CN1803167A - Pharmaceutical composition mainly treating emmeniopathy and post partum disease, and its formulation and uses - Google Patents
Pharmaceutical composition mainly treating emmeniopathy and post partum disease, and its formulation and uses Download PDFInfo
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Abstract
The invention discloses a pharmaceutical composition for treating menopathy and post partum diseases, which is prepared from Chinese medicinal herbs including motherwort, Chinese angelica root, Ligusticum wallichii, root of herbaceous peony, prepared rehmannia and astragalus root.
Description
Technical field:
The invention belongs to Chinese medicine development field, the pharmaceutical composition and preparation and the purposes that relate to a kind of mainly treating emmeniopathy and puerperal disease, be specifically related to a kind of promoting blood flow to regulate menstruation that has, promoting tissue regeneration by removing blood stasis, promoting the circulation of QI to relieve pain, the pharmaceutical composition of effects such as blood-supplementing blood-nourishing, said composition is by Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, the extract of Radix Rehmanniae Preparata and Radix Astragali Six-element Chinese crude drug is formed, this preparation of drug combination technology and suitable preparation have been the invention still further relates to, and in the treatment menoxenia, the dysmenorrhea amenorrhea, menopathys such as metrorrhagia and metrostaxis, postpartum stagnation pain, puerperal asthenia, puerperal blood faints, puerperal disease such as postpartum lochiorrhea, and the big product of women, abortion, artificial abortion's postoperative, put the vagina abnormal bleeding behind the intrauterine device, the hemorrhage dripping application that waits not to the utmost in the complication.
Background technology:
Motherland's traditional medicine thinks that human body is a basis with internal organs, meridians, is usefulness with the QI and blood.Women's physiological characteristics has also determined the specificity of women's pathological changes simultaneously: warp, band, tire, product all can be disease.The women is usefulness based on blood with blood, qi being the governor of blood, and the capable then blood of gas is capable, and therefore the stagnation of QI is blood stasis then, has only QI and blood full, the blood vessels circulation, the uterus sea of blood could the main menstruation of normal performance, main physiological function such as breed.In woman month menstrual period, pregnancy period, puerperal, the QI-blood circulation that any reason causes is not smooth especially, and the blood-vessel obstructive uterus all can cause the many diseases of women.
Menopathy is gynecological's common disease, and its cause of disease has diseases caused by exogenous pathogenic factor and two aspects of internal injury, and diseases caused by exogenous pathogenic factor are based on cold, heat, wet, and internal injury is in the majority with melancholy, think of, compassion, cool person, and these factors often cause disorder of QI and blood, dashes, wantonly two arteries and veins are impaired, generation menstruation disease.Menopathy mainly comprises diseases such as menoxenia, dysmenorrhea, amenorrhea, metrorrhagia.Menoxenia is meant cycle, the menstrual period of menstruation, a class disease of menoxenia.Comprise that preceeded menorrhea, delayed menstrual cycle, irregular menstrual period, menostaxis, menorrhagia, hypomenorrhea, color and luster are purple black or light red, thick or thin etc. through blood concentration.The women before and after the menstruation or menstrual period, lower abdomen or flank pain, even severe pain is unbearably, and, claim abdominal pain during menstruation again along with menstrual cycle continues and outbreak is dysmenorrhea.Motherland's traditional medicine thinks that the mechanism that dysmenorrhea produces is that passages through which vital energy circulates is unfavorable, due to QI-blood circulation is not smooth.Normal person's QI and blood abundance, gas along blood and, dysmenorrhea can not take place; Opposite to deficiency of vital energy insufficiency of blood, qi depression to blood stasis causes through capable unsmooth stagnation of QI and blood may bring about pain.Amenorrhea is meant that the women should have menstruation but surpasses the specified time person of not rising yet.After prepuberty, trimester of pregnancy, age of sucking and menopause except the menolipsis person.Be recorded in the earliest in the Chinese medicine in " interior ask the negative and positive another matter through element ", be referred to as " morbid amenorrhea ", " amenorrhea ", " blood depletion " etc., the cause of disease can be divided into the deficiency and excess two ends, empty person, and deficiency of the liver and kindey, deficient qi and blood, sea of blood inanition, deficiency of YIN blood is dry, and depletion of blood can descend; Reality person, qi depression to blood stasis, stagnation of cold-damp and to cause water channel obstructed, menses must not be descending.The women bleeds profusely menstrual period, or lasting hematochezia, and dripping urine endlessly is called " metrorrhagia ".Amount of bleeding is many, and the more anxious person of the oncoming force is called " collapsing "; Few and the longer duration of amount of bleeding, the slow person of the oncoming force is called " leakage ".Collapse and leak and can transform mutually, its reason mainly is to have heat, stagnation of blood stasis etc. to cause dash appointing impaired in spleen deficiency of kidney-QI, the blood, does not fall ill and the sea of blood is solid.Irregular vagina bleeding as dysfunctional uterine hemorrhage (anovulatory dysfunctional uterine hemorrhage), female sex organs inflammation, tumor etc. occur all belongs to the metrorrhagia category.
