Application of 2, 2 ': 5', 2 ''-trithiophene-5-formaldehyde in preparation of medicine for treating osteoporosis

Abstract

The invention relates to application of 2, 2 ': 5', 2 ''-trithiophene-5-formaldehyde in preparation of medicines for treating osteoporosis, and belongs to the technical field of biological medicines. The application of 2, 2 ': 5', 2 ''-trithiophene-5-formaldehyde in preparation of the medicine for treating osteoporosis is found for the first time, and especially the excellent application of 2, 2 ': 5', 2 ''-trithiophene-5-formaldehyde in preparation of the medicine for treating osteoporosis of postmenopausal women is found. In the cell level, the 2, 2 ': 5', 2 ''-trithiophene-5-formaldehyde shows obvious osteogenesis promotion and adipogenesis inhibition activity. On the animal level, the 2, 2 ': 5', 2 ''-trithiophene-5-formaldehyde can significantly improve bone mass loss of mice with osteoporosis caused by OVX, and promotes bone formation while inhibiting bone resorption. The result shows that the 2, 2 ': 5', 2 ''-trithiophene-5-formaldehyde has a good osteoporosis treatment effect, provides a novel anti-osteoporosis medicine for clinic, and has a wide application prospect and a relatively high application value.

Description

TECHNICAL FIELD

[0001] The application relates to application of 2,2':5',2''-terthiophene-5-formaldehyde in preparation of a drug for treating osteoporosis and belongs to the technical field of biological medicines. BACKGROUND

[0002] Osteoporosis is a systemic metabolic bone disease, mainly manifested as bone mass reduction and bone microstructure damage, leading to increased bone fragility and easy fracture. The disease mainly occurs in postmenopausal women and old men, and has become one of the main health problems in the global aging process. Reducing bone absorption or increasing bone formation is a key strategy for restoring bone remodeling balance and effectively treating osteoporosis. At present, the drugs for treating osteoporosis in the clinic are mainly divided into two categories: one is a drug for promoting bone formation, such as foslosterin; and the other is a drug for inhibiting bone absorption, such as bisphosphonate and denosumab. Although substantial progress has been made in the treatment of osteoporosis, long-term and large-dose drug use may cause hypercalcemia syndrome or hyperphosphatemia and even adverse reactions such as allergy and nausea. It is particularly important to further develop a drug with low toxicity for controlling bone remodeling.

[0003] Bone marrow mesenchymal stem cells (BMSCs) are a kind of stem cells with multiple differentiation potential, mainly existing in bone marrow, and can differentiate into various types of cells, including osteoblasts, adipocytes and chondrocytes, under specific physiological or pathological environment. In the occurrence process of osteoporosis, the number of bone cells is reduced, and the osteogenic differentiation ability is often inhibited. The change of bone marrow microenvironment and chronic low-toxic inflammation reaction leads to the increase of the adipogenic differentiation tendency of BMSCs. Restoring the osteogenic differentiation of BMSCs helps to slow down the bone mass loss caused by osteoporosis and provides a new strategy for its treatment. At present, the BMSCs transplantation therapy by transplanting BMSCs to the bone damage site of osteoporosis patients can promote bone formation and enhance bone strength. In addition, researchers also pay attention to the potential of developing natural products for promoting the osteogenic differentiation of BMSCs, and effectively reverse the pathological changes of osteoporosis by activating specific signal pathways such as Wnt / beta-catenin and BMP pathways.

[0004] Therefore, it is an urgent need in the clinical treatment of osteoporosis to find a new type of anti-osteoporosis drug which is simple, safe, reliable and effective, and has important application potential and social and economic value. SUMMARY

[0005] In view of the deficiencies of the prior art, the application provides application of 2,2':5',2''-terthiophene-5-formaldehyde in preparation of a drug for treating osteoporosis.

[0006] The technical scheme of the application is as follows:

[0007] The present application provides the use of 2,2':5',2"-thiophene-5-formaldehyde in the preparation of a drug for treating osteoporosis.

[0008] The structure of the 2,2':5',2"-thiophene-5-formaldehyde (ecliptal) is shown in the following formula (1);

[0009]

[0010] According to the present application, the osteoporosis is preferably postmenopausal osteoporosis.

[0011] According to the present application, the drug comprises a pharmaceutical composition consisting of 2,2':5',2"-thiophene-5-formaldehyde and an excipient.

