CN107184906A - Chinese medicine composition for treating dysmenorrhoea and preparation method thereof - Google Patents

Chinese medicine composition for treating dysmenorrhoea and preparation method thereof Download PDF

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CN107184906A
CN107184906A CN201710407617.9A CN201710407617A CN107184906A CN 107184906 A CN107184906 A CN 107184906A CN 201710407617 A CN201710407617 A CN 201710407617A CN 107184906 A CN107184906 A CN 107184906A
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chinese medicine
medicine composition
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王志勇
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王志勇
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/906Zingiberaceae (Ginger family)
    • A61K36/9066Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/235Foeniculum (fennel)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484Glycyrrhiza (licorice)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/486Millettia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537Salvia (sage)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/54Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/66Papaveraceae (Poppy family), e.g. bloodroot
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/89Cyperaceae (Sedge family)
    • A61K36/8905Cyperus (flatsedge)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/53Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

Abstract

The present invention relates to pharmaceutical technology field, and in particular to a kind of to be used to treat Chinese medicine composition of dysmenorrhoea and preparation method thereof.Chinese medicine composition provided by the present invention for treating dysmenorrhoea, selected each taste bulk drug includes great Ye delicate fragrance osmanthus, Radix Angelicae Sinensis, Chinese cassia tree, turmeric, corydalis tuber, bamboo shoot, fennel seeds, the red sage root, rhizoma cyperi, reticulate millettia and radix glycyrrhizae, proportioning is scientific and reasonable, utilize coordinated effect each other, reach warming channel and expelling cold, promoting blood circulation and stopping pain, the regulation of qi and blood, effect of nourishing yin and nourishing blood, the therapeutic effect to dysmenorrhoea can be improved, have the advantages that drug effect rapid, good effect, treat both principal and secondary aspect of disease, have no side effect with it is uneasy to recur.

Description

Chinese medicine composition for treating dysmenorrhoea and preparation method thereof
Technical field
The present invention relates to pharmaceutical technology field, more particularly to a kind of Chinese medicine composition and its preparation side for being used to treat dysmenorrhoea Method.
Background technology
Dysmenorrhoea refers to that women carrys out the pain through the appearance of forward and backward and its intermenstrual period, is a kind of common gynecological disease.Mainly Symptom is underbelly or flank pain, has pendant to keenly feel, with the soreness of waist, or even pain and waist sacrum, severe patient can be with nausea and vomiting, cold sweat It is dripping, cold limbs, or even faint, recurred with menstruation week, have a strong impact on quality of life person, can also influence fertility and heredity.
For lighter dysmenorrhoea patient, hot application or food therapy are generally used, hot-water bottle or ginger brown sugar water is such as used, passes through Blood vessel, clearing and activating the channels and collaterals is expanded, makes smooth muscle relaxation to relieve pain;For heavier dysmenorrhoea patient, then need to take anodyne.Western medicine Mainly to relieve pain as target, generally controlled using such as aspirin, scattered sharp pain, naproxen tablet, brufen anti-inflammatory analgesic medicine Treat, but the medicine such as aspirin, gastric mucosa damage is easily caused, long-term taking, side effect is big, and patient is easily periodically multiple Hair.The traditional Chinese medical science thinks that dysmenorrhoea main pathogenesis is in perverse trend that volt or essence, and menses virtual loss causes the QI-blood circulation of uterus not smooth, " not general rule Bitterly ", but existing treatment by Chinese herbs dysmenorrhoea effect again it is not notable.
The content of the invention
It is an object of the present invention to provide a kind of Chinese medicine composition for being used to treat dysmenorrhoea, selected each taste raw material pack Include great Ye delicate fragrance osmanthus, Radix Angelicae Sinensis, Chinese cassia tree, turmeric, corydalis tuber, bamboo shoot, fennel seeds, the red sage root, rhizoma cyperi, reticulate millettia and radix glycyrrhizae, proportioning section Learn reasonable, acted on using coordinated each other, reach warming channel and expelling cold, promoting blood circulation and stopping pain, the regulation of qi and blood, the work(of nourishing yin and nourishing blood Effect, it is possible to increase to the therapeutic effect of dysmenorrhoea, with drug effect is rapid, good effect, treat both principal and secondary aspect of disease, have no side effect with it is uneasy to recur Advantage.
Another object of the present invention is to provide a kind of preparation method of above-mentioned Chinese medicine composition, the preparation method, operation Simply, it is not necessary to which special installation can farthest retain the medicinal efficacy of each medicinal material.
To achieve the above object, the technical solution adopted by the present invention is:
A kind of Chinese medicine composition for being used to treat dysmenorrhoea, by weight meter includes the following raw material medicine:Great Ye delicate fragrance osmanthus 20- 30 parts, 15-25 parts of Radix Angelicae Sinensis, 7-13 parts of Chinese cassia tree, 8-16 parts of turmeric, 10-20 parts of corydalis tuber, 5-10 parts of bamboo shoot, 5-10 parts of fennel seeds, 5-10 parts of 3-7 parts of the red sage root, 5-10 parts of rhizoma cyperi, 3-7 parts of reticulate millettia and radix glycyrrhizae.
