CN114010705A - Preparation for treating premature ovarian failure of women by double-combination therapy and preparation method thereof - Google Patents

Abstract

The invention relates to a double-combination therapy preparation for treating premature ovarian failure and a preparation method thereof. The preparation of the invention has the effects of invigorating spleen, replenishing qi, promoting vital essence generation, regulating qi, activating blood circulation, regulating immunity, supplementing natural estrogenic hormone, maintaining reproductive system and the like.

Description

Preparation for treating premature ovarian failure of women by double-combination therapy and preparation method thereof

Technical Field

The invention relates to the technical field of medical treatment and health, in particular to a preparation for female ovarian premature senility treatment by a dual-combination therapy and a preparation method thereof.

Background

The ovary is located in the female pelvic cavity, and the ovary is an important reproductive organ of the female. The gonads of ovaries, which change in size and shape with age: in the young girl stage, the surface is smooth; after puberty, due to repeated ovulation, scars and unevenness are formed on the surface; the ovary in the sexual maturity stage is the largest, the length is 2.5-5.0 cm, the width is 1.5-3.0 cm, and the thickness is 0.6-1.5 cm. After menopause, the volume is significantly reduced, while in older women, the length, width and thickness are all only about 0.5 cm. Its main functions are to produce and discharge egg cells, and to secrete sex hormones to promote the development and maintenance of female sexual characteristics.

The ovary plays an important role in the physiological health of women, so that the premature failure of the ovarian function has great influence on the health of women. Premature Ovarian Failure (POF) is considered to be a disease of hypoovarial function which seriously affects the reproductive health and physical and mental health of women caused by some reason before the age of 40 years. The ovarian cancer is usually characterized by the reduction of the level of ovarian secreted estrogen (E is less than 73.2 pmol.L) and the increase of the level of pituitary gonadotrophin in serum (FSH is more than 40 U.L), and clinically, the ovarian cancer is mainly characterized by amenorrhea, infertility, flushing with complexion, sweating due to heat, mood fluctuation, leukorrhagia reduction, insomnia, poor appetite, low libido, vaginal dryness and other symptoms of low estrogen and gastrointestinal dysfunction, and B-ultrasonography indicates that the ovary has no organic lesions. The patients not only are easy to suffer from emotional and social problems such as depression, anxiety, hostility, fear and interpersonal difficulty, but also are accompanied by advanced occurrence of diseases such as osteoporosis, cardiovascular diseases and senile dementia, so that the life quality of the patients is seriously affected, and the method is a difficult problem to be solved urgently in modern medicine. Generally, the incidence rate of POF is about l% -3%, and premature ovarian failure is about 2% -10% in amenorrhea patients, and the incidence rate is on the rise in recent years.

The pathogenesis of premature ovarian failure is that autoimmunity is considered to be a main factor at present, and mental stress, physical factors and excessive weight loss are considered to be causes. Some statistics show that premature ovarian failure caused by autoimmunity accounts for about 40-60%; a large amount of clinical data observation shows that patients with autoimmune diseases such as thyroiditis, lupus erythematosus, rheumatoid arthritis, silver skies and the like almost have premature ovarian failure in different degrees. Autoimmunity refers to the phenomenon in which the immune system of the body generates an immune response against self-antigens, producing low levels of antibodies and sensitized lymphocytes. These immune responses to self-antigens lead to inflammation and reduced function or even destruction and withering of the target cells. Modern medicine mostly adopts immunosuppressive agents such as glucocorticoid and estrogen replacement therapy, but long-term use of hormone not only increases the huge risk of cervical cancer and breast cancer, but also generates a plurality of serious side effects such as cervical cancer, breast cancer, hypertension, hyperglycemia, osteoporosis, abnormal fat mobilization and system disorders such as digestion and endocrine, so the safety, acceptability and effectiveness of curative effect of long-term application are questioned.

The pathogenesis of premature ovarian failure is discussed from the theory of traditional Chinese medicine, at present, unified knowledge is not available, and the common pathogenesis of premature ovarian failure is theoretically considered by traditional Chinese medicine, namely the deficiency of kidney qi, essence and blood, deficiency of liver yin and kidney yin, blood stasis and blood stasis, and the difference of blood stasis and blood stasis.

There is no record of premature ovarian failure in traditional Chinese medicine, and it is described by "amenorrhea", "blood depletion", "premature menstruation and water break before the age of the year" and the change of menstrual period. Traditional Chinese medicine considers that the generation of menstruation is a physiological phenomenon that viscera, kidney qi, qi and blood and meridians coordinate and act on the uterus, and the viscera is most closely related to liver and kidney, wherein the kidney plays a leading role in the generation of menstruation, and the inherent kidney is the congenital basis and governs reproductive function. According to traditional Chinese medicine, amenorrhea and blood withering are firstly related to kidneys, the disease location is in the kidneys, and the course of disease is lingering due to kidney deficiency and difficult to cure. Kidney deficiency is mainly due to yin deficiency, so there has been a theory that more than forty yin qi are half of yin, while premature senility is mainly due to the consumption of essence of sex-stimulating essence, and the influence of various internal and external factors causes the deficiency of kidney yin and sex-stimulating essence. As is known: for kidney yin deficiency, it is dry in the water day, or gradually obstructed menstruation before or after dripping. Second, long-term disharmony of the liver and kidney is also involved. It includes deficiency of yin and yang, organ deficiency, essence, qi and spirit, and essence and blood, and belongs to the category of consumptive disease. The symptoms mainly include symptoms of amenorrhea from the beginning of menstruation, flush face, dysphoria with smothery sensation in chest, palms and soles, night sweat with hectic fever, dry and astringent vagina and the like. Kidneys are the innate root, and sex-stimulating essence is the nourishment, and sex-stimulating essence is exhausted due to kidney deficiency, and menstrual arrest, internal heat due to yin deficiency, and deficiency-heat due to heat dryness and blood deficiency. To date, the premature ovarian failure mechanism of the traditional Chinese medicine is mainly 'deficiency theory' and 'stasis theory', while the deficiency theory is the mainstream, and the premature ovarian failure mechanism comprises yin and yang deficiency, organ deficiency, essence and qi consumption and essence and blood loss, and in a word belongs to the category of 'consumptive disease'; the treatment mainly comprises tonifying kidney, soothing liver and regulating Chong and ren channels; the Chinese medicinal materials mainly comprise cornu Cervi, semen Platycladi, herba Lycopi, semen Persicae, radix rehmanniae Preparata, semen Cuscutae, radix Angelicae sinensis, radix astragali, Corni fructus, fructus Ligustri Lucidi, Rubi fructus, herba Leonuri, Achyranthis radix, fructus Lycii, Saviae Miltiorrhizae radix, herba asari, radix Paeoniae Rubra, Carthami flos, and Corni fructus. However, based on the above theory and medication, many clinical cases do not completely correct premature ovarian failure.

Disclosure of Invention

The invention aims to provide a novel preparation for treating premature ovarian failure with obvious and rapid curative effect and a preparation method thereof, and overcomes some defects of the current treatment of premature ovarian failure. The double-combination therapy preparation is formed by combining a preparation for rectal administration and a preparation for vaginal administration together, and corresponding medicines are respectively administered through a rectal administration route and a vaginal administration route. The preparation of the invention has the effects of invigorating spleen, replenishing qi, promoting vital essence generation, regulating qi, activating blood circulation, regulating immunity, supplementing natural estrogenic hormone, maintaining reproductive system and the like.

