CN101559196B - Medicament for treating the hyperplasia of mammary glands and preparation method thereof - Google Patents

Medicament for treating the hyperplasia of mammary glands and preparation method thereof Download PDF

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CN101559196B
CN101559196B CN2008100179980A CN200810017998A CN101559196B CN 101559196 B CN101559196 B CN 101559196B CN 2008100179980 A CN2008100179980 A CN 2008100179980A CN 200810017998 A CN200810017998 A CN 200810017998A CN 101559196 B CN101559196 B CN 101559196B
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radix
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herbaceous peony
breast
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CN101559196A (en
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王捷
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Shaanxi Sanzheng Pharmaceutical Co.,Ltd.
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Abstract

The invention discloses a medicament for treating the hyperplasia of mammary glands, belonging to the technical field of medicine manufacture. The invention also discloses a preparation method. The medicament comprises the following raw material components: 150 to 190 parts of bupleurum, 150 to 190 parts of curcuma longa, 150 to 190 parts of red peony roots, 235 to 275 parts of prunella vulgaris, 150 to 190 parts of rhizoma cyperi, 75 to 95 parts of antler glue, 150 to 190 parts of tangerine seeds, 235 to 275 parts of radix scrophulariae, 75 to 95 parts of fritillary bulb and 150 to 190 parts of seaweed, and is prepared by an ethanol extraction method and a water extraction method. Proved by animal tests, the medicament for treating the hyperplasia of mammary glands has obvious therapeuticaction on the hyperplasia of mammary glands, little toxic side effect, high cure rate and low recurernce rate.

Description

A kind of medicine for the treatment of cyclomastopathy and preparation method thereof
One, technical field
The present invention relates to a kind of medicine, specifically a kind of medicine for the treatment of cyclomastopathy belongs to medicine manufacture technology field, comprises preparation method.
Two, background technology
Cyclomastopathy is with the periodicity distending pain of the breast, and lump in breast is the commonly encountered diseases of the young women of clinical characters, good sending out in 25~50 years old the women of child-bearing age, and maiden and man also have generation.Be a kind of non-inflammation disease of breast portion, in Chinese medicine, belong to " nodules of the breast " category.Claim " milk spleen ", " infantile dyspepsia " again.Motherland's medical science is thought the liver failing to maintain the normal flow of QI, Chong and Ren channel disorder and to cause QI-blood circulation not smooth, qi depression to blood stasis, the expectorant poly-nodules of the breast that forms that condenses." Yangke Xinde Ji, Experience Gained in Treating External Diseases " cloud: " nodule in the breast shape such as ball ovum, pain is not had a fever, and color of the leather is constant, it examines the growth and decline with susceptible to anger, this nodules of the breast ".Modern medicine thinks that the pathogenic factor of primary disease is an endocrine regulation, mainly is that estrogen secretion is too much, and progestogen, Progesterone secretion relative deficiency cause.Sickness rate is domestic to be reported as about 10%, and existing prevalence 38.8%~49.3%, and the danger of generation breast carcinoma is apparently higher than general women.Cyclomastopathy is commonly encountered diseases, the frequently-occurring disease of young women, and at present Western medicine is advocated with hormones, vitamin medicaments treatment more, but curative effect still do not have definitely, and side effect is big, treat not thorough, the easy recurrence.So research is a kind of efficiently, the research utmost point of the medicine treatment by Chinese herbs primary disease of low toxicity has realistic meaning and bright prospects.
Cyclomastopathy title clinically is a lot, and as breast disease, fibrocystic disease of breast, adenosis of breast, cyclomastopathy etc., world health organisation recommendations is called mammary dysplasia disease, and the most scholars of China still commonly use the title of cyclomastopathy.Along with improving constantly of living standard, this disease sickness rate presents the rising situation.Present national average statistics is 50%, and some areas have reached 60%~70%.Most scholars think that this disease is relevant with hypothalamic-pituitary-ovarian-mammary gland endocrine axis disorder, be the result of multiple endocrine hormone imbalance, wherein estrogenic/progestogenic out of proportion make mammary gland under estrogenic stimulation the essence hypertrophy excessively and subinvolution be one of most important reason.
Cyclomastopathy is a main clinical manifestation with two big primary symptoms such as mastalgia and lump in breasies.The pain of early lesion (being mastalgia and cyclomastopathy) is very obvious, and along with further developing of the state of an illness, then pain relief and lump occur to the adenopathy hypertrophy.Develop into cystic hyperplasia, then pain almost disappears and lump shows especially.Therefore, we are divided into pain type, lump type and middle type by its clinical manifestation with hypertrophy.Three types are pressed lesion degree by light arrangement to weight, are followed successively by pain type → middle type → lump type.In pathological change, be equivalent to mastalgia or cyclomastopathy phase respectively, adenopathy proliferative phase and cystic hyperplasia phase.The obvious degree of three type lumps increases successively, and is close gradually with getting in touch of tumor, but pain degree alleviates successively.Mastalgia is a kind of performance of early lesion to a certain extent, and from cyclomastopathy and relationship with canceration, it is actually a kind of signal for "speed OK", and promptly the obvious more person of pain is far away more from canceration.Lump is that cyclomastopathy is main, the sign of most critical, mostly is lamellar or block tuberosity, and the former fills the air and soft, and the latter limits to and tough reality slightly, and is hard and have the profile person answers highly vigilant of to its matter of later stage.
