JP2005232089A - Orally administrable functional agent having bone quantity-increasing activity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an orally administrable functional agent having a bone quantity-increasing activity, capable of improving bone density, promoting growth of joint cartilages, and capable of positively preventing the onset of osteoporosis and cartilage arthritis. <P>SOLUTION: This orally administrable functional agent contains collagen, glucosamine, chondroitins and vitamin C as active ingredients, regulated so that the content of the vitamin C may be ≥50% of the content of the collagen, and the vitamin C may not keep contact with the collagen, the glucosamine and the chondroitins. The orally administrable functional agent can further contain calcium, vitamin Bs, zinc, selenium, or the like. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a functional oral administration agent having a bone mass increasing action useful for bone bone or articular cartilage, which is one of human tissues, for reducing bone mass or preventing and treating arthritis such as knees. About.

  In recent years, with the aging of society, in elderly people, bone density has decreased, and symptoms such as osteoporosis and knee arthritis due to decreased bone mass have developed, and even a slight external force is likely to cause fractures. In many cases, arthritis also occurs. In addition, unbalanced diets or balanced nutritional foods cannot be taken regardless of age. For example, such symptoms are also observed in single people and young people. These symptoms are present at the age of the stage. Athletes have a lot of stress on joints due to excessive exercise from a young age, severe joint wear, and many people cause injuries such as arthritis and joint pain relatively early.

  Especially in elderly people, there is a decrease in bone density in the wrist, hip joint, spine, and shoulder joints, and in this part, it is easy to cause fractures due to falls, etc. Because it is scarce, it takes a long time to treat fractures, and the prevalence of arthritis represents about 6% of the Japanese population, which has long been considered a painful disease. In the future, bone diseases including osteoporosis will become more serious due to the aging society and the convenience of living environment, and the importance of the treatment will increase dramatically.

  As shown in FIG. 1, a bone part such as a human limb consists of a diaphysis (cortex) occupying most of the osseous part and upper and lower diaphysis (cartilage), and the diaphysis includes articular cartilage. Also called. These diaphyseal parts and metaphyseal parts form a human skeleton, and are very important parts for maintaining life and exercise ability. Conventionally, bone mineral density is increased to prevent or treat osteoporosis, chondrocytes are increased, articular cartilage is increased, and collagen, glucosamine and chondroitin are taken orally for the prevention and treatment of arthritis and joint pain. It is generally known that this can be improved.

  Collagen is a major protein component that constitutes the connective tissue of animals, and 16% of human body weight is composed of protein, of which 30-40% is collagen. 70% of the skin and 20% of the bone are made of collagen, and are contained in a large amount in blood vessels, blood, eyeballs, tendons, muscles, and the like, and various types are known (19 types in 1995). Although the action differs slightly depending on each type, what is generally called collagen has an action of adhering calcium to bone, and it is said that calcium cannot adhere without collagen.

  Glucosamine is a kind of amino sugar produced in the body from glutamine and glucose (glucose), forming cartilage and connective tissue as a component of mucopolysaccharide (proteoglycan), improving the function of the lowered joints, It is said that it works to relieve pain.If there is a lot of glucosamine, more proteoglycans are produced and more cartilage is produced.Glucosamine stimulates chondrocytes and regulates cartilage metabolism, thereby reducing cartilage degeneration. It is said to prevent it.

  A typical example of chondroitin is chondroitin sulfate. Chondroitin sulfate is a kind of polysaccharide obtained from animal viscous secretion called mucopolysaccharide consisting of hexosamine, uronic acid and sulfuric acid, and is classified as acidic mucopolysaccharide. Its characteristics are high water retention and lubrication. In the body, in addition to the cornea, the lens, the ciliary muscle, the vitreous body (constituent tissue of the eye), it is often contained in a state where it is bound to proteins such as cartilage, bone, tendon, blood vessel wall, and skin. This chondroitin sulfate suppresses the cartilage-degrading enzyme, collects water in the proteoglycan molecule, and suppresses the degradation of the proteoglycan. Therefore, it is thought that the joint is smooth, elastic, and soothes joint pain. ing.

