Qiangyaoyushu pill, preparation method and application thereof in male infertility

Abstract

The application discloses strong waist pill, a preparation method thereof and application of the strong waist pill in male infertility, and belongs to the technical field of traditional Chinese medicine preparations. The strong waist pill is prepared from 14 raw medicinal materials of Fructus Lycii, salted Eucommia ulmoides, salted Semen Euryae, honey-fried Herba Epimedii, salted Fructus Psoraleae, salted Semen Astragali, mulberry, salted Semen Plantaginis, Semen Cnidii, raspberry, cornu cervi, gallnut, honey-fried Malus prunifolia Borkh, and honey-fried Schisandra chinensis in a weight ratio, and is prepared according to the therapeutic principle of tonifying kidney and essence, strengthening waist and astringency, and expelling dampness and assisting reproduction. The three-dimension synergy of tonifying, consolidating and clearing is adopted, and the combined process of super-micro pulverization and water extraction and alcohol precipitation is adopted, so that the slow-release long-acting and high dissolution rate are considered. The pharmacodynamics and clinical results show that the strong waist pill is significantly better than a simple kidney-tonifying prescription in improving sperm concentration and sperm activity, reducing sperm abnormality rate, increasing serum testosterone, and reducing sperm elastase, and has a definite curative effect on oligospermia, asthenospermia and teratospermia.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a Qiangyao Yuzi Pill for treating male infertility, its preparation method, and the application of the Qiangyao Yuzi Pill in the preparation of drugs for treating male infertility. Background Technology

[0002] Male infertility refers to the inability of a couple of reproductive age to conceive after more than one year of regular, unprotected sexual intercourse, excluding female factors, due to male causes. According to the World Health Organization (WHO), infertility affects approximately 15% of couples of reproductive age globally, with male factors accounting for about half. Typical clinical manifestations include oligospermia, asthenospermia, teratospermia, and semen liquefaction problems. In recent decades, with the accelerated pace of life and the prevalence of unhealthy lifestyles such as prolonged sitting, lack of sleep, and excessive smoking and drinking, the overall quality of semen has been declining. The WHO has lowered the reference lower limit for normal sperm concentration in men from previous values ​​to 15 × 10⁻⁶. 6 The decline in male fertility, measured in mL, has become a pressing public health issue. Patients with oligospermia and asthenospermia often experience symptoms such as lower back and knee pain, dizziness, tinnitus, fatigue, and decreased libido, which can easily lead to anxiety and family conflicts, severely impacting their physical and mental health and quality of life.

[0003] Male infertility has complex causes, involving endocrine disorders, reproductive system infections, varicocele, oxidative stress, and unhealthy lifestyle habits. Among these, oxidative stress and chronic inflammation in the testes and epididymis are crucial factors leading to impaired spermatogenesis and decreased sperm function: excessive reactive oxygen species can damage sperm cell membranes, mitochondria, and sperm DNA, reducing sperm motility and increasing sperm abnormality rates; latent inflammation in the reproductive tract often manifests as elevated levels of seminal plasma elastase, further disrupting the seminal plasma microenvironment and inhibiting sperm survival. From a Traditional Chinese Medicine (TCM) perspective, the aforementioned local inflammation and oxidative damage correspond to the pathogenesis of internal dampness and damp-heat accumulation, suggesting that clearing dampness and improving the reproductive tract microenvironment while tonifying the kidneys and replenishing essence is crucial for restoring fertility. However, most existing kidney-tonifying TCM preparations primarily focus on warming the kidneys and tonifying essence, and long-term oral administration can easily cause discomfort such as excessive heat, lacking synergistic conditioning methods targeting internal dampness and weak seminal control.

[0004] Modern medicine treats male infertility primarily through Western medicine, assisted reproductive technologies, and traditional Chinese medicine. Western medicine commonly uses gonadotropins, androgens, and antioxidants, which can improve some semen parameters in the short term, but long-term use can easily lead to endocrine disorders and liver damage. These medications also have limited targeting and are difficult to improve chronic inflammation of the reproductive system. Assisted reproductive technologies are expensive, complex, and have limited success rates, and cannot fundamentally improve the patient's reproductive health. Traditional Chinese medicine excels in holistic conditioning and syndrome differentiation, possessing unique advantages in improving semen quality and restoring fertility. Traditional Chinese medicine believes that the core pathogenesis of male infertility is kidney essence deficiency and liver and kidney insufficiency, and the treatment principle is mainly to tonify the kidney and replenish essence. The classic fertility formula, Wuzi Yanzong Wan, was first recorded in the Ming Dynasty's *She Sheng Zhong Miao Fang*. Composed of five herbs—goji berries, dodder seeds, raspberries, schisandra berries, and plantain seeds—it tonifies the kidney and replenishes essence, and regulates kidney qi. It is hailed as the premier fertility formula throughout history and has a certain therapeutic effect on infertility caused by kidney deficiency and low sperm count. However, these classic seed formulas tend to be warm and nourishing, mainly for tonifying the kidneys and replenishing essence. Among the ingredients, only Plantago seed has a mild diuretic effect. They lack targeted methods for consolidation and clearing away the weak seminal control and internal dampness that often coexist in patients with oligospermia and asthenospermia.

[0005] There are also improvements to traditional Chinese medicine compound formulas for treating male infertility in the existing technology. Chinese invention patent application with publication number CN117357621A discloses a traditional Chinese medicine compound formula for improving sperm energy metabolism, its preparation method and application. The traditional Chinese medicine compound is composed of raw Astragalus membranaceus, Codonopsis pilosula, Rhodiola rosea, Curculigo orchioides, Epimedium brevicornu, Cuscuta chinensis, Astragalus complanatus, Rehmannia glutinosa (processed), Rehmannia glutinosa (raw), Polygonatum sibiricum (processed), Trionyx sinensis (processed), Curcuma zedoaria, Salvia miltiorrhiza, and Carthamus tinctorius in proportion to weight. The treatment principle is to warm and tonify kidney yang, nourish kidney yin, and promote blood circulation and remove blood stasis. The extract is prepared by decoction and vacuum concentration, and can be further made into tablets, capsules or granules for the preparation of drugs that improve the normal sperm morphology rate and sperm DNA integrity. However, this plan is based on tonifying both Yin and Yang and invigorating Qi and blood to improve sperm mitochondrial energy metabolism. Its formula does not address the common coexistence of weak sperm control and internal dampness and turbidity in patients with oligospermia and asthenospermia, and does not provide synergistic means of consolidation and clearing away these issues. The replenished kidney essence is still easily lost due to weak sperm control, and the semen is not easy to liquefy. Furthermore, the oxidative stress and inflammatory microenvironment caused by internal dampness and turbidity in the testes and reproductive tract are not cleared, which continues to damage sperm. Therefore, it is difficult to simultaneously consolidate the sperm control and clear dampness and turbidity while tonifying the kidney and replenishing essence. It has limited improvement for those with semen non-liquefaction, low sperm motility, and elevated seminal plasma elastase.

