US20050214383A1 - Multi-vitamin and mineral nutritional supplements - Google Patents

Multi-vitamin and mineral nutritional supplements Download PDF

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Publication number
US20050214383A1
US20050214383A1 US11/090,486 US9048605A US2005214383A1 US 20050214383 A1 US20050214383 A1 US 20050214383A1 US 9048605 A US9048605 A US 9048605A US 2005214383 A1 US2005214383 A1 US 2005214383A1
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pharmaceutically acceptable
dosed
compound
vitamin
mcg
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US11/090,486
Inventor
William Bubnis
Richard Cotter
Paul Herman
Judith Moreines
Scott Poxon
Bruce Sutton
Jeffrey Vernon
Denise Walters
Michael Williams
Neil Wittenberg
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Wyeth LLC
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Wyeth LLC
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=35064300&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20050214383(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Wyeth LLC filed Critical Wyeth LLC
Priority to US11/090,486 priority Critical patent/US20050214383A1/en
Assigned to WYETH reassignment WYETH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BUBNIS, WILLIAM, POXON, SCOTT W., SUTTON, BRUCE W., VERNON, JEFFREY V., WALTERS, DENISE L., WILLIAMS, MICHAEL G., COTTER, RICHARD, HERMAN, PAUL W., MOREINES, JUDITH, WITTENBERG, NEIL
Priority to US11/236,570 priority patent/US8968768B2/en
Publication of US20050214383A1 publication Critical patent/US20050214383A1/en
Assigned to WYETH reassignment WYETH RE-RECORD TO CORRECT UNDERLYING DOCUMENT PREVIOUSLY RECORDED UNDER REEL/FRAME NO. 016428/0967 Assignors: COTTER, RICHARD, HERMAN, PAUL W., MOREINES, JUDITH, WITTENBERG, NEIL, BUBNIS, WILLIAM, SUTTON, BRUCE W., VERNON, JEFFREY V., WALTERS, DENISE L., WILLIAMS, MICHAEL G., POXON, SCOTT W.
Priority to US13/023,671 priority patent/US20110223250A1/en
Assigned to WYETH LLC reassignment WYETH LLC CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: WYETH
Priority to US14/031,536 priority patent/US8927012B2/en
Abandoned legal-status Critical Current