Three, summary of the invention
The purpose of this invention is to provide a kind of pure Chinese medicine medicine for the treatment of cyclomastopathy, this medicine embodies the characteristics of traditional Chinese medical science compatibility theory, and mastalgia and lump in breast two big primary symptoms at cyclomastopathy are conceived to eliminate lump, thereby a kind of new therapeutic scheme is provided.
Primary disease is mainly because of feelings will internal injury, and the damp and hot expectorant of stagnation of liver-QI coagulates, due to qi stagnation blood stasis or the Chong and Ren channel disorder.Monarch drug is selected Radix Bupleuri for use in the side, and property is opened and loose and catharsis is the key medicine of dispersing the stagnated live-QI to relieve the stagnation of QI.Radix Curcumae promoting QI circulation for relieving depression, removing heat from blood removing blood stasis with potent drugs, acrid in the mouth are from sun, and main row looses, and goes into edema caused by disorder of QI, can separate the invisible stagnation of QI; Bitter in the mouth is from the moon, and main falling rushed down, and goes into blood system, thus can break tangible blood stasis, for stagnation of liver-QI is not understood QI and blood stasis, the principal agent of distending pain of the breast." book on Chinese herbal medicine is equipped with medicine " carries Radix Curcumae: " circulation of qi promoting, resolving depression; Let out blood, removing blood stasis with potent drugs.Cool heat in the heart, the stagnation of liver-QI of loosing is controlled married woman's passages through which vital energy circulates and is driven in the wrong direction." monarch drug two flavors, a gas one blood, QI and blood is ruled together, promoting flow of QI and blood, resolving depression pain relieving.Ministerial drug is selected Radix Paeoniae Rubra for use, gets its flavor sour in taste acting on the liver, and relieving spasm to stop pain is gentle foster just dirty, stagnating in the promoting the circulation of blood.Spica Prunellae is apt to away scurry, and is longer than sensible meridians, energy hard masses softening and resolving, the detumescence of reducing phlegm.Shennong's Herbal meaning Spica Prunellae: " cure mainly cold and heat, scrofula, scrofula, head sore , Po wei, the wart stagnation of QI that looses, swelling of the feet arthralgia chiefly caused by damp pathogen." Rhizoma Cyperi function depressed liver-energy dispersing and QI regulating, with Radix Bupleuri, Radix Curcumae matches, to help the merit of depressed liver-energy dispersing and QI regulating resolving depression.The Colla cornus cervi salty in the mouth is warm in nature, returns the Liver and kidney warp, energy temperature compensation Liver and kidney, benefiting essence-blood, ministerial drug four flavors, depressed liver-energy dispersing and QI regulating, hard masses softening and resolving.Adjuvant drug is selected the Semen Citri Reticulatae removing obstruction for relieving pain of regulating the flow of vital energy for use.The Radix Scrophulariae clearing away heat and cooling blood, the YIN nourishing detoxifcation." Mingyi Bielu " carries Radix Scrophulariae: " following water ends excessive thirst, and the neck that looses is nuclear, carbuncle down." Bulbus Fritillariae Thunbergii heat clearing away eliminating stagnation, preventing phlegm from forming and stopping coughing." book on Chinese herbal medicine is just " calls it: " fall mental disorder most, kind relieving stagnation is separated pyretic toxicity and is treated sore throat, scrofula, acute mastitis, carbuncle on the back, all carbuncle and ulcer toxic swellings ...." the Sargassum hardship is salty-cold, hard masses softening and resolving, expectorant diuretic.The same usefulness of adjuvant drug four flavor helps the merit of the monarch and his subjects' dissipating phlegm and resolving masses altogether.Colla cornus cervi is warming YANG system the moon in the cold and cool medicine of group, had both avoided medicine to cross cold and cool impairment of YIN, exchanges and dash the merit that plays using corrigent with blood.Full side's medication is the long memorial liver and qi altogether, transfers and dashes and blood, the merit of dissipating phlegm and resolving masses.
The present invention realizes by following scheme:
The consumption of drug component of the present invention also draws through various experimental summaries, and each amounts of components is for all having better curative effect in the following weight parts scope:
150~190 parts of Radix Bupleuri, 150~190 parts of Radix Curcumaes, 150~190 parts of Radix Paeoniae Rubra, 235~275 parts of Spica Prunellaes, 150~190 parts of Rhizoma Cyperis, 75~95 parts of Colla cornus cervis, 150~190 parts of Semen Citri Reticulataes, 235~275 parts of Radix Scrophulariaes, 75~95 parts of Bulbus Fritillariae Thunbergiis, 150~190 parts of Sargassums.
