CN1692933A - Compound traditional Chinese medicine for treating proliferation of mammary gland, and its prepn. method - Google Patents

Abstract

A Chinese medicine for treating mastoplasia is prepared from 5 Chinese-medicinal materials including ash bark, prunella spike, Zhejiang tendrilled fritillary bulb, laminaria, etc through extracting in water or alcohol. Its preparing process is also disclosed.

Description

Compound Chinese medicinal preparation of treatment cyclomastopathy and preparation method thereof

Technical field

The present invention relates to a kind of compound Chinese medicinal preparation for the treatment of cyclomastopathy and preparation method thereof.

Background technology

It is a kind of commonly encountered diseases that cyclomastopathy is commonly called as nodules of the breast, frequently-occurring disease.Can betide the women of all ages and classes, but be mainly in the age at 25-40 about year, and the canceration rate of primary disease reaches 10%-20%, thereby be a kind of great threat women's health.Doctor trained in Western medicine is clinical many with the hormone medicine treatment, has very big side effect and curative effect also not ideal enough.Chinese medicine has long history and abundant dialectical opinion to control experience to its diagnosis and treatment, and clinical therapeutic efficacy is also felt quite pleased.Along with Chinese medicine constantly develops, Chinese patent medicine preparation is paid close attention to by medical scholar.

Summary of the invention

The present invention overcomes the shortcoming of Chinese and western medicine preparation in the past, and a kind of good effect is provided, and the compound Chinese medicinal preparation of the treatment cyclomastopathy that has no side effect and preparation method thereof.

The invention provides a kind of compound Chinese medicinal preparation for the treatment of cyclomastopathy, it is to make active component by the extract of the alcohol and water of following raw materials according or following raw materials according or water extract, and its weight consists of:

Pericarpium Citri Reticulatae Viride 300-700 Spica Prunellae 400-800

Bulbus Fritillariae Thunbergii 300-700 Thallus Laminariae (Thallus Eckloniae) 400-800

Olibanum (vinegar system) 300-700.

Preferred weight of the present invention consists of:

Pericarpium Citri Reticulatae Viride 450-550 Spica Prunellae 550-650

Bulbus Fritillariae Thunbergii 450-550 Thallus Laminariae (Thallus Eckloniae) 550-650

Olibanum (vinegar system) 400-500.

More preferably weight consists of:

Pericarpium Citri Reticulatae Viride 500 Spica Prunellaes 600

Bulbus Fritillariae Thunbergii 500 Thallus Laminariae (Thallus Eckloniae)s 600

Olibanum (vinegar system) 450.

Above-mentioned Chinese medicine preparation, it can be said dosage form on any pharmaceuticss such as decoction, electuary, capsule, tablet, oral liquid or pill, the preparation of Chinese medicine preparation also can be carried out with reference to the method for conventional Chinese medicine preparation, but for improving drug effect, compound Chinese medicinal preparation of the present invention preferably adopts following preparation method.

Preparation method of the present invention is:

(1) take by weighing following traditional Chinese medicines weight raw material:

Pericarpium Citri Reticulatae Viride 300-700 Spica Prunellae 400-800

Bulbus Fritillariae Thunbergii 300-700 Thallus Laminariae (Thallus Eckloniae) 400-800

Olibanum (vinegar system) 300-700;

(2) get Pericarpium Citri Reticulatae Viride, Olibanum and extract volatile oil, aqueous solution device is in addition collected, and medicinal residues are distinguished the flavor of to boil after medicine is soaked with its excess-three and carried, and adds water then and carries out boiling the second time and carry; Merge secondary raffinate, filter the also concentrated and one-tenth extractum of filtrate, add 95% ethanol, after the mixing, placement is spent the night, and extracts supernatant, reclaims ethanol and is condensed into extractum, and drying is pulverizing also;

(3) get volatile oil in addition, use the beta-schardinger dextrin-inclusion, drying for standby;

(4) get dried cream powder and volatile oil clathrate compound, add right amount of auxiliary materials, make granule with marumerization and promptly get the made granule of the present invention.

Its step (2) Chinese medicine slag and its excess-three flavor medicine add 10 times of water gagings of crude drug, soak to boil after 0.5 hour and carry, and open computation time with water.Boil for the first time and carry 1.5 hours; Adding for the second time 8 times of water gagings boils and carries 1.5 hours; Merge secondary raffinate, filter, filtrate is concentrated into the extractum that relative density is 1.05-1.10, adds 95% ethanol, makes to contain alcohol amount and reach 50%, the limit adds the powerful stirring in ethanol limit 2 hours, placement is spent the night (about 24 hours), extracts supernatant, and recovery ethanol is concentrated into the extractum than the 1.30-1.35 that weighs, 80 ℃ of dryings are pulverized.

Solution of the present invention is based on understanding and the Therapeutic Principle of motherland's medical science to nodules of the breast and complication mechanism thereof, with reference to the modern pharmacology achievement in research, on the basis of using " book on Chinese herbal medicine " single Pericarpium Citri Reticulatae Viride soup, with the Pericarpium Citri Reticulatae Viride is monarch drug, and minister is with Spica Prunellae of taking a tonic or nourishing food to build up one's health blood vessels, hard masses softening and resolving and the Bulbus Fritillariae Thunbergii that dispels the heat relieving restlessness, dissipating phlegm and resolving masses; Thallus Laminariae (Thallus Eckloniae) and blood circulation promoting and blood stasis dispelling key medicine Olibanum with hard masses softening and resolving are assistant, more than a few flavor medicines share and cause gas suitable, expectorant disappears, blood is lived, piece removes, pain is separated and is played depressed liver-energy dispersing and QI regulating, the effect of vanishing sputum and dispelling knot, blood circulation promoting and blood stasis dispelling.The disease that is used for nodules of the breast: distending pain of the breast, warp before increases the weight of, nodule in the breast, the pain of touching, feeling of oppression over the chest and distention of hypochondrium, easily anxious susceptible to get angry, insomnia and dreamful sleep, vexed bitter taste, thin white fur of tongue, pulse condition string or stringy and rolling pulse, or cyclomastopathy sees that above-mentioned patient is arranged.

