JP2001500161A - Composition containing calcium, vitamin D and amino acids for treatment of osteoporosis and for promoting healing of damaged bone - Google Patents

Abstract

  (57) [Summary] The present invention relates to a composition for the manufacture of a medicament for the treatment of osteoporosis and / or for promoting the treatment of damaged bone, comprising calcium and vitamin D in the form of calcium gluconate and heptgluconate. About things. In addition, the composition contains amino acids such that the ratio of amino acids to calcium and vitamin D is equal to the ratio of amino acids to calcium and vitamin D found in the organic matrix of human bone tissue. The content of amino acids is 15 to 20% by weight. The composition is prepared for oral administration in the form of a solution, tablet, granule, capsule or the like, which may constitute a food additive.

Description

DETAILED DESCRIPTION OF THE INVENTION   Containing calcium, vitamin D and amino acids, for the treatment of osteoporosis,                  And a composition for promoting the treatment of damaged bone   The present invention is particularly useful for treating osteoporosis and / or facilitating bone fracture repair. A composition for the manufacture of a medicament for treating Contains vitamin D.   Furthermore, the present invention relates to a nutrient aggregate derived from this composition and the use of the aggregate. About.   In order to elucidate the path of the present invention, the fact that bone contains two main components Care must be taken. That is, a) Hydroxyapatite comprising calcium salt and phosphate b) Collagen fiber, a complex substance containing both amino acids and sugars in its structure Is an organic matrix containing, as a main component.   The mechanical properties of bone depend on the interaction of these two components, Men ”and iron structures that make up reinforced concrete. Rix plays a second role, as in other parts of the body, the solution Promotes precipitation and crystallization of calcium and phosphate salts remaining therein.   Bone develops and denuds under the action of osteoclasts and osteoblasts throughout the life of the individual. It should be taken into account that the separation is going on continuously.   Osteoblasts are found on almost all surfaces and voids of bone and secreted collagen fibers. Thus, the formation of hydroxyapatite is promoted.   Osteoclasts, especially found in bone cavities, resorb both the organic and mineral components of bone You. Calcium and phosphate are extracted from the mineral components, and the hydroxyapatite Partially recycled for new formation.   Conversely, by peeling the organic material, amino acids and sugars, which are the basic components of collagen, are removed. It does not, but does release the end product of its metabolism.   Therefore, the supply of sugars and amino acids must be maintained in order to guarantee the formation of new collagen. Is essential. Sugars can be widely obtained in interstitial fluids and blood. Although amino acids are more difficult to obtain, they must be replenished externally. It must always be obtained from ingested food or from other sources.   During growth, bone neoplasia is stronger than its exfoliation. Later, two works Utilities must balance each other. However, in old age, bone debonding It tends to dominate the new formation.   This phenomenon is the most common bone disorder in adults, especially postmenopausal women, and In the case of osteoporosis, which is the most common cause of broken bone, is increased.   To treat normal bone damage and osteoporosis-related damage, Require predominant bone neoplasia. If this process does not proceed, treatment will stop. Or delayed and "callus formation".   In view of this summary, osteoporosis and slow bone sclerosis with persistence of "callus formation" Appropriate treatment methods for bone mineral components and, more importantly, their organic components We come to the conclusion that both supplies must be available. Contribute to its mechanical properties This organic component further promotes the formation of hydroxyapatite. like this The method of treatment is to produce bone, and in particular, collagen fibrous organic matrix. Essential is to supply amino acids.   High protein diets are the best way to achieve this, but unfortunately This method does not produce the desired effect. Numerous reports (Allen et al., 1982; Her gsted, 1986; Hergsted and Linkswillwer, 1981) Tends to cause bone mineral depletion by stimulating urinary calcium secretion There is.   Therefore, a major goal of current osteoporosis treatment modalities is to reconstitute the mineral components of bone. Is Rukoto. Unfortunately, the results obtained in this way are unsatisfactory .   For example, calcium and vitamin D have proven useful, but The effect is not crucial.   Sodium fluoride reduces resorption of mineral parts of bone, but patients with idiosyncratic features Side effects at a certain rate.   Calcitonin is active and relatively well tolerated, especially when administered intranasally. However, their efficacy tends to weaken over time.   Pyrophosphate analogs are promising drugs, but are also effective for long-term treatment. Is questionable.   U.S. Patent No. 5,296,246 and Japanese Patent Publication 1993 161480 Publication to improve the efficient absorption of calcium into the human body and Amino acids and calcium, which promote deposition into the body and inhibit osteoporosis effects Compositions based on these are known.   The product described in U.S. Pat. No. 5,296,246 is 0.0001-0.0 Contains naturally derived calcium with a trace amount of amino acids of 0.05% by weight .   The composition according to Japanese Patent Publication No. 161480/1993 is 0.005 to 0.005. A calcium compound with at least two amino acids at a level of 0.2% by weight. Have   The present invention provides a rapid and resistant method for damaged or osteoporotic bone By providing a composition that facilitates reconstitution, as in It aims to overcome the shortcomings and shortcomings of treatment modalities.   This object is achieved by a composition according to the invention as defined in the preamble of the claims. Is done. That is, it is a ratio of calcium and vitamin D to human bone tissue. Amino acids for calcium and vitamin D, as found in organic matrices And contains amino acids in the same proportion as   Advantageously, it comprises calcium gluconate, calcium heptagluconate, It contains Tamine D3 and the proportion of amino acids ranges from 15 to 20% by weight.   According to a preferred embodiment, the proportion of calcium gluconate is not more than 6% by weight. , The proportion of calcium heptagluconate is essentially equal to 7.5% by weight, The proportion of min D3 is equal to 0.0005% by weight.   In a particularly advantageous manner, the composition is in a form suitable for oral administration, in a solution, capsule, Supplied in any of granules, powders, gel cups and the like.   As described in the claims, in particular for the treatment of osteoporosis and / or breakage A nutritional concentrate comprising a composition for the manufacture of a medicament for promoting bone treatment Development has achieved this goal.   