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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
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    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
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    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
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    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • This invention relates to nutritional supplements.
  • features of the invention include the provision in multi-vitamin and/or mineral supplements of ingredients and micro-nutrients to facilitate reduction of cholesterol, and/or reduction of homocysteine, and/or reduction of low-density lipoprotein-cholesterol (LDL-C) oxidation in humans.
  • the invention relates to multi-vitamin and/or mineral supplements which include at least one component known to reduce cholesterol.
  • vitamins and minerals provide significant value to maintaining an individual in a healthy state and/or treating specific medical conditions even when supplied in relatively small amounts.
  • vitamins and minerals include A, C, D, E and the family of B vitamins and minerals include iron, zinc, calcium and chromium.
  • the human body does not synthesize most of these compounds which are essential to maintaining the health of the human body.
  • these necessary vitamins and minerals must be obtained from an external source.
  • the two most common external sources are foods and nutritional supplements. Food is typically the primary source of obtaining the necessary nutrients; however, the majority of people do not eat foods that consistently provide the necessary daily requirements of vitamins and minerals.
  • vitamin and mineral nutritional supplementation has become a recognized method of meeting accepted medical and health standards.
  • Some herbal/natural vitamin and/or mineral and/or nutritional compositions that contain phytosterols, compounds which are believed to facilitate cholesterol reduction, are commercially available.
  • the efficiency of these herbal/natural product compositions for reducing cholesterol is questionable as they typically contain 20 to 50 mg of phytosterol per dose. This is substantially below the amount that the FDA (Food and Drug Administration) recognizes as an efficacious dose of phytosterol for reducing cholesterol levels.
  • the FDA Food and Drug Administration
  • the FDA indicates that 800 mg/day is the lowest effective intake of the phytosterols to reduce risk of coronary heart disease.
  • the present invention provides a nutritional supplement which facilitates providing an adequate intake of vitamins, minerals and other micro-nutrients desirable for disease prevention, protection against nutritional losses and deficiencies due to inadequate dietary intake patterns and life style factors and provides micro-nutrients to facilitate reduction of cholesterol, and/or reduction of homocysteine, and/or reduction of LDL cholesterol in humans.
  • the invention also provides a method of preparing an efficacious dosage of the nutritional supplement in a practical dosage form and a method for reducing cholesterol levels and/or LDL cholesterol and/or homocystine in humans.
  • the invention provides a nutritional supplement for administration to humans comprising: an effective amount of at least one vitamin selected from the group consisting of Vitamin A; Vitamin C; Vitamin E, Vitamin B 6 , Vitamin B 2 , folate and Vitamin B 12 and an effective amount of at least one cholesterol reducing agent selected from the group consisting of phytosterols, phytostanols, policosanols, and statins.
  • the invention provides a nutritional supplement for administration to humans comprising: an effective amount of at least one mineral selected from the group consisting of selenium, chromium and zinc, and an effective amount of at least one cholesterol reducing agent selected from the group consisting of phytosterols, phytostanols, policosanols, and statins.
  • the invention provides a multi-vitamin and mineral nutritional supplement for administration to humans comprising at least one cholesterol reducing agent from the group consisting of phytosterols, phytostanols, policosanols and statins in an amount effective to reduce cholesterol and an effective of amount of vitamins A, B 2 , B 6 B 12 folate (folic acid), and E.
  • the composition may further comprise at least one of an effective amount of lycopene and an effective amount of selenium.
  • the invention provides a multi-vitamin and mineral nutritional supplement for administration to humans comprising pharmaceutically acceptable forms of the following: at least about 800 mg of phytosterols; at least about 3500 I.U. of vitamin A and/or vitamin A precursors; at least about 60 mg of vitamin C; at least about 400 I.U. of vitamin D; at least about 30 I.U.
  • vitamin E at least about 25 mcg of vitamin K; about 1.5 mg of thiamin; at least about 1.7 mg of vitamin B 2 (riboflavin); at least about 20 mg of niacin; at least about 5 mg of vitamin B 6 ; at least about 800 mcg of folic acid; at least about 200 mcg of vitamin B 12 ; at least about 30 mcg of biotin; at least about 10 mg of pantothenic acid; at least about 6 mg of iron; about 150 mcg of iodine; at least about 210 mg of magnesium; at least about 7.5 mg of zinc; at least about 20 mcg of selenium; at least about 0.7mg of copper; at least about 2 mg of manganese; at least about 108 mg calcium; at least about 80 mg of phosphorus; at least about 75 mcg of molybdenum; at least about 320 mcg boron; at least about 5 mcg nickel; at least about 2 mg silicon; at least about
  • Another embodiment of the invention provides a multi-vitamin and mineral nutritional supplement for administration to humans comprising pharmaceutically acceptable forms of the following: at least one ingredient to facilitate reduction of cholesterol, at least one ingredient to facilitate reduction of homocysteine or facilitate reduction of low-density lipoprotein-cholesterol (LDL-C) and about 1300 I.U. to about 10,000 I.U. of vitamin A and/or vitamin A precursors; about 200 I.U. to 2000 I.U.
  • LDL-C low-density lipoprotein-cholesterol
  • vitamin D about 0 mcg to about 50 mcg of vitamin K; about 1.2 mg to about 4.5 mg of thiamin; about 5 mg to about 40 mg of niacin; about 0 mg to about 550 mg of choline; about 0 mcg to about 1400 mcg of folic acid; about 0 mcg to about 300 mcg of biotin; about 0 mg to about 16 mg of pantothenic acid; about 0 mg to about 18 mg of iron; about 0 mcg to about 300 mcg of iodine; about 0 mg to about 100 mg of magnesium; about 3 mg to about 15 mg of zinc; about 0 mg to about 2 mg of copper; about 0 mg to about 6 mg of manganese; about 0 to about 200 mg calcium; about 0 mg to about 750 mg of phosphorus; about 0 mcg to about 250 mcg of molybdenum; about 0 mcg to about 150 mcg
  • Ingredients to facilitate reduction of cholesterol may comprise one or more of the following ingredients in an amount effective to reduce cholesterol: phytosterols, phytostanols, or their equivalents, in free or esterified form, policosanol and statins.
  • Suitable statins include, for example, atorvastatin, provastatin, simvastatin, lovastatin or flavastatin.
  • Amounts of policosanol of up to about 200 mg may be used in the multi-vitamins and mineral nutritional supplements.
  • Statins may be used in amounts of up to 80 mg and typically are used in amounts of about 40 mg to about 80 mg. More particularly with regard to statins, provastatin and simvastatin are preferably used in amounts of about 40 mg, and atorvastatin, lovastatin and fluvastatin are typically used in amounts of about 80 mg.
  • Ingredients to facilitate reduction of homocystine may comprise one or more of the following: up to about 40 mg of vitamin B 2 (riboflavin); up to about 10 mg of vitamin B 6 ; up to about 1 mg of folate, and up to about 2 mg of vitamin B 12 .
  • Ingredients to facilitate reduction of homocysteine may more preferably comprise one or more of the following: about 1.3 mg to about 5.1 mg of vitamin B 2 (riboflavin); up to about 1400 about 800 mcg folate; about 1 mg to about 6 mg of vitamin B 6 ; and about 2.4 mcg to about 200 mcg of vitamin B 12 .
  • LDL-C low-density lipoprotein-cholesterol cholesterol
  • Ingredients to facilitate reduction of low-density lipoprotein-cholesterol cholesterol (LDL-C) oxidation may comprise one or more of the following: up to about 2 grams of vitamin C; up to about 800 I.U. of vitamin E; up to about 6 grams of lycopene; and up to about 350 mcg of selenium.
  • Ingredients to facilitate reduction of low-density lipoprotein-cholesterol cholesterol (LDL-C) oxidation may more preferably comprise one or more of the following: about 45 mg to about 250 mg of vitamin C; about 20 I.U. to about 200 I.U. of vitamin E; about 0 mcg to about 3 g of lycopene; and about 0 mcg to about 75 mcg of selenium.
  • composition described herein may further include a diluent such as, for example a calcium compound, magnesium compound, microcrystaline cellulose, starch or a combination thereof.
  • a diluent such as, for example a calcium compound, magnesium compound, microcrystaline cellulose, starch or a combination thereof.
  • composition described herein may also include an absorbent such as silicon dioxide, for example.
  • an absorbent such as silicon dioxide, for example.
  • the silicon dioxide may be precipitated, fumed or a mixture thereof.
  • the invention further provides a method of reducing cholesterol levels, reducing homocysteine, and decreasing low-density lipoprotein-cholesterol (LDL-C) oxidation in humans by administering the composition of the invention to a human.
  • LDL-C low-density lipoprotein-cholesterol
  • the invention further includes a method of tableting nutritional supplements comprising at least one phytosterol, the method comprising: providing at least one phytosterol and at least one diluent; granulating the phytosterol and the at least one diluent under high shear granulation conditions to form a granulation; milling the granulation; and adding an absorbent to the granulation.
  • the method may further comprise drying the granulation and the absorbent is preferably added after drying.
  • a fluid bed dryer is exemplary of a suitable dryer for drying the granulation.
  • the method may comprise compressing the granulation to form a tablet.
  • the tableting may be coated with a film coat comprising polyvinyl alcohol (PVA), for example.
  • PVA polyvinyl alcohol
  • a daily efficacious amount of nutritional supplement comprises two tablets, each of the two tablets having a volume less than 2 cubic centimeters.
  • a daily efficacious amount of the nutritional supplement comprises four tablets or fewer. Each tablet having a volume less than 1.5 cubic centimeters.
  • the tablets may have an oblong, oval, modified oval, or capsule shape.
  • a daily efficacious amount of the nutritional supplement may comprise one or more capsules, one or more chewable delivery unit, a powder, or a sachet.
  • FIG. 1 is an end view of an exemplary embodiment of a tablet of the composition of the invention.
  • FIG. 2 is a top view of an exemplary embodiment of a tablet of the composition of the invention.
  • FIG. 3 is a side view of an exemplary embodiment of a table of the composition of the invention.
  • FIG. 4 is a graph showing tablet disintegration data for tablets of two exemplary embodiments of the composition of the invention in water.
  • FIG. 5 is a graph showing tablet disintegration data for tablets of two exemplary embodiments of the invention in acid.
  • the invention provides a nutritional supplement which in one embodiment is a multi-vitamin and mineral nutritional supplement for administration to humans, having at least one ingredient to facilitate reduction of cholesterol.
  • the cholesterol reducing ingredient may include phytosterols and/or stanols, and/or statins, and/or policosanol.
  • the nutritional supplement further includes at least one ingredient for reduction of homocysteine and/or reduction of low-density lipoprotein-cholesterol (LDL-C).
  • the multi-vitamin and mineral nutritional supplement may comprise one or more of: vitamin A and/or vitamin A precursors; vitamin C; vitamin D; vitamin E; vitamin K; thiamin; vitamin B 2 (riboflavin); niacin; vitamin B 6 ; folic acid; vitamin B 12 ; biotin; pantothenic acid; iron; iodine; magnesium; zinc; selenium; copper; manganese; calcium; phosphorus; molybdenum; boron; nickel; silicon; tin; vanadium; chromium; potassium; chloride; choline; lycopene; and lutein.
  • the composition of the invention When administered to a human on a regular basis (for example, daily), the composition of the invention facilitates adequate intake of vitamins and minerals and provision of other micro-nutrients to promote good health including micro-nutrients which facilitate the lowering of cholesterol levels, and/or reduction of homocysteine, and/or decrease of low-density lipoprotein-cholesterol (LDL-C) oxidation in humans.
  • the nutritional supplement may include one or more vitamins in combination with at least one cholesterol lowering ingredient, or at least one mineral in combination with at least one cholesterol-lowering ingredient.
  • the terms “nutritional supplement” or “supplement” should be taken to refer to any or all of the embodiments (e.g.
  • a multi-vitamin and mineral supplement with at least one cholesterol lowering agent a composition comprising at least one vitamin and at least one cholesterol lowering agent, or a composition comprising at least one mineral and at least one cholesterol lowering agent).
  • the nutritional supplement may in some embodiments further comprise other actives such as for example, homocystine lowering actives or one or more other actives that provide a nutritional and/or health benefit.
  • a preferred embodiment of the invention is a multi-vitamin and mineral supplement with at least one cholesterol lowering agent, as such supplement provides a simple method for addressing nutritional deficiencies and promotes compliance in usage by an individual in need of nutritional supplementation.
  • the invention further provides a method for preparing solid dosages forms comprising nutritional supplement components in efficacious amounts in a unit or units compatible with convenient human consumption.
  • nutritional supplement components in efficacious amounts in a unit or units compatible with convenient human consumption.
  • a daily efficacious amount of at least one vitamin and/or mineral supplement and at least one cholesterol reducing ingredient is contained in 2-4 tablets of a size that an adult human can practically swallow.
  • the number and amount of vitamin and mineral components needed to provide a efficacious daily dosage to generally supplement nutritional deficiencies constitutes a substantial tablet volume. Provision of an additional component(s) in the supplement to facilitate the reduction of cholesterol further increases the volume of material to be included in a dosage form.
  • Preparing a solid dosage form containing efficacious amounts of a significant number of vitamins and minerals and phytosterol in a practical dosage unit, for example, is particularly challenging in that a minimum of 800 mg of phytosterol per day is needed to meet the FDA standard for efficacy and phytosterol is a waxy material with a low bulk density.
  • the inventors have addressed these problems by developing a preparation method (e.g. manufacturing process) that employs granulation techniques and/or the use of diluent and/or the use of absorbent excipients to prepare a tableted dosage form comprising efficacious daily amounts of the components of the nutritional supplement in preferably 2-4 tablets of a tablet size suitable to be swallowed by a human.
  • cholesterol lowering agent or “cholesterol reducing agent” means any compound, combination of compounds, including any extract or plant component, naturally found or processed, or synthetic compound that has the property of lowering cholesterol levels when administered in an effective amount. 361 All amounts specified herein are based on milligrams unless otherwise indicated.
  • the term “I.U.” represents International Units.
  • the term “mcg” means micrograms, “mg ” means milligrams, and “g” means grams. Further, it should be understood that the amounts of components disclosed herein are for a daily dosage and that a daily dosage may comprise one dosage unit or a plurality of dosage units.
  • “An efficacious dosage” of a nutrient is at least the minimum amount of the nutrient needed on a daily basis recognized by the United States Food and Drug Administration (FDA) for providing a health or nutritional benefit.
  • FDA United States Food and Drug Administration
  • the FDA recommends that daily dosages of multivitamin and mineral supplements be divided and administered in two dosage units taken at spaced intervals during the day. Typically, with meals or food, for example such as twice daily with meals. Accordingly amounts are given for daily dosages but it should be understood that the daily dosage may be in multiple dosage units and consumption of these units may occur at the same time or different times during the day.
  • phytosterols and stanols derived from plant sources are termed phytosterols and phytostanols.
  • Phytosterols and phytostanols are natural compounds that can be consumed regularly as a part of a healthy diet. Accordingly, while plant derived materials are the preferred source of these compounds, equivalent synthesized stanols and sterols, or stanols and sterols from other sources, may be used in the practice of the invention. Any reference to use of phytosterol or phytostanols herein should be taken to apply to equivalent sterols or stanols from alternative sources. It should be understood in terms of discussing amounts of the composition that sterols or phytosterols may be used in like amounts or vice-versa. It should be understood in terms of discussing amounts of the composition, that stanols or phytostanols may be used in like amount or vice-versa.
  • phytosterols there are multiple specific chemical entities classed as phytosterols, including but not limited to beta-sitosterol, campesterol, and stigmasterol, for example.
  • a single specific chemical species of phytosterol or mixtures comprised of a plurality of specific chemical species of phytosterols may be employed.
  • a mixture of phytosterols having beta-sitosterol, campesterol and sigmasterol as principle components is exemplary of a mixture suitable for use in the practice of the invention.
  • Commercial preparations of mixed phytosterols are available from suppliers such as Cargill and ADM (Archer Daniels Midland), for example.
  • the class phytostanols includes multiple specific chemical species of phytostanols and a single specific chemical species of phytostanol or a mixture of a plurality of specific chemical species of phytostanols may be used in the practice of the invention. Accordingly, reference to phytosterols or phytostanols in compositions discussed herein should be taken to include both single specific chemical species forms as well as mixtures.
  • phytosterols and stanols compete with the cholesterol to decrease cholesterol absorption and reabsorption in the small intestine because they are structurally similar to cholesterol.
  • the more sterol, such as phytosterol, in free form that is present in the intestine following a meal the less cholesterol absorption and reabsorption will occur.
  • consumed phytosterols, phytostanols, and their equivalents are not absorbed to any appreciable extent. Hence, phytosterols are believed to inhibit the uptake of cholesterol by the body and are flushed through the system without absorption.
  • the multi-vitamin and mineral nutritional supplement comprises up to about 3 g of the free form or the esterified form of phytosterols and more preferably at least about 800 mg of phytosterols. Most preferably, the supplement comprises about 800 mg of phytosterols in the free form.
  • the phytosterol may be replaced with phytostanols or a combination of phytosterols and phytostanols may be used.
  • Policosanol is the generic term used for a mixture of long-chain primary aliphatic saturated alcohols that may reduce total serum cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Policosanol is also known as polycosanol, policosanal, policosinal, policosinol, polycosanal, polycosinal and polycosinol. These alcohols are derived from the waxes of such plants as sugar cane ( Saccharum officinarium ) and yams (e.g. Dioscorea opposita ). They are also found in beeswax.
  • the main long-chain alcohol in policosanol is the 28 carbon 1-octanosol, and next most abundant is the 30 carbon 1-triacontanol.
  • Other long-chain alcohols present in much lower concentrations comprise: 1-docosanol (C 22 ), 1-tetracosanol (C 24 ), 1-hexacosanol (C 26 ), 1-heptacosanol (C 27 ), 1-nonacosanol (C 29 ), 1-dotriacontanol (C 32 ) and 1-tetracontanol (C 34 ).
  • These long-chain alcohols are solid waxy substances and are insoluble in water. They are known collectively as aliphatic alcohols.
  • Policosanol may impair cholesterol synthesis between the acetate and mevalonate production steps and/or increase receptor-dependent LDL-C processing. (see “Policosanol: Clinical Pharmacology and Therapeutic Significance of a New Lipid-Lowering Agent.” Am.Heart J. 2002 February; 143(2): 356-65). Others have suggested Policosanol also may reduce lipid peroxidation (see “Effect of Policosanol on In Vitro and In Vivo Rat Liver Microsomal Lipid Peroxidation.” Arch.Med.Res. 1997 Autumn; 28(3): 355-60).
  • policosanol is included in the multivitamin and mineral nutritional supplement.
  • the multi-vitamin and mineral nutritional supplement embodiment including polycosanol comprises up to about 200 mg of policosanol and more preferably about 10 to about 20 mg of policosanol.
  • Statins including atorvastatin, pravastatin, simvastatin, lovastatin, and fluvastatin, are believed to be competitive 3-hydroxy-3 methyl glutaryl CoA, hereinafter referred to as HMGCoA reductase inhibitors. Accordingly, they are believed to be effective in the reduction of cholesterol, and are believed to be effective in preventing not only recurrent heart attacks, but also first heart attacks. In some cases statins may also reduce the risk of strokes. In one embodiment statins may be included in the multi-vitamin and mineral nutritional supplement.
  • the nutritional supplement embodiment including statins may comprise up to about 80 mg of a statin or mixture of statins and more preferably it comprises about 5 to about 80 mg of a statin or mixture of statins.
  • Provastatin and simvastatin are preferably used in amounts of about 40 mg, and atorvastatin, lovastatin and fluvastatin are preferably used in amounts of about 80 mg.
  • this invention provides for a convenient, practical and relatively inexpensive way to facilitate reducing cholesterol levels, and/or reducing homocysteine levels, and/or decreasing LDL-C oxidation in humans.
  • Vitamin C also known as ascorbic acid, is believed to be necessary for the synthesis of collagen and is used as an antioxidant. It is believed that Vitamin C fights infection, reduces inflammation, heals wounds, reduces the risk of heart disease by reduction of LDL-C oxidation, lowers cholesterol, reduces the risk of lung, stomach and esophageal cancers, reduces cervical epithelial abnormalities, inhibits N-nitrosamine, and reduces the severity of colds.
  • the nutritional supplement may comprise up to about 2000 mg of Vitamin C, more preferably about 45 mg to about 250 mg, and most preferably about 60 mg of Vitamin C.
  • Vitamin E is needed for the maintenance of cell membranes and for neurological health. Vitamin E relieves hot flashes, relieves mastodynia, helps in fighting fibrocystic breast disease, reduces mammary tumors, reduces the risk of lung cancer, and reduces the risk of heart disease by reduction of LDL-C cholesterol oxidation. Vitamin E is the generic term for a group of related substances, which include alpha-tocopherol, beta-tocopherol, gamma-tocopherol, and delta-tocopherol. In addition, each of these four compounds has a “d” form, which is the natural form, and a “dl” form, which is the synthetic form. All forms of all substances covered by Vitamin E are included herein.
  • the nutritional supplement may comprise up to about 1500 I.U. of Vitamin E, and more preferably about 15 I.U. to about 800 I.U. Most preferably, the multi-vitamin and mineral nutritional supplement may comprise about 20 I.U. to 200 I.U. of Vitamin E.
  • the nutritional supplement may comprise one or more of B complex vitamins.
  • the B vitamins included in the nutritional supplement may include thiamin (Vitamin B 1 ), riboflavin (Vitamin B 2 ), niacin (Vitamin B 3 ) pantothenic acid (Vitamin B 5 ), pyridoxine (Vitamin B 6 ), biotin, folic acid, and the cobalamins (Vitamin B 12 ) or a combination thereof.
  • the B vitamins are water-soluble. Of these vitamins, B 2 , B 6 , and Vitamin B 12 (e.g. or the cobalamins), are known to reduce homocysteine levels. However, because of the beneficial nature of the B vitamins in general, all of them are contemplated for use in one embodiment of the invention.
  • Vitamin B, or thiamin helps keep collagen-rich connective and mucous membranes healthy, helps to maintain smooth muscles, helps in the formation of blood cells, and is necessary for proper nervous system function.
  • the nutritional supplement may comprise about 0.9 mg to about 100 mg of, more preferably about 1.2 mg to about 4.5 mg and most preferably about 1.5 mg of thiamin.
  • Vitamin B 2 or riboflavin is necessary for healthy hair, nails and mucous membranes and is involved in red blood cell formation, homocysteine reduction, antibody production and overall growth.
  • the nutritional supplement of the invention may comprise up to about 40 mg of riboflavin, more preferably about 0.9 mg to about 5.1 mg and most preferably about 1.3 to 1.7 mg of riboflavin.
  • Vitamin B 3 or niacin helps in the production of most of the sex hormones, dilates blood vessels and helps maintain blood circulation.
  • Niacin is the generic name for a group of compounds, which exhibit niacin activity and includes niacinamide and nicotinic acid.
  • the nutritional supplement may comprise about 5 mg to about 500 mg of niacin, more preferably about 5 mg to about 40 mg and most preferably about 20 mg of niacin as niacinamide.
  • Vitamin B 6 or pyridoxine is involved in the production of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), homocysteine reduction, and many other reactions in the body.
  • Pyridoxine refers to and includes three different compounds: pyridoxine, pyridoxamine, and pyridoxal.
  • the nutritional supplement may comprise about 1 mg to about 10 mg of Vitamin B 6 , more preferably about 1 mg to about 6 mg, and most preferably about 5 mg of Vitamin B 6 .
  • Folic acid is used in the production of red blood cells, the production of hormones, and the synthesis of DNA.
  • the nutritional supplement may comprise up to about 1000 mcg of folic acid, more preferably about 0 mcg to about 800 mcg folate (folic acid), and most preferably, about 800 mcg of folic acid.
  • Vitamin B 12 (e.g. the cobalamins) is necessary for overall metabolism, the function of the nervous system, metabolism of folic acid, homocysteine reduction, and the production of red blood cells.
  • cobalamins There are at least three active forms of cobalamin: cyanocobalamin, hydroxocobalamin, and nitrocobalamin.
  • the nutritional supplement may comprise up to about 2000 mcg of Vitamin B 12 , more preferably about 2.4 mcg to about 200 mcg, and most preferably, about 200 mcg of Vitamin B 12 .
  • Biotin is necessary for the metabolism of carbohydrates, proteins, and fats and is needed for healthy skin and hair.
  • the nutritional supplement may comprise up to about 900 mcg of biotin and more preferably about 0 mcg to about 300 mcg, and most preferably, about 30 mcg of biotin.
  • Pantothenic acid also known as Vitamin B 5
  • the nutritional supplement may comprise up to about 200 mg of pantothenic acid, more preferably about 0 mg to about 10 mg, and most preferably, about 10 mg of pantothenic acid.
  • Vitamin A is also contemplated for use in the multi-vitamin and mineral nutritional supplement of the invention.
  • Vitamin A prevents night blindness and other eye disorders, keeps skin moist and elastic, maintains healthy hair, skin, and gums, reduces the risk of breast cancer, helps alleviate mastodynia, reduces the risk of lung cancer, maintains cell structure and integrity, works as an antioxidant to prevent cell aging, helps prevent infection, and negates skin wrinkling and the effects of sun damage.
  • Vitamin A is a fat-soluble vitamin.
  • Vitamin A is used to include retinol and other chemically similar compounds referred to as retinoids.
  • Vitamin A may be provided as a form of Vitamin A, as Vitamin A precursor carotenoids, such as betacarotene, or as a mixture thereof.
  • carotenoids such as betacarotene
  • the nutritional supplement of the invention may comprise up to about 10,000 I.U. of Vitamin A including Vitamin A precursors, more preferably about 1300 I.U. to about 5000 I.U. and most preferably, about 3500 I.U. of Vitamin A in the form of Vitamin A or Vitamin A and the Vitamin A precursor beta-carotene.
  • Beta-carotene and other carotenoids are provitamins, i.e., vitamin precursors, and are converted to vitamins or vitamin-like substances, as the body requires.
  • the carotenoids include lutein, zeaxanthin and lycopene, amounts of these components are specified specifically herein and any amounts of Vitamin A precursors recited herein should not be interpreted to include any appreciable amount of lutein, zeaxanthin or lycopene.
  • Vitamin D is also an essential mineral which assists in the mineralization and calcification of bone, prevents rickets in children, prevents osteomalacia in adults, preserves bone and tooth growth, and lowers blood pressure.
  • Vitamin D is fat-soluble and cholecalciferol or D 3 is the preferred form.
