CN100457159C - Chronic pharyngolaryngitis effervescence tablet and preparation method and its quality control method - Google Patents
Chronic pharyngolaryngitis effervescence tablet and preparation method and its quality control method Download PDFInfo
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Abstract
The invention provides an effervescent tablet for treating chronic pharyngitis, its preparing process and quality control process, wherein the tablet is prepared from dried rehmannia root, scrophularia root, Chinese white olive, cicada shell, lilyturf root, sterculia seed, adenophora root, pseudostellaria root, dried orange peel and right amount of auxiliary materials.
Description
Technical field:
The present invention relates to a kind of (gold fruit) effervescent tablet and preparation method and method of quality control for the treatment of chronic pharyngolaryngitis, belong to technical field of Chinese medicine.
Background technology:
Chronic pharyngolaryngitis is that mucosa, mucosa reach adenoid diffuse inflammation down, due to many because acute inflammation shows effect repeatedly, other also have tobacco and wine excessively, with bad life habits such as sound are excessive, suck for a long time due to the factors such as chronic disease of harmful gas and vicinity or whole body organ.Existing gold fruit drinks on the market, really buccal tablet is better to the curative effect of chronic pharyngolaryngitis for gold.And along with the raising of Chinese medicine research level, the dosage form that exploitation constantly makes new advances.Effervescent tablet is one of selectable dosage form of form of Chinese drug modernization, all is 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, the composition in the tablet is in time decomposed, principal agent is fully contacted with human organ, improve curative effect of medication and action time to disintegration; 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 gold fruit 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 (gold fruit) effervescent tablet and preparation method and method of quality control for the treatment of chronic pharyngolaryngitis is 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 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 by Radix Rehmanniae 364g, Radix Scrophulariae 273g, FRUCTUS TERMINALIAE IMMATURUS 91g, Periostracum Cicadae 136g, Radix Ophiopogonis 273g, Semen Sterculiae Lychnophorae 91g, Radix Adenophorae 273g, Radix Pseudostellariae 273g, Pericarpium Citri Reticulatae 182g and microcrystalline Cellulose 480g, low-substituted hydroxypropyl cellulose 150g, crospolyvinylpyrrolidone 880g, micropowder silica gel 55g, aspartame 7g, sodium bicarbonate 530g, citric acid 450g, fumaric acid 190g and Oleum menthae be prepared from right amount.
The preparation method of the effervescent tablet of treatment chronic pharyngolaryngitis is: Radix Rehmanniae, Radix Scrophulariae, FRUCTUS TERMINALIAE IMMATURUS, Periostracum Cicadae are added 10 times of water gagings decoct twice, each 30 minutes, collecting decoction filtered, it is 1.14 that filtrate is concentrated into 80 ℃ of relative densities, cool off, add the ethanol of 2 times of amounts, stir evenly, left standstill 24 hours, draw supernatant, be evaporated to 80 ℃ of relative densities and be 1.14 concentrated solution, standby; Other gets Radix Ophiopogonis, Semen Sterculiae Lychnophorae, Radix Adenophorae, Radix Pseudostellariae, Pericarpium Citri Reticulatae adds 10 times of water gagings and decocts twice, 30 minutes for the first time, 20 minutes for the second time, collecting decoction, filter, it is 1.03 concentrated solution that filtrate is concentrated into 80 ℃ of relative densities, merges with above-mentioned standby concentrated solution, vacuum drying, the extractum of oven dry is pulverized, crossed 80 mesh sieves, with microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel, crospolyvinylpyrrolidone, aspartame, the 250g sodium bicarbonate is crossed 80 mesh sieve mix homogeneously, with 95% ethanol system soft material, 30 orders are granulated, 60 ± 5 ℃ of dryings, 30 eye mesh screen granulate, add citric acid in the dried granule, fumaric acid and residual sodium bicarbonate, add Oleum menthae behind the mix homogeneously, airtight, be pressed into 1000, packing, promptly.
The method of quality control of effervescent tablet of treatment chronic pharyngolaryngitis: described method of quality control mainly comprise in character, inspection, discriminating, the assay project partly or entirely; Wherein discriminating is that the thin layer chromatography of FRUCTUS TERMINALIAE IMMATURUS, Pericarpium Citri Reticulatae, Radix Scrophulariae is differentiated; Assay is that Determination of Hesperidin Content in the preparation is measured.
The discrimination method of FRUCTUS TERMINALIAE IMMATURUS is to be contrast with FRUCTUS TERMINALIAE IMMATURUS control medicinal material and gallic acid reference substance, and with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is the thin layer chromatography discrimination method of developing solvent; The discrimination method of Pericarpium Citri Reticulatae is to be contrast with the Pericarpium Citri Reticulatae control medicinal material, and with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is the thin layer chromatography discrimination method of developing solvent; The discrimination method of Radix Scrophulariae is to be contrast with the Radix Scrophulariae control medicinal material, and with chloroform: methanol=5: 1 is the thin layer chromatography discrimination method of developing solvent.
Concrete discrimination method comprises the part or all of of following project:
(1) get 3 in this preparation, porphyrize adds water 100ml, treat foaming fully after, add dilute hydrochloric acid 10ml, heating makes dissolving, filters, filtrate adds ethyl acetate 40ml, jolting is extracted gently, divides and gets acetic acid ethyl fluid, is concentrated into about 2ml, as need testing solution; Other gets FRUCTUS TERMINALIAE IMMATURUS control medicinal material 2g, adds water 100ml, boils 15～20 minutes, constantly drips dilute hydrochloric acid 20～30ml simultaneously, filters while hot, and filtrate adds ether 50ml, and jolting is extracted gently, divides and gets ether solution, is concentrated into about 5ml, in contrast medical material solution; Get the gallic acid reference substance again, add ethyl acetate and make the solution that every 1ml contains 2mg, in contrast product solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of need testing solution 10 μ l, control medicinal material solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is developing solvent, 10～20 ℃ of expansion, take out, dry, spray is with 2% ferric chloride alcoholic solution; In the test sample chromatograph, respectively with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) get 2 in this preparation, porphyrize adds 40ml water, treat foaming fully after, supersound process 10 minutes filters, filtrate adds the ethyl acetate jolting and extracts twice, each 20ml collects acetic acid ethyl fluid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, add water 50ml, decocted 20 minutes, filter, get filtrate, be added on the polyamide column of 60 orders, 2g, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting, collect eluent ethyl acetate liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is developing solvent, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get 6 in this preparation, porphyrize adds ethanol 50ml, supersound process 1 hour leaves standstill, and filters, filtrate evaporate to dryness, residue add water 30ml, and heating makes dissolving, extract 2 times with the ether jolting, each 30ml, the water saturated n-butyl alcohol 30ml of reuse jolting is extracted, get n-butanol extracting liquid, water 10ml washing, n-butyl alcohol liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2.5g, adds ethanol 50ml, and reflux 1 hour filters, and gets filtrate, from " filtrate evaporate to dryness ", shines medical material solution in pairs with legal system; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=5: 1 is developing solvent, presaturation 30 minutes launches, and takes out, dry, spray shows red with 1% vanillin sulfuric acid solution to speckle; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, place the back spot colors and deepen gradually.
The Determination of Hesperidin Content assay method is to be contrast with the Hesperidin reference substance, and with acetonitrile: 0.2% phosphoric acid=22: 78 is the high performance liquid chromatography of mobile phase.
