CN114617944B - Traditional Chinese medicine composition for treating primary dysmenorrhea and preparation method and application thereof - Google Patents

Abstract

The invention discloses a traditional Chinese medicine composition for treating primary dysmenorrhea and a preparation method and application thereof. The invention provides a medicine for treating primary dysmenorrhea, which comprises the following raw materials in parts by weight: 5-25 parts of galangal, 10-40 parts of peach kernel, 5-20 parts of fennel, 5-20 parts of angelica dahurica, 10-40 parts of dried orange peel, 10-30 parts of raspberry, 1-5 parts of rose, 1-5 parts of cinnamon and 1-3 parts of saffron. The invention also provides a preparation method of the extract, which comprises the following steps: mixing the ten traditional Chinese medicine raw materials, and extracting by adopting ethanol solution to obtain an extract. The invention also protects the application of the extract in preparing a medicament for treating primary dysmenorrhea. The medicine provided by the invention has a good effect on primary dysmenorrhea, has no adverse reaction, and has industrial popularization value.

Description

Traditional Chinese medicine composition for treating primary dysmenorrhea and preparation method and application thereof

Technical Field

The invention belongs to the field of traditional Chinese medicines, and in particular relates to a medicine (traditional Chinese medicine composition) for treating primary dysmenorrhea, and a preparation method and application thereof.

Background

Dysmenorrhea, known as "menstrual abdominal pain" in traditional Chinese medicine, was described in the first place in "Jinkui Lloyd Miao. Women's miscellaneous diseases and pulse syndrome and treatment ]: the "dysmenorrhoea with water is unfavorable, and the lower abdomen is full of pain", which is one of the most common gynecological diseases in women. Many clinical practices prove that primary dysmenorrhea is mainly caused by cold congealing, qi stagnation and blood stasis, so the clinical treatment adopts the main treatment principle of warming channels, dispelling cold, activating blood and dissolving stasis.

In western medicine, dysmenorrhea is classified into primary dysmenorrhea and secondary dysmenorrhea. Epidemiological studies show that primary pain channel is a common and frequently occurring disease of gynecology at present, and is a disease which endangers the physical and mental health of women. Primary dysmenorrhoea mainly occurs in adolescent girls and young women who are not married or educated.

The primary dysmenorrhea is usually associated with greedy cold drinks, living and node loss, insufficient intrinsic endowment, poor emotion, long-term illness and deficiency, and the like, and the disease is located in uterus and thoroughfare vessels, is closely related to thoroughfare vessels and conception vessels in aspects of meridians, and is closely related to three zang-fu organs including liver, kidney and spleen.

Disclosure of Invention

The invention aims to provide a medicine (traditional Chinese medicine composition) for treating primary dysmenorrhea, and a preparation method and application thereof.

The invention provides a medicament for treating primary dysmenorrhea, which comprises the following raw materials in part by weight: 5-25 parts of galangal, 10-40 parts of peach kernel, 5-20 parts of fennel, 5-20 parts of angelica dahurica, 10-40 parts of dried orange peel, 10-30 parts of raspberry, 1-5 parts of rose, 1-5 parts of cinnamon and 1-3 parts of saffron.

Specifically, the raw materials are as follows: 15-20 parts of galangal, 15-25 parts of peach kernel, 10-12 parts of fennel, 8-10 parts of angelica, 10-15 parts of radix angelicae, 10-18 parts of dried orange peel, 15-20 parts of raspberry, 3-5 parts of rose, 2-4 parts of cinnamon and 1 part of saffron.

Exemplary, the raw materials are as follows: 15 parts of galangal, 25 parts of peach kernel, 12 parts of fennel, 8 parts of angelica, 12 parts of angelica dahurica, 18 parts of dried orange peel, 15 parts of raspberry, 3 parts of rose, 3 parts of cinnamon and 1 part of saffron.

Exemplary, the raw materials are as follows: 15 parts of galangal, 15 parts of peach kernel, 10 parts of fennel, 10 parts of angelica, 15 parts of angelica dahurica, 12 parts of dried orange peel, 15 parts of raspberry, 5 parts of rose, 4 parts of cinnamon and 1 part of saffron.

Exemplary, the raw materials are as follows: 20 parts of galangal, 20 parts of peach kernel, 10 parts of fennel, 10 parts of angelica dahurica, 10 parts of dried orange peel, 20 parts of raspberry, 4 parts of rose, 2 parts of cinnamon and 1 part of saffron.

