CN100558348C - YINZHIHUANG ZHIJI and preparation method - Google Patents
YINZHIHUANG ZHIJI and preparation method Download PDFInfo
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- CN100558348C CN100558348C CNB2006102005772A CN200610200577A CN100558348C CN 100558348 C CN100558348 C CN 100558348C CN B2006102005772 A CNB2006102005772 A CN B2006102005772A CN 200610200577 A CN200610200577 A CN 200610200577A CN 100558348 C CN100558348 C CN 100558348C
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Abstract
The invention provides a kind of YINZHIHUANG ZHIJI and preparation method and method of quality control, it is to be prepared into chewable tablet with the mixture of Herba Artemisiae Scopariae extract, Fructus Gardeniae extract, baicalin, Flos Lonicerae extract and an amount of mannitol, sucrose, starch and steviosin, citric acid, magnesium stearate; Compared with prior art, chewable tablet good dispersing state provided by the present invention, disintegration time are short, the medicine stripping is rapid; Absorption is fast, bioavailability is high; Good mouthfeel, taking convenience, the patient who especially is fit to the old man and the difficulty of swallowing takes; Method of quality control precision height of the present invention, favorable reproducibility, response rate height has improved the quality control standard of YINZHIHUANG ZHIJI, can effectively guarantee the clinical efficacy of said preparation.
Description
Technical field:
The present invention relates to a kind of YINZHIHUANG ZHIJI and preparation method and method of quality control, belong to technical field of Chinese medicines.
Background technology:
The YINZHIHUANG ZHIJI heat-clearing and toxic substances removing, the dampness removing jaundice eliminating has the effect of jaundice eliminating cellulitis and reduction glutamate pyruvate transaminase; Acute due to being used for accumulateing in the damp and hot malicious heresy, delay property, chronic hepatitis and hepatitis gravis (I type) also can be used for the Comprehensive Treatment of its alloytype hepatitis gravis.The market demand of YINZHIHUANG ZHIJI is very big, and main dosage form has oral liquid, injection etc. at present, but the bibliographical information or the production of the yellow chewable tablet of mattress Cape jasmine are not arranged as yet.Chewable tablet is a kind of quick-effective preparation that development in recent years is got up, and compares with conventional tablet to have the following advantages: good dispersing state, disintegration time are lacked, the medicine stripping is rapid; Absorption is fast, bioavailability is high, taking convenience, and the patient who especially is fit to the old man and the difficulty of swallowing takes.Because chewable tablet is swallowed after need biting into pieces, its mouthfeel is particularly important, and is difficult for adopting general art for coating protection against the tide, so there is certain degree of difficulty in its preparation technology.In addition, the quality control standard of existing YINZHIHUANG ZHIJI is simple, and product quality can not be controlled fully and effectively, thereby has influenced its clinical efficacy.
Summary of the invention:
The objective of the invention is to: a kind of YINZHIHUANG ZHIJI and preparation method and method of quality control are provided, the present invention on the basis of existing technology, by technical study and screening, the chewable tablet good mouthfeel that makes, taking convenience, disintegration time is short, and absorption is fast, bioavailability is high; And studied and defined the rational and effective method of quality control, improved the quality control standard of YINZHIHUANG ZHIJI.
The present invention constitutes like this: calculate according to composition by weight: it mainly is prepared from by Herba Artemisiae Scopariae extract 10-50, Fructus Gardeniae extract 5-40, baicalin 60-150, Flos Lonicerae extract 10-50 and adjuvant.Specifically: it mainly is prepared from by Herba Artemisiae Scopariae extract 30g, Fructus Gardeniae extract 16g, baicalin 100g, Flos Lonicerae extract 20g and adjuvant.
Used Herba Artemisiae Scopariae extract, Fructus Gardeniae extract, baicalin and Flos Lonicerae extract both can be commercially availablely among the present invention, also can prepare as follows:
The preparation of Herba Artemisiae Scopariae extract: get Herba Artemisiae Scopariae, decoct with water 1-5 time, collecting decoction filters, filtrate is concentrated into every 1ml and contains crude drug 0.5-5g, adds ethanol and makes and contain alcohol amount and reach 50-85%, cold preservation 10-60 hour, filter, filtrate recycling ethanol contains crude drug 3-8g to every 1ml, adds ethanol again and makes and contain the alcohol amount and reach 60-95%, cold preservation 10-60 hour, filter, filtrate recycling ethanol extremely every 1ml contains crude drug 7-12g, add 2-10 times of water gaging, cold preservation 20-100 hour, filter, filtrate is condensed into the thick paste shape, vacuum drying, promptly.
The preparation of Fructus Gardeniae extract: get Fructus Gardeniae, be ground into coarse powder, decoct with water 1-5 time, collecting decoction, filter, filtrate is concentrated into every 1ml and contains crude drug 0.5-3g, adds ethanol and makes and contain alcohol amount and reach 50-85%, cold preservation 10-60 hour, filter, filtrate recycling ethanol contains crude drug 2-6g to every 1ml, adds ethanol and makes and contain the alcohol amount and reach 70-90%, cold preservation 10-60 hour, filter, filtrate recycling ethanol extremely every 1ml contains crude drug 3-10g, adds 2-10 times of water gaging, cold preservation 10-60 hour, filter, filtrate is condensed into thick paste, vacuum drying, promptly.
The preparation of baicalin: get Radix Scutellariae, be ground into coarse powder, decoct with water 1-5 time, collecting decoction, filter, filtrate is heated to 80 ℃, adds hydrochloric acid and regulates pH1～3, leaves standstill, filter, precipitate adds water and stirs into pasty state, adds 40% sodium hydroxide and regulates pH to 4～7, filter, filtrate adds equivalent ethanol, is heated to 80 ℃, add hydrochloric acid and regulate pH to 1～3, baicalin is separated out, filter, use washing with alcohol, drying, promptly; This product contains baicalin C
21H
18O
11Must not be less than 90.0%.
The preparation of Flos Lonicerae extract: extracting honeysuckle decocts with water collecting decoction 1-5 time, filter, filtrate is concentrated into every ml and contains crude drug 0.5-5g, is chilled to 30～70 ℃, add 20～40% aqua calcises and regulate pH to 10-14, filter, precipitate adds ethanol, leave standstill, regulate pH value to 1.0～5.0, filter with 50% sulphuric acid, filtrate is regulated pH value to 5.0～7.0 with 40% sodium hydroxide solution, reclaim ethanol, be concentrated into dried, promptly.
