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WO2008152015A1 - Composition for the improvement of functional difficulties due to articular cartilage disorders - Google Patents

Composition for the improvement of functional difficulties due to articular cartilage disorders Download PDF

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Publication number
WO2008152015A1
WO2008152015A1 PCT/EP2008/057151 EP2008057151W WO2008152015A1 WO 2008152015 A1 WO2008152015 A1 WO 2008152015A1 EP 2008057151 W EP2008057151 W EP 2008057151W WO 2008152015 A1 WO2008152015 A1 WO 2008152015A1
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Prior art keywords
composition
functional
oral administration
weight
composition according
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PCT/EP2008/057151
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French (fr)
Inventor
Julian Agut Sanchez
Carlos Fernandez Navarro
Gabriel Espelleta Gil
Miquel Junca Riuro
Josep Junca Busquets
Ferran Junca Riuro
Jaime MELENDO BAÑOS
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Masterfarm, S.L.
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Publication of WO2008152015A1 publication Critical patent/WO2008152015A1/en

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    • AHUMAN NECESSITIES
    • A21BAKING; EDIBLE DOUGHS
    • A21DTREATMENT OF FLOUR OR DOUGH FOR BAKING, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS
    • A21D2/00Treatment of flour or dough by adding materials thereto before or during baking
    • A21D2/08Treatment of flour or dough by adding materials thereto before or during baking by adding organic substances
    • A21D2/14Organic oxygen compounds
    • A21D2/145Acids, anhydrides or salts thereof
    • AHUMAN NECESSITIES
    • A21BAKING; EDIBLE DOUGHS
    • A21DTREATMENT OF FLOUR OR DOUGH FOR BAKING, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS
    • A21D2/00Treatment of flour or dough by adding materials thereto before or during baking
    • A21D2/08Treatment of flour or dough by adding materials thereto before or during baking by adding organic substances
    • A21D2/24Organic nitrogen compounds
    • A21D2/26Proteins
    • A21D2/261Animal proteins
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23CDAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00Milk preparations; Milk powder or milk powder preparations
    • A23C9/12Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/13Fermented milk preparations; Treatment using microorganisms or enzymes using additives
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23CDAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00Milk preparations; Milk powder or milk powder preparations
    • A23C9/12Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/13Fermented milk preparations; Treatment using microorganisms or enzymes using additives
    • A23C9/1322Inorganic compounds; Minerals, including organic salts thereof, oligo-elements; Amino-acids, peptides, protein-hydrolysates or derivatives; Nucleic acids or derivatives; Yeast extract or autolysate; Vitamins; Antibiotics; Bacteriocins
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23CDAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00Milk preparations; Milk powder or milk powder preparations
    • A23C9/152Milk preparations; Milk powder or milk powder preparations containing additives
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23CDAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00Milk preparations; Milk powder or milk powder preparations
    • A23C9/152Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/1526Amino acids; Peptides; Protein hydrolysates; Nucleic acids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23CDAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00Milk preparations; Milk powder or milk powder preparations
    • A23C9/152Milk preparations; Milk powder or milk powder preparations containing additives
    • A23C9/154Milk preparations; Milk powder or milk powder preparations containing additives containing thickening substances, eggs or cereal preparations; Milk gels
    • A23C9/1544Non-acidified gels, e.g. custards, creams, desserts, puddings, shakes or foams, containing eggs or thickening or gelling agents other than sugar; Milk products containing natural or microbial polysaccharides, e.g. cellulose or cellulose derivatives; Milk products containing nutrient fibres
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/142Amino acids; Derivatives thereof
    • A23K20/147Polymeric derivatives, e.g. peptides or proteins
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/163Sugars; Polysaccharides
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/20Feeding-stuffs specially adapted for particular animals for horses
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/40Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/18Peptides; Protein hydrolysates
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23PSHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00Shaping or working of foodstuffs characterised by the products
    • A23P10/40Shaping or working of foodstuffs characterised by the products free-flowing powder or instant powder, i.e. powder which is reconstituted rapidly when liquid is added
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728Hyaluronic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/737Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/01Hydrolysed proteins; Derivatives thereof
    • A61K38/012Hydrolysed proteins; Derivatives thereof from animals
    • A61K38/014Hydrolysed proteins; Derivatives thereof from animals from connective tissue peptides, e.g. gelatin, collagen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a composition comprising polymers of protein origin or cellulose, acrylic or carbohydrate derivatives for the improvement of functional difficulties which are a result of articular cartilage disorders.
  • the present invention relates to uses of the mentioned composition and to functional foods and food supplements comprising it.
  • gelatine hydrolysates are also useful as coadjuvants in the treatments intended to compensate the calcium deficit and that they are also useful in the treatment and prevention of hip dysplasia in dogs as described in patent document ES2104507.
  • the inventors of the present invention developed a high-purity enzymatic collagen hydrolysate with a better bioavailability due to its lower molecular weight (between 5000 and 20000 daltons).
  • This hydrolysate is distributed under the trade name Colatech® and a study was conducted with it in 100 healthy volunteers, this collagen being administered in a dose of 10 g per day to 50 of them and to the other 50 volunteers a dose of 1 .5 g per day of glucosamine sulphate, a product widely used both in Europe and in the United States at this dose for the treatment of articular disorders in general.
  • antioxidants such as lycopene obtained from tomato, resveratrol which can be obtained from Yucca schidigera and even vitamin C are being used as natural anti-inflammatory agents (Riso P, Visioli F, Grande S, Guarneri S, Gardana C, Simonetti P, Porrini M. Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress, J. Agric Food Chem. 2006 Apr 5; 54 (7): 2563-6; Liu X, Qu D, he F, Lu Q, Wang J, Cai D. Effect of Lycopene on the vascular endothelial function and expression of inflammatory agents in hyperhomocysteinemic rats, Asia Pac J Clin Nutr.