Be preferably:
170 parts of Radix Bupleuri, 170 parts of Radix Curcumaes, 170 parts of Radix Paeoniae Rubra, 255 parts of Spica Prunellaes, 170 parts of Rhizoma Cyperis, 85 parts of Colla cornus cervis, 170 parts of Semen Citri Reticulataes, 255 parts of Radix Scrophulariaes, 85 parts of Bulbus Fritillariae Thunbergiis, 170 parts of Sargassums.
Medicine of the present invention can adopt the conventional preparation method of Chinese medicine preparation to make any oral medicinal herb preparation.The preparation method of preferred medicine activity component of the present invention is as follows:
Above-mentioned ten flavors, Colla cornus cervi and Bulbus Fritillariae Thunbergii are ground into fine powder, and Radix Paeoniae Rubra is with 80% alcohol reflux 3 times, and each 1.0 hours, alcohol adding amount was 6 times, merge extractive liquid,, filtration, filtrate recycling ethanol also is evaporated to the thick paste of relative density 1.30~1.35 (80 ℃); Medicinal residues and Radix Bupleuri, Radix Curcumae, Spica Prunellae, Rhizoma Cyperi, Semen Citri Reticulatae, Radix Scrophulariae, Sargassum merge, adding 8 times of medical material water gagings decocts 3 times, each 1.5 hours, collecting decoction filtered, filtrate decompression is concentrated into the clear paste of relative density 1.10~1.15 (80 ℃), add ethanol and make determining alcohol reach 50%, fully stir static 24 hours, filter, filtrate recycling ethanol also is evaporated to the thick paste of relative density 1.30~1.35 (80 ℃); Thick paste and Radix Paeoniae Rubra alcohol extract merge, and add Colla cornus cervi and Bulbus Fritillariae Thunbergii fine powder, and 80 ℃ of drying under reduced pressure are ground into fine powder.
The active component of medicine of the present invention can add various conventional adjuvant required when preparing different dosage form, be prepared into any peroral dosage form commonly used as excipient, diluent, binding agent, disintegrating agent, lubricant etc. with the method for Chinese medicinal of routine, as pill, powder, granule, tablet, syrup, drop pill, capsule, fluid extract and extractum, oral liquid etc.
Good effect of the present invention is: component is few, have only ten flavor raw materials, method for production is simple, pure Chinese medicinal preparation by the pure Chinese medicine of ten flavors such as Radix Bupleuri, Radix Paeoniae Rubra processes through modern crafts according to the theory of Chinese medical science prescription, has liver-smoothing, qi-regulating, transfers and dash and functions such as blood, dissipating phlegm and resolving masses, be used for the treatment of gynaecopathias such as cyclomastopathy clinically, the cure rate height, relapse rate is low, and toxic and side effects is little.
Drug usage consumption of the present invention, oral dose calculated for 20.4 gram/days with the crude drug amount.
Effect experiment
Pharmacodynamic experiment is the result show: this medicine has obvious inhibitory action to the cyclomastopathy of cyclomastopathy rat; The rat paw edema that on Carrageenan causes has obvious inhibitory action, can obviously suppress the swelling of mice caused by dimethylbenzene xylene auricle inflammation, cause swelling of rat granulation and filter paper to cause the mice granulation hyperplasia that the obvious suppression effect is arranged to cotton balls, the mouse peritoneal capillary permeability that Dichlorodiphenyl Acetate causes strengthens obvious inhibitory action, illustrates that the present invention has tangible antiinflammatory action; Medicine of the present invention causes that to hot plate mice pain has significant analgesia role, and the mouse writhing increased frequency that Dichlorodiphenyl Acetate causes has the obvious suppression effect, illustrates that it has significant analgesia role.The present invention can obviously suppress rat vivo and vitro thrombosis, prolongs clotting time, illustrates that this medicine has tangible function of promoting blood circulation to disperse blood clots.And there is not tangible toxic reaction.
Below further set forth the beneficial effect of medicine of the present invention by animal experiment, these tests have comprised that the medicine bavin Chinese herbaceous peony breast that the present invention produced increases the pharmacodynamics test that capsule carries out.
Test material
Laboratory animal: wistar rat, body weight 170~230g female (each experimental animal body weight difference be no more than 50g), the quality certification number: SCXK-(Ji) 2003-0004; Kunming kind white mice, body weight 18~22g, female, the quality certification number: SCXK-(Ji) 2003-0004.All rats, white mice are all available from high-new medical experiment zooscopy center, Changchun.
Trial drug: bavin Chinese herbaceous peony breast increases capsule, and the Jilin Prov. Inst. of Chinese Medicine and Chinese Medical Science provides.Lot number: 040301, the patent medicine specification: the 0.4g/ grain is made into desired concn for gastric infusion with distilled water during experiment.RUKANG PIAN, Ankang Chia Tai Pharmaceutical Co., Ltd. provides.Lot number: 040102, the patent medicine specification: the 0.35g/ sheet is made into desired concn for gastric infusion with distilled water during experiment.Adrenalin hydrochloride (Adr) injection is produced by Tian Feng pharmaceutical factory, Shanghai, lot number: 940501; Chloral hydrate, Gaobeidian City, Hebei spring scenery chemical reagent work produces, lot number: 960908.