Further, meter includes the following raw material medicine by weight:Osmanthus 22-28 parts of great Ye delicate fragrance, 18-22 parts of Radix Angelicae Sinensis, meat Osmanthus 8-12 parts, 10-15 parts of turmeric, 13-17 parts of corydalis tuber, 6-9 parts of bamboo shoot, 6-9 parts of fennel seeds, 4-6 parts of the red sage root, 6-9 parts of rhizoma cyperi, 6-9 parts of 4-6 parts of reticulate millettia and radix glycyrrhizae.
Further, meter includes the following raw material medicine by weight:25 parts of great Ye delicate fragrance osmanthus, 20 parts of Radix Angelicae Sinensis, 10 parts of Chinese cassia tree, 8 parts of 12 parts of turmeric, 15 parts of corydalis tuber, 8 parts of bamboo shoot, 8 parts of fennel seeds, 5 parts of the red sage root, 8 parts of rhizoma cyperi, 5 parts of reticulate millettia and radix glycyrrhizae.
A kind of preparation method of Chinese medicine composition, comprises the following steps:
(a) decoct:Meter weighs bulk drug by weight, adds water, carries out first time decoction, decoction is filtered out, to residue Water is added in the dregs of a decoction, second is carried out and decocts, filter out decoction;
(b) concentrate:The filtrate filtered out twice is merged, heating concentration is carried out, obtains concentrate;
(c) alcohol precipitation:The concentration that ethanol solution to ethanol are added in the concentrate obtained to step (b) is 75-80%, precipitation Overnight, leaching clear liquid.
Further, first bulk drug is soaked 45-60 minutes in water before being decocted for the first time in the step (a).
Further, when being decocted for the first time in the step (a), the amount for adding water is 7-9 times of bulk drug weight, is decocted Time is 60-80 minutes.
Further, in the step (a) during second of decoction, the amount for adding water is 4-6 times of dregs of a decoction weight, during decoction Between be 70-90 minutes.
Further, the concentrate obtained in the step (b) measures relative density for 1.02-1.08 at 60 DEG C.
Further, in addition to step (d) secondary concentration:The clear liquid that heating concentration step (c) is obtained, obtains paste dense Contracting thing.
Further, the paste concentrate obtained in the step (d), adds the auxiliary material pharmaceutically allowed, is made Pulvis, tablet, pill, capsule and oral liquid.
Compared with prior art, the beneficial effects of the present invention are:
1. provided by the present invention for treat dysmenorrhoea Chinese medicine composition, selected each taste bulk drug include great Ye delicate fragrance osmanthus, Radix Angelicae Sinensis, Chinese cassia tree, turmeric, corydalis tuber, bamboo shoot, fennel seeds, the red sage root, rhizoma cyperi, reticulate millettia and radix glycyrrhizae, proportioning are scientific and reasonable, utilize phase Coordinated effect between mutually, reaches warming channel and expelling cold, promoting blood circulation and stopping pain, the regulation of qi and blood, effect of nourishing yin and nourishing blood, it is possible to increase right The therapeutic effect of dysmenorrhoea, have the advantages that drug effect rapid, good effect, treat both principal and secondary aspect of disease, have no side effect with it is uneasy to recur.
2. the preparation method of the Chinese medicine composition provided by the present invention for treating dysmenorrhoea, simple to operate, it is not necessary to special Equipment can farthest retain the medicinal efficacy of each medicinal material, meanwhile, the auxiliary material pharmaceutically allowed can be added, is made many Plant formulation, such as pulvis, tablet, pill, capsule and oral liquid.
Embodiment
Technical scheme is clearly and completely described below in conjunction with embodiment, it is clear that described reality It is a part of embodiment of the invention to apply example, rather than whole embodiments.Based on the embodiment in the present invention, the common skill in this area The every other embodiment that art personnel are obtained under the premise of creative work is not made, belongs to the model that the present invention is protected Enclose.
Provided by the present invention for treat dysmenorrhoea Chinese medicine composition, selected each taste bulk drug, including great Ye delicate fragrance osmanthus, when Return, Chinese cassia tree, turmeric, corydalis tuber, bamboo shoot, fennel seeds, the red sage root, rhizoma cyperi, reticulate millettia and radix glycyrrhizae, utilize coordinated each other Effect, reaches warming channel and expelling cold, promoting blood circulation and stopping pain, the regulation of qi and blood, effect of nourishing yin and nourishing blood, it is possible to increase to the therapeutic effect of dysmenorrhoea.
Chinese medicine composition provided by the present invention for treating dysmenorrhoea, by weight meter include the following raw material medicine:Great Ye 20-30 parts of delicate fragrance osmanthus, 15-25 parts of Radix Angelicae Sinensis, 7-13 parts of Chinese cassia tree, 8-16 parts of turmeric, 10-20 parts of corydalis tuber, 5-10 parts of bamboo shoot, fennel fruit 5-10 parts of fragrant 5-10 parts, 3-7 parts of the red sage root, 5-10 parts of rhizoma cyperi, 3-7 parts of reticulate millettia and radix glycyrrhizae.