The puerperal disease multiple deficiency and stasis.The promotion of process need gas of childbirth, most women are through after the childbirth that reaches surplus in the of ten hour, and virtual images such as spontaneous perspiration, aversion to cold appear in consumption gas thin fluid injury, so how empty puerperal is, it is main also working as tonify deficiency, is just containing then heresy and is going; Not only since after the childbirth but need gas take the photograph the blood hemostasis, hemopoietic returns to the past, and transfers by the suitable rest, food and drink of puerpera and mends, the gas of consumption wounds is gradually again.But if delivery time is long or prolonged labor or plain bromhidrosis void or puerperal the labour feel frustrated then empty person is more empty, deficiency of vital energy blood loses astringency inducing then haemophilia, dripping urine endlessly.Some multiple pregnancies particularly, weak and age greater than the sickness rate of person's puerperal disease more than 30 years old apparently higher than gestation first, strong and the young women of body, fecund many births consumption impairment of QI blood, plain bromhidrosis void or age are excessive, insufficiency of generating and transforming QI and blood all can cause the deficiency of vital energy in puerperal, blood loses and has under one's command and haemophilia, the hemorrhage gas that causes again is with hematochezia, forms the vicious cycle of the deficiency of vital energy-hemorrhage-deficiency in both Qi and blood, final blood deficiency QI prostration and cause postpartum hemorrhage, puerperal blood faints etc., to show as the vaginal hemorrhage amount clinical many more, have a dizzy spell pale complexion, cardiopalmus, muddled vexed discomfort, gradually to dusk not knowing the people, extreme cold of the limbs, cold sweat hands such as spread at deficient syndrome.Under the normal condition, puerperal, uterus self was constantly discharged the turbid liquid of surplus blood, made blood stasis go, hemorrhage ending and the involution of uterus, old removing and tissue regeneration promoting.But if the plain bromhidrosis void of puerpera, or when producing thin fluid injury, vessels of the whole body being deficient, susceptible exopathogen more then cause stagnant blood instantly not down, residual, the blood-stasis internal-depression of deteriorated blood, promptly the deficiency of vital energy causes the stasis of blood, clinically shows as postpartum lochiorrhea more, doctor trained in Western medicine is also referred to as subinvolution of uterus.The traditional Chinese medical science thinks that lochia is to be old blood, and unnecessary blood belongs to blood circulating out of vessels.Tang Rongchuan " treatise on blood trouble ": " all blood circulating out of vessels and flourish blood of supporting the whole body have separated exhausted and have not conformed to, and this blood can not be added on blood at body, and the change machine of anti-drag fresh blood does not go, and then blood is more than, and old blood does not go, and fresh blood is living." blood stasis do not go, the absurd row of fresh blood, the blood that absurd capable arteries and veins is outer stops to form the stasis of blood again, and the promptly hemorrhage one-tenth stasis of blood is so blood stasis-hemorrhage-blood stasis becomes second vicious cycle of puerperal disease again.Void then passages through which vital energy circulates lose to be supported and QI-blood circulation is not smooth; Then QI and blood retardance and not smooth of the stasis of blood, QI and blood is obstructed and produce pain, causes antalgesic in puerperal such as the common puerperal abdonimal pain of puerperal disease.In addition, the vagina abnormal bleeding of women at big product, abortion, artificial abortion's postoperative, after putting intrauterine device, also mostly is because " blood stasis does not go, fresh blood must not return through ", absurd row of blood circulating out of vessels or multiple infection are among the stasis of blood resistance born of the same parents, due to the menoxenia due to disturbance of CHONG meridian.As mentioned above, QI-blood circulation is not smooth, the blood-vessel obstructive uterus is women's menopathy, puerperal disease and artificial abortion's art, put the principal element of diseases such as abnormal vaginal bleeding behind the intrauterine device, and blood circulation promoting and blood stasis dispelling, promoting the circulation of QI to relieve pain, passage, nourishing blood are the main principle of the above-mentioned disease of treatment.
We are to the name side in ancient times of a large amount of treatment gynaecopathias, carried out deep research and discussion through proved recipe, deep understanding the marrow of Chinese medicine gynaecopathia, the principles of formulating prescriptions and the determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs principle for the treatment of this type of disease have been held comprehensively, use for reference the modern pharmacological research achievement of Chinese crude drug simultaneously, according to the requirement of modernization of Chinese medicine development prescription again.We study nearly thirty or forty flavor Chinese crude drug, with them according to the mutual composition of prescription of theory of Chinese medical science, and by a large amount of modern pharmacology experiment carrying out pharmacodynamics checkings, in the hope of determine the foundation of prescription as us with best effect experiment result.For this reason, our prescription is constantly adjusted, is optimized under the theoretical and a large amount of animal pharmacology of Chinese traditional treatment, pharmacodynamic experiment result's guidance.By unremitting for many years research, finally we find to select Chinese crude drug Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, Radix Rehmanniae Preparata and Radix Astragali composition of prescription for use, and the treatment that is used for gynaecologic emmeniopathy, puerperal disease has beyond thought therapeutic effect.But this prescription is promoting blood flow to regulate menstruation, promoting tissue regeneration by removing blood stasis both, but promoting the circulation of QI to relieve pain, blood-supplementing blood-nourishing again, can be widely used in menopathys such as menoxenia, dysmenorrhea amenorrhea, metrorrhagia and metrostaxis, puerperal puerperal disease such as abdominal pain due to blood stasis, postpartum hemorrhage, puerperal blood faints, postpartum lochiorrhea and complication treatment.
Summary of the invention:
The object of the present invention is to provide a kind of Chinese medicine compound that women's menopathy, puerperal disease is had definite therapeutic effect, this compound recipe is made up of Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, Radix Rehmanniae Preparata and Radix Astragali Six-element Chinese crude drug compatibility, has effects such as promoting blood flow to regulate menstruation, promoting tissue regeneration by removing blood stasis, promoting the circulation of QI to relieve pain, blood-supplementing blood-nourishing.
Further purpose of the present invention is to provide the preparation method and the suitable pharmaceutical dosage form of aforementioned pharmaceutical compositions.
Another purpose of the present invention is to provide this pharmaceutical composition in menopathys such as preparation treatment menoxenia, dysmenorrhea amenorrhea, metrorrhagias, puerperal, puerperal disease such as abdominal pain due to blood stasis, postpartum hemorrhage, lochia and miscarriage, artificial abortion's postoperative, was put the application in the medicine of the diseases such as abnormal vaginal bleeding that cause behind the intrauterine device.
The active component of the medicine of the women's of curing mainly menopathy provided by the invention, puerperal disease is to extract medicinal component to combine from Chinese crude drug Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, Radix Rehmanniae Preparata and the Radix Astragali, comprising the ethanol extract of medical material and water extract at interior multiple medicinal component.The extract of this six medicaments can derive from crude drug or tcm and herbal slice.
The medicine that cures mainly female diseases of the present invention is promptly gone up the suitable pharmaceutical excipient of acceptable by said extracted thing and physiology and is formed.Dosage form of the present invention mainly is the oral formulations on the pharmaceutics, comprises tablet such as ordinary tablet, slow releasing tablet, controlled release tablet, dispersible tablet, oral cavity disintegration tablet etc., and hard capsule, soft capsule, granule, pill, drop pill, oral liquid etc.
Following detailed will help further to understand the present invention.