In order to achieve the purpose, the invention provides the following technical scheme:

a preparation for treating female premature ovarian failure comprises rectal administration preparation and vaginal administration preparation;

the rectal administration preparation with unit volume of 100ml comprises the following raw materials: 0.25-10ml of glutinous rice grass concentrated solution, 0.25-10ml of shepherd's purse concentrated solution, 0.25-10ml of gynostemma pentaphylla concentrated solution, 0.25-10ml of sea buckthorn concentrated solution, 0.25-50g of nardostachys chinensis decoction pieces, 0.25-10g of pawpaw seeds, 0.25-50g of raw white peony root decoction pieces, 0.25-10g of radix pseudostellariae, 0.05-5g of snake gall, 0.05-10g of Tabanus, 0.5-10g of sheep ovary, 0.1-10g of soybean isoflavone (fermentation product), 0.5-10g of hive honey and 0.5-70ml of hydrogen-rich water;

the 100ml unit volume vaginal drug delivery preparation comprises the following raw materials: snail mucus extract 0.05-5g, genistein 0.01-5g, rhizoma Phragmitis concentrate 0.5-10ml, Baeckea frutescens 0.5-30g, alfalfa 0.5-30g, Tremella 0.5-10g, folic acid 0.01-0.5g, and hydrogen-rich water 5-70 ml.

Preferably, the glutinous rice grass concentrated solution, the shepherd's purse concentrated solution, the gynostemma pentaphylla concentrated solution and the sea-buckthorn concentrated solution are prepared by the following method: respectively crushing 7.5-300g of fresh glutinous rice grass, shepherd's purse, sea-buckthorn and gynostemma pentaphylla into juice by a crusher, filling the juice into a silk cloth bag, squeezing the juice by a squeezer, adding purified water twice the amount of filter residue into the filter residue, stirring, soaking and washing the filter residue for 30 minutes, squeezing the juice by the squeezer, removing the filter residue, collecting the squeezed juice, concentrating the filtrate at 50 ℃ to obtain the filtrate with the amount equal to one thirtieth of the crude drug amount, and refrigerating the filtrate for later use.

Preferably, 0.25-50g of rhizoma nardostachyos decoction pieces are ground into 80-mesh powder by a grinder, soaked for 4 hours by 10-100ml of 50% ethanol, filtered, the ethanol is evaporated from the filtrate at 60 ℃, the filtrate is concentrated to be one tenth of the crude drug amount of the rhizoma nardostachyos, and the filtrate is refrigerated for standby.

Preferably, 0.25-10g pawpaw seeds are baked dry with slow fire in a tile pot, yellow wine is sprayed wet, baked dry with slow fire for three times, baked to deep yellow, and crushed into 200-mesh micro powder by a crusher for standby. The pawpaw seeds are sprayed with yellow wine and baked, which is more beneficial to the exertion of the drug property.

Preferably, 0.25-50g of raw white paeony root decoction pieces are soaked in 2-4 times of water, and the pH value of the soaking water is adjusted to about 4 by lactic acid or citric acid, so that the total glucosides of paeony is easy to dissolve in an acidic environment; decocting for 40 min, repeating twice, filtering the extract, vacuum drying the filtrate to obtain crude extract which is one tenth of the crude drug amount of radix Paeoniae alba, and pulverizing into 200 mesh micropowder.

Preferably, 0.25-10g of radix pseudostellariae is cut into 2-3mm oblique pieces, the oblique pieces are placed in a tile pot and stir-fried with slow fire, 50-degree white spirit is sprayed to ensure that the oblique pieces are wet, then the oblique pieces are stir-fried and repeated for three times, finally, the oblique pieces are stir-fried with slow fire until the oblique pieces are golden yellow, and the oblique pieces are crushed into 200 meshes of micro powder for standby. The purpose of the slicing and stir-frying of the radix pseudostellariae is to dissolve the components of saponin and sterol in the radix pseudostellariae.

Preferably, 0.05-5g of fresh snake gall is taken and washed clean, soaked in 75% alcohol for 30 minutes, placed in a tile pot with gall bladder and baked to be golden yellow by fire, and crushed into 200-mesh micro powder for standby.

Preferably, 0.05-10g of complete, dry and clean Tabanus is taken, another Cyperus rotundus with the same amount as the Tabanus is taken, the mixture is placed in a tile pot and is stirred and fried with fire, the mixture is fried and sprayed with rice vinegar to be moist, the stir-frying is continued for three times, the stir-frying is repeated for three times until the Tabanus is golden yellow, the Cyperus rotundus is picked out, and the Tabanus is crushed into 200-mesh micro powder for standby. The nutgrass galingale rhizome and the gadfly are fried together by vinegar spraying, so that the breaking of the gadfly can be removed, and the nutgrass galingale rhizome is added to warm and replenish qi, so that the effects of activating blood, dissolving stasis, dredging channels and relieving amenorrhea of the gadfly can be more easily and mildly exerted.

Preferably, 0.5-10g of fresh sheep ovaries are taken, washed clean, soaked in 75% alcohol for 30 minutes, taken out, washed with sterile water to remove alcohol, crushed at high speed, pulped and refrigerated for later use.

Preferably, 0.1-10g of soybean isoflavone is taken and placed in a ceramic water bath tank, 0.2-20ml of hydrogen-rich water is added, the hydrogen dissolution concentration in the hydrogen-rich water is not lower than 1.4ppm/L, 0.5-2g of lactic acid bacteria freeze-dried powder is added, refrigerated sheep ovary pulp is added, the mixture is stirred uniformly, the pH value of lactic acid or citric acid is adjusted to 5.5, the water bath temperature is adjusted to 35-37 ℃, the water bath fermentation is carried out for 24 hours, and the mixture is taken out and refrigerated for later use.

Preferably, placing 0.5-10g of nidus Vespae into double-layer sterilized gauze bag, heating to 50 deg.C in water bath kettle or water bath tank to thin, squeezing to filter out Mel, removing Cera flava, and placing in container for use.

Preferably, the saturated concentration of hydrogen in water is about 1.62PPM, and hydrogen-rich water with a concentration greater than 1.6PPM is supersaturated hydrogen water. The hydrogen concentration above 1.2PPM is called hydrogen-rich water. Hydrogen-rich water of saturated concentration must be forcibly dissolved into water using a special process. The hydrogen-rich water used by the invention is the hydrogen-rich water produced by the high-pressure hydrogen-rich water machine, the concentration of the hydrogen-rich water is 1.5-1.6ppm, and the higher concentration of hydrogen molecules can generate better biological effect in preparations and human bodies.

Preferably, 1-5 healthy snails with the weight of more than 30g are selected, brushed and cleaned, sprayed with 75% alcohol for disinfection, and washed with pure water; placing the snail in purified water with the weight 3-5 times of the weight of the snail and normal temperature in a water bath pot, soaking the snail for 2 hours to allow the snail to freely climb to make foot glands secrete mucus, heating the water bath pot to 70 ℃ slowly after 2 hours, scalding the snail to be dead, removing shells and internal organs, repeatedly washing the snail with water in the water bath pot, soaking for one hour, taking out snail meat, squeezing to dry and leaving the snail for other use. Then filtering the solution soaked and washed by the snail in the water bath pot with double-layer gauze, and then drying in vacuum to obtain the snail mucus extract. Typically a 30 gram snail is subjected to this method to extract 0.5-1 gram of mucus extract. Dissolving mucus extract 0.05-5g in appropriate amount of normal saline, adding chymotrypsin 0.001-0.05g, hydrolyzing at 30 deg.C for one hour, and refrigerating for use. The chymotrypsin is added mainly for hydrolyzing macromolecular mucin to change into micromolecular denatured protein or polypeptide, amino acid, which is convenient for mucous membrane absorption and utilization.

Preferably, 0.01-5g of genistein is dissolved in a proper amount of propylene glycol solution for later use.

Preferably, 15-300g of fresh reed rhizome is taken, smashed and squeezed, juice is collected, the reed rhizome filter residue is added with purified water with the amount twice that of the filter residue, the purified water is stirred and soaked for 15 minutes, a squeezer is used for squeezing out the juice, the filter residue is removed, the squeezed juice is collected, the filtrate is concentrated at 50 ℃, the amount of the filtrate is one thirty times of the raw drug amount of the reed rhizome, and the filtrate is refrigerated for standby.

