Use of dithiocarbamate compounds in preparation of drug for preventing and / or treating osteoporosis

Abstract

Disclosed is the use of dithiocarbamate compounds in the preparation of a drug for preventing and / or treating osteoporosis. The dithiocarbamate compounds can effectively prevent and / or treat osteoporosis, improve bone mineral density in patients with osteoporosis, and reduce the risk of fractures. Moreover, the dithiocarbamate compounds, when used in combination with a calcium supplement, can achieve better preventive and / or therapeutic effects on osteoporosis.

Description

Application of dithiocarbamate compounds in the preparation of drugs for the prevention and / or treatment of osteoporosis Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and particularly relates to the application of dithiocarbamate compounds in the preparation of drugs for the prevention and / or treatment of osteoporosis. Background Technology

[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. It is prevalent among middle-aged and elderly individuals, particularly postmenopausal women. As China gradually enters an aging society, the incidence of osteoporosis is showing a year-on-year upward trend. Currently, clinical treatment for osteoporosis mainly focuses on inhibiting bone resorption. Commonly used drugs can be divided into two main categories: primarily bisphosphonates and nuclear factor kappa B receptor activator ligand (RANKL) inhibitors. However, long-term use of these drugs may cause a series of adverse reactions, including but not limited to: osteonecrosis of the mandible, osteoarthritis and muscle pain, and cellulitis. Therefore, developing new, safer, and more effective treatment options for osteoporosis is of significant clinical importance.

[0003] Parathyroid hormone (PTH) is a linear polypeptide hormone with 84 amino acids arranged in a specific sequence and a molecular weight of 9500. It promotes bone resorption. PTH stimulates lysosomes in osteoclasts, releasing hydrolytic enzymes that break down the bone matrix, releasing calcium and phosphate. Hypocalcemia excites the parathyroid gland, increasing PTH secretion; hypercalcemia inhibits the parathyroid gland, decreasing PTH secretion. Calcitonin, synthesized and secreted by parafollicular cells (C cells) of the thyroid gland, is a polypeptide composed of 32 amino acids. Calcitonin's effect on calcium metabolism is mainly to lower serum calcium, antagonizing the effect of PTH in increasing serum calcium. Both work synergistically to regulate extracellular calcium ion concentration to maintain its homeostasis. Increased serum calcium concentration stimulates calcitonin secretion and inhibits parathyroid hormone secretion; conversely, decreased serum calcium concentration stimulates parathyroid hormone secretion and inhibits calcitonin secretion. The main mechanism by which calcitonin lowers blood calcium is by inhibiting osteoclast function (osteoclasts have calcitonin receptors on their surface), thus reducing bone resorption. Calcitonin can also lower blood phosphorus, allowing inorganic phosphorus to enter bone tissue from the blood and extracellular fluid. In bone tissue, phosphorus binds with calcium to form a complex, reducing calcium release from bone. 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 used in the treatment of osteoporosis. For example, parathyroid hormone is called teriparatide, which is currently the only osteocyte-promoting drug; eel calcitonin (Ecitonin) and salmon calcitonin (Micaxicin) are also used, both of which can reduce bone loss. Summary of the Invention

[0004] This invention provides the use of dithiocarbamate compounds in the preparation of drugs for the prevention and / or treatment of osteoporosis; the structural formula of the dithiocarbamate compound is shown in Formula I, wherein R includes any one of potassium, sodium, and amino groups.

[0005] This invention provides a combination drug composition comprising a dithiocarbamate compound and a calcium supplement; the calcium supplement comprises at least one selected from calcium carbonate, calcium gluconate, and calcium lactate; the dithiocarbamate compound has the structural formula shown in Formula I, wherein R comprises any one of potassium, sodium, and amino groups.

[0006] The present invention provides the dithiocarbamate compounds for the prevention and / or treatment of osteoporosis.

[0007] The present invention provides a combination of the dithiocarbamate compound and the calcium supplement for the prevention and / or treatment of osteoporosis.

[0008] This invention provides a method for preventing and / or treating osteoporosis, comprising administering the dithiocarbamate compound to a subject in need. In some embodiments, the method further comprises administering the calcium supplement.