  Vitamin C is also referred to as ascorbic acid, has various physiological actions, and has an antioxidant action as the main physiological action. It is also said to be involved in collagen production and maintenance (proline and lysine hydroxylation).

  Calcium is one of the important elements as a biological component. In animals, it is important as a component of the endoskeleton and the exoskeleton, and 99% or more of vertebrates are present as phosphates, carbonates, and fluorides in the skeleton.

  Conventionally, many functional foods etc. which use said each component and its combination as an active ingredient have been reported. For example, chondroitin sulfate sodium or an oral osteoporosis preventive and therapeutic agent containing sodium chondroitin sulfate and calcium as active ingredients (see, for example, Patent Document 1), for preventive and therapeutic treatment of degenerative or inflammatory joint diseases As a nutritional supplement or pharmaceutical composition, a composition comprising L-carnitine or lower alkanoyl-L-carnitine and glucosaminoglycan and / or a component thereof, for example, a weight ratio of L-carnitine: chondroitin sulfate: glucosamine A composition in the range of 1: 1: 1 to 1:10:10 (see, for example, Patent Document 2), a lipid-bound glycosaminoglycan in which lipid is bound to glycosaminoglycan, or a pharmacologically acceptable product thereof Bone induction promoter containing salt as an active ingredient (for example, see Patent Document 3) ), A functional food (for example, see Patent Document 4) containing chondroitin sulfate derived from coral or nasal cartilage and birch tree birch tree sap, a bone containing calcium salt containing chondroitin and isoflavone A calcium-containing food composition having a density improving function (for example, see Patent Document 5), a collagen peptide and a glucosamine salt, having a pH of 2 to 5, and further, a taste regulator, vitamin, mineral A joint strengthening beverage containing one or more selected from among fragrances and fragrances (for example, see Patent Document 6), an extract of cat's claw, glucosamine, chondroitin sulfate, and collagen for relieving joint pain Oral compositions (see, for example, Patent Document 7) are known.

Japanese Unexamined Patent Publication No. 7-109222 JP 2000-53569 A JP 2000-212204 A JP 2001-231497 A JP 2002-58452 A JP 2002-125638 A JP 2003-155250 A

  A food or composition capable of enhancing bone density by enhancing bone density by combining bone enhancer with known enhancer and vitamin C, zinc, calcium, etc., and actively preventing the development of osteoporosis and cartilage arthritis. Not proposed. If osteoporosis and cartilage joint can be treated by maintaining or improving bone density by actively taking food or health food on a daily basis, its usefulness is high. An object of the present invention is to provide a functional oral administration agent having an effect of increasing bone mass, which can improve bone density, promote articular cartilage growth, and can actively prevent the development of osteoporosis and chondroarthritis. It is in.

  The present inventor has intensively studied to solve the above problems, and that the simultaneous administration of collagen, glucosamine, chondroitin and vitamin C has a synergistic effect and is essential for improving bone density and promoting growth of articular cartilage. I found it. However, in view of the fact that only a very small amount of vitamin C is blended in this type of blend in the past, in order to investigate the effect of vitamin C on the collagen / chondroitin / glucosamine mixture, vitamins shown in [Table 1] (above) are used. C, collagen, chondroitin, and glucosamine were mixed, placed in a plastic bag and stored in an environment of 50 ° C., and changes in color tone were observed over time. The results are shown in [Table 1] (bottom).

  As a result, as shown in [Table 1] (below), by adding vitamin C, the collagen / chondroitin / glucosamine mixture was added on the 10th and 20th day compared to the amount at the start of mixing. It was observed that the greater the amount of color, the greater the change in color tone, and the collagen / chondroitin / glucosamine mixture without addition of vitamin C, and vitamin C itself were unchanged under the same conditions. Therefore, in order to use a larger amount of vitamin C, it has been found that it is important for stability to keep vitamin C and collagen, glucosamine, and chondroitins separate.

