WO2004108064A2

WO2004108064A2 - Diosgenin-based composition suitable for topical application

Info

Publication number: WO2004108064A2
Application number: PCT/FR2004/001376
Authority: WO
Inventors: Michèle EYMARD
Original assignee: Laboratoire De Dermo-Cosmologie
Priority date: 2003-06-03
Filing date: 2004-06-03
Publication date: 2004-12-16
Also published as: WO2004108064A3; FR2855753B1; FR2855753A1

Abstract

The invention relates to the field of therapeutically and cosmetologically useful compositions. The composition, suitable for topical application, contains diosgenin or a dioscorea extract, preferably dioscorea opposita, dioscorea composita, dioscorea floriburida, dioscorea villosa, dioscorea hypoglauca, yam, and wild yam, at a pure diosgenin concentration of at least 2 % in weight based on the total weight of the composition. The invention finds application in dermatology by acting on the superficial musculo-aponevrotic system or on the estrogen and progesterone cell receptors, as well as in the cosmetic treatment of the skin and keratin fibers.

Description

COMPOSITION BASED ON DIOSGENINE APPLICABLE TOPICALLY

The present invention relates to a composition useful in human or animal therapy, in dermatology and in cosmetology, and more particularly a composition applicable topically based on dioscorea extract, the use of a pure diosgenin extracted from dioscorea in a treatment cosmetic, as well as the use of a dioscorea extract for the manufacture of a medicament for the treatment of dermatological conditions.

Diosgenin is a structural analogue of cholesterol mainly used in therapy because of its anti-inflammatory properties and its action to compensate for the deleterious effects of estrogens, more particularly in perimenopause and menopause periods, as well as in cosmetics and dermatology. for its skin antiseptic properties.

Diosgenin can be extracted from plants of the genus dioscorea, in particular dioscorea opposita, which is a plant used in traditional Chinese medicine. The extraction can be done by the usual techniques, for example by ethanolic extraction, from any part of the plant, and preferably the rhizome, previously dried and ground. A method of cultivating plants of the dioscorea family, in particular dioscorea floriburida and dioscorea composita, making it possible to improve the content of diosgenin is described in patent US-A-3,918,200.

A diosgenin extracted from dioscorea composita is described in patent FR-A-2,367M which mentions its possible use in the treatment of trophic edemas as well as rheumatic and vascular disorders. Patent FR-A-2,786,097 describes slimming cosmetic compositions comprising approximately 5% of extracts of dioscorea opposita, having the effect of acting on the lipid metabolism of the adipocyte by limiting the accumulation of fats' in the cell. ^' US-A-5,804,211 describes a composition in the form of a vegetable-based nasal lotion intended to limit or suppress snoring, and containing an extract of dioscorea, ginger, chamomile and a potassium or sodium salt . The dioscorea extract is preferably dioscorea villosa, used in an amount of 0.01 to 0.4% by weight relative to the total weight of the composition.

The use of diosgenin in therapeutic compositions has also been described, for example in patent EP-A-873,125 relating to a composition associating diosgenin with vitamins, such as vitamin K and vitamin D, which can be administered orally or transdermally , for the treatment of osteoporosis. US Patent 6,030,948 describes hair compositions for the treatment of alopecia comprising tyrosine extracts, optionally supplemented with steroids which can be chosen from a list including DHEA and diosgenin, but no specific example is given. Compositions containing a sapogenin such as diosgenin are described in patent FR 2,837,704, but the doses used are low, less than 1%. Other compositions containing natural extracts rich in sapogenins, for example extracts of wild yam, having an inhibiting effect on the activity of collagenases, are described in patent FR 2,817,747, but the extract itself is used in low doses, less than 1%. DHEA, in the form of wild yam extract, has also been proposed in combination with a natural extract of algae or yeast capable of increasing the synthesis of glycosaminoglycans, and with a metalloproteinase inhibitor, with a view to treat the signs of skin aging. According to this document, DHEA could be replaced by a precursor such as diosgenin. A combination of DHEA and isoflavonoid to treat the signs of skin aging is proposed in the application WO 0205764. Patent EP 1,269,986 describes a technique using a lipophilic amino acid derivative making it possible to make various active principles such as DHEA soluble in water in order to avoid using them in hydro-alcoholic form in compositions cosmetic and dermatological.

