Pharmaceutical composition for preventing female premature ovarian failure as well as preparation method and application thereof

Abstract

The embodiment of the invention discloses a pharmaceutical composition for preventing female premature ovarian failure as well as a preparation method and application thereof, relates to the technical field of medicine preparation, and aims to solve the technical problem of poor prevention effect of existing medicines on premature ovarian failure. The pharmaceutical composition comprises the following components in parts by weight: 10-20 parts of prepared rehmannia root, 10-20 parts of Chinese angelica, 5-15 parts of white paeony root, 1-10 parts of ligusticum wallichii, 1-10 parts of peach kernel, 1-10 parts of safflower and 5-15 parts of cassia twig.

Description

Technical Field

[0001] The present application relates to the technical field of drug preparation, and specifically relates to a drug composition for preventing premature ovarian failure in women, and a preparation method and application thereof. Background Art

[0002] Premature ovarian failure (POF) is a major problem facing the field of female reproductive health today, and has a profound impact on the physical and mental health of women of childbearing age. The so-called premature ovarian failure refers to the condition of hypogonadism in women before the age of 40. It is a difficult and complicated disease in the field of gynecology. The clinical manifestations mainly include symptoms such as amenorrhea, hot flashes, and night sweats, accompanied by increased gonadotropin levels and decreased estrogen levels. This situation seriously affects the ovulation function of women of childbearing age and becomes an important cause of infertility. According to statistics, the incidence of premature ovarian failure is about 1%, while in women under the age of 30, the incidence is only 0.1%. However, in recent years, the incidence of premature ovarian failure has shown an increasing trend year by year, and the age of onset has also tended to be younger.

[0003] The pathogenesis of premature ovarian failure is not yet fully understood, but studies have shown that it may be related to a variety of factors, including chromosomal abnormalities, gene mutations, autoimmune diseases, granulosa cell and mitochondrial dysfunction, etc. In traditional Chinese medicine and other treatments, its mechanism also involves multiple aspects, such as the regulation of reproductive endocrine hormone levels, the improvement of immune function, the regulation of related signal transduction pathways, the inhibition of granulosa cell apoptosis, and the role of non-coding RNA. According to traditional Chinese medicine theory, kidney deficiency and blood stasis are the main etiology and pathogenesis of premature ovarian failure, so the treatment method of tonifying the kidney and activating blood circulation is often used. Modern medical research has also shown that traditional Chinese medicine formulas based on the method of tonifying the kidney and activating blood circulation have a significant regulatory effect on estrogen, can promote the development of follicles and the growth of the endometrium, thereby delaying and preventing the occurrence and development of premature ovarian failure, and improving the ovulation rate and pregnancy rate.

[0004] Since modern medicine has not yet fully elucidated the pathology and pathogenesis of premature ovarian failure, its pathogenesis is relatively complex and there are many inducing factors, so chemical drugs often fail to achieve satisfactory therapeutic effects. In recent years, both at home and abroad, more and more attention has been paid to the preventive role of traditional medicine in the treatment of premature ovarian failure, making traditional Chinese medicine occupy a very important position in the prevention and treatment of this disease.

[0005] In the existing technology, several traditional Chinese medicine or western medicine drug combinations for preventing premature ovarian failure in women have been disclosed based on pharmacological effects. Although there are many prescriptions for the clinical treatment of premature ovarian failure, due to the fact that the effective substances of the compound are not yet fully clear and the preparation technology is not mature enough, there are problems such as unstable clinical efficacy and low treatment efficiency in actual application. These problems seriously restrict the application effect of compound drugs and are in urgent need of further research and improvement. Summary of the invention

[0006] The main purpose of the present application is to provide a pharmaceutical composition for preventing premature ovarian failure in women, and a preparation method and application thereof, in order to solve the technical problem that existing drugs have poor preventive effects on premature ovarian failure.

[0007] To achieve the above objectives, the technical solutions adopted in the embodiments of the present application are as follows:

[0008] In a first aspect, an embodiment of the present application provides a pharmaceutical composition for preventing premature ovarian failure in women, the pharmaceutical composition comprising the following components in parts by weight: 10-20 parts of Rehmannia root, 10-20 parts of Angelica sinensis, 5-15 parts of White Peony Root, 1-10 parts of Chuanxiong, 1-10 parts of Peach Kernel, 1-10 parts of Carthamus tinctorius and 5-15 parts of Cinnamon Twig.

