A kidney-nourishing and turbidity-resolving traditional Chinese medicine composition, preparation method, preparation and application

Abstract

The application provides a kidney-nourishing and turbidity-resolving traditional Chinese medicine composition, a preparation method, a preparation and application. The kidney-nourishing and turbidity-resolving traditional Chinese medicine composition comprises 8-15 parts of raspberry, 8-15 parts of dodder seed, 12-18 parts of radix codonopsis, 8-12 parts of radix alismatis, 8-12 parts of aloe, 8-12 parts of poria and 8-12 parts of fried atractylodes. The kidney-nourishing and turbidity-resolving traditional Chinese medicine composition aims at the pathogenesis of turbidity evil, and uses raspberry and dodder seed as the monarch drug for nourishing kidney and generating essence, radix codonopsis as the minister drug for tonifying middle energizer, benefiting qi and generating fluid, radix alismatis and aloe for resolving dampness and turbidity, and poria and fried atractylodes for removing phlegm and turbidity, so as to treat male infertility, especially male infertility caused by sperm DNA damage.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, and in particular to a traditional Chinese medicine composition, preparation method, formulation and application for tonifying the kidney and clearing turbidity. Background Technology

[0002] In traditional Chinese medicine, male infertility was referred to as "childlessness" or "infertility." In modern medicine, it refers to the inability of a woman to conceive after 12 months of regular, unprotected sexual intercourse among men and women of reproductive age, due to male factors. Sperm DNA damage infertility refers to a group of diseases clinically manifested as male infertility, recurrent miscarriages in the partner, poor embryo quality in assisted reproductive technology, or multiple failed embryo transfers, accompanied by elevated sperm DNA fragmentation index (DFI) in semen analysis.

[0003] Sperm DNA fragmentation (SDF) refers to double-strand or single-strand breaks in sperm nuclear DNA or mitochondrial DNA, resulting in damage to the integrity of paternal genes. DFI is the most commonly used indicator for evaluating sperm DNA damage. Damage to sperm DNA integrity is closely related to male infertility and a decline in natural pregnancy rates. When DFI ≥ 20%, the chance of natural conception begins to decrease; when DFI ≤ 30% ≤ 40% or even higher, the chance of natural pregnancy approaches zero.

[0004] Modern medicine's treatments for this disease include lifestyle modifications, antioxidants, anti-infection measures, surgical treatment of varicocele, and assisted reproductive technologies, but clinical efficacy remains poor. Traditional Chinese medicine often diagnoses this condition as dampness, heat, deficiency, and blood stasis, and its treatment methods focus on dispelling dampness, clearing heat, resolving blood stasis, tonifying the kidneys, and strengthening the spleen; however, the incidence of varicocele (DFI) remains high. For example, Chinese patent application number CN201310077422.4 discloses a traditional Chinese medicine composition for treating infertility due to abnormal semen, with the principle of clearing heat and tonifying the kidneys. The medicine is made from *Spatholobus suberectus*, *Rubus idaeus*, *Rubus parvifolius*, *Cornus officinalis*, *Cuscuta chinensis*, *Dipsacus asper*, *Lonicera japonica*, corn silk, *Eclipta prostrata*, gecko powder, and licorice. It treats infertility due to abnormal semen by tonifying the kidneys and replenishing essence, clearing heat and detoxifying, but the medicine contains many ingredients and the treatment cycle is long. Chinese patent application number 201811204349.1 discloses a traditional Chinese medicine for treating sperm DNA damage, which is based on the principles of invigorating qi and tonifying the kidneys, promoting blood circulation and removing blood stasis. It is made from 30-50 parts of Astragalus membranaceus, 20-30 parts of Lycium barbarum, 15-25 parts of Schisandra chinensis, 12-22 parts of Plantago asiatica and 15-25 parts of Achyranthes bidentata. However, the reproductive outcome is still not ideal.

[0005] Therefore, providing a traditional Chinese medicine with good efficacy in treating sperm DNA damage is of practical significance for clinical treatment. Summary of the Invention

[0006] In view of this, the present invention aims to provide a traditional Chinese medicine composition for tonifying the kidney and clearing turbidity, a preparation method, a pharmaceutical formulation, and an application, in order to solve the problem of poor efficacy of existing traditional Chinese medicine compositions for treating male infertility caused by sperm DNA damage.

