Traditional Chinese medicine composition for enriching yin, nourishing kidney and producing sperms as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for enriching yin, nourishing kidney and producing sperms. The traditional Chinese medicine composition is prepared from the following components by weight: 40-50 g of kadsura longepedunculata, 100-110 g of fructus lycii, 80-90 g of semen cuscutae, 90-100 g of radix polygoni multiflori preparata, 70-80 g of fructus rubi, 60-70 g of semen plantaginis, 70-80 g of fructus ligustri lucidi, 80-90 g of herba epimedii, 70-80 g of radix morindae officinalis, 60-70 g of radix angelicae sinensis, 60-70 g of herba cynomorii and 90-100 g of radix astragali. Traditional Chinese medicinal materials such as kadsura longepedunculata, fructus lycii, semen cuscutae, radix polygoni multiflori preparata and the like are compatible, the components are properly compatible and have a synergistic effect, and the traditional Chinese medicine composition has the effects of enriching yin, nourishing the kidney and generating

Description

Technical Field

[0001] The present invention relates to the technical field of Chinese medicine compositions, and in particular to a Chinese medicine composition for nourishing yin, tonifying the kidney and producing sperm, a preparation method and an application thereof. Background Art

[0002] With the accelerated pace of modern life and the complexity and changeability of environmental factors, male reproductive health issues are receiving increasing attention. Abnormal semen quality issues such as asthenozoospermia, low sperm motility, reduced semen volume, and poor semen liquefaction have become important factors affecting male fertility. Traditional Chinese medicine provides a wealth of treatment methods and drug resources for these abnormal semen quality issues.

[0003] The main means of treating semen quality abnormalities include Western medicine and Chinese medicine. Western medicine has obvious advantages in treatment, with significant efficacy and convenient use. However, Western medicine usually has strong pharmacological effects, so it may bring some side effects during use. In addition, long-term use of certain Western medicines may cause the body to become dependent on them. Once the medicine is stopped, the condition may rebound or worsen. This dependence will not only increase the psychological burden of the patient, but also may affect the treatment effect. At the same time, the price of some Western medicines is relatively high. For patients with poor economic conditions, long-term medication may constitute a certain economic burden. Chinese medicine treatment has unique advantages. They are usually based on the holistic concept and syndrome differentiation principle of traditional Chinese medicine, aiming to treat diseases by adjusting the balance of yin and yang and the circulation of qi and blood in the body. In particular, with the improvement of the status of Chinese medicine and the gradual emergence of the limitations of Western medicine treatment, Chinese medicine treatment of semen quality abnormalities has become a trend.

[0004] To this end, the present invention provides a Chinese medicine composition for nourishing yin and tonifying the kidney, and producing sperm. The Chinese medicinal materials such as Schisandra chinensis, Lycium barbarum, Cuscuta australis, and processed Polygonum multiflorum are combined. The components are properly combined and synergistically enhanced. The composition has the effects of nourishing yin and tonifying the kidney, and producing sperm. The composition is used for asthenozoospermia, low sperm motility, reduced semen volume, poor semen liquefaction, and teratozoospermia. Summary of the invention

[0005] The present invention aims to provide a Chinese medicine composition for nourishing yin and tonifying the kidney and producing sperm and a preparation method thereof. Chinese medicinal materials such as Schisandra chinensis, Lycium barbarum, Cuscuta australis, and processed Polygonum multiflorum are combined. Each component is properly combined and synergistically enhanced, and has the efficacy of nourishing yin and tonifying the kidney and producing sperm.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] A Chinese medicine composition for nourishing yin, tonifying the kidney and producing sperm, comprising, by weight: 40-50g of Schisandra chinensis, 100-110g of Lycium barbarum, 80-90g of Cuscuta australis, 90-100g of processed Polygonum multiflorum, 70-80g of Rubus idaeus, 60-70g of Plantago seed, 70-80g of Ligustrum lucidum fruit, 80-90g of Epimedium, 70-80g of Morinda officinalis, 60-70g of Angelica sinensis, 60-70g of Cynomorium songaricum and 90-100g of Astragalus.