The medicine is prepared from the following traditional Chinese medicine raw materials in parts by mass: 5-25 parts of galangal, 10-40 parts of peach kernel, 5-20 parts of fennel, 5-20 parts of angelica dahurica, 10-40 parts of dried orange peel, 10-30 parts of fructus zizaniae caduciflorae, 1-5 parts of rose, 1-5 parts of cinnamon and 1-3 parts of saffron.

Specifically, the medicine is prepared from the following traditional Chinese medicine raw materials in parts by mass: 15-20 parts of galangal, 15-25 parts of peach kernel, 10-12 parts of fennel, 8-10 parts of angelica, 10-15 parts of radix angelicae, 10-18 parts of dried orange peel, 15-20 parts of raspberry, 3-5 parts of rose, 2-4 parts of cinnamon and 1 part of saffron.

The medicine is prepared from the following traditional Chinese medicine raw materials in parts by mass: 15 parts of galangal, 25 parts of peach kernel, 12 parts of fennel, 8 parts of angelica, 12 parts of angelica dahurica, 18 parts of dried orange peel, 15 parts of raspberry, 3 parts of rose, 3 parts of cinnamon and 1 part of saffron.

The medicine is prepared from the following traditional Chinese medicine raw materials in parts by mass: 15 parts of galangal, 15 parts of peach kernel, 10 parts of fennel, 10 parts of angelica, 15 parts of angelica dahurica, 12 parts of dried orange peel, 15 parts of raspberry, 5 parts of rose, 4 parts of cinnamon and 1 part of saffron.

The medicine is prepared from the following traditional Chinese medicine raw materials in parts by mass: 20 parts of galangal, 20 parts of peach kernel, 10 parts of fennel, 10 parts of angelica dahurica, 10 parts of dried orange peel, 20 parts of fructus zizaniae caduciflorae, 4 parts of rose, 2 parts of cinnamon and 1 part of saffron.

The invention also provides a preparation method of the extract, which comprises the following steps: mixing the ten traditional Chinese medicine raw materials, and extracting by adopting ethanol solution to obtain an extract.

The ten traditional Chinese medicine raw materials and the proportion thereof are as follows: 5-25 parts of galangal, 10-40 parts of peach kernel, 5-20 parts of fennel, 5-20 parts of angelica dahurica, 10-40 parts of dried orange peel, 10-30 parts of raspberry, 1-5 parts of rose, 1-5 parts of cinnamon and 1-3 parts of saffron.

Specifically, the ten traditional Chinese medicine raw materials and the proportions thereof are as follows: 15-20 parts of galangal, 15-25 parts of peach kernel, 10-12 parts of fennel, 8-10 parts of angelica, 10-15 parts of radix angelicae, 10-18 parts of dried orange peel, 15-20 parts of raspberry, 3-5 parts of rose, 2-4 parts of cinnamon and 1 part of saffron.

The ten traditional Chinese medicine raw materials and the proportions thereof are as follows: 15 parts of galangal, 25 parts of peach kernel, 12 parts of fennel, 8 parts of angelica, 12 parts of angelica dahurica, 18 parts of dried orange peel, 15 parts of raspberry, 3 parts of rose, 3 parts of cinnamon and 1 part of saffron.

The ten traditional Chinese medicine raw materials and the proportions thereof are as follows: 15 parts of galangal, 15 parts of peach kernel, 10 parts of fennel, 10 parts of angelica, 15 parts of angelica dahurica, 12 parts of dried orange peel, 15 parts of raspberry, 5 parts of rose, 4 parts of cinnamon and 1 part of saffron.

The ten traditional Chinese medicine raw materials and the proportions thereof are as follows: 20 parts of galangal, 20 parts of peach kernel, 10 parts of fennel, 10 parts of angelica dahurica, 10 parts of dried orange peel, 20 parts of raspberry, 4 parts of rose, 2 parts of cinnamon and 1 part of saffron.

The method further comprises the steps of: after the extraction is completed, filtering and collecting filtrate, and concentrating under reduced pressure until the relative density is 1.0-1.3 (specifically 1.0-1.1, more specifically 1.03), namely an extract-like product, namely an extract.

Illustratively, the method specifically includes the steps of:

(1) Mixing the ten traditional Chinese medicine raw materials, adding ethanol solution, stirring for 40-120 minutes, then filtering, and collecting filtrate;

(2) Adding an ethanol solution into the residue in the step (1), stirring for 20-90 minutes, filtering, and collecting filtrate;

(3) And (3) combining the filtrate obtained in the step (1) with the filtrate obtained in the step (2), and concentrating under reduced pressure to obtain an extractum-like product.