Concrete content assaying method is:
The Hesperidin photograph " an appendix VID of Chinese pharmacopoeia version in 2000 high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; With acetonitrile: 0.2% phosphoric acid=22: 78 is mobile phase; The detection wavelength is 284nm; Number of theoretical plate should be not less than 3000 by the Hesperidin peak;
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every ml contains Hesperidin 10 μ g, promptly;
The powder 0.65g under this preparation tablet weight variation item is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml volumetric flask, adds methanol 40ml, ultrasonic 30min is put coldly, adds methanol constant volume to scale, shakes up, with the filtering with microporous membrane of 0.45 μ m, get subsequent filtrate, promptly;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
Every in this preparation contains Pericarpium Citri Reticulatae with Hesperidin (C
28H
34O
15) meter, must not be less than 1.5mg.
Method of quality control of the present invention comprises:
Character: medicine is a light brown to brown, unilaterally is dispersed in brown or white dot; It is little sweet to distinguish the flavor of, and refrigerant sense is arranged;
Differentiate: (1) gets 3 in this preparation, and porphyrize adds water 100ml, treat foaming fully after, add dilute hydrochloric acid 10ml, heating makes dissolving, filters, filtrate adds ethyl acetate 40ml, jolting is extracted gently, divides and gets acetic acid ethyl fluid, is concentrated into about 2ml, as need testing solution; Other gets FRUCTUS TERMINALIAE IMMATURUS control medicinal material 2g, adds water 100ml, boils 15～20 minutes, constantly drips dilute hydrochloric acid 20～30ml simultaneously, filters while hot, and filtrate adds ether 50ml, and jolting is extracted gently, divides and gets ether solution, is concentrated into about 5ml, in contrast medical material solution; Get the gallic acid reference substance again, add ethyl acetate and make the solution that every 1ml contains 2mg, in contrast product solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of need testing solution 10 μ l, control medicinal material solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is developing solvent, 10～20 ℃ of expansion, take out, dry, spray is with 2% ferric chloride alcoholic solution; In the test sample chromatograph, respectively with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) get 2 in this preparation, porphyrize adds 40ml water, treat foaming fully after, supersound process 10 minutes filters, filtrate adds the ethyl acetate jolting and extracts twice, each 20ml collects acetic acid ethyl fluid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, add water 50ml, decocted 20 minutes, filter, get filtrate, be added on the polyamide column of 60 orders, 2g, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting, collect eluent ethyl acetate liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is developing solvent, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get 6 in this preparation, porphyrize adds ethanol 50ml, supersound process 1 hour leaves standstill, and filters, filtrate evaporate to dryness, residue add water 30ml, and heating makes dissolving, extract 2 times with the ether jolting, each 30ml, the water saturated n-butyl alcohol 30ml of reuse jolting is extracted, get n-butanol extracting liquid, water 10ml washing, n-butyl alcohol liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2.5g, adds ethanol 50ml, and reflux 1 hour filters, and gets filtrate, from " filtrate evaporate to dryness ", shines medical material solution in pairs with legal system; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=5: 1 is developing solvent, presaturation 30 minutes launches, and takes out, dry, spray shows red with 1% vanillin sulfuric acid solution to speckle; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, place the back spot colors and deepen gradually;
Check: get 1 in this preparation disintegration, put in the 250ml beaker that fills 200ml25 ℃ of water, have numerous air-bubble to emit, immediately timing; When bubble stopped to overflow, tablet was dispersed in the water fully, did not have accumulative granule residue; Should in 5 minutes, disintegrate finish;
Other should meet " relevant every regulation under 2005 editions one appendix I D of the Chinese pharmacopoeia tablet item;
Assay: the Hesperidin photograph " an appendix VID of Chinese pharmacopoeia version in 2000 high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; With acetonitrile: 0.2% phosphoric acid=22: 78 is mobile phase; The detection wavelength is 284nm; Number of theoretical plate should be not less than 3000 by the Hesperidin peak;
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every ml contains Hesperidin 10 μ g, promptly;
The powder 0.65g under this preparation tablet weight variation item is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml volumetric flask, adds methanol 40ml, ultrasonic 30min is put coldly, adds methanol constant volume to scale, shakes up, with the filtering with microporous membrane of 0.45 μ m, get subsequent filtrate, promptly;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
Every in this preparation contains Pericarpium Citri Reticulatae with Hesperidin (C
28H
34O
15) meter, must not be less than 1.5mg.
Radix Rehmanniae is cold in nature among the we, and sweet in the mouth, hardship, major function are clearing away heat and cooling blood, Yin-nourishing and body fluid promoting etc.; Radix Scrophulariae is cold in nature, bitter in the mouth, salty, and major function is nourshing Yin and drynsessmoistening prescription, relieving constipation, detoxifcation, softening the hard mass etc.; The Semen Sterculiae Lychnophorae cold nature, sweet in the mouth, light, lung heat clearing, sore-throat relieving, loosening bowel to relieve constipation, detoxifcation; Other composition also has FRUCTUS TERMINALIAE IMMATURUS, Periostracum Cicadae, Radix Ophiopogonis, Radix Adenophorae, Radix Pseudostellariae, Pericarpium Citri Reticulatae, Herba Menthae wet goods, main effect also for heat clearing away, YIN nourishing, reduce phlegm, sound producing.These a few flavor medicines are all prepared at the Chinese medicine cause of disease of chronic pharyngolaryngitis, meet its Therapeutic Principle, determined curative effect.
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 safe in utilization, to the acute and chronic pharyngitis determined curative effect, 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 amount of water
Test method: get the medical material of a recipe quantity, add the water extraction of 12 times, 10 times, 8 times, 6 times amounts respectively, with paste volume (dry extract) index that judges.Determine the optimum extraction amount of water, result of the test is as follows:
| Extract amount of water (doubly) | Four flavor paste volumes (g) such as Radix Rehmanniae | Five tastes paste volumes (g) such as Radix Ophiopogonis |
| 12 | 1027 | 927 |
| 10 | 1020 | 918 |
| 8 | 965 | 863 |
| 6 | 903 | 825 |
Result of the test shows, it is comparatively suitable to adopt when adding 10 times of water gagings and extracting, the paste volume of its paste volume when adding 8 times of amounts and 6 times of amounts, and paste volume does not have significant difference when adding 12 times of water gagings and extract, and determines that therefore extracting amount of water is 10 times of amounts.
2. preparation prescription craft screening
| Form | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 |
| The gold fruit drinks dry extract (g) | A recipe quantity | A recipe quantity | A recipe quantity | A recipe quantity |
| Dextrin (g) | 200g | 100 | 100 | - |
| Mannitol (g) | - | - | 200 | - |
| Microcrystalline Cellulose (g) | - | 200 | 300 | 480 |
| Crospolyvinylpyrrolidone (g) | 250 | 550 | - | 880 |
| Low-substituted hydroxypropyl cellulose (g) | 150 | 150 | 200 | 150 |
| Micropowder silica gel (g) | 150 | 150 | 150 | 55 |
| Aspartame (g) | 15 | - | - | 7 |
| Sodium bicarbonate (g) | 465 | 465 | 465 | 530 |
| Citric acid (g) | 380 | 380 | 380 | 450 |
| Fumaric acid (g) | 210 | 210 | 210 | 190 |
The result: prescription one has the sticking phenomenon in the tabletting process;
The two gained slice, thin pieces of writing out a prescription are unilateral smooth, but disintegrate is defective, produces the sticking phenomenon sometimes, and taste is relatively poor;
The three gained slice, thin pieces of writing out a prescription are unilateral smooth, but disintegrate is defective, and taste is relatively poor;
The four gained slice, thin pieces of writing out a prescription are unilateral smooth, and disintegrate is qualified, and taste is suitable.