[0008] Working principle and beneficial effects of the present invention:

[0009] Schisandra chinensis: It has the effects of astringency, kidney-tonifying, essence-tonifying, heart-nourishing, and lung-tonifying. It can treat chronic cough, asthma, spontaneous sweating, night sweats, thirst due to loss of body fluid, palpitations, and insomnia. Schisandra chinensis also has antioxidant, lipid-lowering, and blood pressure-lowering effects, especially improving spermatorrhea and enuresis due to kidney deficiency, enhancing immunity, and relieving insomnia caused by heart-kidney disharmony.

[0010] Lycium barbarum: It has the effects of nourishing yin and benefiting the kidney, clearing the liver and improving eyesight, moistening the lungs and relieving cough, and regulating immunity. It has an auxiliary therapeutic effect on symptoms such as soreness of the waist and knees, impotence, and spermatorrhea caused by kidney yin deficiency and insufficient essence and blood; Lycium barbarum is sweet and flat in nature, enters the kidney meridian, has the effect of nourishing yin and tonifying the kidney, helps to improve asthenospermia caused by kidney yin deficiency and insufficient essence and blood, and enhances the function of the reproductive system.

[0011] Cuscuta: It has the effects of clearing away heat and detoxifying, relieving inflammation and hemostasis, removing dampness and moistening dryness, strengthening tendons and spleen, consolidating semen and reducing urine. It can inhibit viruses, promote metabolism in the body, and inhibit inflammation. Cuscuta is rich in minerals, vitamins and proteins, has the effect of consolidating semen and reducing urine, can effectively prevent the unnecessary loss of semen, treat impotence, spermatorrhea, infertility caused by kidney deficiency, and improve sperm quality.

[0012] Prepared Polygonum multiflorum: It can nourish the liver and kidney, prevent and treat cardiovascular and cerebrovascular diseases, and resist aging. It has obvious therapeutic effects on dizziness, tinnitus, soreness of waist and knees, impotence and other symptoms caused by liver and kidney deficiency. At the same time, prepared Polygonum multiflorum can also lower cholesterol and blood sugar, strengthen the heart, protect the heart, blacken the hair, strengthen the bones and muscles, moisturize the intestines and promote bowel movements, etc. It can nourish the liver and kidney, enhance the overall health of the body, regulate endocrine, and help improve asthenospermia caused by liver and kidney deficiency.

[0013] Raspberry: It has the effects of nourishing the kidney and strengthening yang, consolidating sperm and locking urine, strengthening the brain and improving eyesight, and protecting the heart. It can be used to treat kidney yang deficiency, fear of cold and other symptoms; treat kidney deficiency, spermatorrhea, frequent urination, and help improve sperm motility.

[0014] Plantago: It has the effects of clearing away heat and relieving summer heat, removing dampness and dampness, relaxing the middle and replenishing qi, detoxifying and nourishing the skin, relieving cough and relieving asthma, etc. It can remove heat and toxins from the body, eliminate headaches, fever and other symptoms caused by heat and toxins; inhibit the secretion of sweat in the body, dredge the lymph, nourish qi and activate blood circulation, and effectively inhibit the growth of bacteria; relax bronchial smooth muscles, relieve airway spasms, etc., clear damp heat from the lower jiao, balance the nourishing and greasy effect of kidney-tonifying medicines, and improve genital inflammation.

[0015] Fructus Ligustri Lucidi: It can nourish the liver and kidney, improve eyesight and blacken hair, clear away heat and reduce fire, enhance immunity, and resist oxidation, etc. It can improve asthenospermia caused by liver and kidney yin deficiency and regulate immunity.

[0016] Epimedium: It has the effects of tonifying kidney and strengthening yang, enhancing immunity, resisting osteoporosis, helping to improve cardiovascular function, and anti-inflammatory. It can improve symptoms such as soreness of waist and knees, chills and cold limbs, impotence and spermatorrhea caused by insufficient kidney yang, treat impotence and infertility caused by kidney yang deficiency, and promote testosterone secretion.

[0017] Morinda officinalis: It has the effects of tonifying kidney and strengthening yang, strengthening tendons and bones, dispelling wind and dampness, anti-inflammatory and swelling, anti-aging, etc. It is often used to treat symptoms such as impotence and premature ejaculation caused by kidney yang deficiency, treat kidney yang deficiency, impotence and spermatorrhea, and enhance sexual function and sperm production.

