Compound traditional Chinese medicine preparation for treating postmenopausal osteoporosis, osteoarthritis and / or premature ovarian insufficiency as well as preparation method and application of compound traditional Chinese medicine preparation

Abstract

The invention discloses a compound traditional Chinese medicine preparation for treating postmenopausal osteoporosis, osteoarthritis and / or premature ovarian insufficiency as well as a preparation method and application of the compound traditional Chinese medicine preparation, and belongs to the technical field of traditional Chinese medicines. The compound traditional Chinese medicine preparation is prepared from the following components: 10 to 30 g of radix rehmanniae preparata, 10 to 30 g of radix angelicae sinensis, 8 to 15 g of rhizoma chuanxiong, 8 to 15 g of radix paeoniae alba, 10 to 30 g of radix codonopsis, 8 to 15 g of rhizoma atractylodis macrocephalae, 10 to 30 g of poria cocos, 5 to 10 g of liquorice root, 10 to 30 g of radix dipsaci, 8 to 15 g of radix achyranthis bidentatae, 8 to 15 g of fructus chaenomelis lagenariae, the compound traditional Chinese medicine preparation provided by the invention realizes effective treatment on osteoporosis, osteoarthritis and early-onset ovarian insufficiency, overcomes various defects of an existing treatment method, remarkably improves the treatment effect, reduces the side effects of medicines, and brings a new treatment choice for patients. And a new thought and a new method are expected to be provided for solving the treatment problem of the three diseases.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, in particular to a compound traditional Chinese medicine preparation for treating postmenopausal osteoporosis, osteoarthritis and / or premature ovarian insufficiency, and a preparation method and application thereof. BACKGROUND

[0002] Postmenopausal osteoporosis is a systemic bone disease, and its pathogenesis is extremely complex. It is closely related to the body function decline caused by age growth, endocrine imbalance triggered by estrogen deficiency, unbalanced nutrition intake, and unhealthy lifestyle (such as long-term lack of exercise, smoking, excessive drinking, etc.). Currently, the commonly used drugs in clinical practice, such as calcium supplements, can supplement calcium elements, but simple calcium supplementation cannot effectively improve the osteoporosis condition; vitamin D can promote calcium absorption, but it cannot independently undertake the treatment task; bisphosphonate drugs can inhibit osteoclast activity, reduce bone resorption, and increase bone density, but long-term use can cause a series of serious adverse reactions, such as gastrointestinal discomfort manifested as nausea, vomiting, abdominal pain, diarrhea, hypocalcemia can cause hand-foot cramps, paresthesia, and jaw necrosis seriously affects the oral function and quality of life of patients. Calcitonin can relieve bone pain to a certain extent, but the effect is relatively limited, and long-term application can easily produce drug resistance, making the treatment effect gradually weaken.

[0003] Osteoarthritis (OA) is a common chronic joint disease, and its pathological process is relatively slow but progressive. Articular cartilage degeneration is the initial pathological change, and with the progression of the disease, hyperostosis and joint space narrowing gradually appear, and then lead to joint pain, swelling, deformity and limited activity, and other clinical manifestations. Currently, the drugs for treating osteoarthritis, non-steroidal anti-inflammatory drugs, by virtue of inhibiting cyclooxygenase activity and reducing prostaglandin synthesis, can play an anti-inflammatory and analgesic role, but only can relieve the surface symptoms, and cannot fundamentally prevent the deterioration process of the disease. Long-term use of such drugs can easily cause gastrointestinal ulcers, manifested as stomach pain, stomach distension, black stool and other symptoms, and can also cause damage to liver and kidney function, affecting normal metabolic function of the body. Cartilage protectants such as glucosamine sulfate and chondroitin sulfate can promote cartilage matrix synthesis to a certain extent and delay cartilage degeneration, but the therapeutic effect appears relatively slowly, and different individuals have large differences in response, making it difficult to ensure consistent therapeutic effect.

[0004] Premature ovarian failure refers to that a woman before the age of 40, due to various reasons (such as genetic factors, autoimmune diseases, iatrogenic damage, etc.) leads to premature decline of ovarian function. This will greatly reduce the secretion of hormones such as estrogen, progesterone, and other hormones, and then cause a series of symptoms. Menstrual disorders are manifested as irregular menstrual cycle, menstrual volume more or less; amenorrhea directly affects the reproductive function of women; infertility brings heavy psychological burden to patients; vasomotor symptoms such as hot flashes and night sweats seriously affect the daily life and sleep quality of patients; at the same time, estrogen deficiency also accelerates bone loss, increases the risk of postmenopausal osteoporosis. The hormone replacement therapy widely used in clinical practice can alleviate the symptoms of patients to a certain extent, prevent complications such as osteoporosis, but long-term application will significantly increase the risk of major diseases such as breast cancer, endometrial cancer, cardiovascular disease, making the therapy face many concerns and restrictions in clinical application.

[0005] The existing treatment methods for osteoporosis, osteoarthritis and premature ovarian failure have obvious problems such as poor efficacy or large side effects. These problems seriously affect the treatment effect and quality of life of patients, so that patients suffer from physical and psychological pain in the long-term treatment process. Traditional Chinese medicine has unique advantages in the treatment of chronic diseases, but the existing compound traditional Chinese medicine preparations often have the problem of insufficient targeting when treating the above three diseases, and it is difficult to achieve multi-target point synergistic therapy, and cannot fully meet the clinical needs. Therefore, it is urgent to develop a new safe and effective therapeutic drug to meet the actual needs of clinical treatment. SUMMARY

[0006] The purpose of the present application is to provide a compound traditional Chinese medicine preparation for treating postmenopausal osteoporosis, osteoarthritis and / or premature ovarian failure, and a preparation method and application thereof, to solve the problems existing in the prior art. The compound traditional Chinese medicine preparation provided by the present application realizes effective treatment of osteoporosis, osteoarthritis and premature ovarian failure, overcomes the drawbacks of existing treatment methods, significantly improves the treatment effect, reduces the side effects of drugs, and brings new treatment options for patients. It is expected to provide new ideas and methods for solving the treatment problems of the above three diseases.

[0007] To achieve the above purpose, the present application provides the following solutions:

[0008] The application provides a compound traditional Chinese medicine preparation for treating postmenopausal osteoporosis, osteoarthritis and / or premature ovarian failure, which comprises the following components: Radix Rehmanniae Preparata 10-30g, Angelica sinensis 10-30g, Ligusticum chuanxiong 8-15g, Radix Paeoniae Alba 8-15g, Radix Codonopsis 10-30g, Rhizoma Atractylodis Macrocephalae 8-15g, Poria cocos 10-30g, Glycyrrhiza 5-10g, Radix Curcumae 10-30g, Radix Milvae 8-15g, Chaenomeles speciosa 8-15g, Dragon bone 8-15g and Oyster shell 8-15g.

[0009] Preferably, the preparation comprises the following components: Radix Rehmanniae Preparata 15g, Angelica sinensis 15g, Ligusticum chuanxiong 10g, Radix Paeoniae Alba 10g, Radix Codonopsis 15g, Rhizoma Atractylodis Macrocephalae 10g, Poria cocos 15g, Glycyrrhiza 5g, Radix Curcumae 15g, Radix Milvae 10g, Chaenomeles speciosa 10g, Dragon bone 10g and Oyster shell 10g.