Instrument: BJ-8402 type hot plate dolorimeter, produce by Chinese Zhejiang; 752 type ultraviolet spectrophotometers are produced by Shanghai the 3rd analytical tool factory.
Test method and result
1, antiinflammatory action:
1.1, the influence of rat paw edema due to the on Carrageenan:
Get 50 of rats, be divided into 5 groups at random.The blank group; RUKANG PIAN 1.12g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.12,0.56, three dosed administration groups of 0.28g/kg.Be administered once every day, successive administration five days.Injected 1% carrageenin 0.1ml/ down only in the right back toes aponeurosis (aponeuroses) of rat in 1 hour after the last administration.And in injecting the rat paw edema degree of surveying respectively in back 1,2,3,4,5,6,24 hour.With two back foot swelling differences as the swelling index.The results are shown in Table 1.
By table 1 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase the rat paw edema that the capsule on Carrageenan causes the obvious suppression effect, and presents certain dose-effect relationship, and bavin Chinese herbaceous peony breast increased capsule 1.12g/kg effect sustainable 24 hours.
1.2, to the bullate influence of rat granuloma
With 50 of healthy rats, lumbar injection pentobarbital sodium 30mg/kg anesthesia, cut the long osculum of 1cm at groin place, the left and right sides of every Mus, autoclaving cotton balls (penicillin and streptomycin mixed liquor 0.2ml immersion with 20mg, 60 ℃ of oven dry) implant from incision subcutaneous, about each skin suture immediately.These rats are divided into 5 groups at random.The blank group; RUKANG PIAN 1.12g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.12,0.56, three dosed administration groups of 0.28g/kg.Be administered once every day, successive administration 7 days.After the last administration 1 hour, open former otch, cotton balls is taken out together with connective tissue on every side, reject fatty tissue, put 70 ℃ of oven dry in the baking oven, weigh.With claim weight deduct the former weight of cotton balls and promptly get granuloma weight.The results are shown in Table 2.
By table 2 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase capsule 1.12,0.56g/kg causes the swelling of rat granulation that the obvious suppression effect is arranged to cotton balls, and present certain dose-effect relationship.
1.3, xylol causes the inhibitory action of Mice Auricle inflammation swelling:
Get 60 mices, be divided into 5 groups at random.The blank group; RUKANG PIAN 1.60g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.60,0.80, three dosed administration groups of 0.40g/kg.Be administered once every day, successive administration 5 days.After the last administration after 1 hour, each is organized all animals dimethylbenzene 0.03ml is applied to the Mice Auricle auris dextra causes swollenly, left ear is done normal control.After 2 hours, put to death animal, draw materials in the punching of auricle same area with the 9mm card punch, weigh respectively, heavily deducting left ear recast with auris dextra is the swelling level index.The results are shown in Table 3.
By table 3 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase capsule 1.60, the 0.80g/kg xylol causes the swelling of Mice Auricle inflammation the obvious suppression effect.
1.4, to the outgrowth influence of mice filter paper granuloma:
Get 60 mices, be divided into 5 groups at random.The blank group; RUKANG PIAN 1.60g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.60,0.80, three dosed administration groups of 0.40g/kg.The mouse web portion routine disinfection is done a little otch that is about 0.3cm in the abdominal part median line, implants the 4mg filter paper of sterilizing subcutaneous, sew up the incision, routine disinfection, postoperative began administration the same day, and be administered once every day, successive administration 8 days, hara kiri skin was peeled off and is taken out filter paper and granuloma with mice execution in the 9th day, place 80 ℃ of oven dryings to take out after one hour and weigh, the weight that deducts former filter paper is granulomatous weight.The results are shown in Table 4.
By table 4 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase capsule 1.60,0.80g/kg causes the mice granulation hyperplasia that the obvious suppression effect is arranged to the mice filter paper.
1.5, to the influence of mouse peritoneal capillary permeability:
Get 60 mices, be divided into 5 groups at random.The blank group; RUKANG PIAN 1.60g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.60,0.80, three dosed administration groups of 0.40g/kg.Be administered once every day, successive administration 5 days.After the last administration 1 hour in mouse tail vein injection 1% Yi Wensilan 0.1ml/10g body weight, lumbar injection 0.7% acetic acid 0.1ml/10g body weight immediately, put to death mice after 20 minutes, with 2ml normal saline flushing abdominal cavity, extract 1.6ml peritoneal irrigation liquid and add normal saline 5ml so far, centrifugal, with 752 type spectrophotometers in 590nm place colorimetric.The results are shown in Table 5.
By table 5 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase capsule 1.60, the 0.80g/kg Dichlorodiphenyl Acetate causes the mouse peritoneal capillary permeability to strengthen the obvious suppression effect.
