Traditional Chinese medicine composition for improving related symptoms of ovarian insufficiency and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for improving related symptoms of ovarian insufficiency and application of the traditional Chinese medicine composition, and belongs to the field of traditional Chinese medicines. The method mainly comprises the following steps: selecting 6-15 parts by weight of artemisia apiacea, 6-12 parts by weight of scutellaria baicalensis, 9-18 parts by weight of morinda officinalis, 15-30 parts by weight of light wheat, 12-24 parts by weight of prepared rehmannia root, 9-18 parts by weight of lily, 3-9 parts by weight of prepared common monkshood daughter root and 15-30 parts by weight of calcined oyster shell, cleaning the raw material medicines to remove non-medicinal parts and impurities, properly crushing the calcined oyster shell to facilitate dissolution of effective components, and drying to obtain the traditional Chinese medicine composition. Soaking the cooked radix aconiti lateralis praeparata slices in saline water, and cooking to reduce the toxicity for later use; through scientific compatibility of traditional Chinese medicines such as artemisia apiacea, scutellaria baicalensis and morinda officinalis, and by following the treatment method of clearing the upper part and warming the lower part and traffic heart and kidney, comprehensive intervention is realized, so that vasomotor symptoms such as hectic fever, night sweat and the like can be remarkably improved, sleep disorders such as insomnia, upset and the like can be relieved, osteoporosis can be prevented and improved through the effects of tonifying kidney and strengthening bone, and meanwhile, the immune imbalance state can be regulated.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for improving symptoms related to ovarian insufficiency and its application. Background Technology

[0002] As modern medicine gains a deeper understanding of the connection between female reproductive endocrinology and overall health, ovarian insufficiency (POI) and its multi-system symptoms—such as hot flashes and night sweats, insomnia and irritability, osteoporosis, immune dysfunction, and menstrual disorders—are receiving increasing attention.

[0003] The prior art patent document CN121102344A discloses "a traditional Chinese medicine composition for treating or improving ovarian reserve deficiency and its application." The composition comprises the following components by weight: Angelica sinensis, stir-fried white peony root, Taxillus chinensis, Cuscuta chinensis, stir-fried Atractylodes macrocephala, Ligusticum chuanxiong, Lycopus lucidus, Albizia julibrissin flower, and prepared licorice root; Morinda officinalis and Ligustrum lucidum are added after ovulation. The formula provided by this invention conforms to the natural laws of the human body, based on the waxing and waning of Qi, blood, Yin, and Yang, simultaneously nourishing and activating blood while tonifying the kidneys, supplementing both Yin and Yang without stagnation, and removing blood stasis without harming the body's vital energy; at the same time, it strengthens the acquired constitution, calms the five internal organs, combines movement and stillness, and adjusts the balance of Qi, blood, Yin, and Yang to achieve harmony.

[0004] The patent document with authorization announcement number CN118403128A discloses "a traditional Chinese medicine composition, preparation and application for improving ovarian function", which includes: 1050 parts of Cuscuta chinensis, 535 parts of Cistanche deserticola, 1050 parts of Lycium barbarum, 1050 parts of Polygonatum sibiricum, 1050 parts of Codonopsis pilosula, 525 parts of Atractylodes macrocephala, 525 parts of Nelumbo nucifera leaf, 525 parts of Dendrobium nobile, 530 parts of Lilium brownii, 530 parts of Rosa rugosa, 530 parts of Rosa chinensis var. chinensis, 525 parts of Paeonia lactiflora, 1050 parts of Salvia miltiorrhiza, and 310 parts of Celosia argentea. Compared with the prior art, the components of the traditional Chinese medicine composition of the present invention are scientifically matched and work synergistically to improve ovarian dysfunction. The preparation method is simple, with significant curative effect and no toxic side effects.

[0005] While existing technologies can improve ovarian function through scientifically formulated traditional Chinese medicine components, while also nourishing blood and promoting blood circulation and tonifying the kidneys, or achieving effects such as tonifying the kidneys and replenishing essence, and soothing the liver and relieving depression, they have certain effects on improving symptoms related to ovarian insufficiency and indicators such as serum hormone levels and the number of antral follicles. They also have the advantages of simple preparation and good safety. However, the formulations of existing technologies do not fully consider the dynamic changes of qi and blood before and after ovulation, and the applicable syndromes are relatively limited, only targeting specific types of ovarian function-related problems. Furthermore, they are not targeted enough for multi-system complications caused by ovarian insufficiency, such as hot flashes, night sweats, osteoporosis, and immune dysfunction. They are difficult to comprehensively cover the individual differences and clinical needs of different patients, and still have shortcomings in terms of applicability and comprehensive improvement effect. Summary of the Invention

[0006] Purpose of the invention: The purpose of this invention is to provide a traditional Chinese medicine composition for improving symptoms related to ovarian insufficiency and its application, so as to solve the problems mentioned in the background art.