The rotational speed of the stirring may be 100-300rpm.

The rotational speed of the stirring may specifically be 200rpm.

In the step (1), the stirring time may be specifically 40 to 120 minutes.

In step (1), the stirring time may be specifically 60 minutes.

In the step (2), the stirring time may be specifically 20 to 90 minutes.

In step (2), the stirring time may be specifically 40 minutes.

The filtering specifically adopts a 300-500 mesh filter screen.

The filtering specifically adopts a 400-mesh filter screen.

The ethanol solution may specifically be an aqueous ethanol solution.

The aqueous ethanol solution may specifically be a 20% (V/V) or more ethanol solution.

The aqueous ethanol solution may specifically be 40% (V/V) or more ethanol solution.

The aqueous ethanol solution may be in particular a 50% -90% (V/V) ethanol solution.

The aqueous ethanol solution may be a 50% -70% (V/V) ethanol solution.

The aqueous ethanol solution may specifically be a 60% (V/V) ethanol solution.

In the method, the ratio of the total mass of the traditional Chinese medicine raw materials, the volume of the ethanol solution in the step (1) and the volume of the ethanol solution in the step (2) can be as follows: 1kg:4-10L:4-10L.

In the method, the ratio of the total mass of the traditional Chinese medicine raw materials, the volume of the ethanol solution in the step (1) and the volume of the ethanol solution in the step (2) can be as follows: 1kg:4-6L:4-6L.

In the method, the ratio of the total mass of the traditional Chinese medicine raw materials, the volume of the ethanol solution in the step (1) and the volume of the ethanol solution in the step (2) can be as follows: 1kg:5L:5L.

In the step (3), the mixture is concentrated under reduced pressure until the relative density is 1.0-1.3.

In the step (3), the mixture is concentrated under reduced pressure until the relative density is 1.0-1.1.

In the step (3), the mixture is concentrated under reduced pressure to a relative density of 1.03.

The relative density may specifically be that at 60 ℃.

The decompression concentration parameters can be specifically as follows: the temperature is 60-80 ℃.

The decompression concentration parameters can be specifically as follows: vacuum degree 0.1Mpa and temperature 70 ℃.

Specifically, the Chinese medicinal materials are crushed before use to obtain granule diameter below 2.0 mm.

The extract has the function of treating primary dysmenorrhea.

The extract prepared by the method also belongs to the protection scope of the invention.

The invention also provides a preparation method of the pharmaceutical preparation, which comprises the following steps: and (3) taking the extract, drying and granulating to obtain a granule preparation with the water content of less than 5%.

And adding auxiliary materials during drying and granulating.

The auxiliary material can be beta-cyclodextrin and/or maltodextrin.

The auxiliary material specifically comprises 1 part by mass of beta-cyclodextrin and 3 parts by mass of maltodextrin.

The ratio of the extract to the auxiliary materials can be specifically as follows: 24.5kg extract: 1-4kg of auxiliary materials.

The ratio of the extract to the auxiliary materials can be specifically as follows: 24.5kg extract: 2.45kg of auxiliary materials.

The preparation method specifically comprises the following steps: weighing auxiliary materials, placing the auxiliary materials in a boiling granulating dryer, adjusting the temperature of an air inlet to 70-100 ℃, and preheating the auxiliary materials in a boiling bed to 45-60 ℃; adding the extract into a feed liquid tank, uniformly stirring, adjusting the atomization pressure until the atomization effect is good, and gradually spraying the extract in the feed liquid tank onto the auxiliary materials boiling in a boiling bed by using a peristaltic pump; and after spraying is finished, continuing to dry for about 20 minutes to obtain the granular preparation with the moisture content less than or equal to 5%.

The preparation method further comprises the following steps: mixing the granule with brown sugar to obtain the final product.

The proportion of the granule preparation to the brown sugar can be specifically as follows: 5.02kg of granular formulation: 10-15kg of brown sugar.

The proportion of the granule preparation to the brown sugar can be specifically as follows: 5.02kg of granular formulation: 12.24kg brown sugar.

The pharmaceutical preparation has the function of treating primary dysmenorrhea.

The pharmaceutical preparation prepared by the method also belongs to the protection scope of the invention.

The invention also provides the application of the extract or the pharmaceutical preparation in preparing a medicament for treating primary dysmenorrhea.

The invention also provides a medicine for treating primary dysmenorrhea, and the active ingredients of the medicine are the extract or the medicine preparation.

