Medicinal and edible traditional Chinese medicine composition capable of improving intestinal flora and contributing to improving ovarian function as well as preparation process and application of medicinal and edible traditional Chinese medicine composition

Abstract

The invention belongs to the field of traditional Chinese medicines and medical health-care foods, and particularly relates to a medicinal and edible traditional Chinese medicine composition for improving intestinal flora and contributing to improving ovarian functions and a preparation process and application thereof, and the composition comprises five parts: an energy supply part, a medicinal and edible traditional Chinese medicine part, a dietary fiber part, a vitamin part and a mineral part. Big data analysis on traditional Chinese medicines of the food composition discovers that the food composition has an effect of assisting reproduction, and related animal experiments prove that the food composition has the effects of improving the ovarian function, regulating serum sex hormone and increasing the pregnancy rate; the relative abundance of bacteroides can be remarkably improved, and the relative abundance of firmichelia is reduced, so that the effect of improving intestinal flora is achieved. Various medicinal and edible traditional Chinese medicines are creatively combined, energy supply, vitamins, mineral substances and dietary fibers are added at the same time, traditional Chinese medicine theories and dialectical treatment are organically fused with modern nutriology, the reproductive function is effectively improved, intestinal flora is adjusted, and nutrients required by pregnancy preparation, pregnancy and lactation are supplemented.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of traditional Chinese medicine and medical health food, and particularly relates to a medicine-food homologous traditional Chinese medicine composition for improving intestinal flora and helping to improve ovarian function, and a preparation process and application thereof. BACKGROUND

[0002] In contemporary society, female reproductive health is facing severe challenges. With the acceleration of people's life pace, the rise of work pressure and the influence of unhealthy eating habits and other adverse factors, reproductive problems caused by female endocrine disorders are highlighted, and the disorder of ovarian function has gradually become an important reason for infertile women, easy miscarriage and production of unhealthy newborns. In women of childbearing age, the proportion of infertility caused by the decline of ovarian reserve function is increasing year by year, and some women after the age of 30 have problems such as the decrease of the number of ovarian follicles and the decline of egg quality, which not only greatly increases the difficulty of natural conception, but also hinders the success rate of assisted reproductive technology. At the same time, the marriage age of modern women is generally delayed, and the ovarian function will naturally decline with age, and the contradiction between the two makes more and more families fall into the predicament of reproduction. Traditional conditioning methods often have problems such as slow effect and insufficient targeting, and it is difficult to meet the needs of women for high-efficiency improvement of ovarian function.

[0003] There is a complex and close internal relationship between intestinal flora and ovarian function, which is called "gut-ovarian axis". As the largest micro-ecosystem in the human body, the balance of intestinal flora directly affects the endocrine function of the ovary, follicular development and egg quality. Intestinal flora can affect estrogen levels and follicular maturation through various pathways such as producing short-chain fatty acids by metabolizing dietary fiber in normal diet, affecting intestinal mucosal barrier, regulating oxidative stress and inflammatory response, and regulating liver-gut circulation of estrogen.

[0004] Traditional Chinese medicine believes that endocrine disorders are related to imbalance of qi and blood and dysfunction of zang-fu organs. Traditional Chinese medicine can improve endocrine disorders through overall conditioning and syndrome differentiation, but individualized medication is needed, and the effect varies from person to person. The concept of food as medicine is a unique concept that combines traditional Chinese medicine and long-term practice of dietary culture, and it is a manifestation of the concept of traditional Chinese medicine "preventive treatment". In the theory of traditional Chinese medicine, food not only meets the basic nutritional needs of the human body, but also has the functions of regulating yin and yang, dredging meridians, and regulating qi and blood. Many foods can be used as medicine for daily diet and disease prevention and treatment. Food as medicine refers to some substances that belong to traditional Chinese medicinal materials and can be eaten as food, and have both medicinal and edible values. From the perspective of "preventing disease before it occurs", the causes of ovarian hypofunction are complex, and food as medicine can provide sustained nutritional support for the ovary and create a stable internal environment for the ovary. From the aspect of "preventing disease from changing", when the ovarian function is slightly decreased (such as irregular menstrual cycle and reduced menstrual flow), food as medicine can play a "slow treatment" advantage. Compared with the side effects of some chemical drugs, food as medicine can regulate multiple targets, improve intestinal flora, and other mild and systematic conditioning methods, which can not only relieve the early symptoms of ovarian hypofunction, but also avoid additional burden on the body, and meet the pursuit of "safe intervention" by modern women.

[0005] Therefore, based on the theory of traditional Chinese medicine syndrome differentiation, it is an urgent need to develop a food as medicine composition that can safely and effectively improve ovarian function, nourish the ovary, improve egg quality and reserve capacity, and help improve female reproductive and fertility capacity, which is a solution to modern reproductive and fertility health problems with traditional wisdom. SUMMARY

[0006] The technical problems solved by the present application are as follows:

[0007] In view of the deficiencies of the prior art, the present application provides a food as medicine composition for improving intestinal flora and improving ovarian function, as well as a preparation process and application thereof, which solves the problems of decreased female reproductive and fertility capacity, decreased pregnancy rate, and low ovarian function.

