CN1785347A - Quality control method of Chinese medicinal preparation for treating child hyperpyrexia - Google Patents
Quality control method of Chinese medicinal preparation for treating child hyperpyrexia Download PDFInfo
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- CN1785347A CN1785347A CN 200510003292 CN200510003292A CN1785347A CN 1785347 A CN1785347 A CN 1785347A CN 200510003292 CN200510003292 CN 200510003292 CN 200510003292 A CN200510003292 A CN 200510003292A CN 1785347 A CN1785347 A CN 1785347A
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- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 1
- 230000001047 pyretic effect Effects 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- BURBOJZOZGMMQF-UHFFFAOYSA-N xanthoxylol Natural products C1=C(O)C(OC)=CC=C1C1C(COC2C=3C=C4OCOC4=CC=3)C2CO1 BURBOJZOZGMMQF-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
A quality control method for the Chinese medicine to treat infantile high fever features that a thin-layer chromatography is used for the identification to its Chinese-medicinal materials and an efficient liquid-phase chromatography is used to measure the content of forsythin.
Description
Technical field:
The present invention relates to a kind of effect of bringing down a fever that has, treat the Chinese medicine preparation method of quality control for the treatment of child hyperpyrexia, particularly relate to the method for quality control of children's antipyretic preparation such as children's antipyretic oral liquid, syrup and granule etc.
Background technology:
Children's's internal organs are tender and lovely, and skin is dredged thin, and weakened defensive QI is felt the heresy of wind heat again, or trembles with fear from transconversion into heat, so fever and aversion to wind; Hold together on the heresy of wind heat and the visitor in the lung pharyngeal swelling of then having a headache; Penting up as pyretic toxicity then has mumps swelling, diseases such as hyperpyrexia.So in a single day hyperpyrexia appears in infantile common cold, be badly in need of bringing down a fever, also need declare catharsis simultaneously, make heresy that outlet be arranged.At present, mainly contain children's antipyretic oral liquid and children's antipyretic granule agent according to above-mentioned pathology treatment infantile hyperpyrexia, list among " the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation " the 6th (WS3-B-1089-92), but because this side's Chinese medicinal components complexity, its quality control is an a great problem, prior art has only proposed the relative density inspection, and physicochemical identification there is no content's index and qualitative identification.Therefore, be necessary that method of quality control to this Chinese medicine preparation has carried out qualitative, quantitative and probed into.
Chinese medicine preparation for a long time, difficult quality is effectively controlled, the quality of effectively controlling tcm product is a great problem, the method for available technology adopting is imperfect, the minority specific aim is not strong, uses these methods to be difficult to reach the purpose of real control of quality.Above children's antipyretic preparation is difficult to control the quality of said preparation owing to lack method of quality control; Brought difficulty for normal production and operation, utilize more known technology to be difficult to the method for quality control that the said preparation product is provided, the present invention is directed to the deficiencies in the prior art, adopt new means that the quality of children's antipyretic preparation is controlled, particularly adopt with the content of phillyrin in this medicine of high effective liquid chromatography for measuring with thin layer chromatography and differentiate Chinese crude drug in the finished product, solved the difficult problem of said preparation quality control.The present invention is directed to the characteristics and the prescription of the present invention of children's antipyretic preparation, a kind of method of quality control of practicality is provided.
Summary of the invention:
The object of the present invention is to provide a kind of Chinese medicine preparation method of quality control for the treatment of treating child hyperpyrexia, method of quality control of the present invention is more effective to the quality control of product, and method precision, sensitivity, stability are all higher.This method comprises following thin layer chromatography discriminating and/or content assaying method.
The present invention be directed to a kind of Chinese medicine preparation for the treatment of treating child hyperpyrexia and propose method of quality control, said preparation specifically comprises oral liquid, granule and syrup etc.
A kind of Chinese medicine preparation for the treatment of treating child hyperpyrexia of the present invention is made by following Chinese medicine raw materials by weight proportion:
Folium Isatidis 150g, Radix Isatidis 90g, Flos Lonicerae 90g, Fructus Forsythiae 90g, Fructus Gardeniae 90g, Cortex Moutan 90g, Radix Scutellariae 90g, Herba Lophatheri 60g, Pheretima 60g, Rhizoma Paridis 45g, Radix Bupleuri 90g, Radix Cynanchi Atrati 60g and appropriate amount of auxiliary materials.
The following method that can adopt of children's antipyretic preparation of the present invention prepares:
By the raw material of Chinese medicine of above-mentioned prescription is processed through extraction or other modes, make pharmaceutically active substance, subsequently, be raw material with this material, add the medicine acceptable carrier when needing, make capsule, granule, tablet according to the routine techniques of galenic pharmacy.Described active substance can obtain by the method that is selected from following mode, as: by pulverize, squeeze, calcine, grind, sieve, percolation, extraction, water are carried, alcohol extraction, ester are carried, methods such as ketone is carried, chromatography obtain, these active substances can be the material of extractum form, can be that dry extract also can be a fluid extract, make different concentration according to the different needs decision of preparation.
Preparation of the present invention can add the medicine acceptable carrier as required when making preparation, these carriers can be any carriers that is fit to make preparation of the present invention.
Children's antipyretic preparation preferred manufacturing procedure of the present invention adopts following method:
Preparation of the present invention adopts following method to make: above raw material, Cortex Moutan, Radix Bupleuri, Fructus Forsythiae pulverizing medicinal materials to all by 45 orders, but can not be crossed 30 orders, and add water by medicated powder and water ratio 1/10, use steam distillation 2h, the collection distillate; Medicinal residues and all the other Folium Isatidis etc. nine flavor adds 10 times of decoctings and boils secondary, and each 1 hour, collecting decoction filtered, and filtrate is concentrated in right amount, adds ethanol and makes that to contain that alcohol measures be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir evenly, leave standstill, get supernatant, filter, filtrate is concentrated in right amount.Formulation method adds different adjuvants routinely, can make oral liquid, granule and syrup respectively.
Method of quality control of the present invention can be used for the Chinese medicine preparation that above method is made, and its step comprises to be differentiated and assay.
Wherein said discriminating is to utilize the particularity of the effective ingredient of Chinese medicine preparation that the composition of preparation is carried out qualitative detection, and discriminating of the present invention is that its discrimination method comprises one or more in the following method at the carrying out of Chinese medicine of the present invention:
(1) get this product, add water, use ether extraction, add water washing, get ether layer, evaporate to dryness, residue adds dissolve with methanol, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes solution, in contrast product solution.According to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000) test, draw need testing solution, reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone is developing solvent, launch, take out airing.
(2) get this product, add water, use ether extraction, abandon ether solution, the water saturated n-butanol extraction of water layer is got n-butyl alcohol liquid, adds the washing of 0.25% sodium hydroxide solution, the water washing that the reuse n-butyl alcohol is saturated, get n-butanol layer, evaporate to dryness, residue adds dissolve with methanol, as need testing solution.Other gets the Fructus Forsythiae control medicinal material, adds ethanol, puts the water-bath reflux, extract,, filters, and filtrate evaporate to dryness, residue add the dissolving of water slight fever, filter, and filtrate is used ether extraction, and remaining step is made control medicinal material solution with the test sample preparation method.Test according to (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid is developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.
(3) get this product, add water, use ethyl acetate extraction, abandon ethyl acetate liquid, the water layer n-butanol extraction is got n-butyl alcohol liquid, evaporate to dryness, and residue adds dehydrated alcohol, and supersound process filters, and filtrate evaporate to dryness, residue add acetone makes dissolving, gets supernatant as need testing solution.Other gets the jasminoidin reference substance, adds methanol and makes solution, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid is developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.