[0007] Technical solution: A traditional Chinese medicine composition for improving symptoms related to ovarian insufficiency and its application, comprising the following steps: S1. Select 6-15 parts of Artemisia annua, 6-12 parts of Scutellaria baicalensis, 9-18 parts of Morinda officinalis, 15-30 parts of Triticum aestivum, 12-24 parts of Rehmannia glutinosa, 9-18 parts of Lilium brownii, 3-9 parts of Aconitum carmichaelii, and 15-30 parts of Ostrea gigas according to weight. Clean each raw material to remove non-medicinal parts and impurities. Crush the Ostrea gigas appropriately to facilitate the dissolution of active ingredients. Soak Aconitum carmichaelii in salt water and cook it to reduce toxicity. Set aside for later use. S2. Mix all the raw materials processed in S1 evenly, add 8-12 times the amount of deionized water to soak, bring to a boil over high heat, then simmer over low heat for 1-1.5 hours, and then filter the decoction; add 6-10 times the amount of deionized water to the dregs and simmer over low heat once more in the same way, and finally combine the two decoctions. S3. Place the combined decoction in a clean container, let it stand and cool to room temperature, and remove the precipitate in the decoction by filtration to obtain the purified clear decoction. S4. Transfer the clarified decoction to a vacuum concentration device, control the concentration temperature at 60-70℃, and concentrate it to a thick extract with a relative density of 1.20-1.35. Use spray drying or vacuum belt drying process to obtain dry extract powder. S5. Formulation and preparation according to target dosage form requirements: When preparing granules, mix dry extract powder with an appropriate amount of dextrin, add ethanol as a wetting agent to make soft material, sieve and granulate, dry, granulate and then package; when preparing capsules or tablets, mix dry extract powder with calcined oyster shell powder, cross-linked carboxymethyl cellulose sodium and lubricant, directly fill empty capsules or compress tablets to obtain traditional Chinese medicine preparations that improve symptoms related to ovarian insufficiency.

[0008] Preferably, in S1, Artemisia annua is the dried aerial part of Artemisia annua (Asteraceae), Scutellaria baicalensis is the dried root of Scutellaria baicalensis (Lamiaceae), Morinda officinalis is the dried root of Morinda officinalis (Rubiaceae), Triticum aestivum is the immature dried light caryopsis of Triticum aestivum (Poaceae), Rehmannia glutinosa is the processed and dried tuberous root of Rehmannia glutinosa (Scrophulariaceae), calcined oyster shell is crushed to 20-40 mesh, and the processing method of processed Aconitum carmichaelii is: soaking in salt water for 2-4 hours, steaming for 1-2 hours, and drying to a moisture content ≤10%; the preferred ratio of each raw material is 8-12 parts Artemisia annua, 8-10 parts Scutellaria baicalensis, 10-15 parts Morinda officinalis, 18-25 parts Triticum aestivum, 15-20 parts Rehmannia glutinosa, 10-15 parts Lilium brownii, 4-7 parts processed Aconitum carmichaelii, and 20-28 parts calcined oyster shell.

[0009] Preferably, in step S2, the raw materials are soaked in deionized water for 30-60 minutes after mixing.

[0010] Preferably, in step S3, the decoction is allowed to stand and cool for 2-4 hours, and the filtration is carried out using double-layer filter paper. The first layer is qualitative filter paper, and the second layer is quantitative filter paper. The filtration speed is controlled at 5-10 mL / min, and the turbidity of the clarified decoction is ≤5 NTU.

[0011] Preferably, in step S4, the vacuum degree of the reduced pressure concentration is 0.06-0.08 MPa, the relative density of the thick extract is measured at 60°C, the inlet temperature of the spray drying is 140-180°C, the outlet temperature is 80-100°C, the temperature of the vacuum belt drying is 60-70°C, the vacuum degree is 0.07-0.09 MPa, the moisture content of the dry extract powder is ≤5%, and the particle size is 80-120 mesh.

[0012] Preferably, in step S5, when preparing granules, the ethanol concentration is 70%-80%, the humidity of the soft material is controlled at 30%-40%, granulation is performed using a 16-24 mesh sieve, the drying temperature is 40-80℃, and the drying time is 2-4 hours. When preparing capsules or tablets, the particle size of the calcined oyster shell powder is 100-120 mesh, and the amount of croscarmellose sodium added is 1%-3% of the weight of the dry extract powder.

[0013] Preferably, during the S2 decoction process, the mixture needs to be stirred regularly. During the first decoction, it should be stirred once every 20-30 minutes, and during the second decoction, it should be stirred once every 15-20 minutes. The stirring speed is 30-50 r / min.

[0014] Preferably, when preparing the granules, volatile oil and excipients encapsulated by the inclusion complex need to be added, mixed evenly, and then packaged.