Preferably, 5-50g of the baeckea frutescens is taken, crushed, placed in proper hot water at 70 ℃ for heat preservation and soaking for 2 hours, so that volatile components can be dissolved out, the soaking liquid is filtered, and the concentrated liquid is concentrated at 60 ℃ to be one fifth of the crude drug of the baeckea frutescens for later use.

Preferably, pulverizing herba Medicaginis 10-100g into coarse powder, soaking in 2-3 times of alkaline solution (sodium carbonate or sodium bicarbonate solution) with pH of 9-10, heating in water bath at 60 deg.C for 2 hr, filtering the extractive solution, and concentrating at 60 deg.C to obtain concentrated solution with dosage one tenth of that of herba Medicaginis. Soaking herba Medicaginis coarse powder in alkaline solution with pH of 9-10 to promote dissolution of effective components such as flavone, isoflavone, coumarin, growth promoting factor, etc.

Preferably, taking 0.5-10g of tremella fuciformis, removing roots, soaking in purified water at normal temperature for 4 hours, cleaning, cutting into pieces, putting into a pressure cooker, adding a proper amount of water, stewing for 40 minutes, cooling to room temperature, pulping by a grinder, filtering by using double-layer gauze, putting into a water bath kettle, and evaporating excessive water to enable the raw medicines of tremella fuciformis pulp and tremella fuciformis to be 1: 1, refrigerating for later use;

preferably, 0.01-0.5g of folic acid is placed in a mortar, ground into uniform superfine powder, taken out, placed in a stainless steel container, added with the tremella pulp, and beaten into uniform pulp for later use by a homogenizing mixer at 1500 rpm.

As another object of the present invention, the present invention also provides a method for preparing the above preparation for a dual therapy, comprising the steps of:

(1) preparation of rectal administration formulation: sequentially adding micro powder obtained by processing pawpaw seeds, raw white paeony root decoction pieces, radix pseudostellariae, snake gall and Tabanus into a mixed solution consisting of a glutinous rice grass concentrated solution, a shepherd's purse concentrated solution, a sea-buckthorn concentrated solution and a gynostemma pentaphyllum concentrated solution, uniformly stirring at 2000 revolutions per minute by using a homogenizing mixer, then adding a mixed fermentation product of soybean isoflavone and sheep ovary pulp, continuously uniformly stirring, adding an extracting solution of nardostachyos decoction pieces, uniformly stirring, finally adding standby nest honey, uniformly stirring at 1000 revolutions per minute by using the homogenizing mixer, weighing, adding hydrogen-rich water to a sufficient amount less than 100ml, standing for 4 hours, and subpackaging after micro bubbles generated by uniform stirring overflow;

(2) preparation of vaginal administration preparation: adding the reed rhizome concentrated solution into the baeckea frutescens concentrated solution, quickly stirring uniformly at 2000 r/min by using a homogenizing stirrer, adding the genistein propylene glycol solution into a mixed solution of the reed rhizome juice and the baeckea frutescens concentrated solution, continuously quickly homogenizing and uniformly stirring, adding the snail mucus extract chymotrypsin solution, and slowly homogenizing and uniformly stirring at 500 r/min; adding folic acid tremella slurry, continuing to slowly homogenize and stir uniformly, adding alfalfa concentrate, continuing to slowly homogenize and stir uniformly, weighing, adding hydrogen-rich water to a sufficient amount of less than 100ml, standing for 4 hours, and subpackaging when micro bubbles generated by homogenizing and stirring overflow.

Preferably, the prepared rectal administration preparation mixed solution is placed in a filling machine, and then is subpackaged into a special sterile anus injector with 5ml per branch, and then is packaged in a sterile aluminum foil or a medical grade sterile plastic bag and is refrigerated for standby at 5-10 ℃.

Preferably, the prepared vaginal administration preparation mixed solution is placed in a filling machine, and then is subpackaged into a special sterile vaginal syringe with the volume of 3ml per branch, and is packaged in a sterile aluminum foil or a medical grade sterile plastic bag and is refrigerated for standby at the temperature of 5-10 ℃.

Compared with the prior art, the invention has the following advantages:

1. according to the new understanding of the spleen source theory, the Chinese herbal medicine for strengthening the spleen, generating sperm and tonifying qi, which is different from the traditional Chinese medicine formula, and the Chinese and western medicines are combined to be used for treating premature ovarian failure, and clinical verification shows that the effect is rapid and good, the understanding and the treatment principle of the traditional Chinese medicine theory on premature ovarian failure are broken through, and the invention has remarkable innovation. The sheep ovaries are used as medicines in the formula for the first time, and some attempts are made for wider medicine use of the sheep ovaries. Premature ovarian failure is actually the hypofunction of the spleen, cannot play the role of the source of the generation and transformation of qi and blood, and the deficiency of essence, qi and blood delivered to the kidney leads to the deficiency of the kidney, the consumption of essence, qi and blood and the loss of essence and blood, and then the deficiency of essence, qi and blood collected by the ovary leads to the hypofunction of the ovary.

2. In the production process, the medicinal properties and characteristics of each medicine are combined, and some adjuvants and different original processing methods are adopted to exert the pharmacological effect to the maximum extent; especially, on the basis of deep pharmacological analysis of some medicinal components, fermentation processing by adding lactobacillus is an innovation. The processed medicines are mixed and prepared according to different sequences and homogenizing and stirring rates according to the characteristics of the processed medicines, so that the suspension stability and the supplement of the medicines are ensured.

3. In the using method, the special injector is used for pushing the preparation for rectal administration into the rectum through the anus for administration, and the pushing depth is 8-9 cm, so that the medicine can contact with mucosa in a larger area; after the medicine is pushed into the rectum, the medicine is quickly absorbed by penetration through the rich capillary vessel network of the rectal mucosa, thereby exerting good treatment effect. The invention uses a special injector to administer medicine through anus and rectum, and simultaneously, the medicine is applied to the special preparation for vagina through vagina, the depth of the injection is 9-10 cm, so that the medicine reaches the cervix, the cervix and the vagina mucosa contact the medicine in a larger area, the absorption and the effect of the medicine are facilitated, and the medicine has the treatment and maintenance functions on the local vagina and cervix mucosa.

The double-therapy preparation is used for rectum and vagina one time each night, 10 days are a treatment course, the use time is further determined according to the alleviation degree of premature ovarian failure symptoms and the promotion condition of blood estrogen level, the effect is obvious after four to six treatment courses are generally used, and the total effective rate after six treatment courses can reach more than 97 percent. The dual therapy of rectal and vaginal simultaneous administration aims at rectal administration to directly treat ovaries and vaginal administration simultaneously, so that symptoms of vaginal and cervical mucosa atrophy and thinning, secretion reduction, vaginal dryness, weak resistance, frigidity, sexual life pain and the like caused by premature ovarian failure are quickly relieved.

4. Through clinical verification and related research, the effect of treating premature ovarian failure by the spleen-tonifying, sperm-producing and qi-benefiting and Chinese and western medicine combined double-channel administration is far better than that of the traditional treatment methods of tonifying the kidney, soothing the liver and regulating Chong and ren channels, the curative effect is consolidated after the treatment, the recurrence rate is low, and a new way for treating refractory premature ovarian failure is developed.

5. The invention is mostly pure natural Chinese herbal medicine components, and the invention is externally applied for administration, and has no toxic or side effect after long-term use.