(4) get this product, add water, use ether extraction, abandon ether solution, wash with water, will wash ether extracted liquid and wave near dried, residue adds dissolve with methanol, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes solution, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate is developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.
Preferred discrimination method comprises one or more in the following method:
(1) get this product 10-25ml, add water 30-50ml, use ether extraction 1-3 time, each 15-25ml merges ether extracted liquid, adds water washing 1-3 time, and each 20-40ml gets ether layer, and evaporate to dryness, residue add methanol 1-3ml dissolving, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes the solution that every 1ml contains 1.0mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 5-10ul, reference substance solution 1-5ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone (2.5-7: 2-5: 0.8-1.3) be developing solvent, launch, take out airing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 5-15ml, add water 15-25ml, use ether extraction 1-3 time, each 15-25ml abandons ether solution, and water layer is with water saturated n-butanol extraction 1-3 time, each 15-25ml merges n-butyl alcohol liquid, adds 0.25% sodium hydroxide solution washing 1-3 time, each 15-25ml, the saturated water washing of reuse n-butyl alcohol 1-3 time, 10-30ml at every turn, get n-butanol layer, evaporate to dryness, residue add methanol 1-3ml dissolving, as need testing solution.Other gets Fructus Forsythiae control medicinal material 1.0-3.0g, add ethanol 40-60ml, put water-bath reflux, extract, 20-40min, filter the filtrate evaporate to dryness, residue adds the dissolving of water 20-40ml slight fever, filter, filtrate is used ether extraction 1-3 time, each 10-30ml, remaining step is made control medicinal material solution with the test sample preparation method.Test according to (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution 5-10ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid (10-14: 1-3: 1.9-2.8: 0.16-0.24) be developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get this product 10-30ml, add water 5-20ml, use ethyl acetate extraction 1-3 time, each 15-25ml abandons ethyl acetate liquid, water layer n-butanol extraction 1-2 time, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add dehydrated alcohol 20ml supersound process 5-15min, filter, filtrate evaporate to dryness, residue add acetone 1-3ml makes dissolving, gets supernatant 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.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 5-10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid (7-11: 2.2-2.8: 1.8-3.4: 0.17-0.24) be developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get this product 5-15ml, add water 15-25ml, use ether extraction 1-2 time, each 15-25ml abandons ether solution, washes with water 2 times, and each 20ml will wash ether extracted liquid and wave near dried, and residue adds methanol 1-3ml and dissolves, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 1-5ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (3.5-7: 0.7-1.4) be developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Preferred discrimination method comprises one or more in the following method:
(1) get this product 20ml, add water 40ml, use ether extraction 3 times, each 20ml merges ether extracted liquid, adds water washing 2 times, and each 30ml gets ether layer, and evaporate to dryness, residue add methanol 1ml dissolving, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes the solution that every 1ml contains 1.0mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 10ul, reference substance solution 5ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone (5: 4: 1) is developing solvent, launch, take out airing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 10ml, add water 20ml, use ether extraction 3 times, each 20ml abandons ether solution, and water layer is with water saturated n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, adds 0.25% sodium hydroxide solution washing 3 times, each 20ml, the saturated water washing of reuse n-butyl alcohol 2 times, each 20ml, get n-butanol layer, evaporate to dryness, residue add methanol 1ml dissolving, as need testing solution.Other gets Fructus Forsythiae control medicinal material 2.0g, adds ethanol 50ml, puts water-bath reflux, extract, 30min, filters, filtrate evaporate to dryness, residue add the dissolving of water 30ml slight fever, filter, and filtrate is used ether extraction 2 times, each 20ml, remaining step is made control medicinal material solution with the test sample preparation method.Test according to (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution 10ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid (12: 2: 2.5: 0.2) be developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get this product 20ml, add water 10ml, use ethyl acetate extraction 2 times, each 20ml abandons ethyl acetate liquid, water layer n-butanol extraction 2 times, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add dehydrated alcohol 20ml supersound process 10min, filter, filtrate evaporate to dryness, residue add acetone 2ml makes dissolving, gets supernatant 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.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid (9: 2.5: 3: 0.2) be developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get this product 10ml, add water 20ml, use ether extraction 2 times, each 20ml abandons ether solution, washes with water 2 times, and each 20ml will wash ether extracted liquid and wave near dried, and residue adds methanol 1ml and dissolves, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 5ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (5: 1) is developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Method of quality control of the present invention, also comprise the method for assay, described assay be to the phillyrin content in the pharmaceutical preparation of the present invention carry out mensuration, its method is:
Measure according to high performance liquid chromatography (an appendix VII of Chinese Pharmacopoeia version in 2000 D); Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Mobile phase: acetonitrile-water (21-27: 66-83); Flow velocity: 1.0ml/min; Column temperature: 28-32 ℃; Detect wavelength 230 ± 2nm.Theoretical cam curve is with phillyrin (C
29H
36O
15) the peak meter, should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the phillyrin reference substance, adds methanol and make the solution that every 1ml contains 0.06-0.08mg, promptly.
The preparation precision of need testing solution is measured this product 10ml under the loading amount item, add water 20ml, colourless with ether extraction to ether layer, the water intaking layer, add water saturated n-butanol extraction 6-8 time (each 30ml or 20ml), merge n-butanol extracting liquid, evaporate to dryness, residue add dissolve with methanol and are transferred in the 10ml measuring bottle, add methanol and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, put in the evaporating dish, steam near and do, add neutral alumina 1g and mix thoroughly, be added on the neutral alumina post, with 80% or 70% or 60% ethanol 120ml eluting, collect eluent, be concentrated into driedly, residue is transferred in the 5ml measuring bottle after adding dissolve with methanol, and be diluted to scale, shake up, filter with microporous filter membrane (0.45 μ m), promptly.
Accurate respectively reference substance solution and each the 2-5 μ l of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
The preferred acetonitrile-water ratio of the numerical range of above-mentioned chromatographic condition mobile phase (24: 76) is best; Column temperature is best for 30 ℃; It is best detecting wavelength 230nm.The solution that 1ml methanol contains 0.07mg phillyrin reference substance is preferably made in the preparation of reference substance solution; It is extractant that water saturated n-butyl alcohol is preferably selected in the preparation of need testing solution for use.And extract best 6 times (30ml, 20ml, 20ml, 20ml, 20ml, 20ml), the neutral alumina post that adds is preferably 200～300 orders, 2g, internal diameter 1.5cm can extract phillyrin fully, on sample, in the elution process of alumina column, select for use 80% ethanol 120ml to make the eluant eluting for best.
Method of quality control of the present invention is more effective to the quality control of product, and method precision, sensitivity, stability are all higher.
The above preparation is oral liquid, syrup and granule preferably.Described granule, every 1g contain Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
, every of described oral liquid contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
, the every 10ml of described syrup contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
The above this product is oral liquid, syrup and granule, for solid preparation, it need be dissolved in the solvent during mensuration, and as test liquid, conventional method is to get granule 1-10g and add the 10-100ml dissolution with solvents.
The used preparation of each experimental example test sample of the present invention all can adopt embodiment 1,2 and 3 described oral liquids, syrup and granule, also can have other preparations that same materials is formed with the described oral liquid of the foregoing description, syrup and granule.
Below be the experimental example of method of quality control of the present invention, be used to further specify.
Experimental example 1Quality control method of the present invention is to the research of preparation ingredient assay
" children's antipyretic preparation " is to be formed by 12 flavor Chinese prescriptions, through each flavor medical material is carried out data consultation, and in conjunction with the preparation technology of this medicine, carried out in the Flos Lonicerae in chlorogenic acid, the Fructus Forsythiae quantity research that contains of jasminoidin in the phillyrin and Fructus Gardeniae.