  • the nutritional supplement may comprise up to about 2000 I.U. of Vitamin D and more preferably about 200 to about 400 I.U. of Vitamin D.
  • Vitamin K is an active blood clotting agent and assists in bone formation. It also may help in removing calcium from atherosclerotic plaques. Phylloquinone or K1 and menoquinone, or K2 are the preferred forms.
  • the nutritional supplement may comprise up to about 1 mg of vitamin K, more preferably about 0 mcg to about 90 mcg of vitamin K and most preferably about 25 mcg vitamin K.
  • Choline is necessary for nervous system function and brain function. It is also important for gall bladder and liver function. Choline helps maintain the structural integrity of membranes surrounding every cell in the body but also can play a role in nerve signaling, cholesterol transport, and energy metabolism.
  • choline may be provided in the form of a pharmaceutically acceptable choline salt, such as, for example, bitartarate.
  • the nutritional supplement may optionally comprise of up to about 3500 mg choline, and more preferably, of about 50 mg to about 550 mg of choline in the form of choline bitartarate.
  • Iron is used in the production of hemoglobin and myoglobin.
  • the iron is dosed in the form of a pharmaceutically acceptable iron compound.
  • pharmaceutically acceptable is a component which is suitable for use in humans without undue side effects, such as irritation, toxicity, and allergic response.
  • Useful pharmaceutically acceptable iron compounds include, but are not limited to, ferrous fumarate, ferrous sulfate, carbonyl iron, ferrous gluconate, ferrous chloride, ferrous lactate, ferrous tartrate, ferrous succinate, ferrous glutamate, ferrous citrate, ferrous pyrophosphate, ferrous cholinisocitrate, ferrous carbonate, iron-sugar-carboxylate complexes, and combinations thereof.
  • the nutritional supplement may comprise up to about 18 mg of iron dosed in a pharmaceutically acceptable iron compound and more preferably, about 5 mg to about 18 mg of iron.
  • Iodine helps to metabolize fats, is necessary for proper thyroid function, and reduces fibrocystic breast conditions.
  • iodine is dosed in the form of a pharmaceutically acceptable iodine compound.
  • useful pharmaceutically acceptable iodine compounds include, but are not limited to, potassium iodide, sodium iodide and combinations thereof.
  • the nutritional supplement may comprise up to about 1100 mcg of iodine dosed in the form of a pharmaceutically acceptable iodine compound, more preferably up to about 150 mcg, and—most preferably, about 150 mcg of iodine.
  • Magnesium is used in bone formation and growth, prevents bone loss, relaxes coronary arteries, is used in managing pre-eclampsia, treating cardiac arrhythmias, and managing diabetes.
  • magnesium is dosed in the form of a pharmaceutically acceptable magnesium compound.
  • Useful pharmaceutically acceptable magnesium compounds include, but are not limited to, magnesium stearate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium sulfate, and combinations thereof.
  • the nutritional supplement may comprise up to about 400 mg of magnesium dosed in the form of a pharmaceutically acceptable magnesium compound, more preferably up to about 350 mg, and most preferably, about 100 mg of magnesium.
  • Zinc is required for proper formation of DNA and RNA and is needed for growth, immunity and sexual development of women.
  • zinc is dosed in the form of a pharmaceutically acceptable zinc compound.
  • Pharmaceutically acceptable zinc compounds include, but are not limited to, zinc sulfate, zinc chloride, zinc oxide, and combinations thereof.
  • the nutritional supplement may comprise about 3 mg to about 40 mg of zinc dosed in the form of a pharmaceutically acceptable zinc compound, more preferably about 3 mg to about 15 mg and most preferably, about 15 mg of zinc.
  • Selenium reduces the risk of heart attacks and heart disease, reduces the risk of cancer, protects against metal poisoning, and is believed to be synergistic with Vitamin E in reducing LDL cholesterol oxidation.
  • Pharmaceutically acceptable selenium compounds include but are not limited to sodium selenate, selenocysteine, selenomethionine or other amino acid chelates, and combinations thereof.
  • the nutritional supplement may comprise up to about 400 mcg of selenium more preferably up to about 75 mcg and most preferably about 15 mcg to about 75 mcg of selenium dosed in a pharmaceutically acceptable form.
  • Copper helps keep blood vessels elastic, is needed for the formation of elastin and collagen, functions as an iron oxidizer, and is needed for the proper functioning of Vitamin C.
  • copper is dosed in a pharmaceutically acceptable copper compound.
  • Pharmaceutically acceptable copper compounds include, but are not limited to, cupric oxide, cupric citrate, cupric sulfate, cupric carbonate, cupric gluconate, and combinations thereof.
  • the nutritional supplement may comprise up to about 10 mg of copper dosed in the form of a pharmaceutically acceptable copper compound, and more preferably, about 1.0 mg of copper dosed in the form of cupric gluconate, sulfate or citrate.
  • Calcium is needed by the body to build and maintain strong bones and teeth, facilitate neural transmission, and regulate muscle contraction and heartbeat. Calcium is lost through shed skin, nails, hair sweat, urine and feces. If intake is not sufficient, the body may remove calcium from bone to obtain the mineral which may adversely affect the bone density and render bones more susceptible to injury.
  • Pharmaceutically acceptable calcium compounds include, but are not limited to, calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium gluconate, calcium lactate, calcium citrate, and combinations thereof.
  • the nutritional supplement may comprise up to about 1500 mg calcium, more preferably up to about 200 mg and most preferably about 100 mg to about 162 mg of calcium dosed in a pharmaceutically acceptable form.
  • a low level of manganese in the body may be associated with diabetes. Accordingly manganese appears to have a role in the control of blood sugar levels. Manganese may also have a role in the metabolism of amino acids and certain vitamins.
  • Pharmaceutically acceptable manganese compounds include, but are not limited to, manganese chloride, manganese sulfate, and combinations thereof.
  • the nutritional supplement may comprise up to about 12 mg manganese dosed in a pharmaceutically acceptable form more preferably the nutritional supplement may comprise about 0 mg to about 4 mg manganese and most preferably about 1 mg manganese.
  • Silicon is believed to be used for the building of collagen for bones and connective tissue.
  • Pharmaceutically acceptable silicone compounds include, but are not limited to, sodium silicate, sodium silicoaluminate, silicon dioxide, and combinations thereof.
  • the nutritional supplement may comprise about 0 mg to about 500 mg silicon dosed in a pharmaceutically acceptable form, more preferably about 0 mg to about 60 mg silicon, and most preferably about 2 mg silicon.
  • Molybdenum may facilitate proper metabolism of fats, carbohydrate and iron and may protect against certain cancers.
  • Pharmaceutically acceptable molybdenum compounds include, but are not limited to, sodium molybdate, molybdenum amino acid chelates, and combinations thereof.
  • the nutritional supplement may comprise up to about 2000 mcg molybdenum dosed in a pharmaceutically acceptable form. More preferably the nutritional supplement may comprise about 0 mcg to about 75 mcg, and most preferably the nutritional supplement comprises about 75 mcg molybdenum.
  • Vanadium is believed to have a role in the regulation of sugar levels in the blood.
  • Pharmaceutically acceptable vanadium compounds include, but are not limited to, ammonium vanadium tartrate, sodium metavanadate, vanadyl sulfate, and combinations thereof.
  • the nutritional supplement may comprise up to about 1.8 mg vanadium in a pharmaceutically acceptable form, more preferably about 6 mcg to about 18 mcg vanadium and most preferably about 10 mcg vanadium.
  • Boron may have a role in mineral metabolism.
  • Pharmaceutically acceptable boron compounds include, but are not limited to, sodium borate, boron citrate, boron amino acid chelates, and combinations thereof.
  • the nutritional supplement may comprise up to about 20 mg of boron dosed in a pharmaceutically acceptable form, more preferably about 0 mcg to about 1.35 mg boron, and most preferably about 150 mcg to about 350 mcg boron.
  • Nickel may activate or inhibit the action of some enzymes or hormones.
  • Pharmaceutically acceptable nickel compounds include, but are not limited to, nickel sulphate.
  • the nutritional supplement may comprise up to about 1.0 mg nickel dosed in a pharmaceutically acceptable form, more preferably about 0 mcg to about 100 mcg nickel and most preferably about 5 mcg nickel.
  • Tin is known to be found in the human body. In rats a tin deficiency may depress growth.
  • Pharmaceutically acceptable tin compounds include, but are not limited to. stannous chloride.
  • the nutritional supplement may comprise up to about 200 mcg tin dosed in a pharmaceutically acceptable form, more preferably about 0 mcg to about 10 mcg tin and most preferably about 10 mcg tin.
  • Phosphorus is needed for bone development and is a constituent in all major classes of biochemical compounds. Phosphorous, in the form of phosphate in adenosine triphosphate is a key energy source required for most metabolic processes.
  • Pharmaceutically acceptable phosphorus compounds include, but are not limited to, forms of calcium phosphate, sodium phosphate, potassium phosphate, ammonium phophate, glycerol phosphate, and combinations thereof.
  • the nutritional supplement may comprise up to about 1250 mg of phosphorus, more preferably about 0 mg to 750 mg, most preferably about 109 mg of phosphorous, dosed in a pharmaceutically acceptable form.
  • Chromium assists in the regulation of glucose metabolism, is used in the synthesis of fatty acids and cholesterol, assists in transporting proteins, lowers LDL blood levels, and raises high density lipoproteins blood levels.
  • chromium is dosed in a pharmaceutically acceptable chromium compound.
  • Useful pharmaceutically acceptable chromium compounds include, but are not limited to, chromium chloride, yeast-bound chromium, picolinate, niacin-bound chromium, and combinations thereof.
  • the nutritional supplement may comprise up to about 10 mg of chromium dosed in a pharmaceutically acceptable form, more preferably about 0 mcg to about 150 mcg chromium, and most preferably about 120 mcg of chromium.
  • Potassium is needed to regulate water balance, levels of acidity, blood pressure and neuromuscular function. Potassium is also required for carbohydrate and protein metabolism.
  • potassium is dosed in the form of a pharmaceutically acceptable potassium compound.
  • Useful pharmaceutically acceptable potassium compounds include, but are not limited to, potassium chloride, potassium sulfate; potassium glycerophosphate, potassium citrate, potassium gluconate, potassium phosphate, and combinations thereof.
  • the nutritional supplement may comprise up to about 3900 mg of potassium dosed in a pharmaceutically acceptable form of potassium compound, more preferably about 0 mg to about 80 mg potassium, and most preferably about 50 mg to about 80 mg of potassium.
  • Lycopene has been found to reduce the risk of cancer and it has also been found to decrease LDL cholesterol oxidation via its antioxidant capabilities. Lycopene is found primarily in tomatoes, red grapefruit, watermelon, and other sources, and is a carotenoid.
  • the nutritional supplement may comprise up to about 6 g lycopene, more preferably about 0 mcg to about 3 g lycopene and most preferably about 300 mcg lycopene.
  • Lutein and zeaxanthin are carotenoid antioxidants that help to maintain healthy eyesight, and have been found to reduce the risk of cancer and heart disease. Lutein has been found to decrease the risk and prevent the progression of macular degeneration, the leading cause of blindness in those over the age of 65. Lutein and zeaxanthin are primarily found in yellow corn, egg yolk, spinach, broccoli and other green leafy vegetables.
  • the nutritional supplement may comprise up to about 6 g lutein in a pharmaceutically acceptable form, more preferably about 0 mcg to about 3 g lutein and most preferably about 250 mcg lutein.
  • the nutritional supplement may comprise up to about 6 g zeaxanthin in a pharmaceutically acceptable form, more preferably about 0 mcg to about 3 g zeaxanthin and most preferably about 300 mcg zeaxanthin.
  • the nutritional supplement comprises up to about 6 g of Omega-3 fatty acids, more preferably about 0 g to about 3 g and most preferably about 1 g of Omega-3 fatty acids.
  • Chloride is needed to help maintain the ionic and fluid balance in the body, and is an essential component of gastric and intestinal secretions.
  • Useful pharmaceutically acceptable chloride compounds include, but are not limited to, sodium chloride, chromium chloride, stannous chloride and potassium chloride.
  • the multi-vitamin and mineral nutritional supplement preferably comprises up to about 100 mg chloride, more preferably about 0 mg to about 80 mg and most preferably about 50 mg to about 75 mg chloride.
  • the multi-vitamin and mineral nutritional supplement of the invention is intended for oral administration and may be provided in a solid form.
  • the multi-vitamin and mineral nutritional supplement may further comprise excipients and processing aides such as: absorbents, diluents, flavorants, colorants, stabilizers, fillers, binders, disintegrants, lubricants, wetting agents, glidants, antiadherents, sugar or film coating agents, preservatives, buffer, artificial sweeteners, natural sweeteners, dispersants, thickeners, solubilizing agents and the like or some combination thereof.
  • the dosage forms of the present invention are typically considered to be solid. However, they may contain liquid or semi-solid components. Suitable “solid dosage forms of the present invention includes, but are not limited to, tablets, caplets, capsules including soft gel capsules, chewable dosage forms of and sachets and the like.
  • the daily dosage may be included in a single delivery unit or may comprise multiple delivery units. Dividing the daily dosage among multiple delivery units may be desirable if a tablet is used, for example, to provide a tablet size that is convenient to swallow. If multiple delivery units are used, they may be administered at one time or administered at intervals during the dosage period (e.g. typically a day) if desired. Present FDA guidelines recommend that the daily dosage be divided and administered in two dosage units taken at spaced intervals.
  • the amounts of the vitamins, minerals and cholesterol reducing agents disclosed herein are for a daily dosage and that dosage may be delivered in a single delivery unit or multiple delivery units.
  • packaging design may be used to facilitate identification of the proper daily dosage to the consumer.
  • a blister pack with labeling to indicate a daily dosage may be used.
  • compositions containing sterols such as phytosterol presents challenges.
  • Phytosterol has a waxy nature, is hydrophobic, typically does not flow well in micronized form and has a low bulk density. These properties cause problems during the tablet making (tableting) process, which include, but are not limited to picking and sticking of materials to tooling, materials sticking to the press turntable during compression and poor tablet weight control.
  • phytosterol is difficult to mill because it tends to clog the mill screen unless cryo-milled.
  • Prior to the present invention tablets high in phytosterol typically exhibited poor compressibility and once compressed had slow tablet disintegration adversely impacting delivery of the phytosterol upon ingestion. Timely disintegration is believed to be important for efficacy. As inventors believe, without wishing to be held to any theory, phytosterol acts in primary particle form in the gastrointestinal lumen.
  • the tablet of the invention disintegrates into primary particles in a time consistent with gastric emptying time, e.g. the compacted phytosterol containing tablet of the invention is believed to substantially disintegrate before reaching the gastrointestinal lumen.
  • at least one half the daily efficacious dose of phytosterol and at least one half the daily efficacious dose of a plurality of vitamins and minerals are tableted in a single tablet that may be swallowed by a human and which disintegrates in time consistent with gastric emptying.
  • a daily efficacious dose of the nutritional supplement is contained in two tablets it is preferable that the volume of each tablet is less than about 2 cubic centimeters.
  • an efficacious daily dose of the nutritional supplement of the invention is tableted in four tablets or less each of a size that can be swallowed by a human.
  • a daily efficacious dosage is contained in three or four tablets each tablet has a volume of about 1.5 cubic centimeters or less.
  • Tablet shape of a nutritional supplement is believed to contribute to several factors that may improve user compliance.
  • the inventors believe, without being held to the theory, that oblong, oval, modified oval, and capsule shaped compacts of about 1.5 cubic centimeters in volume or less, for example are easier for a consumer to swallow than, for example, round compacts of about 1.5 cubic centimeters or less, for example.
  • tablets that are easier to swallow may improve user compliance with the dosing regimen.
  • FIGS. 1 to 3 show an exemplary embodiment of a tablet shape. As one skilled in the art will appreciate this shape is exemplary and any of many other shapes may be equally suitable in the practice of the invention.
  • tablets may be prepared using a high shear wet-granulation method.
  • phytosterol is granulated with at least one diluent.
  • the diluent may comprise one or more of the inorganic mineral nutrients described herein, such as, for example, a magnesium compound, or calcium compound, other active agents; inactive diluents such as, for example celluloses, cellulose derivatives, lactose or other sugars, polyols, starches, starch derivatives, polymers or mixture thereof.
  • Utilizing one or more of the inorganic mineral nutrients as the diluent or a portion of the diluent has the advantage of minimizing added excipients and facilitates forming a smaller tablet.
  • Dibasic calcium phosphate, and magnesium oxide are exemplary of specific magnesium and calcium compounds which both act as a nutrient and are useful as diluents. These diluents are exemplary and other diluents and granulation components or mixtures thereof known to those skilled in the art may be used for the granulation.
  • granulation excipients known to those skilled in the art may be added such as povidone, disintegrants, co-disintegrants, super-disintegrants, surfactants, glidants, lubricants and binders.
  • other actives such as low dose mineral actives may be included in the granulation mixture. Inclusion of other low dose activities in the granulation may contribute only modestly to the granulation properties but addition to the granulation mixture facilitates uniform distribution of these low dose actives.
  • the mixture subjected to granulation comprised the phytosterol, diluents, the binder polyvinyl pyrrolidone (PVP), the excipient crosprovidone, and water. The water was added slowly to the remaining ingredients while they were mixed in a high-shear granulator.
  • PVP polyvinyl pyrrolidone
  • the granulation may be dried.
  • the drying may be performed in a fluid bed dryer, for example.
  • the granulation is milled to a suitable particle size.
  • a 0.05 screen was used.
  • the milled granulation is mixed with an absorbent. Silicon dioxide is exemplary of a suitable absorbent.
  • Other materials known to these skilled in the art as absorbents may also be used in the practice of the invention.
  • vitamins, minerals and cholesterol reducing agent may be blended into the milled granulation with an absorbent preferably in an ordered blending after a portion of the absorbent is combined with the granulation.
  • additional components may be added as single ingredients, preformed mixes or a combination thereof.
  • Other excipients such as flavorants, colorants, stabilizers, fillers, binders, disintegrants, lubricants, milling agents, glidants, antiadherents, preservatives, buffers, sweeteners, dispersants, thickness, solubilizing agent and the like or combination thereof may optionally be included.
  • the composition may be formed into tablets using compression methods, for example.
  • the tablets may be coated using tablet coating materials and methods such as those known to those skilled in the art.
  • the waxy nature of the phyto sterols has been discovered to make adherence of a film-coating material to the tablet core difficult.
  • the inventors have discovered that satisfactory adherence may be obtained using an aqueous based film-coating system comprising polyvinyl alcohol. Further, the inventors believe without wishing to be held to the theory, that using a film-coating comprising polyvinyl alcohol may improve patient compliance by yielding a tablet that is easier to swallow.
  • the inventors believe without wishing to be bound to the theory that their discovery of ordered blending of the phytosterol granulation with absorbent to coat or partially coat the granules facilitates disintegration of the tablet.
  • the inventors' discovery addresses the problem that untreated waxy phytosterols tend to form compacts with long disintegration times which are undesirable.
  • the untreated compact compounds likely pass through the gastrointestinal track with minimum, if any, disintegration to primary particles which are believed to be necessary for efficacy.
  • the inventors further believe that the physical nature and size of the absorbent particle may modify the disintegration rate of the tablet. For example, the inventors have discovered that when the absorbent silicon dioxide was used at a 1:8 w/w ratio with phytosterols, slower disintegration was seen with a fumed silicon dioxide of about 0.2-0.3 micron particle size and about 200 meter squared per gram surface area than with a precipitated silicon dioxide of about 7 micron particle size and about 300 meter squared per gram surface area. The inventors believe that it is preferable to use precipitated silicon dioxide as described above as the absorbent for an immediate release phytosterol nutritional supplement and that a fumed silicon dioxide as described above as the absorbent may be used to modulate disintegration rate.
  • absorbent As the physical nature and size of the absorbent appear to impact the rate of disintegration in some embodiments it may be desirable to use a mixture of absorbent types and/or particle size to facilitate obtaining the desired disintegration profile.
  • silicon dioxide is referred to as an absorbent herein, the inventors note that the silicon dioxide may also function as an adsorbent (e.g. it may be a sorbent).
  • absorbent and adsorbent are not critical and reference to absorbent should be taken to include absorbent, adsorbent, sorbents or combination thereof.
  • FIGS. 4 and 5 show exemplary disintegration date for two examples of the composition of the invention in water and acid, respectively. All examples in FIGS. 4 and 5 have disintegration times compatible with the timely disintegration in the gastrointestinal track. However, times do vary depending on the form of silicon dioxide used as FIGS. 4 and 5 show.
  • the high shear granulation method described herein is exemplary of a suitable method for preparing the composition of the invention.
  • the inventors' also note that the wet granulation method described herein does not require expensive cryo-milling.
  • methods such as dry slugging, dry roller compaction or extrusion could be used to prepare the compositions of the invention.
  • the nutritional supplement may be provided in a liquid and/or semisolid preparation.
  • liquid and/or semisolid preparations may include excipients and processing aides such as: flavorants, colorants, stabilizers, buffers, artificial sweeteners, natural sweeteners, sequestering and/or chelating agents, dispersants, thickeners, solubilizing agents, humectants, antioxidants, emulsifiers, water, ethanol, glycerin, propylene glycol and the like or same combination thereof.
  • excipients and processing aides such as: flavorants, colorants, stabilizers, buffers, artificial sweeteners, natural sweeteners, sequestering and/or chelating agents, dispersants, thickeners, solubilizing agents, humectants, antioxidants, emulsifiers, water, ethanol, glycerin, propylene glycol and the like or same combination thereof.
  • the quantity of active material in a unit dose of the multi-vitamin preparation
  • the multi-vitamin and mineral nutritional supplement may be presented in a controlled release formulation.
  • composition of the invention is preferably intended for administration to humans it should be understood that the formulation may also be utilized in veterinary applications for animals.
  • composition of an exemplary embodiment of the invention is provided in Table 1. This composition is representative and is one of many compositions that are within the scope of the invention and is provided for illustrative purposes.
  • the multi-vitamin and mineral nutritional supplement exemplified in Example 1 is intended to be a daily dosage and typically would be administered in one or more dosage units (e.g. one to four tablets). If multiple dosage units are used they may be taken at one time or spaced intervals during the day.
  • composition of another exemplary embodiment of the invention is provided in Table 2. This is another composition representative of the composition within the scope of the invention and is provided for illustrative purposes.
  • the multi-vitamin and mineral nutritional supplement of Example 2 is intended to be a daily dosage and typically would be administered in one or more dosage units (e.g. one to four tablets). If multiple dosage units are used they may be taken at one time or at spaced intervals during the day.
  • composition of another exemplary embodiment of the invention is provided in Table 3. This is another composition representative of the composition within the scope of the invention and is provided for illustrative purposes.
  • the multi-vitamin and mineral nutritional supplement of Example 3 is intended to be a daily dosage and typically would be administered in one or more dosage units (e.g. one to four tablets). If multiple dosage units are used they may be taken at one time or at spaced intervals during the day.
  • Vitamin K 25 mcg Vitamin E 30 IU Vitamin D 400 IU Vitamin C 60 mg Vitamin B 6 5.0 mg Vitamin B 2 (riboflavin) 1.7 mg Vitamin B 12 20 mcg Vitamin A (and Vitamin A precursors) 3500 IU Vanadium 10 mcg Thiamin 1.5 mg Silicon 2 mg Selenium 20 mcg Potassium 64 mg Phytosterols 800 mg Phosphorous 80 mg Pantothenic Acid 10 mg Nickel 5 mcg Niacin 20 mg Molybdenum 75 mcg Manganese 2.0 mg Magnesium 40 mg Lycopene 300 mcg Lutein 250 mcg Iodine 150 mcg Folic Acid 800 mcg Copper 0.7 mg Chromium 120 mcg Chloride 58 mg Calcium 108 mg Boron 32 mcg Biotin 30 mcg Iron 6 mg Tn 10 mcg
  • One exemplary multi-vitamin and mineral nutritional supplement comprising a plurality of vitamin and mineral nutritional supplement components and phytosterol was prepared using the following wet granulation method.
  • the phytosterol was delumped using a low energy oscillation system equipped with a screen.
  • the delumped phytosterol was then transferred to a high shear granulator and combined with MgO, and dibasic calcium phosphate diluents (which are also actives), ZnO a low dose mineral active, microcrystalline cellulose, super disintegrant and polyvinyl pyrrolidine binder were added to the granulation bowl.
  • Granulation was begun with a low speed blending and water was added gradually with mixing to form an acceptable granulation.
  • One skilled in the art is familiar with the appearance and physical characteristics of an acceptable granulation.
  • the granulation was dried in a fluid bed dryer with air at an airflow inlet temperature of about 90° C.
  • the granulation was dried to a moisture content of not more than about 1.5% w/w as determined by an infrared loss on drying balance.
  • the dried granulation was cooled and milled at a medium speed, with knives forward using a 0.050 screen. Approximately half of the milled granulation was put into a slant cone blender, followed by #20 mesh screened silicon dioxide. The remainder of the milled granulation was added and the mixture was blended.
  • Additional active ingredients and excipients including ascorbic acid and vitamin E acetate, dibasic calcium phosphate (a second portion), chromium chloride, sodium molybdate, stannous chloride, sodium metavanadate, nickelous sulfate, sodium selenate, manganese sulfate, Biotin, vitamin K, riboflavin, thiamine mononitrate, potassium iodide, niacinamide, copper sulfate, calcium pantothenate, pyridoxine hydrochloride, folic acid, cyanocobalamin, potassium chloride, ferrous fumarate, vitamin A acetate, beta carotene, vitamin D 3 , lycopene, lutein, croscarmellose sodium, crospovidone, and microcrystalline cellulose (second portion) were added and blended for approximately 10 minutes. Magnesium stearate screened through a #20 mesh screen was added to the composition and blending continued for approximately 1.5 minutes.
  • the granulation thus obtained was compressed into tablets using tableting techniques known to those skilled in the art using a tablet tooling with an oval shape.
  • a daily efficacious dosage of phytosterol and the indicated vitamins and minerals was tableted in two tablets each tablet having a volume of about 1.2 cm 3 .
  • the tablets were then coated using an aqueous based film-coating system comprising polyvinyl alcohol.