Final definite gold fruit effervescent tablet prescription and preparation technology are as follows:
Dry extract (a prescription medical material is carried)
Microcrystalline Cellulose 480g
Crospolyvinylpyrrolidone 880g
Low-substituted hydroxypropyl cellulose 150g
Micropowder silica gel 55g
Sodium bicarbonate 530g
Citric acid 450g
Fumaric acid 190g
Aspartame 7g
Make 1000 altogether, every heavy 3.40g.
Preparation technology:
Radix Rehmanniae, Radix Scrophulariae, FRUCTUS TERMINALIAE IMMATURUS, Periostracum Cicadae are added 10 times of water gagings to be decocted twice, each 30 minutes, collecting decoction filtered, it is 1.14 (80 ℃) that filtrate is concentrated into relative density, cooling adds 2 times of amounts of ethanol, stirs evenly, left standstill 24 hours, draw supernatant, be evaporated to relative density and be the concentrated solution of 1.14 (80 ℃), standby.Other gets the decocting that adds Radix Ophiopogonis, Semen Sterculiae Lychnophorae, Radix Adenophorae, Radix Pseudostellariae, Pericarpium Citri Reticulatae 10 times of amounts and boils twice, and 30 minutes for the first time, 20 minutes for the second time, collecting decoction filters, and filtrate is concentrated into the concentrated solution of relative density 1.03 (80 ℃), merge vacuum drying with above-mentioned standby concentrated solution.The extractum of oven dry is pulverized, crossed 80 mesh sieves, cross 80 mesh sieves with microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel, crospolyvinylpyrrolidone, aspartame, the sodium bicarbonate (250g) of recipe quantity, mix homogeneously, with 95% ethanol system soft material, 30 orders are granulated, 60 ± 5 ℃ of dryings, 30 eye mesh screen granulate, after adding citric acid, fumaric acid and sodium bicarbonate (280g) mix homogeneously in the dried granule, add Oleum menthae, airtight, be pressed into 1000, the packing, promptly.
3. the result of the test of three batches of pilot products
| Lot number | 050501 | 050502 | 050503 |
| Raw medicinal herbs input amount (kg) | 19.56 | 19.56 | 19.56 |
| Sodium bicarbonate (kg) | 5.30 | 5.30 | 5.30 |
| Microcrystalline Cellulose (kg) | 4.80 | 4.80 | 4.80 |
| Low-substituted hydroxypropyl cellulose (kg) | 1.50 | 1.50 | 1.50 |
| Crospolyvinylpyrrolidone (kg) | 8.80 | 8.80 | 8.80 |
| Aspartame (kg) | 0.07 | 0.07 | 0.07 |
| Micropowder silica gel (kg) | 0.55 | 0.55 | 0.55 |
| Citric acid (kg) | 4.50 | 4.50 | 4.50 |
| Fumaric acid (kg) | 1.90 | 1.90 | 1.90 |
| Theoretical yield (sheet) | 10000 | 10000 | 10000 |
| Actual production (sheet) | 9090 | 8982 | 8784 |
| Yield rate (%) | 90.90 | 89.82 | 87.84 |
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
Gold fruit effervescent tablet is made up of kinds of traditional Chinese medicines, and is as follows with regard to the pharmacodynamics summarization of data of its main Chinese medicinal materials below:
Radix Rehmanniae has pharmacological action widely, and the Radix Rehmanniae crude extract can delay the catabolism effect of hepatocyte to hydrocortisone, when share with exogenous 17-hydroxy-11-dehydrocorticosterone, makes blood plasma cortisol content still can maintain approximate normal level; Rat ip100% every day Radix Rehmanniae injection 1ml, continuous 6d can make the platelet injury of accepting due to 600 gamma-radiations alleviate, and gos up to accelerate; The Radix Rehmanniae decoct has protective effect to mouse experiment carbon tetrachloride poisoning hepatitis, can prevent that hepatic glycogen from reducing; Rabbit sc Radix Rehmanniae alcohol extractum solution 2g/kg or ig4g/kg all can make blood glucose descend; Radix Rehmanniae decocting liquid and pure preserved material 10g/kg gavage every day, and 5d has remarkable detumescence effect to rat experiment formaldehyde swelling of the feet continuously, has antiinflammatory action; Test tube experiment effect Radix Rehmanniae water logging agent has inhibitory action, the tool antifungic action to multiple fungi growth such as trichophyton mentagrophytes, Gypsum Fibrosum sample and Ang Shi microspore Du tinea bacterium; Also have hemostasis, diuresis in addition, rush down inferior effect.
Radix Scrophulariae infusion, pure immersion and decoct can cause blood pressure drops to multiple animals such as anesthetized dog, cat, rabbits.Mice there are calmness, anti-frightened effect, and certain antibacterial action is arranged, staphylococcus aureus, bacillus pyocyaneus, tinea barbae trichobacteria, microsporum canis are all had inhibitory action.
Semen Sterculiae Lychnophorae seed leachate has demulcent discharge function to the intestinal tube of rabbit.Its mechanism is that Semen Sterculiae Lychnophorae back for oral administration increases the enteral volume and produces mechanical irritation, causes the result that the reflexive enterokinesia increases; Semen Sterculiae Lychnophorae core is made 25% solution, and iv, im or po all can make dog, cat blood pressure obviously descend; Semen Sterculiae Lychnophorae has suitable diuresis to anesthetized dog, to each extract of Cavia porcellus sc Semen Sterculiae Lychnophorae, uses the faradize method, proves that pain threshold all has the raising of certain degree; Illustrate that Semen Sterculiae Lychnophorae has effects such as cathartic, blood pressure lowering, diuresis, pain relieving.
Other composition also has FRUCTUS TERMINALIAE IMMATURUS, Periostracum Cicadae, Radix Ophiopogonis, Radix Adenophorae, Radix Pseudostellariae, Pericarpium Citri Reticulatae etc., main effect also for heat clearing away, YIN nourishing, reduce phlegm, sound producing.
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 Hesperidin reference substance derives from Nat'l Pharmaceutical ﹠ Biological Products Control Institute; Lot number 11072-200211;
The FRUCTUS TERMINALIAE IMMATURUS control medicinal material derives from Nat'l Pharmaceutical ﹠ Biological Products Control Institute; Lot number: 946-9903;
The Pericarpium Citri Reticulatae control medicinal material derives from Nat'l Pharmaceutical ﹠ Biological Products Control Institute; Lot number: 120969-200406;
The Radix Scrophulariae control medicinal material derives from Nat'l Pharmaceutical ﹠ Biological Products Control Institute; Lot number: 121008-200505;
The gallic acid reference substance derives from the institute for drug control, Zhejiang Province, lot number: 20000727
(2) character
This preparation forms through granulation, mixing, tabletting for the Chinese medical concrete powder adds appropriate amount of auxiliary materials, through the trial-production of many batch samples, determines that this preparation character is: medicine be light brown to brown, unilaterally be dispersed in brown or white dot; It is little sweet to distinguish the flavor of, and refrigerant sense is arranged.
(3) differentiate
Content under the FRUCTUS TERMINALIAE IMMATURUS in the gold fruit buccal tablet quality standard that records with reference to " Chinese medicine pharmacopeia " version in 2005, Pericarpium Citri Reticulatae, Radix Scrophulariae three flavor medical materials mirror.
