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WO2010096564A2 - Compléments alimentaires contenant des acides gras oméga-3 polyinsaturés et des bactéries probiotiques avec bénéfices gastro-intestinaux et dermatologiques potentiels - Google Patents

Compléments alimentaires contenant des acides gras oméga-3 polyinsaturés et des bactéries probiotiques avec bénéfices gastro-intestinaux et dermatologiques potentiels Download PDF

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Publication number
WO2010096564A2
WO2010096564A2 PCT/US2010/024594 US2010024594W WO2010096564A2 WO 2010096564 A2 WO2010096564 A2 WO 2010096564A2 US 2010024594 W US2010024594 W US 2010024594W WO 2010096564 A2 WO2010096564 A2 WO 2010096564A2
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supplement
fatty acids
per gram
polyunsaturated fatty
skin
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PCT/US2010/024594
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English (en)
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WO2010096564A3 (fr
WO2010096564A4 (fr
Inventor
Yoshiteru Koide
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Probiohealth Llc
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Publication of WO2010096564A3 publication Critical patent/WO2010096564A3/fr
Publication of WO2010096564A4 publication Critical patent/WO2010096564A4/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
    • A61K38/014—Hydrolysed proteins; Derivatives thereof from animals from connective tissue peptides, e.g. gelatin, collagen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/92—Oral administration

Definitions

  • This patent disclosure pertains to the field of dietary supplements, nutrition and neutra- ceuticals, and also to the fields of dermatology, cosmetics, and intestinal microflora.
  • Sephora (San Francisco), a retail beauty product supplier, lists pages of beauty dietary supplements on its Web site.
  • N.V. Perricone M. D. CosmeceuticalsTM (Meriden, CT) created a neutraceutical line "[s]pecially formulated to work from the inside out.
  • [T]Ns nutritional system combines synergistic powerful antioxidants, B-complex energy enhancers, macrominerals, lipotropic factors, enzymes, and herbal extracts.”
  • InjuvTM is a dietary supplement manufactured by Softgel Technologies (Los Angeles) that contains 9% low molecular weight hyaluronic acid. It is promoted to ward off the aging process by helping the body's tissues retain moisture and keep skin smooth and elastic.
  • the cosmetic company Shiseido (Osaka, Japan) developed the Collagen EX Drink for Beautiful SkinTM, which purports to continue collagen growth and contains a balance of moisture ingredients to improve skin's suppleness.
  • Health by Chocolate (New Jersey) offers the organic Instant Bliss Beauty DrinkTM infused with skin-supporting cranberry seed oil for omega 3/6/9, blueberries, lutein, lycopene, beta-carotene, and astaxanthin for their antioxidant properties.
  • nutrients that look particularly promising in fighting the outward signs of aging include tretinoin, a substance in the vitamin A family that has been shown to reduce fine wrinkles, splotchy pigmentation, and rough skin associated with chronic sun exposure; alpha hydroxy acids derived from fruit and milk; retinols of the vitamin A family; and topical antioxidants, especially vitamins C and E, which function to help cells repair damage caused by ultraviolet radiation and smoking.
  • the invention described here is a new family of dietary and nutritional supplements that have been proven in clinical trials to be safe for human consumption.
  • Use of the prototype supplement was associated with subjective observations of improvement in softness and moisture of facial skin, reduction in wrinkles, and improvement in function of the gastrointestinal tract.
  • a dietary supplement according to this invention contains an appropriate or effective amount polyunsaturated fatty acids (PUFAs) (typically at least 100 or 200 mg), and a culture of probiotic organisms (typically at least 5 x 10 8 CFU's).
  • the dietary supplement can be made by combining a source of lipids and a source of probiotic microorganisms at a sufficiently high concentration to attain the desired level of PUFAs in the final product.
  • the PUFAs contained in the supplement typically include omega-3 fatty acids, omega-6 fatty acids, or both, and can be provided by way of a botanical source.
  • Suitable probiotic organisms in the culture include a sub-species of Lactobacillus or Bifidobacterium (or a mixture of strains selected from either or both). Exemplary is the L. casei strain KE-99.
  • the dietary supplement may also contain a separate source of amino acids, either in the form of free amino acids, peptides, or protein. Hydrolyzed collagen, exemplified by fish collagen, is perceived as having particular advantages. Another possible ingredient is vitamin E, which may be added separately, or present as a constitutive component of a botanical oil used as a source of fatty acids.
