An external umbilical therapy preparation for treating male infertility and its preparation method

Abstract

The present invention belongs to the technical field of traditional Chinese medicine, and discloses an external umbilical therapy preparation for treating male infertility and a preparation method thereof. The external umbilical therapy preparation comprises the following raw materials in parts by weight: 12-16 parts of fructus cnidii, 12-18 parts of semen cuscutae, 12-18 parts of fructus lycii, 15-18 parts of galla chinensis, 12-18 parts of fructus mori, 15-18 parts of semen brassicae, 15-18 parts of semen vaccariae, 2-6 parts of flos carthami, 3-6 parts of flos rosae rugosae, 9-15 parts of stigma nelumbinis, 2-5 parts of pilose antler, 2-6 parts of lignum aquilariae resinatum, 15-18 parts of flos caryophylli, and 15-30 parts of ginger powder. The application operation of the umbilical therapy preparation described in the present invention is relatively simple. It adopts the method of combining external moxibustion umbilical paste with application, so as to achieve the purpose of combining medical treatment with nourishment, tonifying the kidney, generating essence and assisting fertility, and has no side effects. It is a method of treating with the characteristics of external treatment of traditional Chinese medicine.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to an external umbilical therapy preparation for treating male infertility and a preparation method thereof. Background Art

[0002] Male infertility is a common disease in andrology clinics, and the prevalence rate shows an increasing trend year by year. According to statistics of the World Health Organization, among the factors causing infertility, male factors account for about half. Male oligospermia and / or asthenospermia is a common cause of male infertility, accounting for 20% - 30% of male infertility. The diagnostic criteria for oligospermia and / or asthenospermia are as follows: ① After abstinence for 2 - 7 days, the semen concentration in more than 3 semen tests is < 15×10 6 / mL or the total sperm count per ejaculation is < 39×10 6 / mL, and other semen routine parameters are basically normal, which is "oligospermia"; ② The proportion of sperm with progressive motility (PR, grade a) + non-progressive motility sperm (NP, grade b) in sperm is < 40% or the proportion of sperm with progressive motility is < 32%, which is "asthenospermia"; ③ If the semen routine results meet the diagnostic criteria of the first two items, it can be diagnosed as "oligospermia and asthenospermia". The causes of oligospermia and asthenospermia are complex and there are many influencing factors. For example, congenital factors: chromosomal aberration; infectious factors: reproductive system infection; autoimmunity factors: sperm antibodies; long-term abstinence factors: sperm aging; environmental factors: endocrine disorders (commonly high prolactin, abnormal blood testosterone levels, etc.); and varicocele. Sperm is an active cell in the body, and the conditions required for its production and survival are high. If any factor is abnormal, there may be manifestations of oligospermia and asthenospermia, affecting the continuation of the couple's family and having offspring.

[0003] Due to the complexity of the etiology, the causes of the disease are not clear in many patients, so the treatment methods of Western medicine for this disease are relatively limited. Western medicine treatment methods for oligoasthenozoospermia are divided into the following: ① Treatment according to the cause to eliminate the causes of oligoasthenozoospermia, such as urinary tract infection and inflammation, varicocele, etc., to restore the patient's ability to produce sperm; ② Hormone drug treatment is used to increase the patient's ability to produce sperm by improving the physiological function of sperm production, reducing estrogen in the patient's body, increasing testosterone, and promoting the improvement of sperm production quality; ③ Directly enhance sperm motility, commonly used drugs include: adenosine triphosphate (ATP), arginine, vasodilator; ④ Nutritional therapy, by letting patients take vitamin A, vitamin C, vitamin E, glutathione GSH, coenzyme Q-10, L-carnitine and other drugs, to achieve the purpose of antioxidant; ⑤ Assisted reproductive technology, for patients with severe oligoasthenozoospermia, artificial insemination, in vitro fertilization or intracytoplasmic sperm injection and other medical means are used to help patients achieve the continuation of offspring. Western medical treatments all have more or less disadvantages of unstable efficacy and many side effects. Therefore, seeking a natural treatment for male oligoasthenospermia that is effective, has few toxic side effects, and is comfortable and simple to treat is a focus of research in the urology and andrology community.

[0004] Oligospermia belongs to the category of "no heir", "sterilization", "no heir due to little sperm", "clear sperm", "cold sperm" and "sperm, clear and cold essence" as described in traditional Chinese medicine. "Treatise on the Causes and Symptoms of Various Diseases·Symptoms of No Heirs" says: "Men who are childless have sperm as clear as water and as cold as ice and iron, which are all signs of childlessness". "Differentiation Record·Seed and Heir" also says: "Men who cannot have children have six diseases, one is cold sperm, two is weak qi, three is little sperm, four is excessive phlegm, five is strong fire, and six is ​​qi stagnation". It clearly points out that there are six causes of male infertility, which shows that the ancients have long recognized that little sperm, clear sperm and cold sperm can all make people childless. "Golden Chamber Synopsis·Blood Bi Deficiency Disease Pulse Symptom and Treatment Chapter 6" says: "Men with floating, weak and astringent pulses are childless and have clear and cold essence and qi". It clearly states that the pulse of cold sperm is floating, weak and astringent, and the pathological causes of oligospermia are insufficient congenital endowment, excessive sexual intercourse, insufficient kidney essence, deficiency of kidney yang, weak fire of life gate, and inability to Warming up the reproductive essence; or improper diet, leading to spleen and kidney deficiency and deficiency, essence and blood deficiency; or suffering from dampness and heat, blood stasis, feeling the evil of dampness and heat, disturbing the sperm chamber, burning semen, and abnormal reproductive essence; or long-term illness of the meridians, the sperm chamber is not nourished or falls and injuries, blood stasis blocks the meridians, and the sperm channel is blocked, resulting in less sperm and weak sperm. Doctors of all dynasties have a considerable understanding of sperm quality pathological changes. "The Treatise on the Causes and Symptoms of Various Diseases" says: "The kidney governs the bone marrow and stores the essence. If the kidney qi is weak due to exhaustion, there will be less sperm and no children." Zhu Danxi believed that "those with weak essence and weak pulse cannot form a fetus", and Chen Tuduo also pointed out that less sperm is one of the six diseases of male infertility. Treatment includes nourishing the liver and kidney, replenishing essence and strengthening essence. The common treatment method is to nourish the kidney, warm the yang and replenish the essence as the main principle, while taking into account nourishing the liver and strengthening the spleen, and treating the kidney, liver and spleen together, complementing each other, and jointly warming the kidney yang, nourishing the kidney yin, activating blood circulation and removing blood stasis, and helping the spleen to function, comprehensively improving the function of the reproductive system and improving semen quality.