[0008] The technical solution of the present application is as follows:

[0009] The raw materials comprise the following components by weight:

[0010] (1) Energy supply part:

[0011] Full-fat milk powder 200-300 parts, lotus root powder 10-20 parts, red bean powder 1-10 parts

[0012] (2) Food as medicine part:

[0013] Sea buckthorn fruit powder 20-30 parts, coix seed extract 1-30 parts, yam extract 1-30 parts, kudzu root extract 1-30 parts, lily extract 1-30 parts, poria cocos extract 1-30 parts, wolfberry extract 1-30 parts, jujube extract 1-30 parts, dried plum extract 1-30 parts, polygonatum extract 1-30 parts, black sesame extract 1-30 parts, jujube seed extract 1-30 parts, celery extract 1-30 parts, mulberry extract 1-30 parts, buckwheat extract 1-30 parts;

[0014] (3) Dietary fiber portion:

[0015] 10-20 parts konjac powder, 1-10 parts inulin

[0016] (4) Proportions of each component in the vitamin and mineral section:

[0017] Vitamin C: Beta-carotene (1%): Vitamin E: Vitamin B1: Vitamin B2: Vitamin B6: Vitamin B12: Vitamin D: Folic acid: Niacin: Pantothenic acid: Iron: Zinc: Casein calcium peptide = 500-2000:100-1000:1-100:1-100:1-100:0.001-0.01:0.005-0.1:1-500:1-100:1-100:1-200:1-100:200-1000.

[0018] In the components of this invention:

[0019] Whole milk powder: Made solely from cow's milk, through concentration and drying. Produced from pure milk, it largely retains the original nutritional components of milk, with protein no less than 24%, fat no less than 26%, and lactose no less than 37%, providing abundant energy.

[0020] Konjac powder contains starch, protein, cellulose, potassium ions, and other components. After ingestion, it can effectively stabilize the heart's pumping ability, lower blood pressure, blood lipids, and blood sugar, and has a certain preventive effect on cardiovascular and cerebrovascular diseases. Because konjac powder contains a large amount of cellulose, it can promote gastrointestinal motility, improve constipation symptoms, and facilitate food digestion and absorption, thus improving appetite in patients with poor appetite. Konjac powder can prevent the formation of blood clots and also has anti-cancer effects.

[0021] Sea buckthorn: Sour and astringent in taste, warm in nature. It enters the spleen, stomach, lung, and heart meridians. It has the effects of strengthening the spleen and promoting digestion, relieving cough and eliminating phlegm, and promoting blood circulation and removing blood stasis. It is used for spleen deficiency with poor appetite, abdominal pain due to food stagnation, cough with excessive phlegm, chest pain, amenorrhea due to blood stasis, and swelling and bruising from falls.

[0022] Radix Puerariae: sweet, sour, and flat. It is attributed to the meridians of the liver, gallbladder, and heart. It resolves the exterior and relieves fever, generates fluid and relieves thirst, promotes rash, raises yang and stops diarrhea, promotes the flow of qi and blood, and relieves alcohol toxicity. It is used for external heat and headache, neck and back pain, thirst, diabetes, measles, dysentery, dizziness, headache, stroke, chest pain, and alcohol toxicity.

[0023] Fritillaria: sweet and cold. It is attributed to the meridians of the heart and lung. It nourishes yin and moistens the lung, and calms the heart and soothes the spirit. It is used for dry cough, labor cough with blood, restlessness, insomnia, and dreaminess.

[0024] Rhizoma Polygonati: sweet and flat. It is attributed to the meridians of the spleen, lung, and kidney. It supplements qi and yin, invigorates the spleen, moistens the lung, and benefits the kidney. It is used for deficiency of the spleen and stomach, fatigue, deficiency of stomach yin, dry mouth, dry cough, labor cough with blood, deficiency of essence and blood, weakness of the waist and knees, premature graying, and diabetes.

[0025] Semen Ziziphi Spinosae: sweet, sour, and flat. It is attributed to the meridians of the liver, gallbladder, and heart. It nourishes the heart and liver, calms the heart and soothes the spirit, astringes sweat, and generates fluid. It is used for restlessness, insomnia, frequent sweating, and thirst.

[0026] Fructus Mori: sweet, sour, and cold. It is attributed to the meridians of the heart, liver, and kidney. It nourishes yin and blood, generates fluid and relieves dryness. It is used for deficiency of the liver and kidney, dizziness, tinnitus, palpitation, insomnia, premature graying, thirst, internal heat, and constipation.

[0027] Semen Euryale: sweet and astringent, flat, attributed to the spleen and kidney meridians. It has the functions of benefiting the kidney and astringing essence, invigorating the spleen and stopping diarrhea, and eliminating dampness and stopping leucorrhea. It is used for dreaminess, spermatorrhea, enuresis, frequent urination, chronic diarrhea, leucorrhea, and leucorrhoea.

[0028] Semen Sesami Nigrum: sweet and flat, attributed to the liver, lung, and kidney meridians. It nourishes the liver and kidney, generates fluid and moistens the intestines, moisturizes the skin and hair, and brightens the eyes.

[0029] Fructus Mume: sour and astringent, flat. It is attributed to the meridians of the liver, spleen, lung, and large intestine. It astringes the lung and intestines, generates fluid, and relieves roundworms. It is used for chronic cough, chronic diarrhea, diabetes, roundworms, and abdominal pain.

[0030] Fructus Jujubae: sweet and warm, attributed to the spleen, stomach, and heart meridians. It supplements the center and benefits qi, nourishes blood and soothes the spirit. It is used for deficiency of the spleen, fatigue, loose stools, restlessness, and irritability.

[0031] Radix Rehmanniae: sweet and cool, attributed to the spleen, stomach, and lung meridians. It benefits water and penetrates dampness, invigorates the spleen and stops diarrhea, removes obstruction, removes toxicity, and resolves masses. It is used for edema, beriberi, difficulty urinating, chronic diarrhea, dampness and obstruction, lung abscess, and intestinal abscess; warts and cancer.

[0032] Radix Rehmanniae: sweet and cool, attributed to the spleen, stomach, and lung meridians. It benefits water and penetrates dampness, invigorates the spleen and stops diarrhea, removes obstruction, removes toxicity, and resolves masses. It is used for edema, beriberi, difficulty urinating, chronic diarrhea, dampness and obstruction, lung abscess, and intestinal abscess; warts and cancer.