The specific embodiment

Embodiment 1: the preparation of Chinese medicinal granule a of the present invention

(1) press column weight amount proportioning and take by weighing each component:

Pericarpium Citri Reticulatae Viride 500 Spica Prunellaes 600

Bulbus Fritillariae Thunbergii 500 Thallus Laminariae (Thallus Eckloniae)s 600

Olibanum (vinegar system) 450

(2) take by weighing five tastes medical material by above-mentioned weight proportion, get Pericarpium Citri Reticulatae Viride, Olibanum extraction volatile oil, aqueous solution device is in addition collected, and medicinal residues and its excess-three flavor medicine add 10 times of water gagings of crude drug, soak to boil after 0.5 hour and carry, and open computation time with water.Boil for the first time and carry 1.5 hours; Adding for the second time 8 times of water gagings boils and carries 1.5 hours; Merge secondary raffinate, filter, filtrate is concentrated into the extractum that relative density is 1.05-1.10, adds 95% ethanol, makes to contain alcohol amount and reach 50%, the limit adds the powerful stirring in ethanol limit 2 hours, placement is spent the night (about 24 hours), extracts supernatant, and recovery ethanol is concentrated into the extractum than the 1.30-1.35 that weighs, 80 ℃ of dryings are pulverized.

(3) get volatile oil in addition, use the beta-schardinger dextrin-inclusion, 50 ℃ of drying for standby.

(4) get dried cream powder and volatile oil clathrate compound, add right amount of auxiliary materials, make granule with marumerization and promptly get the made granule a of the present invention.

Embodiment 2: the preparation of Chinese medicinal granule b of the present invention

(1) press column weight amount proportioning and take by weighing each component:

Pericarpium Citri Reticulatae Viride 400 Spica Prunellaes 450

Bulbus Fritillariae Thunbergii 600 Thallus Laminariae (Thallus Eckloniae)s 500

Olibanum (vinegar system) 400

(2) take by weighing five tastes medical material by above-mentioned weight proportion, get Pericarpium Citri Reticulatae Viride, Olibanum extraction volatile oil, aqueous solution device is in addition collected, and medicinal residues and its excess-three flavor medicine add 12 times of water gagings of crude drug, soak to boil after 1 hour and carry, and open computation time with water.Boil for the first time and carry 2 hours; Adding for the second time 10 times of water gagings boils and carries 1 hour; Merge secondary raffinate, filter, filtrate is concentrated into the extractum that relative density is 1.10-1.20, adds 95% ethanol, makes to contain alcohol amount and reach 70%, the limit adds the powerful stirring in ethanol limit 2 hours, placement is spent the night (about 24 hours), extracts supernatant, and recovery ethanol is concentrated into the extractum than the 1.35-1.40 that weighs, 60 ℃ of dryings are pulverized.

(3) get volatile oil in addition, use the beta-schardinger dextrin-inclusion, 70 ℃ of drying for standby.

(4) get dried cream powder and volatile oil clathrate compound, add right amount of auxiliary materials, with 95% ethanol system soft material, 16 mesh sieves are granulated, 80 ℃ of dryings, and granulate promptly gets the made granule b of the present invention.

Embodiment 3: the preparation of Chinese medicinal tablet c of the present invention

(1) press column weight amount proportioning and take by weighing each component:

Pericarpium Citri Reticulatae Viride 450 Spica Prunellaes 550

Bulbus Fritillariae Thunbergii 400 Thallus Laminariae (Thallus Eckloniae)s 450

Olibanum (vinegar system) 500

(2) take by weighing five tastes medical material by above-mentioned weight proportion, get Pericarpium Citri Reticulatae Viride, Olibanum extraction volatile oil, aqueous solution device is in addition collected, and medicinal residues and its excess-three flavor medicine add 8 times of water gagings of crude drug, soak to boil after 2 hours and carry, and open computation time with water.Boil for the first time and carry 1 hour; Adding for the second time 6 times of water gagings boils and carries 1 hour; Merge secondary raffinate, filter, filtrate is concentrated into the extractum that relative density is 1.10-1.15, adds 95% ethanol, makes to contain alcohol amount and reach 80%, the limit adds the powerful stirring in ethanol limit 2 hours, placement is spent the night (about 24 hours), extracts supernatant, and recovery ethanol is concentrated into the extractum than the 1.35-1.38 that weighs, 70 ℃ of dryings are pulverized.

(3) get volatile oil in addition, use the beta-schardinger dextrin-inclusion, 60 ℃ of drying for standby.

(4) get dried cream powder and volatile oil clathrate compound, add right amount of auxiliary materials, with 70% ethanol system soft material, 18 mesh sieves are granulated, 80 ℃ of dryings, and granulate, it is evenly mixed to add the moderate lubrication agent, and tablet forming promptly gets the made tablet c of the present invention.