Herba Leonuri: or its crude drug, be the herb of labiate Herba Leonuri (Leonurus japonicus Houtt.) and Herba Leonuri Sibirici (Leonurus sibiricus L.), the beginning is stated from " herbal classic ", classifies as top grade.Its acrid in the mouth, little hardship, nontoxic, main effect is promoting blood flow to regulate menstruation, promoting tissue regeneration by removing blood stasis, inducing diuresis to remove edema, is the clinical medicine commonly used of TCM Gynecology, puts down in writing as " Chinese medicine voluminous dictionary ": " control menoxenia, vaginal bleeding during pregnancy difficult labour, retention of placenta, puerperal blood faints, abdominal pain due to blood stasis, metrorrhagia and metrostaxis." have a title of " blood man panacea ", " multiparity good medicine ".
Radix Angelicae Sinensis: or its crude drug, be the root of umbelliferae angelica [Angelica sinensis (Oliv.) Diels] or the tcm and herbal slice of making, the head that is used as medicine is stated from " herbal classic ", and sweet in the mouth, suffering, hardship are warm in nature.What always be regarded as treating the blood system disease will product, gynecological's good medicine particularly, the effect that mainly contains blood circulation promoting and enriching, menstruction regulating and pain relieving, moisturizes laxation.This product is used very extensive in the treatment of gynaecopathia, before all menoxenias, amenorrhea, stomachache, metrorrhagia, leukorrhagia and the tire puerperal all diseases, all available it.Because it is widely used, so the reputation of " ten side's rules for doing division with a one-digit divisor on the abacus ", " king of medicine " is arranged.As record in " book on Chinese herbal medicine just " " Radix Angelicae Sinensis, its sweet in the mouth and weigh, so specially can enrich blood, its gas gently and suffering, so again can promoting the circulation of blood.Invigorating middle warmer has, in the row benefit is arranged, the gas medicine in the sincere blood, and also the panacea in the blood is also.”
Rhizoma Chuanxiong: or its crude drug, be meant the samphire Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.[L.wallichiiauct.non Franch.] tcm and herbal slice of rhizome or its making, the head that is used as medicine is stated from " herbal classic ", classify as top gradely, have the effect of blood circulation promoting and blood stasis dispelling, activating QI to alleviate the depression, wind-expelling pain-stopping; In addition, the effect of qi-supplementing, blood-engendering is also arranged, and can rise with compatibility of drugs, decline, interior, reach outward, penetrate everywhere.Rhizoma Chuanxiong is main effect with blood circulation promoting and blood stasis dispelling, but its gas is hot fragrant, kind energy circulation of qi promoting again.The circulation of qi promoting of Rhizoma Chuanxiong and the merit of invigorating blood circulation are complementary, have circulation of qi promoting concurrently among invigorating blood circulation, circulation of qi promoting is double be sandwiched in invigorate blood circulation among, be called " gas medicine in the blood " as Li Shizhen (1518-1593 A.D.)." book on Chinese herbal medicine converges and says ": " following regulating menstruation water, middle relieving stagnation." so the kind stagnation of QI and blood disease of controlling, particularly gynecological's common drug is widely used in diseases such as menoxenia, amenorrhea dysmenorrhea, the stagnant stomachache of the stasis of blood in puerperal, gets the merit of its blood-activating and qi-promoting, unobstructed QI and blood.
The Radix Paeoniae Alba: or its crude drug, be meant the root of Paeoniaceae plant peony (Paeonia lactiflora Pall.) and comospore Radix Paeoniae [P.lactiflora Pall.Var.trichocarpa (Bunge) Stern] or the tcm and herbal slice of its making, beginning is stated from Shennong's Herbal, classifies middle product as." book on Chinese herbal medicine just ": " mildly bitter flavor, little sweet, slightly acid, property is quite cold." Radix Paeoniae Alba nourishes blood and seek relieving spasm to stop pain, yin fluid astringing easing the affected liver.The Radix Paeoniae Alba " special promoting the circulation of blood sea; married woman's regulating menstruation tire produces; ... know the QI and blood regulating that should use ", so menoxenia, no matter cold and heat, but equal adapted Radix Paeoniae Alba, clinical syndrome of deficiency of blood, the syndrome of yin deficiency and blood heat of can be used for, and the menoxenia due to blood deficiency or the deficiency of YIN heat in blood, abdominal pain during menstruation, diseases such as metrorrhagia and metrostaxis, puerperal abdonimal pain.
Radix Rehmanniae Preparata: or its crude drug, be meant the tuber of scrophulariaceae rehmannia glutinosa plant [Rehmannia glutinosa (Gaertn.) Libosch exFisch.et Mey.], steam to shine through processing and form.Sweet in the mouth is warm in nature, returns liver, kidney channel, the effect that has the YIN nourishing of enriching blood, transfers beneficial Rong Wei, control dash appoint deficient, irregular amenorrhea; umbilicus abdomen Xu pain, metrorrhagia and metrostaxis, the abdominal mass due to blood stasis piece is hard, sends out the pain of having a rest, gestation Su Leng, blood take advantage of a weak point in opponent's defence down more than and puerperal, retention of lochia, the weak all diseases of women's blood deficiency gas such as the lower abdomen being hard and pain.
The Radix Astragali: or its crude drug is meant the root of leguminous plant Radix Astagali (Astragalus membranaceus BungeVar.mongholicus[Bunge] P.K.Hsiao) or Radix Astragali (Astragalus membranaceus[Fisch.] Bunge.) or the tcm and herbal slice of making.The Radix Astragali, the original name Radix Astragali, the beginning is stated from Shennong's Herbal, classifies as top grade.Radix Astragali sweet in the mouth, warm in nature, its nourishing qi to stop, hemopoietic are supported battalion, can make gas congested solid, and Yin grows while yang is generating is subjected to the attention of ancient Chinese medicine doctor, and clinical practice is very extensive.As record in " solar corona ": " Radix Astragali helps the gas strengthening bone and muscle, and the ， Po Disorder addiction of enriching blood of putting on flesh is controlled scrofula ... metrorrhagia, leukorrhagia, dysentery with red and white feces, all diseases of antenatal back, month wait irregular ... Akamu etc." the sweet temperature compensation gas of the Radix Astragali, then blood is prosperous for gas foot, so this product is normal and the same usefulness of key medicine Radix Angelicae Sinensis of enriching blood, with qi-supplementing, blood-engendering, is usually used in treatment of conditions due to the deficiency of both QI and blood.