Great Ye delicate fragrance osmanthus, is the dry root in Sarcococca great Ye delicate fragrance osmanthus;It is mild-natured, pungent hardship;Return liver, stomach, with reason Effect of gas analgesic, dispelling, collateral-activating and replenishing blood and nourishing liver, for treating the diseases such as rheumatalgia pain, dizzy palpitaition, traumatic injury.
In the present invention, the typical but non-limiting content in great Ye delicate fragrance osmanthus is:20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 Part, 26 parts, 27 parts, 28 parts, 29 parts or 30 parts.
Radix Angelicae Sinensis, is the dry root of umbelliferae angelica;It is warm-natured, it is sweet, pungent;Return liver, the heart, the spleen channel;With replenishing and activating blood, Menstruction regulating and pain relieving, the effect relaxed bowel;For treat blood deficiency chlorosis, dizziness palpitaition, irregular menstruation, closed dysmenorrhea, asthenia cold abdominalgia, The diseases such as dry constipation of intestines, arthralgia pain due to rheumatism, injury from falling down and ulcer sores.
In the present invention, the typical but non-limiting content of Radix Angelicae Sinensis is:15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 Part, 22 parts, 23 parts, 24 parts or 25 parts.
Chinese cassia tree, is the dry bark of canella Chinese cassia tree;Extremely hot in nature, it is pungent, sweet;Return kidney, spleen, the heart, Liver Channel;It is fiery with mending Supporing yang, guiding fire to origin, eliminating cold to stop pain, effect of warming meridian, for treating impotence Gong Leng, waist and knee crymodynia, deficiency of the kidney and dyspnea, empty sun The disease such as floating, dizziness hot eyes, trusted subordinate's crymodynia, cold of insufficiency type vomiting and diarrhea, cold hernia stomachache and dysmenorrhoea Amenorrhea.
In the present invention, the typical but non-limiting content of Chinese cassia tree is:7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts or 13 parts.
Turmeric, is the dry rhizome of zingiberaceous plant turmeric;It is warm-natured, pungent, hardship;Returns spleen, Liver Channel;With blood-breaking, lead to Effect of meridian and relieving pain, is twinged, the disease such as dysmenorrhoea Amenorrhea, abdominal mass, rheumatism shoulder arm pain and tumbling and swelling for treating chest side of body.
In the present invention, the typical but non-limiting content of turmeric is:8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts or 16 parts.
Corydalis tuber, is the dry tuber of papaveraceae plant corydalis;It is warm-natured, pungent, hardship;Returns spleen, Liver Channel;With Huoxue San " The stasis of blood, effect of regulating qi-flowing for relieving pain, for treating the diseases such as chest side of body epigastric pain, closed dysmenorrhea, postpartum stasis and tumbling and swelling.
In the present invention, the typical but non-limiting content of corydalis tuber is:10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts.
Bamboo shoot, is the rhizome of labiate bamboo shoot and Mao Ye bamboo shoot;It is mild-natured, sweet, pungent;With removing blood stasis and hemostasis, QI invigorating Li Shui effect, for treating under bleeding from five sense organs or subcutaneous tissue, haematemesis, postpartum abdominal pain, jaundice, oedema, band, the disease such as treatment deficiency of vital energy weak.
In the present invention, the typical but non-limiting content of bamboo shoot is:5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts.
Fennel seeds, are the dry mature fruit of samphire fennel;It is warm-natured, it is pungent;Return liver,kidney,spleen, stomach;Have Effect of eliminating cold to stop pain, regulating qi-flowing for harmonizing stomach, for treating cold hernia stomachache, the testis swelling and hanging down of either of the testes, dysmenorrhoea, few abdomen crymodynia, abdominal distention and food The diseases such as few vomiting and diarrhoea.
In the present invention, the typical but non-limiting content of fennel seeds is:5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts.
The red sage root, is the drying root and rhizome of the labiate red sage root;Cold nature, bitter;The thoughts of returning home, Liver Channel;Stop with dissolving stasis Bitterly, invigorate blood circulation, effect of relieving restlessness that clears away heart-fire, for treating irregular menstruation, closed dysmenorrhea, a lump in the abdomen causing distension and pain, chest and abdomen shouting pain, hot numbness pain Bitterly, the disease such as sore swell and ache curative and dysphoria and insomnia.
In the present invention, the typical but non-limiting content of the red sage root is:3 parts, 4 parts, 5 parts, 6 parts or 7 parts.
Rhizoma cyperi, is the dry rhizome of sedge nutgrass flatsedge;It is mild-natured, pungent, slight bitter, micro-sweet;Return liver, spleen, tri-jiao channel;Tool There are promoting qi circulation and removing obstruction in the collateral, menstruction regulating and pain relieving, for treating stagnation of QI due to depression of the liver, abdominal distention, indigestion, chest gastral cavity ruffian, cold hernia abdomen Bitterly, the disease such as swollen breasts, irregular menstruation, closed dysmenorrhea.
In the present invention, the typical but non-limiting content of rhizoma cyperi is:5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts.
