CN1850268A

CN1850268A - Semen caesalpiniae Chinese medicine preparation for treating cold, its preparing method and quality control method

Info

Publication number: CN1850268A
Application number: CN 200610200187
Authority: CN
Inventors: 余崇福
Original assignee: SHENGQUAN PHARMACY CO Ltd GUIZHOU
Current assignee: SHENGQUAN PHARMACY CO Ltd GUIZHOU
Priority date: 2006-03-01
Filing date: 2006-03-01
Publication date: 2006-10-25

Abstract

The present invention provides a caesalpinia sepiaria Chinese medicine preparation for curing common cold, its preparation method and quality control method. It is made up by using the Chinese medicinal materials of caesalpinia sepiaria, geum aleppicum, verbena officinalis and fresh ginger and adding proper auxiliary material through a certain preparation process.

Description

Semen Caesalpiniae Chinese medicine preparation and the preparation method and the method for quality control of treatment flu

Technical field: the present invention relates to a kind of Semen Caesalpiniae Chinese medicine preparation and preparation method and method of quality control for the treatment of flu, belong to the technical field of herbal pharmaceutical.

Background technology: flu is the upper respiratory tract infection that is caused by cold virus invasion and attack human body, and its clinical symptoms shows as heating, wake tears, sneeze, nasal obstruction, headache, cough, pharyngalgia, antiadoncus and whole body body discomfort; The Therapeutic Principle is that expectorant is driven in antibiotic (virus) antiinflammatory, antipyretic analgesic, antitussive.The Semen Caesalpiniae flu mixture clinical practice of the applicant's research and development for many years, obtain the approval and the welcome of extensive patients, has solid clinical basis, have no side effect, determined curative effect, and rise to national standard (no assay) by Guizhou Province's provincial standard in December, 2002, be decided to be the Class A medication of OTC flu by State Food and Drug Administration in 2003.But by it is carried out dosage form research, find that former dosage form mouthfeel is bad, quality control standard is simple, unstable product quality, and shortcomings such as inconvenience are carried in transportation.Though " Herba Verbenae of recording of Chinese pharmacopoeia version in 2005 includes assay, but measures at the TLCS of ursolic acid wherein.Confirm " Semen Caesalpiniae flu mixture " because technology is water boiling and extraction through years of researches, ursolic acid content only is 0.1/10000th in the preparation, the influence of medical material collecting season, time in addition, and content is extremely unstable.At these situations, we study the dosage form and the method for quality control of this product, under the constant situation of former prescription, are prepared into capsule, granule, syrup, drop pill, tablet, soft extract, will have better market prospect.

Summary of the invention:

The objective of the invention is to: a kind of Semen Caesalpiniae Chinese medicine preparation and preparation method and method of quality control for the treatment of flu is provided, bad to overcome original mixture mouthfeel, quality control standard is simple, places easily precipitation, quality instability, shortcomings such as inconvenience are carried in transportation, make preparation technology more become perfect; And in quality standard, increased assay, improved quality control standard.

The present invention constitutes like this: calculate according to composition by weight, it is with 200 parts in 200 parts of bark of Semen Caesalpiniae, 300 parts of Radix seu Herba Gei aleppici, 300 parts of Herba Verbenae and Rhizoma Zingiberis Recens, adds that suitable adjuvant is prepared from again.Described Chinese medicine preparation is capsule, granule, syrup, drop pill, tablet, soft extract.

The preparation method of the Semen Caesalpiniae Chinese medicine preparation of treatment flu is: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to the alcohol amount of containing, and mixing left standstill 24 hours, filter, and filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste, and add suitable adjuvant, and spray into Rhizoma Zingiberis Recens volatile oil, make different preparations according to a conventional method.

Capsule in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to the alcohol amount of containing, and mixing left standstill 24 hours, filters filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste, 80 ℃ of drying under reduced pressure are pulverized, and adding starch is an amount of, sprays into Rhizoma Zingiberis Recens volatile oil, mixing, airtight, fill, make capsule, promptly.

Granule in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filtered, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds an amount of dextrin, mixing, 80 ℃ of drying under reduced pressure are pulverized, and add protein sugar 20g, citric acid 10g and an amount of Icing Sugar and adjust total amount to 1000g, mixing is granulated 80 ℃ of drying under reduced pressure with 70% ethanol moistening, spray into Rhizoma Zingiberis Recens volatile oil and an amount of fruit essence, mixing, airtight, granulate, packing, promptly.

Syrup in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filter, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds Rhizoma Zingiberis Recens volatile oil and an amount of flavoring syrup, essence, making sugar content is 45%, is adjusted to ormal weight promptly.

Drop pill in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to the alcohol amount of containing, and mixing left standstill 24 hours, filters filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste; After getting an amount of PEG6000 or PEG6000 and the fusion of PEG4000 mixture, with above-mentioned thick paste mix homogeneously, cold slightly back adds Rhizoma Zingiberis Recens volatile oil, and mixing splashes in vegetable oil or the liquid paraffin coolant, promptly.

Tablet in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, mixing, left standstill 24 hours, filter, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds Rhizoma Zingiberis Recens volatile oil and appropriate amount of starch or modified starch, dextrin, granulates, add 0.3%～3% magnesium stearate or 1%～3% Pulvis Talci tabletting again, promptly.

Soft extract in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filtered, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds an amount of Mel, maltose, sucrose and essence, sweeting agent, receives cream, put cold back and add Rhizoma Zingiberis Recens volatile oil, mixing, promptly.

The method of quality control of the Semen Caesalpiniae Chinese medicine preparation of treatment flu: described method of quality control mainly comprise in character, discriminating, inspection, the assay project partly or entirely; Wherein discriminating is that the thin layer of bark of Semen Caesalpiniae, Rhizoma Zingiberis Recens is differentiated; Assay is the assay to verbenalin in the preparation.