Abstract

The invention provides a nutritional supplement which includes micronutrients to facilitate reduction of cholesterol, and/or reduction of homocystein and/or reduction of low-density lipoprotein-cholesterol (LDL-C) oxidation in humans. In one embodiment the supplement is a multi-vitamin, a mineral supplement which includes at least one component known to reduce cholesterol. The invention further provides a method for tableting one fourth to one half of the daily effective dosage of a phytosterol containing nutritional supplement in a practical sized tablet and a method for reducing blood cholesterol in humans.

Description

    CROSS REFERENCE TO RELATED APPLICATION(S)
  • This application claims priority from U.S. Provisional Application 60/557,247 filed Mar. 29, 2004 entitled “Multi-Vitamin and Mineral Nutritional Supplements” the content of which is incorporated herein in its entirety to the extent that it is consistent with this invention and application.
    • BACKGROUND OF THE INVENTION
  • This invention relates to nutritional supplements. Features of the invention include the provision in multi-vitamin and/or mineral supplements of ingredients and micro-nutrients to facilitate reduction of cholesterol, and/or reduction of homocysteine, and/or reduction of low-density lipoprotein-cholesterol (LDL-C) oxidation in humans. In particular, the invention relates to multi-vitamin and/or mineral supplements which include at least one component known to reduce cholesterol.
  • It has long been established that a number of chemical compounds typically referred to as vitamins and minerals provide significant value to maintaining an individual in a healthy state and/or treating specific medical conditions even when supplied in relatively small amounts. Over the years a number of such vitamins and minerals have been identified. For example, vitamins include A, C, D, E and the family of B vitamins and minerals include iron, zinc, calcium and chromium. The human body does not synthesize most of these compounds which are essential to maintaining the health of the human body. Thus these necessary vitamins and minerals must be obtained from an external source. The two most common external sources are foods and nutritional supplements. Food is typically the primary source of obtaining the necessary nutrients; however, the majority of people do not eat foods that consistently provide the necessary daily requirements of vitamins and minerals. Thus, vitamin and mineral nutritional supplementation has become a recognized method of meeting accepted medical and health standards.
  • While certain vitamins and minerals have been shown to be essential for maintaining an individual's health, the use of vitamin and mineral nutritional supplementation has afforded the possibility to include micro-nutrients which, although not absolutely essential to maintaining health, provide significant benefit towards maintaining health. For example, U.S. Pat. No. 6,361,800 to Cooper et al. provides for a multi-vitamin supplement preparation with a composition of micro-nutrients which is purported to decrease plasma homocysteine levels and plasma glucose levels.
  • A significant health concern to many individuals is the problem of high cholesterol. While many medications are available for treating this problem, most of the common medications require doctor's supervision for use and are relatively expensive. Certainly a doctor's care and use of these medications in cases of highly elevated or chronically elevated cholesterol are very important but the medications are used when the cholesterol level is a serious health threat.
  • Some herbal/natural vitamin and/or mineral and/or nutritional compositions that contain phytosterols, compounds which are believed to facilitate cholesterol reduction, are commercially available. However, the efficiency of these herbal/natural product compositions for reducing cholesterol is questionable as they typically contain 20 to 50 mg of phytosterol per dose. This is substantially below the amount that the FDA (Food and Drug Administration) recognizes as an efficacious dose of phytosterol for reducing cholesterol levels. In 21 CFR 101.83 dated Feb. 14, 2003, the FDA indicates that 800 mg/day is the lowest effective intake of the phytosterols to reduce risk of coronary heart disease.
  • Accordingly, it would be desirable to have a convenient, practical and relatively inexpensive way to facilitate reducing cholesterol levels, and/or reducing homocysteine, and/or decreasing LDL-C oxidation in humans before the cholesterol reaches a level to become a serious health threat.
    • SUMMARY OF THE INVENTION
  • The present invention provides a nutritional supplement which facilitates providing an adequate intake of vitamins, minerals and other micro-nutrients desirable for disease prevention, protection against nutritional losses and deficiencies due to inadequate dietary intake patterns and life style factors and provides micro-nutrients to facilitate reduction of cholesterol, and/or reduction of homocysteine, and/or reduction of LDL cholesterol in humans. The invention also provides a method of preparing an efficacious dosage of the nutritional supplement in a practical dosage form and a method for reducing cholesterol levels and/or LDL cholesterol and/or homocystine in humans.
  • In one embodiment the invention provides a nutritional supplement for administration to humans comprising: an effective amount of at least one vitamin selected from the group consisting of Vitamin A; Vitamin C; Vitamin E, Vitamin B6, Vitamin B2, folate and Vitamin B12 and an effective amount of at least one cholesterol reducing agent selected from the group consisting of phytosterols, phytostanols, policosanols, and statins.
  • In one embodiment the invention provides a nutritional supplement for administration to humans comprising: an effective amount of at least one mineral selected from the group consisting of selenium, chromium and zinc, and an effective amount of at least one cholesterol reducing agent selected from the group consisting of phytosterols, phytostanols, policosanols, and statins.
  • In one embodiment the invention provides a multi-vitamin and mineral nutritional supplement for administration to humans comprising at least one cholesterol reducing agent from the group consisting of phytosterols, phytostanols, policosanols and statins in an amount effective to reduce cholesterol and an effective of amount of vitamins A, B2, B6 B 12 folate (folic acid), and E. The composition may further comprise at least one of an effective amount of lycopene and an effective amount of selenium.
  • In another embodiment the invention provides a multi-vitamin and mineral nutritional supplement for administration to humans comprising pharmaceutically acceptable forms of the following: at least about 800 mg of phytosterols; at least about 3500 I.U. of vitamin A and/or vitamin A precursors; at least about 60 mg of vitamin C; at least about 400 I.U. of vitamin D; at least about 30 I.U. of vitamin E; at least about 25 mcg of vitamin K; about 1.5 mg of thiamin; at least about 1.7 mg of vitamin B2 (riboflavin); at least about 20 mg of niacin; at least about 5 mg of vitamin B6; at least about 800 mcg of folic acid; at least about 200 mcg of vitamin B12; at least about 30 mcg of biotin; at least about 10 mg of pantothenic acid; at least about 6 mg of iron; about 150 mcg of iodine; at least about 210 mg of magnesium; at least about 7.5 mg of zinc; at least about 20 mcg of selenium; at least about 0.7mg of copper; at least about 2 mg of manganese; at least about 108 mg calcium; at least about 80 mg of phosphorus; at least about 75 mcg of molybdenum; at least about 320 mcg boron; at least about 5 mcg nickel; at least about 2 mg silicon; at least about 10 mcg tin; at least about 10 mcg vanadium; at least about 120 mcg of chromium; at least about 64 mg of potassium; at least about 78 mg of chloride; at least about 300 mcg of lycopene; and at least about 250 mcg lutein.
  • Another embodiment of the invention provides a multi-vitamin and mineral nutritional supplement for administration to humans comprising pharmaceutically acceptable forms of the following: at least one ingredient to facilitate reduction of cholesterol, at least one ingredient to facilitate reduction of homocysteine or facilitate reduction of low-density lipoprotein-cholesterol (LDL-C) and about 1300 I.U. to about 10,000 I.U. of vitamin A and/or vitamin A precursors; about 200 I.U. to 2000 I.U. of vitamin D; about 0 mcg to about 50 mcg of vitamin K; about 1.2 mg to about 4.5 mg of thiamin; about 5 mg to about 40 mg of niacin; about 0 mg to about 550 mg of choline; about 0 mcg to about 1400 mcg of folic acid; about 0 mcg to about 300 mcg of biotin; about 0 mg to about 16 mg of pantothenic acid; about 0 mg to about 18 mg of iron; about 0 mcg to about 300 mcg of iodine; about 0 mg to about 100 mg of magnesium; about 3 mg to about 15 mg of zinc; about 0 mg to about 2 mg of copper; about 0 mg to about 6 mg of manganese; about 0 to about 200 mg calcium; about 0 mg to about 750 mg of phosphorus; about 0 mcg to about 250 mcg of molybdenum; about 0 mcg to about 150 mcg boron; about 0 mcg to about 100 mcg nickel; about 0 mg to about 40 mg silicon; about 0 mcg to about 35 mcg tin; about 0 mcg to about 25 mcg vanadium; about 0 mcg to about 300 mcg of chromium; about 0 mg to about 125 mg of potassium; about 0 mg to about 120 mg of chloride; about 0 to 3 g of Omega-3 fatty acids; about 0 to 3 g lycopene; about 0 to 3 g zeaxanthin; and about 0 mcg to about 3 g lutein.
  • Ingredients to facilitate reduction of cholesterol may comprise one or more of the following ingredients in an amount effective to reduce cholesterol: phytosterols, phytostanols, or their equivalents, in free or esterified form, policosanol and statins. Suitable statins include, for example, atorvastatin, provastatin, simvastatin, lovastatin or flavastatin. Typically about 0.8 grams to about 3 grams of phytosterols, stanols, or their equivalents, may be used in the multi-vitamins and mineral nutritional supplements. Amounts of policosanol of up to about 200 mg may be used in the multi-vitamins and mineral nutritional supplements. Statins may be used in amounts of up to 80 mg and typically are used in amounts of about 40 mg to about 80 mg. More particularly with regard to statins, provastatin and simvastatin are preferably used in amounts of about 40 mg, and atorvastatin, lovastatin and fluvastatin are typically used in amounts of about 80 mg.
  • Ingredients to facilitate reduction of homocystine may comprise one or more of the following: up to about 40 mg of vitamin B2 (riboflavin); up to about 10 mg of vitamin B6; up to about 1 mg of folate, and up to about 2 mg of vitamin B12. Ingredients to facilitate reduction of homocysteine, may more preferably comprise one or more of the following: about 1.3 mg to about 5.1 mg of vitamin B2 (riboflavin); up to about 1400 about 800 mcg folate; about 1 mg to about 6 mg of vitamin B6; and about 2.4 mcg to about 200 mcg of vitamin B12.
  • Ingredients to facilitate reduction of low-density lipoprotein-cholesterol cholesterol (LDL-C) oxidation, which may comprise one or more of the following: up to about 2 grams of vitamin C; up to about 800 I.U. of vitamin E; up to about 6 grams of lycopene; and up to about 350 mcg of selenium. Ingredients to facilitate reduction of low-density lipoprotein-cholesterol cholesterol (LDL-C) oxidation, may more preferably comprise one or more of the following: about 45 mg to about 250 mg of vitamin C; about 20 I.U. to about 200 I.U. of vitamin E; about 0 mcg to about 3 g of lycopene; and about 0 mcg to about 75 mcg of selenium.
  • The composition described herein may further include a diluent such as, for example a calcium compound, magnesium compound, microcrystaline cellulose, starch or a combination thereof.
  • The composition described herein may also include an absorbent such as silicon dioxide, for example. In some embodiments the silicon dioxide may be precipitated, fumed or a mixture thereof.
  • The invention further provides a method of reducing cholesterol levels, reducing homocysteine, and decreasing low-density lipoprotein-cholesterol (LDL-C) oxidation in humans by administering the composition of the invention to a human.
  • The invention further includes a method of tableting nutritional supplements comprising at least one phytosterol, the method comprising: providing at least one phytosterol and at least one diluent; granulating the phytosterol and the at least one diluent under high shear granulation conditions to form a granulation; milling the granulation; and adding an absorbent to the granulation.
  • For wet granulation methods, the method may further comprise drying the granulation and the absorbent is preferably added after drying. A fluid bed dryer is exemplary of a suitable dryer for drying the granulation.
  • The method may comprise compressing the granulation to form a tablet. The tableting may be coated with a film coat comprising polyvinyl alcohol (PVA), for example.
  • In one embodiment a daily efficacious amount of nutritional supplement comprises two tablets, each of the two tablets having a volume less than 2 cubic centimeters.
  • In one embodiment a daily efficacious amount of the nutritional supplement comprises four tablets or fewer. Each tablet having a volume less than 1.5 cubic centimeters.
  • In some embodiments the tablets may have an oblong, oval, modified oval, or capsule shape.
  • Alternatively a daily efficacious amount of the nutritional supplement may comprise one or more capsules, one or more chewable delivery unit, a powder, or a sachet.
    • DESCRIPTION OF THE FIGURES
  • FIG. 1 is an end view of an exemplary embodiment of a tablet of the composition of the invention.
  • FIG. 2 is a top view of an exemplary embodiment of a tablet of the composition of the invention;
  • FIG. 3 is a side view of an exemplary embodiment of a table of the composition of the invention;
  • FIG. 4 is a graph showing tablet disintegration data for tablets of two exemplary embodiments of the composition of the invention in water; and
  • FIG. 5 is a graph showing tablet disintegration data for tablets of two exemplary embodiments of the invention in acid.
    • DETAILED DESCRIPTION OF THE INVENTION
  • The invention provides a nutritional supplement which in one embodiment is a multi-vitamin and mineral nutritional supplement for administration to humans, having at least one ingredient to facilitate reduction of cholesterol. The cholesterol reducing ingredient may include phytosterols and/or stanols, and/or statins, and/or policosanol. In some embodiments the nutritional supplement further includes at least one ingredient for reduction of homocysteine and/or reduction of low-density lipoprotein-cholesterol (LDL-C). The multi-vitamin and mineral nutritional supplement may comprise one or more of: vitamin A and/or vitamin A precursors; vitamin C; vitamin D; vitamin E; vitamin K; thiamin; vitamin B2 (riboflavin); niacin; vitamin B6; folic acid; vitamin B12; biotin; pantothenic acid; iron; iodine; magnesium; zinc; selenium; copper; manganese; calcium; phosphorus; molybdenum; boron; nickel; silicon; tin; vanadium; chromium; potassium; chloride; choline; lycopene; and lutein. When administered to a human on a regular basis (for example, daily), the composition of the invention facilitates adequate intake of vitamins and minerals and provision of other micro-nutrients to promote good health including micro-nutrients which facilitate the lowering of cholesterol levels, and/or reduction of homocysteine, and/or decrease of low-density lipoprotein-cholesterol (LDL-C) oxidation in humans. In other embodiments, the nutritional supplement may include one or more vitamins in combination with at least one cholesterol lowering ingredient, or at least one mineral in combination with at least one cholesterol-lowering ingredient. The terms “nutritional supplement” or “supplement” should be taken to refer to any or all of the embodiments (e.g. a multi-vitamin and mineral supplement with at least one cholesterol lowering agent, a composition comprising at least one vitamin and at least one cholesterol lowering agent, or a composition comprising at least one mineral and at least one cholesterol lowering agent). The nutritional supplement may in some embodiments further comprise other actives such as for example, homocystine lowering actives or one or more other actives that provide a nutritional and/or health benefit. A preferred embodiment of the invention is a multi-vitamin and mineral supplement with at least one cholesterol lowering agent, as such supplement provides a simple method for addressing nutritional deficiencies and promotes compliance in usage by an individual in need of nutritional supplementation.
  • The invention further provides a method for preparing solid dosages forms comprising nutritional supplement components in efficacious amounts in a unit or units compatible with convenient human consumption. (For example, in a dosage form in which a daily efficacious amount of at least one vitamin and/or mineral supplement and at least one cholesterol reducing ingredient is contained in 2-4 tablets of a size that an adult human can practically swallow.) Typically the number and amount of vitamin and mineral components needed to provide a efficacious daily dosage to generally supplement nutritional deficiencies constitutes a substantial tablet volume. Provision of an additional component(s) in the supplement to facilitate the reduction of cholesterol further increases the volume of material to be included in a dosage form.
  • Preparing a solid dosage form containing efficacious amounts of a significant number of vitamins and minerals and phytosterol in a practical dosage unit, for example, is particularly challenging in that a minimum of 800 mg of phytosterol per day is needed to meet the FDA standard for efficacy and phytosterol is a waxy material with a low bulk density. The inventors have addressed these problems by developing a preparation method (e.g. manufacturing process) that employs granulation techniques and/or the use of diluent and/or the use of absorbent excipients to prepare a tableted dosage form comprising efficacious daily amounts of the components of the nutritional supplement in preferably 2-4 tablets of a tablet size suitable to be swallowed by a human.
  • As used herein, the phrase “cholesterol lowering agent” or “cholesterol reducing agent” means any compound, combination of compounds, including any extract or plant component, naturally found or processed, or synthetic compound that has the property of lowering cholesterol levels when administered in an effective amount. 361 All amounts specified herein are based on milligrams unless otherwise indicated. The term “I.U.” represents International Units. The term “mcg” means micrograms, “mg ” means milligrams, and “g” means grams. Further, it should be understood that the amounts of components disclosed herein are for a daily dosage and that a daily dosage may comprise one dosage unit or a plurality of dosage units.
  • “An efficacious dosage” of a nutrient is at least the minimum amount of the nutrient needed on a daily basis recognized by the United States Food and Drug Administration (FDA) for providing a health or nutritional benefit. We further note that in some guidelines the FDA recommends that daily dosages of multivitamin and mineral supplements be divided and administered in two dosage units taken at spaced intervals during the day. Typically, with meals or food, for example such as twice daily with meals. Accordingly amounts are given for daily dosages but it should be understood that the daily dosage may be in multiple dosage units and consumption of these units may occur at the same time or different times during the day.
  • Typically, sterols and stanols derived from plant sources are termed phytosterols and phytostanols. Phytosterols and phytostanols are natural compounds that can be consumed regularly as a part of a healthy diet. Accordingly, while plant derived materials are the preferred source of these compounds, equivalent synthesized stanols and sterols, or stanols and sterols from other sources, may be used in the practice of the invention. Any reference to use of phytosterol or phytostanols herein should be taken to apply to equivalent sterols or stanols from alternative sources. It should be understood in terms of discussing amounts of the composition that sterols or phytosterols may be used in like amounts or vice-versa. It should be understood in terms of discussing amounts of the composition, that stanols or phytostanols may be used in like amount or vice-versa.
  • There are multiple specific chemical entities classed as phytosterols, including but not limited to beta-sitosterol, campesterol, and stigmasterol, for example. For the nutritional supplements of this invention either a single specific chemical species of phytosterol or mixtures comprised of a plurality of specific chemical species of phytosterols may be employed. For example a mixture of phytosterols having beta-sitosterol, campesterol and sigmasterol as principle components is exemplary of a mixture suitable for use in the practice of the invention. Commercial preparations of mixed phytosterols are available from suppliers such as Cargill and ADM (Archer Daniels Midland), for example. Likewise, the class phytostanols includes multiple specific chemical species of phytostanols and a single specific chemical species of phytostanol or a mixture of a plurality of specific chemical species of phytostanols may be used in the practice of the invention. Accordingly, reference to phytosterols or phytostanols in compositions discussed herein should be taken to include both single specific chemical species forms as well as mixtures.
  • Foods such as fruits, vegetables, breads and other whole grain products, and most vegetable oils contain at least some phytosterols. However, it is difficult to consume enough of these foods on a daily basis to obtain sufficient phytosterol intake to have a cholesterol-lowering effect. Based on clinical trial data on the use of phytosterols in the diet, a daily intake of at least 0.8 grams (800 mg) of phytosterols as part of a diet low in saturated fat and cholesterol is recommended by the FDA to provide significant cholesterol lowering benefits. Consuming the nutritional supplements of this invention is one way to ensure that an effective daily intake is attained.
  • It is believed, but the inventors do not wish to be bound to the theory, that ingested plant sterols and stanols compete with the cholesterol to decrease cholesterol absorption and reabsorption in the small intestine because they are structurally similar to cholesterol. To a point, the more sterol, such as phytosterol, in free form that is present in the intestine following a meal, the less cholesterol absorption and reabsorption will occur. Further, consumed phytosterols, phytostanols, and their equivalents, are not absorbed to any appreciable extent. Hence, phytosterols are believed to inhibit the uptake of cholesterol by the body and are flushed through the system without absorption. One study showed that the overall effect may be an average decline in blood levels of “bad” low-density lipoprotein-cholesterol (e.g. the “LDL-C”) of 8-15%, with no observed or identified adverse effects. (See “Plant Sterol-Fortified Orange Juice Effectively Lowers Cholesterol Levels In Mildly Hypercholesterolemic Healthy Individuals.” Arterioscler. Thromb. Vasc. Biol. 2004 March; 24(3):e25-8. Epub Feb. 5, 2004) Preferably, the multi-vitamin and mineral nutritional supplement comprises up to about 3 g of the free form or the esterified form of phytosterols and more preferably at least about 800 mg of phytosterols. Most preferably, the supplement comprises about 800 mg of phytosterols in the free form. In some embodiments the phytosterol may be replaced with phytostanols or a combination of phytosterols and phytostanols may be used.