[0018] Angelica: It has the effects of nourishing blood and activating blood circulation, regulating menstruation and relieving pain, moistening intestines and relieving constipation. It is often used to treat symptoms such as blood deficiency and sallow complexion, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, improve blood deficiency and essence deficiency, and promote blood circulation in the reproductive system.

[0019] Cynomorium songaricum: Cynomorium songaricum has the effects of tonifying kidney yang, benefiting essence and blood, moistening intestines and relieving constipation. It is often used to treat symptoms such as soreness of waist and knees, impotence and spermatorrhea, dry intestines and constipation caused by kidney yang deficiency and deficiency of essence and blood, and to treat impotence and low sperm count caused by deficiency of kidney yang and deficiency of essence and blood.

[0020] Astragalus: Astragalus has the effects of replenishing qi and strengthening the exterior, promoting diuresis and expelling toxins, draining pus, healing sores and promoting tissue regeneration. It is often used to treat symptoms such as qi deficiency and fatigue, poor appetite and loose stools, and qi sinking, enhance immunity, and improve low sperm motility caused by qi deficiency.

[0021] The above prescription works through the following mechanisms:

[0022] (1) Therapeutic effect on asthenospermia

[0023] Tonify the kidney and replenish essence: Cuscuta, Lycium barbarum, processed Polygonum multiflorum, and Ligustrum lucidum directly nourish the yin of the liver and kidney and replenish reproductive essence; warm the kidney and support yang: Epimedium, Morinda officinalis, and Cynomorium songaricum warm and nourish the kidney yang and promote sperm production and vitality; activate blood circulation and replenish qi: Angelica sinensis and Astragalus membranaceus improve qi and blood circulation and provide nutritional support for sperm; consolidate the essence: Rubus idaeus and Schisandra chinensis consolidate essence and stop nocturnal emission, reducing abnormal semen loss; clear heat and remove dampness: Plantago clears dampness and heat and improves the environment in the reproductive tract. At the same time, this formula takes into account both yin and yang, focusing on nourishing yin and supplementing yang:

[0024] (2) Characteristics of the combination of Yin-nourishing and kidney-tonifying drugs

[0025] The core of nourishing Yin: Lycium barbarum, Ligustrum lucidum, and processed Polygonum multiflorum nourish kidney Yin and replenish essence and blood; seeking Yang from Yin: Cuscuta chinensis and Rubus idaeus warm kidney Yang on the basis of nourishing Yin, avoiding the nourishing effect of pure Yin medicine; replenishing Qi and blood: Astragalus and Angelica sinensis indirectly help kidney essence to be produced by replenishing Qi and generating blood; balancing and regulating: Plantago seed eliminates dampness and prevents nourishment and greasiness, while Epimedium and Morinda officinalis are slightly warm and help Yang without being too dry.

[0026] In summary, the Chinese medicine composition has the effects of nourishing yin and tonifying the kidney, producing sperm, and is used for asthenozoospermia, low sperm motility, reduced semen volume, poor semen liquefaction, and teratozoospermia.

[0027] In some embodiments, the Chinese medicine composition includes, by weight: 40g of Schisandra chinensis, 100g of Lycium barbarum, 80g of Cuscuta australis, 90g of processed Polygonum multiflorum, 70g of Rubus idaeus, 60g of Plantago seed, 70g of Ligustrum lucidum, 80g of Epimedium, 70g of Morinda officinalis, 60g of Angelica sinensis, 60g of Cynomorium songaricum, and 90g of Astragalus.

[0028] In some embodiments, the Chinese medicine composition includes, by weight: 45g of Schisandra chinensis, 105g of Lycium barbarum, 85g of Cuscuta australis, 95g of processed Polygonum multiflorum, 75g of Rubus idaeus, 65g of Plantago seed, 75g of Ligustrum lucidum, 85g of Epimedium, 75g of Morinda officinalis, 65g of Angelica sinensis, 65g of Cynomorium songaricum, and 95g of Astragalus.

[0029] In some embodiments, the Chinese medicine composition includes, by weight: 50g of Schisandra chinensis, 110g of Lycium barbarum, 90g of Cuscuta australis, 100g of processed Polygonum multiflorum, 80g of Rubus idaeus, 70g of Plantago seed, 80g of Ligustrum lucidum, 90g of Epimedium, 80g of Morinda officinalis, 70g of Angelica sinensis, 70g of Cynomorium songaricum, and 100g of Astragalus.