This nutritional accumulation can be mixed with other foods.   The present invention is further described by the following description applied to the treatment of osteoporotic and damaged bone. Better understood.   According to a particularly advantageous embodiment, the composition is obtained in the form of a solution and has a weight of 1 kg. Orally in a dose of 40-50 mg. Amino required for new bone formation Supplying acids to the body in the form of a high protein diet induces the loss of minerals normally found in the body. It has been found that the desired effect can be obtained without guiding.   A suitable combination of calcium and vitamin D is found in the organic matrix of bone. Administration of a product containing the same amino acid proportions as And, despite the surprising improvement in the treatment of damaged bone, all of the above disadvantages Was completely avoided.   The composition can be advantageously supplied in solution form in a 10 ml bottle, adding flavor and preservatives. Contains. Preferably, the composition is as follows:     1.5-2 g of amino acids     0.6 g of calcium gluconate <or = 0.6 g     0.745 g of calcium heptgluconate     Vitamin D3 0.005mg   Early work was understood by many authors, and more recently by Shen et al. (1995). Performed on a classic model for osteoporosis. Determine the active dose range After the preliminary experiment, the experiment was conducted using the following five comparison groups of rats. You.   Group 1: Control group, untreated   Group 2: Ubectomy and bred on a calcium deficient diet.   Group 3: Ovariectomized and fed on a diet supplemented with calcium and vitamin D.   Group 4: as in Group 3 above, additionally with the amino acid composition according to the invention           Is done.   All treatments were administered orally daily. One month later, all animals were sacrificed Then, the density and composition of the bone were measured by a usual measuring method. Briefly, the first group Comparing with the second group, a mineral loss table was reported as reported elsewhere.   In tests in groups 3 and 4, treatments containing only calcium and vitamin D, In addition, treatment with a composition containing amino acids is not clearly shown in the above mineral disappearance table. It was shown to have a significant protective effect. In addition, more important and significant protection effects Obtained with the composition according to the invention, ie in group 4 at a dose of 100 mg / kg body weight Obtained when the composition was administered orally.   In this experiment, the composition contained only amino acids or Significant protective effect in experimental methods for osteoporosis in combination with Lucium and Vitamin D It was shown to be.   This composition is present in the food and its constituents that leave the food during intestinal digestion. Defined as a natural product that falls into the category of nutritional aggregates of therapeutic diets such as amino acids Is defined. The basic difference is that amino acids are supplied in fixed amounts and the normal Served at a controlled rate determined based on composition and the need for a physiological diet It is to be.   As a result, the harmlessness of the composition is guaranteed, and in other applications, it also contains amino acids The solution is passed parenterally without adverse effects directly related to its properties. It is always administered.   In addition, the dosages of calcium and vitamin D may differ from those of various other commercially available nutrient agglomerates. The same amount as Therefore, the composition should be completely tolerated by the patient is there.   These facts were confirmed by experiments performed using experimental animals. Acute toxicity 2 weeks post-dose, measured in necropsied mice. Composition 40 in solution The highest dose that can be administered, equivalent to a dose of ml / kg, Shows no signs of acute or chronic toxicity, either at observation or necropsy Did not. The dose is equivalent to 18 g of amino acid per kg of body weight.   System effects include pupil diameter of the eye, saliva and tear secretion, tone and motor coordination and external Deterioration is determined by evaluating various parameters, including responsiveness to head stimulation. According to the method of Irwin (x) for quantitative and qualitative measurements, And studied. Similarly, in this experiment, the highest possible Deterioration by parameter cannot be clarified.   Next, clinical studies were performed. The first is based on clinical symptoms and laboratory results About 20 women between the ages of 60 and 70 who were diagnosed with osteoporosis These women are not those who have been treated for this condition with drugs.   The patients were divided into two groups, the first being treated with the composition according to the invention Group, or second, treated with the same dose of calcium and vitamin D It is a group to be done. Both compositions were administered orally twice daily before meals . Patients are monitored monthly for symptoms such as joint pain and difficulty walking, and 6 months I had a monthly inspection. The standard test measures bone density and excretes it in urine. Calcium levels were controlled.   All patients have completed the course of treatment and have two groups with minimal side effects. Were equally distributed between.   The second study was between the ages of 45 and 60, most of whom were male, Went to about 20 people. Dividing them into two substantial groups, one of which And the other group treats an equivalent amount of the composition of the present invention. Treated with a composition containing only calcium and vitamin D.   The course of treatment is based on the treatment, based on radiological data and the patient's primary appearance. A regular consultation is performed by an orthopedic surgeon responsible for performing a monthly assessment, It lasted three months.   For this, a score was recorded based on the severity of the problem. According to the obtained results The compositions containing amino acids showed statistically significant differences in the first month. And proved to be more effective.   Taken together, these results indicate that the composition is an organic matrix of human bone tissue. Daily dose corresponding to the intake of 3.5-4 g of amino acids found in When administered to humans, it is also beneficial for osteoporosis and hardening associated with normal bone damage You can see the effect. Based on the data generated in animals, Um and Vitamin D have been shown to be useful in providing the desired effect.   The finding is that high protein diets that supply large amounts of amino acids are actually calcium Has the detrimental effect of causing mineral loss by stimulating urine excretion in the urine In light of the conventional findings that it was, it was not expected.   Therefore, this composition may be included in foods in making nutritional supplements or aggregates. Turning is useful. Above a certain age, take these supplements regularly Doing so is particularly useful for preventing osteoporosis.

