Traditional Chinese medicine composition for treating premature ovarian insufficiency and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating premature ovarian insufficiency and application thereof, and relates to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following components in parts by weight: 60-65 parts of salted morinda officinalis, 60-65 parts of wine-processed glossy privet fruit, 60-65 parts of poria cocos, 60-65 parts of radix rehmanniae recen, 60-65 parts of prepared rehmannia root, 60-65 parts of herba epimedii, 60-65 parts of wine-processed rhizoma polygonati, 60-65 parts of piper wallichii, 92-98 parts of astragalus membranaceus, 60-65 parts of salvia miltiorrhiza, 60-65 parts of spina gleditsiae and 60-65 parts of radix curcumae. The traditional Chinese medicine composition has the main effects of warming kidney to strengthen yang, nourishing blood and regulating menstruation, can treat the early-onset ovarian insufficiency caused by kidney deficiency and blood stasis, can fundamentally improve the ovarian function, and has important clinical application value for improving the clinical treatment effect on the early-onset ovarian insufficiency and meeting the reproductive health requirements of patients.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating early-onset ovarian insufficiency and its application. Background Technology

[0002] Premature ovarian insufficiency (POI) is a common and complex disease in the field of gynecological endocrinology. It refers to a clinical syndrome in which women experience ovarian dysfunction before the age of 40. Core characteristics include menstrual cycle irregularities, decreased menstrual flow, or even amenorrhea, accompanied by elevated serum gonadotropin levels and fluctuating estrogen levels. It is often complicated by infertility and perimenopausal symptoms, seriously affecting the reproductive and psychological health of patients. With the accelerated pace of modern life, changes in environmental factors, and shifts in reproductive attitudes, the incidence of POI is increasing year by year, and the age of onset is gradually becoming younger, making it one of the important issues affecting women's reproductive health.

[0003] The etiology of POI (Potential Ovarian Insufficiency) is not fully understood in modern medicine. Currently, it is believed to be related to multiple factors, including genetic factors, autoimmune diseases, iatrogenic injuries (such as chemotherapy, radiotherapy, and ovarian surgery), exposure to environmental toxins, and unhealthy lifestyle habits. In terms of treatment, modern medicine primarily uses hormone replacement therapy (HRT), which simulates a normal menstrual cycle by supplementing with estrogen and progesterone to alleviate symptoms related to low estrogen, improve menstrual conditions, and to some extent prevent long-term complications such as osteoporosis and cardiovascular disease. Commonly used medications include estradiol tablets / estradiol-dydrogesterone combination preparations. However, this type of treatment has certain limitations: firstly, it cannot fundamentally repair damaged ovarian function, and symptoms are prone to relapse after discontinuation; secondly, long-term use of hormones may increase the risk of adverse reactions such as thrombosis and breast disease, and some patients refuse treatment due to contraindications or safety concerns; thirdly, for patients with fertility needs, hormone replacement therapy has limited effect on improving ovarian reserve function and is unlikely to effectively increase conception rates. In addition, although assisted reproductive technology has provided the possibility of pregnancy for some POI patients, the success rate is low due to the patients' own lack of follicle reserves, and the treatment cost is high, making it difficult to widely use in clinical practice.

[0004] Currently, Traditional Chinese Medicine (TCM) has demonstrated unique advantages in the treatment of POI (Potential Ovarian Inflammation). Through syndrome differentiation and holistic regulation, it has achieved certain results in improving patients' clinical symptoms, regulating endocrine levels, and restoring ovarian reserve. However, existing TCM formulas still have many shortcomings: some formulas lack clear pathogenesis targeting; the clinical efficacy of some formulas is unstable, lacking large-sample, long-term clinical trials for validation; and most formulas have traditional dosage forms, making them inconvenient to take and resulting in poor patient compliance. Furthermore, current research has not explored the mechanism of action of TCM compound formulas in treating POI in sufficient depth, failing to fully elucidate their multi-target, multi-link regulatory mechanisms, thus limiting the widespread application of TCM in this field. Therefore, addressing the limitations of existing treatment methods and combining them with the core pathogenesis of POI, developing a scientifically formulated, effective, and safe TCM composition that can fundamentally improve ovarian function would have significant clinical value in improving the clinical treatment effect of POI and meeting patients' reproductive health needs. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition for treating premature ovarian insufficiency and its application, thereby addressing the problems existing in the prior art. This traditional Chinese medicine composition can effectively treat premature ovarian insufficiency and premature ovarian failure caused by kidney deficiency.