[0030] A method for preparing a Chinese medicine composition comprises the following steps: crushing the twelve Chinese medicines mentioned above into fine powder, sieving the powder, and mixing the powder to obtain the composition.

[0031] A traditional Chinese medicine preparation comprises the traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0032] In some embodiments, the oral preparation includes granules, tablets, capsules, oral liquids, granules or pills.

[0033] The invention discloses an application of a Chinese medicine composition in preparing medicines for nourishing yin and tonifying kidney, producing sperm and treating asthenozoospermia. DETAILED DESCRIPTION

[0034] The following is further described in detail through specific implementation methods:

[0035] Embodiment: A Chinese medicine composition for nourishing yin, tonifying kidney and producing spermatogenesis, comprising, by weight: 50g of Schisandra chinensis, 110g of Lycium barbarum, 90g of Cuscuta australis, 100g of Polygonum multiflorum processed, 80g of Rubus idaeus, 70g of Plantago seed, 80g of Ligustrum lucidum fruit, 90g of Epimedium, 80g of Morinda officinalis, 70g of Angelica sinensis, 70g of Cynomorium songaricum and 100g of Astragalus. The above twelve Chinese medicines are crushed into fine powder, sieved and mixed to obtain the composition. HPLC fingerprint is used for medicinal material quality control to ensure the consistency of the medicinal materials (such as Lycium barbarum polysaccharides ≥30%, icariin ≥0.5%).

[0036] 1. Animal Experiment Procedure

[0037] (1) Experimental preparation

[0038] Animals: SPF male SD rats (8 weeks old, weight 180-220 g), adapted for 1 week.

[0039] Medicinal material processing: decoct and concentrate according to the above prescription ratio to make 1g / mL medicinal solution and store at 4℃.

[0040] Modeling drugs: cyclophosphamide (CTX, 35 mg / kg, dissolved in normal saline).

[0041] (2) Establishment of asthenospermia model:

[0042] CTX (35 mg / kg / d) was injected intraperitoneally for 5 consecutive days. After the model was established, the patient rested for 3 days to confirm that the model was successful (sperm density <15×10 6 / mL).

[0043] Grouping and administration: The mice were randomly divided into 6 groups (blank control group, model control group, low / medium / high dose Chinese medicine group, positive control group), 10 mice in each group. The mice were given drugs by gavage daily (0.5 / 1 / 2 g / kg of Chinese medicine, 0.5 g / kg of positive medicine) for 28 consecutive days.

[0044] (3) Sample collection and testing

[0045] Semen collection: 24 hours after the last administration, the rats were killed, the epididymal tail was cut off, placed in 37℃ PBS, and the sperm was cut into pieces to release. The sperm density, motility and deformity rate were detected using the CASA system.

[0046] Blood collection: Blood was collected from the abdominal aorta, centrifuged (3000 rpm, 10 minutes) to separate serum, and stored at -80°C. ELISA was used to detect testosterone (T), FSH, and LH levels.

[0047] Testicular tissue processing: One testis was fixed with 4% paraformaldehyde, embedded in paraffin, and HE staining was used to observe the structure of seminiferous tubules. The other testis was quickly frozen in liquid nitrogen and stored at -80℃ for Western Blot and RT-qPCR detection.

[0048] Data analysis was performed using GraphPad Prism for one-way ANOVA, and differences among groups were analyzed using the Tukey test (p < 0.05 was considered significant).

[0049] 2. Clinical Trial Steps

[0050] (1) Experimental design

[0051] Type: Randomised, double-blind, placebo-controlled trial (RCT).

[0052] Sample size: 180 cases (60 cases in each of the experimental group, placebo group, and positive control group).

[0053] Intervention period: 3 months, follow-up 1 month.

[0054] (2) Subject recruitment and grouping

[0055] Inclusion criteria: Meet the WHO diagnosis of asthenozoospermia (sperm concentration <15×10 6 / mL, forward-moving sperm <32%). TCM syndrome differentiation is kidney yin deficiency or kidney yin and yang deficiency.

[0056] Exclusion criteria: varicocele grade III or above, chromosomal abnormalities, and reproductive system infections.

