Traditional Chinese medicine composition for dispelling cold, warming uterus and relieving menstrual pain and irregular menstruation as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for dispelling cold, warming uterus and relieving menstrual pain and irregular menstruation and application thereof, and relates to the technical field of traditional Chinese medicines. The composition is prepared from fresh ginger, Chinese dates, peach kernels, radix angelicae, cinnamon, red ginseng, saussurea involucrata culture, saffron crocus extract, donkey-hide gelatin, longan, figs, Chinese wolfberry fruits, poria cocos and licorice roots, comprehensively aims at different syndromes of dysmenorrhea, and has the effects of obviously improving cold in uterus and relieving menstrual pain and irregular menstruation.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and specifically relates to a traditional Chinese medicine composition for dispelling cold, warming the uterus, and relieving menstrual pain and menstrual disorders, as well as a preparation method and application thereof. Background Art

[0002] Dysmenorrhea is a common gynecological disease in women, which affects the quality of life and work efficiency. Dysmenorrhea is especially common in adolescents and women of childbearing age. It not only brings physical pain, but also increases psychological burden and reduces the quality of life. Existing treatments for dysmenorrhea mainly include Western medicine and traditional Chinese medicine. Western medicine treatment mainly relies on non-steroidal anti-inflammatory drugs (NSAIDs) and oral contraceptives, but these drugs may cause side effects and long-term use may be detrimental to health. Traditional Chinese medicine treatment focuses on regulating the circulation of blood and qi, especially Chinese medicine paste prescriptions, which are easy to take, taste good, and are easy to carry. They can effectively relieve the discomfort of dysmenorrhea and are more targeted and effective.

[0003] TCM believes that the occurrence of dysmenorrhea is related to a variety of factors, but the core lies in "pain due to obstruction" or "pain due to lack of nourishment". Among them, "pain due to obstruction" mainly refers to the pain caused by internal evil qi and poor circulation of qi and blood in Chong and Ren meridians, which is mostly caused by bad living habits and emotional depression before or during menstruation; while "pain due to lack of nourishment" refers to the pain caused by deficiency syndrome due to insufficient qi and blood in Chong and Ren meridians, and lack of nourishment to the uterus, which is mostly caused by insufficient qi and blood in the body or excessive sexual intercourse and frequent childbirth.

[0004] Chinese patent CN106215018A discloses a Chinese medicine composition for treating dysmenorrhea, a capsule thereof and a preparation method thereof. The Chinese medicine composition comprises the following raw materials in parts by weight: 10-15 parts of Belamcanda chinensis, 15-25 parts of Atractylodes macrocephala, 20-25 parts of Perilla frutescens, 10-18 parts of Ligusticum chuanxiong, 10-20 parts of Apricot kernel, 10-14 parts of Scutellaria baicalensis, 5-8 parts of Xanthium sibiricum root, 20-35 parts of Citrus aurantium, 6-8 parts of Bupleurum chinense, 12-15 parts of Phoenix lily, 4-6 parts of Polygala tenuifolia, 7-9 parts of roasted Ephedra sinica, 5-8 parts of White Peony Root, 3-5 parts of Gleditsia sinensis Spinosa, 4-6 parts of Cuscuta australis, 8-10 parts of Platycodon grandiflorum, 5-7 parts of Black Morning Glory, 4-7 parts of Angelica sinensis, 3-6 parts of Rhubarb Carbonized, 5-7 parts of Inula japonica, and 7-10 parts of Phragmites australis. The Chinese medicine composition provided by the invention treats the patient's dysmenorrhea through the synergistic combination of multiple raw materials. The drug has significant therapeutic effect, can quickly exert its efficacy, and has a short treatment cycle. It can not only cure the disease, but also has no toxic side effects, and is convenient for patients to take and carry. The preparation method of the Chinese medicine composition is simple and efficient, has good effect in extracting effective ingredients, and is suitable for industrial production.

[0005] The core symptoms of dysmenorrhea are uterine coldness and abdominal pain. Currently, most drugs can only partially relieve the symptoms, and there is a lack of effective products targeting these two core symptoms. Therefore, it is of great significance to develop a Chinese medicine paste that can effectively relieve dysmenorrhea symptoms and improve uterine coldness at the same time. Summary of the invention

[0006] In view of this, the present invention provides a traditional Chinese medicine composition for dispelling cold, warming the uterus, and relieving menstrual pain and irregular menstruation, as well as a preparation method and application thereof, which has good effects of significantly improving uterine cold, relieving menstrual pain and irregular menstruation.

[0007] Terms and Claims of the Present Invention:

[0008] 1. As used herein, the articles "a", "an" and "the" include plural referents unless expressly limited to one or more referents otherwise.

[0009] 2. As used herein, numerical range: Unless otherwise expressly indicated, all ranges or ratios disclosed herein will be understood to include any and all sub-ranges or sub-ratios contained therein. For example, a range or ratio of 1 to 30 stated should be considered to be included between a minimum value of 1 and a maximum value of 30, and any sub-range or sub-ratio, integer, decimal, or sub-range or sub-ratio consisting of integers or decimals including the end points.

[0010] 3. As used herein, the terms "comprises," "including," "have," "have," "may," "contain" and variations thereof mean open-ended conjunctions or terms that do not exclude the possibility of additional compositions or structures.

[0011] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0012] On the one hand, the present invention provides a composition for dispelling cold, warming the uterus, and relieving menstrual pain and irregular menstruation, wherein the composition comprises: ginger, jujube, peach kernel, angelica dahurica, cinnamon, red ginseng, snow lotus culture, saffron extract, donkey-hide gelatin, longan, fig, wolfberry, Poria cocos and licorice.