[0006] In summary, existing traditional Chinese medicine formulas for treating male infertility that tonify the kidneys generally suffer from the same core technical deficiency: it is generally believed in the field that the treatment of oligospermia and asthenospermia should focus on tonifying the kidneys and replenishing essence, and that astringent and consolidating herbs are prone to causing stagnation and retention, and therefore should not be used extensively in fertility formulas. However, in reality, oligospermia and asthenospermia often coexist with the complex pathogenesis of weak seminal control (the replenished kidney essence is lost with the sperm and the semen does not liquefy) and internal dampness and turbidity (oxidative stress and reproductive tract inflammation increase seminal plasma elastase, which damages sperm). Simply tonifying the kidneys and replenishing essence without simultaneously consolidating the kidney essence and clearing away dampness and turbidity leads to the replenished essence being lost with the weak seminal control and damaged by the adverse microenvironment of internal dampness and turbidity. This is the bottleneck mechanism that limits the efficacy of existing kidney-tonifying fertility formulas and their improved formulations. How to ensure that the replenished kidney essence is simultaneously contained within the seminal gate and survives in the low-oxidative stress environment after the removal of dampness and turbidity, without inducing stagnation or obstruction from replenishment, is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0007] To address the aforementioned shortcomings of existing technologies, the present invention aims to provide a kidney-strengthening and spermatogenic pill for treating male infertility. This invention is based on the complex pathogenesis of male infertility, which involves liver and kidney deficiency, insufficient kidney essence, weak seminal control, and internal dampness and turbidity. It breaks through the limitations of simply tonifying the kidney and replenishing essence, establishing a three-dimensional synergistic principle of tonification, consolidation, and clearing. This ensures that the replenished kidney essence is consolidated within the seminal control while simultaneously being in a low-oxidative-stress microenvironment through clearing dampness and turbidity. This effectively solves the efficacy bottleneck caused by existing kidney-tonifying and spermatogenic formulas that tonify without consolidating or clearing, while simultaneously improving sperm count, sperm motility, and semen liquefaction.

[0008] Another object of the present invention is to provide a method for preparing the above-mentioned Qiangyao Yuzi Pill; a further object of the present invention is to provide the application of the above-mentioned Qiangyao Yuzi Pill in the preparation of a drug for treating male infertility.

[0009] To achieve the above objectives, the present invention adopts the following technical solution:

[0010] The Qiangyao Yuzi Pill, used to treat male infertility, is made from the following raw materials in parts by weight: 10-20 parts of wolfberry, 10-20 parts of salted eucommia bark, 10-20 parts of salted dodder seed, 10-20 parts of processed epimedium, 10-20 parts of salted psoralea corylifolia, 10-20 parts of salted astragalus complanatus, 10-20 parts of mulberry, 10-20 parts of salted plantain seed, 10-20 parts of cnidium monnieri, 6-12 parts of raspberry, 3-9 parts of deer antler, 3-9 parts of gallnut, 3-9 parts of processed rosehip, and 3-9 parts of honey-processed schisandra chinensis.

[0011] Preferably, the weight parts of each raw material are as follows: 12-18 parts of wolfberry, 12-18 parts of salted eucommia bark, 12-18 parts of salted dodder seed, 12-18 parts of processed epimedium, 12-18 parts of salted psoralea corylifolia, 12-18 parts of salted astragalus complanatus, 12-18 parts of mulberry, 12-18 parts of salted plantain seed, 12-18 parts of cnidium monnieri, 7-11 parts of raspberry, 4-8 parts of deer antler, 4-8 parts of gallnut, 4-8 parts of processed rosehip, and 4-8 parts of honey-processed schisandra chinensis.

[0012] More preferably, the weight parts of each raw material are as follows: 15 parts of wolfberry, 15 parts of salted eucommia bark, 15 parts of salted dodder seed, 15 parts of processed epimedium, 15 parts of salted psoralea corylifolia, 15 parts of salted astragalus complanatus, 15 parts of mulberry, 15 parts of salted plantain seed, 15 parts of cnidium monnieri, 9 parts of raspberry, 6 parts of deer antler, 6 parts of gallnut, 6 parts of processed rosehip, and 6 parts of honey-processed schisandra chinensis.

[0013] Preferably, the salt-processed Eucommia ulmoides, salt-processed Cuscuta chinensis, salt-processed Psoralea corylifolia, salt-processed Astragalus complanatus, and salt-processed Plantago asiatica are all salt-processed products, and the salt-processed Epimedium brevicornu, salt-processed Rosa laevigata, and honey-processed Schisandra chinensis are all honey-processed products. Salt processing can guide the medicine to the kidneys and enhance the kidney-tonifying and astringent effects of the medicinal materials, while honey processing can moderate the medicinal properties, moisten dryness, and enhance efficacy, making the whole formula tonifying without being drying and astringent without being astringent.

[0014] Preferably, the Qiangyao Yuzi Pill is a water-honey pill or a concentrated pill, each weighing 6-9 g; the powder used to make the Qiangyao Yuzi Pill is ultra-finely pulverized to a particle size D90 ≤ 45 μm to improve the dissolution and bioavailability of the active ingredients; determined by high performance liquid chromatography, on a dried basis, the content of icariin in the Qiangyao Yuzi Pill is not less than 0.10%, the content of osthol is not less than 0.05%, and the content of gallic acid is not less than 0.03%. The above three components are quality markers of processed epimedium, cnidium monnieri, and gallnut, respectively, and the control of their lower limits can ensure the stability of the three-dimensional effects of the formula in tonifying, consolidating, and clearing.

