CN102172356B - Use of taurochenodeoxycholic acid in prevention and treatment of osteoporosis - Google Patents
Use of taurochenodeoxycholic acid in prevention and treatment of osteoporosis Download PDFInfo
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- CN102172356B CN102172356B CN 201110050756 CN201110050756A CN102172356B CN 102172356 B CN102172356 B CN 102172356B CN 201110050756 CN201110050756 CN 201110050756 CN 201110050756 A CN201110050756 A CN 201110050756A CN 102172356 B CN102172356 B CN 102172356B
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Abstract
The invention relates to new use of taurochenodeoxycholic acid, in particular to the new use of the taurochenodeoxycholic acid in prevention and treatment of osteoporosis. Through the study on taurochenodeoxycholic acid, the inventor found that the taurochenodeoxycholic acid can promote bone cells to secrete osteocalcin and improve lowered bone density. Thus, the taurochenodeoxycholic acid can be used in prevention or treatment of osteoporosis. After being administrated directly or being formed into various formulations, the taurochenodeoxycholic acid can be used for preventing or treating osteoporosis and other related diseases or states of osteoporosis.
Description
Technical field
The present invention relates to a kind of new application of Taurochenodeoxycholic Acid, be specifically related to Taurochenodeoxycholic Acid in the new purposes of preventing and treating on the osteoporosis.
Background technology
Taurochenodeoxycholic Acid (Taurochenodeoxycholic Acid, TCDCA) is the conjugated bile acids that mainly is present in the animal biles such as chicken, duck, goose, cattle, sheep, Serpentis.Its chemical name is 3 α, 7 alpha-dihydroxy-s-5 β-24-cholane acyl-N-taurine, and structural formula is as follows:
It is that molecular formula is C by taurine (Taur ine, Tau) and chenodeoxycholic acid (Chenodeoxycholic acid, CDCA) the extremely bitter acid compound of the odorless that forms, white powder, flavor that combines
23(OH)
2H
37CONHCH
2CH
2SO
3H, relative molecular mass are 499.69.TCDCA has the characteristics such as medicament sources is extensive, safe, effective as a kind of main component in the bile.Present research find TCDCA have antiinflammatory (Li Peifeng, Cao Jinshan, Guan Hong etc. Chinese veterinarian's medical magazine, 2002,21 (1): 7-10), body fluid and cellular immunization regulate (Shi Youfei, Li Peifeng, Li Jinlian etc. the Chinese Pharmacological circular, 2007,23 (7): 859-864), anti-intestinal epithelial cell apoptosis (Turner DJ, Alaish SM, Zou T, et al.Ann Surg.2007,245 (3): 415-25) etc.
Osteoporosis (Osteoporsis, OP) is the human endocrine Developmental and Metabolic Disorder, constantly reduces with bone ore deposit composition and bone matrix equal proportion, and the sclerotin attenuation, bone trabecula quantity reduces, and bone fragility increases to a kind of general skeletal diseases of feature.Clinical manifestation is lumbago and backache, is easy to fracture.The patient of this disease is mainly most of postmenopausal women and old people, and the whole world has 200,000,000 people to suffer from osteoporosis approximately at present, and China has patients with osteoporosis more than 8,000 ten thousand now.Along with the process of social population's aging is constantly aggravated, the osteoporosis disease has become a serious social public health problem.The osteoporotic method of existing control generally is Drug therapy, bone peptide sheet, calcitonin or the alendronate etc. of mainly containing commonly used, and said medicine can promote osteogenesis; Also have to adopt and directly replenish calcium preparation to fill up the part of bone-loss, although above-mentioned method has certain effect, have the drawback that the Long-term taking medicine price is higher or side effect is more, can not satisfy well the osteoporotic requirement of control.
Summary of the invention
The inventor is through long-term research to Taurochenodeoxycholic Acid; the inventor can promote osteoblast secretion Bone Gla protein by the research of Taurochenodeoxycholic Acid being found it; and can improve the bone density that has reduced; and then be applied to prevent and treat osteoporosis; directly administration also can be made into various dosage forms and be used for prevention or treatment osteoporosis or other diseases or the state relevant with it.
The invention provides Taurochenodeoxycholic Acid in prevention or prevent and treat application on the osteoporosis; directly administration; also can take it as principal agent, cooperate other adjuvants to prepare the medicine of the various dosage forms such as injection, tablet, powder, granule, capsule, oral agents.