[0012] According to the present application, the excipient comprises any one or a combination of at least two of a diluent, a binder, a wetting agent, a disintegrant, an emulsifier, a co-solvent, a solubilizer, an osmotic pressure regulator, a surfactant, a coating material, an antioxidant, a bacteriostatic agent, or a buffer.

[0013] According to the present application, the dosage form of the drug comprises any one of a suspension, a granule, a capsule, a powder, a tablet, an emulsion, a solution, a dripping pill, an injection, a suppository, an enema, an aerosol, a patch, or a drop.

[0014] The present inventors have screened more than one thousand compounds for the activity of promoting osteogenic differentiation of BMSCs, and found that 2,2':5',2"-thiophene-5-formaldehyde (ecliptal) has significant activity of promoting osteogenesis and inhibiting adipogenesis. The effect of ecliptal on promoting osteogenesis and inhibiting adipogenic differentiation has been verified in experiments of bone marrow mesenchymal stem cells, and the effect of ecliptal on significantly improving the reduction and disorder of bone trabecula and increasing the thickness of cortical bone of bilateral ovariectomized (OVX) mice has been verified in mouse experiments. Therefore, the study of the role of ecliptal in the treatment of osteoporosis has important scientific value and application prospect, especially in the development of new natural drugs for treating osteoporosis.

[0015] The present application has the following beneficial effects:

[0016] The application first discloses an application of 2,2':5',2"-terthiophene-5-formaldehyde in preparation of a drug for treating osteoporosis, and particularly in preparation of a drug for treating osteoporosis of postmenopausal women. At a cell level, 2,2':5',2"-terthiophene-5-formaldehyde shows significant osteogenesis-promoting and adipogenesis-inhibiting activities. At an animal level, 2,2':5',2"-terthiophene-5-formaldehyde can significantly improve bone mass loss of osteoporosis mice caused by OVX, and promote bone formation while inhibiting bone resorption. This shows that 2,2':5',2"-terthiophene-5-formaldehyde has a good effect of treating osteoporosis, and provides a new anti-osteoporosis drug for clinic, and has a wide application prospect and high application value. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 To implement the 2,2':5',2"-terthiophene-5-formaldehyde in promoting BMSCs osteogenic differentiation and inhibiting adipogenic differentiation in example 1;

[0018] In the figure, A is a representative picture of ALP staining, alizarin red staining and oil red staining; B and C are qPCR detection of the influence of 2,2':5',2"-terthiophene-5-formaldehyde on the expression of BMSCs cell osteogenic and adipogenic related genes; D is Western blot detection of the influence of 2,2':5',2"-terthiophene-5-formaldehyde on the level of adipogenic related proteins in BMSCs cells.

[0019] Figure 2 To implement the weight change of the Sham and OVX group mice in example 2 two weeks after the operation.

[0020] Figure 3 To implement the 2,2':5',2"-terthiophene-5-formaldehyde in improving bone density and bone microstructure of osteoporosis mice in example 3;

[0021] In the figure, A is a representative picture of micro-CT scanning of distal femoral cortical bone (the scale is 100 μm); B-E are statistical results of bone volume fraction (BV / TV, %), cortical bone thickness (Ct.Th), bone surface area and bone volume ratio (BS / BV) and bone mineral density (BMD), which are used for quantitative analysis of bone tissue microstructure.

[0022] Figure 4 To implement the 2,2':5',2"-terthiophene-5-formaldehyde in improving serum osteocalcin, osteoprotegerin and alkaline phosphatase content of mice in example 3;

[0023] In the figure, A is a representative picture of Masson staining and H&E staining of mouse femur (the scale is 500 μm); B-D are detection results of serum osteocalcin, osteoprotegerin and alkaline phosphatase content of mice.

[0024] Figure 5 To improve the abnormal osteogenic and adipogenic differentiation of BMSCs of OVX mice by 2,2':5',2"-terthiophene-5-formaldehyde in Example 4;

[0025] In the figure, A is a representative picture of ALP staining and oil red staining; B-G is the effect of 2,2':5',2"-terthiophene-5-formaldehyde on the expression of osteogenic and adipogenic related genes of BMSCs cells detected by qPCR; H is the effect of 2,2':5',2"-terthiophene-5-formaldehyde on the level of adipogenic related protein in BMSCs cells detected by Western blot.