The discrimination method of bark of Semen Caesalpiniae is to be contrast with the bark of Semen Caesalpiniae control medicinal material, and with 60～90 ℃ of petroleum ether: ethyl acetate: the upper solution of formic acid=10: 8: 2 is the thin layer discrimination method of developing solvent; The discrimination method of Rhizoma Zingiberis Recens is to be contrast with the Rhizoma Zingiberis Recens control medicinal material, and with benzene: ethyl acetate: the upper solution of formic acid=9: 0.5: 0.5 is the thin layer discrimination method of developing solvent.

Concrete discrimination method comprises the part or all of of following project:

(1) get this preparation or its content under the content uniformity item, add chloroform or ethanol supersound process 30 minutes, divide and get chloroform layer or filtration, chloroform layer or filtrate water bath method, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets bark of Semen Caesalpiniae control medicinal material 2g, adds dehydrated alcohol 50ml, and supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, in contrast medical material solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw need testing solution 10 μ l, control medicinal material solution 3 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate: the upper solution of formic acid=10: 8: 2 is developing solvent, launch, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with 10% sodium carbonate liquor; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence principal spot of same color;

(2) get this preparation or its content under the content uniformity item, the jolting that adds diethyl ether is extracted, and divides and gets ether solution, and low temperature volatilizes, and residue adds dehydrated alcohol 2ml makes dissolving, as need testing solution; Other gets Rhizoma Zingiberis Recens control medicinal material 3g, the 20～30ml that adds diethyl ether, and merceration 24 hours, filtrate low temperature volatilizes, and residue adds dehydrated alcohol 2ml makes dissolving, in contrast medical material solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the Carboxymethyl cellulose sodium, with benzene: ethyl acetate: the upper solution of formic acid=9: 0.5: 0.5 is developing solvent, launch, take out, dry, spray is with vanillin sulphuric acid test solution, and it is clear to be heated to the speckle colour developing at 105 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.

The content assaying method of verbenalin is to be contrast with the verbenalin reference substance, and with methanol: water=30: 70 is the high performance liquid chromatography of mobile phase.

Concrete content assaying method is:

According to an appendix VID of Chinese Pharmacopoeia version in 2005 high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with the carbon octadecylsilane chemically bonded silica; Methanol: water=30: 70 is mobile phase; The detection wavelength is 240nm, and theoretical cam curve should be not less than 4000 by the verbenalin peak;

It is an amount of that the preparation precision of reference substance solution takes by weighing the verbenalin reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 40ug, promptly;

This preparation or its content under the content uniformity item got in the preparation of need testing solution, and accurate the title decides, and puts in the tool plug conical flask, the accurate 50% ethanol 25ml that adds claims to decide weight, ultrasonic 20 minutes, put cold, claim again to decide weight, supply the weight that subtracts mistake, shake up with 50% ethanol, accurate again absorption 1ml puts in the 5ml volumetric flask,, shake up to scale with 50% ethanol dilution, promptly;

Accurate reference substance solution, each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;

Every of this capsule contains Herba Verbenae with verbenalin C ₁₇H ₂₄O ₁₀Meter must not be less than 2.2mg; This granule contains Herba Verbenae with verbenalin C for every bag ₁₇H ₂₄O ₁₀Meter must not be less than 4.6mg; This syrup contains Herba Verbenae with verbenalin C for every milliliter ₁₇H ₂₄O ₁₀Meter must not be less than 0.2mg; The every gram of this drop pill contains Herba Verbenae with verbenalin C ₁₇H ₂₄O ₁₀Meter must not be less than 3.0mg; Every in this tablet contains Herba Verbenae with verbenalin C ₁₇H ₂₄O ₁₀Meter must not be less than 2.0mg; The every gram of this soft extract contains Herba Verbenae with verbenalin C ₁₇H ₂₄O ₁₀Meter must not be less than 0.2mg.

Method of quality control of the present invention comprises:

Character:

For capsule: the product content thing is the brownish red powder, feeble QI band Jiang Xiang, bitter in the mouth, puckery;

For granule: product is a brown yellow granule, feeble QI band Jiang Xiang, bitter in the mouth, puckery;

For syrup: product is a brown liquid, feeble QI band Jiang Xiang, bitter in the mouth, puckery;

For drop pill: product is a brown ball, feeble QI band Jiang Xiang, bitter in the mouth, puckery;

For tablet: the plain sheet of product is brown, feeble QI band Jiang Xiang, bitter in the mouth, puckery;

For soft extract: product is brownish red or caramel glop, feeble QI band Jiang Xiang, bitter in the mouth, puckery;

Differentiate: (1) gets this preparation or its content under the content uniformity item, adds chloroform or ethanol supersound process 30 minutes, divides and gets chloroform layer or filtration, and chloroform layer or filtrate water bath method, residue add dehydrated alcohol 1ml makes dissolving, as need testing solution; Other gets bark of Semen Caesalpiniae control medicinal material 2g, adds dehydrated alcohol 50ml, and supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add dehydrated alcohol 1ml makes dissolving, in contrast medical material solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw need testing solution 10 μ l, control medicinal material solution 3 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate: the upper solution of formic acid=10: 8: 2 is developing solvent, launch, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with 10% sodium carbonate liquor; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence principal spot of same color;

(2) get this preparation or its content under the content uniformity item, the jolting that adds diethyl ether is extracted, and divides and gets ether solution, and low temperature volatilizes, and residue adds dehydrated alcohol 2ml makes dissolving, as need testing solution; Other gets Rhizoma Zingiberis Recens control medicinal material 3g, the 20～30ml that adds diethyl ether, and merceration 24 hours, filtrate low temperature volatilizes, and residue adds dehydrated alcohol 2ml makes dissolving, in contrast medical material solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the Carboxymethyl cellulose sodium, with benzene: ethyl acetate: the upper solution of formic acid=9: 0.5: 0.5 is developing solvent, launch, take out, dry, spray is with vanillin sulphuric acid test solution, and it is clear to be heated to the speckle colour developing at 105 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;