[0005] Secondary infertility in middle-aged and elderly men has gradually become a difficult problem in the field of reproductive medicine, with the incidence showing an increasing trend. The combined effects of the living environment and lifestyle have led to an increasingly serious problem of male fertility. The efficacy of drugs that were originally effective under normal circumstances has gradually decreased. In particular, various oral Chinese and Western medicines have basically been used with poor results. Therefore, finding methods to treat male infertility other than oral medications is the current research innovation point, and providing an external Chinese medicine for treating oligoasthenospermia remains to be solved. Summary of the Invention

[0006] To solve the above technical problems, the present invention proposes an external umbilical therapy preparation for treating male infertility and its preparation method. By using ginger-separated moxibustion and umbilical application, it has significant efficacy in treating various male infertility diseases mainly of yang deficiency syndrome.

[0007] To achieve the above object, the present invention provides an external umbilical therapy preparation for treating male infertility, comprising the following raw materials in parts by weight:

[0008] 12 - 16 parts of Fructus Cnidii, 12 - 18 parts of Semen Cuscutae, 12 - 18 parts of Fructus Lycii, 15 - 18 parts of Galla Chinensis, 12 - 18 parts of Fructus Mori, 15 - 18 parts of Semen Sinapis Albae, 15 - 18 parts of Semen Vaccariae, 2 - 6 parts of Flos Carthami, 3 - 6 parts of Flos Rosae Rugosae, 9 - 15 parts of Stamen Nelumbinis, 2 - 5 parts of Cornu Cervi Pantotrichum, 2 - 6 parts of Lignum Aquilariae Resinatum, 15 - 18 parts of Flos Caryophylli, and 15 - 30 parts of ginger powder.

[0009] Fructus Cnidii: Pungent, bitter, and warm in nature, mainly entering the kidney meridian, having the functions of drying dampness, expelling wind, and warming the kidney and strengthening yang. Its modern pharmacology is rich: such as anti-arrhythmia; reducing blood pressure; sex hormone-like effects; anti-fungal, insecticidal, and anti-trichomonal effects; expectorant and anti-asthmatic effects; local anesthesia; anti-allergic and anti-mutagenic effects; delaying aging; affecting the metabolism of plasma prostaglandins and cyclic nucleotides; inhibiting smooth muscle contraction; preventing and treating osteoporosis; having sedative and hypnotic effects, etc. Some studies have shown that osthole can reduce the hypoxia injury of sperm cells, and its mechanism may be related to osthole's ability to improve the membrane stability of sperm during oxidative damage, protect cell integrity, and improve sperm motility.

[0010] Cuscuta chinensis: It is of neutral nature, pungent and sweet in taste, and belongs to the Liver Meridian, Kidney Meridian, and Spleen Meridian. Its effects are to tonify the kidney and benefit essence, nourish the liver and improve eyesight. It belongs to the yang-tonifying herbs under the classification of tonic herbs. Clinically, it is commonly used for kidney deficiency low back pain, impotence, premature ejaculation, turbid urine, leukorrhea, frequent urination; threatened abortion; liver and kidney deficiency, blurred vision, and decreased eyesight. Pharmacological studies believe that it has an excitatory effect on the hypothalamus-pituitary-gonad axis; promotes hematopoiesis; enhances immune function; prevents and treats myocardial ischemia; inhibits tumor occurrence; and protects against liver damage. Cuscuta chinensis contains trace elements such as potassium, calcium, phosphorus, sulfur, iron, copper, manganese, selenium, molybdenum, as well as essential amino acids for the human body such as valine, methionine, and isoleucine. Some studies have shown that Cuscuta chinensis has a good therapeutic effect on oligoasthenospermia induced by tripterygium glycosides, and its mechanism may be related to the repair of testicular tissue structure damage, related hormones, and the PI3K / Akt pathway.

[0011] Lycium barbarum: It is of neutral nature, sweet in taste, and belongs to the Liver Meridian and Kidney Meridian. Its effects are to nourish the liver and kidney, and benefit essence and improve eyesight. It belongs to the yin-nourishing herbs under the classification of tonic herbs. Clinically, it is used to treat consumptive fatigue and essence depletion, soreness and weakness of the waist and knees, dizziness and tinnitus, internal heat and thirst, sallow complexion due to blood deficiency, and blurred vision. Pharmacological studies believe that it can enhance immune function, delay aging, anti-tumor, reduce blood lipid, protect the liver, promote hematopoiesis, and protect sperm to a certain extent.

[0012] Galla chinensis: It is of cold nature, sour and astringent in taste, and belongs to the Lung Meridian, Large Intestine Meridian, and Kidney Meridian. It is good at astringing the lung, astringing the intestine, arresting sweating, securing essence, stopping bleeding, and astringing sores, and also reducing fire. It is suitable for various syndromes of excessive discharge, especially those with heat. This product mainly contains components such as tannins, gallic acid, and fatty acids. It is mainly used for chronic cough due to lung deficiency, cough with lung heat phlegm, chronic dysentery, spontaneous sweating and night sweating, diabetes, hematochezia and hemorrhoids bleeding, traumatic bleeding, carbuncles and sores, and skin dampness and erosion.