Detailed Description

The following will clearly and completely describe the technical solutions in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The inventor considers that the premature ovarian failure caused by autoimmunity is not actually related to kidney deficiency, essence and qi loss and essence and blood loss, and more importantly, is closely related to the spleen. In traditional Chinese medicine, essence is the most basic substance for constituting and promoting the growth and development of human body. The generation of human body comes from the mutual combination of the innate essence of parents and then the development of acquired food essence, which mainly comes from the spleen, so it is said that the spleen is the acquired root and the source of qi and blood generation. Therefore, the main functions of the spleen are to store blood, unify blood, generate qi, blood and body fluids, etc., and if the spleen is strong, the viscera and tissues of the whole body can be fully nourished to maintain normal physiological activities. The traditional Chinese medicine considers that the kidney stores essence and the essence generates blood; kidney essence transforming kidney qi; the kidney is a place for collecting essence, receiving qi and transforming essence, qi and blood, the source of essence and qi of the kidney mainly comes from the spleen, and if the spleen function is declined, pathological changes such as insufficient qi and blood generation can be caused. Therefore, kidney deficiency, essence and qi consumption, essence and blood loss, etc. are only superficial phenomena after premature ovarian failure, and the true source is still in the spleen. The spleen delivers essence to the kidney, the kidney essence transforms kidney qi, the kidney qi is divided into yin and yang, and the kidney yin and kidney yang can support, promote and coordinate yin and yang of viscera of the whole body, so that only the spleen has strong functions, the essence, the blood and the qi are continuously delivered to the kidney, the kidney stores the essence and the qi, the essence, the blood and the body fluids are converted and delivered according to the needs of the viscera, the vital function and the activity are vigorous, the functions of reproduction, growth and development of the human body, disease prevention and pathogen prevention and the like can be normally exerted, and the body can be healthy. Premature ovarian failure is actually the hypofunction of the spleen, cannot play the role of the source of the generation and transformation of qi and blood, and the deficiency of essence, qi and blood delivered to the kidney leads to the deficiency of the kidney, the consumption of essence, qi and blood and the loss of essence and blood, and then the deficiency of essence, qi and blood collected by the ovary leads to the hypofunction of the ovary.

Based on the new understanding of the spleen source theory, the inventor screens a large number of Chinese herbal medicines, repeatedly selects and compares the Chinese herbal medicines, designs preparations with different using methods specially used for premature ovarian failure through intensive and rigorous scientific research combination, and the preparations are called as double therapy preparations and comprise preparations administrated through anus and rectum and preparations administrated through vagina simultaneously; the components of the preparation adopt a brand-new formula combining Chinese and western medicines, and are not the same as the traditional Chinese medicine for tonifying kidney, soothing liver and regulating Chong and ren meridians. The preparation has the main effects that: invigorating spleen, replenishing qi, promoting vital essence production, transporting spleen essence to kidney, replenishing kidney qi, promoting qi circulation, and gradually recovering asthenia function of organ; meanwhile, bidirectional immune regulation is carried out, antigen-antibody reaction is inhibited, and the resistance is adjusted to be insufficient, so that the body is recovered to a normal immune state; effectively relieve psychological pressure, relieve depression, regulate nervous system disorder, rapidly eliminate symptoms of fatigue, irritability, dizziness, anorexia, bad sleep and the like of patients, and enhance the confidence of overcoming diseases. And the combination treatment of natural estrogen element supplement, reproductive system maintenance and the like is added, so that the premature ovarian failure can be corrected quickly, and the function can be recovered quickly. The main drugs of formulations for anorectal administration include: glutinous rice grass, shepherd's purse, gynostemma pentaphylla, sea buckthorn, nardostachys chinensis, papaya seed, raw white peony root, radix pseudostellariae, snake gall, Tabanus, sheep ovary, soybean isoflavone (ferment), nest honey and hydrogen-rich water. The Chinese herbal medicine components prepared by the special preparation method are administrated through the rectum and quickly absorbed by the rectal mucosa, and quickly reach the ovary through a capillary network rich in the pelvic cavity, so that the exhausted ovarian cells are nourished and gradually recover the function. The rectal administration has the advantages of quick absorption, high utilization rate, remarkable effect, and avoidance of digestive tract symptoms such as nausea, emesis, abdominal discomfort, etc., and decomposition and destruction of gastric acid and intestinal juice to traditional Chinese medicine components.

The main drugs of the preparation for vaginal administration are: snail mucus extract, genistein, rhizoma Phragmitis, Baeckea frutescens, herba Medicaginis, and Tremella; folic acid; hydrogen rich water; the estrogen reduction caused by premature ovarian failure can cause atrophy of endometrium and cervical and vaginal mucosa, secretion reduction, hyposexuality and sexual intercourse pain, and simultaneously resistance reduction is easy to cause infection and inflammation. The medicine given through vagina mainly has a plurality of efficacies of anti-inflammation, antioxidation, anti-aging, endocrine conditioning, reproductive system maintenance and the like; on one hand, the medicaments have the functions of resisting inflammation, resisting oxidation, resisting aging, preventing function deterioration and promoting secretion on the vagina and cervical mucosa at the local part of the vagina; on the other hand, the absorption through the vaginal mucosa assists the rectal administration to regulate endocrine and maintain reproductive system. The combined treatment of the double combination therapy has satisfactory effect on quickly correcting premature ovarian failure.

Glutinous rice grass: glutinous rice grass is a wild green herbaceous plant, and can be eaten as a medicine. Has the obvious functions of strengthening spleen, eliminating dampness, benefiting vital energy, promoting vital essence generation, detoxifying, reducing swelling, relieving psychological stress and relieving depression. Clinical observation shows that the glutinous rice has remarkable effects of tonifying spleen and qi, and particularly has remarkable regulating effect on patients with spleen deficiency, weak qi and sweating due to deficiency; qi is the motive force for the body to move, blood flows when qi moves, blood stasis when qi stagnation occurs, and qi and feet are beneficial to dredging the triple energizer, and are transported to the kidney through the triple energizer to be converted into kidney essence and kidney qi, thereby nourishing the five internal organs and six internal organs. The glutinous rice grass has obvious effects of relieving psychological stress and resisting depression, and particularly has good effects of relieving fatigue, irritability, dizziness and poor sleep.

Shepherd's purse: is whole herb with root of Capsella bursa-pastoris of Brassicaceae. Sweet in nature, cool in nature and mild in nature, and enter liver, lung and spleen meridians. Has effects in regulating spleen, clearing away heat, promoting diuresis, relieving swelling, calming liver, and improving eyesight; the efficacy of the shepherd's purse and the spleen can promote kidney essence and kidney qi, and according to the theory that five elements of the traditional Chinese medicine are mutually generated and mutually restrained, soil can restrain water and can prevent water from running. If the spleen function is poor, the kidney function gradually enters an abnormal state, such as renal disease due to spleen deficiency. Poor kidney function can cause the distribution of kidney essence and kidney qi to the zang-fu organs, which can affect their functions. Research shows that the shepherd's purse water or alcohol extract has obvious effects of calming and soothing nerves, is effective in relieving mental stress, and is beneficial to relieving depression of premature ovarian failure patients.

And (3) rhizoma nardostachyos: warm in nature, pungent and sweet in flavor. Chinese angelica root-barkSpleen meridian、Stomach channel. Has effects of regulating qi-flowing, relieving pain, resolving stagnation, activating spleen, promoting spleen essence generation, and is beneficial to premature ovarian failure, spleen weakness and qi stagnation. Pharmacological research proves that the nardostachys chinensis batal has good tranquilizing and allaying excitement effects, has good treatment effects on neurasthenia, depression, hysteria, insomnia, easy fright, mental stress and the like, and has a good conditioning effect on nervous system disorder caused by premature ovarian failure. The research also proves that the nardostachys chinensis batal has a protective effect on tissue cells, can relieve the aging of the tissue cells and recover the young state of the tissue cells.