[0015] The present invention also provides a method for preparing the above-mentioned Qiangyao Yuzi Pill, comprising the following steps: (1) weighing each raw material according to the weight parts; (2) taking deer antler separately and crushing it into fine powder to obtain deer antler fine powder; taking Cnidium monnieri separately and crushing it into fine powder, or extracting Cnidium monnieri volatile oil to obtain Cnidium monnieri material; (3) adding water to the remaining raw materials and decocting them 2 to 3 times, combining the decoctions, filtering, and concentrating under reduced pressure to a clear paste with a relative density of 1.05 to 1.15 at 60°C; (4) adding ethanol to the clear paste to a content of 60% to 75%, stirring well, refrigerating and standing for 12 to 24 hours, filtering the supernatant, recovering the ethanol and concentrating under reduced pressure to a thick paste with a relative density of 1.30 to 1.35 at 60°C; (5) mixing the thick paste with the deer antler fine powder and Cnidium monnieri material obtained in step (2), adding refined honey to make water-honey pills or concentrated pills, drying, and thus obtaining the Qiangyao Yuzi Pill. The combined process of ultrafine pulverization and water extraction with alcohol precipitation not only retains the advantages of traditional pills, such as slow release, long-lasting effect, and ease of administration, but also significantly improves the dissolution rate of active ingredients and the purity of the formula through ultrafine pulverization and alcohol precipitation to remove impurities.

[0016] The present invention also provides the application of the above-mentioned Qiangyao Yuzi Pill in the preparation of a drug for treating male infertility; the male infertility is preferably a syndrome of liver and kidney deficiency and kidney essence insufficiency according to traditional Chinese medicine diagnosis, which is clinically manifested as one or more of oligospermia, asthenospermia and teratospermia, and may be accompanied by reproductive system inflammation with elevated seminal plasma elastase.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] Firstly, the formula is scientifically formulated, with significant and targeted efficacy. This invention focuses on tonifying the kidneys and replenishing essence, strengthening the lower back and consolidating essence, and dispelling dampness and promoting fertility. It closely addresses the complex pathogenesis of male infertility, which involves liver and kidney deficiency, insufficient kidney essence, weak seminal control, and internal dampness. It organically combines tonification (replenishing essence and warming yang), consolidation (astringent and astringent), and clearing (drying dampness and promoting diuresis). This approach not only strongly tonifies kidney essence and warms kidney yang, but also consolidates the seminal control and clears dampness, avoiding the compatibility defects of tonification leading to stagnation or consolidation leading to stagnation. Pharmacological experiments show that this invention is significantly superior to classic sperm formulas that simply tonify the kidneys and replenish essence, and to comparative formulas that remove any key components, in increasing sperm concentration and motility, reducing sperm abnormality rate, increasing serum testosterone, and reducing seminal plasma elastase. It also improves oligospermia, asthenospermia, teratospermia, and associated mild inflammation of the reproductive system.

[0019] Secondly, it is safe, non-toxic, and has few side effects. The 14 raw materials used in this invention are all commonly used Chinese medicines that meet national drug standards. After standardized processing, they are mild in nature and have a reasonable combination. The preparation process removes impurities through water extraction and alcohol precipitation, further enhancing the safety of the formula, making it suitable for patients who need long-term conditioning of reproductive function.

[0020] Third, it has a high degree of standardization and is easy to promote. This invention clarifies the fixed formula, precise dosage, standardized preparation process, quantified quality control indicators, and standardized indications, transforming clinical experience formulas into replicable and scalable standardized treatment techniques, overcoming the pain points of traditional experience formulas such as inconsistent dosage, non-standardized processes, and difficulty in quantifying efficacy.

[0021] Fourth, it balances tradition and modernity, and is economical and practical. This invention inherits the core advantages of traditional Chinese medicine's syndrome differentiation and treatment and holistic conditioning, while combining modern pharmaceutical technologies such as ultra-micro pulverization and water extraction with alcohol precipitation, giving traditional prescriptions modern scientific and technological connotations. The medicinal materials used are widely available and their prices are controllable. The preparation process is simple, and the treatment cost is far lower than that of assisted reproductive technology and imported Western medicines, giving it good social value and prospects for promotion. Attached Figure Description

[0022] Figure 1 This is a process flow diagram of the preparation method of the "Strengthening Waist and Promoting Fertility Pill" of the present invention.

[0023] Figure 2 This is a bar chart comparing sperm concentration, sperm motility, and sperm abnormality rate in different groups of rats after treatment in the pharmacodynamic experiment of this invention. Detailed Implementation

[0024] The present invention will be further described below with reference to the accompanying drawings and embodiments, but the scope of protection of the present invention is not limited thereto. Unless otherwise specified, the raw materials used in the present invention all comply with national drug standards, and the methods used are all conventional methods in the art. The relative densities of the clear paste and thick paste mentioned in the present invention, unless otherwise noted, refer to the relative densities measured at 60°C according to the relative density determination method of the Chinese Pharmacopoeia, with water at the same temperature as the reference. The material that is ultra-finely pulverized before pill making in step (5) of the preparation method refers to the material obtained after mixing the thick paste with the deer antler powder and Cnidium monnieri material obtained in step (2).

