CN100490891C - Medicine composition for treating dysmenorrhea and its preparation process - Google Patents

Abstract

The present invention discloses one kind of medicine composition for treating women' s dysmenorrheal, menoxenia and other diseases and its preparation process. The medicine composition is prepared with 14 kinds of Chinese medicinal materials, including tree peony bark, burred tuber, zedoary, diverse wormwood herb, corydalis tuber, etc. The preparation process includes the steps of crushing tree peony bark into fine powder, decocting the other 13 kinds of Chinese medicinal materials while collecting volatile oil, filtering the decoction, concentrating to obtain extractum, mixing with tree peony bark powder, drying, crushing, spraying the volatile oil and mixing. The medicine composition is used in treating women' s dysmenorrheal, menoxenia and other diseases, and has excellent functions of warming the channels, dissolving clots, regulating qi and relieving pain.

Description

A kind of pharmaceutical composition and preparation method for the treatment of dysmenorrhea

Technical field

The present invention relates to a kind of pharmaceutical composition and preparation method thereof and quality determining method, particularly a kind of pharmaceutical composition for the treatment of diseases such as dysmenorrhes, menoxenia and preparation method thereof and quality determining method.

Background technology

Dysmenorrhea is a common gynecological disease.Periodically hypogastralgia appears in the women before and after menstrual period and menstruation, very then severe pain is fainted, and has a strong impact on women's physical and mental health and life, work.According to the investigation of national woman month through the physical constants cooperative groups, in China women, the sickness rate of dysmenorrhea is 33.19%, and primary dysmenorrhea accounts for 36.06%, and the worker of having a strong impact on accounts for 13.5%.Clinical indometacin commonly used, ibuprofen and somedon etc. have many unnecessary side effect to human body.Chinese medicine is of long standing and well established to the research of dysmenorrhea, and ancient Chinese medicine doctor has very penetrating argumentation to this, is no lack of the monograph monograph, has accumulated abundant clinical experience.But the new Chinese medicine of treatment dysmenorrhea is less on market, more lacks the reliable Chinese patent medicine of curative effect.

At present, the new Chinese medicine of used treatment dysmenorrhea all adopts blood circulation promoting and blood stasis dispelling on the market, and high violent dry strong product such as dispelling cold by warming the meridian are formed.Women's physiological characteristics is afraid of blood trouble most for based on blood.And clinical findings, dysmenorrhea patient's etiology and pathogenesis more complicated, the pure real person of pure void seldom most holds reality under the arm for apoplexy due to deficiency, holds void under the arm in fact, and deficiency and excess is held under the arm assorted.Take these medicines, cause toxic and side effects easily.Cause the range of application of these medicines to become very narrow, curative effect is subjected to very big restriction, has run counter to the original intention of researcher.

Summary of the invention

First purpose of the present invention is to disclose a kind of pharmaceutical composition; Second purpose of the present invention is to disclose a kind of pharmaceutical composition for the treatment of diseases such as dysmenorrhes, menoxenia; The 3rd purpose of the present invention is to disclose this preparation of drug combination method; The 4th purpose of the present invention is to disclose the quality determining method of this pharmaceutical composition.

The present invention seeks to be achieved through the following technical solutions:

The crude drug of this pharmaceutical composition consists of:

Rhizoma sparganic 5-30 weight portion, Rhizoma Curcumae 5-30 weight portion, siphonostegia chinensis 5-30 weight portion, Rhizoma Corydalis 5-30 weight portion, Cortex Moutan 5-30 weight portion, Radix Rehmanniae Preparata 5-30 weight portion, Radix Angelicae Sinensis 5-30 weight portion, Radix Paeoniae Alba 5-30 weight portion, Caulis Spatholobi 5-40 weight portion, Flos Campsis 5-30 weight portion, Radix Linderae 5-30 weight portion, Cortex Cinnamomi 5-30 weight portion, Rhizoma Zingiberis Recens 5-30 weight portion, Semen sojae atricolor 5-30 weight portion.

The crude drug composition of this pharmaceutical composition is preferably:

Rhizoma sparganic 12 weight portions, Rhizoma Curcumae 12 weight portions, siphonostegia chinensis 16 weight portions, Rhizoma Corydalis 16 weight portions, Cortex Moutan 12 weight portions, Radix Rehmanniae Preparata 16 weight portions, Radix Angelicae Sinensis 16 weight portions, the Radix Paeoniae Alba 16 weight portions, Caulis Spatholobi 20 weight portions, Flos Campsis 16 weight portions, the Radix Linderae 12 weight portions, Cortex Cinnamomi 12 weight portions, Rhizoma Zingiberis Recens 16 weight portions, Semen sojae atricolor 16 weight portions.

The crude drug composition of this pharmaceutical composition is preferably:

Rhizoma sparganic 6 weight portions, Rhizoma Curcumae 25 weight portions, siphonostegia chinensis 6 weight portions, Rhizoma Corydalis 25 weight portions, Cortex Moutan 6 weight portions, Radix Rehmanniae Preparata 25 weight portions, Radix Angelicae Sinensis 6 weight portions, the Radix Paeoniae Alba 25 weight portions, Caulis Spatholobi 6 weight portions, Flos Campsis 25 weight portions, the Radix Linderae 6 weight portions, Cortex Cinnamomi 25 weight portions, Rhizoma Zingiberis Recens 6 weight portions, Semen sojae atricolor 25 weight portions.

The crude drug composition of this pharmaceutical composition is preferably:

Rhizoma sparganic 25 weight portions, Rhizoma Curcumae 6 weight portions, siphonostegia chinensis 25 weight portions, Rhizoma Corydalis 6 weight portions, Cortex Moutan 25 weight portions, Radix Rehmanniae Preparata 6 weight portions, Radix Angelicae Sinensis 25 weight portions, the Radix Paeoniae Alba 6 weight portions, Caulis Spatholobi 35 weight portions, Flos Campsis 6 weight portions, the Radix Linderae 25 weight portions, Cortex Cinnamomi 6 weight portions, Rhizoma Zingiberis Recens 25 weight portions, Semen sojae atricolor 6 weight portions.

Get the above-mentioned composition crude drug, add conventional adjuvant,, make concentrated pill, capsule, drop pill, granule, tablet, soft capsule, slow releasing agent, oral liquid or lyophilized injectable powder etc. according to common process.

This preparation of pharmaceutical compositions method is optional following a kind of:

Above 14 flavors of A, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water that 8-12 doubly measures, decoct 1-3 time, and 1-3 hour at every turn, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing adds conventional adjuvant, according to common process, makes the oral formulations of clinical acceptance;

Above 14 flavors of B add the water that 8-12 doubly measures, decoct 1-3 time, and 1-3 hour at every turn, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the oral formulations of clinical acceptance;

The above 14 flavor crude drug mixings of C, be ground into 10～20 order coarse granules, add 5～7 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 1-3 time, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the oral formulations of clinical acceptance.