  • Policosanol is the generic term used for a mixture of long-chain primary aliphatic saturated alcohols that may reduce total serum cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Policosanol is also known as polycosanol, policosanal, policosinal, policosinol, polycosanal, polycosinal and polycosinol. These alcohols are derived from the waxes of such plants as sugar cane (Saccharum officinarium) and yams (e.g. Dioscorea opposita). They are also found in beeswax. The main long-chain alcohol in policosanol is the 28 carbon 1-octanosol, and next most abundant is the 30 carbon 1-triacontanol. Other long-chain alcohols present in much lower concentrations comprise: 1-docosanol (C22), 1-tetracosanol (C24), 1-hexacosanol (C26), 1-heptacosanol (C27), 1-nonacosanol (C29), 1-dotriacontanol (C32) and 1-tetracontanol (C34). These long-chain alcohols are solid waxy substances and are insoluble in water. They are known collectively as aliphatic alcohols.
  • The mechanism of action of reported cholesterol-lowering activity of policosanol is unknown and the inventors do not wish to be bound to any theory. Several theories regarding the method of action of policosanol have been suggested in the literature including the suggestion from some animal studies that policosanol may inhibit cholesterol synthesis in the liver by indirectly down-regulating HMG-CoA reductase. (see “Policosanol Safety Down Regulates HMG-CoA Reductase—Potential As A Component of the Esselstyn Regimen.” Med.Hypotheses. 2002 September; 59(3):268-79.) Others have suggested Policosanol may impair cholesterol synthesis between the acetate and mevalonate production steps and/or increase receptor-dependent LDL-C processing. (see “Policosanol: Clinical Pharmacology and Therapeutic Significance of a New Lipid-Lowering Agent.” Am.Heart J. 2002 February; 143(2): 356-65). Others have suggested Policosanol also may reduce lipid peroxidation (see “Effect of Policosanol on In Vitro and In Vivo Rat Liver Microsomal Lipid Peroxidation.” Arch.Med.Res. 1997 Autumn; 28(3): 355-60). It is believed that the long-chain alcohols appear to have different biological activities, e.g. octacosanol by itself may not have the same activities as policosanol and that at least in some instances the combination of all or some of the alcohols in the policosanol may work synergistically. In one embodiment policosanol is included in the multivitamin and mineral nutritional supplement. The multi-vitamin and mineral nutritional supplement embodiment including polycosanol comprises up to about 200 mg of policosanol and more preferably about 10 to about 20 mg of policosanol.
  • Statins, including atorvastatin, pravastatin, simvastatin, lovastatin, and fluvastatin, are believed to be competitive 3-hydroxy-3 methyl glutaryl CoA, hereinafter referred to as HMGCoA reductase inhibitors. Accordingly, they are believed to be effective in the reduction of cholesterol, and are believed to be effective in preventing not only recurrent heart attacks, but also first heart attacks. In some cases statins may also reduce the risk of strokes. In one embodiment statins may be included in the multi-vitamin and mineral nutritional supplement. The nutritional supplement embodiment including statins may comprise up to about 80 mg of a statin or mixture of statins and more preferably it comprises about 5 to about 80 mg of a statin or mixture of statins. Provastatin and simvastatin are preferably used in amounts of about 40 mg, and atorvastatin, lovastatin and fluvastatin are preferably used in amounts of about 80 mg.
  • Several vitamins and minerals are known to facilitate cholesterol reduction, homocysteine reduction, and/or reduction of low-density lipoprotein-cholesterol. By providing one of these agents, or a combination thereof, in a multi-vitamin and nutritional mineral supplement, this invention provides for a convenient, practical and relatively inexpensive way to facilitate reducing cholesterol levels, and/or reducing homocysteine levels, and/or decreasing LDL-C oxidation in humans.
  • Vitamin C, also known as ascorbic acid, is believed to be necessary for the synthesis of collagen and is used as an antioxidant. It is believed that Vitamin C fights infection, reduces inflammation, heals wounds, reduces the risk of heart disease by reduction of LDL-C oxidation, lowers cholesterol, reduces the risk of lung, stomach and esophageal cancers, reduces cervical epithelial abnormalities, inhibits N-nitrosamine, and reduces the severity of colds. The nutritional supplement may comprise up to about 2000 mg of Vitamin C, more preferably about 45 mg to about 250 mg, and most preferably about 60 mg of Vitamin C.
  • Vitamin E is needed for the maintenance of cell membranes and for neurological health. Vitamin E relieves hot flashes, relieves mastodynia, helps in fighting fibrocystic breast disease, reduces mammary tumors, reduces the risk of lung cancer, and reduces the risk of heart disease by reduction of LDL-C cholesterol oxidation. Vitamin E is the generic term for a group of related substances, which include alpha-tocopherol, beta-tocopherol, gamma-tocopherol, and delta-tocopherol. In addition, each of these four compounds has a “d” form, which is the natural form, and a “dl” form, which is the synthetic form. All forms of all substances covered by Vitamin E are included herein. The nutritional supplement may comprise up to about 1500 I.U. of Vitamin E, and more preferably about 15 I.U. to about 800 I.U. Most preferably, the multi-vitamin and mineral nutritional supplement may comprise about 20 I.U. to 200 I.U. of Vitamin E.
  • The nutritional supplement may comprise one or more of B complex vitamins. The B vitamins included in the nutritional supplement may include thiamin (Vitamin B1), riboflavin (Vitamin B2), niacin (Vitamin B3) pantothenic acid (Vitamin B5), pyridoxine (Vitamin B6), biotin, folic acid, and the cobalamins (Vitamin B12) or a combination thereof. The B vitamins are water-soluble. Of these vitamins, B2, B6, and Vitamin B12 (e.g. or the cobalamins), are known to reduce homocysteine levels. However, because of the beneficial nature of the B vitamins in general, all of them are contemplated for use in one embodiment of the invention.
  • Vitamin B, or thiamin helps keep collagen-rich connective and mucous membranes healthy, helps to maintain smooth muscles, helps in the formation of blood cells, and is necessary for proper nervous system function. The nutritional supplement may comprise about 0.9 mg to about 100 mg of, more preferably about 1.2 mg to about 4.5 mg and most preferably about 1.5 mg of thiamin.
  • Vitamin B2 or riboflavin is necessary for healthy hair, nails and mucous membranes and is involved in red blood cell formation, homocysteine reduction, antibody production and overall growth. The nutritional supplement of the invention may comprise up to about 40 mg of riboflavin, more preferably about 0.9 mg to about 5.1 mg and most preferably about 1.3 to 1.7 mg of riboflavin.
  • Vitamin B3 or niacin helps in the production of most of the sex hormones, dilates blood vessels and helps maintain blood circulation. Niacin is the generic name for a group of compounds, which exhibit niacin activity and includes niacinamide and nicotinic acid. The nutritional supplement may comprise about 5 mg to about 500 mg of niacin, more preferably about 5 mg to about 40 mg and most preferably about 20 mg of niacin as niacinamide.
  • Vitamin B6 or pyridoxine is involved in the production of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), homocysteine reduction, and many other reactions in the body. Pyridoxine refers to and includes three different compounds: pyridoxine, pyridoxamine, and pyridoxal. The nutritional supplement may comprise about 1 mg to about 10 mg of Vitamin B6, more preferably about 1 mg to about 6 mg, and most preferably about 5 mg of Vitamin B6.
  • Folic acid is used in the production of red blood cells, the production of hormones, and the synthesis of DNA. The nutritional supplement may comprise up to about 1000 mcg of folic acid, more preferably about 0 mcg to about 800 mcg folate (folic acid), and most preferably, about 800 mcg of folic acid.
  • Vitamin B12 (e.g. the cobalamins) is necessary for overall metabolism, the function of the nervous system, metabolism of folic acid, homocysteine reduction, and the production of red blood cells. There are at least three active forms of cobalamin: cyanocobalamin, hydroxocobalamin, and nitrocobalamin. The nutritional supplement may comprise up to about 2000 mcg of Vitamin B12, more preferably about 2.4 mcg to about 200 mcg, and most preferably, about 200 mcg of Vitamin B12.
  • Biotin is necessary for the metabolism of carbohydrates, proteins, and fats and is needed for healthy skin and hair. The nutritional supplement may comprise up to about 900 mcg of biotin and more preferably about 0 mcg to about 300 mcg, and most preferably, about 30 mcg of biotin.
  • Pantothenic acid, also known as Vitamin B5, is important for the production of adrenal gland hormones, increases overall energy, and helps convert food into energy. The nutritional supplement may comprise up to about 200 mg of pantothenic acid, more preferably about 0 mg to about 10 mg, and most preferably, about 10 mg of pantothenic acid.
  • Vitamin A is also contemplated for use in the multi-vitamin and mineral nutritional supplement of the invention. Vitamin A prevents night blindness and other eye disorders, keeps skin moist and elastic, maintains healthy hair, skin, and gums, reduces the risk of breast cancer, helps alleviate mastodynia, reduces the risk of lung cancer, maintains cell structure and integrity, works as an antioxidant to prevent cell aging, helps prevent infection, and negates skin wrinkling and the effects of sun damage. Vitamin A is a fat-soluble vitamin. The term Vitamin A is used to include retinol and other chemically similar compounds referred to as retinoids.
  • In the practice of the invention, Vitamin A may be provided as a form of Vitamin A, as Vitamin A precursor carotenoids, such as betacarotene, or as a mixture thereof. For example, in a typical embodiment 29% of Vitamin A may be provided as beta-carotene, with the remainder supplied as Vitamin A acetate. The nutritional supplement of the invention may comprise up to about 10,000 I.U. of Vitamin A including Vitamin A precursors, more preferably about 1300 I.U. to about 5000 I.U. and most preferably, about 3500 I.U. of Vitamin A in the form of Vitamin A or Vitamin A and the Vitamin A precursor beta-carotene.
  • Beta-carotene and other carotenoids are provitamins, i.e., vitamin precursors, and are converted to vitamins or vitamin-like substances, as the body requires. Although the carotenoids include lutein, zeaxanthin and lycopene, amounts of these components are specified specifically herein and any amounts of Vitamin A precursors recited herein should not be interpreted to include any appreciable amount of lutein, zeaxanthin or lycopene.
  • Vitamin D is also an essential mineral which assists in the mineralization and calcification of bone, prevents rickets in children, prevents osteomalacia in adults, preserves bone and tooth growth, and lowers blood pressure. Vitamin D is fat-soluble and cholecalciferol or D3 is the preferred form. Preferably, the nutritional supplement may comprise up to about 2000 I.U. of Vitamin D and more preferably about 200 to about 400 I.U. of Vitamin D.
  • Vitamin K is an active blood clotting agent and assists in bone formation. It also may help in removing calcium from atherosclerotic plaques. Phylloquinone or K1 and menoquinone, or K2 are the preferred forms. Preferably, the nutritional supplement may comprise up to about 1 mg of vitamin K, more preferably about 0 mcg to about 90 mcg of vitamin K and most preferably about 25 mcg vitamin K.
  • Choline is necessary for nervous system function and brain function. It is also important for gall bladder and liver function. Choline helps maintain the structural integrity of membranes surrounding every cell in the body but also can play a role in nerve signaling, cholesterol transport, and energy metabolism. In the nutritional supplement, choline may be provided in the form of a pharmaceutically acceptable choline salt, such as, for example, bitartarate. The nutritional supplement may optionally comprise of up to about 3500 mg choline, and more preferably, of about 50 mg to about 550 mg of choline in the form of choline bitartarate.
  • Iron is used in the production of hemoglobin and myoglobin. In the nutritional supplement, the iron is dosed in the form of a pharmaceutically acceptable iron compound. As used herein, “pharmaceutically acceptable” is a component which is suitable for use in humans without undue side effects, such as irritation, toxicity, and allergic response. Useful pharmaceutically acceptable iron compounds include, but are not limited to, ferrous fumarate, ferrous sulfate, carbonyl iron, ferrous gluconate, ferrous chloride, ferrous lactate, ferrous tartrate, ferrous succinate, ferrous glutamate, ferrous citrate, ferrous pyrophosphate, ferrous cholinisocitrate, ferrous carbonate, iron-sugar-carboxylate complexes, and combinations thereof. The nutritional supplement may comprise up to about 18 mg of iron dosed in a pharmaceutically acceptable iron compound and more preferably, about 5 mg to about 18 mg of iron.
  • Iodine helps to metabolize fats, is necessary for proper thyroid function, and reduces fibrocystic breast conditions. In the nutritional supplement of the invention, iodine is dosed in the form of a pharmaceutically acceptable iodine compound. Useful pharmaceutically acceptable iodine compounds include, but are not limited to, potassium iodide, sodium iodide and combinations thereof. The nutritional supplement may comprise up to about 1100 mcg of iodine dosed in the form of a pharmaceutically acceptable iodine compound, more preferably up to about 150 mcg, and—most preferably, about 150 mcg of iodine.
  • Magnesium is used in bone formation and growth, prevents bone loss, relaxes coronary arteries, is used in managing pre-eclampsia, treating cardiac arrhythmias, and managing diabetes. In the nutritional supplement, magnesium is dosed in the form of a pharmaceutically acceptable magnesium compound. Useful pharmaceutically acceptable magnesium compounds include, but are not limited to, magnesium stearate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium sulfate, and combinations thereof. The nutritional supplement may comprise up to about 400 mg of magnesium dosed in the form of a pharmaceutically acceptable magnesium compound, more preferably up to about 350 mg, and most preferably, about 100 mg of magnesium.
  • Zinc is required for proper formation of DNA and RNA and is needed for growth, immunity and sexual development of women. In the multi-vitamin and mineral nutritional supplement of the invention, zinc is dosed in the form of a pharmaceutically acceptable zinc compound. Pharmaceutically acceptable zinc compounds include, but are not limited to, zinc sulfate, zinc chloride, zinc oxide, and combinations thereof. The nutritional supplement may comprise about 3 mg to about 40 mg of zinc dosed in the form of a pharmaceutically acceptable zinc compound, more preferably about 3 mg to about 15 mg and most preferably, about 15 mg of zinc.
  • Selenium reduces the risk of heart attacks and heart disease, reduces the risk of cancer, protects against metal poisoning, and is believed to be synergistic with Vitamin E in reducing LDL cholesterol oxidation. Pharmaceutically acceptable selenium compounds include but are not limited to sodium selenate, selenocysteine, selenomethionine or other amino acid chelates, and combinations thereof. The nutritional supplement may comprise up to about 400 mcg of selenium more preferably up to about 75 mcg and most preferably about 15 mcg to about 75 mcg of selenium dosed in a pharmaceutically acceptable form.
  • Copper helps keep blood vessels elastic, is needed for the formation of elastin and collagen, functions as an iron oxidizer, and is needed for the proper functioning of Vitamin C. In the nutritional supplement, copper is dosed in a pharmaceutically acceptable copper compound. Pharmaceutically acceptable copper compounds include, but are not limited to, cupric oxide, cupric citrate, cupric sulfate, cupric carbonate, cupric gluconate, and combinations thereof. The nutritional supplement may comprise up to about 10 mg of copper dosed in the form of a pharmaceutically acceptable copper compound, and more preferably, about 1.0 mg of copper dosed in the form of cupric gluconate, sulfate or citrate.
  • Calcium is needed by the body to build and maintain strong bones and teeth, facilitate neural transmission, and regulate muscle contraction and heartbeat. Calcium is lost through shed skin, nails, hair sweat, urine and feces. If intake is not sufficient, the body may remove calcium from bone to obtain the mineral which may adversely affect the bone density and render bones more susceptible to injury. Pharmaceutically acceptable calcium compounds include, but are not limited to, calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium gluconate, calcium lactate, calcium citrate, and combinations thereof. The nutritional supplement may comprise up to about 1500 mg calcium, more preferably up to about 200 mg and most preferably about 100 mg to about 162 mg of calcium dosed in a pharmaceutically acceptable form.
  • A low level of manganese in the body may be associated with diabetes. Accordingly manganese appears to have a role in the control of blood sugar levels. Manganese may also have a role in the metabolism of amino acids and certain vitamins. Pharmaceutically acceptable manganese compounds include, but are not limited to, manganese chloride, manganese sulfate, and combinations thereof. The nutritional supplement may comprise up to about 12 mg manganese dosed in a pharmaceutically acceptable form more preferably the nutritional supplement may comprise about 0 mg to about 4 mg manganese and most preferably about 1 mg manganese.
  • Silicon is believed to be used for the building of collagen for bones and connective tissue. Pharmaceutically acceptable silicone compounds include, but are not limited to, sodium silicate, sodium silicoaluminate, silicon dioxide, and combinations thereof. The nutritional supplement may comprise about 0 mg to about 500 mg silicon dosed in a pharmaceutically acceptable form, more preferably about 0 mg to about 60 mg silicon, and most preferably about 2 mg silicon.
  • Molybdenum may facilitate proper metabolism of fats, carbohydrate and iron and may protect against certain cancers. Pharmaceutically acceptable molybdenum compounds include, but are not limited to, sodium molybdate, molybdenum amino acid chelates, and combinations thereof. The nutritional supplement may comprise up to about 2000 mcg molybdenum dosed in a pharmaceutically acceptable form. More preferably the nutritional supplement may comprise about 0 mcg to about 75 mcg, and most preferably the nutritional supplement comprises about 75 mcg molybdenum.
  • Vanadium is believed to have a role in the regulation of sugar levels in the blood. Pharmaceutically acceptable vanadium compounds include, but are not limited to, ammonium vanadium tartrate, sodium metavanadate, vanadyl sulfate, and combinations thereof. The nutritional supplement may comprise up to about 1.8 mg vanadium in a pharmaceutically acceptable form, more preferably about 6 mcg to about 18 mcg vanadium and most preferably about 10 mcg vanadium.
  • Boron may have a role in mineral metabolism. Pharmaceutically acceptable boron compounds include, but are not limited to, sodium borate, boron citrate, boron amino acid chelates, and combinations thereof. The nutritional supplement may comprise up to about 20 mg of boron dosed in a pharmaceutically acceptable form, more preferably about 0 mcg to about 1.35 mg boron, and most preferably about 150 mcg to about 350 mcg boron.
  • Nickel may activate or inhibit the action of some enzymes or hormones. Pharmaceutically acceptable nickel compounds include, but are not limited to, nickel sulphate. The nutritional supplement may comprise up to about 1.0 mg nickel dosed in a pharmaceutically acceptable form, more preferably about 0 mcg to about 100 mcg nickel and most preferably about 5 mcg nickel.
  • Tin is known to be found in the human body. In rats a tin deficiency may depress growth. Pharmaceutically acceptable tin compounds include, but are not limited to. stannous chloride. The nutritional supplement may comprise up to about 200 mcg tin dosed in a pharmaceutically acceptable form, more preferably about 0 mcg to about 10 mcg tin and most preferably about 10 mcg tin.
  • Phosphorus is needed for bone development and is a constituent in all major classes of biochemical compounds. Phosphorous, in the form of phosphate in adenosine triphosphate is a key energy source required for most metabolic processes. Pharmaceutically acceptable phosphorus compounds include, but are not limited to, forms of calcium phosphate, sodium phosphate, potassium phosphate, ammonium phophate, glycerol phosphate, and combinations thereof. The nutritional supplement may comprise up to about 1250 mg of phosphorus, more preferably about 0 mg to 750 mg, most preferably about 109 mg of phosphorous, dosed in a pharmaceutically acceptable form.
  • Chromium assists in the regulation of glucose metabolism, is used in the synthesis of fatty acids and cholesterol, assists in transporting proteins, lowers LDL blood levels, and raises high density lipoproteins blood levels. In the nutritional supplement, chromium is dosed in a pharmaceutically acceptable chromium compound. Useful pharmaceutically acceptable chromium compounds include, but are not limited to, chromium chloride, yeast-bound chromium, picolinate, niacin-bound chromium, and combinations thereof. The nutritional supplement may comprise up to about 10 mg of chromium dosed in a pharmaceutically acceptable form, more preferably about 0 mcg to about 150 mcg chromium, and most preferably about 120 mcg of chromium.
  • Potassium is needed to regulate water balance, levels of acidity, blood pressure and neuromuscular function. Potassium is also required for carbohydrate and protein metabolism. In the nutritional supplement, potassium is dosed in the form of a pharmaceutically acceptable potassium compound. Useful pharmaceutically acceptable potassium compounds include, but are not limited to, potassium chloride, potassium sulfate; potassium glycerophosphate, potassium citrate, potassium gluconate, potassium phosphate, and combinations thereof. The nutritional supplement may comprise up to about 3900 mg of potassium dosed in a pharmaceutically acceptable form of potassium compound, more preferably about 0 mg to about 80 mg potassium, and most preferably about 50 mg to about 80 mg of potassium.
