Application of dithiocarbamic acid compound in preparation of medicine for preventing and / or treating osteoporosis

Abstract

The invention discloses application of a dithiocarbamic acid compound in preparation of a medicine for preventing and / or treating osteoporosis, and belongs to the technical field of medicines. Research finds that the dithiocarbamic acid compound can effectively prevent and / or treat osteoporosis, improve the bone mineral density of osteoporosis patients and reduce the fracture risk. Meanwhile, the research finds that when the dithiocarbamic acid compound and the calcium supplement are combined for medication, the prevention and / or treatment effect on the osteoporosis can be better achieved.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and in particular relates to the application of dithiocarbamate compounds in the preparation of drugs for preventing and / or treating osteoporosis. Background Art

[0002] Osteoporosis is a common systemic metabolic bone disease characterized by decreased bone mass and deterioration of bone microstructure, leading to increased bone fragility and susceptibility to fractures. The disease is common in the middle-aged and elderly population, especially postmenopausal women. As China gradually enters an aging society, the incidence of osteoporosis has shown an increasing trend year by year. At present, the clinical treatment of osteoporosis mainly focuses on inhibiting bone resorption. Commonly used drugs can be divided into two categories: mainly bisphosphonates and receptor activator of nuclear factor κB ligand (RANKL) inhibitors. However, these drugs may cause a series of adverse reactions during long-term use, including but not limited to: mandibular osteonecrosis, bone joint and muscle pain, cellulitis, etc. Therefore, the development of new, safer and more effective osteoporosis treatment options is of great clinical significance.

[0003] Parathyroid hormone (PTH) is a linear polypeptide hormone with 84 amino acids, composed in a specific sequence, and a molecular weight of 9500; it can promote bone resorption. PTH stimulates the lysosomes of osteoclasts to release hydrolases, decompose bone matrix, and release calcium and phosphate. Hypocalcemia excites the parathyroid glands, increasing the secretion of PTH; hypercalcemia inhibits the parathyroid glands and reduces the secretion of PTH. Calcitonin is synthesized and secreted by thyroid parafollicular cells (C cells) and is a polypeptide composed of 32 amino acids. The effect of calcitonin on calcium metabolism is mainly to reduce blood calcium, which antagonizes the effect of PTH on increasing blood calcium. The two work synergistically to regulate the extracellular calcium ion concentration to maintain its constant. When the blood calcium concentration increases, calcitonin secretion is stimulated and parathyroid hormone secretion is inhibited. When the blood calcium concentration decreases, parathyroid hormone secretion is stimulated and calcitonin secretion is inhibited. The main mechanism of calcitonin in lowering blood calcium is to inhibit the function of osteoclasts (there are calcitonin receptors on the surface of osteoclasts) and reduce bone absorption; calcitonin can reduce blood phosphorus, allowing inorganic phosphorus to enter bone tissue from the blood and extracellular fluid, where phosphorus and calcium combine to form a complex, reducing the release of bone calcium. Therefore, considering the effects of parathyroid hormone and calcitonin on blood calcium and the relationship between blood calcium and bone tissue, there are a series of artificially synthesized drugs in the treatment of osteoporosis; for example, parathyroid hormone is called teriparatide, which is also the only osteoblast-promoting drug at present; for example, eel calcitonin (Ecalcin) and salmon calcitonin (Micais), both of which can reduce bone loss. Summary of the invention

[0004] The purpose of the present invention is to provide a drug application that can effectively treat osteoporosis.

[0005] To achieve the above object, in the first aspect of the present invention, the present invention provides the use of dithiocarbamate compounds in the preparation of drugs for preventing and / or treating osteoporosis; the structural formula of the dithiocarbamate compounds is as shown in Formula I, wherein R includes any one of potassium, sodium, and amino,

[0006]

[0007] The present invention has been found through research that dithiocarbamate compounds can effectively prevent and / or treat osteoporosis, improve the bone density of osteoporosis patients, and reduce the risk of fractures; specifically, dithiocarbamate compounds can improve the functions of the thyroid and parathyroid glands, regulate the levels of osteocalcin, calcium ions and calcitonin in the serum of osteoporosis patients, thereby effectively preventing and / or treating osteoporosis by inhibiting osteoclasts and promoting osteoblast proliferation.