This preparation of pharmaceutical compositions method is preferably as follows a kind of:

Above 14 flavors of A, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 10 times of amounts, decoct secondary, and each 2 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction filters, and it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing according to common process, is made the oral formulations of clinical acceptance;

Above 14 flavors of B add the water of 10 times of amounts, decoct 2 times, and each 2 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the oral formulations of clinical acceptance;

The above 14 flavor crude drug mixings of C, be ground into 10～20 order coarse granules, add 7 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 2 times, extract carries out conventional centrifugalize, clean immersion is concentrated between the relative density 1.30～1.35, according to common process, makes the oral formulations of clinical acceptance.

This preparation of pharmaceutical compositions method is preferably as follows a kind of:

Above 14 flavors of A, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 8 times of amounts, decoct 3 times, and each 1 hour, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.33 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing adds conventional adjuvant, according to common process, makes the oral formulations of clinical acceptance;

Above 14 flavors of B add the water of 8 times of amounts, decoct 3 times, and each 1 hour, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the oral formulations of clinical acceptance;

The above 14 flavor crude drug mixings of C, be ground into 10～20 order coarse granules, add 6 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 1 time, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the oral formulations of clinical acceptance.

This preparation of pharmaceutical compositions method is preferably as follows a kind of:

Above 14 flavors of A, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 12 times of amounts, decoct 1 time, and each 3 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing adds conventional adjuvant, according to common process, makes the oral formulations of clinical acceptance;

Above 14 flavors of B add the water of 12 times of amounts, decoct 1 time, and each 3 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the oral formulations of clinical acceptance;

The above 14 flavor crude drug mixings of C, be ground into 10～20 order coarse granules, add 5 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 3 times, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the oral formulations of clinical acceptance.

The quality determining method of this pharmaceutical composition comprises one or more in following discriminating and/or the assay:

Differentiate: A gets this pharmaceutical composition content 5g, the 40ml that adds diethyl ether, and low temperature reflux 1 hour is put coldly, filters, and filtrate is flung to ether, and residue adds acetone 1ml makes dissolving, as need testing solution.Other gets the paeonol reference substance, adds acetone and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, cyclohexane extraction-ethyl acetate with the 2-4:0.5-1.5 ratio is developing solvent, launch, take out, dry, spray is with 5% ferric chloride alcoholic solution of hcl acidifying, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

B gets this pharmaceutical composition content 1g, adds ethanol 100ml, room temperature dipping 1 hour, and jolting constantly filters, and filtrate is as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.5g, shines medical material solution in pairs with legal system; According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with the normal hexane-ethyl acetate of 5-15:0.5-1.5 ratio, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

C gets this pharmaceutical composition content 2g, adds ethanol 30ml, room temperature dipping 1 hour, jolting constantly, filter, filtrate evaporate to dryness, residue add water 30ml makes dissolving, be transferred in the separatory funnel, with water saturated n-butanol extraction 3 times, each 20ml, merge n-butanol extracting liquid, the water 15ml saturated with n-butyl alcohol washs 1 time, discards water liquid, and add active carbon 1g, and stir evenly, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets the peoniflorin reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, chloroform-methanol with the 3-7:1.0-2.5 ratio is developing solvent, launches, and takes out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

D gets this pharmaceutical composition content 2g, adds ethanol 10ml, close plug, and room temperature dipping 1 hour, jolting constantly, filtrate is as need testing solution; Other gets the cinnamic aldehyde reference substance, adds ethanol and makes the solution that every 1ml contains 1 μ l, in contrast product solution; According to the thin layer chromatography test, draw above-mentioned need testing solution 10 μ l, reference substance solution 2 μ l put respectively on same silica gel g thin-layer plate, 60～90 ℃ of petroleum ether-ethyl acetates with the 50-140:5-30 ratio are developing solvent, launch, and take out, dry, spray is with 2,4-dinitrophenylhydrazine test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color; Assay: get the content under this pharmaceutical composition content uniformity item, mix homogeneously is got about 5g, the accurate title, decide, and puts in the 100ml tool plug triangular flask, the accurate methanol 50ml that adds, jump a queue, weigh, supersound process 1 hour, placement is spent the night and is supplied weight, and precision is measured supernatant 25ml, water bath method, residue water 25ml is transferred in the separatory funnel, adds ammonia solution 2ml, shakes up, with chloroform extraction 4 times, each 30ml, combined chloroform liquid is through anhydrous sodium sulfate dehydration, reclaim chloroform to doing, residue adds methanol makes dissolving, and is transferred in the 1ml measuring bottle, adds methanol to scale, shake up, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 0.30mg among every 1ml, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10 μ l, reference substance solution 1 μ l, 3 μ l put respectively on same silica gel g thin-layer plate, and with 5-15: 3-9: 0.5-1.5: the normal hexane-chloroform of 0.5-1.5 ratio-methanol-diethylamine is developing solvent, launch, take out, dry, spray is extremely moistening with rare bismuth potassium iodide test solution, make and present clear spot, on lamellae, cover onesize glass plate, use immobilization with adhesive tape on every side, scan according to thin layer chromatography.Wavelength: λ S=515nm, λ R=700nm, measure test sample trap integrated value with to the illumination integrated value, calculate, promptly;

This pharmaceutical composition contains Rhizoma Corydalis in tetrahydropalmatine, and every must not be less than 8.0 μ g.

The quality determining method of this pharmaceutical composition is preferably as follows one or more in discriminating and/or the assay:

Differentiate: A gets this pharmaceutical composition content 5g, the 40ml that adds diethyl ether, and low temperature reflux 1 hour is put coldly, filters, and filtrate is flung to ether, and residue adds acetone 1ml makes dissolving, as need testing solution; Other gets the paeonol reference substance, adds acetone and makes the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, cyclohexane extraction-ethyl acetate with the 3:1 ratio is developing solvent, launches, and takes out, dry, spray is with 5% ferric chloride alcoholic solution of hcl acidifying, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

B gets this pharmaceutical composition content 1g, adds ethanol 100ml, room temperature dipping 1 hour, and jolting constantly filters, and filtrate is as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.5g, shines medical material solution in pairs with legal system; According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with the normal hexane-ethyl acetate of 9:1 ratio, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

C gets this pharmaceutical composition content 2g, adds ethanol 30ml, room temperature dipping 1 hour, jolting constantly, filter, filtrate evaporate to dryness, residue add water 30ml makes dissolving, be transferred in the separatory funnel, with water saturated n-butanol extraction 3 times, each 20ml, merge n-butanol extracting liquid, the water 15ml saturated with n-butyl alcohol washs 1 time, discards water liquid, and add active carbon 1g, and stir evenly, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the peoniflorin reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with the chloroform-methanol of 5:1.5 ratio, launch, take out, to dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