[0013] Fructus Mori: It is of cold nature, sweet and sour in taste, and belongs to the Heart Meridian, Liver Meridian, and Kidney Meridian. It can enrich the blood and nourish yin, promote the production of body fluid and moisten dryness. It belongs to the blood-nourishing herbs under the classification of tonic herbs. Clinically, it is used to treat dizziness and tinnitus, palpitation and insomnia, premature whitening of hair, thirst due to body fluid injury, internal heat and thirst, constipation due to blood deficiency, etc. Pharmacological studies have shown that it can enhance immune function; reduce the activity of Na + -K + -ATPase, and has various biological activities such as antioxidant, free radical scavenging, anti-cancer, antibacterial, and anti-mutation.

[0014] White Mustard Seed: Pungent and warm in nature. It belongs to the Lung Meridian. Pungent and dispersing, warm and dredging, with a sharp qi that can penetrate rapidly, it specifically enters the Lung Meridian. It can warm the lung, disperse cold phlegm, promote qi movement, dredge the channels, disperse cold nodules, and relieve pain. It is good at treating various syndromes of cold phlegm and phlegm-fluid retention, especially suitable for phlegm located between the skin and muscles or in the channels. It can be used both as medicine and food and is commonly used for seasoning. It mainly contains nitrogen-containing components: sinapine, sinalbin, 4-hydroxy-3-indolylmethyl glucosinolate, and also contains fatty oil, protein, mucilage, and various amino acids. White Mustard Seed has the effects of warming the lung, dispersing phlegm, promoting qi, dissipating masses, dredging channels, and relieving pain. It is used for cold-phlegm cough, distending pain in the chest and hypochondrium, phlegm stagnating in the channels, joint numbness and pain, phlegm-dampness flowing and lodging, and yin abscess and toxic swelling.

[0015] Semen Vaccariae: Neutral in nature and bitter in taste. It belongs to the Liver Meridian and Stomach Meridian, promoting blood circulation to dredge the meridians and promoting lactation to reduce swelling. It is a drug for activating blood circulation and regulating menstruation under the classification of drugs for activating blood circulation to remove stasis. It is used to treat blood stasis, amenorrhea, insufficient lactation, carbuncles and sores, etc.; now it is used to treat herpes zoster, or used for auricular point compression therapy for cholecystitis and cholelithiasis; pharmacological studies suggest that it has effects such as anti-implantation, anti-early pregnancy, exciting the uterus, contracting smooth muscles, and analgesia; Vaccaria segetalis has an obvious improving effect on the penile vascular endothelial function of rats; its component quercetin is a flavonoid compound, which has antioxidant, antiviral, and kidney-protecting effects. Stigmasterol can reduce blood sugar concentration by reducing the release of thyroxine and increasing the concentration of insulin in the blood, and at the same time play its antioxidant activity by reducing liver lipid peroxidation and increasing the activity of catalase, superoxide dismutase, and glutathione; Vaccaria segetalis can significantly improve the erectile function of DMED rats and has a regulatory effect on ICAM-1 and NOS proteins and mRNAs, which may be one of the mechanisms for improving its erectile function.

[0016] Safflower: Pungent and warm in nature. It mainly enters the Heart Meridian and Liver Meridian, and has the effects of promoting blood circulation to dredge the meridians, removing stasis and relieving pain, etc. It is used to treat stasis abdominal pain, traumatic injury, masses and accumulations, etc. The chemical components in safflower mainly include flavonoids, alkaloids, and polyynes, etc. Its pharmacological activities are mainly concentrated in vascular protection, improving hemodynamics, anti-thrombosis, improving peripheral microcirculation disorders, anticoagulation, reducing blood lipid, enhancing hypoxia tolerance, exciting the uterus, relieving intestinal spasms, having immune activity and anti-inflammatory effects. Some studies have found that crocin, as an extract of saffron, has excellent antioxidant effects, which can reduce the content of reactive oxygen species in the oocyte cytoplasm and increase the content of glutathione, and improve the expression of antioxidant and anti-apoptosis-related genes.

[0017] Rose: It is pungent, warm in nature, sweet and slightly bitter in taste, entering the liver and spleen meridians, promoting qi circulation to relieve depression, and activating blood circulation to disperse stasis. It is used to treat liver and stomach qi pain, new and old wind arthralgia, hematemesis and hemoptysis, irregular menstruation, leucorrhea, dysentery, breast abscess, and swelling and toxin. "Compendium of Materia Medica Justice": Rose has the strongest fragrance, clear and not turbid, gentle and not fierce, soothing the liver and waking the stomach, promoting qi and blood circulation, dredging stagnation without the disadvantages of pungent and warm and dryness. It is undoubtedly the most effective and docile one among qi-regulating herbs. Among aromatic herbs, there is hardly its match. "Food Materia Medica": It mainly benefits the lung and spleen, nourishes the liver and gallbladder, dispels evil qi. Eating it is fragrant, sweet and delicious, making people feel refreshed.

[0018] Lotus Stamen: It has the effect of consolidating the kidney and astringing sperm, and is commonly used for spermatorrhea, leucorrhea, and frequent urination. "Synopsis of the Golden Chamber": Lotus Stamen clears the heart and connects to the kidney. Because of its astringent taste, it is an essential herb for astringing essence qi. "Three Causes": It is used in Guzhen Pills and Jushengzi Pills, but it is only suitable for those with excessive sexual desire and thin essence. Lotus flower stamens contain rich trace elements such as zinc, magnesium, and selenium. Relatively high levels of zinc and selenium are beneficial to promoting sperm production and improving sperm quality.