[0008] As a preferred embodiment of the application of the present invention, in the formula I, R includes potassium or sodium.

[0009] The present invention has found that when R is further selected to be potassium or sodium, the corresponding dithiocarbamate compounds have a better effect in preventing and / or treating osteoporosis.

[0010] As a preferred embodiment of the application of the present invention, the osteoporosis is osteoporosis caused by decreased estrogen levels.

[0011] As a preferred embodiment of the application of the present invention, the osteoporosis is osteoporosis caused by hyperthyroidism.

[0012] As a preferred embodiment of the application of the present invention, the dosage form of the dithiocarbamic acid compound includes any one of commonly used preparations such as injection, powder injection, tablet, capsule, transdermal preparation, etc.

[0013] In a second aspect of the present invention, the present invention provides a combined pharmaceutical composition for treating osteoporosis, the combined pharmaceutical composition comprising a dithiocarbamate compound and a calcium supplement;

[0014] The calcium supplement includes at least one of calcium carbonate, calcium gluconate, and calcium lactate;

[0015] The structural formula of the dithiocarbamic acid compound is shown in Formula I, wherein R includes any one of potassium, sodium, and amino.

[0016]

[0017] The present invention has found that when dithiocarbamate compounds and calcium supplements are used in combination, the prevention and / or treatment of osteoporosis can be better achieved; specifically, although calcium supplements can increase the calcium ion concentration in serum to a certain extent, they have almost no effect on the improvement of bone density. When calcium supplements and dithiocarbamate compounds are used simultaneously, compared with the use of dithiocarbamate compounds alone, the increase in bone density can be better achieved, the proliferation of osteoblasts can be promoted, and the effect of preventing and / or treating osteoporosis can be achieved.

[0018] As a preferred embodiment of the combined pharmaceutical composition of the present invention, the single-use mass ratio of the dithiocarbamate compound to the calcium supplement is (1-10):1.

[0019] Preferably, the single-use mass ratio of the dithiocarbamate compound to the calcium supplement is (1-4):1.

[0020] More preferably, the single-use mass ratio of the dithiocarbamate compound to the calcium supplement is (2-3):1.

[0021] The present invention has found that the single-use mass ratio of dithiocarbamate compounds and calcium supplements will also affect the effect of combined medication. When combined medication is further selected, the single-use mass ratio of the two is (1-4):1, especially (2-3:1), the obtained combined medication effect is better.

[0022] As a preferred embodiment of the combined pharmaceutical composition of the present invention, the osteoporosis is osteoporosis caused by decreased estrogen levels.

[0023] As a preferred embodiment of the combined pharmaceutical composition of the present invention, the osteoporosis is osteoporosis caused by hyperthyroidism.

[0024] As a preferred embodiment of the combined pharmaceutical composition of the present invention, the combined pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0025] As a preferred embodiment of the combination pharmaceutical composition of the present invention, in the combination pharmaceutical composition, the dosage form of the dithiocarbamic acid compound includes any one of commonly used preparations such as injection, powder injection, tablet, capsule, transdermal preparation, etc., and the dosage form of the calcium supplement includes any one of tablets, capsules, and liquid.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention provides the use of dithiocarbamic acid compounds in the preparation of drugs for preventing and / or treating osteoporosis. The present invention has found through research that dithiocarbamic acid compounds can effectively prevent and / or treat osteoporosis, improve the bone density of osteoporosis patients, and reduce the risk of fractures; specifically, dithiocarbamic acid compounds can regulate the levels of osteocalcin, calcium ions and calcitonin in the serum of osteoporosis patients, thereby achieving the effect of effectively preventing and / or treating osteoporosis by inhibiting osteoclasts and promoting osteoblast proliferation. At the same time, the present invention also provides a combined pharmaceutical composition of dithiocarbamate compounds and calcium supplements for preventing and / or treating osteoporosis. The present invention has found that when dithiocarbamate compounds and calcium supplements are used in combination, the prevention and / or treatment effect of osteoporosis can be better achieved; specifically, although calcium supplements can increase the calcium ion concentration in serum to a certain extent, they have almost no effect on improving bone density. When calcium supplements and dithiocarbamate compounds are used at the same time, compared with using dithiocarbamate compounds alone, they can better achieve an increase in bone density, promote osteoblast proliferation, and achieve the effect of preventing and / or treating osteoporosis. DETAILED DESCRIPTION