We also know that diosgenin, steroidal saponin, is a chemical precursor of various steroids, and in particular of DHEA which is an important hormone of the human or animal organism, produced by the adrenal glands, and which is transformed into estrogen and testosterone . However, diosgenin does not directly convert into progesterone, and there is nothing in the scientific literature to suggest that diosgenin, especially when administered topically, could have the same activity as DHEA, especially because the enzymes likely to transform it in the body have never been identified. However, we know how to prepare DHEA in the laboratory from diosgenin.

The studies on fibroblasts and epidermal keratinocytes as well as the clinical studies carried out by the applicant have made it possible to show that diosgenin, in particular in the form of dioscorea extract, has properties useful in dermatology and in cosmetics, and in particular an action on the superficial musculo-fascial system when administered topically, externally or transdermally.

The subject of the present invention is therefore a composition based on diosgenin or on dioscorea extract which can be used in therapy, in dermatology and in cosmetology, topically.

The subject of the invention is also a cosmetic and / or dermatological composition with a high content of pure diosgenin or of dioscorea, in particular dioscorea opposita.

The present invention also relates to a composition having an extra- or intra-cellular adaptagenic effect at level of receptors in the cells of the epidermis, hypodermis, dermis and of the superficial musculo-aponeurotic system (SMAS), allowing its application in dermatology and cosmetology, in particular for skin regeneration and restructuring, and in general to fight against the signs of skin aging.

The subject of the invention is finally the use of diosgenin or dioscorea for the manufacture of a dermatological medicament acting by action on the superficial musculo-aponevrotic system and on the cellular receptors of estrogens and progesterone, for the treatment of skin conditions, as well as a method of cosmetic treatment of the skin and keratin fibers using diosgenin or dioscorea. The cosmetic and / or dermatological composition according to the invention is distinguished in that it contains diosgenin, more particularly in the form of dioscorea extract, in relatively high concentration, greater than 2% by weight, expressed as pure diosgenin by relative to the total weight of the composition. Preferably, the content of diosgenin, calculated as pure diosgenin, is between 5% and 50% by weight relative to the total weight of the composition.

The diosgenin used in the present invention is preferably in the form of an extract of dioscorea, more particularly of dioscorea opposita.

According to a variant in accordance with the present invention, an alpha-hydroxy acid such as lactic, glycolic, mandelic, citric, thiolactic, thioglycolic acids, or one of their salts or esters, and preferably glycolic acid, is used together with diosgenin.

According to another variant, the composition also comprises an ino-acid, or a salt or ester, chosen from leucine, proline, thymidine, glucosamine, serine, arginine and lysine. A composition in accordance with the present invention preferably comprises diosgenin, as indicated above, in combination with glycolic acid and / or lysine.

It is particularly advantageous, in accordance with the present invention, to use diosgenin in combination with a mucopolysaccharide or a glycosaminoglycan, in particular a hydrolyzed mucopolysaccharide.

The studies carried out have shown that the compositions with a high diosgenin content according to the invention, applied topically, for example in the form of a gel, cream or lotion, or in the form of a patch for transdermal administration, penetrate better into the epidermis and exhibit excellent bioavailability.

As stated above, diosgenin can be obtained from dioscorea extract.

The dioscorea extract used in the present invention for the preparation of the composition with a high diosgenin content can be any dioscorea extract from the yam family, including the dioscoreaceae, dioscorea opposita, dioscorea composita, dioscorea floriburida, dioscorea villosa, dioscorea hypoglauca, yam, wild yam, and preferably dioscorea opposita. It is obtained in the form of an extract of the whole plant or, preferably, of the rhizome, as a dry extract or essential oil. As indicated above, the compositions according to the present invention contain a high content of diosgenin, which can be between 2% and 50% by weight relative to the total weight of the composition and preferably between 5% and 20% by weight . These contents of pure diosgenin can be chosen according to the mode of administration of the composition of the invention. For example, in the case of a patch for transdermal administration, it is advantageous to use a relatively high dose of diosgenin, which can be of the order of 15 to 20% by weight while in the in the case of a gel or a cream, the content of pure diosgenin is generally between 5 and 15% by weight.

The adaptagenic effect of the composition of the invention results from the relatively high content of pure diosgenin resulting in an activation of the progesterone effect in the organism, and a modulation of the cellular receptors for estrogens and progesterone.

In particular, the composition of the invention exerts its effects on the superficial musculo-aponeurotic system and on all tissues in general, by causing an increase in the sensitivity of the membrane or cytoplasmic receptors of cells to circulating hormones. The superficial musculo-aponeurotic system is a connective fibrous web containing fibroblasts sensitive to circulating estrogens and muscle fibers sensitive to progesterone.