[0009] As some optional embodiments of the present application, the topical pharmaceutical composition also includes the following components in parts by weight: 5-15 parts of purple quartz, 15-25 parts of raspberry, 10-20 parts of complanatus seeds, 15-25 parts of paper mulberry, 5-20 parts of mulberry, 15-25 parts of asparagus, 15-30 parts of peony bark, and 1-10 parts of oriental rhizome.

[0010] As some optional embodiments of the present application, the pharmaceutical composition includes the following components in parts by weight: 12-16 parts of Rehmannia root, 12-16 parts of Angelica sinensis, 6-10 parts of White Peony Root, 3-8 parts of Chuanxiong, 3-8 parts of Peach Kernel, 3-8 parts of Carthamus tinctorius and 9-13 parts of Cinnamon Twig.

[0011] As some optional embodiments of the present application, the topical pharmaceutical composition also includes the following components in parts by weight: 6-10 parts of purple quartz, 16-20 parts of raspberry, 12-16 parts of complanatus seeds, 16-20 parts of paper mulberry, 10-16 parts of mulberry, 16-20 parts of asparagus, 18-26 parts of peony bark, and 3-8 parts of oriental rhizome.

[0012] As some optional embodiments of the present application, the pharmaceutical composition includes the following components in parts by weight: 15 parts of Rehmannia root, 15 parts of Angelica sinensis, 8 parts of White Peony Root, 6 parts of Chuanxiong, 6 parts of Peach Kernel, 5 parts of Carthamus tinctorius and 10 parts of Cinnamon Twig.

[0013] As some optional embodiments of the present application, the pharmaceutical composition also includes the following components in weight: 8 parts of purple quartz, 16 parts of raspberry, 12 parts of complanatus seeds, 16 parts of paper mulberry seeds, 12 parts of mulberry, 16 parts of asparagus, 20 parts of peony bark, and 5 parts of oriental rhizome.

[0014] In a second aspect, the present application embodiment provides a method for preparing the pharmaceutical composition for preventing premature ovarian failure in women as described above, comprising the following steps:

[0015] The raw material components are weighed according to the weight ratio, crushed, and mixed to obtain the pharmaceutical composition for preventing premature ovarian failure in women.

[0016] As some optional embodiments of the present application, the dosage form of the drug is any one of plasters, powders, ointments, suppositories, nasal drops, eye drops, aerosols, pills, tablets, capsules, granules, powders and decoctions.

[0017] In a third aspect, an embodiment of the present application provides an application of the pharmaceutical composition for preventing premature ovarian failure in women as described above, which is used to prepare a drug for preventing premature ovarian failure in women.

[0018] As some optional embodiments of the present application, the drug affects the expression of Akt, mTOR, and GnRHR in ovarian tissue to achieve the purpose of preventing premature ovarian failure.

[0019] Compared with the existing drug technologies on the market, the drug composition proposed in this application contains a series of selected Chinese medicinal materials, including Radix Rehmanniae Preparata, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Chuanxiong, Semen Persicae, Carthamus Tinctorius, Cinnamomum Cassiae, Amethyst, Fructus Rubi, Fructus Astragali, Fructus Cuscutae, Fructus Mori, Rhizoma Asparagopsis, Cortex Moutan, Rhizoma Alismatis, etc. The compatibility of these medicinal materials is mainly based on tonifying the kidney and nourishing yin, while supplemented by the effects of nourishing blood and unblocking meridians. Through this unique formula, the drug composition can regulate the functions of the reproductive system from multiple targets and multiple system levels, thereby achieving significant effects.

[0020] Specifically, the drug composition can effectively improve the receptivity of the endometrium, making it more suitable for embryo implantation and development. In addition, it can also regulate the arterial blood flow of the uterus and ovaries, ensuring that the reproductive organs receive adequate blood supply, thereby maintaining their normal functions. More importantly, the drug composition can also regulate the body's immune balance, which is crucial for maintaining the health of the reproductive system.

[0021] Through these multi-faceted regulatory effects, the pharmaceutical composition proposed in this application can effectively delay the decline of ovarian function, help women maintain a good reproductive health state, and prolong their fertility. This comprehensive treatment plan can not only improve women's reproductive health, but also improve their overall quality of life. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The ovarian pathological sections of female mice with premature ovarian failure involved in the experimental example of this application (HE staining, 100×); wherein A is the normal group; B is the model group; C is the estradiol group; D is the low-dose group of the test article; and E is the high-dose group of the test article;

[0023] Figure 2 The relative expression of genes related to the mitochondrial apoptosis pathway in ovarian tissue of each group involved in the experimental example of this application (x±s, n=6); wherein Normal is the normal group; Model is the model group; E is the estradiol group; Low is the low-dose group of the test article; High is the low-dose group of the test article; compared with the normal group, # P<0.05; compared with the model group, * P<0.05. DETAILED DESCRIPTION