[0028] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0029] Unless otherwise specified, the reagents, methods and equipment used in the present invention are all conventional reagents, methods and equipment in the art; and unless otherwise specified, the raw materials used in parallel experiments are from the same batch of raw materials.

[0030] Example 1

[0031] The present invention explores the preventive effect of dithiocarbamate compounds and a combination of dithiocarbamate compounds and a calcium supplement on ovariectomized osteoporosis model rats, comprising the following steps:

[0032] (1) Preparation of animal model: SD rats (Zhuhai Baishitong Biotechnology Co., Ltd.) were adaptively fed for 3 days and then randomly divided into sham operation group, model group and treatment group 1 according to body weight, with 10 rats in each group. Except for the sham operation group, the other two groups adopted the ovariectomy method to replicate the osteoporosis model; specifically: 1% sodium pentobarbital 30 mg / kg was injected intraperitoneally for anesthesia, and a midline incision was made on the dorsal side under sterile conditions. The ovaries were found near the lower pole of the kidney after entering the abdominal cavity, and the bilateral ovaries were ligated and removed with No. 4 thread, and the incisions were sutured in layers. The surgical procedure of the sham operation group was the same, but the ovaries were not removed;

[0033] (2) Treatment: Step (1) After two weeks of postoperative recovery, treatment group 1 was injected with 108 mg / kg of sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine (GMDTC) for 3 consecutive days per week, once a day, for a total of 10 weeks. The sham operation group and the model group were injected with the same volume of normal saline;

[0034] (3) Post-drug treatment: After the drug administration experiment in step (2) was completed, all rats were anesthetized by intraperitoneal injection of sodium pentobarbital and then killed. The left femur of each rat was removed, the cartilage tissue was shaved off, and the bone density of the entire length, midpoint and distal end of the femur was measured using an X-ray machine; the results obtained are shown in Table 1:

[0035] Table 1

[0036] Group <![CDATA[Total bone (g / cm 2 )]]> <![CDATA[Midpoint (g / cm 2 )]]> <![CDATA[Distal end (g / cm 2 )]]> Sham operation group 0.317±0.005 0.302±0.01 0.463±0.004 Model Group <![CDATA[0.221±0.007 * ]]> <![CDATA[0.193±0.007 * ]]> <![CDATA[0.261±0.007 * ]]> Treatment Group 1 <![CDATA[0.308±0.004 # ]]> <![CDATA[0.281±0.009 # ]]> <![CDATA[0.431±0.006 # ]]>

[0037] Among them, * compared with the sham operation group, P < 0.05, # compared with the model group, P < 0.05.

[0038] As can be seen from Table 1, the bone density of the whole bone, midpoint and distal end of the femur in the model group was lower than that in the sham operation group (p<0.05), indicating that the model was successful. The bone density of the animal GMDTC treatment group 1 increased, and the difference in the whole bone bone density and distal end bone density compared with the model group was statistically significant (p<0.05), indicating that GMDTC can prevent osteoporosis.