  • Natural bioflavonoids such as luteolin, naringin, quercetin, apigenin and genistein are also being widely used in dietary or food supplements due to their antiinflammatory action allowing their application in different disorders presenting inflammation (Nam N. H., Naturally occurring NF-kappaB inhibitors, Mini Rev. Med. Chem. 2006 Aug; 6 (8):945-51 ; Kumazawa Y. Kawaguchi K. Takimoto H., lmmunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha, Curr. Pharm. Des. 2006,12 (32); 4271 -9; Ruiz P. A.
  • Haller D. Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells, J. Nutr. 2006 Mar;136 (3); 664-71 ; Ruiz PA, Braune A, Holziwimmer G, Quintanilla - Fend L, Haller D., Quercetin inhibits TNF-induced NF-kappaB transcription factor recruitment to proinflammatory gene promoters in murine intestinal epithelial cells, J.Nutr. 2007 May; 137 (5); 1208 - 15).
  • Collagen has also been used in the field of food supplements to obtain preparations favouring the recovery of cartilage in animals suffering from diseases linked to this type of tissue.
  • a food supplement must be understood as any additional dietary intake which is consumed orally and contains a "food ingredient" intended to supplement the diet.
  • Some examples of dietary or food supplements are vitamins, minerals, herbs (a single herb or a mixture of several herbs), other botanical products, amino acids and food components such as enzymes.
  • Food supplements are generally distributed in the form of different presentations such as pastilles, capsules, soft gelatine capsules, gelatine capsules, liquids and powders.
  • Functional foods are nowadays also becoming known in the nutrition field. Functional foods are considered to be those foods which are consumed as part of a normal diet and contain biologically active components offering health benefits and reducing the risk of suffering from diseases. Foods containing certain minerals, vitamins, fatty acids or dietary fibre, foods to which biologically active substances such as phytochemicals or other antioxidants have been added, and probiotics, having live cultures of beneficial microorganisms, are emphasized among some examples of functional foods. Some yoghurts with probiotics, some margarines enriched with sterol esters and eggs rich in omega-3-type fatty acids are examples of functional foods.
  • hyaluronic acid When hyaluronic acid is associated with a polymer of protein origin or cellulose, acrylic or carbohydrate derivatives, hydrogen bonds are formed between the structure of the polymer, for example, of the collagen hydrolysate (amino and hydroxyl groups capable of forming this type of bond) and the hyaluronic acid molecule, favouring the passage of the latter through cell membranes and subsequently improving its absorption and causing an improvement in its activity.
  • collagen hydrolysate amino and hydroxyl groups capable of forming this type of bond
  • the polymer is a cellulose derivative, being an enzymatic collagen hydrolysate.
  • the composition for oral administration according to the invention is characterized in that it can further comprise other functional ingredients such as natural bioflavonoids and antioxidants.
  • the enzymatic collagen hydrolysate preferably has a molecular weight comprised between 1 ,000 and 50,000 daltons.
  • the composition for oral administration comprises from 96% to 99.5% by weight of enzymatic collagen hydrolysate, from 0.25% to 0.60% by weight of hyaluronic acid, from 1.0% to 2.5% of antioxidant agents and/or from 0.40% to 0.90% by weight of natural bioflavonoids being able to be incorporated to this association.
  • the natural bioflavonoids are chosen from the group consisting of quercetin, naringin, luteolin, apigenin, genistein, hesperidin or a mixture of at least two of them.
  • hyaluronic acid is in the form of sodium salt.
  • the composition comprises as an antioxidant at least one of those of the group consisting of beta-carotene, lycopene, resveratrol as well as their derivatives.
  • resveratrol refers to its cis and trans isomers and to mixtures thereof, as well to its derivatives by glycosylation of its hydroxyl groups; esterification of said hydroxyl groups or amides thereof in any of its isomeric forms.
  • the composition further comprises vitamin C, which will preferably be in the form of ascorbic acid.
  • composition for oral administration object of the invention further comprises mineral salts.
  • composition for oral administration further comprises B group vitamins and/or coenzymes, liposoluble vitamins and coenzyme Q10.
  • composition for oral administration according to the invention is also characterized in that it further comprises a coadjuvant compound selected from the group consisting of glucosamine sulphate and chondroitin sulphate.
  • composition for oral administration according to the invention is characterized in that it is in the form of a suspension.
  • composition for oral administration according to the invention is characterized in that it is in the form of a powder which is dispersible or soluble in an aqueous medium.
  • composition for oral administration according to the invention is also characterized in that it is in the form of a solution.
  • composition for oral administration according to the invention which is in the form of tablets or capsules is equally preferred.
  • Another object of the present invention is a functional food comprising a composition with polymers of protein origin or cellulose, acrylic or carbohydrate derivatives associated with natural bioflavonoids, antioxidants and hyaluronic acid in the form of acid or of their salts, as has been described above.
  • the functional food is preferably in the form of yoghurt, shake, custards, fruit juices, biscuits or energy bars.
  • Another object of the present invention is the use of the previously described compositions for the preparation of functional foods and food supplements for the improvement of the functional capacity and/or the quality of life of a mammal with functional difficulties derived from articular cartilage disorders.
  • the daily dose of the enzymatic collagen hydrolysate is comprised between 0.075 and 0.200 g per Kg of weight
  • the daily dose of bioflavonoids is comprised between 0.00025 and 0.001 g per Kg of weight
  • the daily dose of hyaluronic acid is comprised between 0.0001 and 0.001 g per Kg of weight
  • the daily dose of antioxidants is comprised between 0.00075 and 0.003 mg per Kg of weight.
