A traditional Chinese medicine composition for treating osteoporosis and a preparation method thereof

Abstract

The application belongs to the field of traditional Chinese medicines, and discloses a traditional Chinese medicine composition for treating osteoporosis and a preparation method thereof. Raw materials of the traditional Chinese medicine composition include prepared rhizome of rehmannia, ebur, angelica sinensis, salvia miltiorrhiza, astragalus root, andpsoralea, etc. The composition can bidirectionally regulate bone metabolism, inhibit RANKL expression, increase OPG level, up-regulate osteogenic differentiation markers ALP and Runx2, reduce bone absorption marker CTX-1, significantly increase femoral bone density and bone biomechanical strength, and is suitable for postmenopausal, senile, and sarcopenia combined osteoporosis.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine drug composition preparation technology, specifically relating to a traditional Chinese medicine formula granule composition for treating osteoporosis and its preparation method. It can be applied to the preparation of clinical oral drugs for postmenopausal osteoporosis, senile osteoporosis, and sarcopenia combined with osteoporosis, and belongs to the research and development of drugs for the treatment of traditional Chinese medicine orthopedics and geriatric diseases. Background Technology

[0002] Osteoporosis (OP) is a systemic skeletal disease characterized by decreased bone mass, deterioration of bone microstructure, and increased bone fragility. With the accelerating aging of the global population, osteoporosis has become a major public health problem that seriously threatens the health of middle-aged and elderly people.

[0003] Currently, Western medicines for treating osteoporosis in clinical practice are mainly divided into three categories: drugs that inhibit osteoclast activity (such as estrogen, calcitonin, bisphosphonates, etc.), drugs that promote osteoblast formation (such as fluoride, parathyroid hormone, etc.), and drugs that promote ossification (such as calcium supplements and vitamin D and its derivatives, etc.). However, these Western medicine treatment regimens generally suffer from poor safety and significant adverse reactions with long-term use. For example, estrogen replacement therapy may increase the risk of breast cancer, long-term use of bisphosphonates can lead to osteonecrosis of the mandible and atypical femoral fractures, and fluoride can increase bone fragility; some drugs are also expensive, placing a heavy financial burden on patients. In addition, existing Western medicines mostly focus on single-target regulation—either only inhibiting bone resorption or only promoting bone formation—making it difficult to achieve comprehensive regulation of bone metabolism balance. Although they can increase bone density in the short term, bone loss rebounds rapidly after discontinuation, making it impossible to maintain bone metabolism balance in the long term, resulting in poor patient compliance.

[0004] Traditional Chinese medicine has a long history and unique advantages in the prevention and treatment of osteoporosis. In recent years, various Chinese herbal medicines used to treat osteoporosis have been reported. Traditional Chinese medicine (TCM) compositions have advantages such as multi-target effects, low toxicity, and long-term use. However, existing TCM preparations have several drawbacks: First, traditional decoctions are cumbersome to prepare, inconvenient to carry, and have significant variations in the quality of the medicinal materials, resulting in noticeable fluctuations in the content of active ingredients. Ordinary TCM compound granules often involve a single decoction of all medicinal materials, which can easily lead to antagonism between the polar active ingredients of different herbs, resulting in low extraction and retention rates of effective components and insufficient bioavailability. Second, existing TCM compound formulations often target only one specific area, focusing primarily on tonifying the kidneys and strengthening bones, lacking synergistic effects such as promoting blood circulation, strengthening the spleen, and replenishing essence. They may only promote bone formation or inhibit bone resorption, making it difficult to regulate bone metabolism in both directions. Third, most existing preparations lack standardized medication guidelines and fail to avoid the interference of high-oxalate and high-salt diets on calcium absorption and bone metabolism, resulting in poor stability of clinical efficacy. Fourth, existing anti-osteoporosis TCM granules lack standardized single-herb compounding processes, and there are no unified specifications for the extraction, drying, and granulation parameters of each medicinal material, leading to significant quality differences between batches and making it difficult to achieve standardized industrial production. Currently, there is a lack of specialized osteoporosis-preventing Chinese medicine granule preparations on the market that are formulated with standardized single-herb Chinese medicine granules, can bidirectionally regulate bone metabolism, have stable preparation processes, and are compatible with dietary intervention programs. There is a significant gap in clinical and industrial development.

