WO2014084427A1 - Composition comprenant de l'acide alginique pour la prévention ou le traitement de l'arthrose - Google Patents

Composition comprenant de l'acide alginique pour la prévention ou le traitement de l'arthrose Download PDF

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WO2014084427A1
WO2014084427A1 PCT/KR2012/010315 KR2012010315W WO2014084427A1 WO 2014084427 A1 WO2014084427 A1 WO 2014084427A1 KR 2012010315 W KR2012010315 W KR 2012010315W WO 2014084427 A1 WO2014084427 A1 WO 2014084427A1
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alginic acid
osteoarthritis
osteoporosis
gluronate
composition
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PCT/KR2012/010315
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English (en)
Korean (ko)
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오석중
김광윤
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주식회사 이코바이오
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/734—Alginic acid
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/206—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
    • A23L29/256—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin from seaweeds, e.g. alginates, agar or carrageenan
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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

Definitions

  • Cartilage is an elastic tissue that connects two bones to each other, imparts mobility to joints, and plays a role in shock relaxation.
  • articular cartilage comprises chondrocytes embedded in a matrix of proteoglycan and type II collagen as connective tissue.
  • the osteoarthritis is known under several different names, for example, degenerative joint disease, osteoarthritis, hypertrophic arthritis, or degenerative arthritis.
  • the osteoarthritis may be characterized by chronic progressive destruction of cartilage tissue in major joints such as fingers, elbows, knees or ankles.
  • cartilage destruction is generally caused by changes or imbalances in metabolic mechanisms related to assimilation and catabolism in the articular cartilage matrix.
  • the surgical method by arthroscopy does not have a constant effect, and in the case of artificial arthroplasty, the life of the artificial joint is limited, which requires further revision surgery. There is a problem that can cause complications such as bleeding or infection in the process.
  • glucosamine sulfate one of the basic components of the disaccharide unit of glycosaminoglycans (GAG)
  • GAG glycosaminoglycans
  • Bone tissue is a very complex and active tissue composed of extracellular matrix composed of minerals such as collagen fibers and hydroxyapatite, and various types of cells such as osteoblasts, osteoclasts, and osteoblasts. Through the action of osteoclasts, the process of aggregate formation is repeated by forming and absorbing continuously throughout life.
  • the collagen fiber is one of the most elements constituting the human body, and is widely distributed not only in bone but also in connective tissues such as the dermis, ligaments, tendons, cartilage, fascia, or blood vessels.
  • the main component of the collagen fiber is a light fiber protein called collagen.
  • Pyridinoline (pyridinoline) and dioxypyridinoline, the mature crosslinking material of collagen, are liberated and excreted in urine upon bone destruction by osteoclasts, and they are mainly present in bone and cartilage. It is used clinically as a reliable biomaker for the evaluation of osteolysis in various pathologies such as osteoarthritis.
  • the aggregate formation process is various growth factors secreted from bone tissues such as hormones such as parathyroid hormone (PTH), calcitonin (calcitonin), estrogen, and IGF-I (insulinlike growth factor I), and TNF- ⁇ (tumor necrosis factor- ⁇ ).
  • hormones such as parathyroid hormone (PTH), calcitonin (calcitonin), estrogen, and IGF-I (insulinlike growth factor I), and TNF- ⁇ (tumor necrosis factor- ⁇ ).
  • PTH parathyroid hormone
  • calcitonin calcitonin
  • estrogen and IGF-I (insulinlike growth factor I)
  • TNF- ⁇ tumor necrosis factor- ⁇
  • Osteoporosis is a representative bone metabolic disease, meaning a metabolic bone disease whose primary lesion is a quantitative decrease in the constituents of bone with significantly reduced bone mass compared to normal people of the same age and gender.
  • Riggs and Melton have classified osteoporosis after age 50 as either type 1 osteoporosis (menopausal osteoporosis, postmenopausal osteoporosis) or primary and type 2 osteoporosis (senile osteoporosis) or secondary osteoporosis. .