[0009] The present invention provides the use of the above-described combination drug composition in the preparation of a medicament for the prevention and / or treatment of osteoporosis.

[0010] In some embodiments, for any of the above technical solutions, the mass ratio of the dithiocarbamate compound and the calcium supplement for a single use is (1-10):1.

[0011] In some embodiments, for any of the above technical solutions, the preferred mass ratio of the dithiocarbamate compound and the calcium supplement for a single use is (1-4):1.

[0012] In some embodiments, for any of the above technical solutions, the osteoporosis is osteoporosis caused by decreased estrogen levels or hyperthyroidism.

[0013] In some embodiments, for any of the above technical solutions, the osteoporosis is osteoporosis caused by a decrease in estrogen levels.

[0014] In some embodiments, for any of the above technical solutions, the osteoporosis is osteoporosis caused by hyperthyroidism.

[0015] In some embodiments, for any of the above technical solutions, the dosage form of the dithiocarbamic acid compound includes any one of commonly used preparations such as injections, powder injections, tablets, capsules, and transdermal preparations.

[0016] In some embodiments, for any of the above-described technical solutions, the combined drug composition further includes pharmaceutically acceptable excipients.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] This invention provides the application of dithiocarbamate compounds in the preparation of drugs for the prevention and / or treatment of osteoporosis. Research has shown that dithiocarbamate compounds can effectively prevent and / or treat osteoporosis, improve bone mineral density in osteoporosis patients, and reduce fracture risk. Specifically, dithiocarbamate 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. Meanwhile, this invention also provides a combined drug composition of dithiocarbamate compounds and calcium supplements for the prevention and / or treatment of osteoporosis. This invention has found that when dithiocarbamate compounds and calcium supplements are used in combination, the preventive and / or therapeutic effects on osteoporosis can be better achieved. Specifically, although calcium supplements can increase serum calcium ion concentration to some extent, they have almost no effect on improving bone density. However, when calcium supplements and dithiocarbamate compounds are used simultaneously, compared to using dithiocarbamate compounds alone, it can better increase bone density, promote osteoblast proliferation, and achieve the effect of preventing and / or treating osteoporosis. Detailed Implementation

[0019] This invention provides a drug that can effectively treat osteoporosis.

[0020] In a first aspect, the present invention provides the use of dithiocarbamate compounds in the preparation of drugs for the prevention and / or treatment of osteoporosis; the structural formula of the dithiocarbamate compound is shown in Formula I, wherein R includes any one of potassium, sodium, and amino groups.

[0021] This invention has found that dithiocarbamate compounds can effectively prevent and / or treat osteoporosis, improve bone density in osteoporosis patients, and reduce fracture risk. 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.

[0022] In some embodiments, R in Formula I comprises potassium or sodium.

[0023] This invention has found that when R is further selected as potassium or sodium, the corresponding dithiocarbamate compounds are more effective in preventing and / or treating osteoporosis.

[0024] In some embodiments, the osteoporosis is osteoporosis caused by a decline in estrogen levels.

[0025] In some embodiments, the osteoporosis is osteoporosis caused by hyperthyroidism.

[0026] It is understood that the osteoporosis mentioned includes, but is not limited to, osteoporosis caused by decreased estrogen levels or hyperthyroidism, and is applicable to various types of osteoporosis (such as glucocorticoid-induced osteoporosis, senile osteoporosis, secondary osteoporosis, etc.). The dithiocarbamate compounds of this invention improve bone mineral density and bone microstructure by regulating osteocalcin, calcium ions, and calcitonin levels; their mechanism of action is not limited to specific causes and can be universally applied to the prevention and treatment of various types of osteoporosis, exhibiting a broad-spectrum osteoprotective effect. Therefore, this compound is not only applicable to bone loss caused by specific hormone level abnormalities, but also universally applicable to the prevention and treatment of osteoporosis under various pathological and physiological conditions.

[0027] In some embodiments, the dosage form of the dithiocarbamate compound includes any one of commonly used preparations such as injections, powder for injection, tablets, capsules, and transdermal preparations.