[0013] The prescription of the present invention is explained as follows: the present invention provides a composition for dispelling cold and warming the uterus, relieving menstrual pain and menstrual disorders, wherein ginger warms the middle and dispels cold, restores yang and dredges the meridians, and directly hits the core pathogenesis of dysmenorrhea caused by cold stagnation and qi stagnation, and serves as the main medicine; jujube, angelica dahurica, and peach kernel, tonify the middle and replenish qi, dispel cold and relieve pain, promote blood circulation and remove blood stasis, promote smooth discharge of menstrual blood, and relieve blood stasis and pain, and play the role of warming the meridians and dispelling cold together with ginger, and serve as the minister medicine; red ginseng, snow lotus culture, and saffron extract are used together to replenish qi and absorb blood, warm the kidney and assist yang, dredge the menstruation and activate blood circulation, and further enhance the power of warming the meridians and dispelling cold, promoting blood circulation and removing blood stasis, and synergize with peach kernel; donkey-hide gelatin, longan, and wolfberry replenish qi and blood, nourish the liver and kidney, enhance the overall tonic effect, and serve as adjuvants. Licorice replenishes the spleen and replenishes qi, clears away heat and detoxifies, and harmonizes various medicines to enhance the overall efficacy, and serves as the guiding medicine. Through the combination of the above specific medicinal materials, the different symptoms of dysmenorrhea are comprehensively targeted, and it has the effect of significantly improving uterine coldness, relieving menstrual pain and irregular menstruation.

[0014] Preferably, the composition comprises, by weight: 40-60 parts of ginger, 20-40 parts of jujube, 15-30 parts of peach kernel, 15-30 parts of angelica, 8-20 parts of cinnamon, 5-20 parts of red ginseng, 2-10 parts of snow lotus culture, 2-10 parts of saffron extract, 2-10 parts of donkey-hide gelatin, 2-10 parts of longan, 2-10 parts of fig, 2-10 parts of wolfberry, 2-10 parts of Poria cocos and 2-10 parts of licorice.

[0015] Further preferably, the composition comprises, by weight: 50 parts of ginger, 29 parts of jujube, 18 parts of peach kernel, 18 parts of angelica dahurica, 12 parts of cinnamon, 10 parts of red ginseng, 4 parts of snow lotus culture, 4 parts of saffron extract, 8 parts of donkey-hide gelatin, 8 parts of longan, 8 parts of fig, 4 parts of wolfberry, 4 parts of Poria cocos and 4 parts of licorice.

[0016] On the other hand, the present invention provides a method for preparing the above-mentioned composition for dispelling cold, warming the uterus, and relieving menstrual pain and menstrual disorders, comprising the following steps:

[0017] (1) extracting the formulated amounts of jujube, peach kernel, angelica root, cinnamon bark, red ginseng, snow lotus culture, saffron extract, donkey hide gelatin, longan, fig, wolfberry, Poria cocos and liquorice with water, combining the extracts, and concentrating to obtain a concentrated solution;

[0018] (2) Squeeze the ginger juice in the prescribed amount and mix it with the concentrated solution obtained in step (1) to obtain an extract.

[0019] Preferably, step (1) is specifically as follows: adding 5-15 times the weight of water to the formulated amount of jujube, peach kernel, angelica dahurica, cinnamon, red ginseng, snow lotus culture, saffron extract, donkey-hide gelatin, longan, fig, wolfberry, poria and licorice, and boiling and extracting for 2-4 times, each extraction time for 0.5-2 hours, combining the extracts, and concentrating to a specific gravity of 1.06-1.10 (90° C.), taking the supernatant to obtain a concentrated solution.

[0020] More preferably, step (1) is specifically as follows: decocting and extracting the formulated amount of jujube, peach kernel, angelica dahurica, cinnamon, red ginseng, snow lotus culture, saffron extract, donkey-hide gelatin, longan, fig, wolfberry, poria and licorice twice, adding 10 times the weight of water each time, the first extraction is 1 hour, the second extraction is 0.5 hour, the extracts are combined, and concentrated to a specific gravity of 1.06-1.10 (90°C), and the supernatant is taken to obtain a concentrated solution.

[0021] The term "specific gravity" refers to the weight ratio of the medicinal material to the extract.

[0022] More preferably, the preparation method further comprises the following steps: concentrating the extract under reduced pressure to obtain an extract, drying, and crushing into powder to obtain an extract.

[0023] More preferably, the preparation method further comprises the following steps: concentrating the extract to a specific gravity of 1.3-1.6 (90° C.), drying at 60-70° C., and crushing into powder to obtain an extract.

[0024] In another aspect, the present invention provides a medicine, the effective ingredient of which includes the above-mentioned Chinese medicine composition, or the extract prepared according to the above-mentioned preparation method.

[0025] The drug can be prepared into dosage forms such as pills, capsules, granules, oral liquids, powders, tablets, lozenges, ointments, etc., and suitable drug carriers in the art can be selected for different dosage forms.

[0026] The pharmaceutical carrier used can be solid, liquid or gas. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0027] When preparing the composition for oral dosage form, any convenient pharmaceutical medium can be used. For example, water, ethanol, oil, alcohol, flavoring agent, preservative, coloring agent, etc. can be used to form oral liquid preparations, such as suspensions and solutions; while carriers, such as starch, sugars, microcrystalline cellulose, diluents, granulating agents, emulsifiers, lubricants, binders, disintegrants can be used to form oral solid preparations, such as powders, capsules and tablets. Tablets and capsules are the preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or non-aqueous techniques.

[0028] Tablets containing the Chinese medicine composition or extract of the present invention can be prepared by tableting or molding, and one or more auxiliary ingredients or adjuvants can be used. The active ingredient can be tableted in a free-flowing form (such as powder or granules) in a suitable machine, and can be mixed with a binder, a lubricant, an inert diluent, a surfactant or a dispersant to prepare a tablet. Molded tablets can be molded in a suitable machine, i.e., a powdered compound mixture moistened with an inert liquid diluent. Each tablet preferably contains about 0.05 mg to about 5 g of active ingredient, and each sachet or capsule preferably contains about 0.05 mg to about 5 g of active ingredient. For example, a preparation intended for oral administration to humans may contain about 0.5 mg to about 5 g of active drug, mixed with an appropriate and convenient carrier material, which may account for about 5% to 95% of the total composition. The unit dosage form usually contains about 1 mg to about 2 g of active ingredient, usually 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.