  • the composition comprises vitamin C in a dose comprised between 0.0005 and 0.002 g per Kg of weight.
  • the use according to the invention is characterized in that the mammal with functional difficulties derived from articular cartilage disorders is a human.
  • the mammal with functional difficulties derived from articular cartilage disorders is an animal selected from the group consisting of dogs, cats and horses.
  • compositions object of the invention are effective due to the synergistic behaviour of their constituents
  • compositions and use examples thereof are detailed below by way of a non-limiting example. Tests which allow viewing the positive effects of these new compositions are also set forth.
  • TEST Comparison between compositions according to the invention and compositions according to the state of the art to determine their efficacy as products for the improvement of the functional capacity and/or the quality of life in mammals with difficulties derived from articular cartilage disorders.
  • a composition according to the invention and as detailed below was designed with the intention of reducing the daily dose of enzymatic collagen hydrolysate to be administered compared to the preparations existing on the market.
  • a typical dose of 10 grams a day was thus reduced to 7 grams, and hyaluronic acid, natural bioflavonoids and natural antioxidants were added to it in the average doses used of these products individually, the composition for the daily dose of said product being as follows:
  • Enzymatic collagen hydrolysate (Colatech®) 7.000 g
  • Hyaluronic acid 0.025 g Tomato extract with 2% Lycopene 0.075 g
  • the enzymatic collagen hydrolysate used has a high purity, i.e., it comprises 99% by weight of hydrolysate of the dry raw material product. Likewise, the molecular weight of said enzymatic collagen hydrolysate is comprised between
  • composition As a base, a suspension was prepared which was stabilized with different pharmaceutical quality excipients and it was suitably flavoured for the purpose of facilitating the consumption thereof.
  • EXAMPLE 1 Functional food in the form of yoghurt.
  • Enzymatic collagen hydrolysate (Colatech®) 7.000 g
  • Tomato concentrate with 2% Lycopene 0.075 g Vitamin C 0.060 g
  • Skimmed milk powder 12.000 g
  • a chocolate dessert with the following composition has been prepared:
  • Enzymatic collagen hydrolysate (Colatech®) 7.000 g
  • Tomato concentrate with 2% Lycopene 0.075 g Vitamin C 0.060 g
  • Pregelatinized corn starch 10.000 g Carrageenan 4.000 g
  • EXAMPLE 3 Food supplement in the form of a vial that is drinkable or can be diluted in aqueous medium and with raspberry flavour.
  • liquid presentation indicated below has been prepared to be taken in 30 g vials, either directly or diluted in water.
  • Enzymatic collagen hydrolysate (Colatech®) 23.334 g
  • Tomato concentrate with 2% Lycopene 0.250 g Vitamin C 0.200 g
  • Antifoam AF 0.040 g Colloidal silicon dioxide 0.02O g
  • EXAMPLE 4 Food supplement in the form of a powder and with strawberry flavour.
  • a mixture of powders has been prepared which can be packaged in jars adding a measuring device allowing the dosing of about 12 g in order to take the product once it has been dispersed in half a glass of water. It can also be packaged in single-dose paper-aluminium-polythene sachets whereby carrying the daily dose to be taken is favoured.
  • Enzymatic collagen hydrolysate (Colatech®) 58.344 g
  • Hyaluronic acid 0.208 g
  • Natural bioflavonoids 0.25O g
  • Vitamin C 0.50O g
  • Vitamin B1 Thiamine HCI 0.02O g
  • Vitamin B2 Raboflavin 0.02O g
  • Vitamin B6 (Pyridoxine HCI) 0.020 g
  • Vitamin B5 (Calcium pantothenate) 0.06O g
  • EXAMPLE 5 Food supplement in the form of a vial that is drinkable or can be diluted in aqueous medium and with vanilla flavour.
  • the liquid presentation indicated below has been prepared to be taken in 30 g vials, either directly or diluted in water.
  • EXAMPLE 6 Food supplement in the form of a vial that is drinkable or can be diluted in aqueous medium and with wild berry flavour.
  • compositions for oral administration comprising an enzymatic collagen hydrolysate or other types of polymer or protein hydrolysates capable of giving hydrogen bonds associated with hyaluronic acid or its salts, and to which natural bioflavonoids and antioxidants can be incorporated, also preferably comprise vitamin C.
  • the vitamin C used can be in its acid or ascorbic acid form; or in the form of acid salts, such as sodium ascorbate or calcium ascorbate.
  • B group vitamins such as vitamins B1 , B2, B6 and B5, as well as any pharmaceutical quality flavouring or flavour enhancer, is also contemplated in order to provide the compositions with improved organoleptic properties.
  • liposoluble vitamins vitamins A, D, E
  • antiradical agent coenzyme Q10 can also be added.
  • compositions can contain mineral salts, such as magnesium carbonate.
  • mineral salts such as magnesium carbonate.
  • Other mineral salts of calcium, magnesium, sodium, potassium, selenium, copper, zinc, molybdenum, etc. can be added, the intake of these types of compounds thus being modulated according to the requirements or deficiencies of the mammals to which the compositions are to be administered.
  • Hyaluronic acid can be used in the form of acid or also in the form of its salts, preferably the sodium salt, according to availability.
  • the natural bioflavonoids used comprise at least one of the following compounds: quercetin, naringin, luteolin, apigenin, genistein and hesperidin, in different proportions according to the plant source of origin.
  • compositions according to the invention can contain plant extracts or products of animal origin, traditionally used to alleviate functional difficulties due to articular cartilage disorders.
  • glucosamine sulphate or chondroitin sulphate which are also widely used for dysfunctions derived from cartilage problems, can be added to said compositions.