[0024] It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0025] Premature Ovarian Failure (POF) is a major challenge currently facing the field of female reproductive health, and has a profound impact on the physical and mental health of women of childbearing age. This disease usually refers to the phenomenon of hypogonadism in women before the age of 40, and is a difficult and complicated disease in the field of gynecology. The clinical manifestations mainly include symptoms such as amenorrhea, hot flashes, and night sweats, accompanied by increased levels of gonadotropins and decreased levels of estrogen. This situation seriously affects the ovulation function of women of childbearing age and is an important cause of infertility. According to statistics, the incidence of premature ovarian failure is about 1%, while in women under the age of 30, the incidence is only 0.1%, but this figure shows an upward trend year by year, and the age of onset is becoming younger and younger.

[0026] The pathogenesis of premature ovarian failure is not yet fully understood, but studies have shown that it may be related to multiple factors such as chromosomal abnormalities, gene mutations, autoimmune diseases, granulosa cell and mitochondrial dysfunction. In terms of treatment, the mechanisms of traditional Chinese medicine and other alternative therapies involve multiple levels, including regulating reproductive endocrine hormone levels, improving immune function, affecting related signal transduction pathways, inhibiting granulosa cell apoptosis, and regulating non-coding RNA. According to traditional Chinese medicine theory, kidney deficiency and blood stasis are the main etiology and pathogenesis of premature ovarian failure, so the treatment method of tonifying the kidney and activating blood circulation is often used. Modern medical research has also shown that traditional Chinese medicine formulas based on the method of tonifying the kidney and activating blood circulation have a significant regulatory effect on estrogen, can promote the development of follicles and the growth of the endometrium, thereby delaying and preventing the occurrence and development of premature ovarian failure, and improving the ovulation rate and pregnancy rate.

[0027] Since modern medicine has not yet fully elucidated the pathology and pathogenesis of premature ovarian failure, and its pathogenesis is relatively complex and has many inducing factors, chemical drugs often fail to achieve satisfactory therapeutic effects. In recent years, both at home and abroad, more and more attention has been paid to the preventive role of traditional drugs in the treatment of premature ovarian failure, making traditional Chinese medicine occupy a very important position in the prevention and treatment of this disease.

[0028] In the prior art, according to the pharmacological effects, a variety of traditional Chinese medicine or Western medicine drug combinations for preventing premature ovarian failure in women have been disclosed. For example, prior art 1 discloses a preparation for treating premature ovarian failure and its preparation method. The preparation comprises the following components by mass: 10 to 25 parts of platelet-rich plasma, 10 to 25 parts of autologous or allogeneic collagen, 1 to 5 parts of hyaluronic acid, and 1 to 3 parts of calcium ion activator.

[0029] In addition, prior art 2 discloses a pharmaceutical composition for treating premature ovarian failure and a preparation method thereof. The scheme discloses a pharmaceutical composition for treating premature ovarian failure, comprising the following ingredients in parts by weight: 10 to 12 parts of Rehmannia glutinosa, 15 to 16 parts of Cornus officinalis, 8 to 10 parts of Ligustrum lucidum, 9 to 11 parts of Lycium barbarum, 8 to 10 parts of Anemarrhena asphodeloides, 15 to 16 parts of stir-fried Atractylodes macrocephala, 6 to 8 parts of Citron, and 5 to 6 parts of Licorice.

[0030] However, the above-mentioned prior art still has problems such as unstable clinical efficacy and low therapeutic efficiency in practical application due to the fact that the effective substances in the compound are not yet fully clear and the preparation technology is relatively backward. These problems seriously restrict the effect of compound drugs in clinical application and further research and improvement are urgently needed.

[0031] In order to overcome the shortcomings and deficiencies in the prior art, the purpose of the present application is to provide a pharmaceutical composition with stable clinical efficacy and effective in preventing premature ovarian failure in women, as well as a preparation method and application thereof.

[0032] That is: a pharmaceutical composition for preventing premature ovarian failure in women, the pharmaceutical composition comprises the following components in parts by weight: 10-20 parts of Rehmannia root, 10-20 parts of Angelica sinensis, 5-15 parts of White Peony Root, 1-10 parts of Chuanxiong, 1-10 parts of Peach Kernel, 1-10 parts of Carthamus tinctorius and 5-15 parts of Cinnamomum cassia twig.