D gets this pharmaceutical composition content 2g, adds ethanol 10ml, close plug, and room temperature dipping 1 hour, jolting constantly, filtrate is as need testing solution; Other gets the cinnamic aldehyde reference substance, adds ethanol and makes the solution that every 1ml contains 1 μ l, in contrast product solution; According to the thin layer chromatography test, draw above-mentioned need testing solution 10 μ l, reference substance solution 2 μ l put respectively on same silica gel g thin-layer plate, 60～90 ℃ of petroleum ether-ethyl acetates with the 85:15 ratio are developing solvent, launch, and take out, dry, spray is with 2,4-dinitrophenylhydrazine test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color; Assay: get the content under this pharmaceutical composition content uniformity item, mix homogeneously is got about 5g, the accurate title, decide, and puts in the 100ml tool plug triangular flask, the accurate methanol 50ml that adds, jump a queue, weigh, supersound process 1 hour, placement is spent the night and is supplied weight, and precision is measured supernatant 25ml, water bath method, residue water 25ml is transferred in the separatory funnel, adds ammonia solution 2ml, shakes up, with chloroform extraction 4 times, each 30ml, combined chloroform liquid is through anhydrous sodium sulfate dehydration, reclaim chloroform to doing, residue adds methanol makes dissolving, and is transferred in the 1ml measuring bottle, adds methanol to scale, shake up, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 0.30mg among every 1ml, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10 μ l, reference substance solution 1 μ l, 3 μ l put respectively on same silica gel g thin-layer plate, with 10: 6: 1: the normal hexane-chloroform of 1 ratio-methanol-diethylamine is developing solvent, launch, take out, dry, spray is extremely moistening with rare bismuth potassium iodide test solution, make and present clear spot, on lamellae, cover onesize glass plate, use immobilization with adhesive tape on every side, scan according to thin layer chromatography.Wavelength: λ S=515nm, λ R=700nm, measure test sample trap integrated value with to the illumination integrated value, calculate, promptly;

This pharmaceutical composition contains Rhizoma Corydalis in tetrahydropalmatine, and every must not be less than 8.0 μ g.

This pharmaceutical composition is monarch with rhizoma sparganic, Rhizoma Curcumae, siphonostegia chinensis, Rhizoma Corydalis blood circulation promoting and blood stasis dispelling, the broken disease heavily fortified point that disappears; Caulis Spatholobi, the pain relieving of Flos Campsis collateral dredging clots absorbing are minister; Radix Angelicae Sinensis, the Radix Paeoniae Alba, Radix Rehmanniae Preparata, Cortex Moutan nourishing blood to suppress the hyperactive liver, peace and dash to appoint and be assistant; Magical effect Cortex Cinnamomi, the Radix Linderae, Rhizoma Zingiberis Recens, Semen sojae atricolor circulation of qi promoting cold expelling are for making.This pharmaceutical composition melts blood circulation promoting and blood stasis dispelling, it is flourish cloudy to nourish blood, the temperature qi and blood circulation promotion is an one, show swelling and the transudation that two kinds of inflammatory models of animal is all had the obvious suppression inflammation through the clinical experiment result, therefore possess good warming the meridian blood stasis dispelling, regulating QI to relieve pain effect, can be used for treating diseases such as dysmenorrhes, menoxenia, be particularly suited for treating the primary dysmenorrhea due to the cold blood stasis, disease see menstrual period and through preceding lower abdomen pain, lumbosacral region ache, rectal tenesmus pain, dark menses, through the row amount less, clot, distending pain of the breast, fear of cold or the hands and feet being not warm etc.

Following experiment and embodiment are used to further specify but are not limited to the present invention.

Experimental example 1 antiinflammatory pharmacological action test

1, to the bullate influence of rat paw due to the agar

40 of healthy rats of experiment, the male and female dual-purpose divides 5 groups at random; (1) dosage group (0.4g/kg) (4) this medicament composition capsule agent small dose group (0.1g/kg) (5) aspirin group (0.15g/kg) in (0.8g/kg) (3) this medicament composition capsule agent of the heavy dose of group of normal saline matched group (2) this medicament composition capsule agent, gastric infusion before the Yu Zhiyan, once a day, continuous three days, caused inflammation at rat paw portion subcutaneous injection 1% agar solution 0.05ml in 30 minutes after the last administration.Measurement causes the following change in volume in rat paw joint, scorching front and back, calculates and relatively causes scorching back 30 minutes, 1,3,5,24 hour and respectively organize average swelling rate, the results are shown in Table 1.

The bullate influence of rat paw due to the table 1 pair agar

Annotate: compare * P＜0.05, * * P＜0.01, * * * P＜0.001 with matched group

The result shows that the heavy dose of group of this pharmaceutical composition causes the effect that scorching back all had obvious inhibition rat paw position swelling in 1-5 hours at agar, and the dosage group also has the trend of certain inhibition swelling effect in this pharmaceutical composition.

2, xylol causes the bullate influence of mouse ear

50 of body weight 17.5-22.5kg mices are selected in experiment for use, and the male and female dual-purpose divides 5 groups at random; (1) dosage group (0.5g/kg) (5) this medicament composition granule agent small dose group (0.1g/kg) in (1.0g/kg) (4) this medicament composition granule agent of the heavy dose of group of normal saline matched group (2) aspirin group (0.2g/kg) (3) this medicament composition granule agent.Irritate stomach every day once, continuous three days, toluene dripped in mouse right ear in 30 minutes after the last administration, put to death animal after 15 minutes, along the punching of left and right sides auricle same area, the both sides auricle is weighed respectively with the 6mm card punch, with two weight differences as the swelling level index, difference between comparative drug group and matched group, and obtain swollen rate, the results are shown in Table 2.

Table 2 xylol causes the bullate influence of mouse ear

The result shows, the heavy dose of group of this medicament composition granule agent and aspirin group all have the effect of obvious inhibition dimethylbenzene induced mice ear inflammation.Observe in the experiment, the control group mice auris dextra is obviously red and swollen, and thickness increases, and interaural difference is different bigger, and the variation of administration group mouse right ear is not obvious, and is consistent with measured value, illustrates that the agent of this medicament composition granule has better resist inflammation on repercussive function to acute shallow layer tissue inflammation.

Experimental example 2 analgesia pharmacological action tests

Get 50 of mices, divide 5 groups at random, every group 10, dosage group (0.5g/kg) (5) this pharmaceutical composition tablet small dose group (0.1g/kg) in this pharmaceutical composition tablet of the heavy dose of group of (1) blank group (2) aspirin group (0.2g/kg) (3) this pharmaceutical composition tablet (1.0g/kg) (4).Irritate stomach every day once, continuous three days, 30 minutes lumbar injection 0.3% acetic acid 0.2ml/ only observed each treated animal in 30 minutes and turn round the body number by what acetic acid brought out after last administration, the results are shown in Table 3.