[0039] Example 2

[0040] The present invention explores the therapeutic effect of dithiocarbamate compounds and a combination of dithiocarbamate compounds and a calcium supplement on ovariectomized osteoporosis model rats, comprising the following steps:

[0041] (1) Preparation of animal model: SD rats (Zhuhai Baishitong Biotechnology Co., Ltd.) were adaptively fed for 3 days and randomly divided into sham operation group, model group, treatment group 1, treatment group 2, treatment group 3, treatment group 4, treatment group 5 and treatment group 6 according to body weight, with 10 rats in each group. Except for the sham operation group, the other groups adopted the ovariectomy method to replicate the osteoporosis model, specifically: 1% sodium pentobarbital 30 mg / kg was injected intraperitoneally for anesthesia, and a midline incision was made on the dorsal side under sterile conditions. The ovaries were found near the lower pole of the kidney after entering the abdominal cavity, and the bilateral ovaries were ligated and removed with No. 4 thread, and the incisions were sutured in layers. The sham operation group followed the same surgical procedure, but the ovaries were not removed.

[0042] (2) Drug treatment: 18 weeks after recovery from the operation in step (1), different groups were given drug treatment, specifically:

[0043] Treatment group 1 was injected with 108 mg / kg dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per week, once a day, and 50 mg calcium gluconate was given by oral gavage every day for a total of 5 weeks;

[0044] Treatment group 2 was injected with 108 mg / kg dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per week, once a day for a total of 5 weeks;

[0045] Treatment group 3 was injected with an equal volume of saline with 108 mg / kg of dithiocarbamate weekly and given 50 mg of calcium gluconate by gavage daily for a total of 5 weeks;

[0046] Treatment group 4 was injected with 54 mg / kg dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per week, once a day, and 60 mg calcium gluconate was given by gavage every day for a total of 5 weeks;

[0047] Treatment group 5 was injected with 108 mg / kg of dithiocarbamate (N-dithiocarboxylic acid amino-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine potassium) for 3 consecutive days, once a day, and 50 mg of calcium gluconate was given by gavage every day for a total of 5 weeks;

[0048] Treatment group 6 was injected with 108 mg / kg dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per week, once a day, and 50 mg calcium carbonate was given by gavage every day for a total of 5 weeks;

[0049] The sham group and the model group were given the same volume of saline instead of dithiocarbamates and calcium supplements, respectively;

[0050] (3) Post-drug treatment: After the drug administration experiment in step (2), all rats were anesthetized by intraperitoneal injection of sodium pentobarbital and then killed. The left femur of each rat was removed, the cartilage tissue was shaved off, and the bone density of the entire length, midpoint and distal end of the femur was measured by X-ray machine. Blood was taken to test serum osteocalcin and calcium ions;

[0051] Among them, the test results of bone density of the whole length, midpoint and distal end of the femur are shown in Table 2; the test results of osteocalcin, calcitonin and calcium ion concentration in serum are shown in Table 3;

[0052] Table 2

[0053]

[0054]

[0055] Among them, * compared with the sham operation group, P < 0.05, # compared with the model group, P < 0.05.

[0056] Table 3

[0057] Group Osteocalcin (ng / mL) Calcitonin (ng / mL) Calcium ion (mmol / L) Sham operation group 1.73±0.21 118.31±28.66 2.53±0.17 Model Group <![CDATA[0.51±0.18 * ]]> <![CDATA[177.29±30.30 * ]]> <![CDATA[1.31±0.21 * ]]> Treatment Group 1 <![CDATA[1.56±0.41 # ]]> <![CDATA[122.18±20.47 # ]]> <![CDATA[2.47±0.16 # ]]> Treatment Group 2 <![CDATA[1.31±0.32 # ]]> <![CDATA[137.41±23.34 # ]]> <![CDATA[2.33±0.18 # ]]> Treatment Group 3 0.56±0.11 189.32±20.47 <![CDATA[2.87±0.16 # ]]> Treatment Group 4 <![CDATA[1.06±0.18 # ]]> <![CDATA[165.44±17.39 # ]]> <![CDATA[2.44±0.19 # ]]> Treatment Group 5 <![CDATA[1.43±0.22 # ]]> <![CDATA[130.14±20.33 # ]]> <![CDATA[2.34±0.17 # ]]> Treatment Group 6 <![CDATA[1.51±0.27 # ]]> <![CDATA[126.68±16.217 # ]]> <![CDATA[2.39±0.11 # ]]>

[0058] Among them, *model group was compared with sham operation group, P<0.05, #treatment group was compared with model group, P<0.05.