1, the thin layer of FRUCTUS TERMINALIAE IMMATURUS is differentiated
(1) get 3 in this preparation, porphyrize adds water 100ml, treat foaming fully after, add dilute hydrochloric acid 10ml, heating makes dissolving, filters, filtrate adds ethyl acetate 40ml, jolting is extracted gently, divides and gets acetic acid ethyl fluid, is concentrated into about 2ml, as need testing solution.Other gets FRUCTUS TERMINALIAE IMMATURUS control medicinal material 2g, adds water 100ml, boils 15～20 minutes, constantly drips dilute hydrochloric acid 20～30ml simultaneously, filters while hot, and filtrate adds ether 50ml, and jolting is extracted gently, divides and gets ether solution, is concentrated into about 5ml, in contrast medical material solution.Get the gallic acid reference substance again, add ethyl acetate and make the solution that every 1ml contains 2mg, in contrast product solution.According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of need testing solution 10 μ l, control medicinal material solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is developing solvent, 10～20 ℃ of expansion, take out, dry, spray is with 2% ferric chloride alcoholic solution.In the test sample chromatograph, respectively with control medicinal material chromatograph and 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 point sample 5 μ l, 10 μ l, speckle is better, comparatively clear when found that need testing solution point sample 10 μ l.So this standard need testing solution selects for use 10 μ l as the point sample amount.
(3) specificity experiment
Get the about 1g of negative sample that lacks FRUCTUS TERMINALIAE IMMATURUS, make negative need testing solution, launch the back and do not have corresponding speckle, illustrate that negative sample is noiseless to this experiment at the reference substance place with the operation of test sample method.
2, the thin layer of Pericarpium Citri Reticulatae is differentiated
(1) selection of extracting method
A, get 2 in this preparation, porphyrize adds 40ml water, treat foaming fully after, supersound process 10 minutes filters, filtrate adds the ethyl acetate jolting and extracts twice, each 20ml collects acetic acid ethyl fluid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, adds water 50ml, decocts 20 minutes, filter, get filtrate, be added in polyamide column (60 orders, 2g) on, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting is collected eluent ethyl acetate liquid, evaporate to dryness, residue adds methanol 1ml makes dissolving, in contrast medical material solution.According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, idea is same respectively is on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate (1: 1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
B, get 2 in this preparation, porphyrize adds ethyl acetate 20ml, and supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, adds water 50ml, decocts 20 minutes, filter, get filtrate, be added in polyamide column (60 orders, 2g) on, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting is collected eluent ethyl acetate liquid, evaporate to dryness, residue adds methanol 1ml makes dissolving, in contrast medical material solution.According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate (1: 1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, not with the corresponding fluorescence speckle of control medicinal material chromatograph.
(2) selection of point sample amount
Through experimental selection need testing solution point sample 5 μ l, 10 μ l, speckle is better, comparatively clear when found that need testing solution 10 μ l.So this standard reference material solution and need testing solution select for use 10 μ l as the point sample amount.
(3) specificity experiment
Get the about 1g of negative sample that lacks Pericarpium Citri Reticulatae, make negative need testing solution, launch the back and do not have corresponding speckle, illustrate that negative sample is noiseless to this experiment at the reference substance place with the operation of a method.
3, the thin layer of Radix Scrophulariae is differentiated
(1) get 6 in this preparation, porphyrize adds ethanol 50ml, supersound process 1 hour leaves standstill, and filters, filtrate evaporate to dryness, residue add water 30ml, and heating makes dissolving, extract 2 times with the ether jolting, each 30ml, the water saturated n-butyl alcohol 30ml of reuse jolting is extracted, get n-butanol extracting liquid, water 10ml washing, n-butyl alcohol liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution.Other gets Radix Scrophulariae control medicinal material 2.5g, adds ethanol 50ml, and reflux 1 hour filters, and gets filtrate, from " filtrate evaporate to dryness ", shines medical material solution in pairs with legal system.According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol (5: 1) is developing solvent, presaturation 30 minutes launches, and takes out, dry, spray shows red with 1% vanillin sulfuric acid solution to speckle.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, place the back spot colors and deepen gradually.
(2) selection of point sample amount
Through experimental selection need testing solution point sample 5 μ l, 10 μ l, speckle is better, comparatively clear when found that need testing solution point sample 10 μ l.So this standard need testing solution selects for use 10 μ l as the point sample amount.
(3) specificity experiment
Get the about 1g of negative sample that lacks Radix Scrophulariae, make negative need testing solution, launch the back and do not have corresponding speckle, illustrate that negative sample is noiseless to this experiment at the reference substance place with the operation of test sample method.
(4) check
1, disintegration
(1) selects foundation
This preparation is an effervescent tablet, according to " carrying out disintegration about the associated description of effervescent tablet under two appendix XA of Chinese pharmacopoeia version in 2000 item detects.
(2) detection method
Get 1 in this preparation, put in the 250ml beaker that fills 200ml25 ℃ of water.Have numerous air-bubble to emit, when bubble stopped to overflow, tablet was dispersed in the water fully, did not have accumulative granule residue.Get 6 in this preparation, measure with method.Each sheet all should finish in 5 minutes in disintegrate.
(3) testing result
Table 1 check result disintegration
| Lot number | 050501 | 050502 | 050503 |
| Disintegration | 4 minutes | 4 minutes | 4 minutes |
2, arsenic salt is by " an appendix IX of Chinese pharmacopoeia version in 2000 F arsenic salt inspection technique first method checks that the result is up to specification.
Table 2 arsenic salt measurement result
| Lot number | 050501 | 050502 | 050503 |
| Arsenic salt | ＜5ppm | ＜5ppm | ＜5ppm |
3, heavy metal is by " an appendix IX of Chinese pharmacopoeia version in 2000 E heavy metal inspection technique second method checks that the 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, and " regulation of Chinese pharmacopoeia tablet weight variation should be got 20 inspections of this preparation three batch samples in ± 5%, the results are shown in following table 4 by version in 2000.
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 2000) check result of three batch samples sees the following form.
Table 5 limit test of microbe result
| 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
1, experiment equipment
Instrument: Agilent 1100 type high performance liquid chromatographs (band automatic sampler), UV-detector, supersound extraction device SB2200 (220V, 50HZ).
Chromatographic column: SinoChrom ODS-BP post (4.6mm * 250mm, 5 μ m) liquid-phase chromatographic column
2, the selection of chromatographic condition:
(1) it is an amount of to get the Hesperidin reference substance, the accurate title, decide, add methanol and make the solution that every 1ml contains 30 μ g, according to spectrophotography (" appendix IVA of Chinese pharmacopoeia version in 2000) in the interscan of 200nm-400nm scope, record absorption maximum position 284nm, so the detection that content of hesperidin is measured is chosen as 284nm.
(2) mobile phase ratio:
With reference to " Pericarpium Citri Reticulatae assay item current downflow phase system in the Chinese pharmacopoeia 2000 editions, selecting the ratio of acetonitrile and 0.2% phosphoric acid is 22: 78, the Hesperidin appearance time is moderate, separator well, peak shape is good, does not trail.
(3) the Hesperidin reference substance is provided (110721-200211) by Chinese pharmaceutical biological product check.Get the Hesperidin reference substance, the photograph high performance liquid chromatography (" appendix VID of Chinese pharmacopoeia version in 2000) measure, surveying purity by area normalization method is 99.9%.
(4) get the negative sample 0.65g that lacks Pericarpium Citri Reticulatae, put in the 50ml measuring bottle, it is an amount of to add methanol, supersound extraction 30min, put cold, add methanol and be diluted to scale, shake up, filter, getting subsequent filtrate 20 μ l measures, the result does not go out the peak on the corresponding position of Hesperidin reference substance, prove that negative sample is noiseless to content of hesperidin mensuration.
3, the drafting of standard curve:
Precision takes by weighing Hesperidin reference substance 5.30mg, puts in the 100ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, and precision is got 2,4,6,8,10,12 μ l and injected chromatograph of liquid, and the record chromatogram the results are shown in Table 6.