The preparation method of YINZHIHUANG ZHIJI of the present invention is: after getting Herba Artemisiae Scopariae extract, Fructus Gardeniae extract, baicalin, Flos Lonicerae extract mix homogeneously, add mannitol, sucrose, starch, steviosin, citric acid and magnesium stearate and be prepared into the yellow chewable tablet of mattress Cape jasmine
Concrete preparation method is: after getting Herba Artemisiae Scopariae extract, Fructus Gardeniae extract, baicalin, Flos Lonicerae extract mix homogeneously, ratio in raw material: adjuvant=0.5-3: 1-5 adds mannitol: the mixture of sucrose: starch=1-10: 0.5-5: 0.5-5 adds 1-10 ‰ steviosin and 0.5-5 ‰ citric acid, mix homogeneously again, 50-95% ethanol moistening system soft material, granulate drying, granulate, fine powder adds the 0.1-1% magnesium stearate, abundant mix homogeneously, tabletting, the bag film-coat is made chewable tablet.
The method of quality control of the yellow chewable tablet of mattress Cape jasmine, capsule and granule mainly comprise in character, discriminating, inspection and the assay project partly or entirely; Wherein differentiate the thin layer chromatography discriminating that comprises baicalin, Herba Artemisiae Scopariae extract, Fructus Gardeniae extract and Flos Lonicerae extract in the preparation; Assay is that content of baicalin in the preparation is measured.
The discrimination method of baicalin is to be contrast with the baicalin reference substance, and with ethyl acetate: butanone: formic acid: water=1-10: 1-10: 0.5-5: 0.5-5 is the thin layer chromatography of developing solvent; The discrimination method of Herba Artemisiae Scopariae extract is to be contrast with the Herba Artemisiae Scopariae control medicinal material, and with 60～90 ℃ of petroleum ether: ethyl acetate: acetone=1-10: 1-10: 0.5-5 is the thin layer chromatography of developing solvent; The discrimination method of Fructus Gardeniae extract is to be contrast with the jasminoidin reference substance, and with ethyl acetate: formic acid: water=5-20: 0.5-5: 0.5-5 is the thin layer chromatography of developing solvent; The discrimination method of Flos Lonicerae extract is to be contrast with the chlorogenic acid reference substance, and with butyl acetate: the upper solution of formic acid: water=1-20: 0.5-10: 0.5-10 is the thin layer chromatography of developing solvent.
Described discrimination method comprises the part or all of of following project:
(1) thing of getting it filled added the 50-90% ethanol ultrasonic extraction 10-100 minute, put coldly, filtered, as need testing solution; Other gets the baicalin reference substance, adds dissolve with methanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned need testing solution and reference substance solution, put respectively on same polyamide film, with ethyl acetate: butanone: formic acid: water=1-10: 1-10: 0.5-5: 0.5-5 is developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;
(2) thing of getting it filled adds water and makes molten loosing, and adds dilute hydrochloric acid, is heated to about 80 ℃, puts coldly, filters, and in the filtrate dislocation separatory funnel, adds ethyl acetate extraction 1-5 time, merging ethyl acetate liquid, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Other gets the Herba Artemisiae Scopariae control medicinal material, adds water boil 3～30 minutes, puts coldly, filters, and filtrate adds ethyl acetate, shines medical material solution in pairs with legal system; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned need testing solution, control medicinal material solution, put respectively on same silica gel g thin-layer plate, with 60～90 ℃ of petroleum ether: ethyl acetate: acetone=1-10: 1-10: 0.5-5 is developing solvent, launch, take out, dry, spray is put under the 200-600nm ultra-violet lamp and is inspected with 5% potassium hydroxide-ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle;
(3) thing of getting it filled adds water and makes molten loosing, and adds dilute hydrochloric acid, is heated to about 80 ℃, puts coldly, filters, and in the filtrate dislocation separatory funnel, adds ethyl acetate extraction 1-5 time, merging ethyl acetate liquid, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Get the jasminoidin reference substance, add dissolve with ethanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: formic acid: water=5-20: 0.5-5: 0.5-5 is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(4) thing of getting it filled adds water and makes molten loosing, and adds dilute hydrochloric acid, is heated to about 80 ℃, puts coldly, filters, and in the filtrate dislocation separatory funnel, adds ethyl acetate extraction 1-5 time, merging ethyl acetate liquid, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Get the chlorogenic acid reference substance, add dissolve with ethanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with butyl acetate: the upper solution of formic acid: water=1-20: 0.5-10: 0.5-10 is developing solvent, launches, take out, dry, spray 10% sulphuric acid ethanol liquid, spray 3% ferric chloride ethanol liquid after drying again, 110 ℃ be heated to clear spot after, inspect under the daylight; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the punctation of same color.
The content of baicalin assay method is to be contrast with the baicalin reference substance, and with methanol or acetonitrile: water: phosphoric acid=20-60: 30-70: 0.1-2 is the high performance liquid chromatography of mobile phase.
Described content assaying method is:
According to the Chinese Pharmacopoeia high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With methanol or acetonitrile: water: phosphoric acid=20-60: 30-70: 0.1-2 is a mobile phase; Flow velocity: 1.0ml/min; Detect wavelength: 280nm; Number of theoretical plate must not calculate with the baicalin peak and is lower than 2500;
The preparation of reference substance solution: get the baicalin reference substance, the accurate title, decide, and adds the ethanol-water solution dissolving and make the solution that every 1ml contains baicalin 20-100 μ g, promptly;
The preparation of need testing solution: get this medicine, the accurate title, decide, porphyrize, and the powder 10-50mg that gets it filled, accurate title is fixed, put in the 100ml measuring bottle, add ethanol-water solution 80-90ml, after supersound extraction 10-30 minute, put cold, add ethanol-water solution to scale, shake up, 0.45 μ m micropore filters, promptly;
Algoscopy: accurate respectively reference substance solution and each 5-25 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; This preparation contains baicalin C
21H
18O
11Should be 90.0～110.1% of labelled amount.