The influence of table 3 pair mice pain effect

Experimental result can cause the more persistent pain stimulation of mice after showing lumbar injection acetic acid, and the extension of abdominal part back leg, hips up (turning round body) reaction appear in mice.The mice pain reaction that each group of administration all has minimizing in various degree to be caused by acetic acid.This pharmaceutical composition tablet heavy dose of group 1.0g/kg and aspirin group analgesic activity are remarkable, (seeing Table).Turn round the body number of times and be starkly lower than matched group, show that this pharmaceutical composition tablet has obvious inhibition of pain effect.

The test of 3 pairs of rat mesentery microcirculation influences of experimental example

Experimental technique: rat is divided into 4 groups at random, and fasting is 12 hours before the experiment, can't help water, pentobarbital sodium 40mg/kg intraperitoneal injection of anesthesia, and back fixation, about 30cm otch is cut off in the right lower abdomen cropping.Pull out one section intestinal, be tiled on the lucite perfusion Xiao Chi, pin is fixed, 30 ℃ of slow perfusions of Rockwell liquid, XTB-01 type microscope amplifies 20 * 2 times and observes blood capillaries, field of excursion, and with high voltage mercury lamp (GcQ50) as cold light source.It is medicinal to separate the femoral vein supply, and intravenous injection 10% high molecular dextran 6ml/kg observes after 10 minutes and record microcirculation disturbance index, and intravenously administrable is observed the variation of administration every index after 20 minutes.

Observation index: (1), blood capillary site crossing number: observe the fixed area internal fixation area blood capillary and the cross point number on border all around; (2), blood flow rate: blood flow rate is divided into Pyatyi: 0 grade: as seen blood capillary but does not have blood stream of cells mistake; The I level: idol has the stream of cells mistake; The II level: hemocyte is full of tube chamber, sluggish flow; The III level: blood flow comparatively fast is line style; The IV level: can not differentiate cell, flow velocity is exceedingly fast; (3), blood flow state: blood flow state divides Pyatyi: 0 grade: achroacyte is assembled; I level: 2-3 cell aggregation becomes fine graininess, do not influence flow velocity; II level: a 4-6 hemocyte is gathered into the coarse granule shape, and as seen little space shape is arranged in the tube chamber; The III level: hemocyte is gathered into lumps and influences blood flow rate; The IV level: blood flow stops or forming microthrombus, and official jargon has bright section.

1, the influence that the capillary network intersection is counted

The open number of blood capillary has directly reflected sanguimotor state.Observe in the experiment, give high molecular dextran after 10 minutes, capillary network intersects the minimizing of counting, the locking of part blood capillary, achroacyte flows through, certain promotion blood capillary opening acting is arranged for Anisodamine 10mg/kg and female Tai'an 50mg/kg, be respectively 3/10 and 2/6, the effect (seeing Table 4) that has the cross point number to increase.

The influence of the table 4 pair open number in blood capillary intersection site

2, to the influence of blood flow rate

After normal microcirculation was given high molecular dextran, blood flow rate was exceedingly fast, can differentiate cell by speed, and is mobile to differentiating cell gradually, have in addition stop to flow.Normal saline is permitted none routine blood flow rate of 6 examples and is improved, and this medicament composition capsule agent (0.1g/kg) and Anisodamine (10mg/kg) group respectively have a routine flow velocity to transfer the III level to from the II level, there are 2 routine blood flow rate to have clear improvement in this medicament composition capsule agent (0.05g/kg) group 6 examples, transfer the II level to and transfer the III level to by the I level respectively.

3, to the influence of blood fluidised form

The results are shown in Table 5: control group administered physiological saline is after 20 minutes, and the blood fluidised form does not have improvement, has 3 examples to have in 6 examples and further increases the weight of trend, and hemocyte is assembled, and blood flow is tending towards stopping.And all have 2 routine blood flow fluidised forms to have clear improvement in each 6 example of two dosage groups of this medicament composition capsule agent.

The influence of table 5 pair rat capillary blood fluidised form

This experimental result shows that the agent of this medicament composition capsule has the improvement effect to the model of microcirculation obstacle that glucosan (500,000 molecular weight high molecular dextran) causes, can promote blood capillary open, increases flow velocity and improves fluidised form etc.; Anisodamine has the expansion blood capillary to this model, promotes the blood capillary opening acting, but improves the velocity flow pattern effect not as good as the agent of this medicament composition capsule.Relevant more than dysmenorrhea, lump, the menoxenia with blood stasis inner product, QI stagnated by cold etc., microcirculation improvement helps to improve the blood supply oxygen supply and the metabolism of local organization or whole body, guarantee unobstructed vessel, " general rule is not bitterly ", therefore, the effect of this medicament composition capsule agent microcirculation improvement can effectively it be treated gynaecopathias such as dysmenorrhea.

The test of 4 pairs of rat uterus of experimental example and development of ovary influence

Get 50 of health rats childhood, divide 5 groups at random, 10 every group (grouping and dosage see Table 1), each group is gastric infusion, once a day, continuous 14 times, weighed sodium pentobarbital (50mg/kg) anesthesia in the 15th day, win uterus and ovary, peel off on every side fat gently, be to weigh on the electronic balance of 1mg at sensibility reciprocal, and be converted into organ index.Ovulation point is observed: get the both sides ovary and put in the plate of normal saline moistening, peel off to the greatest extent around after the fatty tissue, observe the ovary ovulation points with 6 times of magnifieres, the differences of ovulation point between relatively each is organized.

Experimental result shows, this medicament composition capsule agent (0.1,0.4,0.8g/kg) three dosage groups all have the effect that increases rat uterus weight, wherein obvious P＜0.05 of 0.4g/kg group effect.To the influence of ovulation point, the 0.8g/kg group has the trend that increases the ovulation point effect, and the effect of middle group is not obvious.Each dosage group of this medicament composition capsule agent does not have obvious influence to the ovary index.The every index of dysmenorrhes ball group shows the effect that the slight inhibition uterus and the development of ovary are all arranged, but statistical procedures, the not remarkable P of effect＜0.05.

The agent of this medicament composition capsule of table 6 is to the influence of the rat uterus and the development of ovary (* ± SD n=10)

Annotate: compare * P＜0.05. with matched group

The above results shows that the agent of this medicament composition capsule has certain promotion to the rat genital development.

Experimental example 5 animal acute toxicity tests

Get 20 of mices, the back of weighing is given the agent of this medicament composition capsule of clothes by the maximum concentration maximum volume by irritating stomach 20g/kg day at twice, observes 7 days.Observed result is not all found dead and any abnormal phenomena for 20.

Experimental result shows, this medicament composition capsule agent 20g/kg (250 times of quite clinical people's consumptions), and mice is oral not to be found to show the oral safety of this medicament composition capsule agent by any toxic reaction.