Flos Lonicerae mainly contains compositions such as chlorogenic acid, isochlorogenic acid, volatile oil and trace element.In the assay research process of preparation, we once carried out assay to chlorogenic acid in many batch samples, but because the Fructus Gardeniae medical material also contains chlorogenic acid, negative sample has interference in its system suitability test, so determination of chlorogenic acid is not listed in the quality standard text.
Fructus Gardeniae mainly contains organic acid such as pigments such as iridoid glycosides, gardenin, crocins such as jasminoidin and chlorogenic acid.To the assay of Fructus Gardeniae, what bibliographical information was more is the assay of jasminoidin in the Fructus Gardeniae, adopts high performance liquid chromatography more.Follow the trail of according to technology, find that jasminoidin loss behind decoction and precipitate with ethanol is bigger, total recovery is about 18%, so do not carry out the assay of jasminoidin in the Fructus Gardeniae.
Take all factors into consideration above factor, the content of phillyrin in the high effective liquid chromatography for measuring Fructus Forsythiae is adopted in decision.
Experimental example 2The content assaying method research of phillyrin
According to documents and materials, mainly contain compositions such as phillyrin, forsythol, Fructus Forsythiae ester glycoside, oleanolic acid, pinoresinol, Camphora, Borneolum Syntheticum in the Fructus Forsythiae.To the assay of Fructus Forsythiae, what bibliographical information was more is the assay of phillyrin in the Fructus Forsythiae, and its content assaying method has high performance liquid chromatography, thin layer chromatography scanning, thin layer-spectrophotometric to send out etc.With reference to relevant documents and materials, the content of phillyrin in the preparation is measured, and method for measuring is investigated.
7.1 Tianjin, instrument island LC-10Atvp high performance liquid chromatograph, the LC-10Atvp infusion pump; SPD-M10Avp secondary array detector; The SCL-10Avp system controller; CTO-10Asvp thermocolumn case; The CLASS-VP6.1 workstation data processing system; Microsyringe (25 μ L), HAMILTON company; Ultrasonic washing unit (250W, Beijing's armarium two factories).
7.2 reagent ether (analytical pure), n-butyl alcohol (analytical pure), methanol (analytical pure), ethanol (analytical pure), acetonitrile (chromatograph alcohol), water is double distilled water, (Nat'l Pharmaceutical ﹠ Biological Products Control Institute provides the phillyrin reference substance, for assay usefulness, lot number: 0821-200104).
7.3 chromatographic condition chromatographic column: Hypersil ODS2 (5.0 * 200mm) spies of Dalian Erie; Mobile phase: acetonitrile-water (24: 76); Detect wavelength: 230nm; Flow velocity: 1.0ml/min; Column temperature: 30 ℃; Sample size: 5 μ l.
7.4 system suitability test
The negative need testing solution of getting phillyrin reference substance solution, need testing solution and scarce Fructus Forsythiae medical material respectively injects chromatograph of liquid, the record chromatograph.As seen from the figure, the retention time (t of phillyrin
R) being about 13 minutes, the negative sample chromatogram is at non-false positive peak, place, phillyrin peak position, and phillyrin separates fully (separating degree＞1.5) with close impurity peaks, and promptly phillyrin separates with other components fully under this experiment condition.Theoretical cam curve is calculated as 7000 with the phillyrin peak.
7.5 linear relationship is investigated
7.5.1 the preparation of standard solution
Precision takes by weighing phillyrin reference substance 14.24mg, puts in the 100ml measuring bottle, adds methanol to scale, shakes up, and makes phillyrin standard solution (0.1424mg/ml).
7.5.2 the drafting of standard curve
Accurate phillyrin standard solution 2.0,4.0,6.0,8.0ml, the 10.0ml that draws 0.1424mg/ml puts respectively in the 10ml measuring bottle, adds methanol constant volume to scale, shakes up.Accurate respectively each the 5 μ l of above-mentioned five kinds of solution that draw inject chromatograph of liquid, record chromatograph (table 1), with peak area A (μ Vs) mass number X (μ g) being carried out linear regression calculates, getting equation of linear regression is: A=2714056.18 * X+6622.80, and r=0.99998, precision is measured the standard solution 5.0ml of 0.1424mg/ml, put in the 10ml measuring bottle, add methanol to scale, shake up, get reference substance solution (0.0712mg/ml).Precision is measured this reference substance solution 5 μ l and is injected chromatograph of liquid, the gained peak area is 974638, one need testing solution sample introduction is analyzed the gained peak area calculate content with regression equation and one point method respectively, result's relative deviation is 0.11%, so the present invention adopts one point method to calculate content.The phillyrin range of linearity: 0.1424 μ g～0.712 μ g.
Table 1 phillyrin linear relationship is investigated
| Phillyrin sample size (μ g) | Phillyrin peak area (μ Vs) |
| 0.1424 0.2848 0.4272 0.5696 0.712 | 392656 776721 1172533 1550007 1938421 |
Phillyrin is insoluble to ether 7.6 extractant is selected, and in the sample treatment process, removes partial impurities with ether earlier, after to select the ethyl acetate and the n-butyl alcohol that are usually used in extracting glycoside respectively for use be extracting solution, through multiple extraction back mensuration content, measurement result sees Table 2.Result of the test shows, is that extractant can extract phillyrin fully with water saturated n-butyl alcohol, thus the present invention to select water saturated n-butyl alcohol for use be extractant.
The different influences (n=2) of extracting solvent of table 2 to the phillyrin assay
| Extracting method | Ethyl acetate | Water saturated n-butyl alcohol |
| Content (mg/ml) RSD (%) | 0.0395 2.51 | 0.0723 1.37 |
7.7 the extraction time of extracting solution and phillyrin assay result investigate and get " children's antipyretic oral liquid " sample, and be colourless to ether layer with ether extraction, adds water saturated n-butanol extraction, its extraction time and phillyrin assay the results are shown in Table 3.
The assay result (n=2) of table 3 extraction time and phillyrin
| Extraction time | 4 | 5 | 6 | 7 | 8 |
| Content (mg/ml) RSD (%) | 0.0644 3.65 | 0.0709 2.31 | 0.0726 1.36 | 0.0722 2.06 | 0.0729 2.43 |
Extract as seen from the table 6 times with 7 times, 8 times there was no significant difference as a result, prove that extracting 6 times can extract phillyrin fully, therefore is decided to be extraction time 6 times in quality standard of the present invention.
7.8 the selection of eluant
Dissolve in alcoholic acid character per sample, on sample, in the elution process of alumina column, select for use Different concentrations of alcohol 120ml to carry out eluting respectively, collect eluent, standardize solution filters (0.45 μ m), sampling and measuring phillyrin content, its assay the results are shown in Table 4.
The different eluant of table 4 are to the influence (n=2) of phillyrin assay in the preparation
| Eluant | Dehydrated alcohol | 90% ethanol | 80% ethanol | 70% ethanol | 60% ethanol |
| Content (mg/ml) RSD (%) | 0.0332 3.83 | 0.0623 2.61 | 0.0724 1.76 | 0.0721 2.16 | 0.0727 2.24 |
As seen from Table 4, the ethanol of employing 80%, 70%, 60% all can be complete with phillyrin eluting in the preparation, but therefore 70% and 60% ethanol select for use 80% ethanol to make eluant because water content is higher, and the impurity that eluting goes out is more, and phillyrin peak separating degree is relatively poor.
7.9 precision test
Chromatographic condition under the assay item in the quality standard of the present invention, accurate phillyrin reference substance solution (0.0712mg/ml) the 5 μ l that draw inject chromatograph of liquid, measure peak area, repeat sample introduction 5 times, the result lists table 5 in, average peak area is 974977, and RSD is 0.53%.