[0033] Furthermore, the topical pharmaceutical composition also includes the following components in parts by weight: 5-15 parts of purple quartz, 15-25 parts of raspberry, 10-20 parts of complanatus seeds, 15-25 parts of paper mulberry, 5-20 parts of mulberry, 15-25 parts of asparagus, 15-30 parts of peony bark, and 1-10 parts of oriental rhizome.

[0034] In preferred embodiment 1, the pharmaceutical composition comprises the following components in parts by weight: 12-16 parts of Rehmannia root, 12-16 parts of Angelica sinensis, 6-10 parts of White Peony Root, 3-8 parts of Chuanxiong, 3-8 parts of Peach Kernel, 3-8 parts of Carthamus tinctorius and 9-13 parts of Cinnamon Twig.

[0035] Furthermore, the topical pharmaceutical composition also includes the following components in parts by weight: 6-10 parts of purple quartz, 16-20 parts of raspberry, 12-16 parts of complanatus seeds, 16-20 parts of paper mulberry, 10-16 parts of mulberry, 16-20 parts of asparagus, 18-26 parts of peony bark, and 3-8 parts of oriental rhizome.

[0036] In the second preferred embodiment, the pharmaceutical composition comprises the following components in parts by weight: 15 parts of Rehmannia root, 15 parts of Angelica sinensis, 8 parts of White Peony Root, 6 parts of Chuanxiong, 6 parts of Peach Kernel, 5 parts of Carthamus tinctorius and 10 parts of Cinnamon Twig.

[0037] Furthermore, the pharmaceutical composition also includes the following components in parts by weight: 8 parts of purple quartz, 16 parts of raspberry, 12 parts of complanatus seeds, 16 parts of paper mulberry seeds, 12 parts of mulberry, 16 parts of asparagus, 20 parts of peony bark, and 5 parts of oriental rhizome.

[0038] The preparation method of the pharmaceutical composition for preventing premature ovarian failure in women comprises the following steps: weighing each raw material component according to the weight ratio, crushing it, and mixing it to obtain the pharmaceutical composition for preventing premature ovarian failure in women. It should be noted that the dosage form of the drug is any one of plaster, powder, liniment, suppository, nasal drops, eye drops, aerosol, pill, tablet, capsule, granule, powder and decoction.

[0039] The application of the above-mentioned pharmaceutical composition for preventing premature ovarian failure in women is used to prepare a drug for preventing premature ovarian failure in women; that is, the drug affects the expression of Akt, mTOR, and GnRHR in ovarian tissue to achieve the purpose of preventing premature ovarian failure.

[0040] The pharmaceutical composition involved in this application has its own unique pharmacological effects and functions. The following is a detailed description of these raw materials:

[0041] Rehmannia root: It tastes sweet and is slightly warm in nature. It mainly belongs to the meridians of liver and kidney. It has the effects of nourishing blood and yin, replenishing essence and filling marrow. It is suitable for symptoms such as sallow complexion, palpitations, irregular menstruation, metrorrhagia and bleeding caused by blood deficiency. In addition, Rehmannia root also has significant therapeutic effects on symptoms such as soreness of waist and knees, bone steaming and hot flashes, night sweats and spermatorrhea, internal heat and thirst, dizziness and tinnitus, and premature graying of hair caused by liver and kidney yin deficiency.

[0042] Angelica: Sweet, spicy, warm in nature, mainly belongs to the liver, heart, and spleen meridians. Angelica has the effects of promoting blood circulation and relieving pain, replenishing blood and regulating menstruation, and moistening the intestines and relieving constipation. It is suitable for symptoms such as blood deficiency dizziness, irregular menstruation, amenorrhea, dysmenorrhea, sallow complexion, cold abdominal pain, traumatic injury, rheumatic pain, carbuncle, ulcer, and dry intestine constipation.

[0043] White peony root: bitter, sour, slightly cold, mainly belongs to the liver and spleen meridians. White peony root has the effects of nourishing blood and regulating menstruation, restraining yin and stopping sweating, softening liver and relieving pain, and calming liver yang. It is suitable for symptoms such as blood deficiency and chlorosis, irregular menstruation, spontaneous sweating, night sweats, flank pain, abdominal pain, cramps in the limbs, headache and dizziness.

[0044] Chuanxiong: Spicy, warm in nature, mainly belongs to the liver, gallbladder, and pericardium meridians. Chuanxiong has the effects of promoting blood circulation, removing blood stasis, dispelling wind and relieving pain. It is suitable for chest pain, chest and flank pain, swelling and pain due to falls, irregular menstruation, amenorrhea, dysmenorrhea, abdominal pain due to lumps, headache, rheumatic pain and other symptoms.