Experimental example 6 long-term toxicity test for animals

Experimental technique: dividing rat at random is four groups, 20 every group, and the male and female dual-purpose.(1) water matched group; (2) low dose of 1g/kg/ day of this medicament composition capsule agent; (3) dosage 3g/kg/ day in the agent of this medicament composition capsule; (4) heavy dose of 9g/kg/ day of this medicament composition capsule agent, quite clinical 113 times, be gastric infusion, once a day, totally 80 orders.

Administration is weighed after one month once, adjusts dosage according to body weight change.After administration finishes, record body weight, electrocardiogram, heavy dose of group of this medicament composition capsule agent and control animals are put to death half then, and all the other two treated animals are all put to death, and get blood examination and survey every index.The back execution of two weeks is observed in heavy dose and the drug withdrawal of matched group residue animal.Each treated animal is put to death the back and is dissected, the time row pathologic finding, comprise that the heart, lung, liver, spleen, stomach, intestinal, kidney, adrenal gland and genitals's reaches histological examination substantially.

Observation index: general state is observed: observe the reaction of animal after the administration every day, comprise spirit, diet, activity, hair color etc.; Body weight is checked: a forward and backward the end of month of administration and administration finish the back all animals and weigh; Hematological examination: all animals is got blood examination and is looked into every index, comprises numeration of leukocyte, classification, hemoglobin (Hb), and liver, renal function (SGPT|, GOT, BUN) detect; Employing standard two is led record animal electrocardiogram; Main organs is weighed, calculate organ index; Getting each internal organs does and reaches structure observation substantially.

1, general state and body weight are observed: each treated animal there is no aspects such as spiritedness, diet, stool, active situation and hair color variation and shows unusually in the administration process.Body weight the results are shown in Table 7.

The agent of this medicament composition capsule of table 7 is to the influence of rat body weight (X ± SD)

The agent of this medicament composition capsule increases a little higher than matched group to rat body weight as shown in Table 7.

2, blood routine examination: from abdominal aortic blood, blood cell analysis-e/or determining hemoglobin (HP) content and numeration of leukocyte the results are shown in Table 8 with the smear Wright Stain do differential blood count automatically.

The influence of table 8 pair rat hemoglobin, numeration of leukocyte and classification (X ± SD)

Knowing of each administration treated animal resembles index and matched group does not relatively have significant difference as shown in Table 8.

3, liver, renal function detect: GPT, GOT all adopt enzyme process, and BNN detects and adopts the diacetyl method, the results are shown in Table 9.

The influence of table 9 pair DABAI Hepar Mus, renal function (X ± SD)

As shown in Table 9, difference is respectively organized three biochemical indicators and matched group relatively there are no significant in administration.

4, electrocardiogram is observed: administration is after 60 days, and each treated animal electrocardiogram of female Tai'an and matched group relatively do not have significant change.QRS wave group, P-R interval, ST section and all no abnormal change of T ripple, the rhythm and pace of moving things is neat, and the rhythm of the heart is normal.Rhythm of the heart result of calculation sees Table 10.

The influence of table 10 pair rat heart rate (X ± SD)

5, main organs weight check: the results are shown in Table 11.

Table 11, to the exponential influence of rat main organs (X ± SD)

As seen from Table 11, the agent of this medicament composition capsule does not have influence to the rat main organs heart, liver, renal index.

6, pathologic finding: behind the sacrifice of animal, dissect immediately, core, liver, spleen, lung, kidney, adrenal gland, stomach, intestinal and genitals official rank internal organs carry out gross examination of skeletal muscle, and get above organ specimens and fix with formalin solution, carry out conventional dehydration, embedding, film-making, HE dyeing, om observation.Cardinal principle specimen observed result, its size of various internal organs of each treated animal, color is all normal, and administration group and matched group be zero difference relatively.Histological observation the results are shown in Table 12.

The influence of table 12 pair each internal organs of rat (histopathology observation)

As can be seen from Table 12, three dosed administration groups of this medicament composition capsule agent are the same with the various organs and tissues of control animals, all belong to the normal structure structure, do not find that the pathomorphism of drug intoxication changes.The result shows that the agent of this medicament composition capsule is tested safety non-toxic under the used dosage at this.

This animal long term toxicity test is the result show, the long-term gastric infusion of this medicament composition capsule agent does not have overt toxicity and untoward reaction.Animal growth, hemogram and liver, renal function are not all had obvious influence, do not cause that also the tangible pathologic of animal viscera changes and toxic changes, the result proves that this medicament composition capsule agent safety non-toxic can be taken for a long time.

Following embodiment all can realize the effect of above-mentioned experimental example.

The specific embodiment

Embodiment 1: the preparation of concentrated watered pill

Rhizoma sparganic 12kg, Rhizoma Curcumae 12kg, siphonostegia chinensis 16kg, Rhizoma Corydalis 16kg, Cortex Moutan 12kg, Radix Rehmanniae Preparata 16kg, Radix Angelicae Sinensis 16kg, Radix Paeoniae Alba 16kg, Caulis Spatholobi 20kg, Flos Campsis 16kg, Radix Linderae 12kg, Cortex Cinnamomi 12kg, Rhizoma Zingiberis Recens 16kg, Semen sojae atricolor 16kg

This pharmaceutical composition is made concentrated watered pill by common process.

Embodiment 2: the preparation of oral liquid

Rhizoma sparganic 6kg, Rhizoma Curcumae 25kg, siphonostegia chinensis 6kg, Rhizoma Corydalis 25kg, Cortex Moutan 6kg, Radix Rehmanniae Preparata 25kg, Radix Angelicae Sinensis 6kg, Radix Paeoniae Alba 25kg, Caulis Spatholobi 6kg, Flos Campsis 25kg, Radix Linderae 6kg, Cortex Cinnamomi 25kg, Rhizoma Zingiberis Recens 6kg, Semen sojae atricolor 25kg

This pharmaceutical composition is made oral liquid by common process.

Embodiment 3: the preparation of lyophilized injectable powder

Rhizoma sparganic 25kg, Rhizoma Curcumae 6kg, siphonostegia chinensis 25kg, Rhizoma Corydalis 6kg, Cortex Moutan 25kg, Radix Rehmanniae Preparata 6kg, Radix Angelicae Sinensis 25kg, Radix Paeoniae Alba 6kg, Caulis Spatholobi 35kg, Flos Campsis 6kg, Radix Linderae 25kg, Cortex Cinnamomi 6kg, Rhizoma Zingiberis Recens 25kg, Semen sojae atricolor 6kg

This pharmaceutical composition is made lyophilized injectable powder by common process.