Check: should meet " relevant every regulation under each preparation item of appendix I of Chinese pharmacopoeia version in 2005;

Assay: shine an appendix VID of Chinese Pharmacopoeia version in 2005 high effective liquid chromatography for measuring:

Anemofrigid cold is the air-cooled air water viral disease disease that severe pathogenic cold causes, it is cold through it cold disease to press the dialectical ownership of Five Classics lease making, thus its rule of treatment should cold expelling table poison, move back gas.According to cold sick principle of medication with the medicine of a warm nature, use bark of Semen Caesalpiniae among the we, get that it is hot in nature, flavor fiber crops, peppery, move back the effect of gas cough-relieving at tool cold expelling table poison, can be except that cold headache, cough, watery nasal discharge, the disease of coldness of the body discomfort through causing; Be aided with Radix seu Herba Gei aleppici, get that it is hot in nature, flavor is peppery, gas is fragrant, kind cold expelling, complement, move back gas; Be aided with Herba Verbenae, get cold, the puckery of its property, go into cold effect through the tool antipyretic analgesic; Be aided with Rhizoma Zingiberis Recens, get that it is hot in nature, the flavor is peppery, go into coldly to remove severe pathogenic cold, move back the merit of gas cough-relieving, can help the power of principal agent cold expelling, pain relieving, cough-relieving, the coordinating the actions of various ingredients in a prescription effect of holding concurrently again through tool.All medicines share, and are total to the tool cold expelling, show effect malicious, that move back the gas cough-relieving, reach the disease of controlling headache due to invasion of exogenous pathogens, heating, cough, nasal obstruction, watery nasal discharge, coldness of the body discomfort.

The applicant has carried out a series of experimentation, with the preparation technology and the method for quality control science, reasonable, feasible of assurance preparation of the present invention, thereby makes said preparation have good curative effect.

One, Study on Preparation

(1) dosage form selection

The Semen Caesalpiniae flu mixture of the applicant's research and development is used for many years clinically, and prescription is rigorous, and compatibility is reasonable, take in national nonprescription drugs medicine catalogue (the 5th batch of Chinese patent medicine), obtained the approval and the welcome of extensive patients, had solid clinical basis, no obvious toxic-side effects, determined curative effect.But by it is carried out dosage form and quality standard research, find that former dosage form exists quality control standard simple, unstable product quality, shortcomings such as inconvenience are carried in transportation.At these situations, we study the dosage form and the method for quality control of this product, under the constant situation of former prescription, are prepared into granule and capsule etc.Guaranteeing that the granule dose only is 5g under the constant situation of each crude drug content, the capsule dose only is two, simultaneously, overcome mixture and placed easily precipitation, and shortcomings such as quality instability, the storage convenient transportation, it is perfect that preparation technology more becomes.And in quality standard, increased the assay of verbenalin in the Herba Verbenae, improved quality control standard, will have better market prospect.

(2) process conditions determines

1 extracts determining of subtractive process total solid matters yield

1.1 the verbenalin assay is measured according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000).

Chromatographic condition and system suitability test are filler with the carbon octadecylsilane chemically bonded silica; Methanol-water (30: 70) is a mobile phase; The detection wavelength is 240nm, and theoretical cam curve should be not less than 4000 by the verbenalin peak.

It is an amount of that the preparation precision of reference substance solution takes by weighing the verbenalin reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 40ug, promptly.

The preparation extracting sample solution of need testing solution is an amount of, puts in the tool plug conical flask to concentrate near doing, and the accurate 50% ethanol 25ml that adds claims decide weight, and ultrasonic 20 minutes, put coldly, weight decided in title again, supplies the weight that subtracts mistake with 50% ethanol, shakes up, promptly.

Accurate reference substance solution, each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

1.2 total solid matters yield (receiving the cream rate) is measured the accurate thick paste 50ml through standardize solution that makes according to method for making that draws, and puts in the evaporating dish that is dried to constant weight, volatilizes, in 105 ℃ of dryings 3 hours, move in the exsiccator, cooled off 30 minutes, weight decided in accurate rapidly title, calculates, and promptly gets the cream rate of receiving.

1.3 extraction process by water research

Extraction process by water: take by weighing the recipe quantity medical material, Rhizoma Zingiberis Recens extracts volatile oil, distillation rear solution device is in addition collected, and three flavors such as medicinal residues and all the other bark of Semen Caesalpiniae decoct with water three times, add 10 times of amounts of water for the first time, decocted 2 hours, second and third time adds 8 times of amounts of water, decocts 1.5 hours, filters, filtrate and above-mentioned aqueous solution merge, is being concentrated into relative density 1.18～1.22 (50?) clear paste.Result of the test shows that verbenalin mean transferred rate is 63.71%, and average yield of extract is 12.47%, RSD=2.8%.

1.4 alcohol precipitation process research

Alcohol precipitation process: water intaking decocting liquid 1/2, adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filtered, and filtrate recycling ethanol also is concentrated into certain volume.Result of the test shows that verbenalin mean transferred rate is 62.53%, and average yield of extract is 5.16%, RSD=4.07%.

2 concentrate preferred with drying process

2.1 wet grain drying is to the influence of granule

Because former dosage form is oral liquid, do not need concentrate drying, being prepared into granule, then to need to carry out the concentrate drying rear plastic.Therefore, comparative study has been carried out in the variation of verbenalin before and after the concentrate drying.

Get prescription proportional quantities medical material, extract by the technology of working out, clear paste is divided into 4 parts, 1 part of content that is used to measure verbenalin, 3 parts of concentrating under reduced pressure in addition, 80 ℃ of vacuum dryings, dry extract.The content of sampling and measuring verbenalin calculates the rate of transform.

Result of the test shows that behind the concentrate drying, verbenalin mean transferred rate is 61.09%, and average loss rate is 1.64%, illustrates that concentrate drying technology do not have obvious influence to the granule quality.