Reticulate millettia, is the drying rattan of legume spatholobus suberectus;With blood circulation promoting and enriching, menstruction regulating and pain relieving, the work(stimulated the circulation of the blood and cause the muscles and joints to relax Effect, for treating the diseases such as irregular menstruation, dysmenorrhoea, Amenorrhea, arthralgia pain due to rheumatism, paralysis and numbness and blood deficiency chlorosis.
In the present invention, the typical but non-limiting content of reticulate millettia is:3 parts, 4 parts, 5 parts, 6 parts or 7 parts.
Radix glycyrrhizae, is the dry root and rhizome of glycyrrhizic legume, swollen fruit Radix or glycyrrhiza glabra, mild-natured, sweet;The thoughts of returning home, Lung, spleen, stomach;With invigorating the spleen and benefiting qi, clearing heat and detoxicating, expelling phlegm and arresting coughing, relieving spasm to stop pain, coordinating the drug actions of a prescription, for treat it is weakness of the spleen and the stomach, The diseases such as lassitude hypodynamia, palpitation, coughing with a lot of sputum, gastral cavity abdomen, four limbs contraction, carbuncle sore tumefacting virus.
In the present invention, the typical but non-limiting content of radix glycyrrhizae is:5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts.
In the Chinese medicine composition that the present invention is provided, both great Ye delicate fragrance osmanthus and Radix Angelicae Sinensis are monarch drug in a prescription altogether, with replenishing and activating blood, are changed Effect of stasis of blood analgesic;Chinese cassia tree, turmeric and corydalis tuber three are combined into ministerial drug, help monarch drug in a prescription to play a role, draw logical tendon and vessel, blood-breaking row Gas;Bamboo shoot, fennel seeds and red sage root three are combined into adjutant, and promoting blood circulation and stopping pain strengthens the effect of monarch drug in a prescription and ministerial drug, stasis-dispelling and pain-killing, promoting blood circulation Stimulate the menstrual flow;Rhizoma cyperi, reticulate millettia and radix glycyrrhizae three, which are combined into, makes medicine, draws all medicine channel tropisms and coordinating the drug actions of a prescription.
It should be noted that provided by the present invention for treating the Chinese medicine composition of dysmenorrhoea to dysmenorrhoea good therapeutic effect Determined by its specific raw material components and proportioning, if component and its proportioning be not mutually coordinated, what single component was brought Beneficial effect, it is likely that can be cut down by other components and even eliminate, not have whole synthesis effect.The present invention is ground by substantial amounts of Study carefully and verify repeatedly, obtained the optimum combination and proportioning of Chinese medicine composition so that multiple components are combined, mutually assisted Adjust, produce actively synergy, reach warming channel and expelling cold, promoting blood circulation and stopping pain, the regulation of qi and blood, effect of nourishing yin and nourishing blood so that finally make The Chinese medicine composition obtained has good therapeutic effect to dysmenorrhoea.
As the optional embodiment of the present invention, meter by weight includes the following raw material medicine:Great Ye delicate fragrance osmanthus 22-28 Part, 18-22 parts of Radix Angelicae Sinensis, 8-12 parts of Chinese cassia tree, 10-15 parts of turmeric, 13-17 parts of corydalis tuber, 6-9 parts of bamboo shoot, 6-9 parts of fennel seeds, pellet 6-9 parts of 4-6 parts of ginseng, 6-9 parts of rhizoma cyperi, 4-6 parts of reticulate millettia and radix glycyrrhizae.
As the preferred embodiment of the present invention, meter by weight includes the following raw material medicine:25 parts of great Ye delicate fragrance osmanthus, when Return 20 parts, 10 parts of Chinese cassia tree, 12 parts of turmeric, 15 parts of corydalis tuber, 8 parts of bamboo shoot, 8 parts of fennel seeds, 5 parts of the red sage root, 8 parts of rhizoma cyperi, reticulate millettia 5 8 parts of part and radix glycyrrhizae.
The Chinese medicine composition that the present invention is provided, selected various bulk drugs simultaneously carry out scientific matching, utilize association each other Same mating reaction, reaches warming channel and expelling cold, promoting blood circulation and stopping pain, the regulation of qi and blood, effect of nourishing yin and nourishing blood, it is possible to increase the treatment to dysmenorrhoea Effect, have the advantages that drug effect rapid, good effect, treat both principal and secondary aspect of disease, have no side effect with it is uneasy to recur.
The preparation method for the above-mentioned Chinese medicine composition that the present invention is provided, comprises the following steps:
(a) decoct:Meter weighs bulk drug by weight, adds water, carries out first time decoction, decoction is filtered out, to residue Water is added in the dregs of a decoction, second is carried out and decocts, filter out decoction;
(b) concentrate:The filtrate filtered out twice is merged, heating concentration is carried out, obtains concentrate;
(c) alcohol precipitation:The concentration of the middle addition ethanol solution obtained to step (b) to ethanol is 75-80%, precipitates overnight, Leaching clear liquid.
The purpose that step (a) is decocted is to extract the active ingredient in bulk drug, be extracted aqueous soluble active constituent Into water, but many water-solubility impurities are extracted out simultaneously.
Step (b) concentration purpose be in order to ensure removing impurity of being tried one's best during alcohol precipitation, while reduce loss of effective components and Alcohol consumption quantity, it is therefore desirable to which the decoction after decoction is concentrated to certain density concentrate.