Embodiment 4: the preparation of capsule

Rhizoma sparganic 12kg, Rhizoma Curcumae 12kg, siphonostegia chinensis 16kg, Rhizoma Corydalis 16kg, Cortex Moutan 12kg, Radix Rehmanniae Preparata 16kg, Radix Angelicae Sinensis 16kg, Radix Paeoniae Alba 16kg, Caulis Spatholobi 20kg, Flos Campsis 16kg, Radix Linderae 12kg, Cortex Cinnamomi 12kg, Rhizoma Zingiberis Recens 16kg, Semen sojae atricolor 16kg

More than 14 the flavor, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 10 times of amounts, decoct secondary, and each 2 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction filters, and it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing incapsulates, and makes 1000, promptly.

Embodiment 5: the preparation of granule

Rhizoma sparganic 6kg, Rhizoma Curcumae 25kg, siphonostegia chinensis 6kg, Rhizoma Corydalis 25kg, Cortex Moutan 6kg, Radix Rehmanniae Preparata 25kg, Radix Angelicae Sinensis 6kg, Radix Paeoniae Alba 25kg, Caulis Spatholobi 6kg, Flos Campsis 25kg, Radix Linderae 6kg, Cortex Cinnamomi 25kg, Rhizoma Zingiberis Recens 6kg, Semen sojae atricolor 25kg

More than 14 the flavor, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 8 times of amounts, decoct 3 times, and each 1 hour, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.33 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing adds conventional adjuvant, according to common process, makes granule.Embodiment 6: the preparation of tablet

Rhizoma sparganic 25kg, Rhizoma Curcumae 6kg, siphonostegia chinensis 25kg, Rhizoma Corydalis 6kg, Cortex Moutan 25kg, Radix Rehmanniae Preparata 6kg, Radix Angelicae Sinensis 25kg, Radix Paeoniae Alba 6kg, Caulis Spatholobi 35kg, Flos Campsis 6kg, Radix Linderae 25kg, Cortex Cinnamomi 6kg, Rhizoma Zingiberis Recens 25kg, Semen sojae atricolor 6kg

More than 14 the flavor, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 12 times of amounts, decoct 1 time, and each 3 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing adds conventional adjuvant, according to common process, makes tablet.

Embodiment 7: the preparation of capsule

Rhizoma sparganic 12kg, Rhizoma Curcumae 12kg, siphonostegia chinensis 16kg, Rhizoma Corydalis 16kg, Cortex Moutan 12kg, Radix Rehmanniae Preparata 16kg, Radix Angelicae Sinensis 16kg, Radix Paeoniae Alba 16kg, Caulis Spatholobi 20kg, Flos Campsis 16kg, Radix Linderae 12kg, Cortex Cinnamomi 12kg, Rhizoma Zingiberis Recens 16kg, Semen sojae atricolor 16kg

More than 14 flavor crude drug mixings, be ground into 10～20 order coarse granules, add 7 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 2 times, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the capsule of clinical acceptance.

Embodiment 8: the preparation of granule

Rhizoma sparganic 6kg, Rhizoma Curcumae 25kg, siphonostegia chinensis 6kg, Rhizoma Corydalis 25kg, Cortex Moutan 6kg, Radix Rehmanniae Preparata 25kg, Radix Angelicae Sinensis 6kg, Radix Paeoniae Alba 25kg, Caulis Spatholobi 6kg, Flos Campsis 25kg, Radix Linderae 6kg, Cortex Cinnamomi 25kg, Rhizoma Zingiberis Recens 6kg, Semen sojae atricolor 25kg

More than 14 flavor crude drug mixings, be ground into 10～20 order coarse granules, add 6 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 1 time, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the granule of clinical acceptance.

Embodiment 9: the preparation of tablet

Rhizoma sparganic 25kg, Rhizoma Curcumae 6kg, siphonostegia chinensis 25kg, Rhizoma Corydalis 6kg, Cortex Moutan 25kg, Radix Rehmanniae Preparata 6kg, Radix Angelicae Sinensis 25kg, Radix Paeoniae Alba 6kg, Caulis Spatholobi 35kg, Flos Campsis 6kg, Radix Linderae 25kg, Cortex Cinnamomi 6kg, Rhizoma Zingiberis Recens 25kg, Semen sojae atricolor 6kg

More than 14 flavor crude drug mixings, be ground into 10～20 order coarse granules, add 5 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 3 times, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the tablet of clinical acceptance.

Embodiment 10: the preparation of capsule

Rhizoma sparganic 12kg, Rhizoma Curcumae 12kg, siphonostegia chinensis 16kg, Rhizoma Corydalis 16kg, Cortex Moutan 12kg, Radix Rehmanniae Preparata 16kg, Radix Angelicae Sinensis 16kg, Radix Paeoniae Alba 16kg, Caulis Spatholobi 20kg, Flos Campsis 16kg, Radix Linderae 12kg, Cortex Cinnamomi 12kg, Rhizoma Zingiberis Recens 16kg, Semen sojae atricolor 16kg

More than 14 flavors, add the water of 10 times of amounts, decocts 2 times, each 2 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the capsule of clinical acceptance.

Embodiment 11: the preparation of granule

Rhizoma sparganic 6kg, Rhizoma Curcumae 25kg, siphonostegia chinensis 6kg, Rhizoma Corydalis 25kg, Cortex Moutan 6kg, Radix Rehmanniae Preparata 25kg, Radix Angelicae Sinensis 6kg, Radix Paeoniae Alba 25kg, Caulis Spatholobi 6kg, Flos Campsis 25kg, Radix Linderae 6kg, Cortex Cinnamomi 25kg, Rhizoma Zingiberis Recens 6kg, Semen sojae atricolor 25kg

More than 14 flavors, add the water of 8 times of amounts, decocts 3 times, each 1 hour, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the granule of clinical acceptance.

Embodiment 12: the preparation of tablet

Rhizoma sparganic 25kg, Rhizoma Curcumae 6kg, siphonostegia chinensis 25kg, Rhizoma Corydalis 6kg, Cortex Moutan 25kg, Radix Rehmanniae Preparata 6kg, Radix Angelicae Sinensis 25kg, Radix Paeoniae Alba 6kg, Caulis Spatholobi 35kg, Flos Campsis 6kg, Radix Linderae 25kg, Cortex Cinnamomi 6kg, Rhizoma Zingiberis Recens 25kg, Semen sojae atricolor 6kg

More than 14 flavors, add the water of 12 times of amounts, decocts 1 time, each 3 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the tablet of clinical acceptance.