[0010] The application further provides a preparation method of the compound traditional Chinese medicine preparation, which comprises the following steps.

[0011] The components are crushed and sieved, Angelica sinensis, Ligusticum chuanxiong and Radix Paeoniae Alba are mixed, 3-5 times the amount of water is added and decocted for 1-2 hours, the first filtrate and the residue are collected by filtration;

[0012] The residue is mixed with Radix Rehmanniae Preparata, Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Poria cocos, Glycyrrhiza, Radix Curcumae, Chaenomeles speciosa, Radix Milvae, Dragon bone and Oyster shell, 3-5 times the amount of water is added and decocted again, the filtrate is collected by filtration and combined with the first filtrate;

[0013] The combined filtrate is concentrated under reduced pressure, and the compound traditional Chinese medicine preparation is obtained.

[0014] Preferably, the components are crushed and sieved, Angelica sinensis, Ligusticum chuanxiong and Radix Paeoniae Alba are mixed, 3 times the amount of water is added and decocted for 2 hours.

[0015] Preferably, the residue is mixed with Radix Rehmanniae Preparata, Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Poria cocos, Glycyrrhiza, Radix Curcumae, Chaenomeles speciosa, Radix Milvae, Dragon bone and Oyster shell, 3 times the amount of water is added and decocted again.

[0016] The decocting is performed for 2-3 times, and the decocting time is 1.5-2 hours each time.

[0017] Further preferably, the decocting is performed for 2 times, and the decocting time is 2 hours each time.

[0018] The application further provides application of the compound traditional Chinese medicine preparation in preparation of a medicine for treating postmenopausal osteoporosis, osteoarthritis and / or premature ovarian failure.

[0019] The application further provides a medicine for treating postmenopausal osteoporosis, osteoarthritis and / or premature ovarian failure, which comprises the compound traditional Chinese medicine preparation.

[0020] Optionally, the medicine further comprises a pharmaceutically acceptable excipient.

[0021] Optionally, the dosage form of the medicine comprises a pill.

[0022] The present application discloses the following technical effects:

[0023] The prescription is scientific and ingenious: According to the classical theory of traditional Chinese medicine, the present application ingeniously combines the blood-nourishing and blood-activating effects of “Siwu Decoction” (Angelica sinensis, Radix Rehmanniae Preparata, Chuanxiong Rhizoma, Paeonia lactiflora) and the qi-tonifying and spleen-strengthening effects of “Sijunzi Decoction” (Radix Codonopsis, Atractylodes Macrocephala Koidz, Poria Cocos, Glycyrrhiza Uralensis), achieving dual supplementation of qi and blood. On this basis, Chuanxuduan and Niuxi are added to tonify the liver and kidney and strengthen the tendons and bones, and Mugua is added to relax the tendons and collaterals, and Longgu and Muli are added to supplement calcium and strengthen the bones. The present application precisely targets the pathogenesis of osteoporosis, osteoarthritis (bone loss and unsmooth tendons and vessels) and premature ovarian insufficiency (qi and blood deficiency) for treatment, and the prescription is rigorous and the compatibility is ingenious.

[0024] Multi-target synergistic effect: The compound traditional Chinese medicine preparation provided by the present application can synergistically treat the three diseases from multiple targets. On the one hand, it can effectively increase bone density by improving bone metabolism, and significantly relieve the symptoms of osteoporosis; on the other hand, it can relieve joint inflammation and significantly improve joint function, and has a significant effect on osteoarthritis. At the same time, it can also positively improve the function of the ovary by regulating qi and blood, successfully solving the problem of not being able to consider multiple diseases in single disease treatment, and comprehensively improving the treatment effect.

[0025] High safety: The present application uses natural traditional Chinese medicine, which has been verified by long-term clinical practice and has no obvious toxic and side effects. The properties of traditional Chinese medicine ingredients are mild, and during the treatment of diseases, it will not cause serious adverse reactions to the body, especially suitable for long-term use by the elderly and female patients, and has good safety and applicability.

[0026] In addition, the compound traditional Chinese medicine preparation provided by the present application can also improve the drug preparation process to prepare the medicine into a traditional Chinese medicine concentrated water honey pill, which is beneficial for long-term use by patients, and at the same time meets the needs of clinical medication and preparation production, and has high social and clinical value.

[0027] In summary, the compound traditional Chinese medicine preparation provided by the present application realizes effective treatment of osteoporosis, osteoarthritis and premature ovarian insufficiency, overcomes the drawbacks of existing treatment methods, significantly improves the treatment effect, and at the same time reduces the side effects of the medicine, bringing new treatment options for patients. It is expected to provide a new idea and method for solving the treatment problems of the above three diseases. DETAILED DESCRIPTION

[0028] The present application will now be described in detail with reference to a number of exemplary embodiments. This detailed description should not be considered limiting of the present application, but rather a description of certain embodiments thereof, which, together with the accompanying drawings, illustrate some aspects, features and embodiments of the present application.

[0029] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. In addition, where a range of values is provided, it is understood that each intervening value, to the upper and lower limit of the range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed. The upper and lower limits of these smaller ranges can independently be included or excluded in the range.

[0030] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, the preferred methods and materials are described. All patents, patent applications, publications, and descriptions mentioned herein are incorporated by reference in their entirety for the disclosure and

[0031] Many modifications and variations of the present application described in the specific embodiments of the application can be made by those skilled in the art without departing from the spirit or scope of the application. Other embodiments of the application will be apparent to those skilled in the art from consideration of the specification and practice of the application. The specification and examples are illustrative only.

[0032] As used herein, the terms "comprise", "comprising", "include", "including", "have", "having" and the like are open-ended and do not exclude additional elements or steps.

[0033] Composition and preparation of the compound traditional Chinese medicine preparation of Example 1

[0034] 1. Raw material composition

[0035] The compound traditional Chinese medicine preparation is prepared by carefully mixing the following raw medicinal materials:

[0036] Radix Rehmanniae Preparata 10-30g, Angelica sinensis 10-30g, Ligusticum chuanxiong 8-15g, Radix Paeoniae Alba 8-15g, Codonopsis pilosula 10-30g, Atractylodes 8-15g, Poria cocos 10-30g, Glycyrrhiza 5-10g, Dipsacus asper 10-30g, Radix Milvae 8-15g, Chaenomeles speciosa 8-15g, Oyster shell 8-15g, and Dragon bone 8-15g.

[0037] In this example, Radix Rehmanniae Preparata 15g, Angelica sinensis 15g, Ligusticum chuanxiong 10g, Radix Paeoniae Alba 10g, Codonopsis pilosula 15g, Atractylodes 10g, Poria cocos 15g, Glycyrrhiza 5g, Dipsacus asper 15g, Radix Milvae 10g, Chaenomeles speciosa 10g, Oyster shell 10g, and Dragon bone 10g are selected.

[0038] Wherein, Angelica: sweet, pungent, warm, liver, heart, spleen. It has a remarkable effect of blood tonic, regulating menstruation, pain, moistening the intestines and defecation. In the recipe, angelica with its outstanding blood tonic, play a key role in the monarch drug.