2.2 the condition of concentrating is to the influence of capsule

Because former dosage form is oral liquid, do not need concentrate drying, being prepared into capsule, then to need to carry out the concentrate drying rear plastic.Therefore, comparative study has been carried out in the variation of verbenalin before and after the concentrate drying.

Get 2 times of prescription proportional quantities medical materials, extract by the technology of working out, precipitate with ethanol, filtrate is divided into 4 parts, and 1 part of content that is used to measure verbenalin, 3 parts 70 ℃ in addition, 0.08MPa are evaporated to relative density 1.28, and the content of sampling and measuring verbenalin calculates the rate of transform.

Result of the test shows, before and after the concentrate drying, verbenalin mean transferred rate is 62.04%, and average loss rate is 1.63%, illustrates that concentrate drying technology do not have obvious influence to the capsule quality.

2.3 the comparison of different drying conditions

Merge above concentrated solution, be divided into 4 parts, sampling and measuring verbenalin content.

Result of the test shows that the constant pressure and dry time is long, the outward appearance color depth, and the verbenalin rate of transform is lower than vacuum drying.The vacuum drying time is short, verbenalin rate of transform height, and the sample quality is loose, is easy to pulverize.Under the vacuum condition, 60 ℃ and 80 ℃ of dryings are to verbenalin rate of transform no significant difference, thus can be under 60～80 ℃ of conditions vacuum drying.

3 extractum yields and technology stability are investigated

Get 1,2,3 times of recipe quantity medical material respectively, extract, concentrate by preferred technology, precipitate with ethanol, drying is investigated paste-forming rate and stability.Result of the test shows that average yield of extract is 5.19%, RSD=0.68%, and process stabilizing, feasible.

(3) Study on Forming

Granule: by the clear paste that preparation technology extracts, add an amount of dextrin and receive cream, easily dry, the hygroscopicity of dry back dry extract is obviously improved.Granule need add an amount of sucrose, protein sugar, citric acid and make correctives, through experiment sieving with add sucrose 615g, 2% protein sugar is advisable.Adopt the different concentration ethanol wet granulation, the concentration of alcohol the when result granulates is lower than at 70% o'clock, is difficult to granulate, and granule easily lumps after the molding, and it is bad to be higher than 70% o'clock grain forming, and granularity is defective.So select 70% ethanol moistening to granulate, 80 ℃ of vacuum dryings, promptly.

Capsule: the dry extract easy moisture absorption when relative humidity is big by preparation technology extracts, be unfavorable for industrial operation, add appropriate amount of starch and receive cream, the hygroscopicity of dry back dry extract is obviously improved.Behind 80 ℃ of vacuum dryings, pulverize, add starch to 300g promptly.

Syrup: the clear paste that is extracted by preparation technology need add an amount of syrup and essence seasoning, makes its mouthfeel good, is beneficial to and takes.Therefore add an amount of flavoring syrup, essence, making sugar content is 45%, is adjusted to ormal weight promptly.

Drop pill: the clear paste that is extracted by preparation technology must drip in certain substrate makes ball, adopts different materials to compare test as substrate, and the effect that the result makes substrate with the mixture of PEG6000 or PEG6000 and PEG4000 is better.After getting an amount of PEG6000 or PEG6000 and the fusion of PEG4000 mixture, with extraction gained clear paste mix homogeneously, cold slightly back adds Rhizoma Zingiberis Recens volatile oil, and mixing splashes in vegetable oil or the liquid paraffin coolant, promptly.

Tablet: the extractum easy moisture absorption when relative humidity is big by preparation technology extracts, add appropriate amount of starch and dextrin and receive cream, dry back hygroscopicity is obviously improved.Tablet need add an amount of excipient and filler in addition.So add appropriate amount of starch or modified starch, dextrin, granulate, add 0.3%～3% magnesium stearate or 1%～3% Pulvis Talci tabletting again, promptly.

Soft extract: the extractum that is extracted by preparation technology need add an amount of correctives and sweeting agent, to adjust mouthfeel.Select for use an amount of Mel, maltose, sucrose and essence, sweeting agent to receive cream after deliberation, put cold back and add Rhizoma Zingiberis Recens volatile oil, mixing, promptly.

Two, pilot scale

Produce three batches (10 times of recipe quantities) by the preparation technology who works out, every index in the production technology is detected, and with further examination this product preparation technology's reasonability, result of the test shows, preparation were established is reasonable, and the explained hereafter condition meets the plant produced requirement.

Three, method of quality control research

1 discriminating Semen Caesalpiniae cold-treating preparation is made up of bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae, Rhizoma Zingiberis Recens 4 flavor medicines, the medical material of respectively distinguishing the flavor of among applicant the other side has carried out the thin layer chromatography Study on Identification, Radix seu Herba Gei aleppici negative control product have interference as a result, differentiate so the discriminating of quality standard of the present invention is the thin layer discriminating of bark of Semen Caesalpiniae and the thin layer of Rhizoma Zingiberis Recens.

1.1 instrument and reagent REPROSTAR3 thin layer chromatography imaging system (Switzerland GAMAG); Bark of Semen Caesalpiniae control medicinal material (lot number: 1379-200401), Radix seu Herba Gei aleppici control medicinal material (lot number: 1380-200401).Above control medicinal material is all purchased to Chinese pharmaceutical biological product and is identified institute; Ether, chloroform, ethyl acetate, benzene, methanol, ethanol, formic acid, petroleum ether etc. are analytical pure; Silica gel G precoated plate (Haiyang Chemical Plant, Qingdao); Silica gel g thin-layer plate (self-control).

1.2 differentiate

(1) gets this preparation or its content under the content uniformity item, add chloroform or ethanol supersound process 30 minutes, divide and get chloroform layer or filtration, chloroform layer or filtrate water bath method.All the other are with the proper mass standard.