The particulate animal acute toxicity test of zoopery example 1 the present invention:

Carry out the toxic reaction of animal after maximum tolerated dose experiment administration with granule dry extract of the present invention.

20 of experimental animal ICR strain white mice, male and female half and half are irritated stomach 195g/kg//day, divide three administrations (press crude drug and calculate, be equivalent to 220.8 times of clinical consumption), obvious toxicity does not appear in animal before and after the administration, observed 7 days continuously, animal does not have death, also no abnormal performance.

Experiment shows: granule does not have overt toxicity to laboratory animal, and it is safe pointing out this medicine clinical practice.

The particulate long term toxicity test of zoopery example 2 the present invention:

Give the granule dry extract of the present invention toxic reaction that (being mixed with certain density solution) produced to rat filling stomach in continuous 180 days and carry out long term test, by observing the symptom and the order of severity that at first occurs, the target organ of toxicity and recovery thereof and development, determine nontoxic amounts of reactants, provide reference for drafting the human safe dose.

Select 170 of healthy white rats, be divided into 3 groups at random, 40～44 every group, male and female half and half.Matched group is irritated stomach with capacity such as distilled water; The heavy dose of group of granule of the present invention is irritated stomach (press crude drug calculating) with 88g/kg, is equivalent to clinical adult approximately and intends 100 times of consumption every day; Small dose group is irritated stomach (press crude drug calculate) with 22g/kg, is equivalent to clinical adult approximately and intends 25 times of consumption every day.

Every day, gastric infusion was 1 time, and is consistent with the clinical administration approach.Experimental session is observed the general situation of rat, surveys body weight and defecation after 24 hours respectively at reaching drug withdrawal before the administration, gets blood examination and surveys SGPT, BUN and routine blood test.Administration after 6 months every group put to death 2/3rds animals (about 28), core, liver, spleen, lung, kidney, adrenal gland, brain, stomach, large intestine, small intestinal, mesentery, lymph node, testis, ovary send disease to examine.All put to death the back around the drug withdrawal, as above send the disease inspection.

1. general situation and body weight change: pursue mouthful observation and respectively organize the expression of rat, activity, secretions, diet, feces, hair, skin etc., show no obvious abnormalities variation, see Table 1.

The influence (g) of table 1. pair rat body weight

Group		Dosage (g/kg)	Detection time
						Before the administration	Administration 6 months	Around the drug withdrawal
			Heavy dose of	Male	??88				??90.3±7.3	??483.1±34.3	??525.0±21.7
Female	??86.1±7.2	??316.7±24.9				??343.0±29.8
				Low dose of			Male	??22	??90.7±8.3	??487.0±49.5	??510.8±66.9
Female	??86.1±6.7	??292.4±24.1	??314.2±22.0
					Contrast	Male	??--		??90.3±7.8	??486.8±30.6	??517.8±31.9
Female	??86.6±7.9	??316.0±25.0	??337.2±35.7

2. hematological examination: each dosage group Hb, RBC, WBC medication before and after look, have no significant change, each administration group and matched group be no significant difference (P＜0.05) relatively, sees Table 2.

The influence that table 2.. learns rat blood (X ± SD)

Time	Index	Contrast	Heavy dose of	Low dose of
					Before the administration	??RBC(1012/L)	??8.39±0.99	??8.20±1.19	??8.86±1.60
??WBC(109/L)	??12.33±2.07	??11.80±2.29	??12.6±2.07
				??HB(g/L)		??130.30±15.32	??127.33±16.24	??133.17±16.90
??PLT(109/L)	??185.8±23.4	??179.2±20.4	??190.1±25.8
				??HCT(％)		??34.19±3.66	??33.85±4.02	??36.75±5.72
Six months	??RBC(1012/L)	??7.72±0.57	??7.68±0.66						??7.85±0.76
				??WBC(109/L)	??11.72±1.93	??11.74±1.89	??10.89±1.53
	??HB(g/L)	??127.38±17.21	??133.18±10.98					??134.43±16.90
				??PLT(109/L)	??195.0±22.1	??187.9±18.4	??190.0±28.4
	??HCT(％)	??54.97±4.70	??54.38±5.04					??56.81±7.73
				Around the drug withdrawal	??RBC(1012/L)	??7.83±0.55	??7.98±0.53		??7.88±0.38
??WBC(109/L)	??12.05±4.47	??11.41±2.62	??11.66±3.98
					??HB(g/L)	??125.8±17.9	??125.9±13.2	??125.2±18.3
??PLT(109/L)	??190.2±13.5	??190.3±15.0	??187.2±13.9
					??HCT(％)	??55.32±3.83	??57.25±5.31	??56.11±3.19

3. the influence that rat WBC is classified: each dosage group medication before and after look, have no significant change, each administration group and matched group be no significant difference (P＜0.05) relatively, sees Table 3.