The precision test of table 5 phillyrin reference substance
| The sample introduction number of times | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Peak area | 974638 | 968693 | 975645 | 973002 | 982908 | 974977 | 0.53 |
7.10 repeatability test
Precision is measured this product 10ml, and by 5 parts of test liquids of preparation method preparation of test liquid under the assay item in the quality standard of the present invention, sample introduction is measured peak area respectively, and result of calculation is listed table 6 in, and average content is 0.0731mg/ml, and RSD is 1.05%.
The repeatability of phillyrin test in the table 6 preparation test sample
| The sample introduction number of times | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Content (mg/ml) | 0.0731 | 0.0718 | 0.0736 | 0.0733 | 0.0737 | 0.0731 | 1.05 |
7.11 stability test
Precision is measured this product 10ml, in the quality standard of the present invention under the assay item preparation method of test liquid prepare test liquid, measure the phillyrin peak area respectively at 0,1,2,4,8 hour, the result lists table 7 in, the result shows that test sample is good at 8 hours internal stabilities.
The stability test of phillyrin in the table 7 preparation test sample
| The sample introduction number of times | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Peak area | 1003429 | 990826 | 1003239 | 1004843 | 1004623 | 1001392 | 0.59 |
7.12 recovery test
Adopt the application of sample absorption method, precision is measured 5 parts of each 5ml of sample (average content is 0.0731mg/ml) that measured content, and accurate respectively adding phillyrin reference substance solution is (with water as solvent, 0.01748mg/ml) 20ml, shake up, colourless with ether extraction to ether layer, the water intaking layer, add 6 (30ml of water saturated n-butanol extraction, 20ml, 20ml, 20ml, 20ml, 20ml), merge n-butanol extracting liquid, evaporate to dryness, residue add dissolve with methanol and are transferred in the 10ml measuring bottle, add methanol and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, put in the evaporating dish, steam near and do, add neutral alumina 1g and mix thoroughly, be added on neutral alumina post (200～300 orders, 2g, internal diameter 1.5cm) on,, collects eluent with 80% ethanol 120ml eluting, be concentrated into dried, residue is transferred in the 5ml measuring bottle after adding dissolve with methanol, and is diluted to scale, shakes up, filter with microporous filter membrane (0.45 μ m), make test liquid.Accurate respectively each the 5 μ l of above-mentioned 5 duplicate samples that draw inject chromatograph of liquid, and the record chromatograph is measured content, and calculate recovery rate (the results are shown in Table 8.Average recovery rate is 99.40%, and RSD is 2.17%.
The recovery test of phillyrin in the table 8 preparation test sample
| Test number (TN) | Sample size (ml) | Contain phillyrin (mg) | Add phillyrin (mg) | The amount of recording (mg) | The response rate (%) | Average recovery rate (%) | RSD (％) |
| 1 2 | 5 5 | 0.3655 0.3655 | 0.7026 0.7119 | 96.42 99.08 |
| 3 4 5 | 5 5 5 | 0.3655 0.3655 0.3655 | 0.3496 | 0.7102 0.7220 0.7182 | 98.60 102.0 100.9 | 99.40 | 2.17 |
7.13 sample determination
Prepare need testing solution and reference substance solution by quality standard of the present invention, sample introduction 5 μ l write down chromatograph respectively, measure peak area, are calculated as follows content:
In the formula: Ai: the need testing solution peak area
As: reference substance solution peak area
Cs: reference substance solution concentration (mg/ml)
L: test sample sampling amount (10ml)
Phillyrin assay result (seeing Table 9) in 3 batch samples
Phillyrin assay result (n=2) in table 93 batch samples
| Lot number | Content (mg/ml) | Average content (mg/ml) | |
| 1 | 2 | ||
| 031107 031108 031109 | 0.0720 0.0766 0.0775 | 0.0707 0.0750 0.0767 | 0.0714 0.0758 0.0771 |
According to many batches of lab scales and three crowdes of pilot scale sample determination results, the decoction yield of phillyrin, precipitate with ethanol yield and water precipitating yield are respectively about 75%, 60%, 75% in the sample, so the phillyrin content limit is calculated as follows in the preparation:
Phillyrin content limit=preparation contains Fructus Forsythiae medical material (mg/ml) * medical material and contains phillyrin limit (pharmacopeia regulation) * yield * every loading amount (ml)=90000/1000 * 0.15% * 75% * 60% * 75% * 10=0.456mg.
So every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
The specific embodiment:
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1A kind of oral liquid method of quality control for the treatment of treating child hyperpyrexia
[prescription] Folium Isatidis 150g, Radix Isatidis 90g, Flos Lonicerae 90g, Fructus Forsythiae 90g, Fructus Gardeniae 90g, Cortex Moutan 90g, Radix Scutellariae 90g, Herba Lophatheri 60g, Pheretima 60g, Rhizoma Paridis 45g, Radix Bupleuri 90g, Radix Cynanchi Atrati 60g, aspartame 400g, carboxymethyl cellulose sodium 8g and sodium benzoate 1g
[method for making] above 12 flavors to all by 45 orders, but can not be crossed 30 orders with Cortex Moutan, Radix Bupleuri, Fructus Forsythiae pulverizing medicinal materials, add water by medicated powder and water ratio 1/10, promptly add water 2700ml, use steam distillation 2h, the collection distillate; Medicinal residues and all the other Folium Isatidis etc. nine flavor adds water 7350ml and decocts secondary, and each 1 hour, collecting decoction filtered, and filtrate is concentrated in right amount, adds ethanol and makes that to contain that alcohol measures be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into 200ml, add water and stir evenly, leave standstill, get supernatant, filter, filtrate is concentrated in right amount.Other gets aspartame and makes syrup, merges with above-mentioned medicinal liquid and distillate, adds carboxymethyl cellulose sodium, sodium benzoate again, adjusts total amount to 1000ml, stirs evenly filtration, fill, and by every 10ml packing, sterilization, promptly.
This product 20ml is got in [discriminating] (1), adds water 40ml, uses ether extraction 3 times, and each 20ml merges ether extracted liquid, adds water washing 2 times, and each 30ml gets ether layer, and evaporate to dryness, residue add methanol 1ml dissolving, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes the solution that every 1ml contains 1.0mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 10ul, reference substance solution 5ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone (5: 4: 1) is developing solvent, launch, take out airing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 10ml, add water 20ml, use ether extraction 3 times, each 20ml abandons ether solution, and water layer is with water saturated n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, adds 0.25% sodium hydroxide solution washing 3 times, each 20ml, the saturated water washing of reuse n-butyl alcohol 2 times, each 20ml, get n-butanol layer, evaporate to dryness, residue add methanol 1ml dissolving, as need testing solution.Other gets Fructus Forsythiae control medicinal material 2.0g, adds ethanol 50ml, puts water-bath reflux, extract, 30min, filters, filtrate evaporate to dryness, residue add the dissolving of water 30ml slight fever, filter, and filtrate is used ether extraction 2 times, each 20ml, remaining step is made control medicinal material solution with the test sample preparation method.Test according to (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution 10ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid (12: 2: 2.5: 0.2) be developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get this product 20ml, add water 10ml, use ethyl acetate extraction 2 times, each 20ml abandons ethyl acetate liquid, water layer n-butanol extraction 2 times, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add dehydrated alcohol 20ml supersound process 10min, filter, filtrate evaporate to dryness, residue add acetone 2ml makes dissolving, gets supernatant 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.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid (9: 2.5: 3: 0.2) be developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get this product 10ml, add water 20ml, use ether extraction 2 times, each 20ml abandons ether solution, washes with water 2 times, and each 20ml will wash ether extracted liquid and wave near dried, and residue adds methanol 1ml and dissolves, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 5ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-methanol-ethyl acetate (5: 1) is developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The assay of [assay] phillyrin: measure according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 D).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Mobile phase: acetonitrile-water (24: 76); Flow velocity: 1.0ml/min; Column temperature: 30 ℃; Detect wavelength 230nm.Theoretical cam curve is with phillyrin (C
29H
36O
15) the peak meter, should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the phillyrin reference substance, adds methanol and make the solution that every 1ml contains 0.07mg, promptly.