[0006] A comprehensive analysis of the formation mechanism of POI suggests that the TCM pathogenesis of POI is mainly related to the imbalance of the Kidney Qi-Tian Gui-Chong Ren-Uterus axis. In terms of the internal organs, Kidney deficiency is the root cause of POI, while dysfunction between the internal organs and Qi deficiency and blood stasis are important factors leading to POI.

[0007] Based on this, the present invention provides the following solution: This invention provides a traditional Chinese medicine composition for treating early-onset ovarian insufficiency. The composition comprises the following components in parts by weight: 60-65 parts of salt-processed Morinda officinalis, 60-65 parts of wine-processed Ligustrum lucidum, 60-65 parts of Poria cocos, 60-65 parts of raw Rehmannia glutinosa, 60-65 parts of prepared Rehmannia glutinosa, 60-65 parts of Epimedium brevicornu, 60-65 parts of wine-processed Polygonatum sibiricum, 60-65 parts of Photinia serratifolia, 92-98 parts of Astragalus membranaceus, 60-65 parts of Salvia miltiorrhiza, 60-65 parts of Gleditsia sinensis thorns, and 60-65 parts of Curcuma longa.

[0008] Preferably, the traditional Chinese medicine composition comprises the following components in parts by weight: 63 parts of salt-processed Morinda officinalis, 63 parts of wine-processed Ligustrum lucidum, 63 parts of Poria cocos, 63 parts of raw Rehmannia glutinosa, 63 parts of prepared Rehmannia glutinosa, 63 parts of Epimedium brevicornu, 63 parts of wine-processed Polygonatum sibiricum, 63 parts of Photinia serratifolia, 94.5 parts of Astragalus membranaceus, 63 parts of Salvia miltiorrhiza, 63 parts of Gleditsia sinensis thorns, and 63 parts of Curcuma longa.

[0009] The present invention also provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating early-onset ovarian insufficiency.

[0010] Furthermore, the drug includes pharmaceutically acceptable excipients.

[0011] Furthermore, the dosage form of the drug is powder, tablet, granule, capsule, pill, or oral liquid.

[0012] The present invention also provides a medicine for treating early-onset ovarian insufficiency, the raw materials of which include the above-mentioned traditional Chinese medicine composition.

[0013] Furthermore, the drug also includes pharmaceutically acceptable excipients.

[0014] Furthermore, the excipients include fillers, binders, disintegrants, emulsifiers, flavoring agents, preservatives, or colorants.

[0015] Furthermore, the dosage form of the drug is powder, tablet, granule, capsule, pill, or oral liquid.

[0016] This invention also provides a method for preparing Peiyuan Zhuyun Granules for treating early-onset ovarian insufficiency, comprising the following steps: The above-mentioned traditional Chinese medicine composition was decocted and extracted with water to obtain an extract; The extract is concentrated to a clear paste with a relative density of 1.23-1.28, and a binder is added to form granules, which are the Peiyuan Assisted Pregnancy Granules.