2. analgesic activity:
2.1, to the influence of mice hot plate zest pain:
Screen 55 of qualified female mices with hot plate dolorimeter 1 (MGJ-8402 type, 55 ± 0.5 ℃), be divided into 5 groups at random.The blank group; RUKANG PIAN 1.60g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.60,0.80, three dosed administration groups of 0.40g/kg.Be administered once every day, successive administration 5 days.Measure the mice pain threshold in 1,2,3,4,5 hour after the last administration, the results are shown in Table 6.
By table 6 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase capsule hot plate are caused that mice pain has significant analgesia role, and bavin Chinese herbaceous peony breast increases sustainable 5 hours of action time of capsule 1.60g/kg dosed administration group.
2.2, the influence of Dichlorodiphenyl Acetate induced mice pain:
Get 60 mices, be divided into 5 groups at random.The blank group; RUKANG PIAN 1.60g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.60,0.80, three dosed administration groups of 0.40g/kg.Be administered once every day, successive administration 5 days.The interior mouse writhing reaction times of 10min behind each Mus ip0.7% acetic acid 10ml/kg observation in 0.5 hour and the record 5min after the last administration.The results are shown in Table 7.
By table 7 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase capsule 1.60,0.80g/kg group Dichlorodiphenyl Acetate causes the mouse writhing reaction times to increase the obvious suppression effect.
3, blood circulation promoting and blood stasis dispelling experiment
3.1, to the influence of rat thrombus in vivo:
Get 50 of rats, be divided into 5 groups at random.The blank group; RUKANG PIAN 1.12g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.12,0.56, three dosed administration groups of 0.28g/kg.Be administered once every day, successive administration 5 days.Back of the body position was fixing, separated right carotid in animal lumbar injection 300mg/kg chloral hydrate anesthesia in 1 hour after the last administration, form analyzer with experimental thrombus in vivo, far-end is put thermal detector, behind 2.0mA galvanic stimulation 3min, write down its duration of congestion, i.e. thrombus formation time.The results are shown in Table 8.
By table 8 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase capsule 1.12, the 0.56g/kg group is formed with the obvious suppression effect to the rat thrombus in vivo.
3.2, to the thrombotic influence of blood stasis model rats in vitro:
Get 48 of rats, be divided into 6 groups at random.The blank group; The blood stasis model group; RUKANG PIAN 1.12g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.12,0.56, three dosed administration groups of 0.28g/kg.Be administered once every day, successive administration 5 days, in administration the 2nd, the 3rd day except that the blank group all the other each groups subcutaneous injection 0.1% adrenalin hydrochlorides (Adr) 0.1ml/ are only respectively [7], respectively rat is placed 1.5 ℃ of frozen water 5min that swims behind the 30min, only injecting Adr on the 4th day does not carry out ice bath, prepares blood stasis model with this.The blood sampling of abdomen cardinal vein was observed external thrombus and is formed situation on extracorporeal thrombosis forming device, be index with thrombosis length, weight in wet base, dry weight in each treated animal lumbar injection 300mg/kg chloral hydrate anesthesia in 1 hour after the last administration.The results are shown in Table 9.
By table 9 result as seen, bavin Chinese herbaceous peony breast increases capsule 1.12, two dosed administration groups of 0.56g/kg can obviously suppress rats in vitro thrombosis, thrombosis length and thrombus weight.
3.3, to the influence of clotting time of mice:
Get 60 mices, be divided into 5 groups at random.The blank group; RUKANG PIAN 1.60g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.60,0.80, three dosed administration groups of 0.40g/kg.Be administered once every day, successive administration 5 days.After the last administration 1 hour by mice socket of the eye venous blood collection, survey clotting time with slide method.The results are shown in Table 10.
By table 10 result as seen, RUKANG PIAN and bavin Chinese herbaceous peony breast increase capsule 1.60, the 0.80g/kg group can obviously prolong the clotting time of mice.
4, bavin Chinese herbaceous peony breast increases capsule to the outgrowth influence of rat mammary gland
(1) medicine and reagent
Bavin Chinese herbaceous peony breast increases capsule, and the Jilin Prov. Inst. of Chinese Medicine and Chinese Medical Science provides.Lot number: 040301, the patent medicine specification: the 0.4g/ grain is made into desired concn for gastric infusion with distilled water during experiment.The positive drug RUKANG PIAN, Ankang Chia Tai Pharmaceutical Co., Ltd. provides.Lot number: 040102, the patent medicine specification: the 0.35g/ sheet is made into desired concn for gastric infusion with distilled water during experiment.Estradiol benzoate injection is Shanghai General Pharmaceutical Co., ltd., lot number: 050105; Progesterone injection is a Zhejiang Province XianJu Pharmacy stock Co., Ltd, lot number: 050803.Estradiol (Estradiol, E :), (Progestin, P) radioimmunological kit is available from the Fu Rui of Beijing bio-engineering corporation for progesterone.