[0029] The pharmaceutical composition suitable for parenteral administration of the present invention can be prepared as an aqueous solution or suspension of the active compound. Suitable surfactants such as hydroxypropylcellulose can be included. Dispersions can also be prepared in glycerol, liquid polyethylene glycol and oil mixtures thereof. In addition, preservatives can be added to prevent the harmful growth of microorganisms.

[0030] Medicine of the present invention can be in the form suitable for topical use, for example aerosol, cream, ointment, lotion, powder or the like. In addition, composition can be in the form suitable for transdermal administration device. Can use Chinese medicine composition of the present invention, prepare these prescriptions by conventional processing method. For example, by mixing hydrophilic material and water, and about 5wt% to about 10wt% of compound, prepare cream or ointment with required consistency.

[0031] The medicine of the present invention can be in a form suitable for rectal administration, wherein the carrier is a solid. Preferably, the mixture is made into a unit dose suppository. Suitable carriers include cocoa butter and other materials commonly used in the art. Suppositories can be prepared by first forming a composition containing a softened or melted carrier, followed by cooling and shaping in a mold.

[0032] In addition to the above-mentioned carrier components, the above-mentioned pharmaceutical preparations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, adhesives, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. In addition, other excipients, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc., colorants and flavoring agents, etc., may be added. The preparation is made isotonic with the blood of the intended recipient. The components containing the Chinese medicine composition of the present invention can also be prepared in the form of powder or concentrate.

[0033] Preferably, the pharmaceutical preparation is an oral pharmaceutical preparation.

[0034] More preferably, the oral pharmaceutical preparation is any one of a decoction, a pill, a tablet, a capsule, a powder, a granule, an oral liquid, and an ointment, preferably an ointment.

[0035] Finally, the present invention provides the use of the above-mentioned Chinese medicine composition, or the extract prepared according to the above-mentioned preparation method in the preparation of a product having at least one of the functions of dispelling cold and warming the uterus, relieving menstrual pain, and menstrual disorders.

[0036] The beneficial effects of the present invention include:

[0037] The present invention uses a combination of specific medicinal materials, including ginger, jujube, peach kernel, angelica dahurica, cinnamon, red ginseng, snow lotus culture, saffron extract, donkey-hide gelatin, longan, fig, wolfberry, Poria cocos and licorice. It uses a strategy of both tonifying qi and blood and promoting blood circulation and removing blood stasis, and warming yang and dispersing cold and coordinating heat and removing dampness. It comprehensively targets different symptoms of dysmenorrhea and has the effects of significantly improving uterine cold, relieving menstrual pain and menstrual disorders. DETAILED DESCRIPTION

[0038] In order to make the technical means, creative features, purpose and efficacy of the present invention easy to understand, the present invention is further explained in conjunction with specific embodiments below, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without creative work all belong to the protection scope of the present invention. In the following embodiments, unless otherwise specified, the operating methods used are conventional operating methods, the equipment used are conventional equipment, and the equipment materials used in each embodiment are the same.

[0039] In the following examples, the snow lotus culture was purchased from Dalian Precon Biotechnology Co., Ltd., and the product name is snow lotus culture. Saffron extract was purchased from Chengyi Health Technology Group Co., Ltd., and the product name is Saffron extract.

[0040] Example 1

[0041] The formula is as follows: 50 parts of ginger, 29 parts of jujube, 18 parts of peach kernel, 18 parts of angelica dahurica, 12 parts of cinnamon, 10 parts of red ginseng, 4 parts of snow lotus culture, 4 parts of saffron extract, 8 parts of donkey-hide gelatin, 8 parts of longan, 8 parts of fig, 4 parts of wolfberry, 4 parts of Poria cocos, and 4 parts of licorice.

[0042] Preparation method: (1) extract the remaining medicinal materials except ginger with 10 times the amount of water twice, the first time for 1 hour and the second time for 0.5 hour, filter, combine the extracts, concentrate to a specific gravity of 1.08 (90°C), and centrifuge to obtain the supernatant;

[0043] (2) Squeeze the ginger juice in the formula amount, add the obtained freshly squeezed ginger juice to the supernatant, continue to concentrate to a specific gravity of 1.5 (90° C.), obtain an extract, dry at 60-70° C., and grind into powder to obtain an extract.

[0044] Example 2

[0045] The formula is as follows: 40 parts of ginger, 40 parts of jujube, 15 parts of peach kernel, 30 parts of angelica, 8 parts of cinnamon, 20 parts of red ginseng, 2 parts of snow lotus culture, 10 parts of saffron extract, 2 parts of donkey-hide gelatin, 10 parts of longan, 2 parts of fig, 10 parts of wolfberry, 2 parts of Poria cocos, and 10 parts of licorice.

[0046] The preparation method is the same as Example 1.

[0047] Example 3

[0048] The formula is as follows: 60 parts of ginger, 20 parts of jujube, 30 parts of peach kernel, 15 parts of angelica dahurica, 20 parts of cinnamon, 5 parts of red ginseng, 10 parts of snow lotus culture, 2 parts of saffron extract, 10 parts of donkey-hide gelatin, 2 parts of longan, 10 parts of fig, 2 parts of wolfberry, 10 parts of Poria cocos, and 2 parts of licorice.

[0049] The preparation method is the same as Example 1.

[0050] Comparative Example 1

[0051] The formula is as follows: 30 parts of ginger, 45 parts of jujube, 10 parts of peach kernel, 35 parts of angelica, 6 parts of cinnamon, 22 parts of red ginseng, 1 part of snow lotus culture, 12 parts of saffron extract, 1 part of donkey-hide gelatin, 12 parts of longan, 1 part of fig, 15 parts of wolfberry, 1 part of Poria cocos, and 12 parts of licorice.

[0052] The preparation method is the same as Example 1.

[0053] Comparative Example 2

[0054] The formula is as follows: 65 parts of ginger, 15 parts of jujube, 32 parts of peach kernel, 12 parts of angelica, 22 parts of cinnamon, 4 parts of red ginseng, 12 parts of snow lotus culture, 1 part of saffron extract, 14 parts of donkey-hide gelatin, 1 part of longan, 12 parts of fig, 1 part of wolfberry, 14 parts of Poria cocos, and 1 part of licorice.