[0059] As can be seen from Table 2, in the study of osteoporosis after ovarian removal, the bone density of the whole bone, midpoint and distal end of the femur in the model group was lower than that in the sham operation group (p<0.05), indicating that the model was successful. The bone density of treatment groups 1-2 and 4-6 increased, and the difference in the whole bone density and distal end bone density was statistically significant compared with the model group (p<0.05), indicating that treatment groups 1-2 and 4-6 can treat osteoporosis; further, it can be seen from treatment groups 1 and 2 that the combined use of dithiocarbamate compounds and calcium supplements can better restore bone density, while the simple use of calcium supplements in treatment group 3 has almost no effect on the improvement of bone density; it can be seen from treatment groups 1 and 4 that the single dose ratio of dithiocarbamate compounds and calcium supplements will also affect the improvement effect on bone density; it can be seen from treatment groups 1 and 5-6 that the types of dithiocarbamate compounds and calcium supplements will also affect the improvement effect on bone density to a certain extent.

[0060] As can be seen from Table 3, in the study of osteoporosis after ovariectomy, osteocalcin and calcium ions in the model group increased significantly (compared with the sham operation group, p<0.05), and calcitonin decreased significantly (compared with the sham operation group, p<0.05), indicating that the model was successfully established. Osteocalcin and calcium ions in treatment groups 1-2 and 5-6 increased significantly, and calcitonin decreased significantly, and the difference was statistically significant compared with the model group (p<0.05), indicating that treatment groups 1-2 and 5-6 can inhibit osteoclasts and promote osteoblast proliferation, thereby achieving a therapeutic effect on osteoporosis; further, it can be seen from treatment groups 1 and 2 that the combined use of dithiocarbamate compounds and calcium supplements has a better effect on increasing osteocalcin and calcium ions, and a better effect on reducing calcitonin, while the treatment group 3, the simple use of calcium supplements can only increase the calcium ions in serum, and almost no increasing trend is shown for osteocalcin, and almost no decreasing trend is shown for calcitonin; it can be seen from treatment group 1 and treatment group 4 that the single dose ratio of dithiocarbamate compounds and calcium supplements will also affect the concentrations of osteocalcin, calcitonin and calcium ions in serum; it can be seen from treatment group 1 and treatment groups 5-6 that the types of dithiocarbamate compounds and calcium supplements will also affect the concentrations of osteocalcin, calcitonin and calcium ions in serum to a certain extent.

[0061] Example 3

[0062] The present invention explores the therapeutic effect of dithiocarbamate compounds and a combination of dithiocarbamate compounds and a calcium supplement on ovariectomized osteoporosis model rats, comprising the following steps:

[0063] (1) Preparation of animal model: After 3 days of adaptive feeding, SD rats (Zhuhai Baishitong Biotechnology Co., Ltd.) were randomly divided into sham operation group, model group, treatment group 1, treatment group 2, treatment group 3, treatment group 4, treatment group 5 and treatment group 6 according to body weight, with 10 rats in each group. Except for the sham operation group, the other groups were given 100 mg of thyroxine by gavage at 8 am for 12 consecutive weeks. The rats in the sham operation group were replaced with normal saline.