The medicament may further comprise a carrier material. Carrier materials include, but are not limited to, water soluble carrier materials (e.g., polyethylene glycol, polyvinylpyrrolidone, organic acids, etc.), poorly soluble carrier materials (e.g., ethylcellulose, cholesterol stearyl ester, etc.), enteric carrier materials (e.g., cellulose acetate phthalate, carboxymethyl ethyl cellulose, etc.). The materials can be prepared into various dosage forms, including but not limited to tablets, capsules, dripping pills, aerosols, pills, powders, solutions, suspensions, emulsions, granules, liposomes, transdermal agents, buccal tablets, freeze-dried powder injection and the like. Can be common preparation, slow release preparation, controlled release preparation and various microparticle administration systems. For the purpose of shaping the unit dosage form into a tablet, various carriers known in the art can be widely used. Examples of carriers are, for example, diluents and absorbents such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, urea, calcium carbonate, kaolin, microcrystalline cellulose, aluminum silicate, etc.; humectants and binders such as water, glycerin, polyethylene glycol, ethanol, propanol, starch slurry, dextrin, syrup, honey, dextrose solution, acacia slurry, gelatin slurry, sodium carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone, and the like; disintegrants such as dry starch, alginate, agar powder, brown algae starch, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene, sorbitol fatty acid ester, sodium dodecyl sulfonate, methylcellulose, ethylcellulose, and the like; disintegration inhibitors such as sucrose, glyceryl tristearate, cocoa butter, hydrogenated oils and the like; absorption promoters such as quaternary ammonium salts, sodium lauryl sulfate, and the like; lubricants such as talc, silica, corn starch, stearate, boric acid, liquid paraffin, polyethylene glycol, and the like. The tablets may be further formulated into coated tablets, such as sugar coated tablets, film coated tablets, enteric coated tablets, or bilayer and multilayer tablets. For the purpose of formulating the unit dosage form into a pill, various carriers well known in the art can be widely used. Examples of carriers are, for example, diluents and absorbents such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oils, polyvinylpyrrolidone, kaolin, talc, etc.; binding agents such as acacia, tragacanth, gelatin, ethanol, honey, liquid sugar, rice paste or batter, and the like; disintegrants such as agar powder, dry starch, alginate, sodium dodecyl sulfate, methylcellulose, ethylcellulose, etc. For preparing unit dosage forms into injectable preparations such as solutions, emulsions, lyophilized powders and suspensions, all diluents commonly used in the art, for example, water, ethanol, polyethylene glycol, 1, 3-propanediol, ethoxylated isostearyl alcohol, polyoxyisostearyl alcohol, polyoxyethylene sorbitol fatty acid esters, etc. may be used. In addition, in order to prepare an isotonic injection, an appropriate amount of sodium chloride, glucose or glycerin may be added to the preparation for injection, and further, a conventional cosolvent, a buffer, a pH adjuster, and the like may be added. In addition, colorants, preservatives, flavors, flavoring agents, sweeteners, or other materials may also be added to the pharmaceutical formulation, if desired.

The invention also protects the application of ten traditional Chinese medicine raw materials in preparing the medicine for treating primary dysmenorrhea; the ten traditional Chinese medicine raw materials and the proportion thereof are as follows: 5-25 parts of galangal, 10-40 parts of peach kernel, 5-20 parts of fennel, 5-20 parts of angelica dahurica, 10-40 parts of dried orange peel, 10-30 parts of raspberry, 1-5 parts of rose, 1-5 parts of cinnamon and 1-3 parts of saffron.

Specifically, the ten traditional Chinese medicine raw materials and the proportions thereof are as follows: 15-20 parts of galangal, 15-25 parts of peach kernel, 10-12 parts of fennel, 8-10 parts of angelica, 10-15 parts of radix angelicae, 10-18 parts of dried orange peel, 15-20 parts of raspberry, 3-5 parts of rose, 2-4 parts of cinnamon and 1 part of saffron.

The ten traditional Chinese medicine raw materials and the proportions thereof are as follows: 15 parts of galangal, 25 parts of peach kernel, 12 parts of fennel, 8 parts of angelica, 12 parts of angelica dahurica, 18 parts of dried orange peel, 15 parts of raspberry, 3 parts of rose, 3 parts of cinnamon and 1 part of saffron.

The ten traditional Chinese medicine raw materials and the proportions thereof are as follows: 15 parts of galangal, 15 parts of peach kernel, 10 parts of fennel, 10 parts of angelica, 15 parts of angelica dahurica, 12 parts of dried orange peel, 15 parts of raspberry, 5 parts of rose, 4 parts of cinnamon and 1 part of saffron.