[0005] Based on this, the present invention provides a traditional Chinese medicine formula granule composition for treating osteoporosis and its preparation method, in order to overcome the above-mentioned shortcomings of the prior art. Summary of the Invention

[0006] Addressing the shortcomings of existing Western medicines, such as significant side effects, inconvenience of traditional Chinese medicine decoctions, low extraction efficiency of conventional Chinese medicine granules, single target regulation in formulations, inconsistent quality standards, and lack of supporting medication guidance, this invention aims to solve the technical problems of unstable quality control, inconvenient administration, and single mechanism of action in existing Chinese medicine compositions for treating osteoporosis. This invention provides a Chinese medicine formula granule composition for treating osteoporosis and its preparation method, achieving the technical goals of standardized, decoction-free granule preparation, multi-target bidirectional regulation of bone metabolism, controllable preparation process, and stable clinical efficacy.

[0007] To achieve the above-mentioned objectives, the present invention adopts the following complete technical solution: In a first aspect, the present invention provides a traditional Chinese medicine formula granule composition for treating osteoporosis, which is made by mixing the following standardized single-herb traditional Chinese medicine formula granules in parts by weight: 10-20 parts of Rehmannia glutinosa granules, 5-12 parts of Eupolyphaga sinensis granules, 6-10 parts of Angelica sinensis granules, 10-18 parts of Salvia miltiorrhiza granules, 10-22 parts of Astragalus membranaceus granules, 10-16 parts of Psoralea corylifolia granules, 8-15 parts of Epimedium brevicornu granules, 9-15 parts of Cistanche deserticola granules, 3-10 parts of deer antler glue granules, 8-20 parts of Cuscuta chinensis granules, 6-16 parts of Paeonia lactiflora granules, and 6-12 parts of Ziziphus jujuba granules; each single-herb traditional Chinese medicine formula granule is an extract granule obtained by standardized separate extraction, concentration, drying and granulation of the corresponding medicinal material; this composition can bidirectionally regulate bone metabolism by inhibiting RANKL expression and increasing OPG. It can upregulate osteogenic differentiation markers ALP and Runx2, reduce bone resorption marker CTX-1, and significantly improve femoral bone mineral density and bone biomechanical strength. It is suitable for postmenopausal, elderly, and sarcopenia combined with osteoporosis.

[0008] Preferably, the optimal weight ratio of each single-herb formula granules is as follows: 10 parts Rehmannia glutinosa granules, 5 parts Eupolyphaga sinensis granules, 10 parts Salvia miltiorrhiza granules, 10 parts Astragalus membranaceus granules, 15 parts Psoralea corylifolia granules, 15 parts Epimedium brevicornu granules, 15 parts Cistanche deserticola granules, 5 parts Cervi cornu gelatin granules, 20 parts Cuscuta chinensis granules, 10 parts Paeonia lactiflora granules, and 10 parts Ziziphus jujuba granules.

[0009] Further preferred, the composition also includes pharmaceutically acceptable granule excipients selected from one or more of dextrin, lactose, microcrystalline cellulose, and steviol glycosides, with the total weight of the excipients being 10% to 25% of the total weight of the Chinese medicine formula granules; the optimal excipient is a 2:1 mixture of dextrin and lactose, accounting for 18% of the total weight of the Chinese medicine granules, which improves the flowability, solubility, and taste of the granules without any additional interference with the efficacy.

[0010] Secondly, this invention provides a standardized preparation method for the above-mentioned traditional Chinese medicine formula granule composition, comprising four complete steps: S1 raw material extraction, S2 vacuum concentration, S3 drying and granulation, and S4 mixing and packaging; wherein S1 involves decocting and extracting 2-3 times, adding 6-12 times the total weight of purified water each time, with each decoction lasting 1-3 hours; S2 involves vacuum concentration at a temperature of 50-80℃ and a vacuum degree of -0.06 to -0.10 MPa, concentrating to a relative density of 1.10-1.30 extract; S3 involves spray drying or vacuum drying, with the inlet air temperature at 160-200℃ and the outlet air temperature at 80-100℃, the dried extract powder mixed with excipients, wet granulation, and low-temperature drying to obtain single-herb standard formula granules; finally, the granules of each single herb are mixed according to the formula to obtain the finished composition.