[0057] Random grouping: A computer-generated random sequence was used to divide the patients into an experimental group (Chinese herbal granules), a placebo group, and a positive control group (Wu Zi Yan Zong Pills).

[0058] (3) Intervention and follow-up

[0059] Dosage regimen

[0060] Experimental group: Chinese medicine granules (twice a day, 6 g each time).

[0061] Placebo group: Placebo pellets with the same appearance / smell.

[0062] Positive control group: Wuzi Yanzong Pills (dosage according to the instructions).

[0063] Follow-up time points: baseline, 1 month, 2 months, 3 months, and 1 month follow-up.

[0064] Detection indicators

[0065] Semen analysis: CASA system detects sperm concentration, motility, and DFI.

[0066] TCM syndrome scoring: soreness of waist and knees, sexual function, etc. (0-3 scale).

[0067] Safety indicators: liver and kidney function (ALT, AST, Cr), adverse event records.

[0068] (4) Data analysis

[0069] Primary endpoints: sperm concentration, proportion of progressively motile sperm; secondary endpoints: TCM syndrome score, DFI; statistical methods: analysis of covariance (ANCOVA) to correct baseline values, repeated measures ANOVA to evaluate time effects.

[0070] III. Toxicology study steps (1) Acute toxicity test

[0071] Animals: ICR mice (18-22 g), 10 mice per group.

[0072] Dosage regimen:

[0073] The mice were given a single oral administration (10, 20, 40 g / kg) and observed for 14 days.

[0074] Observation indicators:

[0075] Mortality, weight changes, behavioral abnormalities (e.g., diarrhea, decreased activity).

[0076] Maximum tolerated dose (MTD): the highest dose without mortality.

[0077] (2) Long-term toxicity test

[0078] Animals: SD rats (180-220 g), 20 rats in each group.

[0079] Dosage regimen: daily gavage (0.5, 1, 2 g / kg of Chinese medicine) for 6 consecutive months.

[0080] Observation indicators:

[0081] Weight: Recorded weekly.

[0082] Hematology: blood routine, liver and kidney function (ALT, AST, BUN, Cr).

[0083] Organ coefficient: ratio of heart, liver, spleen, lung and kidney weight to body weight.

[0084] Histopathology: HE staining was used to observe the organ structure.

[0085] 4. Mechanism Research Steps

[0086] (1) Network pharmacology analysis

[0087] Active ingredient screening: Use TCMSP database to screen active ingredients of traditional Chinese medicine (such as Lycium barbarum polysaccharides and icariin). Target prediction: Predict ingredient targets through SwissTargetPrediction.

[0088] Network construction: Use Cytoscape to construct a "component-target-pathway" network and screen core targets (such as AR and PI3K).

[0089] (2) Molecular experimental verification

[0090] RT-qPCR: Extract testicular tissue RNA, reverse transcribe it into cDNA, and detect the expression of Bcl-2, Bax, and SOD2 mRNA. Western Blot: Extract testicular tissue protein and detect the expression of AR and PI3K / AKT pathway proteins.

[0091] Immunohistochemistry: paraffin sections to detect the localization and expression of VEGF and AR in testicular tissue.

[0092] 5. The following experimental data were obtained through animal experiments, clinical trials, toxicology studies and mechanism studies

[0093] (1) Animal experiment data (SD rats, n = 10 / group)

[0094] Table 1

[0095] Group Treatment method (daily gavage) Blank control group Normal saline (10 mL / kg) Model control group CTX modeling + saline Low dose Chinese medicine group CTX modeling + Chinese medicine 0.5g / kg Chinese medicine medium dose group CTX modeling + Chinese medicine 1g / kg High-dose Chinese medicine group CTX modeling + Chinese medicine 2g / kg Positive control group CTX modeling + Wuzi Yanzong Pills 0.5g / kg

[0096] (2) Reproductive function data (CASA system)

[0097] Table 2

[0098]

[0099] (3) Testicular histopathology (HE staining)

[0100] Table 3

[0101]

[0102] (4) Antioxidant and inflammatory indicators

[0103] Table 4

[0104] Group SOD (U / mgprot) MDA (nmol / mgprot) IL-6 (pg / mL) Blank control group 125.6±11.3 3.0±0.4 15.2±2.1 Model control group 65.3±7.8* 9.2±1.3* 48.7±5.6* Chinese medicine medium dose group 112.4±9.7# 4.1±0.5# 22.5±3.2#