  • estrogen-like substances used for the treatment of postmenopausal osteoporosis may cause side effects such as nausea, weight gain, irregular uterine bleeding, endometrial cancer and breast cancer with prolonged use, and in recent years, other side effects to compensate for the risk.
  • Research on alternative therapies using natural ingredients derived from herbals and foods that can promote bone formation while minimizing bone loss has been actively conducted.
  • Alginic acid (alginate), alginic acid is ⁇ -L-guluronate and C5 epimer ⁇ -D-manneuronic acid (1,4'- ⁇ -D-mannuronate) is ⁇ -1, Heteropolysaccharide consisting of four bonds or ⁇ -1,4 bonds, is a complex glycopolymer combined in pG block (polyguluronate block), pM block (polymannuronate block) and pM / G stretch form.
  • the alginic acid mainly constitutes the cell wall of brown algae, it can be obtained by extracting from brown algae.
  • the alginic acid has been used extensively since ancient times for its unique physical properties such as gel forming ability, high viscosity, and film forming ability.
  • viscous or gelling agent in various industries including food industry, printing industry and pharmaceutical industry, as raw material of drug delivery system such as microspheres, beads, microcapsules or tablets, matrix in tissue engineering It has been used as a carrier and the like.
  • alginic acid has been reported to have various physiological activities such as restraining obesity, healing constipation through promoting intestinal peristalsis, inhibiting anti-cholesterol, absorbing and removing heavy metals in the body, or inhibiting the toxicity of harmful substances. Research is underway to utilize it.
  • the present invention provides a composition for treating or preventing osteoarthritis or osteoporosis comprising alginic acid as an active ingredient.
  • the alginic acid may be an average weight average molecular weight (Mw) of the alginic acid is 1,500 to 5,000, preferably 2,400 to 2,600.
  • Mw average weight average molecular weight
  • the alginic acid may have an average weight average molecular weight (Mw) of alginic acid of 1,500 to 5,000, and a weight ratio (M / G) of manneuronate and gluronate of alginic acid to 2.0 to 3.4, preferably 2.3 to 2.7. .
  • the alginic acid may be a weight ratio (M / G) of manneuronate and gluronate of alginic acid is 1.6 to 3.8, preferably 2.0 to 3.4, more preferably 2.3 to 2.7.
  • the present invention provides a food composition for preventing or improving osteoarthritis or osteoporosis comprising alginic acid as an active ingredient to achieve the above object.
  • the food composition may be a food, a food additive or a beverage.
  • the alginic acid may have an average weight average molecular weight (Mw) of alginic acid of 1,500 to 5,000, and a weight ratio (M / G) of mannuronate and gluronate of alginic acid to 1.6 to 3.8.
  • Mw average weight average molecular weight
  • M / G weight ratio of mannuronate and gluronate of alginic acid
  • the alginic acid may be an average weight average molecular weight (Mw) of the alginic acid is 1,500 to 5,000, preferably 2,400 to 2,600.
  • Mw average weight average molecular weight
  • the alginic acid has an average weight average molecular weight (Mw) of alginic acid is 1,500 to 5,000, and the weight ratio (M / G) of mannuronate and gluronate of alginic acid is 1.6 to 3.8, preferably 2.0 to 3.4, more Preferably it may be 2.3 to 2.7.
  • Mw average weight average molecular weight
  • M / G weight ratio of mannuronate and gluronate of alginic acid
  • the alginic acid may be a weight ratio (M / G) of manneuronate and gluronate of alginic acid is 1.6 to 3.8, preferably 2.0 to 3.4, more preferably 2.3 to 2.7.
  • the present invention provides a use of alginic acid, specifically for treating, improving or preventing alginic osteoarthritis or osteoporosis in order to achieve the above object.