[0011] Thirdly, this invention provides the application of the traditional Chinese medicine formula granule composition in the preparation of oral anti-osteoporosis drugs. The drug is a granule taken with warm water, divided into two doses per day, with a single dose of 12-18g of raw herb equivalent. During the administration period, standardized dietary guidance is provided: daily salt intake <6g, reducing the intake of high-oxalate foods such as spinach, amaranth, and strong tea to avoid oxalate chelating calcium ions and high salt intake accelerating urinary calcium loss, thereby further improving the effectiveness of the drug in increasing bone density.

[0012] Compared with the prior art, this invention has four core beneficial effects: (1) The formula is precisely formulated and can regulate bone metabolism in a bidirectional manner by multiple targets. This formula uses Rehmannia glutinosa, Psoralea corylifolia, Epimedium brevicornu, Cistanche deserticola, deer antler glue, and Cuscuta chinensis to tonify the kidneys, replenish essence and strengthen bones; Astragalus membranaceus and jujube to invigorate the spleen and replenish qi, and promote calcium absorption; Eupolyphaga sinensis, Angelica sinensis and Salvia miltiorrhiza to invigorate blood and unblock collaterals, and improve bone microcirculation; Paeonia lactiflora to nourish blood and soften tendons, and take into account the accompanying symptoms of sarcopenia; it can simultaneously inhibit bone resorption, promote osteogenic differentiation, downregulate the RANKL / OPG ratio, and increase the expression of ALP and Runx2, overcoming the shortcomings of existing single formulas that only regulate bone metabolism in a single way.

[0013] (2) The standardized single-herb formula granule compounding process is adopted, and the quality is controllable. Each medicinal material is extracted and dried independently to avoid the interaction of active ingredients when multiple medicinal materials are decocted together. The extraction parameters of each herb granule are uniform, and the composition is stable between batches. Each single herb granule is prepared by standardized extraction, drying and granulation process, and the content of effective ingredients is stable and controllable, with good consistency between batches, overcoming the defects of unstable quality of traditional Chinese medicine decoctions and ordinary granules.

[0014] (3) The composition of the present invention is in granule form. The granules have good solubility and can be taken with warm water without decoction. Patients only need to take it with warm water. It is convenient to carry at home and easy to take, solving the problems of cumbersome operation and unstable quality of traditional decoction. Patient compliance is high. At the same time, the ratio of each single granule can be flexibly adjusted according to clinical needs to achieve individualization.

[0015] (4) Optimized preparation process parameters result in high retention rate of active ingredients. By limiting the number of decoctions, the amount of water added, the concentration vacuum degree and the drying temperature, the extraction is gentle and reduces the high-temperature decomposition of active ingredients such as flavonoids and saponins. No organic solvents are required, making the production green and safe, and suitable for large-scale industrial production.

[0016] (4) The first-ever combined drug and dietary intervention program significantly improved clinical efficacy. By restricting high-salt and high-oxalate diets to eliminate factors that interfere with calcium absorption, animal experiments and clinical observations have confirmed that the accompanying dietary guidance can significantly improve bone density, reduce osteoporosis pain scores and long-term fracture incidence, while reducing common gastrointestinal adverse reactions of Western medicines and greatly improving treatment compliance.

[0017] In summary, the traditional Chinese medicine formula granule composition provided by this invention follows the pathogenesis of tonifying the kidney, strengthening the spleen, and promoting blood circulation in traditional Chinese medicine. It is designed with modern molecular mechanisms of bone metabolism in mind. The formulation is standardized, convenient to take, stable in quality, and highly safe. It is equipped with exclusive preparation process and clinical dietary guidance, providing a new, highly effective, and long-term-use, decoction-free traditional Chinese medicine preparation for various types of osteoporosis. It has extremely high clinical promotion and industrialization value. Attached Figure Description

[0018] Figure 1 is a bar chart comparing the body weight, bone mineral content, and body fat content of rats in each group in the experiment of this invention; where A is the comparison of the total weight of rats in each group, B is the comparison of the whole body bone mineral content (BMC) of rats in each group, and C is the comparison of the body fat (FAT) content of rats in each group.