Described method of quality control comprises:
Character:
For chewable tablet: be Film coated tablets, show lark to pale brown color after removing film-coat; Sweet, little hardship of distinguishing the flavor of;
For capsule: content is that lark is to brown yellow granule; Sweet, little hardship of distinguishing the flavor of;
For granule: for lark to brown yellow granule; Sweet, little hardship of distinguishing the flavor of;
Differentiate: (1) thing of getting it filled, added the 50-90% ethanol ultrasonic extraction 10-100 minute, put coldly, filter, as need testing solution; Other gets the baicalin reference substance, adds dissolve with methanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned need testing solution and reference substance solution, put respectively on same polyamide film, with ethyl acetate: butanone: formic acid: water=1-10: 1-10: 0.5-5: 0.5-5 is developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;
(2) thing of getting it filled adds water and makes molten loosing, and adds dilute hydrochloric acid, is heated to about 80 ℃, puts coldly, filters, and in the filtrate dislocation separatory funnel, adds ethyl acetate extraction 1-5 time, merging ethyl acetate liquid, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Other gets the Herba Artemisiae Scopariae control medicinal material, adds water boil 3～30 minutes, puts coldly, filters, and filtrate adds ethyl acetate, shines medical material solution in pairs with legal system; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned need testing solution, control medicinal material solution, put respectively on same silica gel g thin-layer plate, with 60～90 ℃ of petroleum ether: ethyl acetate: acetone=1-10: 1-10: 0.5-5 is developing solvent, launch, take out, dry, spray is put under the 200-600nm ultra-violet lamp and is inspected with 5% potassium hydroxide-ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle;
(3) thing of getting it filled adds water and makes molten loosing, and adds dilute hydrochloric acid, is heated to about 80 ℃, puts coldly, filters, and in the filtrate dislocation separatory funnel, adds ethyl acetate extraction 1-5 time, merging ethyl acetate liquid, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Get the jasminoidin reference substance, add dissolve with ethanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: formic acid: water=5-20: 0.5-5: 0.5-5 is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(4) thing of getting it filled adds water and makes molten loosing, and adds dilute hydrochloric acid, is heated to about 80 ℃, puts coldly, filters, and in the filtrate dislocation separatory funnel, adds ethyl acetate extraction 1-5 time, merging ethyl acetate liquid, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Get the chlorogenic acid reference substance, add dissolve with ethanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with butyl acetate: the upper solution of formic acid: water=1-20: 0.5-10: 0.5-10 is developing solvent, launches, take out, dry, spray 10% sulphuric acid ethanol liquid, spray 3% ferric chloride ethanol liquid after drying again, 110 ℃ be heated to clear spot after, inspect under the daylight; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the punctation of same color;
Check: should meet relevant every regulation under each preparation item of Chinese Pharmacopoeia appendix;
The pharmacopeia high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With methanol or acetonitrile: water: phosphoric acid=20-60: 30-70: 0.1-2 is a mobile phase; Flow velocity: 1.0ml/min; Detect wavelength: 280nm; Number of theoretical plate must not calculate with the baicalin peak and is lower than 2500;
The preparation of reference substance solution: get the baicalin reference substance, the accurate title, decide, and adds the ethanol-water solution dissolving and make the solution that every 1ml contains baicalin 20-100 μ g, promptly;
The preparation of need testing solution: get this medicine, the accurate title, decide, porphyrize, and the powder 10-50mg that gets it filled, accurate title is fixed, put in the 100ml measuring bottle, add ethanol-water solution 80-90ml, after supersound extraction 10-30 minute, put cold, add ethanol-water solution to scale, shake up, 0.45 μ m micropore filters, promptly;
Algoscopy: accurate respectively reference substance solution and each 5-25 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; This preparation contains baicalin C
21H
18O
11Should be 90.0～110.1% of labelled amount.
In order to ensure method of quality control science of the present invention, reasonable, feasible, the discriminating of each composition and content assaying method are studied among applicant the other side, and concrete testing data is as follows:
This preparation is a chewable tablet, compares with conventional tablet, takes more conveniently, swallows because of after biting into pieces, so mouthfeel is particularly important.
One, adjuvant is selected experiment
1, filler is selected
1.1 the screening of filler kind
Can mainly contain as the adjuvant of filler sucrose 1., mannitol 2., 3. starch wait, we do particulate angle of repose, compressibility and hygroscopicity as index to make by experiment, and in the above-mentioned adjuvant one or more are screened.
The screening of table 1 filler kind
In the table result as seen, the easy moisture absorption of sucrose, compressibility are relatively poor, but its mouthfeel is good, and certain cohesive is arranged; Mannitol is difficult for moisture absorption, and mouthfeel is sweet and refrigerant, and is better mobile, can be used as main filler, and starch is difficult for moisture absorption, also scalable slice, thin piece hardness.So we select three kinds of adjuvants to mix as filler.
1.2 prescription screening
1.2.1 determined in early stage on the basis of adjuvant classification, investigated A (filler), 3 factors of B (lubricant), C (usage ratio of crude drug and filler) influence, with the consumption and the proportioning of adjuvant in definite this tablet formulation to the tablet Forming Quality.L
9(3)
4Orthogonal Experiment and Design with outward appearance, weight differential, the hardness of tablet, is done particulate angle of repose, water absorption rate, particle size distribution as investigating index.
Table 2 factor level table
Annotate: G is a mannitol, and T is a sucrose, and D is a starch.
Sample preparation: take by weighing dried cream powder and adjuvant, cross 80 mesh sieves, mix homogeneously, 90% ethanol moistening system soft material, 20 eye mesh screens are granulated, 50～60 ℃ of dryings, 16 mesh sieve granulate, fine powder adds magnesium stearate, abundant mix homogeneously, tabletting.
1.2.2 measure outward appearance, weight differential, the hardness of doing particulate angle of repose, water absorption rate, granularity and tablet, the results are shown in following table.
Table 3L
9(3)
4Orthogonal experiment plan is taken into account the result
Each index methods of marking of table 4
| Index | Methods of marking | Appraisal result |
| Angle of repose (a) | 100/a | |
| Hydroscopicity | 10 times of percent inverse | |
| Granularity | 0.1 times of percent | |
| Outward appearance | Complete bright and clean, color is equal, do not have numb speckle deformity 4 minutes complete bright and clean, color is equal, has uneven 1 minute of complete bright and clean, the color of numb speckle or deformity 2 minutes 4. imperfect bright and clean 0 minute | Each score value addition promptly gets overall score |
| Weight differential | 10 times of percent inverse | |
| Hardness | 0.1 times of numerical value |
1.2.3 variance analysis and conclusion: the results are shown in following table.
Table 5 analysis of variance table
1.2.4 interpretation of result
Investigate by overall score, extreme difference R value size shows that each factor effect primary and secondary is A＞C＞B from table 3; The results of analysis of variance shows: the influence of A factor, C factor all has significance meaning (P＜0.05), and the B factor does not have significant difference (P＞0.05), with A
1C
2B
3Be combined as good.