[0033] Poria cocos: sweet and mild in flavor, and neutral in nature. It is associated with the heart, lung, spleen, and kidney channels. It benefits water metabolism, removes dampness, strengthens the spleen, and calms the heart. It is used for edema, oliguria, dizziness, palpitation, spleen deficiency, poor appetite, diarrhea, and insomnia.

[0034] Medlar: sweet and mild in flavor, and associated with the liver and kidney channels. It nourishes the liver and kidney, and benefits the eyes. It is used for deficiency, kidney deficiency, dizziness, tinnitus, impotence, internal heat, diabetes, blood deficiency, and blurred vision.

[0035] Lotus root: sweet and cold in flavor, and associated with the heart, spleen, and stomach channels. It clears heat, generates fluid, cools blood, disperses blood stasis, supplements the spleen, and stimulates the appetite. It is used for malnutrition, anorexia, iron deficiency anemia, high fever, hematemesis, hematuria, hypertension, diabetes, and constipation.

[0036] Red bean: It has the effects of generating fluid, promoting urination, and reducing swelling. Red beans are suitable for most people to eat. In particular, people who may have edema often eat red beans, which have the effect of reducing swelling. In traditional Chinese medicine, red beans are believed to have the effect of strengthening the spleen. Red beans contain a lot of dietary fiber, which can relieve the pain of constipation. Regular consumption of red beans can help with bowel movements and lower blood pressure. Red beans are rich in folic acid, which can promote the health of babies when pregnant women take it during pregnancy.

[0037] Inulin: Inulin is produced by removing protein, gum, crude fiber and minerals from the root tuber of Jerusalem artichoke (tuberous root), and then through water extraction, ion exchange, membrane filtration, spray drying and other production processes. It provides dietary fiber, which can absorb intestinal fat, form fat-fiber complexes, and then be excreted with feces, thereby reducing blood lipid levels. In addition, it can also lower blood sugar, promote mineral absorption, regulate intestinal flora, improve intestinal health, and prevent constipation. It can also inhibit the production of toxic fermentation products, protect the liver, and prevent colon cancer. Dietary fiber reduces the residence time of food in the gastrointestinal tract and increases the amount of feces, effectively treating constipation. Inulin contains a small amount of fructooligosaccharides, which have been shown to increase the expression of neurotrophic factors in brain cells, protect neurons from corticosterone-induced damage, and have good antidepressant effects.

[0038] Buckwheat: Buckwheat is a food that can supplement the body's iron elements and dietary fiber, making people energetic. A component called flavonoids in buckwheat effectively resists pathogenic bacteria. Buckwheat contains magnesium, which is an essential element for the human body and can prevent the hardening of tissues such as blood vessels.

[0039] Celery: celery nature is sweet, cool, with heat diuresis, antihypertensive effect of fat. Celery rich in protein, carbohydrates, carotene, also has B vitamins, calcium, phosphorus, iron, sodium, etc., while it has liver heat, dispelling dampness, swelling, blood cooling, detoxification, lung, stomach, intestine, lung, cough, etc. Also can lower blood pressure, brain health. Celery contains high iron, can make up for the loss of iron deficiency anemia caused by menstrual blood, excessive menstrual blood, functional uterine bleeding in women more use of celery is very beneficial.

[0040] Vitamins and minerals: the medical community recognized for the very important nutrients during the preparation period is folic acid, in addition to some very important nutrients: vitamin C, vitamin D, vitamin E and other vitamins. These ingredients have a common feature, that is, play an antioxidant role, remove free radicals, against DNA damage to reproductive cells, and thus promote the pregnancy rate.

[0041] The application innovatively adds energy providing part such as milk, vitamin part such as folic acid and mineral supplement part such as iron on the basis of traditional Chinese medicine prescription based on the nutritional support function of the ovary. The selected parts fully combine the ovary nutrition and vitamin demand of women of childbearing age, and the above components are scientifically and reasonably matched, so that the problems such as nutrient and trace element deficiency of women of childbearing age are effectively solved.

[0042] The preparation process of the application comprises the following steps:

[0043] The homoeopathic raw materials of traditional Chinese medicine in the application are mixed in a blender according to the proportion, and the finished product is obtained. The application can also be prepared into capsule, tablet, pill and other pharmaceutical preparations.

[0044] Compared with the prior art, the application has the following advantages and beneficial effects:

[0045] Traditional Chinese medicine believes that "the kidney stores essence and is responsible for reproduction, and the uterus is connected to the kidney", and the deficiency of kidney qi is closely related to the decline of the function of the ovary and the uterus. The application provides a homoeopathic traditional Chinese medicine composition which can improve the intestinal flora and improve the function of the ovary, and is helpful for the health of female reproduction and fertility. The main components of the application include 10 kinds of medicines such as sea buckthorn, medlar, black sesame, yellow ginseng, jujube, Chinese yam, kudzu root, tuckahoe and sour jujube.

