CN100435815C

CN100435815C - Medicine composition for treating pain and preparing method therefor

Info

Publication number: CN100435815C
Application number: CNB2006100568320A
Authority: CN
Inventors: 索伟; 庞永清; 秦婷; 王春民; 李沈明; 计福全
Original assignee: JINGFUKANG PHARMACEUTICAL GROUP CO Ltd CHENGDE
Current assignee: Jingfukang Pharmaceutical Group Co., Ltd.
Priority date: 2006-01-17
Filing date: 2006-03-07
Publication date: 2008-11-26
Anticipated expiration: 2026-03-07
Also published as: CN1850161A

Abstract

The present invention discloses a medicine composition for treating pain and a method for preparing a preparation of the medicine composition. The medicine composition is prepared from nux vomica, ground beeltle, cyathula root, ephedra, olibanum, myrrh, stiff silkorm, atractylodes rhizome, scorpion and radix glycyrrhiza, wherein the nux vomica can be replaced by prepared nux vomica powder. The other aim of the present invention is to provide a method for controlling the quality of the preparation of the Chinese medicine composition and a purpose of the medicine composition for treating pain.

Description

A kind of pharmaceutical composition for the treatment of pain and preparation method thereof

Invention field

The present invention relates to a kind of pharmaceutical composition and preparation method thereof and method of quality control, particularly a kind of pharmaceutical composition for the treatment of pain and preparation method thereof and method of quality control.

Background technology

Lumbago and skelalgia is a kind of commonly encountered diseases, frequently-occurring disease, and the traditional Chinese medical science is arthromyodynia with its ownership.Pain is that this class disease causes the main clinic symptoms that body and mind is painful and life is inconvenient to the patient.According to incompletely statistics, recorded at present kind surplus the oral and external preparation nearly 200 of the treatment lumbago and skelalgia of national standard, oral actually rare but wherein same drug regimen has concurrently with medicines two kinds of preparations of external.

Summary of the invention

The object of the invention is to provide the preparation method of a kind of pharmaceutical composition and preparation thereof, and another purpose of the present invention is to provide the purposes of this Chinese medicine composition and the method for quality control of preparation thereof.

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

Pharmaceutical composition of the present invention is made up of following crude drug:

Semen Strychni 200-500 weight portion Eupolyphaga Seu Steleophaga 80-150 weight portion

Radix Cyathulae 80-150 weight portion Herba Ephedrae 80-150 weight portion

Olibanum 80-150 weight portion Myrrha 80-150 weight portion

Bombyx Batryticatus 80-150 weight portion Rhizoma Atractylodis 80-150 weight portion

Scorpio 80-150 weight portion Radix Glycyrrhizae 80-150 weight portion.

The best proportioning of pharmaceutical composition crude drug of the present invention is as follows:

Semen Strychni 460 weight portion Eupolyphaga Seu Steleophagas 84 weight portions

Radix Cyathulae 143 weight portion Herba Ephedraes 86 weight portions

Olibanum (processed with vinegar) 140 weight portion Myrrha (processed with vinegar) 82 weight portions

Bombyx Batryticatus (parched with bran) 145 weight portion parched with bran Rhizoma Atractylodis 84 weight portions

Scorpio 139 weight portions

Radix Glycyrrhizae 84 weight portions.

Semen Strychni 250 weight portion Eupolyphaga Seu Steleophagas 140 weight portion Radix Cyathulaes 82 weight portions

Herba Ephedrae 142 weight portion Olibanum (processed with vinegar) 84 weight portion Myrrha (processed with vinegar) 139 weight portions

Bombyx Batryticatus (parched with bran) 86 weight portion parched with bran Rhizoma Atractylodis 144 weight portion Scorpios 82 weight portions

Radix Glycyrrhizae 145 weight portions.

Semen Strychni 316 weight portion Eupolyphaga Seu Steleophagas 84 weight portion Radix Cyathulaes 84 weight portions

Herba Ephedrae 84 weight portion Olibanum (processed with vinegar) 84 weight portion Myrrha (processed with vinegar) 84 weight portions

Bombyx Batryticatus (parched with bran) 84 weight portion parched with bran Rhizoma Atractylodis 84 weight portion Scorpios 84 weight portions

Radix Glycyrrhizae 84 weight portions.

Press practice of pharmacy, the above-mentioned raw materials medicine can be prepared into various clinical or pharmaceutically acceptable dosage forms, include but not limited to a kind of in the middle of the following dosage form as: tablet, hard capsule, soft capsule, slow releasing tablet, controlled release tablet, slow releasing capsule, controlled release capsule, oral solution, oral suspensions, Orally taken emulsion, mucilage, oral liquid, Emulsion, colloid solution, mixture, tincture, drop, suspendible drop, pill, drop pill, granule, enteric coated granule, powder, cataplasma or rubber-emplastrum etc.

Semen Strychni in the aforementioned pharmaceutical compositions of the present invention can substitute with the modulation Semen Strychni Pulveratum of 450-500 weight portion, preferably modulates Semen Strychni Pulveratum 460 weight portions, 480 weight portions or 490 weight portions.

Modulation Semen Strychni Pulveratum of the present invention is according to the conventional method in the pharmacopeia, or following method preparation: whenever get Semen Strychni (processed) 100 weight portions, be ground into fine powder, behind method mensuration strychnine content under the assay item of Pharmacopoeia of People's Republic of China Semen Strychni, add starch 5-100 weight portion, after making strychnine C21H22N202 content count 1.09%～1.15% by dry product, mixing is promptly made the modulation Semen Strychni Pulveratum.

Press practice of pharmacy, can be prepared into various clinical or pharmaceutically acceptable dosage forms with containing the above-mentioned raw materials medicine of modulating Semen Strychni Pulveratum, include but not limited to a kind of in the middle of the following dosage form as: tablet, hard capsule, soft capsule, slow releasing tablet, controlled release tablet, slow releasing capsule, controlled release capsule, oral solution, oral suspensions, Orally taken emulsion, mucilage, oral liquid, Emulsion, colloid solution, mixture, tincture, drop, suspendible drop, pill, drop pill, granule, enteric coated granule, powder, powder, cataplasma or rubber-emplastrum etc.

The preparation technology of drug combination preparation of the present invention is as follows:

In the modulation Semen Strychni Pulveratum of per 100 weight portions, add 5%-15% starch slurry 60-100 weight portion, make granule, drying; Get above-mentioned granule, make solvent with 50%-70% ethanol, carry out percolation, collect the liquid of filtering, reclaim ethanol, being evaporated to relative density is that 1.30～1.35 thick paste is standby at 80 ℃; All the other Eupolyphaga Seu Steleophagas nine flavor crude drug, fragmentation, with 85%-95% alcohol reflux 2-4 time, each 1.5-2.5 hour, merge extractive liquid,, filtration, it is 1.15～1.20 clear paste under 60 ℃ that filtrate is concentrated into relative density; Clear paste and above-mentioned thick paste merge, and add conventional adjuvant and make regular dosage form.

Pharmaceutical composition of the present invention is made rubber-emplastrum, wherein the substrate of rubber-emplastrum is made of by weight following raw material: rubber 25-40 weight portion lanoline 4-8 weight portion white oil 2-5 weight portion vaseline 2-4 part by weight of zinc oxide 25-35 weight portion Foral 15-25 weight portion Mentholum 1.5-2.5 weight portion age resistor 2,6-ditertbutylparacresol 1-1.5 weight portion, 120# gasoline 90-150 weight portion.

The preparation technology of the rubber-emplastrum of pharmaceutical composition of the present invention is as follows:

In the modulation Semen Strychni Pulveratum of per 100 weight portions, add 10% starch slurry, 80 weight portions, make granule, drying; Get above-mentioned granule, make solvent with 60%7 alcohol, carry out percolation, collect the liquid of filtering, reclaim ethanol, being evaporated to relative density is that 1.30～1.35 thick paste is standby at 80 ℃; All the other Eupolyphaga Seu Steleophagas nine flavor crude drug, fragmentation, with 90% alcohol reflux 3 times, each 2 hours, merge extractive liquid,, filtration, it is 1.15～1.20 clear paste under 60 ℃ that filtrate is concentrated into relative density; Clear paste and above-mentioned thick paste merge, and other adds the doubly heavy substrate of being made by rubber, Colophonium etc. of 3.0-3.4, makes coating, is coated with cream, cutting, lid lining, section, and packing is made.