  • the alginic acid may be an average weight average molecular weight (Mw) of the alginic acid is 1,500 to 5,000, preferably 2,400 to 2,600.
  • Mw average weight average molecular weight
  • the alginic acid has an average weight average molecular weight (Mw) of alginic acid is 1,500 to 5,000, the weight ratio (M / G) of manneuronate and gluronate of alginic acid is 1.6 to 3.8, preferably 2.0 to 3.4, more preferably May be from 2.3 to 2.7.
  • the alginic acid may be a weight ratio (M / G) of manneuronate and gluronate of alginic acid is 1.6 to 3.8, preferably 2.0 to 3.4, more preferably 2.3 to 2.7.
  • the inventors of the present invention have been searching for substances derived from natural products that can promote the production of collagen and proteoglycans while researching substances derived from natural products that have the effect of treating, improving or preventing osteoarthritis or osteoporosis, which have ensured human safety.
  • Alginic acid a natural product that can be extracted from brown algae in the process, promotes collagen production and production of proteoglycans according to the molecular weight and the ratio of constituent sugars mannuronate (M) and gluuronate (G). It was confirmed that the promoting ability was different.
  • the weight average molecular weight (Mw) is 2,500
  • the production of collagen and proteoglycans is significantly promoted compared to the case where the weight average molecular weight is 98,000
  • mannuronate (M) and gluro included in the alginic acid The ratio of guluronate (G) was found to have the best collagen production promoting ability and proteoglycan production promoting ability in the range of 2.5 to 3.2, most preferably 2.5, based on the weight ratio.
  • the ratio of mannuronate to gluronate was 2.5: 1 (manneuronate: gluronate) to 3.2: 1 (manneuronate: gluronate) based on the weight ratio.
  • the alginate which is preferably 2.5: 1 (manneuronate: gluronate)
  • has the best effect of improving joint damage thereby completing the present invention. The.
  • osteoarthrits refer to a disease in which inflammation and pain occur due to damage to bones and ligaments forming joints due to damage or degenerative changes immediately before point of cartilage protecting the joints.
  • osteoarthritis type II collagen and prothioglyce by the production of nitric oxide, which causes inflammation in the cartilage matrix, the production of interleukin-1 (IL-1) or matrix metalloproteinases (MMPs)
  • IL-1 interleukin-1
  • MMPs matrix metalloproteinases
  • Idiopathic arthritis is caused by factors such as age, sex, genetic factors, obesity, or a specific joint area without a particular organic cause, and is called primary arthritis.
  • the secondary arthritis is caused by trauma, disease, and malformation that can damage joint cartilage, and refers to a case where articular cartilage is destroyed by bacterial arthritis or tuberculous arthritis, or after severe shock or repeated minor trauma. It is called secondary arthritis.
  • Alginic acid of the invention in particular, alginate having a ratio of 2.5 or 3.2 of mannuronate (M) and gluuronate (G), corresponds to the corresponding mannuronate (M) and gluuronate (G).
  • alginic acid having a ratio of less than 2.5 or more than 3.2 it was confirmed that the bone joint improvement function and the bone formation function were excellent.
  • the composition for preventing or treating osteoarthritis or osteoporosis of the present invention may include 0.001 to 99.99% by weight, preferably 0.1 to 99% by weight of the alginic acid, based on the total weight of the composition, and prevent or treat the osteoarthritis or osteoporosis.
  • the content of the active ingredient can be appropriately adjusted depending on the method of use and purpose of use.
  • the composition includes nutrients, vitamins, electrolytes, flavors, colorants, neutralizers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonic acids, in addition to alginic acid.
  • the carbonation agent etc. which are used for a drink can be contained further.
  • the components may be added to the composition independently or in combination.
  • the content of the additional component may be preferably added in the range of 0.1 to 20 parts by weight per 100 parts by weight of the alginic acid.