[0039] Radix Rehmanniae Preparata: sweet, slightly warm, liver, kidney. Radix Rehmanniae Preparata is good at tonifying blood and yin, essence and marrow. With angelica, the two complement each other, greatly enhancing the effect of blood tonic, together as monarch drug, laid a solid foundation for the prescription of blood tonic.

[0040] Chuanxiong: bitter, warm, liver, gallbladder, pericardium. Chuanxiong has the unique effect of promoting blood circulation and qi, dispelling wind and relieving pain. In the prescription, Chuanxiong can help angelica and radix rehmanniae preparata better play the role of blood circulation and blood nourishment, as a ministerial drug, play a synergistic effect.

[0041] White Peony Root: White Peony Root is bitter and sour, slightly cold, liver and spleen, with multiple effects of nourishing blood, regulating menstruation, astringing yin, relieving pain, and calming liver yang; In the recipe, peony can not only nourish blood, but also promote blood circulation, and cooperate with other drugs to play a synergistic effect, as a ministerial drug, enrich the effect of the prescription.

[0042] Codonopsis: sweet, neutral, spleen and lung. Codonopsis has the good effect of invigorating the spleen and lung, nourishing blood and generating fluid. In the prescription, Codonopsis can tonify qi and invigorate the spleen, providing sufficient source for blood and fluid production, as a ministerial drug, plays an important role in improving the overall efficacy.

[0043] White Atractylodes: bitter, sweet, warm, spleen and stomach. White Atractylodes is good at invigorating the spleen and tonifying qi, drying dampness and promoting water, stopping sweating and preventing miscarriage. In the prescription, white atractylodes helps codonopsis to enhance the effect of tonifying qi and invigorating the spleen, as a ministerial drug, further strengthens the regulation of the spleen and stomach function of the prescription.

[0044] Tuckahoe: sweet, mild, heart, lung, spleen, kidney. Tuckahoe has the effect of promoting water and dampness, invigorating the spleen and calming the heart. In the prescription, Tuckahoe is combined with Codonopsis and White Atractylodes to significantly enhance the effect of invigorating the spleen, as a ministerial drug, assisting the monarch and ministerial drugs to play a role.

[0045] Gancao: sweet, neutral, heart, lung, spleen, stomach. Licorice has the effects of tonifying the spleen and qi, moistening the lungs and relieving cough, clearing heat and detoxifying, relieving pain and harmonizing various drugs. In the prescription, licorice mainly plays the role of harmonizing various drugs, as a ministerial drug, ensures the mutual coordination between various drugs in the prescription, and jointly plays the best curative effect.

[0046] Sichuan Dipsacus: bitter, pungent, slightly warm, liver and kidney. Sichuan Dipsacus has the effect of tonifying liver and kidney, strengthening tendons and bones, continuing to break and stop bleeding. In the prescription, Sichuan Dipsacus can tonify liver and kidney, strengthen tendons and bones, as a ministerial drug, directly acting on the skeletal system, providing support for improving bone health.

[0047] Papaya: sour, warm, liver, spleen. Papaya has unique effects of relaxing muscles and tendons, and stomach wet. In the prescription, papaya can effectively relieve joint pain, flexion and other symptoms, as a drug, has a positive significance for the treatment of osteoarthritis.

[0048] Radix Cyathulae: bitter, sweet, sour, flat, liver, kidney. Radix Cyathulae has a variety of effects of removing blood stasis, tonifying liver and kidney, strengthening bones, diuresis, and descending blood. In the prescription, Radix Cyathulae can not only tonify liver and kidney, strengthen bones, but also guide the drug to the disease site, as a drug, enhance the targeting of the prescription.

[0049] Dragon bone: sweet, astringent, flat, heart, liver, kidney. Dragon bone has the effects of calming the nerves, calming the liver and Yang, and astringent. In the prescription, dragon bone mainly plays the role of calcium supplementation and bone strengthening, as a drug, contributes to improving bone density and bone quality.

[0050] Oyster: salty, slightly cold, liver, gallbladder, kidney. Oyster has the effects of heavy calming, calming Yang, softening and resolving. In the prescription, oyster is combined with dragon bone, and the two synergistically enhance the calcium supplementation and bone strengthening, as a drug, promote bone health together.

[0051] That is, the whole prescription uses Angelica sinensis and Codonopsis pilosula as the monarch drug, Radix Rehmanniae Preparata, Chuanxudan, Radix Angelicae Sinensis, Atractylodes Macrocephala Koidz, Poria Cocos as the ministerial drug, Chuanxudan, Radix Cyathulae, Papaya as the auxiliary drug, and Dragon bone, Oyster as the auxiliary drug, and Licorice as the ministerial drug, which conforms to the "monarch, minister, auxiliary and minister" compatibility principle. The compatibility of various drugs regulates qi and blood, treats liver and kidney, and strengthens bones, achieving the effects of tonifying qi and blood, relaxing muscles and tendons, tonifying liver and kidney, and strengthening bones.

[0052] 2. Preparation method

[0053] Medicinal material pretreatment: each raw medicinal material is strictly subjected to a cleaning process, and the moldy and worm-eaten parts are carefully removed to ensure that the medicinal material quality meets the high standard of medicinal requirements. Then, the cleaned medicinal materials are subjected to crushing treatment, so that they all pass through an 80-100 mesh sieve (100 mesh sieve is selected in this embodiment) for subsequent efficient extraction of effective components.

[0054] Extraction: Firstly, the angelica, chuanxiong and white peony root are mixed, 3-5 times the amount of water is added, and soaked for 30-60 minutes (3 times the amount of water is added and soaked for 30 minutes in this example). After the medicine is fully soaked, it is decocted for 1-2 hours (2 hours in this example). During the decocting, the medicine is stirred properly to ensure that the effective components are fully dissolved. After the decocting, the first filtrate is collected while hot, and the residue is reserved for later use. Then, the residue and the rest of the medicine (prepared rhizome of rehmannia, codonopsis, white atractylodes, poria, licorice, kudzu vine, chaenomeles, radix adenosma, and oyster shell) are mixed, and 3-5 times the amount of water is added for decocting again. The decocting is performed for 2-3 times, each time for 1.5-2 hours (3 times the amount of water is added, and the decocting is performed for 2 times, each time for 2 hours in this example). After each decocting, the filtrate is collected while hot, and all the filtrates are combined.

[0055] Concentration: The combined filtrate is concentrated at 60°C by vacuum concentration until the relative density of the clear paste is 1.20-1.30 (1.20 in this example). The vacuum concentration can effectively reduce the concentration temperature, and minimize the loss of heat-sensitive components, thereby ensuring the quality of the medicine. The compound traditional Chinese medicine preparation of the present application is obtained.

[0056] The compound traditional Chinese medicine preparation can be prepared into pills (called Ankun Jian Gu pill). The pill preparation process is as follows: an appropriate amount of honey (or dextrin) is added to the concentrated clear paste as an excipient (10 g of honey and 5 g of dextrin are added in this example) according to the actual needs. The honey has the effects of tonifying the center, moistening dryness, relieving pain, and detoxifying, and can also give the pills good tackiness and plasticity. The dextrin can increase the volume and improve the formability of the pills. The amount of the excipient is accurately controlled, and the mixture is fully stirred and mixed to form a soft material with appropriate texture. Then, the soft material is made into pills with a weight of 0.2-3 g per pill (0.2 g per pill in this example) by using a professional pill making machine.