(2) get this preparation or its content under the content uniformity item, the jolting that adds diethyl ether is extracted, and divides and gets ether solution, and low temperature volatilizes, and residue adds dehydrated alcohol 2ml makes dissolving, as need testing solution.Other gets Rhizoma Zingiberis Recens control medicinal material 3g, the 20～30ml that adds diethyl ether, and merceration 24 hours, filtrate low temperature volatilizes, and residue adds dehydrated alcohol 2ml makes dissolving, in contrast medical material solution.All the other are with the proper mass standard.

(3) thin layer chromatography of Radix seu Herba Gei aleppici medical material is differentiated:

The preparation of need testing solution: get Semen Caesalpiniae cold-treating preparation or its content, add chloroform or ethanol 25ml supersound process 30 minutes, divide and get chloroform layer or filtration, evaporate to dryness in chloroform layer or the filtrate water-bath, residue add methanol makes dissolving for 1 milliliter, as need testing solution.

The preparation of control medicinal material solution: get bark of Semen Caesalpiniae control medicinal material 1g, shine medical material solution in pairs with legal system.

The preparation of negative control solution: remove negative preparation 3 grams, make negative control solution with method except that bark of Semen Caesalpiniae.

The thin layer chromatography condition: the silica gel G plate, developing solvent: chloroform-methanol solution (2: 3), launch, take out, to dry, spray is with 5% vanillin solution, and it is clear to be heated to the speckle colour developing in 105 ℃.Multiple ratio with n-butyl alcohol-ethyl acetate-methanol (4: 1: 0.5) development system is launched, take out, dry, respectively at inspecting under daylight and the 365nm uviol lamp, relatively through repetition test, with chloroform-methanol solution (2: 3) is that developing solvent expansion effect is better, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, the speckle of displaing amaranth, negative control has interference, so quality standard of the present invention is not listed in this discriminating in.

2 check according to " regulation under each preparation item of appendix I of Chinese pharmacopoeia version in 2005 is checked granularity, moisture, melting, content uniformity, disintegration, microbial limit, heavy metal, arsenic salt etc. respectively.

Every check result shows that this product meets the " pertinent regulations under each preparation item of appendix I of Chinese pharmacopoeia version in 2005.

3 assays are according to the chemical composition analysis of the medical material of respectively distinguishing the flavor of among the other side, we in test among the other side the content of the contained verbenalin of Herba Verbenae measure, and assay method is studied.

3.1 Tianjin, instrument island LC-2010CHT high performance liquid chromatograph; The LCsolution chromatographic work station; Ultrasonic washing unit (250W, 29～34kHz; Beijing ultrasonic device factory).

3.2 reagent methanol (chromatographically pure); Ethanol (analytical pure); Water is redistilled water; (U.S. sigma company provides the verbenalin reference substance, content＞99.0%, lot number (Lot): 1077090).

3.3 chromatographic condition chromatographic column: enlightening horse C18 post (250 * 4.6mm, 5um); Mobile phase: methanol-water (30: 70); The detection wavelength is 240nm; Flow velocity: 1.0ml/min; Column temperature: room temperature.

3.4 the system suitability test is got verbenalin reference substance solution, need testing solution respectively and is lacked the negative control solution of Herba Verbenae medical material, blank solvent injection chromatograph of liquid, record chromatogram.As seen from the figure, the retention time of verbenalin is about 11.0 minutes, and promptly verbenalin separates with other components fully under this experimental condition.Theoretical cam curve is calculated as 4000 with the verbenalin peak, verbenalin with and the separating degree of other component peaks greater than 1.5, and consider different chromatographic column ruggedness, so the theorem opinion number of plates should be not less than 4000 in the verbenalin peak.

3.5 linear relationship is investigated

The preparation precision of reference substance storing solution takes by weighing verbenalin reference substance 10.48mg, puts in the 25ml volumetric flask, adds dissolve with methanol and is diluted to scale, shakes up, promptly.

The drafting of standard curve is accurate draws above-mentioned reference substance storing solution 1ml in the 5ml volumetric flask, add methanol and be diluted to scale, shake up, promptly get the reference substance solution that concentration is 83.84 μ g/ml, accurate respectively 1,2,4,6,8,10, the 12 μ l that draw inject chromatograph of liquid, the record chromatograph, with the peak area is that abscissa, sample size are vertical coordinate, gets equation of linear regression: Y=6.90717 * 10 ^-7X+5.20785 * 10 ^-4(r=0.999993), because 5.20785 * 10 ^-4/ 6.90717 * 10 ^-7* 118721=0.64%＜1.0%, visual thus intercept are approximately zero, so can adopt one point external standard method to calculate content.The range of linearity: 0.08384 μ g～1.00608 μ g.

3.6 the preparation of need testing solution

3.6.1 it is the free cpds that extracts because of the contained verbenalin of Herba Verbenae medical material in this product that the test sample verbenalin extracts choice of Solvent, this chemical compound gets final product with the supersound process dissolving.In test, to this product carry out that Different Extraction Method, different solvents are extracted, different extraction times preferred, the result is a solvent with 50% ethanol, the method that water-bath refluxed 1 hour be the best.

3.6.2 it is solvent that the supersound process time is investigated with 50% ethanol, adopts the supersound process different time, the preparation test sample.

The result shows: extract 20 and 40 minutes basically identical as a result, so adopted supersound process 20 minutes.

3.6.3 this product or its content under the content uniformity item are got in the preparation of need testing solution, porphyrize, and accurate the title, decide, and puts in the tool plug conical flask, the accurate 50% ethanol 25ml that adds claims to decide weight, ultrasonic 20 minutes, puts cold, claim again to decide weight, supply the weight that subtracts mistake, shake up, promptly with 50% ethanol.

3.6.4 the negative control product that lack the Herba Verbenae medical material are got in the preparation of negative controls, prepare negative control product solution by the preparation method of need testing solution.

3.7 precision test

Getting concentration is the 83.84ug/ml reference substance, repeats sample introduction 5 times, measures peak area, RSD=0.20%.