[0045] Peach kernel: sweet in taste, warm in nature, mainly belongs to the lung, kidney, and intestine meridians. Peach kernel has the effect of warming and nourishing the lung and kidney, calming asthma and moistening the intestines. It is suitable for symptoms such as kidney deficiency and low back pain, weak legs, asthma and cough due to deficiency and cold, and dry stool.

[0046] Safflower: Spicy and warm in nature, it mainly enters the heart and liver meridians. Safflower has the effects of promoting blood circulation, relieving blood stasis and relieving pain. It is suitable for symptoms such as amenorrhea, dysmenorrhea, lochia retention, abdominal masses, chest pain, abdominal pain due to stasis, stabbing pain in the chest and ribs, injuries from falls, and swelling and pain in sores.

[0047] Cinnamon twig: Spicy and sweet, warm in nature, mainly belongs to the heart, lung and bladder meridians. Cinnamon twig has the effects of sweating and relieving muscles, warming and unblocking meridians, assisting yang and transforming qi, and balancing and descending qi. It is suitable for colds, cold pain in the abdomen, amenorrhea due to cold blood, joint pain, phlegm, edema, palpitations, and running pigs.

[0048] Amethyst: Sweet in taste, warm in nature, mainly belongs to the heart and liver meridians. Amethyst has the effects of calming the heart, calming the nerves, lowering adverse qi, and warming the uterus. It is suitable for symptoms such as asthenia, palpitations, coughing, and infertility due to coldness in the blood sea in women.

[0049] Raspberry: It tastes sweet and sour, and is warm in nature. It mainly enters the liver, kidney, and bladder meridians. Raspberry has the effects of nourishing the kidney, consolidating essence, reducing urine, nourishing the liver, and improving eyesight. It is suitable for symptoms such as spermatorrhea, enuresis, frequent urination, impotence, premature ejaculation, and blurred vision.

[0050] Astragalus: sweet in taste, warm in nature, mainly belongs to the liver and kidney meridians. Astragalus has the effects of nourishing the kidney and yang, consolidating essence and reducing urine, nourishing the liver and improving eyesight. It is suitable for symptoms such as kidney deficiency and low back pain, spermatorrhea and premature ejaculation, enuresis and frequent urination, leucorrhea, dizziness, and blurred vision.

[0051] Cuscuta australis: sweet in taste, cold in nature, mainly belongs to the liver and kidney meridians. Cuscuta australis has the effects of tonifying the kidney and clearing the liver, improving eyesight, and promoting diuresis. It is suitable for symptoms such as liver and kidney deficiency, soreness of waist and knees, asthenia and bone steaming, dizziness, eye film, edema, etc.

[0052] Mulberry: It tastes sweet and sour, and is cold in nature. It mainly enters the heart, liver, and kidney meridians. Mulberry has the effects of nourishing yin and blood, promoting fluid production and moistening the intestines. It is suitable for symptoms such as dizziness and tinnitus, premature graying of hair, amenorrhea due to blood deficiency, thirst due to loss of fluid, internal heat and thirst, and dry intestines and constipation.

[0053] Asparagus cochinchinensis: sweet and bitter in taste, cold in nature, mainly belongs to the lung and kidney meridians. Asparagus cochinchinensis has the functions of nourishing yin and moistening dryness, clearing the lungs and producing body fluid. It is suitable for dry cough due to lung dryness, sticky sputum due to coughing, sore waist and knees, hot flashes due to bone steaming, internal heat and thirst, damage to body fluid due to fever, dry throat and thirst, dry intestines and constipation, etc.

[0054] Peony bark: bitter, pungent, slightly cold, mainly belongs to the heart, liver, and kidney meridians. Peony bark has the effects of clearing heat and cooling blood, promoting blood circulation and removing blood stasis. It is suitable for symptoms such as heat entering the blood, fever and rashes, vomiting blood and epistaxis, night heat and morning coolness, no sweat and bone steaming, amenorrhea, dysmenorrhea, carbuncle, sore and poison.

[0055] Alisma: Sweet, light, cold in nature, mainly belongs to the kidney and bladder meridians. Alisma has the functions of promoting water and removing dampness, relieving heat, clearing turbidity and reducing lipids. It is suitable for symptoms such as difficulty in urination, edema, diarrhea, oliguria, phlegm and dizziness, hot stranguria, and hyperlipidemia.