  As described above, in the present invention, the simultaneous administration of collagen, glucosamine, chondroitin and vitamin C has a synergistic effect and is necessary for improving bone density and growth of articular cartilage. Based on the knowledge that it is necessary to keep collagen, glucosamine, chondroitins and vitamin C in different tablets, etc., in a non-contact state, it has been completed. is there. Further, in addition to collagen, glucosamine, chondroitin and vitamin C, in addition to calcium and vitamin B, it was confirmed that the bone mass increasing action was further improved by adding zinc and selenium as trace components. Has been completed.

  That is, the present invention contains collagen, glucosamine, chondroitin and vitamin C as active ingredients, the vitamin C content is 50% or more of the collagen content, and collagen, glucosamine, chondroitin and vitamin C are not in contact with each other A functional food having a bone mass increasing action and a functional food having the above bone mass increasing action further containing calcium and / or vitamin B, and zinc and / or selenium. The functional food having the above bone mass increasing action, the functional food having the above bone mass increasing action in which zinc and selenium are blended as zinc-containing yeast and selenium-containing yeast, and chondroitin are shark fin extract Certain functional foods with the above bone mass increasing action and bone mass increasing action are It is a growth enhancement effect of the cartilage related to functional oral agents having a bone mass increasing action of the.

  The functional oral dosage form of the present invention can be taken for a long time without toxicity by combining materials that have been confirmed to be effective in improving bone density, growth of articular cartilage, etc. It is useful for the prevention and treatment of osteoporosis, and for the prevention and treatment of aging. In addition, by increasing chondrocytes, the articular cartilage is increased to prevent arthritis and joint pain. Pain can be effectively relieved. Therefore, the present composition can be applied to a wide range of joint pains such as prevention of fractures caused by osteoporosis and arthritis.

  The functional oral administration agent of the present invention has an effect of increasing bone mass, contains collagen, glucosamine, chondroitin and vitamin C as active ingredients, the vitamin C content is 50% or more of the collagen content, and If it contains collagen, glucosamine, chondroitin, and vitamin C in the state which does not contact, it will not restrict | limit in particular. Here, the bone mass increasing action refers to the calcium content increasing action in the diaphyseal tissue and the metaphyseal tissue, and in addition to this bone mass increasing action, it has a bone density improving action and a joint cartilage growth promoting action. Preferably, these can be confirmed by measuring alkaline phosphatase activity, which is a calcification promoting enzyme in bone tissue, or by measuring the amount of DNA in bone tissue that becomes the Mercum of the number of cells in bone tissue.

  As the collagen, collagen existing in cartilaginous tissues, bones, organs, tendons, etc. of mammals such as cattle and pigs, birds such as chickens, fish such as sharks, and molluscs such as squid can be used. These can be mixed and used, or a commercially available product can also be used.

  As said glucosamine, free thing, glucosamine hydrochloride, and N-acetylglucosamine can be used, and these are made into a chitin decomposition product so that chitin obtained from crustaceans is easy to digest, and are marketed. These may be used as a mixture.

  As chondroitins, for example, shark fin extract containing chondroitin, or chondroitin sulfate, for example, commercially available sodium chondroitin sulfate described in the Japanese Pharmacopoeia Standards for Pharmaceutical Components may be used.

  Since vitamin C is generally commercially available, such a commercially available product can be used. However, vitamin C content needs to be 50% or more of collagen content, and vitamin C 50-200 per 100 parts by weight of collagen. Parts by weight, preferably 50 to 80 parts by weight, more preferably 50 to 60 parts.

As the functional oral administration agent having bone mass increasing action of the present invention, in addition to the collagen, glucosamine, chondroitin and vitamin C, those containing trace elements such as zinc and selenium in addition to calcium and vitamin B preferable. Calcium includes natural or synthetic calcium salt forms such as inorganic salts such as calcium carbonate, organic acid calcium salts such as acetic acid, L-lactic acid, citric acid and malic acid, and foods rich in calcium such as eggshell calcium. Can be used. Vitamin B ₂ is preferable as the vitamin B, and as trace elements such as zinc and selenium, in addition to fine powders such as zinc and selenium, commercially available yeast with high zinc content (containing 10% zinc) and selenium-containing yeast (0 .2% selenium content) can be used advantageously.