The influence of table 3. couple rat WBC (X ± SD)

Time	Index	Contrast	Heavy dose of	Low dose of
					Before the administration	Lymph	??71.90±3.13	??72.90±3.32	??72.40±2.98
Middle grain	??26.45±3.18	??26.15±3.37	??25.95±3.19
				Monokaryon		??1.65±0.67	??1.70±0.66	??1.65±0.67
Six months	Lymph	??71.85±6.47	??71.40±6.46						??71.70±6.99
				Middle grain	??26.80±6.38	??27.25±6.60	??26.95±6.94
	Monokaryon	??1.40±0.60	??1.35±0.67					??1.35±0.59
				Around the drug withdrawal	Lymph	??71.50±6.57	??71.58±6.35		??74.00±6.29
Middle grain	??27.50±6.52	??27.08±6.50	??24.64±5.66
					Monokaryon	??1.50±0.80	??1.33±0.49	??1.45±0.69

4.BUM check result: each dosage group and matched group no significant difference (P＜0.05) see Table 4

The influence of table 4. couple rat BUM (mmol/LX ± SD n=20)

Group	Dosage (g/kg)	Detection time
					Before the administration	Administration 6 months	Around the drug withdrawal
		Heavy dose of	??88	??4.98±0.61				??5.54±0.71	??5.56±1.05
Low dose of	??22				??5.19±0.71	??5.31±0.74	??5.25±1.05
		Contrast	??--	??5.12±0.76				??5.48±0.63	??5.32±0.56

4. after around administration 6 months and the drug withdrawal, the rat perusal of each dosage group, no abnormality seen, the disease inspection internal organs and the matched group of each dosage group relatively do not have obvious pathological change

5. after around administration 6 months and the drug withdrawal, organ coefficient result of calculation, each dosage group Rats Organs and Tissues coefficient and matched group be no significant difference (P＜0.05) relatively.

Above result shows that granule clinical practice of the present invention is safe.

Zoopery 3 granules of the present invention cure mainly relevant Pharmacodynamic test of active extract with function

Effect is tested to the particulate inhibition cyclomastopathy of the present invention, provides foundation for correctly estimating its pharmacological action and effectiveness.

One, preparation granules of the present invention is to the inhibitory action of rat mammary gland model of hyperplasia

Female with the Wistar rat, the injection estradiol is induced hyperplasia of mammary gland model, per os gives compound Chinese medicinal preparation extractum 2.65g crude drug/kg of the present invention and 5.3g crude drug/kg (3.6 times of clinical application amounts) simultaneously, and contrasts drug effect with RUKUAIXIAO 0.18g sheet/kg (3 times of clinical application amounts).Successive administration 30 days.The result shows that preparation hyperplasia of mammary gland model of the present invention has the inhibition proliferative effect, and two groups in preparation of the present invention has significant difference (P＜0.05) with the model group ratio.Histopathology is changed into: mammary gland glandular lobule decreased number, and the glandular lobule area is little, and stroma is many.Secretions reduces in the lumen of gland.Preparation of the present invention can reduce the trend because of uterine hydrops that estrogen is induced.RUKUAIXIAO is not obvious to the cyclomastopathy inhibitory action, and growth has a significant effect to rat body weight.

This experiment purpose is in order to compare preparation of the present invention and the commercially available RUKUAIXIAO tablet inhibition effect to the living model of experimental mammary gland, for clinical practice provides experimental basis.

Brief summary

1, two groups in preparation of the present invention induces the rat mammary gland hypertrophy that obvious inhibitory action is arranged to estradiol, and significant difference (P＜0.05%) is arranged between its inhibitory action and model group.

2, there is not tangible dose-effect relationship between preparation various dose group of the present invention.

3, preparation of the present invention can alleviate estradiol and brings out the rat uterus hydrops, trends such as uterine cavity expansion.

4, two kinds of medicines do not cause all that to rat ovary the pathological tissue form changes.

Two, preparation of the present invention is to the analgesic activity (writhing method) of mice

Kunming mouse gives preparation extractum 4.42g of the present invention, 8.84g and 17.68g crude drug/kg body weight (dosing was 5,10,20 times in quite clinical day); The Dichlorodiphenyl Acetate abdomen is annotated inductive mice and is caused pain writhing method number of times, and group obviously reduces (P＜0.05) 8.84g crude drug/kg more than, than etc. clinical multiple RUZENGNING PIAN analgesic activity obvious.Show that this medicine has the analgesia drug action.

Brief summary

1, the above group of preparation 8.84g crude drug of the present invention/kg body weight Dichlorodiphenyl Acetate inducing mouse writhing response number of times has obvious inhibitory action, and is a certain amount of effect relationship.

2, preparation of the present invention and breast increase peaceful two medicines and are waiting under clinical day clothes 10 multiple doses, and preparation analgesic activity of the present invention is better than breast and increases rather.

Three, preparation of the present invention is to the influence of rat choleretic effect

Wistar is a male rat, a duodenum gives preparation 4.42g crude drug/kg of the present invention above (being equivalent to the clinical application amount more than 5 times), and secretion has obvious facilitation to rat bile, between each dosage group a certain amount of effect relationship is arranged, sustainable 150 minutes of the above group of 8.84g crude drug/kg.Breast increases peaceful 3.42g tablet/kg group (being equivalent to 20 times of clinical application amounts) and also obviously promotes bile secretion.Two medicine comparisons preparation of the present invention promotes but the juice secretory action obviously is better than breast increases rather.Show that this prescription has the pharmacological action of depressed liver-energy dispersing and QI regulating, resolving depression.

Preparation of the present invention is a clinical treatment benign hyperplasia of mammary glands disease proved recipe.In the clinical treatment liver energy depression and phlegm stagnation type nodules of the breast disease there is better curative effect.Pericarpium Citri Reticulatae Viride is a monarch drug in this prescription, has depressed liver-energy dispersing and QI regulating, the effect of eliminating stagnation expectorant (1).For the pharmacological action of the depressed liver-energy dispersing and QI regulating that confirms this prescription, carried out this test.And make pharmacodynamic action with listing " breast increases rather " and compare.