This action is particularly effective on the skin showing signs of skin aging by compensating for the hormonal loss by an increase in activity linked to the increase in the sensitivity of the receptors. This activity can be advantageously used in the treatment of signs of skin aging by causing an increase in skin thickness and a densification of the structure of the epidermis, dermis and hypodermis, as well as the dermis of the system. superficial musculo-aponeurotic. These signs of skin aging which can be advantageously treated with the composition according to the invention are more particularly those which are characterized by a loosening of the skin structure and a reduction in the thickness of the skin. Because of this activity, the compositions of the invention are also useful in dermatological treatments and cosmetic surgery by providing densification and restructuring of the skin and an increase in muscle tension, especially of the face. Another advantageous dermatological application of the invention is the treatment of burns, scarring, and the associated treatment, for example, of venous insufficiency or localized adiposities, because of its anti-edematous action. More particularly, the compositions according to the present invention are suitable for the treatment of burns whatever their origin, for example burns of the skin resulting from the effect of UVA and UVB during excessive exposure to the sun, burns from chemicals, flame, or contact with a hot surface. They are also suitable for treating the epidermis following laser treatment.

The compositions of the invention have also been found to be effective in the treatment of inflammation, in particular post-operative inflammation, and in the treatment of interstitial edema after surgery, in general or cosmetic surgery, for example in post-lipoplasty treatment. In another cosmetological application, the compositions of the invention can be advantageously used for straightening keratin fibers, eyelashes or hair, more particularly in the case of compositions containing diosgenin in combination with thiolactic acid or acid thioglycolic or one of their salts or esters.

Finally, the composition according to the invention is useful in the treatment of overweight. Indeed, estrogens and progesterones are the known hormonal agents of obesity in members of the human body. At the level of adipocytes, the distribution of α-adrenergic receptors and β-adrenergic receptors is approximately 85/15. In addition, it is known that the antero-internal side of the thigh includes type I fats having a particular sensitivity to estrogens and a high lipase lipoprotein activity, while the external side of the thigh has a sensitivity peculiar to progesterone, the antioedematous action of which is known. Thus, hormonal regulation disorders can cause a decrease, or even a disappearance, of the β-adrenergic receptors which promotes lipolysis more particularly in the pelvic region and inside the knees, which can cause dysmorphisms of these regions. In addition, vascular disorders can further promote the disappearance of β sensors. This results in an accumulation of fat on the inner side of the thighs, especially in a hyperoestrogenic woman with circulatory disorders.

The composition according to the invention makes it possible to fight against these overweight by restoring a cutaneous trophism and a normal microcirculation allowing the release of certain β-adrenergic receptors. The reestablishment of lipolysis and perinodular microcirculation is demonstrated by the increase in amplitude and the modification of plethysmographic traces.

Various known active ingredients can be associated with diosgenin in the compositions according to the invention, and in particular anti-inflammatories, anesthetics, veinotonics, or healing agents.

The diosgenin and / or the dioscorea extracts according to the present invention can be formulated according to the usual techniques and can be administered in the form of emulsions, gels, masks, lotions, solutions for spraying, transdermal patches, etc. The emulsions can be of the oil in water (O / W) or water in oil (W / O) type, for example gels or creams. It is also possible to use encapsulation techniques and in particular encapsulation in liposomes.

The emulsifier used for the composition of the invention is chosen according to the formulations and the conditions of administration. For example, the emulsifier can be chosen from high molecular weight carboxyvinyl polymers (for example Carbopol ^® ), polysorbates (for example Tween 20 ^® or Tween 60 ^® ), sorbitan esters and in particular a monostearate, a tristearate, a monopalmitate, and a sorbitan laurate (for example emulsifiers known under the brand name Arlacel ^® ). It is also possible to use other emulsifying agents such as various derivatives of stearic or palmitic acid, and for example the stearate of PEG 100® or PEG 20® or a C12-C20 ester of PEG 8 or PEG 9, glycerides stearic or palmitic acid, glycerol stearate, a polyethylene glycol stearate, a self-emulsifying propylene glycol stearate, a steareth or a ceteareth (for example ceteareth 20), or also polyglyceryl-2-sesquioleate, l polyoxyethylene cetyl ether, or an emulsifiable silicone. In addition to the various emulsifiers, the compositions can contain various usual adjuvants of the techniques used for the preparation of cosmetic and dermatological compositions, and for example preservatives, thickeners, hydrophilic or lipophilic gelling agents, antioxidants, hydrating agents, surfactants, complexing agents such as EDTA, perfumes, dyes, pigments, fillers and various additives intended to improve the physical properties of the composition. It may also be advantageous to incorporate into the composition of the invention, sun screens or filters active in UVA and / or UVB, chosen according to the degree of protection sought.