The ten traditional Chinese medicine raw materials and the proportions thereof are as follows: 20 parts of galangal, 20 parts of peach kernel, 10 parts of fennel, 10 parts of angelica dahurica, 10 parts of dried orange peel, 20 parts of raspberry, 4 parts of rose, 2 parts of cinnamon and 1 part of saffron.

The traditional Chinese medicine formula comprises the following components: the cinnamon, the fennel, the galangal and the like are adopted as pungent and warm materials Wen Huachong, the peach kernel dredges thoroughfare and conception vessels, and the dried orange peel and the stomach are harmonized and lowered, so that the effects of regulating qi and blood are combined; adopts peach kernel, common fennel fruit, galangal rhizome, basin-covered seed and the like to regulate viscera (liver, kidney and spleen); adopts angelica, saffron, rose and the like to promote blood circulation and remove blood stasis; radix angelicae is adopted to dispel wind and cold, dry dampness and stop leukorrhagia, and has the effect of relieving pain. In conclusion, the product achieves the purposes of warming channels, dispelling cold, promoting blood circulation and removing blood stasis from the aspects of qi and blood and viscera recuperation, relieving pain and treating symptoms, thereby realizing the formula of treating primary dysmenorrhea with urgent symptoms and slow 'both symptoms and root causes', and clinically verifying the effectiveness and safety of the traditional Chinese medicine.

The medicine provided by the invention has a good effect on primary dysmenorrhea, has no adverse reaction, and has industrial popularization value.

Detailed Description

The following detailed description of the invention is provided in connection with the accompanying drawings that are presented to illustrate the invention and not to limit the scope thereof. The examples provided below are intended as guidelines for further modifications by one of ordinary skill in the art and are not to be construed as limiting the invention in any way.

The experimental methods in the following examples, unless otherwise specified, are conventional methods, and are carried out according to techniques or conditions described in the literature in the field or according to the specifications of the products. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified. Beta-cyclodextrin is a product of Huaxing biochemical industry Limited liability company in Monzhou, lot number 20210809. Maltodextrin was available from Shandong West Wang Tangye Co., ltd., lot number 20210622.

The galangal, peach kernel, fennel, angelica dahurica, dried orange peel, raspberry, rose, cinnamon and saffron used as raw materials in the embodiment are all traditional Chinese medicinal materials (dry products), and all meet the relevant regulations under each medicinal material item of a text of Chinese pharmacopoeia (2020 edition). Before feeding, each medicinal material object accords with the name through identification, and the quality accords with the standard.

The rhizoma Alpiniae Officinarum is dried rhizome of rhizoma Alpiniae Officinarum Alpinia officinarum Hance of Zingiberaceae. The Chinese medicinal material semen Persicae is dried mature seed of Prunus persica (L.) Batsch or Prunus davidiana (Carr.) Franch of Rosaceae. The Chinese medicinal material fructus Foeniculi is dried mature fruit of Foeniculum vulgare Foeniculum vulgare Mill of Umbelliferae. The Chinese medicinal material radix Angelicae sinensis is dry root of Angelica sinensis Angelica sinensis (Oliv.) Diels of Umbelliferae. The Chinese medicinal material radix Angelicae Dahuricae is dried root of radix Angelicae Dahuricae Angelica dahurica (Fisch, ex Hoffm.) or radix Angelicae Dahuricae Angelica dahurica (Fisch. Ex Hoffm.) of Umbelliferae. The pericarpium Citri Tangerinae is dried mature fruit skin of Rutaceae plant orange Citrus reticulata Blanco and its cultivar. The Rubi fructus is dry fruit of Rubus chingii Hu of Rosaceae. The Chinese medicinal material flos Rosae Rugosae is dried flower bud of Rosa rugosa Thunb. The Chinese medicinal material cortex Cinnamomi is dried bark of Cinnamomum cassia Cinnamomum cassia Presl belonging to Lauraceae. The Chinese medicinal material stigma croci is dry stigma of Crocus sativus L.

Example 1 obtaining of Chinese herbal formulation

Through a large number of formula optimization and effect verification, the inventor finally obtains the traditional Chinese medicine formula which can be widely applied to primary menstrual pain crowd and has the best effect.