(2) method and result
Get 60 of rats, be divided into 6 groups at random.The blank group; The hyperplasia of mammary gland model group; RUKANG PIAN 1.12g/kg dosed administration group; Bavin Chinese herbaceous peony breast increases capsule 1.12,0.56, three dosed administration groups of 0.28g/kg.Except that the blank group, each group is used estradiol benzoate 0.5mg/kg intramuscular injection 25 days, uses progesterone injection 4mg/kg intramuscular injection 5 days again instead, preparation rat mammary gland hypertrophy disease model.Be administered once every day simultaneously at the injection estradiol benzoate injection, successive administration 30 days was got blood, serum measured by radioimmunoassay E2 and P concentration in 24 hours behind last injection progesterone injection; The results are shown in Table 11.The 2nd pair of breast of clip chest, slide gauge are accurately measured papilla diameter, highly; The results are shown in Table 12.Again breast is immersed in 10% formalin solution fixing, under the mirror to mammary gland acinus, conduit and between the hyperplasia degree of matter mark respectively, 3 accumulated values of marking are the cyclomastopathy degree, and calculate the cyclomastopathy rate.Normally: (one), 1 minute; Slight hypertrophy: (+), 2 minutes; Moderate hypertrophy: (++), 3 minutes; The severe hypertrophy: (+++), 4 minutes.The results are shown in Table 13.
By table 11 result as seen, the rat mammary gland model of hyperplasia of estradiol benzoate and Progesterone preparation can make E2 rising in the rat blood serum, the imbalance of E2/P ratio; And bavin Chinese herbaceous peony breast increases capsule and can suppress obviously in the rat blood serum that E2 raises, the imbalance of E2/P ratio, and 1.12g/kg dosed administration group effect is best.
By table 12 result as seen, the rat mammary gland model of hyperplasia of estradiol benzoate and Progesterone preparation can make rat papilla diameter and height of nipples increase, and bavin Chinese herbaceous peony breast increases the increase that capsule can obviously suppress cyclomastopathy rat papilla diameter and height of nipples.
By table 13 result as seen, the rat mammary gland model of hyperplasia of estradiol benzoate and Progesterone preparation can make the rat mammary gland hypertrophy, and bavin Chinese herbaceous peony breast increases the cyclomastopathy that capsule can obviously suppress the cyclomastopathy rat.
Experiment conclusion
Pharmacodynamic experiment is the result show, bavin Chinese herbaceous peony breast increases capsule has obvious inhibitory action to the cyclomastopathy of cyclomastopathy rat; Bavin Chinese herbaceous peony breast increases the rat paw edema that the capsule on Carrageenan causes obvious inhibitory action, can obviously suppress the swelling of mice caused by dimethylbenzene xylene auricle inflammation, cause swelling of rat granulation and filter paper to cause the mice granulation hyperplasia that the obvious suppression effect is arranged to cotton balls, the mouse peritoneal capillary permeability that Dichlorodiphenyl Acetate causes strengthens obvious inhibitory action, illustrates that bavin Chinese herbaceous peony breast increases capsule tangible antiinflammatory action is arranged; Bavin Chinese herbaceous peony breast increases capsule hot plate is caused that mice pain has significant analgesia role, and the mouse writhing increased frequency that Dichlorodiphenyl Acetate causes has the obvious suppression effect, illustrates that bavin Chinese herbaceous peony breast increases capsule significant analgesia role is arranged.Bavin Chinese herbaceous peony breast increases capsule can obviously suppress rat vivo and vitro thrombosis, prolongs clotting time, illustrates that this medicine has tangible function of promoting blood circulation to disperse blood clots.
In sum, experimental results show that more than drug prepared bavin Chinese herbaceous peony breast of the present invention increases capsule and provides full and accurate experimental basis at gynaecopathias such as treatment cyclomastopathy.
Acute toxicity testing is the result show, limits because of administration concentration and volume, fails to measure the LD that bavin Chinese herbaceous peony breast increases the capsule gastric infusion 50Animal is in good condition after the administration, body weight gain is normal, breathing, activity, diet, defecation are all normal, mouth, eye, the no abnormal secretions of nose, no any abnormal response in 14 days, and none animal dead, the maximum dosage-feeding that records gastric infusion in its 24 hours is 40g/kg, 583.3 times of quite clinical consumption.
Long term toxicity test is the result show, bavin Chinese herbaceous peony breast increases capsule and gives rat oral gavage administration 180 days with 8.0-2.0g/kg dosage, growth of animal state, movable diet, hematology, blood biochemical, organ index and organs and tissues structure all there is not obvious influence, wherein bavin Chinese herbaceous peony breast increases capsule with 8.0g/kg, 116.7 times of quite clinical consumption.
Four, the specific embodiment
The preparation method of embodiment 1 medicinal tablet of the present invention is to count ratio by following crude drug to make:
Radix Bupleuri 150 grams, Radix Curcumae 150 grams, Radix Paeoniae Rubra 150 grams, Spica Prunellae 235 grams, Rhizoma Cyperi 150 grams, Colla cornus cervi 75 grams, Semen Citri Reticulatae 150 grams, Radix Scrophulariae 235 grams, Bulbus Fritillariae Thunbergii 75 grams, Sargassum 150 grams.