[0064] (2) Drug administration: After 12 weeks of continuous treatment in step (1), drug administration was performed according to different groups, specifically:

[0065] Treatment group 1 was injected with 108 mg / kg dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per week, once a day, and 50 mg calcium gluconate was given by gavage every day for a total of 4 weeks;

[0066] Treatment group 2 was injected with 108 mg / kg dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per week, once a day for a total of 4 weeks;

[0067] Treatment group 3 was injected with an equal volume of saline containing 108 mg / kg of dithiocarbamates continuously every week and given 50 mg of calcium gluconate by gavage every day for a total of 4 weeks;

[0068] Treatment group 4 was injected with 54 mg / kg dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per week, once a day, and 60 mg calcium gluconate was given by gavage every day for a total of 4 weeks;

[0069] Treatment group 5 was injected with 108 mg / kg of dithiocarbamate (N-dithiocarboxylic acid amino-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine potassium) for 3 consecutive days, once a day, and 50 mg of calcium gluconate was given by gavage every day for a total of 4 weeks;

[0070] Treatment group 6 was injected with 108 mg / kg dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per week, once a day, and 50 mg calcium carbonate was given by gavage every day for a total of 4 weeks;

[0071] The sham operation group and the model group were given the same volume of normal saline instead of dithiocarbamates and calcium supplements, respectively;

[0072] (3) Post-drug treatment: After the drug administration experiment in step (2), all rats were anesthetized by intraperitoneal injection of sodium pentobarbital and then killed. The left femur of each rat was removed, and the cartilage tissue was shaved off. The bone density of the entire length, midpoint and distal end of the femur was measured by X-ray machine, and blood was collected to detect free triiodothyronine (FT3), free thyroxine (FT4) and bone metabolism indicators calcium ion (Ca) and parathyroid hormone (PTH) content;

[0073] Among them, the test results of bone mineral density of the whole length, midpoint and distal end of the femur are shown in Table 4; the test results of free triiodothyronine (FT3), free thyroxine (FT4) and bone metabolism indicators calcium ion (Ca) and parathyroid hormone (PTH) content are shown in Table 5;

[0074] Table 4

[0075] Group <![CDATA[Total bone (g / cm 2 )]]> <![CDATA[Midpoint (g / cm 2 )]]> <![CDATA[Distal end (g / cm 2 )]]> Sham operation group 0.295±0.007 0.299±0.002 0.460±0.004 Model Group <![CDATA[0.174±0.004 * ]]> <![CDATA[0.170±0.003 * ]]> <![CDATA[0.241±0.003 * ]]> Treatment Group 1 <![CDATA[0.263±0.003 # ]]> <![CDATA[0.247±0.005 # ]]> <![CDATA[0.366±0.005 # ]]> Treatment Group 2 <![CDATA[0.227±0.005 # ]]> <![CDATA[0.207±0.004 # ]]> <![CDATA[0.326±0.005 # ]]> Treatment Group 3 0.181±0.003 0.178±0.003 0.258±0.007 Treatment Group 4 <![CDATA[0.213±0.002 # ]]> <![CDATA[0.215±0.002 # ]]> <![CDATA[0.314±0.003 # ]]> Treatment Group 5 <![CDATA[0.247±0.003 # ]]> <![CDATA[0.235±0.004 # ]]> <![CDATA[0.338±0.005 # ]]> Treatment Group 6 <![CDATA[0.254±0.002 # ]]> <![CDATA[0.238±0.003 # ]]> <![CDATA[0.351±0.002 # ]]>

[0076] Among them, *model group was compared with sham operation group, P<0.05, #treatment group was compared with model group, P<0.05.

[0077] Table 5

[0078]

[0079] Among them, *model group was compared with sham operation group, P<0.05, #treatment group was compared with model group, P<0.05.