Prescription of the present invention is made up of Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, Radix Rehmanniae Preparata, Radix Astragali Six-element Chinese crude drug compatibility, and wherein the monarch drug Herba Leonuri is kind wanders away, clots absorbing and do not hinder newly, and beneficial blood and not being detained has the merit of promoting blood circulation to restore menstrual flow, promoting tissue regeneration by removing blood stasis.The sweet benefit of Radix Angelicae Sinensis is hot looses, hardship rushes down that temperature is logical, matter profit and be bored with, the power of invigorating blood circulation is arranged in nourishing blood, and the empty blood stasis of kind hemostasis bitterly; The hot temperature of Rhizoma Chuanxiong and dry, be good at walking, have the merit of blood-activating and qi-promoting, wind-expelling pain-stopping, the two is ministerial drug altogether, wherein Radix Angelicae Sinensis relatively nourishes blood and blood, and Rhizoma Chuanxiong is partial to the diffusing blood of circulation of qi promoting, the two phase 5, invigorate blood circulation, nourish blood, the promoting the circulation of blood three develops simultaneously, and moisturize Ji mutually, but the profit Rhizoma Chuanxiong (processed) suffering of Radix Angelicae Sinensis is dry, Rhizoma Chuanxiong is hot dry can prevent that again Radix Angelicae Sinensis is greasy, make blood stasis dispelling and wasting QI-blood not, nourish blood and exempt from hyperamization and stop up the stagnation of QI, play blood circulation promoting and blood stasis dispelling altogether, nourish blood and the merit of blood the effect of more apparent blood-activating and qi-promoting, stasis-dispelling and pain-killing.The Radix Paeoniae Alba is nourished blood and battalion, relieving spasm to stop pain, yin fluid astringing easing the affected liver, relatively convergence; Radix Rehmanniae Preparata enrich blood YIN nourishing, transfer beneficial Rong Wei; The sweet tepor of Radix Astragali nature and flavor is good at QI invigorating, is longer than yang invigorating again, and three medicines are adjuvant drug altogether.Full side's compatibility has the effect of promoting blood flow to regulate menstruation, promoting tissue regeneration by removing blood stasis, promoting the circulation of QI to relieve pain, blood-supplementing blood-nourishing, can be used for the treatment of menopathys such as menoxenia, dysmenorrhea amenorrhea, metrorrhagia and metrostaxis, puerperal puerperal disease and women's miscarriage, artificial abortion's postoperative such as abdominal pain due to blood stasis, postpartum hemorrhage, puerperal blood faints, postpartum lochiorrhea, put the vagina abnormal bleeding that causes behind the intrauterine device, the hemorrhage dripping complication that waits not to the utmost.
Compositions origin of the present invention comes from the extract of Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, Radix Rehmanniae Preparata and Radix Astragali Six-element Chinese crude drug in specific " proportion " to be formed, and the consumption proportion scope of Six-element medical material is: Herba Leonuri 10-40g, Radix Angelicae Sinensis 5-30g, Rhizoma Chuanxiong 5-30g, Radix Paeoniae Alba 5-20g, Radix Rehmanniae Preparata 5-20g, Radix Astragali 5-20g; Optimum ratio is Herba Leonuri 15g, Radix Angelicae Sinensis 10g, Rhizoma Chuanxiong 10g, Radix Rehmanniae Preparata 8g, Radix Paeoniae Alba 8g, Radix Astragali 10g.Pharmaceutical composition of the present invention mainly comprises that by the extract of above-mentioned Six-element medical material the medicinal component of ethanol extract and water extract forms, and its preparation method is as described below:
(1) crude drug Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, Radix Rehmanniae Preparata and the Radix Astragali are carried out selected, clean, oven dry pulverizes;
(2) the powder adding 4-10 that step (1) is obtained doubly measures soak with ethanol 1-2 days of 60-95%, preferred 90% ethanol, after the filtration medicinal residues are soaked twice again, each soak time 1-2 days, filter, medicinal residues are standby, and the filtrate after three times are soaked merges, concentrate and reclaim ethanol, concentrate drying and grinding under vacuum promptly gets desired ethanol extract;
(3) add 4-12 water doubly in the medicinal residues of step (2) gained, decoct under 60-90 ℃ water temperature, preferred 70 ℃ water temperature decocted 2-3 hour, after the filtration, medicinal residues decoct 2 times again, time 1-1.5 hour, filter, discard medicinal residues, three water extracts are merged;
(4), grind and promptly get desired water extract with the water extract concentrating under reduced pressure drying of step (3) gained;
(5) ethanol extract of step (2) gained and the water extract of step (4) gained are merged, fully mixing promptly gets the used compound extract of the present invention.
The present invention also proposes to go up the Pharmaceutical composition that the acceptable pharmaceutical excipient is formed by said extracted thing and physiology.Except that adding pharmaceutical excipient, effective ingredient, effective site, synthetic or the semi-synthetic that can also add other are as medicine in the process of making dosage form.The dosage form of this medicine mainly is an oral formulations, comprises tablet such as ordinary tablet, slow releasing tablet, controlled release tablet, dispersible tablet, oral cavity disintegration tablet etc., and hard capsule, soft capsule, pill, granule, drop pill, oral liquid etc.