[0007] Based on a renewed exploration of the etiology and pathogenesis of male infertility caused by sperm DNA damage, the applicant believes that "turbidity" is a crucial pathological product mediating sperm DNA damage. Reproductive system infections, varicocele, obesity, and advanced age—risk factors for high sperm DNA infertility (DFI)—are breeding grounds for "turbidity." Dampness, heat, deficiency, blood stasis, and phlegm are the symptoms, while turbidity is the underlying pathogenesis. Damage to the sperm nucleus is a specific pathological condition of infertility resulting from the interaction of multiple etiologies and pathogenesis. By focusing on turbidity as a key pathogenic factor, and considering that in the progression of the disease, excess can lead to turbidity, turbidity can lead to deficiency, deficiency can generate turbidity, and turbidity can lead to excess, treatment should address the root cause and address the underlying condition. To achieve the above objectives, this invention modifies and adjusts classic prescriptions to obtain the following technical solution:

[0008] A traditional Chinese medicine composition for tonifying the kidneys and clearing away turbidity comprises, by weight, 8-30 parts of raspberry, 8-30 parts of dodder seed, 10-20 parts of codonopsis, 2-15 parts of dioscorea hypoglauca, 2-15 parts of acorus tatarinowii, 2-15 parts of poria cocos, and 2-15 parts of stir-fried atractylodes lancea. Preferably, the composition further comprises 10-30 parts of spatholobus suberectus, 1-8 parts of scalded leech, and 2-6 parts of prepared licorice root.

[0009] Based on years of clinical experience and high-risk factors for infertility in recent years, this invention is the first to recognize that "turbidity" may be an important pathological stage of sperm nucleus damage. Targeting this pathogenic element of "turbidity," the invention combines the "turbidity" of the local spermatogenic microenvironment with the "turbidity" of the macroenvironment of the body in its drug formulation. Specifically, raspberry and dodder seed are used as the principal herbs to tonify the kidneys and promote spermatogenesis; raspberry is yin in nature while dodder seed is yang in nature, providing a balanced tonification of the kidneys. Codonopsis pilosula is used as the assistant herb, tonifying the middle jiao, replenishing qi, and promoting body fluid production. Dioscorea hypoglauca and Acorus tatarinowii are used together to resolve dampness and turbidity; Poria cocos and stir-fried Atractylodes lancea are used together to clear phlegm and turbidity; and Sargentodoxa cuneata and scalded leech are used together to disperse blood stasis and turbidity, achieving the effect of removing turbidity and promoting spermatogenesis. These are all used as adjuvant herbs. Prepared licorice root harmonizes all the herbs. The combined use of these herbs aims to treat male infertility, especially male infertility caused by DNA damage.

[0010] Preferably, it is made from the following raw materials: 9-12 parts of raspberry, 9-12 parts of dodder seed, 14-16 parts of codonopsis, 9-12 parts of dioscorea hypoglauca, 9-12 parts of acorus tatarinowii, 9-12 parts of poria cocos, 9-12 parts of stir-fried atractylodes lancea, 18-22 parts of sarsaparilla, 2-4 parts of scalded leech, and 2-4 parts of prepared licorice root.

[0011] More preferably, it is made from the following raw materials: 10 parts raspberry, 10 parts dodder seed, 15 parts codonopsis root, 10 parts dioscorea hypoglauca, 10 parts acorus tatarinowii, 10 parts poria cocos, 10 parts stir-fried atractylodes lancea, 20 parts sargentodoxa cuneata, 3 parts scalded leech, and 3 parts prepared licorice root. The codonopsis root is preferably *Codonopsis pilosula*, and the poria cocos is preferably *Poria cocos*.

[0012] The Codonopsis pilosula produced in the Shangdang region of Shanxi Province is considered to be of superior quality, known as Lu Codonopsis pilosula. It is characterized by its long, slender stems, thick texture, pure taste, yellow skin, red flesh, and vibrant color. It has three to five leaves, a pine-flower-like head, pale yellow flowers, and a fragrant aroma, making it a high-quality and authentic Chinese medicinal material. White broken Poria cocos refers to white or grayish-white fragments or pieces of varying sizes produced during the processing of Poria cocos.

[0013] According to the Chinese Pharmacopoeia and the Dictionary of Traditional Chinese Medicine, the pharmacological effects of the traditional Chinese medicine involved in this invention are as follows:

[0014] Raspberry: Sweet and sour in taste, warm in nature. It enters the kidney and bladder meridians. Its functions and indications include tonifying the kidneys, consolidating essence, and reducing urination. It is used for kidney deficiency causing enuresis, frequent urination, impotence, premature ejaculation, and spermatorrhea.

[0015] Cuscuta seed: Sweet and warm in nature. It enters the liver, kidney, and spleen meridians. Its functions and indications include nourishing the liver and kidneys, consolidating essence and reducing urination, calming the fetus, improving eyesight, and stopping diarrhea. It is used for impotence, seminal emission, dribbling urination, enuresis, frequent urination, soreness and weakness of the lower back and knees, blurred vision and tinnitus, kidney deficiency with threatened abortion, fetal restlessness, and diarrhea due to spleen and kidney deficiency; externally, it is used to treat vitiligo.

[0016] Codonopsis pilosula: Sweet in taste, neutral in nature. Enters the spleen and lung meridians. Functions: Tonifies the middle energizer, replenishes qi, and generates fluids. Indications: Weakness of the spleen and stomach, deficiency of both qi and blood, fatigue, poor appetite, thirst, chronic diarrhea, and rectal prolapse.

