CN101313936A - Medicament composition for dispelling wind and relieving pain, preparation method and quality control method thereof - Google Patents
Medicament composition for dispelling wind and relieving pain, preparation method and quality control method thereof Download PDFInfo
- Publication number
- CN101313936A CN101313936A CNA2007100999468A CN200710099946A CN101313936A CN 101313936 A CN101313936 A CN 101313936A CN A2007100999468 A CNA2007100999468 A CN A2007100999468A CN 200710099946 A CN200710099946 A CN 200710099946A CN 101313936 A CN101313936 A CN 101313936A
- Authority
- CN
- China
- Prior art keywords
- solution
- weight portion
- weight
- radix
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a medicine composition for dispelling wind and relieving pain, a preparation method thereof and a quality control method thereof. The medicine composition comprises the following raw material medicines of Chuangxiong, angelica, notopterygium, asarum, root of gentian, mint, kudzu root and glycyrrhiza. The preparation method of the medicine composition comprises the following steps that: for the eight medicines, the Chuangxiong, the angelica, the notopterygium, the asarum, the divaricate saposhnikovia root and the glycyrrhiza are respectively added with water to be boiled, and the boiled solutions are mixed and filtered to prepare a medicinal liquor; the mint and fineleaf schizonepeta herb are added with water and distilled to extract volatile oil, the water solution left is filtered to obtain filtrate, and the filtrate and the medicinal liquor are mixed and concentrated to be clear extract; and the clear extract is taken out and added with common auxiliary materials to prepare the preparation clinically used by the prior method. The medicine composition of the invention has good curative effects of treating headache caused by pathogenic wind or symptoms such as chillness, fever and nasal obstruction, etc.
Description
Invention field
The present invention relates to a kind of pharmaceutical composition and preparation method and method of quality control, particularly a kind of pharmaceutical composition of dispelling wind and relieving and preparation method and method of quality control.
Background technology
Headache is common clinically subjective symptoms, can occur separately, also can come across among the multiple acute and chronic diseases, as hypertension, the cerebral tumor, angioneurotic headache etc.Wherein headache due to invasion of exogenous pathogens is many because of experiencing exopathogen such as wind, cold, wet, heat, and based on ailment said due to cold or exposure.Do when headache is seen headache due to the ailment said due to cold or exposure, pain connects person's back, and meet wind play especially, or the aversion to wind fear of cold is arranged, nasal obstruction, thin white fur of tongue, floating pulses etc. bring great inconvenience for people's work, study and life.Western medicines such as the analgesic of the many employings of treatment ailment said due to cold or exposure headache were at present taken medicine in long-term every month, body were developed immunity to drugs and addiction, and side effect is fairly obvious.
Summary of the invention
The object of the invention is to provide a kind of pharmaceutical composition; Another purpose of the present invention is to provide a kind of pharmaceutical composition of dispelling wind and relieving; The 3rd purpose of the present invention is to provide this preparation of drug combination method; The 4th purpose of the present invention is to provide the method for quality control of this pharmaceutical composition.
The present invention seeks to be achieved through the following technical solutions:
The crude drug of pharmaceutical composition of the present invention consists of: Rhizoma Chuanxiong 200-360 weight portion, Radix Angelicae Dahuricae 90-200 weight portion, Rhizoma Et Radix Notopterygii 90-200 weight portion, Herba Asari 20-130 weight portion, Radix Gentianae Macrophyllae 50-150 weight portion, Herba Menthae 500-600 weight portion, Radix Puerariae 200-360 weight portion, Radix Glycyrrhizae 90-200 weight portion.
The crude drug of pharmaceutical composition of the present invention is formed can also be Rhizoma Chuanxiong 200-360 weight portion, Radix Angelicae Dahuricae 90-200 weight portion, Rhizoma Et Radix Notopterygii 90-200 weight portion, Herba Asari 20-130 weight portion, Radix Saposhnikoviae 50-150 weight portion, Herba Menthae 500-600 weight portion, Herba Schizonepetae 200-360 weight portion, Radix Glycyrrhizae 90-200 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Rhizoma Chuanxiong 200-250 weight portion, Radix Angelicae Dahuricae 90-110 weight portion, Rhizoma Et Radix Notopterygii 90-110 weight portion, Herba Asari 20-50 weight portion, Radix Saposhnikoviae 50-80 weight portion, Herba Menthae 500-530 weight portion, Herba Schizonepetae 200-250 weight portion, Radix Glycyrrhizae 90-110 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Rhizoma Chuanxiong 210 weight portions, the Radix Angelicae Dahuricae 105 weight portions, Rhizoma Et Radix Notopterygii 95 weight portions, Herba Asari 45 weight portions, Radix Saposhnikoviae 55 weight portions, Herba Menthae 520 weight portions, Herba Schizonepetae 210 weight portions, Radix Glycyrrhizae 105 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Rhizoma Chuanxiong 240 weight portions, the Radix Angelicae Dahuricae 95 weight portions, Rhizoma Et Radix Notopterygii 105 weight portions, Herba Asari 25 weight portions, Radix Saposhnikoviae 75 weight portions, Herba Menthae 510 weight portions, Herba Schizonepetae 245 weight portions, Radix Glycyrrhizae 95 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Rhizoma Chuanxiong 290-360 weight portion, Radix Angelicae Dahuricae 130-200 weight portion, Rhizoma Et Radix Notopterygii 130-200 weight portion, Herba Asari 90-130 weight portion, Radix Saposhnikoviae 120-150 weight portion, Herba Menthae 560-600 weight portion, Herba Schizonepetae 290-360 weight portion, Radix Glycyrrhizae 130-200 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Rhizoma Chuanxiong 300 weight portions, the Radix Angelicae Dahuricae 190 weight portions, Rhizoma Et Radix Notopterygii 140 weight portions, Herba Asari 120 weight portions, Radix Saposhnikoviae 130 weight portions, Herba Menthae 590 weight portions, Herba Schizonepetae 300 weight portions, Radix Glycyrrhizae 190 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Rhizoma Chuanxiong 350 weight portions, the Radix Angelicae Dahuricae 140 weight portions, Rhizoma Et Radix Notopterygii 190 weight portions, Herba Asari 100 weight portions, Radix Saposhnikoviae 140 weight portions, Herba Menthae 570 weight portions, Herba Schizonepetae 350 weight portions, Radix Glycyrrhizae 140 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Rhizoma Chuanxiong 260-280 weight portion, Radix Angelicae Dahuricae 120-140 weight portion, Rhizoma Et Radix Notopterygii 120-140 weight portion, Herba Asari 60-80 weight portion, Radix Saposhnikoviae 90-110 weight portion, Herba Menthae 540-550 weight portion, Herba Schizonepetae 260-280 weight portion, Radix Glycyrrhizae 120-140 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably: Rhizoma Chuanxiong 272.7 weight portions, the Radix Angelicae Dahuricae 136.4 weight portions, Rhizoma Et Radix Notopterygii 136.4 weight portions, Herba Asari 68.2 weight portions, Radix Saposhnikoviae 102.3 weight portions, Herba Menthae 545.5 weight portions, Herba Schizonepetae 272.7 weight portions, Radix Glycyrrhizae 136.4 weight portions.
Get the above-mentioned composition crude drug, add conventional adjuvant, according to common process, make the dosage form of clinical acceptance, include but not limited to concentrated pill, capsule, drop pill, granule, tablet, soft capsule, slow releasing agent, oral liquid or lyophilized injectable powder.
Preparation of pharmaceutical compositions method of the present invention is: above eight flavors, and Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 1-3 time, add water 6-10 for the first time and doubly measure decoction 0.5-2.5 hour, add for the second time water 4-8 and doubly measure decoction 0.5-1.5 hour, collecting decoction filters, and gets medicinal liquid; Herba Menthae, Herba Schizonepetae add water 8-12 doubly measures after distillation extracted volatile oil in 4-8 hour, and its water liquid filters, filtrate and medicinal liquid merging, the clear paste that to be concentrated into 80 ℃ of relative densities be 1.10-1.50; Qinghuo reagent adds conventional adjuvant, through conventional method, makes the preparation of clinical acceptance.
Preparation of pharmaceutical compositions method of the present invention is preferably: above eight flavors, and Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 2 times, add 8 times of amounts of water for the first time and decoct 1.5 hours, adding for the second time 6 times of amounts of water decocted 1 hour, collecting decoction filters, and gets medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 10 times in water amount extracted volatile oil in 6 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.30 clear paste; Qinghuo reagent adds conventional adjuvant, through conventional method, makes the preparation of clinical acceptance.
The invention described above medicament composition granule agent preparation method can also be after being prepared into clear paste, optional following a kind of method preparation:
A, qinghuo reagent 300-500 weight portion, cane sugar powder 300-500 weight portion, dextrin 300-500 weight portion is made granule, drying, mixing promptly gets granule;
B, qinghuo reagent 300-500 weight portion, cane sugar powder 1000-2000 weight portion, drying, mixing is granulated, and promptly gets granule;
C, qinghuo reagent 300-500 weight portion, dextrin 300-500 weight portion, drying, mixing is granulated, and promptly gets granule.
Medicament composition granule agent preparation method of the present invention can also be preferably as follows a kind of method preparation after being prepared into clear paste:
A, qinghuo reagent 400 weight portions, cane sugar powder 400 weight portions, dextrin 400 weight portions are made granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 1000 weight portions, promptly gets granule;
B, qinghuo reagent 400 weight portions, cane sugar powder 1600 weight portions are made granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 1600 weight portions, promptly gets granule;
C, qinghuo reagent 400 weight portions, dextrin 400 weight portions are made granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 800 weight portions, promptly gets granule.