  • the dietary supplements of this invention can be provided in capsule or tablet form, or as a food item such as a chocolate confectionary.
  • the invention includes multiple daily doses of the supplement packaged in a container for human use, optionally with written information on consumption of the product or possible use. Also included are methods of manufacture.
  • the supplement may be used or prescribed for any dietary or health related objective, such as to augment consumption of polyunsaturated fatty acids, improve skin health or appearance, or to manage microflora in the gastrointestinal tract, with related health benefits.
  • the prototype contains cranberry seed oil as a source of omega-3 and omega-6 polyunsaturated fatty acids, and a source of Vitamin E.
  • the prototype supplement contains a special strain of Lactobacillus casei as a probiotic culture. It also contains the optional ingredient of hydrolyzed fish collagen.
  • the three ingredients are combined for easy consumption in vegetable- source hydroxypropylmethylcellulose capsule, or as a chocolate confectionary. Each of the three ingredients confer dietary benefits on their own, as described below, allowing the consumer to get three beneficial supplements in the convenience of a single product.
  • ingredients also work together synergistically in a manner that powerfully enhances each other's activity, further promoting the beneficial effects.
  • the source of polyunsaturated fatty acids and the collagen are believed to supply nutrients directly beneficial to the skin, with the probiotic bacteria promoting their absorption and utilization.
  • Direct benefits of the dietary supplements of this invention include augmentation of essential fatty acids and vitamins in the diet, and rebalancing of gut bacteria which helps to improve or sustain gastrointestinal health.
  • the clinical trial detailed in Example 1 demonstrates that the dietary supplement is safe and also has the potential to provide downstream benefits: in particular a cross- dimensional improvement in characteristics of facial skin of the consumer.
  • Unsaturated fatty acids The dietary supplements of this invention contain polyunsaturated fatty acids (PUFAs), typically from one or more natural sources.
  • PUFAs polyunsaturated fatty acids
  • Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) play a key role in human physiochemistry, including inflammatory and neurological pathways. They are referred to as essential fatty acids and are primarily obtained from diet.
  • Mammalian tissue sources can provide one or more PUFAs selected from the omega-3 fatty acids eicosapentaenoic acid (EPA) (20:5) and docosahexaenoic acid (DHA) (22:6), and the omega- 6 fatty acids gamma-linolenic acid (GLA) (18:3), dihomo-gamma-linoenic acid (DGLA) (20:3), and arachidonic acid (AA) (20:4).
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • GLA gamma-linolenic acid
  • DGLA dihomo-gamma-linoenic acid
  • AA arachidonic acid
  • Vegetable oils typically contain ⁇ -linolenic acid (18:3, omega-3), and/or linoleic acid (18:2, omega-6).
  • Good sources of ⁇ -linolenic acid include rapeseed (canola) oil, soybean oil, cranberry seed oil, walnut oil, flaxseed (linseed) oil, perilla oil, chia oil, and hemp oil.
  • Good sources of linoleic acid include corn oil, cottonseed oil, soybean oil, safflower oil, poppy seed oil, hemp oil, walnut oil, sunflower oil, wheat germ oil, grape seed oil, and cranberry seed oil.
  • oils can be separated by distillation or other means to further enrich the proportion of PUFAs.
  • the reader can use a combination of sources with at least one PUFA from each group, or choose a single source that provides both.
  • Cranberry seed oil is exemplary, in part because it provides linoleic acid and ⁇ -linolenic acid in about a 1 :1 ratio.
  • the fatty acid profile is between about 70% and 95% total PUFA by weight, with 30-38% linoleic acid (omega-6), 20-38% ⁇ -linolenic acid (omega-3), 22-26% oleic acid (omega- 9), and 2-6% palmitic acid (a saturated fatty acid).
  • Cranberry seed oil extract includes a concentrated source of potent antioxidant phenolics and anthocyanin with phenolics at a concentration of 1 1 mg/g and anthocyanin at 1.5 mg/g.
  • the oil also contains Vitamin E (tocopherols and tocotrienols; about 30 mg/g), phytosterols, phospholipids and Vitamin A. Besides its nutritional value, the Vitamin E helps to extend the shelf life of the oil.