  • compositions and/or functional foods and/or food supplements indicated above allow, as is deduced from the previous test, increasing the rate of action with regard to the improvement of the functional capacity and/or the quality of life of people or animals that are physically or socially impaired due to articular cartilage disorders.

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Abstract

The invention relates to a composition for oral administration comprising an enzymatic collagen hydrolysate or other types of polymer or protein hydrolysates capable of giving hydrogen bonds with hyaluronic acid in the form of acid or of its salts, and which furthermore may comprise natural bioflavonoids and antioxidants. The composition is used for the preparation of functional foods and food supplements intended for the improvement of the functional capacity and/or the quality of life of a mammal with functional difficulties derived from articular cartilage disorders.

Description

D E S C R I P T I O N
"COMPOSITION FOR THE IMPROVEMENT OF FUNCTIONAL DIFFICULTIES DUE TO ARTICULAR CARTILAGE DISORDERS"
Technical field of the invention
The present invention relates to a composition comprising polymers of protein origin or cellulose, acrylic or carbohydrate derivatives for the improvement of functional difficulties which are a result of articular cartilage disorders. Likewise, the present invention relates to uses of the mentioned composition and to functional foods and food supplements comprising it.
Background of the invention
Prior investigations had already proved that when gelatine hydrolysates with low collagen content and with molecular weights of up to 100,000 daltons are regularly consumed by athletes and people making a special effort in their normal activities, they maintained or improved the integrity of articular cartilage (United States Patent 6,21 1 ,143).
It is also known from patent document ES2087030 that gelatine hydrolysates are also useful as coadjuvants in the treatments intended to compensate the calcium deficit and that they are also useful in the treatment and prevention of hip dysplasia in dogs as described in patent document ES2104507.
Several recently conducted studies have proved that enzymatic collagen hydrolysate is well absorbed when it is orally administered and is distributed with high affinity preferably in articular cartilage tissues (Oesser S, Adam M, Babel W, Seifert J. Oral administration of 14C Labelled Gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL). J Nutr 1999; 129: 1891 - 1895.), increasing the cartilaginous mass volume and carrying out its action with the subsequent reduction of pain and of inflammation and the improvement of the motility of said joints (Adam M. Therapie der osteoarthrosis. Welche Wirkung haben gelatinepraparate? Therapiewoche 1991 , 41 : 2458-2461 ; Arquer A, Pujol P. Physical exercise in the elderly people. Selecciόn 1996; 5 (3):121 -128; Ribas J, Molinero O. Effects of gelatine hydrolysates in the prevention of sportsmen and woman injuries. Arch Med Deport 1998; XV no. 66: 277-282; Trentham D, Dynesius-Trentham R, Orav E, et al. Effects of oral administration of type Il collagen on rheumatoid arthritis. Science 1993; 261 : 1727-1730.).
According to the investigations on collagen hydrolysates and their use for articular improvement, the inventors of the present invention developed a high-purity enzymatic collagen hydrolysate with a better bioavailability due to its lower molecular weight (between 5000 and 20000 daltons). This hydrolysate is distributed under the trade name Colatech® and a study was conducted with it in 100 healthy volunteers, this collagen being administered in a dose of 10 g per day to 50 of them and to the other 50 volunteers a dose of 1 .5 g per day of glucosamine sulphate, a product widely used both in Europe and in the United States at this dose for the treatment of articular disorders in general. Several studies validate that the administration of glucosamine is an effective means for improving the pain and the mobility of joints with dysfunctions due to articular cartilage disorders (Rindone J, Hiller D, Collacot E, et al. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med 2000; 172: 91 -94; Noack W, Fischer M, Forster KK, et al. Glucosamine sulphate in osteoarthritis of the knee. Osteoarthritis Cartilage 1994; 2(1): 51 -59; Reginster JY, Deroisy R, Rovatti LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001 ; 357: 251 -256; Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology 2002; 41 : 279-284).
The results of the studies with enzymatic collagen hydrolysate between 5000 and 20000 daltons proved the effectiveness of this collagen (Colatech®), the effectiveness of which was greater than that obtained with glucosamine sulphate. In addition, hyaluronic acid, a product which is normally used as an intraarticular injectable for improving joints in people with arthrosis, has recently been started to be used orally in dietary supplements in doses ranging between 0.1 and 0.5 mg/Kg of weight/day in the prevention of articular problems and ligament problems, both in a single administration and together with other products such as glucosamine and chondroitin sulphate (BJ. Bergin, S.W. Pierce, L.R. Bramlage and A.Stomberg. Oral hyaluronan gel reduces post operative tarsocrural effusion in the yearling Thoroughbred. Equine Veterinary Journal (2006) 38 (4) 375-378).
In addition, natural antioxidants such as lycopene obtained from tomato, resveratrol which can be obtained from Yucca schidigera and even vitamin C are being used as natural anti-inflammatory agents (Riso P, Visioli F, Grande S, Guarneri S, Gardana C, Simonetti P, Porrini M. Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress, J. Agric Food Chem. 2006 Apr 5; 54 (7): 2563-6; Liu X, Qu D, he F, Lu Q, Wang J, Cai D. Effect of Lycopene on the vascular endothelial function and expression of inflammatory agents in hyperhomocysteinemic rats, Asia Pac J Clin Nutr. 2007; 16 Suppl 1 : 244- 8; Pattison DJ, Silman AJ, Goodson NJ, Lunt M, Bunn D, Luben R, Welch A, Bingham S, Khaw KT, Day N, Symmons DP, Vitamin C and the risk of developing inflammatory polyarthritis: prospective nested case-control study, Ann Rheum Dis. 2002 JuI; 63 (7): 843-7; El-Saadany MA, Rawel HM, Raila J, El-Dashlooty MS, Schweigert FJ., Antioxidants modulate the IL-6 induced inhibition of negative acute- phase protein secretion in HepG2 cells, Cell Biochem Fund 2007 Apr 4; (Epub ahead of print)).