Pharmaceutical composition method of quality control of the present invention comprises one or more in following discrimination method and/or the assay:
Differentiate: A, get this drug combination preparation 1/5-1 day and use dosage, put in the tool plug bottle, the 10-30ml that adds diethyl ether, jolting was placed 20-40 minute, filtration, the filtrate cryoconcentration is to 1ml, as need testing solution; Other gets the Mentholum reference substance, adds diethyl ether to make the solution that every 1ml contains 1-3mg, in contrast product solution; Test according to thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same and contain on the silica gel g thin-layer plate that sodium carboxymethyl cellulose is a binding agent, with 60-95: the benzene-ethyl acetate of 5-25 ratio is developing solvent, launch, take 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;
B, get this drug combination preparation 1/3-1 day and use dosage, add ethanol 50ml, supersound process 20-40 minute, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid reference substance, adds ethanol and makes the solution that every 1ml contains 0.5-1.5mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 4-8: 4-8: 0.5-2.5: the benzene-chloroform-methanol of 0.1-1.0 ratio-glacial acetic acid is developing solvent, launches, and takes 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;
Assay:
A, chromatographic condition and system suitability experiment: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; 40-80: 20-50: the methanol-water-acetic acid of 2-6 ratio is mobile phase; The detection wavelength is 316nm, and number of theoretical plate calculates by aristolochic acid A should be not less than 2005;
The preparation of reference substance solution: get the aristolochic acid A reference substance 5mg that is dried to constant weight, the accurate title, decide, and making its concentration with the methanol dilution is 0.05 μ g/ml;
The preparation of need testing solution: get this drug combination preparation 1/5-4/5 day and use dosage, the accurate title, decide, to the 100ml measuring bottle, it is an amount of to add methanol, precision weighing, close plug, supersound process 20-60 minute, take out, put cold, weight decided in accurate again title, supplies the quantity of methyl alcohol of loss, shakes up, filter, discard the about 15ml of filtrate just, the accurate subsequent filtrate 75ml that draws, water bath method, residue adds 0.05-0.15mol/L sodium hydroxide solution 25ml gradation dissolving, changes in the separatory funnel, adds chloroform extraction 2-4 time, each 5-25ml, discard chloroformic solution, aqueous alkali adds the 4-6mol/L hydrochloric acid solution and transfers pH=2, adds chloroform extraction 3-5 time, each 5-25ml, combined chloroform solution, water bath method, residue add methanol gradation dissolving, change in the 10ml volumetric flask, add methanol to scale, shake up; Filter with 0.45 μ m microporous filter membrane before the sample introduction, promptly;
Assay method: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; In the corresponding retention time of test sample and reference substance absworption peak must not be arranged;
B, chromatographic condition and system suitability test: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; 15-35: 50-100: the methanol-water-glacial acetic acid of 0.5-2.5 ratio is a mobile phase; The detection wavelength is 330nm, and number of theoretical plate calculates by ferulic acid should be not less than 2005;
The preparation of reference substance solution: precision takes by weighing ferulic acid, adds 70-110: the mixed solution of the methanol-formic acid of 4-6 ratio, make the solution that every 1ml contains 40-60 μ g, and filter with 0.45 μ m microporous filter membrane, promptly;
The preparation of need testing solution: get this drug combination preparation, porphyrize, precision takes by weighing uses dosage 1/10-3/5 day, put in the tool plug conical flask, the accurate 70-110 that adds: the methanol of 4-6 ratio-formic acid mixed solution 20-40ml claims to decide weight, power 250W, frequency 40KHZ supersound process 20-40 minute is put coldly, claims to decide weight again, use 70-110: after the methanol of 4-6 ratio-formic acid mixed solution is supplied the weight that subtracts mistake, shake up, filter with the 0.45um microporous filter membrane, promptly;
Assay method: accurate respectively reference substance liquid and each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; Contain Rhizoma Chuanxiong in ferulic acid C10H10O4, must not be less than and 0.1-0.3mg/ day use dosage.
Pharmaceutical composition method of quality control of the present invention is preferably as follows one or more in discrimination method and/or the assay:
Differentiate: A, get this drug combination preparation and used dosage on 1/2nd, put in the tool plug bottle, the 20ml that adds diethyl ether, jolting was placed 30 minutes, filtration, the filtrate cryoconcentration is to 1ml, as need testing solution; Other gets the Mentholum reference substance, adds diethyl ether to make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same and contain on the silica gel g thin-layer plate that sodium carboxymethyl cellulose is a binding agent, benzene-ethyl acetate with 85: 15 ratios is developing solvent, launch, take 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;
B, get this drug combination preparation and used dosage on 2/3rd, add ethanol 50ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid 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 need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 6: 6: 1.8: the benzene-chloroform-methanol of 0.5 ratio-glacial acetic acid was developing solvent, launched, and took 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;
Assay:
A, chromatographic condition and system suitability experiment: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; Methanol-water-the acetic acid of 60: 36: 4 ratios is mobile phase; The detection wavelength is 316nm, and number of theoretical plate calculates by aristolochic acid A should be not less than 2005;
The preparation of reference substance solution: get the about 5mg of aristolochic acid A reference substance that is dried to constant weight, the accurate title, decide, and making its concentration with the methanol dilution is 0.05 μ g/ml;
The preparation of need testing solution: get this drug combination preparation and used dosage on the 2/5th, the accurate title, decide, to the 100ml measuring bottle, it is an amount of to add methanol, precision weighing, close plug, supersound process 40 minutes is taken out, and puts cold, weight decided in accurate again title, supplies the quantity of methyl alcohol of loss, shakes up, filter, discard the about 15ml of filtrate just, the accurate subsequent filtrate 75ml that draws, water bath method, residue adds 0.1mol/L sodium hydroxide solution 25ml gradation dissolving, changes in the separatory funnel, adds chloroform extraction 3 times, each 15ml, discard chloroformic solution, aqueous alkali adds the 5mol/L hydrochloric acid solution and transfers pH=2, adds chloroform extraction 4 times, each 15ml, combined chloroform solution, water bath method, residue add methanol gradation dissolving, change in the 10ml volumetric flask, add methanol to scale, shake up; Filter with 0.45 μ m microporous filter membrane before the sample introduction, promptly;
Assay method: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; In the corresponding retention time of test sample and reference substance absworption peak must not be arranged;
B, chromatographic condition and system suitability test: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; Methanol-water-the glacial acetic acid of 25: 75: 1.8 ratios is a mobile phase; The detection wavelength is 330nm, and number of theoretical plate calculates by ferulic acid should be not less than 2005;
The preparation of reference substance solution: precision takes by weighing ferulic acid, adds the mixed solution of the methanol-formic acid of 95: 5 ratios, makes the solution that every 1ml contains 50 μ g, filters with 0.45 μ m microporous filter membrane, promptly;
The preparation of need testing solution: get this drug combination preparation, porphyrize, precision takes by weighing used dosage on the 1/5th, put in the tool plug conical flask, the accurate methanol-formic acid mixed solution 30ml that adds 95: 5 ratios claims to decide weight, power 250W, frequency 40KHZ supersound process 30 minutes is put coldly, claims to decide weight again, after supplying the weight that subtracts mistake with the methanol-formic acid mixed solution of 95: 5 ratios, shake up, filter with the 0.45um microporous filter membrane, promptly;
Assay method: accurate respectively reference substance liquid and each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; Contain Rhizoma Chuanxiong in ferulic acid C10H10O4, must not be less than and 0.24mg/ day use dosage.
The daily dosage of the different preparations of pharmaceutical composition of the present invention (every day taking dose or every day using dosage) is different because of preparation, but it is identical to contain suitable crude drug amount in the daily dosage of different preparations.Quality determining method of the present invention is a measurement unit with daily dosage.
Description of drawings:
Granule moisture absorption percentage rate under the accompanying drawing 1 different relative humiditys
Pharmaceutical composition Ligusticum wallichii promoting blood circulation by removing wind of the present invention ends headache and is monarch drug in a prescription; Peppermint is hot loose up, and dispelling wind is evil, the hot fragrant tepor of the root of kudzu vine thoroughly, and the loose saturating heresy of wind is ministerial drug altogether; Notopterygium root, the root of Dahurain angelica, the root of Chinese wild ginger, bark of ash dispelling wind and relieving are adjutant altogether, the Radix Glycyrrhizae coordinating the drug actions of a prescription. Full side's compatibility dispelling wind medicine is heavy, and the pain relieving effect is grand. Be used for the treatment of the ailment said due to cold or exposure headache, or have aversion to cold, heating, nasal obstruction that good effect is arranged. Pharmaceutical composition of the present invention confirms through experimental study: the effect of removing the vascular smooth muscle spasm, improving microcirculation, anti-platelet aggregation is arranged.
The present composition is compared existing preparation and is possessed good drug effect, and scope of the present invention through screening, finds in some scope of composition, to possess more outstanding drug effect unexpectedly when can realizing drug effect of the present invention; The auxiliary material of pharmaceutical composition of the present invention is through screening, and optimum auxiliary material is the compatibility of sucrose and dextrin, can reach preferably curative effect; The method of quality control of Chinese medicine composition provided by the present invention, by obtaining behind a large amount of concrete creative experiment sievings, pass through the screening to sample treatment in the discrimination method, the selection of solvent, so that differentiate that specificity is fine, and method is economic and practical, the result is quick, and can both use different lamellaes. Pass through the screening to sample, test sample processing method in the content assaying method, the selection of solvent, so that content assaying method can effectivelyly carry out quality control to product, and with the product that the method is measured compare product that additive method measures drug effect show more stable.