[0055] The preparation method is the same as Example 1.

[0056] Comparative Example 3

[0057] The recipe is as follows: 50 parts ginger and 29 parts jujube.

[0058] Preparation method: (1) Add 10 times the amount of water to the formulated amount of jujube and extract twice, the first time for 1 hour and the second time for 0.5 hour, filter, combine the extracts, concentrate to a specific gravity of 1.08 (90°C), and centrifuge to obtain the supernatant;

[0059] (2) Squeeze the ginger juice in the formula amount, add the obtained freshly squeezed ginger juice to the supernatant, continue to concentrate to a specific gravity of 1.5 (90° C.), obtain an extract, dry at 60-70° C., and grind into powder to obtain an extract.

[0060] Comparative Example 4

[0061] The recipe is as follows: 8 parts of donkey-hide gelatin, 29 parts of jujube, 4 parts of wolfberry, and 8 parts of longan.

[0062] Preparation method: Add 10 times the amount of water to the formulated amount of medicinal materials and extract twice, the first time for 1 hour and the second time for 0.5 hour, filter, combine the extracts, and concentrate to a specific gravity of 1.5 (90°C) to obtain an extract liquid, dry at 60-70°C, and crush into powder to obtain an extract.

[0063] Comparative Example 5

[0064] The formula is as follows: 4 parts of wolfberry, 4 parts of Poria cocos, 29 parts of jujube, 18 parts of Angelica dahurica, 12 parts of cinnamon, 8 parts of longan, 18 parts of peach kernel, 4 parts of snow lotus culture, and 8 parts of donkey-hide gelatin.

[0065] Preparation method: Add 10 times the amount of water to the formulated amount of medicinal materials and extract twice, the first time for 1 hour and the second time for 0.5 hour, filter, combine the extracts, and concentrate to a specific gravity of 1.5 (90°C) to obtain an extract liquid, dry at 60-70°C, and crush into powder to obtain an extract.

[0066] Results

[0067] 1. Therapeutic effect on rats with cold-coagulation and blood stasis

[0068] 1. Construction of rat model of cold coagulation and blood stasis

[0069] The rats were placed in a 0-4℃ ice water bath and swam for 4 minutes for 7 consecutive days, once a day. On the 8th day, 0.1% DL-epinephrine hydrochloride (0.6mL / kg) was injected subcutaneously, and 2 hours later, the rats were placed in a 0-4℃ ice water bath and swam for 4 minutes. 2 hours later, the same amount of DL-epinephrine hydrochloride was injected subcutaneously again, and fasting but not water was allowed overnight. During the entire modeling process, the rats' weight, mental state, exercise status, tail blood stasis, fur, auricular veins, and water intake were continuously recorded.

[0070] Compared with normal rats, the model rats showed symptoms such as weight loss, fear of cold and preference for warmth, shivering, curling up and less movement, dark purple nails, purple and black ecchymosis on the tail, and reduced water and food intake after modeling, indicating that the cold stagnation and blood stasis type rat model was successfully established.

[0071] 2. Experimental animals and groups

[0072] Healthy clean grade SD female rats, 3 months old, weighing 230 g ± 20 g, were selected and provided by Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. Animal breeding environment: temperature: (20 ± 2) ℃, humidity: 50% ± 5%, 12h light and dark alternation. Before the experiment, the rats were adaptively fed for 7 days, during which they were free to drink water and eat.

[0073] SD rats were divided into 12 groups according to the random number table method, with 10 rats in each group. The groups were set as: normal control group (normal group), model control group (model group), Chinese patent medicine control group (Shaofu Zhuyu Pills), Example 1 low-dose group, Example 1 high-dose group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, and Comparative Example 5 group.

[0074] 3. Drug preparation and daily dosage

[0075] The drug preparations for each group are as follows:

[0076] (1) Blank control group: distilled water.

[0077] (2) Model control group: distilled water.

[0078] (3) Shaofu Zhuyu Pills group (Chinese patent medicine positive control): Shaofu Zhuyu Pills, purchased from Jilin National Pharmaceutical Company, approval number: National Medicine Standard Z34020557; specification: 9 g × 10 pills / box; dosage: 2 3.21 g·kg -1 ·d -1 , dissolved in distilled water.

[0079] (4) Example 1 Low-dose group: Dosage: 2.14 g·kg -1 ·d -1 , dissolved in distilled water.

[0080] (5) Example 1 High-dose group: Dosage: 3.21 g·kg -1 ·d -1 , dissolved in distilled water.

[0081] (6) Example 2 group: dosage: 3.21 g·kg -1 ·d -1 , dissolved in distilled water.

[0082] (7) Example 3 group: dosage: 3.21 g·kg -1 ·d -1 , dissolved in distilled water.

[0083] (8) Comparative Example 1: Dosage: 3.21 g kg -1 ·d -1 , dissolved in distilled water.

[0084] (9) Comparative Example 2: Dosage: 3.21 g·kg -1 ·d -1 , dissolved in distilled water.

[0085] (10) Comparative Example 3: Dosage: 3.21 g·kg -1 ·d -1 , dissolved in distilled water.

[0086] (11) Comparative Example 4: Dosage: 3.21 g·kg -1 ·d -1 , dissolved in distilled water.

[0087] (12) Comparative Example 5: Dosage: 3.21 g·kg -1 ·d -1 , dissolved in distilled water.

[0088] All animals were given the same amount of ordinary feed + drinking water. After the drugs in each group were made into solutions, they were administered to the animals in each group by gavage according to the above daily dosage, with a gavage volume of 10 mL·kg -1 ·d -1 , administered continuously for 8 days.

[0089] (1) Syndrome observation:

[0090] During the whole process of modeling, the rats' weight, mental state, exercise, degree of blood stasis in the tail, fur, auricular veins, drinking and food intake were continuously recorded. Compared with normal rats, the model rats showed weight loss, fear of cold and preference for warmth, shivering, curling up and less movement, dark purple nails, purple and black ecchymosis on the tail, and reduced drinking and food intake after modeling, which means that the cold stagnation and blood stasis rat model was successfully established.