[0057] Post-processing: The prepared pills are dried at 60-80°C to accurately remove excess water, so that the water content of the pills strictly meets the quality standards. The dried pills are sterilized by reliable methods such as moist heat sterilization and radiation sterilization to ensure that the pills are sterile and the quality and safety of the medicine are guaranteed in all aspects. The sterilized pills are tightly packaged to obtain the Ankun Jian Gu pill finished product. Each bottle of Ankun Jian Gu pill is equivalent to 250 mL of traditional Chinese medicine decoction of the compound traditional Chinese medicine preparation, and the batch number is Guangdong Pharmaceutical Preparation Z20080076.

[0058] Verification Example 1: Treatment effect of Ankun Jian Gu pill on postmenopausal osteoporosis

[0059] 1. Data and methods

[0060] 1.1General information

[0061] 156 patients with PMOP admitted to our hospital from September 1, 2023 to September 30, 2024 were randomly assigned to the observation group (89 cases) and the control group (67 cases). There was no statistically significant difference in age, disease duration, menopause time, body mass index and other general information between the two groups of patients (Table 1). This study was approved by the hospital ethics committee and the informed consent of the patients was obtained.

[0062] Table 1 Comparison of general information between the two groups of patients

[0063]

[0064]

[0065] 1.2 Inclusion and exclusion criteria

[0066] The inclusion criteria and exclusion criteria were set according to the 'Guidelines for Diagnosis and Treatment of Primary Osteoporosis (2022)', 'Guidelines for Diagnosis and Treatment of Postmenopausal Osteoporosis (Bone Atrophy) (2019 Edition)' and 'Expert Consensus on Prevention and Treatment of Osteoporosis in Perimenopausal and Postmenopausal Women'.

[0067] Inclusion criteria: meet the diagnostic criteria for postmenopausal osteoporosis (PMOP). Based on dual-energy X-ray absorptiometry, all patients were detected in the central bone lumbar spine L2-4, T value ≤-2.5 SD, natural menopause in women aged 50-65 years, with symptoms of back pain, limb joint pain and other bone pain.

[0068] Exclusion criteria: secondary osteoporosis, fracture within 6 months, use of drugs affecting bone metabolism within 6 months, severe diseases of important organs such as heart, lung, liver and kidney, drug allergy.

[0069] Exclusion and dropout criteria: after entering the group, due to the use of drugs or treatment that may affect the research results, refusal to continue medication and other unpredictable factors. Refuse to accept related index detection or incomplete index detection; voluntarily withdraw due to various reasons; do not return for follow-up; feel unwell and cannot continue treatment during treatment; due to adverse reactions such as severe liver and kidney function damage, drug intolerance, very urgent acute diseases, and even life-threatening conditions; dropouts should be registered according to requirements.

[0070] 1.3 Grouping and treatment methods

[0071] The patients were grouped using the digital lottery randomized controlled trial method. Under the premise of fully communicating the disease, the two diagnostic and treatment measures, the research content and the risk, and signing the informed consent, the patients were randomly divided into the control group and the observation group. No drugs affecting bone metabolism such as denosumab and alendronate sodium were used in this study to reduce the interference factors of bone metabolism.

[0072] Basic treatment: Both groups of patients orally took 1200 mg of elemental calcium and 250 iu of vitamin D per day.

[0073] Control group: Oral placebo (traditional Chinese medicine honey pills with the same appearance as Ankun Jian Gu pills, ingredients are carbohydrates such as starch, and the production method is the same as Ankun Jian Gu pills, as follows: use 150 g of starch, add appropriate amount of water and excipients (10 g of honey and 5 g of dextrin) according to actual needs, then use a professional pill making machine to make pills with the same appearance, shape and size as Ankun Jian Gu pills, each pill weighs 0.2 g), 10 g each time, 3 times a day; treatment for 6 months.

[0074] Observation group: Oral Ankun Jian Gu pills prepared in Example 1, 10 g each time, 3 times a day; treatment for 6 months.

[0075] Drug information: Calcium carbonate D3 tablets (trade name: Caltrate D600), specifications: each tablet contains 600 mg of calcium carbonate and 25 iu of vitamin D, batch number: L29899, produced by American Wyeth Pharmaceuticals Co., Ltd.

[0076] 1.4 Observation of detection indicators

[0077] Clinical efficacy evaluation: Referring to the standard for diagnosing and evaluating the efficacy of traditional Chinese medicine syndromes formulated by the State Administration of Traditional Chinese Medicine. Marked effect: pain basically disappeared, normal functional activity; effective: pain relief, basically normal functional activity; ineffective: no pain relief, no improvement in functional activity. The total effective rate is the percentage of marked effect plus the percentage of effectiveness.

[0078] The clinical efficacy evaluation method is Efficacy Index (EI) = [(total syndrome score before treatment - total syndrome score after treatment) / total syndrome score before treatment] x 100%. Marked effect: EI ≥ 80%; effective: 30% ≤ EI < 80%; ineffective: EI < 30%.

[0079] Traditional Chinese medicine syndrome score: According to the standard for quantifying traditional Chinese medicine syndrome score based on the distribution of symptoms of postmenopausal osteoporosis, the main symptoms are low back pain, soreness and weakness of the waist and knees, and the secondary symptoms are calf cramps, limb weakness and fatigue, and pale complexion. According to the severity of symptoms, 1-3 points are assigned in turn, and the total score is finally calculated, as shown in Table 2.

[0080] Visual Analogue Scale (VAS): VAS was used to evaluate the subjective pain intensity of patients before and after treatment. The score was 0-10, 0 was no pain, 10 was severe pain, and the higher the score, the more severe the pain.

[0081] Table 2 Quantitative grading score table of TCM syndrome of postmenopausal osteoporosis

[0082]

[0083] Note: Total score = a x 3 + b x 2 + c x 1 + d x 1 + e x 1.

[0084] Bone Mineral Density (BMD) measurement method: Dual-energy X-ray absorptiometry was used to detect the BMD (g·cm -2 )

[0085] Serological examination: Before and after treatment, 5 mL of fasting venous blood was taken from all patients, serum was extracted using a centrifuge, and five bone markers were detected using enzyme-linked immunosorbent assay, including total type I collagen N-terminal lengthening peptide (P1NP), N-terminal middle osteocalcin (N-MID), β-collagen degradation products (β-CTX), 25 hydroxy-vitamin D3 (25-OH-D3), and total parathyroid hormone (PTH).

[0086] 1.5 Safety indicators

[0087] During medication, headache, fatigue, unexplained muscle pain, loss of appetite, nausea, abdominal distension, constipation or diarrhea, anxiety, restlessness, irritability, skin rash, and other allergic reactions were recorded. Liver and kidney function was detected before and after treatment, and further examination of complications was performed at the last follow-up.

[0088] 1.6 Statistical methods

[0089] SPSS 25.0 statistical software was used for data analysis. Normal distribution test and variance test were performed on the measurement data. If the data were normally distributed and the variances were equal, the mean ± standard deviation was described. If the data were not normally distributed, the rank sum test in non-parametric test was used. The count data were analyzed using X 2For clinical statistical data, the rank-sum test was used, and the correlation test was performed using Pearson correlation analysis. A p-value < 0.05 was considered statistically significant.