Compare with prior art, this product has following novelty and advance on the whole: at first, from the compatibility of drugs aspect, this product is under the guidance of and modern pharmacology result of study theoretical in Chinese traditional treatment, to tens flavor Chinese crude drugs screen, optimum organization, final determine to carry out compatibility by Six-element Chinese medicine.The monarch drug Herba Leonuri is kind in the side wanders away, and has the merit of promoting blood circulation to restore menstrual flow, promoting tissue regeneration by removing blood stasis; Radix Angelicae Sinensis is kind can blood circulation promoting and enriching and blood nourishes blood, kind pain relieving again, and three arteries and veins are dashed, appoint, are with in conditioning, strengthen the effect of blood circulation promoting and blood stasis dispelling, and it is logical that other adds the hot temperature of loosing of Rhizoma Chuanxiong, gets its blood-activating and qi-promoting, the merit of unobstructed QI and blood, and increase the effect of Radix Angelicae Sinensis promoting tissue regeneration by removing blood stasis, the two is ministerial drug altogether; The Radix Paeoniae Alba is nourished blood and battalion, relieving spasm to stop pain, yin fluid astringing easing the affected liver; Radix Rehmanniae Preparata enrich blood YIN nourishing, transfer beneficial Rong Wei; Reenter Radix Astragali QI invigorating, yang invigorating, tonify deficiency, consolidating superficial resistance, three medicines are adjuvant drug altogether.The full side's compatibility of six medicines is played multiple efficacies such as promoting blood flow to regulate menstruation, promoting tissue regeneration by removing blood stasis, promoting the circulation of QI to relieve pain, blood-supplementing blood-nourishing altogether.The used medicine of this product is all the common drug of successive dynasties treatment gynaecopathia, six medicine compatibilities, both avoided big compound recipe to go into the various deficiency of flavour of a drug number, demonstrated fully the scientific and reasonable compatibility of modern Chinese medicine, simultaneously also meet the selected drug effect of Chinese traditional treatment disease and complement each other, the characteristics of performance comprehensively regulating effect; Secondly, this product adopts the extraction process of modern Chinese medicine that the medicinal ingredient in the Six-element Chinese crude drug is extracted, remove useless impurity, change shortcomings such as the Chinese medicine conventional formulation is thick, big, black simultaneously, adopted oral formulations such as capsule in the medicine modern formulation, tablet, taking dose is little, and is easy to carry, accepted by the patient easily, complied with the requirement of modernization of Chinese medicine development; Once more, from the curative effect aspect, the selected medicine of this product all is the significant medicines of effect that screen from Chinese medicine, preferably come out, and is the good medicine of diseases such as ancient Chinese medicine doctor treatment menoxenia, amenorrhea dysmenorrhea, puerperal abdonimal pain; We have made a large amount of animal experimental models in R﹠D process of the present invention, carried out the research of pharmacology, pharmacodynamics, the zoopery result has confirmed that this product has surprising therapeutic effect really in multiple diseases such as treatment menopathy, puerperal disease and complication thereof, it is not only strengthening uterine contraction, reduce the vaginal hemorrhage amount, reduce the bleeding time, help the endometrium reparation so that there is excellent curative aspects such as the involution of uterus, but also have tangible antalgic and inflammation relieving effect.
This product has multiple efficacies such as promoting blood flow to regulate menstruation, promoting tissue regeneration by removing blood stasis, promoting the circulation of QI to relieve pain, blood-supplementing blood-nourishing, be mainly used in menopathys such as treatment menoxenia, dysmenorrhea amenorrhea, metrorrhagia and metrostaxis, puerperal puerperal disease and women's miscarriage, artificial abortion's postoperative such as abdominal pain due to blood stasis, postpartum hemorrhage, puerperal blood faints, postpartum lochiorrhea, put the vagina abnormal bleeding that causes behind the intrauterine device, the hemorrhage dripping complication that waits not to the utmost.This product has no side effect substantially, and evident in efficacy, is the pure natural medical of treatment gynecological of a new generation, obstetrics' disease.
Description of drawings:
Fig. 1 is the process chart of embodiment 1.1;
Fig. 2 is the process chart of embodiment 1.2;
Fig. 3 is the process chart of embodiment 2;
Fig. 4 is the process chart of embodiment 3;
Fig. 5 is to the experimental result to the influence of mouse experiment dysmenorrhea;
Fig. 6 is to the experimental result to the influence of rat experiment dysmenorrhea model;
Fig. 7 is the experimental result to the influence in isolated rat uterus;
Fig. 8 is the experimental result of influence that isolated uterine due to the oxytocin is shunk;
Fig. 9 is the experimental result to the influence in mice bleeding time;
Figure 10 is the experimental result to the influence of clotting time of mice;
Figure 11 is the experimental result to the influence in rat vagina bleeding time;
Figure 12 is the experimental result to hemorheological influence;
Figure 13 is the experimental result of the influence of xylol induced mice ear swelling;
Figure 14 is the experimental result to the bullate influence of rat granuloma;
Figure 15 is the experimental result of the influence of Dichlorodiphenyl Acetate induced mice pain reaction;
Figure 16 is the experimental result to the influence of hot plate method analgesic activity.
The invention will be further described by the following examples, but be not limited in this.
Specific embodiment
The preparation method of embodiment 1 compound extract
1. the preparation method of ethanol extract:
Get that crude drug Herba Leonuri 15g, Radix Angelicae Sinensis 10g, Rhizoma Chuanxiong 10g, Radix Rehmanniae Preparata 8g, Radix Paeoniae Alba 8g, Radix Astragali 10g after selected cleans, oven dry is pulverized; The powder that obtains is added the soak with ethanol 3 times of 8 times of amounts 90%, and each soak time is 1 day, filters, and medicinal residues are standby, and the filtrate after three times are soaked merges, and concentrates recovery ethanol, and concentrate drying and grinding under vacuum promptly gets desired ethanol extract.Its technological process sees Figure of description 1 for details.
2. the preparation method of water extract:
Add the water of 6 times of amounts in the medicinal residues of gained, 70 ℃ water temperature, decocted 2 hours, after the filtration, medicinal residues decoct 2 times again, and the time 1 be hour that filtration discards medicinal residues, with three water extracts merging; The amalgamation liquid concentrating under reduced pressure drying of gained is ground and is promptly got desired water extract.
Its technological process sees Figure of description 2 for details.
Ethanol extract and water extract that said method is extracted merge, and fully mixing promptly gets the used compound extract of the present invention.
Embodiment 2 capsules
Get an amount of compound extract, drying, pulverizing, mistake 80 mesh sieves are crossed 80 mesh sieve mix homogeneously with microcrystalline Cellulose, the ethanol system granule with 95%, and forced air drying, with 20 mesh sieve granulate, the fill capsule, the polishing packing gets final product.
Prescription is formed (1000) grain compound extract 200g
Microcrystalline Cellulose 75g
Figure of description 3 is seen in its technological process.
Embodiment 3 tablets
Get an amount of compound extract, dry, pulverize, cross 80 mesh sieves, cross 80 mesh sieve mix homogeneously with microcrystalline Cellulose, carboxymethyl starch sodium, with 5%PVP system granule, forced air drying with 20 mesh sieve granulate, adds magnesium stearate, tabletting.