  • the dietary supplements of this invention contain probiotics. These are microorganisms, particularly bacteria or yeast that (as defined by the World Health Organization) have the potential when administered in adequate amounts to confer a health benefit on the host. Health benefits of probiotics are well established. Their primary effect is to help restore balance to the microflora in the gastrointestinal tract. Direct benefits of this include improved regularity and less gas. Probiotics are also thought to strengthen the immune system to combat allergies, and help the body deal with excessive alcohol intake, stress, exposure to toxic substances, and certain diseases. It is also a hypothesis of this invention that (in conjunction with the other ingredients in the dietary supplement), probiotics are beneficial for the skin.
  • probiotic culture refers to a plurality of probiotic microorganisms that (upon suspension or reconstitution in a suitable growth medium) will create a proliferating and sustainable source of live cells.
  • the probiotic culture is not growing while in the dietary supplement, but has been freeze-dried or otherwise preserved in a manner that enables it to be reconstituted in the laboratory or in the gastrointestinal tract into a growing cell population.
  • Probiotic organisms that may be suitable for use in this invention include Bifidobacterium bifidum, B. breve, B. infantis, B. lactis, B. longum, Lactobacillus acidophilus, L brevis, L. bulgaricus, L casei, L paracasei, L plantarum, L rhamnosus, L. salivarius, L lactis, Streptococcus thermophilus, and Sacchromyces boulardii, all of which are available from MAK Wood lnc (Grafton Wl).
  • Exemplary is the L. casei strain KE-99 (also designated KE-01 ) available from the American Type Culture Collection (ATCC), 10801 University Boulevard., Manassas VA 20110, U.S.A., under Accession No. PTA-3945.
  • ATCC American Type Culture Collection
  • the strain and edible oil derivatives are protected by U.S. Patent Nos. 6,797,266 and 7,214,370.
  • the KE-99 strain was selected from traditional fermented yogurt-like Asian dairy products with at least a ten-year history of safe human consumption.
  • the strain was identified as having the following characteristics: i) resistance to low pancreatic juice; ii) adherence ability to sub-epithelial matrices such as BiocoatTM Matrigel (Becton Dickinson, Bedford, Mass.) and to cultured intestinal epithelial cells (Caco-2 cell line); iii) an ability to competitively exclude enterohemorrhagic E. coli serotype O157:H7 adherent to collagen matrices; and iv) a capacity to reduce ammonia and sulfide containing compounds.
  • KE-99 When fed to piglets, KE-99 resulted in colonization of the gut and fecal shedding of lactobacilli. There was a corresponding reduction of fecal coliform counts, ammonia products, and sulfide products in the gut, resulting in weight gains in the treated animals.
  • KE-99 can be grown in a suitable nutrient medium (such as Lactobacilli MRS broth from
  • freeze-dried powder the microbial mass is harvested in a sanitized separator and the slurry of cell concentrate is freeze-dried, typically in a mixture of carriers containing anhydrous dextrose and trehalose. Spray-dried Grade-A low-heat non-fat pasteurized milk can also be included as a cryoprotectant.
  • the freeze-dried KE01 concentrate can then be milled to fine powder for combining with the other components in the supplement.
  • the dietary supplements of this invention optionally also contain a source of amino acids: either as free amino acids, small peptides, or protein.
  • a source of amino acids either as free amino acids, small peptides, or protein.
  • most or all of the essential amino acids are supplied: i.e., the L-enantiomers of phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, leucine, and lysine.
  • Amino acids thought to be important in skin growth, maintenance and prepare include arginine, cysteine, methionine, glycine, and proline.
  • Essential amino acids can be supplied in the form of an animal protein (such as whey protein), or a mixture of plant proteins from different sources.
  • Type I collagen is an important structural constituent of human skin.
  • Collagen is a left- handed triple peptide helix containing high levels of glycine and of proline in standard or hydroxylated form.
  • Collagen in the diet will contain about the same balance of amino acids as collagen in the skin.
  • collagen in dietary supplements according to this invention (if included) will be in the form of hydrolyzed collagen which has been chemically, physically, or enzymatically processed into a lower molecular weight form (e.g., an average of about 1 kDa, 3 kDa, or 5 kDa) so that it can more easily be handled by the gastrointestinal tract.
  • Hydrolyzed collagen consists of water-soluble peptides which are rich sources of the amino acids glycine, L-proline and L-hydroxyproline.
