CN1895410A

CN1895410A - Medicinal composition for treating cough and its preparation

Info

Publication number: CN1895410A
Application number: CN 200610086471
Authority: CN
Inventors: 徐新盛
Original assignee: Individual
Current assignee: Individual
Priority date: 2006-06-23
Filing date: 2006-06-23
Publication date: 2007-01-17

Abstract

A Chinese medicine in the form of oral liquid for treating cold is prepared from 11 Chinese-medicinal materials including pueraria root, loneysuckle flower, chrysanthemum flower, scutellaria root, etc. Its preparing process and quality control method are disclosed.

Description

A kind of pharmaceutical composition and preparation technology thereof who treats anemopyretic cold

Technical field

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

Background technology

Flu is common exterior syndrome, the traditional Chinese medical science think the flu generation, be that row epidemic disease poison is attacked due to the human body during by six climate exopathogens (wind, cold, summer-heat, wet, dry, six kinds of pathogenic factor of fire), according to different seasons and climatic characteristic, paathogenic factor has differences such as wind and cold, wind heat, heat-damp in summer, autumn-dryness disease.Anemopyretic cold, be the heresy invasion and attack human body of wind heat caused with generate heat heavily, aversion to cold is light or sweating not smooth etc. be the common exterior syndrome of main clinical manifestation.Anemopyretic cold all can take place throughout the year, and more to see spring more.How by abrupt change of climate, cold warm imbalance, the heresy of wind heat seizes the opportunity to worm one's way into human body, attacks lung and violates and defend, and Wei Yangyu holds back, and battalion defends and becomes estranged, struggle between vital QI and pathogen, and see Table the card of defending.

At present, the medicine that is used for the treatment of flu is many, but has its dosage form of medicine of better treatment anemopyretic cold still to remain further to be improved, satisfying clinical application, for medical personnel and patient provide more selection.

Summary of the invention

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

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

The raw material of pharmaceutical composition of the present invention consists of:

Radix Puerariae 100-200 weight portion Radix Angelicae Dahuricae 50-150 weight portion Flos Lonicerae 100-200 weight portion

Flos Chrysanthemi 100-200 weight portion Fructus Forsythiae 50-150 weight portion Radix Scutellariae 100-200 weight portion

Fructus Gardeniae 50-150 weight portion Radix Isatidis 100-200 weight portion Folium Isatidis 100-200 weight portion

Herba Artemisiae Scopariae 100-200 weight portion Rhizoma Osmundae 100-200 weight portion sodium alginate 5-15 weight portion

Sucrose 50-150 weight portion aspartame 1-4 weight portion citric acid 1-6 weight portion

Potassium sorbate 0.5-2 weight portion.

Above-mentioned raw materials preferred weight proportioning is as follows:

The Radix Puerariae 150 weight portion Radixs Angelicae Dahuricae 100 weight portion Flos Loniceraes 150 weight portion Flos Chrysanthemis 150 weight portions

Fructus Forsythiae 100 weight portion Radix Scutellariaes 150 weight portion Fructus Gardeniaes 100 weight portion Radix Isatidis 150 weight portions

Folium Isatidis 150 weight portion Herba Artemisiae Scopariaes 150 weight portion Rhizoma Osmundae 150 weight portion sodium alginates 10 weight portions

Sucrose 100 weight portion aspartames 2 weight portion citric acid 3 weight portion potassium sorbate 1 weight portion.

Above-mentioned raw materials preferred weight proportioning is as follows:

The Radix Puerariae 105 weight portion Radixs Angelicae Dahuricae 145 weight portion Flos Loniceraes 110 weight portion Flos Chrysanthemis 195 weight portions

Fructus Forsythiae 55 weight portion Radix Scutellariaes 180 weight portion Fructus Gardeniaes 65 weight portion Radix Isatidis 190 weight portions

Folium Isatidis 115 weight portion Herba Artemisiae Scopariaes 185 weight portion Rhizoma Osmundae 115 weight portion sodium alginates 14 weight portions

Sucrose 70 weight portion aspartames 1.5 weight portion citric acid 5 weight portion potassium sorbate 0.6 weight portion.

Above-mentioned raw materials preferred weight proportioning is as follows:

The Radix Puerariae 195 weight portion Radixs Angelicae Dahuricae 65 weight portion Flos Loniceraes 190 weight portion Flos Chrysanthemis 110 weight portions

Fructus Forsythiae 145 weight portion Radix Scutellariaes 115 weight portion Fructus Gardeniaes 140 weight portion Radix Isatidis 120 weight portions

Folium Isatidis 185 weight portion Herba Artemisiae Scopariaes 125 weight portion Rhizoma Osmundae 180 weight portion sodium alginates 6 weight portions

Sucrose 135 weight portion aspartames 3 weight portion citric acid 2 weight portion potassium sorbate 1.5 weight portions.

The preparation technology of pharmaceutical composition gel preparation of the present invention is as follows:

Extracting honeysuckle, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae were soaked 0.5-2 hour, extracted volatile oil, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 95% ethanol 800-1000 parts by volume, soaks 0.5-2 hour, reflux 0.5-2 hour, filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add above-mentioned medicinal residues and extracting solution, after soaking 0.5-2 hour again, decoct with water 2-4 time, each 0.5-1.5 hour, collecting decoction, filter, filtrate is concentrated into the 250-350 parts by volume, adds 95% ethanol 250-350 parts by volume, stirs evenly, left standstill 12 hours, and filtered; Get filtrate and Herba Artemisiae Scopariae extracting solution and merge, reclaim ethanol and be concentrated into the 150-250 parts by volume, add the dilution of 400-900 parts by volume water, filter; Other gets sucrose, aspartame, citric acid and potassium sorbate, adds water and is heated to dissolving, filters, and joins in the above-mentioned medicinal liquid; Add sodium alginate again, add the water stirring and boil the gel that is 1.05-1.25 to 75-85 ℃ of following relative density.

The preferred for preparation technology of pharmaceutical composition gel preparation of the present invention is as follows:

Extracting honeysuckle, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae were soaked 1 hour, extracted volatile oil, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 95% ethanol, 900 parts by volume, soaks 1 hour, and reflux 1 hour filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add above-mentioned medicinal residues and extracting solution, after soaking 1 hour again, decoct with water three times 1 hour for the first time, second and third time each 45 minutes, collecting decoction filters, and filtrate is concentrated into 300 parts by volume, add 95% ethanol, 300 parts by volume, stir evenly, left standstill 12 hours, filter; Get filtrate and Herba Artemisiae Scopariae extracting solution and merge, reclaim ethanol and be concentrated into 200 parts by volume, add the dilution of 650 parts by volume water, filter; Other gets sucrose, aspartame, citric acid and potassium sorbate, adds water and is heated to dissolving, filters, and joins in the above-mentioned medicinal liquid, adds sodium alginate, and adding that water stirs and boil to 80 ℃ of following relative densities is 1.06 gel preparation.