Natural bioflavonoids such as luteolin, naringin, quercetin, apigenin and genistein are also being widely used in dietary or food supplements due to their antiinflammatory action allowing their application in different disorders presenting inflammation (Nam N. H., Naturally occurring NF-kappaB inhibitors, Mini Rev. Med. Chem. 2006 Aug; 6 (8):945-51 ; Kumazawa Y. Kawaguchi K. Takimoto H., lmmunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha, Curr. Pharm. Des. 2006,12 (32); 4271 -9; Ruiz P. A. Haller D., Functional diversity of flavonoids in the inhibition of the proinflammatory NF-kappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells, J. Nutr. 2006 Mar;136 (3); 664-71 ; Ruiz PA, Braune A, Holziwimmer G, Quintanilla - Fend L, Haller D., Quercetin inhibits TNF-induced NF-kappaB transcription factor recruitment to proinflammatory gene promoters in murine intestinal epithelial cells, J.Nutr. 2007 May; 137 (5); 1208 - 15).
There is however a need on the market for finding or formulating new compositions which have quicker and/or more intense effects than existing compositions, i.e., which allow palliating and/or preventing functional difficulties derived from articular cartilage disorders more quickly and generally with fewer doses of active components.
In addition, the population is increasingly concerned about both animal and human dietetics and nutrition. Multiple preparations known as food supplements providing animals and people with the necessary amount of vitamins, mineral salts - A -
or essential amino acids have therefore appeared on the market. Collagen has also been used in the field of food supplements to obtain preparations favouring the recovery of cartilage in animals suffering from diseases linked to this type of tissue.
A food supplement must be understood as any additional dietary intake which is consumed orally and contains a "food ingredient" intended to supplement the diet. Some examples of dietary or food supplements are vitamins, minerals, herbs (a single herb or a mixture of several herbs), other botanical products, amino acids and food components such as enzymes. Food supplements are generally distributed in the form of different presentations such as pastilles, capsules, soft gelatine capsules, gelatine capsules, liquids and powders.
The so-called functional foods are lately also becoming known in the nutrition field. Functional foods are considered to be those foods which are consumed as part of a normal diet and contain biologically active components offering health benefits and reducing the risk of suffering from diseases. Foods containing certain minerals, vitamins, fatty acids or dietary fibre, foods to which biologically active substances such as phytochemicals or other antioxidants have been added, and probiotics, having live cultures of beneficial microorganisms, are emphasized among some examples of functional foods. Some yoghurts with probiotics, some margarines enriched with sterol esters and eggs rich in omega-3-type fatty acids are examples of functional foods.
Both functional foods and food supplements are scientifically associated to the improvement of the quality of life of people or animals consuming them. They have also been associated to the feeling of general wellbeing that they cause, taken alone or as a supplement to certain therapeutic treatments. Although it is a term that is difficult to define, quality of life must be understood as any evaluation of the experience that subjects have of their own life. Thus, most authors understand quality of life as a complex and multifactorial construction on which some forms of objective measurement can be developed through a series of a indicators, but where the lived experience that the subject may have of him or herself has a considerable specific weight. Some of the indicators for determining or assessing the quality of life of a subject are the physical function and role, body pain, general health, vitality, etc. Disclosure of the invention
For the purpose of finding a treatment that is as effective as possible for a patient suffering from articular problems, the inventors have surprisingly found after an exhaustive investigation that new compositions combining hyaluronic acid or salts thereof with polymers of protein origin or cellulose, acrylic or carbohydrate derivatives have synergistic effects and involve an advantage over the existing compositions used for the preparation of medicaments, functional foods or food supplements for the improvement of mobility and/or functional difficulties derived from articular cartilage disorders. When hyaluronic acid is associated with a polymer of protein origin or cellulose, acrylic or carbohydrate derivatives, hydrogen bonds are formed between the structure of the polymer, for example, of the collagen hydrolysate (amino and hydroxyl groups capable of forming this type of bond) and the hyaluronic acid molecule, favouring the passage of the latter through cell membranes and subsequently improving its absorption and causing an improvement in its activity.
This same mechanism can be achieved with any types of proteins, peptides and cellulose and acrylic polymers which are capable of forming this type of hydrogen bond with the hyaluronic acid molecule, as well as with sugar-type carbohydrates with different molecular weights or polyalcohols. Examples of these types of products could be casein, vegetable or animal lactic-type protein hydrolysates, methylcellulose, hydroxyethylcellulose, polyvinylpyrrolidone, carbomer, polydextrose, sucrose, sorbitol,....
In a preferred embodiment, the polymer is a cellulose derivative, being an enzymatic collagen hydrolysate. The composition for oral administration according to the invention is characterized in that it can further comprise other functional ingredients such as natural bioflavonoids and antioxidants.
The enzymatic collagen hydrolysate preferably has a molecular weight comprised between 1 ,000 and 50,000 daltons. According to another feature of the invention, the composition for oral administration comprises from 96% to 99.5% by weight of enzymatic collagen hydrolysate, from 0.25% to 0.60% by weight of hyaluronic acid, from 1.0% to 2.5% of antioxidant agents and/or from 0.40% to 0.90% by weight of natural bioflavonoids being able to be incorporated to this association. According to a preferred embodiment, the natural bioflavonoids are chosen from the group consisting of quercetin, naringin, luteolin, apigenin, genistein, hesperidin or a mixture of at least two of them.
In a preferred embodiment, hyaluronic acid is in the form of sodium salt. According to another preferred embodiment, the composition comprises as an antioxidant at least one of those of the group consisting of beta-carotene, lycopene, resveratrol as well as their derivatives.