[0026] Figure 6 To repair the atrophy of uterus of osteoporotic mice by 2,2':5',2"-terthiophene-5-formaldehyde in Example 5;

[0027] In the figure, A is a representative picture of the uterus of mice after 8 weeks; B is the ratio of the wet weight of uterus to the body weight of mice; C and D are the effect of 2,2':5',2"-terthiophene-5-formaldehyde on the expression of estrogen receptor mediated target genes of mice detected by qPCR; E is the effect of 2,2':5',2"-terthiophene-5-formaldehyde on the proliferation of endometrial cells detected by immunohistochemistry; F-G are the quantitative analysis of BrdU positive cells (brown) in glandular epithelium and luminal epithelium.

[0028] Figure 7 To evaluate the safety of 2,2':5',2"-terthiophene-5-formaldehyde on the main organs of mice at the used dose;

[0029] In the figure, A is the H&E staining result of the tissue structure of heart, liver, spleen, lung and kidney of mice in each experimental group; B-F are the indexes of each organ. DETAILED DESCRIPTION

[0030] In order to better understand the essence of the present application, the content of the present application will be further described below in combination with examples, but it cannot be regarded as a limitation to the present application.

[0031] The 2,2':5',2"-terthiophene-5-formaldehyde (ecliptal, EC) described in the present application is commercially available from Aladdin Reagent (Shanghai) Co., Ltd. (CAS: 7342-41-8), and its structure is shown in the following formula:

[0032]

[0033] Example 1, 2,2':5',2"-terthiophene-5-formaldehyde promotes the osteogenic differentiation of BMSCs

[0034] BMSCs have the potential of multi-directional differentiation, and can differentiate into osteoblasts, adipocytes, chondrocytes and other cells under appropriate microenvironment and signal stimulation. Therefore, promoting osteogenic differentiation is crucial for bone metabolism and bone health.

[0035] In this example, 3-4 week old male C57BL / 6J mice (purchased from Beijing Vital River Laboratory) were used as materials to obtain a large number of BMSCs with proliferation and differentiation capacity from femur, and the effect of 2,2':5',2"-terthienyl-5-formaldehyde on promoting osteogenic differentiation of BMSCs (including osteogenic induction and adipogenic induction) was determined.

[0036] The specific steps of osteogenic induction were as follows: ①, after BMSCs were cultured to 70-80% confluence, the osteogenic induction medium (10% FBS, 100 nM dexamethasone, 10 mM β-glycerophosphate, 50 μg / mL ascorbic acid) was used to replace the growth medium for induction, and 2,2':5',2"-terthienyl-5-formaldehyde (EC) was added at a final concentration of 1, 5 and 10 μM, respectively; at the same time, BMSCs with the same amount of DMSO added were used as a control; ②, the BMSCs in each group were continuously cultured in the induction medium, and the medium was replaced every 3 days, and after 7 days and 21 days of culture, alkaline phosphatase (ALP) and alizarin red S (ARS) staining were performed, respectively, to observe the osteogenic differentiation, and the results are shown in Figure 1 A; and the expression changes of osteogenic related genes, including collagen type I (Col1a1), bone morphogenetic protein 4 (Bmp4), alkaline phosphatase (Alp) and nuclear receptor related transcription factor 2 (Runx2), were analyzed by real-time fluorescence quantitative PCR (qPCR), and the results are shown in Figure 1 B.

[0037] The specific steps of adipogenic induction were as follows: ①, after BMSCs were cultured to contact inhibition, the adipogenic induction medium (containing 10% FBS, 0.5 mmol / L IBMX, 1 μmol / L dexamethasone and 850 nmol / L insulin) was used for induction, and 2,2':5',2"-terthienyl-5-formaldehyde (EC) was added at a final concentration of 1, 5 and 10 μM, respectively; at the same time, BMSCs with the same amount of DMSO added were used as a control; after 48 hours of intervention, the maintenance differentiation medium (containing 10% FBS and 850 nmol / L insulin) was used to replace; ②, the BMSCs in each group were continuously cultured in the maintenance differentiation medium, and the medium was replaced every 2 days, and after 6 days of culture, Oil Red O staining was used to observe the formation of lipid droplets, and the results are shown in Figure 1A, and the mRNA expression levels of lipogenesis-related genes such as fatty acid binding protein 4 (Fabp4), lipoprotein lipase (Lpl), and peroxisome proliferator-activated receptor gamma (Pparγ) were detected by qPCR, and the expression levels of lipogenesis-related proteins including fatty acid synthase (FASN), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element binding protein 1c (SREBP-1c) were analyzed by Western blot, and the results are shown in Figure 1 C and D.

[0038] The primers used for adipogenic induction and osteogenic induction qPCR are shown in Table 1.