[0015] Beneficial Effects: By scientifically combining Artemisia annua, Scutellaria baicalensis, Morinda officinalis, and other traditional Chinese medicines, and following the treatment principle of "clearing the upper body and warming the lower body, harmonizing the heart and kidneys," comprehensive intervention is achieved. This not only significantly improves vasomotor symptoms such as hot flashes and night sweats, and alleviates sleep disorders such as insomnia and irritability, but also prevents and improves osteoporosis through its kidney-tonifying and bone-strengthening effects. Simultaneously, it regulates immune imbalances, filling the gap in existing drug formulations for complex syndromes. This composition uses natural traditional Chinese medicines, avoiding hormone-related adverse reactions, ensuring good safety. Furthermore, the raw materials are widely available, cost-effective, and have high medical accessibility. Clinical and animal experiments have demonstrated that it can effectively regulate sex hormone levels, improve bone metabolism, and reduce inflammatory factors, providing a safe and effective alternative for patients who are unwilling or unable to undergo hormone therapy. This aligns with the policy direction of promoting the widespread use of traditional Chinese medicine, has a wide range of applications, and good patient compliance. Attached Figure Description

[0016] Figure 1This is a schematic diagram of the method flow of the present invention. Detailed Implementation

[0017] To make the technical solution of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0018] Example 1 A traditional Chinese medicine composition for improving symptoms related to ovarian insufficiency and its application, comprising: Preparation of decoction: (1) Weigh out the raw medicinal materials: 10 parts Artemisia annua, 9 parts Scutellaria baicalensis, 12 parts Morinda officinalis, 20 parts Triticum aestivum, 18 parts Rehmannia glutinosa, 12 parts Lilium brownii, 6 parts Aconitum carmichaelii, and 25 parts Calcined Oyster Shell.

[0019] (3) Clean each raw material to remove non-medicinal parts and impurities; crush calcined oyster shell to 20-40 mesh to facilitate the dissolution of active ingredients; soak cooked aconite root slices in salt water for 3 hours, then steam for 1.5 hours and dry to a moisture content of ≤10% to reduce toxicity, and set aside for later use.

[0020] (4) Mix all the processed raw materials evenly, add 10 times the amount of deionized water and soak for 45 minutes. After boiling over high heat, turn to low heat and keep it simmering for 80 minutes. Stir once every 25 minutes during this period, with a stirring speed of 40 r / min. Then filter the liquid.

[0021] (5) Add 8 times the amount of deionized water to the dregs and simmer over low heat for 60 minutes, stirring once every 18 minutes at a speed of 35 r / min. After filtering the liquid, combine the two decoctions.

[0022] (6) Place the combined decoction in a clean container and let it stand and cool to room temperature for 3 hours. Filter it with double-layer filter paper (the first layer is qualitative filter paper and the second layer is quantitative filter paper) and control the filtration speed to 8 mL / min to remove the precipitate in the decoction and obtain a clear decoction with turbidity ≤ 5 NTU.

[0023] (7) Transfer the clarified decoction to a vacuum concentration device, control the vacuum degree to 0.07 MPa and the concentration temperature to 65°C, and concentrate it to a thick extract with a relative density of 1.28 (measured at 60°C).

[0024] (8) Mix the compound decoction and edible preservative, and then package them to obtain a traditional Chinese medicine decoction that improves symptoms related to ovarian insufficiency.

[0025] Example 2 A traditional Chinese medicine composition for improving symptoms related to ovarian insufficiency and its application, comprising: Pill preparation: (1) Weigh out the raw medicinal materials: 10 parts Artemisia annua, 9 parts Scutellaria baicalensis, 12 parts Morinda officinalis, 20 parts Triticum aestivum, 18 parts Rehmannia glutinosa, 12 parts Lilium brownii, 6 parts Aconitum carmichaelii, and 25 parts Calcined Oyster Shell.

[0026] (2) The raw materials are cleaned and processed according to step (2) in Example 1 and then prepared for use.

[0027] (3) Mix all the processed raw materials evenly, add 10 times the amount of deionized water and soak for 40 minutes. After boiling over high heat, reduce to low heat and simmer for 80 minutes, stirring once every 20 minutes at a stirring speed of 30 r / min. Filter the decoction. Add 8 times the amount of deionized water to the dregs and simmer over low heat for 60 minutes, stirring once every 15 minutes at a stirring speed of 30 r / min. Filter the decoction and combine the two decoctions.

[0028] (4) Following step (5) in Example 1, the combined decoction was allowed to stand, cooled, and filtered to obtain a clear decoction.

[0029] (5) Transfer the clarified decoction to a vacuum concentration device, control the vacuum degree to 0.06 MPa and the concentration temperature to 60°C, and concentrate it to a thick extract with a relative density of 1.20 (measured at 60°C).

[0030] (6) Take the above thick extract, add an appropriate amount of excipient, mix thoroughly and make into pills, place in an environment of 40-80℃ to dry for 2-4 hours, and then package into pills.