3.8 replica test is got a test sample (20040819), preparation method by need testing solution in the quality standard of the present invention, prepare each 3 parts of 3 variable concentrations need testing solutions, injecting chromatograph 10 μ l measure peak area respectively, calculate, average content 2.5620mg/g, RSD=0.52%, result show that repeatability is good.

3.9 stability test is got a test sample (20040819), prepares need testing solution by the preparation method of need testing solution in the quality standard of the present invention, time sample introduction is in accordance with regulations measured, and the result shows that verbenalin is stable in 8 hours in the preparation need testing solution.

3.10 the recovery test precision takes by weighing (20040819) 9 parts of test samples measuring content, by 3 variable concentrations, the accurate verbenalin reference substance that adds is an amount of, prepare need testing solution by quality standard of the present invention, sample introduction 10ul measures peak area respectively, calculates, the result shows that the response rate of verbenalin is good.

3.11 sample determination prepares need testing solution and reference substance solution by quality standard of the present invention, sample introduction writes down chromatograph respectively, measures peak area, is calculated as follows content:

C _Right: reference substance concentration

V _Right: the reference substance sampling volume

V _Sample: the test sample sampling volume

A _Sample: the test sample peak area

A _Right: the reference substance peak area

Ten batches of formulation content determination datas

Lot number	Sampling amount (g)		Peak area		Verbenalin content (mg/g)		Average content (mg/g)	Grand mean (mg/g)
Lot number	Sampling amount (g)		Peak area		Verbenalin content (mg/g)		Average content (mg/g)	Grand mean (mg/g)		1	2	1	2	1	2	1.1913
20040819	0.4025	0.4035	333176	331980	1.4607	1.4519	1.4563			1	2	1	2	1	2
20040819	0.4025	0.4035	333176	331980	1.4607	1.4519	1.4563	20040820	0.4018	0.4027	332172	332567	1.4588	1.4573	1.4581
20040822	0.4019	0.4041	232958	224289	1.0229	0.9794	1.0011	20040820	0.4018	0.4027	332172	332567	1.4588	1.4573	1.4581
20040822	0.4019	0.4041	232958	224289	1.0229	0.9794	1.0011	20040826	0.4038	0.4029	231566	236373	1.0120	1.0353	1.0236
20040831	0.4025	0.4022	254290	267432	1.1149	1.1733	1.1441	20040826	0.4038	0.4029	231566	236373	1.0120	1.0353	1.0236
20040831	0.4025	0.4022	254290	267432	1.1149	1.1733	1.1441	20040903	0.4019	0.4037	320468	330864	1.4071	1.4463	1.4267
20040905	0.4038	0.4022	338925	336611	1.4811	1.4769	1.4790	20040903	0.4019	0.4037	320468	330864	1.4071	1.4463	1.4267
20040905	0.4038	0.4022	338925	336611	1.4811	1.4769	1.4790	20040908	0.4021	0.4031	208872	207942	0.9166	0.9103	0.9135
20040910	0.4036	0.4046	227236	234282	0.9935	1.0218	1.0077	20040908	0.4021	0.4031	208872	207942	0.9166	0.9103	0.9135
20040910	0.4036	0.4046	227236	234282	0.9935	1.0218	1.0077	20040915	0.4023	0.4028	228003	229415	1.0001	1.0050	1.0026

3.12 sample verbenalin content limit is from 10 crowdes of Semen Caesalpiniae cold-treating preparation pilot scale sample determination results as seen, in each lot number sample the verbenalin extraction ratio all more than 50%, so in the preparation verbenalin extraction ratio by being not less than 50%.The verbenalin content limit is calculated as follows in every bag of granule: verbenalin content limit=preparation contains Herba Verbenae medical material (g) * Herba Verbenae medical material and contains verbenalin limit * extraction ratio * 5g/ preparation amount (g)=600g * 0.30% * 50% * 5 * 1000/1000g=4.5mg/ bag, so tentative this granule contains Herba Verbenae with verbenalin (C for every bag ₁₇H ₂₄O ₁₀) meter, must not be less than 4.6mg.The verbenalin content limit is calculated as follows in every seed lac wafer: verbenalin content limit=preparation contains Herba Verbenae medical material (g) * Herba Verbenae medical material and contains verbenalin limit * extraction ratio * 0.3 (g)/preparation amount (g)=1500g * 0.30% * 50% * 0.3 * 1000/300g=2.25mg/ grain, so tentative every of this capsule contains Herba Verbenae with verbenalin (C ₁₇H ₂₄O ₁₀) meter, must not be less than 2.2mg.Same calculating can get: this syrup contains Herba Verbenae with verbenalin C for every milliliter ₁₇H ₂₄O ₁₀Meter must not be less than 0.2mg.The every gram of this drop pill contains Herba Verbenae with verbenalin C ₁₇H ₂₄O ₁₀Meter must not be less than 3.0mg.Every in this tablet contains Herba Verbenae with verbenalin C ₁₇H ₂₄O ₁₀Meter must not be less than 2.0mg.The every gram of this soft extract contains Herba Verbenae with verbenalin C ₁₇H ₂₄O ₁₀Meter must not be less than 0.2mg.

Compared with prior art, preparation of the present invention can be covered the bitterness when oral, and overcome former mixture and placed easily precipitation, shortcomings such as quality instability, it is perfect that preparation technology more becomes, and the storage convenient transportation has enriched the dosage form kind; And the thin layer chromatography that has increased assay and medical material in quality standard is differentiated, has improved quality control standard, thereby has guaranteed the clinical efficacy of said preparation.

The specific embodiment:

Embodiments of the invention 1: bark of Semen Caesalpiniae 1000g, Radix seu Herba Gei aleppici 1500g, Herba Verbenae 1500g, Rhizoma Zingiberis Recens 1000g

Get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filter filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste, 80 ℃ of drying under reduced pressure, pulverize, it is an amount of to add starch, sprays into Rhizoma Zingiberis Recens volatile oil, mixing, airtight, fill, make 1000 of capsules, promptly get capsule.This product oral: 1～2 of child one time, 3 times on the one; Be grown up one time 2～4,3 times on the one.