[0017] Dioscorea hypoglauca: Bitter in taste and neutral in nature. It enters the kidney and stomach meridians. Functions: Promotes diuresis and eliminates turbidity, dispels wind and relieves numbness. Indications: Used for chyluria, leukorrhea, excessive vaginal discharge, rheumatic pain, joint stiffness, and lower back and knee pain.

[0018] Sweet flag (Acorus calamus): Pungent, bitter, and warm in nature. It enters the Heart and Stomach meridians. Functions: It resolves dampness and stimulates appetite, opens the orifices and clears phlegm, refreshes the mind and improves intelligence. Used for epigastric fullness and lack of appetite, aphthous stomatitis and diarrhea, delirium and epilepsy, forgetfulness and deafness.

[0019] Poria cocos: Sweet, bland, and neutral in nature. It enters the heart, lung, spleen, and kidney meridians. Functions: Promotes diuresis and eliminates dampness, strengthens the spleen and calms the mind. Used for edema with scanty urine, phlegm retention with dizziness and palpitations, spleen deficiency with poor appetite, loose stools and diarrhea, restlessness, palpitations, and insomnia.

[0020] Stir-fried Atractylodes lancea, also known as bran-fried Atractylodes lancea, is pungent, bitter, and warm in nature. It enters the spleen, stomach, and liver meridians. Functions: It dries dampness and strengthens the spleen, dispels wind and cold, and improves eyesight. It is used for abdominal distension, diarrhea, edema, rheumatic pain, colds due to wind and cold, and night blindness.

[0021] *Sargentodoxa cuneata*: Bitter and neutral in nature. It enters the large intestine and liver meridians. Functions: Clears heat and detoxifies, invigorates blood, and dispels wind. Used for intestinal abscess and abdominal pain, amenorrhea and dysmenorrhea, rheumatic pain, and traumatic swelling and pain.

[0022] Leech: Bitter and neutral in nature, slightly toxic. Enters the liver and bladder meridians. Functions: Breaks up blood stasis, removes blood stasis, and promotes menstruation. Treats blood stasis, abdominal masses, accumulations, amenorrhea in women, tuberculosis caused by blood stasis, injuries from falls, eye pain, and corneal opacity.

[0023] Prepared licorice root: Sweet and neutral in nature, it enters the heart, lung, spleen, and stomach meridians. It tonifies qi and strengthens the middle jiao, clears heat and detoxifies, resolves phlegm and relieves cough, alleviates spasms and pain, and harmonizes the properties of other herbs. It is used for palpitations and irregular pulse due to insufficient heart qi, sores caused by heat toxins, and sore throat.

[0024] Compared with the prior art, the traditional Chinese medicine composition for tonifying the kidney and resolving turbidity described in this invention has the following advantages: The traditional Chinese medicine composition for tonifying the kidney and resolving turbidity described in this application regulates reproductive essence by tonifying the kidney, and is supplemented with herbs for resolving dampness, dispersing blood stasis, and eliminating phlegm. When all the herbs are used together, they resolve turbidity and remove blood stasis, strengthen the spleen and tonify the kidney, and promote sperm production to treat male infertility caused by sperm DNA damage, with significant therapeutic effects.

[0025] This invention also provides a method for preparing a traditional Chinese medicine composition for tonifying the kidney and clearing turbidity, wherein the raw materials are weighed according to the weight parts, and the weighed raw materials are mixed, decocted, filtered, and concentrated into a decoction for oral administration; or the raw materials are weighed according to the weight parts, and an extract is obtained by using traditional Chinese medicine extraction technology, and prepared into a clinically usable dosage form with one or more pharmaceutically acceptable carriers.

[0026] The extraction techniques for traditional Chinese medicine include, but are not limited to, decoction, maceration, percolation, modified gelatin, reflux, solvent extraction, steam distillation, sublimation, enzyme extraction, semi-bionic extraction, supercritical fluid extraction, membrane extraction and separation, ultrafine pulverization, and flocculation separation of traditional Chinese medicine.

[0027] This invention also provides a pharmaceutical preparation containing the powder, extract, or decoction of the kidney-tonifying and turbidity-resolving traditional Chinese medicine composition as described above. Preferably, the pharmaceutical preparation is a capsule, tablet, decoction, granule, syrup, drop pill, water pill, honey pill, or sustained-release preparation for oral use. Preferably, the preparation method of the granule is as follows: 1) Weigh the raw materials according to the weight proportions, dry and pulverize them separately to obtain fine powder, mix the fine powder thoroughly, and set aside; 2) Boil over high heat, simmer over low heat at 95°C for 1.5 hours; 3) Filter, add 95% ethanol and reflux at 65°C for 1 hour, combine the extract and decoction, add magnesium stearate, filter, concentrate, spray dry, and pulverize to D 90 <20μm, to obtain drug-containing micro powder; 3) Add an appropriate amount of magnesium stearate and hydroxymethyl cellulose to the above drug-containing micro powder particles, mix well, make soft material, and obtain granules by sieving, drying, granulation and sieving.