[0031] Example 3 A traditional Chinese medicine composition for improving symptoms related to ovarian insufficiency and its application, comprising: Granule preparation: (1) Weigh out the raw medicinal materials: 10 parts Artemisia annua, 9 parts Scutellaria baicalensis, 12 parts Morinda officinalis, 20 parts Triticum aestivum, 18 parts Rehmannia glutinosa, 12 parts Lilium brownii, 6 parts Aconitum carmichaelii, and 25 parts Calcined Oyster Shell.

[0032] (2) The raw materials are cleaned and processed according to step (2) in Example 1 and then prepared for use.

[0033] (3) Mix all the processed raw materials evenly, add 10 times the amount of deionized water and soak for 50 minutes. After boiling over high heat, reduce to low heat and simmer for 80 minutes, stirring once every 30 minutes at a speed of 50 r / min. Filter the decoction. Add 8 times the amount of deionized water to the dregs and simmer over low heat for 60 minutes, stirring once every 20 minutes at a speed of 40 r / min. Filter the decoction and combine the two decoctions.

[0034] (4) Following step (5) in Example 1, the combined decoction was allowed to stand, cooled, and filtered to obtain a clear decoction.

[0035] (5) Transfer the clarified decoction to a vacuum concentration device, control the vacuum degree to 0.08 MPa and the concentration temperature to 70°C, and concentrate it to a thick extract with a relative density of 1.35 (measured at 60°C).

[0036] (6) The thick extract is processed by spray drying process, with the inlet temperature set at 140-180℃ and the outlet temperature at 80-100℃, to obtain dry extract powder with a moisture content of ≤5% and a particle size of 80-120 mesh.

[0037] (7) Mix the dry extract powder with an appropriate amount of dextrin, add 75% ethanol as a wetting agent to make soft material, control the moisture content of the soft material at 35%, sieve through a 20-mesh sieve to granulate, dry in an environment of 40-80℃ for 2-4 hours, add volatile oil and excipients encapsulated by the inclusion complex after granulation, mix evenly and then package to obtain granules.

[0038] The traditional Chinese medicine compositions used in Examples 1-3 above strictly follow the TCM theory of "principal, assistant, adjuvant, and guide" and the core treatment principle of "clearing the upper body and warming the lower body, harmonizing the heart and kidneys." The formulation logic is clear and the synergistic effect is well-defined. The principal herbs are Rehmannia glutinosa (processed) and Morinda officinalis. Rehmannia glutinosa is slightly warm in nature and sweet in taste. It enters the liver and kidney meridians and has the effects of nourishing yin and blood, replenishing essence and marrow. It precisely targets the core pathogenesis of "kidney deficiency and essence depletion" in ovarian insufficiency. Morinda officinalis is slightly warm in nature and sweet and pungent in taste. It enters the kidney and liver meridians and can tonify kidney yang, strengthen tendons and bones, and dispel wind and dampness. When used together with Rehmannia glutinosa, it can tonify both yin and yang and work together to tonify the kidney and replenish essence, and warm and nourish the ovaries. The assistant herbs are Artemisia annua and Scutellaria baicalensis. Artemisia annua is cold in nature, bitter and pungent in taste, and enters the liver and gallbladder meridians. It is good at clearing deficiency heat, eliminating bone steaming, and stopping night sweats. It is specifically used to treat tidal fever symptoms caused by deficiency heat in the upper burner. Scutellaria baicalensis is cold in nature, bitter in taste, and enters the lung, gallbladder, spleen, large intestine, and small intestine meridians. It clears heat and dries dampness, drains fire and detoxifies. It helps Artemisia annua enhance its ability to clear deficiency heat in the upper burner. The two herbs work together to clear deficiency heat and relieve discomfort related to vasomotor function. The adjuvant herbs are floating wheat, lily bulb, and calcined oyster shell. Floating wheat is cool in nature and sweet in taste. It enters the heart meridian and invigorates qi, clears heat, and stops sweating. It specifically improves stubborn night sweats. Lily bulb is slightly cold in nature and sweet in taste. It enters the lung and heart meridians and nourishes yin and moistens the lungs. It clears the heart and calms the mind and relieves insomnia and irritability. Calcined oyster shell is slightly cold in nature and salty in taste. It enters the liver and kidney meridians and calms the mind, subdues yang and nourishes yin, softens hardness and dissipates nodules. It not only helps floating wheat and lily bulb enhance the effects of stopping sweating and calming the mind, but also invigorates the kidneys and strengthens bones, and prevents osteoporosis. The herb is prepared aconite root, which is very hot in nature, pungent and sweet in taste, and enters the heart, kidney and spleen meridians. It warms the kidney and assists yang, dispels cold and relieves pain, and harmonizes the coldness of artemisia annua and scutellaria baicalensis with the warmth of prepared rehmannia root and morinda root. It connects the heart and kidneys and harmonizes the cold and heat in the upper and lower body. After being processed by soaking in salt water for 2-4 hours and steaming for 1-2 hours, its toxicity is significantly reduced (moisture content ≤10%), which not only ensures the safety of medication, but also helps to implement the whole prescription treatment method.