Extracting honeysuckle, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae were soaked 0.5 hour, extracted volatile oil, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 95% ethanol, 810 parts by volume, soaks 1.5 hours, and reflux 0.5 hour filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add above-mentioned medicinal residues and extracting solution, soak 1.5 hours again after, decoct with water 2 times, each 1.5 hours, collecting decoction filtered, filtrate is concentrated into 260 parts by volume, adds 95% ethanol, 320 parts by volume, stirs evenly, left standstill 12 hours, filter, get filtrate and Herba Artemisiae Scopariae extracting solution and merge, reclaim ethanol and be concentrated into 160 parts by volume, add the dilution of 850 parts by volume water, filter; Other gets sucrose, aspartame, citric acid and potassium sorbate, adds water and is heated to dissolving, filters, and joins in the above-mentioned medicinal liquid, adds sodium alginate, and adding that water stirs and boil to 88 ℃ of following relative densities is 1.24 gel preparation.

Extracting honeysuckle, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae were soaked 1.5 hours, extracted volatile oil, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 95% ethanol, 980 parts by volume, soaks 0.5 hour, and reflux 1.5 hours filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add above-mentioned medicinal residues and extracting solution, soak 0.5 hour again after, decoct with water 4 times, each 0.5 hour, collecting decoction filtered, filtrate is concentrated into 340 parts by volume, adds 56% ethanol, 260 parts by volume, stirs evenly, left standstill 12 hours, filter, get filtrate and Herba Artemisiae Scopariae extracting solution and merge, reclaim ethanol and be concentrated into 230 parts by volume, add the dilution of 450 parts by volume water, filter; Other gets sucrose, aspartame, citric acid and potassium sorbate, adds water and is heated to dissolving, filters, and joins in the above-mentioned medicinal liquid, adds sodium alginate, and adding that water stirs and boil to 76 ℃ of following relative densities is 1.06 gel.

The pass of above-mentioned weight portion and parts by volume is the relation of gram and milliliter.

The method of quality control of pharmaceutical composition gel preparation of the present invention comprises one or more in following discrimination method or the assay:

A. physicochemical identification: get pharmaceutical composition gel preparation 5g of the present invention, add ethanol 10ml, be heated to and boil, put cold filtration, filtrate is according to following method test: get filtrate 1ml, add 3 of 1% ethanol solution of ninhydrin, put in the water-bath and heat, show blueness or aubergine; Get filtrate with capillary tube, put on filter paper, do rearmounted 254nm uviol lamp and observe down, show yellow-green fluorescence;

B. get pharmaceutical composition gel preparation 4g of the present invention, add methanol 30ml, use 350W, ultrasonic 30 minutes of 55KHz filters, and filtrate is concentrated into 1ml, as need testing solution; Lack Radix Puerariae negative sample solution with the method preparation; Other gets the puerarin reference substance, adds methanol and makes the reference substance solution that every 1ml contains 0.5mg; According to the thin layer chromatography experiment, draw each 3 μ l of above-mentioned solution, put respectively on same silica gel H plate, be developing solvent with chloroform-methanol-water 6-8: 2-3: 0.1-0.4, launch, take out, dry, put under the 365nm uviol lamp and inspect; The result in the test sample chromatograph, with reference substance chromatograph relevant position on the fluorescence speckle of same color is arranged;

C. get pharmaceutical composition gel preparation of the present invention, porphyrize takes by weighing 5g, and adding alcohol-water is 1: 0.5-2 solution 30ml, use 350W, and 55KHz supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution and each 5ul of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate-acetone-glacial acetic acid-water 4-6: 0.5-2: 0.5-2: 0.5-2 is developing solvent, presaturation 20 minutes launches, and takes out, dry, spray is with 5% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;

D. get pharmaceutical composition gel preparation 5g of the present invention, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 4-6 time, each 10-15ml merges n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, be developing solvent with chloroform-methanol-acetonitrile-ammonia 3-5: 3-4: 0.5-2: 0.1-0.4, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-0.5% glacial acetic acid 18-26: 74-82 is a mobile phase; The detection wavelength is 250nm; Number of theoretical plate calculates by puerarin peak should be not less than 3000;

The reference substance solution preparation: precision takes by weighing the puerarin reference substance, adds methanol and makes the reference substance solution that every 1ml contains 50 μ g;

The need testing solution preparation: get pharmaceutical composition gel preparation of the present invention, be ground into pulpous state, get 1g, the accurate title, decide; Put in the tool plug conical flask, add 30% ethanol 50ml, weigh, ultrasonic 45 minutes, put to room temperature, weigh once more, supply the weight that subtracts mistake with 30% ethanol, shake up, filter; Get subsequent filtrate and cross 0.45 μ m microporous filter membrane, promptly;

Algoscopy: accurate above-mentioned test sample and each 10 μ l of reference substance solution of drawing, inject chromatograph of liquid, measure, calculate, promptly;

The every gram of pharmaceutical composition gel preparation of the present invention contains Radix Puerariae with puerarin C ₂₁H ₂₀O ₉Meter must not be less than 0.6mg.

The method of quality control of pharmaceutical composition gel preparation of the present invention is preferably as follows one or more in discrimination method or the assay:

B. get pharmaceutical composition gel preparation 4g of the present invention, add methanol 30ml, use 350W, ultrasonic 30 minutes of 55KHz filters, and filtrate is concentrated into 1ml, as need testing solution; Lack Radix Puerariae negative sample solution with the method preparation; Other gets the puerarin reference substance, adds methanol and makes the reference substance solution that every 1ml contains 0.5mg; According to the thin layer chromatography experiment, draw each 3 μ l of above-mentioned solution, put respectively on same silica gel H plate, be at 7: 2.5: 0.25 developing solvent with chloroform-methanol-water, launch, take out, dry, put under the 365nm uviol lamp and inspect; The result in the test sample chromatograph, with reference substance chromatograph relevant position on the fluorescence speckle of same color is arranged;

C. get pharmaceutical composition gel preparation of the present invention, porphyrize takes by weighing 5g, and adding alcohol-water is 1: 1 solution 30ml, uses 350W, and 55KHz supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution and each 5ul of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate-acetone-glacial acetic acid-water 5: 1: 1: 1 was developing solvent, and presaturation 20 minutes launches, take out, dry, spray is with 5% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;