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
Experimental example 1: the medicine group is to the pharmacodynamics test of the influence of the pain caused reaction of thermostimulation
Medicine group I (Rhizoma Chuanxiong 210g, Radix Angelicae Dahuricae 105g, Rhizoma Et Radix Notopterygii 95g, Herba Asari 45g, Radix Saposhnikoviae 55g, Herba Menthae 520g, Herba Schizonepetae 210g, Radix Glycyrrhizae 105g)
Medicine group II (Rhizoma Chuanxiong 350g, Radix Angelicae Dahuricae 140g, Rhizoma Et Radix Notopterygii 190g, Herba Asari 100g, Radix Saposhnikoviae 140g, Herba Menthae 570g, Herba Schizonepetae 350g, Radix Glycyrrhizae 140g)
Medicine group III (Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g, Radix Gentianae Macrophyllae 102.3g, Herba Menthae 545.5g, Radix Puerariae 272.7g, Radix Glycyrrhizae 136.4g)
Medicine group IV (Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g, Radix Saposhnikoviae 102.3g, Herba Menthae 545.5g, Herba Schizonepetae 272.7g, Radix Glycyrrhizae 136.4g)
Matched group: commercially available CHUANQIONG SHIGAO YIN
Get Kunming mouse, body weight 20 ± 18g, basal body temperature is between 36～37 ℃, be divided into 4 groups at random, each organizes equal SC15% draft beer yeast suspension, (fervescence is at 0.7 ℃) beginning administration after 4 hours, experimental group gives medicine I of the present invention respectively, II, III, IV irritates stomach, and positive controls gives commercially available CHUANQIONG SHIGAO YIN, and the blank group gives isometric(al) normal saline 0.2ml/10g, after administration, surveyed the anus temperature 1 time every 1 hour, totally 4 times, add different pharmaceutical group medicine then, observe before and after the administration, influence to the pain caused reaction of thermostimulation compares, and the results are shown in Table 1:
Table 1 is respectively organized medicine to the influence of the pain caused reaction of thermostimulation (x ± SD)
Annotate: 1. compare P＜0.05 with matched group; 2. compare P＜0.05 with medicine group IV.
The result shows: medicine group I, II, III, IV and matched group relatively all have significant difference (P＜0.05) to the influence of the pain caused reaction of thermostimulation, and the pain caused reagentia of thermostimulation is better than matched group; Medicine group I, medicine group II and medicine group IV have significant difference (P＜0.05), and medicine group I, medicine group II are more remarkable to the influence of the pain caused reaction of thermostimulation than medicine group IV.
Experimental example 2
(1) experiment condition
Instrument and reagent
The instrument Constant Temp. Oven; The Sartorius balance; KUDOS ultrasonic cleaner-SK3300H
Reagent dry extract and the granule of making, adjuvant (lactose, sucrose+dextrin, starch, microcrystalline Cellulose, xylitol, mannitol), ethanol, crucible.
The preparation of granule
Take by weighing dry extract 5g, Icing Sugar and dextrin take by weighing 5g after crossing 40 mesh sieves; Dry extract and Icing Sugar are crossed 40 mesh sieves 3 times together, make its mix homogeneously; Dry extract and Icing Sugar are put into crucible, drip ethanol (choose according to circumstances or change concentration), and with the continuous kneading of finger, mixing is to " hands is pinched agglomerating, pressure promptly diffusing "; The system soft material is granulated on 14 mesh sieves, puts into baking oven, and 60 ℃, 3h.
Adjuvant is with after dry extract mixes, if viscosity greatly then increases concentration of alcohol.
The adjuvant screening
Adjuvant is selected foundation: select particulate hygroscopicity, mouldability, melting, bulk density and angle of repose appropriate adjuvant according to making behind adjuvant and the extract powder mixing.
(2) experimental technique:
Get the recipe quantity medical material by after the optimum extraction process extraction that optimizes, remove impurity, concentrating, spray drying gets dry extract, gets ormal weight extract powder and adjuvant (1: 1) mixing by table 2, measures mouldability, bulk density, angle of repose, melting and hygroscopicity.And be the index comprehensive evaluation with mouldability, bulk density, angle of repose, melting and hygroscopicity, preferred best adjuvant.
Aggregative indicator=(15/ maximum mouldability value) * mouldability value+(15/ maximum bulk density value) * bulk density value+(minimum angle of repose value * 15)/angle of repose value+(20/ maximum melting value) * melting value+(minimum hydroscopicity value * 35)/hydroscopicity value
The compatibility prescription of table 2 different auxiliary material and extract powder
1, the mensuration of mouldability
Experimental technique is weighed the granule for preparing, and crosses earlier sieve No. one, and after No. four sieves, collecting can be by a sieve but can not pass through the granule that sieves for No. four, weighs.
Ratio of briquetting=back granular mass/granular mass * 100% before sieving sieves
The mouldability score value calculates using formula: (15/ maximum mouldability value) * mouldability value the results are shown in Table 3.
The mensuration of table 3 mouldability
| Adjuvant | Ratio of briquetting (%) | Score value (15 minutes) |
| Lactose | 57.80 | 12.37 |
| Sucrose+dextrin | 53.01 | 11.34 |
| Starch | 58.59 | 12.54 |
| Microcrystalline Cellulose | 70.11 | 15.00 |
| Xylitol | 61.58 | 13.18 |
| Mannitol | 33.88 | 7.25 |
2, the mensuration of bulk density
Bulk density claims apparent density or bulk density again, means the particulate quality of unit volume.The used volume of bulk density is meant that the space is at interior cumulative volume between granule and itself space and granule and the granule.It is little that particulate bulk density is greatly promptly piled volume, and the degree of particle packing and decision volume divided dose what can be represented.
Experimental procedure: the granule after will sieving is put into exsiccant graduated cylinder, and the ml number (V) at its nearly scale place is read in vibration gently; As M (g), both ratio is bulk density with the quality after sieving.
Bulk density=M/V
The bulk density score value calculates using formula: (15/ maximum bulk density value) * bulk density value the results are shown in Table 4.
The mensuration of table 4 bulk density
| Adjuvant | M(g) | V(ml) | Bulk density (g/ml) | Score value (15 minutes) |
| Lactose | 3.4789 | 8.1 | 0.4296 | 13.43 |
| Sucrose+dextrin | 3.8760 | 9.4 | 0.4132 | 12.92 |
| Starch | 4.6236 | 16.0 | 0.2952 | 9.23 |
| Microcrystalline Cellulose | 4.8084 | 17.1 | 0.2812 | 8.79 |
| Mannitol | 2.6159 | 11.6 | 0.2255 | 7.05 |
| Xylitol | 5.7548 | 12.0 | 0.4796 | 15.00 |
3, the mensuration of angle of repose
Flowability is one of critical nature of granule, and mobile quality is relevant with the accuracy of particulate quality, divided dose, uses turnover rate on the pharmaceutics always and represents angle of repose.Angle of repose is littler, and flowability better.Usually the granule that particle diameter is more little or particle size distribution is wide, its angle of repose is bigger; And particle diameter is round, big and homogeneous granules easily flows, and angle of repose is little.
Experimental procedure: adopt the fixed funnel method, with the series connection of 3 funnels and be fixed in the height place of 1cm on the graph paper of horizontal positioned, carefully granule is poured into along hopper walls in the funnel of going up most till the granule cone tip that forms on the graph paper touches bell mouth, measure the diameter (2R) of conical base by graph paper, calculate angle of repose tga=H/R. and do calculating mean value 5 times.
Angle of repose, score value calculated using formula: (be worth * 15 minimum angle of repose)/be worth angle of repose, the results are shown in Table 5.
The mensuration of table 5 angle of repose
4, dissolve the mensuration of rate
Experimental procedure: add the accurate fixed granule that claims in the 5ml of dry constant weight centrifuge tube (minimum scale 0.1ml), the accurate boiling water 5ml that adds stirs vibration 5min, the centrifugal 15min of 3000r/min, abandoning supernatant is dried residue to constant weight at 80 ℃, the accurate title, decide, and calculates the rate of dissolving.The results are shown in Table 5.
Dissolve rate=dissolve granular mass/granular mass * 100%
Dissolve the rate score value and calculate using formula: (20/ maximum melting value) * melting value the results are shown in Table 6.
Table 6 dissolves rate to be measured
| Adjuvant | Dissolve rate (%) | Score value (15 minutes) |
| Lactose | 95.32 | 20.00 |
| Sucrose+dextrin | 94.65 | 19.86 |
| Starch | 42.20 | 8.85 |
| Microcrystalline Cellulose | 42.18 | 8.84 |
| Xylitol | 82.75 | 17.36 |
| Mannitol | 95.05 | 19.94 |
5, hygroscopic mensuration
Experimental procedure: get a certain amount of extract powder, put constant weight 48h in 30 ℃ of baking ovens.The bottom is placed with regularly puts into NaCl in the glass exsiccator of NaCl saturated solution up to forming the NaCl supersaturated solution, the relative humidity in this moment exsiccator is 75%.Put into the medicated powder of thick about 2mm in the flat weighing botle bottom of constant weight, accurately weighing is placed on above-mentioned exsiccator interior (flat weighing botle is opened).The moisture absorption percentage rate is calculated in weighing behind the 48h.Do two groups altogether, calculating mean value.