The method of quality control of rubber-emplastrum of the present invention comprises in the following method one or more:

A, get 2 of this pharmaceutical composition rubber-emplastrums, tear the lid lining off, shred, add 3 → 100 sulfuric acid solution 100ml, ultrasonic 10-20 minute, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 15-25ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 2ml makes dissolving, as need testing solution.Get the strychnine reference substance, chlorination is copied into the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 3-5: 4-6: 0.5-0.7: 0.3-0.5 toluene-acetone-ethanol-strong ammonia solution is developing solvent, launches, and takes out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

B, get 2 of this pharmaceutical composition rubber-emplastrums, tear the lid lining off, shred, add 3 → 100 sulfuric acid solution 100ml, ultrasonic 10-20 minute, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 15-25ml, combined chloroform liquid adds 1 → 10 methanol hydrochloride solution 1ml, evaporate to dryness, add methanol 0.5ml and make dissolving, as need testing solution.Other gets the ephedrine hydrochloride reference substance and adds methanol and make the solution that every 1ml contains 0.2mg, in contrast product solution.According to the thin layer chromatography test, draw each 5 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with 15-25: 3-5: 0.3-0.6 chloroform-methanol-strong ammonia solution is developing solvent, launches, and takes out, dry, spray is with ninhydrin solution, and it is clear to dry by the fire to the speckle colour developing in 105 ℃.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

C, get 10 of this pharmaceutical composition rubber-emplastrums, remove the lid lining, shred, put in the 500ml round-bottomed flask, add water 300ml, connect volatile oil extractor, add water to scale from the determinator top, and till overflow goes in the bottle, add normal hexane 1ml again, little boiling extracted 1-3 hour, put cold, divide and get normal hexane, as need testing solution.Water layer keeps for Radix Cyathulae differentiates usefulness.Other gets Rhizoma Atractylodis control medicinal material 0.5g, adds normal hexane 2ml, and supersound extraction 10-20 minute, filter, filtrate is medical material solution in contrast.Test according to thin layer chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 60～90 ℃ of petroleum ether-8-12: 0.1 ethyl acetate is developing solvent, launch, take out, dry, spray is heated to clear spot with the 5%-15% ethanol solution of sulfuric acid of 3%-7% dimethylaminobenzaldehyde at 100-110 ℃.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on the dirty green speckle of same color is arranged.

D, get and differentiate C item water layer down, filtration, filtrate is concentrated into about 80ml, filter, residue washes with water 2 times, each 5-15ml, merging filtrate adds diethyl ether and extracts 3 times, each 20-40ml, discard ether solution, aqueous solution extracts 4 times with the chloroform jolting, each 20-40ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution.Other gets Radix Cyathulae control medicinal material 1g, add 90% ethanol 10ml, reflux 1-3 hour, filter, filtrate is concentrated into does not have the alcohol flavor, add water 100ml, reflux 0.5-1.5 hour, filter the filtrate extraction that adds diethyl ether, with the need testing solution operation, make control medicinal material solution from " add diethyl ether and extract 3 times ".According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 6-10: 2-6: 1 benzene-chloroform-acetone is developing solvent, launches, and takes out, and dries, and puts under the 365nm uviol lamp and inspects.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the sapphirine fluorescence speckle of same color.

E; get 3 of this pharmaceutical composition rubber-emplastrums removes lid lining, shreds; add 10% ethanol 40-60ml, adds 1mol/L hydrochloric acid solution 10ml reflux 0.5-1.5 hour, filters; add concentrated hydrochloric acid in the filtrate and make its concentration be about 5%, reflux 1-3 hour, filters; filtrate adds the chloroform jolting extracts 3 times, each 5-15ml, combined chloroform extracting solution; extract 3 times with 5% sodium carbonate liquor, and each 10ml merges alkali liquor; with ether extraction 3 times; each 3-8ml, discard ether solution, transferring pH with hydrochloric acid is 1～2; extract 3 times with the chloroform jolting; 5-15ml at every turn, combined chloroform liquid, evaporate to dryness; add dehydrated alcohol 1ml and make dissolving, as need testing solution.Extracting liquorice control medicinal material 0.2g shines medical material solution in pairs with legal system in addition.According to thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, point sample is on same silica gel g thin-layer plate respectively, with 3-7: 10-20: 4-10: 0.5,30～60 ℃ of petroleum ether-toluene-ethyl acetate-glacial acetic acid are developing solvent, launch, take out, dry, spray is with the 5-15% ethanol solution of sulfuric acid of 3-7% vanillin, and 105 ℃ are heated to clear spot.In the sample chromatogram, with the corresponding position of control medicinal material chromatograph on, show the yellow spotting of same color.

F, chromatographic condition and system suitability test are filler with eight alkyl silane bonded silica gels; With 80-120: 450-500: 20-50 methanol-water-glacial acetic acid, regulate pH value to 2.5-3.5, as mobile phase with triethylamine; The detection wavelength is 254nm.Number of theoretical plate calculates by the strychnine peak should be not less than 5000.It is an amount of that the preparation precision of reference substance solution takes by weighing the strychnine reference substance, adds mobile phase and make the solution that every 1ml contains 2-3 μ g approximately, promptly.1/4 of this pharmaceutical composition rubber cream is got in the preparation of need testing solution, shreds, and puts in the ground triangular flask, adds chloroform 15-25ml, strong aqua ammonia 1.0ml, close plug, supersound process 5-15 minute.Extracting solution moves in the separatory funnel, and with 20-40ml chloroform gradation washing triangular flask, washing liquid is incorporated in the separatory funnel, with 0.5mol/L sulphuric acid solution extraction 5 times, each 5-15ml merges sulphuric acid liquid, add strong ammonia solution and regulate pH value to 9～10, use chloroform extraction 5 times, each 5-15ml, combined chloroform liquid, evaporate to dryness, residue add the mobile phase dissolving, be transferred in the 50ml measuring bottle, and be diluted to scale, and shake up, filter.Precision is measured subsequent filtrate 1ml and is put in the 10ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, promptly.According to high effective liquid chromatography for measuring, accurate respectively reference substance solution and each 15-25 μ l of need testing solution of drawing injects chromatograph of liquid, measures, promptly;

Contain strychnine C in the every rubber cream ₂₁H ₂₂N ₂O ₂Should be 3.5～6.5mg.

Method of quality control preferably includes in the following method one or more:

A, get 2 of this pharmaceutical composition rubber-emplastrums, tear the lid lining off, shred, add 3 → 100 sulfuric acid solution 100ml, ultrasonic 15 minutes, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 2ml makes dissolving, as need testing solution.Get the strychnine reference substance, chlorination is copied into the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 4: 5: 0.6: 0.4 toluene-acetone-ethanol-strong ammonia solution is developing solvent, launches, and takes out, and dries, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

B, get 2 of this pharmaceutical composition rubber-emplastrums, tear the lid lining off, shred, add 3 → 100 sulfuric acid solution 100ml, ultrasonic 15 minutes, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 20ml, combined chloroform liquid adds 1 → 10 methanol hydrochloride solution 1ml, evaporate to dryness, add methanol 0.5ml and make dissolving, as need testing solution.Other gets the ephedrine hydrochloride reference substance and adds methanol and make the solution that every 1ml contains 0.2mg, in contrast product solution.According to the thin layer chromatography test, draw each 5 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with 20: 4: 0.5 chloroform-methanol-strong ammonia solutions was developing solvent, launched, and took out, dry, spray is with ninhydrin solution, and it is clear to dry by the fire to the speckle colour developing in 105 ℃.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

C, get 10 of this pharmaceutical composition rubber-emplastrums, remove the lid lining, shred, put in the 500ml round-bottomed flask, add water 300ml, connect volatile oil extractor, add water to scale from the determinator top, and till overflow goes in the bottle, add normal hexane 1ml again, little boiling extracted 2 hours, put cold, divide and get normal hexane, as need testing solution.Water layer keeps for Radix Cyathulae differentiates usefulness.Other gets Rhizoma Atractylodis control medicinal material 0.5g, adds normal hexane 2ml, and supersound extraction 15 minutes filters, and filtrate is medical material solution in contrast.Test according to thin layer chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 10: 0.1,60～90 ℃ of petroleum ether-ethyl acetates were developing solvent, launched, take out, dry, spray is heated to clear spot with 10% ethanol solution of sulfuric acid of 5% dimethylaminobenzaldehyde at 105 ℃.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on the dirty green speckle of same color is arranged.