[0017] The present invention discloses the following technical effects: This invention develops a traditional Chinese medicine composition for the treatment of premature ovarian insufficiency and premature ovarian failure caused by kidney deficiency, characterized by delayed menarche, scanty menstruation, and eventual amenorrhea; dizziness and tinnitus; severe lower back pain; aversion to cold and cold limbs; frequent urination with clear urine; nocturia; loose stools; sallow complexion; pale tongue with white coating; and deep and thready pulse. It has the effects of warming and tonifying the kidney, replenishing essence and marrow, strengthening the spleen and replenishing qi, and nourishing blood.

[0018] In this traditional Chinese medicine composition, salt-processed Morinda officinalis and Epimedium are the principal herbs, warming and tonifying kidney yang; wine-processed Ligustrum lucidum tonifies kidney yin while seeking yang, while wine-processed Polygonatum sibiricum, Rehmannia glutinosa (processed and raw) nourish yin and replenish essence, serving as the assistant herbs; Poria cocos strengthens the spleen and promotes diuresis, preventing the yin-nourishing herbs from being too greasy and hindering the stomach, serving as the adjuvant herbs; Gleditsia sinensis thorns and Photinia serratifolia dredge the meridians and collaterals, Astragalus membranaceus and Salvia miltiorrhiza tonify qi and invigorate blood, while Curcuma longa clears the heart and soothes the liver, serving as the guiding herbs. The entire formula works together to warm the kidneys and assist yang, nourish blood and regulate menstruation. Detailed Implementation

[0019] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0020] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0021] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0022] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be obvious to those skilled in the art. This specification and embodiments are merely exemplary.

[0023] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0024] Modern physicians generally believe that the main cause and pathogenesis of POI (Potential Infertility) is the deficiency of Yin, Yang, essence, and blood in the kidneys. The kidneys are the foundation of innate constitution and govern reproduction. When kidney Qi is sufficient, Tian Gui (menstrual blood) is generated, and the Chong and Ren meridians and the uterus are nourished, resulting in regular menstruation and fertility. If there is congenital deficiency or acquired malnourishment leading to a deficiency of kidney essence and Qi, then Tian Gui will not be sufficient, the Chong and Ren meridians will be malnourished, causing menstrual irregularities, amenorrhea due to blood deficiency, and infertility.

[0025] Based on this, the inventor, combining clinical treatment experience, developed a formula to nourish the kidneys and aid fertility. This formula is based on ingredients such as salt-processed Morinda officinalis, wine-processed Ligustrum lucidum, Poria cocos, raw Rehmannia glutinosa, prepared Rehmannia glutinosa, Epimedium, wine-processed Polygonatum sibiricum, Photinia serratifolia, Astragalus membranaceus, Salvia miltiorrhiza, Gleditsia sinensis, and Curcuma longa. Its main functions are to warm the kidneys and invigorate Yang, nourish blood and regulate menstruation to treat premature ovarian insufficiency (POI) caused by kidney deficiency and blood stasis.

[0026] Example 1 Ingredients: 63g of salt-processed Morinda officinalis, 63g of wine-processed Ligustrum lucidum, 63g of Poria cocos, 63g of raw Rehmannia glutinosa, 63g of processed Rehmannia glutinosa, 63g of Epimedium brevicornu, 63g of wine-processed Polygonatum sibiricum, 63g of Photinia serratifolia, 94.5g of Astragalus membranaceus, 63g of Salvia miltiorrhiza, 63g of Gleditsia sinensis thorns, and 63g of Curcuma longa.

[0027] Preparation method of Peiyuan Assisted Fertility Granules: Weigh out each ingredient according to the above formula, add water and decoct twice. For the first decoction, add 8 times the amount of water and decoct for 40 minutes, then filter to obtain the first filtrate and residue. For the second decoction, add 6 times the amount of water to the residue, decoct for 30 minutes, and filter to obtain the second filtrate. Combine the two filtrates and concentrate to a clear extract with a relative density of 1.23-1.28 (60℃), then cool. Add soluble starch, mix well, wet granulate, dry, and granulate to make 1000g granules, which are then packaged into 20g bags.