[0091] (2) Blood rheology and coagulation function tests:

[0092] The rats in each group were anesthetized by intraperitoneal injection of 10% chloral hydrate, and 8 mL of blood was collected from the abdominal aorta and placed in a blood collection tube with sodium heparin as the anticoagulant. Another 4 mL of blood was collected in a blood collection tube with sodium citrate as the anticoagulant. The blood rheology indexes were detected by automatic blood rheometer, automatic coagulation analyzer and platelet aggregation instrument.

[0093] (whole blood viscosity (WBV), hematocrit (HTC), (erythrocyte sedimentation rate), coagulation function indicators (prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB)) and platelet aggregation rate (PAG).

[0094] 4. Test results

[0095] 4.1 Effects on rat body weight

[0096] The body weight of rats before and after administration was recorded, and variance analysis was performed. The results are shown in Table 1. Compared with the blank control group rats, the model control group rats showed weight loss, fear of cold and warmth, shivering, curling up and less movement, dark purple nails, purple and black ecchymosis on the tail, and reduced drinking and food intake, indicating that the model was successfully established. Compared with the model group rats, each administration group had a significant increase in body weight (P<0.01), and behavioral symptoms were improved, among which the Example 1-3 group and the positive drug group had the best effect.

[0097] Table 1. Effects of different Chinese medicine compositions on body weight of model rats ( n=10)

[0098] Group Dosage (g / kg) Net weight gain / g Normal control group — 46.6±2.36** Model control group — -14.19±3.11 Chinese patent medicine control group 2 33.71±3.3** Example 1 Low dose group 1.07 29.43±2.48**## Example 1 High dose group 3.21 34.11±3.42** Example 2 Group 3.21 35.56±2.42** Example 3 Group 3.21 35.55±2.89** Comparative Example 1 3.21 22.34±3.21##** Comparative Example 2 3.21 25.65±3.58##** Comparative Example 3 3.21 18.21±2.75##** Comparative Example 4 3.21 19.87±2.69##** Comparative Example 5 3.21 19.03±2.94##**

[0099] Note: Compared with the model group, * p<0.05, ** p<0.01, *** p<0.001;

[0100] Compared with the high-dose group of Tongjing ointment prescription, # p<0.05, ## p<0.01, ### p<0.001.

[0101] 4.2 Effects on blood rheology in rats with cold-coagulation and blood stasis model

[0102] As shown in Table 2, relative to the normal group, the blood viscosity values ​​of the model control group were significantly increased at all shear rates, indicating that the blood fluidity of the model group was poor. Compared with the model control group, the Chinese patent medicine control group, the high-dose group of Example 1, the Example 2 group, and the Example 3 group can significantly reduce the whole blood viscosity (P<0.01), and it can be seen that the high-dose group of Example 1 can significantly improve the blood fluidity, and the effect is equivalent to the positive drug group. Compared with the low-dose group of Example 1, the high-dose group of Example 1 and the Example 2-3 group showed significance (P<0.01). Compared with the high-dose group of Example 1, there was no significant difference in the Example 2-3 group, and there was a significant difference in the Comparative Example 1-5 group (P<0.01), suggesting that the drug combination of this prescription is the best, and the ratio should be within a certain range. The above results show that the Example 1-3 group can significantly reduce the whole blood viscosity and improve the blood fluidity of mice.

[0103] Table 2. Effects of different Chinese medicine compositions on blood rheology changes in model rats ( n=10)

[0104]

[0105] Note: Compared with the model group, * p<0.05, **p<0.01, *** p<0.001;

[0106] Compared with the high-dose group of Tongjing ointment prescription, # p<0.05, ## p<0.01, ### p<0.001.

[0107] 4.3 Effects on ESR and Hct in Rats with Cold-Stagnation Blood Stasis Model

[0108] The erythrocyte sedimentation rate and hematocrit of the model control group were significantly increased (p < 0.01), indicating that the cold coagulation and blood stasis model was successfully established. Compared with the model control group, the erythrocyte sedimentation rate index of the Chinese patent medicine control group was significantly reduced (p < 0.01), and the hematocrit was also significantly lower than that of the model control group (p < 0.01). The erythrocyte sedimentation rate and hematocrit of the high-dose group of embodiment 1 and the 2-3 groups of embodiments were significantly lower than those of the model control group (p < 0.01), which was equivalent to the Chinese patent medicine group. Compared with the high-dose group of embodiment 1, there was no significant difference in the 2-3 groups of embodiments, and there was a significant difference in the 1-5 groups of comparative examples (p < 0.01), suggesting that the drug combination of this prescription has the best effect, and the ratio should be within a certain range. The above results show that the 1-3 groups of embodiments can significantly reduce the erythrocyte sedimentation rate and hematocrit of rats, and improve the symptoms of cold coagulation and blood stasis in rats.

[0109] Table 3. Effects of different Chinese medicine compositions on erythrocyte sedimentation rate and hematocrit in model rats

[0110]

[0111]

[0112] Note: Compared with the model group, * p<0.05, ** p<0.01, *** p<0.001;

[0113] Compared with the high-dose group of Tongjing ointment prescription, # p<0.05, ## p<0.01, ### p<0.001.

[0114] 4.4 Effect on coagulation function in rats with cold-coagulation and blood stasis model

[0115] As shown in Table 4, compared with the blank group, the prothrombin time (PT), activated partial thromboplastin (APPT), and thrombin time (TT) of the model group rats were significantly reduced (P < 0.01), and the fibrinogen content (FIB) was significantly increased (P < 0.01), indicating that the coagulation time of the model rats was shortened, the coagulation function was abnormally enhanced, and they were in a state of blood coagulation and blood stasis, and the model was successfully replicated.

[0116] Compared with the model control group, the present prescription embodiments 1-3 and the Chinese patent medicine control group had significant differences (P<0.01) in PT, APPT, TT, and FIB indicators compared with the model control group, showing an anticoagulant effect, and the high dose of the present prescription was equivalent to the Chinese patent medicine group. Compared with the high dose group of Example 1, there was no significant difference in the Example 2-3 group, and there was a significant difference in the Comparative Example 1-5 group (P<0.01), indicating that the drug combination of the present prescription had the best effect, and the ratio should be within a certain range. The above results show that Examples 1-3 can significantly increase the PT, APPT, and TT contents of rats, reduce the FIB content, and improve the symptoms of blood coagulation and blood stasis in rats.