2, the screening of correctives
Chewable tablet must have better mouthfeel, is just easily accepted by patient.Selected a large amount of mannitol in the filler for use, mannitol flavor is sweet and refrigerant also to be correctives preferably, but the granule sweet taste of making is not enough, must add a small amount of sweeting agent again.Also once added 0.5 ‰ citric acid in the Yinzhihuang oral liquid, through screening, we select for use steviosin and citric acid as correctives at this.The results are shown in following table.
The screening of table 6 correctives
| Correctives | Steviosin | Citric acid |
| Consumption (‰) | 2 3 5 | 0.5 1 1.5 |
| Mouthfeel | ++ +++ ++ | ++ +++ + |
Annotate :+good, ++ better, +++fine.
Evaluation of result: from table 6 result as seen, when correctives is made in adding steviosin 3 ‰ and the conduct of 1 ‰ citric acid, mouthfeel the best.
Two, quality standard research
(1) content of baicalin study on determination method
1, baicalin is the main effective ingredient in this preparation, and bibliographical information is more in the content of baicalin assay method spectrophotography, a high performance liquid chromatography etc.Discover through us, this preparation adopts spectrophotography that baicalin in the preparation is carried out assay, its specificity is not strong, error is big, the measurement result instability, relative standard deviation more efficient liquid chromatography is big, so the present invention adopts the high effective liquid chromatography for measuring content of baicalin, below is that preparation of the present invention adopts high performance liquid chromatography and spectrophotometry result relatively:
High performance liquid chromatography and spectrophotometry result (n=5)
2, high effective liquid chromatography for detecting research:
2.1 ultrasonic extraction solvent is investigated: the about 30mg of thing fine powder that gets it filled, put in the 100ml measuring bottle, add methanol, ethanol, the about 90ml of 70% ethanol respectively, supersound extraction is after 40 minutes, put coldly, solubilizer shakes up to scale, filter (0.45 μ m), promptly get test liquid, measure content of baicalin.Measurement result sees the following form.
Different influences (n=2) of extracting solvent to content of baicalin mensuration
Result of the test shows, it is higher that methanol is made the baicalin extraction ratio of solvent, but consider that ethanol is little than methanol toxicity, and cost is lower, so select for use ethanol to do solvent extraction, the optimum extraction solvent is 70% ethanol.
2.2 precision test: accurate baicalin reference substance solution (60.0 μ g/ml) the 10 μ l that draw, inject chromatograph of liquid, measure peak area, repeat sample introduction 5 times, average peak area is 2127967.4, RSD is 0.83%.Show that precision is good.
The test of baicalin reference substance solution precision
| The sample introduction number of times | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Peak area | 2098221 | 2140328 | 2132525 | 2127573 | 2141190 | 2127967.4 | 0.83 |
2.3 replica test: the thing fine powder of getting it filled, the preparation method by test liquid under the assay item among the present invention prepares 5 parts of test liquids respectively, and sample introduction is measured peak area, and the baicalin average content is 0.2049g/g, and RSD is 0.55%.Show that repeatability is good.
The replica test of baicalin in the preparation test sample
| The sample introduction number of times | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Content (g/g) | 0.2040 | 0.2058 | 0.2053 | 0.2059 | 0.2034 | 0.2049 | 0.55 |
2.4 stability test: the thing fine powder of getting it filled, prepare test liquid by the preparation method of test liquid under the assay item among the present invention, measure its baicalin peak area respectively at 0,2,4,6,8 hour, average peak area is 1980407, RSD is 1.11%.Show that jasminoidin is stable in 8 hours in the need testing solution.
The stability test of baicalin in the preparation test sample
| Time (hour) | 0 | 2 | 4 | 6 | 8 | Meansigma methods | RSD(％) |
| Peak area | 1962940 | 1974857 | 2018887 | 1973849 | 1971504 | 1980407 | 1.11 |
2.5 recovery test: adopt the application of sample absorption method, it is an amount of to get this preparation (average content is 0.2049g/g) respectively, and accurate the title decides, put in the 100ml measuring bottle, accurate baicalin reference substance (containing baicalin is 0.2158mg/ml) the solution 15ml that adds presses the quality standard draft, makes test liquid.The accurate respectively 10 μ l of absorption inject chromatograph of liquid, and the record chromatograph is measured content, calculate recovery rate.Average recovery rate is 99.07%, and RSD is 1.23%, proves that this method is feasible.
Baicalin is measured recovery test in the need testing solution
(2) thin layer chromatography of baicalin research
With baicalin in the baicalin reference substance discriminating side.
Reference substance solution preparation method: get the baicalin reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution.
Need testing solution preparation method one: the thing 0.2g that gets it filled, porphyrize adds methanol 20ml, and supersound process 20 minutes filters, and filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Get negative sample 2g, get negative control solution with legal system by the scarce baicalin of prepared.
Need testing solution preparation method two: the thing of getting it filled, porphyrize adds 70% alcoholic solution 100ml, and supersound extraction is after 20 minutes, puts coldly, filters, promptly; Get negative sample, get negative control solution with legal system by the scarce baicalin of prepared.
Developing solvent is selected: with the mixed solution of ethyl acetate, butanone, formic acid different proportion, the mixed solution of ethyl acetate, butanone, formic acid, water different proportion is developing solvent.
Result: with ethyl acetate: butanone: formic acid: water=1-10: 1-10: 0.5-5: 0.5-5 is developing solvent.According to the need testing solution of method two preparation, the speckle separator well, the method repeatability is better.Best developing solvent is an ethyl acetate: butanone: formic acid: water=5: 3: 1: 1.In addition, find in research process that put in being on the silica gel g thin-layer plate of adhesive with the carboxymethylcellulose sodium solution that contains 4% sodium acetate, speckle separates relatively poor mostly, the principal spot hangover is serious; Point speckle colour developing on polyamide film is clear, negative noiseless, the method favorable reproducibility.
(3) thin layer chromatography of Herba Artemisiae Scopariae research
With Herba Artemisiae Scopariae extract in the Herba Artemisiae Scopariae control medicinal material discriminating side.
The reference substance solution preparation method: get Herba Artemisiae Scopariae control medicinal material 3g, add water 50ml, boiled 5～10 minutes, put coldly, filter, filtrate adds ethyl acetate 10ml, shines medical material solution in pairs with legal system.