[0039] From the perspective of modern pharmacological research, Rehmannia glutinosa polysaccharide in Rehmannia glutinosa can regulate the function of ovarian granulosa cells, promote the secretion of estradiol (E2), and improve the imbalance of sex hormone levels. Morinda officinalis polysaccharide in Morinda officinalis can enhance antioxidant capacity and protect ovarian tissue from oxidative damage. Artemisinin in Artemisia annua and baicalin in Scutellaria baicalensis have anti-inflammatory and immune-regulating effects, and can reduce the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Flavonoids in Triticum aestivum and polysaccharide in Lilium brownii can calm the nerves and improve sleep quality. Calcined oyster shell is rich in minerals such as calcium and zinc and oyster polysaccharide, which can supplement bone nutrition, reduce the level of the bone resorption marker β-CTX, increase bone density, and delay the progression of osteoporosis. The synergistic effect of multiple components and multiple targets in the whole formula forms a comprehensive intervention advantage.

[0040] The traditional Chinese medicine composition of this invention has clear efficacy and can be used to prevent and / or treat ovarian insufficiency and related symptoms such as hot flashes and night sweats, insomnia and irritability, lower back and knee pain and coldness, menstrual disorders, immune dysfunction and osteoporosis. Its efficacy has been fully verified by clinical research and animal experiments (see subsequent test examples 1 and 2 for details), providing solid experimental data support for clinical application.

[0041] Experimental Example 1 To verify the overall clinical efficacy of the present invention, the following clinical observations were conducted, including: 1. Research Methods Study design: Randomized, positive-drug controlled clinical trial.

[0042] Number of cases: 20, randomly divided into two groups at a ratio of 1:1.

[0043] Inclusion criteria: meeting the diagnostic criteria for perimenopausal syndrome and having a Kupperman score ≥20.

[0044] Exclusion criteria: Use of hormone medications within the past 3 months, or serious organic diseases.

[0045] 2. Treatment Plan Experimental group: Take the traditional Chinese medicine decoction prepared in Example 1, one dose per day, decocted in water to obtain 300ml of juice, taken warm twice a day, morning and evening.

[0046] Control group: Oral administration of Zhi Bai Di Huang Wan.

[0047] Treatment duration: 12 weeks.

[0048] 3. Observation Indicators Key metric: Kupperman score.

[0049] Secondary indicators: E2 (estradiol), FSH (follicle-stimulating hormone), bone mineral density, β-CTX (bone resorption marker), TNF-α (tumor necrosis factor α).

[0050] Safety indicators: liver and kidney function, adverse events.

[0051] 4. Research Results 4.1. Evaluation of efficacy: The Kupperman score of the experimental group decreased significantly after treatment, and all minor indicators were significantly improved. The Kupperman score and some minor indicators of the control group improved after treatment, but the overall improvement was not as great as that of the experimental group.

[0052] 4.2. Comparison of overall effectiveness: Experimental group: 1 case was clinically cured, 5 cases showed significant improvement, 3 cases showed improvement, and 1 case was ineffective, with a total effective rate of 90%; Control group: 0 cases of clinical cure, 3 cases of significant effect, 5 cases of effect, 2 cases of no effect, with a total effective rate of 80%.

[0053] 4.3. Safety evaluation: During the treatment, one patient in the experimental group experienced mild gastrointestinal discomfort, with an adverse reaction rate of 10%; one patient in the control group experienced mild dizziness, with an adverse reaction rate of 10%. All symptoms resolved spontaneously and did not affect the treatment. No abnormalities were observed in liver and kidney function in either group.

[0054] 5. Medical Record Analysis Ms. Zhang, 48 years old, presented with paroxysmal hot flashes and night sweats for over six months, which had worsened and were accompanied by insomnia for one month. She also experienced irritability, lower back and knee pain, and coldness. Her test results showed FSH: 48.5 mIU / mL, E2: 28.3 pg / mL, lumbar spine L1-L4 bone mineral density T-score: -1.8, and TNF-α: 38.9 pg / mL. After 4 weeks of treatment with the drug of this invention, the frequency of hot flashes decreased to 5-6 times per day, night sweats were significantly reduced, sleep improved (5-6 hours of sleep per night), limbs warmed up, and nocturia decreased to 1-2 times per night. After 8 weeks of treatment with the drug of this invention, hot flashes occurred 2-3 times a day with only slight sweating, sleep improved further, mood improved significantly, and symptoms of lower back and knee weakness were significantly reduced. Follow-up examination showed FSH: 32.1 mIU / mL, E2: 42.5 pg / mL. After 12 weeks of treatment with the drug of this invention, symptoms such as hot flashes, night sweats, and insomnia were significantly improved, and the menstrual cycle became more regular. Follow-up tests showed that FSH was 24.8 mIU / mL, E2 was 52.1 pg / mL, bone mineral density T value was -1.5, and TNF-α was 24.5 pg / mL, with all indicators showing improvement compared to before.