[0080] As can be seen from Table 4, in the hyperthyroidism model, the bone density of the whole bone, midpoint and distal end of the femur in the model group was lower than that in the sham operation group (p<0.05), indicating that the model was successfully established. The bone density of treatment groups 1-2 and 4-6 increased, and the difference in the whole bone density and distal end bone density compared with the model group was statistically significant (p<0.05), indicating that treatment groups 1-2 and 4-6 can treat osteoporosis; further, it can be seen from treatment groups 1 and 2 that the combined use of dithiocarbamate compounds and calcium supplements can better restore bone density, while the simple use of calcium supplements in treatment group 3 has almost no effect on the improvement of bone density; it can be seen from treatment groups 1 and 4 that the single dose ratio of dithiocarbamate compounds and calcium supplements will also affect the improvement effect on bone density; it can be seen from treatment groups 1 and 5-6 that the types of dithiocarbamate compounds and calcium supplements will also affect the improvement effect on bone density to a certain extent.

[0081] As can be seen from Table 5, in the hyperthyroidism model, the FT3, FT4, parathyroid hormone, calcitonin and calcium ions in the model group were significantly different from those in the sham operation group (compared with the sham operation group, p<0.05), indicating that the model was successfully established. The FT3, FT4, parathyroid hormone, and calcitonin in treatment groups 1-2 and 4-6 were significantly decreased, and the calcium ions were significantly increased, which were statistically significant compared with the model group (p<0.05), indicating that treatment groups 1-2 and 4-6 can improve the phenomenon of increased parathyroid hormone and calcitonin caused by hyperthyroidism, and inhibit osteoclasts and promote osteoblast proliferation by regulating thyroxine and parathyroid hormone, thereby achieving the therapeutic effect on osteoporosis; further, it can be seen from treatment groups 1 and 2 that the combined use of dithiocarbamate compounds and calcium supplements can significantly reduce the levels of FT3, FT4, parathyroid hormone, and calcitonin. The lowering effect was better, and the effect of increasing calcium ions was also better, while the simple use of calcium supplements in treatment group 3 could only simply increase the calcium ions in serum, and almost no decreasing trend was shown for FT3, FT4, parathyroid hormone and calcitonin; it can be seen from treatment group 1 and treatment group 4 that the single dose ratio of dithiocarbamate compounds and calcium supplements will also affect the contents of FT3, FT4, parathyroid hormone, calcitonin and calcium ions; it can be seen from treatment group 1 and treatment groups 5-6 that the types of dithiocarbamate compounds and calcium supplements will also affect the contents of FT3, FT4, parathyroid hormone, calcitonin and calcium ions to a certain extent.

[0082] Finally, it should be noted that the above embodiments are intended to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. Use of dithiocarbamic acid compounds in the preparation of drugs for preventing and / or treating osteoporosis; the structural formula of the dithiocarbamic acid compounds is as shown in Formula I, wherein R comprises any one of potassium, sodium, and amino, 2. The use according to claim 1, characterized in that: The osteoporosis is osteoporosis caused by decreased estrogen levels or hyperthyroidism.

3. The use according to claim 1, characterized in that: The dosage form of the dithiocarbamic acid compound includes any one of common preparations such as injection, powder injection, tablet, capsule, transdermal preparation, etc.

4. A combined drug composition for treating osteoporosis, characterized in that: The combined drug composition comprises a dithiocarbamate compound and a calcium supplement; The calcium supplement includes at least one of calcium carbonate, calcium gluconate, and calcium lactate; The structural formula of the dithiocarbamic acid compound is shown in Formula I, wherein R includes any one of potassium, sodium, and amino.

5. The combined pharmaceutical composition according to claim 4, characterized in that: The single-use mass ratio of the dithiocarbamic acid compound to the calcium supplement is (1-10):

1.

6. The combined pharmaceutical composition according to claim 5, characterized in that: The single-use mass ratio of the dithiocarbamate compound to the calcium supplement is preferably (1-4):

1.

7. The combined pharmaceutical composition according to claim 4, characterized in that: The osteoporosis is osteoporosis caused by decreased estrogen levels.

8. The combined pharmaceutical composition according to claim 4, characterized in that: The osteoporosis is osteoporosis caused by hyperthyroidism.

9. The combined pharmaceutical composition according to claim 4, characterized in that: The combined pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

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