  • Nutritional supplements containing hydrolyzed collagen are marketed for osteoporosis, osteoarthritis, rheumatoid arthritis, weight loss, and to assist in recovery from exercise and sports-related injuries.
  • Fish collagen is exemplary, because it has substantial levels of L-threonine and L- methionine, two essential amino acids. Threonine has a role in the elastin of skin. Methionine is important for growth, healthy nails and skin. Eastoe JE, Biochem J. 1957; 65(2): 363-368.
  • dietary supplements may contain one or more vitamins or other micronutrients. These include Vitamin E, Vitamin C, and Vitamin A retinols, their precursors, and related compounds having the same activity. Other possible constituents are coenzyme Q10, lycopene, and L-hydroxyproline.
  • a dietary supplement can be described as having a "substantial amount" of any of these components if a daily dose contains at least 10% (preferably at least 50%) of the recommended daily allowance or daily value, as recommended by the Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences in partnership with Health Canada.
  • the RDA for Vitamins E, C, and A are 30 IU (about 20 mg), 60 mg, and 5,000 IU, respectively.
  • These ingredients may each be added separately during manufacture, or they may be a constitutive component in one of the other ingredients: for example, Vitamin E and its functional equivalents are constitutively present in cranberry seed oil.
  • the dietary supplements may also contain nutrients or prebiotics to support the growth of the probiotic microorganisms.
  • prebiotics refers to non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improve host health, and are often in the form of oligosaccharides.
  • Some oligosaccharides that are used in this manner are fructooligosaccharides (FOS), xylooligosaccharides (XOS), polydextrose and galactooligosaccharides (GOS).
  • Trehalose Cargill, Minneapolis MN
  • Fillers and non-toxic preservatives can also be included if desired. Appropriate selection of ingredients (as illustrated in Example 2) can yield a product that has an acceptable shelf-life (at least 1 month, preferably at least 6 months) with no added preservatives.
  • the ingredients of the dietary supplements of this invention are believed to work together synergistically in a manner that powerfully enhances each other's activity, further promoting the beneficial effects.
  • the polyunsaturated fatty acids and the amino acid source supply nutrients that may be directly beneficial to the skin, with the probiotic bacteria promoting their absorption and utilization.
  • the probiotic culture can improve gastrointestinal health and function, which in turn is believed to improve absorption of polyunsaturated fatty acids and vitamins, thereby boosting their systemic and dermatological effects.
  • the probiotic microorganisms also generate arylamidases: Oakey HJ, Harty DWS, Knox KW, J. Appl. Bacteriology 1995; 78:142-148.
  • Arylamidases are protein-digesting enzymes that may help break down small peptides in the hydrolyzed collagen and other dietary protein, improving absorption and subsequent processing.
  • the source of polyunsaturates and the collagen in the supplement are believed to have a prebiotic effect, supporting the probiotic culture so that it may overgrow less beneficial microorganisms that may otherwise be present in the G.I. tract.
  • the fatty acids may also act as a storage and transport medium for the probiotic culture, which makes it easier to encapsulate and more suitable for long-term storage with limited loss of probiotic activity.
  • Antioxidants like Vitamin E and other phytonutrients in the fatty acid source may help keep the probiotic bacteria in a quiescent state, and otherwise help prevent spoilage, thereby improving long-term stability and storage of the combined dietary supplement.
  • the dietary supplements of the invention are assembled by combining together the source(s) of polyunsaturated fatty acid, the probiotic(s), and one or more of the optional components (if included).
  • freeze-dried L. casei strain KE-99 can be combined with standard nutritional (GRAS) or USP grade cranberry seed oil and GRAS or USP grade hydrolyzed fish collagen.
  • each of the sources is sufficiently concentrated to yield a product that enables the consumer to receive the benefit of all the active ingredients in a daily dose of between 200 mg and 5 grams.
  • the supplement will typically comprise at least 50, 100, 200, or 500 mg, up to about 800 mg of fatty acids per gram, of which preferably at least 50% are polyunsaturates.
  • the supplement will also typically comprise at least 0.2 billion, 1 billion, 5 billion or 20 billion colony forming units (CFU's) of probiotic organisms per gram, often between 1 and 10 billion CFU's (or about 2.5 mg of bacteria) per gram. If the supplement contains hydrolyzed collagen or other amino acid source, the amount present will typically be at least 50, 200, or 500 mg, up to about 800 mg per gram.