[0055] Experimental Example 2 By establishing a castrated rat model to simulate the perimenopausal period and POI (early-onset ovarian insufficiency) state, the effects of the traditional Chinese medicine composition obtained in the examples on improving vasomotor symptoms, osteoporosis, and abnormal immune function were comprehensively evaluated. The specific steps included: (1) Take 50 SPF-grade 12-week-old female SD rats with a weight of 200±20g; the test drug is the granules prepared from the traditional Chinese medicine composition obtained in Example 3 (raw material ratio: 10 parts Artemisia annua, 9 parts Scutellaria baicalensis, 12 parts Morinda officinalis, 20 parts Triticum aestivum, 18 parts Rehmannia glutinosa, 12 parts Lilium brownii, 6 parts Aconitum carmichaelii, 25 parts Ostrea gigas); prepare enzyme-linked immunosorbent assay (ELISA) kit (for detecting E2, FSH, LH, TNF-α, IL-6, PINP, β-CTX, etc.), dual-energy X-ray bone densitometer and other reagents and instruments for later use.

[0056] (2) After acclimatizing the rats for 1 week, they were randomly divided into 5 groups (10 rats in each group): sham surgery group (only the abdominal cavity was opened, the ovaries were not removed, and an equal volume of pure water was given), model group (bilateral oophorectomy (OVX) was performed, and an equal volume of pure water was given after the operation), high-dose group of the drug of the present invention (OVX + the drug of the present invention, the dose was 2 times the clinical equivalent dose), medium-dose group of the drug of the present invention (OVX + the drug of the present invention, the dose was the clinical equivalent dose), and low-dose group of the drug of the present invention (OVX + the drug of the present invention, the dose was 0.5 times the clinical equivalent dose).

[0057] (3) One week after the operation, rats in each group were given oral administration once a day for four consecutive weeks. After the last administration, the rats were anesthetized, blood was collected through the abdominal aorta, and serum was separated. The uterus was quickly removed and weighed (the uterine coefficient was calculated). The left tibia and L4-L6 lumbar vertebrae were taken for later use.

[0058] (4) The levels of E2, FSH, LH, TNF-α, IL-6, PINP and β-CTX in serum were detected by enzyme-linked immunosorbent assay (ELISA); the bone mineral density of the lumbar spine was detected by dual-energy X-ray absorptiometry.

[0059] (5) The test results are shown in Tables 1-3 below: Table 1: Effects of OVX rat serum hormone levels and uterine coefficient As shown in Table 1, compared with the sham surgery group, the model group showed a significant decrease in E2 level, a significant increase in FSH level, and a significant decrease in uterine coefficient. Compared with the model group, all dosage groups of the drug of this invention can regulate sex hormone levels and increase uterine coefficient, indicating that it has a clear effect on improving endocrine disorders.

[0060] Table 2: Effects on bone mineral density and bone metabolism in OVX rats As shown in Table 2, the lumbar spine bone mineral density was significantly reduced and the β-CTX level was significantly increased in the model group. The drug of the present invention can increase bone mineral density and reduce the level of bone resorption markers in each dose group, which reflects its effect of improving vasomotor symptoms and preventing osteoporosis.

[0061] Table 3: Effects on serum inflammatory factors in OVX rats As shown in Table 3, the levels of TNF-α and IL-6 in the model group were significantly increased; the drug of this invention can reduce the level of pro-inflammatory cytokines and has an immunomodulatory effect.

[0062] (6) Summary The drug of this invention can significantly regulate sex hormone levels and improve ovarian insufficiency, while also improving vasomotor symptoms and preventing osteoporosis; it can effectively regulate immune imbalance and reduce inflammatory factor levels, demonstrating the unique advantages brought by the combination of artemisia annua and other drugs.

[0063] Comparative Example 1 The difference between Comparative Example 1 and Examples 1-3 is that Comparative Example 1 uses a "nourishing water and nourishing wood, cultivating yin and nourishing blood" formula plus conventional decoction process (refer to comparative document CN115779035B), and regulates ovarian function only through the yin-nourishing and blood-nourishing components, including the following steps: Weigh the ingredients by weight as follows: 15g of North American ginseng, 10g of vinegar-processed tortoise shell, 15g of wine-processed privet fruit, 10g of angelica sinensis, 10g of prepared rehmannia root, 15g of wine-processed cornus officinalis, 10g of dodder seed, 15g of wolfberry fruit, 10g of wine-processed cistanche deserticola, 15g of polygonatum odoratum, 10g of white peony root, 10g of vinegar-processed cyperus rhizome, and 10g of mulberry fruit.

[0064] Mix all the ingredients and boil them with water at least twice. Combine the two decoctions to obtain the decoction.