Weight * 100% before moisture absorption percentage rate %=(the preceding weight of weight-moisture absorption after the moisture absorption)/moisture absorption
The hydroscopicity score value calculates using formula: (minimum hydroscopicity value * 35)/hydroscopicity value the results are shown in Table 7.
The hygroscopic mensuration of table 7
| Adjuvant | Granule heavy (g) before the moisture absorption | Granule heavy (g) after the moisture absorption | Moisture absorption percentage rate (%) | Meansigma methods (%) | Score value (15 minutes) |
| Lactose | 1.0018 | 0.2769 | 17.64 | 31.72 | 20.23 |
| 1.0000 | 0.3580 | 35.80 | |||
| Sucrose+dextrin | 1.0000 | 0.1643 | 16.43 | 18.33 | 35.00 |
| 1.0006 | 0.2024 | 20.23 | |||
| Starch | 0.9984 | 0.2373 | 23.77 | 24.66 | 26.02 |
| 1.0005 | 0.2556 | 25.55 | |||
| Microcrystalline Cellulose | 1.0019 | 0.1932 | 19.28 | 20.77 | 30.89 |
| 1.0000 | 0.4121 | 41.20 | |||
| Xylitol | 1.0000 | 0.2099 | 20.99 | 21.84 | 29.38 |
| 1.0006 | 0.2270 | 22.69 | |||
| Mannitol | 0.9721 | 0.2894 | 29.77 | 31.97 | 20.07 |
| 1.0007 | 0.3418 | 34.16 |
6, character description
Table 8 character description
| Adjuvant | Granule | Hardness | Caking | Color |
| Lactose | Evenly | Moderate | Do not have | Taupe brown |
| Sucrose+dextrin | Evenly | Moderate | Do not have | Taupe brown |
| Starch | Inhomogeneous, coarse granule is more | Hands is pinched promptly broken | Seldom | Pale brown color |
| Microcrystalline Cellulose | Evenly | Greatly | Do not have | Taupe brown |
| Xylitol | Even slightly | Hands is pinched promptly broken | Do not have | Dark-brown |
| Mannitol | Inhomogeneous | Hands is pinched promptly broken | Less | Pale brown color |
7, comprehensive grading carries out overall merit to above-mentioned 5 test results, the results are shown in Table 9.
Table 9 comprehensive grading
| Adjuvant | Ratio of briquetting (15) | Bulk density (15) | Angle of repose (15) | Melting (20) | Hygroscopicity (35) | Total points |
| Lactose | 12.37 | 13.43 | 14.95 | 20.00 | 20.23 | 80.89 |
| Sucrose+dextrin | 11.34 | 12.92 | 15.00 | 19.86 | 35.00 | 94.12 |
| Starch | 12.54 | 9.23 | 13.50 | 8.85 | 26.02 | 70.14 |
| Microcrystalline Cellulose | 15.00 | 8.79 | 13.20 | 8.84 | 30.89 | 76.73 |
| Xylitol | 13.18 | 15.00 | 15.00 | 17.36 | 16.94 | 77.48 |
| Mannitol | 7.25 | 7.05 | 14.86 | 19.94 | 20.07 | 69.17 |
Can find out that according to aggregation of data scoring in the table score value of sucrose+dextrin is the highest, be 94.12, so the optimum adjuvant that screens is sucrose+dextrin.
8, critical relative humidity
Experimental technique: the particle drying that will prepare with sucrose+dextrin and dry extract is to constant weight, put into the granule of thick about 2mm in the flat weighing botle bottom of constant weight, accurately weighing is placed in the exsiccator of supersaturated solution of 8 kinds of different salt of different RH%, keeps weighing behind the 7d in room temperature.Because ambient humidity is very big to granule fill influence, has measured the granule critical relative humidity for this reason.
Press the supersaturated solution of the different salt of table 9 preparation, place the glass exsiccator respectively, room temperature was placed 48 hours, made its interior humidity balance constitute the environment of different relative humiditys, the sample particle 1.0g that is dried to constant weight is put in the flat weighing botle of constant weight, precision weighing is opened the weighing bottle cap, puts into the exsiccator of above-mentioned different humidity, moisture absorption is to constant weight in the constant temperature, the accurate devise a stratagem that claims is calculated hydroscopicity, measures critical relative humidity (CRH), the results are shown in Table 11 and accompanying drawing 1.
The relative humidity of the different salt saturated solutions of table 10 in the time of 25 ℃
| Saturated salt | H 2O | KNO 3 | KCl | NaCl | NaBr | K 2CO 3 | MgCl 2 | CH 3COOK |
| Relative humidity | 100.00 | 92.48 | 84.26 | 75.28 | 57.70 | 42.76 | 33.00 | 22.45 |
Table 11 critical relative humidity determination data
With the moisture absorption percentage rate % in the table 11 is vertical coordinate, and relative humidity RH% is the abscissa mapping.The tangent line at curve two ends in the mapping, the abscissa of two point of intersection of tangents correspondences is critical relative humidity.By above experimental project as can be known, the critical relative humidity CRH of sucrose+dextrin is 72%, i.e. granulation, packing and when storing, and ambient humidity must be controlled at below 72%, to reduce the influence of moisture to pharmaceutical properties and stability.
Following embodiment all can realize the described effect of above-mentioned experimental example
Embodiment 1
Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g, Radix Gentianae Macrophyllae 102.3g, Herba Menthae 545.5g, Radix Puerariae 272.7g, Radix Glycyrrhizae 136.4g
This pharmaceutical composition adds conventional adjuvant, makes pill by common process.
Embodiment 2
Rhizoma Chuanxiong 210g, Radix Angelicae Dahuricae 105g, Rhizoma Et Radix Notopterygii 95g, Herba Asari 45g, Radix Saposhnikoviae 55g, Herba Menthae 520g, Herba Schizonepetae 210g, Radix Glycyrrhizae 105g
This pharmaceutical composition adds conventional adjuvant, makes tablet by common process.
Embodiment 3
Rhizoma Chuanxiong 240g, Radix Angelicae Dahuricae 95g, Rhizoma Et Radix Notopterygii 105g, Herba Asari 25g, Radix Saposhnikoviae 75g, Herba Menthae 510g, Herba Schizonepetae 245g, Radix Glycyrrhizae 95g
This pharmaceutical composition adds conventional adjuvant, makes granule by common process.
Embodiment 4
Rhizoma Chuanxiong 300g, Radix Angelicae Dahuricae 190g, Rhizoma Et Radix Notopterygii 140g, Herba Asari 120g, Radix Saposhnikoviae 130g, Herba Menthae 590g, Herba Schizonepetae 300g, Radix Glycyrrhizae 190g
This pharmaceutical composition adds conventional adjuvant, makes drop pill by common process.
Embodiment 5
Rhizoma Chuanxiong 350g, Radix Angelicae Dahuricae 140g, Rhizoma Et Radix Notopterygii 190g, Herba Asari 100g, Radix Saposhnikoviae 140g, Herba Menthae 570g, Herba Schizonepetae 350g, Radix Glycyrrhizae 140g
This pharmaceutical composition adds conventional adjuvant, makes oral liquid by common process.
Embodiment 6
Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g, Radix Saposhnikoviae 102.3g, Herba Menthae 545.5g, Herba Schizonepetae 272.7g, Radix Glycyrrhizae 136.4g
This pharmaceutical composition adds conventional adjuvant, makes capsule by common process.
Embodiment 7
Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g, Radix Gentianae Macrophyllae 102.3g, Herba Menthae 545.5g, Radix Puerariae 272.7g, Radix Glycyrrhizae 136.4g
More than eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 1 time, add for the first time 10 times of amounts of water and decoct 0.5 hour, add 8 times of amounts of water for the second time and decoct 0.5 hour, collecting decoction filters, medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 12 times in water amount extracted volatile oil in 4 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.40 clear paste; Qinghuo reagent adds conventional adjuvant, through conventional method, makes the soft capsule of clinical acceptance.
Embodiment 8
Rhizoma Chuanxiong 210g, Radix Angelicae Dahuricae 105g, Rhizoma Et Radix Notopterygii 95g, Herba Asari 45g, Radix Saposhnikoviae 55g, Herba Menthae 520g, Herba Schizonepetae 210g, Radix Glycyrrhizae 105g
More than eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 3 times, add for the first time 6 times of amounts of water and decoct 2.5 hours, add 4 times of amounts of water for the second time and decoct 1.5 hours, collecting decoction filters, medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 8 times in water amount extracted volatile oil in 8 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.20 clear paste; Qinghuo reagent adds conventional adjuvant, through conventional method, makes the concentrated watered pill of clinical acceptance.
Embodiment 9
Rhizoma Chuanxiong 240g, Radix Angelicae Dahuricae 95g, Rhizoma Et Radix Notopterygii 105g, Herba Asari 25g, Radix Saposhnikoviae 75g, Herba Menthae 510g, Herba Schizonepetae 245g, Radix Glycyrrhizae 95g
More than eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 2 times, add for the first time 8 times of amounts of water and decoct 1.5 hours, add 6 times of amounts of water for the second time and decoct 1 hour, collecting decoction filters, medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 10 times in water amount extracted volatile oil in 6 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.30 clear paste; Qinghuo reagent adds conventional adjuvant, through conventional method, makes the tablet of clinical acceptance.
