CN1843424A - Cassia twig tuckahoe effervescence tablet and preparation method and its quality control method - Google Patents
Cassia twig tuckahoe effervescence tablet and preparation method and its quality control method Download PDFInfo
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- CN1843424A CN1843424A CN 200610200120 CN200610200120A CN1843424A CN 1843424 A CN1843424 A CN 1843424A CN 200610200120 CN200610200120 CN 200610200120 CN 200610200120 A CN200610200120 A CN 200610200120A CN 1843424 A CN1843424 A CN 1843424A
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- 244000037364 Cinnamomum aromaticum Species 0.000 title claims abstract description 24
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 title claims abstract description 24
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- 238000002360 preparation method Methods 0.000 title claims description 70
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- 244000248825 Peltandra virginica Species 0.000 title claims 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 276
- UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical compound COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 claims description 154
- YLTGFGDODHXMFB-UHFFFAOYSA-N isoacetovanillon Natural products COC1=CC=C(C(C)=O)C=C1O YLTGFGDODHXMFB-UHFFFAOYSA-N 0.000 claims description 77
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides effervescent tablets, the preparing process and quality control method, wherein the tablets are prepared from cassia twig 240g, poria cocos wolf 240g, bark of peony root 240g, root of herbaceous peony 240g, peach kernel 240g and right amount of auxiliary materials.
Description
Technical field: the present invention relates to a kind of cassia twig tuckahoe effervescence tablet and preparation method and method of quality control, belong to technical field of Chinese medicine.
Background technology: existing cassia twig and poria cocos preparation on the market (ball, capsule etc.), be used for the treatment of women's chronic pelvic inflammatory disease, hysteromyoma, ovarian cyst, chronic nephritis, menoxenia and infertility etc., effect is better, but the effervescent tablet supply is not arranged as yet.And effervescent tablet has its tangible dosage form advantage, all be better than general formulation at aspects such as using method, absorption of human body and therapeutic effect: on the one hand, utilize acid, alkali composition in the effervescent after meeting water neutralization reaction to take place, produce a large amount of carbon dioxide gas puffs to disintegration, composition in the tablet is in time decomposed, principal agent is fully contacted with human organ, improve curative effect of medication and action time; On the other hand, the carbonic acid of generation can play the effect of shielding bitter taste of drug, tablet dissolve fully the back one glass of good to eat, medicinal liquid of soda flavor slightly, consumer can not produced when medication detests the medicine emotion, improve compliance.Therefore, will having cassia twig and poria cocos preparation now, to change agent be effervescent tablet, can significantly improve its bioavailability, better improves patient's compliance, makes things convenient for patient's medication.In addition,, guarantee its clinical efficacy, need to formulate rationally and the stabilized quality control method for investigate and control the quality of preparation of the present invention comprehensively.
Summary of the invention:
The objective of the invention is to: a kind of cassia twig tuckahoe effervescence tablet and preparation method and method of quality control are provided, the present invention on the basis of existing technology, provide a kind of dissolving fast, high, the good stability of bioavailability, and the new formulation-effervescent tablet of taking convenience, scientific and reasonable technology and method of quality control been have also have been studied and defined, to control effectively and to improve the quality of products.
The present invention constitutes like this: it is to be prepared from by Ramulus Cinnamomi 240g, Poria 240g, Cortex Moutan 240g, Radix Paeoniae Alba 240g, Semen Persicae 240g and microcrystalline Cellulose 272g, low-substituted hydroxypropyl cellulose 96g, micropowder silica gel 96g, crospolyvinylpyrrolidone 125g, aspartame 10g, sodium bicarbonate 304g, citric acid 243g, fumaric acid 134g.
The preparation method of cassia twig tuckahoe effervescence tablet is: get Poria 192g, be ground into fine powder; The Cortex Moutan vapor distillation is collected distillate, divides and gets volatile ingredient, and is standby; Medicinal residues and Ramulus Cinnamomi, the Radix Paeoniae Alba, Semen Persicae, and remaining Poria with 90% ethanol extraction secondary, merge extractive liquid, reclaims ethanol and does not distinguish the flavor of to there being alcohol, relative density 1.10～1.20 when being evaporated to 25 ℃; Medicinal residues decoct with water secondary again, filter, merging filtrate, relative density 1.10～1.20 when being evaporated to 25 ℃, merge with above-mentioned concentrated solution, with Poria fine powder mixing, drying is pulverized again, cross 80 mesh sieves, with microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel, crospolyvinylpyrrolidone, aspartame, sodium bicarbonate, citric acid, fumaric acid and Cortex Moutan volatile ingredient mix homogeneously, compacting is packed promptly in flakes then.
The method of quality control of cassia twig tuckahoe effervescence tablet: described method of quality control mainly comprise in character, inspection, discriminating, the assay project partly or entirely; Wherein discriminating is that the gas chromatogram of Ramulus Cinnamomi is differentiated; Assay is the assay to paeonol in the preparation.
The discrimination method of Ramulus Cinnamomi is to be the gas chromatography of contrast with the cinnamic aldehyde reference substance.
Concrete discrimination method is:
Get 10 in this preparation, the accurate title, decide, and porphyrize is got 1.6g, the accurate title, decide, and uses vapor distillation, collects distillate 400ml, extracts 4 times with the chloroform jolting, merge chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, promptly get need testing solution; It is an amount of to get the cinnamic aldehyde reference substance, adds chloroform and makes the solution that every 1ml contains 5 He, in contrast product solution; According to an appendix VIE of Chinese Pharmacopoeia version in 2005 gas chromatography test, draw reference substance solution respectively and need testing solution is an amount of, inject gas chromatograph should present the chromatographic peak identical with the reference substance retention time in the test sample chromatograph.
The content assaying method of paeonol is to be the gas chromatography of contrast with the paeonol reference substance.
Concrete content assaying method is:
According to 2005 editions one appendix VIE gas chromatography determination of Chinese Pharmacopoeia:
Chromatographic condition and system suitability test HP-1 fused-silica capillary column (30m * 0.25mm * 0.25 μ m); Column temperature: 120 ℃; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000; The separating degree of paeonol peak and internal standard substance mass peak should be greater than 2;
It is an amount of that correction factor mensuration is got Pentadecane, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.3mg, as inner mark solution; It is an amount of to get the paeonol reference substance, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.4mg, in contrast product solution; Precision is measured reference substance solution and each 2ml of inner mark solution, puts in the 5ml measuring bottle, adds chloroform to scale, shakes up, and draws 2 μ l, inject gas chromatograph, the calculation correction factor;
Algoscopy is got 10 in this preparation, and accurate the title decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 times, merge chloroform liquid with the chloroform jolting, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, precision is measured 2ml, put in the 5ml measuring bottle, add inner mark solution 2ml, add chloroform to scale, shake up, draw 2 μ l inject gas chromatographs, measure, promptly;
Every in this preparation contains Cortex Moutan with paeonol C
9H
10O
3Meter must not be less than 1.2mg.