[0046] In the prescription, the wolfberry, black sesame and polygonatum are the monarch drugs, the wolfberry can "nourish liver and kidney, and benefit essence and eyesight", the black sesame can "nourish liver and kidney, and benefit essence and blood", and the polygonatum can "nourish qi and nourish yin, and strengthen spleen and kidney", the three can enhance the effect of nourishing kidney and filling essence, strengthen the ovarian reserve function, and consolidate the reproductive foundation. In the prescription, the Chinese yam, jujube and tuckahoe are the minister drugs, the Chinese yam can "nourish spleen and stomach, and benefit lung", the jujube can "nourish center and benefit qi, and nourish blood and tranquilize mind", and the tuckahoe can "promote water and dampness, and strengthen spleen and calm heart", the three can synergistically strengthen spleen and blood, and strengthen the function of spleen and stomach to provide material guarantee for the reproductive system, and build the source of qi and blood. In the prescription, the pueraria, jujube kernel and wild plum are the auxiliary drugs, the pueraria can "dissolve muscle and reduce fever, and benefit saliva", the jujube kernel can "nourish heart and liver, and tranquilize mind", and the wild plum can "nourish lung, astringe intestines, and benefit saliva", and the three can harmonize qi and blood and emotion. The sea buckthorn is the messenger, the sea buckthorn can "strengthen spleen and digest food, and activate blood and remove stasis", and the three can harmonize the medicinal properties of various drugs, dredge collaterals, and make the nourishing and blood-activating without stagnation and injury.

[0047] In terms of nutrition, based on the original traditional medicine-food homologous formula, based on the modern nutrition theory, the protein, lipid, carbohydrate, vitamin, mineral and dietary fiber required by the human body are added to meet the nutritional support of women of childbearing age for reproduction and fertility. The present application makes up for the shortcomings of the existing market, and all the selected traditional Chinese medicines come from the medicine-food homologous list, are safe and non-toxic, and have no contraindications and side effects for patients with different constitutions. The present application has simple manufacturing process and wide market prospect. BRIEF DESCRIPTION OF DRAWINGS

[0048] Figure 1 Effects of the group formula 1-3 on the diestrous phase and postestrous phase of rats;

[0049] Figure 2 Effects of the group formula 1-3 on the proestrous phase and estrous phase of rats;

[0050] Figure 3 Effects of the optimal group formula on the uterus index of rats;

[0051] Figure 4 Effects of the optimal group formula on the ovary index of rats;

[0052] Figure 5 Effects of the optimal group formula on the ovary tissue morphology of rats;

[0053] Figure 6 Effects of the optimal group formula on the follicle number of rats;

[0054] Figure 7 Effects of the optimal group formula on the firmicutes of rats;

[0055] Figure 8 Effect of optimal formula on rat Bacteroidetes;

[0056] Figure 9 Effect of comparison formula 1-4 on the proportion of proestrous and estrous rats;

[0057] Figure 10 Effect of comparison formula 1-4 on the proportion of inter-estrous and post-estrous rats. DETAILED DESCRIPTION

[0058] The above content of the present application will be further illustrated in the form of examples, but it should not be understood that the above-mentioned subject matter of the present application is limited to the following examples, and any technology achieved based on the above-mentioned content of the present application falls within the scope of the present application.

[0059] Example 1: Optimal formula screening experiment

[0060] The present embodiment provides a medicinal and edible homologous traditional Chinese medicine composition for improving intestinal flora, improving ovarian function, and helping to improve female reproductive and fertility capacity. The main components of the traditional Chinese medicine composition include 10 kinds of medicines such as sea buckthorn, medlar, black sesame, yellow ginseng, jujube, Chinese yam, kudzu root, and poria cocos.

[0061] Formula 1: A medicinal and edible homologous traditional Chinese medicine composition for improving intestinal flora, improving ovarian function, and helping to improve female reproductive and fertility capacity, which is composed of the following components in weight percentage: sea buckthorn fruit powder 20 parts, yiyi ren extract 10 parts, Chinese yam extract 10 parts, kudzu root extract 10 parts, lily extract 10 parts, poria cocos extract 10 parts, medlar extract 10 parts, jujube extract 10 parts, black sesame extract 10 parts, yellow ginseng extract 10 parts, and acid jujube extract 10 parts, celery extract 1 part, mulberry extract 10 parts, and buckwheat extract 1 part.

[0062] Formula 2: A medicinal and edible homologous traditional Chinese medicine composition for improving intestinal flora, improving ovarian function, and helping to improve female reproductive and fertility capacity, which is composed of the following components in weight percentage: sea buckthorn fruit powder 20 parts, yiyi ren extract 10 parts, Chinese yam extract 10 parts, kudzu root extract 5 parts, lily extract 5 parts, poria cocos extract 10 parts, medlar extract 10 parts, jujube extract 5 parts, black sesame extract 10 parts, yellow ginseng extract 10 parts, and acid jujube extract 10 parts, celery extract 15 parts, mulberry extract 5 parts, and buckwheat extract 1 part.

[0063] Composition 3: a kind of improving intestinal flora, improving ovarian function, help to improve the female reproductive fertility of the Chinese medicine composition of food, by the following weight fraction components consisting of: sea buckthorn fruit powder 25 parts, 25 parts of medlar extract, 25 parts of yellow milk extract, 25 parts of black sesame extract, 5 parts of coix seed extract, 10 parts of yam extract, 10 parts of radix puerariae extract, 5 parts of lily extract, 15 parts of poria cocos extract, 10 parts of jujube extract, 5 parts of plum extract, 15 parts of semen ziziphi spinosae extract, 1 part of celery extract, 5 parts of mulberry extract, 1 part of buckwheat extract.

[0064] The preparation process of the composition is: weigh the appropriate amount of each raw material respectively, remove impurities, purify, dry, crush, pass through 120 mesh sieve, mix the powder uniformly and then use for experiment.

[0065] 1. Test material

[0066] Main material is health food composition

[0067] (1) Energy supply part:

[0068] Full-fat milk powder 200-300 parts, lotus root powder 10-20 parts, red bean powder 1-10 parts

[0069] (2) Food-medicinal part:

[0070] Sea buckthorn fruit powder 20-30 parts, coix seed extract 1-30 parts, yam extract 1-30 parts, radix puerariae extract 1-30 parts, lily extract 1-30 parts, poria cocos extract 1-30 parts, medlar extract 1-30 parts, jujube extract 1-30 parts, plum extract 1-30 parts, yellow milk extract 1-30 parts, black sesame extract 1-30 parts, semen ziziphi spinosae extract 1-30 parts, celery extract 1-30 parts, mulberry extract 1-30 parts, buckwheat extract 1-30 parts.