Preparation method is:
1) above ten flavors, Colla cornus cervi and Bulbus Fritillariae Thunbergii are ground into fine powder, and Radix Paeoniae Rubra is with 80% alcohol reflux 3 times, and each 1.0 hours, alcohol adding amount was 6 times, merge extractive liquid,, filtration, filtrate recycling ethanol also is evaporated to the thick paste of relative density 1.30~1.35 (80 ℃); Medicinal residues and Radix Bupleuri, Radix Curcumae, Spica Prunellae, Rhizoma Cyperi, Semen Citri Reticulatae, Radix Scrophulariae, Sargassum merge, adding 8 times of medical material water gagings decocts 3 times, each 1.5 hours, collecting decoction filtered, filtrate decompression is concentrated into the clear paste of relative density 1.10~1.15 (80 ℃), add ethanol and make determining alcohol reach 50%, fully stir static 24 hours, filter, filtrate recycling ethanol also is evaporated to the thick paste of relative density 1.30~1.35 (80 ℃); Thick paste and Radix Paeoniae Rubra alcohol extract merge, and add Colla cornus cervi and Bulbus Fritillariae Thunbergii fine powder, and 80 ℃ of drying under reduced pressure are ground into fine powder.
2) adjuvant of the conventional film-making agent of adding, tabletting.
The preparation of embodiment 2 medicine capsules of the present invention
It is made by following crude drug:
Radix Bupleuri 170 grams, Radix Curcumae 170 grams, Radix Paeoniae Rubra 170 grams, Spica Prunellae 255 grams, Rhizoma Cyperi 170 grams, Colla cornus cervi 85 grams, Semen Citri Reticulatae 170 grams, Radix Scrophulariae 255 grams, Bulbus Fritillariae Thunbergii 85 grams, Sargassum 170 grams.
Preparation method comprises: step 1) is with embodiment 1;
2) incapsulate.
The preparation of embodiment 3 medicinal granules of the present invention
It is made by following crude drug:
Radix Bupleuri 190 grams, Radix Curcumae 190 grams, Radix Paeoniae Rubra 190 grams, Spica Prunellae 275 grams, Rhizoma Cyperi 190 grams, Colla cornus cervi 95 grams, Semen Citri Reticulatae 190 grams, Radix Scrophulariae 275 grams, Bulbus Fritillariae Thunbergii 95 grams, Sargassum 190 grams;
Preparation method comprises: step 1) is with embodiment 1;
2) add starch, granulate drying.
Figure S2008100179980D00101
Table 2. bavin Chinese herbaceous peony breast increases capsule to the granulomatous influence of rat (X ± s)
Group Mus number (only) Granulation weight (mg)
Matched group 10 111.30±3.86
RUKANG PIAN 1.12g/kg 10 94.90±5.55
Bavin Chinese herbaceous peony breast increases capsule 1.12g/kg 10 80.40±4.74 ※※※
Bavin Chinese herbaceous peony breast increases capsule 0.56g/kg 10 96.80±6.14
Bavin Chinese herbaceous peony breast increases capsule 0.28g/kg 10 101.80±5.43
Table 3. bavin Chinese herbaceous peony breast increases capsule to the influence of mice dimethylbenzene dropsy of ear (X ± s)
Group Mus number (only) Two ear weight differences (mg)
Matched group 12 15.17±3.74
RUKANG PIAN 1.60g/kg 12 10.75±3.44
Bavin Chinese herbaceous peony breast increases capsule 1.60g/kg 12 8.67±3.45 ※※
Bavin Chinese herbaceous peony breast increases capsule 0.80g/kg 12 10.25±3.86
Bavin Chinese herbaceous peony breast increases capsule 0.40g/kg 12 13.25±4.03
Table 4. bavin Chinese herbaceous peony breast increases capsule to the granulomatous influence of mice (X ± s)
Group Mus number (only) Granulation weight (mg)
Matched group 12 19.33±2.42
RUKANG PIAN 1.60g/kg 12 15.75±2.38 ※※
Bavin Chinese herbaceous peony breast increases capsule 1.60g/kg 12 13.83±1.85 ※※※
Bavin Chinese herbaceous peony breast increases capsule 0.80g/kg 12 16.33±2.02 ※※
Bavin Chinese herbaceous peony breast increases capsule 0.40g/kg 12 18.67±1.97
Table 5. bavin Chinese herbaceous peony breast increases capsule to the influence of mouse peritoneal capillary permeability (X ± s)
Group Mus number (only) The OD value
Matched group 12 0.74±0.077
RUKANG PIAN 1.60g/kg 12 0.54±0.179 ※※※
Bavin Chinese herbaceous peony breast increases capsule 1.60g/kg 12 0.53±0.130 ※※
Bavin Chinese herbaceous peony breast increases capsule 0.80g/kg 12 0.60±0.11
Bavin Chinese herbaceous peony breast increases capsule 0.40g/kg 12 0.65±0.147
Figure S2008100179980D00121
Table 7. bavin Chinese herbaceous peony breast increases the influence that the capsule Dichlorodiphenyl Acetate brings out the mouse writhing reaction
Figure S2008100179980D00131
Group Mus number (only) Turn round body number of times (inferior)