Embodiment 10
Rhizoma Chuanxiong 300g, Radix Angelicae Dahuricae 190g, Rhizoma Et Radix Notopterygii 140g, Herba Asari 120g, Radix Saposhnikoviae 130g, Herba Menthae 590g, Herba Schizonepetae 300g, Radix Glycyrrhizae 190g
More than eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 1 time, add for the first time 10 times of amounts of water and decoct 0.5 hour, add 8 times of amounts of water for the second time and decoct 0.5 hour, collecting decoction filters, medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 12 times in water amount extracted volatile oil in 4 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.40 clear paste; Qinghuo reagent 500g, cane sugar powder 500g, dextrin 300g makes granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 1200g, promptly gets granule.
Embodiment 11
Rhizoma Chuanxiong 350g, Radix Angelicae Dahuricae 140g, Rhizoma Et Radix Notopterygii 190g, Herba Asari 100g, Radix Saposhnikoviae 140g, Herba Menthae 570g, Herba Schizonepetae 350g, Radix Glycyrrhizae 140g
More than eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 3 times, add for the first time 6 times of amounts of water and decoct 2.5 hours, add 4 times of amounts of water for the second time and decoct 1.5 hours, collecting decoction filters, medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 8 times in water amount extracted volatile oil in 8 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.20 clear paste; Qinghuo reagent 500g, cane sugar powder 300g, dextrin 500g makes granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 800g, promptly gets granule.
Embodiment 12
Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g, Radix Saposhnikoviae 102.3g, Herba Menthae 545.5g, Herba Schizonepetae 272.7g, Radix Glycyrrhizae 136.4g
More than eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 2 times, add for the first time 8 times of amounts of water and decoct 1.5 hours, add 6 times of amounts of water for the second time and decoct 1 hour, collecting decoction filters, medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 10 times in water amount extracted volatile oil in 6 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.30 clear paste; Qinghuo reagent 400g, cane sugar powder 1600g makes granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 1600g, promptly gets granule.
Embodiment 13
Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g, Radix Saposhnikoviae 102.3g, Herba Menthae 545.5g, Herba Schizonepetae 272.7g, Radix Glycyrrhizae 136.4g
More than eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 2 times, add for the first time 8 times of amounts of water and decoct 1.5 hours, add 6 times of amounts of water for the second time and decoct 1 hour, collecting decoction filters, medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 10 times in water amount extracted volatile oil in 6 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.30 clear paste; Qinghuo reagent 400g, dextrin 400g makes granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 800g, promptly gets granule.
Embodiment 14
Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g, Radix Saposhnikoviae 102.3g, Herba Menthae 545.5g, Herba Schizonepetae 272.7g, Radix Glycyrrhizae 136.4g
More than eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 2 times, add for the first time 8 times of amounts of water and decoct 1.5 hours, add 6 times of amounts of water for the second time and decoct 1 hour, collecting decoction filters, medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 10 times in water amount extracted volatile oil in 6 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.30 clear paste; Qinghuo reagent 400g, cane sugar powder 400g, dextrin 400g makes granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 1000g, promptly gets granule.
The method of quality control of embodiment 15 preparations of the present invention
Differentiate: A, get this pharmaceutical composition tablet and used dosage on 1/2nd, put in the tool plug bottle, the 20ml that adds diethyl ether, jolting was placed 30 minutes, filtration, the filtrate cryoconcentration is to 1ml, as need testing solution; Other gets the Mentholum reference substance, adds diethyl ether to make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same and contain on the silica gel g thin-layer plate that sodium carboxymethyl cellulose is a binding agent, benzene-ethyl acetate with 85: 15 ratios is developing solvent, launch, take 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;
B, get this pharmaceutical composition tablet and used dosage on 2/3rd, add ethanol 50ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid 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 need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 6: 6: 1.8: the benzene-chloroform-methanol of 0.5 ratio-glacial acetic acid was developing solvent, launched, and took 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.
The method of quality control of embodiment 16 preparations of the present invention
Assay:
A, chromatographic condition and system suitability experiment: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; Methanol-water-the acetic acid of 60: 36: 4 ratios is mobile phase; The detection wavelength is 316nm, and number of theoretical plate calculates by aristolochic acid A should be not less than 2005;
The preparation of reference substance solution: get the about 5mg of aristolochic acid A reference substance that is dried to constant weight, the accurate title, decide, and making its concentration with the methanol dilution is 0.05 μ g/ml;
The preparation of need testing solution: get the agent of this medicament composition capsule and used dosage on the 2/5th, the accurate title, decide, to the 100ml measuring bottle, it is an amount of to add methanol, precision weighing, close plug, supersound process 40 minutes is taken out, and puts cold, weight decided in accurate again title, supplies the quantity of methyl alcohol of loss, shakes up, filter, discard the about 15ml of filtrate just, the accurate subsequent filtrate 75ml that draws, water bath method, residue adds 0.1mol/L sodium hydroxide solution 25ml gradation dissolving, changes in the separatory funnel, adds chloroform extraction 3 times, each 15ml, discard chloroformic solution, aqueous alkali adds the 5mol/L hydrochloric acid solution and transfers pH=2, adds chloroform extraction 4 times, each 15ml, combined chloroform solution, water bath method, residue add methanol gradation dissolving, change in the 10ml volumetric flask, add methanol to scale, shake up; Filter with 0.45 μ m microporous filter membrane before the sample introduction, promptly;
Assay method: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; In the corresponding retention time of test sample and reference substance absworption peak must not be arranged;
B, chromatographic condition and system suitability test: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; Methanol-water-the glacial acetic acid of 25: 75: 1.8 ratios is a mobile phase; The detection wavelength is 330nm, and number of theoretical plate calculates by ferulic acid should be not less than 2005;
The preparation of reference substance solution: precision takes by weighing ferulic acid, adds the mixed solution of the methanol-formic acid of 95: 5 ratios, makes the solution that every 1ml contains 50 μ g, filters with 0.45 μ m microporous filter membrane, promptly;
The preparation of need testing solution: get the agent of this medicament composition capsule, porphyrize, precision takes by weighing used dosage on the 1/5th, put in the tool plug conical flask, the accurate methanol-formic acid mixed solution 30ml that adds 95: 5 ratios claims to decide weight, power 250W, frequency 40KHZ supersound process 30 minutes is put coldly, claims to decide weight again, after supplying the weight that subtracts mistake with the methanol-formic acid mixed solution of 95: 5 ratios, shake up, filter with the 0.45um microporous filter membrane, promptly;
Assay method: accurate respectively reference substance liquid and each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; Contain Rhizoma Chuanxiong in ferulic acid C10H10O4, must not be less than and 0.24mg/ day use dosage.
The method of quality control of embodiment 17 preparations of the present invention
Differentiate: A, get the agent of this medicament composition granule and used dosage on 1/2nd, put in the tool plug bottle, the 20ml that adds diethyl ether, jolting was placed 30 minutes, filtration, the filtrate cryoconcentration is to 1ml, as need testing solution; Other gets the Mentholum reference substance, adds diethyl ether to make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same and contain on the silica gel g thin-layer plate that sodium carboxymethyl cellulose is a binding agent, benzene-ethyl acetate with 85: 15 ratios is developing solvent, launch, take 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;
B, get the agent of this medicament composition granule and used dosage on 2/3rd, add ethanol 50ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid 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 need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 6: 6: 1.8: the benzene-chloroform-methanol of 0.5 ratio-glacial acetic acid was developing solvent, launched, and took 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;
Assay:
A, chromatographic condition and system suitability experiment: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; Methanol-water-the acetic acid of 60: 36: 4 ratios is mobile phase; The detection wavelength is 316nm, and number of theoretical plate calculates by aristolochic acid A should be not less than 2005;
The preparation of reference substance solution: get the about 5mg of aristolochic acid A reference substance that is dried to constant weight, the accurate title, decide, and making its concentration with the methanol dilution is 0.05 μ g/ml;
The preparation of need testing solution: get the agent of this medicament composition granule and used dosage on the 2/5th, the accurate title, decide, to the 100ml measuring bottle, it is an amount of to add methanol, precision weighing, close plug, supersound process 40 minutes is taken out, and puts cold, weight decided in accurate again title, supplies the quantity of methyl alcohol of loss, shakes up, filter, discard the about 15ml of filtrate just, the accurate subsequent filtrate 75ml that draws, water bath method, residue adds 0.1mol/L sodium hydroxide solution 25ml gradation dissolving, changes in the separatory funnel, adds chloroform extraction 3 times, each 15ml, discard chloroformic solution, aqueous alkali adds the 5mol/L hydrochloric acid solution and transfers pH=2, adds chloroform extraction 4 times, each 15ml, combined chloroform solution, water bath method, residue add methanol gradation dissolving, change in the 10ml volumetric flask, add methanol to scale, shake up; Filter with 0.45 μ m microporous filter membrane before the sample introduction, promptly;
Assay method: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; In the corresponding retention time of test sample and reference substance absworption peak must not be arranged;
B, chromatographic condition and system suitability test: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; Methanol-water-the glacial acetic acid of 25: 75: 1.8 ratios is a mobile phase; The detection wavelength is 330nm, and number of theoretical plate calculates by ferulic acid should be not less than 2005;
The preparation of reference substance solution: precision takes by weighing ferulic acid, adds the mixed solution of the methanol-formic acid of 95: 5 ratios, makes the solution that every 1ml contains 50 μ g, filters with 0.45 μ m microporous filter membrane, promptly;
The preparation of need testing solution: get the agent of this medicament composition granule, porphyrize, precision takes by weighing used dosage on the 1/5th, put in the tool plug conical flask, the accurate methanol-formic acid mixed solution 30ml that adds 95: 5 ratios claims to decide weight, power 250W, frequency 40KHZ supersound process 30 minutes is put coldly, claims to decide weight again, after supplying the weight that subtracts mistake with the methanol-formic acid mixed solution of 95: 5 ratios, shake up, filter with the 0.45um microporous filter membrane, promptly;
Assay method: accurate respectively reference substance liquid and each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; Contain Rhizoma Chuanxiong in ferulic acid C10H10O4, must not be less than and 0.24mg/ day use dosage.