Secretion has obvious facilitation to brief summary preparation of the present invention to rat bile in each group (being equivalent to the clinical application amount more than 5 times) more than 4.42g crude drug/kg, between each dosage group a certain amount of effect relationship is arranged.8.84g sustainable 150 minutes of the above group of crude drug/kg, breast increases peaceful 3.42g tablet/kg group (being equivalent to 20 times of clinical application amounts) and also obviously promotes bile secretion.The effect of two medicine comparisons preparation promotion of the present invention bile secretion obviously is better than breast and increases rather.Show that this prescription has the pharmacological action of depressed liver-energy dispersing and QI regulating, resolving depression.

Four, preparation of the present invention is induced the influence of rat uterus variation to estradiol

With Wistar is from newborn female rats, body weight 45～59g, the subcutaneous injection estradiol induces female Mus uterus picked-up moisture content to increase and the ovary variation model, per os gives preparation 4.4g crude drug/kg of the present invention, 13.2g crude drug/kg and 26.4g crude drug/kg (respectively quite clinical day dosing 5,15,30 times), and the positive control drug breast increases peaceful 2.03g tablet/kg (be equivalent to clinical day dosing 15 times), and each is 30 days.The result shows that three dosage groups of preparation of the present invention all do not have notable difference with the estradiol group to the inductive rat uterus weight change of estradiol, cavity of uterus hydrops, growth, serum estradiol content and morphological examination dried/wet ratio, the promotion ovary, promptly there is not the antagonism estradiol not strengthen the effect of estradiol yet, breast increases peaceful group does not equally have obvious antagonism or potentiation yet, but body weight gain is had obvious inhibitory action.

Preparation of the present invention is used for the treatment of the non-breast phase benign hyperplasia of mammary glands disease that is subjected to, and good efficacy [1] is arranged clinically, and zoopery shows that this medicine has obvious inhibitory action to the hypertrophy and the secretion of galactophore epithelial cell.Whether this medicine is due to the estrogenic effect of antagonism to the effect of rat mammary gland epithelial cell, has designed this test for this reason, induces rat uterus to take the photograph water and weight change rat model with estradiol, detects the change after per os gives this medicine.In the hope of further understanding this medicine estrogen there is not antagonism.

Brief summary

1, each group of preparation of the present invention is to the inductive female Mus uterus weight of estradiol, dirty/body ratio, dried/weight in wet base ratio, the no obvious antagonism of cavity of uterus hydrops variation.

2, each group of preparation of the present invention does not have obvious antagonism to the inductive female Mus development of ovary inhibitory action of estradiol, only shows that increasing the corpus luteum number with dosage also slightly increases.

3, preparation height of the present invention, middle group are to the not obviously influence of female Mus serum estradiol content, and the low group of preparation of the present invention serum estradiol content is starkly lower than estradiol group (P＜0.05).

4, breast increases rather each index of the inductive female Mus of estradiol to be changed does not have obvious antagonism, and serum estradiol content is apparently higher than the low group of preparation of the present invention.The uterus is dirty/and body ratio is starkly lower than in the preparation of the present invention and organizes.Body weight gain there is obvious inhibitory action.

Application examples 1 granule therapy cyclomastopathy 306 routine clinical observations of the present invention

Objective evaluation preparation granules treatment nodules of the breast of the present invention (cystic hyperplasia of breast) belongs to the clinical efficacy and the safety thereof of stagnation of QI due to depression of the liver, expectorant blood coagulation stasis of blood patient.

Object and method

One, qualified experimenter's determines

1. diagnostic criteria

1) Western medicine diagnose

(1) good sending out in 35～45 years old married woman.

(2) mastalgia is generally not serious, mostly is bilateral, also can be one-sided, for dull pain, distending pain, dull pain or twinge, scurry pain, weigh down pain, burning pain, normal companion's tenderness.Can increase the weight of before the menstruation or during anxious state of mind.

(3) lump in breast: mostly be bilateral, it is in the majority to go up quadrant in addition.

Single lump: capsule, clear-cut margin, mobility is big.

Most lumps: multiple capsule tuberosity, can involve full milk or two breast, obscure boundary.

The mammary gland sector tuberosity: tuberosity is pressed the latex dust system and is distributed, and subtriangular, the base is positioned at the mammary gland edge, is irregular agglomerate, or plate-like agglomerate, lamellar agglomerate, combines strip, graininess, and not of uniform size, soft or hard does not wait, and obscure boundary is with the skin adhesion.

(4) nipple discharge: discharge or when touching voluntarily by certain latex dust system, can cause nipple discharge, mostly be yellow serosity.

(5) X radiodiagnosis x: increase in density, but inhomogeneous, blur margin.

(6) near infrared ray inspection: be cloud and mist lump shadow, blur margin.

(7) ultrasound diagnosis: mammary gland tissue thickens, and fills the air distribution, differ in size, the opaque dark area of fluid, rounded or oval, cyst wall is smooth, ventilative sound is good, between the capsule between matter echo strengthen.

(8) pathological diagnosis: typical cystic hyperplasia of breast sexually transmitted disease (STD) reason changes.

2) Chinese medical discrimination

(1) Liver depression and Qi stagnation

Based on mastalgia, mostly be distending pain, scurry pain, the growth and decline with menstrual cycle and emotion changes, the lump soft or hard does not wait in the breast, companion's breast side of body feeling of distension and oppression, irritated irritability, thin white fur of tongue, stringy pulse.