[0071] (3) Dietary fiber part:

[0072] Konjac flour 10-20 parts, 1-10 parts of chrysanthemum powder

[0073] (4) Vitamin and mineral part ratio:

[0074] Vitamin C: beta-carotene (1%): vitamin E: vitamin B1: vitamin B2: vitamin B6: vitamin B12: vitamin D: folic acid: niacin: pantothenic acid: iron: zinc: casein calcium peptide = 500-2000: 100-1000: 1-100: 1-100: 1-100: 1-100: 0.001-0.01: 0.005-0.1: 1-500: 1-100: 1-100: 1-200: 1-100: 200-1000.

[0075] 2. Experimental animal grouping and administration method

[0076] 5-6 week-old SD female rats 40, male rats 20, body weight 180-220 g, feeding environment 23℃±2℃, relative humidity 50-70%, 12h light, free food and water, conventional adaptation feeding for one week. Randomly selected 8 as blank control group, the other female rats were divided into 5 groups, model group, prescription 1 group, prescription 2 group, prescription 3 group, 8 in each group. The blank control group was given normal feed, and the other groups were given high-fat feed(20% crude protein, 45% crude fat, 35% carbohydrate); The blank control group and the model group were given normal saline by gavage every day, and the traditional Chinese medicine compound was given by gavage at 300mg / kg once a day. During feeding, each group was free to eat and drink clean water, and the body weight was measured every week. After 8 weeks, at 9 o'clock every morning, vaginal smear of rats was observed to observe the change of estrous cycle of rats.

[0077] 3. Experimental procedure

[0078] Hold the rat with your hand, use a pipette to take 40ul of fresh normal saline, gently insert it into the vaginal orifice, and repeat the suction 2-3 times until the liquid is turbid, drop an appropriate amount on the glass slide, and after the glass slide is naturally dried, fix it with 4% paraformaldehyde for 30min, stain with Giemsa staining solution for 15min, and record the experimental results under the optical microscope after washing and drying, and take pictures. Take 4 days as a cycle, and calculate the ratio of estrous cycle of rats in each cycle.

[0079] 4. Data analysis

[0080] The data was statistically analyzed by SPSS 26.0 software, the comparison between groups was analyzed by one-way ANOVA, and the comparison between two groups was analyzed by Turkey HSD post hoc test method, and the experimental data was expressed as mean±standard deviation. P<0.05 was considered to have significant difference.

[0081] 5. Experimental results

[0082] During the experiment, the behavior of female rats in the prescription test group was normal, and there was no death phenomenon. Compared with the control group, the behavior of male rats in the test group was more excited, and there was no death phenomenon. The food and water intake of each experimental group was normal.

[0083] Compared with the blank, the model group had a disturbed estrous cycle, which was manifested as prolonged and stagnated estrous cycle, and under the microscope, it was observed that it was in the late estrous phase and interphase for a long time. Prescription 1-3 shortened the time of estrous phase and interphase to different degrees, among which prescription 3 shortened the interphase and estrous phase most obviously, with significant difference(P<0.05, see Figure 1); compared with the blank, the model group was significantly shortened in proestrus and estrus under long-term observation, while the prescription groups 1-3 improved the shortening of estrus cycle to different degrees, among which the prescription group 3 was the most significant (P<0.05, see Figure 2 Based on the above, the prescription group 3 was selected as the optimal prescription for the pharmacodynamic experiment.

[0084] Traditional Chinese medicine in prescription group 2

[0085] 1. Experimental principle and method

[0086] Network pharmacology is a new discipline developed on the basis of systems biology, proteomics and genomics. Based on the understanding of the interaction network of "drug-target-gene-disease phenotype", the intervention and influence of drugs on diseases are observed through network analysis, so that the drug development is closer to the actual situation of the disease, and the success rate of drug development is improved. Traditional Chinese medicine is a complex system containing rich ingredients. The application of network pharmacology and bioinformatics to the study of traditional Chinese medicine system can analyze the interaction between molecules-targets-diseases, and screen and analyze the components and targets of 10 medicinal materials in the composition of the application, i.e. Hippophae rhamnoides L., Fructus Lycii, Sesamum indicum L., Polygonatum sibiricum, Prunus mume, Fructus Jujubae, Dioscorea opposita, Pueraria lobata, Poria cocos and Semen Ziziphi Spinosae, to screen the targets and genes related to female ovary diseases, and provide theoretical support for the development and optimization of the composition of the application.

[0087] TCMSP database (http: / / sm.nwsuaf.edu.cn / lsp / tcmsp.php);

[0088] Uniprot database (http: / / www.uniprot.org / );

[0089] DAVID database (https: / / david.ncifcrf.gov / summary.jsp);

[0090] Genecards database (https: / / www.genecards.org / ).

[0091] 2. Experimental results

[0092] The effective components of sea buckthorn, medlar, black sesame, Chinese yam, kudzu root, poria cocos, and sour jujube were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP, https: / / tcmspw.com / tcmsp.php / ) database. Since traditional Chinese medicines are mostly oral preparations, the effective components were screened based on the pharmacokinetic parameters, with the oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18. Sea buckthorn contained 33 effective components, medlar 45, black sesame 12, Chinese yam 12, medlar 8, jujube 29, yam 16, kudzu root 4, poria cocos 15, and sour jujube 9. After removing the repeated components, a total of 142 components were obtained. Table 1 shows the effective components with more repeated components in the prescription.