  • Lycopene has been found to reduce the risk of cancer and it has also been found to decrease LDL cholesterol oxidation via its antioxidant capabilities. Lycopene is found primarily in tomatoes, red grapefruit, watermelon, and other sources, and is a carotenoid. The nutritional supplement may comprise up to about 6 g lycopene, more preferably about 0 mcg to about 3 g lycopene and most preferably about 300 mcg lycopene.
  • Lutein and zeaxanthin are carotenoid antioxidants that help to maintain healthy eyesight, and have been found to reduce the risk of cancer and heart disease. Lutein has been found to decrease the risk and prevent the progression of macular degeneration, the leading cause of blindness in those over the age of 65. Lutein and zeaxanthin are primarily found in yellow corn, egg yolk, spinach, broccoli and other green leafy vegetables. The nutritional supplement may comprise up to about 6 g lutein in a pharmaceutically acceptable form, more preferably about 0 mcg to about 3 g lutein and most preferably about 250 mcg lutein. The nutritional supplement may comprise up to about 6 g zeaxanthin in a pharmaceutically acceptable form, more preferably about 0 mcg to about 3 g zeaxanthin and most preferably about 300 mcg zeaxanthin.
  • Epidemiological and intervention trials have demonstrated a cardio-vascular benefit from increased levels of Omega-3 fatty acids. In a recent (2002) meta-analysis Bucher et al. looked at the beneficial effects of Omega-3 fatty acids in randomized controlled trials. This analysis included 11 trials with 7951 patients. Bucher et al. “N-3 Polyunsaturated Fatty Acids in Coronary Heart Disearch: A meta-Analysis of Randomized Control Trials;” Am. J. Med.; Mar. 2002, 112(4): pp 298-304. The trials included both dietary and supplement sources of Omega-3 fatty acids. They confirmed a statistically significant 30% reduction in the rate of sudden cardiac death in the population with increased Omega-3 fatty acid intakes from both diet and supplement sources. Preferably the nutritional supplement comprises up to about 6 g of Omega-3 fatty acids, more preferably about 0 g to about 3 g and most preferably about 1 g of Omega-3 fatty acids.
  • Chloride is needed to help maintain the ionic and fluid balance in the body, and is an essential component of gastric and intestinal secretions. Useful pharmaceutically acceptable chloride compounds include, but are not limited to, sodium chloride, chromium chloride, stannous chloride and potassium chloride. The multi-vitamin and mineral nutritional supplement preferably comprises up to about 100 mg chloride, more preferably about 0 mg to about 80 mg and most preferably about 50 mg to about 75 mg chloride.
  • The multi-vitamin and mineral nutritional supplement of the invention is intended for oral administration and may be provided in a solid form. In addition to the active material, the multi-vitamin and mineral nutritional supplement may further comprise excipients and processing aides such as: absorbents, diluents, flavorants, colorants, stabilizers, fillers, binders, disintegrants, lubricants, wetting agents, glidants, antiadherents, sugar or film coating agents, preservatives, buffer, artificial sweeteners, natural sweeteners, dispersants, thickeners, solubilizing agents and the like or some combination thereof.
  • The dosage forms of the present invention are typically considered to be solid. However, they may contain liquid or semi-solid components. Suitable “solid dosage forms of the present invention includes, but are not limited to, tablets, caplets, capsules including soft gel capsules, chewable dosage forms of and sachets and the like. The daily dosage may be included in a single delivery unit or may comprise multiple delivery units. Dividing the daily dosage among multiple delivery units may be desirable if a tablet is used, for example, to provide a tablet size that is convenient to swallow. If multiple delivery units are used, they may be administered at one time or administered at intervals during the dosage period (e.g. typically a day) if desired. Present FDA guidelines recommend that the daily dosage be divided and administered in two dosage units taken at spaced intervals. However, we note that at least three current clinical studies indicate that once daily dosing of phytosterols is efficacious. (See Plat J, et al. Effects On Serum Lipids, Lipoproteins and Fat Soluble Antioxidant Concentrations of Consuption Frequency of Margarines and Shortenings Enriched With Plant Sterol Esters. Eur J Clin Nutr 2000, 54:671-677; Matvienko OA et al. A Single Daily Dose of Soybean Phytosterols in Ground Beef Decreases Serum Total Cholesterol and LDL Cholesterol in Young Mildly Hypercholesterolemeic Men. Am J Clin Nutr 2002, 76:57-64; and Volpe, R. et al. Effects of Yogurt Enriched With Plant Sterols on Serum Lipids in Patients With Moderate Hypercholesterolemia. British Journal of Nutrition. 2001; 86:233-39.)
  • Accordingly it should be understood that the amounts of the vitamins, minerals and cholesterol reducing agents disclosed herein are for a daily dosage and that dosage may be delivered in a single delivery unit or multiple delivery units. In some embodiments packaging design may be used to facilitate identification of the proper daily dosage to the consumer. For example, a blister pack with labeling to indicate a daily dosage may be used.
  • Tableting compositions containing sterols such as phytosterol presents challenges. Phytosterol has a waxy nature, is hydrophobic, typically does not flow well in micronized form and has a low bulk density. These properties cause problems during the tablet making (tableting) process, which include, but are not limited to picking and sticking of materials to tooling, materials sticking to the press turntable during compression and poor tablet weight control. Further, phytosterol is difficult to mill because it tends to clog the mill screen unless cryo-milled. Prior to the present invention tablets high in phytosterol typically exhibited poor compressibility and once compressed had slow tablet disintegration adversely impacting delivery of the phytosterol upon ingestion. Timely disintegration is believed to be important for efficacy. As inventors believe, without wishing to be held to any theory, phytosterol acts in primary particle form in the gastrointestinal lumen.
  • The inventors have surprisingly discovered that use of certain granulating methods can yield a tablet containing at least one half the daily efficacious dose of phytosterol and at least one other vitamin or mineral in a single tablet which is a size that may be swallowed by a human. Further, the tablet of the invention disintegrates into primary particles in a time consistent with gastric emptying time, e.g. the compacted phytosterol containing tablet of the invention is believed to substantially disintegrate before reaching the gastrointestinal lumen. In one embodiment at least one half the daily efficacious dose of phytosterol and at least one half the daily efficacious dose of a plurality of vitamins and minerals are tableted in a single tablet that may be swallowed by a human and which disintegrates in time consistent with gastric emptying. In an embodiment in which a daily efficacious dose of the nutritional supplement is contained in two tablets it is preferable that the volume of each tablet is less than about 2 cubic centimeters.
  • In another embodiment an efficacious daily dose of the nutritional supplement of the invention is tableted in four tablets or less each of a size that can be swallowed by a human. Preferably when a daily efficacious dosage is contained in three or four tablets each tablet has a volume of about 1.5 cubic centimeters or less.
  • Tablet shape of a nutritional supplement is believed to contribute to several factors that may improve user compliance. The inventors believe, without being held to the theory, that oblong, oval, modified oval, and capsule shaped compacts of about 1.5 cubic centimeters in volume or less, for example are easier for a consumer to swallow than, for example, round compacts of about 1.5 cubic centimeters or less, for example. In some instances tablets that are easier to swallow may improve user compliance with the dosing regimen. FIGS. 1 to 3 show an exemplary embodiment of a tablet shape. As one skilled in the art will appreciate this shape is exemplary and any of many other shapes may be equally suitable in the practice of the invention.
  • In one embodiment, tablets may be prepared using a high shear wet-granulation method. In an exemplary high shear wet granulation method phytosterol is granulated with at least one diluent. The diluent may comprise one or more of the inorganic mineral nutrients described herein, such as, for example, a magnesium compound, or calcium compound, other active agents; inactive diluents such as, for example celluloses, cellulose derivatives, lactose or other sugars, polyols, starches, starch derivatives, polymers or mixture thereof. Utilizing one or more of the inorganic mineral nutrients as the diluent or a portion of the diluent has the advantage of minimizing added excipients and facilitates forming a smaller tablet. Dibasic calcium phosphate, and magnesium oxide are exemplary of specific magnesium and calcium compounds which both act as a nutrient and are useful as diluents. These diluents are exemplary and other diluents and granulation components or mixtures thereof known to those skilled in the art may be used for the granulation. Other granulation excipients known to those skilled in the art may be added such as povidone, disintegrants, co-disintegrants, super-disintegrants, surfactants, glidants, lubricants and binders. Further, other actives such as low dose mineral actives may be included in the granulation mixture. Inclusion of other low dose activities in the granulation may contribute only modestly to the granulation properties but addition to the granulation mixture facilitates uniform distribution of these low dose actives. In one exemplary embodiment the mixture subjected to granulation comprised the phytosterol, diluents, the binder polyvinyl pyrrolidone (PVP), the excipient crosprovidone, and water. The water was added slowly to the remaining ingredients while they were mixed in a high-shear granulator.
  • Optionally the granulation may be dried. The drying may be performed in a fluid bed dryer, for example. The granulation is milled to a suitable particle size. In one exemplarily embodiment a 0.05 screen was used. However, as one skilled in the art will appreciate this is exemplary and other sizes may be employed. After milling, the milled granulation is mixed with an absorbent. Silicon dioxide is exemplary of a suitable absorbent. Other materials known to these skilled in the art as absorbents may also be used in the practice of the invention.
  • Other vitamins, minerals and cholesterol reducing agent may be blended into the milled granulation with an absorbent preferably in an ordered blending after a portion of the absorbent is combined with the granulation. These additional components may be added as single ingredients, preformed mixes or a combination thereof. Other excipients such as flavorants, colorants, stabilizers, fillers, binders, disintegrants, lubricants, milling agents, glidants, antiadherents, preservatives, buffers, sweeteners, dispersants, thickness, solubilizing agent and the like or combination thereof may optionally be included.
  • After blending the composition may be formed into tablets using compression methods, for example. Optionally the tablets may be coated using tablet coating materials and methods such as those known to those skilled in the art. The waxy nature of the phyto sterols has been discovered to make adherence of a film-coating material to the tablet core difficult. The inventors have discovered that satisfactory adherence may be obtained using an aqueous based film-coating system comprising polyvinyl alcohol. Further, the inventors believe without wishing to be held to the theory, that using a film-coating comprising polyvinyl alcohol may improve patient compliance by yielding a tablet that is easier to swallow.
  • The inventors believe without wishing to be bound to the theory that their discovery of ordered blending of the phytosterol granulation with absorbent to coat or partially coat the granules facilitates disintegration of the tablet. Thus the inventors' discovery addresses the problem that untreated waxy phytosterols tend to form compacts with long disintegration times which are undesirable. The untreated compact compounds likely pass through the gastrointestinal track with minimum, if any, disintegration to primary particles which are believed to be necessary for efficacy.
  • The inventors further believe that the physical nature and size of the absorbent particle may modify the disintegration rate of the tablet. For example, the inventors have discovered that when the absorbent silicon dioxide was used at a 1:8 w/w ratio with phytosterols, slower disintegration was seen with a fumed silicon dioxide of about 0.2-0.3 micron particle size and about 200 meter squared per gram surface area than with a precipitated silicon dioxide of about 7 micron particle size and about 300 meter squared per gram surface area. The inventors believe that it is preferable to use precipitated silicon dioxide as described above as the absorbent for an immediate release phytosterol nutritional supplement and that a fumed silicon dioxide as described above as the absorbent may be used to modulate disintegration rate. As the physical nature and size of the absorbent appear to impact the rate of disintegration in some embodiments it may be desirable to use a mixture of absorbent types and/or particle size to facilitate obtaining the desired disintegration profile. Although silicon dioxide is referred to as an absorbent herein, the inventors note that the silicon dioxide may also function as an adsorbent (e.g. it may be a sorbent). For the purposes of this disclosure the distinction between absorbent and adsorbent is not critical and reference to absorbent should be taken to include absorbent, adsorbent, sorbents or combination thereof.
  • FIGS. 4 and 5 show exemplary disintegration date for two examples of the composition of the invention in water and acid, respectively. All examples in FIGS. 4 and 5 have disintegration times compatible with the timely disintegration in the gastrointestinal track. However, times do vary depending on the form of silicon dioxide used as FIGS. 4 and 5 show.
  • The high shear granulation method described herein is exemplary of a suitable method for preparing the composition of the invention. The inventors' also note that the wet granulation method described herein does not require expensive cryo-milling. Alternatively, methods such as dry slugging, dry roller compaction or extrusion could be used to prepare the compositions of the invention.
  • Optionally the nutritional supplement may be provided in a liquid and/or semisolid preparation. In addition to the active material such liquid and/or semisolid preparations may include excipients and processing aides such as: flavorants, colorants, stabilizers, buffers, artificial sweeteners, natural sweeteners, sequestering and/or chelating agents, dispersants, thickeners, solubilizing agents, humectants, antioxidants, emulsifiers, water, ethanol, glycerin, propylene glycol and the like or same combination thereof. The quantity of active material in a unit dose of the multi-vitamin preparation is varied according to the particular application and potency of the active ingredients.
  • Determination of the proper dosage for a particular situation is within the skill of the art. Optionally, the multi-vitamin and mineral nutritional supplement may be presented in a controlled release formulation.
  • Although the composition of the invention is preferably intended for administration to humans it should be understood that the formulation may also be utilized in veterinary applications for animals.
    • EXAMPLE 1 Multi-Vitamin and Mineral Nutritional Supplement—
  • The composition of an exemplary embodiment of the invention is provided in Table 1. This composition is representative and is one of many compositions that are within the scope of the invention and is provided for illustrative purposes. The multi-vitamin and mineral nutritional supplement exemplified in Example 1 is intended to be a daily dosage and typically would be administered in one or more dosage units (e.g. one to four tablets). If multiple dosage units are used they may be taken at one time or spaced intervals during the day.
    TABLE 1
    Ingredient Amount/Day
    Zinc 7.5 mg
    Vitamin K
    25 mcg
    Vitamin E 100 IU
    Vitamin D 400 IU
    Vitamin C
    60 mg
    Vitamin B
    6 5 mg
    Vitamin B2 (riboflavin) 1.7 mg
    Vitamin B12 200 mcg
    Vitamin A (and Vitamin A precursors) 3500 IU
    Vanadium
    10 mcg
    Tin
    10 mcg
    Thiamin 1.5 mg
    Silicon 2 mg
    Selenium
    40 mcg
    Potassium
    80 mg
    Phytosterols 800 mg
    Phosphorous 109 mg
    Pantothenic Acid
    10 mg
    Nickel
    5 mcg
    Niacin
    20 mg
    Molybdenum 75 mcg
    Manganese 2 mg
    Magnesium 100 mg
    Lycopene 300 mcg
    Lutein 250 mcg
    Iron 6 mg
    Iodine 150 mcg
    Folic Acid 800 mcg
    Copper 0.7 mg
    Chromium 120 mcg
    Chloride 72 mg
    Calcium 162 mg
    Boron 150 mcg
    Biotin
    30 mcg
    • EXAMPLE 2 Multi-Vitamin and Mineral Nutritional Supplement
  • The composition of another exemplary embodiment of the invention is provided in Table 2. This is another composition representative of the composition within the scope of the invention and is provided for illustrative purposes. The multi-vitamin and mineral nutritional supplement of Example 2 is intended to be a daily dosage and typically would be administered in one or more dosage units (e.g. one to four tablets). If multiple dosage units are used they may be taken at one time or at spaced intervals during the day.
    TABLE 2
    Ingredient Amount/Day
    Zinc 7.5 mg
    Zeaxanthin 300 mcg
    Vitamin K
    25 mcg
    Vitamin E 45 IU
    Vitamin D 400 IU
    Vitamin C 90 mg
    Vitamin B6 3 mg
    Vitamin B2 (riboflavin) 1.7 mg
    Vitamin B
    12 25 mg
    Vitamin A (and Vitamin A precursors) 3500 IU
    Vanadium
    10 mcg
    Thiamin 1.5 mg
    Silicon 2 mg
    Selenium 55 mg
    Potassium
    80 mcg
    Phytosterols 800 mg
    Phosphorous 100 mg
    Pantothenic Acid
    10 mg
    Nickel
    5 mcg
    Niacin 16 mg
    Molybdenum 45 mcg
    Manganese 2.3 mg
    Magnesium 100 mg
    Lycopene 600 mcg
    Lutein 500 mcg
    Iodine 150 mcg
    Folic Acid 600 mcg
    Copper 0.7 mg
    Chromium 50 mcg
    Choline 55 mg
    Chloride 72 mg
    Calcium 200 mg
    Boron 150 mcg
    Biotin
    30 mcg
    • EXAMPLE 3 Multi-Vitamin and Mineral Nutritional Supplement—
  • The composition of another exemplary embodiment of the invention is provided in Table 3. This is another composition representative of the composition within the scope of the invention and is provided for illustrative purposes. The multi-vitamin and mineral nutritional supplement of Example 3 is intended to be a daily dosage and typically would be administered in one or more dosage units (e.g. one to four tablets). If multiple dosage units are used they may be taken at one time or at spaced intervals during the day.
    TABLE 3
    Ingredient Amount/Day
    Zinc 7.5 mg
    Vitamin K
    25 mcg
    Vitamin E
    30 IU
    Vitamin D 400 IU
    Vitamin C
    60 mg
    Vitamin B6 5.0 mg
    Vitamin B2 (riboflavin) 1.7 mg
    Vitamin B
    12 20 mcg
    Vitamin A (and Vitamin A precursors) 3500 IU
    Vanadium
    10 mcg
    Thiamin 1.5 mg
    Silicon 2 mg
    Selenium
    20 mcg
    Potassium 64 mg
    Phytosterols 800 mg
    Phosphorous
    80 mg
    Pantothenic Acid
    10 mg
    Nickel
    5 mcg
    Niacin
    20 mg
    Molybdenum 75 mcg
    Manganese 2.0 mg
    Magnesium
    40 mg
    Lycopene 300 mcg
    Lutein 250 mcg
    Iodine 150 mcg
    Folic Acid 800 mcg
    Copper 0.7 mg
    Chromium 120 mcg
    Chloride 58 mg
    Calcium 108 mg
    Boron 32 mcg
    Biotin
    30 mcg
    Iron 6 mg
    Tn
    10 mcg
    • EXAMPLE 4
  • Method of Preparing the Nutritional Supplement—
  • One exemplary multi-vitamin and mineral nutritional supplement comprising a plurality of vitamin and mineral nutritional supplement components and phytosterol was prepared using the following wet granulation method.
  • The phytosterol was delumped using a low energy oscillation system equipped with a screen. The delumped phytosterol was then transferred to a high shear granulator and combined with MgO, and dibasic calcium phosphate diluents (which are also actives), ZnO a low dose mineral active, microcrystalline cellulose, super disintegrant and polyvinyl pyrrolidine binder were added to the granulation bowl. Granulation was begun with a low speed blending and water was added gradually with mixing to form an acceptable granulation. One skilled in the art is familiar with the appearance and physical characteristics of an acceptable granulation.
  • Once an acceptable granulation was obtained the granulation was dried in a fluid bed dryer with air at an airflow inlet temperature of about 90° C. The granulation was dried to a moisture content of not more than about 1.5% w/w as determined by an infrared loss on drying balance.
  • The dried granulation was cooled and milled at a medium speed, with knives forward using a 0.050 screen. Approximately half of the milled granulation was put into a slant cone blender, followed by #20 mesh screened silicon dioxide. The remainder of the milled granulation was added and the mixture was blended.
  • Additional active ingredients and excipients including ascorbic acid and vitamin E acetate, dibasic calcium phosphate (a second portion), chromium chloride, sodium molybdate, stannous chloride, sodium metavanadate, nickelous sulfate, sodium selenate, manganese sulfate, Biotin, vitamin K, riboflavin, thiamine mononitrate, potassium iodide, niacinamide, copper sulfate, calcium pantothenate, pyridoxine hydrochloride, folic acid, cyanocobalamin, potassium chloride, ferrous fumarate, vitamin A acetate, beta carotene, vitamin D3, lycopene, lutein, croscarmellose sodium, crospovidone, and microcrystalline cellulose (second portion) were added and blended for approximately 10 minutes. Magnesium stearate screened through a #20 mesh screen was added to the composition and blending continued for approximately 1.5 minutes.
  • The granulation thus obtained was compressed into tablets using tableting techniques known to those skilled in the art using a tablet tooling with an oval shape. The inventors believe that oblong, modified oval, and capsule shaped compacts may be easier for a consumer to swallow than round compacts of similar volume. In this embodiment a daily efficacious dosage of phytosterol and the indicated vitamins and minerals was tableted in two tablets each tablet having a volume of about 1.2 cm3.
  • The tablets were then coated using an aqueous based film-coating system comprising polyvinyl alcohol.
  • Although the foregoing invention has been described in some detail by way of illustration and examples for purposes of clarity of understanding it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims. Modification of the above-described modes of practicing the invention that are obvious to persons of skill or the art are intended to be included within the scope of the following claims.

