticipated that the composition may be used by application without wetting followed by removal through, for example, wiping. This is the case for soepless cleansers.
[002611 One aspect of the invention is a method of applying an ective compound to a surface, for example, skin or hair comprising; providing a composition comprising an active compound encapsulated into a sol-gel microcapsule having a high zeta potential; and applying the composition to the surface, for example, skin or hair. Any of the high zeta potential microcapsules described above can be used in the method.
[00262] The microcapsules osa be formulated to break open in various types of conditions ineluding friction, temperature, light, pH, enzymes, or some combination of these. The capsule can include components that break down when exposed to these conditions, causing release of the contents. In some cases, the components are released immediately upon initial application to a surPace including skin or hair. In some embodiments, 1, 2, 5,10, 20, 30, 40, 50, 60, 70, 80, 90 pereent or more of the encapsuhaed active is released substaatially on contact with a surface including skin or hair. In some cssos the actives are released over time. In some cases it is desirable to have the active is released quickly, in other cases, it is desired that the active be released over a long period of time. The releaso can be controlled by eontrolling the permeability of the capsule to the additive, including controlling the porosity of the capsule. The release can also be controlled by controlling the amount of breakage of the capsules over time. In some embodiments 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, percent or more of the encapsulated active is released within 10 minutes of exposuro to the surface.
ln some embodiments 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more oftbe encapsulated active is released within 10 minutes of exposure to the skin. In some embodiments 1, 2, 5,10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more of the encapsulated active is released within 30 minutes of exposure to the skin. In some embodimeats 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more of the encapsulated active is released within l hour of exposure to the skin. In some embodiments 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more of the encapsulated active is released within 4 hours of exposure to the skin. In some embodiments 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more of the encapsulated active is released within 6 hours of exposure to the skin. In some embodiments 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more of the enoapaulated active is released within 8 hours of exposure to the skin. In some embodiments 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70,75, 80, 90 percent or more of the encapsulated active is released within 12 hours of exposure to the skin. In some embodiments 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more of the encapsulated active is released within 24 hours of exposure to the skin. In some embodiments 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more of the encapsulated active is released within 48 hours of exposure to the skin. In some cases, all of the release is due to breakage of the capsules. These are cases where the capsule shell is substantially impetmeable with respect to the active ingredient. In other cases, 1, 2, 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 percent or more of the release is due to the breakage of the capsules.
[00263] In some cases, the surface can be pre-treated or post-treated with an agent that will cause the sol-gel capsules to break or will prevent the sol-gel capsules from breaking when they come into contact with the treated surfaee or are rosiding on the surfaoo. Tlu pre-or post- treatcnent agent can either be a gel, crEme, lotion or solid or other coating which may contain an substance which can react with or modify the sol-gel capsules either enrymatically, or by pH change, light, pressure or other type of biochemical or physical influence to release or modify the sol-gel capsules. The agent may, for example, relesse the capsules content or manipulate the way the capsule effocts the substrate by either bonding or surrounding the area in which the capsule is present.
[00264] The amount of release can be measured either by measuring the surface, such as hair or skin directly, or by obtaining samples by a strip test, or by rubbing the surface, such as skin with a pad containing water or a solvent. The strip test involves adhering an adhesive strip to the surface such as skin or hair and subaequently removing it. The adhesive strip will have a pottion of the surface such as hair and skin bound to it and can be either directly analyzed, for instance by a light microscope or electron microscope, or can be extracted, and the presence of the capsules and or the ingredients can be measured. The strip test followed by microscopy also allows the breakage of the capsules to be measurod by counting tho broken and intact capsules. The rubbing method allows for the quantitation of material on the surface by measuring what has been rubbed off. The amount removed can be controlled by the extent of rubbing and the solvent used. In some cases, water is used, and the rubbing method can be used to determine how strongly the capsules and additives are bound. In other cases, solvents such as methanol, ethanol, or chloroform can be used which can be chosen to extraot a substantial amount of the material on the surface such as skin or hair. The extract can be analyzed, for oxample with ehtrnnatographic methods such as HPLC. In some cases, dyes or other indicators, such as fluorescent dyes cen be added to the topical formulations in order to assist in the measurement.
[00266] A related measurement method is the rinse method. The rinso method involves carrying out successive rinse steps on an aroe of surface such as skin in order to determine the amount of active and number of capsules that remain bound. A rinse metbod is described above for the measurement of SPF. This method can also be adapted to be used with other ackives and for use with other surfaces.
[002661 In some embodiments, pH sensitive polymers can be inoorporated to cause release at a given pH. Materials useful for pH-mediated relesse are known in the art. (see, for example, U.S.
Patents 7,053,034, 7,098,032, 7,138,382. Polymers that pH-sensitive are have found broad application, for instance, in the area of drug delivery exploiting various physiologicel and intracellulat pH gradients for the purpose of controlled release of drugs . pH
sensitivity can be as any change in polymei's physico-chemioal propeRies over cortain range of pH.
pH-sensitivity usually involves the presence of ionizable groups in the polymer (polyion).
Examples of polyions are polyacids, polybasas and polyampholytes. Use of pH-sensitive polyacids in drug delivery applications usually relies on their ability to become soluble with the pH
increase (acid/salt conversion), to form complex with other polymers over change of pH or undergo signifioant change in hydrophobicity/hydrophilicity balance. Combinations of all tht+oe above factors am also possible.
1002671 Copolymers of polymethacrylic acid are polymers which can be insoluble at lower pH
but readily solubilized at higher pH. A typical example of pH-dependent complexation is copolymers of polyaerylate(graft)ethyleneglyool which can be formulated into various pH-sensitive hydrogels which exhibit pH-dependent swelling and release.
Hydrophobioally-modified N-isopropylaerylamide-methaorylic acid copolymer can render regular egg PC
liposomes pH-sensitive by pH-dependent interaction of gratted aliphatic chains with lipid bilayer. An example of a polybase for cattrolled pH release is polyethyleneimine. Polymers with pH-mediated hydrophobicity (like polyethylaorylic acid) can also be used.