The diosgenin and the dioscorea extracts according to the present invention can be used for the manufacture of a dermatological medicament acting by action on the superficial musculo-fascial system, for the treatment of various skin conditions, as well as in a treatment method cosmetic of the skin consisting in applying to the area to be treated, an effective amount of diosgenin, alone or in combination with acceptable excipients and carriers. The following examples illustrate the invention in more detail without limiting its scope.

Example 1

Using the usual techniques of dermatological formulations, an anti-wrinkle cream based on pure diosgenin extracted from dioscorea opposita is prepared having the following composition, indicated in parts by weight: diosgenin 10.0

Cι ₂ _ ₂₀ PEG-8 ester 14.0 propylene glycol decaprylate dicaprate 5.0 saccharides isomerate 1.0 silk amino acids 1.0 hydrolysed glycosaminoglycans 1.0 preservative 0.5 perfume 0.5 water qs 100.0

This cream is used by application on the skin, twice a day. The anti-wrinkle effect is observed at the end of the second week of application on the areas of the face and the neck of patients with signs of skin aging consisting mainly of wrinkles.

Example 2

By proceeding as indicated in Example 1, an anti-wrinkle cream is prepared having the following composition by weight: diosgenin 12.0

Cι ₂ _ ₂₀ PEG-8 ester 14.0 glycolic acid 15.0 propylene glycol decaprylate dicaprate 5.0 ammonium hydroxide 3.0 saccharides isomerate 1.0 silk amino acids 1.0 preservative 0.5 perfume 0, 5 water qs 100.0 This anti-wrinkle cream is used like that of Example 1 above.

Example 3 By proceeding as indicated in Example 1, a lightening cream is prepared having the following composition by weight: diosgenin 5.0 kojic acid 1.0 phytic acid 1.0 sodium polyacrylate 1.0 cetearyl isononanoate 14.0 stearate glyceryl - PEG-20 7.0 preservative 0.2 perfume 0.5 water qs 100.0

This lightening cream is used by application to the skin, once or twice a day.

Claims

1. Composition useful in dermatology and in cosmetology for topical application, characterized in that it comprises diosgenin or a dioscorea extract at a concentration of pure diosgenin greater than or equal to 2% by weight relative to the total weight of the composition.

2. Composition according to claim 1, characterized in that the dioscorea extract is chosen from dioscorea opposita, dioscorea composita, dioscorea floriburida, dioscorea villosa, dioscorea hypoglauca, yam, and wild yam.

3. Composition according to any one of claims 1 and 2, characterized in that the content of pure diosgenin is between 5% and 20% by weight relative to the total weight of the composition.

4. Composition according to claim 1, characterized in that it further comprises an alpha-hydroxy acid or a salt or ester of alpha-hydroxy acid.

5. Composition according to claim 4, characterized in that the alpha-hydroxy acid is chosen from acids, lactic, glycolic, mandelic, citric, thiolactic, thioglycolic, or one of their salts or esters.

6. Composition according to claim 1, characterized in that it comprises an amino acid chosen from leucine, proline, thymidine, glucosamine, serine, arginine and lysine.

7. Composition according to any one of claims 5 and 6, characterized in that it comprises diosgenin in combination with glycolic acid and / or lysine.

8. Composition according to any one of the preceding claims, characterized in that it also comprises a mucopolysaccharide or a glycosaminoglycan.

9. Use of diosgenin or a dioscorea extract according to claim 1 for the manufacture of a dermatological drug acting by action on the superficial musculo-fascial system and on the cellular estrogen and progesterone receptors, for the treatment of skin conditions.

10. Use of diosgenin or a dioscorea extract according to claim 1 for the manufacture of a dermatological medicament for the treatment of burns, scarring and post-operative inflammation.

11. Use of diosgenin or a dioscorea extract according to claim 1 for the manufacture of a dermatological medicament for the treatment of venous insufficiency and localized adiposity.

12. A method of cosmetic treatment of the skin and keratin fibers consisting in applying to the area to be treated, an effective amount of diosgenin or of dioscorea extract according to claim 1.