Method of quality control of the present invention comprises:
Character: medicine is that light brown is to brown; Feeble QI perfume (or spice), it is little sweet to distinguish the flavor of;
Differentiate: get 10 in this preparation, the accurate title, decide, and porphyrize is got 1.6g, the accurate title, decide, and uses vapor distillation, collects distillate 400ml, extracts 4 times with the chloroform jolting, merge chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, promptly get need testing solution; It is an amount of to get the cinnamic aldehyde reference substance, adds chloroform and makes the solution that every 1ml contains 5 He, in contrast product solution; According to an appendix VIE of Chinese Pharmacopoeia version in 2005 gas chromatography test, draw reference substance solution respectively and need testing solution is an amount of, inject gas chromatograph should present the chromatographic peak identical with the reference substance retention time in the test sample chromatograph.
Check: should meet relevant every regulation under an appendix ID of Chinese Pharmacopoeia version in 2005 the tablet item;
Assay: shine 2005 editions one appendix VIE gas chromatography determination of Chinese Pharmacopoeia:
Chromatographic condition and system suitability test HP-1 fused-silica capillary column (30m * 0.25mm * 0.25 μ m); Column temperature: 120 ℃; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000; The separating degree of paeonol peak and internal standard substance mass peak should be greater than 2;
It is an amount of that correction factor mensuration is got Pentadecane, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.3mg, as inner mark solution; It is an amount of to get the paeonol reference substance, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.4mg, in contrast product solution; Precision is measured reference substance solution and each 2ml of inner mark solution, puts in the 5ml measuring bottle, adds chloroform to scale, shakes up, and draws 2 μ l, inject gas chromatograph, the calculation correction factor;
Algoscopy is got 10 in this preparation, and accurate the title decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 times, merge chloroform liquid with the chloroform jolting, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, precision is measured 2ml, put in the 5ml measuring bottle, add inner mark solution 2ml, add chloroform to scale, shake up, draw 2 μ l inject gas chromatographs, measure, promptly;
Every in this preparation contains Cortex Moutan with paeonol C
9H
10O
3Meter must not be less than 1.2mg.
The Ramulus Cinnamomi temperature gas that activates yang among the we stagnates with circulation of qi promoting; Radix Paeoniae Alba regulating nutrient QI and blood, relieving spasm to stop pain; Cortex Moutan, Semen Persicae blood circulation promoting and blood stasis dispelling, and logical stasis of blood resistance; Poria eliminating dampness and diuresis and middle spleen invigorating.The five tastes share, and play the merit of promoting flow of QI and blood, blood stasis-eliminating and stagnation-dissipating altogether, over against " dysmenorrhea ", “ mass in the abdomen " pathogenesis, be used for the treatment of women's chronic pelvic inflammatory disease, hysteromyoma, ovarian cyst, chronic nephritis, menoxenia and infertility etc., effect is better.
Compared with prior art, effervescent tablet of the present invention has dissolving soon, the bioavailability height, and the advantage of good stability, and also easy to carry and use, be particularly useful for child, old people and the crowd of the solid preparation that is difficult for swallowing use; This preparation is taken safety, has no side effect and untoward reaction, and is evident in efficacy, also can better improve patient's compliance, makes things convenient for patient's medication.In addition, method of quality control precision height of the present invention, favorable reproducibility, measurement result is accurate, can effectively guarantee the clinical efficacy of said preparation.
The applicant has carried out preparation technology and the method for quality control that preparation of the present invention is selected in a series of experiments, guaranteeing its science, reasonable, feasible, and has good curative effect.
One, Study on Preparation
1. extract determining of alcohol adding amount and amount of water
Test method: get the medical material of a recipe quantity, add 90% ethanol and the water extraction of 12 times, 10 times, 8 times, 6 times amounts respectively, with paste volume (dried cream) index that judges, determine optimum extraction alcohol adding amount and amount of water, result of the test is as follows:
| Extract alcohol adding amount (doubly) | Paste volume (g) | Extract amount of water (doubly) | Paste volume (g) |
| 12 | 55 | 12 | 78 |
| 10 | 53 | 10 | 75 |
| 8 | 46 | 8 | 62 |
| 6 | 41 | 6 | 57 |
Fruit shows in test, it is comparatively suitable when employing adds 10 times of amount 90% ethanol and 10 times of water gagings extractions, its paste volume is apparently higher than adding the 8 times of amounts and the paste volume in 6 times of whens amount, and paste volume does not have significant difference when adding 12 times of amounts and extract, and therefore determines to extract to add amount of alcohol and amount of water is respectively 10 times of amounts.
2. preparation prescription craft screening
| Form | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | |
| Cassia twig tuckahoe dry extract (g) | A recipe quantity | A recipe quantity | A recipe quantity | A recipe quantity | |
| Cortex Moutan volatile ingredient (g) | 2 | 2 | 2 | 2 | |
| Microcrystalline Cellulose (g) | 300 | 272 | 272 | 272 | |
| Low-substituted hydroxypropyl cellulose (g) | 96 | 125 | 96 | 76 | |
| Micropowder silica gel (g) | 96 | 96 | 96 | 116 | |
| Sodium bicarbonate (g) | 320 | 304 | 304 | 304 | |
| Aspartame (g) | 10 | 10 | 10 | 10 | |
| Crospolyvinylpyrrolidone (g) | 125 | 96 | 125 | 125 | |
| Citric acid (g) | 243 | 134 | 243 | 134 | |
| Fumaric acid (g) | 146 | 243 | 134 | 243 | |
| Quality evaluation | Unilateral | Unilateral coarse | More even | Color and luster is even | More even |
| Hardness | More difficult tabletting | 4-5kg | 4-5kg | 4-5kg | |
| Disintegration time | Greater than 5 minutes | Greater than 6 minutes | 3.5 in minute | About 5 minutes | |
| Taste | Relatively poor | Relatively poor | Suitable | Suitable | |
The result: final definite prescription 3 is the prescription of cassia twig tuckahoe effervescence tablet, and prescription and preparation technology are as follows:
Prescription: dry extract (a prescription medical material is carried)
Microcrystalline Cellulose 272g
Crospolyvinylpyrrolidone 125g
Low-substituted hydroxypropyl cellulose 96g
Micropowder silica gel 96g
Sodium bicarbonate 304g
Citric acid 243g
Fumaric acid 134g
Aspartame 10g
Make 1000 altogether, every heavy 1.60g.