[0090] 2. Results

[0091] 2.1 Clinical efficacy

[0092] The clinical efficacy of the two groups of patients after treatment was compared. The total effective rate of the observation group was 93.26%, which was significantly higher than that of the control group (71.64%, P<0.001), as shown in Table 3.

[0093] Table 3 Comparison of clinical efficacy between the two groups of patients (n, %)

[0094]

[0095] 2.2 Comparison of TCM syndrome total score and BMD

[0096] Before treatment, there was no statistically significant difference in the total TCM syndrome score and BMD between the two groups (P>0.05), indicating that the data were comparable. After treatment, both groups showed improvement in total TCM syndrome score and BMD compared to before treatment (P<0.05), with the observation group showing significantly better improvement than the control group (P<0.05), as shown in Table 4.

[0097] Table 4 Comparison of total TCM syndrome scores and bone mineral density (BMD) between the two groups of patients

[0098]

[0099] 2.3 Comparison of serological indicators

[0100] Before treatment, there were no statistically significant differences in P1NP, N-MID, β-CTX, 25-OH-D3, and PTH levels between the two groups (P>0.05). After treatment, P1NP, β-CTX, and PTH levels decreased in both groups, while N-MID and 25-OH-D3 levels increased compared to before treatment.

[0101] Within-group comparisons, regarding decreasing indicators, both groups showed significant decreases in P1NP and β-CTX (P<0.05), while the decrease in PTH was not significant (P>0.05). Regarding increasing indicators, both groups showed significant increases in 25-OH-D3 (P<0.05), while the increase in N-MID was not significant (P>0.05).

[0102] In the comparison between groups, in terms of the decreasing indicators, the decrease in the P1NP index of the two groups of patients was significantly different (P<0.05), and the decrease in the β-CTX and PTH indexes of the two groups of patients was not statistically significant (P>0.05). In terms of the increasing indicators, the increase in the N-MID and 25-OH-D3 indexes of the two groups of patients was not significant (P>0.05), as shown in Table 5.

[0103] Table 5 Comparison of serological indexes of two groups of patients

[0104]

[0105] 2.4 Safety evaluation

[0106] During the treatment, no serious adverse reactions occurred in both groups of patients. In the control group, 5 cases had dry stools and 2 cases had constipation. In the observation group, 2 cases had nausea, 6 cases had dry stools, and 1 case had constipation. The adverse reactions of both groups of patients improved after increasing water intake and foods rich in dietary fiber. Dry stools and constipation were considered to be caused by taking calcium carbonate tablets, and nausea was caused by gastrointestinal discomfort stimulated by taking traditional Chinese medicine pills.

[0107] To sum up, this verification example found that Ankun Jiangu Pills can effectively improve symptoms such as low back and back pain in patients and increase the BMD of patients. The clinical efficacy, total score of traditional Chinese medicine syndromes, and BMD of the observation group were all better than those of the control group (P<0.05). By supplementing calcium and vitamin D3 to the observation group and the control group, without using drugs that affect bone metabolism such as denosumab and alendronate sodium, this invention found that after supplementing calcium and vitamin D3, the bone metabolism markers such as P1NP and β-CTX in the control group of patients also improved significantly (P<0.05), suggesting that calcium and vitamin D3 should be actively supplemented to PMOP patients. Compared with the control group, the improvement of bone metabolism markers such as P1NP, N-MID, and β-CTX in the observation group of patients was better than that of the control group. The differences in P1NP and β-CTX between groups were significant (P<0.05), and the difference in N-MID was not significant (P>0.05). It is suggested that Ankun Jiangu Pills can balance bone formation and absorption, effectively improve the high-turnover bone metabolism state of PMOP patients, and make symptoms such as pain in PMOP patients improve and BMD increase.

[0108] Verification example 2 Therapeutic effect of Ankun Jiangu Pills on osteoarthritis

[0109] 1. Data and methods

[0110] 1.1 General information

[0111] Clinical screening included 86 patients with knee osteoarthritis admitted to our hospital from September 1, 2023 to December 31, 2024. These patients were randomly assigned to an observation group (47 cases) and a control group (39 cases). There were no statistically significant differences in age, disease duration, body mass index, or other general characteristics between the two groups (Table 6). This study was approved by the hospital's ethics committee, and informed consent was obtained from all patients. Both groups were followed up for 12 weeks, and no patients dropped out. There were no statistically significant differences between the two groups in terms of age, gender, disease duration, and pre-treatment Western Ontario and McMaster Universities (WOMAC) assessment, making them comparable.

[0112] Table 6 Comparison of general information between the two groups of patients

[0113]

[0114] 1.2 Selection and Exclusion Criteria

[0115] Inclusion and exclusion criteria were set with reference to the "Guidelines for the Diagnosis and Treatment of Knee Osteoarthritis with Integrated Traditional Chinese and Western Medicine (2023 Edition)" and the "Expert Consensus on Clinical Drug Treatment of Knee Osteoarthritis in China (2023)".

[0116] ① Recurrent knee pain within the past month; ② X-ray showing narrowing of the joint space, subchondral bone sclerosis and / or cystic changes, and osteophyte formation at the joint margins; ③ Clear, viscous synovial fluid with a white blood cell (WBC) count <2000 / mL; ④ Age ≥40 years; ⑤ Morning stiffness duration ≤30 minutes; ⑥ Palpation of bone crepitus during activity. A diagnosis can be confirmed if the patient meets the criteria ① and ②, or ①, ③, ⑤, and ⑥, or ①, ④, ⑤, and ⑥.

[0117] The TCM diagnostic criteria refer to the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine" regarding wind-cold-dampness bi syndrome and liver-kidney deficiency syndrome. The primary symptom is joint pain or partial muscle soreness, heaviness, and numbness, which, if prolonged, can lead to limb stiffness and even joint swelling. Secondary symptoms include migratory pain in the limbs and joints, with no fixed location, sometimes accompanied by chills and fever, a yellow and greasy tongue coating, and a floating pulse; generalized or localized joint pain, with a fixed location, slightly relieved by heat and aggravated by cold, a white tongue coating, and a wiry and tense pulse; joint pain, numbness of the skin, with a fixed location, which can be aggravated by dampness, rain, and cold, a white and greasy tongue coating, and a soft and slow pulse. A deep and thready or deep and weak pulse is also present. If the primary symptom is present, and the secondary symptoms, tongue, and pulse are considered, this syndrome is diagnosed.

[0118] The X-ray grading references the Kellgren-Lawrance grading system for osteoarthritis in the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine". Grade 0: Normal; Grade I: Mild osteophytes; Grade II: Obvious osteophytes, suspected narrowing of the joint space; Grade III: Moderate narrowing of the joint space, subchondral bone sclerosis; Grade IV: Numerous osteophytes, significantly narrowed joint space, severe subchondral bone sclerosis and obvious deformity.