The preparation precision of need testing solution is measured this product 10ml under the loading amount item, adds water 20ml, and is colourless to ether layer with ether extraction, the water intaking layer adds 6 (30ml of water saturated n-butanol extraction, 20ml, 20ml, 20ml, 20ml, 20ml), merge n-butanol extracting liquid, evaporate to dryness, residue adds dissolve with methanol and is transferred in the 10ml measuring bottle, adds methanol and is diluted to scale, shakes up, filter, precision is measured subsequent filtrate 5ml, puts in the evaporating dish, steams near and does, adding neutral alumina 1g mixes thoroughly, be added on the neutral alumina post (200～300 orders, 2g, internal diameter 1.5cm), with 80% ethanol 120ml eluting, collect eluent, be concentrated into driedly, residue is transferred in the 5ml measuring bottle after adding dissolve with methanol, and be diluted to scale, shake up, filter with microporous filter membrane (0.45 μ m), promptly.
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
Embodiment 2A kind of syrup method of quality control for the treatment of treating child hyperpyrexia
[prescription] Folium Isatidis 150g, Radix Isatidis 90g, Flos Lonicerae 90g, Fructus Forsythiae 90g, Fructus Gardeniae 90g, Cortex Moutan 90g, Radix Scutellariae 90g, Herba Lophatheri 60g, Pheretima 60g, Rhizoma Paridis 45g, Radix Bupleuri 90g, Radix Cynanchi Atrati 60g, sucrose 400g, carboxymethyl cellulose sodium 8g and sodium benzoate 1g
[method for making] above 12 flavors to all by 45 orders, but can not be crossed 30 orders with Cortex Moutan, Radix Bupleuri, Fructus Forsythiae pulverizing medicinal materials, add water by medicated powder and water ratio 1/10, promptly add water 2700ml, use steam distillation 2h, the collection distillate; Medicinal residues and all the other Folium Isatidis etc. nine flavor adds water 7350ml and decocts secondary, and each 1 hour, collecting decoction filtered, and filtrate is concentrated in right amount, adds ethanol and makes that to contain that alcohol measures be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into 200ml, add water and stir evenly, leave standstill, get supernatant, filter, filtrate is concentrated in right amount.Other gets sucrose 400g and makes simple syrup, merges with above-mentioned medicinal liquid and distillate, adds carboxymethyl cellulose sodium, sodium benzoate again, adjusts total amount to 1000ml, stirs evenly filtration, fill, and by every 10ml packing, sterilization, promptly.
[method of quality control]
Discriminating, content assaying method are with embodiment 1, and wherein every contains Radix Glycyrrhizae with glycyrrhizic acid (C
42H
62O
16) must not count and be less than 4.38mg.
Embodiment 3Children's antipyretic granule
[prescription] Folium Isatidis 150g, Radix Isatidis 90g, Flos Lonicerae 90g, Fructus Forsythiae 90g, Fructus Gardeniae 90g, Cortex Moutan 90g, Radix Scutellariae 90g, Herba Lophatheri 60g, Pheretima 60g, Rhizoma Paridis 45g, Radix Bupleuri 90g, Radix Cynanchi Atrati 60g, sucrose 400g, carboxymethyl cellulose sodium 8g and sodium benzoate 1g
[method for making] above 12 flavors to all by 45 orders, but can not be crossed 30 orders with Cortex Moutan, Radix Bupleuri, Fructus Forsythiae pulverizing medicinal materials, add water by medicated powder and water ratio 1/10, promptly add water 2700ml, use steam distillation 2h, the collection distillate; Medicinal residues and all the other Folium Isatidis etc. nine flavor adds water 7350ml and decocts secondary, and each 1 hour, collecting decoction filtered, and filtrate is concentrated in right amount, adds ethanol and makes that to contain that alcohol measures be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into 200ml, add water and stir evenly, leave standstill, get supernatant, filter, be condensed into the extractum of relative density about 1.20 (50 ℃).With an amount of sucrose and above-mentioned extractum mixing, drying is pulverized in addition, granulate, and oven dry, mixing is made granule 1000g, packing, promptly.
[method of quality control] discriminating, content assaying method are with embodiment 1, and wherein every gram granule contains Radix Glycyrrhizae with glycyrrhizic acid (C
42H
62O
16) must not count and be less than 4.38mg.
[assay] measured according to high performance liquid chromatography (an appendix VII of Chinese Pharmacopoeia version in 2000 D).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Mobile phase: acetonitrile-water (24: 76); Flow velocity: 1.0ml/min; Column temperature: 30 ℃; Detect wavelength 230nm.Theoretical cam curve is with phillyrin (C
29H
36O
15) the peak meter, should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the phillyrin reference substance, adds methanol and make the solution that every 1ml contains 0.07mg, promptly.
The preparation precision of need testing solution is measured this product 10ml under the loading amount item, adds water 20ml, and is colourless to ether layer with ether extraction, the water intaking layer adds 6 (30ml of water saturated n-butanol extraction, 20ml, 20ml, 20ml, 20ml, 20ml), merge n-butanol extracting liquid, evaporate to dryness, residue adds dissolve with methanol and is transferred in the 10ml measuring bottle, adds methanol and is diluted to scale, shakes up, filter, precision is measured subsequent filtrate 5ml, puts in the evaporating dish, steams near and does, adding neutral alumina 1g mixes thoroughly, be added on the neutral alumina post (200～300 orders, 2g, internal diameter 1.5cm), with 80% ethanol 120ml eluting, collect eluent, be concentrated into driedly, residue is transferred in the 5ml measuring bottle after adding dissolve with methanol, and be diluted to scale, shake up, filter with microporous filter membrane (0.45 μ m), promptly.
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
Embodiment 4A kind of syrup method of quality control for the treatment of treating child hyperpyrexia
[prescription] Folium Isatidis 150g, Radix Isatidis 90g, Flos Lonicerae 90g, Fructus Forsythiae 90g, Fructus Gardeniae 90g, Cortex Moutan 90g, Radix Scutellariae 90g, Herba Lophatheri 60g, Pheretima 60g, Rhizoma Paridis 45g, Radix Bupleuri 90g, Radix Cynanchi Atrati 60g, aspartame 400g, carboxymethyl cellulose sodium 8g and sodium benzoate 1g
[method for making] above 12 flavors to all by 45 orders, but can not be crossed 30 orders with Cortex Moutan, Radix Bupleuri, Fructus Forsythiae pulverizing medicinal materials, add water by medicated powder and water ratio 1/10, promptly add water 2700ml, use steam distillation 2h, the collection distillate; Medicinal residues and all the other Folium Isatidis etc. nine flavor adds water 7350ml and decocts secondary, and each 1 hour, collecting decoction filtered, and filtrate is concentrated in right amount, adds ethanol and makes that to contain that alcohol measures be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into 200ml, add water and stir evenly, leave standstill, get supernatant, filter, filtrate is concentrated in right amount.Other gets aspartame and makes syrup, merges with above-mentioned medicinal liquid and distillate, adds carboxymethyl cellulose sodium, sodium benzoate again, adjusts total amount to 1000ml, stirs evenly filtration, fill, and by every 10ml packing, sterilization, promptly.