  • composition for treating or preventing osteoarthritis or osteoporosis comprising the alginic acid as an active ingredient may be a pharmaceutical composition or a pharmaceutical composition for treating or preventing osteoarthritis or osteoporosis.
  • the present invention may be a pharmaceutical composition containing the alginic acid as an active ingredient, and having a therapeutic or prophylactic effect of osteoarthritis or osteoporosis or osteoarthritis or osteoporosis-related diseases.
  • the pharmaceutical composition for the treatment or prevention of osteoarthritis or osteoporosis or osteoarthritis or osteoporosis-related diseases comprising the alginic acid of the present invention is 0.001 to 99.99% by weight, preferably 0.1 to 99% by weight, based on the total weight of the composition. It may include.
  • composition for the prevention or treatment of osteoarthritis or osteoporosis or a disease related to osteoarthritis or osteoporosis may further include appropriate carriers, excipients and diluents commonly used in the preparation thereof.
  • compositions for the prevention or treatment of osteoarthritis or osteoporosis or osteoarthritis or osteoporosis-related diseases comprising the alginic acid as an active ingredient, respectively, according to conventional methods, oral formulations such as powders, granules, tablets, suspensions, emulsions, syrups, etc. Can be used.
  • excipients and diluents that can be included in the pharmaceutical composition for the prevention or treatment of osteoarthritis or osteoporosis or osteoarthritis or osteoporosis related diseases including alginic acid as an active ingredient, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol , Maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium Stearates and mineral oils.
  • alginic acid as an active ingredient
  • lactose lactose
  • dextrose sucrose
  • sorbitol mannitol
  • xylitol erythritol
  • Maltitol starch
  • the pharmaceutical composition for the prevention or treatment of osteoarthritis or osteoporosis or osteoarthritis or osteoporosis-related diseases containing the alginic acid as an active ingredient is a solid preparation for oral administration, tablets, pills, powders, granules, capsules, and the like are included.
  • Solid preparations are prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin and the like in the extract.
  • lubricants such as magnesium stearate and talc are also used.
  • the pharmaceutical composition for the prevention or treatment of osteoarthritis or osteoporosis or osteoarthritis or osteoporosis-related diseases is a liquid preparation for oral administration
  • the liquid preparation includes a suspension, a solution, an emulsion, a syrup, and the like.
  • various excipients may be included, for example, wetting agents, sweeteners, fragrances, preservatives, and the like.
  • the preferred dosage of the pharmaceutical composition for the prevention or treatment of osteoarthritis or osteoporosis or osteoarthritis or osteoporosis-related diseases including the alginic acid as an active ingredient varies depending on the condition and weight, the degree of the disease, the form of the drug, the route of administration, and the duration. Can be appropriately selected. Preferably from 0.0001 to 1000 mg / kg per day based on the alginic acid of the present invention, to be more effective may be administered in 0.01 to 100 mg / kg, but is not limited thereto. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
  • the present invention includes the alginic acid as an active ingredient, and may be a food composition having an improvement or prevention effect of osteoarthritis or osteoporosis or osteoarthritis or osteoporosis related diseases.
  • Alginic acid included in the food composition as an active ingredient may be an average weight average molecular weight (Mw) of the alginic acid is 1,500 to 5,000, preferably 2,000 to 4,000, more preferably 2,000 to 3,000, even more preferably 2,400 to 2,600 have.
  • Mw average weight average molecular weight
  • the molecular weight (g / mol) may be an average molecular weight, and the measured molecular weight is a weight average molecular weight (Mw).
  • the alginic acid included in the food composition as an active ingredient has a weight average molecular weight (Mw) of 1,500 to 5,000, preferably 2,000 to 4,000, more preferably 2,000 to 3,000, even more preferably 2,400 to 2,600,
  • Mw weight average molecular weight
  • the ratio (M / G) of mannuronate (M) and gluuronate (G), which constitute the alginic acid, is 1.6 to 3.8, preferably 2.0 to 3.4, more preferably based on the weight ratio.