[0117] Table 4. Coagulation function of rats in each group after administration of cold coagulation and blood stasis model

[0118]

[0119]

[0120] Note: Compared with the model group, * p<0.05, ** p<0.01, *** p<0.001;

[0121] Compared with the high-dose group of Tongjing ointment prescription, # p<0.05, ## p<0.01, ### p<0.001.

[0122] 2. Therapeutic effect on mice with primary dysmenorrhea of ​​cold-dampness stagnation type induced by oxytocin combined with cold stimulation 1. Construction of mouse model of primary dysmenorrhea of ​​cold-dampness stagnation type induced by oxytocin combined with cold stimulation Non-pregnant ICR female mice were intraperitoneally injected with 10 mg·kg-1·d-1 of estradiol benzoate for 3 consecutive days, and the hind limbs and lower abdomen of the mice were immersed in (20±2)℃ cold water (room temperature 23±2℃) for cold stimulation, once a day for 10 minutes each time. On the 4th day of modeling, 0.4 mL / mouse (4 U /

[0123] Only).

[0124] 2. Experimental animals and groups

[0125] Healthy SPF-grade ICR female mice weighing 20 g ± 2 g were selected and provided by Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. Animal breeding environment: temperature: (20 ± 2) ℃, humidity: 50% ± 5%, 12 h light and dark alternation. Before the experiment, the mice were adaptively fed for 7 days, during which they were free to drink water and eat.

[0126] ICR female mice were divided into 12 groups according to the random number table method, with 10 mice in each group. The groups were set as: normal control group (normal group), model control group (model group), patent medicine control group (Shaofu Zhuyu Pills), low-dose group of Example 1, high-dose group of Example 1, Example 2 group, Example 3 group, comparative example 1 group, comparative example 2 group, comparative example 3 group, comparative example 4 group, and comparative example 5 group.

[0127] 3. Drug preparation and daily dosage

[0128] The drug preparations for each group are as follows:

[0129] (1) Blank control group: distilled water.

[0130] (2) Model control group: distilled water.

[0131] (3) Shaofu Zhuyu Pills group (Chinese patent medicine positive control): Shaofu Zhuyu Pills, purchased from Jilin National Pharmaceutical Company, approval number: National Medicine Standard Z34020557; specification: 9 g × 10 pills / box; dosage: 2 g kg -1 ·d -1 , dissolved in distilled water.

[0132] (4) The examples and comparative examples are the same as the corresponding parts of Experiment 1.

[0133] All animals were given the same amount of ordinary feed + drinking water. After the drugs in each group were made into solutions, they were administered to the animals in each group by gavage according to the above daily dosage, with a gavage volume of 10 mL·kg -1 ·d -1 , after modeling, the drug was given every day for 4 consecutive days.

[0134] 30 minutes after the last administration, 4 U of oxytocin injection was injected intraperitoneally. The number of mouse twisting within 30 minutes after injection was recorded and the inhibition rate of twisting reaction was calculated.

[0135] 4. Test results

[0136] As shown in Table 5, relative to the normal control group, the model control group significantly increased the number of twists. Compared with the model control group, the Chinese patent medicine control group and the embodiment 1-3 groups can significantly reduce the number of twists, and the twist inhibition rates are respectively: 63.03%, 68.62%, 67.96%, 68.22%, with significant differences (P<0.01), and the high-dose effect of this prescription is equivalent to the positive drug. Relative to the high-dose group of embodiment 1, the twist inhibition rate of the comparative example 1-5 group is significantly reduced, and the twist inhibition rate is only 25.13%, 24.08%, 18.16%, 12.50%, 12.30%, indicating that the prescription drug combination effect is the best, and the ratio should be within a certain range. The above results show that the high-dose group of this prescription can significantly improve the number of twists of the cold-damp stagnation type primary dysmenorrhea mice induced by oxytocin combined cold stimulation, and improve uterine cold and uterine pain.

[0137] Table 5. Inhibitory effects of different Chinese herbal medicine compositions on writhing in mice with primary dysmenorrhea caused by cold-dampness stagnation ( n=10)

[0138]

[0139]

[0140] Note: Compared with the model group, * p<0.05, ** p<0.01, *** p<0.001;

[0141] Compared with the high-dose group, # p<0.05, ## p<0.01, ### p<0.001.

[0142] 3. Clinical treatment trial for dysmenorrhea caused by qi stagnation, cold coagulation and blood stasis

[0143] Inclusion criteria:

[0144] 1. TCM diagnostic criteria: Women experience periodic lower abdominal pain during menstruation or before and after menstruation (within 1 week) as the main symptom, accompanied by other discomforts that affect their work or life.

[0145] 2. TCM syndrome differentiation standard: Qi stagnation, cold coagulation and blood stasis syndrome. Symptoms: cold pain in the lower abdomen before or during menstruation, scanty menstrual flow, irregular menstruation, dark purple blood with clots, dark purple tongue or with petechiae, white or greasy tongue coating, deep and tight pulse.

[0146] 3. Western medicine diagnostic criteria: primary dysmenorrhea or secondary dysmenorrhea.

[0147] 4. Grading standards for the severity of dysmenorrhea:

[0148] (1) Severe: Unbearable pain in the lower abdomen during or before and after menstruation, which causes restlessness and serious impact on work, study and daily life, and requires bed rest. It is accompanied by back pain, pale face, cold sweat, cold limbs, vomiting and diarrhea, or anal swelling, and no significant relief after taking analgesic measures.

[0149] (2) Moderate: Severe lower abdominal pain during or before and after menstruation, accompanied by back pain, nausea and vomiting, and cold limbs. Analgesics are used to temporarily relieve the pain.

[0150] (3) Mild: Obvious lower abdominal pain during or before and after menstruation, accompanied by back pain, but the patient can continue to work, has no systemic symptoms, and sometimes needs to take painkillers.

