JP4923236B2 - Bone density improver, anti-osteoporosis drug and anti-osteoporosis food - Google Patents

Description

  The present invention relates to a bone density improving agent, an anti-osteoporosis drug, and an anti-osteoporosis food useful for prevention / treatment of a decrease in bone density in bone metabolic diseases such as osteoporosis.

Osteoporosis, which is common in postmenopausal women and older men, is thought to result from disruption of the balance of bone remodeling by osteoblasts responsible for bone formation and osteoclasts responsible for bone resorption. It is a well-known fact that the spinal cord, thigh, neck, etc. are easily damaged. Currently, calcitonin involved in calcium metabolism, female hormones, activated vitamin D _{3 and the} like are used as therapeutic agents.

In recent years, as elucidation of the mechanism of bone metabolic diseases and the search for preventive / therapeutic methods, it has been clarified that various substances act in various modes on biological reactions related to bone metabolism. In the previous studies, the present inventors also found that rat calvaria-derived primary cultured osteoblasts under culture conditions lacking pyruvic acid lead to cell death due to increased DNA binding ability of specific transcription factors, It has been found that pyruvic acid has a protective effect against cell death of the cell, and has already been reported (Non-patent Document 1).
Eiichi Hinoi, Sayumi Fujimori, Akihiro Takemori, Yukio Yoneda, Cell death by pyruvate deficiency in proliferative cultured calvarial osteoblasts, Biochemical and Biophysical Research Communications 294 (2002) 1177-1183

However, there are still many unclear points in bone metabolic diseases, and the actual situation is that the prevention and treatment methods have not yet reached a satisfactory stage. Drugs that are effective in preventing and treating bone density have long been desired, and several candidate substances have been proposed, but the emergence of better drugs in terms of efficacy and safety is awaited. Yes.
Accordingly, an object of the present invention is to provide a bone density improving agent, an anti-osteoporosis drug, and an anti-osteoporosis food useful for preventing or treating a decrease in bone density in bone metabolic diseases such as osteoporosis.

  As a result of intensive research in view of the technical background as described above, the present inventor has found that pyruvic acid having a cell death protecting effect on osteoblasts in the early stage of culture is It has been found that it has an effect of improving bone density. This finding cannot be predicted from the action of pyruvic acid on osteoblasts under the specific culture conditions described above. This is because the above-mentioned pyruvate cell death protection effect is in an in vitro experimental system using primary cultured osteoblasts, and the fact that pyruvate addition exerts a protective effect against cell death associated with medium exchange. This is because the pathophysiological significance of osteoblast death associated with this culture medium exchange in the living body is completely unknown. In contrast, osteoporosis such as postmenopausal osteoporosis and senile osteoporosis is caused by the failure of the equilibrium between bone formation by osteoblasts and bone resorption by osteoclasts. In other words, as long as the effect on osteoclasts is unknown, even if pyruvic acid has a protective effect on osteoblast cell death associated with medium exchange, pyruvic acid is in vivo in an ovariectomized animal that is a postmenopausal osteoporosis model. Inducing the increase in bone density by daily administration in the experimental system is beyond the expectation. In addition, bones are composed not only of osteoblasts and osteoclasts but also chondrocytes and blood cells in the bone marrow, etc. in vivo. It is impossible to predict the bone density increasing effect of acid. The discovery of osteoporosis treatment effects in the in vivo experimental system of pyruvate is solely due to our outstanding originality and insight.

The bone density improving agent of the present invention made based on the above findings comprises pyruvic acid or a pharmaceutically acceptable salt thereof (excluding calcium pyruvate) as an active ingredient as described in claim 1. And
The anti-osteoporosis drug of the present invention is characterized in that pyruvic acid or a pharmaceutically acceptable salt thereof (excluding calcium pyruvate) is an active ingredient as described in claim 2.

  According to the present invention, it is possible to provide a bone density improving agent, an anti-osteoporosis drug, and an anti-osteoporosis food useful for the prevention / treatment of a decrease in bone density in bone metabolic diseases such as osteoporosis.

  Pyruvate, which is an active ingredient in the bone mineral density improving agent of the present invention, is biosynthesized from glucose as a glycolytic metabolite in the cell, enters the TCA circuit in the mitochondria under aerobic conditions, and is a source of cellular energy. ATP is produced, and is an extremely safe substance. For the purpose of supplementing energy, pyruvic acid is often contained in infusion nutrient solutions for the elderly, and from these facts, the possibility of significant side effects appearing after administration to the body Inferred to be low. Examples of pharmaceutically acceptable salts of pyruvic acid include sodium salts, potassium salts, and calcium salts.

  Pyruvic acid or a pharmaceutically acceptable salt thereof is formulated into granules, tablets, capsules, etc. by a method known per se, and is taken to give an anti-osteoporosis drug (prophylactic and / or Or as a therapeutic). The dose can be appropriately determined depending on the age, sex, weight, physical condition, symptom, etc. of the user in the range of 10 mg / day to 100 g / day, for example. The administration form may be parenteral administration. In addition, pyruvic acid or a pharmaceutically acceptable salt thereof is added to various forms of foods (including supplements) in an effective amount sufficient to exert a bone density improving action, thereby preventing and / or treating osteoporosis. It may be eaten as an anti-osteoporosis food that brings about

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited at all by the following description.

Test Example 1: Confirmation test for the effect of pyruvate on bone density improvement using ovariectomized model mice (test method)
Ovariectomy was performed on 8-week-old female mice, and 250 mg / kg of pyruvic acid dissolved in phosphate buffered saline was administered intraperitoneally daily from the first day after surgery. The bone density of the tibia and femur was measured by the SEXA method using a bone mineral content measuring apparatus (ALOKA, DCS-600R). As a result (ovariectomy + pyruvate administration group: n = 13), bone density at 4 weeks after surgery when the same surgical treatment was performed without ovariectomy (sham treatment group: n = 37). ), And bone density (ovariectomy group: n = 37) at 4 weeks after surgery when pyruvate was not administered after ovariectomy is shown in FIG.

(Test results)
As is clear from FIG. 1, significant recovery of bone density was recognized by the administration of pyruvic acid. From this result, it was found that pyruvic acid is useful for prevention / treatment of bone density decrease in bone metabolic diseases such as osteoporosis.

Formulation Example 1: Tablet 5 g of pyruvic acid, 80 g of lactose and 15 g of magnesium stearate, 100 g in total, were uniformly mixed to obtain tablets according to a conventional method.

Formulation Example 2: Granules 10 g of pyruvic acid, 35 g of starch, 55 g of lactose and 100 g in total were mixed uniformly to obtain granules according to a conventional method.

Formulation Example 3 Biscuits 1 g of pyruvic acid, 32 g of flour, 16 g of whole eggs, 16 g of butter, 24 g of sugar, 10 g of water, 1 g of baking powder, and a total of 100 g were used to make biscuits according to a conventional method.

  INDUSTRIAL APPLICABILITY The present invention has industrial applicability in that it can provide a bone density improving agent, an anti-osteoporosis drug, and an anti-osteoporosis food useful for the prevention and treatment of a decrease in bone density in bone metabolic diseases such as osteoporosis. Have.

It is a graph which shows the result of the confirmation test of the bone density improvement effect of pyruvic acid using the ovariectomized model mouse in an Example.

Claims (2)

A bone density improver comprising pyruvic acid or a pharmaceutically acceptable salt thereof (excluding calcium pyruvate) as an active ingredient. An anti-osteoporosis drug comprising pyruvic acid or a pharmaceutically acceptable salt thereof (excluding calcium pyruvate) as an active ingredient.