[0056] From the perspective of the pharmaceutical composition involved in this application, it is mainly composed of ingredients such as Rehmannia glutinosa, white peony root, Chuanxiong, Angelica sinensis, safflower, and cinnamon twig. These ingredients work together to make the pharmaceutical composition have significant kidney-tonifying and yin-nourishing effects. At the same time, by supplementing with ingredients that nourish blood and dredge meridians, its therapeutic effect is further enhanced. Specifically, two medicinal materials, Angelica sinensis and cinnamon twig, are added to the formula, which can warm the meridians and dispel cold, nourish blood and dredge meridians, thereby effectively strengthening the therapeutic effect of the monarch and ministerial drugs.

[0057] On the basis of invigorating the liver and kidney, by nourishing blood and unblocking meridians, the symptoms of premature ovarian failure such as soreness of waist and knees caused by weakness of nutrient blood and unfavorable blood heart can be effectively alleviated. The compatibility of the whole formula is reasonable, and there is a significant preventive and therapeutic effect for premature ovarian failure in women. In addition, the formula also adds peony bark and oriental rhizome. Peony bark is good at clearing the floating heat of yin kidney, and the symptoms such as fever, bone steaming and hot flashes due to yin deficiency, which can effectively alleviate these discomforts. Oriental rhizome is good at clearing kidney fire and bladder heat, has the effect of diuresis and heat relief, and has a good mitigating effect on the symptoms of damp heat in the lower jiao. Through the reasonable compatibility of these ingredients, the pharmaceutical composition of the present application is provided with unique advantages and significant effects in treating premature ovarian failure in women.

[0058] In order to facilitate those skilled in the art to further understand the technical solution described in the present application, the technical solution described in the present application is described in detail below in conjunction with specific embodiments:

[0059] Example 1

[0060] A pharmaceutical composition comprises the following components in parts by weight: 15 parts of Rehmannia root, 15 parts of Angelica sinensis, 8 parts of White Peony Root, 6 parts of Chuanxiong, 6 parts of Peach Kernel, 5 parts of Carthamus tinctorius, 10 parts of Cinnamomum cassia, 8 parts of Amethyst, 16 parts of Rubus idaeus, 12 parts of Astragalus membranaceus, 16 parts of Cuscuta australis, 12 parts of Mulberry, 16 parts of Asparagus cochinchinensis, 20 parts of Paeonia suffruticosa, and 5 parts of Alisma orientalis.

[0061] Example 2

[0062] A pharmaceutical composition comprises the following components in parts by weight: 13 parts of Rehmannia root, 15 parts of Angelica sinensis, 7 parts of White Peony Root, 7 parts of Chuanxiong, 4 parts of Peach Kernel, 7 parts of Carthamus tinctorius, 10 parts of Cinnamomum cassia twig, 8 parts of Amethyst, 17 parts of Rubus idaeus, 12 parts of Astragalus membranaceus, 20 parts of Cuscuta australis, 10 parts of Mulberry, 19 parts of Asparagus cochinchinensis, 19 parts of Paeonia suffruticosa, and 7 parts of Alisma orientalis.

[0063] Example 3

[0064] A pharmaceutical composition comprises the following components in parts by weight: 16 parts of Rehmannia root, 12 parts of Angelica sinensis, 10 parts of White Peony Root, 3 parts of Chuanxiong, 7 parts of Peach Kernel, 4 parts of Carthamus tinctorius, 11 parts of Cinnamomum cassia, 8 parts of Amethyst, 18 parts of Rubus idaeus, 14 parts of Astragalus membranaceus, 18 parts of Cuscuta australis, 15 parts of Mulberry, 18 parts of Asparagus cochinchinensis, 25 parts of Paeonia suffruticosa, and 4 parts of Alisma orientalis.

[0065] Example 4

[0066] A pharmaceutical composition comprises the following components in parts by weight: 10 parts of Rehmannia root, 20 parts of Angelica sinensis, 5 parts of White Peony Root, 10 parts of Chuanxiong, 1 part of Peach Kernel, 10 parts of Carthamus tinctorius, 5 parts of Cinnamomum cassia, 15 parts of Amethyst, 15 parts of Rubus idaeus, 20 parts of Astragalus membranaceus, 15 parts of Cuscuta australis, 20 parts of Mulberry, 15 parts of Asparagus cochinchinensis, 30 parts of Paeonia suffruticosa, and 1 part of Alisma orientalis.

[0067] Example 5

[0068] A pharmaceutical composition comprises the following components in parts by weight: 20 parts of Rehmannia root, 10 parts of Angelica sinensis, 15 parts of White Peony Root, 1 part of Ligusticum chuanxiong, 10 parts of Peach Kernel, 1 part of Carthamus tinctorius, 15 parts of Cinnamomum cassia twig, 5 parts of Amethyst, 25 parts of Rubus idaeus, 10 parts of Astragalus membranaceus, 25 parts of Cuscuta australis, 5 parts of Mulberry, 25 parts of Asparagus cochinchinensis, 15 parts of Paeonia suffruticosa, and 10 parts of Alisma orientalis.