[0151] Dosage regimen:

[0152] The powder of Example 1 was used to prepare granules, 3 times a day, 1 bag (8 g) each time, taken 5 days before menstruation, and taken for 7 consecutive days. Before the next menstruation, it was taken in this way, and taken continuously for 2 menstrual cycles, which was a course of treatment.

[0153] Efficacy criteria:

[0154] (1) Cured: Abdominal pain and other symptoms disappear after taking the medicine and do not recur after stopping the medicine for 3 menstrual cycles.

[0155] (2) Significant effect: After treatment, abdominal pain is significantly relieved, other symptoms improve, and the patient can continue to work without taking painkillers.

[0156] (3) Effective: After treatment, abdominal pain was alleviated and the patient was able to continue working while taking painkillers.

[0157] (4) Ineffective: Abdominal pain and its symptoms remain unchanged.

[0158] Test results:

[0159] A total of 43 cases were observed in this group, all of which were patients with dysmenorrhea. Among them, 21 cases were mild dysmenorrhea, 13 cases were moderate dysmenorrhea, and 9 cases were severe dysmenorrhea. After the treatment, the judgment criteria were used for evaluation, among which 27 cases were cured, accounting for 63%, 9 cases were effective, 6 people were effective, and 1 person was ineffective, accounting for 2%. Self-control observation before and after treatment, the statistical results showed significant differences (P<0.01). Before and after treatment, blood, urine, stool routine and liver, kidney function, electrocardiogram were tested and no abnormal changes with clinical significance related to the medication of the test group were found, and no obvious adverse reactions were found during the treatment. It shows that the Chinese medicine composition of the present invention has a definite therapeutic effect and is safe to use.

[0160] 4. Observation on the efficacy of treating gynecological menstrual disorders

[0161] Clinical data: The Chinese medicinal material of Example 1 of the present invention was applied to 110 cases for clinical observation.

[0162] The clinical data included 110 cases, including:

[0163] 39 cases were aged 18 to 30 years, 41 cases were aged 31 to 40 years, 30 cases were aged 41 years and above, with an average age of 38.5 years. The shortest course of disease was one year and the longest was 10 years. Among them, 22 cases had early menstruation, 19 cases had late menstruation, 31 cases had irregular menstruation, 20 cases had menorrhagia, and 18 cases had oligomenorrhea.

[0164] Indications: Menstrual disorders. All cases are diagnosed in accordance with the diagnostic criteria for menstrual disorders in the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Certificates" issued by the State Administration of Traditional Chinese Medicine. Early menstruation: the menstrual cycle is advanced by more than 7 days; late menstruation: the menstrual cycle is delayed by more than 7 days; irregular menstruation: menstruation does not come according to the cycle, or it comes earlier or later; menorrhagia: the menstrual cycle is normal, but the menstrual volume exceeds normal menstruation; oligomenorrhea: the menstrual cycle is normal, but the menstrual volume is significantly reduced, or the menstrual time is shortened or it stops with a few drops.

[0165] Treatment method: Take the Chinese medicine composition of Example 1, one dose per day, divided into 2 doses, once in the morning and once in the evening. One month is one course of treatment, and two courses of treatment are required.

[0166] Efficacy criteria:

[0167] Cure: Menstrual blood volume and menstrual cycle returned to normal, and there was no recurrence in 5 menstrual cycles after stopping the medication.

[0168] Markedly effective: Menstrual blood volume and menstrual cycle were basically normal, with significant improvement. There was no recurrence within 5 menstrual cycles after stopping the medication.

[0169] Ineffective: No significant improvement in menstrual blood volume and menstrual cycle.

[0170] Treatment results:

[0171] In the Chinese medicine group, 62 cases were cured, 37 cases were markedly effective, 11 cases were ineffective, and the effective rate (cured + markedly effective) was 92%. The Chinese medicine composition for treating gynecological menstrual disorders of the present invention has a significant effect and a high effective rate.

[0172] Typical Cases

[0173] Zhang, 30 years old, began to have irregular menstruation after childbirth, or a tide every 45-50 days, or once every half a month, the menstrual flow is slightly less and dark red, breast swelling before menstruation, dizziness, fatigue, back pain, clear and long urine, cold limbs, general appetite, and excessive leucorrhea. The complexion is dark yellow with dark spots, the tongue is pale and slightly dark, the tongue coating is white, and the pulse is deep, thin and weak. The menstruation started at the age of 16, 28 days before the cycle. The last menstruation is 40 days ago. After taking the Chinese medicine of Example 1 for one week, the patient's fatigue and weakness were alleviated, and she had a slight appetite. Menstruation came, the cycle was 47 days, the menstruation lasted for 7 days, the menstrual flow was slightly less, and the color was red. After taking the Chinese medicine composition of the present invention for a course of treatment, the usual dizziness and fatigue basically disappeared,

[0174] The complexion improved, and the leucorrhea was normal. After taking the Chinese medicine composition of the present invention for 1 month, the next menstruation came, the cycle was 30 days, the menstruation lasted for 6 days, and the premenstrual breast swelling was not obvious. After taking the Chinese medicine composition of the present invention for one month, the patient's physique improved and the complexion was ruddy. Follow-up for half a year showed that the menstrual cycle was normal and there was no recurrence.

[0175] Tang, 35 years old, suffered from early menstruation, heavy menstrual blood and gynecological diseases for more than one year. Taking Tiaojing tablets, Siwu Yimu pills and other medicines had little effect. Fatigue, lumbar pain, dizziness and tinnitus. Physical examination: yellow complexion, thin. After taking the Chinese medicine composition for treating menstrual disorders described in Example 1 for two courses of treatment, breast distending pain during menstruation was significantly alleviated, the menstrual period was two days earlier than last month, and the menstrual blood volume was also reduced. Another course of treatment was taken. During the next menstrual period, the symptoms of breast distending pain basically disappeared, the menstrual period and blood volume were normal, and there was no recurrence thereafter.