[0093] Table 1 shows the 7 core effective components in the fertility-aiding prescription.

[0094]

[0095]

[0096] The target genes corresponding to the core components were retrieved from the TCMSP database. β-Sitosterol obtained 38 target genes, stigmasterol obtained 30 target genes, cholesterol obtained 4 target genes, quercetin obtained 100 target genes, daucosterol obtained 3 target genes, diosgenin obtained 2 target genes, and 3'-methoxy daidzein obtained 19 target genes. After removing the repeated target genes, a total of 133 target genes were obtained. The target genes corresponding to the drug-related core components were converted through the Uniport database, and a total of 128 target genes corresponding to the core components were obtained.

[0097] The Genecards database was searched for female infertility-related and diseases: "Polycystic ovarian syndrome" (multiple cystic ovarian syndrome), Premature Ovarian Failure (premature ovarian failure), Premature Ovarian Insufficiency (early ovarian insufficiency), and Obesity (obesity). A total of 2775 POS-related genes, 3990 POI-related genes, 4577 POF-related genes, and 9481 OBE-related genes were obtained. The intersection of the drug-related target gene set and the disease-related target gene set obtained a total of 93 common genes.

[0098] The common target genes were subjected to GO function enrichment analysis and KEGG pathway enrichment analysis using the David website (https: / / david.ncifcrf.gov / ). A total of 709 entries were obtained by GO function enrichment analysis, including 450 entries of biological process (BP), 47 entries of cell composition (CC), and 99 entries of molecular function (MF).

[0099] A total of 113 pathways were obtained by KEGG pathway enrichment analysis, mainly including estrogen signaling pathway, VEGF signaling pathway, ErbB signaling pathway, prolactin signaling pathway, oxytocin signaling pathway, and progesterone-mediated oocyte maturation related pathways (Table 2).

[0100] Table 2. Functional and pathway enrichment analysis of common target genes

[0101]

[0102]

[0103] Example 3: Pharmacodynamic evaluation of the effect of the optimal prescription on assisted reproduction

[0104] The optimal prescription selected in Example 1 was used for pharmacodynamic evaluation to confirm its effect of improving female reproductive and fertility capacity.

[0105] Optimal prescription: a medicinal and food homologous traditional Chinese medicine composition for improving intestinal flora, enhancing ovarian function, and helping to improve female reproductive and fertility capacity, containing sea buckthorn fruit powder 20 parts, yiyi extract 5 parts, yam extract 10 parts, radix puerariae extract 10 parts, lily extract 5 parts, poria cocos extract 25 parts, medlar extract 20 parts, jujube extract 10 parts, dark plum extract 5 parts, rhizoma polygonati extract 25 parts, black sesame extract 25 parts, semen ziziphi spinosae extract 20 parts, celery extract 1 part, mulberry extract 1 part, buckwheat extract 1 part.

[0106] The preparation process of the composition is as follows: weigh appropriate amounts of each raw material, remove impurities, purify, dry, crush, and pass through a 120-mesh sieve. The powder is mixed uniformly and can be used for experiments.

[0107] 1. Experimental animal grouping and administration method

[0108] 5-6 weeks old SD female rats 40, male rats 20, body weight 180-220 g, feeding environment 23℃±2℃, relative humidity 50-70%, 12h light, free food and water, conventional adaptation feeding for one week. Randomly selected 8 as blank control group, the other female rats were divided into 5 groups, model group, low dose group, middle dose group, high dose group, 8 in each group. The blank control group was given normal feed, and the other groups were given high-fat feed(20% crude protein, 45% crude fat, 35% carbohydrate); the blank control group and the model group were given normal saline by gavage every day, and the traditional Chinese medicine compound was given by gavage at 150mg / kg, 300mg / kg, 600mg / kg once a day for 8 weeks. During feeding, each group was free to eat and drink clean water, and the body weight was measured every week.

[0109] 2. Experimental steps

[0110] 1) According to the ratio of 2:1, the rats were combined. The pregnancy rate of rats was recorded. The number of offspring of each pregnant mouse was recorded on the day of production.

[0111] 2) The ovaries and uteruses of rats in each group were taken and weighed, and the uterine index was calculated(uterine index=100×uterine wet weight(g) / body weight(g)×100%); the ovarian index was recorded(ovarian index=ovarian wet weight(mg) / body weight(g)×100%).

[0112] 3) The ovaries of rats in each group were taken, and the left ovaries of rats in each group were fixed in 4% paraformaldehyde, dehydrated with ethanol, embedded in paraffin, sectioned, HE stained, neutral resin mounted, and the morphological changes of ovarian tissue were observed under optical microscope, and the total number of follicles was counted.

[0113] 3. Data analysis

[0114] The same as example 1.

[0115] 4. Experimental results

[0116] Effect of optimal prescription on pregnancy rate of female rats

[0117] The female rats in each dose group of the optimal prescription were in good condition, and the pregnancy rate was improved compared with the model group.