[0028] In a second aspect, the present invention provides a combination drug composition for treating osteoporosis, the combination drug composition comprising a dithiocarbamate compound and a calcium supplement;

[0029] The calcium supplement includes at least one of calcium carbonate, calcium gluconate, and calcium lactate.

[0030] The structural formula of the dithiocarbamate compound is shown in Formula I, wherein R includes any one of potassium, sodium, and amino groups.

[0031] This invention has found that combining dithiocarbamate compounds with calcium supplements can better achieve the preventive and / or therapeutic effects on osteoporosis. Specifically, although calcium supplements can increase the concentration of calcium ions in the serum to some extent, they have almost no effect on improving bone density. However, when calcium supplements and dithiocarbamate compounds are used simultaneously, compared with the use of dithiocarbamate compounds alone, it can better increase bone density, promote osteoblast proliferation, and achieve the effect of preventing and / or treating osteoporosis.

[0032] It is understood that the calcium supplements are not limited to calcium carbonate, calcium gluconate, or calcium lactate, but may also include other pharmaceutically acceptable calcium salts or calcium-containing compounds, such as, but not limited to, calcium citrate, calcium phosphate, calcium lactate, calcium acetate, calcium aspartate, calcium ascorbate, etc. Any calcium supplement that can provide calcium ions in the body and support bone metabolism is suitable for the combination therapy regimens of this invention.

[0033] In some embodiments, the mass ratio of the dithiocarbamate compound to the calcium supplement for a single use is (1-10):1.

[0034] In some embodiments, the mass ratio of the dithiocarbamate compound to the calcium supplement for a single use is (1-4):1.

[0035] In some embodiments, the mass ratio of the dithiocarbamate compound to the calcium supplement for a single use is (2-3):1.

[0036] This invention has found that the single-use mass ratio of dithiocarbamate compounds and calcium supplements also affects the efficacy of combined medication. When further selecting combined medication, the single-use mass ratio of the two is (1-4):1, especially (2-3):1, which yields better combined medication effects.

[0037] In some embodiments, the osteoporosis is osteoporosis caused by a decline in estrogen levels.

[0038] In some embodiments, the osteoporosis is osteoporosis caused by hyperthyroidism.

[0039] In some embodiments, the combination drug composition further includes pharmaceutically acceptable excipients.

[0040] In some embodiments, the dosage form of the dithiocarbamate compound in the combined drug composition includes any one of commonly used preparations such as injections, powder injections, tablets, capsules, and transdermal preparations, and the dosage form of the calcium supplement includes any one of tablets, capsules, and liquids.

[0041] It is understood that the term "combined medication" in this invention refers to the use of dithiocarbamate compounds and calcium supplements in any reasonable form of administration to achieve the effect of treating and / or preventing osteoporosis. Such combined medication methods include, but are not limited to: separate preparation and administration within the same treatment cycle (e.g., preparing dithiocarbamate compounds as injections and calcium supplements as oral formulations, administering them to patients separately within the same treatment cycle in a manner including but not limited to simultaneous administration, sequential administration, and alternating administration); co-formulation into the same pharmaceutical composition (e.g., preparing dithiocarbamate compounds and calcium supplements together into a single dosage form such as tablets, capsules, granules, or oral liquid, where a single administration contains both active ingredients); and freely combinable administration regimens (e.g., the administration time, dosage frequency, and dosage form of the two active ingredients can be flexibly adjusted according to clinical needs, as long as they are used in combination during the overall treatment process). Therefore, the scope of protection of this invention covers all forms of medication in which dithiocarbamate compounds and calcium supplements are used synergistically for the prevention and / or treatment of osteoporosis, and is not limited to specific formulations or administration sequences.

[0042] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0043] Unless otherwise specified, the reagents, methods and equipment used in this invention are all conventional reagents, methods and equipment in the field; and unless otherwise specified, the raw materials used in parallel experiments are from the same batch.