[0039] Table 1

[0040]

[0041]

[0042] From Figure 1 It can be seen that 2,2':5',2"-terthienyl-5-carboxaldehyde at 10 μM significantly promotes the osteogenic differentiation of BMSCs. Among them, ALP staining shows that the intracellular purple precipitate in the 2,2':5',2"-terthienyl-5-carboxaldehyde treatment group is significantly deepened, suggesting that it promotes early osteogenic differentiation. Alizarin red S staining further confirms that 2,2':5',2"-terthienyl-5-carboxaldehyde intervention significantly increases the number, staining range and intensity of calcium salt nodules, indicating that it enhances the mineralization ability of the late osteogenic differentiation stage. The qPCR analysis results show that 2,2':5',2"-terthienyl-5-carboxaldehyde significantly up-regulates the transcription level of the osteogenic differentiation inducer Bmp4, and activates the expression of the downstream core transcription factor Runx2 and its effector genes Col1a1 and Alp; at the same time, ecliptal inhibits the adipogenic differentiation of BMSCs in a dose-dependent manner. Oil red O staining shows that with the increase of the intervention concentration, the accumulation of intracellular lipid droplets gradually decreases; at the same time, the mRNA levels of the key transcription factor Pparγ and the downstream effector genes Fabp4 and Lpl of adipogenesis are significantly down-regulated. Further Western blot results show that the expression levels of the key regulatory proteins PPARγ, SREBP-1c and the downstream key enzyme FASN of fat synthesis are significantly reduced.

[0043] Example 2, Construction of Osteoporosis Mouse Model by Ovariectomy (OVX)

[0044] Mouse ovariectomy (ovariectomy, OVX for short) is a relatively mature animal model. By bilateral ovariectomy, an animal model simulating estrogen deficiency-induced osteoporosis can be successfully established, and the construction method is as follows.

[0045] Six-week-old female C57BL / 6 mice (purchased from Vital River Laboratories, Beijing) were acclimatized for two weeks and then randomly divided into four groups of six mice each: a sham surgery group, an OVX group, an OVX+5mg / kg group (OVX+5EC), and an OVX+10mg / kg group (OVX+10EC). The mice were weighed, injected intraperitoneally with an anesthetic (400μL / 20g mouse body weight), and fixed on a surgical board. Hair was removed from the back. A 0.5–1cm incision was made along the midline of the back using surgical scissors, separating the skin and muscle. The adipose tissue was gently grasped with forceps and pulled out of the incision. At this point, the ovary appeared cauliflower-like. The adipose tissue around the ovary was dissected, and the ovary was completely removed with surgical scissors. The adipose tissue was pushed back into the abdominal cavity (OVX). In the Sham group, a portion of surrounding adipose tissue, roughly the same volume as the ovary, was removed. The tunica albuginea and muscle layer were sutured together first, followed by suturing the skin. Ovarian removal induced estrogen deficiency in the mice, leading to weight gain. Therefore, comparing the weight changes between the Sham and OVX groups allowed for observation and determination of the success of osteoporosis model establishment. The results are as follows... Figure 2 As shown.

[0046] Depend on Figure 2 It can be seen that the body weight of OVX mice was significantly higher than that of the Sham group two weeks after surgery, which can preliminarily indicate that the osteoporosis mouse model was successfully established and can be used for subsequent experiments.

[0047] Example 3: 2,2′:5′,2″-trithiophene-5-formaldehyde treatment reduced bone loss caused by OVX and improved bone metabolism.

[0048] Bone mineral density and bone microstructure reflect the basic condition of bone. Estrogen is an important hormone in the body, playing a crucial role in regulating bone metabolism and maintaining homeostasis. Low estrogen levels are considered a major cause of postmenopausal osteoporosis. Therefore, by measuring the above indicators, the effect of 2,2′:5′,2″-trithiophene-5-carboxaldehyde on bone metabolism in OVX-induced bone loss can be determined.

[0049] This embodiment uses the osteoporosis mouse model constructed in Example 2 as material to determine the effects of 2,2′:5′,2″--trithiophene-5-carboxaldehyde on bone mineral density and bone microstructure in osteoporosis mice.