Table 6 content of hesperidin is measured linear result
| Sample size (μ g) | 0.106 | 0.212 | 0.318 | 0.424 | 0.530 | 0.636 |
| Peak area | 179.6 | 374.1 | 542.3 | 722.8 | 904.8 | 1087.7 |
With peak area sample size is made linear regression, get regression equation: Y=1701.64X+3.9167, γ=0.9999
The result shows that Hesperidin is in 0.106 μ g～0.636 μ g scope, and linear relationship is good.
4, extracting method is selected:
With reference to method under Fupoganmao capsule standard WS-10009 (ZD-0009)-2002 Pericarpium Citri Reticulatae assay item, adopt ultrasonic method to extract Hesperidin in the test sample, method is easy and simple to handle fast, extracts fully.
5, extraction solvent is selected:
Get 10 in this preparation, the accurate title, decided porphyrize, get the about 0.65g of fine powder, the accurate title, decide, and puts in the 50ml measuring bottle, add ethanol respectively and methanol is an amount of, supersound extraction 30min is put cold, add aforementioned solution to scale, shake up, filter, get subsequent filtrate 20 μ l and inject chromatograph of liquid, measure by containing quantifier below method, the results are shown in Table 7.
The comparison of table 7 Hesperidin extraction solvent
| Solvent | Ethanol | Methanol |
| Content (mg/ sheet) | 2.16 | 2.56 |
The result shows that methanol extraction Hesperidin extraction ratio is higher, so select methanol as extracting solvent.
6, extraction time is selected:
Get 10 in this preparation, the accurate title, decided porphyrize, get the about 0.65g of fine powder, the accurate title, decide, and puts in the 50ml measuring bottle, it is an amount of to add methanol, supersound extraction 10,20,30,40min are put cold and are added methanol to scale, shake up, filter, get subsequent filtrate 20 μ l and inject chromatograph of liquid, measure, the results are shown in Table 8 by containing quantifier below method.
The comparison of table 8 Hesperidin extraction time
| Ultrasonic time (min) | 10 | 20 | 30 | 40 |
| Content (mg/ sheet) | 2.08 | 2.31 | 2.52 | 2.56 |
The result shows, just can extract Hesperidin more completely in ultrasonic 30 minutes.
7, precision:
It is an amount of to get the Hesperidin reference substance, and accurate the title decides, and adds methanol and is mixed with the solution that every 1ml contains Hesperidin 10 μ g approximately, shakes up, and filters, and gets subsequent filtrate 20 μ l and injects chromatograph of liquid, and continuous sample introduction 5 times the results are shown in Table 9.
Table 9 Hesperidin is measured Precision test result
The result shows that the sample introduction precision of this assay method is good.
8, stability test:
Get (050501) 10 in this preparation, the accurate title, decided porphyrize, get the about 0.65g of fine powder, the accurate title, decide, and presses method extraction under the assay item, put coldly, standardize solution shakes up, placed 12 hours in room temperature, respectively at 0,2,4,8,12 hour, filter, get subsequent filtrate 20 μ l sample introductions, the record liquid chromatogram the results are shown in Table 10.
Table 10 stability of solution result
The result shows that Hesperidin is stable within 12 hours in methanol.
9, repeatability test:
Get (050501) 10 in this preparation, the accurate title, decided porphyrize, get five parts of each about 0.65g of fine powder, the accurate title, decide, and puts respectively in the 50ml measuring bottle, it is an amount of to add methanol, and supersound extraction 30min is put cold, add methanol and be diluted to scale, shake up, filter, get subsequent filtrate 20 μ l, measure by containing quantifier below method, the results are shown in Table 11.
Table 11 content of hesperidin is measured reproducible test results
The result shows: the repeatability of content of hesperidin assay method is good.
10, determination of recovery rates
Get five parts of this preparation (050501) fine powders of known content, each about 0.36g, accurate claim fixed, put respectively in the 50ml measuring bottle, add Hesperidin reference substance (concentration is 0.343mg/ml) 1ml respectively, it is an amount of to add methanol, supersound extraction 30min is put coldly, adds methanol and is diluted to scale, shake up, filter, get subsequent filtrate 20 μ l, measure by containing quantifier below method, calculate recovery rate the results are shown in Table 12.
Table 12 content of hesperidin is measured recovery test
The result shows that this method is measured content of hesperidin, and the response rate is good.
11, content of hesperidin is measured in the sample:
Measure according to high performance liquid chromatography (" appendix VID of Chinese pharmacopoeia version in 2000):
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; With acetonitrile: 0.2% phosphoric acid (22: 78) is mobile phase; The detection wavelength is 284nm.Number of theoretical plate should be not less than 3000 by the Hesperidin peak.
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every ml contains Hesperidin 10 μ g, promptly.
The powder 0.65g under this preparation tablet weight variation item is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml volumetric flask, adds methanol 40ml, ultrasonic 30min is put coldly, adds methanol constant volume to scale, shakes up, with the filtering with microporous membrane of 0.45 μ m, get subsequent filtrate, promptly.
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Every in this preparation contains Pericarpium Citri Reticulatae with Hesperidin (C
28H
34O
15) meter, must not be less than 1.5mg.
12, measure three batches of test samples as stated above, data see Table 13.
Table 13 content of hesperidin measurement result
| Lot number | 050501 | 050502 | 050503 |
| Content (mg/ sheet) | 2.49 | 2.53 | 2.48 |
According to measurement result and this preparation prescription, with reference to " middle content of hesperidin limit of Chinese pharmacopoeia version in 2000 is decided to be limit every in this preparation temporarily and contains Pericarpium Citri Reticulatae with Hesperidin (C
28H
34O
15) meter, must not be less than 1.5mg.