C. Busia<em Methods [002681 The invention also encompasses methods of doing business in the field of topical delivery of cosmeceuticals and the tranadermal delivery of pharmaceuticals using lathering products, including everyday soap and shampoo, as the delivery agents.
[002691 Consumers spend more than $30 billion annualty on products that take advantage of topical and transdermal delivery methods. Despite enormous growth in this area, there have been few major innovations. Most delivery methods still rely on lotions, creams or patches_ By combining a cosmetic or even phannaceutical regimen with an activity as routine as washing up or showering, the business methods of the invention capture a significant share of the topical and transdermal delivery market. Products enable personal care product makers to secure a piece of the growing market for cosmeoeutieals, like sunscreen, by enhancing existing product lines.
They will also enable drug makers to offer consumers more appealing ways to administer proscription and over-the-counter pharmaceuticals (002701 Business methods of the invention encompass a method of doing business comprising marketing an additive for use with an existing bodywash, wherein the additive, when combined with the bodywash, causes an additional effect to the normal effect of the soap or the bodywash.
The business methods include methods involving any of the additives described herein, including sunscreens, insect repellants, anti-acne medications, anti-wrinkling agents, deodorants, and all others described herein In some embodiments, the methods include marketing a sunsoreen benefit agent (additive) for use with a bodywash, e.g., bar and liquid soaps, and shampoos, to add the benefit of a sunscreen. The sunscreen may be any one of the sunscreen additives described herein. This embodiment is designed to appeal to soap manufacturers looking to broaden the market for their products among the growing population of consumers concemed about skin cancer and wrinkles. C}enerally, the benefit agent is marketed as a brand-neutrai additive for use with existing brands. In some cases, a stand-alone brand may be created.
1002711 The sunscreen or other benefit agent may be licensed as an additive, in both liquid and bar soap forms, to personal care product makers of all sizes, to enhance and differentiate their branded product offerings. The license may be exclusive or non-exclusive. If exclusive, it may be exclusive in a defined geographieal territory, for a defined time period (often with an option to renew or right of first refusal at the expiration of the time period), for a defined type of skin care product, or any combination of these. The methods also include supplying one or more customers with an option to lieense or buy the additive, generally for a defined period of time.
As with licenses, such an option may be exclusive or non-exclusive.
Alternatively, the sunscreen or other benefit agent may be manufactured and supplied to personal care product makers. A
further alternative is to tnanufaehrce a stand-alone brand of soap/bodywash that includes the additive.
1002721 A futtlter component of the business methods of the invention typically includes receiving payment for supplying the additive, license, or the like, to the customer. It will be appreciated that "payment" may be any form of consideration, included monetary considaration.
Typically, license payments take the form of an up-front payment, royahies, license maintenance feea or some combination thereof. Also included in payment options are equity in the company recaiving the additive or the license to the additive. It will be appreciated that any other form of consideretion may also constitute payment in the business methods of the invention 1002731 The business methods of the invention may further include manufaexuring the additive and/or the additive/bodywash. In some embodiments, different entities perform different aspects;
for example, a first entity may manufacture the additive and a second entity may market and/or distribute it. In some embodiments, a single entity performs both manufacturing and marketing.
[00274] Business methods of the invention further include a method including the steps of: a) designing an additive for uae in a personal care product; b) testing tbe additive for safety and effectiveness in humans; c) arrnnging for distribution and marketing of the additive. In some embodiments, steps a) and c) are performed by a first entity, typically a businoss entity, and step b) is performed by a second entity, such as a business entity or an acadomic entity. In some or these embodiments, step b) is performed as a joint venmre between the two entities.
[00275] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if eaoh individual publication or patent application was specifioally and individually indicated to be incorporated by refenence.