When resveratrol is mentioned in the present invention, it refers to its cis and trans isomers and to mixtures thereof, as well to its derivatives by glycosylation of its hydroxyl groups; esterification of said hydroxyl groups or amides thereof in any of its isomeric forms.
In an equally preferred embodiment, the composition further comprises vitamin C, which will preferably be in the form of ascorbic acid.
According to another feature of the composition for oral administration object of the invention, such composition further comprises mineral salts.
According to another feature of the invention, the composition for oral administration further comprises B group vitamins and/or coenzymes, liposoluble vitamins and coenzyme Q10.
The composition for oral administration according to the invention is also characterized in that it further comprises a coadjuvant compound selected from the group consisting of glucosamine sulphate and chondroitin sulphate.
The composition for oral administration according to the invention is characterized in that it is in the form of a suspension.
The composition for oral administration according to the invention is characterized in that it is in the form of a powder which is dispersible or soluble in an aqueous medium.
The composition for oral administration according to the invention is also characterized in that it is in the form of a solution.
A composition for oral administration according to the invention which is in the form of tablets or capsules is equally preferred.
Another object of the present invention is a functional food comprising a composition with polymers of protein origin or cellulose, acrylic or carbohydrate derivatives associated with natural bioflavonoids, antioxidants and hyaluronic acid in the form of acid or of their salts, as has been described above. The functional food is preferably in the form of yoghurt, shake, custards, fruit juices, biscuits or energy bars.
Another object of the present invention is the use of the previously described compositions for the preparation of functional foods and food supplements for the improvement of the functional capacity and/or the quality of life of a mammal with functional difficulties derived from articular cartilage disorders.
In the particular variant where the polymer is a cellulose derivative, being enzymatic collagen hydrolysate, and in which the composition further comprises bioflavonoids and antioxidants, the daily dose of the enzymatic collagen hydrolysate is comprised between 0.075 and 0.200 g per Kg of weight, the daily dose of bioflavonoids is comprised between 0.00025 and 0.001 g per Kg of weight, the daily dose of hyaluronic acid is comprised between 0.0001 and 0.001 g per Kg of weight and the daily dose of antioxidants is comprised between 0.00075 and 0.003 mg per Kg of weight. The use according to the invention contemplates that the composition comprises vitamin C in a dose comprised between 0.0005 and 0.002 g per Kg of weight.
The use according to the invention for the increase of the rate of action in the improvement in the functional capacity and/or the quality of life of a mammal with functional difficulties derived from articular cartilage disorders
The use according to the invention is characterized in that the mammal with functional difficulties derived from articular cartilage disorders is a human.
Alternatively, the mammal with functional difficulties derived from articular cartilage disorders is an animal selected from the group consisting of dogs, cats and horses.
Detailed description of the drawings
In order to solve the problems of the state of the art and prove that the compositions object of the invention are effective due to the synergistic behaviour of their constituents, several compositions and use examples thereof are detailed below by way of a non-limiting example. Tests which allow viewing the positive effects of these new compositions are also set forth.
TEST: Comparison between compositions according to the invention and compositions according to the state of the art to determine their efficacy as products for the improvement of the functional capacity and/or the quality of life in mammals with difficulties derived from articular cartilage disorders.
A composition according to the invention and as detailed below was designed with the intention of reducing the daily dose of enzymatic collagen hydrolysate to be administered compared to the preparations existing on the market. A typical dose of 10 grams a day was thus reduced to 7 grams, and hyaluronic acid, natural bioflavonoids and natural antioxidants were added to it in the average doses used of these products individually, the composition for the daily dose of said product being as follows:
Enzymatic collagen hydrolysate (Colatech®) 7.000 g
Hyaluronic acid 0.025 g Tomato extract with 2% Lycopene 0.075 g
Natural bioflavonoids (Quercetin) 0.030 g
Ascorbic acid (Vitamin C) 0.060 g
The enzymatic collagen hydrolysate used has a high purity, i.e., it comprises 99% by weight of hydrolysate of the dry raw material product. Likewise, the molecular weight of said enzymatic collagen hydrolysate is comprised between
1 ,000 and 50,000 daltons.
With this composition as a base, a suspension was prepared which was stabilized with different pharmaceutical quality excipients and it was suitably flavoured for the purpose of facilitating the consumption thereof.
Then, a pilot study in 10 volunteers was designed in which the effect of the daily oral administration of this synergistic composition of products was studied against the administration of the 10 g of Colatech® successfully used in prior studies of the same inventors. Each of the products was administered in 10 volunteers for a total of 90 days with intermediate controls after 15, 30 and 60 days. The parameter studied was the analgesic activity of both products on the pain caused by osteoarthritis of the knee evaluated by means of a visual analogue scale (VAS). In contrast to expectations, a greater activity of the preparation after 90 days of treatment was not achieved although, and taking into account that the dose of enzymatic collagen hydrolysate was 7 g, the same activity as when using 10 g thereof was achieved. However, a result that was surprising is that the rate of action of the combination of products was much higher than that achieved with the single administration of enzymatic collagen hydrolysate, although the dose was larger. It was verified that the analgesic activity of the association of products was actually much higher after 15 days of treatment, after 30 days, and slightly higher after 60 days, becoming equal after 90 days of such treatment.
This factor is very important in these types of treatments because as the results are slow, there are many abandonments from it, whereas upon achieving these quicker results with the combination of products, the completion of the treatments will be much higher because an improvement in the reduction of pain will be noticed from the beginning of the treatment.
Having verified the improvement in the quickness of action of the product, different formulas allowing its administration in a pleasant manner have been prepared taking into account the duration of the treatment. Said formulas are detailed by way of non-limiting embodiments in the following examples.
EXAMPLE 1: Functional food in the form of yoghurt.