[0050] Specific determination method: four groups of osteoporosis mice constructed in Example 2 were given 0.3% CMC-Na, 0.3% CMC-Na, 5 mg / kg 2,2':5',2"-terthienyl-5-formaldehyde, 10 mg / kg 2,2':5',2"-terthienyl-5-formaldehyde, 3 times a week, for 8 weeks. After 8 weeks, the femur was taken and collected for micro-CT scanning, H&E staining and Masson staining to evaluate the effect of 2,2':5',2"-terthienyl-5-formaldehyde on bone loss repair in osteoporosis mice. The levels of Osteoprotegerin (OPG) and Osteocalcin (OC) were detected by serum ELISA experiment, and the content of serum ALP was detected by biochemical experiment to evaluate the effect of 2,2':5',2"-terthienyl-5-formaldehyde on bone metabolism, and the results are shown in Figure 3 、 Figure 4

[0051] Figure 3 、 4 It can be seen from Figure 3 , Figure 4 A) that 2,2':5',2"-terthienyl-5-formaldehyde effectively reversed the changes of bone mineral density, bone microstructure damage, trabecular thinning and cortical bone thickness reduction caused by osteoporosis Figure 4 B-D). And 22,2':5',2"-terthienyl-5-formaldehyde improves bone strength and overall bone health by regulating bone metabolism, promoting osteogenesis and inhibiting bone resorption, thus showing its potential for treating osteoporosis.

[0052] Example 4, 2,2':5',2"-terthienyl-5-formaldehyde restores the osteogenic differentiation ability of endogenous BMSCs in osteoporosis mice

[0053] In OVX mice, due to the lack of estrogen, the hormone level and cytokine imbalance in the microenvironment, the osteogenic differentiation ability of BMSCs is significantly impaired. This damage is manifested as the decrease of the proliferation and osteogenic differentiation ability of BMSCs, thus exacerbating the occurrence of osteoporosis.

[0054] This example takes the osteoporosis mouse model constructed in Example 2 as the material, a large number of BMSCs with proliferation and differentiation ability are obtained from the femur, and the effect of 2,2':5',2"-terthienyl-5-formaldehyde on promoting the osteogenic differentiation of BMSCs is determined according to the method described in Example 1.

[0055] The same as Example 1, the specific method includes osteogenic induction, adipogenic induction, ALP staining, qPCR and Western blot detection of the expression changes of osteogenic and adipogenic related genes and proteins, etc. The results are shown in​​Figure 5 As shown.

[0056] Depend on Figure 5 It was found that in the osteogenic induction experiment, compared with the Sham group, the ALP activity of BMSCs in the OVX group was significantly decreased, the staining color was lighter and the positive area was smaller, indicating impaired osteogenic differentiation. After intervention with 2,2′:5′,2″-trithiophene-5-carboxaldehyde, ALP activity was enhanced, and the number and extent of positive deposits increased. Figure 5 A). qPCR showed upregulated expression of osteogenic genes Runx2, Alp, and Col1a1. Figure 5 B~D). In the adipogenic induction experiment, lipid droplet accumulation in BMSCs from OVX mice was significantly increased; lipid deposition was reduced after intervention with 2,2′:5′,2″-trithiophene-5-carboxaldehyde, with the high-dose group showing the most significant effect. Molecular detection showed that 2,2′:5′,2″-trithiophene-5-carboxaldehyde dose-dependently downregulated the mRNA expression of the adipogenic transcription factor Pparγ and its downstream genes Fabp4 and Lpl, while inhibiting the protein levels of PPARγ, SREBP-1c, and FASN ( Figure 5 E~H).

[0057] The above results indicate that 2,2′:5′,2″--trithiophene-5-carboxaldehyde can effectively improve the abnormal osteogenic differentiation of BMSCs in OVX mice, effectively alleviate the pathological fattyization of bone marrow stromal cells, and improve the bone microenvironment in osteoporotic mice.

[0058] Example 5: 2,2′:5′,2″-trithiophene-5-formaldehyde effectively repaired uterine atrophy in osteoporotic mice.

[0059] In osteoporosis (OVX) model mice, uterine atrophy is typically observed after ovariectomy due to a significant drop in estrogen levels. This is specifically manifested as decreased uterine weight, thinning of the endometrium, reduction in the number of glands, and degeneration of uterine structure.

[0060] This embodiment uses the osteoporosis mouse model constructed in Example 2 as material to determine the effect of 2,2′:5′,2″--trithiophene-5-carboxaldehyde on the uterus of osteoporosis mice.