[0118] Table 3. Effect of prescription on pregnancy rate and number of offspring of rats

[0119]

[0120]

[0121] Note: compared with the normal diet group, **P<0.01, compared with the high-fat diet group, #P<0.05, ##P<0.01 n=8

[0122] Effect of optimal formula on uterus and ovary index of rats

[0123] Compared with the blank control group, the uterus index of the model group was significantly decreased (P<0.01), and compared with the model group, the uterus index of the optimal formula medium-dose and high-dose groups was significantly increased (P<0.05) as shown in Table 1; compared with the blank control group, the ovary index of the model group was significantly decreased (P<0.0001), and compared with the model group, the ovary index of the optimal formula low-dose, medium-dose and high-dose groups was significantly increased (P<0.01) as shown in Table 2. Figure 3 Figure 4

[0124] Effect of optimal formula on ovary morphology and follicular development of rats

[0125] The ovary tissue of the blank control group rats showed various follicles with clear outlines and orderly arrangement, and the granulosa cells around the follicles had multiple layers, dense arrangement and rich blood vessels; the ovary tissue of the high-fat-induced obese model group rats showed no dominant follicles, few growing follicles, and large atretic follicles, and the granulosa cells had fewer layers, loose arrangement and reduced blood vessels, showing regressive development (as shown in FIG. 2). Compared with the blank control group, the total number of follicles of the model group was significantly decreased (P<0.001). Compared with the model group, the follicle count of the ovary tissue of the optimal formula medium-dose and high-dose groups was increased (P<0.05) as shown in Table 3. Figure 5 Figure 6

[0126] Example 4: Regulation of optimal formula on serum sex hormones of rats

[0127] 1. Experimental animal grouping and administration method

[0128] Same as Example 3

[0129] 2. Experimental steps

[0130] The animals were anesthetized by intraperitoneal injection of 2% pentobarbital at 40 mg / kg body weight, and blood was taken from the abdominal aorta. After standing at room temperature for 1 h, the supernatant was immediately absorbed at 3000 r / min and stored at -80°C for detection. The hormone levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and anti-Mullerian hormone (AMH) in the serum of rats in each group were detected by ELISA, and the specific operation was strictly performed according to the instruction.

[0131] 3. Data analysis

[0132] Same as Example 1.

[0133] 4. Experimental results

[0134] ​​​​Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Mullerian hormone (AMH) are commonly used indicators for evaluating ovarian function in clinic. Therefore, the serum FSH, LH, E2, AMH levels of each group of rats were detected, and the results are shown in Figure 8 As shown in Table 1, compared with the blank control group, the serum FSH and LH levels of the model group rats were significantly increased (P<0.01), and the E2 and AMH levels were significantly decreased (P<0.05); compared with the model group, the serum FSH and LH levels of the rats in each dose of the optimal group formula were significantly decreased (P<0.05), and the E2 and AMH levels in the optimal group formula were significantly increased (P<0.05).

[0135] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

[0136] Example 5: Modulatory effect of the optimal group formula on intestinal flora of high-fat rats

[0137] 1. Experimental animal grouping and administration method

[0138] The same as example 3

[0139] 2. Experimental steps

[0140] Fresh feces in the rectum of rats in each group was taken for intestinal flora detection. Based on the PacBio sequencing platform, the marker gene was sequenced by single molecule real-time sequencing (SMRT Cell), and then the CCS (Circular Consensus Sequencing) sequence was filtered, clustered or denoised, and species annotation and abundance analysis were further performed for flora analysis.

[0141] 3. Data analysis

[0142] The same as example 1.

[0143] 4. Experimental results

[0144] At the level of comparative analysis of abundance of phylum, compared with the blank control group, the abundance of Firmicutes in the feces of the model group rats was significantly increased (P<0.01) (as shown in Table 2), and the proportion of Bacteroidetes was significantly reduced (P<0.01) (as shown in Table 3). Figure 7 Figure 8 ​The results show that high-fat diet can cause the increase of the number of bacteria in the Firmicutes phylum and the decrease of the number of bacteria in the Bacteroidetes phylum, and this imbalance of flora can cause hormone level disorder and affect pregnancy. The dose group of the optimal formula can reduce the relative abundance of the Firmicutes phylum (P<0.01) and increase the abundance of the Bacteroidetes phylum (P<0.01), so as to regulate the intestinal flora and further regulate the reproductive related hormones and help reproduction. Therefore, the optimal formula can regulate the intestinal flora structure change induced by high-fat diet.

[0145] Example 6: Comparison analysis of optimal formula and disassembled formula

[0146] In order to further verify the rationality and effectiveness of the optimal formula, the four main ingredients in the optimal formula were replaced respectively to obtain comparison formulas 1-4, which were used for comparison with the optimal formula (as shown below).

[0147] The optimal formula is a medicinal and edible homologous traditional Chinese medicine composition for improving intestinal flora, improving ovarian function and helping to improve female reproductive and fertility ability, which is composed of the following components in weight fraction: sea buckthorn fruit powder 25 parts, wolfberry extract 25 parts, rhizoma polygonati extract 25 parts, black sesame extract 25 parts, coix seed extract 5 parts, yam extract 10 parts, pueraria extract 10 parts, lily extract 5 parts, poria cocos extract 15 parts, jujube extract 10 parts, Fructus Mume extract 5 parts, Semen Ziziphi Spinosae extract 15 parts, celery extract 1 part, mulberry extract 5 parts, buckwheat extract 1 part.

[0148] Comparison formula 1 is a medicinal and edible homologous traditional Chinese medicine composition for improving intestinal flora, improving ovarian function and helping to improve female reproductive and fertility ability, which is composed of the following components in weight fraction: licorice 25 parts, wolfberry extract 25 parts, rhizoma polygonati extract 25 parts, black sesame extract 25 parts, coix seed extract 5 parts, yam extract 10 parts, pueraria extract 10 parts, lily extract 5 parts, poria cocos extract 15 parts, jujube extract 10 parts, Fructus Mume extract 5 parts, Semen Ziziphi Spinosae extract 15 parts, celery extract 1 part, mulberry extract 5 parts, buckwheat extract 1 part, and the preparation process is the same as that of Example 1.