The purpose of step (c) alcohol precipitation is to retain effective ingredient to remove impurity.
In the present invention, first bulk drug is soaked 45-60 minutes in water before being decocted for the first time in step (a), to make original Active ingredient in material medicine can be leached easily.
Soak time is typical in step (a) but non-limiting is:45 minutes, 46 minutes, 47 minutes, 48 minutes, 49 minutes, 50 minutes, 51 minutes, 52 minutes, 53 minutes, 54 minutes, 55 minutes, 56 minutes, 57 minutes, 58 minutes, 59 minutes or 60 points Clock.
In the present invention, the amount that water is added when being decocted for the first time in step (a) is 7-9 times of bulk drug weight, decocting time For 60-80 minutes.
When being decocted for the first time in step (a), the amount for adding water is that the typical but non-limiting multiple of bulk drug weight is:7 Again, 8 times or 9 times.
When being decocted for the first time in step (a), decocting time is typical but non-limiting to be:60 minutes, 61 minutes, 62 minutes, 63 minutes, 64 minutes, 65 minutes, 66 minutes, 67 minutes, 68 minutes, 69 minutes, 70 minutes, 71 minutes, 72 minutes, 73 minutes, 74 minutes, 75 minutes, 76 minutes, 77 minutes, 78 minutes, 79 minutes or 80 minutes.
In the present invention, in step (a) during second of decoction, the amount for adding water is 4-6 times of dregs of a decoction weight, and decocting time is 70-90 minutes.
In step (a) during second of decoction, the amount for adding water is that the typical but non-limiting multiple of dregs of a decoction weight is:4 times, 5 times or 6 times.
In step (a) during second of decoction, decocting time is typical but non-limiting to be:70 minutes, 71 minutes, 72 minutes, 73 minutes, 74 minutes, 75 minutes, 76 minutes, 77 minutes, 78 minutes, 79 minutes, 80 minutes, 81 minutes, 82 minutes, 83 minutes, 84 minutes, 85 minutes, 86 minutes, 87 minutes, 88 minutes, 89 minutes or 90 minutes.
In the present invention, the concentrate obtained in step (b) measures relative density for 1.02-1.08 at 60 DEG C.
In the present invention, step (d) secondary concentration can also be included:The clear liquid that heating concentration step (c) is obtained, obtains thick paste Shape concentrate.
In the present invention, the paste concentrate obtained in step (d) adds the auxiliary material pharmaceutically allowed, pulvis, piece is made Agent, pill, capsule and oral liquid.
In the present invention, pharmaceutically acceptable carrier refers to nontoxic solid-state, semisolid or liquid filler, diluent, buffering Agent, protective agent, preservative, lapping or other pharmaceutical adjuncts.
Embodiment 1
The Chinese medicine composition that embodiment 1 is provided, by weight meter include the following raw material medicine:25 parts of great Ye delicate fragrance osmanthus, when Return 20 parts, 10 parts of Chinese cassia tree, 12 parts of turmeric, 15 parts of corydalis tuber, 8 parts of bamboo shoot, 8 parts of fennel seeds, 5 parts of the red sage root, 8 parts of rhizoma cyperi, reticulate millettia 5 8 parts of part and radix glycyrrhizae.
Follow the steps below preparation:
(a) decoct:Meter weighs bulk drug by weight, adds 8 times of water, soaks 50 minutes, carries out first time decoction, Decocting time is 70 minutes, filters out decoction, and 5 times of water is added into the remaining dregs of a decoction, carries out second and decocts, decocting time is 80 minutes, filter out decoction;
(b) concentrate:The filtrate filtered out twice is merged, heating concentration is carried out, obtains concentrate, is measured at 60 DEG C relative Density is 1.02-1.08;
(c) alcohol precipitation:The concentration that ethanol solution is added in the concentrate obtained to step (b) to ethanol is 78%, is precipitated Night, leaching clear liquid;
(d) secondary concentration:The clear liquid that heating concentration step (c) is obtained, obtains paste concentrate, adds auxiliary material, is made Pulvis.
Embodiment 2
The Chinese medicine composition that embodiment 2 is provided, by weight meter include the following raw material medicine:22 parts of great Ye delicate fragrance osmanthus, when Return 22 parts, 8 parts of Chinese cassia tree, 15 parts of turmeric, 13 parts of corydalis tuber, 9 parts of bamboo shoot, 6 parts of fennel seeds, 6 parts of the red sage root, 9 parts of rhizoma cyperi, reticulate millettia 4 6 parts of part and radix glycyrrhizae.
Preparation method be the same as Example 1.
Embodiment 3
The Chinese medicine composition that embodiment 3 is provided, by weight meter include the following raw material medicine:28 parts of great Ye delicate fragrance osmanthus, when Return 18 parts, 12 parts of Chinese cassia tree, 10 parts of turmeric, 17 parts of corydalis tuber, 6 parts of bamboo shoot, 9 parts of fennel seeds, 4 parts of the red sage root, 6 parts of rhizoma cyperi, reticulate millettia 6 9 parts of part and radix glycyrrhizae.
Preparation method be the same as Example 1.