D, get and differentiate C item water layer down, filtration, filtrate is concentrated into about 80ml, filter, residue washes with water 2 times, each 10ml, merging filtrate adds diethyl ether and extracts 3 times, each 30ml, discard ether solution, aqueous solution extracts 4 times with the chloroform jolting, each 30ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution.Other gets Radix Cyathulae control medicinal material 1g, adds 90% ethanol 10ml, and reflux 2 hours filters, filtrate is concentrated into does not have the alcohol flavor, adds water 100ml, and reflux 1 hour filters, the filtrate extraction that adds diethyl ether is operated with need testing solution from " add diethyl ether and extract 3 times ", makes control medicinal material solution.According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with 8: 4: 1 benzene-chloroform-acetone, launch, take out, dry, put under the 365nm uviol lamp and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the sapphirine fluorescence speckle of same color.

E; get 3 of this pharmaceutical composition rubber-emplastrums removes the lid lining, shreds; add 10% ethanol 50ml, adds 1mol/L hydrochloric acid solution 10ml reflux 1 hour, filters; add concentrated hydrochloric acid in the filtrate and make its concentration be about 5%, and reflux 2 hours filters; filtrate adds chloroform jolting extraction 3 times, each 10ml, combined chloroform extracting solution; extract 3 times with 5% sodium carbonate liquor; each 10ml, merges alkali liquor, uses ether extraction 3 times; each 5ml+ discards ether solution; transferring pH with hydrochloric acid is 1～2, extracts 3 times with the chloroform jolting, at every turn 10ml; combined chloroform liquid; evaporate to dryness adds dehydrated alcohol 1ml and makes dissolving, as need testing solution.Extracting liquorice control medicinal material 0.2g shines medical material solution in pairs with legal system in addition.According to thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, point sample is on same silica gel g thin-layer plate respectively, with 5: 15: 7: 0.5,30～60 ℃ of petroleum ether-toluene-ethyl acetate-glacial acetic acid were developing solvent, launched, take out, dry, spray is with 10% ethanol solution of sulfuric acid of 5% vanillin, and 105 ℃ are heated to clear spot.In the sample chromatogram, with the corresponding position of control medicinal material chromatograph on, show the yellow spotting of same color.

F, chromatographic condition and system suitability test are filler with eight alkyl silane bonded silica gels; With 100: 480: 35 methanol-water-glacial acetic acid, regulate pH value to 3.1 with triethylamine, as mobile phase; The detection wavelength is 254nm; Number of theoretical plate calculates by the strychnine peak should be not less than 5000; It is an amount of that the preparation precision of reference substance solution takes by weighing the strychnine reference substance, adds mobile phase and make the solution that every 1ml contains 2.5 μ g approximately, promptly; 1/4 of this pharmaceutical composition rubber cream is got in the preparation of need testing solution, shreds, and puts in the ground triangular flask, adds chloroform 20ml, strong aqua ammonia 1.0ml, close plug, supersound process 10 minutes; Extracting solution moves in the separatory funnel, and with 30ml chloroform gradation washing triangular flask, washing liquid is incorporated in the separatory funnel, with 0.5mol/L sulphuric acid solution extraction 5 times, each 10ml merges sulphuric acid liquid, add strong ammonia solution and regulate pH value to 9～10, use chloroform extraction 5 times, each 10ml, combined chloroform liquid, evaporate to dryness, residue add the mobile phase dissolving, be transferred in the 50ml measuring bottle, and be diluted to scale, and shake up, filter; Precision is measured subsequent filtrate 1ml and is put in the 10ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, promptly; According to high effective liquid chromatography for measuring, accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing inject chromatograph of liquid, measure, promptly; Contain strychnine C in the every rubber cream ₂₁H ₂₂N ₂O ₂Be 4.6～5.8mg.

This pharmaceutical composition card cream is on the basis of this medicament composition capsule of medicine that is exclusively used in treatment lumbago and skelalgia and rheumatic arthralgia, through changing the new Chinese medicine for external application of route of administration and preparation process.This medicament composition capsule is deferred to the Traditional Chinese medical theory scientific composition, by invading cold, wet heresy outward, temperature three-way meridian pain relieving, real, double the controlling of the stasis of blood two cards.From the side of choosing, prescription is to the approval list marketing, the clinical practice of going through so far more than 30 year is used, and proves that this product has excellent curative to the various diseases that cures mainly.The treatment lumbago and skelalgia disease clinical and experimental study result who carries out in how tame hospital shows that total effective rate reaches more than 90%.

Zunhua, Hebei province hospital adopts this medicament composition capsule combining oral external application for curing osteoarthritis 300 examples, 98 examples of fully recovering (32.67%) in clinical practice, produce effects 177 examples (59.00%), effective 16 examples (5.33%), invalid 9 examples (3.00%), total effective rate 97.00%; Matched group 150 examples, 14 examples of fully recovering (9.33%), produce effects 47 examples (31.33%), effective 58 examples (38.66%), invalid 31 examples (20.66%), 79.33% liang of group of total effective rate relatively has significant difference.Point out the external of this medicament composition capsule to have therapeutic effect equally, and have synergism with oral medication.

Lumbago and skelalgia is a local symptom, and this pharmaceutical composition card cream is directly used in patient part, acts directly on patient part performance therapeutical effect after the effective ingredient percutaneous of medicine absorbs, and makes curative effect more rapid and remarkable, uses also more convenient.This pharmaceutical composition card cream and this medicament composition capsule are united use and can be worked in coordination with mutually, further improve therapeutic effect.

In existing patent medicine preparation, rarely have and to make collaborative use of the different preparations with external for oral administration with a kind of drug regimen, according to existing clinical application practice experience, this pharmaceutical composition card cream is except that having significant therapeutical effect, also can with this medicament composition capsule inside and outside and use, improve therapeutic effect, possess certain novelty and novelty.

The effect that this medicament composition capsule has reducing swelling and alleviating pain, evacuates cold-evil, promoting the flow of QI in the collateral by warming the meridian is used for prolapse of lumbar intervertebral disc, hyperosteogeny disease, sciatica, lumbar muscle strain, psoas myofibrositis, diseases such as chronic rheumatic arthritis, and clinical efficacy is definite.Because its main disease to be treated mostly occurs in the part, thereby also have capsule 's content furnishing paste back outer clinically in order to reach the situation of therapeutic purposes.Each flavour of a drug effective ingredient mostly is liposoluble constituent in this medicament composition capsule prescription, has certain percutaneous permeability, so external effectively is possible.Show through pharmacodynamics and studies on acute toxicity result: under the same dose, the drug effect of this pharmaceutical composition external and this medicament composition capsule (oral administration) are suitable, and external is than oral administration LD ₅₀Improved manyfold, promptly under the prerequisite that drug effect guarantees, safety significantly improves.Following experimental example is used to further specify but is not limited to the present invention.

Experimental example 1 extraction process trial test

Select water, two kinds of Chinese medicine extraction solvents commonly used of ethanol, the living respectively prescription Chinese crude drug extraction process experimentation of having gone is the galenic pharmacy evaluation index with the paste-forming rate; With this medicament composition capsule is the contrast medicine, analgesia (to photoelectricity stimulate the influence of mice whipping, to the influence of mice acetic acid twisting), antiinflammatory (mice carrageenin toes are swollen) act as the pharmacodynamics evaluation index, and the extract of different extraction processes preparations has been carried out overall merit.

Result of the test: galenic pharmacy evaluation: the paste-forming rate of alcohol extraction process is lower than extraction process by water, is suitable for preparing rubber-emplastrum.

Pharmacodynamics is estimated: this medicament composition capsule has good analgesic and anti-inflammatory effects;

Be equivalent under the equal crude drug dosage, the extract topical administration of two kinds of extraction processes, analgesia, antiinflammatory action are not less than former dosage form; The analgesic activity of ethanol extract is better than water extract, the two indifference of antiinflammatory action.Conclusion: this pharmaceutical composition rubber unguentum material extracts should adopt alcohol extraction process.

Experimental example 2 Semen Strychni Pulveratums extract experimental study

Semen Strychni Pulveratum is the above fine powders of 80 orders, and directly feeding intake, it is very slow to carry out percolation speed.For addressing this problem, the starch slurry with 10% is to carry out percolation again after binding agent is made 20 purpose granules with Semen Strychni Pulveratum, makes percolation to carry out under normal speed.