  • the manufacturer can supply the dietary supplement in the form of a powder or oil that can be measured out on a daily basis. More conveniently, a daily dose can be compounded into one or more capsules, such as vegetable-source hydroxypropylmethylcellulose. Alternatively, tablets can be formed by combining the active ingredients with a compatible dry excipient, such as dried milk fat powder with a moisture level below 5%, and then pressing or drying the mixture into tablet shape. The desired dosage may be divided between multiple capsules or tablets, so that two or more constitute a daily allotment of the supplement.
  • a daily dose can be compounded into one or more capsules, such as vegetable-source hydroxypropylmethylcellulose.
  • tablets can be formed by combining the active ingredients with a compatible dry excipient, such as dried milk fat powder with a moisture level below 5%, and then pressing or drying the mixture into tablet shape.
  • the desired dosage may be divided between multiple capsules or tablets, so that two or more constitute a daily allotment of the supplement.
  • the dietary supplement is compounded in the form of a food item, such as a high-energy or compact food with a shelf-life of a month or more.
  • a food item such as a high-energy or compact food with a shelf-life of a month or more.
  • Sweet or savory items such as snack foods or confectionaries are exemplary.
  • chocolate has a stabilizing effect on probiotics such as L. casei KE-99.
  • a daily dose of probiotic is combined with dark chocolate, milk chocolate, or white chocolate along with a daily dose of omega-3 fatty acids and optionally hydrolyzed fish collagen or another source of amino acids as described above.
  • the amount of chocolate and other food or filler ingredients is chosen to provide a food product where one mouthful or small serving (perhaps 5, 10, or 20 g) has the intended daily dose of active ingredients.
  • single chocolate wafers manufactured in this way were subsequently determined to have essentially no loss of probiotic activity, retaining 6.5 to 7.9 billion CFU of L. casei KE-99 per wafer.
  • a yogurt bar was manufactured that was subsequently determined to contain 350 million CFU L. casei KE-99 per 10 g.
  • One or more weeks' or months' supply of any of these dosage forms can be packaged in a suitable container for commercial distribution.
  • the package may have (or may be distributed in conjunction with) written information about consumption of the product or possible use of the product to improve skin health or appearance.
  • Dietary supplements are produced in compliance with the requirements of regulatory authorities for the jurisdiction in which they will be distributed. In the U.S., manufacturing should comply with current good manufacturing practices (cGMP), using controls that result in a consistent product free of contamination, with accurate labeling.
  • cGMP current good manufacturing practices
  • the reader is referred to the following textbooks: Bennett B & Cole G eds., Guide to Pharmaceuticals Production (Institution of Chemical Engineers, Great Britain, 2003). Gad SC, Pharmaceutical Manufacturing Handbook (Wiley-lnterscience, 2008). Bunn G and NaIIy JD, Good Manufacturing Practices for Dietary Supplements: A Compliance Manual (Amer Pharmaceutical Assn, 2009).
  • the dietary supplements of this invention may be consumed or prescribed in any amount or frequency that the user determines is appropriate.
  • the daily dose is typically at least 200 mg of the supplement, typically between about 0.5 and 3 grams.
  • the daily dose may be scaled back in proportion to their weight and metabolic needs.
  • the supplements may be consumed once daily or in divided doses.
  • the supplements have been designed primarily with a view for consumption by human subjects. Veterinary use is also feasible, incorporating adaptations in formulation and dosage where appropriate.
  • the products of this invention provide a supplementary source of essential fatty acids, probiotic microorganisms, amino acids (when included), and other micronutrients. Dietary consumption of polyunsaturated fatty acids and amino acids in general will increase their bioavailability (i.e., the ability of metabolic systems in the body to access or make use of these components).
  • Probiotic bacteria and other microorganisms in a dietary supplement of this invention may improve the balance of microflora in the gut, thereby benefiting the gastrointestinal system in terms of general health and function.
  • Example 1 shows that the dietary supplement can be used to reduce intestinal gas, increase regularity, and otherwise assist in reduction of gastrointestinal upset.
  • Example 1 also demonstrates that the dietary supplements of the invention are safe, and have a potential to improve characteristics of facial skin. Regular consumption of such supplements may ultimately inspire the mirror on the wall to proclaim that the user is indeed the fairest of them all.