Embodiment 18
[prescription] Rhizoma Chuanxiong 272.7g, Radix Angelicae Dahuricae 136.4g, Rhizoma Et Radix Notopterygii 136.4g, Herba Asari 68.2g Radix Saposhnikoviae 102.3g, Herba Menthae 545.5g, Herba Schizonepetae 272.7g, Radix Glycyrrhizae 136.4g
[method for making] above eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water secondary, add 8 times of amounts of water for the first time and decoct 1.5 hours, add 6 times of amounts of water for the second time and decoct 1 hour, and collecting decoction filters; After Herba Menthae, Herba Schizonepetae added 10 times of amount distillations of water extraction in 6 hours volatile oil, its water liquid filtered, and filtrate and above-mentioned medicinal liquid merge, and being concentrated into relative density is the clear paste 400g of 1.30 (80 ℃); Qinghuo reagent 400g, cane sugar powder 400g, dextrin 400g makes granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 1000g, promptly;
This product powder 7g is got in [discriminating] (1), puts in the tool plug bottle, and the 20ml that adds diethyl ether, jolting was placed 30 minutes, filtered, and the filtrate cryoconcentration is to 1ml, as need testing solution; Other gets the Mentholum reference substance, adds diethyl ether to make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of each 10ul of solution, put respectively in same and contain on the silica gel g thin-layer plate that sodium carboxymethyl cellulose is a binding agent, with benzene-ethyl acetate (85: 15) is developing solvent, launch, take 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;
(2) get this product powder 10g, add ethanol 50ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (Chinese Pharmacopoeia version appendix in 2005 VI B), draw need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with benzene-chloroform-methanol-glacial acetic acid (6: 6: 1.8: 0.5) be developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
The inspection of [assay] aristolochic acid A
Adopt according to the high-efficient liquid phase color popularize law and measure:
Chromatographic condition and system suitability experiment are filler (4.6 * 150mm, 5 μ m) with octadecylsilane chemically bonded silica; Methanol-water-acetic acid (60: 36: 4) is mobile phase; The detection wavelength is 316nm, and number of theoretical plate calculates by aristolochic acid A should be not less than 2005;
The about 5mg of aristolochic acid A reference substance that is dried to constant weight is got in the preparation of reference substance solution, and accurate the title decides, and making its concentration with the methanol dilution is 0.05 μ g/ml;
The about 6g of this product fine powder is got in the preparation of need testing solution, and accurate the title decides, and to the 100ml measuring bottle, it is an amount of to add methanol, precision weighing, close plug, supersound process 40 minutes is taken out, put coldly, accurate again the title, decided weight, supplies the quantity of methyl alcohol of loss, shakes up, filter, discard the about 15ml of filtrate just, the accurate subsequent filtrate 75ml that draws, water bath method, residue add 0.1mol/L sodium hydroxide solution 25ml gradation dissolving, change in the separatory funnel, add chloroform extraction 3 times, each 15ml discards chloroformic solution, aqueous alkali is molten
Liquid adds the 5mol/L hydrochloric acid solution and transfers pH=2, adds chloroform extraction 4 times, and each 15ml, combined chloroform solution, water bath method, residue add methanol gradation dissolving, change in the 10ml volumetric flask, add methanol to scale, shake up; Filter with 0.45 μ m microporous filter membrane before the sample introduction, promptly;
Accurate respectively reference substance liquid, each the 10 μ l injection chromatograph of liquid of test sample liquid drawn of assay method measured, promptly;
In the corresponding retention time of test sample and reference substance absworption peak must not be arranged;
Other should meet every regulation relevant under the granule item (appendix IC of Chinese Pharmacopoeia version in 2005);
[assay] measured according to high performance liquid chromatography (Chinese Pharmacopoeia version appendix in 2005 VID);
Chromatographic condition and system suitability test are filler (4.6 * 150mm, 5 μ m) with octadecylsilane chemically bonded silica; Methanol-water-glacial acetic acid (25: 75: 1.8) is a mobile phase; The detection wavelength is 330nm, and number of theoretical plate calculates by ferulic acid should be not less than 2005;
It is an amount of that the preparation precision of reference substance solution takes by weighing ferulic acid, adds the mixed solution of methanol-formic acid (95: 5), makes the solution that every 1ml contains 50 μ g, filters with microporous filter membrane (0.45 μ m), promptly;
This product that the preparation of need testing solution is got under the content uniformity is an amount of, porphyrize, and precision takes by weighing about 3g, put in the tool plug conical flask, the accurate mixed solution 30ml that adds methanol-formic acid (95: 5) claims to decide weight, supersound process (power 250W, frequency 40KHZ) 30 minutes, put coldly, claim to decide weight again, after supplying the weight that subtracts mistake with the mixed solution of methanol-formic acid (95: 5), shake up, filter with microporous filter membrane (0.45um), promptly;
Accurate respectively reference substance liquid and each the 10 μ l injection chromatograph of liquid of test sample liquid drawn of assay method measured, promptly;
This product contains Rhizoma Chuanxiong with ferulic acid (C for every bag
10H
10O
4) meter, must not be less than 0.12mg.
Claims (14)
1, a kind of pharmaceutical composition of dispelling wind and relieving is characterized in that the crude drug of this pharmaceutical composition consists of: Rhizoma Chuanxiong 200-360 weight portion, Radix Angelicae Dahuricae 90-200 weight portion, Rhizoma Et Radix Notopterygii 90-200 weight portion, Herba Asari 20-130 weight portion, Radix Gentianae Macrophyllae 50-150 weight portion, Herba Menthae 500-600 weight portion, Radix Puerariae 200-360 weight portion, Radix Glycyrrhizae 90-200 weight portion.
2, the pharmaceutical composition of a kind of dispelling wind and relieving as claimed in claim 1, the crude drug that it is characterized in that this pharmaceutical composition replaces with Radix Saposhnikoviae 50-150 weight portion with Radix Gentianae Macrophyllae 50-150 weight portion in forming, and Radix Puerariae 200-360 weight portion replaces with Herba Schizonepetae 200-360 weight portion.
3, the pharmaceutical composition of a kind of dispelling wind and relieving as claimed in claim 2 is characterized in that the crude drug of this pharmaceutical composition consists of: Rhizoma Chuanxiong 272.7 weight portions, the Radix Angelicae Dahuricae 136.4 weight portions, Rhizoma Et Radix Notopterygii 136.4 weight portions, Herba Asari 68.2 weight portions, Radix Saposhnikoviae 102.3 weight portions, Herba Menthae 545.5 weight portions, Herba Schizonepetae 272.7 weight portions, Radix Glycyrrhizae 136.4 weight portions.
4, the pharmaceutical composition of a kind of dispelling wind and relieving as claimed in claim 2 is characterized in that the crude drug of this pharmaceutical composition consists of: Rhizoma Chuanxiong 200-250 weight portion, Radix Angelicae Dahuricae 90-110 weight portion, Rhizoma Et Radix Notopterygii 90-110 weight portion, Herba Asari 20-50 weight portion, Radix Saposhnikoviae 50-80 weight portion, Herba Menthae 500-530 weight portion, Herba Schizonepetae 200-250 weight portion, Radix Glycyrrhizae 90-110 weight portion.
5, the pharmaceutical composition of a kind of dispelling wind and relieving as claimed in claim 4 is characterized in that the crude drug of this pharmaceutical composition consists of: Rhizoma Chuanxiong 210 weight portions, the Radix Angelicae Dahuricae 105 weight portions, Rhizoma Et Radix Notopterygii 95 weight portions, Herba Asari 45 weight portions, Radix Saposhnikoviae 55 weight portions, Herba Menthae 520 weight portions, Herba Schizonepetae 210 weight portions, Radix Glycyrrhizae 105 weight portions.
6, the pharmaceutical composition of a kind of dispelling wind and relieving as claimed in claim 2 is characterized in that the crude drug of this pharmaceutical composition consists of: Rhizoma Chuanxiong 290-360 weight portion, Radix Angelicae Dahuricae 130-200 weight portion, Rhizoma Et Radix Notopterygii 130-200 weight portion, Herba Asari 90-130 weight portion, Radix Saposhnikoviae 120-150 weight portion, Herba Menthae 560-600 weight portion, Herba Schizonepetae 290-360 weight portion, Radix Glycyrrhizae 130-200 weight portion.