The rate of transform with main pharmacodynamics composition strychnine in the Semen Strychni Pulveratum is the technology assessment index, and key process parameters such as the alcoholic strength of extraction solvent, solvent consumption, percolation speed have been carried out the orthogonal optimum seeking test.Determine that the Semen Strychni Pulveratum extraction process is: with feed intake 60% ethanol percolation of weight of 16 times of Semen Strychni Pulveratums.The about 5ml/kg/min of percolation speed.Extract Semen Strychni Pulveratum by this technology, the strychnine rate of transform on average can reach 96%.

Nine flavor medicines such as experimental example 3 Eupolyphaga Seu Steleophagas extract experimentation

The solvent nine flavor medicament extracts under the same conditions of different wine precision are added Semen Strychni Pulveratum extraction extractum in the ratio in the prescription, with analgesia (mice acetic acid twisting method), antiinflammatory (mice carrageenin toes are swollen) pharmacodynamic experiment is evaluation index, determines the optimum extraction solvent.Extracting best solvent is 90% ethanol;

Combination of process parameters such as solvent addition, extraction time, extraction time are carried out orthogonal test, are evaluation index screening technology parameter with the paste volume.Determine that through preferred the extraction processes of nine flavor medicines such as Eupolyphaga Seu Steleophaga are: with 90% alcohol reflux of 4 times of amounts 3 times, each 2 hours.

Concentration technology: concentrating under reduced pressure, Semen Strychni Pulveratum extractum are concentrated into 1.30-1.35 (80 ℃), and nine flavor medicines are concentrated into 1.15-1.20 (60 ℃).

Experimental example 4The research of extraction pilot experiment

Carried out 3 batches (40,000 adhesion doses/batch, inventory Semen Strychni Pulveratum 19.2kg/ criticizes; Nine flavor medicine 30.24kg/ such as Eupolyphaga Seu Steleophaga criticize) research of extraction pilot experiment.Semen Strychni Pulveratum extracts test strychnine mean transferred rate and reaches 89.79%; Nine flavor medicines extract test paste volume average 23.44%.Approaching substantially with little test result.

Experimental example 5The preparations shaping technical study

Determining of patch substrate: with reference to the proportioning of each composition of rubber plaster, adding drug extract, is that evaluation index is adjusted each components in proportions in the substrate with viscosity, thermostability, selects to determine best matrix components proportioning and drug extract and substrate composition.Determine that according to prescription crude drug amount, extraction paste-forming rate, extractum and substrate composition the paste containing amount of rubber cream should be no less than 1.6g/100cm ²

The mount selection of material: on calico and colour of skin elastic force cloth, pleasant degree is investigated the influence of material to assay of mounting with rubber mastic slurry separate application.The result selects the mount material of colour of skin elastic force cloth as rubber cream.

Study on Preparation:, formulated substrate preparation technology and rubber cream preparation technology with reference to existing rubber-emplastrum production common processes rules.

Sample trial-production: in prepared in laboratory three batches of this pharmaceutical composition rubber cream, be evaluation index with viscosity and thermostability, compare, determine that the rubber cream that extractum and substrate prepares is more satisfactory under 1: 3.3 proportioning.

The research of rubber cream pilot plant test: carried out 3 batches, theoretical yield is that 40,000 medicinal material extract of pasting/criticizing and rubber cream are produced pilot plant test research.Three batches of rubber cream yield rates are respectively 85.0%, 83.5%, 87.0%.The regulation that meets quality standard through check.

Experimental example 6 quality researches experiment

Determining of prescription:

This medicament composition capsule prescription:

This pharmaceutical composition rubber cream is the new drug that changes technology and route of administration development on this medicament composition capsule prescription basis.Result of study shows, the main pharmacodynamics of rubber cream and capsule is suitable under the equal crude drug content, is defined as a daily dose identical (identical with the contained crude drug amount of 4 capsules) with this medicament composition capsule so every of this pharmaceutical composition rubber cream is contained the crude drug amount.Corresponding rubber cream prescription is:

The research of quality standard: the content assaying method to strychnine in the rubber cream has carried out experimentation, adopts reversed phase high efficiency liquid phase method to measure strychnine content detecting method in this pharmaceutical composition rubber cream, has determined strychnine content limit in the rubber cream; Studied and defined in the rubber cream thin layer discrimination method of index components in Semen Strychni, Herba Ephedrae, Rhizoma Atractylodis, Radix Cyathulae, the Radix Glycyrrhizae.

Stability test research: with test agent in three batches is experiment material, and at 40 ℃, the stability experiment that has carried out in the environment of relative humidity 70% under accelerated stability test research and the home is studied.A preliminary stable experimental studies results showed that every quality index of rubber cream was stable, meets the requirement of quality standard in completed 6 months.

Experimental example 7 pharmacology pharmacodynamic experimentatioies

Research contents:

Investigational agent: this pharmaceutical composition rubber cream Chinese medical concrete;

Contrast medicine: this medicament composition capsule;

The excipient tester;

Dosage: 0.075 gram crude drug/kg, 0.15g crude drug/kg, 0.3g crude drug/kg (quite clinical dosage is 2.5,5,10 times).

1 analgesic test research: carried out influence to the reflection of mice acetic acid twisting; Influence to the reaction of rat water-bath whipping; Mice photoelectricity is stimulated the three kinds of analgesic test researchs that influence of whipping reflection.

Antiinflammatory experimentation: carried out to the bullate influence of Fructus Crotonis oiliness mouse ear; To the bullate influence of rat carrageenan foot; Three kinds of antiinflammatory experimental studies to the bullate influence of rat granuloma.

2 activating blood circulation to dissipate blood stasis experimentatioies: observe to the rat packed cell volume influence of whole blood viscosity under high shearing, the low-rate-of-shear.

3 influences: observe influence to mice self absorption of hematoma to self absorption of hematoma.

Result of study:

The Pharmacodynamic test of active extract of this medicine shows that its action intensity is not less than this medicament composition capsule of same dose.The test of mice acetic acid twisting shows that its suppression ratio that animal is turned round body is respectively 69.2%, 53.8%, 38.5%, demonstrates very strong analgesic effect; Tail-flick test shows that this medicine is rapid-action, promptly demonstrates significant analgesia role in 0.5 hour behind the medicine, and the analgesic test proves that this pharmaceutical composition rubber cream can improve the pain threshold of chemical stimulation, photo-thermal stimulation, pain that warm stimulation causes very significantly.The antiinflammatory test shows that this medicine has the antiinflammatory action of highly significant to 3 kinds of acute and chronic experimental inflammatory models, and has onset time fast, keeps the long characteristics of effective drug duration.Simultaneously rheology test shows that medicine also has certain function of promoting blood circulation to disperse blood clots, shows that medicine plays the effect of relaxing muscles and tendons to promote blood circulation, promoting blood circulation and stopping pain by blood circulation promoting and blood stasis dispelling, and this also is beneficial to the recovery of damaged tissues.Absorption of hematoma test is shown medicine can promote the absorption of self hematoma, accelerates repair of damaged tissues.Point out this medicine external also to have the treatment traumatic injury, eliminate the effect that congestion swells and ache.

Conclusion (of pressure testing):

This pharmaceutical composition rubber cream is the same with this medicament composition capsule, mainly promote damaged tissues absorption of hematoma, anti-inflammatory and antalgic and certain function of promoting blood circulation to disperse blood clots to treat the pain that various soft tissue injurys or chronic strain cause by it, the function of result of the test and this medicine also cures mainly and matches, and provides experimental basis for this medicine uses clinically.

Specific embodiment is as follows:

Embodiment 1:Rubber-emplastrum is prepared as follows

Get Semen Strychni 316g Eupolyphaga Seu Steleophaga 84g Radix Cyathulae 84g Herba Ephedrae 84g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 84g Bombyx Batryticatus (parched with bran) 84g parched with bran Rhizoma Atractylodis 84g Scorpio 84g Radix Glycyrrhizae 84g, wherein Semen Strychni is made the modulation Semen Strychni Pulveratum as follows: get Semen Strychni 316g, be ground into fine powder, measure strychnine content 1.7% according to method under the assay item of Pharmacopoeia of People's Republic of China Semen Strychni, add starch 177g then, make strychnine C ₂₁H ₂₂N ₂O ₂After content counted 1.09% by dry product, mixing promptly got and modulates the about 493g of Semen Strychni Pulveratum.