[0028] Example 2 Ingredients: 60g of salt-processed Morinda officinalis, 65g of wine-processed Ligustrum lucidum, 60g of Poria cocos, 65g of raw Rehmannia glutinosa, 60g of prepared Rehmannia glutinosa, 65g of Epimedium, 60g of wine-processed Polygonatum sibiricum, 65g of Photinia serratifolia, 92g of Astragalus membranaceus, 65g of Salvia miltiorrhiza, 60g of Gleditsia sinensis thorns, and 65g of Curcuma longa.

[0029] Preparation method of Peiyuan Assisted Fertility Granules: Weigh out each ingredient according to the above formula, add water and decoct twice. For the first decoction, add 8 times the amount of water and decoct for 40 minutes, then filter to obtain the first filtrate and residue. For the second decoction, add 6 times the amount of water to the residue, decoct for 30 minutes, and filter to obtain the second filtrate. Combine the two filtrates and concentrate to a clear extract with a relative density of 1.23–1.28 (60℃), then cool. Add soluble starch, mix well, wet granulate, dry, and granulate to make 1000g granules, which are then packaged into 20g bags.

[0030] Example 3 Ingredients: 65g of salt-processed Morinda officinalis, 60g of wine-processed Ligustrum lucidum, 65g of Poria cocos, 60g of raw Rehmannia glutinosa, 65g of prepared Rehmannia glutinosa, 60g of Epimedium brevicornu, 65g of wine-processed Polygonatum sibiricum, 60g of Photinia serratifolia, 98g of Astragalus membranaceus, 60g of Salvia miltiorrhiza, 65g of Gleditsia sinensis thorns, and 60g of Curcuma longa.

[0031] Preparation method of Peiyuan Assisted Fertility Granules: Weigh out each ingredient according to the above formula, add water and decoct twice. For the first decoction, add 8 times the amount of water and decoct for 40 minutes, then filter to obtain the first filtrate and residue. For the second decoction, add 6 times the amount of water to the residue, decoct for 30 minutes, and filter to obtain the second filtrate. Combine the two filtrates and concentrate to a clear extract with a relative density of 1.23–1.28 (60℃), then cool. Add soluble starch, mix well, wet granulate, dry, and granulate to make 1000g granules, which are then packaged into 20g bags.

[0032] Example 1 of effect verification 1. Selection of qualified test subjects 1.1 Western Medicine Diagnostic Criteria Referring to "Selection and Application of Examination Items for Gynecological Endocrine Diseases" and "Practical Gynecological Endocrinology", the diagnostic criteria for decreased ovarian reserve function are formulated as follows: (1) The age range is 18-40 years old; (2) Clinical manifestations: patients with a normal menstrual cycle or a normal reproductive history suddenly experience menstrual disorders, scanty menstruation, or even amenorrhea and infertility. Some patients also have perimenopausal symptoms such as facial flushing, sleep disorders, and decreased libido.

[0033] (3) Measurement of basal sex hormone levels: On day 2 of the menstrual cycle, venous blood was drawn on an empty stomach, and the serum basal follicle stimulating hormone (FSH) and basal luteinizing hormone (LH) levels were measured by electrochemiluminescence method: 10 m IU / ml < FSH < 40 m IU / ml or FSH / LH > 2-3.6.

[0034] (4) Color Doppler ultrasound examination: Color Doppler ultrasound (hereinafter referred to as B-ultrasound) examination is performed on the 5th day of the menstrual cycle, and the bilateral antral follicle count (AFC) is <4.

[0035] 1.2 Traditional Chinese Medicine Diagnostic Criteria The diagnostic criteria for menstrual disorders and infertility were formulated with reference to the "Traditional Chinese Medicine Gynecology" and the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs".

[0036] Main symptoms: ① Irregular menstrual cycle or delayed menstruation, or reduced menstrual flow, pale color and thin consistency; Secondary symptoms: ① Soreness and weakness in the lower back and knees; ② Insomnia and excessive dreaming; ③ Dizziness and tinnitus; ④ Fatigue and weakness; ⑤ Hot flashes and sweating; ⑥ Palpitations; ⑦ Irritability and anger.