[0176] Wang, female, 20 years old. The patient complained of menstruation that the menstruation was not enough for one month. The patient's body was deficient. The menstruation was advanced for one year, and even the menstruation was not enough for one month. The menstruation was sometimes more and sometimes less, the color was fresh and there were clots, the stool was difficult and dry, and the night was restless. Symptoms: thin and timid body, yellow face and pale face. The pulse was thin and stringy, and the tip of the tongue was red. The diagnosis was: early menstruation, qi and yin deficiency and blood heat type. After taking the Chinese medicine composition of the present invention for one course of treatment, the menstruation came the next month, the cycle was 28 days, the menstrual volume was more, the color was red and thick. After taking the Chinese medicine composition of the present invention for one month, the menstrual cycle returned to normal, the cycle was 29 days, the menstrual volume was normal, and the follow-up was six months, and the menstrual cycle was normal for 28-30 days:

[0177] The present invention is very effective in treating patients with menstrual disorders. Various raw materials can be coordinated with each other to maximize the efficacy, effectively improve the self-coordination ability of the patient's body, significantly improve the function of internal organs and clinical symptoms, and also has the advantages of no toxic side effects and low cost. Clinical verification shows that it has a good therapeutic effect on menstrual disorders.

[0178] In summary, in the experimental study of rats with cold coagulation and blood stasis model, the high-dose group of this prescription can significantly increase the body weight of animals with cold coagulation and blood stasis model, improve the blood rheology and coagulation function of the model animals, and there is no significant difference between the positive drug group and the Example 2-3 group, and it is significantly better than the low-dose group of this prescription and the comparative example 1-5 group. In the experimental study of primary dysmenorrhea in mice with cold-damp coagulation type, the high-dose group of this prescription can enhance the inhibitory effect of twisting of mice with primary dysmenorrhea model of cold-damp coagulation, and is significantly better than the low-dose group of this prescription and the comparative example 1-5 group, and there is no significant difference between the positive drug and the Example 2-3 group. In addition, clinical data prove that this prescription has a good effect on dysmenorrhea of ​​qi stagnation, cold coagulation and blood stasis syndrome and gynecological menstrual disorders. The above results all show that the prescription has the effect of significantly improving uterine cold, relieving menstrual pain and menstrual disorders, and at the same time, it is suggested that the prescription combination has the best effect, and the combination must be within a certain range. The Chinese medicine composition of the present invention can significantly improve uterine coldness, relieve menstrual pain and menstrual disorders, and its therapeutic effect is equivalent to that of positive drugs, and is superior to compositions whose component proportions are not within the range and other combinations of medicinal flavors.

[0179] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A composition for dispelling cold, warming the uterus, and relieving menstrual pain and menstrual disorders, characterized in that: The composition includes ginger, jujube, peach kernel, angelica root, cinnamon bark, red ginseng, snow lotus culture, saffron extract, donkey-hide gelatin, longan, fig, wolfberry, tuckahoe and liquorice.

2. The composition according to claim 1, characterized in that The composition comprises, by weight, 40-60 parts of ginger, 20-40 parts of jujube, 15-30 parts of peach kernel, 15-30 parts of angelica dahurica, 8-20 parts of cinnamon, 5-20 parts of red ginseng, 2-10 parts of snow lotus culture, 2-10 parts of saffron extract, 2-10 parts of donkey-hide gelatin, 2-10 parts of longan, 2-10 parts of fig, 2-10 parts of wolfberry, 2-10 parts of poria and 2-10 parts of liquorice.

3. The composition according to claim 2, characterized in that The composition comprises, by weight, 50 parts of ginger, 29 parts of jujube, 18 parts of peach kernel, 18 parts of angelica dahurica, 12 parts of cinnamon, 10 parts of red ginseng, 4 parts of snow lotus culture, 4 parts of saffron extract, 8 parts of donkey-hide gelatin, 8 parts of longan, 8 parts of fig, 4 parts of wolfberry, 4 parts of poria and 4 parts of liquorice.

4. A method for preparing the composition according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) extracting the formulated amounts of jujube, peach kernel, angelica root, cinnamon bark, red ginseng, snow lotus culture, saffron extract, donkey hide gelatin, longan, fig, wolfberry, Poria cocos and liquorice with water, combining the extracts, and concentrating to obtain a concentrated solution; (2) Squeeze the ginger juice in the prescribed amount and mix it with the concentrated solution obtained in step (1) to obtain an extract.

5. The preparation method according to claim 4, characterized in that: Step (1) is specifically as follows: adding 5-15 times the weight of water to the formulated amount of jujube, peach kernel, angelica dahurica, cinnamon, red ginseng, snow lotus culture, saffron extract, donkey-hide gelatin, longan, fig, wolfberry, poria and licorice, and boiling and extracting for 2-4 times, each time for 0.5-2 hours, combining the extracts, concentrating to a specific gravity of 1.06-1.10 (90° C.), taking the supernatant, and obtaining a concentrated solution.

6. The preparation method according to claim 5, characterized in that: Step (1) is: decocting and extracting jujube, peach kernel, angelica dahurica, cinnamon bark, red ginseng, snow lotus culture, saffron extract, donkey-hide gelatin, longan, fig, wolfberry, poria cocos and licorice in a formula amount for 2 times, adding 10 times the weight of water for each extraction, the first extraction is for 1 hour, the second extraction is for 0.5 hour, the extracts are combined, and concentrated to a specific gravity of 1.06-1.10 (90° C.), and the supernatant is taken to obtain a concentrated solution.

7. The preparation method according to claim 4, characterized in that: The preparation method further comprises the following steps: concentrating the extract under reduced pressure to obtain an extract, drying, and crushing the extract into powder to obtain the extract.

8. The preparation method according to claim 7, characterized in that: The preparation method further comprises the following steps: concentrating the extract to a specific gravity of 1.3-1.6, drying at 60-70° C., and crushing into powder to obtain an extract.

9. A drug, characterized in that The active ingredient comprises the composition according to any one of claims 1 to 3, or the extract prepared by the preparation method according to any one of claims 4 to 8.

10. Use of the composition according to any one of claims 1 to 3, or the extract prepared by the preparation method according to any one of claims 5 to 8, in the preparation of a product having at least one of the effects of dispelling cold and warming the uterus, relieving menstrual pain, and relieving menstrual disorders.

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