(2) expectorant blood coagulation blood stasis syndrome

Based on lump in breast, quality is harder, touches a tender spot obviously, mostly is twinge, dimly red tongue or ecchymosis, petechia are arranged, white and greasy fur, hesitant pulse or stringy and thready pulse or stringy and rolling pulse.

3) state of an illness weight classification

Light-duty: mastalgia is dull pain, scurry pain, and one-sided or bilateral lump in breast is single little lump, or is graininess and scope is little, or is streak thing, and is softer, is confined to a quadrant.

Medium-sized: mastalgia is dull pain or scurries pain and tenderness is arranged that distending pain is obvious, and lump is bigger, or in the form of sheets, plate-like, involve two breasts, but scope is at two quadrants.

Heavy: mastalgia is touched a tender spot obviously for weighing down pain or twinge, and lump is big, and multiple capsule tuberosity involves two breasts, and scope is at two more than the quadrant.

2. include standard in

(1) the cyclomastopathy patient traditional Chinese medical science distinguishes that rate belongs to stagnation of QI due to depression of the liver, expectorant blood coagulation blood stasis syndrome person

(2) age 19-55 year

3. exclusion standard

(1) the cyclomastopathy Chinese medical discrimination does not meet stagnation of QI due to depression of the liver, expectorant blood coagulation blood stasis syndrome person

(2) amenorrhea patients that causes of endocrinopathy

(3) mastitis patient

(4) high prolactin antagonist disease patient

(5) galactocele patient

(6) breast carcinoma is doubted and is examined or the person of making a definite diagnosis

(7) mammary gland fibroma is doubted and is examined or the person of making a definite diagnosis

(8) adolescence women

(9) menopausal women

(10) age is at under-18s or more than 55 years old, gestation or women breast-feeding their children

(11) be associated with serious primary disease such as cardiovascular, cerebrovascular, liver, kidney and hemopoietic system, psychotic

(12) mismatch therapist

Two, embodiment

1. case grouping

The test phase I adopt single at random blind controlled trial method with qualified experimenter with 1: 1 pro rate to treatment group and matched group.Single at random blind controlled trial method that the test second stage adopt to enlarge with qualified experimenter to be not more than 3: 1 pro rate to treatment group and matched group.Two stages, the hospital more than three families carried out simultaneously.The case group technology adopts the simple randomization method.Observe routine number: treatment is organized more than 300 examples, more than matched group 100 examples.

2. random method

By random number keyboard (INV on operation casio (fx-1600p) computer, RAN), establishment random assortment card, give each clinical hospital after the numbering sealing, the clinical research personnel enter the sequencing of research by qualified experimenter, according to the envelope numbering, the Kaifeng card taking carries into execution a plan by the grouping of card regulation.

3. single blind method is implemented

Preparation granules of the present invention and RUKUAIXIAO KELI are labelled again, and the blue or green breast of called after disappears granule I number respectively, and blue or green breast disappears granule II number.

4. the contrast medicine is selected

Select RUKUAIXIAO KELI for use, the Beijing Yadong Biology Pharmacy Co., Ltd produces.

5. Therapeutic Method

Treatment group: preparation granules of the present invention, each one bag (10g), a twice-daily.

Matched group: RUKUAIXIAO KELI, each one bag (10g), three times on the one.

Two medicines all began to take medicine at menstrual cycle on the 5th day, if be less than 5 days menstrual period, then the man month begins to take medicine after the cycle is clean, takes continuously about 22 days, and during to menstrual period drug withdrawal is about about 7 days.

Duration of test is withdrawn other relevant medicine such as hormone drug, analgesic and other Chinese medicine preparation etc.

The course of treatment: 3 months

Three, observation item

1. safety observation

1) blood, urine, just conventional

2) heart, liver, renal function

3) untoward reaction is observed: whether must record faithfully any untoward reaction that occurs after the medication, comprise general untoward reaction and gastrointestinal reaction, also should write down needs drug withdrawal, whether takes treatment measures.

2. general data: name, age, the course of disease, medical history, marrital history, motherhood history, suckling situation etc.

3. health giving quality observation (detect and carried out in 7-10 days) at menstrual cycle

(1) related symptoms: distending pain of the breast, tenderness, distending pain in the chest and hypochondrium, feelings will etc.

(2) menstruation: menstrual period, through color, through amount, menstrual cycle etc.

(3) picture of the tongue, pulse condition

(4) sign: lump in breast position, size, number, border, quality, tenderness etc.

(5) lab testing

1. breast B super scanning (must examine item, after menstruation, check in the week and check)

2. the X line is taken the photograph sheet (must examine item, check in the week and check) after menstruation

3. near infrared ray galactophore scanning (Selected Inspection item)

4. distending pain of the breast, tenderness classification, lump size observation procedure:

(1) distending pain of the breast

0 grade: no breast distending pain

I level: slight distending pain, numbness when not noting

II level: often feel to have distending pain

III level: tangible distending pain is arranged

The IV level: distending pain of the breast is serious, wears the clothes and all feels pain, even influence the upper limb activity

(2) breast tenderness

0 grade: do not have and touch a tender spot

I level: the slight tenderness

II level: moderate tenderness

III level: obviously touch a tender spot, the automatic action of dodging is arranged during inspection

IV level: obviously avoid or refuse checking because of touching a tender spot

(3) lump in breast size

By auxiliary detection synthetic determinations such as palpation, B ultrasonic, molybdenum targets, with cm2 (transverse diameter * perpendicular footpath) expression.