Embodiments of the invention 2: bark of Semen Caesalpiniae 400g, Radix seu Herba Gei aleppici 600g, Herba Verbenae 600g, Rhizoma Zingiberis Recens 400g

Get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filtered, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds an amount of dextrin, mixing, 80 ℃ of drying under reduced pressure are pulverized, and add protein sugar 20g, citric acid 10g and an amount of Icing Sugar and adjust total amount to 1000g, mixing is granulated 80 ℃ of drying under reduced pressure with 70% ethanol moistening, spray into Rhizoma Zingiberis Recens volatile oil and an amount of fruit essence, mixing, airtight, granulate is sub-packed in the aluminum foil bag, promptly gets granule.This product oral: one time 0.5～1 bag of child, 3 times on the one; One time 1～2 bag of being grown up, 3 times on the one.

Embodiments of the invention 3: bark of Semen Caesalpiniae 200g, Radix seu Herba Gei aleppici 300g, Herba Verbenae 300g, Rhizoma Zingiberis Recens 200g

Get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filter, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds Rhizoma Zingiberis Recens volatile oil and an amount of flavoring syrup, essence, making sugar content is 45%, is adjusted to ormal weight and promptly gets syrup.

Embodiments of the invention 4: bark of Semen Caesalpiniae 600g, Radix seu Herba Gei aleppici 900g, Herba Verbenae 900g, Rhizoma Zingiberis Recens 600g

Get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to the alcohol amount of containing, and mixing left standstill 24 hours, filters filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste; After getting an amount of PEG6000 or PEG6000 and the fusion of PEG4000 mixture, with above-mentioned thick paste mix homogeneously, cold slightly back adds Rhizoma Zingiberis Recens volatile oil, and mixing splashes in vegetable oil or the liquid paraffin coolant, promptly gets drop pill.

Embodiments of the invention 5: bark of Semen Caesalpiniae 800g, Radix seu Herba Gei aleppici 1200g, Herba Verbenae 1200g, Rhizoma Zingiberis Recens 800g

Get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, mixing, left standstill 24 hours, filter, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds Rhizoma Zingiberis Recens volatile oil and appropriate amount of starch or modified starch, dextrin, granulates, add 0.3%～3% magnesium stearate or 1%～3% Pulvis Talci tabletting again, promptly get tablet.

Embodiments of the invention 6: bark of Semen Caesalpiniae 400g, Radix seu Herba Gei aleppici 600g, Herba Verbenae 600g, Rhizoma Zingiberis Recens 400g

Get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, for the first time add 10 times of amounts of water, decocted 2 hours, second and third time adds 8 times of amounts of water, decocted 1.5 hours, filter, filtrate and the merging of above-mentioned aqueous solution are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filtered, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds an amount of Mel, maltose, sucrose and essence, sweeting agent, receives cream, put cold back and add Rhizoma Zingiberis Recens volatile oil, mixing promptly gets soft extract.

Embodiments of the invention 7: described method of quality control comprises following content:

Character:

Embodiments of the invention 8: method of quality control can comprise following content:

Character:

Check: should meet " relevant every regulation under each preparation item of appendix I of Chinese pharmacopoeia version in 2005.

Embodiments of the invention 9: method of quality control can comprise following content:

Character:

Differentiate: get this preparation or its content under the content uniformity item, the jolting that adds diethyl ether is extracted, and divides and gets ether solution, and low temperature volatilizes, and residue adds dehydrated alcohol 2ml makes dissolving, as need testing solution; Other gets Rhizoma Zingiberis Recens control medicinal material 3g, the 20～30ml that adds diethyl ether, and merceration 24 hours, filtrate low temperature volatilizes, and residue adds dehydrated alcohol 2ml makes dissolving, in contrast medical material solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw each 15 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the Carboxymethyl cellulose sodium, with benzene: ethyl acetate: the upper solution of formic acid=9: 0.5: 0.5 is developing solvent, launch, take out, dry, spray is with vanillin sulphuric acid test solution, and it is clear to be heated to the speckle colour developing at 105 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;

Embodiments of the invention 10: method of quality control can comprise following content:

Character:

Claims

1. Semen Caesalpiniae Chinese medicine preparation for the treatment of flu is characterized in that: calculate according to composition by weight, it is with 200 parts in 200 parts of bark of Semen Caesalpiniae, 300 parts of Radix seu Herba Gei aleppici, 300 parts of Herba Verbenae and Rhizoma Zingiberis Recens, adds that suitable adjuvant is prepared from again.

2. according to the Semen Caesalpiniae Chinese medicine preparation of the described treatment flu of claim 1, it is characterized in that: described Chinese medicine preparation is capsule, granule, syrup, drop pill, tablet, soft extract.

3. treat the preparation method of the Semen Caesalpiniae Chinese medicine preparation of flu as claimed in claim 1 or 2, it is characterized in that: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, and medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, add 10 times of amounts of water for the first time, decocted 2 hours, second and third time adds 8 times of amounts of water, decocts 1.5 hours, filters, filtrate and above-mentioned aqueous solution merge, and are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to the alcohol amount of containing, and mixing left standstill 24 hours, filter, and filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste, and add suitable adjuvant, and spray into Rhizoma Zingiberis Recens volatile oil, make different preparations according to a conventional method.

4. according to the preparation method of the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 3 flu, it is characterized in that: the capsule in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, and medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, add 10 times of amounts of water for the first time, decocted 2 hours, second and third time adds 8 times of amounts of water, decocts 1.5 hours, filters, filtrate and above-mentioned aqueous solution merge, and are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to the alcohol amount of containing, and mixing left standstill 24 hours, filters filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste, 80 ℃ of drying under reduced pressure are pulverized, and adding starch is an amount of, sprays into Rhizoma Zingiberis Recens volatile oil, mixing, airtight, fill, make capsule, promptly.