[0019] Flower Velvet Antler: It is warm in nature, sweet and salty in taste, belonging to the kidney meridian and liver meridian, strengthening yang qi, nourishing essence and blood, strengthening tendons and bones, regulating thoroughfare and conception vessels, and supporting anti-toxic substances. It belongs to the yang-tonifying herbs under the classification of tonifying deficiency herbs. It is used to treat impotence and spermatorrhea, infertility due to cold uterus, emaciation, fatigue, fear of cold, dizziness, tinnitus, deafness, cold pain in the waist and spine, flaccidity of tendons and bones, metrorrhagia and leukorrhea, non-healing yin carbuncle, ground into powder and taken orally. It is recorded in "Universal Prescription": Treating impotence due to weakness, unclear complexion, frequent urination, and loss of appetite. Pharmacological research believes that velvet antler extract has effects such as strengthening, protecting the liver, anti-aging, antioxidant, increasing immune function, anti-inflammatory, and enhancing gonadal function; this product mainly contains estrogen-like active ingredients such as estradiol and estrone; it also contains various phospholipids such as cephalin and lecithin, various nucleic acids, amino acids, fatty acids, polysaccharides, etc.; this product can promote growth and development, improve the cellular immunity and humoral immunity of the body, and can improve the mental and physical strength of the human body, relieve fatigue, improve sleep, increase appetite, promote nucleic acid and protein synthesis, regulate metabolism, regulate endocrine; it has gonadotropin-like effects; it can also promote hematopoietic function, especially promoting the regeneration of red blood cells; velvet antler also has obvious anti-lipid peroxidation effects, and its phospholipid components can inhibit the activity of monoamine oxidase; for ulcers and wounds that do not heal for a long time and have poor regeneration, it can promote accelerated healing; in addition, velvet antler polysaccharide also has obvious anti-inflammatory effects; there is research that velvet antler protein can improve the fatigue symptoms of kidney-yang deficiency mice, and the signal pathways involved in its action include Nrf2 / ARE and PI3K / Akt signal pathways.

[0020] Clove: spicy, warm. It enters the spleen, stomach, lung, and kidney meridians, and plays a role in tonifying the kidney and supporting yang. It is mainly used clinically to treat kidney deficiency, impotence, spleen and stomach deficiency and coldness. "Rihuazi Bencao" records: it treats bad breath, nausea, kidney qi, running pig qi, yin pain, aphrodisiac, and warms the waist and knees; according to relevant medical books, it can be clearly seen that cloves are spicy, warm in nature, and born with pure yang qi. They have excellent maintenance effects on the body's kidneys, can strengthen yang, warm the genitals, and can also assist gallnuts and enter the foot Shaoyin kidney meridian; eugenol is the main active ingredient of cloves, which can promote transdermal absorption, and cloves also have good antibacterial effects, and have good inhibitory effects on Candida albicans and Cryptococcus neoformans. Cloves contain a large amount of aromatic volatile oils, which are mainly excreted through the urinary tract during excretion, and have a mild stimulation to the male urethra, which can reflexively cause sexual excitement.

[0021] Agarwood: pungent, bitter, slightly warm. It enters the kidney meridian, spleen meridian, and stomach meridian. It has the effects of promoting qi and relieving pain, warming the middle and stopping vomiting, and relieving asthma. It is a qi-regulating medicine. It is used to treat chest and abdominal distension and pain, stomach cold vomiting and hiccups, kidney deficiency, qi reversal and shortness of breath, and male semen coldness; "Compendium of Materia Medica" records: "Agarwood has a pungent smell, is slightly warm and non-toxic, and has the effects of lowering qi, absorbing the kidney, warming the middle, and clearing the liver", "treats upper heat and lower cold, qi reversal and shortness of breath, large intestine deficiency, urinary gas, and male semen coldness"; Agarwood is used in many prescriptions and has been proven to have the effects of warming and removing cold and dampness, and tonifying the kidney and producing sperm to treat male infertility and oligoasthenospermia.

[0022] Ginger powder: pungent, slightly warm, enters the lung, spleen and stomach meridians. It can induce sweating and relieve the symptoms of vomiting, warm the middle and stop vomiting, warm the lungs and stop coughing, and detoxify fish and crabs. It is suitable for treating exogenous wind-cold, headache, phlegm, cough, stomach cold and vomiting. After being attacked by ice, snow, water and cold, drinking ginger soup can promote blood circulation and dispel the cold evil.

[0023] Preferably, the following raw materials are included in parts by weight: 15 parts of Cnidium monnieri, 15 parts of Cuscuta australis, 15 parts of Lycium barbarum, 15 parts of Gallnut, 15 parts of Morus alba, 15 parts of Sinapis alba, 15 parts of Semen Ligustici Lingnan, 6 parts of Safflower, 6 parts of Rose, 12 parts of Lotus Stamens, 3 parts of Deer Antler, 3 parts of Agarwood, 15 parts of Cloves and 22.5 parts of Ginger Powder.

[0024] Preferably, the external umbilical therapy preparation is in the form of pills or powders.

[0025] The present invention also provides a preparation method of the external umbilical therapy preparation, comprising the following steps: mixing and crushing cnidium monnieri, dodder seed, wolfberry fruit, gallnut, mulberry seed, white mustard seed, semen lycoris, safflower, rose, lotus stamen, velvet antler, agarwood, clove and ginger powder to obtain the external umbilical therapy preparation.

[0026] Preferably, the crushed particle size is 80 to 120 meshes.

[0027] The present invention also provides the use of the external umbilical therapy preparation in the preparation of a medicament for assisting in treating or treating male infertility.

[0028] The present invention also provides the use of the external umbilical therapy preparation in the preparation of a medicament for assisting in treating or treating oligoasthenospermia in men.

[0029] Preferably, the external umbilical therapy preparation is used for the Shenque acupoint.