Need testing solution preparation method one: the thing 1g that gets it filled, porphyrize adds ethyl acetate 10ml reflux, extract, 30 minutes, filters, and filtrate evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution.Get negative sample 2g, get negative control solution with legal system by the scarce Herba Artemisiae Scopariae of prepared.
Need testing solution preparation method two: the thing 1g that gets it filled, porphyrize adds water 10ml and makes molten loosing, add dilute hydrochloric acid 1ml, be heated to about 80 ℃, put cold, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 2 times, each 10ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution.Get negative sample 2g, get negative control solution with legal system by the scarce Herba Artemisiae Scopariae of prepared.
Developing solvent is selected: with the mixed solution of petroleum ether (60～90 ℃), ethyl acetate, methanol different proportion; Mixed solution with petroleum ether (60～90 ℃), ethyl acetate, acetone different proportion is developing solvent; Mixed solution with petroleum ether (60～90 ℃), benzene, acetone different proportion is developing solvent, launches, and takes out, and dries, and spray is put under the ultra-violet lamp and inspected with 5% potassium hydroxide-ethanol solution.
Result: with 60～90 ℃ of petroleum ether: ethyl acetate: acetone=1-10: 1-10: 0.5-5 is developing solvent.According to the need testing solution of method two preparation, the speckle separator well, the method repeatability is better.Best developing solvent is 60～90 ℃ of petroleum ether: ethyl acetate: acetone=5: 3: 2.
(4) thin layer chromatography of Fructus Gardeniae research
With Fructus Gardeniae extract in the jasminoidin reference substance discriminating side.
Reference substance solution preparation method: get the jasminoidin reference substance, add ethanol and make the solution that every 1ml contains 1mg, in contrast product solution.
Need testing solution preparation method one: the thing 1g that gets it filled, porphyrize, the 15ml that adds diethyl ether, jolting 10 minutes discards ether solution, and residue volatilizes, and adds ethyl acetate 15ml, and reflux 1 hour filters, and filtrate volatilizes, and residue adds ethanol 1ml makes dissolving, as need testing solution.Get negative sample 2g, get negative control solution with legal system by the scarce Fructus Gardeniae of prepared.
Need testing solution preparation method two: the thing 1g that gets it filled, porphyrize adds water 10ml and makes molten loosing, add dilute hydrochloric acid 1ml, be heated to about 80 ℃, put cold, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 2 times, each 10ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution.Get negative sample 2g, get negative control solution with legal system by the scarce Fructus Gardeniae of prepared.
Developing solvent is selected: with the mixed solution of ethyl acetate, acetone, formic acid, water different proportion; Mixed solution with ethyl acetate, formic acid, water different proportion; Mixed solution with ethyl acetate, acetone, ethyl acetate, water different proportion is developing solvent, launches, and takes out, dry, spray respectively with 10% ethanol solution of sulfuric acid, be heated to the clear and spray of speckle colour developing with 5% vanillin sulfuric acid solution at 110 ℃, it is clear that hot blast blows to the speckle colour developing.
Result: according to the need testing solution of method two preparation, with ethyl acetate: formic acid: water=5-20: 0.5-5: 0.5-5 is developing solvent, launch, take out airing, spray is with 5% vanillin sulfuric acid solution, it is clear that hot blast blows to the speckle colour developing, and this method ambient interferences is little, and the speckle colour developing is clear, negative noiseless, the method favorable reproducibility.Best developing solvent is an ethyl acetate: formic acid: water=10: 2: 1.
(5) thin layer chromatography of Flos Lonicerae research
With Flos Lonicerae extract in the chlorogenic acid reference substance discriminating side.
Reference substance solution preparation method: get the chlorogenic acid reference substance, add methanol and make the solution that every 1ml contains 2mg, in contrast product solution.
Need testing solution preparation method one: get this medicine 1g, porphyrize adds water 10ml and makes molten loosing, add dilute hydrochloric acid 1ml, be heated to about 80 ℃, put cold, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 2 times, each 10ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution.Get negative sample 2g, get negative control solution with legal system by the scarce Fructus Gardeniae of prepared.
Need testing solution preparation method two: get this medicine 1g, porphyrize adds methanol 10ml, places 12 hours, filters, and filtrate is concentrated into 2ml as need testing solution.Get negative sample 2g, get negative control solution with legal system by the scarce Flos Lonicerae of prepared.
Result: with butyl acetate: the upper solution of formic acid: water=1-20: 0.5-10: 0.5-10 is developing solvent, launch, take out, dry, following respectively surface colour development mode develops the color and inspects: (1) is put under the ultra-violet lamp (365nm) and is inspected, and method one and method two all have negative the interference; (2) spray with 10% sulphuric acid ethanol liquid, after 110 ℃ of heating, method one speckle paler colour, unintelligible, inconvenience is inspected, and the method two ambient interferences is big, and speckle is unintelligible; (3) spray is with 3% ferric chloride ethanol liquid, and " method one plate " and " method two plate " all have negative the interference; (4) spray 3% ferric chloride ethanol liquid again behind the spray 10% sulphuric acid ethanol liquid airing earlier, after 110 ℃ of heating, " method one plate " punctation is clear, negative noiseless, " method two plate " on the corresponding position of reference substance chromatograph, shows the speckle of different colours in the test sample chromatograph.
So select need testing solution preparation method one for use, with butyl acetate: the upper solution of formic acid: water=1-20: 0.5-10: 0.5-10 is developing solvent, launch, take out, dry, the colour developing mode is earlier sprayed 3% ferric chloride ethanol liquid behind the spray 10% sulphuric acid ethanol liquid airing again for (4), 110 ℃ be heated to clear spot after, daylight is inspected.Best developing solvent is: butyl acetate: formic acid: the upper solution of water=7: 2.5: 2.5.
Compared with prior art, chewable tablet good dispersing state provided by the present invention, disintegration time are short, the medicine stripping is rapid; Absorption is fast, bioavailability is high; Good mouthfeel, taking convenience, the patient who especially is fit to the old man and the difficulty of swallowing takes; Method of quality control precision height of the present invention, favorable reproducibility, response rate height has improved the quality control standard of YINZHIHUANG ZHIJI, can effectively guarantee the clinical efficacy of said preparation.
Further specify the present invention by the following examples, but not as limitation of the present invention.