[0037] Tongue and pulse: The tongue is pale and dark, with a thin white coating, and the pulse is deep and wiry or thin and hesitant.

[0038] If one of the main symptoms is present, along with three of the secondary symptoms, and the tongue and pulse are also present, the condition can be diagnosed as kidney deficiency and liver stagnation.

[0039] 1.3 Inclusion criteria: ① Age between 18 and 40 years old, meeting the above diagnostic criteria in both traditional Chinese and Western medicine; ②The patients and their families were fully informed about the content of this study and voluntarily signed informed consent forms; ③ The patient has no obvious underlying diseases: heart disease, liver and kidney disease; ④ No immune diseases, blood diseases, or mental illness; ⑤ Conscious and of normal thinking; ⑥ No other medications were used within the past 2 months.

[0040] 1.4 Exclusion Criteria: ① Patients whose ovarian reserve has declined due to surgery or trauma; ② Patients with menstrual disorders caused by diseases such as hypothyroidism; ③ Comorbid severe mental illness, liver and kidney disease, etc.; ④ Patients with severe organic lesions such as endometriosis; ⑤ Patients with severe thromboembolic diseases; ⑥ For patients taking Zuogui Wan or Femoston; ⑦ Patients who cannot be followed up, or whose medical records are incomplete or missing; ⑧ Those who do not agree to sign the informed consent form.

[0041] 2. Clinical Implementation Plan 2.1 Test Methods Based on the order of enrollment, 140 patients with decreased ovarian reserve were divided into a treatment group (n=100) and a control group (n=40) using a random number table.

[0042] 2.2 Treatment methods The control group was treated with Femoston (manufacturer: Abbott Biologicals BV, Netherlands; batch number: 351601). Femoston's composition: This product is a compound preparation of estradiol and dydrogesterone tablets. The brick-red tablets are estradiol tablets, and the yellow tablets are dydrogesterone tablets. Oral administration: One tablet daily. For the first 14 days, take one brick-red tablet daily, and for the following 14 days, take one yellow tablet daily. One course of treatment consists of three consecutive menstrual cycles.

[0043] Patients in the treatment group were treated with the Peiyuan Zhuyun Granules prepared in Example 1. The medication was taken orally, one sachet each time, twice a day, morning and evening. Medication was discontinued during menstruation, and a course of treatment consisted of three consecutive menstrual cycles.

[0044] 2.3 Observation Items and Indicators The improvement of patients' clinical symptoms, serum sex hormone levels, and color Doppler blood flow in the ovarian interstitial artery was observed before treatment and after one course of treatment.

[0045] 2.3.1 Observe the changes in patients' clinical symptoms before and after treatment. The TCM syndrome scoring standard was formulated with reference to the Kupperman scoring standard in "Traditional Chinese Medicine Gynecology" and the 2002 edition of "Guiding Principles for Clinical Research of New Chinese Medicine Drugs". See Tables 1 and 2 for details.

[0046] Table 1. Scoring criteria for main symptoms Table 2 Symptom Scoring Criteria 2.3.2 Observe the changes in serum sex hormone levels before and after treatment. On day 2 of the menstrual cycle, blood was drawn to check FSH, LH, and estradiol (E2).

[0047] 2.3.3 Color Doppler ultrasound examination of the ovary and vagina before and after treatment Bilateral ovarian volume (OV), AFC, and the maximum average diameter of the ovary mod (MOD) were monitored on day 5 of the menstrual cycle.

[0048] 3. Clinical trial records 1) All cases were observed according to the trial protocol, and the medical record report forms were filled out carefully.

[0049] 2) Carefully record the patient's medication usage, and provide detailed records of situations such as all medications used, missed medications, more than half of the medications not used, and no medications used.