[0044] Example 1

[0045] This invention investigates the preventive effects of dithiocarbamate compounds and combinations of dithiocarbamate compounds and calcium supplements on ovariectomized osteoporosis model rats, including the following steps:

[0046] (1) Preparation of animal models: SD rats (Zhuhai Baishitong Biotechnology Co., Ltd.) were randomly divided into sham-operated group, model group and treatment group 1 according to body weight after 3 days of adaptive feeding, with 10 rats in each group. Except for the sham-operated group, the other two groups used the ovariectomy method to replicate the osteoporosis model; specifically, 1% sodium pentobarbital 30mg / kg was injected intraperitoneally for anesthesia, and an incision was made in the midline of the dorsal side under sterile conditions to enter the abdominal cavity and find the ovaries near the lower pole of the kidneys. The ovaries were ligated with No. 4 sutures and removed bilaterally, and the incision was sutured in layers. The sham-operated group had the same surgical procedure, but the ovaries were not removed;

[0047] (2) Drug administration: Step (1) Two weeks after the operation, the treatment group 1 was injected with 108 mg / kg N-dithiocarboxylic acid sodium-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium (GMDTC) for 3 consecutive days every week, once a day for a total of 10 weeks. The sham surgery group and the model group were given the same volume of physiological saline.

[0048] (3) Post-administration treatment: After the drug administration experiment in step (2), all rats were anesthetized by intraperitoneal injection of sodium pentobarbital and then sacrificed. The left femur of each rat was removed, the cartilage tissue was removed, and the bone mineral density of the entire length, midpoint, and distal end of the femur was measured by X-ray machine. The results are shown in Table 1.

[0049] Table 1

[0050] Among them, * compared with the sham surgery group, P<0.05, and # compared with the model group, P<0.05.

[0051] As shown in Table 1, the bone mineral density (BMD) of the whole femur, midpoint, and distal end in the model group was lower than that in the sham-operated group (p<0.05), indicating successful model establishment. The bone mineral density of the animal GMDTC treatment group 1 was increased, and the differences in whole-bone BMD and distal end BMD compared to the model group were statistically significant (p<0.05), indicating that GMDTC can prevent osteoporosis.

[0052] Example 2

[0053] This invention investigates the therapeutic effects of dithiocarbamate compounds and combinations of dithiocarbamate compounds and calcium supplements on ovariectomized osteoporosis model rats, including the following steps:

[0054] (1) Preparation of animal models: SD rats (Zhuhai Baishitong Biotechnology Co., Ltd.) were randomly divided into sham-operated 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-operated group, the other groups adopted the ovariectomy method to replicate the osteoporosis model. Specifically, 1% sodium pentobarbital 30mg / kg was injected intraperitoneally for anesthesia. Under sterile conditions, a midline incision was made on the dorsal side, and the ovaries were found near the lower pole of the kidneys in the abdominal cavity. The ovaries were ligated with No. 4 suture and removed bilaterally. The incision was sutured in layers. The sham-operated group had the same surgical procedure, but the ovaries were not removed.

[0055] (2) Drug administration: After 18 weeks of postoperative recovery following step (1), drug administration was administered according to different groups, specifically as follows:

[0056] Treatment group 1 received weekly injections of 108 mg / kg of dithiocarbamate compound (N-dithiocarboxylic acid sodium-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium, GMDTC) for 3 consecutive days, once daily, and daily oral administration of 50 mg / kg calcium gluconate for a total of 5 weeks;

[0057] Treatment group 2 received continuous injections of 108 mg / kg of dithiocarbamate compound (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium, GMDTC) for 3 days a week, once a day, for a total of 5 weeks;

[0058] Treatment group 3 received weekly injections of an equal volume of physiological saline containing 108 mg / kg of dithiocarbamate compounds, and daily oral gavage of 50 mg / kg of calcium gluconate for a total of 5 weeks.