D. get pharmaceutical composition gel preparation 5g of the present invention, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 5 times, be respectively 15ml, 15ml, 15ml, 10ml, 10ml at every turn, merge n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 4: 3.6: 1: 0.2 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-0.5% glacial acetic acid is a mobile phase at 22: 78; The detection wavelength is 250nm; Number of theoretical plate calculates by puerarin peak should be not less than 3000;

The reference substance solution preparation: precision takes by weighing the puerarin reference substance, adds methanol and makes the reference substance solution that every 1ml contains 50 μ g; The need testing solution preparation: get pharmaceutical composition gel preparation of the present invention, be ground into pulpous state, get 1g, the accurate title, decide; Put in the tool plug conical flask, add 30% ethanol 50ml, weigh, ultrasonic 45 minutes, put to room temperature, weigh once more, supply the weight that subtracts mistake with 30% ethanol, shake up, filter; Get subsequent filtrate and cross 0.45 μ m microporous filter membrane, promptly;

B. get pharmaceutical composition gel preparation 4g of the present invention, add methanol 30ml, use 350W, ultrasonic 30 minutes of 55KHz filters, and filtrate is concentrated into 1ml, as need testing solution; Lack Radix Puerariae negative sample solution with the method preparation; Other gets the puerarin reference substance, adds methanol and makes the reference substance solution that every 1ml contains 0.5mg; According to the thin layer chromatography experiment, draw each 3 μ l of above-mentioned solution, put respectively on same silica gel H plate, be at 6: 3: 0.15 developing solvent with chloroform-methanol-water, launch, take out, dry, put under the 365nm uviol lamp and inspect; The result in the test sample chromatograph, with reference substance chromatograph relevant position on the fluorescence speckle of same color is arranged;

C. get pharmaceutical composition gel preparation of the present invention, porphyrize takes by weighing 5g, and adding alcohol-water is 1: 0.6 solution 30ml, uses 350W, and 55KHz supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution and each 5ul of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate-acetone-glacial acetic acid-water 4: 1.8: 0.6: 1.8 was developing solvent, and presaturation 20 minutes launches, take out, dry, spray is with 5% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;

D. get pharmaceutical composition gel preparation 5g of the present invention, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 4 times, each 15ml merges n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 3: 4: 0.6: 0.35 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-0.5% glacial acetic acid is a mobile phase at 19: 81; The detection wavelength is 250nm; Number of theoretical plate calculates by puerarin peak should be not less than 3000;

C. get pharmaceutical composition gel preparation of the present invention, porphyrize takes by weighing 5g, and adding alcohol-water is 1: 1.8 solution 30ml, uses 350W, and 55KHz supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution and each 5ul of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate-acetone-glacial acetic acid-water 6: 0.6: 1.8: 0.7 was developing solvent, and presaturation 20 minutes launches, take out, dry, spray is with 5% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;

D. get pharmaceutical composition gel preparation 5g of the present invention, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 6 times, each 10ml merges n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 5: 3.1: 1.8: 0.15 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Assay: chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-0.5% glacial acetic acid is a mobile phase at 25: 75; The detection wavelength is 250nm; Number of theoretical plate calculates by puerarin peak should be not less than 3000;

The volatile oil extraction process of pharmaceutical composition gel preparation of the present invention, capillanol extraction process, water extraction alcohol precipitation process and whole extraction process repeatability are good.The experiment of technology repeatability shows that the preparation technology of pharmaceutical composition of the present invention and gel preparation has repeatability and feasibility preferably.The selection of assay experiment medium wavelength: take by weighing the puerarin reference substance, the wave-length coverage interscan at 200nm～400nm has maximum absorption wavelength at the 250nm place, selects the detection wavelength of 250nm as pharmaceutical composition gel of the present invention.Mobile phase is selected proof: methanol: water (25: 75), from appearance time, the time of separating degree and whole chromatogram, this condition is suitable for content of puerarin mensuration in the pharmaceutical composition gel of the present invention.Linear relationship is investigated experiment and shown: puerarin is good linear relationship in the 0.00902-0.0902mg/ml concentration range.The precision experiment: RSD is 1.0%, shows that the precision of instrument is good.Stability experiment: RSD is 1.0%, shows that need testing solution is basicly stable in 8 hours.The repeatability experiment: RSD is 0.89%, shows that this method repeatability is good.The average recovery experiment: RSD is 1.6%, shows that this law has the good response rate.Pharmaceutical composition gel preparation sugariness of the present invention is moderate, and mouthfeel is better.

Anti-sense detoxification particles is reliable to the determined curative effect of anemopyretic cold, is comparatively ideal at present anemopyretic cold curative drug.At present, existing anti-sense detoxicating preparation has tablet, granule, oral liquid, and children's is difficult for swallowing when taking tablet; Because main component all is dissolved in the solution, the taste of some composition was difficult to cover, and makes the child be unwilling to take when granule and oral liquid were taken.Pharmaceutical composition gel preparation of the present invention is to have made the fruit jelly gel that liked by the child on the basis of original prescription, because active component is in gel-type vehicle, covered disagreeable taste, it is good in mouthfeel when the patient takes, taste is suitable, children's extremely is ready to take, and has improved the compliance of medication in children.

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

Experimental example 1: volatile oil extracts orthogonal experiment

(1) preliminary experiment: take by weighing medical material: Flos Lonicerae 150g, Flos Chrysanthemi 150g, Radix Angelicae Dahuricae 100g, Fructus Forsythiae 100g, amount to 500g, put in the volatile oil extractor, add 8 times of water gagings, soak after 1 hour, reflux and extracted volatile oil in 8 hours, observe the increase situation of volatilization oil mass.After waiting to reflux 7 hours, the amount of volatile oil no longer increases.Collection contains the Aromatic water of volatile oil, through salting out method separate volatile oil.Get volatile oil 1.352g at last.

(2) factor level: choose and add water multiple, soak time, three factors of return time, respectively get three levels: add the water multiple and choose 6,8,10 times of three levels as investigating object; Soak time chooses 0.5,1, three levels of 1.5h; Return time is chosen three levels 4,6,8 times.

The factor level table is as shown in table 1 below.