[0050] 3) Clinical medical record reports are original records and must not be altered.

[0051] 4) All implementation data should be recorded accurately, and the original examination reports should be pasted on the medical record report form.

[0052] 5) Laboratory data within the normal range should also be recorded accurately.

[0053] 4. Methods for recording and reporting adverse events and adverse reactions For any adverse events or reactions that occur during the trial, their type, severity, time of occurrence, duration, treatment measures, and treatment process should be recorded in the medical record report form. Furthermore, based on a comprehensive consideration of comorbidities and concomitant medications, their relevance to the investigational drug should be evaluated, and the physician should record them in detail.

[0054] In addition, when adverse events or adverse reactions are discovered, the observing physician may decide whether to discontinue observation based on the patient's condition. Cases in which medication should be discontinued due to adverse events or adverse reactions should be followed up and the results recorded in detail.

[0055] If any abnormalities occur in the test indicators (clinical symptoms, serum sex hormone levels, and improvement in color Doppler ultrasound blood flow in the ovarian interstitial artery) during or after treatment, a follow-up examination must be conducted at an appropriate time, and the results should be comprehensively analyzed in conjunction with the subject's onset and treatment to determine whether they are related to the investigational drug.

[0056] 5. Efficacy Evaluation Criteria The standards are formulated with reference to the efficacy evaluation content in the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs". The formula for judging efficacy is: Efficacy Index (n) = (TCM symptom score before treatment - TCM symptom score after treatment) / TCM symptom score before treatment × 100%.

[0057] ① Cured: This means that all symptoms of the patient have completely disappeared after treatment, n>95%; ②Significant effect: This means that all symptoms of the patient were significantly relieved after treatment, with 70%≤n≤95%; ③ Effective: This means that after treatment, the patient's symptoms were partially relieved, with 30% ≤ n < 70%; 6. Data Management, Statistical Processing, and Data Summarization Data results are expressed as mean ± standard deviation (x±s) for continuous data, and t-tests are used for comparisons between groups; categorical data are expressed as percentages, and the chi-square test is used for comparisons between groups. 2 Test. P < 0.05 is considered statistically significant.

[0058] Data verification: During clinical trials, clinical investigators review the data according to the clinical trial protocol, checking for any omissions and ensuring consistency of units of measurement. Any errors should be recorded, a manual error report form completed, and promptly returned to the clinical investigator for correction. Finally, data processing and statistical personnel conduct a comprehensive verification and check of the data's completeness and accuracy before data entry.

[0059] Statistical Analysis: Before statistical analysis of clinical trial data, analysts develop a statistical analysis plan, clearly defining detailed statistical analysis steps. Clinical trial data are carefully verified and confirmed before statistical analysis. The primary and secondary efficacy endpoints are statistically analyzed. Efficacy analysis includes comparisons of overall efficacy between groups and comparisons of scores on various scales.

[0060] The choice of statistical methods: Independent t-tests were used for comparisons between groups when continuous data conformed to a normal distribution; paired t-tests were used for comparisons within groups before and after treatment; Wlicoxon tests were used for comparisons that did not conform to a normal distribution. Meanwhile, for count data expressed as percentages, chi-square tests were used.

[0061] 7. Clinical trial results This invention included 140 patients who met the inclusion criteria, of whom 100 were treated with Peiyuan Zhuyun Fang and 40 were treated with Femoston.

[0062] 7.1 Comparison of TCM symptom scores and therapeutic effects before and after treatment in the treatment group and the control group. After 3 months of treatment, 34 patients in the treatment group were cured, 23 showed significant improvement, 23 showed improvement, and 20 showed no improvement; 9 patients in the control group were cured, 7 showed significant improvement, 8 showed improvement, and 16 showed no improvement. The total effective rate of the treatment group (80.0%) was significantly higher than that of the control group (60%), and the difference was statistically significant (P<0.05), as shown in Table 3.