[0065] Dosage: 1 dose per day, taken warm 30 minutes after breakfast and dinner, for 3 consecutive menstrual cycles, without stopping during menstruation.

[0066] Comparative Example 2 The difference between Comparative Example 2 and Examples 1-3 is that Comparative Example 2 uses a "tonifying kidney and replenishing essence, soothing the liver and relieving depression" formula plus a pulverizing and decoction process (refer to the prior art CN118403128A in the background section above), which improves ovarian function only through the kidney-tonifying and blood-activating components, including the following steps: Weigh the raw materials by weight as follows: 20 parts Cuscuta chinensis, 10 parts Cistanche deserticola, 15 parts Lycium barbarum, 15 parts Polygonatum sibiricum, 15 parts Codonopsis pilosula, 10 parts Atractylodes macrocephala, 10 parts Nelumbo nucifera, 10 parts Dendrobium nobile, 5 parts Lilium brownii, 5 parts Rosa rugosa, 5 parts Rosa chinensis, 15 parts Paeonia lactiflora, 15 parts Salvia miltiorrhiza, and 3 parts Celosia argentea.

[0067] The raw materials are crushed, mixed with water and decocted for 1.5 hours. The decoction is then filtered. The residue is mixed with water and decocted for another 1.5 hours. The decoctions are combined and dried to obtain the traditional Chinese medicine composition.

[0068] Administration: One dose per day, decocted in water and taken warm in two divided doses. One course of treatment is 15 days, and three courses of treatment are required.

[0069] Comparative Example 3 The difference between Comparative Example 3 and Examples 1-3 is that Comparative Example 3 uses a "blood-nourishing, blood-activating, kidney-tonifying, and essence-replenishing" formula for regulating menstruation combined with a conventional decoction process (refer to the prior art document CN121102344A in the background section above). It improves ovarian function solely through pre- and post-ovulation administration of medication, including the following steps: Before ovulation, weigh out the following ingredients: Angelica sinensis 10g, stir-fried white peony root 10g, Taxillus chinensis 12g, Cuscuta chinensis 12g, stir-fried Atractylodes macrocephala 10g, Ligusticum chuanxiong 4g, Lycopus lucidus 10g, Albizia julibrissin flower 12g, and prepared licorice root 6g. After ovulation, add Morinda officinalis 10g and Ligustrum lucidum 10g.

[0070] Mix the ingredients, soak them in water, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter the decoction. Add water to the residue and simmer for another 30 minutes using the same method. Combine the two decoctions.

[0071] Dosage: 1 dose daily, 150ml taken warm half an hour after breakfast and dinner. Each course of treatment is 28 days, and 3 courses of treatment are required. Do not stop taking the medication during menstruation.

[0072] To illustrate the improvement of ovarian insufficiency-related symptoms described in this invention, tests were conducted on Examples 1-3 and Comparative Examples 1-3. These tests included the improvement rate of the Kupperman score, the increase in estradiol (E2), the decrease in follicle-stimulating hormone (FSH), the increase in lumbar spine bone mineral density, the decrease in tumor necrosis factor-α (TNF-α), the overall effective rate, and the incidence of adverse reactions. The Kupperman score was assessed using a clinical symptom rating scale. Hormone levels and inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA). Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA). The overall effective rate was determined based on a comprehensive assessment of the degree of improvement in clinical symptoms and changes in indicators. The incidence of adverse reactions was statistically analyzed by recording adverse events during the treatment period. The test results are shown in the table below: As can be seen from the comparison of the examples and comparative examples, the present invention uses the treatment principle of "clearing the upper body and warming the lower body, and harmonizing the heart and kidneys" combined with traditional Chinese medicines such as Artemisia annua, Scutellaria baicalensis, and Morinda officinalis, integrating multiple effects such as nourishing yin and clearing heat, tonifying the kidneys and warming yang. This significantly improves the effect of improving the symptoms of multiple systems in ovarian insufficiency. Compared with traditional formulas, the present invention is more effective in regulating sex hormones, and can also simultaneously improve vasomotor symptoms, delay bone loss, and regulate immune imbalance. It has a high overall effective rate and a low adverse reaction rate. The present invention solves the problems of poor applicability and insufficient comprehensive effect of traditional formulas through multi-component synergy. At the same time, it has the safety of natural Chinese medicines, avoids the risks of hormone therapy, and has a wide range of raw materials and simple preparation, providing more comprehensive treatment options for relevant patients and facilitating clinical promotion.