The traditional Chinese medicine formula of the invention is as follows: 5-25 parts of galangal, 10-40 parts of peach kernel, 5-20 parts of fennel, 5-20 parts of angelica dahurica, 10-40 parts of dried orange peel, 10-30 parts of raspberry, 1-5 parts of rose, 1-5 parts of cinnamon and 1-3 parts of saffron.

The specific traditional Chinese medicine formula can be a traditional Chinese medicine formula I, a traditional Chinese medicine formula II or a traditional Chinese medicine formula III.

The first traditional Chinese medicine formula: 15 parts of galangal, 25 parts of peach kernel, 12 parts of fennel, 8 parts of angelica, 12 parts of angelica dahurica, 18 parts of dried orange peel, 15 parts of raspberry, 3 parts of rose, 3 parts of cinnamon and 1 part of saffron.

And a traditional Chinese medicine formula II: 15 parts of galangal, 15 parts of peach kernel, 10 parts of fennel, 10 parts of angelica, 15 parts of angelica dahurica, 12 parts of dried orange peel, 15 parts of raspberry, 5 parts of rose, 4 parts of cinnamon and 1 part of saffron.

And the traditional Chinese medicine formula III: 20 parts of galangal, 20 parts of peach kernel, 10 parts of fennel, 10 parts of angelica dahurica, 10 parts of dried orange peel, 20 parts of raspberry, 4 parts of rose, 2 parts of cinnamon and 1 part of saffron.

Dang Gui is pungent and sweet in nature and warm in nature, and can make blood enter its own place; is a monarch drug. Galangal has the effects of warming stomach and dispelling cold, fennel has the effects of warming kidney and dispelling cold, and Jiao Wen is taken downwards to relieve pain, and two medicines are used together to warm without dryness, dispel cold and warm uterus; is a ministerial drug. The stigma croci is combined with peach kernels to activate blood and dissipate stagnation, break stasis and remove swelling; is an adjuvant drug. Raspberry nourishes liver and kidney, benefits essence and blood, strengthens waist and knee, consolidates primordial qi and assists kidney yang. Dried orange peel, pericarpium Citri Tangerinae, radix Angelicae Dahuricae, cortex Cinnamomi, and cortex Cinnamomi can be used for regulating qi-flowing, relieving restlessness, relieving pain, relieving inflammation, and warming uterus. The rose has the effects of beautifying and promoting blood circulation. The group of herbs are compatible, can move without being blocked, can tonify without being greasy, and has good effect on the constitution of the people with upper heat and lower cold.

Example 2 preparation of Chinese medicinal preparation

1. Preparation of extractum

1. Weighing the powder of each medicinal material according to a second traditional Chinese medicine formula, wherein the specific weight is as follows: weighing 1.8kg of galangal, 1.8kg of peach kernel, 1.2kg of fennel, 1.2kg of angelica, 1.8kg of angelica dahurica, 1.44kg of dried orange peel, 1.8kg of raspberry, 0.6kg of rose, 0.48kg of cinnamon and 0.12kg of saffron, and mixing together. All the medicinal materials are crushed before being weighed, so that the particle size is less than 2.0 mm.

2. The mixture of step 1 was taken, 61.2L of 60% (V/V) aqueous ethanol solution was added, stirred at 200rpm for 60 minutes, and then filtered with a 400-mesh filter, and the filtrate (total 52.3L) was collected.

3. To the residue of step 2, 61.2L of 60% (V/V) aqueous ethanol solution was added, and stirred at 200rpm for 40 minutes, followed by filtration through a 400-mesh sieve, and the filtrate (59.4L in total) was collected.

4. And (3) combining the filtrate obtained in the step (2) and the filtrate obtained in the step (3), and concentrating under reduced pressure (the vacuum degree is 0.1Mpa and the temperature is 70 ℃) until the relative density is 1.03 (the relative density at 60 ℃), thus obtaining an extractum-like product, wherein the total amount of the extractum-like product is 24.5kg.

2. Preparation of granular formulations

Weighing 2.45kg of auxiliary materials (the auxiliary materials consist of 1 part by mass of beta-cyclodextrin and 3 parts by mass of maltodextrin), placing the auxiliary materials into a boiling type granulating dryer, adjusting the temperature of an air inlet to 70-100 ℃, and preheating the auxiliary materials in a boiling bed to 45-60 ℃. And adding the prepared 24.5kg of extractum-shaped product into a feed liquid tank, uniformly stirring, adjusting the atomization pressure to have good atomization effect, and gradually spraying the extractum in the feed liquid tank onto the auxiliary materials boiling in the boiling bed by using a peristaltic pump. After spraying, the product obtained is granular preparation (moisture content is less than or equal to 5%) after drying is continued for about 20 minutes.