  • 2.2 to 3.2 even more preferably 2.5 to 3.2 or 2.3 to 2.7, most preferably 2.5.
  • fermented milk cheese, etc.
  • other processed foods kimchi, pickles (various kimchi, pickles, etc.)
  • beverages examples include, but are not limited to, fruits, vegetable drinks, soy milk, fermented beverages, and the like, and natural seasonings (eg, ramen soup).
  • the food, beverage or food additives may be prepared by a conventional manufacturing method.
  • the functional food may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of functional foods.
  • the drink is a generic term for drinking to quench thirst or to enjoy the taste and is intended to include a functional drink.
  • the beverage is not particularly limited to other ingredients other than including the alginic acid as an active ingredient in the indicated proportions as an active ingredient, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • Functional beverage in the present invention is a biological defense rhythm control, disease prevention and the like having a beverage group or a beverage composition that has added value to the beverage by using physical, biochemical, biotechnological techniques, etc. to function and express the function of the beverage to a specific purpose Means a beverage that is designed and processed to fully express the gymnastics function related to recovery.
  • the functional beverage is not particularly limited to other ingredients except for containing the alginic acid of the present invention as an essential ingredient in the ratio indicated, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates examples include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. .
  • the present invention also relates to the use of alginic acid, in particular to the use of alginic acid for the treatment, amelioration or prevention of osteoarthritis or osteoporosis.
  • the alginic acid may be an average weight average molecular weight (Mw) of the alginic acid is 1,500 to 5,000, preferably 2,400 to 2,600.
  • Mw average weight average molecular weight
  • the alginic acid has an average weight average molecular weight (Mw) of alginic acid is 1,500 to 5,000, the weight ratio (M / G) of manneuronate and gluronate of alginic acid is 1.6 to 3.8, preferably 2.0 to 3.4, more preferably May be 2.2 to 3.2, even more preferably 2.5 to 3.2 or 2.3 to 2.7, most preferably 2.5.
  • Mw average weight average molecular weight
  • M / G weight ratio
  • Alginic acid of from 2.7 to 2.7, most preferably 2.5 has significantly superior collagen production and proteoglycan production promoting properties in chondrocytes compared to alginic acid having a different range of molecular weight or different ranges of mannuronate and gluronate.
  • Alginic acid of the present invention as a result of experiments using chondrocytes, has a significantly superior collagen synthesis promoting ability and proteoglycan synthesis promoting ability, compared to alginic acid having a molecular weight or weight ratio of mannuronate and gluronate in different ranges, osteoarthritis
  • the alginate as the active ingredient can be prepared from brown algae, which is an algae used as a food, and is expected to have no problems with side effects. Or as a new prophylactic or therapeutic agent such as osteoporosis is expected to be very valuable.
  • FIG. 1 This is a photograph of the joint surface of the thigh of the experimental animal administered with the alginic acid of 1.6
  • Figure 4 is a test animal administered with alginic acid having a weight ratio (M / G) of mannuronate and gluronate of alginic acid of 2.5
  • Figure 5 is a photograph of the joint surface of the femoral part
  • Figure 5 is a photograph of the joint surface of the femoral section of the experimental animal administered alginic acid having a weight ratio (M / G) of alginate mannuronate and gluronate of 3.2
  • Figure 6 Manneuronate and glurone of alginic acid
  • the weight ratio of agent (M / G) is a photograph taken of the femoral articular surface of the experimental animals treated with 3.8 of alginic acid.
  • alginate lyase alginate lyase, sigma, USA, was added, followed by a decomposition reaction for 20 hours.
  • the temperature of the fermentation tube was raised to 90 ° C. to stop the decomposition reaction by the enzyme, and the aqueous sodium alginate solution was cooled by circulating the cooling water.