  The dosage form of the functional oral dosage form of the present invention is not particularly limited as long as it is a dosage form in which collagen, glucosamine, chondroitin and vitamin C can be orally administered in a non-contact state. Tablets, powders, granules , Capsules, drinks, syrups, pastes, etc., tablets, powders, granules, capsules, etc. containing collagen, glucosamine, chondroitin and the like, tablets, powders containing vitamin C A combination agent with an agent, a granule, a capsule, etc. can be illustrated suitably. When preparing these tablets, powders, granules, capsules, etc., excipients such as lactose, starch, sorbitol, lubricants such as talc, magnesium stearate, sucrose fatty acid ester, hydroxypropylcellulose, polyvinylpyrrolidone In addition to disintegrants such as carboxymethylcellulose, stabilizers, sweeteners, colorants, emulsifiers, solubilizers, and the like can be blended. Moreover, the functional oral administration agent of this invention can also be added to a food raw material, and can also be administered as a functional food.

  As the compounding ratio of each component in the functional oral administration agent of the present invention, collagen 100 parts by weight, chondroitin (as shark fin extract) 75 to 90 parts by weight, glucosamine 55 to 75 parts by weight, and another form of vitamin C50 to Preferred examples include tablets, powders, granules, capsules and the like with 60 parts by weight.

  EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, the technical scope of this invention is not limited to these illustrations.

(Test animal)
Wistar male rats (weight 80 to 90 g; 4 weeks old) were used as test animals. During the experimental period, rats were given free access to purified distilled water and chow (oriental yeast MF; containing 1.1% calcium, 1.1% phosphorus, 57.4% carbohydrates).

(Preparation of administration sample)
Those having the composition shown in [Table 2] containing collagen, glucosamine, chondroitin and vitamin C as active ingredients (test group), and containing collagen, glucosamine and chondroitin as active ingredients but not containing vitamin C [ The composition shown in Table 3] (reference zone A) and the composition shown in [Table 4] containing vitamin C as an active ingredient but not containing collagen, glucosamine or chondroitin (reference zone B) Each was prepared. The combination of (Reference Zone A) and (Reference Zone B) is the functional oral dosage form of the present invention containing collagen, glucosamine, chondroitin and vitamin C in a state where they are not contacted, (Reference Zone A) A combination of each component with (Reference Zone B) by adjusting the amount of excipient and the like corresponds to (Test Zone). (Test Zone), (Reference Zone A), (Reference Zone B) were suspended using purified distilled water, and 15 mg test zone / ml (test group 15) and 30 mg test zone / ml (test group 30), and Sample solutions of 30 mg reference group A / ml (reference group A30) and 30 mg reference group B / ml (reference group B30) were prepared.

(Analysis and measurement items)
Each of these sample solutions was orally administered at a dose of 1 ml per 100 g of rat body weight using a gastric sonde once a day for 7 days, and dissected under light ether anesthesia at 24 hours after the final administration. Was extracted. The femur, except for the muscle composition, was washed and removed from the bone marrow and divided into a diaphysis (cortical bone) and a metaphysis (also referred to as cartilage and cancellous bone), and each was used to measure bone components. The amount of calcium in the bone tissue was colorimetrically determined by drying the bone tissue at 100 ° C. for 5 hours, measuring the weight, and then decomposing it in 100 ml of concentrated nitric acid at 100 ° C. for 24 hours. Alkaline phosphatase (bone mineralization promoting enzyme) activity in bone tissue was measured. In addition, the amount of DNA as an index of the number of cells in the bone tissue was measured. The blood was allowed to stand at room temperature for 30 minutes and then centrifuged (3000 rpm for 5 minutes) to obtain serum. The amount of serum calcium, inorganic phosphorus and zinc was measured using a commercially available kit. Statistical processing of the obtained data was performed using Student's-test (t test). The control group was administered with purified distilled water.

(Weight fluctuation)
Changes in body weight were examined when each sample solution was orally administered for 7 days. The results are shown in [Table 5]. As a result, (Test Group 15) and (Test Group 30) did not cause significant fluctuations in body weight. Further, even when (Reference group A30) or (Reference group B30) was orally administered, no significant change in weight gain was observed. From this, the toxicity of (Test Zone), (Reference Zone A) or (Reference Zone B) is considered to be extremely low.