[0105] 2. Clinical trial data (randomized double-blind controlled, n=60 / group)

[0106] (1). Improvement of semen parameters (after 3 months)

[0107] Table 5

[0108]

[0109] (2) Changes in TCM syndrome scores (0-3 points)

[0110] Table 6

[0111] symptom Experimental group (baseline → 3 months) Placebo group (baseline → 3 months) Weakness in waist and knees 2.6±0.7→1.1±0.3# 2.5±0.6→2.4±0.5 Sexual dysfunction 2.2±0.6→1.0±0.2# 2.1±0.5→1.9±0.4

[0112] (3) Safety data (liver and kidney function)

[0113] Table 7

[0114] index Experimental group (baseline → 3 months) Placebo group (baseline → 3 months) ALT(U / L) 24.3±4.2→25.6±5.1 23.8±3.9→24.1±4.3 Cr(μmol / L) 68.5±8.3→70.2±9.1 67.9±7.8→68.5±8.6

[0115] 3. Toxicology study data

[0116] (1) Acute toxicity test (mice)

[0117] Maximum tolerated dose (MTD): 40g / kg (equivalent to 20 times the clinical equivalent dose), with no death or organ damage.

[0118] Symptoms: The high-dose group (40 g / kg) experienced transient diarrhea (recovered within 24 hours).

[0119] (2) Long-term toxicity study (rats, 6 months)

[0120] Table 8

[0121]

[0122] 4. Molecular experimental verification (testicular tissue)

[0123] Table 9

[0124] index Model control group Chinese medicine medium dose group Bcl-2 / Bax 0.7±0.1 1.9±0.2# SOD2mRNA 0.3±0.05 0.9±0.1# AR protein expression 0.4±0.1 1.1±0.2#

[0125] 6. Experimental Conclusion

[0126] 1. In-depth analysis of animal experiment data

[0127] (1) Sperm quality and reproductive function

[0128] Compared with the blank control group: the sperm motility of the blank control group was 86.2%, and the motility of the model control group (CTX modeling) dropped significantly to 30.4%, indicating that the modeling successfully induced asthenospermia.

[0129] Dose effect of Chinese medicine: Low-dose group (0.5g / kg): sperm motility increased to 48.7%, and deformity rate decreased to 26.3%, showing preliminary efficacy. Medium-dose group (1g / kg): motility further increased to 64.9%, significantly better than the positive control group (Wuzi Yanzong Pills, 60.1%); deformity rate (14.5%) was close to the blank control group (7.8%), with outstanding repair effect. High-dose group (2g / kg): motility (70.2%) and deformity rate (13.5%) were close to the blank group, indicating that increasing the dose can further optimize the efficacy.

[0130] (2) Testicular tissue repair:

[0131] The diameter of seminiferous tubules (175 μm) and the number of cell layers (2.0 layers) in the model control group were significantly lower than those in the blank group (255 μm, 5.3 layers). The diameter of seminiferous tubules in the medium-dose group of Chinese medicine recovered to 235 μm and 4.5 layers, close to the blank group, indicating that the compound promoted the regeneration and structural reconstruction of spermatogenic cells.

[0132] (3) Antioxidant and anti-inflammatory effects

[0133] SOD and MDA: The SOD activity of the model control group (65.3U / mg prot) was significantly lower than that of the blank group (125.6), and MDA (9.2nmol / mgprot) was significantly increased, reflecting oxidative stress damage.

[0134] Chinese medicine intervention: SOD in the medium-dose group recovered to 112.4 (close to the blank group), and MDA dropped to 4.1 (better than the positive control group), indicating that the compound protected spermatogenic cells by scavenging free radicals and reducing lipid peroxidation.

[0135] Inflammatory factor IL-6: IL-6 (48.7pg / mL) in the model group increased significantly, and dropped to 22.5pg / mL in the medium-dose Chinese medicine group, close to the blank group (15.2), indicating that the compound inhibits the damage of the inflammatory microenvironment to the testicles.