[0025] This invention, the Strong Waist and Fertility Pill, is made from 14 raw medicinal materials in specific weight proportions. Salt-processed Eucommia ulmoides, salt-processed Cuscuta chinensis, salt-processed Psoralea corylifolia, salt-processed Astragalus complanatus, and salt-processed Plantago asiatica are processed using salt-roasting techniques, while roasted Epimedium brevicornu, roasted Rosa laevigata, and honey-processed Schisandra chinensis are processed using honey-roasting techniques. These processing methods enhance the kidney-tonifying, astringent, and diuretic effects of the medicinal materials, aligning with the traditional Chinese medicine theory of enhanced efficacy through processing. The entire formula follows the principles of principal, assistant, adjuvant, and guide herbs, with each herb working synergistically to address both the root cause and the symptoms. Salt-processed Eucommia ulmoides, deer antler, and salt-processed Cuscuta chinensis are the principal herbs: salt-processed Eucommia ulmoides tonifies the liver and kidneys and strengthens tendons and bones; deer antler, being a substance rich in blood and flesh, strongly tonifies kidney essence and promotes sperm production and development; salt-processed Cuscuta chinensis enhances its kidney-tonifying and astringent effects, preventing sperm loss due to weak seminal control. The formula uses wolfberry, mulberry, salt-processed psoralea, processed epimedium, and salt-processed astragalus seed as assistant herbs: wolfberry and mulberry nourish kidney essence and yin, counteracting the warming and drying properties of the principal herbs; salt-processed psoralea and processed epimedium warm and tonify kidney yang, improving sperm motility; salt-processed astragalus seed tonifies the kidney and astringes, assisting in consolidating kidney essence. The formula uses gallnut, processed rosehip, raspberry, honey-processed schisandra, cnidium, and salt-processed plantain seed as adjuvant herbs: the first four astringe and consolidate, consolidating essence and calming the mind; cnidium warms the kidney and strengthens yang, dries dampness and eliminates dampness, improving inflammation of the reproductive system; salt-processed plantain seed promotes diuresis and eliminates dampness, guiding the medicine to the kidneys, clearing dampness and unblocking the seminal ducts. The salt-processed herbs act as guiding herbs, directing them to the kidneys and the affected area, harmonizing the properties of the entire formula.

[0026] The processed medicinal materials used in this invention can be prepared as follows: Salt-processed products are prepared by taking cleaned Eucommia ulmoides, Cuscuta chinensis, Psoralea corylifolia, Astragalus complanatus, and Plantago asiatica, mixing them thoroughly with a salt solution, allowing them to soak until fully hydrated, placing them in a stir-frying container, and stir-frying over a low heat until the specified degree is reached, then cooling to obtain salted Eucommia ulmoides, salted Cuscuta chinensis, salted Psoralea corylifolia, salted Astragalus complanatus, and salted Plantago asiatica. The amount of salt used is generally 2-3 kg per 100 kg of medicinal materials. Honey-processed products are prepared by taking cleaned Epimedium brevicornu, Rosa laevigata, and Schisandra chinensis, adding an appropriate amount of refined honey and diluted with boiling water, mixing thoroughly, allowing them to soak, placing them in a stir-frying container, and stir-frying over a low heat until they are no longer sticky, then cooling to obtain processed Epimedium brevicornu, processed Rosa laevigata, and honey-processed Schisandra chinensis. The amount of refined honey used is generally 20-30 kg per 100 kg of medicinal materials. Salt-processed herbs guide the medicine to the kidneys and enhance their kidney-tonifying and astringent effects, while honey-processed herbs moderate the medicinal properties and enhance their moisturizing and nourishing effects. This makes the whole formula nourishing without causing dryness and astringent without causing stagnation, which is consistent with the three-dimensional compatibility principle of tonifying, astringing, and clearing in this invention.

[0027] The key to this invention lies in constructing a three-dimensional synergistic formula of tonification, consolidation, and clearing. In terms of tonification, deer antler, salt-processed Eucommia ulmoides, salt-processed Cuscuta chinensis, salt-processed Psoralea corylifolia, and processed Epimedium brevicornu strongly tonify kidney essence and warm and tonify kidney yang, directly addressing the root cause of liver and kidney deficiency and insufficient kidney essence. In terms of consolidation, Gallnut, processed Rosa laevigata, honey-processed Schisandra chinensis, Rubus idaeus, and salt-processed Astragalus complanatus astringe and consolidate, securing the seminal orifice, preventing the loss of tonified kidney essence due to a weakened seminal orifice, and helping to improve semen liquefaction problems. In terms of clearing, Cnidium monnieri dries and eliminates dampness, while salt-processed Plantago asiatica promotes diuresis and eliminates dampness, forming a dual channel of drying dampness and promoting diuresis, clearing the oxidative stress and inflammatory microenvironment caused by internal dampness and turbidity. Most importantly, this invention combines the astringent and sour properties of Gallnut and Rosa laevigata with the damp-drying and diuretic properties of Cnidium monnieri and Plantago asiatica. Conventionally, strong astringents can lead to excessive astringency, hindering semen liquefaction and the expulsion of dampness, while damp-drying and diuretic substances can counteract the astringent effect. However, in this invention, the astringent substances strengthen the seminal vesicles without obstructing them, while the diuretic substances remove dampness without harming the kidney essence. The two work in reverse synergy, achieving a balance of tonification without stagnation and strengthening without obstruction. This synergistic effect is difficult for those skilled in the art to anticipate based on existing formulation knowledge and is the core of this invention's inventiveness.

[0028] Modern pharmacological studies also support the above-mentioned combination. Lycium barbarum polysaccharides in Lycium barbarum can improve testicular spermatogenesis and enhance sperm motility; icariin in Epimedium can regulate the hypothalamic-pituitary-gonadal axis and improve semen parameters; total flavonoids in Cuscuta chinensis can protect testicular spermatogenic cells; eucommia flavonoids in Eucommia ulmoides can regulate reproductive endocrine function and promote testosterone secretion; and deer antler polypeptides in deer antler can promote spermatogenesis and improve sperm quality. The main active ingredient in Cnidium monnieri, osthol, has androgen-like and gonadotropin-like effects, promoting the production of luteinizing hormone, follicle-stimulating hormone, and testosterone. It also possesses antioxidant, anti-inflammatory, and antibacterial activities. Studies have shown that Cnidium monnieri can increase testicular weight, epididymal sperm count, and sperm motility. Its dampness-drying and dampness-removing effects correspond to modern pharmacological effects in improving reproductive system inflammation and reducing seminal plasma elastase levels. Gallnut is rich in tannins and gallic acid, possessing astringent, antioxidant, and antibacterial effects, which help reduce oxidative stress levels in seminal plasma. Plantain seed polysaccharides can improve reproductive system inflammation and reduce seminal plasma elastase concentration. The modern pharmacological effects of each herb align with their functional positioning in the three-dimensional combination of tonifying, consolidating, and clearing, synergistically enhancing the therapeutic effect.