[0119] Inclusion criteria: ① Individuals with knee osteoarthritis meeting the diagnostic criteria of both Western and Traditional Chinese Medicine and classified as grade 0 to II in the Kellgren-Lawrance classification; ② No gender restrictions, aged 45 to 75 years; ③ No use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the past two months; ④ No infections around the knee joint; ⑤ No concurrent diseases of major organs such as the heart, brain, liver, and kidneys; ⑥ This protocol has been approved by the hospital's ethics committee, and patients participate voluntarily and sign informed consent forms.

[0120] Exclusion criteria: ① Those who do not meet the aforementioned diagnostic criteria; ② Those aged >70 years or <40 years; ③ Those whose cases are not within the scope of action of this drug; ④ Those with grade 0 or IV of the radiological grading criteria for osteoarthritis; ⑤ Those with massive joint effusion due to acute synovitis; ⑥ Those with comorbidities affecting the joints, such as psoriasis, metabolic bone disease, acute trauma, etc.; ⑦ Those with allergies or allergies to the drug components contained in this formula; ⑧ Those with serious underlying medical conditions such as heart, brain, liver, kidney, and respiratory system diseases, mental disorders, or hereditary diseases; those with major systemic diseases such as cancer patients; ⑨ Women who are breastfeeding, pregnant, or planning to become pregnant; ⑩ Those with poor compliance and difficulty in attending follow-up appointments on time.

[0121] Exclusion and dropout criteria: Exclusions include those who, after enrollment, use medications or treatments that may affect research results due to illness, refuse to continue medication, or other unforeseen factors. Exclusions include: refusal to undergo relevant indicator testing or incomplete indicator testing; voluntary withdrawal for any reason; failure to attend follow-up appointments in a timely manner; feeling unwell during treatment and unable to continue treatment; adverse reactions such as severe liver or kidney damage, drug intolerance, or highly urgent sudden illnesses that may even be life-threatening. Dropout cases should be registered according to requirements.

[0122] 1.3 Grouping and Treatment Methods

[0123] Patients were grouped using a digital randomized controlled trial method. After fully communicating their condition, the two treatment methods, the research content and risks, and obtaining informed consent, patients were randomly assigned to a control group and an observation group.

[0124] Basic treatment: Both groups of patients performed quadriceps resistance training twice a day for 30 minutes each time. During the treatment period, both groups of patients took the nonsteroidal anti-inflammatory drug celecoxib capsules, one capsule once a day. Intra-articular injections of sodium hyaluronate, hormones, and other similar medications were avoided, and traditional Chinese medicine external therapies, acupuncture, and massage were temporarily suspended.

[0125] Control group: Oral placebo (Chinese herbal water-honey pills with the same appearance as Ankun Jian Gu Wan, the ingredients are starch and other carbohydrates, and the preparation method is the same as in 1.3 of verification case 1), 10g each time, 3 times a day; treatment for 6 months.

[0126] Observation group: The patient was given 10g of Ankun Jian Gu Wan prepared in Example 1 orally, 3 times a day, for 6 months.

[0127] 1.4 Observation and detection indicators

[0128] Clinical efficacy evaluation: Referencing the diagnostic and efficacy guidelines for TCM diseases and syndromes formulated by the State Administration of Traditional Chinese Medicine and the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs." The criteria for judging clinical efficacy are divided into the following three levels:

[0129] Significant effect: Pain basically disappears, functional activities are basically normal or slightly limited, and knee joint function score is reduced by ≥80%;

[0130] Effective: Symptoms are basically eliminated, joint movement is slightly restricted, and the knee joint function score is reduced by ≥30% and <80%;

[0131] Ineffective: No significant improvement in symptoms and joint mobility, and a decrease in knee joint function score of <30%.

[0132] The total effective rate is the sum of the percentage of markedly effective rate and the percentage of effective rate.

[0133] The clinical efficacy evaluation method is the Efficacy Index (EI) = [(Total syndrome score before treatment - Total syndrome score after treatment) / Total syndrome score before treatment] × 100%. Marked effect: EI ≥ 80%; Effective: 30% ≤ EI < 80%; Ineffective: EI < 30%.

[0134] Observation indicators: Knee pain was assessed using the VAS (Visual Analogue Scale) to evaluate the subjective pain intensity of patients before and after treatment. Scores ranged from 0 to 10, with 0 indicating no pain and 10 indicating severe pain; higher scores indicated more severe pain. The Word-of-Mouth Assessment (WOMAC) score was also used. Assessments were conducted before treatment and again 12 weeks after treatment.

[0135] Serological examination: All patients underwent joint aspiration of the affected knee before and after treatment. The levels of IL-1, IL-6, TNF-α and NO in the joint fluid were detected by enzyme-linked immunosorbent assay (ELISA). The IL-1, IL-6 and TNF-α ELISA kits (DGbiotech, product numbers EK101A2-96T, EK1062-96T and EK1822-96T, respectively) were strictly followed according to the instructions.

[0136] 1.5 Safety Indicators

[0137] Record any headaches, fatigue, unexplained muscle pain, loss of appetite, nausea, abdominal distension, constipation or diarrhea, anxiety, restlessness, irritability, allergic reactions such as rashes during medication. Monitor liver and kidney function before and after treatment. Further check for complications at the last follow-up visit.

[0138] 1.6 Statistical Methods

[0139] SPSS 25.0 statistical software was used to analyze the data. Normality and variance tests were performed on the measurement data. The data conformed to a normal distribution and had homogeneous variances. The mean ± standard deviation was used as the approximation. The description states that if the data meets the criteria, a t-test is used; if it does not conform to a normal distribution, a rank-sum test (a non-parametric test) is used. For categorical data, a chi-square test is used. 2 For clinical statistical data, the rank-sum test was used, and the correlation test was performed using Pearson correlation analysis. A p-value < 0.05 was considered statistically significant.

[0140] 2. Results

[0141] 2.1 Clinical efficacy

[0142] The clinical efficacy of the two groups of patients after treatment was compared. The total effective rate of the observation group was 91.49%, which was significantly higher than that of the control group (69.23%, P<0.05), as shown in Table 7.

[0143] Table 7 Comparison of clinical efficacy between the two groups of patients (n, %)

[0144]

[0145] 2.2 Comparison of serological markers

[0146] Comparison of IL-1, IL-6, TNF-α, and NO levels in the synovial fluid of the two groups of patients: Compared with before treatment, the levels of IL-1, IL-6, TNF-α, and NO in the synovial fluid of both groups decreased significantly after treatment (P < 0.05); there was no significant difference in the levels of IL-1 and IL-6 in the synovial fluid of the two groups after treatment (P > 0.05), while the levels of TNF-α and NO decreased significantly (P < 0.05). See Table 8.

[0147] Table 8 Comparison of serological indicators between the two groups of patients

[0148]

[0149] 2.3 Pain score

[0150] Before treatment, there was no difference in pain scores between the two groups (P>0.05). After treatment, pain scores in both groups decreased significantly, with significant differences between and within groups (P<0.05). See Table 9.

[0151] Table 9 Comparison of VAS between the two groups of patients

[0152]

[0153]

[0154] 2.4 Knee joint function score

[0155] Before treatment, there was no difference in the knee joint function scores between the two groups of patients (P>0.05). After treatment, the knee joint function scores of both groups of patients decreased, and the differences between groups and within groups were significant (P<0.05). See Table 10.