[00276] It will be apparent to one of ordinary skill in the att that many changes and modification can be made to the disclosures presented herein without departing from the spirit or scope of the appended claims.

ERAMPLES

1002771 A sunscreen additive for addition to a bodywash was prepered as follows: To 13.7 g water was added I g of polyquaternium-4 (CELQUAT-200), 1.5 gm of MOISTUREGUARD, and 12 g of UV PEARLS. The mixture was stirred until uniform, to produce Phase I. Seperately, 1 g of PARSOL 1789 was added to 4 g of Octocrylene with heating, and stirred until uniform, to produce Phase II. Phase I and Phase II wore combined with gentle agitation until uniform to produce Phase III, a sunscreen additive.
[00278] The sunscreen additive of Phase III was added to 64.5 g of SUAVE
Bodywash and stirred until uniform. Finally, 2.3 g of titanium dioxide were added with stirring. The final composition was a sunscreen/bodywash.

1002791 The sunscreen/bodywash of Example I was tested for SPF capability as follows: 50 om2 of testing site was wettod with 10m1 of water defivered with a syringe. The test sample was applied as per FDA monograph C.F.R. 21 to the area. Lather was worked into the subjeet for 3 minutes to allow the product to absorb into the skin. The area was rinsed after 2 additional minutes with 20mI of water, then the araa was patted dry and allowed 15 minutes before exposure to radiation as per FDA monograph. The skin was exposed to UV radiation and the MED was noted and compared to the MED for skin without areatrnent. Results are shown in the Table below.
Table (Lather Method") Subject Sex MED/ I Sldn MED I MED II STD SPF
ID # Hr (Amps) Type J/MZ J/M' (8% HMS) Value 468676 F 127.8 7.0 II 46.20 48.20 4.40 15.00 503379 F 126.4 7.0 11 46.20 46.20 4.00 18.00 380202 F 125.8 7.0 II 46.20 48.20 4.40 21.60 562392 F 125.8 7.0 II 46.20 48.20 4.00 18.00 501415 F 125.8 7.0 11 48.20 48.20 4.40 21.60 MEAN (x) 4.24 18.84 STANDARD DEV (a) 0.22 2.80 STD. ERROR 0.10 1.25 S.E. % OF MEAN 2.36 6.63 MED: Minimal Erythemal Dose I: Intenaity of light souroe [00280] This Example demonstrates that the sunscreen/bod}wash enhanced the sun protection as meesured by this protocol, as compared to untreated skin, by an average SPF of over 18.
E%AMPLE 3 [00281] A sunscreen/bodywash is prepared by mixing the following ingredients:
0.1 to 7.5 parts by weight of octylmethoxy cinnamate, 0.1 to 6 parts by weight of octyl salicylate, 0.1 to 5 parts by weight of oxybenzone, I to 10 parts by weight of cationic surfactant, 0.01 to 1 part by weight of a quatemized compound and 0.01 to L part by weigbt of a preservative.

[00282] A sunscreen/bodywash is prepared by mixing the foilowing ingredients:
Water 20-65%
Polyquat 4 .01-3.75%
Dimethicone .01-7%
Octylmethoxycinnamate in amorphous silica Petrolatum .01-10%
Titanium Dioxide .01-20%
Octocrylene .01-10%
Parsol 1789(Avobenzone) .01-3%
Kathon .01-2%
Bodywash gmeric 5-99%