  • Filtration was performed using an ultrafiltration membrane (Millipore UF filtration, MWCO 10,000) in order to obtain alginic acid according to each molecular weight range from the aqueous alginic acid solution subjected to the decomposition reaction by the enzyme.
  • the molecular weight of the alginic acid obtained by the ultrafiltration membrane was measured by GPC (Gel Permeation Chromatography), and it was confirmed that the mass average molecular weight (Mw) of the alginic acid was 2,500.
  • alginic acid having an alginate mass average molecular weight (Mw) of 98,000 and 2,500
  • Mw alginate mass average molecular weight
  • G gluuronate
  • the weight ratio (M / G ratio) of the alginate to mannuronate and gluronate is poly-mannuronic acid (PMA) and polygluronate (poly-guluronic acid, PGA) from alginate. After partial extraction, the weight was measured after lyophilization, and the weight ratio (M / G weigh ratio) of mannuronate and gluronate was determined.
  • Cartilage was collected from the knee joints of two-week-old rabbits (Korea Research Institute of Life Science, Korea), and submerged in the culture medium, specifically, 1.6 ml of serum-free DMEM (Pharmacia Biotech. USA), followed by 1% collagenase. 0.4 ml (Sigma, USA) was added.
  • the culture solution containing cartilage added with collagenase was placed in a CO 2 incubator at 37 ° C., followed by a reaction for about 6 hours while shaking the cells every 30 minutes to decompose collagen in the cartilage tissue with collagenase, Chondrocytes of chondrocytes were separated into single cell units. After the above procedure, the supernatant was discarded by centrifuging the culture solution containing cartilage, and 1 ml of complete medium (serum-containing DMEM) was added and diluted in 2 ml of normal medium (10% FBS DMEM) per rabbit. To make a cell suspension.
  • Example 3 the control group is not treated at all, and the low molecular weight alginic acid treatment group and the polymer alginic acid treatment group are each treated with 100 mg / L of the alginic acid, the control group, low molecular weight alginic acid treatment group and The polymer alginic acid treated group was incubated for 48 hours in a CO 2 incubator at 37 °C, the OD value of the culture was measured. The experiment was repeated three times in total, and the quantitative results of the three repeated results are shown in Table 2 below.
  • proteoglycan which is a cartilage matrix molecule
  • the amount of proteoglycan was significantly increased in the low molecular weight alginic acid treated group compared to the control group, but in the case of the polymer alginic acid treated group, It was found that the amount of proteoglycans did not increase significantly.
  • the weight ratio (M / G) of mannuronate to gluronate was higher in collagen production than in the case of adding no alginic acid or the polymer alginic acid identified in Example 3 in the range of 1.6 to 3.8
  • the weight ratio (M / G) of mannuronate to gluronate suitable for promoting the production of collagen synthesis was found to be markedly excellent collagen production promoting ability compared to the case outside the above range in the range of 2.5 to 3.2
  • the weight ratio (M / G) of neuronate was found to have the best collagen production promoting ability in the case of 2.5.
  • proteoglycan production was found to be the highest, and the ratio of manneuronate to gluronate of alginic acid (M / G) was 3.2, and the ratio of manneuronate to gluronate of alginic acid (M / G) was 2.5. Although almost similar to, the weight ratio (M / G) of mannuronate to gluronate of alginic acid was again found to be significantly reduced proteoglycan production at 3.8.
  • Example 7-2 Measurement of Osteoarthritis Treatment Efficacy
  • osteoarthritis was induced in the experimental animals bred in Example 6-1.
  • the osteoarthritis was induced by the right cruciate ligament dissection method.
  • xylazine hydrochloride (3 mg / kg) and ketamine hydrochloride (50 mg / kg) were injected intramuscularly to the experimental animal by general anesthesia. Disinfection was performed using% povidone-iodine solution. Of the right posterior part of the depilation and disinfection, the medial knee was exposed by 2 cm incision, the fascia and articular cap were incision, and the patella was folded outward to expose the cruciate ligament. The exposed cruciate ligament was excised using No. 11 blade, and then washed with physiological saline.