A total of 5.02kg of a granular formulation was obtained.

3. Preparation of medicaments

And (3) uniformly mixing 5.02kg of the granular preparation obtained in the step (II) with 12.24kg of brown sugar, and packaging with the packaging specification of 14 g/bag.

Example 3 evaluation of clinical Effect

Dysmenorrhea diagnostic criteria: the women with periodic pain in lower abdomen or lumbosacral pain, even severe syncope, during or before and after menstrual period (within one week) can be diagnosed as dysmenorrhea.

Subject inclusion criteria (inclusion after all criteria were met at the same time): (1) syndrome of cold coagulation and blood stasis; (2) VAS of one day before menstrual period or during menstrual period, which is most painful, is more than or equal to 4; (3) symptoms of dysmenorrhea appear in the period of 3 months before or on the same day as menstrual flow; (4) regular menstrual cycle, 21-35 days, 3-7 days during menstruation; (5) ages 16-35 years (including 16 and 35 years).

Diagnostic criteria for cold coagulation and stasis syndrome:

main evidence: premenstrual or menstrual lower abdomen cold pain refuses to press, and heat pain is reduced;

secondary syndrome: (a) little menstrual blood volume, unsmooth menstruation or after pushing; (b) dark menstrual violet with blobs, reduced bloody pain; (c) soreness of the waist or distension of the anus; (d) pale complexion, aversion to cold and cold limbs;

tongue pulse: dark tongue or with blood stasis points, wiry or deep pulse;

the main syndrome is necessary, and three or more secondary syndromes can be combined with tongue pulse to diagnose.

Subject exclusion criteria (meeting more than one, i.e., exclusion): (1) secondary dysmenorrhea caused by endometriosis, adenomyosis, pelvic inflammatory disease, etc.; (2) analgesic drugs such as non-steroidal anti-inflammatory drugs or other methods of treating dysmenorrhea have been used for the last month; (3) traditional Chinese medicine and Chinese patent medicine with functions of regulating qi and removing blood stasis are used in the last month; (4) has gynecological tumor, uterine disease, abortion history, and gynecological operation history; (5) menstrual cycle is extremely irregular (cycle < 20 days or > 45 days); (6) lactating women or women recently prepared for gestation; (7) other researchers consider unsuitable to participate in the clinical trial of the history of medication, allergy history, serious primary disease, etc.

A total of 30 subjects. The time of the drug effect test is 3 menstrual cycles (taking medicine is started 10+/-1 day before each menstrual cycle according to the prior menstrual cycle, and the medicine is continuously taken until the end of the menstrual cycle (taking medicine for 10 days at most each menstrual cycle) 1 time per day, and the medicine dosage of each subject is 1 bag of the medicine prepared in example 2 (taking medicine after dissolving with hot water).

The pharmacodynamic test was carried out on the previous menstruation (before treatment) and the state, pain duration and changes in symptoms of the traditional Chinese medicine were recorded.

After the drug effect test, one menstruation (after treatment) was completed, the state, pain duration and changes in symptoms of traditional Chinese medicine were recorded.

Adverse reactions and side effects, including the presence or absence of allergic reactions, blood pressure changes, nausea, vomiting, diarrhea edema, were recorded during the efficacy test. The effect of the drug on menstrual period, quantity, color and quality was recorded during the efficacy test.

Dysmenorrhea status and pain duration were treated with Minitab 15 statistical software and the metering data were paired with t-test to

And (3) representing.

1. Evaluation of Total efficacy

After the completion of the drug efficacy test, the drug efficacy was evaluated. The drug effect evaluation is divided into four types of cure, obvious effect, effective and ineffective. And (3) curing: after the drug effect test is finished, the abdominal pain and other symptoms disappear in menstrual period, the drug is not repeated in 3 continuous menstrual periods after stopping, and the pain degree is recovered to be 0. The effect is shown: after the drug effect test is finished, the menstrual abdominal pain is obviously relieved, and the rest symptoms disappear or are relieved. The method is effective: after the drug effect test is finished, the abdominal pain in menstrual period is reduced, and the rest symptoms are improved. Invalidation: after the drug effect test is finished, menstrual abdominal pain and other symptoms are unchanged. The results of the drug efficacy evaluation are shown in Table 1.