Claims (33)

1. A nutritional supplement for administration to humans comprising:
an effective amount of at least one vitamin selected from the group consisting of Vitamin A; Vitamin C; Vitamin B6; Vitamin B2; folate; Vitamin B12; Vitamin E; and an effective amount of at least one cholesterol reducing agent selected from the group consisting of phytostanols; phytosterols, policosanols, and statins.
2. A nutritional supplement for administration to humans comprising:
an effective amount of at least one mineral selected from the group consisting of selenium, chromium and zinc, and an effective amount of at least one cholesterol reducing agent selected from the group consisting of phytosterols, phytostanols, policosanols, and statins.
3. A nutritional and mineral supplement for administration to humans comprising:
an effective amount of Vitamin A;
an effective amount of Vitamin C;
an effective amount of Vitamin B6;
an effective amount of Vitamin B2;
an effective amount of folate;
an effective amount of Vitamin B12;
an effective amount of Vitamin E; and
at least one cholesterol reducing agent selected from the group consisting of phytosterols, phytostanols, policosanols, and statins wherein the at least one cholesterol reducing agent is present in an amount effective to reduce cholesterol.
4. The composition of claim 3 further comprising at least one of an effective amount of lycopene and an effective amount of selenium.
5. A nutritional supplement for administration to humans, the supplement comprising:
at least about 800 mg of a phytosterol;
at least about 3500 I.U. of vitamin A and vitamin A precursors;
at least about 60 mg of Vitamin C;
at least about 400 I.U. of Vitamin D;
at least about 30 I.U. of vitamin E;
at least about 25 mcg of vitamin K;
at least about 1.5 mg of thiamin;
at least about 1.7 mg of vitamin B2 (riboflavin);
at least about 20 mg of niacin;
at least about 5 mg of vitamin B6;
at least about 800 mcg of folic acid;
at least about 200 mcg of vitamin B12;
at least about 30 mcg of biotin;
at least about 10 mg of pantothenic acid;
at least about 6 mg of iron dosed in the form of a pharmaceutically acceptable iron compound;
at least about 150 mcg of iodine dosed in the form of a pharmaceutically acceptable iodine compound;
at least about 40 mg of magnesium dosed in the form of a pharmaceutically acceptable magnesium compound;
at least about 7.5 mg of zinc dosed in the form of a pharmaceutically acceptable zinc compound;
at least about 20 mcg of selenium dosed in the form of a pharmaceutically acceptable selenium compound;
at least about 0.7 mg of copper dosed in the form of a pharmaceutically acceptable copper compound;
at least about 2 mg of manganese dosed in the form of a pharmaceutically acceptable manganese compound;
at least about 108 mg calcium dosed in the form of a pharmaceutically acceptable calcium compound;
at least about 80 mg of phosphorus dosed in a pharmaceutically acceptable phosphorus compound;
at least about 75 mcg of molybdenum dosed in a pharmaceutically acceptable molybdenum compound;
at least about 32 mcg boron dosed in a pharmaceutically acceptable boron compound;
at least about 5 mcg nickel dosed in a pharmaceutically acceptable nickel compound;
at least about 2 mg silicon dosed in a pharmaceutically acceptable silicon compound;
at least about 10 mcg tin dosed in a pharmaceutically acceptable tin compound;
at least about 10 mcg vanadium dosed in a pharmaceutically acceptable vanadium compound;
at least about 120 mcg of chromium dosed in the form of a pharmaceutically acceptable chromium compound;
at least about 64 mg of potassium dosed in the form of a pharmaceutically acceptable potassium compound;
at least about 58 mg of chloride dosed in the form of a pharmaceutically acceptable chloride compound;
at least about 300 mcg of lycopene dosed in the form of a pharmaceutically acceptable lycopene compound; and
at least about 250 mcg lutein dosed in the form of a pharmaceutically acceptable lutein compound.
6. A nutritional supplement for administration to humans, the supplement comprising:
about 800 mg to about 3 g phytosterols;
about 1300 I.U. to about 12,000 I.U. of vitamin A;
about 45 mg to about 250 mg of vitamin C;
about 200 I.U. to about 2000 I.U. of vitamin D;
about 20 I.U. to about 200 I.U. of vitamin E;
about 10 mcg to about 90 mcg of vitamin K;
about 1.2 mg to about 4.5 mg of thiamin;
about 1.3 mg to about 5.1 mg of vitamin B2 (riboflavin);
about 0 mg to about 550 mg of choline;
about 5 mg to about 40 mg of niacin;
about 1 mg to about 8 mg of vitamin B6;
about 0 mcg to about 1400 mcg of folic acid;
about 2.4 mcg to about 400 mcg of vitamin B12;
about 0 mcg to 300 mcg of biotin;
about 0 mg to about 16mg of pantothenic acid;
about 0 mg to about 18 mg of iron dosed in the form of a pharmaceutically acceptable iron compound;
about 0 mcg to about 300 mcg of iodine dosed in the form of a pharmaceutically acceptable iodine compound;
about 0 mg to about 100 mg of magnesium dosed in the form of a pharmaceutically acceptable magnesium compound;
about 3 mg to about 15 mg of zinc dosed in the form of a pharmaceutically acceptable zinc compound;
about 15 mcg to about 75 mcg of selenium dosed in the form of a pharmaceutically acceptable selenium compound;
about 0 mg to about 10 mg of copper dosed in the form of a pharmaceutically acceptable copper compound;
about 0 mg to about 6 mg of manganese dosed in the form of a pharmaceutically acceptable manganese compound;
about 0 mg to about 200 mg calcium dosed in the form of a pharmaceutically acceptable calcium compound;
about 0 mg to about 750 mg of phosphorus dosed in a pharmaceutically acceptable phosphorus compound;
about 0 mcg to about 250 mcg of molybdenum dosed in a pharmaceutically acceptable molybdenum compound;
about 0 mg to about 1.35 mg boron dosed in a pharmaceutically acceptable boron compound;
about 0 mcg to about 100 mcg nickel dosed in a pharmaceutically acceptable nickel compound;
about 0 mg to about 40 mg silicon dosed in a pharmaceutically acceptable silicon compound;
about 0 mcg to about 35 mcg tin dosed in a pharmaceutically acceptable tin compound;
about 6 mcg to about 25 mcg vanadium dosed in a pharmaceutically acceptable vanadium compound
about 0 mcg to about 300 mcg of chromium dosed in the form of a pharmaceutically acceptable chromium compound;
about 0 mg to about 125mg of potassium dosed in the form of a pharmaceutically acceptable potassium compound;
about 0 mg to about 120 mg of chloride dosed in the form of a pharmaceutically acceptable chloride compound;
about 0 g to about 3 g of omega-3 fatty acids;
about 0 g to about 3 g of lycopene dosed in the form of a pharmaceutically acceptable lycopene compound.;
about 0 g to about 3 g of zeaxanthin dosed in the form of a pharmaceutically acceptable zeaxanthin compound; and
about 0 g to about 3 g lutein dosed in the form of a pharmaceutically acceptable lutein compound.
7. A nutritional supplement for administration to humans, the supplement comprising:
up to about 3 g phytosterols or phytostanols,
up to about 20 mg of policosanol;
up to about 40 to 80 mg of statins;
up to about 10,000 I.U. of vitamin A and vitamin A precursors;
up to about 2 g of vitamin C;
up to about 2000 I.U. of vitamin D;
up to about 1500 I.U. of vitamin E;
up to about 1 mg of vitamin K;
up to about 100 mg of thiamin;
up to about 40 mg of vitamin B2 (riboflavin);
up to about 500 mg of niacin;
up to about 10 mg of vitamin B6;
up to about 1.5 mg of folic acid;
up to about 2 mg of vitamin B12;
up to about 900 mcg of biotin;
up to about 200 mg of pantothenic acid;
up to about 3500 mg of choline dosed in the form of a pharmaceutically acceptable choline compound;
up to about 18 mg of iron dosed in the form of a pharmaceutically acceptable iron compound;
up to about 1100 mcg of iodine dosed in the form of a pharmaceutically acceptable iodine compound;
up to about 400 mg of magnesium dosed in the form of a pharmaceutically acceptable magnesium compound;
up to about 40 mg of zinc dosed in the form of a pharmaceutically acceptable zinc compound;
up to about 400 mcg of selenium dosed in the form of a pharmaceutically acceptable selenium compound;
up to about 10 mg of copper dosed in the form of a pharmaceutically acceptable copper compound;
up to about 12 mg of manganese dosed in the form of a pharmaceutically acceptable manganese compound;
up to about 1500 mg calcium dosed in the form of a pharmaceutically acceptable calcium compound;
up to about 1250 mg of phosphorus dosed in a pharmaceutically acceptable phosphorus compound;
up to about 2000 mcg of molybdenum dosed in a pharmaceutically acceptable molybdenum compound;
up to about 20 mg boron dosed in a pharmaceutically acceptable boron compound;
up to about 1 mg nickel dosed in a pharmaceutically acceptable nickel compound;
up to about 500 mg silicon dosed in a pharmaceutically acceptable silicon compound;
up to about 200 mcg tin dosed in a pharmaceutically acceptable tin compound;
up to about 1.8 mg vanadium dosed in a pharmaceutically acceptable vanadium compound;
up to about 10 mg of chromium dosed in the form of a pharmaceutically acceptable chromium compound;
up to about 3900 mg of potassium dosed in the form of a pharmaceutically acceptable potassium compound;
up to about 150 mg of chloride dosed in the form of a pharmaceutically acceptable chloride compound;
up to about 6 g of omega-3 fatty acids;
up to about 6 g of lycopene dosed in the form of a pharmaceutically acceptable lycopene compound;
up to about 6 g of zeaxanthin dosed in the form of a pharmaceutically acceptable zeaxanthin compound; and
up to about 6 g lutein dosed in the form of a pharmaceutically acceptable lutein compound.
8. The nutritional supplement of any of claims 1-7 further comprising a diluent.
9. The nutritional supplement of claim 8 wherein the diluent is selected from the group consisting of calcium compounds, magnesium compounds, microcrystalline cellulose, starch and a combination thereof.
10. The nutritional supplement of any of claims 1-9 further comprising an absorbent.
11. The nutritional supplement of claim 10 wherein the absorbent is silicon dioxide.
12. The nutritional supplement of claim 11 wherein the silicon dioxide is selected from the group consisting of fumed silicon dioxide, precipitated silicon dioxide and a mixture thereof.
13. A method of a nutritional supplementation for a human which facilitates reduction of blood cholesterol comprising providing a human an effective amount of the nutritional supplement of any one of claims 1-12.
14. A method of making a granulation for use in tableting a nutritional supplement which comprises at least one phytosterol, the method comprising:
providing at least one phytosterol and at least one diluent;
granulating the phytosterol and the at least one diluent under high shear granulation conditions to form a granulation;
milling the granulation; and
adding an absorbent to the granulation,
and compressing the granulation to form a tablet.
15. The method of claim 14 is further comprising, adding at least one nutrient selected from the group consisting of vitamins and minerals and mixtures thereof.
16. The method of claim 14 further comprising drying the granulation.
17. The method of claim 16 wherein the drying is performed in a fluid bed dryer.
18. The method of claim 14 wherein is the diluent comprises at least one mineral.
19. The method of claim 14 wherein at least a portion of the diluent is selected from a calcium compound and a magnesium compound or a mixture thereof.
20. The method of claim 14 wherein the absorbent is silicon dioxide.
21. The method of claim 20 wherein the silicon dioxide is selected from fumed silicon dioxide, precipitated silicon dioxide and a mixtures thereof.
22. The method of claim 14 wherein once formed the tablet is coated.
23. The method of claim 22 wherein the tablet is coated with a film coat the film coat comprising polyvinyl alcohol.
24. The supplement of any of claims 1 to 12, wherein the supplement is in the form selected from a tablet, a caplet, a capsule, a chewable dosage unit or a sachet.
25. The supplement of claim 24, wherein the supplement is in the form of a tablet.
26. The supplement of claim 25, wherein the tablet is coated.
27. The supplement of claim 26, wherein the coating is a film coating.
28. The supplement of claim 27, wherein the film coat comprises polyvinyl alcohol.
29. A method of a nutritional supplementation for a human, wherein the supplementation lowers or reduces cholesterol, lowers or reduces homocystine levels or lowers or reduces low-density lipoprotein cholesterol oxidation comprising providing a human an effective amount of the nutritional supplement of any of claims 1-12.
30. The nutritional supplement of any of claims 1 to 12 wherein a daily efficacious amount of nutritional supplement comprises two tablets and wherein each of the two tablets has a volume less than about 2 cubic centimeters.
31. The nutritional supplement of any of claims 1 to 12 wherein a daily efficacious amount comprises four tablets or fewer and wherein each tablet has a volume less than 1.5 cubic centimeters.
32. The nutritional supplement of claims 30 and 31 wherein the tablets have an oblong, capsule, modified oval or oval shape.
33. The nutritional supplement of any of claims 30-32 wherein the tablets are coated with a film coating comprising polyvinyl alcohol.
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Cited By (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060210692A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Baby food composition
US20060210621A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Solid dosage form for providing a dietary supplement
US20060210516A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Article with skin protecting and moisturizing compound
US20060210688A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Dehydrated sports drink powder
US20060210697A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Infant formula composition
US20060210496A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Compositions for skin protection from ultraviolet damage
US20060210517A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Skin cleansing article
US20060292217A1 (en) * 2005-06-03 2006-12-28 Schmidt Robbin D Nutritional supplement and soft gelatin capsule delivery system
US20070020358A1 (en) * 2005-03-18 2007-01-25 Mower Thomas E Sports drink concentrate
US20080248129A1 (en) * 2007-04-05 2008-10-09 Pmc Formulas, Inc. Compounds and methods for promoting cellular health and treatment of cancer
US20090118228A1 (en) * 2007-11-07 2009-05-07 Bristol-Myers Squibb Company Carotenoid-containing compositions and methods
US20090137617A1 (en) * 2007-11-23 2009-05-28 Andrew Levy Use of haptoglobin genotyping in diagnosis and treatment of cardiovascular disease
US20090163452A1 (en) * 2007-12-20 2009-06-25 Schwartz Janice B Compositions and methods for lowering serum cholesterol
WO2009100271A1 (en) * 2008-02-07 2009-08-13 Ralph Brown Prevention of micronutrient deficiencies associated with common disabilities in the over 50 adult
US20090220619A1 (en) * 2006-04-05 2009-09-03 Wyeth Nutritional formulation
US20090269399A1 (en) * 2009-04-10 2009-10-29 Cypress Pharmaceutical, Inc. Phosphate-binding magnesium salts and uses thereof
EP2136821A2 (en) * 2007-03-12 2009-12-30 Pipex Pharmaceuticals, Inc. Oral zinc medicants useful for safely lowering free copper absorption and free copper levels
WO2010056318A2 (en) * 2008-11-12 2010-05-20 Andrew Loblaw Nutritional supplement
US20100239553A1 (en) * 2007-04-05 2010-09-23 Bartunek Arthur W Methods for promoting cellular health and treatment of cancer
US20100291240A1 (en) * 2009-05-13 2010-11-18 Wyeth Llc Method to Stabilize a Dietary Supplement to Facilitate Joint Health in Humans
US20110015277A1 (en) * 2007-12-17 2011-01-20 Wilhelmus Johannes Gertrudes Thielen Method of producing egg yolk based functional food product and products obtainable thereby
US7879375B1 (en) * 2006-06-23 2011-02-01 Arizona Pharmaceuticals, LLC Pharmaceutical composition
US7901710B2 (en) 2005-08-04 2011-03-08 Vertical Pharmaceuticals, Inc. Nutritional supplement for use under physiologically stressful conditions
US20110135753A1 (en) * 2009-12-04 2011-06-09 John Wigneswaran Nutritional Supplement For Patients With Chronic Heart Failure
US20110142766A1 (en) * 2009-12-16 2011-06-16 Sal Rafanelli Effervescent Multi-Vitamin Formulation and Methods of Use Thereof
US7998500B2 (en) 2005-08-04 2011-08-16 Vertical Pharmaceuticals, Inc. Nutritional supplement for women
US7998476B2 (en) 2006-11-22 2011-08-16 Standard Biologics, Inc. Method of treatment using Aspergillus oryzae protease
US20110223250A1 (en) * 2004-03-29 2011-09-15 Wyeth Llc Multi-vitamin and mineral nutritional supplements
US20110280955A1 (en) * 2009-01-23 2011-11-17 Wyeth Llc Nutritional Supplements For 50+ Individuals For Improving Vitality, Immunity, Eye And Bone Health
US8168611B1 (en) 2011-09-29 2012-05-01 Chemo S.A. France Compositions, kits and methods for nutrition supplementation
US8183227B1 (en) 2011-07-07 2012-05-22 Chemo S. A. France Compositions, kits and methods for nutrition supplementation
US8202546B2 (en) 2005-08-04 2012-06-19 Vertical Pharmaceuticals, Inc. Nutritional supplement for use under physiologically stressful conditions
US8263137B2 (en) 2005-08-04 2012-09-11 Vertical Pharmaceuticals, Inc. Nutritional supplement for women
WO2012137209A1 (en) * 2011-04-07 2012-10-11 Lycored Ltd Synergistic compositions and methods
US20120329764A1 (en) * 2010-01-08 2012-12-27 Beth Israel Deaconess Medical Center, Inc. Methods and compositions for the treatment of migraine headaches
US8343517B1 (en) 2011-03-08 2013-01-01 Bezzek Mark S Multivitamin-mineral longevity regimen
US20130156746A1 (en) * 2010-08-27 2013-06-20 Persavita Ltd. Composition and method of manufacture
US20140127297A1 (en) * 2011-03-08 2014-05-08 Laurent Didden Nutraceutical composition for limiting the absorption of dietary lipids and for inducing weight loss, comprising, as active agent, at least one extract of carrot
US20140216481A1 (en) * 2010-12-07 2014-08-07 Steven R. Freeman Vegetable based tobacco alternatives and articles comprising same
WO2014145072A1 (en) * 2013-03-15 2014-09-18 Everett Laboratories, Inc. Gummy compositions for nutritional supplementation
US8846061B1 (en) 2011-03-08 2014-09-30 Mark S. Bezzek Multivitamin-mineral regimens for longevity and wellness
GB2512314A (en) * 2013-03-26 2014-10-01 Kartar Singh Lalvani Statin composition
US20150079149A1 (en) * 2009-06-18 2015-03-19 Alessandra Grassi Dissolvable dietary supplement strip and methods for using the same
EP2915431A1 (en) * 2014-03-04 2015-09-09 Lifewave, Inc. A nutritional product composition for the mind
EP2915433A1 (en) * 2014-03-04 2015-09-09 Lifewave, Inc. A nutritional product composition for energy
EP2915434A1 (en) * 2014-03-04 2015-09-09 Lifewave, Inc. A nutritional product composition for increasing human growth hormone and nitric oxide production
US20160193164A1 (en) * 2013-08-15 2016-07-07 Board Of Regents, The University Of Texas System Calcium formate as a supplement to prevent neural tube defects
US9394318B2 (en) 2012-11-30 2016-07-19 Cypress Pharmaceuticals, Inc. Crystal polymorph of magnesium glycinate dihydrate and process for its preparation
EA025844B1 (en) * 2012-05-08 2017-02-28 Общество С Ограниченной Ответственностью "Лигур-М" Means for correction of hypercholesterolemia
EP3220906A4 (en) * 2014-11-19 2018-04-25 Rush University Medical Center Compositions and methods for treating lysosomal disorders
WO2018081048A1 (en) 2016-10-24 2018-05-03 Callion Pharma Antioxidant-enriched multivitamin composition and methods of use
US10039765B1 (en) 2016-02-26 2018-08-07 Michelle Ann Toothman Vitamin supplement compositions with enhanced bioavailability
US10617700B1 (en) 2016-02-26 2020-04-14 Michelle Ann Toothman Vitamin supplement compositions with enhanced bioavailability
US11007159B2 (en) * 2016-04-27 2021-05-18 Abergavenny Nv Food supplement and composition comprising choline butyrate salt and/or butyrylcholine

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20160130526A (en) * 2009-01-23 2016-11-11 와이어쓰 엘엘씨 A multivitamin/mineral formulation to combat the effects of environmental stress; improve immunity and improve energy while addressing vitamin and mineral deficiencies without the negative side effects of a mega dose nutritional supplement
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UA112182C2 (en) * 2011-05-03 2016-08-10 Сігма-Тау Індустріє Фармасьютіке Ріуніте С.П.А. Composition useful for the treatment of lipid metabolism disorders
GB201121519D0 (en) * 2011-12-14 2012-01-25 Ip Science Ltd Fat-based food products
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US9801821B2 (en) 2013-03-27 2017-10-31 Psm Healthcare Limited Stabilized vitamin D formulations
ITRM20130237A1 (en) * 2013-04-19 2013-07-19 Pelliccia Francesco FORMULATION FOR ORAL ADMINISTRATION OF A COMBINATION OF FOOD SUPPLEMENTS USEFUL FOR ENJOY CORRECT CHOLESTEROL LEVELS
US11191755B2 (en) 2014-01-17 2021-12-07 Cornell University Compositions and methods for providing cardioprotective effects
EP3094380B1 (en) 2014-01-17 2021-04-28 Cornell University Methods of treating metabolic syndrome related conditions using retinoic acid receptor agonists
CH710567A1 (en) * 2014-12-30 2016-06-30 Häcki Simone Hair growth preparation or food supplement.
BR112017018166B8 (en) * 2015-02-26 2022-07-12 Cura Global Health Bvi Ltd Mineral-enriched natural supplements
BR112018007634A2 (en) * 2015-10-16 2018-11-06 Dee Kennie stable coated oral tablet
CN107441117A (en) * 2016-05-30 2017-12-08 上海诺成药业股份有限公司 A kind of Muhivitamin Formula With Minerals calcium preparation and preparation method thereof
US11344575B2 (en) * 2016-08-15 2022-05-31 Summit Innovation Labs, LLC Vascular calcification prevention and treatment
US11357250B2 (en) 2016-08-15 2022-06-14 Summit Innovation Labs LLC Treatment and prevention of diabetes and obesity
CN106723066A (en) * 2017-01-12 2017-05-31 浙江格蕾斯生物科技有限公司 A kind of boron selenium and multivitamin compound additive
BR102019012637A2 (en) * 2019-06-18 2020-12-29 Farmoquímica S/A nutraceutical composition combining probiotics, vitamins and minerals
US20220395473A1 (en) * 2019-11-25 2022-12-15 Li Lian XU Dietary supplement
USD914868S1 (en) * 2020-04-23 2021-03-30 Access Business Group International Llc. Supplement tablet
KR102271734B1 (en) 2020-10-21 2021-07-01 한국프라임제약주식회사 Pharmaceutical composition for dry-granulation process comprising multivitamins as active pharmaceutical ingredient
DE102021117780A1 (en) 2021-07-09 2023-01-12 Aixbio Gmbh Biomimetic food supplement
DE202022106411U1 (en) 2022-11-15 2022-11-21 Aixbio Gmbh Biomimetic dietary supplement

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4021582A (en) * 1976-02-13 1977-05-03 Societe D'assistance Technique Pour Produits Nestle S.A. Water-dispersible composition and process for production
US5932561A (en) * 1997-10-24 1999-08-03 Rexall Sundown, Inc. Dietary composition with lipid binding properties for weight management and serum lipid reduction
US6087353A (en) * 1998-05-15 2000-07-11 Forbes Medi-Tech Inc. Phytosterol compositions and use thereof in foods, beverages, pharmaceuticals, nutraceuticals and the like
US6197832B1 (en) * 1999-09-14 2001-03-06 Harlan Lee Sorkin, Jr. Composition for reducing serum cholesterol levels
US6352737B1 (en) * 1999-06-25 2002-03-05 Cognis Deutschland Gmbh Use of nanoscale sterols and sterol esters
US6361800B1 (en) * 2000-04-13 2002-03-26 Cooper Concepts, Inc. Multi-vitamin and mineral supplement
US6376481B2 (en) * 1998-09-02 2002-04-23 Mcneil-Ppc, Inc. Sterol esters in tableted solid dosage forms
US20020068095A1 (en) * 2000-12-01 2002-06-06 Chen Qi Cholesterol lowering supplement
US20020103139A1 (en) * 2000-12-01 2002-08-01 M. Weisspapir Solid self-emulsifying controlled release drug delivery system composition for enhanced delivery of water insoluble phytosterols and other hydrophobic natural compounds for body weight and cholestrol level control
US6544973B1 (en) * 1995-07-28 2003-04-08 Raisio Benecol Ltd. Substance for lowering high cholesterol level in serum and methods for preparing and using the same
US6576285B1 (en) * 2000-11-14 2003-06-10 Sunpure Ltd. Cholesterol lowering beverage
US20030108591A1 (en) * 2001-08-10 2003-06-12 Lipton, Division Of Conopco Composition for lowering blood cholesterol
US6589588B1 (en) * 1998-05-06 2003-07-08 Raisio Benecol Oy Phytosterol compositions
US20030133965A1 (en) * 2000-05-15 2003-07-17 Bruno Roberto Luis Application of phytosterols (and their isomers), folic acid, cyanocobalamin and pyridoxin in dietetic (alimentary) fibers
US20030203854A1 (en) * 2002-04-23 2003-10-30 Ivo Pischel Composition for effecting serum cholesterol levels
US6673831B1 (en) * 1996-04-17 2004-01-06 Merck & Co., Inc. Combination therapy for reducing the risks associated with cardiovascular disease
US20040018248A1 (en) * 2001-11-29 2004-01-29 Adrianne Bendich Composition containing statins and calcium for improved cardiovascular health
US20040033202A1 (en) * 2002-06-10 2004-02-19 Elan Pharma International, Ltd. Nanoparticulate sterol formulations and novel sterol combinations