  • dietary supplements of the invention may promote health in other physiological processes, such as urinary, neurological, vascular, and circulatory function, and reduction in inflammation or circulating cholesterol levels has not escaped us.
  • embodiments of the invention may or may not have any of the biological activities or benefits referred to in this disclosure.
  • discussion of synergies between the components of the dietary supplements in this disclosure is provided to enhance the understanding and interest of the reader, and is not intended to be limiting.
  • embodiments of the invention may or may not provide direct evidence of the functional synergies referred to earlier in this disclosure.
  • Example 1 Clinical evaluation
  • Daily dose for this study was 4 capsules, each containing 275 mg cranberry seed oil, 5 billion CFU's of KE-99, and 120 mg hydrolyzed fish collagen.
  • Study design A baseline skin system and corneometer readings for each subject were taken and recorded upon entry into the study and were repeated every two weeks to assess the moisturizing, smoothening and anti-wrinkle effect of the test product.
  • the skin system and the corneometry readings for each subject were taken from the designated area of the face.
  • a template of the test areas were made for every patient to ensure that the skin system and corneometer readings were taken from the same area on subsequent follow-ups.
  • the subjects were given one week's supply of the supplement and were instructed to take two capsules twice daily. They were advised to avoid prolonged sun-exposure and refrain from applying any moisturizers or any anti-aging products on the face. Supplement refills were provided weekly. The subjects were brought back to the test center every 2 weeks for subjective and instrumental evaluation.
  • a structured interview questionnaire was to determine the subject's experience with possible gastro-intestinal discomfort or improvement in skin condition, according to the following scale:
  • the skin smoothening efficacy was evaluated as moderate to marked in 35% of the subjects as early as week 4. By week 8 the moderate to marked evaluation increased to 67% of the subjects.
  • SkinSysTM (Sometech, Seoul, South Korea) is professional skin analysis and treatment software that provide well-organized scientific evaluation of cosmetic products.
  • the skin analysis and measuring functions are (i) analyze dry, oily, normal and combination skin, (ii) analyze the skin curvature with showing 3D analysis method, (anti-wrinkle) (iii) analyze keratin through precise edge detection algorithm, (iv) Analyze the exact size of pore and pigmentation, (v) advise the cause of skin condition and solution through a skin diagnosis wizard.
  • CoScamTM 3E (Skin and Hair Diagnosing Digital Camera System) (Beauty Korea World Co Ltd., Seoul, South Korea) is an image management system with the following features: (i) provides clear image using illuminating cap to reduce reflection, (ii) provides various magnification ratios of X12, X14, X40, X50, and X100, (iii) more effective for diagnosis of scalp and hair cuticle conditions using X400-X500 lens and guide cap and (iv) can diagnose capillary expansion and pigmented area in dermis layer.
  • the measurement sites were the right and the left area of facial skin over the cheek bone. Results are shown in the following table (p values were determined by Student's f-test, comparing levels after treatment with the measurement taken at onset of the study, Week 0).
  • Corneometer quantifies the degree of moisture/hydration state of the skin surface. While the skin's sebaceous glands excretes sebum, the skin's sweat glands excretes sweat forming an emulsion that serve as the skin's natural acid protection barrier known as the skin's hydrophilic firm, that serves to hydrate or moisture the skin to keep the skin supple, and to prevent the penetration of harmful external substance. According to the Corneometer principle, epidermal moisture of the stratum corneum is measured on the basis of capacitance. Corneometer determination of skin- moisture levels provides data on condition and type of skin as well as on the effects of drugs and cosmetics on the moisture contents of stratum corneum.
  • each gelcap contained the following: 330 mg of cranberry seed oil, 2.5 mg of Lactobacillus casei strain KE-99 (5 billion CFU), and 220 mg of hydrolyzed fish collagen. It can be manufactured for commercial distribution using the following ingredients according to the following procedure.
  • Cranberry seed oil is obtained from Green Source Organics, Boynton Beach FL. It is manufactured by a CO 2 expeller extraction of cranberry seeds using low shear methods, which reduces heat. No solvents or chemicals are used during any step of the process. The product is an unrefined oil which is then lightly filtered and flushed with nitrogen and then packaged. Typical concentration of polyunsaturated amino acids (wt/wt) are Omega-3 30 to 35%; Omega-6 32 to 37%; Omega-9 20 to 24%. Typical concentration of Vitamin E and Vitamin E analogs are ⁇ -tocopherol 241 ⁇ g/g; ⁇ -tocopherol 110 ⁇ g/g; ⁇ -tocotrienol 1700 ⁇ g/g.