[0028] The above-mentioned kidney-tonifying and turbidity-clearing traditional Chinese medicine composition is used in the preparation of a medicament for treating male infertility. Preferably, the male infertility is caused by sperm DNA damage. Preferably, the male infertility patient also has chronic prostatitis, varicocele, or obesity. Detailed Implementation

[0029] It should be noted that, unless otherwise specified, the embodiments and features described in the embodiments of this invention can be combined with each other. The invention will now be described in detail with reference to the embodiments. Unless otherwise specified, the experimental methods used in the embodiments of this invention are conventional methods. Unless otherwise specified, the materials and reagents used in the embodiments of this invention are commercially available.

[0030] Male infertility due to sperm DNA damage falls under the categories of "infertility," "childlessness," "lack of offspring," and "difficulty in having children" in traditional Chinese medicine. Current Western medical treatments for sperm DNA damage primarily include oral antioxidants, surgical treatment of varicocele, frequent sperm aspiration, sperm optimization techniques, and testicular sperm retrieval. These treatments have only improved pregnancy outcomes in some patients with high DFI (disease-free sperm infertility), and the overall effectiveness remains unsatisfactory. Traditional Chinese medicine believes that the kidney governs reproduction, with kidney deficiency as the root cause and qi stagnation, damp-heat, and blood stasis as the manifestations, classifying it as a condition of deficiency in the root and excess in the branch. Treatment often focuses on tonifying the kidney and promoting blood circulation, with prescriptions primarily consisting of kidney-tonifying herbs combined with blood-activating and stasis-removing drugs. However, the clinical efficacy of this approach remains controversial.

[0031] In exploring the etiology of sperm nucleus damage, the applicant discovered a transitional phase between the conventional pathological elements of dampness, heat, deficiency, and blood stasis and the eventual outcome of sperm nucleus damage. The presence of "turbid evil" (a concept in Traditional Chinese Medicine) may mediate this process. High-risk factors for sperm DNA damage include unhealthy lifestyle habits such as smoking, excessive alcohol consumption, and staying up late, as well as internal environmental disorders such as reproductive tract inflammation, varicocele, and obesity. Traditional Chinese medicine's macroscopic diagnosis and treatment often focuses on lifestyle, subjective symptoms, and the correlation between the five internal organs. "Etiological differentiation" is an experience in TCM for improving semen quality. From the high-risk factors for sperm DNA damage, we found that reproductive system infections, fibroids, obesity, and advanced age are high-DFI risk factors and a breeding ground for "turbid evil," which is an important pathological product mediating the high-risk factors and sperm nucleus damage.

[0032] Therefore, based on clinical practice, the applicant conducted exploratory research and creatively proposed the following technical solution based on this pathogenesis.

[0033] Example 1

[0034] A traditional Chinese medicine composition for tonifying the kidneys and clearing away turbidity is made from the following raw materials: 15g of raspberry, 8g of dodder seed, 12g of codonopsis root, 9g of dioscorea hypoglauca, 10g of acorus tatarinowii, 10g of poria cocos, and 10g of stir-fried atractylodes lancea.

[0035] The preparation method is as follows: 1) Weigh the raw materials according to the weight ratio, mix them, add 1.3 times (V / M) of water to cover the surface of the medicine by 0.5cm and soak for 30min; 2) Boil over high heat, keep warm over low heat to 95℃ and decoct for 1.5h, decoct 3 times to obtain decoction; (3) Combine the decoction, filter, concentrate and obtain the soup.

[0036] Example 2

[0037] A traditional Chinese medicine composition for tonifying the kidneys and clearing away turbidity is made from the following raw materials: 15g of raspberry, 8g of dodder seed, 12g of codonopsis, 9g of dioscorea hypoglauca, 10g of acorus tatarinowii, 10g of poria cocos, 10g of stir-fried atractylodes lancea, 20g of sarsaparilla, 3g of scalded leech, and 3g of prepared licorice root.

[0038] The preparation method is as follows: 1) Weigh the raw materials according to the weight ratio, mix them, add 1.3 times (V / M) of water to cover the surface of the medicine by 0.7cm and soak for 20min; 2) Boil over high heat, keep warm over low heat to 99℃ and decoct for 1.1h, decoct twice to obtain decoction; (3) Combine the decoction, filter, concentrate and obtain the soup.

[0039] Example 3

[0040] A traditional Chinese medicine composition for tonifying the kidneys and clearing away turbidity is made from the following raw materials: 11g of raspberry, 15g of dodder seed, 16g of codonopsis, 6g of dioscorea hypoglauca, 4g of acorus tatarinowii, 7g of poria cocos, 6g of stir-fried atractylodes lancea, 30g of sarsaparilla, 8g of scalded leech, and 7g of prepared licorice root.