5. observational technique: above-mentioned symptom, picture of the tongue, pulse condition, sign all need per two all observed and recordeds once, routine blood test, routine urinalysis, size routine, electrocardiogram, liver function, kidney function test project can each detect once before and after treatment as far as possible, B ultrasonic, molybdenum target inspection must respectively be carried out once before and after treatment, can not carry out the molybdenum target inspection when following up a case by regular visits to.After taking medicine two months, in the time of clinical recovery may being judged as curative effect, must carry out inspections such as B ultrasonic, molybdenum target.

6. follow up a case by regular visits to:

The back curative effect of the end course of treatment is judged as produce effects and recent clinical recovery person need carry out follow-up observation in month by a definite date.

For ease of carrying out the late result observation after the drug withdrawal, in addition with placebo granule called after preparation granules III of the present invention number, the patient who gives between follow-up period takes.

Four, curative effect determinate standard

1. clinical recovery: mastalgia and mammary gland tumor disappear

2. produce effects: mastalgia disappears, and heavy type becomes light-duty, and mammary gland tumor dwindles＞and 1/2

3. effective: mastalgia disappears or alleviates, and medium-sizedly becomes light-dutyly, and that heavy type becomes is medium-sized, mammary gland tumor is dwindled≤and 1/2

4. invalid: mastalgia does not alleviate on the contrary and increases the weight of, and mammary gland tumor is not dwindled or increase person on the contrary

Five, the summarization of data and date processing

After clinical trial finished, all clinical datas gathered to Traditional Chinese Medicine University Of Guangzhou clinical pharmacology base, and the input computer is set up the data base, carries out data management, carries out statistical analysis with Epi Info software.The clinical efficacy and the safety thereof of last objective evaluation preparation granules treatment nodules of the breast of the present invention (cystic hyperplasia of breast).

Statistical method:

Group data is checked with X2, and ranked data are with the relatively Wilcoxon rank test (corrections) of two samples, and two sample means are relatively with the t check, relatively matches rank test with paired t-test or Wilcoxon before and after self.

Discuss

Single at random blind controlled trial method is adopted in this research, and it has observed cyclomastopathy patient 437 examples, and 306 examples are organized in preparation granules treatment wherein of the present invention, RUKUAIXIAO KELI matched group 131 examples.Chinese medical discrimination belongs to Liver depression and Qi stagnation 261 examples (190 examples are organized in treatment, 71 groups of matched groups), expectorant blood coagulation blood stasis syndrome 21 examples (21 examples are organized in treatment, 9 groups of matched groups), stagnation of QI due to depression of the liver expectorant blood coagulation blood stasis syndrome 155 examples (104 examples are organized in treatment, matched group 51 examples) of holding concurrently.

Comparability detects and shows, age, the course of disease, tcm syndrome, severity extent, lump in breast distributions, lump size, lump number, breast tenderness degree, mastalgia degree etc. influence the principal element comparison of Drug therapy prognosis before two groups of treatments, difference there are no significant meaning.Point out two groups to have harmony.Clinical total effects observed result shows that treatment group clinical recovery rate is 15.7%, and obvious effective rate is 37.6%, and effective percentage is 41.8%, and clinical recovery rate and obvious effective rate are 53.3%, and total effective rate is 95.1%; Matched group clinical recovery rate is 3.1%, and obvious effective rate is 21.4%, and effective percentage is 56.5%, and clinical recovery rate and obvious effective rate are 24.5%, and total effective rate is 80.9%.Two groups relatively, and difference has the significance meaning.Point out the clinical total effects of preparation granules treatment cyclomastopathy of the present invention to be higher than contrast medicine RUKUAIXIAO KELI.

Preparation granules of the present invention all has clinical efficacy preferably to one-sided, bilateral breast hypertrophy disease, but its treatment clinical total effects one-sided, bilateral breast hypertrophy disease is higher than contrast medicine RUKUAIXIAO KELI.

Preparation granules of the present invention all has clinical efficacy preferably to one-sided, bilateral breast hypertrophy disease, but its treatment curative effect one-sided, bilateral breast hypertrophy disease is compared, and difference does not have the significance meaning.

Two groups of clinical efficacies to one-sided cyclomastopathy compare, and difference has the significance meaning; Two groups of clinical efficacies to bilateral breast hypertrophy disease compare, and difference also has the significance meaning.No matter prompting is that treatment is one-sided, still treat bilateral breast hypertrophy disease, the clinical efficacy of preparation granules of the present invention all is higher than contrast medicine RUKUAIXIAO KELI.

Different tcm syndrome clinical efficacy results show:

Preparation granules Liver depression and Qi stagnation treatment group clinical recovery rate of the present invention is 16.8%, and obvious effective rate is 35.8%, and effective percentage is 42.1%, and clinical recovery rate and obvious effective rate are 52.6%, and total effective rate is 94.7%; Matched group clinical recovery rate is 4.2%, and obvious effective rate is 19.7%, and effective percentage is 63.4%, and clinical recovery rate and obvious effective rate are 23.9%, and total effective rate is 77.3%.Two groups relatively, and difference has the significance meaning.

The preparation granules of the present invention treatment stagnation of QI due to depression of the liver expectorant blood coagulation blood stasis syndrome cyclomastopathy clinical recovery rate of holding concurrently is 15.4%, and obvious effective rate is 41.3%, and effective percentage is 39.4%, and clinical recovery rate and obvious effective rate are 56.7%, and total effective rate is 96.2%; Matched group clinical recovery rate is 2.0%, and obvious effective rate is 21.6%, and effective percentage is 47.1%, and clinical recovery rate and obvious effective rate are 23.6%, and total effective rate is 70.6%.Two groups relatively, and difference has the significance meaning.