[0029] In addition to the principal and adjuvant herbs that clear heat and promote diuresis, the modern pharmacology of the assistant and adjuvant herbs in this invention also corroborates their compatibility and functions. Psoralea corylifolia contains psoralen and isopsoralen, which have androgen-like effects, promoting testosterone secretion from interstitial cells of the testes and improving spermatogenesis; Astragalus complanatus contains Astragalus complanatus flavonoids, which have antioxidant and reproductive endocrine-regulating effects, helping to reduce oxidative stress damage to spermatogenic cells; Rubus idaeus and Rosa laevigata are rich in flavonoids, tannins, and organic acids, possessing both antioxidant and astringent effects, and their astringent function can be manifested in modern pharmacology as stabilizing the seminal plasma environment and reducing abnormal sperm loss; Schisandra chinensis contains schisandrin, which has significant antioxidant and protective effects, scavenging reactive oxygen species and protecting sperm cell membranes and mitochondrial function. The antioxidant and astringent effects of the above-mentioned medicinal materials, together with the anti-inflammatory and enzyme-lowering effects of Cnidium monnieri and Plantago asiatica, work together to reduce the oxidative stress and inflammation levels in seminal plasma. This supports the technical effect of the present invention in improving semen quality through a three-dimensional synergistic approach of supplementation, astringency, and cleansing at the molecular level. It also explains why the complete formula is significantly more effective than the formula that removes any key component.

[0030] Example 1

[0031] Weigh the raw materials according to the following proportions: 150 g of wolfberry, 150 g of salt-processed eucommia bark, 150 g of salt-processed dodder seed, 150 g of processed epimedium, 150 g of salt-processed psoralea corylifolia, 150 g of salt-processed astragalus complanatus seed, 150 g of mulberry, 150 g of salt-processed plantain seed, 150 g of cnidium monnieri fruit, 90 g of raspberry, 60 g of deer antler, 60 g of gallnut, 60 g of processed rosehip, and 60 g of honey-processed schisandra fruit. Prepare according to... Figure 1 The process flow shown is as follows: (1) Take deer antler and crush it separately, pass it through the No. 5 sieve of the pharmacopoeia to obtain deer antler fine powder, and set it aside; take Cnidium monnieri and extract volatile oil by steam distillation, collect the volatile oil of Cnidium monnieri and retain the medicine liquid and medicine residue after oil extraction, and set it aside; (2) Take wolfberry, salted Eucommia ulmoides, salted Cuscuta chinensis, roasted Epimedium, salted Psoralea corylifolia, salted Astragalus complanatus, mulberry, salted Plantago asiatica, raspberry, gallnut, roasted Rosa laevigata, honey-roasted Schisandra chinensis, a total of twelve herbs, and the medicine residue after oil extraction of Cnidium monnieri, add water with a total weight of 8 times the weight of the raw materials, decoct twice, 1.5 h each time, combine the decoction, filter, and concentrate the filtrate under reduced pressure to a clear paste with a relative density of 1.10 at 60°C; (3) Slowly add 95% ethanol to the clear paste to make the alcohol content reach 70%, stir well, and refrigerate at 4°C for 24 hours. h, filter the supernatant, recover the ethanol under reduced pressure, and continue to concentrate to a thick paste with a relative density of 1.32 at 60°C; (4) mix the thick paste with deer antler powder and Cnidium monnieri volatile oil, pulverize it into ultrafine powder and granulate it to a particle size D90≤45 μm, add an appropriate amount of refined honey to make water-honey pills, dry under reduced pressure at 60°C, each pill weighs 6 g, and that is the result.

[0032] Example 2

[0033] Weigh the raw materials according to the following proportions by weight: 100 g of wolfberry, 100 g of salted eucommia bark, 100 g of salted dodder seed, 100 g of roasted epimedium, 100 g of salted psoralea corylifolia, 100 g of salted astragalus complanatus, 100 g of mulberry, 100 g of salted plantain seed, 100 g of cnidium monnieri, 60 g of raspberry, 30 g of deer antler, 30 g of gallnut, 30 g of roasted rosehip, and 30 g of honey-roasted schisandra chinensis. The preparation process is the same as in Example 1, except that in step (2), water equal to 6 times the total weight of the raw materials is added and decocted twice, 2 hours each time; in step (3), the alcohol content is increased to 60%; and concentrated pills weighing 9 g each are made.

[0034] Example 3

[0035] Weigh the raw materials according to the following proportions by weight: 200 g of wolfberry, 200 g of salted eucommia bark, 200 g of salted dodder seed, 200 g of roasted epimedium, 200 g of salted psoralea corylifolia, 200 g of salted astragalus complanatus, 200 g of mulberry, 200 g of salted plantain seed, 200 g of cnidium monnieri, 120 g of raspberry, 90 g of deer antler, 90 g of gallnut, 90 g of roasted rosehip, and 90 g of honey-roasted schisandra chinensis. The preparation process is the same as in Example 1, except that in step (2), water equal to 10 times the total weight of the raw materials is added and decocted 3 times, 1 hour each time; in step (3), the alcohol content is increased to 75%; and water-honey pills weighing 6 g each are made.

[0036] Example 4

[0037] The contents of icariin, osthol, and gallic acid in the Qiangyao Yuzi Pill obtained in Example 1 were determined by high-performance liquid chromatography (HPLC). The chromatographic conditions were as follows: octadecylsilane-bonded silica gel as the packing material; gradient elution using acetonitrile-0.1% phosphoric acid aqueous solution as the mobile phase; column temperature 30°C; flow rate 1.0 mL / min; and detection wavelengths of 270 nm (icariin), 322 nm (osthol), and 273 nm (gallic acid). The results showed that, based on dried product, the contents of icariin, osthol, and gallic acid in the Qiangyao Yuzi Pill obtained in Example 1 were 0.14%, 0.07%, and 0.04%, respectively, all meeting the quality control requirements of this invention. This indicates that the combined ultrafine pulverization and water extraction / alcohol precipitation process can effectively retain the quality markers corresponding to the three-dimensional effects of replenishment, consolidation, and cleansing.