The specific embodiment:
Embodiments of the invention 1: Herba Artemisiae Scopariae extract 30g, Fructus Gardeniae extract 16g, baicalin 100g, Flos Lonicerae extract 20g, mannitol: sucrose: mixture, steviosin, citric acid, the magnesium stearate of starch=3: 1: 1 (weight ratio)
Get the fine powder mixing of Herba Artemisiae Scopariae extract, Fructus Gardeniae extract, baicalin and Flos Lonicerae extract, press raw material: the part by weight of filler=1: 2 adds mannitol: sucrose: the mixture of starch=3: 1: 1 (weight ratio) adds 3 ‰ steviosin and 1 ‰ citric acid again, mix homogeneously, 90% ethanol moistening system soft material, 20 eye mesh screens are granulated, 50～60 ℃ of dryings, 16 mesh sieve granulate, fine powder adds 0.4% magnesium stearate, abundant mix homogeneously, tabletting, the bag film-coat, promptly.This product is chewed clothes, one time 4,3 times on the one.
Embodiments of the invention 2: Herba Artemisiae Scopariae extract 50g, Fructus Gardeniae extract 5g, baicalin 60g, Flos Lonicerae extract 50g, mannitol: sucrose: mixture, steviosin, citric acid, the magnesium stearate of starch=1: 5: 0.5 (weight ratio)
After getting Herba Artemisiae Scopariae extract, Fructus Gardeniae extract, baicalin, Flos Lonicerae extract mix homogeneously, in raw material: the ratio of adjuvant=3: 1 adds mannitol: sucrose: the mixture of starch=1: 5: 0.5 adds 10 ‰ steviosin and 5 ‰ citric acid, mix homogeneously again, 50% ethanol moistening system soft material, granulate drying, granulate, fine powder adds 0.1% magnesium stearate, abundant mix homogeneously, tabletting, the bag film-coat is made chewable tablet.This product is chewed clothes, one time 4,3 times on the one.
Embodiments of the invention 3: Herba Artemisiae Scopariae extract 10g, Fructus Gardeniae extract 40g, baicalin 150g, Flos Lonicerae extract 10g mannitol: sucrose: mixture, steviosin, citric acid, the magnesium stearate of starch=10: 0.5: 5 (weight ratio)
After getting Herba Artemisiae Scopariae extract, Fructus Gardeniae extract, baicalin, Flos Lonicerae extract mix homogeneously, in raw material: the ratio of adjuvant=0.5: 5 adds mannitol: sucrose: the mixture of starch=10: 0.5: 5 adds 1 ‰ steviosin and 0.5 ‰ citric acid, mix homogeneously again, 95% ethanol moistening system soft material, granulate drying, granulate, fine powder adds 1% magnesium stearate, abundant mix homogeneously, tabletting, the bag film-coat is made chewable tablet.This product is chewed clothes, one time 4,3 times on the one.
Embodiments of the invention 4: described chewable tablet method of quality control comprises:
Character: be Film coated tablets, remove and show lark behind the film-coat to pale brown color; Sweet, little hardship of distinguishing the flavor of;
Differentiate: (1) gets this preparation or its content, and accurate the title decided porphyrize, the about 30mg of the powder of getting it filled, the accurate title, decide, and puts in the 100ml measuring bottle, add the about 90ml of 70% ethanol, after the supersound extraction 20 minutes, put coldly, add 70% ethanol to scale, shake up, 0.45 μ m micropore filters, and gets subsequent filtrate, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to the test of Chinese Pharmacopoeia appendix thin layer chromatography, draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l, put respectively on same polyamide film, with ethyl acetate: butanone: formic acid: water=5: 3: 1: 1 is developing solvent, launches, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;
(2) get this preparation or its content, porphyrize adds water 10ml and makes molten loosing, and adds dilute hydrochloric acid 1ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 2 times, each 10ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Other gets Herba Artemisiae Scopariae control medicinal material 3g, adds water 50ml, boils 5～10 minutes, puts coldly, filters, and filtrate adds ethyl acetate 10ml, shines medical material solution in pairs with legal system; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned need testing solution 2 μ l, control medicinal material solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 60～90 ℃ of petroleum ether: ethyl acetate: acetone=5: 3: 2 is developing solvent, launches, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with 5% potassium hydroxide-ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle;
(3) get this preparation or its content, porphyrize adds water 10ml and makes molten loosing, and adds dilute hydrochloric acid 1ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 2 times, each 10ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Get the jasminoidin reference substance, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, each 3 μ l of need testing solution of drawing and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: formic acid: water=10: 2: 1 is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(4) get this preparation or its content, porphyrize adds water 10ml and makes molten loosing, and adds dilute hydrochloric acid 1ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 2 times, each 10ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Get the chlorogenic acid reference substance, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to Chinese Pharmacopoeia appendix thin layer chromatography, draw each 4 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with butyl acetate: formic acid: the upper solution of water=7: 2.5: 2.5 is developing solvent, launches, take out, dry, spray 10% sulphuric acid ethanol liquid, spray 3% ferric chloride ethanol liquid behind the airing again, 110 ℃ be heated to clear spot after, daylight is inspected; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the punctation of same color;
Check: should meet relevant every regulation under the Chinese Pharmacopoeia appendix tablet item;
Assay: shine Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol: water: phosphoric acid=47: 53: 0.2 is mobile phase; Flow velocity: 1.0ml/min; Detect wavelength: 280nm; Number of theoretical plate must not calculate with the baicalin peak and is lower than 2500;
The preparation of reference substance solution: get baicalin reference substance 10.0mg, the accurate title, decide, and puts in the 50ml measuring bottle, adds 70% ethanol to scale, shake up, precision is measured 15ml, puts in the 50ml measuring bottle, adds 70% ethanol to scale, shake up, make the solution that every 1ml contains baicalin 60.0 μ g, promptly;
The preparation of need testing solution: get this preparation or its content, the accurate title, decide, porphyrize, and the about 30mg of the powder of getting it filled, accurate title is fixed, put in the 100ml measuring bottle, add the about 90ml of 70% ethanol, supersound extraction was put cold after 20 minutes, add 70% ethanol to scale, shake up, 0.45 μ m micropore filters, promptly;
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly;
This preparation contains baicalin C
21H
18O
11Should be 90.0～110.1% of labelled amount.