Table 1 volatile oil extracts orthogonal experiment factor level table

Level	Factor
	Factor			A adds water multiple (doubly)	B soak time (h)	C return time (h)
	1 2 3	6 8 10	0.5 1.0 1.5	A adds water multiple (doubly)	B soak time (h)	C return time (h)	4 6 8

(3) experimental technique and data: take by weighing nine parts of medical materials according to preliminary experiment: Flos Lonicerae 150g, Flos Chrysanthemi 150g, Radix Angelicae Dahuricae 100g, Fructus Forsythiae 100g amount to 500g, the L that selects for use by table 2 ₉(3 ⁴) the table experiment arrangement, carry out reflux, extract, with reference to determination of volatile oil method (" appendix XD of Chinese pharmacopoeia version in 2000), must contain the Aromatic water of volatile oil.Collection contains the Aromatic water of volatile oil, is transferred in the separatory funnel, adds the NaCl be equivalent to Aromatic water 1/10, standing demix, separate volatile oil, claim fixed its quality.The results are shown in Table 2.

Table 2 volatile oil extracts orthogonal experiment design and data

The experiment number	Factor				Volatilization oil mass (mg)
	Factor					A (doubly)	B(h)	C(h)	D (blank)
	1 2 3 4 5 6 7 8 9 K1 K2 K3 R SS	1 1 1 2 2 2 3 3 3 1207.3 1248.3 1282.7 75.3 8534.9	1 2 3 1 2 3 1 2 3 1174.3 1276.3 1287.7 113.3 23376.9	1 2 3 2 3 1 3 1 2 1010.7 1348.0 1379.7 369.0 250957.6		A (doubly)	B(h)	C(h)	D (blank)	1 2 3 3 1 2 2 3 1 1237.0 1239.7 1261.7 24.7 1099.6	891 1333 1398 1294 1403 1048 1338 1093 1417

(4) variance analysis: the orthogonal experiment data the results are shown in Table 3 through variance analysis.

Table 3 volatile oil must be measured analysis of variance table

Source of error	SS	f	S	F	Significance test
Source of error	SS	f	S	F	Significance test	A B C D (error)	8534.9 23376.9 250957.6 1099.6	2 2 2 2	4267.4 11688.4 125478.8 549.8	7.8 21.3 228.2	Significantly extremely not remarkable

F _0.01(2，2)＝99.0 F _0.05(2，2)＝19.0 F _0.10(2，2)＝9.0

Conclusion: the amount with volatile oil serves as to investigate index, and by the size demonstration of extreme difference R value, the primary and secondary of each factor effect is respectively C＞B＞A.The results of analysis of variance shows: the influence of C factor is very remarkable; The B factor affecting is remarkable; The A factor affecting is not remarkable.From produce reality, save time and the energy, reduce cost and set out, determine that the optimum process condition that volatile oil extracts is A ₁B ₂C ₂, that is, add the water of 6 times of medical material amounts, behind the immersion 1h, reflux, extract, 6h.

(5) volatile oil extracts confirmatory experiment: take by weighing three parts of medical materials according to preliminary experiment: Flos Lonicerae 150g, Flos Chrysanthemi 150g, Radix Angelicae Dahuricae 100g, Fructus Forsythiae 100g, amount to 500g,, promptly add the water of 6 times of medical material amounts by the optimised process that above-mentioned orthogonal experiment is determined, after soaking 1h, backflow 6h extracts volatile oil.Collection contains the Aromatic water of volatile oil, separate through saltouing volatile oil.The results are shown in Table 4.

Table 4 volatile oil extracts confirmatory experiment (n=3)

The experiment number	Volatile oil must be measured (g)
The experiment number	Volatile oil must be measured (g)	123 meansigma methodss	1.342 1.329 1.334 1.335

Experimental result shows: repeat 3 experiments by preferred technology, and the amount no significant difference of volatile oil, the data opposing parallel, the technology repeatability is good.

Experimental example 2: capillanol extraction process confirmatory experiment

Take by weighing Herba Artemisiae Scopariae medical material 150g, add 60% ethanol 900ml, soaked 1 hour, reflux 1 hour filters, and decompression filtrate recycling ethanol also is condensed into thick paste, and 70 ℃ of vacuum dryings get dry extract.Test three times, to verify the stability of this technology.The results are shown in Table 5.

Table 5 capillanol extraction process confirmatory experiment

The experiment number	1	2	3
The experiment number	1	2	3	The dried cream yield of the dried cream amount of medical material amount (g) (g) (%)	150 16.5 11.00	150 17.2 11.47	150 16.8 11.20

Conclusion: upward data show that three parts of dried cream yield are more or less the same, and show that this process stabilizing is feasible in the table, and repeatability is good.

Experimental example 3: the water extraction alcohol precipitation process is to confirmatory experiment when

Take by weighing medical material: Flos Lonicerae 150g, Flos Chrysanthemi 150g, Radix Angelicae Dahuricae 100g, Fructus Forsythiae 100g, Radix Puerariae 150g, Radix Scutellariae 150g, Radix Isatidis 150g, Folium Isatidis 150g, Fructus Gardeniae 100g, Rhizoma Osmundae 150g, amount to 1350g, take by weighing nine parts.The design amount of water is three kinds of levels of 6,8,10 times of amounts, each horizontal triplicate experiment.Flos Lonicerae, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae add the water of 6 times of medical material amounts in every part of medical material, soak 1h after, backflow 6h extracts volatile oil, medicinal residues and extracting solution are standby; All the other Six-elements add medicinal residues and extracting solution, soak 1 hour after, according to the design amount of water decoct with water three times, 1 hour for the first time, second and third time each 45 minutes, collecting decoction, filter, filtrate is concentrated into 300ml, adds ethanol 300ml, stir evenly, left standstill 12 hours, filter, decompression filtrate recycling ethanol also is condensed into thick paste, and 70 ℃ of vacuum dryings get dry extract, claim to decide weight, measure wherein content of puerarin.The results are shown in Table 6.

Table 6 water extraction precipitate with ethanol is to confirmatory experiment (n=9) when

The experiment number	1	2	3	4	5	6	7	8	9
The experiment number	1	2	3	4	5	6	7	8	9	Clear cream amount (ml) adds the average total amount of the average dried cream yield of the dried cream yield of the dried cream amount of amount of alcohol (ml) (g) (%) puerarin content (mg/g) Puerarin total amount (mg) (%) Puerarin (mg) before medicinal material amount (g) amount of water (doubly) alcohol precipitation	1350 6 302.1 300 101.2 7.50 10.84 1097.01	1350 6 300.8 300 100.6 7.45 10.85 1091.51 7.49 1096.64	1350 6 299.7 300 101.7 7.53 10.83 1101.41	1350 8 301.3 300 103.9 7.70 10.84 1126.28	1350 8 301.6 300 104.6 7.75 10.83 1132.82 7.71 1128.44	1350 8 300.5 300 103.8 7.69 10.85 1126.23	1350 10 302.0 300 103.7 7.68 10.85 1125.15	1350 10 300.4 300 104.5 7.74 10.84 1132.78 7.73 1130.62	1350 10 298.9 300 104.8 7.76 10.82 1133.94

Conclusion: 4, average dried cream yield and the average total amount of puerarin of 5, No. 6 experiments and 7,8, No. 9 experiments all near and obviously test greater than 1,2, No. 3, consider production cost, determine to add 8 times of water gagings at every turn and decoct three times, 1 hour for the first time, second and third time each 45 minutes.