Prescription is formed: (1000) compound extract 200g
Carboxymethyl starch sodium 5g
Microcrystalline Cellulose 68g
Magnesium stearate 2g
Figure of description 4 is seen in its technological process.
Illustrate its drug action with The pharmacological results below:
One, to the therapeutical effect of experimental dysmenorrhea animal model
1, to the influence of mouse experiment dysmenorrhea
Experimental technique:
Choose 40 of body weight 18～22g Healthy female mices, be divided into 4 groups at random, promptly normal control group, administration I group (low dose group), administration II group (middle dosage group), administration III organize (high dose group).Each only organizes mouse subcutaneous injection diethylstilbestrol 0.2mg/, every day 1 time, for three days on end, animal is in heat.The 3rd day oral administration, behind the administration 40min, lumbar injection PGE
212ug/10g, mice dysmenorrhea writhing response number of times in the 30min is turned round body incubation period and each treated animal incidence rate after the record administration.Data are handled with the statistics t method of inspection.
Experimental result:
Three dosage groups of this product can obviously reduce PGE
2The induced mice dysmenorrhea is turned round the body number of times, and heavy dose of group can also prolong writhing response incubation period, turn round the body incidence rate and be respectively 100%, 80%, 80%.Show that this product can antagonism PGE
2The induced mice dysmenorrhea.Data see Figure of description 5 for details (to be annotated: compare with matched group
*P＜0.05,
*P＜0.01).
2, to the influence of rat experiment dysmenorrhea model
Experimental technique:
Get 50 of Wistar rats, female unpregnancy, body weight 150 ± 10g is divided into 5 groups at random, and promptly normal control group, aspirin group, administration I group (low dose group), administration II group (middle dosage group), administration III organize (high dose group).Each only organizes rat skin lower injection diethylstilbestrol 0.4mg/, and (doubling in the 1st day and the 10th day) every day 1 time, continuous 10 days, is in heat animal.The administration group is in the 9th day beginning gastric infusion, for three days on end.Behind the last administration 40min, lumbar injection oxytocin 2u/ only writes down writhing response number of times and each treated animal incidence rate in the 30min.Shrink indent with writhing response with rat abdomen, trunk and hind leg stretch, and a buttocks and a side limbs inward turning are observation index.
Experimental result:
The obviously violent contraction of rat uterus due to the antagonism oxytocin of dosage group and heavy dose of group reduces the writhing response frequency in this product, prolongs to turn round body incubation period, and other three dosage do not have influence to turning round the body incidence rate.Data see accompanying drawing 6 for details (to be annotated: compare with matched group
*P＜0.05,
*P＜0.01).
Two, to the influence of isolated uterine
1, to the influence in isolated rat uterus
Experimental technique:
Get 100 of the female Mus of healthy unpregnancy of body weight 140～240g, tested preceding 2 days, every day subcutaneous injection SC diethylstilbestrol 0.1mg/kg, to improve the sensitivity in uterus, put to death rat with the cervical vertebra dislocation method, cut open the belly and take out the uterus and place the glass dish that fills Rockwell liquid immediately, softly peel off the fatty tissue and the connective tissue that are attached on the Uterus wall, the two ends of one side cornua uteri are pricked with toe-in respectively, one end is connected with tension pick-up, and the other end is fixed, and operating temperature remains on about 30 ℃, the mist (19: 1) of continuous aerating oxygen and carbon dioxide in nutritive canal, the bubble of per second 1～2.Simultaneously, for the active state that guarantees that the uterus is more stable, the uterus is added the heavy load of 1g, stablize the medicinal liquid that medicine is made into behind the 15min three variable concentrations and add in the nutritive canal, observe the variation of number of contractions, amplitude, frequency and the vigor of the interior uterine smooth muscle of 10min after the administration then.Be subjected to the concentration of reagent liquid to be respectively 10%, 5%, 2.5%, data are handled with statistics t check.
Experimental result:
Prompting this product can make the shrinkage amplitude of normal rat isolated uterine reduce, and showing has inhibitory action to normal uterine smooth muscle autonomic movement, but not obvious to the frequency of uterine contraction influence.Data see Figure of description 7 for details.(compare with matched group
*P＜0.05,
*P＜0.01)
2, the influence that isolated uterine due to the oxytocin is shunk
Experimental technique: the preparation and the working condition of isolated uterine are the same, after writing down one section proper motion curve, add oxytocin 10mu/ml, add different pharmaceutical (pH value of medicine all is adjusted to 7) when the oxytocin effect is obvious behind the 10min, observe the influence that 10min medicine after the administration shrinks isolated uterine due to the oxytocin.
Experimental result: oxytocin (10mu/ml) strengthens normal uterus smooth muscle contraction amplitude, smooth muscle contraction frequency and tension force and uterine motility obviously increase, and the uterine smooth muscle that all can resist to some extent in this product effect 10min due to the oxytocin shrinks, along with its effect of increase of dosage is strengthened.Show that this product has tangible antagonism and blocking effect to the contraction of normal uterus smooth muscle due to the oxytocin.Data see Figure of description 8 for details and (compare #P＜0.05 with the blank group; Compare with model control group
*P＜0.05).
Three, hemostasis experiment
1, to the influence in mice bleeding time:
Experimental technique:
Choose 50 of 18g～22g kunming mice, male and female half and half are divided 5 groups: the normal control group, be subjected to reagent I group, II group and III group, YIMUCAO PIAN group at random.Gastric infusion 20ml/kg, once a day, continuous 3d.1h after the last administration, fixing mice, with milimeter scale measure the length of Mus tail and labelling it, with shears that mouse tail point 3mm place is cross-section respectively then, treating that blood overflows voluntarily picks up counting, inhale to dehematize with filter paper every 15s and drip 1 time, till blood stops (depletion of blood when filter paper is inhaled) naturally, calculate the bleeding time.
Experimental result: three dosage groups of this product can both shorten the mice docking bleeding time, and prompting this product has anastalsis.Detailed results is seen Figure of description 9.