This product 10ml is got in [method of quality control] (1), adds water 30ml, uses the 15ml ether extraction, gets ether extracted liquid, adds the 20ml water washing, gets ether layer, and evaporate to dryness, residue add methanol 1ml dissolving, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes the solution that every 1ml contains 1.0mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 5ul, reference substance solution 1ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone (2.5: 2: 0.8) is developing solvent, launch, take out airing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 5ml, add water 15ml, use the 15ml ether extraction, abandon ether solution, water layer is got n-butyl alcohol liquid with the water saturated n-butanol extraction of 15ml, adds the washing of 15ml0.25% sodium hydroxide solution, the saturated water washing of reuse n-butyl alcohol 2 times, each 20ml gets n-butanol layer, evaporate to dryness, residue adds methanol 1ml dissolving, as need testing solution.Other gets Fructus Forsythiae control medicinal material 1.0g, adds ethanol 40ml, puts water-bath reflux, extract, 20min, filters, filtrate evaporate to dryness, residue add the dissolving of water 20ml slight fever, filter, and filtrate is used ether extraction 3 times, each 10ml, remaining step is made control medicinal material solution with the test sample preparation method.Test according to (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution 5ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid (10: 1: 1.9: 0.16) be developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get this product 10ml, add water 5ml, use ethyl acetate extraction 2 times, each 20ml, abandon ethyl acetate liquid, water layer 20ml n-butanol extraction is got n-butyl alcohol liquid, evaporate to dryness, residue adds dehydrated alcohol 20ml supersound process 5min, filters the filtrate evaporate to dryness, residue adds acetone 1ml makes dissolving, gets supernatant 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.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 5ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid (7: 2.2: 1.8: 0.17) be developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get this product 5ml, add water 15ml, use the 15ml ether extraction, abandon ether solution, wash with water 2 times, each 20ml will wash ether extracted liquid and wave near dried, and residue adds methanol 3ml dissolving, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 1ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (3.5: 0.7) is developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
[assay] measured according to high performance liquid chromatography (an appendix VII of Chinese Pharmacopoeia version in 2000 D).
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Mobile phase: acetonitrile-water (21: 66); Flow velocity: 1.0ml/min; Column temperature: 28 ℃; Detect wavelength 228nm.Theoretical cam curve is with phillyrin (C
29H
36O
15) the peak meter, should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the phillyrin reference substance, adds methanol and make the solution that every 1ml contains 0.06mg, promptly.
The preparation precision of need testing solution is measured this product 10ml under the loading amount item, adds water 20ml, and is colourless to ether layer with ether extraction, the water intaking layer adds water saturated n-butanol extraction 7 times (each 30ml), merges n-butanol extracting liquid, evaporate to dryness, residue add dissolve with methanol and are transferred in the 10ml measuring bottle, add methanol and are diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, put in the evaporating dish, steam near and do, add neutral alumina 1g and mix thoroughly, be added on the neutral alumina post, with 70% ethanol 120ml eluting, collect eluent, be concentrated into driedly, residue is transferred in the 5ml measuring bottle after adding dissolve with methanol, and be diluted to scale, shake up, filter with microporous filter membrane (0.45 μ m), promptly.
Accurate respectively reference substance solution and each the 2 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
Embodiment 5A kind of granule method of quality control for the treatment of treating child hyperpyrexia
Folium Isatidis 150g, Radix Isatidis 90g, Flos Lonicerae 90g, Fructus Forsythiae 90g, Fructus Gardeniae 90g, Cortex Moutan 90g, Radix Scutellariae 90g, Herba Lophatheri 60g, Pheretima 60g, Rhizoma Paridis 45g, Radix Bupleuri 90g, Radix Cynanchi Atrati 60g, sucrose 400g, carboxymethyl cellulose sodium 8g and sodium benzoate 1g
[method for making] above 12 flavors to all by 45 orders, but can not be crossed 30 orders with Cortex Moutan, Radix Bupleuri, Fructus Forsythiae pulverizing medicinal materials, add water by medicated powder and water ratio 1/10, promptly add water 2700ml, use steam distillation 2h, the collection distillate; Medicinal residues and all the other Folium Isatidis etc. nine flavor adds water 7350ml and decocts secondary, and each 1 hour, collecting decoction filtered, and filtrate is concentrated in right amount, adds ethanol and makes that to contain that alcohol measures be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into 200ml, add water and stir evenly, leave standstill, get supernatant, filter, be condensed into the extractum of relative density about 1.20 (50 ℃).With an amount of sucrose and above-mentioned extractum mixing, drying is pulverized in addition, granulate, and oven dry, mixing is made granule 1000g, packing, promptly.
[method of quality control] discrimination method comprises one or more in the following method:
(1) get this product 25ml, add water 50ml, use ether extraction 3 times, each 25ml merges ether extracted liquid, adds water washing 3 times, and each 40ml gets ether layer, and evaporate to dryness, residue add methanol 3ml dissolving, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes the solution that every 1ml contains 1.0mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 10ul, reference substance solution 5ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone (7: 5: 1.3) is developing solvent, launch, take out airing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 15ml, add water 25ml, use ether extraction 3 times, each 25ml abandons ether solution, and water layer is with water saturated n-butanol extraction 3 times, each 25ml merges n-butyl alcohol liquid, adds 0.25% sodium hydroxide solution washing 3 times, each 25ml, the saturated water washing of reuse n-butyl alcohol 3 times, each 30ml, get n-butanol layer, evaporate to dryness, residue add methanol 3ml dissolving, as need testing solution.Other gets Fructus Forsythiae control medicinal material 3.0g, adds ethanol 60ml, puts water-bath reflux, extract, 40min, filters, filtrate evaporate to dryness, residue add the dissolving of water 40ml slight fever, filter, and filtrate is used ether extraction 3 times, each 30ml, remaining step is made control medicinal material solution with the test sample preparation method.Test according to (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution 10ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid (14: 3: 2.8: 0.24) be developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get this product 30ml, add water 20ml, use ethyl acetate extraction 3 times, each 25ml abandons ethyl acetate liquid, water layer n-butanol extraction 2 times, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add dehydrated alcohol 20ml supersound process 15min, filter, filtrate evaporate to dryness, residue add acetone 3ml makes dissolving, gets supernatant 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.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid (11: 2.8: 3.4: 0.24) be developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get this product 15ml, add water 25ml, use ether extraction 2 times, each 25ml abandons ether solution, washes with water 2 times, and each 20ml will wash ether extracted liquid and wave near dried, and residue adds methanol 3ml and dissolves, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 5ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (7: 1.4) is developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
[assay] chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Mobile phase: acetonitrile-water (27: 83); Flow velocity: 1.0ml/min; Column temperature: 32 ℃; Detect wavelength 232nm.Theoretical cam curve is with phillyrin (C
29H
36O
15) the peak meter, should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the phillyrin reference substance, adds methanol and make the solution that every 1ml contains 0.08mg, promptly.
The preparation precision of need testing solution is measured this product 10ml under the loading amount item, adds water 20ml, and is colourless to ether layer with ether extraction, the water intaking layer adds water saturated n-butanol extraction 8 times (each 20ml), merges n-butanol extracting liquid, evaporate to dryness, residue add dissolve with methanol and are transferred in the 10ml measuring bottle, add methanol and are diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, put in the evaporating dish, steam near and do, add neutral alumina 1g and mix thoroughly, be added on the neutral alumina post, with 60% ethanol 120ml eluting, collect eluent, be concentrated into driedly, residue is transferred in the 5ml measuring bottle after adding dissolve with methanol, and be diluted to scale, shake up, filter with microporous filter membrane (0.45 μ m), promptly.
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Every of this product contains Fructus Forsythiae with phillyrin (C
29H
36O
15) meter, must not be less than 0.456mg.