Highlv CharQed Miorocensules from oil-in-water (O/W) emulsion -encepsulation of Homosal. Vitamin A and Vitamin E
[00283] First the non-polar ingredients homomenthyl salicylate (Homosal) (18-22 parts) and a mixture of Vitamin A and Vitamin B, (0.5-2 parts) are combined, added with deionized water (50-60 parts) and mixed with a PT 3100 mnter at 6,000 rpm for about 15 minutes at a temperature of about 65 C to form an emulsion. Aliquots of the emulsion are removed and analyzed by microscope to estimata the droplet size. To the emulsion is added sodium lauryl sulfate (0.08 -0.16 parts). Copolyiner surfactant Atlox 49-12 (0.05 to 0.10) parts can also be added. Tetraethyl ortho silicate (TEOS) (15 - 25 parts) is added to the emulsion. Polyquaternium - 4(0.03 to 0.5 parts) is added to the emulsion. A l0% HCI solution is then added a drop at a time while mixing the emulsion to bring the pH to about 3.8. The emulsion is then mixed for about 2 to 2.5 hours while the TEOS hydrolyzes and the sol-gel capsules aro formed. TLe pH is monitored, and adjusted to pH 3.8 if needed. An afiquot of capsules in solution can be removed and the zeta potential of the capsules determined. If the zeta potential is lower than desired, the capsules can be tteated with a cationic agent such as polyquaternium-4 in order to increase the zeta potential on the particles. The reaction mixture is filtered with a Buchner funnel using a I micron fiher.
The capsules are rinsed 2- 3 times with deionized water. The moist capsules are then placed in an oven at 40'C - 55 C for 24 to 48 hours to dry the capsules, [002841 In an alternative embodiment of the above example, the Polyquaternium -4(0.03 to 0.5 parts) is added to the reaction mixture a8er the capsules have been formed rather than being added to the emulsion before formation of the capsules.
[00285[ In another alternative embodiment of the above example, the Polyquatemium - 4(0.03 to 0.5 parts) is dissolved in an aqueous solution, which is applied to the capsules after they are dried.
After the addition of the Polyquatemium-4, the moist capsules are plac ed in an oven at 40 C -55 C for 24 to 48 houra a second timc to dry the charged capsules.

Highly Charged Miorocansules from a water-in-oil (W/O) emulsion Encansulation of Glvicerin [00286] Glycerin (10 - 20 parts), water (10 - 20 perts), and siloxano fluid (Dow Corning 245) (45-55 parts), and sorbitan oleate surfactant (Crill 3 NF) (0.08 - 0.16) are combined and mixed with a PT 3100 mixer at 2,000 - 4,000 rpm for about 10 minutes at a temperature of about 55 C
to form a water-in-oil emulsion. Aliquots of the emulsion are removed and analyzed by microscope to estimate the droplet size. A copolymer surfactant with HLB value of 2 to 6 can also be added if needed to stabiBze the emulsion. Tetraethyl ortho silicate (TEOS) (15 - 25 parts) is added to the emulsion. Polyquatemium - 4(0.03 to 0.5 parts) is added to the emulsion. A
10% HCI solution is then added a drop at a time while mixing the emulsion to bring the pH to about 3.8. The emulsion is then mixed for about I to 2 hours while the TEOS
hydrolyzes and the sol-gel capsules are formed. The pH is monitored, and adjusted to pH 3.8 if needed. The reaction mixture is filtered with a Buchner funnet using a 1 micron filter. An aliquot of capsules in solution can be removed and the zeta potential of the capsules deterniined.
If the zeta potential is lower than desired, the capsules can be treated with a cationic agent such as polyquaternium-4 in order to inorease the zeta potential on the particles. The capsules are rinsed 2- 3 times with deionized water. The moist capsules are then placed in an oven at 40 C - 55 C
for 24 to 48 hours to dry the capsules.
1002871 In an altemative embodiment of the above example, the Polyquaternium -4(0.03 to 0.5 parts) is added to the reaction mixture after the capsules have been formed ratber than being added to the emulsion before forntation ofthe capsules.
[00288] In another alternative embodiment of the above example, the Polyquaternium - 4(0.03 to 0.5 parts) is dissolved in an aqueous solution, which is applied to the capsules after they are dried.
After the addition of the Polyquaternium-4, the moist capsules ara placed in an oven at 40 C -55 C for 24 to 48 hours a second time to dry the charged capsules.