[0041] The preparation method is as follows: 1) Weigh the raw materials according to the weight ratio, mix them, add 1.5 times the amount of water (V / M) to cover the surface of the medicine by 0.3cm and soak for 15min; 2) Boil over high heat, keep warm over low heat to 92℃ and decoct for 1.6h, decoct 3 times to obtain decoction; (3) Combine the decoction, filter, concentrate and obtain the decoction.

[0042] Example 4

[0043] A traditional Chinese medicine composition for tonifying the kidneys and clearing turbidity is made from the following raw materials: 12g of raspberry, 15g of dodder seed, 15g of codonopsis root, 4g of dioscorea hypoglauca, 6g of acorus tatarinowii, 12g of poria cocos, 15g of stir-fried atractylodes lancea, 10g of sarsaparilla, 1g of scalded leech, and 3g of prepared licorice root. The preparation method is the same as in Example 3.

[0044] Example 5

[0045] A traditional Chinese medicine composition for tonifying the kidneys and clearing away turbidity is made from the following raw materials: 15g of raspberry, 8g of dodder seed, 12g of codonopsis, 115g of dioscorea hypoglauca, 15g of acorus tatarinowii, 3g of poria cocos, 6g of stir-fried atractylodes lancea, 12g of sarsaparilla, 1g of scalded leech, and 3g of prepared licorice root; the preparation method is the same as in Example 3.

[0046] Example 6

[0047] A traditional Chinese medicine composition for tonifying the kidneys and clearing away turbidity is made from the following raw materials: 10g of raspberry, 10g of dodder seed, 15g of codonopsis, 10g of dioscorea hypoglauca, 10g of acorus tatarinowii, 10g of poria cocos, 10g of stir-fried atractylodes lancea, 20g of sarsaparilla, 3g of scalded leech, and 3g of prepared licorice root; the preparation method is the same as in Example 3.

[0048] Comparative Example 1

[0049] The traditional Chinese medicine liquid prepared according to Example 4 of Chinese Patent Application No. 201811204349.1.

[0050] Experimental Example 1

[0051] To verify the beneficial effects of the traditional Chinese medicine composition described in this invention, 150 male infertility patients who visited our department from October 2017 to May 2021 were selected. The inclusion criteria are as follows:

[0052] Western medicine diagnostic criteria refer to the World Health Organization's Manual of Standardized Examination and Treatment of Male Infertility and the diagnostic criteria for male infertility in Andrology: Married couples who have cohabited for more than one year, have regular sexual intercourse, and have not used contraception are infertile, while excluding female infertility factors; abstinence for 3-7 days, and after more than two tests, sperm DFI > 25%, accompanied by sperm concentration < 15 × 10⁻⁶. 6 / ml or sperm forward motility rate <32%.

[0053] The diagnostic criteria for spleen and kidney deficiency syndrome are based on the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine" (State Administration of Traditional Chinese Medicine, 1994) and the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs (Trial Implementation)" (Zheng Xiaoyu, 2002). The main symptoms are: soreness and weakness of the lower back and knees, decreased libido, poor appetite, and fatigue. Secondary symptoms include: dizziness, tinnitus, seminal emission, premature ejaculation, abdominal distension after meals, dull abdominal pain, epigastric fullness, nausea, and difficulty defecating; pale tongue with a white coating, and a deep, weak pulse. A diagnosis can be made if two or more of the main symptoms and two or more of the secondary symptoms are present, with one or more of each of the two main symptoms affecting the spleen and kidney, and one or more of each of the two secondary symptoms affecting the spleen and kidney.

[0054] Exclusion criteria: ① Patients with severe oligospermia, asthenospermia, teratospermia, or necrospermia; ② Patients with severe erectile dysfunction, retrograde ejaculation, or ejaculatory dysfunction; ③ Patients with abnormal gonadal function as detected by endocrine testing; ④ Patients with uncontrolled bacterial prostatitis or recent fever, or other factors affecting fertility; ⑤ Patients taking anti-epileptic or anti-tumor drugs that affect spermatogenesis and sperm motility; ⑥ Patients with congenital malformations of the external genitalia, obstruction of the seminal ducts, or testicular atrophy; ⑦ Patients with allergies or allergies to the test drug; ⑧ Patients concurrently using other medications; ⑨ Patients who have not followed the prescribed medication regimen or whose data is incomplete, affecting the assessment of efficacy or safety.

[0055] Statistics show that the patients' ages ranged from 24 to 44 years, with an average age of 27.7 years; their marriage duration ranged from 1 to 23 years, with an average of 3.6 years. The traditional Chinese medicine composition prepared according to the clinical symptoms was appropriately modified, and the data were statistically analyzed.