Embodiments of the invention 5: described capsule method of quality control comprises:
Character: content is that lark is to brown yellow granule; Sweet, little hardship of distinguishing the flavor of;
Differentiate: (1) thing of getting it filled, accurate claim fixed, porphyrize, the about 30mg of the powder of getting it filled, the accurate title, decide, put in the 100ml measuring bottle, add the about 90ml of 90% ethanol, supersound extraction is after 10 minutes, puts coldly, adds 90% ethanol to scale, shake up, 0.45 μ m micropore filters, and gets subsequent filtrate, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to Chinese Pharmacopoeia appendix thin layer chromatography, draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l, put respectively on same polyamide film, with ethyl acetate: butanone: formic acid: water=10: 1: 5: 5 is developing solvent, launches, and takes out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;
(2) thing of getting it filled, porphyrize adds water 10ml and makes molten loosing, and adds dilute hydrochloric acid 1ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 1 time, each 30ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Other gets Herba Artemisiae Scopariae control medicinal material 3g, adds water 50ml, boils 3 minutes, puts coldly, filters, and filtrate adds ethyl acetate 10ml, shines medical material solution in pairs with legal system; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned need testing solution 5 μ l, control medicinal material solution 5 μ l, put respectively on same silica gel g thin-layer plate, with 60～90 ℃ of petroleum ether: ethyl acetate: acetone=10: 1: 0.5 is developing solvent, launches, take out, dry, spray is put under the 200nm ultra-violet lamp and is inspected with 5% potassium hydroxide-ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle;
(3) thing of getting it filled, porphyrize adds water 10ml and makes molten loosing, and adds dilute hydrochloric acid 1ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 1 time, each 30ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Get the jasminoidin reference substance, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: formic acid: water=20: 0.5: 0.5 is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(4) thing of getting it filled, porphyrize adds water 10ml and makes molten loosing, and adds dilute hydrochloric acid 1ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 3 times, each 30ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Get the chlorogenic acid reference substance, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with butyl acetate: formic acid: the upper solution of water=20: 0.5: 0.5 is developing solvent, launches, take out, dry, spray 10% sulphuric acid ethanol liquid, spray 3% ferric chloride ethanol liquid after drying again, 110 ℃ be heated to clear spot after, inspect under the daylight; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the punctation of same color.
Check: should meet relevant every regulation under the Chinese Pharmacopoeia appendix capsule item;
Assay: shine Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With acetonitrile: water: phosphoric acid=20: 70: 0.1 is mobile phase; Flow velocity: 1.0ml/min; Detect wavelength: 280nm; Number of theoretical plate must not calculate with the baicalin peak and is lower than 2500;
The preparation of reference substance solution: get the baicalin reference substance, the accurate title, decide, and adds 90% dissolve with ethanol solution and make the solution that every 1ml contains baicalin 20 μ g, promptly;
The preparation of need testing solution: get this medicine, the accurate title, decide, porphyrize, and the powder 10mg that gets it filled, accurate title is fixed, put in the 100ml measuring bottle, add 90% alcoholic solution 90ml, after supersound extraction 10-30 minute, put cold, add 90% alcoholic solution to scale, shake up, 0.45 μ m micropore filters, promptly;
Algoscopy: accurate respectively reference substance solution and each 25 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; This preparation contains baicalin C
21H
18O
11Should be 90.0～110.1% of labelled amount.
Embodiments of the invention 6: described granular mass control method comprises:
Character: for lark to brown yellow granule; Sweet, little hardship of distinguishing the flavor of;
Differentiate: (1) thing of getting it filled, accurate claim fixed, porphyrize, the about 30mg of the powder of getting it filled, the accurate title, decide, put in the 100ml measuring bottle, add the about 90ml of 50% ethanol, supersound extraction is after 100 minutes, puts coldly, adds 70% ethanol to scale, shake up, 0.45 μ m micropore filters, and gets subsequent filtrate, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to Chinese Pharmacopoeia appendix thin layer chromatography, draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l, put respectively on same polyamide film, with ethyl acetate: butanone: formic acid: water=1: 10: 0.5: 0.5 is developing solvent, launches, and takes out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;
(2) thing of getting it filled, porphyrize adds water 50ml and makes molten loosing, and adds dilute hydrochloric acid 5ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 5 times, each 40ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Other gets Herba Artemisiae Scopariae control medicinal material 5g, adds water 100ml, boils 30 minutes, puts coldly, filters, and filtrate adds ethyl acetate 10ml, shines medical material solution in pairs with legal system; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned need testing solution 3 μ l, control medicinal material solution 10 μ l, put respectively on same silica gel g thin-layer plate, with 60～90 ℃ of petroleum ether: ethyl acetate: acetone=1: 10: 5 is developing solvent, launches, take out, dry, spray is put under the 600nm ultra-violet lamp and is inspected with 5% potassium hydroxide-ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical blue-fluorescence speckle;
(3) thing of getting it filled, porphyrize adds water 50ml and makes molten loosing, and adds dilute hydrochloric acid 5ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 5 times, each 40ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Get the jasminoidin reference substance, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; According to the test of Chinese Pharmacopoeia thin layer chromatography, draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: formic acid: water=5: 5: 5 is developing solvent, launches, and takes out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(4) thing of getting it filled, porphyrize adds water 50ml and makes molten loosing, and adds dilute hydrochloric acid 5ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 5 times, each 40ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Get the chlorogenic acid reference substance, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with butyl acetate: formic acid: the upper solution of water=1: 10: 10 is developing solvent, launches, take out, dry, spray 10% sulphuric acid ethanol liquid, spray 3% ferric chloride ethanol liquid after drying again, 110 ℃ be heated to clear spot after, inspect under the daylight; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the punctation of same color.
Check: should meet relevant every regulation under the Chinese Pharmacopoeia appendix granule item;
Assay: shine Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With methanol: water: phosphoric acid=60: 30: 2 is mobile phase; Flow velocity: 1.0ml/min; Detect wavelength: 280nm; Number of theoretical plate must not calculate with the baicalin peak and is lower than 2500;
The preparation of reference substance solution: get the baicalin reference substance, the accurate title, decide, and adds 30% dissolve with ethanol solution and make the solution that every 1ml contains baicalin 100 μ g, promptly;
The preparation of need testing solution: get this medicine, the accurate title, decide, porphyrize, and the powder 50mg that gets it filled, accurate title is fixed, put in the 100ml measuring bottle, add 30% alcoholic solution 80ml, supersound extraction was put cold after 10 minutes, add 30% alcoholic solution to scale, shake up, 0.45 μ m micropore filters, promptly;
Algoscopy: accurate respectively reference substance solution and each 5 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly; This preparation contains baicalin C
21H
18O
11Should be 90.0～110.1% of labelled amount.