Embodiment 4
The Chinese medicine composition that embodiment 4 is provided, by weight meter include the following raw material medicine:20 parts of great Ye delicate fragrance osmanthus, when Return 25 parts, 7 parts of Chinese cassia tree, 16 parts of turmeric, 10 parts of corydalis tuber, 10 parts of bamboo shoot, 10 parts of fennel seeds, 3 parts of the red sage root, 5 parts of rhizoma cyperi, reticulate millettia 7 parts and 5 parts of radix glycyrrhizae.
Follow the steps below preparation:
(a) decoct:Meter weighs bulk drug by weight, adds 9 times of water, soaks 45 minutes, carries out first time decoction, Decocting time is 80 minutes, filters out decoction, and 4 times of water is added into the remaining dregs of a decoction, carries out second and decocts, decocting time is 70 minutes, filter out decoction;
(b) concentrate:The filtrate filtered out twice is merged, heating concentration is carried out, obtains concentrate, is measured at 60 DEG C relative Density is 1.02-1.08;
(c) alcohol precipitation:The concentration that ethanol solution is added in the concentrate obtained to step (b) to ethanol is 76%, is precipitated Night, leaching clear liquid;
(d) secondary concentration:The clear liquid that heating concentration step (c) is obtained, obtains paste concentrate, adds auxiliary material, is made Tablet.
Embodiment 5
The Chinese medicine composition that embodiment 5 is provided, by weight meter include the following raw material medicine:30 parts of great Ye delicate fragrance osmanthus, when Return 15 parts, 13 parts of Chinese cassia tree, 8 parts of turmeric, 20 parts of corydalis tuber, 5 parts of bamboo shoot, 5 parts of fennel seeds, 7 parts of the red sage root, 10 parts of rhizoma cyperi, reticulate millettia 3 10 parts of part and radix glycyrrhizae.
Follow the steps below preparation:
(a) decoct:Meter weighs bulk drug by weight, adds 6 times of water, soaks 60 minutes, carries out first time decoction, Decocting time is 60 minutes, filters out decoction, and 6 times of water is added into the remaining dregs of a decoction, carries out second and decocts, decocting time is 90 minutes, filter out decoction;
(b) concentrate:The filtrate filtered out twice is merged, heating concentration is carried out, obtains concentrate, is measured at 60 DEG C relative Density is 1.02-1.08;
(c) alcohol precipitation:The concentration that ethanol solution is added in the concentrate obtained to step (b) to ethanol is 77%, is precipitated Night, leaching clear liquid;
(d) secondary concentration:The clear liquid that heating concentration step (c) is obtained, obtains paste concentrate, adds auxiliary material, is made Pill.
Comparative example 1
The Chinese medicine composition that comparative example 1 is provided, by weight meter include the following raw material medicine:10 parts of great Ye delicate fragrance osmanthus, when Return 30 parts, 5 parts of Chinese cassia tree, 20 parts of turmeric, 5 parts of corydalis tuber, 15 parts of bamboo shoot, 3 parts of fennel seeds, 10 parts of the red sage root, 4 parts of rhizoma cyperi, reticulate millettia 8 12 parts of part and radix glycyrrhizae.
Preparation method be the same as Example 1.
Comparative example 2
The Chinese medicine composition that comparative example 2 is provided, by weight meter include the following raw material medicine:35 parts of great Ye delicate fragrance osmanthus, when Return 10 parts, 15 parts of Chinese cassia tree, 5 parts of turmeric, 25 parts of corydalis tuber, 3 parts of bamboo shoot, 12 parts of fennel seeds, 2 parts of the red sage root, 12 parts of rhizoma cyperi, reticulate millettia 10 parts and 2 parts of radix glycyrrhizae.
Preparation method be the same as Example 1.
Comparative example 3
The Chinese medicine composition that comparative example 3 is provided, the difference with embodiment 1 is not containing great Ye delicate fragrance osmanthus, specifically pressed Parts by weight meter includes the following raw material medicine:20 parts of Radix Angelicae Sinensis, 10 parts of Chinese cassia tree, 12 parts of turmeric, 15 parts of corydalis tuber, 8 parts of bamboo shoot, fennel seeds 8 parts of 8 parts, 5 parts of the red sage root, 8 parts of rhizoma cyperi, 5 parts of reticulate millettia and radix glycyrrhizae.
Preparation method be the same as Example 1.
Effect example clinical test
(1) patient is tested:With reference first to《Gynecology of Chinese Medicine》In diagnostic criteria made a definite diagnosis.Dysmenorrhoea is women on the occasion of warp There is periodicity underbelly pain in phase around menstrual period, or even severe pain causes the person of fainting, and with other not just as mammary swelling, hands Pin is ice-cold etc., so that influence work and life.Married femle excludes life through gynecologial examination, unmarried female through B-mode ultrasonography Grow organ organic disease.
Choose meet above-mentioned standard 200, unmarried 122, married 78;Age is minimum 15 years old, maximum 35 years old;The course of disease - 5 years 6 months.
(2) efficacy assessment standard:
Integrated first by dysmenorrhoea clinical index, by the state of an illness be divided into gently (8 points of <), in (8-13.5 divide), again (13.5 points of >).