[0019] Figure 2 shows a comparison of whole-body DXA scan imaging and skeletal muscle mass index of rats in the experiment of this invention; where A is the whole-body dual-energy X-ray scan localization map of rats, B is the skeletal muscle mass index (SMI) bar chart of each group, and C is the skeletal muscle mass index (RSMI) bar chart of the limbs.

[0020] Figure 3 shows the bar charts of whole-body and femoral bone mineral density (BMD) measurements of rats in each group of the present invention; where A represents the comparison of whole-body bone mineral density and B represents the comparison of femoral bone mineral density.

[0021] Figure 4 shows a comparison of microscopic parameters of trabecular bone in the femur of rats tested in this invention using microCT; including six indicators: bone volume fraction (BV / TV), bone surface density (BS / BV), BS / TV, trabecular thickness [Tb.Th] (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N).

[0022] Figure 4 Comparison of microscopic parameters of trabecular bone in rat femur using microCT.

[0023] Figure 5 is a bar chart showing the detection of serum bone metabolism markers in rats in this invention; where A is the osteogenic marker AKP, B is the bone resorption marker β-CTx, C is IGF-1, and D is serum estrogen E2. Detailed Implementation The technical solution of the present invention will be fully and clearly described below with reference to preferred embodiments. The following embodiments are only preferred implementation schemes of the present invention, and not all embodiments. All equivalent substitutions and fine-tuning ratio schemes obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the protection scope of the present invention. Example 1:

[0024] 1.1 Raw material ratio (parts by weight) for single-herb Chinese medicine granule formula 10 parts Rehmannia glutinosa granules, 5 parts Eupolyphaga sinensis granules, 10 parts Salvia miltiorrhiza granules, 10 parts Astragalus membranaceus granules, 15 parts Psoralea corylifolia granules, 15 parts Epimedium brevicornu granules, 15 parts Cistanche deserticola granules, 5 parts Cervi cornu gelatin granules, 20 parts Cuscuta chinensis granules, 10 parts Paeonia lactiflora granules, and 10 parts Ziziphus jujuba granules.

[0025] Excipients: Dextrin and lactose are compounded in a 2:1 ratio, and the total weight of the excipients is 18% of the total weight of the above-mentioned Chinese medicine granules.

[0026] 1.2 Standardized preparation of single-herb formulation granules (S1~S3, general process for single-herb medicinal materials) S1 Extraction: Take the corresponding Chinese medicinal herb slices, add 10 times the total weight of the herb in purified water, soak for 1.5 hours, bring to a boil over high heat, then simmer over low heat for 2 hours, filter and collect the first decoction; add 8 times the amount of purified water to the dregs, simmer for 1.5 hours, collect the second decoction, and combine the two filtrates.

[0027] S2 Vacuum Concentration: The combined filtrate is transferred to a vacuum concentration tank at a temperature of 65℃ and a vacuum degree of -0.08MPa to concentrate the herbal extract to a relative density of 1.20 at 60℃.

[0028] S3 Drying and Granulation: The extract is spray-dried at an inlet air temperature of 180℃ and an outlet air temperature of 90℃ to obtain a dry extract powder; the special excipients for this medicinal material (dextrin: lactose = 2:1) are added to the dry extract powder, mixed well, wet-granulated with 75% ethanol, dried at a low temperature of 60℃, and granulated to obtain standardized single-herb Chinese medicine formula granules, which are sealed and stored separately for later use.

[0029] 1.3 Finished product compounding (S4) Weigh all the single-herb formula granules according to 1.1 parts by weight, put them into a three-dimensional mixer and mix for 30 minutes, then package them into 5g granules per bag (each bag contains 15g of raw herb equivalent dose) to obtain the finished Chinese herbal formula granule composition of the present invention.