Embodiment 6A kind of oral liquid method of quality control for the treatment of treating child hyperpyrexia
[prescription] Folium Isatidis 150g, Radix Isatidis 90g, Flos Lonicerae 90g, Fructus Forsythiae 90g, Fructus Gardeniae 90g, Cortex Moutan 90g, Radix Scutellariae 90g, Herba Lophatheri 60g, Pheretima 60g, Rhizoma Paridis 45g, Radix Bupleuri 90g, Radix Cynanchi Atrati 60g, aspartame 400g, carboxymethyl cellulose sodium 8g and sodium benzoate 1g
[method for making] is with embodiment 1
[method of quality control]
Discrimination method comprises one or more in the following method:
(1) get this product 20ml, add water 45ml, use ether extraction 2 times, each 20ml merges ether extracted liquid, adds water washing 2 times, and each 35ml gets ether layer, and evaporate to dryness, residue add methanol 2.5ml dissolving, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes the solution that every 1ml contains 1.0mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 8ul, reference substance solution 4ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone (6: 4.0: 1.2) is developing solvent, launch, take out airing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 8ml, add water 25ml, use ether extraction 2 times, each 18ml abandons ether solution, and water layer is with water saturated n-butanol extraction 2 times, each 18ml merges n-butyl alcohol liquid, adds 0.25% sodium hydroxide solution washing 2 times, each 20ml, the saturated water washing of reuse n-butyl alcohol 2 times, each 25ml, get n-butanol layer, evaporate to dryness, residue add methanol 2ml dissolving, as need testing solution.Other gets Fructus Forsythiae control medicinal material 2.5g, adds ethanol 55ml, puts water-bath reflux, extract, 35min, filters, filtrate evaporate to dryness, residue add the dissolving of water 35ml slight fever, filter, and filtrate is used ether extraction 2 times, each 25ml, remaining step is made control medicinal material solution with the test sample preparation method.Test according to (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of solution 8ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid (13: 2.5: 2.6: 0.19) be developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(3) get this product 25ml, add water 18ml, use ethyl acetate extraction 2 times, each 20ml abandons ethyl acetate liquid, water layer n-butanol extraction 2 times, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add dehydrated alcohol 20ml supersound process 8min, filter, filtrate evaporate to dryness, residue add acetone 2ml makes dissolving, gets supernatant 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.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 8ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid (9: 2.7: 3.0: 0.19) be developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(4) get this product 10ml, add water 15ml, use ether extraction 1 time, each 20ml abandons ether solution, washes with water 2 times, and each 20ml will wash ether extracted liquid and wave near dried, and residue adds methanol 2ml and dissolves, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw above-mentioned two kinds of each 4ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate (6: 1.2) is developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Measure according to high performance liquid chromatography (an appendix VII of Chinese Pharmacopoeia version in 2000 D); Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Mobile phase: acetonitrile-water (26: 80); Flow velocity: 1.0ml/min; Column temperature: 29 ℃; Detect wavelength 231nm.Theoretical cam curve is with phillyrin (C
29H
36O
15) the peak meter, should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the phillyrin reference substance, adds methanol and make the solution that every 1ml contains 0.065mg, promptly.
The preparation precision of need testing solution is measured this product 10ml under the loading amount item, adds water 20ml, and is colourless to ether layer with ether extraction, the water intaking layer adds water saturated n-butanol extraction 7 times (each 25ml), merges n-butanol extracting liquid, evaporate to dryness, residue add dissolve with methanol and are transferred in the 10ml measuring bottle, add methanol and are diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, put in the evaporating dish, steam near and do, add neutral alumina 1g and mix thoroughly, be added on the neutral alumina post, with 80% ethanol 120ml eluting, collect eluent, be concentrated into driedly, residue is transferred in the 5ml measuring bottle after adding dissolve with methanol, and be diluted to scale, shake up, filter with microporous filter membrane (0.45 μ m), promptly.
Accurate respectively reference substance solution and each the 4 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Claims (9)
1, a kind of method of quality control of children's antipyretic preparation is characterized in that, it is characterized in that, comprises the step of discriminating and assay.
2, the method for claim 1 is characterized in that, described children's antipyretic preparation is an oral formulations.
3, the method for claim 2 is characterized in that, described oral formulations is an oral liquid, syrup or granule.
4, the method for claim 1 is characterized in that, described discrimination method is selected from one or more in the following method:
A. get this product, add water, use ether extraction, add water washing, get ether layer, evaporate to dryness, residue adds dissolve with methanol, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes solution, in contrast product solution; According to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography test, draw need testing solution, reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone is developing solvent, launch, take out airing;
B. get this product, add water, use ether extraction, abandon ether solution, the water saturated n-butanol extraction of water layer is got n-butyl alcohol liquid, adds the washing of 0.25% sodium hydroxide solution, the water washing that the reuse n-butyl alcohol is saturated, get n-butanol layer, evaporate to dryness, residue adds dissolve with methanol, as need testing solution.Other gets the Fructus Forsythiae control medicinal material, adds ethanol, puts the water-bath reflux, extract,, filters, and filtrate evaporate to dryness, residue add the dissolving of water slight fever, filter, and filtrate is used ether extraction, and remaining step is made control medicinal material solution with the test sample preparation method; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid is developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing;
C. get this product, add water, use ethyl acetate extraction, abandon ethyl acetate liquid, the water layer n-butanol extraction is got n-butyl alcohol liquid, evaporate to dryness, and residue adds dehydrated alcohol, and supersound process filters, and filtrate evaporate to dryness, residue add acetone makes dissolving, gets supernatant as need testing solution.Other gets the jasminoidin reference substance, adds methanol and makes solution, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid is developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing;
D. get this product, add water, use ether extraction, abandon ether solution, wash with water, will wash ether extracted liquid and wave near dried, residue adds dissolve with methanol, as need testing solution; Other gets the paeonol reference substance, adds methanol and makes solution, in contrast product solution.Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate is developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing;
The method of wherein said assay, step is as follows:
According to an appendix VII of Chinese Pharmacopoeia version in 2000 D high effective liquid chromatography for measuring; Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Mobile phase: acetonitrile-water 21-27: 66-83; Flow velocity: 1.0ml/min; Column temperature: 28-32 ℃; Detect wavelength 230 ± 2nm; Theoretical cam curve is with phillyrin C
29H
36O
15The peak meter should be not less than 3000;
It is an amount of that the preparation precision of reference substance solution takes by weighing the phillyrin reference substance, adds methanol and make the solution that every 1ml contains 0.06-0.08mg, promptly;
The preparation precision of need testing solution is measured this product 10ml under the loading amount item, adds water 20ml, and is colourless to ether layer with ether extraction, the water intaking layer, add water saturated n-butanol extraction 6-8 time, each 30ml or 20ml merge n-butanol extracting liquid, evaporate to dryness, residue adds dissolve with methanol and is transferred in the 10ml measuring bottle, adds methanol and is diluted to scale, shakes up, filter, precision is measured subsequent filtrate 5ml, puts in the evaporating dish, steams near and does, adding neutral alumina 1g mixes thoroughly, be added on the neutral alumina post,, collect eluent with 80% or 70% or 60% ethanol 120ml eluting, be concentrated into dried, residue is transferred in the 5ml measuring bottle after adding dissolve with methanol, and is diluted to scale, shakes up, filter with microporous filter membrane 0.45 μ m, promptly;
Accurate respectively reference substance solution and each the 2-5 μ l of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly;
Every of this product contains Fructus Forsythiae with phillyrin C
29H
36O
15Meter must not be less than 0.456mg.