The specific embodiment:
Embodiments of the invention 1: Radix Rehmanniae 364g, Radix Scrophulariae 273g, FRUCTUS TERMINALIAE IMMATURUS 91g, Periostracum Cicadae 136g, Radix Ophiopogonis, 273g, Semen Sterculiae Lychnophorae 91g, Radix Adenophorae 273g, Radix Pseudostellariae 273g, Pericarpium Citri Reticulatae 182g, microcrystalline Cellulose 480g, low-substituted hydroxypropyl cellulose 150g, crospolyvinylpyrrolidone 880g, micropowder silica gel 55g, aspartame 7g, sodium bicarbonate 530g, citric acid 450g, fumaric acid 190g and Oleum menthae were an amount of
Radix Rehmanniae, Radix Scrophulariae, FRUCTUS TERMINALIAE IMMATURUS, Periostracum Cicadae are added 10 times of water gagings to be decocted twice, each 30 minutes, collecting decoction filtered, it is 1.14 that filtrate is concentrated into 80 ℃ of relative densities, cool off, add the ethanol of 2 times of amounts, stir evenly, left standstill 24 hours, draw supernatant, be evaporated to 80 ℃ of relative densities and be 1.14 concentrated solution, standby; Other gets Radix Ophiopogonis, Semen Sterculiae Lychnophorae, Radix Adenophorae, Radix Pseudostellariae, Pericarpium Citri Reticulatae adds 10 times of water gagings and decocts twice, 30 minutes for the first time, 20 minutes for the second time, collecting decoction, filter, it is 1.03 concentrated solution that filtrate is concentrated into 80 ℃ of relative densities, merges with above-mentioned standby concentrated solution, vacuum drying, the extractum of oven dry is pulverized, crossed 80 mesh sieves, with microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel, crospolyvinylpyrrolidone, aspartame, the 250g sodium bicarbonate is crossed 80 mesh sieve mix homogeneously, with 95% ethanol system soft material, 30 orders are granulated, 60 ± 5 ℃ of dryings, 30 eye mesh screen granulate, add citric acid in the dried granule, fumaric acid and residual sodium bicarbonate, add Oleum menthae behind the mix homogeneously, airtight, be pressed into 1000, 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 a light brown to brown, unilaterally is dispersed in brown or white dot; It is little sweet to distinguish the flavor of, and refrigerant sense is arranged;
Differentiate: (1) gets 3 in this preparation, and porphyrize adds water 100ml, treat foaming fully after, add dilute hydrochloric acid 10ml, heating makes dissolving, filters, filtrate adds ethyl acetate 40ml, jolting is extracted gently, divides and gets acetic acid ethyl fluid, is concentrated into about 2ml, as need testing solution; Other gets FRUCTUS TERMINALIAE IMMATURUS control medicinal material 2g, adds water 100ml, boils 15～20 minutes, constantly drips dilute hydrochloric acid 20～30ml simultaneously, filters while hot, and filtrate adds ether 50ml, and jolting is extracted gently, divides and gets ether solution, is concentrated into about 5ml, in contrast medical material solution; Get the gallic acid reference substance again, add ethyl acetate and make the solution that every 1ml contains 2mg, in contrast product solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of need testing solution 10 μ l, control medicinal material solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is developing solvent, 10～20 ℃ of expansion, take out, dry, spray is with 2% ferric chloride alcoholic solution; In the test sample chromatograph, respectively with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) get 2 in this preparation, porphyrize adds 40ml water, treat foaming fully after, supersound process 10 minutes filters, filtrate adds the ethyl acetate jolting and extracts twice, each 20ml collects acetic acid ethyl fluid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, add water 50ml, decocted 20 minutes, filter, get filtrate, be added on the polyamide column of 60 orders, 2g, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting, collect eluent ethyl acetate liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is developing solvent, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get 6 in this preparation, porphyrize adds ethanol 50ml, supersound process 1 hour leaves standstill, and filters, filtrate evaporate to dryness, residue add water 30ml, and heating makes dissolving, extract 2 times with the ether jolting, each 30ml, the water saturated n-butyl alcohol 30ml of reuse jolting is extracted, get n-butanol extracting liquid, water 10ml washing, n-butyl alcohol liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2.5g, adds ethanol 50ml, and reflux 1 hour filters, and gets filtrate, from " filtrate evaporate to dryness ", shines medical material solution in pairs with legal system; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=5: 1 is developing solvent, presaturation 30 minutes launches, and takes out, dry, spray shows red with 1% vanillin sulfuric acid solution to speckle; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, place the back spot colors and deepen gradually;
Check: get 1 in this preparation disintegration, put in the 250ml beaker that fills 200ml25 ℃ of water, have numerous air-bubble to emit, immediately timing; When bubble stopped to overflow, tablet was dispersed in the water fully, did not have accumulative granule residue; Should in 5 minutes, disintegrate finish;
Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item;
Assay: the Hesperidin photograph " an appendix VID of Chinese pharmacopoeia version in 2000 high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; With acetonitrile: 0.2% phosphoric acid=22: 78 is mobile phase; The detection wavelength is 284nm; Number of theoretical plate should be not less than 3000 by the Hesperidin peak;
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every ml contains Hesperidin 10 μ g, promptly;
The powder 0.65g under this preparation tablet weight variation item is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml volumetric flask, adds methanol 40ml, ultrasonic 30min is put coldly, adds methanol constant volume to scale, shakes up, with the filtering with microporous membrane of 0.45 μ m, get subsequent filtrate, promptly;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
Every in this preparation contains Pericarpium Citri Reticulatae with Hesperidin (C
28H
34O
15) meter, must not be less than 1.5mg.
Embodiments of the invention 3: method of quality control can comprise following content:
Character: medicine is a light brown to brown, unilaterally is dispersed in brown or white dot; It is little sweet to distinguish the flavor of, and refrigerant sense is arranged;
Differentiate: get 6 in this preparation, porphyrize adds ethanol 50ml, supersound process 1 hour leaves standstill, and filters, filtrate evaporate to dryness, residue add water 30ml, and heating makes dissolving, extract 2 times with the ether jolting, each 30ml, the water saturated n-butyl alcohol 30ml of reuse jolting is extracted, get n-butanol extracting liquid, water 10ml washing, n-butyl alcohol liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2.5g, adds ethanol 50ml, and reflux 1 hour filters, and gets filtrate, from " filtrate evaporate to dryness ", shines medical material solution in pairs with legal system; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=5: 1 is developing solvent, presaturation 30 minutes launches, and takes out, dry, spray shows red with 1% vanillin sulfuric acid solution to speckle; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, place the back spot colors and deepen gradually;
Check: get 1 in this preparation disintegration, put in the 250ml beaker that fills 200ml25 ℃ of water, have numerous air-bubble to emit, immediately timing; When bubble stopped to overflow, tablet was dispersed in the water fully, did not have accumulative granule residue; Should in 5 minutes, disintegrate finish;
Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item;
Assay: the Hesperidin photograph " an appendix VID of Chinese pharmacopoeia version in 2000 high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; With acetonitrile: 0.2% phosphoric acid=22: 78 is mobile phase; The detection wavelength is 284nm; Number of theoretical plate should be not less than 3000 by the Hesperidin peak;
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every ml contains Hesperidin 10 μ g, promptly;
The powder 0.65g under this preparation tablet weight variation item is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml volumetric flask, adds methanol 40ml, ultrasonic 30min is put coldly, adds methanol constant volume to scale, shakes up, with the filtering with microporous membrane of 0.45 μ m, get subsequent filtrate, promptly;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
Every in this preparation contains Pericarpium Citri Reticulatae with Hesperidin (C
28H
34O
15) meter, must not be less than 1.5mg.
Embodiments of the invention 4: method of quality control can comprise following content:
Character: medicine is a light brown to brown, unilaterally is dispersed in brown or white dot; It is little sweet to distinguish the flavor of, and refrigerant sense is arranged;
Differentiate: (1) gets 3 in this preparation, and porphyrize adds water 100ml, treat foaming fully after, add dilute hydrochloric acid 10ml, heating makes dissolving, filters, filtrate adds ethyl acetate 40ml, jolting is extracted gently, divides and gets acetic acid ethyl fluid, is concentrated into about 2ml, as need testing solution; Other gets FRUCTUS TERMINALIAE IMMATURUS control medicinal material 2g, adds water 100ml, boils 15～20 minutes, constantly drips dilute hydrochloric acid 20～30ml simultaneously, filters while hot, and filtrate adds ether 50ml, and jolting is extracted gently, divides and gets ether solution, is concentrated into about 5ml, in contrast medical material solution; Get the gallic acid reference substance again, add ethyl acetate and make the solution that every 1ml contains 2mg, in contrast product solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of need testing solution 10 μ l, control medicinal material solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is developing solvent, 10～20 ℃ of expansion, take out, dry, spray is with 2% ferric chloride alcoholic solution; In the test sample chromatograph, respectively with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) get 2 in this preparation, porphyrize adds 40ml water, treat foaming fully after, supersound process 10 minutes filters, filtrate adds the ethyl acetate jolting and extracts twice, each 20ml collects acetic acid ethyl fluid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, add water 50ml, decocted 20 minutes, filter, get filtrate, be added on the polyamide column of 60 orders, 2g, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting, collect eluent ethyl acetate liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is developing solvent, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get 6 in this preparation, porphyrize adds ethanol 50ml, supersound process 1 hour leaves standstill, and filters, filtrate evaporate to dryness, residue add water 30ml, and heating makes dissolving, extract 2 times with the ether jolting, each 30ml, the water saturated n-butyl alcohol 30ml of reuse jolting is extracted, get n-butanol extracting liquid, water 10ml washing, n-butyl alcohol liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2.5g, adds ethanol 50ml, and reflux 1 hour filters, and gets filtrate, from " filtrate evaporate to dryness ", shines medical material solution in pairs with legal system; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=5: 1 is developing solvent, presaturation 30 minutes launches, and takes out, dry, spray shows red with 1% vanillin sulfuric acid solution to speckle; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, place the back spot colors and deepen gradually;
Check: get 1 in this preparation disintegration, put in the 250ml beaker that fills 200ml25 ℃ of water, have numerous air-bubble to emit, immediately timing; When bubble stopped to overflow, tablet was dispersed in the water fully, did not have accumulative granule residue; Should in 5 minutes, disintegrate finish;
Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item.