Highly Charr¾ad Microcaasules from an aqueous solution with Phosgholipid temniete Encansulation of GIyC.P,rin [00289] Deionized water (45-55 parts), Glycerin (5 - 15 parts), and phospholipid (Phospholipon 85G) (18 - 28 patts) are combined and mixed with a PT 3100 mixer at 3,000 -6,000 rpm for about 10 minutes at a temperatura of about 42 C - 65 C to form an aqueous solution comprising liposomes. Tetraethyl ortho silicate (TEOS) (15 - 25 parts) is added to the reaction mixture.
Polyquatemium - 4(0.03 to 0.5 parts) is added to the reaction mixture. A 10%
H2SO4 solution is then added a drop at a time while mixing the emulsion to bring the pH to about 3.4. The emulsion is then mixed for about 1 to 2 hours while the TEOS hydrolyzes and the sol-gel capsules are fnrmed. The pH is monitored, and adjusted to pH 3.4 if needed. An aliquot of capsules in solution can be removed and the zeta potential of the capsules determined. If the zeta potential is lower than desired, the capsules ean be treated with a cationic agent such as polyquaternium-0 in order to increase the zeta potential on thb particles. The reaction mixture is fihered with a Buchner futmel using a 1 micron filter. The capsules are rinsed 2- 3 times with deionized water. The moist capsules are then placed in an oven at 40 C - 55 C
for 24 to 48 hours to dry the capsules.
[00290] In an altemative embodiment of the above example, the Polyquaternium -4(0.03 to 0_5 parts) is added to the reaotion mixture after the capsules have been foRUed rather than being added to the emulsion before formation of the capsules.
[110297] In another alternative embodiment of the above example, the Polyquaternium - 4(0.03 to 0.5 parts) is dissolved in an aqueous solution, which is applied to the capsules a8er they are dried.
After the addition of the Polyquaternium-4, the moist capsules are placed in an oven at 40 C -55 C for 24 to 48 hours a seaond time to dry the charged capsules.
[00292] In the above metbod, phospholipid liposomes are used as the templates.
In a variation of the above method, polymer microcapsules such those formed from polystyrene, hydroxyethylcellulose, polyaerylamide, where the polymer microcapsule comprises an active ingredient, can be used as templates to fonu highly charged microcapsules.

(002931 While certain embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing Erom the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention.
It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims (113)

1. A sol-gel microcapsule with a zeta potential of at least about 40 mV.

2. The sol-gel microcapsule of claim 1, wherein the zeta potential is at least about 50 mV.

3. The sol-gel microcapsule of claim 1, wherein the zeta potential is at least about 55 mV.

4. The sol-gel microcapsule of claim 1, wherein the zeta potential is at least about 60 mV.

5. A plurality of sol-gel microcapsules capable of binding to a surface wherein an average of at least about 50% of the microcapsules remain bound to the surface for an average of greater than at least about 4 hours.

6. The sol-gel microcapsule of claims 1-4 wherein the microcapsule comprises a cationic agent.

7. The sol-gel microcapsule of claim 6 wherein the cationic agent comprises a cationic polymer.

8. The sol-gel microcapsule of claim 7 wherein the cationic polymer comprises polyquaternium-4, -7, -11, -22, -27, -44, 51, or -64.

9. The sol-gel microcapsule of claim 7 wherein the cationic polymer comprises polyquaternium-4.

10. The sol-gel microcapsule of claim 1 wherein the microcapsule is associated with an additive.

11. The sol-gel microcapsule of claim 10 wherein the additive is encapsulated in the microcapsule.

12. The sol-gel microcapsule of claim 10 wherein the additive is located substantially within the sol-gel microcapsule.

13. The sol-gel microcapsule of claim 10, wherein the additive is selected from the group consisting of steroidal anti-inflammatory actives, analgesic actives, antifungals, antibacterials, antiparasitics, anti-virals, anti-allergenics, anti-cellulite additives, medicinal actives, skin rash, skin disease and dermatitis medications, insect repellant actives, antioxidants, hair growth promoter, hair growth inhibitor, hair bleaching agents, deodorant compounds, sunless tanning actives, skin lightening actives, anti-acne actives, anti-skin wrinkling actives, anti-skin aging actives, vitamins, nonsteroidal anti-inflammatory actives, anesthetic actives, anti-pruritic actives, anti-microbial actives, dental care agents, personal care agents, nutraceuticals, pharmaceuticals, fragrances, antifouling agents, pesticides, lubricants, etchants, and mixtures and combinations thereof.

14. The sol-gel microcapsule of claim 10 wherein the additive is selected from the group consisting of sunscreens, skin lightening actives, anti-aging additives, fragrances, pharmaceuticals, antibacterials, moisturizers, anti-acne actives, and insect repellants.