Last table 4,5, No. 6 experimental results show, dried cream yield and the equal no significant difference of puerarin total amount, and the data opposing parallel, the technology repeatability is good.

Experimental example 4: whole extraction process confirmatory experiment

According to taking by weighing medical material: Radix Puerariae 150g, Radix Angelicae Dahuricae 100g, Flos Lonicerae 150g, Flos Chrysanthemi 150g, Fructus Forsythiae 100g, Radix Scutellariae 150g, Fructus Gardeniae 100g, Radix Isatidis 150g, Folium Isatidis 150g, Herba Artemisiae Scopariae 150g, Rhizoma Osmundae 150g.

Method for making: above ten simply, is total to 1500g, and Flos Lonicerae, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae add the water of 6 times of medical material amounts, soak after 1 hour, refluxes and extracted volatile oil in 6 hours, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 60% ethanol 900ml, soaks 1 hour, and reflux 1 hour filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add medicinal residues and extracting solution, soak 1 hour again after, add 8 times of water gagings at every turn and decoct three times, 1 hour for the first time, second and third time each 45 minutes, collecting decoction, filter, filtrate is concentrated into 300ml, adds ethanol 300ml, stir evenly, left standstill 12 hours, filter, getting filtrate and Herba Artemisiae Scopariae extracting solution merges, reclaim ethanol and be concentrated into 200ml, claim to decide weight, measure wherein content of puerarin.The results are shown in Table 7.

The whole extraction process confirmatory experiment of table 7

The experiment number	1	2	3
The experiment number	1	2	3	Clear cream amount (ml) adds total clear cream weight (g) puerarin content (mg/g) the Puerarin total amount (mg) of the total clear cream amount (ml) of amount of alcohol (ml) before medicinal material total amount (g) water extract-alcohol precipitation medicinal material amount (g) alcohol precipitation	1500 1350 301.1 300 200.6 248.4 4.54 1127.74	1500 1350 300.5 300 199.9 246.5 4.57 1126.51	1500 1350 299.9 300 199.8 246.9 4.55 1123.40

Experimental result shows in the last table, and three batches of puerarin total amounts are more or less the same, and show this feasible process, and the technology repeatability is good.

Experimental example 5: technology repeatability experiment

The experiment of table 8 technology repeatability

Lot number	041213	041214	041215
Lot number	041213	041214	041215	Total medicinal material amount (g) volatile oil extracts before medicinal material amount (g) volatile oil amount (g) oriental wormwood alcohol extracting medicinal material amount (g) water extract-alcohol precipitation medicinal material total amount (g) alcohol precipitation clear cream amount (ml) and adds total clear cream weight (g) puerarin content (mg/g) sucrose (g) aspartame (g) citric acid (g) sodium alginate (g) the sorbic acid potassium (g) of the total clear cream amount (ml) of amount of alcohol (ml) and add water to the theoretical quantity of (g) finished product quantity (bag) (bag) finished product yield (%) proterties puerarin content (mg/ bag)	The opaque semisolid of 1,500 500 1.335 150 1,350 300.5 300 201.2 249.3 4.57 100 23 10 1 1,000 95 100 95 sepias; It is sweet to distinguish the flavor of, and little bitter 11.38	The opaque semisolid of 1,500 500 1.328 150 1,350 299.4 300 201.5 248.5 4.53 100 23 10 1 1,000 95 100 95 sepias; It is sweet to distinguish the flavor of, and little bitter 11.23	The opaque semisolid of 1,500 500 1.334 150 1,350 301.3 300 200.4 247.7 4.57 100 23 10 1 1,000 94 100 94 sepias; It is sweet to distinguish the flavor of, and little bitter 11.31

Last table experimental result as can be known, the preparation of three batches of gels that undertaken by pharmaceutical composition gel preparation of the present invention and preparation technology, the every index basically identical of sample shows that this prescription and technology have repeatability and feasibility preferably, and promptly this prescription and technology are reliable and stable and feasible.

Test agent and concrete parameter thereof in 6: three batches of the experimental examples

Test agent and concrete parameter thereof in three batches in the table 9

Lot number	050901	050902	050903
Lot number	050901	050902	050903	Total medicinal material amount (kg) volatile oil extracts before medicinal material amount (kg) volatile oil amount (g) oriental wormwood alcohol extracting medicinal material amount (kg) water extract-alcohol precipitation medicinal material total amount (kg) alcohol precipitation clear cream amount (L) and adds total clear cream weight (kg) sucrose (kg) aspartame (g) citric acid (g) sodium alginate (g) the sorbic acid potassium (g) of the total clear cream amount (L) of amount of alcohol (L) and add water to the theoretical quantity of (kg) finished product quantity (bag) (bag) finished product yield (%) proterties puerarin content (mg/ bag) microorganism limit bacterium mould Escherichia coli	The opaque semisolid of 15 5 13.40 1.5 13.5 2.99 3 2.02 2.48 1 20 30 100 10 10 958 1,000 95.8 sepias; It is sweet to distinguish the flavor of, and little bitter 15.6205 30/g＜10/g does not detect	The opaque semisolid of 15 5 13.34 1.5 13.5 3.02 3 2.02 2.49 1 20 30 100 10 10 955 1,000 95.5 sepias; It is sweet to distinguish the flavor of, and little bitter 15.6531 40/g＜10/g does not detect	The opaque semisolid of 15 5 13.38 1.5 13.5 3.01 3 2.01 2.47 1 20 30 100 10 10 962 1,000 96.2 sepias; It is sweet to distinguish the flavor of, and little bitter 15.1980 20/g＜10/g does not detect

Experimental example 7: the investigation of extracting solvent

Get pharmaceutical composition gel preparation 50g of the present invention, be ground into pulpous state, precision takes by weighing 6 parts (every part of 1g), puts in the tool plug conical flask first part of accurate methanol 25ml that adds respectively; Second part of accurate 30% ethanol 25ml that adds; The 3rd part of accurate 50% ethanol 25ml that adds weighs respectively.Ultrasonic (350W, 55KHz) 45 minutes, put to room temperature, supply the weight that subtracts mistake with solvent separately respectively, shake up, filter, cross microporous filter membrane (0.45 μ m) and be need testing solution, measure by the chromatographic condition of drafting, the results are shown in Table 10.