Claims (1)

[Claims] 1. Contains calcium and vitamin D, and further contains calcium and vitamin D The ratio of amino acids to calcium is similar to calcium found in the organic matrix of human bone tissue. Include amino acids in an amount equal to the ratio of amino acids to vitamin D For the treatment of osteoporosis characterized and / or to promote the treatment of broken bone A composition for the manufacture of a medicament. 2. Furthermore, calcium gluconate, calcium heptagluconate and vitamin D 3. The composition according to claim 1, wherein the composition contains 3. 3. The content of amino acid is 15 to 20% by weight. The composition according to claim 1. 4. The ratio of the contained calcium gluconate is 6% by weight. Item 3. The composition according to Item 2. 5. The content of calcium heptagluconate is 7.5% by weight. 3. The composition according to claim 2, wherein the composition is characterized by: 6. The content of vitamin D3 is 0.0005% by weight. A composition according to claim 2. 7. Solutions, capsules, granules, powders, gel cups, etc. suitable for oral administration 2. The composition according to claim 1, wherein the composition is provided as: 8. Particularly for the treatment of osteoporosis and / or according to any of claims 1 to 7. Or a composition for the manufacture of a medicament for promoting the treatment of damaged bone Nutrition accumulation. 9. As a nutritional accumulation mixed with other foods, according to any one of claims 1 to 8 Use of the composition. 10. Amino acids, calcium and vitamin D, The ratio of Min D to calcium and calcium found in the organic matrix of human bone tissue Oral composition containing equal to the ratio of amino acids to vitamin D For treating osteoporosis and / or treating broken bone Ways to promote.