A yoghurt with the following composition has been prepared with good results:
Milk 76.71 O g
Enzymatic collagen hydrolysate (Colatech®) 7.000 g
Hyaluronic acid 0.025 g
Natural bioflavonoids 0.030 g
Tomato concentrate with 2% Lycopene 0.075 g Vitamin C 0.060 g
Skimmed milk powder 12.000 g
Cream 4.000 g
Milk ferments 0.100 g EXAMPLE 2: Functional food in the form of chocolate custard.
A chocolate dessert with the following composition has been prepared:
Skimmed milk 37.61 O g
Enzymatic collagen hydrolysate (Colatech®) 7.000 g
Hyaluronic acid 0.025 g
Natural bioflavonoids 0.030 g
Tomato concentrate with 2% Lycopene 0.075 g Vitamin C 0.060 g
Sugar 15.000 g
Lactose 10.000 g
Cream 5.000 g
Pregelatinized corn starch 10.000 g Carrageenan 4.000 g
Fat-reduced cocoa 10.000 g
Gelatine 1.000 g
Emulsifier 0.200 g
EXAMPLE 3: Food supplement in the form of a vial that is drinkable or can be diluted in aqueous medium and with raspberry flavour.
The liquid presentation indicated below has been prepared to be taken in 30 g vials, either directly or diluted in water.
Enzymatic collagen hydrolysate (Colatech®) 23.334 g
Hyaluronic acid 0.085 g
Natural bioflavonoids 0.100 g
Tomato concentrate with 2% Lycopene 0.250 g Vitamin C 0.200 g
Fructose 10.500 g
Maltodextrin 8.600 g
Pregelatinized starch 1.800 g
Anhydrous citric acid 1.000 g Potassium sorbate 0.190 g
Raspberry flavour 0.060 g
Acesulfame K 0.040 g
Antifoam AF 0.040 g Colloidal silicon dioxide 0.02O g
Cellulase 0.006 g
Purified water 53.775 g
EXAMPLE 4: Food supplement in the form of a powder and with strawberry flavour.
A mixture of powders has been prepared which can be packaged in jars adding a measuring device allowing the dosing of about 12 g in order to take the product once it has been dispersed in half a glass of water. It can also be packaged in single-dose paper-aluminium-polythene sachets whereby carrying the daily dose to be taken is favoured.
Enzymatic collagen hydrolysate (Colatech®) 58.344 g
Hyaluronic acid 0.208 g Natural bioflavonoids 0.25O g
Tomato concentrate with 5% Lycopene 0.250 g
Vitamin C 0.50O g
Magnesium carbonate 6.000 g
Vitamin B1 (Thiamine HCI) 0.02O g Vitamin B2 (Riboflavin) 0.02O g
Vitamin B6 (Pyridoxine HCI) 0.020 g
Vitamin B5 (Calcium pantothenate) 0.06O g
Strawberry flavour 1.120 g
Aspartame 0.140 g Anhydrous citric acid 1.83O g
Fructose 31.248 g
EXAMPLE 5: Food supplement in the form of a vial that is drinkable or can be diluted in aqueous medium and with vanilla flavour. The liquid presentation indicated below has been prepared to be taken in 30 g vials, either directly or diluted in water.
Lactic protein hydrolysate 20.00O g
Hyaluronic acid 0.085 g
Sodium chloride 1.000 g
Fructose 19.000 g
Maltodextrin 8.600 g Pregelatinized starch 1.80O g
Anhydrous citric acid 1.000 g
Potassium sorbate 0.190 g
Vanilla flavour 0.060 g
Acesulfame K 0.040 g Antifoam AF 0.040 g
Colloidal silicon dioxide 0.020 g
Cellulase 0.006 g
Purified water 48.159 g
EXAMPLE 6: Food supplement in the form of a vial that is drinkable or can be diluted in aqueous medium and with wild berry flavour.
The liquid presentation indicated below has been prepared to be taken in 30 g vials, either directly or diluted in water. Enzymatic collagen hydrolysate (Colatech®) 23.334 g
Hyaluronic acid 0.085 g
Sodium chloride 0.550 g
Fructose 10.500 g
Maltodextrin 8.600 g Pregelatinized starch 1.80O g
Anhydrous citric acid 1.000 g
Potassium sorbate 0.190 g
Wild berry flavour 0.060 g
Acesulfame K 0.040 g Antifoam AF 0.040 g
Colloidal silicon dioxide 0.020 g
Cellulase 0.006 g
Purified water 53.775 g
As is deduced from previous Examples 1 to 6, the compositions for oral administration comprising an enzymatic collagen hydrolysate or other types of polymer or protein hydrolysates capable of giving hydrogen bonds associated with hyaluronic acid or its salts, and to which natural bioflavonoids and antioxidants can be incorporated, also preferably comprise vitamin C. The vitamin C used can be in its acid or ascorbic acid form; or in the form of acid salts, such as sodium ascorbate or calcium ascorbate.
The use of B group vitamins, such as vitamins B1 , B2, B6 and B5, as well as any pharmaceutical quality flavouring or flavour enhancer, is also contemplated in order to provide the compositions with improved organoleptic properties. If appropriate, liposoluble vitamins (vitamins A, D, E) and the antiradical agent coenzyme Q10 can also be added.
Likewise, and according to Example 4, the compositions can contain mineral salts, such as magnesium carbonate. Other mineral salts of calcium, magnesium, sodium, potassium, selenium, copper, zinc, molybdenum, etc. can be added, the intake of these types of compounds thus being modulated according to the requirements or deficiencies of the mammals to which the compositions are to be administered.
Hyaluronic acid can be used in the form of acid or also in the form of its salts, preferably the sodium salt, according to availability.