Sea-buckthorn: it enters spleen, stomach, lung and heart meridians. Has the functions of invigorating spleen, promoting digestion, relieving cough, eliminating phlegm, promoting blood circulation and dissipating blood stasis. Modern medical research proves that: fructus Hippophae has antiaging, organism activity enhancing and anticancer effects. Especially, the seabuckthorn fruit extract can regulate immunity, prevent premature aging of body tissues caused by free radicals, repair damaged cell tissues, promote tissue regeneration and epithelial tissue healing, and is beneficial to functional recovery of premature ovarian cell failure.

Papaya seeds: warm in nature and sour and bitter in taste. Dispel dampness, dredge collaterals, regulate qi, regulate yingfen and weifen, and help paddy. Researches show that the pawpaw seeds have obvious effects of promoting physiological functions, resisting oxidation and regulating immunity. The analysis of the basic components of the pawpaw seeds shows that the pawpaw seeds have 24.9 percent of crude protein, 32.2 percent of crude fat, rich mineral elements and low heavy metal content; wherein, the total content of 16 amino acids accounts for 22.6 percent of the total content of protein; the protein of the pawpaw seeds has complete types of essential amino acids, and contains 7 of 8 essential amino acids, including lysine 2.67, phenylalanine 0.65, methionine 0.22, threonine 0.88, leucine 0.79, isoleucine 0.57 and valine 1.77, wherein the essential amino acids account for 68.6% of the total amino acids; essential amino acids (essential amino acids): meaning that the human body (or other vertebrate) is unable to synthesize or the rate of synthesis is far from adequate for the body's needs, and must be supplied by food proteins, these amino acids are called essential amino acids. The amount of essential amino acids required for adults is about 20% to 37% of the amount required for proteins. There are 8 essential amino acids. Wherein lysine accounts for 10.7% of total amino acids, and can promote brain development, is effective in promoting fat metabolism, regulating pineal gland, mammary gland, corpus luteum and ovary, and preventing cell degeneration; methionine accounts for 0.9% of total amino acids, and participates in hemoglobin, tissue and serum, and has functions of promoting spleen, pancreas and lymph; isoleucine accounts for 2.3% of the total amino acid content, and participates in the regulation and metabolism of thymus, spleen and subconcephalic gland; the gonadotropins secreted by the hypogonadism act on the thyroid gland and the gonad; valine accounts for 7.1% of the total amino acid content, and acts on corpus luteum, mammary gland and ovary to prevent atrophy.

Gynostemma pentaphylla: cold in nature, bitter in taste; chinese angelica root-barkLung meridian、Spleen meridian、Kidney channel. Has the effects of tonifying qi and spleen, eliminating phlegm and relieving cough, and tranquilizing mind. The gynostemma pentaphylla is called as southern ginseng and has obvious adaptogenic function and tonifying effect. Pharmacological, toxicological and clinical tests prove that the compound has obvious inhibition effect on various cancer cells; gynostemma pentaphylla also has the effects of reducing blood fat, blood pressure and blood sugar, tranquilizing, hypnotizing, resisting tension, ulcer and fatigue, prolonging cell life, stimulating appetite, enhancing resistance, resisting aging and the like.

Raw white peony root: slightly cold in nature, bitter and sour in taste. Chinese angelica root-barkLiver meridian、Spleen meridian. Radix Paeoniae alba has effects of suppressing hyperactive liver, relieving pain, nourishing blood, regulating menstruation, astringing yin, and suppressing sweat. It is mostly indicated for blood deficiency, sallow complexion, vertigo, amenorrhea due to scanty menstruation, and astringing yin by blood. Research shows that the white peony root contains about 4-6% of total glucosides of paeony, and the total glucosides of paeony have obvious effects of autoimmunity resistance, inflammation resistance and depression resistance. In autoimmune diseases, abnormal activation of T cells plays an important role in the development of the disease. The research finds that the paeoniflorin can reduce the CD4 in the peripheral blood by increasing the methylation level of the ITGAL gene promoter⁺The expression level of CD11a in T cells reveals a possible mechanism of inhibition of autoimmune response by total paeoniflorin. Inflammatory responses, whether those caused by autoimmune reactions or other inflammatory factors, underlie the development of many diseases, and a variety of inflammatory cells are involved, including dendritic cells, macrophages, monocytes, T-lymphocytes, and B-lymphocytes, among others. The research finds that the paeoniflorin can inhibit the function of dendritic cells by blocking a T4/5 signal channel, thereby relieving immune-mediated inflammatory reaction. In induced inflammatory response experiments, the total glucosides of paeony produce negative regulation on macrophage functions, including inhibiting the expression of macrophage migration inhibitory factor in T cells, down-regulating macrophage migration inhibitory factor-extracellular signal-regulated kinase 1/2-cyclooxygenase 2 signals, and lipopolysaccharide-induced production of tumor necrosis factor alpha and nitric oxide. In human peripheral blood mononuclear cells, human recombinant interleukin 1 beta up-regulates phagocytosis of monocytes, prostaglandin E₂And TNF-alpha production and HLA-DR and CD80 expression, while total paeoniflorin treatment inhibited these changes, indicating that total paeoniflorin is capable of alleviating chronic inflammation by inhibiting the action of monocytes. Total glucosides of paeony have antidepressant effects on corticosterone-induced depression, which is related to the antioxidant capacity and the capacity of increasing the protein level of hippocampal and frontal cortex brain-derived neurotrophic factors of rats. The total glucosides of paeony can inhibit the activity of monoamine oxidase A and B in the brain of a mouse, and the result shows that the antidepressant effect of the total glucosides of paeony is probably mediated by monoamine oxidase inhibition. These effects of total glucosides of paeony have beneficial effects on premature ovarian failure caused by autoimmune reaction.

Snake bile: bitter, slightly sweet and cool in nature; enter liver and spleen meridians. Has effects in clearing away heat and toxic materials, expelling pathogenic wind, removing dampness, improving eyesight, clearing away heart-fire, promoting qi circulation, and refreshing mind; clinical observation shows that the snake gall can regulate and supplement the nervous system, the endocrine system and the immune system of a human body and delay the aging of the body. Especially has bidirectional regulation effect on the immune system of the body so as to maintain the immune balance of the body. Medical research shows that: the snake gall contains rich trace elements of copper, iron, calcium, magnesium, vitamin C, E and the like, and plays an important role in life activities such as maintaining hormones in a human body, delaying aging of the human body, improving functions of various systems and the like; the microelements and nutrients can regulate internal environment of human body, improve organism circulation, balance immunity, and achieve the purpose of treating external diseases internally.

Tabanus: has the effects of removing blood stasis, removing food retention and dredging channels. Has the effects of promoting blood circulation, removing blood stasis, dredging channels and relieving amenorrhea for blood stagnation and menstrual flow obstruction caused by premature ovarian failure.

Radix pseudostellariae: sweet and bitter with slight cold entering heart, spleen and lung meridians. Has the functions of replenishing qi to invigorate the spleen, arresting sweating, promoting the production of body fluid and fixing deficiency palpitation. Is mainly used for spleen deficiency, weakness, qi and yin deficiency, palpitation, spontaneous perspiration, mental fatigue, lassitude, weakness, spontaneous perspiration, thirst and the like. Animal experiments prove that: the radix pseudostellariae can obviously resist weight loss of thymus and spleen caused by cyclophosphamide (Cy), reduce positive incidence rate of spleen deficiency of mice, increase weight, anal temperature, thymus index and spleen index of spleen deficiency mice, and increase content of thymus DNA, RNA and spleen DNA. Modern medical research shows that the radix pseudostellariae phospholipid component has obvious immunoregulation function, can protect the integrity of cells, prevent the damage of immune factors to cell membranes, enhance the anti-oxidation function, delay aging and have obvious effects of strengthening the body and resisting fatigue.