[0038] To investigate the effect of ultrafine grinding on the dissolution of active ingredients, the Qiangyao Yuzi Pills obtained in Example 1 and a control pill (powder passed through an 80-mesh sieve) were compared, and the dissolution behavior of icariin was examined using the dissolution test method. The results showed that, within the same time period, the cumulative dissolution rate of icariin in the pills of Example 1, which were ultrafine ground to a particle size D90 ≤ 45 μm, was significantly higher than that in the control pills, and the dissolution rate was also faster. This indicates that the combined process of ultrafine grinding and water extraction / alcohol precipitation can significantly improve the dissolution of active ingredients, overcoming the shortcomings of traditional pills such as slow onset of action and low dissolution rate of active ingredients. The stability of the Qiangyao Yuzi Pills obtained in Example 1 was examined under accelerated testing conditions. Its properties, moisture content, and icariin content showed no significant changes during the testing period, indicating that the formulation of this invention has good stability and controllable quality.

[0039] Comparative Example 1 is the classic seed formula Wuzi Yanzong Wan, composed of Lycium barbarum, Cuscuta chinensis (salted), Rubus idaeus, Schisandra chinensis (honey-processed), and Plantago asiatica (salted) in equal proportions, with the dosages identical to those in Example 1, and the preparation process is the same as in Example 1. Comparative Example 2 is the prescription of Example 1 with the removal of Galla chinensis and Rosa laevigata (removing the astringent group), while the remaining herbs, dosages, and processes are identical to those in Example 1. Comparative Example 3 is the prescription of Example 1 with the removal of Cnidium monnieri (removing the drying and dampness group), while the remaining herbs, dosages, and processes are identical to those in Example 1. Comparative Example 4 is the prescription of Example 1 with the removal of deer antler (removing the drastic tonifying group), while the remaining herbs, dosages, and processes are identical to those in Example 1. The above comparative examples correspond to the key components in the three-dimensional combination of tonification, consolidation, and clearing in this invention, and are used to verify the contribution of each dimension to the overall therapeutic effect.

[0040] Example 5

[0041] Healthy male SD rats were randomly divided into four groups: a blank control group, a model control group, comparative example 1, comparative example 2, comparative example 3, comparative example 4, and example 1 of this invention, with 12 rats in each group. Except for the blank control group, all other groups were administered Tripterygium wilfordii polyglycoside suspension by gavage at a dose of 25 mg / kg for 4 consecutive weeks to establish a rat model of renal deficiency, oligospermia, and asthenospermia. After successful modeling, the blank control group and the model control group were administered an equal volume of physiological saline by gavage, while the other groups were administered an aqueous suspension of the corresponding test sample by gavage. The dosage was calculated according to the clinical equivalent dose, and the administration was once daily for 8 consecutive weeks. After the administration was completed, epididymal tail sperm suspension was collected, and sperm concentration, grade a+b sperm motility rate, and sperm abnormality rate were detected according to the methods in the World Health Organization's "Laboratory Manual for the Examination and Processing of Human Semen". Serum was collected to determine the levels of testosterone, follicle-stimulating hormone, and luteinizing hormone. Seminal plasma was collected to determine the concentration of seminal plasma elastase. Testicular tissue was collected for hematoxylin-eosin staining to observe the morphology of seminiferous tubules. Data were expressed as mean ± standard deviation. One-way ANOVA was performed using SPSS 26.0 software, with P < 0.05 considered statistically significant. Sperm quality parameters for each group are as follows: Figure 2As shown in Table 1, the specific data are shown in Table 2, and the serum hormone and seminal plasma elastase levels are shown in Table 2.

[0042] Table 1 Comparison of sperm quality parameters in rats after treatment (mean ± standard deviation, n=12)

[0043] Group <![CDATA[Sperm concentration (×10 6 / mL)]]> Grade A+B sperm motility (%) Sperm deformity rate (%) Blank control group 58.6±6.2 68.4±5.1 12.3±2.1 Model control group 22.4±4.3 31.2±4.8 34.6±3.9 Comparative Example 1 (Wuzi Yanzong Wan) 38.7±5.1 46.8±4.5 24.1±3.2 Comparative Example 2 (for removing astringency) 42.3±4.8 49.2±4.2 22.8±2.9 Comparative Example 3 (Dehumidification) 43.1±5.0 50.6±4.1 21.4±3.0 Comparative Example 4 (with deer antlers removed) 40.2±4.6 47.9±4.4 23.2±3.1 Example 1 of the present invention 52.8±5.5 63.7±4.9 14.8±2.4

[0044] Table 2 Comparison of serum hormone and seminal plasma elastase levels in rats after treatment in each group (mean ± standard deviation, n=12)

[0045] Group Testosterone (ng / mL) Follicle-stimulating hormone (mIU / mL) Luteinizing hormone (mIU / mL) Seminal plasma elastase (ng / mL) Blank control group 4.82±0.51 2.14±0.38 1.86±0.31 128±22 Model control group 2.31±0.44 3.86±0.52 3.42±0.48 356±41 Comparative Example 1 (Wuzi Yanzong Wan) 3.52±0.48 3.01±0.45 2.68±0.42 268±35 Comparative Example 2 (for removing astringency) 3.71±0.49 2.86±0.43 2.53±0.40 247±33 Comparative Example 3 (Dehumidification) 3.68±0.50 2.92±0.43 2.55±0.40 312±38 Comparative Example 4 (with deer antlers removed) 3.28±0.46 3.05±0.44 2.71±0.41 259±34 Example 1 of the present invention 4.51±0.53 2.38±0.40 2.02±0.35 156±26

[0046] From Table 1, Table 2 and Figure 2 It was found that the model control group showed significantly reduced sperm concentration and motility, increased sperm abnormality rate, decreased serum testosterone, compensatory increases in follicle-stimulating hormone and luteinizing hormone, and significantly increased seminal plasma elastase, indicating successful model establishment accompanied by reproductive endocrine disorders and reproductive tract inflammation. In Example 1 of this invention, all indicators were significantly improved and approached the levels of the blank control group. Furthermore, the sperm concentration, sperm motility, sperm abnormality rate, serum testosterone, and seminal plasma elastase levels were significantly better than those of Comparative Examples 1 to 4 (P<0.05), demonstrating that the complete formula of this invention, with its three-dimensional synergistic effect of tonifying, consolidating, and clearing, has a significantly better overall therapeutic effect than simple kidney-tonifying and sperm-replenishing formulas or formulas that remove any key component.