Table 10 extracts the investigation result of solvent

More than data show that 30% ethanol extraction effect is best in the table.

Experimental example 8: the investigation of extracting method

Get pharmaceutical composition gel preparation 50g of the present invention, be ground into pulpous state, precision takes by weighing 4 parts (every part of 1g), puts respectively in the tool plug conical flask, and the accurate respectively 30% ethanol 25ml that adds weighs respectively.Two parts of ultrasonic (power 350W wherein, frequency 55KHz) 45 minute, in addition two parts of reflux, extract, are 60 minutes, put to room temperature, claim to decide weight, supply the weight that subtracts mistake with 30% ethanol, shake up, filter, cross microporous filter membrane (0.45 μ m) and be need testing solution, measure by the chromatographic condition of drafting, the results are shown in following table 11.

The investigation result of table 11 extracting method

More than data show that the supersound extraction effect is best in the table.

Experimental example 9: the investigation experiment of extraction time

Get pharmaceutical composition gel preparation 50g of the present invention, porphyrize, precision takes by weighing 6 parts (every part of 1g), puts respectively in the tool plug conical flask, and the accurate 30% ethanol 25ml that adds weighs first part of ultrasonic (350W, 55KHz) 30 minutes; Second part of ultrasonic (350W, 55KHz) 45 minutes; The 3rd part ultrasonic (350W, 55KHz) 60 minutes, put to room temperature, supply the weight that subtracts mistake with 30% ethanol respectively, shake up, filter, cross microporous filter membrane (0.45 μ m) and be need testing solution, measure by the chromatographic condition of drafting, the results are shown in Table 12.

The investigation result of table 12 different extraction times

Data from above table, ultrasonic 45 minutes little with ultrasonic 60 minutes content difference, therefore selects ultrasonic 45 minutes as extraction time.

Experimental example 10: sample determination

Accurate respectively absorption reference substance solution and need testing solution 10 μ l measure according to above-mentioned spectral condition, calculate content.Sample determination the results are shown in Table 13.

Table 13 sample determination is n=10 as a result

Lot number	Puerarin content (mg/ bag)	Average content (mg/ bag)
Lot number	Puerarin content (mg/ bag)	Average content (mg/ bag)	050111 050112 050113 050510 050511 050512 050513 050901 050902 050903	11.971 11.856 14.374 14.302 12.244 12.213 11.920 11.873 12.469 12.38 11.836 11.759 11.646 11.6 15.234 15.340 15.453 15.362 14.948 14.762	12.12 14.66 12.54 12.075 12.712 11.991 11.86 15.620 15.653 15.198

According to 10 batches of data that detect gained, pharmaceutical composition gel preparation of the present invention, every gram contain Radix Puerariae with puerarin (C ₂₁H ₂₀O ₉) meter, must not be less than 0.6mg.

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

The specific embodiment:

Embodiment 1:

Radix Puerariae 150g Radix Angelicae Dahuricae 100g Flos Lonicerae 150g Flos Chrysanthemi 150g Fructus Forsythiae 100g

Radix Scutellariae 150g Fructus Gardeniae 100g Radix Isatidis 150g Folium Isatidis 150g Herba Artemisiae Scopariae 150g

Rhizoma Osmundae 150g sodium alginate 10g sucrose 100g aspartame 2g citric acid 3g

Potassium sorbate 1g.

Extracting honeysuckle, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae were soaked 1 hour, extracted volatile oil, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 95% ethanol 900ml, soaks 1 hour, and reflux 1 hour filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add medicinal residues and extracting solution, soak 1 hour again after, decoct with water three times, 1 hour for the first time, second and third time each 45 minutes, collecting decoction, filter, filtrate is concentrated into 300ml, adds 95% ethanol 300ml, stir evenly, left standstill 12 hours, filter, getting filtrate and Herba Artemisiae Scopariae extracting solution merges, reclaim ethanol and be concentrated into 200ml, add the dilution of 650ml water, filter; Other gets sucrose, aspartame, citric acid and potassium sorbate, adds water and is heated to dissolving, filters, and joins in the above-mentioned medicinal liquid, adds sodium alginate, and adding that water stirs and boil to 80 ℃ of following relative densities is 1.06 gel preparation.

Embodiment 2:

Radix Puerariae 105g Radix Angelicae Dahuricae 145g Flos Lonicerae 110g Flos Chrysanthemi 195g Fructus Forsythiae 55g

Radix Scutellariae 180g Fructus Gardeniae 65g Radix Isatidis 190g Folium Isatidis 115g Herba Artemisiae Scopariae 185g

Rhizoma Osmundae 115g sodium alginate 14g sucrose 70g aspartame 1.5g citric acid 5g

Potassium sorbate 0.6g.

Extracting honeysuckle, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae were soaked 1.5 hours, extracted volatile oil, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 95% ethanol 980ml, soaks 0.5 hour, and reflux 1.5 hours filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add above-mentioned medicinal residues and extracting solution, soak 0.5 hour again after, decoct with water 4 times, each 0.5 hour, collecting decoction filtered, filtrate is concentrated into 340ml, adds 95% ethanol 260ml, stirs evenly, left standstill 12 hours, filter, get filtrate and Herba Artemisiae Scopariae extracting solution and merge, reclaim ethanol and be concentrated into 230ml, add the dilution of 450ml water, filter; Other gets sucrose, aspartame, citric acid and potassium sorbate, adds water and is heated to dissolving, filters, and joins in the above-mentioned medicinal liquid, adds sodium alginate, and adding that water stirs and boil to 76 ℃ of following relative densities is 1.06 gel.

Embodiment 3:

Radix Puerariae 195g Radix Angelicae Dahuricae 65g Flos Lonicerae 190g Flos Chrysanthemi 110g Fructus Forsythiae 145g

Radix Scutellariae 115g Fructus Gardeniae 140g Radix Isatidis 120g Folium Isatidis 185g Herba Artemisiae Scopariae 125g

Rhizoma Osmundae 180g sodium alginate 6g sucrose 135g aspartame 3g citric acid 2g

Potassium sorbate 1.5g.

