JPH0541606B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a preventive/therapeutic agent for hypocalcemia and bone metabolic disorders, and more specifically to a preventive/therapeutic agent for hypocalcemia and osteomalacia, which has no side effects and can be administered over a long period of time.
The present invention relates to preventive and therapeutic agents for various diseases caused by calcium deficiency in living tissues, such as bone metabolic disorders such as osteoporosis. [Conventional technology] Calcium exists in the body as a main component of bones and teeth, and also plays a role in the differentiation and proliferation of fertilized cells, secretion of hormones, blood coagulation, activation of enzymes, stimulus responses of immune cells, and nerve functions. It plays an important role in transmission of energy, contraction of muscle cells, etc.
In order to carry out these actions smoothly, the calcium concentration in the blood is controlled by secondary glandular hormones and active vitamins.
It is kept constant by the action of D ₃ . A state in which the concentration of calcium in the blood decreases due to insufficient calcium intake, malabsorption of calcium from the small intestine, imbalance of the regulatory factors, pregnancy, etc. is called hypocalcemia. This is one of the causes of tetany symptoms, which are typified by excessive excitement of nerves and muscles, spasm of blood vessels and respiratory muscles, osteomalacia, and osteoporosis. Currently, prevention and treatment of hypocalcemia and the above diseases is currently underway.
As therapeutic agents, calcium preparations such as calcium lactate, calcium carbonate, calcium gluconate, bone/shell powder, and active vitamin D ₃ (1α,25-dihydroxyvitamin D ₃ ) are used. [Problems to be solved by the invention] These calcium preparations have poor absorption; poor uptake of calcium into the blood and bones;
It has some drawbacks, such as being difficult to take due to its bad odor, while active vitamin D ₃ can cause loss of appetite, nausea, headaches, etc.
It had the disadvantage of having serious side effects such as delayed fetal bone formation. [Means for Solving the Problems] As a result of intensive research to solve the above problems, the present inventors found that hexose calcium phosphate increases blood calcium concentration, and also has an effect of increasing bone calcium content and improving bone It has a strength increasing effect,
The present invention was completed based on the discovery that the present invention is useful as a preventive/therapeutic agent for hypocalcemia and bone metabolic disorders. That is, the present invention provides a prophylactic/therapeutic agent for hypocalcemia and bone metabolic disorders containing calcium hexose phosphate as an active ingredient. Examples of the hexose calcium phosphate used in the present invention include calcium phosphates of hexoses such as glucose, fructose, mannose, galactose, tagatose, sorbose, fucose, quinobose, and rhamnose, among which glucose calcium phosphate is preferred. Also,
For example, glucose-1-calcium phosphate has the following structural formula (a) or (b). There are the following, and any of them can be used in the present invention, but the one represented by (a) is particularly preferred. The method for producing glucose-1-calcium phosphate is shown in Japanese Patent Publication No. 43-10620 and Japanese Patent Publication No. 56-23998, and its physiological effects include inhibiting dental caries (Japanese Patent Publication No. 46-7599), promoting mineralization of cartilage, It has been reported that it has a fatigue recovery effect, but it also significantly improves blood calcium concentration, has preventive and therapeutic effects on hypocalcemia, and also improves bone metabolic abnormalities and is effective against osteomalacia, osteoporosis, etc. It is not known to have therapeutic or preventive effects. The preventive/therapeutic agent for hypocalcemia and bone metabolic disorders of the present invention is preferably administered orally, and if necessary, necessary pharmaceutical carriers, excipients, etc. are added,
Tablets, granules, capsules,
It can be in the form of an oral solution or the like. The dosage of this prophylactic/therapeutic agent is 1 to 50 g, preferably 10 to 30 g, as hexose calcium phosphate per day for adults. Note that the acute oral toxicity of glucose-1-calcium phosphate in mice is 15,000 mg/Kg or more, making it extremely safe. [Effects of the Invention] The preventive/therapeutic agent for hypocalcemia and bone metabolic disorders of the present invention has good absorbability, can increase calcium concentration in the blood, and has a high absorption rate into bones. , it is possible to increase bone calcium content and bone strength. [Examples] The present invention will be described in more detail with reference to Examples below, but the present invention is not limited to these Examples. Example 1 Wistar male rats (weighing approximately 250 g, one group)
(10 mice) were fed the low calcium diet shown in Table 1 for 2 weeks (average of 20 g per day). During the rearing period, glucose-1-calcium phosphate aqueous solution (1 g/100 ml purified water) containing the compounds of structural formulas (a) and (b) at a ratio of 9:1 (weight ratio), glucose-1 of structural formula (a)
1-Calcium phosphate aqueous solution (1g/100ml purified water), calcium lactate aqueous solution (1g/100ml purified water) or calcium gluconate aqueous solution (1g/100ml purified water)
100 ml of purified water) was allowed to drink ad libitum (1
(average of about 30ml per day). Serum calcium concentration was measured on the day of completion of rearing. The results are shown in Table 2. As a control, a control diet-water intake group and a low-calcium diet-water intake group shown in Table 1 were provided.

【table】

[Table] * Harpa mixture

[Table] From the above results, it was revealed that administration of glucose-1-calcium phosphate increases serum calcium concentration. Example 2 Comparison of bone strength: Wistar male rats (body weight approximately 250 g, one group)
A glucose-1-calcium phosphate aqueous solution (1 g/100 ml purified water) represented by the above structural formula (a) and the compounds of structural formulas (a) and (b) were added to 10 mice (9:1 (weight ratio)).
3.5 ml of glucose-1-calcium phosphate aqueous solution (1 g/100 ml purified water) containing
Each dose was administered intragastrically for 5 months. On the final day of administration, the femur was decapitated and sacrificed, and measured using a fracture characteristic measuring device (DYN-1255 manufactured by Iio Electric) at a plansheer speed of 100 mm/min and a chart speed of 1200 mm/min.
The specimen was broken under the conditions of min and full scale of 25 kg, and the breaking force was calculated. Calcium chloride (1
g/100ml purified water), calcium lactate (1g/100ml
ml purified water) and a purified water administration group. The results are shown in Table 3.

[Table] Example 3 Comparison of bone calcium content: The calcium content of the rat femurs excised in Example 2 was measured. Accurately weigh 500 mg of femur, add 5 ml of nitric acid-perchloric acid mixture (4:1), and heat at 80°C for 1 hour.
It was incinerated at 140°C for 1 hour. Jarrell Atsushi
The calcium content of the ashed sample was measured using AA-8200 and FIA Hitachi K-1000. The results are shown in Table 4.

【table】

[Table] From the results of Examples 2 and 3, glucose-1
- Administration of calcium phosphate was found to increase bone fracture properties and bone calcium content.

Claims (1)

[Claims] 1. A prophylactic/therapeutic agent for hypocalcemia and bone metabolic disorders containing calcium hexose phosphate as an active ingredient.