5, the method for claim 1 is characterized in that, described discrimination method is selected from one or more in the following method:
A. get this product 10-25ml, add water 30-50ml, use ether extraction 1-3 time, each 15-25ml merges ether extracted liquid, adds water washing 1-3 time, and each 20-40ml gets ether layer, and evaporate to dryness, residue add methanol 1-3ml dissolving, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes the solution that every 1ml contains 1.0mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw need testing solution 5-10ul, reference substance solution 1-5ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone 2.5-7: 2-5: 0.8-1.3 is developing solvent, launch, take out airing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
B. get this product 5-15ml, add water 15-25ml, use ether extraction 1-3 time, each 15-25ml abandons ether solution, and water layer is with water saturated n-butanol extraction 1-3 time, each 15-25ml merges n-butyl alcohol liquid, adds 0.25% sodium hydroxide solution washing 1-3 time, each 15-25ml, the saturated water washing of reuse n-butyl alcohol 1-3 time, 10-30ml at every turn, get n-butanol layer, evaporate to dryness, residue add methanol 1-3ml dissolving, as need testing solution; Other gets Fructus Forsythiae control medicinal material 1.0-3.0g, add ethanol 40-60ml, put water-bath reflux, extract, 20-40min, filter the filtrate evaporate to dryness, residue adds the dissolving of water 20-40ml slight fever, filter, filtrate is used ether extraction 1-3 time, each 10-30ml, remaining step is made control medicinal material solution with the test sample preparation method.Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of solution 5-10ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid 10-14: 1-3: 1.9-2.8: 0.16-0.24 is developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
C. get this product 10-30ml, add water 5-20ml, use ethyl acetate extraction 1-3 time, each 15-25ml abandons ethyl acetate liquid, water layer n-butanol extraction 1-2 time, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add dehydrated alcohol 20ml supersound process 5-15min, filter, filtrate evaporate to dryness, residue add acetone 1-3ml makes dissolving, gets supernatant 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.Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of each 5-10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone benzene-formic acid 7-11: 2.2-2.8: 1.8-3.4: 0.17-0.24 is developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
D. get this product 5-15ml, add water 15-25ml, use ether extraction 1-2 time, each 15-25ml abandons ether solution, washes with water 2 times, and each 20ml will wash ether extracted liquid and wave near dried, and residue adds methanol 1-3ml and dissolves, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of each 1-5ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate 3.5-7: 0.7-1.4 is developing solvent, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
6, the method for claim 1 is characterized in that, described discrimination method is selected from one or more in the following method:
A. get this product 20ml, add water 40ml, use ether extraction 3 times, each 20ml merges ether extracted liquid, adds water washing 2 times, and each 30ml gets ether layer, and evaporate to dryness, residue add methanol 1ml dissolving, as need testing solution.Other gets the indirubin reference substance, adds methanol and makes the solution that every 1ml contains 1.0mg, in contrast product solution; According to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography test, draw need testing solution 10ul, reference substance solution 5ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with benzene-chloroform-acetone is developing solvent at 5: 4: 1, launch, take out airing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
B. get this product 10ml, add water 20ml, use ether extraction 3 times, each 20ml abandons ether solution, and water layer is with water saturated n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, adds 0.25% sodium hydroxide solution washing 3 times, each 20ml, the saturated water washing of reuse n-butyl alcohol 2 times, each 20ml, get n-butanol layer, evaporate to dryness, residue add methanol 1ml dissolving, as need testing solution; Other gets Fructus Forsythiae control medicinal material 2.0g, adds ethanol 50ml, puts water-bath reflux, extract, 30min, filters, filtrate evaporate to dryness, residue add the dissolving of water 30ml slight fever, filter, and filtrate is used ether extraction 2 times, each 20ml, remaining step is made control medicinal material solution with the test sample preparation method.Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of solution 10ul, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform-methanol-acetone-formic acid 12: 2: 2.5: 0.2 was developing solvent, launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
C. get this product 20ml, add water 10ml, use ethyl acetate extraction 2 times, each 20ml abandons ethyl acetate liquid, water layer n-butanol extraction 2 times, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add dehydrated alcohol 20ml supersound process 10min, filter, filtrate evaporate to dryness, residue add acetone 2ml makes dissolving, gets supernatant 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.Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 9: 2.5: 3: 0.2 chloroform-methanol-acetone benzene-formic acid was developing solvent, launch, take out airing, spray is with vanillin sulphuric acid test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
D. get this product 10ml, add water 20ml, use ether extraction 2 times, each 20ml abandons ether solution, washes with water 2 times, and each 20ml will wash ether extracted liquid and wave near dried, and residue adds methanol 1ml and dissolves, as need testing solution.Other gets the paeonol reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2000 thin layer chromatography, draw above-mentioned two kinds of each 5ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate is developing solvent at 5: 1, launch, take out airing, spray is with 3% ferric chloride ethanol test solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
7, according to any one method of claim 4-6, it is characterized in that described preparation is selected from oral liquid, syrup and granule.
According to the method for claim 7, it is characterized in that 8, every of described oral liquid contains Fructus Forsythiae with phillyrin C
29H
36O
15Meter must not be less than 0.456mg; The every 10ml of described syrup contains Fructus Forsythiae with phillyrin C
29H
36O
15Meter must not lack 0.456mg; Described granule, every 1g contain Fructus Forsythiae with phillyrin C
29H
36O
15Meter must not be less than 0.456mg.
According to the method for claim 1, it is characterized in that 9, described children's antipyretic preparation is made by following Chinese medicine raw materials by weight proportion:
Folium Isatidis 150g, Radix Isatidis 90g, Flos Lonicerae 90g, Fructus Forsythiae 90g, Fructus Gardeniae 90g, Cortex Moutan 90g, Radix Scutellariae 90g, Herba Lophatheri 60g, Pheretima 60g, Rhizoma Paridis 45g, Radix Bupleuri 90g, Radix Cynanchi Atrati 60g.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102145134A (en) * | 2007-03-23 | 2011-08-10 | 北京亚东生物制药有限公司 | Pharmaceutical composition for treatment of wind-heat cold of children and preparation and detection methods of pharmaceutical composition |
| CN103675189A (en) * | 2012-09-05 | 2014-03-26 | 亚宝药业集团股份有限公司 | Quality detection method for fructus forsythiae leaf medicinal materials |
| CN105327179A (en) * | 2015-11-30 | 2016-02-17 | 四川美大康药业股份有限公司 | Preparation method of infantile febrifugal oral liquid preparation |
| CN110873776A (en) * | 2018-08-30 | 2020-03-10 | 四川新绿色药业科技发展有限公司 | A kind of identification method of gardenia and fried gardenia formula granules |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101279056B (en) * | 2008-05-28 | 2012-03-07 | 山东沃华医药科技股份有限公司 | Children's antipyretic granule |
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2005
- 2005-11-21 CN CNB2005100032925A patent/CN100388940C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102145134A (en) * | 2007-03-23 | 2011-08-10 | 北京亚东生物制药有限公司 | Pharmaceutical composition for treatment of wind-heat cold of children and preparation and detection methods of pharmaceutical composition |
| CN102145134B (en) * | 2007-03-23 | 2012-10-31 | 北京亚东生物制药有限公司 | Detection methods of pharmaceutical composition for treatment of wind-heat cold of children |
| CN103675189A (en) * | 2012-09-05 | 2014-03-26 | 亚宝药业集团股份有限公司 | Quality detection method for fructus forsythiae leaf medicinal materials |
| CN103675189B (en) * | 2012-09-05 | 2016-06-29 | 亚宝药业集团股份有限公司 | A kind of quality determining method of Folium Forsythiae medical material |
| CN105327179A (en) * | 2015-11-30 | 2016-02-17 | 四川美大康药业股份有限公司 | Preparation method of infantile febrifugal oral liquid preparation |
| CN110873776A (en) * | 2018-08-30 | 2020-03-10 | 四川新绿色药业科技发展有限公司 | A kind of identification method of gardenia and fried gardenia formula granules |
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