[0030] The umbilical therapy preparation of the present invention adopts the method of moxibustion on the umbilicus, and the application site is the umbilicus, that is, where the Shenque acupoint is located. "The Origin of Medicine" states: "The umbilicus is the moving qi between the kidneys... reaching up to the Niwan and down to the Yongquan." This acupoint is in the center of the umbilicus, being the innate life stalk and the acquired qi residence, between the middle and lower energizers, connecting the five zang-organs and six fu-organs, and linking the whole body's blood vessels, being the place where the genuine qi is stored. "Huangdi Neijing·Suwen" says: "The Conception Vessel starts from the lower abdomen and runs straight up through the center of the umbilicus"; it also says: "The Penetrating Vessel... runs upward along the umbilicus and scatters in the chest." The Shenque acupoint is the place where the Conception Vessel and Penetrating Vessel circulate, so it is closely related to the reproductive system. Research shows that the mechanism of action of moxibustion in promoting blood circulation and dredging collaterals may be achieved by improving the body's microcirculation and regulating hemorheological indexes, following the principle of "the external treatment method is the internal treatment method". The present invention is mainly formulated with wolfberry fruits, mulberry fruits, cnidium fruits, rose flowers, agarwood, and cloves in a certain proportion. Moxibustion on the umbilicus with the medicine is carried out at this acupoint. By stimulating the Shenque acupoint through medicine ironing and moxibustion, using the pure yang property of moxa and the fact that fire inherently belongs to yang, the two yangs combine to stimulate the acupoint, giving play to the dual effects of medicine and moxibustion, and achieving the effects of invigorating yang qi and warming and dredging collaterals.

[0031] Compared with the prior art, the present invention has the following advantages and technical effects:

[0032] The umbilical therapy preparation of the present invention uses sub-category drugs to treat male sperm diseases, which is a classic application of "analogy" in traditional Chinese medicine. The predecessors of the Shanghai School believe that flowers are also reproductive organs of plants, so flower-based Chinese medicines are added to treat male infertility together. Adhering to the principle that "the principle of external treatment is the principle of internal treatment, and the medicine for external treatment is also the medicine for internal treatment. The only difference is the method", the innovative use of flower-based drugs combined with aromatic transdermal Chinese medicines to treat male infertility through umbilical therapy has a good clinical effect. In the umbilical therapy preparation of the present invention, Cuscuta and Cnidium warm the yang and tonify the kidney; Lycium barbarum and Morus alba nourish the kidney yin; Gallnut and Lotus root nourish the kidney and consolidate the essence; White mustard resolves phlegm, Semen Ligusticum chuanxiong, Safflower and Rose regulate qi, activate blood circulation and dredge the menstruation; In addition, aromatic drugs such as Agarwood and Clove penetrate the skin and enter the collaterals, and guide the medicine into the Shenque. All the medicines work together to tonify the kidney, produce essence, activate blood circulation and dredge the menstruation into the collaterals. Pharmacological studies have shown that Cuscuta and Lycium barbarum can significantly improve sperm quality, significantly reduce the monoploid and polyploid sperm in sperm DNA, and increase the number of normally developed haploid sperm; Lotus root contains rich trace elements such as zinc, magnesium and selenium, and relatively high levels of zinc and selenium are beneficial to promote sperm production and improve sperm quality; the above single-flavor drugs have a certain effect on the external treatment of male reproductive diseases in clinical use. The umbilical therapy preparation of the present invention is relatively simple to operate, and only the external moxibustion umbilical patch combined with the application plays the purpose of combining medical care with nourishment, tonifying the kidney, producing sperm and assisting fertility, has no side effects, and is a method of traditional Chinese medicine external treatment with special characteristics. DETAILED DESCRIPTION

[0033] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0034] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0035] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0036] Without departing from the scope or spirit of the present invention, various improvements and variations can be made to the specific embodiments of the description of the present invention, which will be obvious to those skilled in the art. Other embodiments obtained from the description of the present invention will be obvious to those skilled in the art. The description and examples of the present invention are merely exemplary.

[0037] Regarding the use of "comprising", "including", "having", "containing", etc. in this article, they are all open-ended terms, meaning including but not limited to.

[0038] Example 1

[0039] Weigh 15 g of Cnidium monnieri (L.) Cuss., 15 g of Cuscuta chinensis Lam., 15 g of Lycium barbarum L., 15 g of Galla chinensis, 15 g of Morus alba L. fruit, 15 g of Brassica alba (L.) Boiss., 15 g of Vaccaria segetalis (Neck.) Garcke, 6 g of Carthamus tinctorius L., 6 g of Rosa rugosa Thunb., 12 g of stigma nelumbinis, 3 g of Cornu Cervi Pantotrichum, 3 g of Aquilariae Lignum Resinatum, 15 g of Flos Caryophylli, and 22.5 g of ginger powder.

[0040] Mix Cnidium monnieri (L.) Cuss., Cuscuta chinensis Lam., Lycium barbarum L., Galla chinensis, Morus alba L. fruit, Brassica alba (L.) Boiss., Vaccaria segetalis (Neck.) Garcke, Carthamus tinctorius L., Rosa rugosa Thunb., stigma nelumbinis, Cornu Cervi Pantotrichum, Aquilariae Lignum Resinatum, Flos Caryophylli, and ginger powder, pulverize to 100 mesh, stir evenly to obtain an external umbilical therapy preparation, and prepare it into Preparation No. 1 according to 3 g per portion.

[0041] Example 2

[0042] Weigh 13 g of Cnidium monnieri (L.) Cuss., 12 g of Cuscuta chinensis Lam., 13 g of Lycium barbarum L., 15 g of Galla chinensis, 12 g of Morus alba L. fruit, 15 g of Brassica alba (L.) Boiss., 15 g of Vaccaria segetalis (Neck.) Garcke, 5 g of Carthamus tinctorius L., 4 g of Rosa rugosa Thunb., 10 g of stigma nelumbinis, 2 g of Cornu Cervi Pantotrichum, 4 g of Aquilariae Lignum Resinatum, 15 g of Flos Caryophylli, and 15 g of ginger powder.

[0043] Mix Cnidium monnieri (L.) Cuss., Cuscuta chinensis Lam., Lycium barbarum L., Galla chinensis, Morus alba L. fruit, Brassica alba (L.) Boiss., Vaccaria segetalis (Neck.) Garcke, Carthamus tinctorius L., Rosa rugosa Thunb., stigma nelumbinis, Cornu Cervi Pantotrichum, Aquilariae Lignum Resinatum, Flos Caryophylli, and ginger powder, pulverize to 80 mesh, stir evenly to obtain an external umbilical therapy preparation, and prepare it into Preparation No. 2 according to 3 g per portion.

[0044] Example 3

[0045] Weigh 16 g of Cnidium monnieri (L.) Cuss., 13 g of Cuscuta chinensis Lam., 13 g of Lycium barbarum L., 16 g of Galla chinensis, 14 g of Morus alba L. fruit, 16 g of Brassica alba (L.) Boiss., 17 g of Vaccaria segetalis (Neck.) Garcke, 3 g of Carthamus tinctorius L., 4 g of Rosa rugosa Thunb., 11 g of stigma nelumbinis, 3 g of Cornu Cervi Pantotrichum, 6 g of Aquilariae Lignum Resinatum, 16 g of Flos Caryophylli, and 18 g of ginger powder.

[0046] Mix Cnidium monnieri (L.) Cuss., Cuscuta chinensis Lam., Lycium barbarum L., Galla chinensis, Morus alba L. fruit, Brassica alba (L.) Boiss., Vaccaria segetalis (Neck.) Garcke, Carthamus tinctorius L., Rosa rugosa Thunb., stigma nelumbinis, Cornu Cervi Pantotrichum, Aquilariae Lignum Resinatum, Flos Caryophylli, and ginger powder, pulverize to 120 mesh, stir evenly to obtain an external umbilical therapy preparation, and prepare it into Preparation No. 3 according to 3 g per portion.

[0047] Example 4

[0048] Weigh 13 g of Cnidium monnieri, 13 g of Cuscuta chinensis, 12 g of Lycium barbarum, 17 g of Galla chinensis, 13 g of Morus alba, 15 g of Brassica alba, 16 g of Vaccaria segetalis, 5 g of Carthamus tinctorius, 6 g of Rosa rugosa, 11 g of Stigma nelumbinis, 5 g of Cornu Cervi Pantotrichum, 2 g of Aquilaria sinensis, 17 g of Eugenia caryophyllata, and 24 g of ginger powder.

[0049] Mix Cnidium monnieri, Cuscuta chinensis, Lycium barbarum, Galla chinensis, Morus alba, Brassica alba, Vaccaria segetalis, Carthamus tinctorius, Rosa rugosa, Stigma nelumbinis, Cornu Cervi Pantotrichum, Aquilaria sinensis, Eugenia caryophyllata, and ginger powder, pulverize to 100 mesh, stir evenly to obtain an external umbilical therapy preparation, and prepare it into Preparation No. 4 according to 2 g per portion.

[0050] Example 5

[0051] Weigh 16 g of Cnidium monnieri, 13 g of Cuscuta chinensis, 14 g of Lycium barbarum, 16 g of Galla chinensis, 12 g of Morus alba, 16 g of Brassica alba, 16 g of Vaccaria segetalis, 6 g of Carthamus tinctorius, 4 g of Rosa rugosa, 11 g of Stigma nelumbinis, 4 g of Cornu Cervi Pantotrichum, 5 g of Aquilaria sinensis, 15 g of Eugenia caryophyllata, and 30 g of ginger powder.

[0052] Mix Cnidium monnieri, Cuscuta chinensis, Lycium barbarum, Galla chinensis, Morus alba, Brassica alba, Vaccaria segetalis, Carthamus tinctorius, Rosa rugosa, Stigma nelumbinis, Cornu Cervi Pantotrichum, Aquilaria sinensis, Eugenia caryophyllata, and ginger powder, pulverize to 100 mesh, stir evenly to obtain an external umbilical therapy preparation, and prepare it into Preparation No. 5 according to 2 g per portion.

[0053] Experimental Example 1

[0054] Clinical patient treatment experiment

[0055] I. Case inclusion criteria

[0056] (1) Meeting the diagnostic criteria for male infertility as referred to in the "WHO Manual for the Standard Examination and Diagnosis of Infertile Couples (Fifth Edition)": having normal sexual life, normal fertility of the female partner, and not being pregnant after more than 1 year of marriage without taking any contraceptive measures.

[0057] (2) Referring to the relevant criteria in the "WHO Manual for the Standard Examination and Diagnosis of Infertile Couples (Fifth Edition)" for oligozoospermia and asthenozoospermia at the time of enrollment: ① After abstinence for 3 - 5 days, the semen test concentration < 15×10 6 / mL or the total sperm count per ejaculation < 39×10 6 / mL, with other semen routine parameters basically normal, being "oligozoospermia"; ② In the semen routine examination, within 60 minutes, the proportion of sperm with progressive motility grade (PR) + non - progressive motility grade (NP) in sperm < 40% or the proportion of sperm with progressive motility grade (PR) in sperm < 32%, being "asthenozoospermia"; ③ If the semen routine results meet the diagnostic criteria of the first two items, it can be diagnosed as "oligozoospermia and asthenozoospermia".

[0058] (3) The course of disease is within 12 months.

[0059] (4) Volunteer subjects aged 22 - 55 years old.

[0060] (5) Stop using other Chinese and Western medicines for treating oligospermia and asthenospermia.

[0061] (6) Traditional Chinese medicine syndrome differentiation conforms to the professional standard. Refer to "Planning Textbooks for National Higher Medical Colleges and Universities - Andrology of Integrated Traditional Chinese and Western Medicine", the 2nd edition published by Science Press, for the syndrome of kidney essence deficiency in male infertility - oligospermia and asthenospermia: the semen volume is small or large and thin. Symptoms include fatigue, soreness and weakness of the waist and knees, tidal fever and night sweats, sexual apathy, erectile dysfunction, insomnia and forgetfulness; hair loss; dark eye sockets, premature whitening of hair and beard; if 2 or more of the above symptoms are present, combined with a red tongue with little coating and a weak pulse in the chi position.

[0062] II. Case exclusion criteria

[0063] ① Patients with severe oligospermia and necrospermia; ② Spouses with infertility disorders, as well as those with abnormal sexual life, retrograde ejaculation or anejaculation; ③ Infertile patients caused by clear genetic factors or sex hormone disorders; ④ Those with congenital malformations, ejaculatory duct obstruction, testicular atrophy, varicocele greater than grade II; ⑤ Patients who are taking drugs that interfere with sperm production and motility, such as anti - epilepsy and anti - tumor drugs; ⑥ Patients with severe primary diseases of the cardiovascular, liver, kidney, and hematopoietic systems, as well as psychiatric patients; ⑦ Patients with allergic constitution or allergic to the drugs used in this study; ⑧ Those who have taken spermatogenic drugs in the past 3 months; ⑨ Those engaged in special occupations such as radiation and electric welding; ⑩ Those who have not received treatment as prescribed, making it impossible to judge the curative effect, or those with incomplete data affecting the judgment of curative effect or safety.

[0064] III. Treatment methods

[0065] 1. Control group: Vitamin E capsules (Shanghai Xinyi Pharmaceutical Factory, national drug approval number H31020237), 100 mg each time, twice a day, orally; Shizi Sanhua Decoction, 1 dose per day, decocted in water, taken separately in the morning and evening; the course of treatment is 3 months. The formula of Shizi Sanhua Decoction: Cuscuta chinensis, Astragalus complanatus, Rubus chingii, Fructus cnidii, Lycium barbarum, Ligustrum lucidum, Schisandra chinensis, Plantago asiatica, Rosa rugosa, Astragalus membranaceus, Rehmannia glutinosa, Allium tuberosum. The dosage is adjusted according to the syndrome differentiation of the patient's disease course.

[0066] 2. Treatment group: The treatment method of the control group (i.e., the same treatment method as described in 1) + treatment with Preparation No. 1 prepared in Example 1.

[0067] Treatment method: The patient lies supine. First, mix flour with warm boiled water to form a strip, and wind it around the navel once (the inner diameter is half an inch). Then fill the patient's navel with salt, making it 3 - 5 mm higher than the navel surface. Place an moxa cone on the salt and light it. After continuously moxibusting 2 cones, remove the salt in the navel. This process preheats and warms the Shenque acupoint. Salt is used because salty flavor enters the kidney meridian and opens the acupoints. Take 0.1 g of musk powder and put it into the navel. Take the Preparation No. 1 prepared in Example 1, add 1 drop of fresh flower essential oil, stir well, fill the navel hole to the edge of the inner diameter of the strip, lay a ginger slice on it, puncture several holes, place an moxa cone on the ginger slice and light it. Each time, moxibust frequently for 9 cones. After moxibustion, remove the ginger slice, add 2 more drops of fresh flower essential oil, cover it with a sterile dressing, and fix it with adhesive tape. The dressing should be fixed for at least 5 h. If the patient's skin can tolerate the dressing well, the maximum dressing time is 2 days, depending on the patient's tolerance of the dressing. Perform umbilical therapy once every 3 days. 10 times, that is, 30 days, is one cycle. 3 cycles are one course of treatment, and one course of treatment is 3 months.

[0068] IV. Observation Items and Methods

[0069] 1. Semen Index

[0070] Detect the semen index before and after treatment respectively. Abstain from sexual intercourse for 3 - 5 days before the examination, and collect semen by masturbation into a clean container. After the semen liquefies at 37°C, according to the WHO recommended standard, use a fully automatic sperm analyzer to conduct a routine semen analysis. The main items include sperm concentration, total sperm motility, total sperm count, and percentage of sperm with forward motility. Centrifuge the semen specimen at 3000×g for 15 min to separate the seminal plasma, and use the seminal plasma detection reagent prepared by the Clinical Laboratory of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine according to the fifth edition of the WHO Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction to detect the seminal plasma.

[0071] 2. Efficacy Evaluation Criteria

[0072] After the course of treatment, evaluate the clinical efficacy with reference to the relevant criteria in the "Manual for Standard Examination and Diagnosis of Infertile Couples".

[0073] ① Recovery: The spouse becomes pregnant; ② Marked effect: The spouse does not become pregnant, but after treatment, the sperm quantity and motility of male infertility reach normal, that is: semen test concentration ≥ 15×10 6 / mL or total sperm count per ejaculation ≥ 39×10 6 / mL; In routine semen analysis, within 60 minutes, the ratio of sperm with progressive motility grade (PR) + non-progressive motility grade (NP) to total sperm is ≥40% or the ratio of sperm with progressive motility grade (PR) to total sperm is ≥32%; ③ Effective: The spouse is not pregnant, and the sperm count and motility are effectively improved, that is: the semen concentration or the total number of sperm per ejaculation increases by ≥30% compared with that before treatment; the ratio of sperm with progressive motility grade (PR) + non-progressive motility grade (NP) to total sperm increases by ≥30% compared with that before treatment or the ratio of sperm with progressive motility grade (PR) to total sperm increases by ≥30% compared with that before treatment; ④ Ineffective: The spouse is not pregnant, and the sperm count and motility are ineffectively improved, that is: the semen concentration or the total number of sperm per ejaculation increases by <30% compared with that before treatment or there is no improvement, and the ratio of sperm with progressive motility grade (PR) + non-progressive motility grade (NP) to total sperm increases by <30% compared with that before treatment or there is no improvement.

[0074] V. Statistics

[0075] The SPSS 25.0 statistical software package was used to perform statistical processing on the data. Measurement data: First, a normality test was performed. For data that conformed to a normal distribution, statistical description was carried out using the mean ± standard deviation. Comparison with the baseline value before treatment was made using the paired t-test to compare the differences before and after within the group. Count data were analyzed using the X 2 test; Ranked data: The rank sum test was used. All hypothesis tests were two-sided, and the significance level of the difference was α = 0.05.