Extracting honeysuckle, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae were soaked 0.5 hour, extracted volatile oil, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 95% ethanol 810ml, soaks 1.5 hours, and reflux 0.5 hour filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add above-mentioned medicinal residues and extracting solution, soak 1.5 hours again after, decoct with water 2 times, each 1.5 hours, collecting decoction filtered, filtrate is concentrated into 260ml, adds 95% ethanol 320ml, stirs evenly, left standstill 12 hours, filter, get filtrate and Herba Artemisiae Scopariae extracting solution and merge, reclaim ethanol and be concentrated into 160ml, add the dilution of 850ml water, filter; Other gets sucrose, aspartame, citric acid and potassium sorbate, adds water and is heated to dissolving, filters, and joins in the above-mentioned medicinal liquid, adds sodium alginate, and adding that water stirs and boil to 88 ℃ of following relative densities is 1.24 gel preparation.

Embodiment 4:

Discrimination method:

A. physicochemical identification: get embodiment 1 content 5g, add ethanol 10ml, be heated to and boil, put cold filtration, filtrate is according to following method test: get filtrate 1ml, add 3 of 1% ethanol solution of ninhydrin, put in the water-bath and heat, show blueness or aubergine; Get filtrate with capillary tube, put on filter paper, do rearmounted 254nm uviol lamp and observe down, show yellow-green fluorescence.

B. get embodiment 1 content 4g, add methanol 30ml, use 350W, ultrasonic 30 minutes of 55KHz filters, and filtrate is concentrated into 1ml, as need testing solution; Lack Radix Puerariae negative sample solution with the method preparation; Other gets the puerarin reference substance, adds methanol and makes the reference substance solution that every 1ml contains 0.5mg; According to the thin layer chromatography experiment, draw each 3 μ l of above-mentioned solution, put respectively on same silica gel H plate, be at 7: 2.5: 0.25 developing solvent with chloroform-methanol-water, launch, take out, dry, put under the 365nm uviol lamp and inspect; The result in the test sample chromatograph, with reference substance chromatograph relevant position on the fluorescence speckle of same color is arranged;

C. get embodiment 1 content, porphyrize takes by weighing 5g, and adding alcohol-water is 1: 1 solution 30ml, uses 350W, and 55KHz supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution and each 5ul of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate-acetone-glacial acetic acid-water 5: 1: 1: 1 was developing solvent, and presaturation 20 minutes launches, take out, dry, spray is with 5% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;

D. get embodiment 1 content 5g, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 5 times, be respectively 15ml, 15ml, 15ml, 10ml, 10ml at every turn, merge n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 4: 3.6: 1: 0.2 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-0.5% glacial acetic acid is a mobile phase at 22: 78; The detection wavelength is 250nm; Number of theoretical plate calculates by puerarin peak should be not less than 3000;

Embodiment 5:

Discrimination method:

A. physicochemical identification: get embodiment 2 content 5g, add ethanol 10ml, be heated to and boil, put cold filtration, filtrate is according to following method test: get filtrate 1ml, add 3 of 1% ethanol solution of ninhydrin, put in the water-bath and heat, show blueness or aubergine; Get filtrate with capillary tube, on the idea filter paper, do rearmounted 254nm uviol lamp and observe down, show yellow-green fluorescence.

B. get embodiment 2 content 4g, add methanol 30ml, use 350W, ultrasonic 30 minutes of 55KHz filters, and filtrate is concentrated into 1ml, as need testing solution; Lack Radix Puerariae negative sample solution with the method preparation; Other gets the puerarin reference substance, adds methanol and makes the reference substance solution that every 1ml contains 0.5mg; According to the thin layer chromatography experiment, draw each 3 μ l of above-mentioned solution, put respectively on same silica gel H plate, be at 6: 3: 0.15 developing solvent with chloroform-methanol-water, launch, take out, dry, put under the 365nm uviol lamp and inspect; The result in the test sample chromatograph, with reference substance chromatograph relevant position on the fluorescence speckle of same color is arranged;

C. get embodiment 2 contents, porphyrize takes by weighing 5g, and adding alcohol-water is 1: 0.6 solution 30ml, uses 350W, and 55KHz supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution and each 5ul of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate-acetone-glacial acetic acid-water 4: 1.8: 0.6: 1.8 was developing solvent, and presaturation 20 minutes launches, take out, dry, spray is with 5% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;

D. get embodiment 2 content 5g, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 4 times, each 15ml merges n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 3: 4: 0.6: 0.35 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-0.5% glacial acetic acid is a mobile phase at 19: 81; The detection wavelength is 250nm; Number of theoretical plate calculates by puerarin peak should be not less than 3000;

The need testing solution preparation: get embodiment 2 contents, be ground into pulpous state, get 1g, the accurate title, decide; Put in the tool plug conical flask, add 30% ethanol 50ml, weigh, ultrasonic 45 minutes, put to room temperature, weigh once more, supply the weight that subtracts mistake with 30% ethanol, shake up, filter; Get subsequent filtrate and cross 0.45 μ m microporous filter membrane, promptly;

Embodiment 6:

Discrimination method:

A. physicochemical identification: get embodiment 3 content 5g, add ethanol 10ml, be heated to and boil, put cold filtration, filtrate is according to following method test: get filtrate 1ml, add 3 of 1% ethanol solution of ninhydrin, put in the water-bath and heat, show blueness or aubergine; Get filtrate with capillary tube, put on filter paper, do rearmounted 254nm uviol lamp and observe down, show yellow-green fluorescence.

B. get embodiment 3 content 4g, add methanol 30ml, use 350W, ultrasonic 30 minutes of 55KHz filters, and filtrate is concentrated into 1ml, as need testing solution; Lack Radix Puerariae negative sample solution with the method preparation; Other gets the puerarin reference substance, adds methanol and makes the reference substance solution that every 1ml contains 0.5mg; According to the thin layer chromatography experiment, draw each 3 μ l of above-mentioned solution, put respectively on same silica gel H plate, be developing solvent with chloroform-methanol-water 6-8: 2-3: 0.1-0.4, launch, take out, dry, put under the 365nm uviol lamp and inspect; The result in the test sample chromatograph, with reference substance chromatograph relevant position on the fluorescence speckle of same color is arranged;

C. get embodiment 3 contents, porphyrize takes by weighing 5g, and adding alcohol-water is 1: 1.8 solution 30ml, uses 350W, and 55KHz supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution and each 5ul of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate-acetone-glacial acetic acid-water 6: 0.6: 1.8: 0.7 was developing solvent, and presaturation 20 minutes launches, take out, dry, spray is with 5% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;

D. get embodiment 3 content 5g, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 6 times, each 10ml merges n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 5: 3.1: 1.8: 0.15 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Embodiment 7:

Assay:

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-0.5% glacial acetic acid is a mobile phase at 25: 75; The detection wavelength is 250nm; Number of theoretical plate calculates by puerarin peak should be not less than 3000;

Embodiment 8:

Discrimination method:

Assay:

Embodiment 9:

Discrimination method:

Assay:

Embodiment 10:

Discrimination method:

Assay:

Claims

1, a kind of pharmaceutical composition for the treatment of anemopyretic cold is characterized in that the raw material of this pharmaceutical composition consists of:

Potassium sorbate 0.5-2 weight portion.

2, pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:

The Radix Puerariae 150 weight portion Radixs Angelicae Dahuricae 100 weight portion Flos Loniceraes 150 weight portions

Flos Chrysanthemi 150 weight portion Fructus Forsythiaes 100 weight portion Radix Scutellariaes 150 weight portions

Fructus Gardeniae 100 weight portion Radix Isatidis 150 weight portion Folium Isatidiss 150 weight portions

Herba Artemisiae Scopariae 150 weight portion Rhizoma Osmundae 150 weight portion sodium alginates 10 weight portions

Sucrose 100 weight portion aspartames 2 weight portion citric acid 3 weight portions

Potassium sorbate 1 weight portion.

3, pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:

The Radix Puerariae 105 weight portion Radixs Angelicae Dahuricae 145 weight portion Flos Loniceraes 110 weight portions

Flos Chrysanthemi 195 weight portion Fructus Forsythiaes 55 weight portion Radix Scutellariaes 180 weight portions

Fructus Gardeniae 65 weight portion Radix Isatidis 190 weight portion Folium Isatidiss 115 weight portions

Herba Artemisiae Scopariae 185 weight portion Rhizoma Osmundae 115 weight portion sodium alginates 14 weight portions

Sucrose 70 weight portion aspartames 1.5 weight portion citric acid 5 weight portions

Potassium sorbate 0.6 weight portion.

4, pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:

The Radix Puerariae 195 weight portion Radixs Angelicae Dahuricae 65 weight portion Flos Loniceraes 190 weight portions

Flos Chrysanthemi 110 weight portion Fructus Forsythiaes 145 weight portion Radix Scutellariaes 115 weight portions

Fructus Gardeniae 140 weight portion Radix Isatidis 120 weight portion Folium Isatidiss 185 weight portions

Herba Artemisiae Scopariae 125 weight portion Rhizoma Osmundae 180 weight portion sodium alginates 6 weight portions

Sucrose 135 weight portion aspartames 3 weight portion citric acid 2 weight portions

Potassium sorbate 1.5 weight portions.

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

6, preparation of drug combination method as claimed in claim 5 is characterized in that the preparation method of gel preparation is:

7, preparation of drug combination method as claimed in claim 5 is characterized in that the preparation method of gel preparation is:

8, preparation of drug combination method as claimed in claim 5 is characterized in that the preparation method of gel preparation is:

Extracting honeysuckle, Flos Chrysanthemi, the Radix Angelicae Dahuricae, Fructus Forsythiae were soaked 1.5 hours, extracted volatile oil, and medicinal residues and extracting solution are standby; Herba Artemisiae Scopariae adds 95% ethanol, 980 parts by volume, soaks 0.5 hour, and reflux 1.5 hours filters filtrate for later use; Radix Puerariae, Radix Scutellariae, Radix Isatidis, Folium Isatidis, Fructus Gardeniae, Rhizoma Osmundae add above-mentioned medicinal residues and extracting solution, soak 0.5 hour again after, decoct with water 4 times, each 0.5 hour, collecting decoction filtered, filtrate is concentrated into 340 parts by volume, adds 95% ethanol, 260 parts by volume, stirs evenly, left standstill 12 hours, filter, get filtrate and Herba Artemisiae Scopariae extracting solution and merge, reclaim ethanol and be concentrated into 230 parts by volume, add the dilution of 450 parts by volume water, filter; Other gets sucrose, aspartame, citric acid and potassium sorbate, adds water and is heated to dissolving, filters, and joins in the above-mentioned medicinal liquid, adds sodium alginate, and adding that water stirs and boil to 76 ℃ of following relative densities is 1.06 gel.

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

D. get pharmaceutical composition gel preparation 5g of the present invention, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 4-6 time, each 10-15ml merges n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, be developing solvent with chloroform-methanol-acetonitrile-ammonia 3-5: 3-4: 0.5-2: 0.1-0.4, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

Assay:

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

D. get pharmaceutical composition gel preparation 5g of the present invention, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 5 times, be respectively 15ml, 15ml, 15ml, 10ml, 10ml at every turn, merge n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 4: 3.6: 1: 0.2 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

11, the method for quality control of pharmaceutical composition as claimed in claim 9 is characterized in that this method comprises one or more in following discriminating or the assay:

Discrimination method: A. physicochemical identification: get pharmaceutical composition gel preparation 5g of the present invention, add ethanol 10ml, be heated to and boil, put cold filtration, filtrate is shone following method test: get filtrate 1ml, add 3 of 1% ethanol solution of ninhydrin, put in the water-bath and heat, show blueness or aubergine; Get filtrate with capillary tube, put on filter paper, do rearmounted 254nm uviol lamp and observe down, show yellow-green fluorescence;

D. get pharmaceutical composition gel preparation 5g of the present invention, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 4 times, each 15ml merges n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 3: 4: 0.6: 0.35 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

12, the method for quality control of pharmaceutical composition as claimed in claim 9 is characterized in that this method comprises one or more in following discriminating or the assay:

D. get pharmaceutical composition gel preparation 5g of the present invention, porphyrize adds dehydrated alcohol 10ml, shake up, placed 20 minutes, use 350W, 55KHz sonic oscillation 20 minutes, room temperature is placed half an hour, filters, reclaim solvent to doing, residue adds 15ml water makes dissolving, with water saturated n-butanol extraction 6 times, each 10ml merges n-butanol extracting liquid, evaporate to dryness, residue adds methanol 5ml makes dissolving, as need testing solution; Other gets the jasminoidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 μ l of above-mentioned solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol-acetonitrile-ammonia 5: 3.1: 1.8: 0.15 was developing solvent, after ammonia is saturated, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and 105 ℃ were dried by the fire 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

13, as claim 1-4 arbitrary as described in the application of pharmaceutical composition in preparation treatment anemopyretic cold medicine.