[0156] Table 10 Comparison of knee joint function scores between two groups of patients

[0157]

[0158] 2.5 Safety evaluation

[0159] During the treatment period, no severe adverse reactions occurred in both groups of patients. 3 cases of nausea and retching occurred in the control group. 2 cases of dry mouth occurred in the observation group. The adverse reactions of both groups of patients improved after increasing water intake and foods rich in dietary fiber. Nausea and retching were considered to be caused by the stimulation of the gastrointestinal tract by taking celecoxib capsules, and dry mouth was considered to be caused by taking traditional Chinese medicine pills for tonifying qi and blood.

[0160] To sum up, in this verification case, Ankun Jiangu Pills were used to treat OA by the method of nourishing qi and blood. Clinical observation found that the method of replenishing qi and nourishing blood had good clinical efficacy, reduced the knee joint pain score, improved the knee joint function, reduced the serum inflammatory levels such as IL-1, IL-6, TNF-α and NO, and moreover, the composition of this formula had no toxic drugs and had a good safety evaluation, and no severe adverse reactions were found in clinical observation.

[0161] Verification Case 3 Therapeutic effect of Ankun Jiangu Pills on premature ovarian insufficiency

[0162] 1. Data and methods

[0163] 1.1 General data

[0164] 65 patients with premature ovarian insufficiency admitted to our hospital from January 1, 2024 to December 31, 2024 were clinically screened and randomly assigned to the observation group (32 cases) and the control group (33 cases). There was no statistically significant difference in general data such as age, course of disease, and body mass index between the two groups of patients (Table 11). This study was reviewed and approved by the hospital ethics committee, and informed consent was obtained from the patients. Both groups were followed up for 12 weeks without dropout.

[0165] Table 11 Comparison of general data between two groups of patients

[0166]

[0167]

[0168] 1.2 Selection and Exclusion Criteria

[0169] Inclusion and exclusion criteria were set with reference to the "Guidelines for the Diagnosis and Treatment of Premature Ovarian Insufficiency with Integrated Traditional Chinese and Western Medicine" and the "Expert Consensus on the Clinical Diagnosis and Treatment of Premature Ovarian Insufficiency (2023 Edition)".

[0170] The relevant diagnostic criteria for premature ovarian insufficiency in Western medicine are: amenorrhea for ≥4 months before the age of 40, and estradiol level <20 ng / L. -1 ≥2 FSH tests > 40 IU·L -1 The interval between two examinations should be greater than 30 days.

[0171] Traditional Chinese Medicine diagnostic criteria: Meets the relevant diagnostic criteria for early-onset ovarian insufficiency syndrome of Qi and Blood deficiency in the "Traditional Chinese Medicine Treatment Strategies for Gynecological Diseases".

[0172] Main symptoms: fatigue, lack of energy and reluctance to speak, and irregular menstruation.

[0173] Secondary symptoms include: dizziness, palpitations, pale complexion, spontaneous sweating or sweating upon exertion, forgetfulness, insomnia, poor appetite, lethargy, low libido, frequent urination of clear urine, vaginal dryness, and infertility.

[0174] Pulse characteristics: Pale tongue, thin white coating, thready and weak or slow pulse.

[0175] Diagnostic criteria: A diagnosis can be made if all the main symptoms are present, along with at least three secondary symptoms, combined with tongue and pulse diagnosis.

[0176] Inclusion criteria: ① Voluntarily signed informed consent form; ② Meets the above-mentioned diagnostic criteria of both traditional Chinese medicine and Western medicine; ③ Good compliance and cooperation with this study; ④ Has not received immunosuppressant or hormone therapy within 3 months; ⑤ Age < 40 years and ≥ 18 years.

[0177] Exclusion criteria: ① Individuals with mental disorders; ② Pregnant and lactating women; ③ Individuals with allergic constitutions; ④ Individuals with severe heart, liver, or kidney dysfunction; ⑤ Individuals with congenital genital malformations, polycystic ovary syndrome, pituitary tumors, or other acquired organic diseases, or secondary or primary amenorrhea caused by injury; ⑥ Other endocrine or immune system diseases; ⑦ Hematopoietic system abnormalities.

[0178] Exclusion and dropout criteria: Exclusions due to unforeseen factors such as use of medications or treatments that may affect study results after enrollment, refusal to continue medication, etc. Exclusions include: refusal to undergo relevant indicator testing or incomplete indicator testing; voluntary withdrawal for any reason; failure to attend follow-up appointments in a timely manner; feeling unwell during treatment and unable to continue treatment; adverse reactions such as severe liver or kidney damage, drug intolerance, or highly urgent sudden illnesses that may be life-threatening. Dropout cases should be registered according to requirements.

[0179] 1.3 Grouping and Treatment Methods

[0180] Patients were grouped using a digital randomized controlled trial method. After fully communicating their condition, the two treatment methods, the research content and risks, and obtaining informed consent, patients were randomly assigned to a control group and an observation group.

[0181] Basic treatment: After diagnosis and enrollment, both groups of patients were given estradiol valerate tablets (Zhejiang Xianju Pharmaceutical Co., Ltd., National Drug Approval Number H20020299) for 21 days, 1 mg once a day; from day 22, progesterone capsules (Zhejiang Pharmaceutical Co., Ltd. Xinchang Pharmaceutical Factory, National Drug Approval Number H20040982) were added, 200 mg once a day, for 3 consecutive months.

[0182] Control group: Oral placebo (Chinese herbal water-honey pills with the same appearance as Ankun Jian Gu Wan, the ingredients are starch and other carbohydrates, and the preparation method is the same as in 1.3 of verification case 1), 10g each time, 3 times a day; treatment for 6 months.

[0183] Observation group: The patient was given 10g of Ankun Jian Gu Wan prepared in Example 1 orally, 3 times a day, for 6 months.

[0184] 1.4 Observation and detection indicators

[0185] 1.4.1 Traditional Chinese Medicine Symptom Scores

[0186] Referring to the diagnostic and therapeutic guidelines for TCM diseases and syndromes formulated by the State Administration of Traditional Chinese Medicine and the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," the symptom scores of the two groups of patients before and 3 months after treatment were compared. Primary symptoms such as fatigue, lethargy, and irregular menstruation, as well as secondary symptoms such as decreased libido, frequent urination, and vaginal dryness, were categorized into four levels based on their presence and severity: none, mild, moderate, and severe, with corresponding scores of 0, 1, 2, and 3 points. Tongue and pulse were not scored. The TCM symptom scores were calculated using the nimodipine method.

[0187] Traditional Chinese Medicine Symptom Score = (Pre-treatment Score - Post-treatment Score) / Pre-treatment Score × 100%.

[0188] 1.4.2 Evaluation of Clinical Efficacy

[0189] Based on the TCM symptom score assessment, the clinical efficacy of the two groups of patients was divided into three levels, with the specific judgment criteria as follows:

[0190] Significant effect: physical signs and symptoms basically disappear, and symptom scores are reduced by ≥80%;

[0191] Effective: Signs and symptoms improve, symptom scores decrease by ≥30% and <80%;

[0192] Ineffective: The above criteria are not met, or the condition is even worsening, with a symptom score reduction of <30%.

[0193] Overall effectiveness rate = (significantly effective + effective) / n × 100%.