[0149] Comparison formula 2 is a medicinal and edible homologous traditional Chinese medicine composition for improving intestinal flora, improving ovarian function and helping to improve female reproductive and fertility ability, which is composed of the following components in weight fraction: sea buckthorn fruit powder 25 parts, dry ginger extract 25 parts, rhizoma polygonati extract 25 parts, black sesame extract 25 parts, coix seed extract 5 parts, yam extract 10 parts, pueraria extract 10 parts, lily extract 5 parts, poria cocos extract 15 parts, jujube extract 10 parts, Fructus Mume extract 5 parts, Semen Ziziphi Spinosae extract 15 parts, celery extract 1 part, mulberry extract 5 parts, buckwheat extract 1 part, and the preparation process is the same as that of Example 1.

[0150] Comparative formula 3: a kind of improving intestinal flora, improving ovarian function, help to improve the pharmaceutical and food homologous traditional Chinese medicine composition of female reproductive fertility, by following raw material weight fraction component group consists of: sea buckthorn fruit powder 25 parts, 25 parts of medlar extract, 25 parts of aconite extract, 25 parts of black sesame extract, 5 parts of coix seed extract, 10 parts of Chinese yam extract, 10 parts of radix puerariae extract, 5 parts of lily extract, 15 parts of poria cocos extract, 10 parts of jujube extract, 5 parts of plum extract, 15 parts of semen ziziphi spinosae extract, 1 part of celery extract, 5 parts of mulberry extract, 1 part of buckwheat extract, preparation process same as example 1.

[0151] Comparative formula 4: a kind of improving intestinal flora, improving ovarian function, help to improve the pharmaceutical and food homologous traditional Chinese medicine composition of female reproductive fertility, by following raw material weight fraction component group consists of: sea buckthorn fruit powder 25 parts, 25 parts of medlar extract, 25 parts of radix polygonati extract, 25 parts of dried tangerine or orange peel extract, 5 parts of coix seed extract, 10 parts of Chinese yam extract, 10 parts of radix puerariae extract, 5 parts of lily extract, 15 parts of poria cocos extract, 10 parts of jujube extract, 5 parts of plum extract, 15 parts of semen ziziphi spinosae extract, 1 part of celery extract, 5 parts of mulberry extract, 1 part of buckwheat extract, preparation process same as example 1.

[0152] Experimental method:

[0153] 1. Animal grouping and administration

[0154] Same as example 1.

[0155] 2. Experimental step 2

[0156] Same as example 1.

[0157] 3. Data analysis

[0158] Same as example 1.

[0159] 4. Experimental results

[0160] The model group estrous cycle disorder, compared with the blank control group, the model group after estrus and interestrus extended (such as Figure 9 , P<0.001), the proportion of pre-estrus and estrus decreased (such as Figure 10 , P<0.001).

[0161] Compared with the model group, the proportion of proestrus and estrus in the optimal group was significantly increased (P<0.01), and the proportion of metestrus and diestrus was significantly decreased (P<0.01); compared with the optimal group, the proportions of metestrus and diestrus in the comparison groups 1-4 were not significantly reduced (P>0.05), and the proportion of proestrus and estrus was not significantly increased (P>0.05). At the same time, compared with the optimal group, the comparison groups 1-4 were significantly different (P<0.05), indicating that replacing any component of the optimal group cannot play a significant role, and the medicinal material ratio of the optimal group is the optimal ratio, which is unique and important in playing a role.

[0162] The details of the present application are well known.

[0163] Although embodiments of the present application have been shown and described, it is to be understood that various modifications, substitutions, replacements and changes can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A medicinal and edible herbal composition that improves gut microbiota and helps enhance ovarian function, characterized in that, The ingredients comprise the following parts by weight: (1) Energy supply section: 200-300 parts whole milk powder, 10-20 parts lotus root powder, 1-10 parts red bean powder (2) The part that is both food and medicine: Sea buckthorn fruit powder 20-30 parts, coix seed extract 1-30 parts, yam extract 1-30 parts, kudzu root extract 1-30 parts, lily extract 1-30 parts, poria cocos extract 1-30 parts, wolfberry extract 1-30 parts, jujube extract 1-30 parts, dried plum extract 1-30 parts, polygonatum extract 1-30 parts, black sesame extract 1-30 parts, jujube seed extract 1-30 parts, celery extract 1-30 parts, mulberry extract 1-30 parts, buckwheat extract 1-30 parts; (3) Dietary fiber portion: 10-20 parts konjac powder, 1-10 parts inulin (4) Proportions of each component in the vitamin and mineral section: Vitamin C: Beta-carotene (1%): Vitamin E: Vitamin B1: Vitamin B2: Vitamin B6: Vitamin B12: Vitamin D: Folic acid: Niacin: Pantothenic acid: Iron: Zinc: Casein calcium peptide = 500-2000:100-1000:1-100:1-100:1-100:0.001-0.01:0.005-0.1:1-500:1-100:1-100:1-200:1-100:200-1000.

2. A preparation process for a medicinal and edible herbal composition as described in claim 1, which improves intestinal flora and helps enhance ovarian function, characterized in that, Includes the following steps: Weigh each of the raw materials as described in claim 1 according to the weight proportions, remove impurities, purify, dry, pulverize, and pass through a 120-mesh sieve to obtain each medicinal powder; Add the energy supply component, the food and medicine component, and the dietary fiber component in proportion, mix well, then add the vitamin and mineral component, mix well with a three-dimensional mixer to obtain the finished product.

3. The medicinal and edible herbal composition according to claims 1 and 2, which improves intestinal flora and helps enhance ovarian function, is characterized in that... It can be prepared into oral formulations as needed, including tablets, capsules, powders, granules, effervescent tablets, or sachets.

4. The medicinal and edible herbal composition according to claim 1, which improves intestinal flora and helps enhance ovarian function, for use in functional foods.

5. The use in functional foods according to claim 4, characterized in that, The functional food is a beverage or food.

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