The modulation Semen Strychni Pulveratum adds 10% starch slurry 390g, makes granule, drying; Get above-mentioned granule, make solvent with 60% ethanol, carry out percolation, collect the liquid of filtering, reclaim ethanol, being evaporated to relative density is that 1.30～1.35 thick paste is standby at 80 ℃.All the other Eupolyphaga Seu Steleophagas etc. nine flavor, fragmentation, with 90% alcohol reflux 3 times, each 2 hours, merge extractive liquid,, filtration, it is 1.15～1.20 clear paste at 60 ℃ that filtrate is concentrated into relative density.Merge with above-mentioned thick paste, other adds the substrate of being made by rubber, Colophonium etc. of 3.0～3.4 times of weights, makes coating, is coated with cream, cutting, lid lining, section, makes 1000, packing, promptly.

Embodiment 2:Rubber-emplastrum is prepared as follows

Modulation Semen Strychni Pulveratum 480g Eupolyphaga Seu Steleophaga 84g Radix Cyathulae 84g Herba Ephedrae 84g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 84g Bombyx Batryticatus (parched with bran) 84g parched with bran Rhizoma Atractylodis 84g Scorpio 84g Radix Glycyrrhizae 84g, the modulation Semen Strychni Pulveratum adds 10% starch slurry 385g, make granule, drying; Get above-mentioned granule, make solvent with 60%7 alcohol, carry out percolation, collect the liquid of filtering, reclaim ethanol, being evaporated to relative density is that 1.30～1.35 thick paste is standby at 80 ℃.All the other Eupolyphaga Seu Steleophagas etc. nine flavor, fragmentation is extracted 3 times with 90%7 alcohol refluxs, and each 2 hours, merge extractive liquid,, filtration, it is 1.15～1.20 clear paste at 60 ℃ that filtrate is concentrated into relative density.Merge with above-mentioned thick paste, other adds the substrate of being made by rubber, Colophonium etc. of 3.0～3.4 times of weights, makes coating, is coated with cream, cutting, lid lining, section, makes 1000, packing, promptly.

Embodiment 3:The preparation of granule

Modulation Semen Strychni Pulveratum 460g Eupolyphaga Seu Steleophaga 84g Radix Cyathulae 143g Herba Ephedrae 86g Olibanum (processed with vinegar) 140g Myrrha (processed with vinegar) 82g Bombyx Batryticatus (parched with bran) 145g parched with bran Rhizoma Atractylodis 84g Scorpio 139g Radix Glycyrrhizae 84g, more than ten the flavor, the modulation Semen Strychni Pulveratum adds 10% starch slurry 385g, makes granule, drying; Get above-mentioned granule, make solvent with 60%7 alcohol, carry out percolation, collect the liquid of filtering, reclaim ethanol, being evaporated to relative density is that 1.30～1.35 thick paste is standby at 80 ℃.All the other Eupolyphaga Seu Steleophagas etc. nine flavor, fragmentation, with 90% alcohol reflux 3 times, each 2 hours, merge extractive liquid,, filtration, it is 1.15～1.20 clear paste at 60 ℃ that filtrate is concentrated into relative density.Merge with above-mentioned thick paste, add conventional adjuvant and make granule.

Embodiment 4:Capsular preparation

Modulation Semen Strychni Pulveratum 490g Eupolyphaga Seu Steleophaga 140g Radix Cyathulae 82g Herba Ephedrae 142g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 139g Bombyx Batryticatus (parched with bran) 86g parched with bran Rhizoma Atractylodis 144g Scorpio 82g Radix Glycyrrhizae 145g adds conventional adjuvant, makes encapsulated according to a conventional method.

Embodiment 5:The preparation of tablet

Modulation Semen Strychni Pulveratum 480g Eupolyphaga Seu Steleophaga 84g Radix Cyathulae 84g Herba Ephedrae 84g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 84g Bombyx Batryticatus (parched with bran) 84g parched with bran Rhizoma Atractylodis 84g Scorpio 84g Radix Glycyrrhizae 84g adds conventional adjuvant, makes tablet according to a conventional method.

Embodiment 6:The preparation of powder

Get Semen Strychni 316g Eupolyphaga Seu Steleophaga 84g Radix Cyathulae 84g Herba Ephedrae 84g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 84g Bombyx Batryticatus (parched with bran) 84g parched with bran Rhizoma Atractylodis 84g Scorpio 84g Radix Glycyrrhizae 84g, make powder, every bag of 3g.

Embodiment 7:The preparation of oral administration solution

Get Semen Strychni 250g Eupolyphaga Seu Steleophaga 140g Radix Cyathulae 82g Herba Ephedrae 142g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 139g Bombyx Batryticatus (parched with bran) 86g parched with bran Rhizoma Atractylodis 144g Scorpio 82g Radix Glycyrrhizae 145g, add adjuvants such as solvent, correctives, emulsifying agent, make oral administration solution, every bottle of 100ml.

Embodiment 8:The preparation of slow releasing tablet

Get Semen Strychni 316g Eupolyphaga Seu Steleophaga 84g Radix Cyathulae 84g Herba Ephedrae 84g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 84g Bombyx Batryticatus (parched with bran) 84g parched with bran Rhizoma Atractylodis 84g Scorpio 84g Radix Glycyrrhizae 84g, Semen Strychni is made synthetic Semen Strychni Pulveratum, add other crude drug and adjuvant, make slow releasing tablet according to a conventional method.

Embodiment 9:The preparation of controlled release capsule

Get Semen Strychni 316g Eupolyphaga Seu Steleophaga 84g Radix Cyathulae 84g Herba Ephedrae 84g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 84g Bombyx Batryticatus (parched with bran) 84g parched with bran Rhizoma Atractylodis 84g Scorpio 84g Radix Glycyrrhizae 84g, add adjuvant, make controlled release capsule according to a conventional method, every 0.3g.

Embodiment 10:The preparation of drop pill

Get Semen Strychni 316g Eupolyphaga Seu Steleophaga 84g Radix Cyathulae 84g Herba Ephedrae 84g Olibanum (processed with vinegar) 84g Myrrha (processed with vinegar) 84g Bombyx Batryticatus (parched with bran) 84g parched with bran Rhizoma Atractylodis 84g Scorpio 84g Radix Glycyrrhizae 84g, Semen Strychni is made synthetic Semen Strychni Pulveratum, add other crude drug and adjuvant, make drop pill according to a conventional method.

Embodiment 11:Discrimination method in the quality control

A. get 2 of this pharmaceutical composition rubber-emplastrums of embodiment 1, tear the lid lining off, shred, add sulfuric acid solution (3 → 100) 100ml, ultrasonic 15 minutes, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 2ml makes dissolving, as need testing solution.Get the strychnine reference substance, chlorination is copied into the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene-acetone-ethanol-strong ammonia solution (4: 5: 0.6: 0.4) be developing solvent, launch, take out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

B. get 2 of this pharmaceutical composition rubber-emplastrums of embodiment 1, tear the lid lining off, shred, add sulfuric acid solution (3 → 100) 100ml, ultrasonic 15 minutes, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 20ml, combined chloroform liquid adds methanol hydrochloride solution (1 → 10) 1ml, evaporate to dryness, add methanol 0.5ml and make dissolving, as need testing solution.Other gets the ephedrine hydrochloride reference substance and adds methanol and make the solution that every 1ml contains 0.2mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 5 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-strong ammonia solution (20: 4: 0.5) is developing solvent, launch, take out, dry, spray is with ninhydrin solution, and it is clear to dry by the fire to the speckle colour developing in 105 ℃.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

C. get 10 of this pharmaceutical composition rubber-emplastrums of embodiment 1, remove the lid lining, shred, put in the 500ml round-bottomed flask, add water 300ml, connect volatile oil extractor, add water to scale from the determinator top, and till overflow goes in the bottle, add normal hexane 1ml again, little boiling extracted 2 hours, put cold, divide and get normal hexane, as need testing solution.(water layer keep for Radix Cyathulae differentiate with) get Rhizoma Atractylodis control medicinal material 0.5g in addition, add normal hexane 2ml, supersound extraction 15 minutes, filtration, filtrate is medical material solution in contrast.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively on same silica gel g thin-layer plate, with petroleum ether (60～90 ℃)-ethyl acetate (10: 0.1) is developing solvent, launch, take out, dry, spray is heated to clear spot with 10% ethanol solution of sulfuric acid of 5% dimethylaminobenzaldehyde at 105 ℃.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on the dirty green speckle of same color is arranged.