7, the pharmaceutical composition of a kind of dispelling wind and relieving as claimed in claim 6 is characterized in that the crude drug of this pharmaceutical composition consists of: Rhizoma Chuanxiong 350 weight portions, the Radix Angelicae Dahuricae 140 weight portions, Rhizoma Et Radix Notopterygii 190 weight portions, Herba Asari 100 weight portions, Radix Saposhnikoviae 140 weight portions, Herba Menthae 570 weight portions, Herba Schizonepetae 350 weight portions, Radix Glycyrrhizae 140 weight portions.
8, as the preparation of drug combination method of the arbitrary described a kind of dispelling wind and relieving of claim 1-7, it is characterized in that this method is: above eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 1-3 time, add for the first time water 6-10 and doubly measure decoction 0.5-2.5 hour, add for the second time water 4-8 and doubly measure decoction 0.5-1.5 hour, collecting decoction filters, and gets medicinal liquid; Herba Menthae, Herba Schizonepetae add water 8-12 doubly measures after distillation extracted volatile oil in 4-8 hour, and its water liquid filters, filtrate and medicinal liquid merging, the clear paste that to be concentrated into 80 ℃ of relative densities be 1.10-1.50; Qinghuo reagent adds conventional adjuvant, through conventional method, makes the preparation of clinical acceptance.
9, the preparation of drug combination method of a kind of dispelling wind and relieving as claimed in claim 8, it is characterized in that this method is: above eight flavors, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Rhizoma Et Radix Notopterygii, Herba Asari, Radix Saposhnikoviae, Radix Glycyrrhizae decoct with water 2 times, adding for the first time 8 times of amounts of water decocted 1.5 hours, adding for the second time 6 times of amounts of water decocted 1 hour, collecting decoction filters, and gets medicinal liquid; Herba Menthae, Herba Schizonepetae add the distillation of 10 times in water amount extracted volatile oil in 6 hours after, its water liquid filters, filtrate and medicinal liquid merging are concentrated into 80 ℃ of relative densities and are 1.30 clear paste; Qinghuo reagent adds conventional adjuvant, through conventional method, makes the preparation of clinical acceptance.
10, the preparation of drug combination method of a kind of dispelling wind and relieving as claimed in claim 8 is characterized in that wherein process for producing granula is after being prepared into clear paste, optional following a kind of method preparation:
A, qinghuo reagent 300-500 weight portion, cane sugar powder 300-500 weight portion, dextrin 300-500 weight portion is made granule, drying, mixing promptly gets granule;
B, qinghuo reagent 300-500 weight portion, cane sugar powder 1000-2000 weight portion, drying, mixing is granulated, and promptly gets granule;
C, qinghuo reagent 300-500 weight portion, dextrin 300-500 weight portion, drying, mixing is granulated, and promptly gets granule.
11, the preparation of drug combination method of a kind of dispelling wind and relieving as claimed in claim 9 is characterized in that wherein process for producing granula is after being prepared into clear paste, optional following a kind of method preparation:
A, qinghuo reagent 300-500 weight portion, cane sugar powder 300-500 weight portion, dextrin 300-500 weight portion is made granule, drying, mixing promptly gets granule;
B, qinghuo reagent 300-500 weight portion, cane sugar powder 1000-2000 weight portion, drying, mixing is granulated, and promptly gets granule;
C, qinghuo reagent 300-500 weight portion, dextrin 300-500 weight portion, drying, mixing is granulated, and promptly gets granule.
12, a kind of preparation of drug combination method of dispelling wind and relieving as claimed in claim 8 or 9, it is characterized in that wherein process for producing granula is after being prepared into clear paste, optional following a kind of method preparation: A, qinghuo reagent 400 weight portions, cane sugar powder 400 weight portions, dextrin 400 weight portions, make granule, drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, mixing, make 1000 weight portions, promptly get granule;
B, qinghuo reagent 400 weight portions, cane sugar powder 1600 weight portions are made granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 1600 weight portions, promptly gets granule;
C, qinghuo reagent 400 weight portions, dextrin 400 weight portions are made granule, and drying sprays into Herba Menthae, Herba Schizonepetae volatile oil, and mixing is made 800 weight portions, promptly gets granule.
13, as the quality determining method of the pharmaceutical composition of the arbitrary described a kind of dispelling wind and relieving of claim 1-7,
It is characterized in that this method comprises one or more in following discrimination method and/or the assay:
Differentiate: A, get this drug combination preparation 1/5-1 day and use dosage, put in the tool plug bottle, the 10-30ml that adds diethyl ether, jolting was placed 20-40 minute, filtration, the filtrate cryoconcentration is to 1ml, as need testing solution; Other gets the Mentholum reference substance, adds diethyl ether to make the solution that every 1ml contains 1-3mg, in contrast product solution; Test according to thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same and contain on the silica gel g thin-layer plate that sodium carboxymethyl cellulose is a binding agent, with 60-95: the benzene-ethyl acetate of 5-25 ratio is developing solvent, launch, take 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;
B, get this drug combination preparation 1/3-1 day and use dosage, add ethanol 50ml, supersound process 20-40 minute, filter, filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid reference substance, adds ethanol and makes the solution that every 1ml contains 0.5-1.5mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 4-8: 4-8: 0.5-2.5: the benzene-chloroform-methanol of 0.1-1.0 ratio-glacial acetic acid is developing solvent, launches, and takes 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;
Assay:
A, chromatographic condition and system suitability experiment: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; 40-80: 20-50: the methanol-water-acetic acid of 2-6 ratio is mobile phase; The detection wavelength is 316nm, and number of theoretical plate calculates by aristolochic acid A should be not less than 2005;
The preparation of reference substance solution: get the aristolochic acid A reference substance 5mg that is dried to constant weight, the accurate title, decide, and making its concentration with the methanol dilution is 0.05 μ g/ml;
The preparation of need testing solution: get this drug combination preparation 1/5-4/5 day and use dosage, the accurate title, decide, to the 100ml measuring bottle, it is an amount of to add methanol, precision weighing, close plug, supersound process 20-60 minute, take out, put cold, weight decided in accurate again title, supplies the quantity of methyl alcohol of loss, shakes up, filter, discard the about 15ml of filtrate just, the accurate subsequent filtrate 75ml that draws, water bath method, residue adds 0.05-0.15mol/L sodium hydroxide solution 25ml gradation dissolving, changes in the separatory funnel, adds chloroform extraction 2-4 time, each 5-25ml, discard chloroformic solution, aqueous alkali adds the 4-6mol/L hydrochloric acid solution and transfers pH=2, adds chloroform extraction 3-5 time, each 5-25ml, combined chloroform solution, water bath method, residue add methanol gradation dissolving, change in the 10ml volumetric flask, add methanol to scale, shake up; Filter with 0.45 μ m microporous filter membrane before the sample introduction, promptly;
Assay method: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; In the corresponding retention time of test sample and reference substance absworption peak must not be arranged;
B, chromatographic condition and system suitability test: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; 15-35: 50-100: the methanol-water-glacial acetic acid of 0.5-2.5 ratio is a mobile phase; The detection wavelength is 330nm, and number of theoretical plate calculates by ferulic acid should be not less than 2005;
The preparation of reference substance solution: precision takes by weighing ferulic acid, adds 70-110: the mixed solution of the methanol-formic acid of 4-6 ratio, make the solution that every 1ml contains 40-60 μ g, and filter with 0.45 μ m microporous filter membrane, promptly;
The preparation of need testing solution: get this drug combination preparation, porphyrize, precision takes by weighing uses dosage 1/10-3/5 day, put in the tool plug conical flask, the accurate 70-110 that adds: the methanol of 4-6 ratio-formic acid mixed solution 20-40ml claims to decide weight, power 250W, frequency 40KHZ supersound process 20-40 minute is put coldly, claims to decide weight again, use 70-110: after the methanol of 4-6 ratio-formic acid mixed solution is supplied the weight that subtracts mistake, shake up, filter with the 0.45um microporous filter membrane, promptly;
Assay method: accurate respectively reference substance liquid and each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; Contain Rhizoma Chuanxiong in ferulic acid C10H10O4, must not be less than and 0.1-0.3mg/ day use dosage.