[0194] 1.4.3 Serological examination

[0195] To compare the sex hormone levels of the two groups of patients before and after treatment, 6 mL of fasting antecubital venous blood was drawn from the patients on the second day of menstruation. Luteinizing hormone (LH), estrogen (E2), and follicle stimulating hormone (FSH) were measured by enzyme-linked immunosorbent assay (ELISA) using a Backman Lx20 fully automated biochemical analyzer from the United States.

[0196] 1.5 Safety Indicators

[0197] Record any headaches, fatigue, unexplained muscle pain, loss of appetite, nausea, abdominal distension, constipation or diarrhea, anxiety, restlessness, irritability, allergic reactions such as rashes during medication. Monitor liver and kidney function before and after treatment. Further check for complications at the last follow-up visit.

[0198] 1.6 Statistical Methods

[0199] SPSS 25.0 statistical software was used to analyze the data. Normality and variance tests were performed on the measurement data. The data conformed to a normal distribution and had homogeneous variances. The mean ± standard deviation was used as the approximation. The description states that if the data meets the criteria, a t-test is used; if it does not conform to a normal distribution, a rank-sum test (a non-parametric test) is used. For categorical data, a chi-square test is used. 2 For clinical statistical data, the rank-sum test was used, and the correlation test was performed using Pearson correlation analysis. A p-value < 0.05 was considered statistically significant.

[0200] 2 Results

[0201] 2.1 Traditional Chinese Medicine Syndrome Scoring

[0202] Compared with before treatment, the TCM symptom scores of both groups decreased significantly after treatment, and the decrease in TCM symptom scores in the observation group was greater than that in the control group, with statistically significant differences (P < 0.05). See Table 12.

[0203] Table 12 Comparison of TCM syndrome scores between the two groups of patients (n, )

[0204]

[0205] 2.2 Clinical efficacy

[0206] Compare the clinical efficacy of the two groups of patients after treatment. The total effective rate of the observation group was 90.63%, which was significantly higher than that of the control group (66.67%, P<0.05), as shown in Table 13.

[0207] Table 13 Comparison of clinical efficacy between two groups of patients (n, %)

[0208]

[0209] 2.3 Comparison of serological indicators

[0210] Before treatment, there were no significant differences in the levels of LH, FSH, and E2 between the two groups of patients (P>0.05). After treatment, the levels of LH, FSH, and E2 in both groups of patients were significantly improved compared with those before treatment, and the differences within and between groups were statistically significant (P<0.05); when comparing between groups, the E2 level in the observation group was higher than that in the control group, and the LH and FSH levels were lower than those in the control group (P<0.05). See Table 14.

[0211] Table 14 Comparison of serological indicators between two groups of patients

[0212]

[0213]

[0214] 2.5 Safety evaluation

[0215] During the treatment period, no serious adverse reactions occurred in both groups of patients. 5 cases of nausea and retching occurred in the control group. 1 case of dry stool and 1 case of constipation occurred in the observation group. The adverse reactions of both groups of patients improved after increasing water intake and foods rich in dietary fiber. Nausea and retching are considered to be caused by the drug stimulating the gastrointestinal tract, and dry stool and constipation are considered to be caused by taking traditional Chinese medicine pills for tonifying qi and blood.

[0216] To sum up, this verification example is based on the theory of qi and blood, and proposes the method of nourishing qi and blood to treat premature ovarian insufficiency. By using Ankun Jiangu Pills to replenish qi and blood, promote qi and activate blood circulation, it treats premature ovarian insufficiency, achieves good clinical efficacy, improves the TCM syndrome scores of patients, increases the E2 level, improves the metabolism of LH and FSH, and realizes the harmony of thoroughfare and conception vessels qi and blood and the restoration of ovarian function in such patients. Moreover, the composition of this prescription has no toxic drugs, and the safety evaluation is good. No serious adverse reactions were found in the clinical observation.

[0217] The embodiments described above are only descriptions of the preferred embodiments of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. A compound traditional Chinese medicine preparation for treating postmenopausal osteoporosis, osteoarthritis, and / or early-onset ovarian insufficiency, characterized in that, It includes the following components: Rehmannia glutinosa 10-30g, Angelica sinensis 10-30g, Ligusticum chuanxiong 8-15g, Paeonia lactiflora 8-15g, Codonopsis pilosula 10-30g, Atractylodes macrocephala 8-15g, Poria cocos 10-30g, Glycyrrhiza uralensis 5-10g, Dipsacus asper 10-30g, Achyranthes bidentata 8-15g, Chaenomeles speciosa 8-15g, Os draconis 8-15g, and Ostrea gigas 8-15g.

2. The compound traditional Chinese medicine preparation as described in claim 1, characterized in that, It includes the following components: 15g Rehmannia glutinosa, 15g Angelica sinensis, 10g Ligusticum chuanxiong, 10g Paeonia lactiflora, 15g Codonopsis pilosula, 10g Atractylodes macrocephala, 15g Poria cocos, 5g Glycyrrhiza uralensis, 15g Dipsacus asper, 10g Achyranthes bidentata, 10g Chaenomeles speciosa, 10g Os draconis, and 10g Ostrea gigas.

3. The method for preparing the compound traditional Chinese medicine preparation as described in claim 1, characterized in that, It includes the following steps. Crush and sieve each component. Take Angelica sinensis, Ligusticum chuanxiong and Paeonia lactiflora, mix them together, add 3-5 times the amount of water and decoct for 1-2 hours. Filter and collect the first filtrate and the dregs. Mix the dregs with Rehmannia glutinosa, Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, Glycyrrhiza uralensis, Dipsacus asper, Chaenomeles speciosa, Achyranthes bidentata, fossilized bone and oyster shell, add 3-5 times the amount of water and decoct again, filter, and collect the filtrate and combine it with the first filtrate. The combined filtrate is concentrated under reduced pressure to obtain the final product.

4. The preparation method according to claim 3, characterized in that, Crush and sieve each component, then mix Angelica sinensis, Ligusticum chuanxiong and Paeonia lactiflora, add 3 times the amount of water and decoct for 2 hours.

5. The preparation method according to claim 3, characterized in that, Mix the dregs with Rehmannia glutinosa, Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, Glycyrrhiza uralensis, Dipsacus asper, Chaenomeles speciosa, Achyranthes bidentata, fossilized bone and oyster shell, add 3 times the amount of water and decoct again; The process of decocting the ingredients again is repeated 2-3 times, with each decoction lasting 1.5-2 hours.

6. The preparation method according to claim 5, characterized in that, The process of decocting the ingredients twice is described, with each decoction lasting for 2 hours.

7. The use of the compound traditional Chinese medicine preparation as described in claim 1 in the preparation of a drug for treating postmenopausal osteoporosis, osteoarthritis and / or early-onset ovarian insufficiency.

8. A drug for treating postmenopausal osteoporosis, osteoarthritis, and / or early-onset ovarian insufficiency, characterized in that, The drug comprises the compound traditional Chinese medicine preparation as described in claim 1.

9. The medicament as described in claim 8, characterized in that, The drug also contains pharmaceutically acceptable excipients.

10. The medicament as claimed in claim 8, characterized in that, The dosage form of the drug includes pills.

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