[0059] Treatment group 4 received weekly injections of 54 mg / kg of dithiocarbamate compound (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium, GMDTC) for 3 consecutive days, once daily, and daily oral administration of 60 mg / kg calcium gluconate for a total of 5 weeks;

[0060] Treatment group 5 received weekly injections of 108 mg / kg of dithiocarbamate compound (N-dithiocarboxylic acid amino-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine potassium) for 3 consecutive days, once daily, and daily oral administration of 50 mg / kg calcium gluconate for a total of 5 weeks;

[0061] The treatment group 6 received 108 mg / kg of dithiocarbamate compound (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium, GMDTC) once a day for 3 consecutive weeks, and were given 50 mg / kg of calcium carbonate by gavage daily for a total of 5 weeks.

[0062] The sham surgery group and the model group were replaced with the same volume of physiological saline instead of dithiocarbamate compounds and calcium supplements, respectively.

[0063] (3) Post-administration treatment: After the drug administration experiment in step (2), all rats were anesthetized by intraperitoneal injection of sodium pentobarbital and then sacrificed. The left femur of each rat was removed, the cartilage tissue was removed, and the bone density of the entire length, midpoint and distal end of the femur was measured by X-ray machine. Blood was collected to detect serum osteocalcin and calcium ions.

[0064] Table 2 shows the results of bone mineral density measurements along the entire length of the femur, at its midpoint, and at the distal end of the femur; Table 3 shows the results of serum osteocalcin, calcitonin, and calcium ion concentrations.

[0065] Table 2

[0066] Among them, * compared with the sham surgery group, P<0.05, and # compared with the model group, P<0.05.

[0067] Table 3

[0068] Among them, *the model group was compared with the sham surgery group, P<0.05, and #the treatment group was compared with the model group, P<0.05.

[0069] As shown in Table 2, in the study of osteoporosis after ovarian removal, the bone mineral density of the whole femur, midpoint, and distal end in the model group was lower than that in the sham surgery group (p<0.05), indicating that the model was successfully established. Bone mineral density (BMD) increased in treatment groups 1-2 and 4-6, with statistically significant differences in total bone mineral density and distal bone mineral density compared to the model group (p<0.05), indicating that treatment groups 1-2 and 4-6 can treat osteoporosis. Further analysis of treatment groups 1 and 2 shows that the combined use of dithiocarbamate compounds and calcium supplements resulted in better BMD recovery, while calcium supplementation alone had almost no effect on BMD improvement in treatment group 3. Treatment groups 1 and 4 show that the single-dose ratio of dithiocarbamate compounds to calcium supplements also affects the improvement in BMD. Treatment groups 1 and 5-6 show that although the type of dithiocarbamate compound and calcium supplement can influence the improvement in BMD to some extent, different types of dithiocarbamate compounds, and their combinations with different types of calcium supplements, can all improve BMD.

[0070] Table 3 shows that in the study of osteoporosis after oophorectomy, osteocalcin and calcium ions in the model group were significantly increased (p<0.05 compared with the sham-operated group), while calcitonin was significantly decreased (p<0.05 compared with the sham-operated group), indicating successful model establishment. In treatment groups 1-2 and 5-6, osteocalcin and calcium ions were significantly increased, and calcitonin was significantly decreased, with statistically significant differences compared with the model group (p<0.05). This indicates that treatment groups 1-2 and 5-6 can inhibit osteoclasts and promote osteoblast proliferation, achieving a therapeutic effect on osteoporosis. Furthermore, in treatment groups 1 and 2, the combined use of dithiocarbamate compounds and calcium supplements showed a better effect on increasing osteocalcin and calcium ions and decreasing calcitonin. In contrast, in treatment group 3, the use of calcium supplements alone only increased serum calcium ions, with almost no effect on osteocalcin. There was no increasing trend, and almost no decreasing trend for calcitonin. Treatment groups 1 and 4 showed that the single-dose ratio of dithiocarbamate compounds to calcium supplements also affected serum concentrations of osteocalcin, calcitonin, and calcium ions. Treatment groups 1 and 5-6 showed that although the type of dithiocarbamate compound and calcium supplement also affected serum concentrations of osteocalcin, calcitonin, and calcium ions to some extent, different types of dithiocarbamate compounds, and their combinations with different types of calcium supplements, all increased osteocalcin and calcium ion concentrations while decreasing calcitonin concentrations.