Embodiment 13: the quality determining method of preparation of the present invention

Getting embodiment 7 contents differentiates: A gets this pharmaceutical composition content 5g, the 40ml that adds diethyl ether, and low temperature reflux 1 hour is put coldly, filters, and filtrate is flung to ether, and residue adds acetone 1ml makes dissolving, as need testing solution; Other gets the paeonol reference substance, adds acetone and makes the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, cyclohexane extraction-ethyl acetate with the 3:1 ratio is developing solvent, launches, and takes out, dry, spray is with 5% ferric chloride alcoholic solution of hcl acidifying, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

B gets this pharmaceutical composition content 1g, adds ethanol 100ml, room temperature dipping 1 hour, and jolting constantly filters, and filtrate is as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.5g, shines medical material solution in pairs with legal system; According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with the normal hexane-ethyl acetate of 9:1 ratio, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

C gets this pharmaceutical composition content 2g, adds ethanol 30ml, room temperature dipping 1 hour, jolting constantly, filter, filtrate evaporate to dryness, residue add water 30ml makes dissolving, be transferred in the separatory funnel, with water saturated n-butanol extraction 3 times, each 20ml, merge n-butanol extracting liquid, the water 15ml saturated with n-butyl alcohol washs 1 time, discards water liquid, and add active carbon 1g, and stir evenly, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the peoniflorin reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with the chloroform-methanol of 5:1.5 ratio, launch, take out, to dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

D gets this pharmaceutical composition content 2g, adds ethanol 10ml, close plug, and room temperature dipping 1 hour, jolting constantly, filtrate is as need testing solution; Other gets the cinnamic aldehyde reference substance, adds ethanol and makes the solution that every 1ml contains 1 μ l, in contrast product solution; According to the thin layer chromatography test, draw above-mentioned need testing solution 10 μ l, reference substance solution 2 μ l put respectively on same silica gel g thin-layer plate, 60～90 ℃ of petroleum ether-ethyl acetates with the 85:15 ratio are developing solvent, launch, and take out, dry, spray is with 2,4-dinitrophenylhydrazine test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Embodiment 14: the quality determining method of preparation of the present invention

Get that content carries out assay among the embodiment 5: get the content under this pharmaceutical composition content uniformity item, mix homogeneously is got about 5g, the accurate title, decide, and puts in the 100ml tool plug triangular flask, the accurate methanol 50ml that adds, jump a queue, weigh, supersound process 1 hour, placement is spent the night and is supplied weight, and precision is measured supernatant 25ml, water bath method, residue water 25ml is transferred in the separatory funnel, adds ammonia solution 2ml, shakes up, with chloroform extraction 4 times, each 30ml, combined chloroform liquid is through anhydrous sodium sulfate dehydration, reclaim chloroform to doing, residue adds methanol makes dissolving, and is transferred in the 1ml measuring bottle, adds methanol to scale, shake up, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 0.30mg among every 1ml, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10 μ l, reference substance solution 1 μ l, 3 μ l put respectively on same silica gel g thin-layer plate, are developing solvent with the normal hexane-chloroform-methanol-diethylamine of 10:6:1:1 ratio, launch, take out, dry, spray is extremely moistening with rare bismuth potassium iodide test solution, make and present clear spot, on lamellae, cover onesize glass plate, use immobilization with adhesive tape on every side, scan according to thin layer chromatography.Wavelength: λ S=515nm, λ R=700nm, measure test sample trap integrated value with to the illumination integrated value, calculate, promptly;

This pharmaceutical composition contains Rhizoma Corydalis in tetrahydropalmatine, and every must not be less than 8.0 μ g.

Embodiment 15: the quality determining method of preparation of the present invention

Getting embodiment 4 contents differentiates: A gets this pharmaceutical composition content 5g, the 40ml that adds diethyl ether, and low temperature reflux 1 hour is put coldly, filters, and filtrate is flung to ether, and residue adds acetone 1ml makes dissolving, as need testing solution; Other gets the paeonol reference substance, adds acetone and makes the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, cyclohexane extraction-ethyl acetate with the 3:1 ratio is developing solvent, launches, and takes out, dry, spray is with 5% ferric chloride alcoholic solution of hcl acidifying, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

B gets this pharmaceutical composition content 1g, adds ethanol 100ml, room temperature dipping 1 hour, and jolting constantly filters, and filtrate is as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.5g, shines medical material solution in pairs with legal system; According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with the normal hexane-ethyl acetate of 9:1 ratio, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;

C gets this pharmaceutical composition content 2g, adds ethanol 30ml, room temperature dipping 1 hour, jolting constantly, filter, filtrate evaporate to dryness, residue add water 30ml makes dissolving, be transferred in the separatory funnel, with water saturated n-butanol extraction 3 times, each 20ml, merge n-butanol extracting liquid, the water 15ml saturated with n-butyl alcohol washs 1 time, discards water liquid, and add active carbon 1g, and stir evenly, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the peoniflorin reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with the chloroform-methanol of 5:1.5 ratio, launch, take out, to dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

D gets this pharmaceutical composition content 2g, adds ethanol 10ml, close plug, and room temperature dipping 1 hour, jolting constantly, filtrate is as need testing solution; Other gets the cinnamic aldehyde reference substance, adds ethanol and makes the solution that every 1ml contains 1 μ l, in contrast product solution; According to the thin layer chromatography test, draw above-mentioned need testing solution 10 μ l, reference substance solution 2 μ l put respectively on same silica gel g thin-layer plate, 60～90 ℃ of petroleum ether-ethyl acetates with the 85:15 ratio are developing solvent, launch, and take out, dry, spray is with 2,4-dinitrophenylhydrazine test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color; Get that content carries out assay among the embodiment 4: get the content under this pharmaceutical composition content uniformity item, mix homogeneously is got about 5g, the accurate title, decide, and puts in the 100ml tool plug triangular flask, the accurate methanol 50ml that adds, jump a queue, weigh, supersound process 1 hour, placement is spent the night and is supplied weight, and precision is measured supernatant 25ml, water bath method, residue water 25ml is transferred in the separatory funnel, adds ammonia solution 2ml, shakes up, with chloroform extraction 4 times, each 30ml, combined chloroform liquid is through anhydrous sodium sulfate dehydration, reclaim chloroform to doing, residue adds methanol makes dissolving, and is transferred in the 1ml measuring bottle, adds methanol to scale, shake up, as need testing solution; Other gets the tetrahydropalmatine reference substance, adds methanol and makes the solution that contains 0.30mg among every 1ml, in contrast product solution; Test according to thin layer chromatography, draw need testing solution 10 μ l, reference substance solution 1 μ l, 3 μ l put respectively on same silica gel g thin-layer plate, are developing solvent with the normal hexane-chloroform-methanol-diethylamine of 10:6:1:1 ratio, launch, take out, dry, spray is extremely moistening with rare bismuth potassium iodide test solution, make and present clear spot, on lamellae, cover onesize glass plate, use immobilization with adhesive tape on every side, scan according to thin layer chromatography.Wavelength: λ S=515nm, λ R=700nm, measure test sample trap integrated value with to the illumination integrated value, calculate, promptly; This pharmaceutical composition contains Rhizoma Corydalis in tetrahydropalmatine, and every must not be less than 8.0 μ g.