[0030] 1.4 Usage and accompanying dietary guidance For oral administration, dissolve one sachet in warm water and take twice a day. Throughout the course of treatment, patients should be advised to consume less than 6g of salt per day and to avoid or limit high-oxalate foods such as spinach, amaranth, and strong tea.

[0031] 1.5 Quality Inspection Finished product testing: Total flavonoid content ≥7.2%, total saponin content ≥5.8%; completely dissolves in warm water within 3 minutes; accelerated stability test: after 6 months of storage at 40℃ / RH75%, the decrease in effective components is <4%.

[0032] 1.6 Pharmacodynamic validation (OVX castrated rat model) Eight-week-old female SD rats were selected, and a model of osteoporosis was established by bilateral ovariectomy. The rats were divided into a sham-operated group, a model group, a positive control group of Xianling Gubao, a low-dose group of this embodiment, and a high-dose group of this embodiment. The rats were administered the treatment by gavage for 12 consecutive weeks.

[0033] Results: In this embodiment, the femoral BMD, trabecular bone volume ratio (BV / TV), and total nitric acid (Tb.N) in the high-dose group were significantly higher than those in the model group; serum AKP, IGF-1, and E2 were significantly increased, while β-CTx was significantly decreased; skeletal muscle SMI and RSMI significantly improved, and gastrocnemius muscle fiber atrophy was significantly reduced; the RANKL / OPG ratio was significantly downregulated, and ALP and Runx2 protein expression was significantly upregulated, showing better effects than the positive control drug. Example 2:

[0034] 2.1 Raw material weight parts 10 parts Rehmannia glutinosa granules, 5 parts Eupolyphaga sinensis granules, 6 parts Angelica sinensis granules, 10 parts Salvia miltiorrhiza granules, 10 parts Astragalus membranaceus granules, 10 parts Psoralea corylifolia granules, 8 parts Epimedium brevicornu granules, 9 parts Cistanche deserticola granules, 3 parts Cervi cornu gelatin granules, 8 parts Cuscuta chinensis granules, 6 parts Paeonia lactiflora granules, and 6 parts Ziziphus jujuba granules.

[0035] Excipients: Dextrin and lactose in a 2:1 ratio, accounting for 10% of the total weight of the Chinese medicine granules.

[0036] 2.2 Preparation process The extraction, concentration, drying, and granulation parameters for the single-herb granules are the same as in Example 1; after mixing and packaging, each bag contains 5g, and a single dose of raw herb is equivalent to 12g, to be taken twice a day.

[0037] 2.3 Brief Description of Effects It can significantly improve mild osteoporosis in the elderly, with a bone density increase slightly lower than in Example 1, and is suitable for long-term conditioning in people with mild osteoporosis. Example 3:

[0038] 3.1 Raw material weight parts 20 parts of Rehmannia glutinosa granules, 12 parts of Eupolyphaga sinensis granules, 10 parts of Angelica sinensis granules, 18 parts of Salvia miltiorrhiza granules, 22 parts of Astragalus membranaceus granules, 16 parts of Psoralea corylifolia granules, 15 parts of Epimedium brevicornu granules, 15 parts of Cistanche deserticola granules, 10 parts of deer antler glue, 20 parts of Cuscuta chinensis granules, 16 parts of Paeonia lactiflora granules, and 12 parts of Ziziphus jujuba granules.

[0039] Excipients: Dextrin and lactose in a 2:1 ratio, accounting for 25% of the total weight of the Chinese medicine granules.

[0040] 3.2 Preparation and Use The preparation process is the same as in Example 1; each bag contains 5g, and a single dose of raw drug is equivalent to 18g, taken twice a day; suitable for patients with severe postmenopausal osteoporosis and sarcopenia.

[0041] 3.3 Test Results The total flavonoid and total saponin content is higher than that in Example 1, the bidirectional regulatory effect on bone metabolism is stronger, and the effect on improving bone pain and muscle weakness is outstanding. Example 4:

[0042] The formulation of the granules is exactly the same as in Example 1, except that the excipients are replaced with microcrystalline cellulose and steviol glycosides (weight ratio 5:1), and the amount of excipients added is 15% of the total weight of the Chinese medicine granules. The preparation process remains the same, but the granules are sweeter and more suitable for patients who cannot tolerate bitterness. There is no significant difference in efficacy. Comparative Example 1 (Control Group without Blood-Activating Components)

[0043] Remove the granules of Eupolyphaga sinensis, Angelica sinensis, and Salvia miltiorrhiza, and keep the remaining proportions the same as in Example 1; the preparation process is the same.