[0071] Example 3

[0072] This invention investigates the therapeutic effects of dithiocarbamate compounds and combinations of dithiocarbamate compounds and calcium supplements on ovariectomized osteoporosis model rats, including the following steps:

[0073] (1) Preparation of animal models: SD rats (Zhuhai Baishitong Biotechnology Co., Ltd.) were randomly divided into sham-operated 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 after 3 days of adaptive feeding, with 10 rats in each group; except for the sham-operated group, the other groups were given 100mg / kg thyroxine by gavage at 8 am every day for 12 consecutive weeks; the rats in the sham-operated group were replaced with physiological saline.

[0074] (2) Drug administration: After 12 weeks of continuous treatment in step (1), drug administration was carried out according to different groups, specifically as follows:

[0075] Treatment group 1 received weekly injections of 108 mg / kg of dithiocarbamate compound (N-dithiocarboxylic acid sodium-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium, GMDTC) for 3 consecutive days, once daily, and daily oral administration of 50 mg / kg calcium gluconate for a total of 4 weeks;

[0076] Treatment group 2 received continuous injections of 108 mg / kg of dithiocarbamate compound (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium, GMDTC) for 3 days a week, once a day, for a total of 4 weeks;

[0077] Treatment group 3 received weekly injections of an equal volume of physiological saline containing 108 mg / kg of dithiocarbamate compounds, and daily oral gavage of 50 mg / kg of calcium gluconate for a total of 4 weeks.

[0078] Treatment group 4 received weekly injections of 54 mg / kg of dithiocarbamate compound (sodium N-dithiocarboxylate-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium, GMDTC) for 3 consecutive days, once daily, and daily oral administration of 60 mg / kg calcium gluconate for a total of 4 weeks;

[0079] Treatment group 5 received weekly injections of 108 mg / kg of dithiocarbamate compound (N-dithiocarboxylic acid amino-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine potassium) for 3 days, once a day, and daily oral administration of 50 mg / kg calcium gluconate for a total of 4 weeks;

[0080] The treatment group 6 received 108 mg / kg of dithiocarbamate compound (N-dithiocarboxylic acid sodium-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)-L-methionine sodium, GMDTC) once a day for 3 consecutive weeks, and were given 50 mg / kg of calcium carbonate by gavage daily for a total of 4 weeks.

[0081] The sham surgery group and the model group were replaced with the same volume of physiological saline instead of dithiocarbamate compounds and calcium supplements, respectively.

[0082] (3) Post-administration treatment: After the drug administration experiment in step (2), all rats were anesthetized by intraperitoneal injection of sodium pentobarbital and then sacrificed. The left femur of each rat was removed, the cartilage tissue was removed, and the bone mineral density of the femur at its full length, midpoint and distal end was measured by X-ray machine. Blood was collected to detect the contents of free triiodothyronine (FT3), free thyroxine (FT4) and bone metabolism indicators calcium ion (Ca) and parathyroid hormone (PTH).

[0083] Table 4 shows the results of bone mineral density measurements of the entire femur length, midpoint, and distal femur; Table 5 shows the results of measurements of free triiodothyronine (FT3), free thyroxine (FT4), and bone metabolism indicators calcium ions (Ca) and parathyroid hormone (PTH).

[0084] Table 4

[0085] Among them, *the model group was compared with the sham surgery group, P<0.05, and #the treatment group was compared with the model group, P<0.05.

[0086] Table 5

[0087] Among them, *the model group was compared with the sham surgery group, P<0.05, and #the treatment group was compared with the model group, P<0.05.

