Use of dithiocarbamic acid compounds for the preparation of a medicament for the prevention and / or treatment of osteoporosis

Abstract

The application discloses application of a dithio carbamic acid compound in preparation of a medicine for preventing and / or treating osteoporosis, and belongs to the technical field of medicines; researches show that the dithio carbamic acid compound can effectively prevent and / or treat osteoporosis, improve bone density of osteoporosis patients, and reduce the risk of bone fracture; meanwhile, researches show that when the dithio carbamic acid compound and a calcium supplement are combined for use, the prevention and / or treatment effect on osteoporosis can be better realized.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and in particular relates to the use of dithiocarbamic acid 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 fracture. The disease is prevalent among middle-aged and elderly people, with postmenopausal women being particularly susceptible. As China gradually enters an aging society, the incidence of osteoporosis has been increasing annually. Currently, clinical treatment for osteoporosis focuses primarily on inhibiting bone resorption. Commonly used drugs can be divided into two major categories: primarily bisphosphonates and receptor activator of nuclear factor κB ligand (RANKL) inhibitors. However, long-term use of these drugs may cause a range of adverse reactions, including but not limited to: osteonecrosis of the jaw, bone and joint pain, and muscle pain, and cellulitis. 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 composed of 84 amino acids arranged in a specific sequence with a molecular weight of 9500. It promotes bone resorption. PTH stimulates the lysosomes of osteoclasts, releasing hydrolytic enzymes that break down the bone matrix, releasing calcium and phosphate. Hypocalcemia stimulates the parathyroid glands, increasing PTH secretion; hypercalcemia inhibits the parathyroid glands, decreasing PTH secretion. Calcitonin is synthesized and secreted by thyroid parafollicular cells (C cells). It is a 32-amino acid polypeptide. Its effect on calcium metabolism is primarily to lower serum calcium, antagonizing the effect of PTH that increases serum calcium. The two work synergistically to regulate extracellular calcium concentration to maintain a constant level. When serum calcium concentration rises, calcitonin secretion is stimulated and parathyroid hormone secretion is inhibited. When serum calcium concentration decreases, parathyroid hormone secretion is stimulated and calcitonin secretion is inhibited. The primary mechanism by which calcitonin lowers blood calcium is by inhibiting the function of osteoclasts (osteoclasts have calcitonin receptors on their surface), reducing bone resorption. Calcitonin can also lower blood phosphorus, allowing inorganic phosphorus to enter bone tissue from the blood and extracellular fluid. Within bone, phosphorus combines with calcium 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, a series of synthetic drugs are available for the treatment of osteoporosis. For example, parathyroid hormone is also known as teriparatide, the only osteoblast-stimulating drug currently available. Other drugs include eel calcitonin (Ecalcin) and salmon calcitonin (Miacalci), 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 objectives, in a first aspect of the present invention, the present invention provides the use of a dithiocarbamic acid compound in the preparation of a drug for preventing and / or treating osteoporosis; the structural formula of the dithiocarbamic acid compound is as shown in Formula I, wherein R comprises 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 function 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 dithiocarbamic acid 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, a better effect of preventing and / or treating osteoporosis can be achieved; specifically, although calcium supplements can increase the concentration of calcium ions in serum to a certain extent, they have almost no effect on improving bone density. When calcium supplements and dithiocarbamate compounds are used simultaneously, compared with the use of dithiocarbamate compounds alone, a better increase in bone density can be achieved, osteoblast proliferation 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 mass ratio of the dithiocarbamic acid compound to the calcium supplement in a single use is (1-10):1.

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

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

[0021] The present invention found that the single-use mass ratio of dithiocarbamate compounds and calcium supplements also affects the effect of combined medication. When combined medication is further selected, when 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 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 effects 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 simultaneously, compared with the use of dithiocarbamate compounds alone, the increase in bone density can be better achieved, osteoblast proliferation can be promoted, and the effect of preventing and / or treating osteoporosis can be achieved. 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 effects of dithiocarbamic acid compounds and a combination of dithiocarbamic acid 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 under sterile conditions, a midline incision was made on the dorsal side, and the abdominal cavity was entered to find the ovaries near the lower pole of the kidney. The 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: After two weeks of postoperative recovery in step (1), treatment group 1 was injected with 108 mg / kg 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), 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 femur along the entire length, at the midpoint, and at the distal end of the femur was measured using an X-ray machine. The results 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 shown in Table 1, the BMD of the whole femur, midpoint, and distal end of the model group were lower than those in the sham group (p < 0.05), indicating successful modeling. BMD increased in the GMDTC-treated group, with significant differences in whole-bone and distal end BMD compared with the model group (p < 0.05), indicating that GMDTC can prevent osteoporosis.

[0039] Example 2

[0040] The present invention explores the therapeutic effects of dithiocarbamic acid compounds and a combination of dithiocarbamic acid compounds and a calcium supplement on ovariectomized osteoporosis 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 then 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 under sterile conditions, a midline incision was made on the dorsal side, and the ovaries were found near the lower pole of the kidney. 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) Medication treatment: 18 weeks after recovery from the surgery in step (1), different groups were given medication treatment, specifically:

[0043] Treatment group 1 received a continuous injection of 108 mg / kg dithiocarbamate compound (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) once a day for 3 days a week and 50 mg calcium gluconate was given orally every day for a total of 5 weeks;

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

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

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

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

[0048] Treatment group 6 received a 108 mg / kg injection of dithiocarbamate (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine, GMDTC) for 3 consecutive days per day and 50 mg of calcium carbonate was administered orally daily for a total of 5 weeks.