[0056] 1. Grouping and Treatment Methods

[0057] 150 qualified subjects were selected for randomized trial and randomly divided into 3 groups using a random number table. The treatment group consisted of 90 subjects, who received appropriate adjustments to the traditional Chinese medicine composition prepared according to their clinical symptoms, twice daily, taken after meals. The control groups 1 and 2 each consisted of 30 subjects, who received Comparative Example 1 and L-carnitine oral solution, respectively. The control group 1 also received the same treatment, twice daily, taken after meals, while the control group 2 received one vial of L-carnitine oral solution three times daily for 3 months.

[0058] 2. Clinical efficacy

[0059] Based on the infertility-related content in the "Guiding Principles," the following criteria are proposed: ① Cured: Sperm DFI <15% during drug treatment or the partner becomes pregnant during treatment; ② Significantly effective: The partner does not become pregnant, but semen analysis parameters and sperm DFI index return to normal, 15% ≤ DFI < 30%; ③ Effective: The main parameters of semen analysis improve, sperm DFI ≥ 30% and the decrease rate is > 30%; ④ Ineffective: There is no significant change in semen analysis parameters and DFI compared to before treatment, or even a worsening of the condition.

[0060] The overall effective rate was calculated as (cured + significantly effective + effective) / total number of cases × 100%, and the results are shown in Table 1.

[0061] Table 1 Overall efficacy data for each group

[0062]

[0063] Considering that "turbid evil" is a high-risk factor for disease and an important pathological product of sperm nucleus damage, this application also takes kidney deficiency as the root cause and resolving turbidity as the manifestation, treating both the root and the manifestation, and adjusting the dosage according to different indications. As shown in Table 1, the total effective rate of the treatment group I, after taking the traditional Chinese medicine composition prepared by this invention, was 97.8%, which was significantly higher than that of the control groups I and II, demonstrating a significant therapeutic effect on male infertility.

[0064] Experiment Example 2

[0065] In the *Neijing* (Inner Canon of Medicine), the meaning of "turbidity" is broad. Physiological turbidity is described in phrases such as "those who receive grains are turbid," "turbid yin exits through the lower orifices...turbid yin travels through the five viscera...turbid yin returns to the six bowels," and "turbidity is the defensive qi." These all refer to physiological turbidity, generally encompassing the essence of food and water, waste products, and defensive qi. Physiological turbidity is described in phrases such as "cold qi generates turbidity," "turbid qi is in the middle," "blood is black and turbid, its qi is sluggish and slow," and "turbid fluids all belong to heat." These all summarize the pathological production of turbidity and its symptoms, whether caused by external pathogenic factors (the six evils) or internal damage to the spleen and stomach, resulting in symptoms like "black and turbid blood" or "turbid fluids."

[0066] There exists a transitional stage between the conventional pathogenesis elements of dampness, heat, deficiency, and blood stasis and the outcome of spermatogenesis impairment. The presence of "turbid pathogens" may mediate this process. Chronic prostatitis, fibroids, obesity, and advanced age are high-risk factors for DNA damage-induced infertility (DFI), which can become breeding grounds for these "turbid pathogens." The evaluation methods for these DFI risk factors are existing technologies and will not be elaborated upon here. Therefore, the applicant conducted a statistical analysis of the treatment efficacy for male infertility caused by DNA damage accompanied by different high-risk factors in the above cases. The results are as follows:

[0067] 2.1 Muscle tumors causing turbidity

[0068] Among the above patients, 41 patients had varicocele. Among them, 34 patients did not have other high-risk factors such as inflammation or obesity. 29 cases were unilateral and 5 cases were bilateral. They were treated with the decoction of Example 3. For specific treatment methods, please refer to Experimental Example 1.

[0069] The SSA-II automated sperm detection and analysis system (Beijing Suijia Software Co., Ltd.) was used to analyze parameters such as sperm concentration and forward sperm motility according to the WHO Laboratory Manual for Examination and Processing of Human Semen (5th Edition). The sperm diffusion fraction (DFI) was also detected using the chromatin diffusion assay. The results are shown in Table 2.

[0070] Table 2 Comparison of biochemical indicators before and after treatment

[0071]

[0072] As shown in Table 2, the sperm concentration increased after treatment, but the difference was not significant compared with before treatment. Compared with before treatment, the forward motility rate of sperm increased significantly, while the DFI index (18.4%) decreased significantly, indicating good treatment effect.

[0073] The overall therapeutic effect was evaluated using the method in Experiment Example 1, and the results are shown in Table 3.