Preparation technology is:
The five tastes in the prescription are got Poria 192g, are ground into fine powder; The Cortex Moutan vapor distillation is collected distillate, divides and gets volatile ingredient, and is standby; Medicinal residues and Ramulus Cinnamomi, the Radix Paeoniae Alba, Semen Persicae and remaining Poria are with 90% ethanol extraction secondary, and merge extractive liquid, reclaims ethanol to there not being the alcohol flavor, is evaporated to an amount of; Medicinal residues decoct with water secondary again, filter, merging filtrate is evaporated to an amount of, merge with above-mentioned concentrated solution, with Poria fine powder mixing, drying is pulverized again, cross 80 mesh sieves, with microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel, crospolyvinylpyrrolidone, aspartame, sodium bicarbonate, citric acid, fumaric acid and the Cortex Moutan volatile ingredient mix homogeneously of recipe quantity, be pressed into 1000 then, packing promptly.
3. adopt above-mentioned technology to carry out the result of the test of three batches of pilot products:
| Lot number | 050501 | 050502 | 050503 |
| The raw medicinal herbs total amount (kg) that feeds intake | 12.0 | 12.0 | 12.0 |
| Extractum amount (kg) | 3.18 | 3.23 | 3.21 |
| Paste-forming rate (%) | 26.5 | 26.9 | 26.75 |
| Poria crude drug fine powder inventory (kg) | 1.92 | 1.92 | 1.92 |
| Sodium bicarbonate (kg) | 3.04 | 3.04 | 3.04 |
| Microcrystalline Cellulose (kg) | 2.72 | 2.72 | 2.72 |
| Low-substituted hydroxypropyl cellulose (kg) | 0.96 | 0.96 | 0.96 |
| Crospolyvinylpyrrolidone (kg) | 1.25 | 1.25 | 1.25 |
| Aspartame (kg) | 0.1 | 0.1 | 0.1 |
| Micropowder silica gel (kg) | 0.96 | 0.96 | 0.96 |
| Citric acid (kg) | 2.43 | 2.43 | 2.43 |
| Fumaric acid (kg) | 1.34 | 1.34 | 1.34 |
| Theoretical yield (sheet) | 10000 | 10000 | 10000 |
| Actual production (sheet) | 9105 | 9210 | 9195 |
| Yield rate (%) | 91.05 | 92.10 | 91.95 |
Conclusion: three batches of pilot product trial results of this preparation show that its technology is reasonable, stable, and the finished product recovery rate is higher, and the gained finished product is through quality inspection, and the result shows all up to specification.
Two, pharmacodynamic study
1, cassia twig and poria cocos preparation is to the influence of endometriosis (EM) rat model angiogenesis factor (VEGF) and Ectopic Endometrium microvessel density (MVD)
The modeling of SD rat, rat with the modeling success after 3 weeks is divided into not medication group (U) at random, cassia twig and poria cocos preparation group (GFW), danazol group (D) and drug combination group (S), if sham operated rats (C) is contrast, give respective handling after 4 weeks, observe and respectively organize dystopy endometrium volume and morphologic variation, counting peritoneal fluid macrophage, measured by radioimmunoassay is respectively organized the rat peripheral blood, peritoneal fluid and macrophage culture fluid interleukin 8 (III-8), tumor necrosis factor (TNF-a), the SABC method is measured the expression of VEGF (VEGF) in Ectopic Endometrium, and, measure its microvessel density (MVD) by CDM labelling dystopy blood vessels of endometrium.Result: GFW group, D group and S group Ectopic Endometrium present atrophy in various degree, body of gland obviously reduces, peritoneal fluid macrophage counting reduces, GFW group, D group and S group rat peripheral blood, peritoneal fluid and macrophage culture fluid III-8, TNF-a reduce, the Ectopic Endometrium vegf expression weakens, MVD also obviously reduces, and is wherein obvious with the S group.Conclusion: cassia twig and poria cocos preparation and danazol can suppress the angiogenesis of EM rat model Ectopic Endometrium, make the Ectopic Endometrium atrophy, when the two drug combination, act on stronger.
2, hematology's research
Cassia twig and poria cocos preparation has tangible blood coagulation resisting function; The Japan scholar knits Tian Zhenzhi and has studied this side to the effect of tip circulation, proposes blood clotting and platelet system inhibition by force and to a little less than the fibrinolytic system effect; The anti-IC that the experiment of Ji Chuan quick proposes this side act as that full side's 5 flavor medicines are common to be produced; Secondly letter man in cherry river further points out: take this side for a long time to promote that microcirculatory effect is the result that red cell agglutination is improved and whole blood viscosity reduces.
3, function of immune system influences the research of aspect
Originally can promote macrophage activity, allergic inflammation is had certain inhibitory action.And domestic scholars Xie Shi etc. have also done relevant research to we's antiinflammatory action, the result shows that cassia twig and poria cocos preparation all has obvious inhibitory action to rat acute, subacute, chronic inflammatory disease, little to adrenal stimulation, the main path of its antiinflammatory action is not the adjusting by hypophysis-adrenal system, but many links of inflammatory process are played the facedown effect, promptly to the release of inflammatory mediator in the body, capillary permeability increases, ooze out, edema, and link such as granulation hyperplasia to play the facedown effect relevant.
4, the research of endocrine aspect
We have certain protective role to hypophysis one adrenal cortex, and the clinical effect of getting of gynaecopathia is relevant with estrogenic activity.
5, other
We have calmness, analgesia and certain antitumor action.
Three, method of quality control research
(1) sample and reference substance source
Sample: our company's self-control, lot number is: 050501,050502,050503.
The reference substance source: the cinnamic aldehyde reference substance is provided by Nat'l Pharmaceutical ﹠ Biological Products Control Institute, lot number 110710-200212; Paeonol reference substance: lot number 0708-9704 is provided by Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
(2) character
This preparation is an effervescent tablet, is that Chinese medical concrete powder (containing the crude drug powder) adds appropriate amount of auxiliary materials, and mixed pressuring plate forms, and through many batch sample trial-productions, determines that this preparation character is: medicine is that light brown is to brown; Feeble QI perfume (or spice), it is little sweet to distinguish the flavor of.
(3) differentiate
With reference to the content under Chinese Pharmacopoeia version Ramulus Cinnamomi in 2005 the Poria capsule discriminating item, with the method for thin layer our principal agent Cortex Moutan, the Radix Paeoniae Alba are differentiated, with the method for gas phase Ramulus Cinnamomi is differentiated.
1, the thin layer of Cortex Moutan is differentiated
(1) get 7 in this preparation, porphyrize is put in the apparatus,Soxhlet's, and it is an amount of to add diethyl ether, and heating and refluxing extraction 2 hours is put coldly, filters, and filtrate volatilizes, and residue adds methanol 1ml makes dissolving, as need testing solution.Other gets Cortex Moutan control medicinal material 1g, shines medical material solution in pairs with legal system.According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with toluene-chloroform-Ethyl formate-formic acid (5: 6: 6: 3) be developing solvent, launch, take out, dry, spray is with the acid 5% ferric chloride alcoholic solution of hydrochloric acid, about 5 minutes of 105 ℃ of heating.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) selection of point sample amount
Through experimental selection need testing solution and reference substance solution each point sample 2 μ l, 5 μ l, 10 μ l, speckle is better, comparatively clear when found that need testing solution and reference substance solution point sample 5 μ l, 10 μ l.So this standard reference material solution and need testing solution select for use 5 μ l as the point sample amount.
(3) specificity experiment
Get the negative sample that lacks Cortex Moutan, make negative need testing solution, launch the back and corresponding speckle occurs, illustrate that negative sample has interference to this experiment at the reference substance place with the operation of test sample method.So differentiate and exclude content of the present invention.
2, the thin layer of the Radix Paeoniae Alba is differentiated
(1) extracts choice of Solvent
A, get 7 in this preparation, porphyrize is put in the apparatus,Soxhlet's, and it is an amount of to add methanol, and heating and refluxing extraction 2 hours is put coldly, filters, and filtrate is reclaimed methanol and made dissolving to about 2ml, as need testing solution.Other gets Radix Paeoniae Alba control medicinal material 1g, shines medical material solution in pairs with legal system.According to " each 5 μ l of above-mentioned two solution are drawn in the test of 2005 editions one appendix VIB thin layer chromatography of Chinese pharmacopoeia, put respectively in same be the silica gel G F of adhesive with the sodium carboxymethyl cellulose
254On the lamellae, be developing solvent, launch, take out, dry that spray is with the anisaldehyde test solution, about 10 minutes of 105 ℃ of heating with lower floor's solution of chloroform-methanol-water (26: 14: 5).In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, do not have corresponding speckle.
B, get 7 in this preparation, porphyrize, the 50ml that adds diethyl ether, low-temperature heat refluxed 1 hour, filter, medicinal residues add ethanol 20ml, and supersound process 15 minutes filters, filtrate evaporate to dryness, residue add water 15ml makes dissolving, extracts 2 times in order to water saturated n-butyl alcohol jolting, each 20ml, merge n-butyl alcohol liquid, wash with water 2 times, each 10ml merges n-butyl alcohol liquid, wash with water 2 times, each 10ml discards water lotion, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, and residue adds ethanol 1ml makes dissolving, as need testing solution.Other gets the peoniflorin reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with chloroform-ethyl acetate-methanol-formic acid (40: 5: 10: 0.2) be developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical bluish violet speckle.
(2) selection of point sample amount
Through experimental selection need testing solution point sample 10 μ l and reference substance solution point sample 5 μ l, each point sample 5 μ l of need testing solution and reference substance solution, speckle is better, comparatively clear when found that need testing solution point sample 10 μ l and reference substance solution point sample 5 μ l.So this standard need testing solution point sample 10 μ l, reference substance solution point sample 5 μ l.
(3) specificity experiment
Get the negative sample that lacks the Radix Paeoniae Alba, make negative need testing solution, launch the back and corresponding speckle occurs, illustrate that negative sample has interference to this experiment at the reference substance place with the operation of test sample b method.So differentiate and exclude content of the present invention.
3, the gas phase of Ramulus Cinnamomi is differentiated
Differentiate in this preparation prescription that the Ramulus Cinnamomi medical material contains cinnamic aldehyde, Chinese Pharmacopoeia version GUIZHI FULING JIAONANG in 2005 differentiates that item has the gas chromatography retention time discriminating mensuration to this composition down, so adopt gas chromatography to carry out the discriminating of cinnamic aldehyde.
The preparation of reference substance solution: it is an amount of that precision takes by weighing the cinnamic aldehyde reference substance, and add chloroform and make the solution that contains 5 μ g among every 1ml approximately, product solution in contrast, promptly.
The preparation of need testing solution: get 10 in this preparation, the accurate title, decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 (60ml, 40ml with the chloroform jolting, 40ml 30ml), merges chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform, to an amount of, be transferred in the 5ml measuring bottle, add chloroform to scale, shake up, promptly.
Specificity: prepare the negative preparation that does not contain Ramulus Cinnamomi according to recipe quantity, according to the preparation method operation of above-mentioned need testing solution, promptly.Draw above-mentioned solution 2 μ l, injecting chromatograph, record chromatogram.Experiment shows that negative preparation does not have chromatographic peak and occurs in cinnamic aldehyde reference substance relevant position.
Detection limit: stepwise dilution cinnamic aldehyde reference substance solution, sample introduction is measured respectively, and the result determines that 1 μ g/ml is its detection limit (split ratio 1: 20).
Ruggedness: when using column temperature instead and being 130 ℃, the cinnamic aldehyde peak is disturbed by other assorted peak in the sample.
Three batch samples are measured: three batch samples all have chromatographic peak in cinnamic aldehyde reference substance solution retention time position.
(4) check
1, disintegration
(1) selects foundation
This preparation is an effervescent tablet, detects according to carrying out disintegration about the associated description of effervescent tablet under an appendix XIIA of Chinese Pharmacopoeia version in 2005 item.
(2) detection method
Get 1 in this preparation, put in the 250ml beaker that fills 15～25 ℃ of water of 200ml, have numerous air-bubble to emit, when bubble stopped to overflow, tablet should dissolve or be dispersed in the water fully, and it is left not have accumulative granule.Get 6 in this preparation, measure with method, each sheet all should finish in 5 minutes in disintegrate.
(3) testing result
Table 1 effervescent tablet check result disintegration
| Lot number | 050501 | 050502 | 050503 |
| Disintegration | 4 minutes | 4 minutes | 4 minutes |
2, arsenic salt checks that by an appendix IXB of Chinese Pharmacopoeia version in 2005 arsenic salt inspection technique first method result is up to specification.
Table 2 arsenic salt measurement result
| Lot number | 050501 | 050502 | 050503 |
| Arsenic salt | ＜5ppm | ＜5ppm | ＜5ppm |
3, heavy metal checks that by an appendix IXE of Chinese Pharmacopoeia version in 2005 heavy metal inspection technique second method result is up to specification.
Table 3 determining heavy metals result
| Lot number | 050501 | 050502 | 050503 |
| Heavy metal | ＜10ppm | ＜10ppm | ＜10ppm |
4, tablet weight variation
This preparation sheet is great in 0.3g, presses a regulation of Chinese Pharmacopoeia version in 2005 tablet weight variation and should get 20 inspections of this preparation three batch samples in ± 5%, the results are shown in following table 4.
Table 4 tablet weight variation check result
This preparation three batch sample measurement results show that tablet weight variation is all within prescribed limit.
5, microbial limit
Check that according to microbial limit test (appendix XIII of Chinese Pharmacopoeia version in 2005) check result of three batch samples sees the following form.
Table 5 limit test of microbe result
| Lot number | 050501 | 050502 | 050503 |
| Bacterial population (individual/g) | Up to specification | Up to specification | Up to specification |
| Fungi count (individual/g) | Up to specification | Up to specification | Up to specification |
| Escherichia coli (individual/g) | Do not detect | Do not detect | Do not detect |
| Demodicid mite alive (individual/g) | Do not detect | Do not detect | Do not detect |
(5) assay
Measure according to gas chromatography (2005 editions appendix VIE of Chinese Pharmacopoeia).
1, instrument and reagent
Instrument: HP6890 gas chromatograph
Reference substance: paeonol: provide (lot number 0708-9704) by Nat'l Pharmaceutical ﹠ Biological Products Control Institute, reagent is analytical pure.
2, with reference to assay sample preparation methods in GUIZHI FULING JIAONANG of Chinese Pharmacopoeia version in 2005, adopt vapor distillation to extract paeonol, because of the pilot sample dosage form is a tablet, different with the dosage form in the standards of pharmacopoeia, for guaranteeing the ruggedness of this standard method, carry out the long-pending examination of vapor distillation liquid, the results are shown in Table 6.
The examination of table 6 distillate volume
| Distillate volume (ml) | Paeonol content in the sample (mg/g) |
| 100 | 0.72 |
| 200 | 1.05 |
| 300 | 1.22 |
| 400 | 1.24 |
The result shows that when adopting the vapor distillation method that paeonol in the sample is extracted, when collecting distillate greater than 300ml, content tends towards stability, according to result of the test, with reference to the method in the pharmacopeia, determine that equally vapor distillation liquid is 400ml, as the volume of collecting distillate.
3, adopt capillary chromatographic column because of this test, and official method adopts packed column to measure paeonol, so selected similar polar capillary chromatographic column for use, the selection of internal standard substance and the examination of column temperature have been carried out, selected for use n-tetradecane, Pentadecane and hexadecane as internal standard substance during test, found that n-tetradecane and paeonol are on HP-1 (30m * 0.53mm * 0.32 μ m) capillary column, could better separate when having only column temperature to be less than or equal to 110 ℃, flow rate of carrier gas also can not surpass 1.5ml/min; Then between 120 ℃～130 ℃, flow velocity is between the 2.0-2.5ml/min, and good separating degree is all arranged for Pentadecane and paeonol; When adopting hexadecane, find that hexadecane under 130 ℃ of conditions, goes out the peak too late, be not suitable for interior mark as paeonol, find paeonol in the test under this capillary column, column temperature is at the number of theoretical plate of 120 ℃ of following apparent number of theoretical plates under greater than 130 ℃.Therefore having selected Pentadecane for use is internal standard substance, and column temperature is at 120 ℃, and flow rate of carrier gas is per minute 2.0ml, is the chromatographic condition of this test.
4, chromatographic condition and system suitability test: HP-1 fused-silica capillary column (30m * 0.53mm * 0.32 μ m); Column temperature: 120 ℃, flow rate of carrier gas: per minute 2.0ml; Split sampling, split ratio: 20: 1.Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000, and the separating degree of paeonol peak and internal standard substance mass peak should be greater than 2.
The separating degree of paeonol peak and internal standard substance mass peak meets the requirements under this chromatographic condition.
5, the content detection of paeonol method of stating is seen below in inner mark solution, reference substance solution and need testing solution preparation.
6, linear relationship is investigated: precision takes by weighing paeonol reference substance 10.60mg and puts in the 25ml measuring bottle, add the chloroform dissolving and be diluted to scale, precision is measured this solution 0.5,1.0,2.0,2.5 respectively, 3.0ml puts in the 5ml measuring bottle, add inner mark solution 2.0ml respectively, add chloroform and be diluted to scale, shake up.Getting 2 μ l inject gas chromatographs respectively, is vertical coordinate with the ratio of paeonol area and interior mark peak area, and paeonol concentration (mg/ml) is abscissa (seeing Table 7), regression equation: Y=3.7308X+0.1976, r=0.9994; Paeonol concentration has good linear relationship in 0.0424mg/ml～0.2544mg/ml scope.
Table 7 paeonol linear relationship is investigated the result
| Numbering | 1 | 2 | 3 | 4 | 5 |
| Paeonol concentration (mg/ml) | 0.0424 | 0.0848 | 0.1696 | 0.212 | 0.2544 |
| Paeonol peak area and interior mark peak area ratio | 0.3565 | 0.5194 | 0.8165 | 0.9906 | 1.1522 |
7, specificity test: get scarce Cortex Moutan negative test sample, press the content assaying method sample introduction, the result shows that not having the chromatographic peak appearance with paeonol reference substance same position negative control is noiseless.
8, precision: get with a reference substance solution, press the chromatographic condition under the assay, continuous sample introduction 6 times, mark and paeonol peak area in measuring, the ratio of calculating paeonol peak area sum and interior mark peak area, RSD is 0.31% as a result, sees Table 8.
Table 8 Precision test result
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods | RSD％ |
| Paeonol peak area and interior mark peak area ratio | 0.76879 | 0.76679 | 0.76673 | 0.76244 | 0.76767 | 0.77534 | 0.76648 | 0.31 |
9, stability: get with a reference substance solution, press the assay chromatographic condition, at interval the certain hour sample introduction, mark and paeonol peak area in measuring, calculate the ratio of paeonol peak area sum and interior mark peak area, the result shows that need testing solution is stable in 8 hours, sees Table 9.
Table 9 stability test result
| Time (hour) | 0 | 2 | 4 | 6 | 8 | Meansigma methods | RSD(％) |
| Paeonol peak area and interior mark peak area ratio | 0.7864 | 0.7812 | 0.7795 | 0.7831 | 0.7950 | 0.7851 | 0.78 |
10, repeatability: (lot number: 050501) sample is 6 parts, presses content assaying method mensuration and calculates paeonol content, and the paeonol average content is the 2.04mg/ sheet as a result, and RSD is 2.14% (n=6), sees Table 10 to get same lot number.
Table 10 repeatability result of the test
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods | RSD％ |
| Paeonol content (mg/ sheet) | 2.02 | 1.99 | 2.12 | 2.03 | 2.07 | 2.05 | 2.04 | 2.14 |
11, the response rate: the accurate respectively sample (lot number: 050501) an amount of (totally six parts) that takes by weighing known paeonol content, and the accurate respectively paeonol reference substance solution 2.5ml (0.4240mg/ml) that adds, use vapor distillation, and press content assaying method and measure paeonol content and calculate, the result shows that average recovery rate is 100.4%, RSD is 1.41% (seeing Table 11).
Table 11 recovery test result
| Known paeonol amount (mg) in the sample | Addition (mg) | The amount of recording (mg) | The response rate (%) | Average recovery rate | RSD(％) |
| 0.8173 | 1.0600 | 1.8676 | 99.1％ | 100.4％ | 1.41 |
| 0.9740 | 1.0600 | 2.0499 | 101.5％ | ||
| 0.8223 | 1.0600 | 1.8687 | 98.7％ | ||
| 1.1315 | 1.0600 | 2.1883 | 99.7％ | ||
| 1.3780 | 1.0600 | 2.4690 | 102.0％ | ||
| 1.1545 | 1.0600 | 2.2305 | 101.5％ |
12, serviceability test, because of this method has been used capillary column instead, so carried out necessary serviceability test, in the above in the test of the examination of internal standard substance and column temperature and carrier gas flux flow velocity, with the Pentadecane is internal standard substance, column temperature is between 120 ℃～130 ℃, and flow velocity paeonol between per minute 2.0～2.5ml all separates well with interior mark, and number of theoretical plate also meets the requirements.
13, content detection of paeonol in the sample: measure according to gas chromatography (2005 editions appendix VIE of Chinese Pharmacopoeia).
Chromatographic condition and system suitability test HP-1 fused-silica capillary column (30m * 0.25mm * 0.25 μ m); Column temperature: 120 ℃, flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000.The separating degree of paeonol and internal standard substance mass peak should be greater than 2.
It is an amount of that correction factor mensuration is got Pentadecane, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.3mg, as inner mark solution.It is an amount of to get the paeonol reference substance, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.4mg, in contrast product solution, precision is measured reference substance solution and inner mark solution 2ml, puts in the 5ml measuring bottle, adds chloroform to scale, shake up, draw 2 μ l inject gas chromatographs, the calculation correction factor.
Algoscopy is got 10 in this preparation, and accurate the title decided porphyrize, get about 1.6g, the accurate title, decide, and uses vapor distillation, collect the about 400ml of distillate, extract 4 (60ml, 40ml with the chloroform jolting, 40ml 30ml), merges chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, precision is measured 2ml, puts in the 5ml measuring bottle, add inner mark solution 2ml, add chloroform to scale, shake up, draw 2 μ l inject gas chromatographs, measure, promptly.
Every in this preparation contains Cortex Moutan with paeonol (C
9H
10O
3) meter, must not be less than 1.2mg.
Measure three batches batches of product as stated above, the results are shown in Table 12.
Table 12 sample determination result
| Numbering | Lot number | Content (mg/ sheet) |
| 1 | 050501 | 2.04 |
| 2 | 050502 | 2.00 |
| 3 | 050503 | 2.00 |
| 4 | Lab scale 1 | 2.02 |
| 5 | Lab scale 2 | 1.95 |
| 6 | Lab scale 3 | 2.00 |
| 7 | Lab scale 4 | 2.01 |
According to measurement result and this preparation prescription,, temporarily limit is decided to be every in this preparation and contains Cortex Moutan with paeonol (C with reference to paeonol content limit in 2005 editions GUIZHI FULING JIAONANG of Chinese Pharmacopoeia
9H
10O
3) meter, must not be less than 1.2mg.
The specific embodiment:
Embodiments of the invention 1: Ramulus Cinnamomi 240g, Poria 240g, Cortex Moutan 240g, Radix Paeoniae Alba 240g, Semen Persicae 240g, microcrystalline Cellulose 272g, low-substituted hydroxypropyl cellulose 96g, micropowder silica gel 96g, crospolyvinylpyrrolidone 125g, aspartame 10g, sodium bicarbonate 304g, citric acid 243g, fumaric acid 134g
Get Poria 192g, be ground into fine powder; The Cortex Moutan vapor distillation is collected distillate, divides and gets volatile ingredient, and is standby; Medicinal residues and Ramulus Cinnamomi, the Radix Paeoniae Alba, Semen Persicae, and remaining Poria with 90% ethanol extraction secondary, merge extractive liquid, reclaims ethanol and does not distinguish the flavor of to there being alcohol, is evaporated to relative density 1.17 (25 ℃); Medicinal residues decoct with water secondary again, filter, merging filtrate is evaporated to relative density 1.17 (25 ℃), merge with above-mentioned concentrated solution, with Poria fine powder mixing, drying is pulverized again, cross 80 mesh sieves, with microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel, crospolyvinylpyrrolidone, aspartame, sodium bicarbonate, citric acid, fumaric acid and Cortex Moutan volatile ingredient mix homogeneously, be pressed into 1000 then, packing promptly.This product is dissolved in after the suitable quantity of water oral, one time 3,3 times on the one.
Embodiments of the invention 2: described method of quality control comprises following content:
Character: medicine is that light brown is to brown; Feeble QI perfume (or spice), it is little sweet to distinguish the flavor of;
Differentiate: get 10 in this preparation, the accurate title, decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 (60ml, 40ml with the chloroform jolting, 40ml 30ml), merges chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform, to an amount of, be transferred in the 5ml measuring bottle, add chloroform to scale, shake up, promptly get need testing solution; It is an amount of to get the cinnamic aldehyde reference substance, adds chloroform and makes the solution that every 1ml contains 5 He, in contrast product solution; According to an appendix VIE of Chinese Pharmacopoeia version in 2005 gas chromatography test, draw reference substance solution respectively and need testing solution is an amount of, inject gas chromatograph should present the chromatographic peak identical with the reference substance retention time in the test sample chromatograph.
Check: should meet relevant every regulation under an appendix ID of Chinese Pharmacopoeia version in 2005 the tablet item;
Assay: shine 2005 editions one appendix VIE gas chromatography determination of Chinese Pharmacopoeia:
Chromatographic condition and system suitability test HP-1 fused-silica capillary column (30m * 0.25mm * 0.25 μ m); Column temperature: 120 ℃; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000; The separating degree of paeonol peak and internal standard substance mass peak should be greater than 2;
It is an amount of that correction factor mensuration is got Pentadecane, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.3mg, as inner mark solution; It is an amount of to get the paeonol reference substance, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.4mg, in contrast product solution; Precision is measured reference substance solution and each 2ml of inner mark solution, puts in the 5ml measuring bottle, adds chloroform to scale, shakes up, and draws 2 μ l, inject gas chromatograph, the calculation correction factor;
Algoscopy is got 10 in this preparation, and accurate the title decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 (60ml, 40ml with the chloroform jolting, 40ml 30ml), merges chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, precision is measured 2ml, puts in the 5ml measuring bottle, add inner mark solution 2ml, add chloroform to scale, shake up, draw 2 μ l inject gas chromatographs, measure, promptly;
Every in this preparation contains Cortex Moutan with paeonol C
9H
10O
3Meter must not be less than 1.2mg.
Embodiments of the invention 3: method of quality control can comprise following content:
Character: medicine is that light brown is to brown; Feeble QI perfume (or spice), it is little sweet to distinguish the flavor of;
Check: should meet relevant every regulation under an appendix ID of Chinese Pharmacopoeia version in 2005 the tablet item;
Assay: shine 2005 editions one appendix VIE gas chromatography determination of Chinese Pharmacopoeia:
Chromatographic condition and system suitability test HP-1 fused-silica capillary column (30m * 0.25mm * 0.25 μ m); Column temperature: 120 ℃; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000; The separating degree of paeonol peak and internal standard substance mass peak should be greater than 2;
It is an amount of that correction factor mensuration is got Pentadecane, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.3mg, as inner mark solution; It is an amount of to get the paeonol reference substance, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.4mg, in contrast product solution; Precision is measured reference substance solution and each 2ml of inner mark solution, puts in the 5ml measuring bottle, adds chloroform to scale, shakes up, and draws 2 μ l, inject gas chromatograph, the calculation correction factor;
Algoscopy is got 10 in this preparation, and accurate the title decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 (60ml, 40ml with the chloroform jolting, 40ml 30ml), merges chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform to an amount of, be transferred in the 5ml measuring bottle, add chloroform to scale, shake up, precision is measured 2ml, puts in the 5ml measuring bottle, add inner mark solution 2ml, add chloroform, shake up to scale, draw 2 μ l inject gas chromatographs, measure, promptly;
Every in this preparation contains Cortex Moutan with paeonol C
9H
10O
3Meter must not be less than 1.2mg.
Embodiments of the invention 4: method of quality control can comprise following content:
Character: medicine is that light brown is to brown; Feeble QI perfume (or spice), it is little sweet to distinguish the flavor of;
Differentiate: get 10 in this preparation, the accurate title, decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 (60ml, 40ml with the chloroform jolting, 40ml 30ml), merges chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform, to an amount of, be transferred in the 5ml measuring bottle, add chloroform to scale, shake up, promptly get need testing solution; It is an amount of to get the cinnamic aldehyde reference substance, adds chloroform and makes the solution that every 1ml contains 5 He, in contrast product solution; According to an appendix VIE of Chinese Pharmacopoeia version in 2005 gas chromatography test, draw reference substance solution respectively and need testing solution is an amount of, inject gas chromatograph should present the chromatographic peak identical with the reference substance retention time in the test sample chromatograph.
Check: should meet relevant every regulation under an appendix ID of Chinese Pharmacopoeia version in 2005 the tablet item.
Embodiments of the invention 5: method of quality control can comprise following content:
Character: medicine is that light brown is to brown; Feeble QI perfume (or spice), it is little sweet to distinguish the flavor of;
Differentiate: get 10 in this preparation, the accurate title, decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 (60ml, 40ml with the chloroform jolting, 40ml 30ml), merges chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform, to an amount of, be transferred in the 5ml measuring bottle, add chloroform to scale, shake up, promptly get need testing solution; It is an amount of to get the cinnamic aldehyde reference substance, adds chloroform and makes the solution that every 1ml contains 5 He, in contrast product solution; According to an appendix VIE of Chinese Pharmacopoeia version in 2005 gas chromatography test, draw reference substance solution respectively and need testing solution is an amount of, inject gas chromatograph should present the chromatographic peak identical with the reference substance retention time in the test sample chromatograph.
Assay: shine 2005 editions one appendix VIE gas chromatography determination of Chinese Pharmacopoeia:
Chromatographic condition and system suitability test HP-1 fused-silica capillary column (30m * 0.25mm * 0.25 μ m); Column temperature: 120 ℃; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000; The separating degree of paeonol peak and internal standard substance mass peak should be greater than 2;
It is an amount of that correction factor mensuration is got Pentadecane, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.3mg, as inner mark solution; It is an amount of to get the paeonol reference substance, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.4mg, in contrast product solution; Precision is measured reference substance solution and each 2ml of inner mark solution, puts in the 5ml measuring bottle, adds chloroform to scale, shakes up, and draws 2 μ l, inject gas chromatograph, the calculation correction factor;
Algoscopy is got 10 in this preparation, and accurate the title decides, and porphyrize is got 1.6g, the accurate title, decide, and uses vapor distillation, collects distillate 400ml, extract 4 (60ml, 40ml, 40ml with the chloroform jolting, 30ml), merge chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform, to an amount of, be transferred in the 5ml measuring bottle, add chloroform to scale, shake up, precision is measured 2ml, puts in the 5ml measuring bottle, add inner mark solution 2ml, add chloroform, shake up to scale, draw 2 μ l inject gas chromatographs, measure, promptly;
Every in this preparation contains Cortex Moutan with paeonol C
9H
10O
3Meter must not be less than 1.2mg.
Claims (8)
1. cassia twig tuckahoe effervescence tablet, it is characterized in that: it is prepared from by Ramulus Cinnamomi 240g, Poria 240g, Cortex Moutan 240g, Radix Paeoniae Alba 240g, Semen Persicae 240g and microcrystalline Cellulose 272g, low-substituted hydroxypropyl cellulose 96g, micropowder silica gel 96g, crospolyvinylpyrrolidone 125g, aspartame 10g, sodium bicarbonate 304g, citric acid 243g, fumaric acid 134g.
2. the preparation method of cassia twig tuckahoe effervescence tablet as claimed in claim 1 is characterized in that: get Poria 192g, be ground into fine powder; The Cortex Moutan vapor distillation is collected distillate, divides and gets volatile ingredient, and is standby; Medicinal residues and Ramulus Cinnamomi, the Radix Paeoniae Alba, Semen Persicae, and remaining Poria with 90% ethanol extraction secondary, merge extractive liquid, reclaims ethanol and does not distinguish the flavor of to there being alcohol, relative density 1.10～1.20 when being evaporated to 25 ℃; Medicinal residues decoct with water secondary again, filter, merging filtrate, relative density 1.10～1.20 when being evaporated to 25 ℃, merge with above-mentioned concentrated solution, with Poria fine powder mixing, drying is pulverized again, cross 80 mesh sieves, with microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel, crospolyvinylpyrrolidone, aspartame, sodium bicarbonate, citric acid, fumaric acid and Cortex Moutan volatile ingredient mix homogeneously, compacting is packed promptly in flakes then.
3. the method for quality control of cassia twig tuckahoe effervescence tablet as claimed in claim 1 or 2 is characterized in that: described method of quality control mainly comprise in character, inspection, discriminating, the assay project partly or entirely; Wherein discriminating is that the gas chromatogram of Ramulus Cinnamomi is differentiated; Assay is the assay to paeonol in the preparation.
4. according to the method for quality control of the described cassia twig tuckahoe effervescence tablet of claim 3, it is characterized in that: the discrimination method of Ramulus Cinnamomi is to be the gas chromatography of contrast with the cinnamic aldehyde reference substance.
5. according to the method for quality control of claim 3 or 4 described cassia twig tuckahoe effervescence tablets, it is characterized in that: concrete discrimination method is:
Get 10 in this preparation, the accurate title, decide, and porphyrize is got 1.6g, the accurate title, decide, and uses vapor distillation, collects distillate 400ml, extracts 4 times with the chloroform jolting, merge chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, promptly get need testing solution; It is an amount of to get the cinnamic aldehyde reference substance, adds chloroform and makes the solution that every 1ml contains 5 μ g, in contrast product solution; According to an appendix VIE of Chinese Pharmacopoeia version in 2005 gas chromatography test, draw reference substance solution respectively and need testing solution is an amount of, inject gas chromatograph should present the chromatographic peak identical with the reference substance retention time in the test sample chromatograph.
6. according to the method for quality control of the described cassia twig tuckahoe effervescence tablet of claim 3, it is characterized in that: the content assaying method of paeonol is to be the gas chromatography of contrast with the paeonol reference substance.
7. according to the method for quality control of claim 3 or 6 described cassia twig tuckahoe effervescence tablets, it is characterized in that: concrete content assaying method is:
According to 2005 editions one appendix VIE gas chromatography determination of Chinese Pharmacopoeia:
The HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Column temperature: 120 ℃; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000; The separating degree of paeonol peak and internal standard substance mass peak should be greater than 2;
It is an amount of that correction factor mensuration is got Pentadecane, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.3mg, as inner mark solution; It is an amount of to get the paeonol reference substance, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.4mg, in contrast product solution; Precision is measured reference substance solution and each 2ml of inner mark solution, puts in the 5ml measuring bottle, adds chloroform to scale, shakes up, and draws 2 μ l, inject gas chromatograph, the calculation correction factor;
Algoscopy is got 10 in this preparation, and accurate the title decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 times, merge chloroform liquid with the chloroform jolting, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, precision is measured 2ml, put in the 5ml measuring bottle, add inner mark solution 2ml, add chloroform to scale, shake up, draw 2 μ l inject gas chromatographs, measure, promptly;
Every in this preparation contains Cortex Moutan in paeonol C9H10O3, must not be less than 1.2mg.
8. according to the method for quality control of the described cassia twig tuckahoe effervescence tablet of claim 3, it is characterized in that: described method of quality control comprises:
Character: medicine is that light brown is to brown; Feeble QI perfume (or spice), it is little sweet to distinguish the flavor of;
Differentiate: get 10 in this preparation, the accurate title, decide, and porphyrize is got 1.6g, the accurate title, decide, and uses vapor distillation, collects distillate 400ml, extracts 4 times with the chloroform jolting, merge chloroform liquid, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, promptly get need testing solution; It is an amount of to get the cinnamic aldehyde reference substance, adds chloroform and makes the solution that every 1ml contains 5 μ g, in contrast product solution; According to an appendix VI of Chinese Pharmacopoeia version in 2005 E gas chromatography test, draw reference substance solution respectively and need testing solution is an amount of, inject gas chromatograph should present the chromatographic peak identical with the reference substance retention time in the test sample chromatograph;
Check: should meet relevant every regulation under an appendix ID of Chinese Pharmacopoeia version in 2005 the tablet item;
Assay: shine 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination:
The HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Column temperature: 120 ℃; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the paeonol peak and is calculated, and should be not less than 10000; The separating degree of paeonol peak and internal standard substance mass peak should be greater than 2;
It is an amount of that correction factor mensuration is got Pentadecane, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.3mg, as inner mark solution; It is an amount of to get the paeonol reference substance, and accurate the title decides, and adds chloroform and makes the solution that every 1ml contains 0.4mg, in contrast product solution; Precision is measured reference substance solution and each 2ml of inner mark solution, puts in the 5ml measuring bottle, adds chloroform to scale, shakes up, and draws 2 μ l, inject gas chromatograph, the calculation correction factor;
Algoscopy is got 10 in this preparation, and accurate the title decided porphyrize, get 1.6g, the accurate title, decide, and uses vapor distillation, collect distillate 400ml, extract 4 times, merge chloroform liquid with the chloroform jolting, add anhydrous sodium sulfate 2.0g and make dehydration, filter, get filtrate, with chloroform liquid 10ml gradation washing anhydrous sodium sulfate and container, filter, merge chloroform liquid, in 70 ℃ of water-baths, reclaim chloroform,, be transferred in the 5ml measuring bottle to an amount of, add chloroform to scale, shake up, precision is measured 2ml, put in the 5ml measuring bottle, add inner mark solution 2ml, add chloroform to scale, shake up, draw 2 μ l inject gas chromatographs, measure, promptly;
Every in this preparation contains Cortex Moutan in paeonol C9H10O3, must not be less than 1.2mg.
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