[0136] 2. Comparison of Clinical Trial Data Systems

[0137] (1) Improvement of semen parameters

[0138] Test group vs. placebo group: Sperm concentration: The test group increased from baseline to 18.9×106 / mL, significantly higher than the placebo group (11.5), and close to the WHO lower limit of normal (15×106 / mL). Forward motility sperm (PR%): The test group reached 39.5%, significantly better than the placebo group (23.8%), and close to the positive control group (34.6%). DFI (DNA fragmentation index): The test group (18.3%) was significantly lower than the placebo group (29.7%), indicating that the compound reduced sperm DNA damage and improved fertilization potential.

[0139] Experimental group vs positive control group: The experimental group performed better in sperm concentration (18.9 vs 16.7) and PR% (39.5 vs 34.6), suggesting that the compound is superior to traditional Chinese patent medicine (Wu Zi Yan Zong Wan) in clinical application.

[0140] (2) Improvement of TCM symptoms

[0141] Kidney deficiency symptoms were relieved: the test group's waist and knee weakness score dropped from 2.6 to 1.1, and the sexual function score dropped from 2.2 to 1.0, which was significantly better than the placebo group (no significant change in the score). Although the positive control group showed some improvement, the test group had a greater advantage in the speed and magnitude of symptom relief, reflecting the compound's comprehensive conditioning ability of "nourishing yin and tonifying the kidney".

[0142] (3) Security Verification

[0143] There was no significant change in the liver and kidney function indicators (ALT, Cr) in the experimental group and the placebo group within 3 months, indicating that the compound has good safety at the clinically recommended dose and is suitable for long-term use.

[0144] 3. Safety support for toxicology research

[0145] (1) Acute toxicity experiment: The maximum tolerated dose (MTD) was 40 g / kg (20 times the clinical equivalent dose). Only the high-dose group experienced transient diarrhea (recovered within 24 hours), and no organ damage or death was observed, demonstrating that the acute toxicity of the compound was extremely low.

[0146] Long-term toxicity experiment: After 6 months of continuous administration, there was no significant difference in body weight growth rate (26.8%), organ coefficient (liver 3.5g / 100g, kidney 0.8g / 100g) and liver and kidney function (ALT 38.6U / L) between the high-dose Chinese medicine group (2g / kg) and the blank control group (28.5%, liver 3.2, kidney 0.7, ALT 35.2), indicating that there is no cumulative toxicity risk with long-term medication.

[0147] 4. Multi-dimensional analysis of the mechanism of action

[0148] Core pathway regulation: PI3K / AKT pathway: By upregulating the Bcl-2 / Bax ratio (1.9 vs 0.7 in the model group), it inhibits spermatogenic cell apoptosis and promotes proliferation (consistent with the testicular tissue repair data).

[0149] Nrf2 antioxidant pathway: activates SOD2 mRNA expression (0.9 vs 0.3 in the model group), enhances antioxidant defense capacity, and reduces oxidative stress damage (consistent with SOD and MDA data).

[0150] Androgen receptor (AR) signaling: Upregulates AR protein expression (1.1 vs 0.4 in the model group), regulates testosterone levels, and improves spermatogenesis (consistent with the improvement of sperm motility and the TCM theory of "warming yang").

[0151] Multi-ingredient synergistic effect:

[0152] Active ingredients such as Lycium barbarum polysaccharides (≥30%) and icariin (≥0.5%) achieve the comprehensive therapeutic effect of "tonifying the kidney and replenishing essence, promoting blood circulation and removing blood stasis" through multi-target synergy, which is in line with the TCM principle of "monarch, minister, assistant and envoy" compatibility.

[0153] 5. Summary Conclusion and Clinical Significance

[0154] Efficacy advantage: In animal and clinical experiments, the compound significantly reversed the pathological state of asthenospermia, and its effect was better than the positive control group (Wuzi Yanzong Pills) in terms of sperm motility, DNA integrity and improvement of TCM symptoms. The medium dose (1g / kg) is the best treatment window, taking into account both efficacy and safety.

[0155] Safety guarantee: The acute toxicity is extremely low, and long-term use will not cause liver and kidney damage. It is suitable for patients with asthenospermia who need long-term conditioning.

[0156] The mechanism of action is clear: the compound achieves multi-dimensional treatment of "anti-oxidation - anti-inflammatory - pro-proliferation - hormone regulation" by regulating the PI3K / AKT, Nrf2 and AR signaling pathways, scientifically interpreting the TCM theory of "tonifying the kidney and producing sperm".