2, to the influence of clotting time of mice
Experimental technique:
Choose 50 of 18g～22g kunming mice, male and female half and half are divided 5 groups: the normal control group, be subjected to reagent I group, II group and III group, YIMUCAO PIAN group at random.Gastric infusion 20ml/kg, once a day, continuous 3d.In last administration 1h, with internal diameter is that the capillary tube of 1mm inserts mice endocanthion ball rear vein beard and gets blood blood post to the capillary tube and reach 5cm, a bit of every the 30s capillary tube that fractures, and checks to have or not clotting strands, calculating is taken a blood sample to from capillary tube and the clotting strands time occurred, is clotting time.Data are done statistics t check and are handled, and the result represents with x ± sd.
Experimental result: dosage and heavy dose of group can significantly shorten clotting time of mice in this product, have the effect of coagulant blood.Detailed results is seen Figure of description 10.
3, to the influence in rat vagina bleeding time
Experimental technique:
Get 40 of female rats, 20 of male rats mate with 2: 1, check cloudy bolt every morning, are pregnant 1d to find cloudy bolt.Pregnant rat is divided into 4 groups at random, the normal control group, organized by reagent I group, II group and III.All irritate stomach, continuously 6d in pregnant 5d.Give anti-early pregnancy drug Mif10mg/kg every day in pregnant 7d and irritate stomach, logotype 3d, pregnant 8d give anti-early pregnancy drug Mis120ug/kg and irritate stomach, logotype 3d every days.After the drug withdrawal, cotton pellet is filled in rat vagina, every 12h observes 1 vaginal hemorrhage situation.
Experimental result:
Three dosage groups of this product can both shorten the vaginal hemorrhage time, with matched group significant difference are arranged relatively.Detailed results is seen Figure of description 11.
Four, hemorheological influence
Experimental technique:
Get 50 Wister female rats, be divided into 5 groups at random, 10 every group.Comprise normal control group, blood stasis model group, be subjected to reagent I group, II group and III organize.Each organizes equal gastric infusion (water) 1ml/100g, 1 time/d * 7d.Behind the last administration 1h, except that the blank group, each organizes rat skin lower injection 0.1% epinephrine 0.8mg/kg twice, at interval 4h.The centre is carried out cold stimulation 1 time, is about to rat and soaks 5min taking-up, overnight fasting in 4 ℃ of frozen water.Respectively organize rat 20% urethane 0.3ml/100g intraperitoneal injection of anesthesia next day.After the anesthesia, common carotid artery is got blood in anticoagulant heparin Guan Zhongyong hemorheology detector, measures the whole blood height and cuts viscosity, the low rheology indexs such as viscosity, plasma viscosity (η p), packed cell volume of cutting.
Experimental result:
Dosage group and high dose group all can reduce the high shear rate and the low shear rate of whole blood viscosity in this product, reduce plasma viscosity.Compare with model control group, significant difference (P＜0.05) is arranged.Show that this product has the effect of blood circulation promoting and blood stasis dispelling.Detailed results is seen Figure of description 12 (notes
#P＜0.05,
###Compare with normal group P＜0.001;
*Compare with model group P＜0.05).
Five, antiinflammatory experiment
1, the influence of xylol induced mice ear swelling
Experimental technique:
Choose 50 of 18g～22g kunming mice, male and female half and half are divided 5 groups: the normal control group, be subjected to reagent I group, II group and III group, aspirin group at random.Gastric infusion 20ml/kg, once a day, continuous 3d.In last administration 1h dimethylbenzene 50ul is applied to and respectively organizes mice left side ear and cause inflammation, put to death mice behind the 40min, punch along left and right sides auricle same area with the card punch of 6mm, weigh,, compare the swelling degree difference of administration group and normal control group, and obtain suppression ratio as the swelling degree with two auricle weight differences.
Experimental result:
Three dosage groups of this product all can suppress the mice caused by dimethylbenzene xylene auricle edema, and inhibitory rate of intumesce is respectively 23.5%, 41.7%, and 41.8%.Data are seen Figure of description 13.
2, to the bullate influence of rat granuloma
Experimental technique:
Choose body weight 50 of the rats of 120～155g, be equally divided into 5 groups at random, 10 every group, that is: normal control group (0.5%CMC-Na), aspirin group (0.2g/kg), beneficial FUKANG I group (0.2g/kg), beneficial FUKANG II group (0.1g/kg), beneficial FUKANG III organize (0.05g/kg).Sterilized cotton ball at subcutaneous each the heeling-in one 30 ± 1mg of rat groin.Postoperative administration on the same day, continuous 7 days, put to death animal on the 8th day, peel off and take out the cotton balls granulation tissue, weigh after putting 60 ℃ of oven dried 12h, deduct the raw cotton ball weight, be the granuloma net weight.Obtain the granuloma dry weight (mg/100g body weight) of each Mus, and calculate inhibitory rate of intumesce, experimental data is handled with statistics t check, and the result represents with x ± sd.
Experimental result:
The heavy dose of group of this product can suppress the bullate formation of rat granuloma, and remarkable with the model group comparing difference, inhibitory rate of intumesce is 23.4%.Receipt sees Figure of description 14 for details.
Six, analgesic experiment
1, the influence of Dichlorodiphenyl Acetate induced mice pain reaction
Experimental technique: choose 50 of 18g～22g kunming mice, male and female half and half are divided 5 groups: the normal control group, be subjected to reagent I group, II group and III group, aspirin group at random.Gastric infusion 20ml/kg, once a day, continuous 3d.1h after each administration, ip1% acetic acid physiological salt liquid 0.2ml/ only turns round the body number of times in each mice 30min of observed and recorded, turns round the incubation period (min) of body.Compare each group difference, and calculate and turn round the body suppression ratio.
Experimental result:
Reaction has the obvious suppression effect to the mice acetic acid twisting for dosage and heavy dose of group in this product, with matched group relatively, that can reduce mice turns round the body number of times, heavy dose of group can also prolong and turn round body incubation period, turns round body suppression ratio respectively 27.3%, 48.0%.Show that this product has certain analgesic activity.Data are seen Figure of description 15 (notes
*P＜0.05,
*P＜0.01,
* *Compare with the blank group P＜0.001).