The natural bioflavonoids used comprise at least one of the following compounds: quercetin, naringin, luteolin, apigenin, genistein and hesperidin, in different proportions according to the plant source of origin.
Although in Examples 1 to 4 lycopene is used as the main antioxidant agent, equivalent results are obtained with beta-carotene and resveratrol.
The compositions according to the invention can contain plant extracts or products of animal origin, traditionally used to alleviate functional difficulties due to articular cartilage disorders. In this same sense, glucosamine sulphate or chondroitin sulphate, which are also widely used for dysfunctions derived from cartilage problems, can be added to said compositions.
All the compositions and/or functional foods and/or food supplements indicated above allow, as is deduced from the previous test, increasing the rate of action with regard to the improvement of the functional capacity and/or the quality of life of people or animals that are physically or socially impaired due to articular cartilage disorders.

Claims

C L A I M S
1.- A composition for oral administration comprising:
- polymers of protein origin or cellulose, acrylic or carbohydrate derivatives; and
- hyaluronic acid in the form of acid or salts thereof.
2.- The composition according to claim 1 , characterized in that the polymer is a cellulose derivative, being an enzymatic collagen hydrolysate.
3.- The composition according to claim 2, characterized in that it further comprises natural bioflavonoids and antioxidants.
4.- The composition according to claims 2 or 3, wherein the enzymatic collagen hydrolysate has a molecular weight comprised between 1 ,000 and 50,000 daltons.
5.- The composition according to any one of claims 2 to 4, characterized in that it comprises from 96% to 99.5% by weight of enzymatic collagen hydrolysate and from 0.25% to 0.60% by weight of hyaluronic acid.
6.- The composition according to claim 5, characterized in that it further comprises from 0.40% to 0.90% by weight of natural bioflavonoids and from 1.0% to 2.5% of antioxidants.
7.- The composition according to any one of claims 3 to 6, characterized in that the bioflavonoids are chosen from the group consisting of quercetin, naringin, luteolin, apigenin, genistein, hesperidin or a mixture of at least two of them.
8.- The composition according to any one of the previous claims, characterized in that hyaluronic acid is in the form of sodium salt.
9.- The composition according to any one of claims 3 to 8, characterized in that as antioxidants at least one of those of the group consisting of beta-carotene, lycopene, resveratrol, as well as salts or derivatives thereof, is chosen.
10.- The composition according to any one of claims 1 to 7, characterized in that it further comprises vitamin C.
1 1.- The composition according to the previous claim, characterized in that vitamin C is in the form of ascorbic acid.
12.- The composition for oral administration according to any one of claims 1 to 7, characterized in that it further comprises mineral salts.
13.- The composition for oral administration according to any one of claims 1 to 7, characterized in that it further comprises B group vitamins and/or coenzymes, liposoluble vitamins and coenzyme Q10.
14.- The composition for oral administration according to any one of claims 1 to 7, characterized in that it further comprises a coadjuvant compound selected from the group consisting of glucosamine sulphate and chondroitin sulphate.
15.- The composition for oral administration according to any one of the previous claims, characterized in that it is in the form of a suspension.
16.- The composition for oral administration according to any one of claims 1 to 14, characterized in that it is in the form of a powder which is dispersible or soluble in an aqueous medium.
17.- The composition for oral administration according to any one of claims 1 to 14, characterized in that it is in the form of a solution.
18.- The composition for oral administration according to any one of claims 1 to 14, characterized in that it is in the form of tablets or capsules.
19.- A functional food comprising a composition according to any one of claims 1 to 18.
20.- The functional food according to claim 19, characterized in that it is in the form of yoghurt, shake, custards, fruit juices, biscuits or energy bars.
21.- A use of a composition according to any one of claims 1 to 18 for the preparation of functional foods and food supplements for the improvement of the functional capacity and/or the quality of life of a mammal with functional difficulties derived from articular cartilage disorders.
22.- The use according to the previous claim when it depends on claims 3 to 18, wherein the daily dose of hyaluronic acid is comprised between 0.0001 and 0.001 g per Kg of weight, the daily dose of enzymatic collagen hydrolysate is comprised between 0.075 and 0.200 g per Kg of weight, the daily dose of bioflavonoids is comprised between 0.00025 and 0.001 g per Kg of weight, and the daily dose of antioxidants is comprised between 0.00075 and 0.003 mg per Kg of weight.
23.- The use according to any one of claims 21 or 22, wherein the composition comprises vitamin C in a dose comprised between 0.0005 and 0.002 g per Kg of weight.
24.- The use according to any one of claims 21 to 23, to increase the rate of action in the improvement of the functional capacity and/or the quality of life of a mammal with functional difficulties derived from articular cartilage disorders
25.- The use according to any one of claims 21 to 24, wherein the mammal with functional difficulties derived from articular cartilage disorders is a human.
26.- The use according to any one of claims 21 to 24, wherein the mammal with functional difficulties derived from articular cartilage disorders is an animal selected from the group consisting of dogs, cats and horses.
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WO2006116452A1 (en) * 2005-04-22 2006-11-02 Molecular Regenix, Llc Nutritional composition comprising hyaluronic acid and superoxide dismutase and methods of making and using same
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ITMI20111925A1 (en) * 2011-10-25 2013-04-26 Apharm Srl COMPOSITIONS BASED ON HYALURONIC ACID AND NATURAL FIBERS FOR ORAL USE TO INCREASE INTESTINAL PERISTALTIC ACTIVITY.
DE102017006532A1 (en) * 2017-07-11 2019-01-17 Carlo Bermes Medicines and drink for the improvement of joint and bone disorders
WO2019011911A1 (en) 2017-07-11 2019-01-17 Bermes Carlo Medicament and beverage for improving joint and bone diseases

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