Sheep ovary: the sheep ovary is similar to almond in appearance, the size of the sheep ovary is different according to age, variety, nutritional status and oestrus cycle, the left ovary and the right ovary are respectively 1 and are almond-shaped, the length of the sheep ovary is about 1.0-1.5 cm, and the width of the sheep ovary is about 0.5-0.8 cm. The average weight per ovary was about 3-4 grams. The ovary has two functions, the production of ova and estrogen. There are two classes of estrogen, one is estrogen (estradiol and estrone) and one is progestin (progesterone). The ovary is divided into cortex and medulla. The former is the lateral genital epithelium, which contains large and small follicles of different degrees of development, also called the follicular part. The latter extends from the ovary portal to the center of the ovary, mainly the artery, vein and nerve, also called the vascular section. There is no clear boundary between cortex and medulla. The cortex is the site of ovum formation and is also the site of secretion of hormones, where a wide variety of follicles and corpus luteum can be seen in the process of maturation and degeneration. The primordial follicles, which develop to a lesser extent, are located in the superficial layer, the deep layer are the growing follicles, and those which protrude from the ovarian surface and are in the form of small pimples are the mature follicles. Estrogens are secreted from the inner membrane of mature follicles. It acts mainly on the female reproductive tract and some effects are achieved by the synergistic cooperation of progestogen. It promotes vaginal epithelium proliferation and keratinization to facilitate mating; stimulating the growth of uterus, so that the contractility of uterine muscles and the blood circulation of endometrium are enhanced; promoting the movement of the fallopian tube; estrogens also act on the brain to cause libido, causing the ewes to be in estrus. The progestagen is secreted by the corpus luteum. It inhibits the activity of the uterine muscles and fallopian tubes, but promotes the proliferation of the endometrium to facilitate the restitution of the embryo, and is therefore essential for the maintenance of pregnancy. It acts in coordination with estrogen in promoting the expression of estrus in ewes. Data retrieval shows that the sheep ovary has not been used as a precedent for the range and use of the traditional Chinese medicine; however, the structural research of the sheep ovary shows that a plurality of follicles with different maturity in the sheep ovarian cortex can synthesize or secrete estrogen, and the primordial follicle and the growing follicle contain more estrogen elements and have the property of natural estrogen. The invention firstly tries to use sheep ovaries for medicine taking to supplement natural estrogen elements for premature ovarian failure patients, and is beneficial to improving the estrogen level in vivo. Clinical application shows that the sheep ovary has obvious effect of relieving premature ovarian failure symptoms. The sheep ovary used by the invention can be a sheep ovary or a goat ovary.

Soy isoflavones (fermentation products) isoflavones have a structure similar to estrogen, and are generally regarded as precursors of hormones. The soybean isoflavone is a plant effective component extracted from natural soybeans, and is sometimes called as 'phytoestrogen' because the soybean isoflavone has very similar molecular structure with estrogen, can be combined with estrogen receptors in female bodies and has a bidirectional regulation effect on the estrogen, but has low physiological activity. The natural soybean isoflavone is mainly divided into free type aglycone and combined type glucoside. Wherein the bound glycoside is deglycosylated by hydrolysis with enzyme or dilute acid to form soy isoflavone aglycone. The free type soybean isoflavone aglycone includes genistin, daidzein and daidzein. Researches have considered that a key substance for the physiological action of the soybean isoflavone is equol which has higher pharmacological activity, so that whether the organism can metabolize the soybean into the equol is a key factor for determining whether the soybean isoflavone can exert higher medicinal value. We observe and find that the water-soluble soybean isoflavone is dissolved in hydrogen-rich water, and is added with lactobacillus for fermentation at 35-37 ℃, so that the efficiency of converting the soybean isoflavone into the equol can be obviously improved, the content of the equol is increased, and the medicinal value of the soybean isoflavone estrogen is greatly exerted. The method is innovative in the specific application of the soybean isoflavone.

The nest honey is brewed with honey and sealed with wax cover, and is one kind of ripe honey comprising honeycomb and honey and has nutritious components and active components higher than common honey. The comb honey contains rich biological enzyme, vitamins, various trace elements, propolis, beeswax, protein, free amino acids, free fatty acids, nucleic acids and other compounds, is an excellent product in honey, and contains pollen powder, so that the comb honey has high human health care value! The comb honey has the effects of resisting bacteria, diminishing inflammation, regulating immunity, benefiting spleen, nourishing kidney, nourishing lung, moistening intestine, removing toxic substance, protecting liver, promoting hematopoiesis, improving sleep, enhancing tissue regeneration, relieving fatigue, enhancing physical strength, resisting aging, etc.

Hydrogen-rich water "means water containing a certain amount of hydrogen molecules in water. Because hydrogen is difficult to dissolve in water and has poor solubility, at the temperature of 20 ℃, 1 liter of water can only dissolve 18 milliliters of hydrogen at most, and the mass concentration is equivalent to 1.62 ppm; however, the hydrogen molecule has high bioactivity, and the hydrogen concentration can reach 0.05ppm to show obvious bioactivity. Therefore, such a concentration is high from the biological point of view, and a hydrogen-dissolved water having a hydrogen water concentration of not less than 1.2ppm is generally called hydrogen-rich water. The hydrogen-rich water has the functions of activating organism cells, delaying senility, eliminating harmful substances in cell membranes or blood vessels and inhibiting oxygen free radicals; has strong permeability, improved cell activity, activated mucosa cell, improved blood circulation function, promoted metabolism, and balanced endocrine.

The formulations of the examples of the invention are shown in the following table:

TABLE 1 formulation examples for rectal administration the ratio of the components is given in the table

TABLE 2 formulation for vaginal administration example the ratio of each component

The application of the invention is as follows: filling the medicament of the embodiment into a special sterile dispenser, wherein the filling amount of each rectal administration preparation is 5 ml; the volume of each vagina administration preparation is 3 ml; packaging with sterilized aluminum foil bag or pharmaceutical grade sterilized plastic bag, sealing, and refrigerating at 5-10 deg.C for use.

The application method of the product of the invention comprises the following steps: when in use, the aluminum foil bag package is torn, the medicine feeder filled with the medicine is taken out, the protective cover at the front part of the medicine feeder is taken down, the protective cover at the tail end of the medicine feeder is removed, and the protective cover is used as a push rod to be inserted into the jack at the tail end of the medicine feeder; the rectal administration can be squatting or supine position, stool is applied forcibly, anus is relaxed, the prepared rectal administration device is taken, the medicament with the size of soybean particles is firstly pushed out to lubricate the anus, then the injector is rotated and slowly inserted into the rectum, the insertion depth is 8-9 cm, all the medicaments are slowly injected, then the push tube is slowly pulled out, and the local part is wiped by using a wet tissue. Then, the supine position is adopted, the hip is raised by 20-30 cm, the two legs are bent and separated, the medicine feeder for vaginal medicine feeding is slowly inserted into the deep vagina with the insertion depth of 9-10 cm, the push rod is pushed, all the medicines are pushed into the deep vagina, the medicine feeder is pulled out, and the body position is kept for 30 cm.

The double-combination therapy preparation is used for rectum and vagina one time each night, 10 days are taken as a treatment course, and the use time is further determined according to the alleviation degree of premature ovarian failure symptoms and the promotion condition of blood estrogen level.

Clinical application study example of the invention

First, clinical data

1. General data

78 outpatient premature ovarian failure patients are aged 26-40 years, have scanty menstruation or amenorrhea time of 6-19 months, and 78 patients are often mixed with climacteric symptoms such as hectic fever, night sweat, vexation, insomnia, testiness, inappetence and the like, and symptoms such as vaginal dryness, hyposexuality and the like with different degrees. The average serum FSH (gonadotropin) of 78 patients is more than or equal to 58.6IU/L, and the average E2 (serum estradiol) is less than or equal to 54.1 pmol/L;

2. diagnostic criteria

According to the Chinese medicine gynecological clinical diagnosis and treatment guideline ● premature ovarian failure: 1. premature menstruation, hypomenorrhea or amenorrhea before age 40; 2. more than two times of serum FSH (gonadotropin) is more than or equal to 40 IU/L; 3. e2 (serum estradiol) is less than or equal to 73.2 pmol/L;

3. grouping:

78 cases were randomly divided into two groups, namely 40 cases of the inventive formulation group and 38 cases of the control group.

4. The treatment method comprises the following steps: 40 cases of the formulation group of example 3 were used; in 38 cases of the control group, the traditional treatment of tonifying kidney and soothing liver and regulating thoroughfare and conception vessels is adopted, and the basic formula is as follows: 20g of angelica sinensis, 20g of astragalus membranaceus, 20g of prepared rehmannia root, 20g of semen cuscutae, 15g of raspberry, 15g of motherwort, 15g of achyranthes root, 15g of red paeony root, 15g of cornus officinalis, 15g of wolfberry fruit, 15g of prepared fleece-flower root, 15g of eucommia bark, 15g of dried orange peel, 15g of glossy privet fruit, 15g of platycladi seed and 15g of cornu cervi degelatinatum. The formulation group of the invention requires rectal and vaginal administration in accordance with the application of the formulation doublet; the control group is decocted according to the basic traditional Chinese medicine prescription, each dose of the medicines is decocted twice, the decoction is combined, and the decoction is concentrated to 200ml, 100ml each time, and is taken in the morning and evening respectively. Two groups are continuously applied for 10 days as a treatment course, and six treatment courses are continuously applied;

second, evaluation of therapeutic efficacy

(I) evaluation criteria

1. Regulating menstrual cycle

Refer to the "clinical research guidelines for treating menoxenia with new Chinese medicine" (published Chinese medicine science and technology, 2002).

And (3) healing: the menstrual period is recovered to be normal, and the menstrual cycle and menstrual flow are normal;

the effect is shown: the menstrual period is recovered to be normal, and the menstrual cycle and menstrual flow are basically normal;

the method has the following advantages: menstruation can come regularly;

and (4) invalidation: the menstrual period, the period and the menses amount are not changed.

2. Evaluation standard of traditional Chinese medicine syndrome curative effect

The traditional Chinese medicine syndrome curative effect is judged by the syndrome curative efficiency.

And (3) healing: after treatment, each symptom disappears, and the syndrome integral value is reduced by more than or equal to 95 percent;

the effect is shown: after treatment, each symptom is obviously relieved, and the integral value of the syndrome is reduced by more than or equal to 70 percent and less than 95 percent;

the method has the following advantages: all symptoms are relieved after treatment, and the integral value of the syndrome is reduced by more than or equal to 30 percent and less than 70 percent;

and (4) invalidation: after treatment, the symptoms are not reduced or aggravated, and the integral value of the symptoms is reduced by less than 30 percent.

3. Evaluation standard of physical and chemical indexes

And (3) healing: after treatment, the blood FSH is less than or equal to 10U/L;

the effect is shown: 10U/L < blood FSH < 40U/L after treatment;

the method has the following advantages: after treatment, the blood FSH is more than or equal to 40U/L and has a descending trend, but is reduced compared with before treatment;

and (4) invalidation: there was no change or increase in hormone levels after treatment.

Three, result in

See tables 3-4 below.

TABLE 3 treatment of pre-and post-symptomatic changes in premature ovarian failure with the formulations of the present invention

TABLE 4 treatment of premature ovarian failure with the conventional Chinese medicinal basic prescription

The data from both groups were statistically treated with P <0.05, indicating significant differences between the groups.

Many clinical practices show that the traditional treatment method for tonifying the kidney, soothing the liver and regulating thoroughfare and conception vessels is usually one treatment course for three months, generally, patients are required to take the traditional treatment method for more than three treatment courses, and the patients are usually long in time, inconvenient to decoct, obvious in gastrointestinal side effects, slow in effect and incapable of being half-way to waste due to persistence. Compared with the traditional prescription for tonifying the kidney, soothing the liver and regulating thoroughfare and conception vessels, the Chinese medicinal preparation has the advantages of short treatment course, high effective rate, no gastrointestinal reaction, convenient local administration and obvious advantages. Especially, the vagina lotion is locally administrated through the vagina, and has remarkable curative effect on relieving the symptoms of vaginal dryness and hyposexuality. The traditional treatment of tonifying the kidney, soothing the liver and regulating thoroughfare and conception vessels is to wait until the estrogen of a patient reaches the normal level, the symptoms of vaginal dryness and hyposexuality can be gradually relieved, which usually needs a long time.

Claims (10)

1. A preparation for treating female premature ovarian failure by a dual-combination therapy is characterized by consisting of a rectal administration preparation and a vaginal administration preparation;

the rectal administration preparation with unit volume of 100ml comprises the following raw materials: 0.25-10ml of glutinous rice grass concentrated solution, 0.25-10ml of shepherd's purse concentrated solution, 0.25-10ml of gynostemma pentaphylla concentrated solution, 0.25-10ml of sea buckthorn concentrated solution, 0.25-50g of nardostachys chinensis decoction pieces, 0.25-10g of pawpaw seeds, 0.25-50g of raw white peony root decoction pieces, 0.25-10g of radix pseudostellariae, 0.05-5g of snake gall, 0.05-10g of Tabanus, 0.5-10g of sheep ovary, 0.1-10g of soybean isoflavone (fermentation product), 0.5-10g of hive honey and 0.5-70ml of hydrogen-rich water;

the 100ml unit volume vaginal drug delivery preparation comprises the following raw materials: snail mucus extract 0.05-5g, genistein 0.01-5g, rhizoma Phragmitis concentrate 0.5-10ml, Baeckea frutescens 0.5-30g, alfalfa 0.5-30g, Tremella 0.5-10g, folic acid 0.01-0.5g, and hydrogen-rich water 5-70 ml.

2. The preparation for the doubletherapy according to claim 1, wherein the glutinous rice grass concentrated solution, the shepherd's purse concentrated solution, the gynostemma pentaphylla concentrated solution and the sea buckthorn concentrated solution are prepared by the following steps: respectively crushing 7.5-300g of fresh glutinous rice grass, shepherd's purse, sea-buckthorn and gynostemma pentaphylla into juice by a crusher, filling the juice into a silk cloth bag, squeezing the juice by a squeezer, adding purified water twice the amount of filter residue into the filter residue, stirring, soaking and washing the filter residue for 30 minutes, squeezing the juice by the squeezer, removing the filter residue, collecting the squeezed juice, concentrating the filtrate at 50 ℃ to obtain the filtrate with the amount equal to one thirtieth of the crude drug amount, and refrigerating the filtrate for later use.

3. The preparation of claim 1, wherein the decoction pieces of radix Et rhizoma Nardostachyos are pulverized into 80 mesh powder by a pulverizer, soaked in 10-100ml of 50% ethanol for 4 hr, filtered, the filtrate is subjected to evaporation of ethanol at 60 deg.C and concentrated to give a filtrate equivalent to one tenth of the crude drug amount of radix Et rhizoma Nardostachyos, and refrigerated for further use.

4. The preparation according to claim 1, wherein 0.25-10g pawpaw seeds are baked with slow fire in a earthen bowl, sprayed with yellow wine, baked with slow fire for three times, baked to deep yellow, and ground into 200 mesh micropowder by a grinder for use. The pawpaw seeds are sprayed with yellow wine and baked, which is more beneficial to the exertion of the drug property;

soaking 0.25-50g of radix Paeoniae alba decoction pieces in 2-4 times of water, and regulating pH of the soaking water to about 4 with lactic acid or citric acid to make radix Paeoniae alba total glycosides easily dissolve out in acidic environment; decocting for 40 min, repeating twice, filtering the extract, vacuum drying the filtrate to obtain crude extract which is one tenth of the crude drug amount of radix Paeoniae alba, and pulverizing into 200 mesh micropowder;

cutting radix Pseudostellariae 0.25-10g into 2-3mm oblique pieces, parching in a tile bowl with slow fire, spraying 50% (v/v) Chinese liquor to moisten, parching to dry, repeating for three times, parching with slow fire to golden yellow, and pulverizing into 200 mesh micropowder;

washing 0.05-5g of fresh snake gall, soaking in 75% alcohol for 30 minutes, placing the snake gall with gall bladder in a tile pot, baking the snake gall with fire to be golden yellow, and crushing the snake gall with fire to 200 meshes of micro powder for later use;

taking 0.05-10g of complete, dry and clean Tabanus, taking another rhizoma Cyperi with the same amount as the Tabanus, putting the other rhizoma Cyperi in a tile pot, stir-frying with Chinese fire, spraying rice vinegar to moisten the heated Tabanus, continuously frying to dry, repeating for three times, baking until the Tabanus is golden yellow, removing the rhizoma Cyperi, and pulverizing the Tabanus into 200-mesh micropowder for later use;

washing 0.5-10g of fresh sheep ovary, soaking in 75% alcohol for 30 min, taking out, washing with sterile water to remove alcohol, pulverizing at high speed, pulping, and refrigerating for later use.

5. The preparation of claim 1, wherein the preparation is prepared by placing soybean isoflavone 0.1-10g in ceramic water bath tank, adding hydrogen-rich water 0.2-20ml with hydrogen dissolved concentration of not less than 1.4ppm/L, adding lactobacillus lyophilized powder 0.5-2g, adding refrigerated sheep ovary pulp, stirring, adjusting pH to 5.5 with lactic acid or citric acid, adjusting water bath temperature to 35-37 deg.C, fermenting in water bath for 24 hr, taking out, and refrigerating;

placing 0.5-10g of nidus Vespae into double-layer sterilized gauze bag, placing into water bath kettle or water bath tank, heating to 50 deg.C to thin, squeezing to filter out Mel, removing Cera flava, and placing into container for use.

6. The preparation for doubletherapy according to claim 1, wherein 1-5 healthy snails with more than 30g are selected, washed with shell, sterilized by spraying 75% alcohol, and washed with alcohol with purified water; placing the snail in purified water with the weight 3-5 times of the weight of the snail and normal temperature in a water bath pot, soaking the snail for 2 hours to allow the snail to freely climb to make foot glands secrete mucus, heating the water bath pot to 70 ℃ slowly after 2 hours, scalding the snail to be dead, removing shells and internal organs, repeatedly washing the snail with water in the water bath pot, soaking for one hour, taking out snail meat, squeezing to dry and leaving the snail for other use. Then filtering the solution soaked and washed by the snail in the water bath pot with double-layer gauze, and then drying in vacuum to obtain the snail mucus extract. Typically a 30 gram snail is subjected to this method to extract 0.5-1 gram of mucus extract. Dissolving mucus extract 0.05-5g in appropriate amount of normal saline, adding chymotrypsin 0.001-0.05g, hydrolyzing at 30 deg.C for one hour, and refrigerating for use. The chymotrypsin is added mainly for hydrolyzing macromolecular mucin to change into micromolecular denatured protein or polypeptide, amino acid, which is convenient for mucous membrane absorption and utilization.

7. The preparation for doubletherapy according to claim 1, wherein 15-300g of fresh rhizoma phragmitis is taken to be crushed and squeezed to obtain juice, the juice is collected, purified water with twice of the amount of the filter residue is added into the rhizoma phragmitis filter residue, the filter residue is stirred, soaked and washed for 15 minutes, the juice is squeezed out by a squeezer, the filter residue is removed, the squeezed juice is collected, the filtrate is concentrated at 50 ℃, the amount of the filtrate is one-thirtieth of the raw drug amount of the rhizoma phragmitis, and the filtrate is refrigerated for standby;

pulverizing 5-50g of Baeckea frutescens, soaking in proper hot water at 70 deg.C for 2 hr to dissolve out volatile components, filtering the extractive solution, and concentrating at 60 deg.C to obtain concentrated solution equivalent to one fifth of the crude drug of Baeckea frutescens;

pulverizing herba Medicaginis 10-100g into coarse powder, soaking in 2-3 times of alkaline solution with pH of 9-10, heating in water bath at 60 deg.C for 2 hr, filtering the extractive solution, and concentrating at 60 deg.C to obtain concentrated solution equivalent to one tenth of the crude drug amount of herba Medicaginis;

taking 0.5-10g of tremella, removing roots, soaking in purified water at normal temperature for 4 hours, cleaning, cutting into pieces, putting into a pressure cooker, adding a proper amount of water, stewing for 40 minutes, cooling to room temperature, pulping by a grinder, filtering by using double-layer gauze, putting into a water bath kettle, evaporating excessive water, and enabling the raw dosages of tremella pulp and tremella to be 1: 1, refrigerating for later use;

placing 0.01-0.5g folic acid in a mortar, grinding into uniform superfine powder, taking out, placing in a stainless steel container, adding Tremella pulp, and stirring with a homogenizing mixer at 1500 rpm to obtain homogenized pulp.

8. A process for the preparation of a dual therapy formulation as claimed in any one of claims 1 to 7, comprising the steps of:

(1) preparation of rectal administration formulation: sequentially adding micro powder obtained by processing pawpaw seeds, raw white paeony root decoction pieces, radix pseudostellariae, snake gall and Tabanus into a mixed solution consisting of a glutinous rice grass concentrated solution, a shepherd's purse concentrated solution, a sea-buckthorn concentrated solution and a gynostemma pentaphyllum concentrated solution, uniformly stirring at 2000 revolutions per minute by using a homogenizing mixer, then adding a mixed fermentation product of soybean isoflavone and sheep ovary pulp, continuously uniformly stirring, adding an extracting solution of nardostachyos decoction pieces, uniformly stirring, finally adding standby nest honey, uniformly stirring at 1000 revolutions per minute by using the homogenizing mixer, weighing, adding hydrogen-rich water to a sufficient amount less than 100ml, standing for 4 hours, and subpackaging after micro bubbles generated by uniform stirring overflow;

(2) preparation of vaginal administration preparation: adding the reed rhizome concentrated solution into the baeckea frutescens concentrated solution, quickly stirring uniformly at 2000 r/min by using a homogenizing stirrer, adding the genistein propylene glycol solution into a mixed solution of the reed rhizome juice and the baeckea frutescens concentrated solution, continuously quickly homogenizing and uniformly stirring, adding the snail mucus extract chymotrypsin solution, and slowly homogenizing and uniformly stirring at 500 r/min; adding folic acid tremella slurry, continuing to slowly homogenize and stir uniformly, adding alfalfa concentrate, continuing to slowly homogenize and stir uniformly, weighing, adding hydrogen-rich water to a sufficient amount of less than 100ml, standing for 4 hours, and subpackaging when micro bubbles generated by homogenizing and stirring overflow.

9. The method of preparing a combination therapy formulation according to claim 8, wherein the dispensing of the rectally administrable formulation comprises: placing the mixed solution of the rectal administration preparation in a filling machine, subpackaging in a special sterile injector for anus of 5 ml/piece, packaging in sterile aluminum foil or medical grade sterile plastic bag, and refrigerating at 5-10 deg.C for use.

10. The method for preparing a formulation for doublet therapy according to claim 8, wherein the sub-packaging of the formulation for vaginal administration comprises: the mixed solution of the vaginal administration preparation is placed into a filling machine, and then is subpackaged into a special sterile vaginal syringe with the volume of 3ml per piece, and is packaged into a sterile aluminum foil or a medical grade sterile plastic bag, and is refrigerated at the temperature of 5-10 ℃ for standby.