  • L. casei strain KE-99 is supplied by Probioferm LLC, Des Moines Iowa. Following fermentation of starter culture in medium in a fermentation tank, the bacteria are separated by centrifugation, made into a slurry, freeze-dried, and powdered. The product is generally refrigerated or stored frozen before use in making the supplement . Colony forming units (CFU's, a measure of live bacteria) are assayed by standard plate assay before and after fermentation, in the slurry, and after freeze-drying. Concentration is typically about 200 billion (2 x 10 11 ) CFU's per gram, which means that 50 mg contains -10 billion CFU's.
  • CFU's Colony forming units
  • Hydrolyzed fish collagen is supplied by Norland Products Inc., Cranbury NJ.
  • the collagen is extracted according to standard methods from the skin of deep water ocean fish: primarily cod, haddock or pollock.
  • the extract is then hydrolyzed with acid and then further hydrolyzed with a food grade enzyme to break down the molecular weight to an average of about 3,000.
  • After filtering, purification and concentration, the collagen was sterilized by steam injection and spray-dried.
  • Fish collagen prepared in this fashion has a high protein content, is very water soluble and has minimal odor and taste. It meets the purity requirements of the United States, European and Japanese pharmacopeia.
  • the product is manufactured using standard cGMP practices for over-the-counter nutritional products with documentation showing how the product was made and tested. Manufacturing and testing, operational methodologies and procedures (such as manufacturing, cleaning, and analytical testing) are validated as suitable for preparing the product for human consumption.
  • the L. Casei and collagen are measured and mixed together using a standard pharmaceutical wet/dry blender.
  • the cranberry seed oil is then added to the dry ingredients.
  • the mixture is then incorporated into hydroxypropylmethylcellulose capsules using a standard pharmaceutical liquid injection machine and then double sealed to prevent leakage.
  • the weight of the filled capsule is 553 grams. No preservatives are required.

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Abstract

Cette invention porte sur une nouvelle famille de compléments alimentaires contenant des acides gras polyinsaturés, une culture probiotique et facultativement du collagène hydrolysé. Le complément prototype contient de l'huile de graines de canneberges en tant que source d'acides gras oméga 3 et oméga 6, conjointement avec de la vitamine E. Le complément prototype contient également une souche spéciale de Lactobacillus casei ainsi que du collagène de poisson. Les compléments nutritionnels de cette invention peuvent être fournis sous forme de gélule ou de comprimé, ou sous forme d'articles alimentaires tels que des confiseries à base de chocolat. Chacun des trois ingrédients confère un bénéfice propre, permettant au consommateur d'obtenir trois compléments alimentaires avec la commodité d'un seul produit. Les ingrédients sont également pensés fonctionner de manière synergique pour obtenir un effet global plus important et plus durable. Dans des essais cliniques humains, la consommation du complément alimentaire a été associée à des observations subjectives d'amélioration de la douceur et de l'hydratation de la peau du visage, la réduction des rides, et l'amélioration de la fonction du tractus gastro-intestinal.