[0088] As shown in Table 4, in the hyperthyroidism model, the bone mineral density of the whole femur, midpoint, and distal end in the model group was lower than that in the sham surgery group (p<0.05), indicating that the model was successfully established. Bone mineral density (BMD) increased in treatment groups 1-2 and 4-6, with statistically significant differences in total bone mineral density and distal bone mineral density compared to the model group (p<0.05), indicating that treatment groups 1-2 and 4-6 can treat osteoporosis. Further analysis of treatment groups 1 and 2 shows that the combined use of dithiocarbamate compounds and calcium supplements resulted in better BMD recovery, while calcium supplementation alone had almost no effect on BMD improvement in treatment group 3. Treatment groups 1 and 4 show that the single-dose ratio of dithiocarbamate compounds to calcium supplements also affects the improvement in BMD. Treatment groups 1 and 5-6 show that although the type of dithiocarbamate compound and calcium supplement can influence the improvement in BMD to some extent, different types of dithiocarbamate compounds, and their combinations with different types of calcium supplements, can all improve BMD.

[0089] As shown in Table 5, in the hyperthyroidism model, the levels of FT3, FT4, parathyroid hormone, calcitonin, and calcium ions in the model group were significantly different from those in the sham-operated group (p<0.05 compared with the sham-operated group), indicating that the model was successfully established. In treatment groups 1-2 and 4-6, FT3, FT4, parathyroid hormone, and calcitonin levels decreased significantly, while calcium ion levels increased significantly, with statistically significant differences compared to the model group (p<0.05). This indicates that treatment groups 1-2 and 4-6 can improve the elevated parathyroid hormone and calcitonin levels caused by hyperthyroidism. By regulating thyroid hormones and parathyroid hormone, they inhibit osteoclasts and promote osteoblast proliferation, thereby achieving a therapeutic effect on osteoporosis. Furthermore, in treatment groups 1 and 2, the combined use of dithiocarbamate compounds and calcium supplements showed a better effect in decreasing FT3, FT4, parathyroid hormone, and calcitonin levels, and a better effect in increasing calcium ion levels. In contrast, in treatment group 3, the use of calcium supplements alone only had a simple effect... Increasing serum calcium ions had almost no decreasing effect on FT3, FT4, parathyroid hormone, and calcitonin. Treatment groups 1 and 4 showed that the single-dose ratio of dithiocarbamate compounds to calcium supplements also affected the levels of FT3, FT4, parathyroid hormone, calcitonin, and calcium ions. Treatment groups 1 and 5-6 showed that while the type of dithiocarbamate compound and calcium supplement could influence the levels of FT3, FT4, parathyroid hormone, calcitonin, and calcium ions to some extent, different types of dithiocarbamate compounds, and their combinations with different types of calcium supplements, could all increase or decrease the levels of FT3, FT4, parathyroid hormone, and calcitonin, as well as increase calcium ion levels.

[0090] Finally, it should be noted that the above embodiments are used to illustrate the technical solutions of the present invention and not 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 modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. Use of a dithiocarbamic compound in the manufacture of a medicament for preventing and / or treating osteoporosis, said dithiocarbamic compound having a structure according to Formula I: ###00001### wherein R is any one of potassium, sodium, and amino.

2. Use according to claim 1, characterized in that, The osteoporosis mentioned is osteoporosis caused by a decrease in estrogen levels or hyperthyroidism.

3. Use according to claim 1, characterized in that, The dosage forms of the dithiocarbamate compounds include any one of the commonly used preparations such as injections, powder injections, tablets, capsules, and transdermal preparations.

4. A combination drug composition, characterized in that, The combined drug composition includes dithiocarbamate compounds and calcium supplements; The calcium supplement includes at least one of calcium carbonate, calcium gluconate, and calcium lactate. The structural formula of the dithiocarbamic compound is shown in Formula I, wherein R includes any one of potassium, sodium, and amino, 5. The combination of claim 4, wherein the combination is a pharmaceutical composition. The mass ratio of the dithiocarbamate compound to the calcium supplement for a single use is (1-10):

1.

6. The combination of claim 5, wherein The preferred mass ratio of the dithiocarbamate compound and the calcium supplement for a single use is (1-4):

1.

8. The combination of claim 4, wherein The osteoporosis mentioned is osteoporosis caused by a decrease in estrogen levels.

9. The combination of claim 4, wherein The osteoporosis mentioned is osteoporosis caused by hyperthyroidism.

10. The combination of claim 4, wherein The combination drug composition also includes pharmaceutically acceptable excipients.