[0044] Efficacy results: It can only slightly promote osteogenesis, cannot improve bone microcirculation, and has a significantly reduced inhibitory effect on CTX-1 bone resorption markers. The increase in bone density is 31.2% lower than that in Example 1, proving that blood-activating herbs are the key components for achieving bidirectional bone metabolism regulation. Comparative Example 2 (Clinical Group without Dietary Intervention)

[0045] Sixty patients with primary osteoporosis were selected to take the granules from Example 1 without any restrictions on salt or high-oxalate diets; another 60 patients received concurrent dietary guidance and were treated continuously for 12 months.

[0046] Results: The group receiving dietary guidance showed a 22.9% greater increase in lumbar spine and femoral neck bone mineral density compared to the group without intervention, a more significant decrease in VAS pain scores, and a 29.7% reduction in fracture incidence, confirming that dietary intervention can significantly amplify the clinical efficacy of this combination. Comparative Example 3 (Traditional Mixed Decoction Granules Control Group)

[0047] All medicinal materials were mixed and then extracted, concentrated, and granulated in one step using water decoction, with the same proportions as in Example 1. Tests showed that the retention rates of total flavonoids and total saponins were 18.5% lower than those of the single-herb extraction process, the dissolution rate was slower, and the composition fluctuated greatly between batches, thus verifying the quality advantages of the single-herb independent extraction and compounding process.

[0048] Figure 1 is a bar chart comparing the body weight, bone mineral content, and body fat content of rats in each group in the experiment of this invention; where A is the comparison of the total weight of rats in each group, B is the comparison of the whole body bone mineral content (BMC) of rats in each group, and C is the comparison of the body fat (FAT) content of rats in each group.

[0049] Figure 2 shows a comparison of whole-body DXA scan imaging and skeletal muscle mass index of rats in the experiment of this invention; where A is the whole-body dual-energy X-ray scan localization map of rats, B is the skeletal muscle mass index (SMI) bar chart of each group, and C is the skeletal muscle mass index (RSMI) bar chart of the limbs.

[0050] Figure 3 shows the bar charts of whole-body and femoral bone mineral density (BMD) measurements of rats in each group of the present invention; where A represents the comparison of whole-body bone mineral density and B represents the comparison of femoral bone mineral density.

[0051] Figure 4 shows a comparison of microscopic parameters of trabecular bone in the femur of rats tested in this invention using microCT; including six indicators: bone volume fraction (BV / TV), bone surface density (BS / BV), BS / TV, trabecular thickness [Tb.Th] (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N).

[0052] Figure 4 Comparison of microscopic parameters of trabecular bone in rat femur using microCT.

[0053] Figure 5 is a bar chart showing the detection of serum bone metabolism markers in rats in this invention; where A is the osteogenic marker AKP, B is the bone resorption marker β-CTx, C is IGF-1, and D is serum estrogen E2. Based on the combined results of all embodiments and comparative experiments, it can be seen that the formula weight range defined by this invention, the single-herb independent extraction and granulation process, the optimized excipient system, and the accompanying low-salt and low-oxalate dietary intervention can achieve multi-target bidirectional regulation of bone metabolism and improve the muscle atrophy symptoms associated with osteoporosis. The preparation is a non-decoction granule with a high degree of standardization, convenient administration, and good stability. Compared with existing Western medicines and traditional Chinese medicine preparations, it has significant technical advantages and clinical promotion value.

[0054] The above are merely preferred embodiments of the present invention. Any equivalent modifications, substitutions, and improvements made based on the formulation, preparation process, and protection concept of the present invention shall fall within the protection scope defined by the claims of the present invention.