[0049] The sham group and the model group were treated with the same volume of normal saline instead of dithiocarbamate compounds 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, and the cartilage tissue was shaved off. The bone density of the femur at the full length, midpoint, and distal end was measured using an X-ray machine, and blood was collected to test serum osteocalcin and calcium ions;

[0051] The test results of bone density of the femur at the full length, midpoint and distal end are shown in Table 2; the test results of serum osteocalcin, calcitonin and calcium ion concentrations 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 shown in Table 2, in the study of ovariectomized osteoporosis, the femoral bone density at the whole bone, midpoint, and distal end of the model group was lower than that of the sham group (p < 0.05), indicating successful modeling. Bone density increased in treatment groups 1-2 and 4-6, with statistically significant differences in whole bone and distal end BMD compared with the model group (p < 0.05), indicating that treatment groups 1-2 and 4-6 can treat osteoporosis. Furthermore, in treatment groups 1 and 2, the combined use of dithiocarbamates and calcium supplements resulted in better recovery of bone density, while calcium supplementation alone had little effect on bone density in treatment group 3. In treatment groups 1 and 4, the single-dose ratio of dithiocarbamates to calcium supplements also influenced the improvement in bone density. In treatment groups 1 and 5-6, the type of dithiocarbamates and calcium supplements also influenced the improvement in bone density to a certain extent.

[0060] As can be seen from Table 3, in the study of ovariectomized osteoporosis, the osteocalcin and calcium ions in the model group increased significantly (compared with the sham operation group, p<0.05), and the calcitonin decreased significantly (compared with the sham operation group, p<0.05), indicating that the model was successful. The osteocalcin and calcium ions in treatment groups 1-2 and 5-6 increased significantly, and the calcitonin decreased significantly. 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. It can be further 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 use of calcium supplements alone can only simply increase the calcium ion content 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 effects of dithiocarbamic acid compounds and a combination of dithiocarbamic acid compounds and a calcium supplement on ovariectomized osteoporosis rats, comprising the following steps:

[0063] (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, 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, all other groups were given 100 mg of thyroxine by gavage at 8:00 in the morning for 12 consecutive weeks. The rats in the sham operation group were replaced with normal saline.

[0064] (2) Dosage treatment: After 12 weeks of continuous treatment in step (1), different groups were given medication, specifically:

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

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

[0067] Treatment group 3 received weekly injections of an equal volume of normal saline with 108 mg / kg of dithiocarbamate and daily oral administration of 50 mg of calcium gluconate for a total of 4 weeks;

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

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

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

[0071] The sham group and the model group were treated with the same volume of normal saline instead of dithiocarbamate compounds 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 femur along the entire length, midpoint, and distal end was measured using an X-ray machine. Blood was collected to detect free triiodothyronine (FT3), free thyroxine (FT4), and bone metabolism indicators calcium ion (Ca) and parathyroid hormone (PTH);

[0073] The test results of bone mineral density at the full 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) are shown in Table 5;

[0074] Table 4

[0075] Group <![CDATA[Total bone (g / cm 2 )]]> <![CDATA[Midpoint (g / cm 2 )]]> <![CDATA[Far 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 shown in Table 4, in the hyperthyroidism model, BMD of the femur at the whole bone, midpoint, and distal end of the model group was lower than that of the sham group (p < 0.05), indicating successful modeling. BMD increased in treatment groups 1-2 and 4-6, with statistically significant differences in total bone and distal end BMD compared with the model group (p < 0.05), indicating that treatment groups 1-2 and 4-6 can treat osteoporosis. Furthermore, in treatment groups 1 and 2, the combined use of dithiocarbamates and calcium supplements resulted in better recovery of BMD, whereas calcium supplementation alone had little effect on BMD in treatment group 3. In treatment groups 1 and 4, the single-dose ratio of dithiocarbamates to calcium supplements also affected the improvement in BMD. In treatment groups 1 and 5-6, the type of dithiocarbamates and calcium supplements also influenced the improvement in BMD 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, and the differences 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 thyroid hormone 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 dithiocarbamic acid 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 in treatment group 3, the simple use of calcium supplements 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 can also affect the levels 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 can also affect the levels 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 solutions 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 preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. Use of a dithiocarbamic acid compound in the preparation of a drug for preventing and / or treating osteoporosis; the dithiocarbamic acid compound is sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine.

2. The use according to claim 1, characterized in that The osteoporosis is osteoporosis caused by decreased estrogen levels or hyperthyroidism.

3. A combined drug composition for treating osteoporosis, characterized in that: The combined drug composition is a dithiocarbamic acid compound and a calcium supplement; The calcium supplement is at least one of calcium carbonate, calcium gluconate, and calcium lactate; The dithiocarbamic acid compound is sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine.

4. The combined pharmaceutical composition according to claim 3, characterized in that The single-use mass ratio of the dithiocarbamic acid compound to the calcium supplement is (1-10):

1.

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 (1-4):

1.

6. The combined pharmaceutical composition according to claim 3, characterized in that The combined pharmaceutical composition further includes pharmaceutically acceptable excipients.

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