Matched group 12 18.42±4.89
RUKANG PIAN 1.60g/kg 12 7.75±3.60 ※※
Bavin Chinese herbaceous peony breast increases capsule 1.60g/kg 12 7.83±3.38 ※※※
Bavin Chinese herbaceous peony breast increases capsule 0.80g/kg 12 9.42±3.84 ※※
Bavin Chinese herbaceous peony breast increases capsule 0.40g/kg 12 10.67±5.19
Table 8. bavin Chinese herbaceous peony breast increases the influence of capsule to the rat thrombus in vivo
Figure S2008100179980D00132
Group Mus number (only) Thrombus formation time (branch)
Matched group 10 7.32±1.11
RUKANG PIAN 1.12g/kg 10 8.78±1.07
Bavin Chinese herbaceous peony breast increases capsule 1.12g/kg 10 9.80±1.09 ※※※
Bavin Chinese herbaceous peony breast increases capsule 0.56g/kg 10 8.47±0.97 ※※
Bavin Chinese herbaceous peony breast increases capsule 0.28g/kg 10 7.82±0.91
Table 10. bavin Chinese herbaceous peony breast increases the influence of capsule to clotting time of mice
Figure S2008100179980D00133
Group Mus number (only) Clotting time (branch)
Matched group 12 3.23±0.70
RUKANG PIAN 1.60g/kg 12 4.28±0.76 ※※
Bavin Chinese herbaceous peony breast increases capsule 1.60g/kg 12 4.73±0.76 ※※※
Bavin Chinese herbaceous peony breast increases capsule 0.80g/kg 12 4.17±0.66 ※※
Bavin Chinese herbaceous peony breast increases capsule 0.40g/kg 12 3.68±0.63
Figure S2008100179980D00151

Claims (4)

1. medicine for the treatment of cyclomastopathy is characterized in that this medicine is the medicament of being made by the raw material of following ratio of weight and number:
150~190 parts of 150~190 parts of Radix Paeoniae Rubra of 150~190 portions of Radix Curcumaes of Radix Bupleuri
75~95 parts of 150~190 parts of Colla cornus cervis of 235~275 portions of Rhizoma Cyperis of Spica Prunellae
75~95 parts of 235~275 parts of Bulbus Fritillariae Thunbergiis of 150~190 portions of Radix Scrophulariaes of Semen Citri Reticulatae
150~190 parts of Sargassums.
2. a kind of medicine for the treatment of cyclomastopathy as claimed in claim 1 is characterized in that this medicine is the medicament of being made by the raw material of following ratio of weight and number:
170 parts of 170 parts of Radix Paeoniae Rubra of 170 portions of Radix Curcumaes of Radix Bupleuri
85 parts of 170 parts of Colla cornus cervis of 255 portions of Rhizoma Cyperis of Spica Prunellae
85 parts of 255 parts of Bulbus Fritillariae Thunbergiis of 170 portions of Radix Scrophulariaes of Semen Citri Reticulatae
170 parts of Sargassums.
3. a kind of medicine for the treatment of cyclomastopathy as claimed in claim 1 or 2 is characterized in that: comparing the dosage form of being manufactured with above-mentioned material component number is acceptable clinically all oral medicinal herb preparations.
4. a kind of preparation method for the treatment of the medicine of cyclomastopathy described in the production claim 3 is characterized in that:
More than ten the flavor, Colla cornus cervi and Bulbus Fritillariae Thunbergii are ground into fine powder; Radix Paeoniae Rubra is with 80% alcohol reflux 3 times, and each 1.0 hours, alcohol adding amount was 6 times, and merge extractive liquid, filters, and filtrate recycling ethanol is also surveyed the thick paste of relative density 1.30~1.35 when being evaporated to 80 ℃; Radix Paeoniae Rubra medicinal residues and Radix Bupleuri, Radix Curcumae, Spica Prunellae, Rhizoma Cyperi, Semen Citri Reticulatae, Radix Scrophulariae, Sargassum merge, adding 8 times of medical material water gagings decocts 3 times, each 1.5 hours, collecting decoction filtered, when being concentrated into 80 ℃, filtrate decompression surveys the clear paste of relative density 1.10~1.15, add ethanol and make determining alcohol reach 50%, fully stir static 24 hours, filter, filtrate recycling ethanol is also surveyed the thick paste of relative density 1.30~1.35 when being evaporated to 80 ℃; Thick paste and Radix Paeoniae Rubra alcohol extract thick paste merge, and add Colla cornus cervi and Bulbus Fritillariae Thunbergii fine powder, and 80 ℃ of drying under reduced pressure are ground into fine powder, make the suitable for oral administration dosage form.
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CN1857670A (en) * 2006-03-21 2006-11-08 吉林省中医中药研究院 Medicine for treating hyperplasia of mammary glands and its preparing method

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