[0069] Experimental Example 1

[0070] 1) Modeling:

[0071] Cisplatin: before injection, add 50 mg of cisplatin powder to normal saline to prepare a fresh aqueous solution of 1 mg / mL for later use.

[0072] 42 SPF healthy female SD rats, 7-8 weeks old, with a body weight of (150±10) g, were randomly divided into a blank group (7 rats) and a modeling group (35 rats). The blank group was not treated, and the modeling group was intraperitoneally injected with 4.0 mg / kg cisplatin aqueous solution once a week for a total of 2 times to establish a rat model of premature ovarian failure. Vaginal exfoliated cell smears were performed from the first day after the modeling, and the estrous cycle changes of the modeling group rats were observed for 7 consecutive days. Vaginal exfoliated cells of rats were collected at a fixed time every day, and 10 μL of physiological saline was sucked with a pipette and blown in the rat vagina several times. The liquid was sucked out and evenly smeared on a slide numbered in advance. After the smear was naturally dried, 2 drops (about 20 μL) of Wright's stain were added, and 1.5 times PBS was added after 1 minute. After 10 minutes, it was rinsed with running water, and then sealed and examined under a microscope after drying. The normal estrous cycle of rats should appear in the order of proestrus, estrus, metestrus and diestrus, and one cycle is 4 to 5 days on average. If the estrous cycle is chaotic or prolonged (more than 6 days) or stays in a certain period for a long time, it is considered that the rat estrous cycle is disordered, indicating that the model is successfully established.

[0073] After the modeling was completed, the rats with successful modeling were randomly divided into a model group, a positive control group (0.01 mg / mL estradiol valerate tablets aqueous solution) and a low-, medium- and high-dose group (1 and 3 g crude drug / mL) of the pharmaceutical composition for preventing premature ovarian failure in women, with 6 rats in each group. Each medication group was given the corresponding drug for 30 consecutive days.

[0074] 2) Index evaluation:

[0075] Before modeling, the rats in each group were in good spirits, with shiny fur and lively appearance. The changes in the estrous cycles of the rats in each group were as follows: 2 weeks after modeling, except for the rats in the blank group which still maintained a normal estrous cycle (proestrus, estrus, metestrus and diestrus), the estrous cycles of the other rats were disordered, most of them were in diestrus or proestrus, and even no complete estrous cycle was observed, which indicated that the ovaries of the rats were damaged. The pathological examination results are shown in Table 1 and Figure 1It can be seen that in the normal group, follicles in different stages can be seen in the ovarian cortex, collagen fibers and blood vessels can be seen in the interstitium, mature follicles are distributed on the surface of the cortex, primordial follicles are distributed under the tunica albuginea, and growing follicles are in the cortex. The ovaries in the D-galactose model group were significantly smaller, the follicles in the ovarian cortex were significantly atrophied, there were fewer mature follicles, obvious interstitial collagen hyperplasia, and fewer corpora lutea. Compared with the D-galactose model group, follicles in various stages can be seen in the ovaries of the estradiol group, some follicles are in the growing follicle stage, but atrophied follicles can also be seen, corpora lutea can be seen, and a small amount of collagen hyperplasia in the interstitium; follicles in various stages can be seen in the ovaries of the Dendrobium officinale juice and polysaccharide groups, follicle atrophy and interstitial collagen hyperplasia have improved, and corpora lutea can be seen. Among them, there are fewer follicles in the growing follicle stage in the juice group, and the interstitial collagen hyperplasia in the polysaccharide group has significantly improved.

[0076] Table 1 Scoring table for pathological damage of uterus and ovary in female mice with premature ovarian failure (M(Q1, Q3), n=6)

[0077]

[0078] Note: Uterus: H = 16.643, P = 0.002, ovary: H = 18.860, P = 0.001, compared with the normal group, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01

[0079] This experimental example also detected the effect of the test article on the expression of genes related to the mitochondrial apoptosis pathway in ovarian tissue. Figure 2 It can be seen that compared with the normal group, the relative expression of Bcl-2 mRNA in the ovarian tissue of mice in the D model group was significantly reduced (P<0.05), Bax and p53 showed an upward trend, but there was no statistical significance, and the Bcl-2 / Bax expression ratio was significantly reduced (P<0.01); compared with the model group, the low-dose and high-dose groups of the test product could significantly increase the relative expression of Bcl-2 mRNA (P<0.05), and the high-dose group could significantly increase the Bcl-2 / Bax expression ratio (P<0.05), and the effect on other genes was not obvious. It suggests that the test product can increase the expression of Bcl-2 mRNA in the aging ovarian tissue of female mice and alleviate the decrease of the Bcl-2 / Bax expression ratio in the aging ovarian tissue.