Table 1 results of evaluation of efficacy

2. Pain state scoring

The light and heavy grading standard of dysmenorrhea refers to the scoring method in the guidelines of clinical study for treating dysmenorrhea by traditional Chinese medicine. The pain channel symptom scoring criteria are shown in table 2. Severe: the integral is 13-15 minutes. And (3) moderately: the integral is 8-12 minutes. Light: the integration is 5-7 minutes. The results of the subject's score comparisons of pain states before and after treatment are shown in Table 3. The integral of abdominal pain state of the subject after treatment is obviously reduced compared with that before treatment, and the difference has obvious statistical significance (P is smaller than 0.05), which indicates that the abdominal pain degree of the subject after treatment is obviously relieved compared with that before treatment.

TABLE 2 score criteria for dysmenorrhea symptoms

Table 3 subject integral of pain states before and after treatment

Number of examples	Integration before treatment	Post-treatment integration	t	P
					30	9.367±1.217	7.567±1.073	14.84	0.000

3. Abdominal pain duration scoring

Abdominal pain duration score: no (0 min), less than 12h (2 min), 12-24h (4 min), more than 24h (6 min). Abdominal pain duration efficacy evaluation criteria; efficacy index (n) = (pre-treatment abdominal pain duration integral-post-treatment abdominal pain duration)/pre-treatment abdominal pain duration integral x 100%; and (3) curing: more than or equal to 90 percent; the effect is shown: 90% n is more than or equal to 70%; effective rate is 70 percent, n is more than or equal to 30 percent; invalidation: less than 30%. The duration of abdominal pain treatment analysis of the patients after treatment is shown in Table 4. The results of the comparison of the abdominal pain duration scores of the subjects before and after treatment are shown in Table 5. The results show that: the integral of the duration of abdominal pain in the subjects after treatment is significantly reduced compared with that before treatment, and the difference has significant statistical significance (P < 0.05), which indicates that the duration of abdominal pain in the subjects after treatment is significantly reduced compared with that before treatment.

TABLE 4 analysis of duration of treatment efficacy of abdominal pain after treatment

Number of examples	Healing of the wound	Has obvious effect	Effective and effective	Invalidation of	Total effective rate
						30	6	9	13	2	93.67％

Table 5 comparison of abdominal pain duration integral before and after treatment

Number of examples	Integration before treatment	Post-treatment integration	t	P
					30	4.533±1.383	2.400±1.329	23.03	0.000

4. Clinical index of traditional Chinese medicine and analysis of side reaction

Through continuous administration of three continuous menstrual cycles, the symptoms of dysmenorrheal such as little menstrual blood, dark menstrual blood, breast swelling and pain, cold sweat dribbling, nausea and vomiting of the subject are obviously improved. Meanwhile, no obvious side effects such as anaphylaxis, diarrhea edema, blood pressure change and the like are found in the clinical research process.

The present invention is described in detail above. It will be apparent to those skilled in the art that the present invention can be practiced in a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the invention and without undue experimentation. While the invention has been described with respect to specific embodiments, it will be appreciated that the invention may be further modified. In general, this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. The application of some of the basic features may be done in accordance with the scope of the claims that follow.

Claims (3)

1. A traditional Chinese medicine composition for treating cold coagulation stasis type primary dysmenorrhea is prepared from the following traditional Chinese medicine raw materials in parts by mass: 15-20 parts of galangal, 15-25 parts of peach kernel, 10-12 parts of fennel, 8-10 parts of angelica, 10-15 parts of radix angelicae, 10-18 parts of dried orange peel, 15-20 parts of raspberry, 3-5 parts of rose, 2-4 parts of cinnamon and 1 part of saffron.

2. The application of the traditional Chinese medicine composition in preparing a medicine for treating cold coagulation stasis type primary dysmenorrhea, disclosed in claim 1, is characterized in that:

the preparation method of the extract comprises the following steps: mixing the ten traditional Chinese medicine raw materials, and extracting by adopting 60% ethanol solution to obtain an extract;

or preparing the traditional Chinese medicine composition into a granular preparation, wherein the preparation method of the granular preparation comprises the following steps: drying and granulating the extract to obtain granule with water content below 5%.

3. A medicine for treating cold coagulation stasis type primary dysmenorrhea comprises an extract or a granular preparation prepared from the traditional Chinese medicine composition as claimed in claim 1 as an active ingredient;

the preparation method of the extract comprises the following steps: mixing the ten traditional Chinese medicine raw materials, and extracting by adopting 60% ethanol solution to obtain an extract;

the preparation method of the granular preparation comprises the following steps: drying and granulating the extract to obtain granule with water content below 5%.