The above results prompting preparation granules treatment of the present invention cyclomastopathy belongs to the stagnation of QI due to depression of the liver expectorant blood coagulation blood stasis syndrome of holding concurrently clinical efficacy preferably, is higher than matched group.

The clinical symptoms efficacy result shows:

Two groups of back breast tenderness, mastalgia symptoms to the cyclomastopathy patient of treatment all have significantly improvement effect, and the improvement rate of the back breast tenderness to the patient of preparation granules treatment of the present invention, mastalgia symptom is apparently higher than matched group (P＜0.05), and breast tenderness, mastalgia, irritated irritability transference cure rate are also apparently higher than matched group (P＜0.05).

Two groups of treatment back cyclomastopathy patients' lump in breast size all has obviously dwindles, and preparation granules treatment group of the present invention treatment rear udder attachment lump obviously dwindles than matched group, and disappearance rate is apparently higher than matched group (P＜0.05).

Can obviously improve cyclomastopathy patient's main clinic symptoms after pointing out preparation granules treatment of the present invention, and curative effect is higher than the contrast medicine.

After finishing three months courses of treatment, the patient of efficacy determination clinical recovery, produce effects has all carried out following up a case by regular visits to of drug withdrawal 1 month in the treatment group.The result shows that preparation granules treatment cyclomastopathy of the present invention has late result preferably.

The safety testing result shows, blood, urine, stool routine examination, liver function (GPT), renal function (BUN), electrocardiogram testing result before and after the part patient, and failing has infringement to the heart, liver, renal function and blood system after the prompting treatment.

The untoward reaction incident is observed and is shown all have the part patient (treatment group occurrence rate are 8.5%, and the matched group occurrence rate is 6.9%) such as nausea,vomiting,diarrhea, dizziness, advanced menstruation, menorrhagias to occur after two groups of medications.Organizing 2 routine patients, matched group 1 routine patient except that treatment needs symptom is died away after the drug withdrawal, and all the other are all not drug withdrawals in therapeutic process, also do not take any treatment measures, and symptom can be died away.Above-mentioned data shows, preparation granules clinical practice safety of the present invention.

Claims (5)

1, a kind of compound Chinese medicinal preparation for the treatment of cyclomastopathy is characterized in that it is to make active component by the extract or the water extract of the alcohol and water of following raw materials according or following raw materials according, and its weight consists of:

Pericarpium Citri Reticulatae Viride 300-700 Spica Prunellae 400-800

Bulbus Fritillariae Thunbergii 300-700 Thallus Laminariae (Thallus Eckloniae) 400-800

Olibanum (processed with vinegar) 300-700.

2,, it is characterized in that its weight consists of according to the described compound Chinese medicinal preparation of claim 1:

Pericarpium Citri Reticulatae Viride 450-550 Spica Prunellae 550-650

Bulbus Fritillariae Thunbergii 450-550 Thallus Laminariae (Thallus Eckloniae) 550-650

Olibanum (processed with vinegar) 400-500.

3,, it is characterized in that its weight consists of according to the described compound Chinese medicinal preparation of claim 1:

Pericarpium Citri Reticulatae Viride 500 Spica Prunellaes 600

Bulbus Fritillariae Thunbergii 500 Thallus Laminariae (Thallus Eckloniae)s 600

Olibanum (processed with vinegar) 450.

4, a kind of preparation method for the treatment of the compound Chinese medicinal preparation of cyclomastopathy, its preparation process is:

(1) take by weighing following traditional Chinese medicines weight raw material:

Pericarpium Citri Reticulatae Viride 300-700 Spica Prunellae 400-800

Bulbus Fritillariae Thunbergii 300-700 Thallus Laminariae (Thallus Eckloniae) 400-800

Olibanum (processed with vinegar) 300-700;

(2) get Pericarpium Citri Reticulatae Viride, Olibanum and extract volatile oil, aqueous solution device is in addition collected, and medicinal residues are distinguished the flavor of to boil after medicine is soaked with its excess-three and carried, and adds water then and carries out boiling the second time and carry; Merge secondary raffinate, filter the also concentrated and one-tenth extractum of filtrate, add 95% ethanol, after the mixing, placement is spent the night, and extracts supernatant, reclaims ethanol and is condensed into extractum, and drying is pulverizing also;

(3) get volatile oil in addition, use the beta-schardinger dextrin-inclusion, drying for standby;

(4) get dried cream powder and volatile oil clathrate compound, add right amount of auxiliary materials, make granule with marumerization and promptly get the made granule of the present invention.

5, preparation method according to claim 4 is characterized in that step (2) Chinese medicine slag and its excess-three flavor medicine adds 10 times of water gagings of crude drug, soaks to boil after 0.5 hour and carries, and opens computation time with water.Boil for the first time and carry 1.5 hours; Adding for the second time 8 times of water gagings boils and carries 1.5 hours; Merge secondary raffinate, filter, filtrate is concentrated into the extractum that relative density is 1.05-1.10, adds 95% ethanol, make and contain alcohol amount and reach 50%, the limit adds the powerful stirring in ethanol limit 2 hours, and placement is spent the night, about 24 hours, extract supernatant, recovery ethanol is concentrated into the extractum than the 1.30-1.35 that weighs, and 80 ℃ of dryings are pulverized.