[0157] Precision application of the population: It is especially recommended for patients with asthenospermia due to kidney yin deficiency or deficiency of both kidney yin and yang. It can significantly improve semen quality and kidney deficiency symptoms, and fill the gaps in traditional Chinese patent medicines in targeted treatment.

[0158] The above experiments have verified that the compound significantly improves the sperm quality of asthenospermia models and patients by tonifying the kidney and replenishing essence, warming yang and replenishing qi, and promoting blood circulation and removing blood stasis. The specific mechanisms include: promoting the proliferation and differentiation of spermatogenic cells, restoring testicular spermatogenic function, enhancing antioxidant capacity, reducing sperm DNA damage, regulating sex hormone levels, improving kidney deficiency-related symptoms, and no significant liver and kidney function damage. The compound works synergistically through multiple components, multiple targets, and multiple pathways, mainly involving: PI3K / AKT pathway: promoting spermatogenic cell survival and proliferation. Nrf2 pathway: enhancing antioxidant capacity, reducing oxidative stress damage, AR signaling: regulating androgen levels, and improving reproductive function. The compound can be used as an adjuvant treatment for asthenospermia, especially for patients with kidney yin deficiency or kidney yin and yang deficiency.

Claims

1. A Chinese medicine composition for nourishing yin, tonifying the kidney and producing sperm, characterized in that: Measured by weight, it includes: 40-50g of Schisandra chinensis, 100-110g of Lycium barbarum, 80-90g of Cuscuta australis, 90-100g of processed Polygonum multiflorum, 70-80g of Rubus idaeus, 60-70g of Plantago seed, 70-80g of Ligustrum lucidum fruit, 80-90g of Epimedium, 70-80g of Morinda officinalis, 60-70g of Angelica sinensis, 60-70g of Cynomorium songaricum, and 90-100g of Astragalus.

2. The Chinese medicine composition for nourishing yin, tonifying kidney and producing sperm according to claim 1, characterized in that: Measured by weight, it includes: 40g of Schisandra chinensis, 100g of Lycium barbarum, 80g of Cuscuta australis, 90g of processed Polygonum multiflorum, 70g of Rubus idaeus, 60g of Plantago seed, 70g of Ligustrum lucidum fruit, 80g of Epimedium, 70g of Morinda officinalis, 60g of Angelica sinensis, 60g of Cynomorium songaricum, and 90g of Astragalus membranaceus.

3. The Chinese medicine composition for nourishing yin, tonifying kidney and producing spermatogenesis according to claim 1, characterized in that: Measured by weight, it includes: 45g of Schisandra chinensis, 105g of Lycium barbarum, 85g of Cuscuta australis, 95g of processed Polygonum multiflorum, 75g of Rubus idaeus, 65g of Plantago seed, 75g of Ligustrum lucidum fruit, 85g of Epimedium, 75g of Morinda officinalis, 65g of Angelica sinensis, 65g of Cynomorium songaricum, and 95g of Astragalus membranaceus.

4. The Chinese medicine composition for nourishing yin, tonifying kidney and producing spermatogenesis according to claim 1, characterized in that: Measured by weight, it includes: 50g of Schisandra chinensis, 110g of Lycium barbarum, 90g of Cuscuta australis, 100g of processed Polygonum multiflorum, 80g of Rubus idaeus, 70g of Plantago seed, 80g of Ligustrum lucidum fruit, 90g of Epimedium, 80g of Morinda officinalis, 70g of Angelica sinensis, 70g of Cynomorium songaricum, and 100g of Astragalus.

5. A method for preparing a Chinese medicine composition, according to the Chinese medicine composition according to claims 2 to 4, characterized in that: Grind the above twelve Chinese medicinal materials into fine powder, sieve and mix well.

6. A Chinese medicine preparation comprising the Chinese medicine composition according to any one of claims 1 to 4 and pharmaceutically acceptable excipients.

7. The Chinese medicine preparation according to claim 6, characterized in that: Oral preparations include granules, tablets, capsules, oral solutions, granules or pills.

8. Use of the Chinese medicine composition according to any one of claims 1 to 4 in the preparation of drugs for nourishing yin and tonifying the kidney, producing sperm, and treating asthenozoospermia.

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