[0074] Table 3 Overall efficacy data

[0075]

[0076] Varicocele is one of the common causes of male infertility. Traditional Chinese medicine calls it "spermatocele". The main symptoms are the abnormal extension, dilation, and tortuosity of the pampiniform venous plexus within the spermatic cord. The pathogenesis is kidney deficiency and blood stasis. Kidney deficiency is the root cause, and blood stasis is the superficial cause. Kidney deficiency and blood stasis interact with each other. Kidney deficiency leads to blood stasis, and blood stasis leads to kidney deficiency. Prolonged stasis turns into toxin, and the toxin damages the healthy qi. This toxin is actually the endogenous "turbid pathogen". The generation of the turbid pathogen is due to the three pathological products of stasis, dampness, and heat in the scrotum. They ferment with each other and accumulate in the collaterals of the external testis system. Over time, the testis is damaged, the production of reproductive sperm decreases, the motility declines, and the sperm nucleus is damaged. Blood stasis is the superficial cause of the disease. "Turbidity" is the pathological state during the oxidative stress reaction after the microcirculation disorder of the spermatic cord. And the "turbid pathogen" is the core link from blood stasis to the damage of the kidney essence nucleus. By combining the animal medicine - leech and Sargentodoxa cuneata, and appropriately increasing their dosages to remove stasis and turbidity. As can be seen from Table 3, the traditional Chinese medicine composition described in Example 3 of this application has good curative effects on male infertility caused by DNA damage and patients with varicocele.

[0077] 2.2 Infection-induced "turbidity"

[0078] Among the above patients, �6 had chronic prostatitis. Among them, 30 patients did not have other risk factors such as varicocele and obesity. Among them, 29 were unilateral and 1 was bilateral. The decoction of Example 4 was used for treatment. The specific treatment method is shown in Experimental Example 1; the sperm indexes and detections were the same as in 2.1, and the results are shown in Table 4; the comprehensive curative effect was evaluated by the method of Experimental Example 1, Table 5.

[0079] Table 4 Comparison of biochemical indexes before and after treatment

[0080]

[0081] As can be seen from Table 2, the sperm concentration increased after treatment, but the difference was not obvious compared with that before treatment; compared with before treatment, the forward motility rate of sperm increased significantly, while the DFI index (19.1%) decreased significantly, and the treatment effect was ideal.

[0082] Table 5 Overall curative effect data

[0083]

[0084] Genitourinary tract infections are a significant cause of male infertility. Studies have shown that sperm DNA fragmentation is significantly higher in men with reproductive system infections who test positive for seminal elastase and leukocytes compared to uninfected individuals. Semen CT, MG, and UU infections significantly increase sperm DNA fragmentation (DFI) compared to infertile patients without infection. When leukocytes in seminal fluid participate in anti-inflammatory responses such as phagocytosis of pathogens, they produce large amounts of reactive oxygen species, causing lipid peroxidation of the sperm membrane and resulting in toxic effects on sperm. Simultaneously, large amounts of elastase are produced in the seminal plasma. These free elastases hydrolyze cellular proteins, producing peroxidized substances that attack sperm DNA, causing sperm DNA damage. While reproductive system microbial infections are temporary, the subsequent induced persistent inflammatory response and oxidative stress products are the main pathological mechanisms leading to sperm nucleus damage.

[0085] The basic pathogenesis of infectious infertility is kidney deficiency, damp-heat, and blood stasis. Kidney deficiency is the root cause, while damp-heat and blood stasis are the symptoms. From the perspective of the symptoms, damp-heat descending is the early stage of the disease, which then affects the changes in Qi and leads to blood stasis. Further, damp-heat and blood stasis "transform into turbidity," obstructing the internal flow of turbidity, hindering the production of reproductive essence, and damaging the sperm nucleus. Dampness and stasis are the initial stage of turbidity, while turbidity is the gradual stage of dampness and stasis. "Turbidity" refers to the inflammatory products and oxidative stress response produced after microbial infection of the reproductive system, while "turbidity" is the transitional pathological product that causes damage to the sperm nucleus. As shown in Table 5, the applicant modified the basic formula by appropriately increasing the dosage of Dioscorea hypoglauca and Acorus tatarinowii to obtain the Chinese herbal composition of Example 5, which achieves the effect of resolving dampness and turbidity and has a good therapeutic effect on male infertility caused by DNA damage in patients with chronic prostatitis.

[0086] 2.3 Obesity causes turbidity

[0087] Eighteen obese patients were included, of whom 16 did not have other high-risk factors such as varicocele or inflammation. They were treated with the decoction of Example 5. For details of the treatment method, please refer to Experimental Case 1.

[0088] Sperm indicators and testing were the same as in 2.1, and the results are shown in Table 6; the comprehensive therapeutic effect was evaluated using the method of Experiment 1, as shown in Table 7.

[0089] Table 6 Comparison of biochemical indicators before and after treatment

[0090]

[0091] As shown in Table 6, the sperm concentration increased after treatment, but the difference was not significant compared with before treatment. Compared with before treatment, the forward motility rate of sperm increased significantly, while the DFI index (19.8%) decreased significantly, indicating that the treatment effect was ideal.