[0047] Further analysis reveals that the results of each comparative example confirm the necessity of the key components of this invention and the validity of the underlying compatibility principle. Comparative Example 1 (Wuzi Yanzong Wan) showed some improvement compared to the model control group, but the improvement was limited. Its sperm concentration, motility recovery, and sperm abnormality rate reduction were significantly weaker than in Example 1, indicating that simply tonifying the kidneys and replenishing essence is insufficient to reverse the decline in semen quality caused by complex pathogenesis, consistent with the bottleneck in the efficacy of existing seed formulas pointed out in the background art. Comparative Example 2 (Qugushi), after removing gallnut and roasted rosehip, although retaining the tonifying and clearing dimensions, still showed a less significant improvement in sperm concentration and motility than in Example 1, indicating that the astringent dimension is indispensable for consolidating kidney essence and reducing sperm loss. Comparative Example 3 (Quzaoshi), after removing Cnidium monnieri, showed a significantly higher level of seminal plasma elastase than in Example 1 and close to the model control group, with insufficient reduction in sperm abnormality rate. This directly demonstrates the crucial role of Cnidium monnieri's dampness-removing, anti-inflammatory, and enzyme-lowering clearing dimensions in improving the inflammatory microenvironment of the reproductive tract and protecting sperm morphology. Comparative Example 4 (without deer antler): After removing the potent tonic containing blood and flesh, the sperm concentration recovery was significantly insufficient, indicating that the potent kidney-tonifying effect of deer antler cannot be replaced by herbal products.

[0048] The above results verify the inventiveness of this invention from both the underlying and component levels. At the underlying level, the synergistic principle of tonification, consolidation, and clearing is the source of efficacy. Removing any dimension (removing astringency, drying dampness, or strong tonification) significantly reduces the overall efficacy. Only when all three dimensions are present can the optimal effect be achieved, proving that it is the overall principle of compatibility, rather than a single herb, that drives the efficacy. At the component level, the contributions of gallnut and roasted rosehip to consolidation, cnidium monnieri to clearing and draining, and deer antler to strong tonification can be separated and quantified, and each contribution corresponds one-to-one with its functional positioning in the three-dimensional compatibility, constituting specific component innovations naturally arising from the underlying principle. Furthermore, in Example 1, the astringent and sour herbs Gallnut and processed Rosa laevigata were used together with the damp-drying and diuretic herbs Cnidium monnieri and salt-processed Plantago asiatica. There was no mutual cancellation of the therapeutic effects caused by astringency hindering liquefaction or diuresis damaging sperm. On the contrary, there were simultaneous benefits in both sperm survival (motility) and inflammation clearance (decreased seminal plasma elastase). This confirms the reverse synergistic effect of consolidating the sperm duct without obstructing the seminal canal and removing dampness and turbidity without damaging kidney essence. This effect is difficult for those skilled in the art to predict based on existing compatibility knowledge.

[0049] Histopathological observation of testicular tissue further supports the above conclusions. In the model control group, the seminiferous tubules showed atrophy, reduced seminiferous epithelial layers, and few mature sperm in the lumen. In Comparative Example 1 and Comparative Examples 2 to 4 (with key components removed), the morphology of the seminiferous tubules recovered to varying degrees, but some tubules were still disordered. In Example 1 of this invention, the seminiferous tubule structure was relatively complete, the seminiferous epithelial layers were clear, the spermatogenic cells at all levels were arranged regularly, and a large number of mature sperm were visible in the lumen, close to the blank control group. In addition, the examination of semen liquefaction showed that the semen liquefaction time was prolonged in the model control group and Comparative Example 2 (with astringent removal), while the semen liquefaction time was significantly shortened in Example 1 of this invention. This indicates that this invention, while consolidating the seminal vesicles, did not hinder semen liquefaction. On the contrary, it improved the overall quality of semen through the three-dimensional synergy of replenishment, consolidation, and clarification, further confirming the reverse synergistic effect of consolidating the seminal vesicles without obstructing the seminal ducts.

[0050] Example 6

[0051] Male infertility patients who are diagnosed with liver and kidney deficiency and insufficient kidney essence by traditional Chinese medicine syndrome differentiation in outpatient clinics are selected. Their clinical manifestations include one or more of oligospermia, asthenospermia, and teratospermia. Some patients are accompanied by soreness and weakness in the waist and knees, dizziness and tinnitus, decreased libido, and elevated seminal plasma elastase. The Qiangyao Yuzi Pills obtained in Example 1 of the present invention are given orally, one pill at a time, twice a day, and taken with warm water 30 minutes after meals for 3 months as a treatment course. It can be continuously taken for 1 - 2 treatment courses according to the condition. It is prohibited for those with hyperactivity of fire due to yin deficiency, those allergic to any medicinal material in this prescription, and minors. The curative effect is judged by combining the traditional Chinese medicine syndrome score and routine semen examination, referring to the "Laboratory Manual for the Examination and Processing of Human Semen" of the World Health Organization, which is divided into four levels: cured, markedly effective, effective, and ineffective. The retrospective statistical results show that the cure rate of patients can reach more than 35%, and the total effective rate can reach more than 85%. The sperm concentration, sperm motility, and sperm teratogenesis rate are significantly improved compared with those before treatment. Symptoms such as soreness and weakness in the waist and knees, dizziness and tinnitus, and decreased libido are also relieved. No obvious adverse reactions are seen during the medication period, and only a few patients experience mild nausea and abdominal distension, which can be relieved after reducing the dosage. The above clinical application results show that the present invention has definite curative effect and good safety, and is suitable for the long-term conditioning of male infertility patients with liver and kidney deficiency and insufficient kidney essence syndrome.