PCT/US2010/024594 2009-02-19 2010-02-18 Compléments alimentaires contenant des acides gras oméga-3 polyinsaturés et des bactéries probiotiques avec bénéfices gastro-intestinaux et dermatologiques potentiels WO2010096564A2 (fr)

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2973650A1 (fr) * 2011-04-08 2012-10-12 Frederic Pottecher Moyens pour masquer le gout et l'odeur d'hydrolysats peptidiques
EP2710901A1 (fr) * 2012-09-20 2014-03-26 Symrise AG Composition de supplément diététique
EP2749288A3 (fr) * 2012-12-28 2014-07-23 Aromtech Ltd Capsule et composition comprenant de l'huile de graines
US9211277B2 (en) 2013-02-07 2015-12-15 Young Living Essential Oils, Lc Dietary supplement composition
US9427012B2 (en) 2010-08-10 2016-08-30 R.P. Scherer Technologies, Llc Process of manufacturing a stable softgel capsule containing microencapsulated probiotic bacteria
US20190091159A1 (en) * 2017-09-26 2019-03-28 Captek Softgel International Orally available articles containing at least one stabilized supplement therein
EP3595695A1 (fr) * 2017-03-15 2020-01-22 Rousselot B.V. Compositions de peptides de collagène hydrolysé et de micro-organismes commensaux et leurs procédés
IT201900008394A1 (it) * 2019-06-07 2020-12-07 Sofar Spa Composizione per uso nel trattamento delle malattie infiammatorie croniche intestinali
EP3806867A4 (fr) * 2018-07-16 2022-07-06 Lonza Consumer Health Inc. Supplément de collagène et de matière cellulaire et son procédé d'administration
WO2024144735A1 (fr) * 2022-12-28 2024-07-04 Chivalric Regulus Biyoteknoloji Anonim Sirketi Complément alimentaire microencapsulé contenant des micro-organismes probiotiques
WO2024167478A1 (fr) * 2023-02-06 2024-08-15 Toplu Celal Chocolat, gaufrette, gaufrette au tahini, biscuit à la crème et biscuit à la crème au tahini enrichis en acide alpha-linolénique oméga-3 essentiel

Family Cites Families (4)

* Cited by examiner, † Cited by third party
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US20040009160A1 (en) * 2001-06-22 2004-01-15 Villamar Daniel F Bioactive food complex, method for making bioactive food complex product and method for controlling disease
DK1992351T3 (en) * 2007-05-18 2016-06-06 Nestec Sa Lactobacillus johnsonii for the prevention of post-surgical infection
EP2173856A1 (fr) * 2007-06-28 2010-04-14 Chr. Hansen A/S Traitement de suspension de cellules
MX2010001260A (es) * 2007-08-03 2010-04-07 Shaklee Corp Sistema de suplemento nutricional.

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9427012B2 (en) 2010-08-10 2016-08-30 R.P. Scherer Technologies, Llc Process of manufacturing a stable softgel capsule containing microencapsulated probiotic bacteria
WO2012137146A3 (fr) * 2011-04-08 2013-03-28 Pottecher Frederic Moyens pour masquer le gout et l'odeur d'hydrolysats peptidiques
FR2973650A1 (fr) * 2011-04-08 2012-10-12 Frederic Pottecher Moyens pour masquer le gout et l'odeur d'hydrolysats peptidiques
EP2710901A1 (fr) * 2012-09-20 2014-03-26 Symrise AG Composition de supplément diététique
EP2749288A3 (fr) * 2012-12-28 2014-07-23 Aromtech Ltd Capsule et composition comprenant de l'huile de graines
US9211277B2 (en) 2013-02-07 2015-12-15 Young Living Essential Oils, Lc Dietary supplement composition
EP3595695A1 (fr) * 2017-03-15 2020-01-22 Rousselot B.V. Compositions de peptides de collagène hydrolysé et de micro-organismes commensaux et leurs procédés
US20190091159A1 (en) * 2017-09-26 2019-03-28 Captek Softgel International Orally available articles containing at least one stabilized supplement therein
US11896720B2 (en) * 2017-09-26 2024-02-13 Captek Softgel International Orally available articles containing at least one stabilized supplement therein
EP3806867A4 (fr) * 2018-07-16 2022-07-06 Lonza Consumer Health Inc. Supplément de collagène et de matière cellulaire et son procédé d'administration
IT201900008394A1 (it) * 2019-06-07 2020-12-07 Sofar Spa Composizione per uso nel trattamento delle malattie infiammatorie croniche intestinali
EP3979825A1 (fr) * 2019-06-07 2022-04-13 SOFAR S.p.A. Composition destinée à être utilisée dans un procédé de prévention ou de traitement de la malnutrition chez un sujet souffrant de maladies intestinales inflammatoires chroniques
WO2024144735A1 (fr) * 2022-12-28 2024-07-04 Chivalric Regulus Biyoteknoloji Anonim Sirketi Complément alimentaire microencapsulé contenant des micro-organismes probiotiques
WO2024167478A1 (fr) * 2023-02-06 2024-08-15 Toplu Celal Chocolat, gaufrette, gaufrette au tahini, biscuit à la crème et biscuit à la crème au tahini enrichis en acide alpha-linolénique oméga-3 essentiel

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