The inventor finds by experiment, when directly by oral administration, can significantly promote osteoblast secretion Bone Gla protein, and Bone Gla protein is a kind of noncollagen protein of emiocytosis in the osteogenetic process, is Ca
2+Be combined with hydroxyapatite, the essential composition of sclerotin mineralising.Cell with osteogenic activity can produce Bone Gla protein in the maturation period in later stage.Because the osteocalcin secretion level is the embodiment of Oesteoblast growth and function status, is osteoplastic sign.So, promoted the secretion of Bone Gla protein, illustrate and improved osteoblastic vigor, be conducive to the formation of bone.In addition; Taurochenodeoxycholic Acid can improve the bone density by the osteoporosis model of dexamethasone preparation; because this model has general representativeness, confirmed that Taurochenodeoxycholic Acid can improve the bone density that has reduced, and then confirmed that it is in the application that prevents and treats on the osteoporosis.
In addition; the inventor also finds; when in food or feedstuff, directly adding Taurochenodeoxycholic Acid; by normal feed digestion process; also can promote osteoblast secretion Bone Gla protein to improve bone density; therefore also can adopt the above-mentioned form of mixtures that contains Taurochenodeoxycholic Acid, prevent and treat osteoporosis such as forms such as health foods.
By above-mentioned research, the present invention is for prevention or prevent and treat osteoporosis, and a brand-new approach is provided, and then provides technical foundation for the exploitation of a series of control medicine for treating osteoporosis.Taurochenodeoxycholic Acid is as the effective ingredient of animal body, and its untoward reaction is little, as the medicine of replenishing the calcium, can prevent and treat the osteoporosis disease by life-time service.
Description of drawings
Fig. 1-5 takes the photograph sheet for x-ray among the embodiment 2 and estimates Taurochenodeoxycholic Acid to the osteoporotic comparison chart that affects; Wherein Fig. 1 is normal group x-ray sketch map; Fig. 2 is model group x-ray sketch map; Fig. 3 is low dose group x-ray sketch map; Fig. 4 is middle dosage group x-ray sketch map, and Fig. 5 is high dose group x-ray sketch map.
The specific embodiment
Embodiment 1
Be divided into normal group, model group and low dosage, middle dosage, three administration groups of high dose during experiment, every group is 10 mices.Normal group only gavages distilled water; It is that the 20mg/kg dexamethasone carries out subcutaneous injection to mice that model group adopts dosage, every injection in a day once, continues 14 days, preparation mice osteoporosis model; The administration after model preparation is finished of administration group, administration group TCDCA dosage are respectively 0.05,0.1 and 0.2g/kg, and route of administration is gastric infusion, every day 1 time, successive administration 7 days.
Normal group, model group and administration group are carried out the blood sampling of eyeball venous plexus, adopt radioimmunology to detect BGP content in the mice serum, the results are shown in Table 1.Low, middle dosage group is compared with normal group, has improved significantly serum osteocalcin content; Basic, normal, high dosage group is compared with model group, but the utmost point improves serum osteocalcin content significantly.
Table 1TCDCA is on the impact of mice serum Bone Gla protein
Annotate: * represents and normal group comparing difference remarkable (P＜0.05); * represents and the poor heteropole of normal group remarkable (P＜0.01); △ represents and model group comparing difference remarkable (P＜0.05); △ △ represents and the poor heteropole of model group remarkable (P＜0.01).
Embodiment 2
Be divided into normal group, model group and low dosage, middle dosage, three administration groups of high dose during experiment, every group is 10 mices.Normal group only gavages distilled water; It is that the 20mg/kg dexamethasone carries out subcutaneous injection to mice that model group adopts dosage, every injection in a day once, continues 14 days, preparation mice osteoporosis model; The administration after model preparation is finished of administration group, administration group TCDCA dosage are respectively 0.05,0.1 and 0.2g/kg, and route of administration is gastric infusion, every day 1 time, successive administration 7 days.
Normal group, model group and administration group mice are carried out x-ray take the photograph sheet, see Fig. 1-5.Use the ImageJ image analysis software and measure the gray value of mice left side and right side femur, the gray value on the x-ray can reflect bone density indirectly.The results are shown in Table 2.Can find out that basic, normal, high dosage group is compared with model group, the utmost point promotes the model group bone density to recover significantly.
Table 2TCDCA is on the impact of mouse femur bone density
Annotate: * represents and normal group comparing difference remarkable (P＜0.05); * represents and the poor heteropole of normal group remarkable (P＜0.01); △ represents and model group comparing difference remarkable (P＜0.05); △ △ represents and the poor heteropole of model group remarkable (P＜0.01).
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