[0063] Table 3 Comparison of TCM syndrome efficacy before and after treatment in the two groups of patients Within-group comparisons, after treatment, scores for menstrual cycle, color and amount of menstrual flow, lower back and knee weakness, dizziness and tinnitus, insomnia and dreaminess, hot flashes and sweating, irritability, palpitations, and fatigue all decreased significantly compared to before treatment (P<0.05). The total scores after treatment were also significantly lower in both the treatment and control groups (P<0.05). Between-group comparisons, there were no statistically significant differences in TCM symptom scores or total scores between the two groups before treatment (P>0.05). However, after treatment, the TCM symptom scores and total scores in the treatment group were significantly lower than those in the control group (P<0.05). See Table 4 for details.

[0064] Table 4 Comparison of TCM symptom scores before and after treatment in the two groups of patients Note: Compared with before treatment, P<0.05, compared with the control group, # P<0.05.

[0065] 7.2 Comparison of sex hormone levels before and after treatment in the treatment group and the control group Within both the treatment and control groups, the levels of FSH, LH, and FSH / LH all decreased after treatment and were significantly lower than before treatment (P<0.05). Between the two groups, there were no statistically significant differences in any sex hormone levels before treatment (P>0.05), but after treatment, the FSH and FSH / LH levels in the treatment group were significantly lower than those in the control group (P<0.05). See Table 5 for details.

[0066] Table 5 Comparison of sex hormone levels before and after treatment in the two groups of patients Note: Compared with before treatment, P<0.05, compared with the control group, # P<0.05.

[0067] 7.3 Color Doppler ultrasound examination of the ovary and vagina before and after treatment in the treatment group and the control group. Within both the treatment and control groups, the AFC, OV, and MOD values ​​all increased after treatment and were significantly better than before treatment (P<0.05). Between the two groups, there were no statistically significant differences in AFC, OV, and MOD values ​​before treatment (P>0.05), but after treatment, the AFC, OV, and MOD values ​​in the treatment group were significantly better than those in the control group (P<0.05). See Table 6 for details.

[0068] Table 6 Comparison of ovarian volume and antral follicle examination results before and after treatment in the two groups of patients. 8. Adverse Reactions No adverse reactions were observed in patients during the experimental process of this invention.

[0069] 9. Discussion Premature ovarian insufficiency (POI) refers to the decline in ovarian function in women before the age of 40, mainly manifested as menstrual irregularities, elevated gonadotropin levels, and fluctuating decline in estrogen levels. Traditional Chinese medicine believes that the main pathogenesis of this disease is a deficiency of yin, yang, essence, and blood in the kidneys. The kidneys are the foundation of innate constitution and govern reproduction. Sufficient kidney qi allows for the generation of Tian Gui (menstrual blood), nourishing the Chong and Ren meridians and the uterus, resulting in regular menstruation and fertility. Congenital deficiency or acquired malnourishment leading to a deficiency of kidney essence and qi results in insufficient Tian Gui, malnourishment of the Chong and Ren meridians, causing menstrual irregularities, amenorrhea due to blood deficiency, and infertility. Traditional Chinese medicine has significant advantages in improving ovarian reserve function and preventing and delaying the onset of premature ovarian failure, making it the most promising direction for breakthroughs in the treatment of POI.