D. get the water layer under [discriminating] C item, filter, filtrate is concentrated into about 80ml, filter, residue washes with water 2 times, each 10ml, merging filtrate adds diethyl ether and extracts 3 times, each 30ml, discard ether solution, aqueous solution extracts 4 times with the chloroform jolting, each 30ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution.Other gets Radix Cyathulae control medicinal material 1g, adds 90% ethanol 10ml, and reflux 2 hours filters, filtrate is concentrated into does not have the alcohol flavor, adds water 100ml, and reflux 1 hour filters, the filtrate extraction that adds diethyl ether is operated with need testing solution from " add diethyl ether and extract 3 times ", makes control medicinal material solution.According to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with benzene-chloroform-acetone (8: 4: 1) is developing solvent, launches, and takes out, dry, put under the uviol lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the sapphirine fluorescence speckle of same color.

E. get 3 of this pharmaceutical composition rubber-emplastrums of embodiment 1, remove the lid lining, shred, add 10% ethanol 50ml, add 1mol/L hydrochloric acid solution 10ml reflux 1 hour, filter, add concentrated hydrochloric acid in the filtrate and make its concentration be about 5%, reflux 2 hours filters, filtrate adds the chloroform jolting extracts 3 times, each 10ml, combined chloroform extracting solution, extract 3 times with 5% sodium carbonate liquor, each 10ml merges alkali liquor, with ether extraction 3 times, each 5ml discards ether solution, and transferring pH with hydrochloric acid is 1～2, extract 3 times with the chloroform jolting, each 10ml, combined chloroform liquid, evaporate to dryness, add dehydrated alcohol 1ml and make dissolving, as need testing solution.Extracting liquorice control medicinal material 0.2g shines medical material solution in pairs with legal system in addition.According to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 10 μ l of above-mentioned two kinds of solution, point sample is on same silica gel g thin-layer plate respectively, with petroleum ether (30～60 ℃)-toluene-ethyl acetate-glacial acetic acid (5: 15: 7: 0.5) be developing solvent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid of 5% vanillin, and 105 ℃ are heated to clear spot.In the sample chromatogram, with the corresponding position of control medicinal material chromatograph on, show the yellow spotting of same color.

Embodiment 12:Content assaying method in the quality control

Chromatographic condition and system suitability test are filler with eight alkyl silane bonded silica gels; With methanol-water-glacial acetic acid (100: 480: 35), regulate pH value to 3.1 with triethylamine, as mobile phase; The detection wavelength is 254nm.Number of theoretical plate calculates by the strychnine peak should be not less than 5000.

It is an amount of that the preparation precision of reference substance solution takes by weighing the strychnine reference substance, adds mobile phase and make the solution that every 1ml contains 2.5 μ g approximately, promptly.

1/4 of this pharmaceutical composition rubber cream of embodiment 1 is got in the preparation of need testing solution, shreds, and puts in the ground triangular flask, adds chloroform 20ml, strong aqua ammonia 1.0ml, close plug, supersound process 10 minutes.Extracting solution moves in the separatory funnel, and with 30ml chloroform gradation washing triangular flask, washing liquid is incorporated in the separatory funnel, with 0.5mol/L sulphuric acid solution extraction 5 times, each 10ml merges sulphuric acid liquid, add strong ammonia solution and regulate pH value to 9～10, use chloroform extraction 5 times, each 10ml, combined chloroform liquid, evaporate to dryness, residue add the mobile phase dissolving, be transferred in the 50ml measuring bottle, and be diluted to scale, and shake up, filter.Precision is measured subsequent filtrate 1ml and is put in the 10ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, promptly.

Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Every contains strychnine (C ₂₁H ₂₂N ₂O ₂) should be 3.5～6.5mg.

Embodiment 13:Method of quality control

A. get 2 of this pharmaceutical composition rubber-emplastrums of embodiment 2, tear the lid lining off, shred, add sulfuric acid solution (3 → 100) 100ml, ultrasonic 15 minutes, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 2ml makes dissolving, as need testing solution.Get the strychnine reference substance, chlorination is copied into the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene-acetone-ethanol-strong ammonia solution (4: 5: 0.6: 0.4) be developing solvent, launch, take out, dry, spray is with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

B. get 2 of this pharmaceutical composition rubber-emplastrums of embodiment 2, tear the lid lining off, shred, add sulfuric acid solution (3 → 100) 100ml, ultrasonic 15 minutes, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 20ml, combined chloroform liquid adds methanol hydrochloride solution (1 → 10) 1ml, evaporate to dryness, add methanol 0.5ml and make dissolving, as need testing solution.Other gets the ephedrine hydrochloride reference substance and adds methanol and make the solution that every 1ml contains 0.2mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 5 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-strong ammonia solution (20: 4: 0.5) is developing solvent, launch, take out, dry, spray is with ninhydrin solution, and it is clear to dry by the fire to the speckle colour developing in 105 ℃.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

C. get 10 of this pharmaceutical composition rubber-emplastrums of embodiment 2, remove the lid lining, shred, put in the 500ml round-bottomed flask, add water 300ml, connect volatile oil extractor, add water to scale from the determinator top, and till overflow goes in the bottle, add normal hexane 1ml again, little boiling extracted 2 hours, put cold, divide and get normal hexane, as need testing solution.(water layer keep for Radix Cyathulae differentiate with) get Rhizoma Atractylodis control medicinal material 0.5g in addition, add normal hexane 2ml, supersound extraction 15 minutes, filtration, filtrate is medical material solution in contrast.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively on same silica gel g thin-layer plate, with petroleum ether (60～90 ℃)-ethyl acetate (10: 0.1) is developing solvent, launch, take out, dry, spray is heated to clear spot with 10% ethanol solution of sulfuric acid of 5% dimethylaminobenzaldehyde at 105 ℃.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on the dirty green speckle of same color is arranged.

E. get 3 of this pharmaceutical composition rubber-emplastrums of embodiment 2, remove the lid lining, shred, add 10% ethanol 50ml, add 1mol/L hydrochloric acid solution 10ml reflux 1 hour, filter, add concentrated hydrochloric acid in the filtrate and make its concentration be about 5%, reflux 2 hours filters, filtrate adds the chloroform jolting extracts 3 times, each 10ml, combined chloroform extracting solution, extract 3 times with 5% sodium carbonate liquor, each 10ml merges alkali liquor, with ether extraction 3 times, each 5ml discards ether solution, and transferring pH with hydrochloric acid is 1～2, extract 3 times with the chloroform jolting, each 10ml, combined chloroform liquid, evaporate to dryness, add dehydrated alcohol 1ml and make dissolving, as need testing solution.Extracting liquorice control medicinal material 0.2g shines medical material solution in pairs with legal system in addition.According to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 10 μ l of above-mentioned two kinds of solution, point sample is on same silica gel g thin-layer plate respectively, with petroleum ether (30～60 ℃)-toluene-ethyl acetate-glacial acetic acid (5: 15: 7: 0.5) be developing solvent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid of 5% vanillin, and 105 ℃ are heated to clear spot.In the sample chromatogram, with the corresponding position of control medicinal material chromatograph on, show the yellow spotting of same color.

The drug combination preparation of getting embodiment 2 carries out assay.

1/4 of this pharmaceutical composition rubber cream is got in the preparation of need testing solution, shreds, and puts in the ground triangular flask, adds chloroform 20ml, strong aqua ammonia 1.0ml, close plug, supersound process 10 minutes.Extracting solution moves in the separatory funnel, and with 30ml chloroform gradation washing triangular flask, washing liquid is incorporated in the separatory funnel, with 0.5mol/L sulphuric acid solution extraction 5 times, each 10ml merges sulphuric acid liquid, add strong ammonia solution and regulate pH value to 9～10, use chloroform extraction 5 times, each 10ml, combined chloroform liquid, evaporate to dryness, residue add the mobile phase dissolving, be transferred in the 50ml measuring bottle, and be diluted to scale, and shake up, filter.Precision is measured subsequent filtrate 1ml and is put in the 10ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, promptly.

Every contains strychnine (C ₂₁H ₂₂N ₂O ₂) to should be 3.5～6.5mg.

Claims

1, a kind of pharmaceutical composition for the treatment of lumbago and skelalgia and rheumatic arthralgia is characterized in that the crude drug of this pharmaceutical composition is composed as follows:

Modulation Semen Strychni Pulveratum 450-500 weight portion Eupolyphaga Seu Steleophaga 80-150 weight portion Radix Cyathulae 80-150 weight portion Herba Ephedrae 80-150 weight portion Olibanum 80-150 weight portion Myrrha 80-150 weight portion Bombyx Batryticatus 80-150 weight portion Rhizoma Atractylodis 80-150 weight portion Scorpio 80-150 weight portion Radix Glycyrrhizae 80-150 weight portion;

Wherein modulating Semen Strychni Pulveratum is to be obtained by following method: whenever get Semen Strychni (processed) 100 weight portions, be ground into fine powder, behind the mensuration strychnine content, add starch 5-100 weight portion, make strychnine C ₂₁H ₂₂N ₂O ₂After content counts 1.09%～1.15% by dry product, mixing, promptly.

2, pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition is composed as follows:

Modulation Semen Strychni Pulveratum 460 weight portion Eupolyphaga Seu Steleophagas 84 weight portion Radix Cyathulaes 143 weight portion Herba Ephedraes 86 weight portion Olibanum (processed with vinegar) 140 weight portion Myrrha (processed with vinegar) 82 weight portion Bombyx Batryticatus (parched with bran) 145 weight portion parched with bran Rhizoma Atractylodis 84 weight portion Scorpios 139 weight portion Radix Glycyrrhizaes 84 weight portions;

3, pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition is composed as follows:

Modulation Semen Strychni Pulveratum 490 weight portion Eupolyphaga Seu Steleophagas 140 weight portion Radix Cyathulaes 82 weight portion Herba Ephedraes 142 weight portion Olibanum (processed with vinegar) 84 weight portion Myrrha (processed with vinegar) 139 weight portion Bombyx Batryticatus (parched with bran) 86 weight portion parched with bran Rhizoma Atractylodis 144 weight portion Scorpios 82 weight portion Radix Glycyrrhizaes 145 weight portions;

4, pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition is composed as follows:

Modulation Semen Strychni Pulveratum 480 weight portion Eupolyphaga Seu Steleophagas 84 weight portion Radix Cyathulaes 84 weight portion Herba Ephedraes 84 weight portion Olibanum (processed with vinegar) 84 weight portion Myrrha (processed with vinegar) 84 weight portion Bombyx Batryticatus (parched with bran) 84 weight portion parched with bran Rhizoma Atractylodis 84 weight portion Scorpios 84 weight portion Radix Glycyrrhizaes 84 weight portions;

5, as claim 1,2,3 or 4 described pharmaceutical compositions, it is characterized in that this pharmaceutical composition is made tablet, hard capsule, soft capsule, slow releasing tablet, controlled release tablet, slow releasing capsule, controlled release capsule oral solution, oral suspensions, Orally taken emulsion, mucilage, oral liquid, Emulsion, colloid solution, mixture, tincture, drop, suspendible drop, aerosol, spray, pill, drop pill, granule, enteric coated granule, powder, cataplasma or rubber-emplastrum.

6, as the arbitrary described preparation of drug combination method of claim 1-4, it is characterized in that this method is:

7, as the arbitrary described pharmaceutical composition of claim 1-4, it is characterized in that adding substrate when said composition is made rubber-emplastrum, substrate is made of by weight following composition:

Rubber 25-40 weight portion lanoline 4-8 weight portion white oil 2-5 weight portion vaseline 2-4 part by weight of zinc oxide 25-35 weight portion Foral 15-25 weight portion Mentholum 1.5-2.5 weight portion

Age resistor 2,6 ditertiary butyl p cresol 1-1.5 weight portion 120# gasoline 90-150 weight portion.

8, the preparation method of Chinese medicine composition as claimed in claim 7 is characterized in that this method is:

In the modulation Semen Strychni Pulveratum of per 100 weight portions, add 10% starch slurry, 80 weight portions, make granule, drying; Get above-mentioned granule, make solvent with 60% ethanol, carry out percolation, collect the liquid of filtering, reclaim ethanol, being evaporated to relative density is that 1.30～1.35 thick paste is standby at 80 ℃; All the other Eupolyphaga Seu Steleophagas nine flavor crude drug, fragmentation, with 90% alcohol reflux 3 times, each 2 hours, merge extractive liquid,, filtration, it is 1.15～1.20 clear paste under 60 ℃ that filtrate is concentrated into relative density; Clear paste and above-mentioned thick paste merge, and other adds the doubly heavy substrate of being made by rubber, Colophonium etc. of 3.0-3.4, makes coating, is coated with cream, cutting, lid lining, section, and packing is made.

9,, it is characterized in that this method comprises one or more in the following method as the method for quality control of the arbitrary described Chinese medicine composition of claim 1-4:

A, get 2 of this pharmaceutical composition rubber-emplastrums, tear the lid lining off, shred, add 3 → 100 sulfuric acid solution 100ml, ultrasonic 10-20 minute, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 15-25ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 2ml makes dissolving, as need testing solution; Get the strychnine reference substance, chlorination is copied into the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 3-5: 4-6: 0.5-0.7: 0.3-0.5 toluene-acetone-ethanol-strong ammonia solution is developing solvent, launches, and takes out, dry, spray is with rare bismuth potassium iodide test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

B, get 2 of this pharmaceutical composition rubber-emplastrums, tear the lid lining off, shred, add 3 → 100 sulfuric acid solution 100ml, ultrasonic 10-20 minute, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 15-25ml, combined chloroform liquid adds 1 → 10 methanol hydrochloride solution 1ml, evaporate to dryness, add methanol 0.5ml and make dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance and adds methanol and make the solution that every 1ml contains 0.2mg, in contrast product solution; According to the thin layer chromatography test, draw each 5 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with 15-25: 3-5: 0.3-0.6 chloroform-methanol-strong ammonia solution is developing solvent, launches, and takes out, dry, spray is with ninhydrin solution, and it is clear to dry by the fire to the speckle colour developing in 105 ℃; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

C, get 10 of this pharmaceutical composition rubber-emplastrums, remove the lid lining, shred, put in the 500ml round-bottomed flask, add water 300ml, connect volatile oil extractor, add water to scale from the determinator top, and till overflow goes in the bottle, add normal hexane 1ml again, little boiling extracted 1-3 hour, put cold, divide and get normal hexane, as need testing solution; Water layer keeps for Radix Cyathulae differentiates usefulness; Other gets Rhizoma Atractylodis control medicinal material 0.5g, adds normal hexane 2ml, and supersound extraction 10-20 minute, filter, filtrate is medical material solution in contrast; Test according to thin layer chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 60～90 ℃ of petroleum ether-ethyl acetate 8-12: 0.1 is developing solvent, launch, take out, dry, spray is heated to clear spot with the 5%-15% ethanol solution of sulfuric acid of 3%-7% dimethylaminobenzaldehyde at 100-110 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on the dirty green speckle of same color is arranged;

D, get and differentiate C item water layer down, filtration, filtrate is concentrated into about 80ml, filter, residue washes with water 2 times, each 5-15ml, merging filtrate adds diethyl ether and extracts 3 times, each 20-40ml, discard ether solution, aqueous solution extracts 4 times with the chloroform jolting, each 20-40ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Cyathulae control medicinal material 1g, add 90% ethanol 10ml, reflux 1-3 hour, filter, filtrate is concentrated into does not have the alcohol flavor, add water 100ml, reflux 0.5-1.5 hour, filter the filtrate extraction that adds diethyl ether, with the need testing solution operation, make control medicinal material solution from " add diethyl ether and extract 3 times "; According to thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 6-10: 2-6: 1 benzene-chloroform-acetone is developing solvent, launches, and takes out, and dries, and puts under the 365nm uviol lamp and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the sapphirine fluorescence speckle of same color;

E; get 3 of this pharmaceutical composition rubber-emplastrums removes lid lining, shreds; add 10% ethanol 40-60ml, adds 1mol/L hydrochloric acid solution 10ml reflux 0.5-1.5 hour, filters; add concentrated hydrochloric acid in the filtrate and make its concentration be about 5%, reflux 1-3 hour, filters; filtrate adds the chloroform jolting extracts 3 times, each 5-15ml, combined chloroform extracting solution; extract 3 times with 5% sodium carbonate liquor, and each 10ml merges alkali liquor; with ether extraction 3 times; each 3-8ml, discard ether solution, transferring pH with hydrochloric acid is 1～2; extract 3 times with the chloroform jolting; 5-15ml at every turn, combined chloroform liquid, evaporate to dryness; add dehydrated alcohol 1ml and make dissolving, as need testing solution; Extracting liquorice control medicinal material 0.2g shines medical material solution in pairs with legal system in addition; According to thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, point sample is on same silica gel g thin-layer plate respectively, with 3-7: 10-20: 4-10: 0.5,30～60 ℃ of petroleum ether-toluene-ethyl acetate-glacial acetic acid are developing solvent, launch, take out, dry, spray is with the 5-15% ethanol solution of sulfuric acid of 3-7% vanillin, and 105 ℃ are heated to clear spot; In the sample chromatogram, with the corresponding position of control medicinal material chromatograph on, show the yellow spotting of same color;