Embodiments of the invention 5: method of quality control can comprise following content:
Character: medicine is a light brown to brown, unilaterally is dispersed in brown or white dot; It is little sweet to distinguish the flavor of, and refrigerant sense is arranged;
Differentiate: (1) gets 3 in this preparation, and porphyrize adds water 100ml, treat foaming fully after, add dilute hydrochloric acid 10ml, heating makes dissolving, filters, filtrate adds ethyl acetate 40ml, jolting is extracted gently, divides and gets acetic acid ethyl fluid, is concentrated into about 2ml, as need testing solution; Other gets FRUCTUS TERMINALIAE IMMATURUS control medicinal material 2g, adds water 100ml, boils 15～20 minutes, constantly drips dilute hydrochloric acid 20～30ml simultaneously, filters while hot, and filtrate adds ether 50ml, and jolting is extracted gently, divides and gets ether solution, is concentrated into about 5ml, in contrast medical material solution; Get the gallic acid reference substance again, add ethyl acetate and make the solution that every 1ml contains 2mg, in contrast product solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of need testing solution 10 μ l, control medicinal material solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is developing solvent, 10～20 ℃ of expansion, take out, dry, spray is with 2% ferric chloride alcoholic solution; In the test sample chromatograph, respectively with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) get 2 in this preparation, porphyrize adds 40ml water, treat foaming fully after, supersound process 10 minutes filters, filtrate adds the ethyl acetate jolting and extracts twice, each 20ml collects acetic acid ethyl fluid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, add water 50ml, decocted 20 minutes, filter, get filtrate, be added on the polyamide column of 60 orders, 2g, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting, collect eluent ethyl acetate liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is developing solvent, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
Assay: the Hesperidin photograph " an appendix VID of Chinese pharmacopoeia version in 2000 high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; With acetonitrile: 0.2% phosphoric acid=22: 78 is mobile phase; The detection wavelength is 284nm; Number of theoretical plate should be not less than 3000 by the Hesperidin peak;
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every ml contains Hesperidin 10 μ g, promptly;
The powder 0.65g under this preparation tablet weight variation item is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml volumetric flask, adds methanol 40ml, ultrasonic 30min is put coldly, adds methanol constant volume to scale, shakes up, with the filtering with microporous membrane of 0.45 μ m, get subsequent filtrate, promptly;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
Every in this preparation contains Pericarpium Citri Reticulatae with Hesperidin (C
28H
34O
15) meter, must not be less than 1.5mg.
Claims (7)
1. effervescent tablet for the treatment of chronic pharyngolaryngitis, it is characterized in that: it is by Radix Rehmanniae 364g, Radix Scrophulariae 273g, FRUCTUS TERMINALIAE IMMATURUS 91g, Periostracum Cicadae 136g, Radix Ophiopogonis 273g, Semen Sterculiae Lychnophorae 91g, Radix Adenophorae 273g, Radix Pseudostellariae 273g, Pericarpium Citri Reticulatae 182g and microcrystalline Cellulose 480g, low-substituted hydroxypropyl cellulose 150g, crospolyvinylpyrrolidone 880g, micropowder silica gel 55g, aspartame 7g, sodium bicarbonate 530g, citric acid 450g, fumaric acid 190g and Oleum menthae are in right amount according to following method preparation: with Radix Rehmanniae, Radix Scrophulariae, FRUCTUS TERMINALIAE IMMATURUS, Periostracum Cicadae adds 10 times of water gagings and decocts twice, each 30 minutes, collecting decoction, filter, it is 1.14 that filtrate is concentrated into 80 ℃ of relative densities, cooling, the ethanol that adds 2 times of amounts, stir evenly, left standstill 24 hours, draw supernatant, be evaporated to 80 ℃ of relative densities and be 1.14 concentrated solution, standby; Other gets Radix Ophiopogonis, Semen Sterculiae Lychnophorae, Radix Adenophorae, Radix Pseudostellariae, Pericarpium Citri Reticulatae adds 10 times of water gagings and decocts twice, 30 minutes for the first time, 20 minutes for the second time, collecting decoction, filter, it is 1.03 concentrated solution that filtrate is concentrated into 80 ℃ of relative densities, merges with above-mentioned standby concentrated solution, vacuum drying, the extractum of oven dry is pulverized, crossed 80 mesh sieves, with microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, micropowder silica gel, crospolyvinylpyrrolidone, aspartame, the 250g sodium bicarbonate is crossed 80 mesh sieve mix homogeneously, with 95% ethanol system soft material, 30 orders are granulated, 60 ± 5 ℃ of dryings, 30 eye mesh screen granulate, add citric acid in the dried granule, fumaric acid and residual sodium bicarbonate, add Oleum menthae behind the mix homogeneously, airtight, tablet forming, packing, promptly.
2. treat the method for quality control of the effervescent tablet of chronic pharyngolaryngitis according to claim 1, it 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 thin layer chromatography of FRUCTUS TERMINALIAE IMMATURUS, Pericarpium Citri Reticulatae, Radix Scrophulariae is differentiated; Assay is that Determination of Hesperidin Content in the preparation is measured.
3. according to the method for quality control of the effervescent tablet of the described treatment chronic pharyngolaryngitis of claim 2, it is characterized in that: the discrimination method of FRUCTUS TERMINALIAE IMMATURUS is to be contrast with FRUCTUS TERMINALIAE IMMATURUS control medicinal material and gallic acid reference substance, and with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is the thin layer chromatography discrimination method of developing solvent; The discrimination method of Pericarpium Citri Reticulatae is to be contrast with the Pericarpium Citri Reticulatae control medicinal material, and with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is the thin layer chromatography discrimination method of developing solvent; The discrimination method of Radix Scrophulariae is to be contrast with the Radix Scrophulariae control medicinal material, and with chloroform: methanol=5: 1 is the thin layer chromatography discrimination method of developing solvent.