Claims (9)

1, a kind of pharmaceutical composition for the treatment of dysmenorrhes, menoxenia disease is characterized in that the crude drug of this pharmaceutical composition is:

Rhizoma sparganic 5-30 weight portion, Rhizoma Curcumae 5-30 weight portion, siphonostegia chinensis 5-30 weight portion, Rhizoma Corydalis 5-30 weight portion, Cortex Moutan 5-30 weight portion, Radix Rehmanniae Preparata 5-30 weight portion, Radix Angelicae Sinensis 5-30 weight portion, Radix Paeoniae Alba 5-30 weight portion, Caulis Spatholobi 5-40 weight portion, Flos Campsis 5-30 weight portion, Radix Linderae 5-30 weight portion, Cortex Cinnamomi 5-30 weight portion, Rhizoma Zingiberis Recens 5-30 weight portion, Semen sojae atricolor 5-30 weight portion.

2, the pharmaceutical composition of treatment dysmenorrhes as claimed in claim 1, menoxenia disease is characterized in that the crude drug of this pharmaceutical composition is:

Rhizoma sparganic 12 weight portions, Rhizoma Curcumae 12 weight portions, siphonostegia chinensis 16 weight portions, Rhizoma Corydalis 16 weight portions, Cortex Moutan 12 weight portions, Radix Rehmanniae Preparata 16 weight portions, Radix Angelicae Sinensis 16 weight portions, the Radix Paeoniae Alba 16 weight portions, Caulis Spatholobi 20 weight portions, Flos Campsis 16 weight portions, the Radix Linderae 12 weight portions, Cortex Cinnamomi 12 weight portions, Rhizoma Zingiberis Recens 16 weight portions, Semen sojae atricolor 16 weight portions.

3, the pharmaceutical composition of treatment dysmenorrhes as claimed in claim 1, menoxenia disease is characterized in that the crude drug of this pharmaceutical composition is:

Rhizoma sparganic 6 weight portions, Rhizoma Curcumae 25 weight portions, siphonostegia chinensis 6 weight portions, Rhizoma Corydalis 25 weight portions, Cortex Moutan 6 weight portions, Radix Rehmanniae Preparata 25 weight portions, Radix Angelicae Sinensis 6 weight portions, the Radix Paeoniae Alba 25 weight portions, Caulis Spatholobi 6 weight portions, Flos Campsis 25 weight portions, the Radix Linderae 6 weight portions, Cortex Cinnamomi 25 weight portions, Rhizoma Zingiberis Recens 6 weight portions, Semen sojae atricolor 25 weight portions.

4, the pharmaceutical composition of treatment dysmenorrhes as claimed in claim 1, menoxenia disease is characterized in that the crude drug of this pharmaceutical composition is:

Rhizoma sparganic 25 weight portions, Rhizoma Curcumae 6 weight portions, siphonostegia chinensis 25 weight portions, Rhizoma Corydalis 6 weight portions, Cortex Moutan 25 weight portions, Radix Rehmanniae Preparata 6 weight portions, Radix Angelicae Sinensis 25 weight portions, the Radix Paeoniae Alba 6 weight portions, Caulis Spatholobi 35 weight portions, Flos Campsis 6 weight portions, the Radix Linderae 25 weight portions, Cortex Cinnamomi 6 weight portions, Rhizoma Zingiberis Recens 25 weight portions, Semen sojae atricolor 6 weight portions.

5,, it is characterized in that this method is optional following a kind of as the preparation of drug combination method of the arbitrary described treatment dysmenorrhes of claim 1-4, menoxenia disease:

Above 14 flavors of A, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water that 8-12 doubly measures, decoct 1-3 time, and 1-3 hour at every turn, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing adds conventional adjuvant, according to common process, makes the oral formulations of clinical acceptance;

Above 14 flavors of B add the water that 8-12 doubly measures, decoct 1-3 time, and 1-3 hour at every turn, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the oral formulations of clinical acceptance;

The above 14 flavor crude drug mixings of C, be ground into 10～20 order coarse granules, add 5～7 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 1-3 time, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the oral formulations of clinical acceptance.

6, the preparation of drug combination method of treatment dysmenorrhes as claimed in claim 5, menoxenia disease is characterized in that this method is optional following a kind of:

Above 14 flavors of A, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 10 times of amounts, decoct secondary, and each 2 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction filters, and it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing according to common process, is made the oral formulations of clinical acceptance;

Above 14 flavors of B add the water of 10 times of amounts, decoct 2 times, and each 2 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the oral formulations of clinical acceptance;

The above 14 flavor crude drug mixings of C, be ground into 10～20 order coarse granules, add 7 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 2 times, extract carries out conventional centrifugalize, clean immersion is concentrated between the relative density 1.30～1.35, according to common process, makes the oral formulations of clinical acceptance.

7, the preparation of drug combination method of treatment dysmenorrhes as claimed in claim 5, menoxenia disease is characterized in that this method is optional following a kind of:

Above 14 flavors of A, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 8 times of amounts, decoct 3 times, and each 1 hour, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.33 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing adds conventional adjuvant, according to common process, makes the oral formulations of clinical acceptance;

Above 14 flavors of B add the water of 8 times of amounts, decoct 3 times, and each 1 hour, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the oral formulations of clinical acceptance;

The above 14 flavor crude drug mixings of C, be ground into 10～20 order coarse granules, add 6 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 1 time, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the oral formulations of clinical acceptance.

8, the preparation of drug combination method of treatment dysmenorrhes as claimed in claim 5, menoxenia disease is characterized in that this method is optional following a kind of:

Above 14 flavors of A, Cortex Moutan is ground into fine powder; All the other 13 flavors add the water of 12 times of amounts, decoct 1 time, and each 3 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds the Cortex Moutan fine powder, and drying is ground into fine powder, sprays into above-mentioned volatile oil, and mixing adds conventional adjuvant, according to common process, makes the oral formulations of clinical acceptance;

Above 14 flavors of B add the water of 12 times of amounts, decoct 1 time, and each 3 hours, in the decoction process, collect volatile oil simultaneously, collecting decoction, filtration, it is 1.30～1.35 clear paste that filtrate is concentrated into 60 ℃ of relative densities; Clear paste adds ethanol to be made and contains the alcohol amount and reach 50～70%, leaves standstill, and gets supernatant, reclaims ethanol, is condensed into thick paste, sprays into above-mentioned volatile oil, according to common process, makes the oral formulations of clinical acceptance;

The above 14 flavor crude drug mixings of C, be ground into 10～20 order coarse granules, add 5 times in water, with the continuous extraction below 60 ℃ of conventional microwave extracting method 3 times, extract carries out conventional centrifugalize, and clean immersion is concentrated between the relative density 1.30～1.35, adds conventional adjuvant, according to common process, make the oral formulations of clinical acceptance.

9, as the application of the arbitrary described pharmaceutical composition of claim 1-4 in the medicine of preparation treatment dysmenorrhes or menoxenia disease.