[0052] In the above curative effect judgment, the traditional Chinese medicine syndrome score adopts the syndrome score table of liver and kidney deficiency syndrome in male infertility in the "Diagnostic and Therapeutic Criteria for Traditional Chinese Medicine Diseases and Syndromes", including six symptoms: soreness and weakness in the waist and knees, dizziness and tinnitus, fatigue, insomnia and dreaminess, decreased libido, premature ejaculation and spermatorrhea. Each symptom is scored 0 points, 2 points, 4 points, and 6 points according to none, mild, moderate, and severe respectively. The higher the total score, the more serious the condition. The routine semen examination is carried out according to the standards of the "Laboratory Manual for the Examination and Processing of Human Semen" of the World Health Organization. Cured means that the traditional Chinese medicine syndrome score is reduced by no less than 90% and the semen parameters return to normal and the spouse successfully conceives; markedly effective and effective are judged by grading according to the reduction range of the syndrome score and the improvement degree of the semen parameters; ineffective means that the syndrome score is reduced by less than 30% and the semen parameters show no obvious improvement. If gastrointestinal discomfort occurs during the medication period, the dosage can be reduced or the medication can be suspended, and resume taking after the symptoms are relieved. If taking other drugs at the same time, it is necessary to consult a doctor in advance to avoid drug interactions.

[0053] The above is only the preferred implementation mode of the present invention. It should be noted that for those of ordinary skill in the art of this technology, several improvements and refinements made without departing from the principle of the present invention should be regarded as the protection scope of the present invention. The processes of cleaning, drying of each raw material medicine not described in detail in the present invention, as well as the packaging and storage of pills, etc., can all be realized by conventional methods in this field and will not be elaborated here.

Claims

1. A kidney-strengthening and fertility-enhancing pill, characterized in that, It is made from the following raw materials in parts by weight: 10-20 parts of wolfberry, 10-20 parts of salted eucommia bark, 10-20 parts of salted dodder seed, 10-20 parts of processed epimedium, 10-20 parts of salted psoralea corylifolia, 10-20 parts of salted astragalus complanatus, 10-20 parts of mulberry, 10-20 parts of salted plantain seed, 10-20 parts of cnidium monnieri, 6-12 parts of raspberry, 3-9 parts of deer antler, 3-9 parts of gallnut, 3-9 parts of processed rosehip, and 3-9 parts of honey-processed schisandra chinensis.

2. The waist-strengthening and fertility-enhancing pill according to claim 1, characterized in that, It is made from the following raw materials in parts by weight: 12-18 parts of wolfberry, 12-18 parts of salted eucommia bark, 12-18 parts of salted dodder seed, 12-18 parts of processed epimedium, 12-18 parts of salted psoralea corylifolia, 12-18 parts of salted astragalus complanatus seed, 12-18 parts of mulberry, 12-18 parts of salted plantain seed, 12-18 parts of cnidium monnieri, 7-11 parts of raspberry, 4-8 parts of deer antler, 4-8 parts of gallnut, 4-8 parts of processed rosehip, and 4-8 parts of honey-processed schisandra chinensis.

3. The waist-strengthening and fertility-enhancing pill according to claim 2, characterized in that, It is made from the following raw materials in parts by weight: 15 parts wolfberry, 15 parts salted eucommia bark, 15 parts salted dodder seed, 15 parts processed epimedium, 15 parts salted psoralea corylifolia, 15 parts salted astragalus complanatus, 15 parts mulberry, 15 parts salted plantain seed, 15 parts cnidium monnieri, 9 parts raspberry, 6 parts deer antler, 6 parts gallnut, 6 parts processed rosehip, and 6 parts honey-processed schisandra chinensis.

4. The Qiangyao Yuzi Pill according to claim 3, characterized in that, The salt-processed Eucommia ulmoides, salt-processed Cuscuta chinensis, salt-processed Psoralea corylifolia, salt-processed Astragalus complanatus, and salt-processed Plantago asiatica are all salt-processed products, while the salt-processed Epimedium brevicornu, salt-processed Rosa laevigata, and honey-processed Schisandra chinensis are all honey-processed products.

5. The waist-strengthening and fertility-enhancing pill according to claim 4, characterized in that, The Qiangyao Yuzi Pill is a water-honey pill or a concentrated pill, each weighing 6-9 g; the powder used to make the Qiangyao Yuzi Pill is ultra-finely pulverized to a particle size D90≤45 μm; by high performance liquid chromatography, the content of icariin, osthol, and gallic acid in the Qiangyao Yuzi Pill is not less than 0.10%, not less than 0.05%, and not less than 0.03% on a dried basis.

6. The method for preparing the Qiangyao Yuzi Pill according to any one of claims 1 to 5, characterized in that, The steps include: (1) weighing each raw material according to the weight proportions; (2) pulverizing deer antler into fine powder to obtain deer antler fine powder; pulverizing Cnidium monnieri into fine powder or extracting Cnidium monnieri volatile oil to obtain Cnidium monnieri material; (3) decocting the remaining raw materials with water 2-3 times, combining the decoctions, filtering, and concentrating under reduced pressure to a clear paste with a relative density of 1.05-1.15 at 60°C; (4) adding ethanol to the clear paste to a content of 60%-75%, stirring well, refrigerating and standing for 12-24 hours, filtering the supernatant, recovering the ethanol and concentrating under reduced pressure to a thick paste with a relative density of 1.30-1.35 at 60°C; (5) mixing the thick paste with the deer antler fine powder and Cnidium monnieri material obtained in step (2), adding refined honey to make water-honey pills or concentrated pills, drying, and thus obtaining the Strong Waist and Fertility Pill.

7. The preparation method according to claim 6, characterized in that, In step (3), add water in a volume of 6 to 10 times the total weight of the raw materials and decoct for 1 to 2 hours each time; in step (5), before making pills, mix the thick paste, deer antler powder and Cnidium monnieri material and then pulverize the resulting material into ultrafine powder with a particle size D90≤45 μm.

8. The use of the Qiangyao Yuzi Pill according to any one of claims 1 to 5 in the preparation of a drug for treating male infertility.

9. The application according to claim 8, characterized in that, The male infertility described herein is diagnosed in Traditional Chinese Medicine as a deficiency of liver and kidney, or insufficiency of kidney essence, and its clinical manifestations include one or more of oligospermia, asthenospermia, and teratospermia.

10. The application according to claim 9, characterized in that, The male infertility is accompanied by inflammation of the reproductive system, with elevated seminal plasma elastase levels.

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