2, to the influence of hot plate method analgesic activity
Experimental technique:
With 55 ℃ of hot plates female mice is screened in advance, the qualified mice that is of foot reaction in 10～30s, occurs adding.Get qualified mice and be divided into 5 groups at random: the normal control group, be subjected to reagent I group, II group and III group, aspirin group.Gastric infusion 20ml/kg, once a day, continuous 3d.15min, 30min, 60min place each group mice in the hot plate after each administration, the record mice add sufficient time, i.e. pain threshold.If sufficient reaction do not occur adding in the 60s, pain threshold is designated as 60s.
Experimental result:
Three dosage groups of this product 30min after the administration begins the stimulation of antagonism hot plate to mice, and continues to 60min and still have tangible effect, can postpone mice and the sufficient response time occur adding, improves pain threshold.Show that this product has obvious and persistent analgesic activity.Data are seen Figure of description 16 (notes
*P＜0.05,
*P＜0.01,
* *Compare with the blank group P＜0.001).
Claims (7)
1, the pharmaceutical composition of a kind of mainly treating emmeniopathy, puerperal disease is characterized in that this pharmaceutical composition mainly is made up of the extract of Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, Radix Rehmanniae Preparata and Radix Astragali Six-element Chinese crude drug.
2, according to the pharmaceutical composition of claim 1, the extract that it is characterized in that above-mentioned Six-element Chinese crude drug comprises the ethanol extract and the water extract of medical material.
3, according to the pharmaceutical composition of claim 2, the amount ranges that it is characterized in that being used to extracting the Six-element Chinese crude drug of medicinal component is: Herba Leonuri 10-40g, Radix Angelicae Sinensis 5-30g, Rhizoma Chuanxiong 5-30g, Radix Paeoniae Alba 5-20g, Radix Rehmanniae Preparata 5-20g, Radix Astragali 5-20g.
4, according to the pharmaceutical composition of claim 3, the preferable amount that it is characterized in that being used to extracting the Six-element Chinese crude drug of medicinal component is: Herba Leonuri 15g, Radix Angelicae Sinensis 10g, Rhizoma Chuanxiong 10g, Radix Rehmanniae Preparata 8g, Radix Paeoniae Alba 8g, Radix Astragali 10g.
5, according to the pharmaceutical composition of claim 1, it is characterized in that in this pharmaceutical composition, adding suitable pharmaceutical excipient, be prepared into suitable pharmaceutical formulation.
6, according to the preparation of the pharmaceutical composition of claim 5, it is characterized in that said preparation mainly based on oral formulations, comprises tablet such as ordinary tablet, slow releasing tablet, controlled release tablet, dispersible tablet, oral cavity disintegration tablet etc. and hard capsule, soft capsule, pill, granule, oral liquid etc.
7, according to the pharmaceutical composition of claim 1, it is characterized in that this pharmaceutical composition at puerperal disease such as menopathy, puerperal abdonimal pain, postpartum hemorrhage, puerperal blood faints, postpartum lochiorrhea such as preparation treatment menoxenia, dysmenorrhea, amenorrhea, metrorrhagias, post-abortion, artificial abortion's postoperative, put the application in abnormal vaginal bleeding behind the intrauterine device, the dripping medicine that waits complication not to the utmost.
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| CN101301395B (en) * | 2008-06-30 | 2011-01-26 | 陈秀民 | External-use composition mainly for treating postpartum problems and preparation thereof |
| CN102343009A (en) * | 2011-10-18 | 2012-02-08 | 文登市口腔医院 | Traditional Chinese medicine for treating dysmenorrhea |
| CN102886033A (en) * | 2012-09-20 | 2013-01-23 | 山东省妇幼保健所 | Traditional Chinese medicine preparation for promoting postpartum recovery of parturients and shortening lochial time |
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| CN102988736A (en) * | 2012-11-28 | 2013-03-27 | 青岛文创科技有限公司 | Chinese medicinal composition for treating postpartum abdominal pain |
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| CN105267925A (en) * | 2015-11-17 | 2016-01-27 | 王倩 | Medicine for treating postpartum pelvic blood stagnation and method for preparing medicine |
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| CN101301395B (en) * | 2008-06-30 | 2011-01-26 | 陈秀民 | External-use composition mainly for treating postpartum problems and preparation thereof |
| CN102343009A (en) * | 2011-10-18 | 2012-02-08 | 文登市口腔医院 | Traditional Chinese medicine for treating dysmenorrhea |
| CN102343009B (en) * | 2011-10-18 | 2013-09-18 | 刘运波 | Traditional Chinese medicine for treating dysmenorrhea |
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| CN102886033B (en) * | 2012-09-20 | 2014-04-23 | 山东省妇幼保健所 | Traditional Chinese medicine preparation for promoting postpartum recovery of parturients and shortening lochial time |
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| CN102988736A (en) * | 2012-11-28 | 2013-03-27 | 青岛文创科技有限公司 | Chinese medicinal composition for treating postpartum abdominal pain |
| CN103990082A (en) * | 2013-09-24 | 2014-08-20 | 无棣县中心医院 | Traditional Chinese medicine for treating gynecological inflammation and manufacturing method thereof |
| CN104826079A (en) * | 2015-05-30 | 2015-08-12 | 路云香 | Traditional Chinese medicine for treating parturient paresis |
| CN104983833A (en) * | 2015-07-03 | 2015-10-21 | 包莉丽 | Drug used for treating irregular menstruation |
| CN105267925A (en) * | 2015-11-17 | 2016-01-27 | 王倩 | Medicine for treating postpartum pelvic blood stagnation and method for preparing medicine |
| CN105596527A (en) * | 2016-01-14 | 2016-05-25 | 吴媛 | Traditional Chinese medicine for treating postpartum anemic fainting and preparation method thereof |
| CN106729006A (en) * | 2016-11-15 | 2017-05-31 | 黄叶玉 | Treat the medicine of postpartum abdominal pain |
| CN111991473A (en) * | 2020-09-01 | 2020-11-27 | 江西济民可信药业有限公司 | Preparation method of blood-nourishing paste |
| CN113577224A (en) * | 2021-08-25 | 2021-11-02 | 徐州康正中医药科技有限公司 | A Chinese medicinal composition used by puerperal women for invigorating qi, replenishing blood and tonifying deficiency |
| CN115054643A (en) * | 2022-08-08 | 2022-09-16 | 甘肃省中医院 | Traditional Chinese medicine composition for reducing occult blood loss after total knee replacement, and preparation method and application thereof |
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