F, chromatographic condition and system suitability test are filler with eight alkyl silane bonded silica gels; With 80-120: 450-500: 20-50 methanol-water-glacial acetic acid, regulate pH value to 2.5-3.5, as mobile phase with triethylamine; The detection wavelength is 254nm; Number of theoretical plate calculates by the strychnine peak should be not less than 5000; It is an amount of that the preparation precision of reference substance solution takes by weighing the strychnine reference substance, adds mobile phase and make the solution that every 1ml contains 2-3 μ g approximately, promptly; 1/4 of this pharmaceutical composition rubber cream is got in the preparation of need testing solution, shreds, and puts in the ground triangular flask, adds chloroform 15-25ml, strong aqua ammonia 1.0ml, close plug, supersound process 5-15 minute; Extracting solution moves in the separatory funnel, and with 20-40ml chloroform gradation washing triangular flask, washing liquid is incorporated in the separatory funnel, with 0.5mol/L sulphuric acid solution extraction 5 times, each 5-15ml merges sulphuric acid liquid, add strong ammonia solution and regulate pH value to 9～10, use chloroform extraction 5 times, each 5-15ml, combined chloroform liquid, evaporate to dryness, residue add the mobile phase dissolving, be transferred in the 50ml measuring bottle, and be diluted to scale, and shake up, filter; Precision is measured subsequent filtrate 1ml and is put in the 10ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, promptly; According to high effective liquid chromatography for measuring, accurate respectively reference substance solution and each 15-25 μ l of need testing solution of drawing injects chromatograph of liquid, measures, promptly; Every contains strychnine C ₂₁H ₂₂N ₂O ₂Should be 3.5～6.5mg.

10, the method for quality control of Chinese medicine composition as claimed in claim 9 is characterized in that this method comprises one or more in the following method:

A, get 2 of this pharmaceutical composition rubber-emplastrums, tear the lid lining off, shred, add 3 → 100 sulfuric acid solution 100ml, ultrasonic 15 minutes, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 20ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 2ml makes dissolving, as need testing solution; Get the strychnine reference substance, chlorination is copied into the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 4: 5: 0.6: 0.4 toluene-acetone-ethanol-strong ammonia solution is developing solvent, launches, and takes out, and dries, spray is with rare bismuth potassium iodide test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

B, get 2 of this pharmaceutical composition rubber-emplastrums, tear the lid lining off, shred, add 3 → 100 sulfuric acid solution 100ml, ultrasonic 15 minutes, soaked overnight, filter, filtrate adds ammonia and transfers pH9～10, uses chloroform extraction 3 times, each 20ml, combined chloroform liquid adds 1 → 10 methanol hydrochloride solution 1ml, evaporate to dryness, add methanol 0.5ml and make dissolving, as need testing solution; Other gets the ephedrine hydrochloride reference substance and adds methanol and make the solution that every 1ml contains 0.2mg, in contrast product solution; According to the thin layer chromatography test, draw each 5 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with 20: 4: 0.5 chloroform-methanol-strong ammonia solutions was developing solvent, launched, and took out, dry, spray is with ninhydrin solution, and it is clear to dry by the fire to the speckle colour developing in 105 ℃; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

C, get 10 of this pharmaceutical composition rubber-emplastrums, remove the lid lining, shred, put in the 500ml round-bottomed flask, add water 300ml, connect volatile oil extractor, add water to scale from the determinator top, and till overflow goes in the bottle, add normal hexane 1ml again, little boiling extracted 2 hours, put cold, divide and get normal hexane, as need testing solution; Water layer keeps for Radix Cyathulae differentiates usefulness; Other gets Rhizoma Atractylodis control medicinal material 0.5g, adds normal hexane 2ml, and supersound extraction 15 minutes filters, and filtrate is medical material solution in contrast; Test according to thin layer chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 10: 0.1,60～90 ℃ of petroleum ether-ethyl acetates were developing solvent, launched, take out, dry, spray is heated to clear spot with 10% ethanol solution of sulfuric acid of 5% dimethylaminobenzaldehyde at 105 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on the dirty green speckle of same color is arranged;

D, get and differentiate C item water layer down, filtration, filtrate is concentrated into about 80ml, filter, residue washes with water 2 times, each 10ml, merging filtrate adds diethyl ether and extracts 3 times, each 30ml, discard ether solution, aqueous solution extracts 4 times with the chloroform jolting, each 30ml, combined chloroform liquid, evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Cyathulae control medicinal material 1g, adds 90% ethanol 10ml, and reflux 2 hours filters, filtrate is concentrated into does not have the alcohol flavor, adds water 100ml, and reflux 1 hour filters, the filtrate extraction that adds diethyl ether is operated with need testing solution from " add diethyl ether and extract 3 times ", makes control medicinal material solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with 8: 4: 1 benzene-chloroform-acetone, launch, take out, dry, put under the 365nm uviol lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the sapphirine fluorescence speckle of same color;

E; get 3 of this pharmaceutical composition rubber-emplastrums removes lid lining, shreds; add 10% ethanol 50ml, adds 1mol/L hydrochloric acid solution 10ml reflux 1 hour, filters; add concentrated hydrochloric acid in the filtrate and make its concentration be about 5%, and reflux 2 hours filters; filtrate adds the chloroform jolting extracts 3 times, each 10ml, combined chloroform extracting solution; extract 3 times with 5% sodium carbonate liquor, and each 10ml merges alkali liquor; with ether extraction 3 times; each 5ml, discard ether solution, transferring pH with hydrochloric acid is 1～2; extract 3 times with the chloroform jolting; 10ml at every turn, combined chloroform liquid, evaporate to dryness; add dehydrated alcohol 1ml and make dissolving, as need testing solution; Extracting liquorice control medicinal material 0.2g shines medical material solution in pairs with legal system in addition; According to thin layer chromatography, draw each 10 μ l of above-mentioned two kinds of solution, point sample is on same silica gel g thin-layer plate respectively, with 5: 15: 7: 0.5,30～60 ℃ of petroleum ether-toluene-ethyl acetate-glacial acetic acid were developing solvent, launched, take out, dry, spray is with 10% ethanol solution of sulfuric acid of 5% vanillin, and 105 ℃ are heated to clear spot; In the sample chromatogram, with the corresponding position of control medicinal material chromatograph on, show the yellow spotting of same color;

F, chromatographic condition and system suitability test are filler with eight alkyl silane bonded silica gels; With 100: 480: 35 methanol-water-glacial acetic acid, regulate pH value to 3.1 with triethylamine, as mobile phase; The detection wavelength is 254nm; Number of theoretical plate calculates by the strychnine peak should be not less than 5000; It is an amount of that the preparation precision of reference substance solution takes by weighing the strychnine reference substance, adds mobile phase and make the solution that every 1ml contains 2.5 μ g approximately, promptly; 1/4 of this pharmaceutical composition rubber cream is got in the preparation of need testing solution, shreds, and puts in the ground triangular flask, adds chloroform 20ml, strong aqua ammonia 1.0ml, close plug, supersound process 10 minutes; Extracting solution moves in the separatory funnel, and with 30ml chloroform gradation washing triangular flask, washing liquid is incorporated in the separatory funnel, with 0.5mol/L sulphuric acid solution extraction 5 times, each 10ml merges sulphuric acid liquid, add strong ammonia solution and regulate pH value to 9～10, use chloroform extraction 5 times, each 10ml, combined chloroform liquid, evaporate to dryness, residue add the mobile phase dissolving, be transferred in the 50ml measuring bottle, and be diluted to scale, and shake up, filter; Precision is measured subsequent filtrate 1ml and is put in the 10ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, promptly; According to high effective liquid chromatography for measuring, accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing inject chromatograph of liquid, measure, promptly; Every contains strychnine C ₂₁H ₂₂N ₂O ₂Be 4.6～5.8mg.

11, as the application of the arbitrary described pharmaceutical composition of claim 1-4 in the medicine of preparation treatment lumbago and skelalgia and rheumatic arthralgia.

12, the application of pharmaceutical composition as claimed in claim 5 in the medicine of preparation treatment lumbago and skelalgia and rheumatic arthralgia.