[0073] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A traditional Chinese medicine composition for improving symptoms associated with ovarian dysfunction and uses thereof, characterized in that, It comprises the following steps: S1, selecting by weight parts Artemisia annua 6-15 parts, Scutellaria baicalensis 6-12 parts, Morinda officinalis 9-18 parts, Triticum vulgare 15-30 parts, Radix Rehmanniae Preparata 12-24 parts, Lilium brownii 9-18 parts, Fritillaria cirrhosa 3-9 parts, Oyster Shell 15-30 parts, treating each raw material to remove non-medicinal parts and impurities, crushing Oyster Shell to facilitate effective component dissolution, soaking Fritillaria cirrhosa in salt water, and steaming and cooking to reduce toxicity for standby; S2, mixing all the raw materials treated in S1 uniformly, adding 8-12 times of deionized water for soaking, then boiling with strong fire and keeping micro-boiling with weak fire for 1-1.5 hours, then filtering the liquid; adding 6-10 times of deionized water to the residue, and boiling with weak fire again, finally combining the two times of decoction; S3, placing the combined decoction in a clean container, cooling to room temperature, removing the precipitate in the decoction by filtration, and obtaining the purified clear decoction; S4, transferring the clear decoction into a reduced pressure concentration device, controlling the concentration temperature at 60-70℃, concentrating to thick extract with relative density of 1.20-1.35, and obtaining dry extract powder by spray drying or vacuum belt drying process; S5, according to the requirements of target dosage form, preparing by molding: when preparing granules, mixing dry extract powder and appropriate amount of dextrin uniformly, adding ethanol as wetting agent to prepare soft material, sieving, drying, and whole granulating, and then packaging; when preparing capsules or tablets, mixing dry extract powder, Oyster Shell powder, cross-linked sodium carboxymethyl cellulose, and lubricant uniformly, and then filling into empty capsules or pressing into tablets, to obtain traditional Chinese medicine preparation for improving symptoms related to ovarian dysfunction. 2.The traditional Chinese medicine composition for improving the symptoms associated with ovarian dysfunction and uses thereof according to claim 1, characterized in that, In S1, Artemisia annua is the dried aerial part of Chrysanthemum morifolium, Scutellaria baicalensis is the dried root of Scutellaria baicalensis, Morinda officinalis is the dried root of Morinda officinalis, Triticum vulgare is the immature dry light and floating chaff of Triticum aestivum, Radix Rehmanniae Preparata is the processed and steamed root of Lamiaceae, Oyster Shell is crushed to 20-40 mesh, and the processing technology of Fritillaria cirrhosa is: soaking in salt water for 2-4 hours, steaming and cooking for 1-2 hours, and drying to water content≤10%; the preferred ratio of each raw material is Artemisia annua 8-12 parts, Scutellaria baicalensis 8-10 parts, Morinda officinalis 10-15 parts, Triticum vulgare 18-25 parts, Radix Rehmanniae Preparata 15-20 parts, Lilium brownii 10-15 parts, Fritillaria cirrhosa 4-7 parts, and Oyster Shell 20-28 parts. 3.The traditional Chinese medicine composition for improving the symptoms associated with ovarian dysfunction and uses thereof according to claim 1, characterized in that, In S2, the soaking time of raw materials in deionized water is 30-60 minutes. 4.The traditional Chinese medicine composition for improving the symptoms associated with ovarian dysfunction and uses thereof according to claim 1, characterized in that, In S3, the cooling time of decoction is 2-4 hours, the filtration is performed by double-layer filter paper, the first layer is qualitative filter paper, and the second layer is quantitative filter paper, the filtration speed is controlled at 5-10 mL / min, and the turbidity of clear decoction is≤5 NTU. 5.The traditional Chinese medicine composition for improving the symptoms associated with ovarian dysfunction and uses thereof according to claim 1, characterized in that, In S4, the vacuum degree of reduced pressure concentration is 0.06-0.08 MPa, the relative density of thick extract is measured at 60℃, the inlet temperature of spray drying is 140-180℃, the outlet temperature is 80-100℃, the temperature of vacuum belt drying is 60-70℃, the vacuum degree is 0.07-0.09 MPa, the water content of dry extract powder is≤5%, and the particle size is 80-120 mesh. 6.The traditional Chinese medicine composition for improving the symptoms associated with ovarian dysfunction and uses thereof according to claim 1, characterized in that, In the S5, when preparing granules, the concentration of ethanol is 70%-80%, the humidity of soft material is controlled in 30%-40%, the screen granulation adopts 16-24 mesh screen, the drying temperature is 40-80 ℃, the drying time is 2-4 hours, when preparing capsules or tablets, the particle size of calcined oyster shell powder is 100-120 mesh, the adding amount of cross-linked sodium carboxymethyl cellulose is 1%-3% of the weight of dry extract powder. 7.The traditional Chinese medicine composition for improving the symptoms associated with ovarian dysfunction and uses thereof according to claim 1, characterized in that, The S2 needs to be stirred regularly during the decocting process, and the stirring speed is 30-50 r / min. 8.The traditional Chinese medicine composition for improving the symptoms associated with ovarian dysfunction and uses thereof according to claim 6, characterized in that, When preparing granules, volatile oil and excipients wrapped by inclusion compound are added, and then mixed uniformly before being divided and packed.

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