Efficacy assessment standard reference《New Chinese medicine guideline of clinical investigations》(the 1st volume), it is specific as follows:
Recovery from illness:Stomachache and other symptoms disappear, and 3 menstrual cycles of being discontinued do not recur, and dysmenorrhoea clinical symptoms integration is 0;
It is effective:Stomachache substantially mitigates, and other symptoms disappear or mitigated, and refuses to obey that anodyne can adhere to work, dysmenorrhoea clinical condition 1/2 integrated before shape integration≤treatment;
Effectively:Stomachache mitigates, and other symptoms are taken a turn for the better, and work, dysmenorrhoea clinical symptoms integration≤treatment can be adhered to by taking anodyne The 1/3 of preceding integration;
It is invalid:Stomachache and other symptoms are without change.
Total effective rate=cure rate+obvious effective rate+effective percentage
(3) test method:
Above-mentioned 200 patients are grouped at random, 10 groups are divided into, are divided into test group 1-5 and control group 1-5, every group 20 patients.
The Chinese medicine composition that test group 1 is prepared using embodiment 1,
The Chinese medicine composition that test group 2 is prepared using embodiment 2,
The Chinese medicine composition that test group 3 is prepared using embodiment 3,
The Chinese medicine composition that test group 4 is prepared using embodiment 4,
The Chinese medicine composition that test group 5 is prepared using embodiment 5,
The Chinese medicine composition that control group 1 is prepared using comparative example 1,
The Chinese medicine composition that control group 2 is prepared using comparative example 2,
The Chinese medicine composition that control group 3 is prepared using comparative example 3,
Control group 4 uses commercially available ibuprofen sustained release capsules;
Control group 5 uses commercially available Nuangong Qiwei pill;
Usage:Once in the morning and once at night taken to patient, each course for the treatment of is one month, takes three courses for the treatment of.
(4) each group is shown in Table 1 to the therapeutic effect of dysmenorrhoea.
Therapeutic effect of each group of table 1 to dysmenorrhoea
From table 1 it follows that the Chinese medicine composition of embodiment 1-5 offers is respectively adopted in test group 1-5, treatment dysmenorrhoea Total effective rate is not less than 80%, in particular by the test group 1-3 of the embodiment 1-3 Chinese medicine compositions provided, treatment dysmenorrhoea Total effective rate, while carrying out follow-up to patient after 6 months, is found without rebound phenomenon up to 90%, and without any adverse reaction.
The Chinese medicine composition that control group 1 and control group 2 are provided using comparative example 1-2, the proportioning that it is constituted is not in the present invention Protection domain in, test group 1-5 is less than to the therapeutic effect of dysmenorrhoea, and there is 1 patient to occur in that adverse reaction, it is seen that The Chinese medicine composition that the present invention is provided determined to dysmenorrhoea good therapeutic effect by its specific raw material components and proportioning, If component and its not mutually coordinated, the beneficial effect that single component is brought of proportioning, it is likely that can be by other components abatement even Eliminate, do not have whole synthesis effect.
The Chinese medicine composition that control group 3 is provided using comparative example 3, it does not contain great Ye delicate fragrance osmanthus, treats always having for dysmenorrhoea Efficiency only has 65%, it is seen that provided by the present invention for treat dysmenorrhoea Chinese medicine composition be to dysmenorrhoea good therapeutic effect by Each raw material components mutually cooperate with common role.
Control group 4 treats the efficient up to 90%, instant effect, energy of dysmenorrhoea using the ibuprofen sustained release capsules of commercially available Western medicine Enough rapid recovery dysmenorrhoeas, but in drug administration process, there are 2 patients to occur in that adverse reaction, at the same patient is carried out after 6 months with Visit, discovery there are 3 Patients on Recurrence.
Control group 5 is treated the efficient than relatively low only 60% of dysmenorrhoea, seen simultaneously using the Nuangong Qiwei pill of commercially available Chinese medicine Effect is slow.
In summary, the Chinese medicine composition that the present invention is provided works well to dysmenorrhea treatment and with security, no secondary anti- Should, while uneasy to recur.
It is exemplified below the effect that several model cases further illustrate the present invention:
Case 1
Chen, female, 23 years old, hypogastralgia unbearably, was on tenterhooks, pale, trick is ice-cold, weak all over, and tongue nature is dark and gloomy Livid purple, while there is the stasis of blood purple, tongue is thin and yellow, and deeptensepulse is puckery, and with vomiting.The Chinese medicine composition of the offer of the embodiment of the present invention 1 is provided, Once in the morning and once at night, continuously take 15 days, menstrual period are normal, follow-up after 6 months, no recurrence.
Case 2
Mr. Wang, female 31 years old, has dysmenorrhoea medical history 2 years, and each menstrual period hurt like hell is taken Western medicine tablet for alleviating pain, can only temporarily delayed Pain is solved, the next menstrual period recurs again.The Chinese medicine composition of the offer of the embodiment of the present invention 2 is taken, once in the morning and once at night, to warp next time It was discontinued before phase, of that month painful menstrual periods mitigate many, after menstrual period terminate, and take medicine 20 days again, are discontinued, 3 menstrual periods are normal, 6 Follow-up after individual month, no relapse.