Claims

1. A traditional Chinese medicine formula granule composition for treating osteoporosis, characterized in that, This formula is made by mixing the following single-herb Chinese medicine granules in the following weight proportions: 10-20 parts of Rehmannia glutinosa granules, 5-12 parts of Eupolyphaga sinensis granules, 6-10 parts of Angelica sinensis granules, 10-18 parts of Salvia miltiorrhiza granules, 10-22 parts of Astragalus membranaceus granules, 10-16 parts of Psoralea corylifolia granules, 8-15 parts of Epimedium brevicornu granules, 9-15 parts of Cistanche deserticola granules, 3-10 parts of deer antler glue granules, 8-20 parts of Cuscuta chinensis granules, 6-16 parts of Paeonia lactiflora granules, and 6-12 parts of Ziziphus jujuba granules. Each of the single herbal medicine formula granules corresponds to a single herbal extract granule that has undergone standardized extraction, drying and granulation; the composition is used to bidirectionally regulate bone metabolism, inhibit RANKL expression, increase OPG level, upregulate osteogenic differentiation markers ALP and Runx2, reduce bone resorption marker CTX-1, and increase femoral bone mineral density and bone biomechanical strength.

2. The traditional Chinese medicine formula granule composition for treating osteoporosis according to claim 1, characterized in that, The preferred weight ratio of each single-herb formula granule is as follows: 10 parts Rehmannia glutinosa granules, 5 parts Eupolyphaga sinensis granules, 10 parts Salvia miltiorrhiza granules, 10 parts Astragalus membranaceus granules, 15 parts Psoralea corylifolia granules, 15 parts Epimedium brevicornu granules, 15 parts Cistanche deserticola granules, 5 parts Cervi cornu gelatin granules, 20 parts Cuscuta chinensis granules, 10 parts Paeonia lactiflora granules, and 10 parts Ziziphus jujuba granules.

3. A traditional Chinese medicine formula granule composition for treating osteoporosis according to claim 1 or 2, characterized in that, It also contains pharmaceutically acceptable granular excipients, which are one or more of dextrin, lactose, microcrystalline cellulose, and steviol glycosides, and the total weight of the excipients is 10% to 25% of the total weight of the Chinese herbal medicine formula granules.

4. The traditional Chinese medicine formula granule composition for treating osteoporosis according to claim 3, characterized in that, The excipients are a compound of dextrin and lactose in a weight ratio of 2:1, and the compound excipients account for 18% of the total weight of the Chinese medicine formula granules.

5. A method for preparing a traditional Chinese medicine formula granule composition for treating osteoporosis according to any one of claims 1 to 4, characterized in that, Includes the following steps: S1. Extraction: Weigh each raw material according to the formula, mix them, add water and decoct to extract, and collect the extract; S2. Concentration: The extract is concentrated under reduced pressure to a paste with a relative density of 1.10-1.30; S3. Drying and granulation: Dry the extract, pulverize it into dry extract powder, add pharmaceutically acceptable excipients, mix well, granulate, and dry to obtain Chinese medicine formula granules.

6. The preparation method according to claim 5, characterized in that, The extraction process described in step S1 involves adding water and decocting 2-3 times, with each addition of water being 6-12 times the total weight of the raw materials, and each decoction lasting 1-3 hours.

7. The preparation method according to claim 5, characterized in that, The vacuum concentration in step S2 is carried out at a temperature of 50-80°C and a vacuum degree of -0.06MPa to -0.10MPa.

8. The preparation method according to claim 5, characterized in that, The drying process described in step S3 is either spray drying or vacuum drying. The inlet air temperature for spray drying is 160-200℃, and the outlet air temperature is 80-100℃.

9. The use of the traditional Chinese medicine formula granule composition according to any one of claims 1 to 4 in the preparation of a drug for treating osteoporosis, characterized in that, The osteoporosis mentioned includes postmenopausal osteoporosis, senile osteoporosis, and osteoporosis with sarcopenia; the drug is an oral granule preparation, taken twice daily with warm water, with a single dose of 12-18g of raw herb equivalent.

10. The application according to claim 9, characterized in that, During the administration of the medication, patients were simultaneously instructed to control their daily salt intake to <6g and reduce their intake of high-oxalate foods such as spinach, amaranth, and strong tea to improve the efficacy of the drug in increasing bone density.

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