4. according to the method for quality control of the effervescent tablet of claim 2 or 3 described treatment chronic pharyngolaryngitiss, it is characterized in that: concrete discrimination method comprise following project partly or entirely:
(1) get 3 in this preparation, porphyrize adds water 100ml, treat foaming fully after, add dilute hydrochloric acid 10ml, heating makes dissolving, filters, filtrate adds ethyl acetate 40ml, jolting is extracted gently, divides and gets acetic acid ethyl fluid, is concentrated into about 2ml, as need testing solution; Other gets FRUCTUS TERMINALIAE IMMATURUS control medicinal material 2g, adds water 100ml, boils 15～20 minutes, constantly drips dilute hydrochloric acid 20～30ml simultaneously, filters while hot, and filtrate adds ether 50ml, and jolting is extracted gently, divides and gets ether solution, is concentrated into about 5ml, in contrast medical material solution; Get the gallic acid reference substance again, add ethyl acetate and make the solution that every 1ml contains 2mg, in contrast product solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of need testing solution 10 μ l, control medicinal material solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is developing solvent, 10～20 ℃ of expansion, take out, dry, spray is with 2% ferric chloride alcoholic solution; In the test sample chromatograph, respectively with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) get 2 in this preparation, porphyrize adds 40ml water, treat foaming fully after, supersound process 10 minutes filters, filtrate adds the ethyl acetate jolting and extracts twice, each 20ml collects acetic acid ethyl fluid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, add water 50ml, decocted 20 minutes, filter, get filtrate, be added on the polyamide column of 60 orders, 2g, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting, collect eluent ethyl acetate liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is developing solvent, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get 6 in this preparation, porphyrize adds ethanol 50ml, supersound process 1 hour leaves standstill, and filters, filtrate evaporate to dryness, residue add water 30ml, and heating makes dissolving, extract 2 times with the ether jolting, each 30ml, the water saturated n-butyl alcohol 30ml of reuse jolting is extracted, get n-butanol extracting liquid, water 10ml washing, n-butyl alcohol liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2.5g, adds ethanol 50ml, and reflux 1 hour filters, and gets filtrate, from " filtrate evaporate to dryness ", shines medical material solution in pairs with legal system; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=5: 1 is developing solvent, presaturation 30 minutes launches, and takes out, dry, spray shows red with 1% vanillin sulfuric acid solution to speckle; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, place the back spot colors and deepen gradually.
5. according to the method for quality control of the effervescent tablet of the described treatment chronic pharyngolaryngitis of claim 2, it is characterized in that: the Determination of Hesperidin Content assay method is to be contrast with the Hesperidin reference substance, and with acetonitrile: 0.2% phosphoric acid=22: 78 is the high performance liquid chromatography of mobile phase.
6. according to the method for quality control of the effervescent tablet of claim 2 or 5 described treatment chronic pharyngolaryngitiss, it is characterized in that: concrete content assaying method is:
The Hesperidin photograph " an appendix VI of Chinese pharmacopoeia version in 2000 D high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; With acetonitrile: 0.2% phosphoric acid=22: 78 is mobile phase; The detection wavelength is 284nm; Number of theoretical plate should be not less than 3000 by the Hesperidin peak;
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every ml contains Hesperidin 10 μ g, promptly;
The powder 0.65g under this preparation tablet weight variation item is got in the preparation of need testing solution, accurate claims surely, puts in the 50ml volumetric flask, adds methanol 40ml, and ultrasonic 30min is put coldly, adds methanol constant volume to scale, shakes up, and with the filtering with microporous membrane of 0.45 μ m, gets subsequent filtrate, promptly;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
Every in this preparation contains Pericarpium Citri Reticulatae in Hesperidin, must not be less than 1.5mg.
7. according to the method for quality control of the effervescent tablet of the described treatment chronic pharyngolaryngitis of claim 2, it is characterized in that: described method of quality control comprises:
Character: medicine is a light brown to brown, unilaterally is dispersed in brown or white dot; It is little sweet to distinguish the flavor of, and refrigerant sense is arranged;
Differentiate: (1) gets 3 in this preparation, and porphyrize adds water 100ml, treat foaming fully after, add dilute hydrochloric acid 10ml, heating makes dissolving, filters, filtrate adds ethyl acetate 40ml, jolting is extracted gently, divides and gets acetic acid ethyl fluid, is concentrated into about 2ml, as need testing solution; Other gets FRUCTUS TERMINALIAE IMMATURUS control medicinal material 2g, adds water 100ml, boils 15～20 minutes, constantly drips dilute hydrochloric acid 20～30ml simultaneously, filters while hot, and filtrate adds ether 50ml, and jolting is extracted gently, divides and gets ether solution, is concentrated into about 5ml, in contrast medical material solution; Get the gallic acid reference substance again, add ethyl acetate and make the solution that every 1ml contains 2mg, in contrast product solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw each 5 μ l of need testing solution 10 μ l, control medicinal material solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: butyl acetate: methanol: formic acid=4: 1: 0.6: 0.7 is developing solvent, 10～20 ℃ of expansion, take out, dry, spray is with 2% ferric chloride alcoholic solution; In the test sample chromatograph, respectively with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) get 2 in this preparation, porphyrize adds 40ml water, treat foaming fully after, supersound process 10 minutes filters, filtrate adds the ethyl acetate jolting and extracts twice, each 20ml collects acetic acid ethyl fluid, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Pericarpium Citri Reticulatae control medicinal material 0.25g, adds water 50ml, decocts 20 minutes, filters, and gets filtrate, is added on the polyamide column of 60 orders, 2g, with 30% ethanol 20ml eluting, reuse ethyl acetate 30ml eluting, collects ethyl acetate and washes
Take off liquid, evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with 60～90 ℃ of petroleum ether: ethyl acetate=1: 1 is developing solvent, launch, take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get 6 in this preparation, porphyrize adds ethanol 50ml, supersound process 1 hour leaves standstill, and filters, filtrate evaporate to dryness, residue add water 30ml, and heating makes dissolving, extract 2 times with the ether jolting, each 30ml, the water saturated n-butyl alcohol 30ml of reuse jolting is extracted, get n-butanol extracting liquid, water 10ml washing, n-butyl alcohol liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material 2.5g, adds ethanol 50ml, and reflux 1 hour filters, and gets filtrate, from " filtrate evaporate to dryness ", shines medical material solution in pairs with legal system; According to " 2005 editions one appendix VIB thin layer chromatography test of Chinese pharmacopoeia, draw need testing solution 10 μ l, control medicinal material solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=5: 1 is developing solvent, presaturation 30 minutes launches, and takes out, dry, spray shows red with 1% vanillin sulfuric acid solution to speckle; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, place the back spot colors and deepen gradually;
Check: get 1 in this preparation disintegration, put in the 250ml beaker that fills 200ml25 ℃ of water, have numerous air-bubble to emit, immediately timing; When bubble stopped to overflow, tablet was dispersed in the water fully, did not have accumulative granule residue; Should in 5 minutes, disintegrate finish;
Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item;
Assay: the Hesperidin photograph " an appendix VID of Chinese pharmacopoeia version in 2000 high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; With acetonitrile: 0.2% phosphoric acid=22: 78 is mobile phase; The detection wavelength is 284nm; Number of theoretical plate should be not less than 3000 by the Hesperidin peak;
It is an amount of that the Hesperidin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every ml contains Hesperidin 10 μ g, promptly;
The powder 0.65g under this preparation tablet weight variation item is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml volumetric flask, adds methanol 40ml, ultrasonic 30min is put coldly, adds methanol constant volume to scale, shakes up, with the filtering with microporous membrane of 0.45 μ m, get subsequent filtrate, promptly;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
Every in this preparation contains Pericarpium Citri Reticulatae in Hesperidin, must not be less than 1.5mg.
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| CN106721861A (en) * | 2016-12-24 | 2017-05-31 | 山东建筑大学 | The preparation method and products obtained therefrom of a kind of sterculia seed throat-clearing throat-moistening fermentation effervescent tablet |
| CN109884238B (en) * | 2019-01-30 | 2021-05-28 | 广西壮族自治区食品药品检验所 | Spleen enlightening pill identification method |
| CN110927322B (en) * | 2019-11-07 | 2022-05-17 | 石药集团中奇制药技术（石家庄）有限公司 | Detection method of Huoxiang Zhengqi mixture |
| CN113633714A (en) * | 2021-08-24 | 2021-11-12 | 江西济民可信药业有限公司 | Preparation method of golden fruit beverage |
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