  • Alginic acid type was divided into groups of low molecular weight alginic acid, and 30 mg / kg (BW) of each alginic acid was dissolved in 0.5 ml / kg (BW) physiological saline.
  • Both the control group and the experimental group were orally administered every day from the next day after surgery to the fifth week.
  • Example 7 using the animal model were confirmed to have the same tendency as those of Examples 5 and 6 confirming collagen production promoting ability and proteoglycan production promoting ability in in vitro experiments ( invitro ).

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Abstract

La présente invention concerne une composition comprenant de l'acide alginique, en tant que substance active, pour le traitement ou la prévention de l'arthrose ou l'ostéoporose. La composition pour le traitement ou la prévention de l'arthrose ou de l'ostéoporose peut être une composition pharmaceutique. La présente invention concerne en outre une composition alimentaire comprenant de l'acide alginique, en tant que substance active, pour soulager ou prévenir l'arthrose ou l'ostéoporose. La composition de la présente invention est identifiée comme ayant une condition optimale pour le traitement, la prévention ou le soulagement de l'arthrose ou l'ostéoporose en termes de poids moléculaire de l'acide alginique et du mannuronate et du guluronate. La composition de la présente invention comprend de l'acide alginique, en tant que substance active, qui est inoffensif pour les humains, et n'a donc pas d'effets secondaires et présente d'excellents effets dans le traitement de l'arthrose ou l'ostéoporose. Par conséquent, la composition de la présente invention peut être efficacement utilisée dans le traitement de l'arthrose ou l'ostéoporose.
PCT/KR2012/010315 2012-11-30 2012-11-30 Composition comprenant de l'acide alginique pour la prévention ou le traitement de l'arthrose WO2014084427A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017222302A1 (fr) * 2016-06-21 2017-12-28 전남대학교 산학협력단 Composition pour améliorer la capacité à l'exercice et traiter l'ostéoporose, contenant un oligosaccharide à base d'acide mannuronique, insaturé et à extrémité non réductrice

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5563124A (en) * 1991-04-22 1996-10-08 Intermedics Orthopedics/ Denver, Inc. Osteogenic product and process
US20100048506A1 (en) * 2008-08-19 2010-02-25 Mochida Pharmaceutical Co., Ltd. Composition for treating arthritic disorder
US20100080788A1 (en) * 2006-10-12 2010-04-01 The Johns Hopkins University Alginate and alginate lyase compositions and methods of use
KR20100088687A (ko) * 2007-10-24 2010-08-10 모찌다 세이야쿠 가부시끼가이샤 관절 질환 치료용 조성물
US20120156288A1 (en) * 2009-09-02 2012-06-21 Lipofoods, S.L. Microcapsules containing salts for food products

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5563124A (en) * 1991-04-22 1996-10-08 Intermedics Orthopedics/ Denver, Inc. Osteogenic product and process
US20100080788A1 (en) * 2006-10-12 2010-04-01 The Johns Hopkins University Alginate and alginate lyase compositions and methods of use
KR20100088687A (ko) * 2007-10-24 2010-08-10 모찌다 세이야쿠 가부시끼가이샤 관절 질환 치료용 조성물
US20100048506A1 (en) * 2008-08-19 2010-02-25 Mochida Pharmaceutical Co., Ltd. Composition for treating arthritic disorder
US20120156288A1 (en) * 2009-09-02 2012-06-21 Lipofoods, S.L. Microcapsules containing salts for food products

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017222302A1 (fr) * 2016-06-21 2017-12-28 전남대학교 산학협력단 Composition pour améliorer la capacité à l'exercice et traiter l'ostéoporose, contenant un oligosaccharide à base d'acide mannuronique, insaturé et à extrémité non réductrice

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