14, the quality determining method of the pharmaceutical composition of a kind of dispelling wind and relieving as claimed in claim 13, its
Be characterised in that this method is:
Differentiate:
A, get this drug combination preparation and used dosage on 1/2nd, put in the tool plug bottle, the 20ml that adds diethyl ether, jolting was placed 30 minutes, filtered, and the filtrate cryoconcentration is to 1ml, as need testing solution; Other gets the Mentholum reference substance, adds diethyl ether to make the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same and contain on the silica gel g thin-layer plate that sodium carboxymethyl cellulose is a binding agent, benzene-ethyl acetate with 85: 15 ratios is developing solvent, launch, take 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;
B, get this drug combination preparation and used dosage on 2/3rd, add ethanol 50ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; Other gets the ferulic acid 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 need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 6: 6: 1.8: the benzene-chloroform-methanol of 0.5 ratio-glacial acetic acid was developing solvent, launched, and took 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;
Assay:
A, chromatographic condition and system suitability experiment: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; Methanol-water-the acetic acid of 60: 36: 4 ratios is mobile phase; The detection wavelength is 316nm, and number of theoretical plate calculates by aristolochic acid A should be not less than 2005;
The preparation of reference substance solution: get the about 5mg of aristolochic acid A reference substance that is dried to constant weight, the accurate title, decide, and making its concentration with the methanol dilution is 0.05 μ g/ml;
The preparation of need testing solution: get this drug combination preparation and used dosage on the 2/5th, the accurate title, decide, to the 100ml measuring bottle, it is an amount of to add methanol, precision weighing, close plug, supersound process 40 minutes is taken out, and puts cold, weight decided in accurate again title, supplies the quantity of methyl alcohol of loss, shakes up, filter, discard the about 15ml of filtrate just, the accurate subsequent filtrate 75ml that draws, water bath method, residue adds 0.1mol/L sodium hydroxide solution 25ml gradation dissolving, changes in the separatory funnel, adds chloroform extraction 3 times, each 15ml, discard chloroformic solution, aqueous alkali adds the 5mol/L hydrochloric acid solution and transfers pH=2, adds chloroform extraction 4 times, each 15ml, combined chloroform solution, water bath method, residue add methanol gradation dissolving, change in the 10ml volumetric flask, add methanol to scale, shake up; Filter with 0.45 μ m microporous filter membrane before the sample introduction, promptly;
Assay method: accurate respectively reference substance liquid, each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; In the corresponding retention time of test sample and reference substance absworption peak must not be arranged;
B, chromatographic condition and system suitability test: with 4.6 * 150mm, the octadecylsilane chemically bonded silica of 5 μ m is a filler; Methanol-water-the glacial acetic acid of 25: 75: 1.8 ratios is a mobile phase; The detection wavelength is 330nm, and number of theoretical plate calculates by ferulic acid should be not less than 2005;
The preparation of reference substance solution: precision takes by weighing ferulic acid, adds the mixed solution of the methanol-formic acid of 95: 5 ratios, makes the solution that every 1ml contains 50 μ g, filters with 0.45 μ m microporous filter membrane, promptly;
The preparation of need testing solution: get this drug combination preparation, porphyrize, precision takes by weighing used dosage on the 1/5th, put in the tool plug conical flask, the accurate methanol-formic acid mixed solution 30ml that adds 95: 5 ratios claims to decide weight, power 250W, frequency 40KHZ supersound process 30 minutes is put coldly, claims to decide weight again, after supplying the weight that subtracts mistake with the methanol-formic acid mixed solution of 95: 5 ratios, shake up, filter with the 0.45um microporous filter membrane, promptly;
Assay method: accurate respectively reference substance liquid and each 10 μ l injection chromatograph of liquid of test sample liquid drawn, measure, promptly; Contain Rhizoma Chuanxiong in ferulic acid C10H10O4, must not be less than and 0.24mg/ day use dosage.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100999468A CN101313936A (en) | 2007-06-01 | 2007-06-01 | Medicament composition for dispelling wind and relieving pain, preparation method and quality control method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100999468A CN101313936A (en) | 2007-06-01 | 2007-06-01 | Medicament composition for dispelling wind and relieving pain, preparation method and quality control method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101313936A true CN101313936A (en) | 2008-12-03 |
Family
ID=40105180
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007100999468A Pending CN101313936A (en) | 2007-06-01 | 2007-06-01 | Medicament composition for dispelling wind and relieving pain, preparation method and quality control method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101313936A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102759598A (en) * | 2012-07-31 | 2012-10-31 | 山东阿如拉药物研究开发有限公司 | Quality detection method for 29-componnet stagnation dissipation powder as Tibetan medicinal composition and preparations thereof |
| CN103315296A (en) * | 2013-06-27 | 2013-09-25 | 叶建斌 | Cold dispelling healthy food and preparation method |
| CN103340987A (en) * | 2013-07-30 | 2013-10-09 | 王皓之 | Pharmaceutical composition for abatement of fever |
| CN103784505A (en) * | 2014-02-24 | 2014-05-14 | 福州华凯医药科技有限公司 | Ligusticum wallichii tea prepartion |
| CN103816223A (en) * | 2014-02-24 | 2014-05-28 | 贵州威门药业股份有限公司 | Sugar-free Ligusticum wallichii tea-mixed granules |
| CN104147158A (en) * | 2014-07-24 | 2014-11-19 | 刘广宇 | Plaster for treating cervical spondylosis, scapulohumeral periarthritis and pain in waist and lower extremities |
| CN107991419A (en) * | 2017-12-21 | 2018-05-04 | 湖南天地恒制药有限公司 | Aristolochic acid A limitation inspection method in a kind of Zhuifengtougu capsules |
| CN108478626A (en) * | 2016-06-01 | 2018-09-04 | 湖南安邦制药有限公司 | A kind of extraction process of volatile oil |
| CN113237989A (en) * | 2021-05-07 | 2021-08-10 | 上海凯宝药业股份有限公司 | Quality control method of ligusticum wallichii in capsule for dispelling wind and relieving pain |
-
2007
- 2007-06-01 CN CNA2007100999468A patent/CN101313936A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102759598A (en) * | 2012-07-31 | 2012-10-31 | 山东阿如拉药物研究开发有限公司 | Quality detection method for 29-componnet stagnation dissipation powder as Tibetan medicinal composition and preparations thereof |
| CN102759598B (en) * | 2012-07-31 | 2014-10-15 | 山东阿如拉药物研究开发有限公司 | Quality detection method for 29-componnet stagnation dissipation powder as Tibetan medicinal composition and preparations thereof |
| CN103315296A (en) * | 2013-06-27 | 2013-09-25 | 叶建斌 | Cold dispelling healthy food and preparation method |
| CN103340987A (en) * | 2013-07-30 | 2013-10-09 | 王皓之 | Pharmaceutical composition for abatement of fever |
| CN103340987B (en) * | 2013-07-30 | 2015-03-25 | 王皓之 | Pharmaceutical composition for abatement of fever |
| CN103784505A (en) * | 2014-02-24 | 2014-05-14 | 福州华凯医药科技有限公司 | Ligusticum wallichii tea prepartion |
| CN103816223A (en) * | 2014-02-24 | 2014-05-28 | 贵州威门药业股份有限公司 | Sugar-free Ligusticum wallichii tea-mixed granules |
| CN103784505B (en) * | 2014-02-24 | 2016-08-24 | 北京三泉医药技术有限公司 | 'Chuan Xiong Tea ' |
| CN104147158A (en) * | 2014-07-24 | 2014-11-19 | 刘广宇 | Plaster for treating cervical spondylosis, scapulohumeral periarthritis and pain in waist and lower extremities |
| CN108478626A (en) * | 2016-06-01 | 2018-09-04 | 湖南安邦制药有限公司 | A kind of extraction process of volatile oil |
| CN107991419A (en) * | 2017-12-21 | 2018-05-04 | 湖南天地恒制药有限公司 | Aristolochic acid A limitation inspection method in a kind of Zhuifengtougu capsules |
| CN113237989A (en) * | 2021-05-07 | 2021-08-10 | 上海凯宝药业股份有限公司 | Quality control method of ligusticum wallichii in capsule for dispelling wind and relieving pain |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101313936A (en) | Medicament composition for dispelling wind and relieving pain, preparation method and quality control method thereof | |
| CN101274025B (en) | Quality control method of Chinese medicinal composition with functions of reducing fever, purging the intense heat and detoxification | |
| CN101301425B (en) | Formulation for treating diabetes and promoting coronary circulation and quality control method | |
| CN101396544B (en) | Traditional Chinese medicine composition capable of ventilating the lung and relieving asthma and preparation method thereof | |
| CN101057926B (en) | Gynaecologic menstruation regulating preparation for treating gynecopathy and its preparation method and detection method | |
| CN102114075B (en) | Serial Chinese medicinal preparation for treating child common cold and preparation process and detection method thereof | |
| CN101002909B (en) | Antiviral traditional Chinese medicine, its preparing method and quality control method | |
| CN1876039B (en) | Detection method of pharmaceutical composition for treating upper respiratory tract infection | |
| CN101496870B (en) | Chinese medicinal composition for resolving phlegm and suppressing cough as well as preparation method and quality control method thereof | |
| CN102114155A (en) | Serial Chinese medicinal preparation for treating phaseolus cold and preparation process and quality control method thereof | |
| CN102145146B (en) | Method for detecting medicinal composition for treating urinary system diseases | |
| CN101933996B (en) | Chinese medicinal composition having effects of clearing heat, relieving fire and eliminating toxins and preparation and detection methods thereof | |
| CN108524616A (en) | A kind of white peony root dispensing granule agent and preparation method thereof | |
| CN102288701B (en) | Method for detecting Chinese medicinal composition for freeing lung and relieving asthma | |
| CN101195007B (en) | Medicament for treating common cold cough, method for preparing its preparation and quality control method thereof | |
| CN101244202B (en) | Chinese medicine oral administration solid preparations, preparation, quality control method and uses thereof | |
| CN101411758B (en) | Chinese medicine solid formulation for treating insomnia and preparation method thereof | |
| CN100571756C (en) | A kind of Chinese medicine composition for the treatment of flu and preparation method thereof and detection method | |
| CN1994373A (en) | Formulation with basil, ginkgo leaf and notoginseng, preparation process and quality control method | |
| CN100585401C (en) | Detection method for orally administered formulation for reducing fat and expelling toxins | |
| CN102048929B (en) | Xiaoyukang tablet and preparation method thereof | |
| CN101385834B (en) | Medicine composition for treating urinary system disease and quality control method thereof | |
| CN101485736B (en) | Medicament composition with stone-eliminating and expelling functions and preparation method thereof | |
| CN101711827B (en) | Traditional Chinese medicine preparation for clearing heat, cooling blood and nourishing yin and kidneys, preparation method and detection method thereof | |
| CN100475241C (en) | Yankening medicine preparation and preparing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20081203 |