Case 3
It is high certain, female, 20 years old, during menstrual onset, underbelly pain was more through measuring, and with nausea and vomiting when weighing, accompanies clot.Clothes The Chinese medicine composition provided with the embodiment of the present invention 4, takes, when menstrual period come, pain substantially mitigates, and takes three for premenstrual 5 days Symptom is wholly absent after the course for the treatment of, follow-up after 6 months, no relapse.
Finally it should be noted that:Various embodiments above is merely illustrative of the technical solution of the present invention, rather than its limitations;To the greatest extent The present invention is described in detail with reference to foregoing embodiments pipe, it will be understood by those within the art that:Its according to So the technical scheme described in foregoing embodiments can be modified or which part or all technical characteristic are entered Row equivalent substitution;And these are changed or replace, the essence of appropriate technical solution is departed from various embodiments of the present invention technology The scope of scheme.

Claims (10)

1. a kind of Chinese medicine composition for being used to treat dysmenorrhoea, it is characterised in that meter includes the following raw material medicine by weight:Great Ye 20-30 parts of delicate fragrance osmanthus, 15-25 parts of Radix Angelicae Sinensis, 7-13 parts of Chinese cassia tree, 8-16 parts of turmeric, 10-20 parts of corydalis tuber, 5-10 parts of bamboo shoot, fennel fruit 5-10 parts of fragrant 5-10 parts, 3-7 parts of the red sage root, 5-10 parts of rhizoma cyperi, 3-7 parts of reticulate millettia and radix glycyrrhizae.
2. Chinese medicine composition according to claim 1, it is characterised in that meter includes the following raw material medicine by weight:Greatly It is osmanthus 22-28 parts of leaf delicate fragrance, 18-22 parts of Radix Angelicae Sinensis, 8-12 parts of Chinese cassia tree, 10-15 parts of turmeric, 13-17 parts of corydalis tuber, 6-9 parts of bamboo shoot, small 6-9 parts of 6-9 parts of fennel, 4-6 parts of the red sage root, 6-9 parts of rhizoma cyperi, 4-6 parts of reticulate millettia and radix glycyrrhizae.
3. Chinese medicine composition according to claim 1, it is characterised in that meter includes the following raw material medicine by weight:Greatly 25 parts of leaf delicate fragrance osmanthus, 20 parts of Radix Angelicae Sinensis, 10 parts of Chinese cassia tree, 12 parts of turmeric, 15 parts of corydalis tuber, 8 parts of bamboo shoot, 8 parts of fennel seeds, 5 parts of the red sage root, 8 parts of 8 parts of rhizoma cyperi, 5 parts of reticulate millettia and radix glycyrrhizae.
4. the preparation method of the Chinese medicine composition as described in claim any one of 1-3, it is characterised in that comprise the following steps:
(a) decoct:Meter weighs bulk drug by weight, adds water, carries out first time decoction, decoction is filtered out, to the remaining dregs of a decoction In add water, carry out second and decoct, filter out decoction;
(b) concentrate:The filtrate filtered out twice is merged, heating concentration is carried out, obtains concentrate;
(c) alcohol precipitation:The concentration that ethanol solution is added in the concentrate obtained to step (b) to ethanol is 75-80%, is precipitated Night, leaching clear liquid.
5. preparation method according to claim 4, it is characterised in that first by original before being decocted for the first time in the step (a) Material medicine soaks 45-60 minutes in water.
6. preparation method according to claim 4, it is characterised in that when being decocted for the first time in the step (a), adds water Amount be 7-9 times of bulk drug weight, decocting time is 60-80 minutes.
7. preparation method according to claim 4, it is characterised in that in the step (a) during second of decoction, adds water Amount be 4-6 times of filter residue weight, decocting time is 70-90 minutes.
8. preparation method according to claim 4, it is characterised in that the concentrate obtained in the step (b) is at 60 DEG C Under measure relative density for 1.02-1.08.
9. the preparation method according to claim any one of 4-8, it is characterised in that also including step (d) secondary concentration:Plus The clear liquid that hot concentration step (c) obtains, obtains paste concentrate.
10. preparation method according to claim 9, it is characterised in that the paste concentration obtained in the step (d) Thing, adds the auxiliary material pharmaceutically allowed, pulvis, tablet, pill, capsule and oral liquid is made.
CN201710407617.9A 2017-06-02 2017-06-02 Chinese medicine composition for treating dysmenorrhoea and preparation method thereof Pending CN107184906A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113694173A (en) * 2021-10-19 2021-11-26 山东大学 Traditional Chinese medicine composition for treating dysmenorrhea and preparation method and application thereof

Non-Patent Citations (2)

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Title
刘雁等: "针药结合治疗寒凝血瘀型原发性痛经24例疗效观察", 《山东中医杂志》 *
谢文英: "《很灵的老偏方验方治病一本通》", 31 October 2014, 科学技术文献出版社 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113694173A (en) * 2021-10-19 2021-11-26 山东大学 Traditional Chinese medicine composition for treating dysmenorrhea and preparation method and application thereof

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Application publication date: 20170922