15. The sol-gel microcapsule of claim 10, wherein the additive comprises a sunscreen.

16. The sol-gel microcapsule of claim 15, wherein the sunscreen is selected from the group consisting of aminobenzoic acid, avobenzone, cinnoxate, dioxybenzone, homosalate, menthyl anthranilate, octocrylene, octyl methoxycinnamate, octyl salicylate, oxybenzone, padimate O, phenylbenzimidazole sulfonic acid, sulisobenzone, and trolamine salicylate.

17. The sol-gel microcapsule of claim 15, wherein the sunscreen comprises a UVA-absorbing sunscreen, a UVB-absorbing sunscreen, and a physical blocker sunscreen.

18. The sol-gel microcapsule of claim 17 wherein (i) the UVB-absorber sunscreen is selected from the group consisting of aminobenzoic acid, cinoxate, dioxybenzone, homosalate, octocrylene, octyl methoxycinnamate, octyl salicylate, oxybenzone, padimate O, phenylbenzimidazole sulfonic acid, sulisobenzone, and trolamine salicylate; (ii) the UVA-absorber sunscreen is selected from the group consisting of avobenzone and menthyl anthranilate; and (iii) the physical blocker sunscreen is selected from the group consisting of titanium dioxide and zinc oxide.

19. A composition comprising the sol-gel microcapsule of claim 10, and further comprising a vehicle suitable for treatment of surfaces in topical, agricultural, textile, industrial, transportation, marine, pharmaceutical, or personal care.

20. The composition of claim 19 wherein the composition comprises a wash-on product.

21. The composition of claim 19 wherein the composition comprises a leave-on product.

22. The composition of claim 19 wherein the microcapsules in the composition experience an average of greater than about 50% breakage when applied to the surface.

23. The composition of claim 22 wherein the breakage substantially occurs on initial application to the surface.

24. The composition of claim 22 wherein the average of greater than 50%
breakage occurs over a period of about 1 hour.

25. The composition of claim 22 wherein the average of greater than 50%
breakage occurs over a period of about 6 hours.

26. The composition of claim 22 wherein the average of greater than 50%
breakage occurs over a period of about 12 hours.

27. The composition of claim 22 wherein the average of greater than 50%
breakage occurs over a period of about 24 hours.

28. The composition of claim 22 wherein the breakage occurs due to the conditions of surface application.

29. The composition of claim 28 wherein the condition of surface application is friction, pressure, light, pH change, or enzymatic action.

30. A method of applying an active compound to a surface comprising;
providing a composition comprising an active compound encapsulated into a sol-gel microcapsule having a zeta potential of greater than about 30 mV; and applying the composition to the surface.

31. The method of claim 30 wherein the zeta potential is greater than 30 mV.

32. The method of claim 30 wherein the zeta potential is greater than 40 mV.

33. The method of claim 30 wherein the zeta potential is greater than 55 mV.

34. The method of claim 30 wherein the zeta potential is greater than 60 mV.

35. The method of claim 30 wherein the capsules comprise a cationic polymer.

36. The method of claim 35 wherein the cationic polymer comprises a polyquaternium.

37. The method of claim 35 wherein the cationic polymer comprises polyquaternium-4, -7, -11, -22, -27, -44, 51, or -64.

38. The method of claim 30, wherein the additive is selected from the group consisting of steroidal anti-inflammatory actives, analgesic actives, antifungals, antibacterials, antiparasitics, anti-virals, anti-allergenics, anti-cellulite additives, medicinal actives, skin rash, skin disease and dermatitis medications, insect repellant actives, antioxidants, hair growth promoter, hair growth inhibitor, hair bleaching agents, deodorant compounds, sunless tanning actives, skin lightening actives, anti-acne actives, anti-skin wrinkling actives, anti-skin aging actives, vitamins, nonsteroidal anti-inflammatory actives, anesthetic actives, anti-pruritic actives, anti-microbial actives, dental care agents, personal care agents, nutraceuticals, pharmaceuticals, fragrances, antifouling agents, pesticides, lubricants, etchants, and mixtures and combinations thereof.

39. The method of claim 30 wherein the additive is selected from the group consisting of sunscreens, skin lightening actives, anti-aging additives, fragrances, pharmaceuticals, antibacterials, moisturizers, anti-acne actives, and insect repellants.