[0092] Table 5 Overall therapeutic efficacy data

[0093]

[0094] "Oily people" are what Traditional Chinese Medicine calls obese people. These people live pampered lives with reduced physical activity, leading to the accumulation of fat in their bodies. This fat enters the blood vessels, causing the blood to become turbid and stagnant. Fat and turbidity often transform into each other, coexisting and causing disease simultaneously; hence, "fat and turbidity" are used together. Both fat and turbidity are pathological products of abnormal transformation of subtle substances. When fat enters the blood vessels and remains flowing, it becomes "turbidity"; when it deposits in the blood vessels or stagnates on the vessel walls, it becomes "phlegm." Turbidity and phlegm obstruct qi and blood, causing body fluids and blood to stagnate and become stagnant. Prolonged turbidity, phlegm, and stasis can transform into heat, fire, and toxins. "Turbidity, phlegm, stasis, heat, and toxins" damage the five internal organs, obstruct the meridians, injure yin and deplete qi, damage essence and blood, harm the spirit, and lead to a multitude of complications.

[0095] Obese individuals often suffer from spleen deficiency, leading to impaired digestive function. The rich and fatty foods fail to transform into vital energy, blood, and essence, resulting in stagnation of essence and qi. This stagnation causes the clear to transform into turbidity, which accumulates internally, stagnating in the blood vessels and infiltrating the meridians. This obstruction of the collaterals leads to malnourishment of the external genitalia, resulting in a deficiency of reproductive essence and damage to the sperm nucleus. Therefore, turbidity is an intermediate transitional state, a byproduct of oxidative stress produced by hyperlipidemia associated with obesity. It is a crucial pathogenesis in which the spleen's function of dispersing essence is disrupted by the transformation of turbid substances into toxins that damage the essence. Table 5 shows that the applicant modified the basic formula, appropriately increasing the dosage of Atractylodes lancea and Atractylodes macrocephala to obtain the herbal composition of Example 5, achieving the effect of clearing phlegm and turbidity. This composition showed a total effective rate of 93.8% in obese patients with male infertility caused by DNA damage, demonstrating excellent therapeutic efficacy.

[0096] 2.4 Other

[0097] Nine patients among the above-mentioned patients had at least two high-risk factors for DFA, including advanced age. They were treated with the decoction of Example 6, with the specific treatment method described in Experiment 1, the difference being that sperm indicators and detection were the same as in 2.1, and the results are shown in Table 8; the overall efficacy was evaluated using the method of Experiment 1, as shown in Table 9.

[0098] Table 8 Comparison of biochemical indicators before and after treatment

[0099]

[0100]

[0101] As shown in Table 8, the sperm concentration increased after treatment, but the difference was not significant compared with before treatment. Compared with before treatment, the forward motility rate of sperm increased, while the DFI index (24.5%) decreased, indicating that the treatment effect was relatively ideal.

[0102] Table 9 Overall therapeutic efficacy data

[0103]

[0104] The pathogenesis of male infertility due to sperm DNA damage can be summarized as follows: external factors causing "turbidity," often due to the invasion of imbalances in the four seasons; internal factors causing "turbidity," often due to spleen deficiency leading to internal dampness, which eventually transforms into turbidity. The interaction between internal and external factors results in a complex state of deficiency and excess in the body, making the condition chronic and difficult to cure. From a Western medical perspective, the mechanism of sperm DNA damage is usually summarized as: abnormal sperm nucleoprotein typography, abnormal apoptosis, and oxidative stress. Simply eliminating free radicals is clearly ineffective. Based on clinical practice, the applicant has identified the pathogenesis of "turbidity" caused by phlegm, dampness, and blood stasis obstructing the lower abdomen, leading to malnourishment of the male reproductive organs and damage to the reproductive essence. The stagnation of turbidity and poor blood circulation easily lead to spleen deficiency, which in turn aggravates the turbidity and further malnourishes the reproductive essence. The applicant has developed a rational combination of drugs and applied multi-target, multi-pathway treatment based on syndrome differentiation, achieving significant therapeutic effects.

[0105] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. The application of a traditional Chinese medicine composition for tonifying the kidneys and clearing turbidity in the preparation of a drug for treating male infertility, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: 12g of raspberry, 15g of dodder seed, 15g of codonopsis root, 4g of dioscorea hypoglauca, 6g of acorus tatarinowii, 12g of poria cocos, 15g of stir-fried atractylodes lancea, 10g of sarsaparilla, 1g of scalded leech, and 3g of prepared licorice root. The preparation method is as follows: weigh the raw materials according to the weight proportions, mix the weighed raw materials, decoct, filter, and concentrate into a decoction for oral administration; or, weigh the raw materials according to the weight proportions, obtain the extract using traditional Chinese medicine extraction technology, and prepare it into a clinically usable dosage form with one or more pharmaceutically acceptable carriers. The male infertility is caused by sperm DNA damage and accompanied by chronic prostatitis.

2. The application according to claim 1, characterized in that, The traditional Chinese medicine composition is in the form of capsules, tablets, decoctions, granules, syrups, drop pills, water pills, or honey pills for oral use.

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