(Changes in serum components)
Changes in serum calcium, inorganic phosphorus and zinc were examined. The results are shown in [Table 6]. As a result, (Test group 15) and (Test group 30) did not cause significant fluctuations in serum calcium, inorganic phosphorus and zinc. Further, even when (Reference group A30) or (Reference group B30) was orally administered, no significant changes in calcium, inorganic phosphorus and zinc in the serum were observed. From this, the toxicity of (Test Zone), (Reference Zone A) or (Reference Zone B) is considered to be extremely low.

(Changes in bone tissue calcium)
The effect of administration on bone tissue calcium content was investigated. The results are shown in [Table 7]. As a result, oral administration of (Test Group 30) significantly increased the amount of calcium in the diaphysis and metaphysis tissue. The amount of calcium in the diaphysis was significantly increased with the dose of (Test group 15), but no significant effect was found in the metaphysis. In (Reference group A30), the amount of calcium in the diaphysis was significantly increased. In Reference Group B30, the amount of calcium in the diaphysis increased significantly, but did not increase significantly in the metaphysis. From these results, it was revealed that in order to increase the amount of calcium in bone tissue, it is necessary to co-administer vitamin C in addition to collagen, glucosamine and chondroitin.

(Changes in alkaline phosphatase activity in bone tissue)
The effect of administration on alkaline phosphatase activity of calcification-promoting enzyme in bone tissue was investigated. The results are shown in [Table 8]. As a result, it was recognized that alkaline phosphatase activity at the diaphysis and metaphysis was significantly increased by administration of (Test group 15) and (Test group 30) and (Reference group A30) and (Reference group B30). . Among them, (Test group 30) exhibited a strong effect.

(Change in bone tissue DNA amount; change in cell number)
The effect of administration on the amount of DNA in bone tissue was examined. The results are shown in [Table 9]. As a result, the amount of DNA in the diaphyseal tissue was not significantly changed by the administration of (Test group 15) and (Test group 30) and (Reference group A30) and (Reference group B30), but there were many cells. The amount of DNA in the metaphyseal tissue was significantly increased by administration of (Test group 30) and (Reference group A30). From this, it is considered that collagen, glucosamine, and chondroitin included in both (Test group 30) and (Reference group A30) function as active ingredients and promote the function and proliferation of osteoblasts. .

(Synergy)
The results of (Test group 30), (Reference group A30) and (Reference group B30) at a dose of 30 mg / 100 g of body weight are summarized in [Table 10]. As can be seen from [Table 10], the amount of calcium in the metaphyseal tissue was not significantly increased by administration of (Reference group A30) or (Reference group B30), but collagen, glucosamine, chondroitins and vitamin C Was found to increase significantly in the test group 30 (test group 30). This demonstrates that the simultaneous administration of collagen, glucosamine, chondroitins and vitamin C has a synergistic effect.

It is a figure which shows the diaphysis part (cortical bone) and the metaphyseal part (cartilage) of a hand and a leg.

Claims (7)

Collagen, glucosamine, chondroitin and vitamin C are contained as active ingredients, vitamin C content is 50% or more of collagen content, and collagen, glucosamine, chondroitin and vitamin C are contained in a state where they are not in contact with each other. A functional oral administration agent having a bone mass increasing action. The functional oral administration agent having a bone mass increasing action according to claim 1, further comprising calcium and / or vitamin B. 3. The functional oral administration agent having bone mass increasing action according to claim 1, further comprising zinc and / or selenium. The functional oral administration agent having a bone mass increasing effect according to claim 3, wherein zinc and selenium are blended as zinc-containing yeast and selenium-containing yeast. The functional oral administration agent having a bone mass increasing action according to any one of claims 1 to 4, wherein the chondroitin is a shark fin extract. The functional oral administration agent having a bone mass increasing action according to any one of claims 1 to 5, which has a bone density improving action. 7. The functional oral administration agent having an action of increasing bone mass according to any one of claims 1 to 6, which has an action of promoting the growth of articular cartilage.

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