[0061] The test method was as follows: ① After intervention with 2,2′:5′,2″--trithiophene-5-formaldehyde for 8 weeks as described in Example 2, the morphology of the mouse uterus was observed and the wet weight ratio of the uterus was recorded. The results are as follows: Figure 6As shown in A-B; ② Two weeks after oophorectomy, patients were administered 0.3% CMC-Na, 5 mg / kg 2,2′:5′,2″-trithiophene-5-carboxaldehyde, and 10 mg / kg 2,2′:5′,2″-trithiophene-5-carboxaldehyde by gavage. Six hours after treatment, RNA was extracted from uterine tissue, and the expression levels of estrogen receptor-mediated target genes, including the early proto-oncogenes FOS (c-Fos) and vascular endothelial growth factor (Vegf), were detected by qPCR. The primers used for qPCR are shown in Table 2. The results are as follows. Figure 6 As shown in C–D; ③ After 3 days of gavage treatment, bromodeoxyuridine (BrdU) (30 mg / kg body weight) was injected. Sixteen hours later, the mice were dissected, and the uterus was removed for paraffin sectioning, staining, and the percentage of BrdU-positive epithelial cells in the sections was calculated. The results are as follows: Figure 6 As shown in EG;

[0062] Table 2

[0063]

[0064] Depend on Figure 6 It was found that gavage administration of 2,2′:5′,2″-trithiophene-5-formaldehyde significantly improved the morphological changes of the mouse uterus, manifested as reduced uterine shrinkage and increased wet weight in mice. Figure 6 (A~B). Furthermore, 2,2′:5′,2″--trithiophene-5-carboxaldehyde significantly enhanced estrogen receptor-mediated gene (c-Fos, Vegf), indicating that it improves uterine atrophy and dysfunction by activating the estrogen receptor pathway. Figure 6 (C~D). Simultaneously, the proliferation of endometrial epithelial cells significantly increased in the 2,2′:5′,2″--trithiophene-5-formaldehyde treatment group, promoting uterine tissue repair. Figure 6 E~G).

[0065] Example 6: 2,2′:5′,2″-trithiophene-5-carboxaldehyde showed no significant toxic side effects in mice.

[0066] This embodiment uses the osteoporosis mouse model constructed in Example 2 as material to determine whether 2,2′:5′,2″-trithiophene-5-carboxaldehyde has obvious toxic side effects.

[0067] The assay method was as follows: After 8 weeks of intervention with 2,2′:5′,2″-trithiophene-5-formaldehyde as described in Example 2, the major organs of mice in each group were collected for H&E staining and organ index assessment. The results are as follows: Figure 7 As shown.

[0068] Depend on Figure 7 It was found that the heart, liver, spleen, lungs, and kidneys of mice in all groups maintained normal tissue structure, with no obvious pathological damage observed. Figure 7A). Meanwhile, as a key indicator for evaluating drug safety and potential toxicity, the organ index test results showed that there was no significant difference in the heart, liver, spleen, lung and kidney index of the four groups of mice Figure 7 B~F). In summary, within the dose and intervention period used in the present application, 2,2':5',2"-terthiophene-5-formaldehyde did not cause obvious organ toxicity, further verifying its good biological safety.

[0069] In summary, the present application first discovered the application of 2,2':5',2"-terthiophene-5-formaldehyde in the preparation of drugs for treating osteoporosis, especially in the preparation of drugs for treating postmenopausal osteoporosis. At the cellular level, 2,2':5',2"-terthiophene-5-formaldehyde showed significant osteogenic and adipogenic inhibitory activity. At the animal level, 2,2':5',2"-terthiophene-5-formaldehyde can significantly improve the bone loss of OVX mice with osteoporosis, and at the same time, inhibit bone resorption and promote bone formation. This shows that 2,2':5',2"-terthiophene-5-formaldehyde has good effects on treating osteoporosis, providing new anti-osteoporosis drugs for clinical use, and has a wide application prospect and high application value.

Claims

The application of 1.2,2':5',2”-trithiophene-5-carboxaldehyde in the preparation of drugs for treating osteoporosis, characterized in that, The structure of the 2,2':5',2”-trithiophene-5-formaldehyde is shown in the following formula (1); 2. The application as described in claim 1, characterized in that, The osteoporosis mentioned refers to postmenopausal osteoporosis.

3. The application as described in claim 1, characterized in that, The drug comprises a pharmaceutical composition consisting of 2,2':5',2”-trithiophene-5-carboxaldehyde and excipients.

4. The application as described in claim 3, characterized in that, The excipients include any one or a combination of at least two of the following: diluents, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, surfactants, coating materials, antioxidants, antibacterial agents, or buffers.

5. The application as described in claim 1, characterized in that, The dosage form of the drug includes any one of the following: suspension, granules, capsules, powders, tablets, emulsions, solutions, pellets, injections, suppositories, enemas, aerosols, patches, or drops.

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