Embodiments of the invention 7: described capsule method of quality control can comprise:
Character: content is that lark is to brown yellow granule; Sweet, little hardship of distinguishing the flavor of;
Differentiate: (1) gets this preparation or its content, and accurate the title decided porphyrize, the about 30mg of the powder of getting it filled, the accurate title, decide, and puts in the 100ml measuring bottle, add the about 90ml of 70% ethanol, after the supersound extraction 20 minutes, put coldly, add 70% ethanol to scale, shake up, 0.45 μ m micropore filters, and gets subsequent filtrate, as need testing solution; Other gets the baicalin reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; According to the test of Chinese Pharmacopoeia appendix thin layer chromatography, draw above-mentioned need testing solution 4 μ l, reference substance solution 2 μ l, put respectively on same polyamide film, with ethyl acetate: butanone: formic acid: water=5: 3: 1: 1 is developing solvent, launches, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show identical dirty-green speckle;
(2) get this preparation or its content, porphyrize adds water 10ml and makes molten loosing, and adds dilute hydrochloric acid 1ml, is heated to about 80 ℃, put coldly, filter, in the filtrate dislocation separatory funnel, add ethyl acetate extraction 2 times, each 10ml, merge ethyl acetate liquid, evaporate to dryness, residue add ethanol 2ml makes dissolving, as need testing solution; Get the jasminoidin reference substance, add ethanol and make the solution that every 1ml contains 2mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, each 3 μ l of need testing solution of drawing and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: formic acid: water=10: 2: 1 is developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
Check: should meet relevant every regulation under the Chinese Pharmacopoeia appendix capsule item;
Assay: shine Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol: water: phosphoric acid=47: 53: 0.2 is mobile phase; Flow velocity: 1.0ml/min; Detect wavelength: 280nm; Number of theoretical plate must not calculate with the baicalin peak and is lower than 2500;
The preparation of reference substance solution: get baicalin reference substance 10.0mg, the accurate title, decide, and puts in the 50ml measuring bottle, adds 70% ethanol to scale, shake up, precision is measured 15ml, puts in the 50ml measuring bottle, adds 70% ethanol to scale, shake up, make the solution that every 1ml contains baicalin 60.0 μ g, promptly;
The preparation of need testing solution: get this preparation or its content, the accurate title, decide, porphyrize, and the about 30mg of the powder of getting it filled, accurate title is fixed, put in the 100ml measuring bottle, add the about 90ml of 70% ethanol, supersound extraction was put cold after 20 minutes, add 70% ethanol to scale, shake up, 0.45 μ m micropore filters, promptly;
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly;
This preparation contains baicalin C
21H
18O
11Should be 90.0～110.1% of labelled amount.
Embodiments of the invention 8: described chewable tablet method of quality control can comprise:
Character: be Film coated tablets, remove and show lark behind the film-coat to pale brown color; Sweet, little hardship of distinguishing the flavor of;
Check: should meet relevant every regulation under the Chinese Pharmacopoeia appendix tablet item;
Assay: shine Chinese Pharmacopoeia appendix high effective liquid chromatography for measuring:
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; With methanol: water: phosphoric acid=60: 30: 2 is mobile phase; Flow velocity: 1.0ml/min; Detect wavelength: 280nm; Number of theoretical plate must not calculate with the baicalin peak and is lower than 2500;
The preparation of reference substance solution: get the baicalin reference substance, the accurate title, decide, and adds 30% dissolve with ethanol solution and make the solution that every 1ml contains baicalin 100 μ g, promptly;
The preparation of need testing solution: get this medicine, the accurate title, decide, porphyrize, and the powder 50mg that gets it filled, accurate title is fixed, put in the 100ml measuring bottle, add 30% alcoholic solution 80ml, supersound extraction was put cold after 10 minutes, add 30% alcoholic solution to scale, shake up, 0.45 μ m micropore filters, promptly;
Algoscopy: accurate respectively reference substance solution and each 5 Ma of need testing solution drawn, inject chromatograph of liquid, measure, promptly; This preparation contains baicalin C
21H
18O
11Should be 90.0～110.1% of labelled amount.
Claims (1)
1. YINZHIHUANG ZHIJI is characterized in that: calculate according to composition by weight: it is by Herba Artemisiae Scopariae extract 30g, Fructus Gardeniae extract 16g, baicalin 100g, Flos Lonicerae extract 20g, mannitol: sucrose: the weight ratio of starch is that 3: 1: 1 mixture, steviosin, citric acid and magnesium stearate is prepared from chewable tablet;
Preparation technology is: get the fine powder mixing of Herba Artemisiae Scopariae extract, Fructus Gardeniae extract, baicalin and Flos Lonicerae extract, press crude drug: the part by weight of filler=1: 2 adds mannitol: sucrose: 3: 1: 1 mixture of the weight ratio of starch adds 3 ‰ steviosin and 1 ‰ citric acid again, mix homogeneously, 90% ethanol moistening system soft material, 20 eye mesh screens are granulated, 50～60 ℃ of dryings, 16 mesh sieve granulate, fine powder adds 0.4% magnesium stearate, abundant mix homogeneously, tabletting, the bag film-coat, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006102005772A CN100558348C (en) | 2006-06-16 | 2006-06-16 | YINZHIHUANG ZHIJI and preparation method |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2006102005772A CN100558348C (en) | 2006-06-16 | 2006-06-16 | YINZHIHUANG ZHIJI and preparation method |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008103011958A Division CN101264148B (en) | 2006-06-16 | 2006-06-16 | Quality control method of yinzhihuang preparation |
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| CN1895411A CN1895411A (en) | 2007-01-17 |
| CN100558348C true CN100558348C (en) | 2009-11-11 |
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| CN102675387B (en) * | 2011-03-18 | 2015-02-18 | 四川济生堂药业有限公司 | Method for extracting baicalin from scutellaria baicalensis |
| CN105412291B (en) * | 2015-12-09 | 2019-08-20 | 贵州瑞和制药有限公司 | The proheparin that relaxes is preparing the application in treatment diabetic neuropathy and complication medicine |
| JP7277081B2 (en) * | 2017-05-15 | 2023-05-18 | ロート製薬株式会社 | Oral Composition, Method for Improving Aftertaste of Sweetness, and Method for Suppressing Discoloration |
| CN107655989B (en) * | 2017-09-18 | 2019-07-05 | 鲁南制药集团股份有限公司 | The method for building up and its standard diagram of Yinzhihuang" granula HPLC finger-print |
| CN108653550A (en) * | 2018-07-10 | 2018-10-16 | 天长亿帆制药有限公司 | A kind of fiber crops a kind of reed mentioned in ancient books disappears cough drug and preparation method thereof and detection method |
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