[0080] Based on this experimental example, it can be seen that the premature ovarian failure model was induced by intraperitoneal injection of 4.0 mg / kg cisplatin aqueous solution, and it was found that the estrous cycle of the model group was disordered, most of them were in the estrus or proestrus, and even no complete estrous cycle was seen, which indicated that the rat ovaries were damaged, resulting in an ovarian weakness state that was very similar to human premature ovarian failure; the pharmaceutical composition of the present application could improve follicular atrophy and interstitial collagen hyperplasia, and corpora lutea could be seen, among which the juice extraction group had fewer follicles in the growing follicle stage, and the interstitial collagen hyperplasia in the polysaccharide group was significantly improved.

[0081] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A pharmaceutical composition for preventing premature ovarian failure in women, characterized in that: The pharmaceutical composition comprises the following components in parts by weight: 10-20 parts of Rehmannia root, 10-20 parts of Chinese angelica root, 5-15 parts of white peony root, 1-10 parts of Chuanxiong, 1-10 parts of peach kernel, 1-10 parts of safflower and 5-15 parts of cassia twig.

2. The pharmaceutical composition for preventing premature ovarian failure in women according to claim 1, characterized in that: The external medicinal composition also includes the following components in parts by weight: 5-15 parts of purple quartz, 15-25 parts of raspberry, 10-20 parts of complanatus seeds, 15-25 parts of mulberry, 5-20 parts of asparagus, 15-25 parts of peony bark, and 1-10 parts of oriental rhizome.

3. The pharmaceutical composition for preventing premature ovarian failure in women according to claim 1, characterized in that: The pharmaceutical composition comprises the following components in parts by weight: 12-16 parts of Rehmannia root, 12-16 parts of Chinese angelica root, 6-10 parts of white peony root, 3-8 parts of Chuanxiong, 3-8 parts of peach kernel, 3-8 parts of safflower and 9-13 parts of cassia twig.

4. The pharmaceutical composition for preventing premature ovarian failure in women according to claim 3, characterized in that: The topical pharmaceutical composition further comprises the following components in parts by weight: 6-10 parts of purple quartz, 16-20 parts of raspberry, 12-16 parts of complanatus seeds, 16-20 parts of mulberry, 10-16 parts of asparagus, 16-20 parts of peony bark, and 3-8 parts of oriental rhizome.

5. The pharmaceutical composition for preventing premature ovarian failure in women according to claim 1, characterized in that: The pharmaceutical composition comprises the following components in parts by weight: 15 parts of Rehmannia root, 15 parts of Chinese angelica root, 8 parts of white peony root, 6 parts of Chuanxiong root, 6 parts of peach kernel, 5 parts of safflower and 10 parts of cassia twig.

6. The pharmaceutical composition for preventing premature ovarian failure in women according to claim 5, characterized in that: The pharmaceutical composition further comprises the following components in parts by weight: 8 parts of purple quartz, 16 parts of raspberry, 12 parts of complanatus seeds, 16 parts of mulberry seeds, 12 parts of asparagus, 16 parts of peony bark, and 5 parts of oriental rhizome.

7. A method for preparing a pharmaceutical composition for preventing premature ovarian failure in women as claimed in any one of claims 1 to 6, characterized in that: The following steps are involved: The raw material components are weighed according to the weight ratio, crushed, and mixed to obtain the pharmaceutical composition for preventing premature ovarian failure in women.

8. The method for preparing the pharmaceutical composition for preventing premature ovarian failure in women according to claim 7, characterized in that: The dosage form of the drug is any one of plaster, powder, liniment, suppository, nasal drops, eye drops, aerosol, pill, tablet, capsule, granule, powder and decoction.

9. Use of a pharmaceutical composition for preventing premature ovarian failure in women as claimed in any one of claims 1 to 6, characterized in that: Used to prepare medicines for preventing premature ovarian failure in women.

10. The use of the pharmaceutical composition for preventing premature ovarian failure in women according to claim 9, characterized in that: The drug affects the expression of Akt, mTOR and GnRHR in ovarian tissue to achieve the purpose of preventing premature ovarian failure.

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