40. The method of claim 30 wherein the additive comprises a sunscreen.

41. The method of claim 30 wherein the sunscreen is selected from the group consisting of aminobenzoic acid, avobenzone, cinnoxate, dioxybenzone, homosalate, menthyl anthranilate, octocrylene, octyl methoxycinnamate, octyl salicylate, oxybenzone, padimate O, phenylbenzimidazole sulfonic acid, sulisobenzone, and trolamine salicylate.

42. The method of claim 30 wherein the sunscreen comprises a UVA-absorbing sunscreen, a UVB-absorbing sunscreen, and a physical blocker sunscreen.

43. The method of claim 30 wherein (i) the UVB-absorber sunscreen is selected from the group consisting of aminobenzoic acid, cinoxate, dioxybenzone, homosalate, octocrylene, octyl methoxycinnamate, octyl salicylate, oxybenzone, padimate O, phenylbenzimidazole sulfonic acid, sulisobenzone, and trolamine salicylate; (ii) the UVA-absorber sunscreen is selected from the group consisting of avobenzone and menthyl anthranilate; and (iii) the physical blocker sunscreen is selected from the group consisting of titanium dioxide and zinc oxide.

44. The method of claim 30 wherein the microcapsules in the composition experience an average of greater than about 50% breakage when applied to the surface.

45. The method of claim 30 wherein the breakage substantially occurs on initial application to the surface.

46. The method of claim 30 wherein the breakage occurs over a period of 1 hour.

47. The method of claim 30 wherein the breakage occurs over a period of 6 hours.

48. The method of claim 30 wherein the breakage occurs over a period of 12 hours.

49. The method of claim 30 wherein the breakage occurs over a period of 24 hours.

50. A method of manufacturing a highly charged sol-gel microcapsule comprising a non-polar active ingredient comprising:

(a) combining the non-polar active ingredient, optional non-polar diluent, and aqueous phase;

(b) agitating the combination formed in (a) to form an oil-in-water (O/W) emulsion wherein the non-polar active ingredient and optional non-polar diluent comprise the dispersed phase;

(c) adding one or more surfactants;
(d) adding a cationic agent;

(e) adding a gel precursor to the O/W emulsion; and (f) mixing the composition from step (e) while the gel precursor hydrolyzes and sol-gel capsules are formed which comprise the non-polar active ingredient.

51. The method of claim 50 further comprising step (g) filtering the sol-gel microcapsules and step (h) rinsing the sol-gel microcapsules.

52. The method of claim 51 further comprising step (i) drying the microcapsules.

53. The method of claim 50 wherein the method of manufacturing produces a microcapsule having zeta potential of at least about 30 mV.

54. The method of claim 50 wherein the method of manufacturing produces a microcapsule having a zeta potential of at least about 40 mV.

55. The method of claim 50 wherein the method of manufacturing produces a microcapsule zeta potential of at least about 55 mV.

56. The method of claim 50 wherein the method of manufacturing produces a microcapsule having zeta potential of at least about 60 mV.

57. The method of claim 50 wherein the steps are carried out in the order listed.

58. The method of claim 50 wherein the cationic agent is added after the addition of the gel precursor.

59. The method of claim 50 wherein the cationic agent is added during step (f).

60. The method of claim 50 wherein the cationic agent is added after step (f).

61. The method of claim 51 wherein the cationic agent is added during step (h) of rinsing the sol-gel microcapsules.

62. The method of claim 52 wherein the cationic agent is added after step (i) of drying the sol-gel microcapsules.

63. The method of claim 50 wherein the cationic agent comprises a cationic polymer.

64. The method of claim 63 wherein the cationic polymer comprises polyquaternium-4, -7, -11, -22, -27, -44, 51, or -64.

65. The method of claim 64, wherein the cationic polymer comprises polyquaternium-4.

66. The method of claim 50 wherein the cationic agent comprises a proton donor.

67. The method of claim 50 wherein step (f) is carried out at acidic pH.

68. The method of claim 67 wherein step (f) is carried out at a pH from 3.6 to 4Ø

69. The method of claim 50 wherein the one or more surfactants comprises a copolymer surfactant.

70. The method of claim 50 wherein the one or more surfactants have a combined hydrophile-lipophile balance (HLB) of between 9 and 11.

71. A method of manufacturing a highly charged sol gel microcapsule comprising a polar active ingredient comprising:

(a) combining the polar active ingredient, water, optional polar diluent, and a non-polar (oil) phase;

(b) agitating the combination formed in (a) to form an water-in-oil (W/O) emulsion wherein the polar active ingredient, water, and optional polar diluent comprise the dispersed phase;

(c) adding one or more surfactants;
(d) adding a cationic agent;

(e) adding a gel precursor to the W/O emulsion; and (f) mixing the composition from step (e) while the gel precursor hydrolyzes and sol-gel capsules are formed which comprise the polar active ingredient.