[0070] In this invention, the TCM syndrome score was used as the efficacy standard. After 3 months of treatment, the clinical efficacy of the Peiyuan Assisted Fertility Formula group was as follows: 34 patients in the treatment group were cured, 23 showed significant improvement, 23 showed improvement, and 20 showed no effect; 9 patients in the control group were cured, 7 showed significant improvement, 8 showed improvement, and 16 showed no effect. The total effective rate of the treatment group (80%) was significantly higher than that of the control group (60%), and the difference between the two groups was statistically significant (P<0.05). This statistically significant difference indicates that the combination of Peiyuan Assisted Fertility Formula and Femoston can improve the overall efficacy. Furthermore, in intra-group comparisons between the two groups, the treatment group showed a significant decrease in scores regarding menstrual cycle, color and amount of menstrual flow, lower back and knee pain, dizziness and tinnitus, insomnia and dreaminess, hot flashes and sweating, irritability, palpitations, and fatigue after treatment, with statistically significant differences compared to before treatment. Additionally, the treatment group experienced a significant reduction in FSH, LH, and FSH / LH levels, and an increase in AFC, OV, and MOD levels after treatment, demonstrating that Peiyuan Assisted Fertility Formula plays a crucial and positive role in improving ovarian reserve function.

[0071] This may be related to the fact that the traditional Chinese medicine formula for nourishing the kidneys and promoting fertility can make overall adjustments through multiple links, targets, and systems. The human body is an organic whole with multiple organs and meridians, which can coordinate and work together physiologically and are interconnected pathologically. Therefore, if one part is damaged, other parts will also be affected. If the key part is treated, the other parts will not be a threat. Moreover, the kidney-nourishing and fertility-promoting paste has the effect of tropism, which can connect the meridians, link them together, conduct and transport them, thereby achieving the effect of nourishing yin and replenishing blood, balancing yin and yang, and balancing the body, so as to alleviate and restore POI.

[0072] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for treating early-onset ovarian insufficiency, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: 60-65 parts of salt-processed Morinda officinalis, 60-65 parts of wine-processed Ligustrum lucidum, 60-65 parts of Poria cocos, 60-65 parts of raw Rehmannia glutinosa, 60-65 parts of prepared Rehmannia glutinosa, 60-65 parts of Epimedium brevicornu, 60-65 parts of wine-processed Polygonatum sibiricum, 60-65 parts of Photinia serratifolia, 92-98 parts of Astragalus membranaceus, 60-65 parts of Salvia miltiorrhiza, 60-65 parts of Gleditsia sinensis thorns, and 60-65 parts of Curcuma longa.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: 63 parts of salt-processed Morinda officinalis, 63 parts of wine-processed Ligustrum lucidum, 63 parts of Poria cocos, 63 parts of raw Rehmannia glutinosa, 63 parts of prepared Rehmannia glutinosa, 63 parts of Epimedium brevicornu, 63 parts of wine-processed Polygonatum sibiricum, 63 parts of Photinia serratifolia, 94.5 parts of Astragalus membranaceus, 63 parts of Salvia miltiorrhiza, 63 parts of Gleditsia sinensis thorns, and 63 parts of Curcuma longa.

3. The use of a traditional Chinese medicine composition as described in claim 1 or 2 in the preparation of a medicament for treating early-onset ovarian insufficiency.

4. The application according to claim 3, characterized in that, The drug includes pharmaceutically acceptable excipients.

5. The application according to claim 4, characterized in that, The dosage form of the drug is powder, tablet, granule, capsule, pill, or oral liquid.

6. A drug for treating early-onset ovarian insufficiency, characterized in that, The raw materials include the traditional Chinese medicine composition as described in claim 1 or 2.

7. The drug according to claim 6, characterized in that, The drug also includes pharmaceutically acceptable excipients.

8. The drug according to claim 6, characterized in that, The excipients include fillers, binders, disintegrants, emulsifiers, flavoring agents, preservatives, or colorants.

9. The drug according to claim 7, characterized in that, The dosage form of the drug is powder, tablet, granule, capsule, pill, or oral liquid.

10. A method for preparing Peiyuan Zhuyun Granules for treating early-onset ovarian insufficiency, characterized in that, Includes the following steps: The traditional Chinese medicine composition according to claim 1 or 2 is extracted by decocting with water to obtain an extract; The extract is concentrated to a clear paste with a relative density of 1.23-1.28, and a binder is added to form granules, which are the Peiyuan Assisted Pregnancy Granules.

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