[0076] VI. Data analysis and comparison of clinical efficacy

[0077] General information: All 75 cases were male infertility patients with oligospermia and asthenospermia admitted to the outpatient department of urology and andrology of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from October 2020 to April 2023. In the treatment group, the age was 27 - 54 years old, and the course of disease was 1 - 5 years; in the control group, the age was 28 - 53 years old, and the course of disease was 1 - 5 years. There was no significant statistical difference between the two groups (P > 0.05).

[0078] A total of 75 patients were included. During the research process, 1 case in the control group was excluded due to economic reasons, and 2 cases were excluded due to non-compliance with the requirements of taking traditional Chinese medicine. They were not included in the analysis. Both groups of patients had a semen test report before a positive COVID-19 test. Before enrollment, there were no significant differences in the data between the treatment group and the control group (P > 0.05).

[0079] At the end of the treatment course, there were 36 cases in the treatment group, 2 cases were cured, 7 cases were markedly effective, 14 cases were effective, and the total effective rate was 63.89%; there were 36 cases in the control group, 1 case was cured, 2 cases were markedly effective, 12 cases were effective, and the total effective rate was 41.67%. There were statistically significant differences in the efficacy grades of the two groups after treatment (P < 0.05), see Table 1.

[0080] Table 1 Comparison of clinical efficacy between the treatment group and the control group (cases)

[0081] Group Number of cases Cured Markedly effective Effective Ineffective Total effective rate (%) Treatment group 36 2 7 14 13 63.89* Control group 36 1 2 12 21 41.67

[0082] Note: When comparing the treatment group with the control group, *P < 0.05.

[0083] VII. Analysis of changes in semen indexes

[0084] When comparing within each group before and after treatment, the sperm concentration, total motility, and percentage of PR progressive motile sperm in the treatment group were significantly better than those before treatment (*P < 0.05), while only the concentration in the control group was significantly better than that before treatment (*P < 0.05); when comparing between groups, the improvement of sperm concentration and total sperm motility in the treatment group before and after treatment was significantly better than that in the control group, and the difference was statistically significant (#P < 0.05), but there was no significant difference in the total sperm count and percentage of PR progressive motile sperm between the two groups before and after treatment (P > 0.05), as shown in Table 2.

[0085] Table 2 Comparison of changes in semen indexes between the treatment group and the control group

[0086]

[0087] Note: There was a statistical difference when comparing with before and after treatment in the same group, *P < 0.05; there was a statistical difference when comparing between the treatment group and the control group, #P < 0.05.

[0088] VIII. Adverse events

[0089] Among the 36 cases completed in the control group, 1 case had mild gastric discomfort after taking the medicine, and 1 case in the treatment group had epidermal itching and swelling after taking the medicine. They persisted in treatment until the end of the course, and it did not affect the course. No obvious abnormal changes were seen in the treatment group.

[0090] In summary, the external umbilical therapy preparation prepared by the present invention in combination with oral medicine can effectively treat male oligoasthenospermia, and is superior to the traditional method of only taking traditional Chinese medicine orally. The external application can be used when the semen quality of male infertility patients of childbearing age is damaged, so as to increase the curative effect of traditional oral Chinese medicine, and no obvious side effects are seen, which has very important clinical promotion and application value.

[0091] The embodiments described above are only descriptions of the preferred embodiments of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention should fall within the protection scope determined by the claims of the present invention.

Claims

1. An external umbilical therapy preparation for treating male infertility, characterized in that, It is made from the following raw materials by weight: 12-16 parts of fructus cnidii, 12-18 parts of semen cuscutae, 12-18 parts of fructus lycii, 15-18 parts of galla chinensis, 12-18 parts of fructus mori, 15-18 parts of semen brassicae, 15-18 parts of semen vaccariae, 2-6 parts of flos carthami, 3-6 parts of flos rosae rugosae, 9-15 parts of stigma nelumbinis, 2-5 parts of cornus cervi pantotrichum, 2-6 parts of lignum aquilariae resinatum, 15-18 parts of flos caryophylli, and 15-30 parts of ginger powder.

2. The external umbilical therapy preparation according to claim 1, wherein It is made from the following raw materials by weight: 15 parts of fructus cnidii, 15 parts of semen cuscutae, 15 parts of fructus lycii, 15 parts of galla chinensis, 15 parts of fructus mori, 15 parts of semen brassicae, 15 parts of semen vaccariae, 6 parts of flos carthami, 6 parts of flos rosae rugosae, 12 parts of stigma nelumbinis, 3 parts of cornus cervi pantotrichum, 3 parts of lignum aquilariae resinatum, 15 parts of flos caryophylli, and 22.5 parts of ginger powder.

3. The external umbilical therapy preparation according to claim 1, characterized in that, The external umbilical therapy preparation is a pill or powder.

4. The preparation method of the external umbilical therapy preparation according to any one of claims 1 to 3, characterized in that, It includes the following steps: Fructus cnidii, semen cuscutae, fructus lycii, galla chinensis, fructus mori, semen brassicae, semen vaccariae, flos carthami, flos rosae rugosae, stigma nelumbinis, cornus cervi pantotrichum, lignum aquilariae resinatum, flos caryophylli, and ginger powder are mixed and pulverized to obtain the external umbilical therapy preparation.

5. The preparation method according to claim 4, characterized in that, The particle size of the pulverization is 80-120 mesh.

6. Use of the external umbilical therapy preparation according to any one of claims 1-3 in the preparation of a drug for assisting in the treatment or treating male infertility.

7. Use of the external umbilical therapy preparation according to any one of claims 1-3 in the preparation of a drug for assisting in the treatment or treating male oligospermia and asthenospermia.

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