72. The method of claim 71 further comprising step (g) filtering the sol-gel microcapsules and step (h) rinsing the sol-gel microcapsules.

73. The method of claim 52 further comprising step (i) drying the microcapsules.

74. The method of claim 71 wherein the method of manufacturing produces a microcapsule having zeta potential of at least 30 mV.

75. The method or claim 71 wherein the method of manufacturing produces a microcapsule having a zeta potential of at least 40 mV.

76. The method of claim 71 wherein the method of manufacturing produces a microcapsule zeta potential of at least 55 mV.

77. The method of claim 71 wherein the method of manufacturing produces a microcapsule having zeta potential of at least 60 mV.

78. The method of claim 71 wherein the steps are carried out in the order listed.

79. The method of claim 71 wherein the cationic agent is added after the addition of the gel precursor.

80. The method of claim 71 wherein the cationic agent is added during step (f).

81. The method of claim 71 wherein the cationic agent is added after step (f).

82. The method of claim 72 wherein the cationic agent is added during step (h) of rinsing the sol-gel microcapsules.

83. The method of claim 73 wherein the cationic agent is added after step (i) of drying the sol-gel microcapsules.

84. The method of claim 71 wherein the cationic agent comprises a cationic polymer.

85. The method of claim 84 wherein the cationic polymer comprises polyquaternium-4, -7, -11, -22, -27, -44, 51, or -64.

86. The method of claim 85, wherein the cationic polymer comprises polyquaternium-4.

87. The method of claim 71 wherein the cationic agent comprises a proton donor.

88. The method of claim 71 wherein step (f) is carried out at acidic pH.

89. The method of claim 88 wherein step (f) is carried out at a pH from 3.6 to 4Ø

90. The method of claim 71 wherein the one or more surfactants comprises a copolymer surfactant.

91. The method of claim 71 wherein the one or more surfactants have a combined hydrophile-lipophile balance (HLB) of between 2 and 6.

92. A method of forming a highly charged sol-gel microcapsule comprising an active ingredient within a template comprising:

(a) forming a dispersion of templates, wherein the templates comprise an active ingredient, in an aqueous continuous phase;

(b) adding a cationic agent;

(c) adding a gel precursor to the aqueous continuous phase; and (d) mixing the composition from step (c) while the gel precursor hydrolyzes and sol-gel capsules are formed.

93. The method of claim 92 further comprising step (e) filtering the sol-gel microcapsules and step (f) rinsing the sol-gel microcapsules.

94. The method of claim 93 further comprising step (g) drying the microcapsules.

95. The method of claim 92 wherein the method of manufacturing produces a microcapsule having zeta potential of at least 30 mV.

96. The method of claim 92 wherein the method of manufacturing produces a microcapsule having a zeta potential of at least 40 mV.

97. The method of claim 92 wherein the method of manufacturing produces a microcapsule zeta potential of at least 55 mV.

98. The method of claim 92 wherein the method of manufacturing produces a microcapsule having zeta potential of at least 60 mV.

99. The method of claim 92 wherein the steps are carried out in the order listed.

100. The method of claim 92 wherein the cationic agent is added after the addition of the gel precursor.

101. The method of claim 92 wherein the cationic agent is added during step (c).

102. The method of claim 92 wherein the cationic agent is added after step (c).

103. The method of claim 93 wherein the cationic agent is added during step (f) of rinsing the sol-gel microcapsules.

104. The method of claim 94 wherein the cationic agent is added after step (g) of drying the sol-gel microcapsules.

105. The method of claim 92 wherein the cationic agent comprises a cationic polymer.

106. The method of claim 105 wherein the cationic polymer comprises polyquaternium-4, -7, -11, -22, -27, -44, 51, or -64.

107. The method of claim 106, wherein the cationic polymer comprises polyquaternium-4.

108. The method of claim 92 wherein the cationic agent comprises a proton donor.

109. The method of claim 92 wherein step (d) is carried out at acidic pH.

110. The method of claim 92 wherein step (d) is carried out at a pH from 3.6 to 4Ø

111. The method of claim 92 wherein the template comprises a microsphere.

112. The method of claim 92 wherein the template comprises a polymer, liposome or micelle.

113. The method of claim 112 wherein the template comprises a phospholipid.