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3881005A (en) * 1973-08-13 1975-04-29 Lilly Co Eli Pharmaceutical dispersible powder of sitosterols and a method for the preparation thereof
FR2693876A1 (en) * 1992-07-24 1994-01-28 Vani Micro-nutrient compsn. to combat the effects of stress - contains B vitamin(s), octacosanol, calcium, magnesium, chromium and zinc and opt. other micro-nutrients
CH685283A5 (en) 1993-09-21 1995-05-31 Inpharma Sa cholesterol-lowering dietary compositions.
US5869084A (en) * 1994-06-20 1999-02-09 K-V Pharmaceuticals Co. Multi-vitamin and mineral supplements for women
US6488956B1 (en) * 1994-06-20 2002-12-03 Drugtech Corporation Multi-vitamin and mineral supplements for women
US5571441A (en) * 1994-11-01 1996-11-05 The Procter & Gamble Company Nutrient supplement compositions providing physiologic feedback
ES2079327B1 (en) * 1994-12-13 1996-08-01 Lilly Sa PHARMACEUTICAL FORMULATIONS OF CEFACLOR.
US6139832A (en) 1995-02-08 2000-10-31 Human Genome Sciences, Inc. Leukocyte adhesion inhibitor-1 (LAI-1) Polypeptides
US6197862B1 (en) * 1995-09-18 2001-03-06 Daikin Industries, Ltd. Filled polytetrafluoroethylene granular powder and process for the production thereof
EP0904082A4 (en) * 1996-04-17 2001-09-26 Merck & Co Inc Combination therapy for reducing the risks associated with cardiovascular disease
US5654011A (en) * 1996-07-30 1997-08-05 Energetics, Inc. Dietary supplements
US6929807B1 (en) * 1996-08-09 2005-08-16 Mannatech, Inc. Compositions of plant carbohydrates as dietary supplements
US6139872A (en) * 1996-08-14 2000-10-31 Henkel Corporation Method of producing a vitamin product
SI1037634T1 (en) * 1997-12-08 2006-02-28 Altana Pharma Ag Oral administration form comprising a proton pump inhibitor (e.g.pantoprazole)
US5952393A (en) * 1998-02-12 1999-09-14 Sorkin, Jr.; Harlan Lee Composition for reducing serum cholesterol levels
US6110502A (en) * 1998-02-19 2000-08-29 Mcneil-Ppc, Inc. Method for producing water dispersible sterol formulations
ZA994696B (en) * 1998-09-09 2000-01-31 Pharmachoice Healthcare Pty Lt Nutritional healthcare formulation.
WO2000015201A2 (en) 1998-09-10 2000-03-23 Forbes Medi-Tech Inc. Compositions comprising one or more phytosterols, phytostanols or mixtures of both and one or more alpha, beta, delta, or gamma tocotrienols or derivatives thereof and use of the compositions in treating or preventing cardiovascular disease, its underlying conditions and other disorders
US6274170B1 (en) * 1999-02-18 2001-08-14 Richard Heibel Compounds for cardiovascular treatment comprising multi-vitamin and anti-platelet aggregating agents and methods for making and using the same
US6914073B2 (en) * 1999-03-18 2005-07-05 Bristol Myers Squibb Company Vitamin formulation for cardiovascular health
ATE273992T1 (en) * 1999-06-23 2004-09-15 Forbes Medi Tech Inc CONJUGATES OF ASCORBIC ACID AND PHYTOSTEROLS OR PHYTOSTANOLS AND THEIR USE IN THE TREATMENT OF VASCULAR DISEASES
JP4381543B2 (en) * 2000-02-17 2009-12-09 株式会社ファンケル Food composition and method for producing the same
US6299896B1 (en) * 2000-04-13 2001-10-09 Cooper Concepts, Inc. Multi-vitamin and mineral supplement
BR0001794A (en) * 2000-05-15 2001-12-26 Laboratorios Biosintetica Ltda Application of phytosteroids (and their isomers), folic acid, cyanocobalamin and pyridoxine in dietary fibers (food)
US20030165572A1 (en) * 2000-09-01 2003-09-04 Nicolas Auriou Water-dispersible encapsulated sterols
US20030096018A1 (en) * 2000-12-15 2003-05-22 Schloss Caroline Maxine Multi-vitamin and hormone replacement supplement
BRPI0206641B8 (en) * 2001-01-26 2021-05-25 Merck Sharp & Dohme use of a sterol absorption inhibitor
DE60221367T2 (en) * 2001-03-15 2008-04-03 Dsm Ip Assets B.V. COMPOSITION FOR THE PREVENTION OF OSTEOPOROSIS CONSISTING OF A COMBINATION OF ISOFLAVONES AND POLYUNG-SATURATED FATTY ACIDS
US7090862B2 (en) * 2001-03-30 2006-08-15 Abbott Laboratories Method of improving the antioxidant status of an infant
CN1827766B (en) * 2001-06-28 2010-08-25 徐荣祥 In vitro cell cultivation method
DK1443912T3 (en) * 2001-10-12 2008-01-21 Elan Pharma Int Ltd Compositions with a combination of immediate and controlled release properties
WO2003090723A1 (en) * 2002-04-23 2003-11-06 Bristol-Myers Squibb Company Modified-release vasopeptidase inhibitor formulation, combinations and method
WO2003103640A1 (en) 2002-06-10 2003-12-18 Elan Pharma International, Ltd Nanoparticulate formulations comprising hmg coa reductase inhibitor derivatives (“statins”), novel combinations thereof as well as manufacturing of these pharmaceutical compositions
US6953588B2 (en) * 2002-10-25 2005-10-11 Cooper Concepts, Inc. Multi-vitamin and mineral supplement
DE20316876U1 (en) 2003-11-03 2004-02-05 China Vital Med E.K. Food supplement, useful for preventing deficiency states and illness and for increasing body defenses, contains vitamins C, E and B12, isoflavones, polyphenols, beta-carotene, selenium, lycopene and zinc
US8968768B2 (en) * 2004-03-29 2015-03-03 Wyeth Llc Phytosterol nutritional supplements
MY151326A (en) * 2004-03-29 2014-05-15 Wyeth Corp Multi-vitamin and mineral nutritional supplements
WO2008049196A1 (en) * 2006-10-27 2008-05-02 Iomedix Development International Srl Composition for improving blood cholesterol levels
US8491937B2 (en) * 2007-02-15 2013-07-23 Wyeth Llc Stability in vitamin and mineral supplements
US20080254119A1 (en) * 2007-04-16 2008-10-16 Wyeth Imbedded liquid lubricants for tableting
CA2691691C (en) * 2007-06-20 2013-09-24 Seth J. Baum Compositions and methods of treating chronic kidney disease

Patent Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4021582A (en) * 1976-02-13 1977-05-03 Societe D'assistance Technique Pour Produits Nestle S.A. Water-dispersible composition and process for production
US6544973B1 (en) * 1995-07-28 2003-04-08 Raisio Benecol Ltd. Substance for lowering high cholesterol level in serum and methods for preparing and using the same
US6673831B1 (en) * 1996-04-17 2004-01-06 Merck & Co., Inc. Combination therapy for reducing the risks associated with cardiovascular disease
US5932561A (en) * 1997-10-24 1999-08-03 Rexall Sundown, Inc. Dietary composition with lipid binding properties for weight management and serum lipid reduction
US6589588B1 (en) * 1998-05-06 2003-07-08 Raisio Benecol Oy Phytosterol compositions
US6087353A (en) * 1998-05-15 2000-07-11 Forbes Medi-Tech Inc. Phytosterol compositions and use thereof in foods, beverages, pharmaceuticals, nutraceuticals and the like
US6376481B2 (en) * 1998-09-02 2002-04-23 Mcneil-Ppc, Inc. Sterol esters in tableted solid dosage forms
US6352737B1 (en) * 1999-06-25 2002-03-05 Cognis Deutschland Gmbh Use of nanoscale sterols and sterol esters
US6197832B1 (en) * 1999-09-14 2001-03-06 Harlan Lee Sorkin, Jr. Composition for reducing serum cholesterol levels
US20010034338A1 (en) * 1999-09-14 2001-10-25 Sorkin Harlan Lee Composition and method for reducing serum cholesterol levels
US6361800B1 (en) * 2000-04-13 2002-03-26 Cooper Concepts, Inc. Multi-vitamin and mineral supplement
US20030133965A1 (en) * 2000-05-15 2003-07-17 Bruno Roberto Luis Application of phytosterols (and their isomers), folic acid, cyanocobalamin and pyridoxin in dietetic (alimentary) fibers
US6576285B1 (en) * 2000-11-14 2003-06-10 Sunpure Ltd. Cholesterol lowering beverage
US20020068095A1 (en) * 2000-12-01 2002-06-06 Chen Qi Cholesterol lowering supplement
US20020103139A1 (en) * 2000-12-01 2002-08-01 M. Weisspapir Solid self-emulsifying controlled release drug delivery system composition for enhanced delivery of water insoluble phytosterols and other hydrophobic natural compounds for body weight and cholestrol level control
US20030108591A1 (en) * 2001-08-10 2003-06-12 Lipton, Division Of Conopco Composition for lowering blood cholesterol
US20040018248A1 (en) * 2001-11-29 2004-01-29 Adrianne Bendich Composition containing statins and calcium for improved cardiovascular health
US20030203854A1 (en) * 2002-04-23 2003-10-30 Ivo Pischel Composition for effecting serum cholesterol levels
US20040033202A1 (en) * 2002-06-10 2004-02-19 Elan Pharma International, Ltd. Nanoparticulate sterol formulations and novel sterol combinations

Cited By (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110223250A1 (en) * 2004-03-29 2011-09-15 Wyeth Llc Multi-vitamin and mineral nutritional supplements
US7749545B2 (en) 2005-03-18 2010-07-06 Sakura Properties, Llc Fucoidan compositions and methods for dietary and nutritional supplements
US7666448B2 (en) 2005-03-18 2010-02-23 Sakura Properties, Llc Skin cleansing article
US20060210688A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Dehydrated sports drink powder
US20060210697A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Infant formula composition
US20060210496A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Compositions for skin protection from ultraviolet damage
US20060211652A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Method of making a partially hydrolyzed fucoidan composition
US20060210517A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Skin cleansing article
US20060210516A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Article with skin protecting and moisturizing compound
US20070020358A1 (en) * 2005-03-18 2007-01-25 Mower Thomas E Sports drink concentrate
US7838004B2 (en) 2005-03-18 2010-11-23 Sakura Properties, Llc Method of making a partially hydrolyzed fucoidan composition
US20060210692A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Baby food composition
US7776365B2 (en) 2005-03-18 2010-08-17 Sakura Properties, Llc Article with skin protecting and moisturizing compound
US20060210621A1 (en) * 2005-03-18 2006-09-21 Mower Thomas E Solid dosage form for providing a dietary supplement
US7722902B2 (en) 2005-03-18 2010-05-25 Sakura Properties, Llc Solid dosage form for providing a dietary supplement
US20060292217A1 (en) * 2005-06-03 2006-12-28 Schmidt Robbin D Nutritional supplement and soft gelatin capsule delivery system
US7901710B2 (en) 2005-08-04 2011-03-08 Vertical Pharmaceuticals, Inc. Nutritional supplement for use under physiologically stressful conditions
US8263137B2 (en) 2005-08-04 2012-09-11 Vertical Pharmaceuticals, Inc. Nutritional supplement for women
US8197854B2 (en) 2005-08-04 2012-06-12 Vertical Pharmaceuticals, Inc. Nutritional supplement for use under physiologically stressful conditions
US8202546B2 (en) 2005-08-04 2012-06-19 Vertical Pharmaceuticals, Inc. Nutritional supplement for use under physiologically stressful conditions
US7998500B2 (en) 2005-08-04 2011-08-16 Vertical Pharmaceuticals, Inc. Nutritional supplement for women
US8263667B2 (en) 2005-08-04 2012-09-11 Vertical Pharmaceuticals, Inc. Nutritional supplement for use under physiologically stressful conditions
US20090220619A1 (en) * 2006-04-05 2009-09-03 Wyeth Nutritional formulation
US20120294983A1 (en) * 2006-04-05 2012-11-22 Wyeth Llc Nutritional Formulation
US9420819B2 (en) * 2006-04-05 2016-08-23 Wyeth Llc Nutritional formulation
US7879375B1 (en) * 2006-06-23 2011-02-01 Arizona Pharmaceuticals, LLC Pharmaceutical composition
US7998476B2 (en) 2006-11-22 2011-08-16 Standard Biologics, Inc. Method of treatment using Aspergillus oryzae protease
EP2136821A4 (en) * 2007-03-12 2013-01-16 Pipex Pharmaceuticals Inc Oral zinc medicants useful for safely lowering free copper absorption and free copper levels
EP2136821A2 (en) * 2007-03-12 2009-12-30 Pipex Pharmaceuticals, Inc. Oral zinc medicants useful for safely lowering free copper absorption and free copper levels
US7794758B2 (en) * 2007-04-05 2010-09-14 Pmc Formulas, Inc. Compounds and methods for promoting cellular health and treatment of cancer
US20080248129A1 (en) * 2007-04-05 2008-10-09 Pmc Formulas, Inc. Compounds and methods for promoting cellular health and treatment of cancer
US8394425B2 (en) 2007-04-05 2013-03-12 Pmc Formulas, Inc. Methods for promoting cellular health and treatment of cancer
US20100239553A1 (en) * 2007-04-05 2010-09-23 Bartunek Arthur W Methods for promoting cellular health and treatment of cancer
US20090118228A1 (en) * 2007-11-07 2009-05-07 Bristol-Myers Squibb Company Carotenoid-containing compositions and methods
US20090137617A1 (en) * 2007-11-23 2009-05-28 Andrew Levy Use of haptoglobin genotyping in diagnosis and treatment of cardiovascular disease
US20110015277A1 (en) * 2007-12-17 2011-01-20 Wilhelmus Johannes Gertrudes Thielen Method of producing egg yolk based functional food product and products obtainable thereby
US20090163452A1 (en) * 2007-12-20 2009-06-25 Schwartz Janice B Compositions and methods for lowering serum cholesterol
WO2009100271A1 (en) * 2008-02-07 2009-08-13 Ralph Brown Prevention of micronutrient deficiencies associated with common disabilities in the over 50 adult
US20110165291A1 (en) * 2008-11-12 2011-07-07 Andrew Loblaw Nutritional supplement
WO2010056318A3 (en) * 2008-11-12 2010-07-29 Andrew Loblaw Nutritional supplement
WO2010056318A2 (en) * 2008-11-12 2010-05-20 Andrew Loblaw Nutritional supplement
US9398776B2 (en) * 2009-01-23 2016-07-26 Wyeth Llc Nutritional supplements for 50+ individuals for improving vitality, immunity, eye and bone health
US20110280955A1 (en) * 2009-01-23 2011-11-17 Wyeth Llc Nutritional Supplements For 50+ Individuals For Improving Vitality, Immunity, Eye And Bone Health
AU2010206796B2 (en) * 2009-01-23 2014-03-27 Pf Consumer Healthcare 1 Llc Nutritional supplements for 50+ individuals for improving vitality, immunity, eye and bone health
US8236358B1 (en) 2009-04-10 2012-08-07 Cypress Pharmaceutical, Inc. Phosphate-binding magnesium salts and uses thereof
US9889157B2 (en) 2009-04-10 2018-02-13 Cypress Pharmaceuticals, Inc. Phosphate-binding magnesium salts and uses thereof
US9339481B2 (en) 2009-04-10 2016-05-17 Cypress Pharmaceuticals, Inc. Phosphate-binding magnesium salts and uses thereof
US20090269399A1 (en) * 2009-04-10 2009-10-29 Cypress Pharmaceutical, Inc. Phosphate-binding magnesium salts and uses thereof
US8247000B2 (en) * 2009-04-10 2012-08-21 Cypress Pharmaceutical, Inc. Phosphate-binding magnesium salts and uses thereof
US9610267B2 (en) 2009-04-10 2017-04-04 Cypress Pharmaceuticals, Inc. Phosphate-binding magnesium salts and uses thereof
US20110045063A2 (en) * 2009-04-10 2011-02-24 Cypress Pharmaceutical, Inc. Phosphate-binding magnesium salts and uses thereof
US9592202B2 (en) * 2009-05-13 2017-03-14 Wyeth Llc Method to stabilize a dietary supplement to facilitate joint health in humans
US20100291240A1 (en) * 2009-05-13 2010-11-18 Wyeth Llc Method to Stabilize a Dietary Supplement to Facilitate Joint Health in Humans
US9498434B2 (en) * 2009-06-18 2016-11-22 Alessandra Grassi Dissolvable dietary supplement strip and methods for using the same
US20150079149A1 (en) * 2009-06-18 2015-03-19 Alessandra Grassi Dissolvable dietary supplement strip and methods for using the same
WO2011068920A1 (en) * 2009-12-04 2011-06-09 Nephroceuticals, Llc Nutritional supplement for patients with chronic heart failure
US20110135753A1 (en) * 2009-12-04 2011-06-09 John Wigneswaran Nutritional Supplement For Patients With Chronic Heart Failure
US20110142766A1 (en) * 2009-12-16 2011-06-16 Sal Rafanelli Effervescent Multi-Vitamin Formulation and Methods of Use Thereof
US20120329764A1 (en) * 2010-01-08 2012-12-27 Beth Israel Deaconess Medical Center, Inc. Methods and compositions for the treatment of migraine headaches
US9486464B2 (en) * 2010-08-27 2016-11-08 Persavita Ltd Composition and method of manufacture
US20130156746A1 (en) * 2010-08-27 2013-06-20 Persavita Ltd. Composition and method of manufacture
US20140216481A1 (en) * 2010-12-07 2014-08-07 Steven R. Freeman Vegetable based tobacco alternatives and articles comprising same
US11206863B2 (en) * 2010-12-07 2021-12-28 Steven R. Freeman Vegetable based tobacco alternatives and articles comprising same
US20140127297A1 (en) * 2011-03-08 2014-05-08 Laurent Didden Nutraceutical composition for limiting the absorption of dietary lipids and for inducing weight loss, comprising, as active agent, at least one extract of carrot
US9161565B1 (en) 2011-03-08 2015-10-20 Mark S. Bezzek Multivitamin-mineral regimens for longevity and wellness
US9167839B1 (en) 2011-03-08 2015-10-27 Mark S. Bezzek Multivitamin-mineral regimens for longevity and wellness
US8343517B1 (en) 2011-03-08 2013-01-01 Bezzek Mark S Multivitamin-mineral longevity regimen
US8846061B1 (en) 2011-03-08 2014-09-30 Mark S. Bezzek Multivitamin-mineral regimens for longevity and wellness
AU2012240955B2 (en) * 2011-04-07 2017-05-11 Lycored Ltd Synergistic compositions and methods
US8460718B2 (en) 2011-04-07 2013-06-11 Lycored Ltd. Synergistic compositions and methods
WO2012137209A1 (en) * 2011-04-07 2012-10-11 Lycored Ltd Synergistic compositions and methods
US8183227B1 (en) 2011-07-07 2012-05-22 Chemo S. A. France Compositions, kits and methods for nutrition supplementation
US8168611B1 (en) 2011-09-29 2012-05-01 Chemo S.A. France Compositions, kits and methods for nutrition supplementation
US8545896B2 (en) 2011-09-29 2013-10-01 Chemo S. A. France Compositions, kits and methods for nutrition supplementation
EA025844B1 (en) * 2012-05-08 2017-02-28 Общество С Ограниченной Ответственностью "Лигур-М" Means for correction of hypercholesterolemia
US10150784B2 (en) 2012-11-30 2018-12-11 Cypress Pharmaceuticals, Inc. Crystal polymorph of magnesium glycinate dihydrate and process for its preparation
US9394318B2 (en) 2012-11-30 2016-07-19 Cypress Pharmaceuticals, Inc. Crystal polymorph of magnesium glycinate dihydrate and process for its preparation
WO2014145072A1 (en) * 2013-03-15 2014-09-18 Everett Laboratories, Inc. Gummy compositions for nutritional supplementation
GB2512314A (en) * 2013-03-26 2014-10-01 Kartar Singh Lalvani Statin composition
US20160193164A1 (en) * 2013-08-15 2016-07-07 Board Of Regents, The University Of Texas System Calcium formate as a supplement to prevent neural tube defects
US9895328B2 (en) * 2013-08-15 2018-02-20 Board Of Regents, The University Of Texas System Calcium formate as a supplement to prevent neural tube defects
EP2915434A1 (en) * 2014-03-04 2015-09-09 Lifewave, Inc. A nutritional product composition for increasing human growth hormone and nitric oxide production
EP2915433A1 (en) * 2014-03-04 2015-09-09 Lifewave, Inc. A nutritional product composition for energy
EP2915431A1 (en) * 2014-03-04 2015-09-09 Lifewave, Inc. A nutritional product composition for the mind
EP3220906A4 (en) * 2014-11-19 2018-04-25 Rush University Medical Center Compositions and methods for treating lysosomal disorders
US10617700B1 (en) 2016-02-26 2020-04-14 Michelle Ann Toothman Vitamin supplement compositions with enhanced bioavailability
US10039765B1 (en) 2016-02-26 2018-08-07 Michelle Ann Toothman Vitamin supplement compositions with enhanced bioavailability
US11318150B1 (en) 2016-02-26 2022-05-03 Michelle Ann Toothman Vitamin supplement compositions with enhanced bioavailability
US11007159B2 (en) * 2016-04-27 2021-05-18 Abergavenny Nv Food supplement and composition comprising choline butyrate salt and/or butyrylcholine
US11642322B2 (en) 2016-04-27 2023-05-09 Abergavenny Nv Food supplement and composition comprising choline butyrate salt and/or butyrylcholine
US20190281876A1 (en) * 2016-10-24 2019-09-19 Callion Pharma, Llc Antioxidant-enriched multivitamin composition and methods of use
WO2018081048A1 (en) 2016-10-24 2018-05-03 Callion Pharma Antioxidant-enriched multivitamin composition and methods of use
US11229230B2 (en) * 2016-10-24 2022-01-25 Callion Pharma, Llc Antioxidant-enriched multivitamin composition and methods of use

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