5. according to the preparation method of the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 3 flu, it is characterized in that: the granule in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, and medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, add 10 times of amounts of water for the first time, decocted 2 hours, second and third time adds 8 times of amounts of water, decocts 1.5 hours, filters, filtrate and above-mentioned aqueous solution merge, and are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filtered, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds an amount of dextrin, mixing, 80 ℃ of drying under reduced pressure are pulverized, and add protein sugar 20g, citric acid 10g and an amount of Icing Sugar and adjust total amount to 1000g, mixing is granulated 80 ℃ of drying under reduced pressure with 70% ethanol moistening, spray into Rhizoma Zingiberis Recens volatile oil and an amount of fruit essence, mixing, airtight, granulate, packing, promptly.

6. according to the preparation method of the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 3 flu, it is characterized in that: the syrup in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, and medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, add 10 times of amounts of water for the first time, decocted 2 hours, second and third time adds 8 times of amounts of water, decocts 1.5 hours, filters, filtrate and above-mentioned aqueous solution merge, and are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filter, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds Rhizoma Zingiberis Recens volatile oil and an amount of flavoring syrup, essence, making sugar content is 45%, is adjusted to ormal weight promptly.

7. according to the preparation method of the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 3 flu, it is characterized in that: the drop pill in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, and medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, add 10 times of amounts of water for the first time, decocted 2 hours, second and third time adds 8 times of amounts of water, decocts 1.5 hours, filters, filtrate and above-mentioned aqueous solution merge, and are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to the alcohol amount of containing, and mixing left standstill 24 hours, filters filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste; After getting an amount of PEG6000 or PEG6000 and the fusion of PEG4000 mixture, with above-mentioned thick paste mix homogeneously, cold slightly back adds Rhizoma Zingiberis Recens volatile oil, and mixing splashes in vegetable oil or the liquid paraffin coolant, promptly.

8. according to the preparation method of the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 3 flu, it is characterized in that: the tablet in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, and medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, add 10 times of amounts of water for the first time, decocted 2 hours, second and third time adds 8 times of amounts of water, decocts 1.5 hours, filters, filtrate and above-mentioned aqueous solution merge, and are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, mixing, left standstill 24 hours, filter, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds Rhizoma Zingiberis Recens volatile oil and appropriate amount of starch or modified starch, dextrin, granulates, add 0.3%～3% magnesium stearate or 1%～3% Pulvis Talci tabletting again, promptly.

9. according to the preparation method of the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 3 flu, it is characterized in that: the soft extract in the described preparation prepares like this: get Rhizoma Zingiberis Recens and extract volatile oil, distillation rear solution device is in addition collected, and medicinal residues and bark of Semen Caesalpiniae, Radix seu Herba Gei aleppici, Herba Verbenae three flavors decoct with water three times, add 10 times of amounts of water for the first time, decocted 2 hours, second and third time adds 8 times of amounts of water, decocts 1.5 hours, filters, filtrate and above-mentioned aqueous solution merge, and are concentrated into 50 ℃ of relative densities and are 1.18～1.22 clear paste; Adding ethanol is 75% to containing the alcohol amount, and mixing left standstill 24 hours, filtered, filtrate recycling ethanol and to be concentrated into 50 ℃ of relative densities be 1.25～1.30 thick paste adds an amount of Mel, maltose, sucrose and essence, sweeting agent, receives cream, put cold back and add Rhizoma Zingiberis Recens volatile oil, mixing, promptly.

10. as the method for quality control of the Semen Caesalpiniae Chinese medicine preparation of treatment flu as described in the claim 1,2 or 3, it is characterized in that: described method of quality control mainly comprise in character, discriminating, inspection, the assay project partly or entirely; Wherein discriminating is that the thin layer of bark of Semen Caesalpiniae, Rhizoma Zingiberis Recens is differentiated; Assay is the assay to verbenalin in the preparation.

11. method of quality control according to the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 10 flu, it is characterized in that: the discrimination method of bark of Semen Caesalpiniae is to be contrast with the bark of Semen Caesalpiniae control medicinal material, and with 60～90 ℃ of petroleum ether: ethyl acetate: the upper solution of formic acid=10: 8: 2 is the thin layer discrimination method of developing solvent; The discrimination method of Rhizoma Zingiberis Recens is to be contrast with the Rhizoma Zingiberis Recens control medicinal material, and with benzene: ethyl acetate: the upper solution of formic acid=9: 0.5: 0.5 is the thin layer discrimination method of developing solvent.

12. the method for quality control according to the Semen Caesalpiniae Chinese medicine preparation of claim 10 or 11 described treatments flu is characterized in that: concrete discrimination method comprise following project partly or entirely:

13. method of quality control according to the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 10 flu, it is characterized in that: the content assaying method of verbenalin is to be contrast with the verbenalin reference substance, and with methanol: water=30: 70 is the high performance liquid chromatography of mobile phase.

14. according to the method for quality control of the Semen Caesalpiniae Chinese medicine preparation of claim 10 or 13 described treatments flu, it is characterized in that: concrete content assaying method is:

According to an appendix VI of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring:

Every of this capsule contains Herba Verbenae in verbenalin C17H24O10, must not be less than 2.2mg; This granule contains Herba Verbenae in verbenalin C17H24O10 for every bag, must not be less than 4.6mg; This syrup contains Herba Verbenae in verbenalin C17H24O10 for every milliliter, must not be less than 0.2mg; The every gram of this drop pill contains Herba Verbenae in verbenalin C17H24O10, must not be less than 3.0mg; Every in this tablet contains Herba Verbenae in verbenalin C17H24O10, must not be less than 2.0mg; The every gram of this soft extract contains Herba Verbenae in verbenalin C17H24O10, must not be less than 0.2mg.

15. according to the method for quality control of the Semen Caesalpiniae Chinese medicine preparation of the described treatment of claim 10 flu, it is characterized in that: described method of quality control comprises:

Character:

Assay: shine an appendix VI of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring: