CN1857445A - Quality control method for Desheng preparation - Google Patents
Quality control method for Desheng preparation Download PDFInfo
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Abstract
The present invention relates to quality control method for Desheng preparation. The quality control method includes identification through thin layer chromatography process and content measurement through spectrophotometric process. The quality control method is precise, sensitive and stable, and can ensure the quality of product.
Description
Technical field:
The present invention relates to a kind of method of quality control of Chinese medicine preparation, particularly give birth to the method for quality control of granular preparation.
Background technology:
Must give birth to the former dosage form of granule and be to such an extent that raw cook is listed in " the 3rd in the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation ", prescription consists of: Six-element medical materials such as Herba Leonuri, Radix Bupleuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, the Radix Paeoniae Alba, the Radix Aucklandiae are formed, and have regulating menstruation and nourishing blood, regulating the flow of QI to dissipate blood stasis.Be used for menoxenia, abdominal pain in menstruation, stagnation of QI and blood, lump in the abdomen mass in the abdomen.
Existing 'Desheng ' exists method of quality control to fall behind the uppity shortcoming of product quality.Its composition is not differentiated in the existing method of quality control, or its composition is carried out the content of assay.So existing method of quality control can not effectively be controlled the quality of 'Desheng ', thereby will influence the production of product and ensure the quality of products.
For effectively controlling product quality, we have set up the new method of quality control of 'Desheng ', and this method adopts thin layer chromatography to differentiate, adopt spectrophotography to carry out assay.This method of quality control precision, sensitivity, stability are all good, guarantee " safety, the homogeneous, stable, effective, controlled " of product quality.
Summary of the invention:
The object of the invention is to provide the method for quality control of 'Desheng '.
The 'Desheng ' prescription consists of:
[prescription]
Herba Leonuri 451.8g Radix Bupleuri 75.3g Radix Angelicae Sinensis 150.6g
Rhizoma Chuanxiong 37.6g Radix Paeoniae Alba 150.6g Radix Aucklandiae 37.6g
Must give birth to the granule method for making: above Six-element, Herba Leonuri decocts with water secondary, and 2 hours for the first time, 1 hour for the second time; Radix Bupleuri boils back warm macerating secondary, and 2 hours for the first time, 1 hour for the second time, collecting decoction and warm macerating liquid were condensed into cream; Radix Angelicae Sinensis is made solvent with 95% ethanol for the first time, and 60% ethanol is made solvent for the second time, according to percolation (appendix IO of Chinese Pharmacopoeia version in 2000) under fluid extract and the extractum item, percolation secondary; Rhizoma Chuanxiong, the Radix Paeoniae Alba, the Radix Aucklandiae are made solvent with 60% alcohol, carry out percolation.The liquid of filtering more than the merging reclaims ethanol, is condensed into thick paste, merges with above-mentioned condensed cream, adds right amount of auxiliary materials, and mixing is granulated, drying, and granulate is made 1000g, promptly.
The present invention be directed to such an extent that give birth to granular preparation and propose method of quality control, but also be not limited to give birth to granular preparation, also can comprise tablet, capsule, syrup, pill, etc. must give birth to other oral formulations of ball.
The present invention includes must give birth to its prescription of other dosage forms and must to give birth to granular preparation identical, composition is by weight as proportioning, can increase or minimizing according to corresponding proportion when producing, and be no more than 100% at most.
Large-scale production can be unit with the kilogram, or is unit with the ton.More than composition can be made into 1000 doses of pharmaceutical preparatioies, described 1000 doses of fingers, and the final drug preparation of making, as make 1000 of capsule preparations, and 1000 in tablet, granule 1000g, liquid preparation 1000ml etc.,
The preparation method that must give birth to other dosage forms of the present invention can adopt following method:
By the raw material of Chinese medicine of above-mentioned prescription is processed through extraction or other modes, making pharmaceutically active substance, subsequently, is raw material with this material, add the medicine acceptable carrier when needing, make capsule, tablet, syrup, granule according to the routine techniques of galenic pharmacy.Described active substance can obtain by the method that is selected from following mode, as: by pulverize, squeeze, calcine, grind, sieve, percolation, extraction, water are carried, alcohol extraction, ester are carried, methods such as ketone is carried, chromatography obtain, these active substances can be the materials of extractum form, can be that dry extract also can be a fluid extract, can also be the high-purity extract, make different concentration according to the different needs decision of preparation.
Of the present inventionly must give birth to other dosage forms, when making preparation, can add the medicine acceptable carrier as required, these carriers can be any carriers that is fit to make preparation of the present invention, as: benzoic acid or potassium salt, mannitol, sorbitol, sorbic acid or potassium salt, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, Nepal's methyl ester, Nepal's ethyl ester, Nepal's propyl ester, Nepal's butyl ester, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin A, vitamin C, vitamin E, vitamin D, azone, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, silicon derivative, cellulose and derivant thereof, alginate, gelatin, polyvinylpyrrolidone, glycerol, propylene glycol, ethanol, soil temperature 60-80, Arlacel-80, Cera Flava, lanoline, liquid paraffin, hexadecanol, gallate ester, agar, triethanolamine, basic amino acid, carbamide, allantoin, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, phospholipid material etc.
'Desheng ' of the present invention, particularly granular preparation, it is as follows that its function cures mainly usage and dosage:
[function with cure mainly] regulating menstruation and nourishing blood, regulating the flow of QI to dissipate blood stasis.Be used for menoxenia, abdominal pain in menstruation, stagnation of QI and blood, lump in the abdomen mass in the abdomen.
[attention] is not taken by pregnant women.
[specification] every packed 5g
[storage] sealing.
The present invention is to provide the method for quality control at above 'Desheng ', particularly granular preparation, be the quality of control 'Desheng '.At its characteristics and prescription of the present invention, we provide following method of quality control:
Method of quality control of the present invention may further comprise the steps:
The observation of character, the discriminating of content, the inspection of content is carried out assay to the composition that contains, and therefore, the main step of method of quality control of the present invention is:
The observation of character, step is:
[character] this product is yellow to filemot granule; It is sweet to distinguish the flavor of.
The discriminating of content, step is:
This product 5g is got in [discriminating] (1), adds ethanol 30ml, and ultrasonic 30 minutes, put coldly, filter, filtrate is concentrated into about 5ml, is added on active carbon-alumina column (active carbon 0.5g; Neutral alumina 100～120 orders, 2g, internal diameter 10mm) on, with ethanol 30ml eluting, collect eluent, evaporate to dryness, residue add ethanol 0.5ml makes dissolving, as need testing solution.Other gets the stachydrine hydrochloride reference substance, adds ethanol and becomes every 1ml to contain the solution of 5mg, product solution in contrast.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with acetone-dehydrated alcohol-hydrochloric acid (10: 6: 1) is developing solvent, launches, and takes out, dry, 105 ℃ the heating 10 minutes, put cold, the spray with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 10g, the 30ml that adds diethyl ether, ultrasonic 30 minutes, filter, filtrate evaporate to dryness, residue add ethyl acetate 1ml makes dissolving, as need testing solution.Get Rhizoma Chuanxiong, each 0.5g of Radix Angelicae Sinensis control medicinal material respectively in addition, shine medical material solution in pairs with legal system.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned 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 normal hexane-ethyl acetate (9: 1) is developing solvent, launches, and takes 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 two same colors.
(3) get this product 10g, add water 30ml and make its dissolving, with water saturated n-butanol extraction twice, each 30ml merges n-butyl alcohol liquid, extracts with isopyknic ammonia solution, gets n-butyl alcohol liquid, and evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Radix Bupleuri control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), 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 chloroform-methanol-water (65: 32: 10) below 10 ℃, lower floor's solution that placement is spent the night is developing solvent, launch, take out, dry, spray is dried by the fire to clear spot at 105 ℃ to contain 40% sulfuric acid solution of 4% paradime thylaminobenzaldehyde, puts under the ultra-violet lamp (365nm) and inspects.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the principal spot of same color.
The inspection of content, step is:
[inspection] should meet every regulation relevant under the granule item (Chinese Pharmacopoeia version one in 2005 is produced appendix IC).
The composition that contains is carried out assay, and step is:
[assay] measured according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2005).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Acetonitrile-0.1% phosphoric acid solution (14: 86) is a mobile phase; The detection wavelength is 230nm.Number of theoretical plate calculates by the peoniflorin peak should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the peoniflorin reference substance, adds methanol and make the solution that every 1ml contains 0.1mg, promptly.
The content that the preparation of need testing solution is got under this product content uniformity item is an amount of, mixing, and porphyrize is got about 2.0g, and accurate the title, decide, put in the 50ml measuring bottle, it is an amount of to add methanol, and supersound process 30 minutes is put coldly, is diluted to scale with methanol, shake up, filter, get subsequent filtrate, promptly with 0.45 μ m microporous filter membrane.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
This product contains the Radix Paeoniae Alba with peoniflorin (C for every bag
23H
28O
11) meter, must not be less than 6.0mg.
The present invention changes agent on former dosage form basis, simultaneously production technology reformed,
Study on extraction
We at former Herba Leonuri extraction process by water only clear and definite isoparametric situation of extraction time, extraction time, so we have investigated the influence of different solvents consumption to result of the test, and serve as to investigate index with main component stachydrine hydrochloride in the monarch drug Herba Leonuri among its side, determine the amount of solubilizer in conjunction with dried cream yield, finally we determine solvent load for the first time with 10 times of amounts, for the second time with 8 times of amounts.
We at former Radix Bupleuri boil back warm macerating technology only clear and definite isoparametric situation of extraction time, extraction time, so we have investigated the influence of different solvents consumption to result of the test, and determine the amount of solubilizer with its dried cream yield, finally we determine solvent load for the first time with 10 times of amounts, for the second time with 8 times of amounts.
We at former Radix Angelicae Sinensis technology clear and definite solvent concentration, so on this basis, solvent consumption and percolation speed etc. are not determined that factor adopts single factor experiment method to investigate, and be to investigate index with the paste-forming rate, finally we determine the speed with 5ml/min/kg, the first time is with 95% ethanol percolation of 13 times of volumes, for the second time with 12 times of 95% ethanol percolations of measuring volumes.
We at former Rhizoma Chuanxiong, the Radix Paeoniae Alba, Radix Aucklandiae technology clear and definite solvent concentration, so on this basis, solvent consumption and percolation speed etc. are not determined that factor adopts single factor experiment method to investigate, and with the main effective ingredient content of paeoniflorin in the Radix Paeoniae Alba as evaluation index, and with reference to its paste-forming rate, finally we determine the speed with 5ml/min/kg, carry out percolation with 60% ethanol of 10 times of volumes.
4, preparation process research
In Study on Forming, we select for use dextrin and sucrose as diluent, and this consumption has been carried out volt choosing, and final to determine to select the dextrin consumption be 1.2 times of thick paste, and the molding particles situation was better when the sucrose consumption was 2.4 times of thick paste.
14.2 the testing data of quality research work
Differentiate in the former preparation quality standard and the assay item, make into to such an extent that we study its quality standard behind the life granule, increased by three qualitative identification and an assay.
14.2.1 differentiate
14.2.1.1 differentiating the thin layer of Herba Leonuri in (1) side of being differentiates
With the effective ingredient stachydrine hydrochloride in the Herba Leonuri in contrast product differentiate, get negative control simultaneously, the result, negative noiseless, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.And examine entirely three batches all up to specification, so the standard of including in.
14.2.1.2 differentiating the thin layer of Rhizoma Chuanxiong, Radix Angelicae Sinensis in (2) side of being differentiates
We serve as that Study on Identification is carried out in contrast with Rhizoma Chuanxiong, Radix Angelicae Sinensis control medicinal material, make negative control simultaneously, and the result shows that negative control is not seen interference, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.And examine entirely three batches all up to specification, so this discriminating is listed in this product quality standard.
14.2.13 differentiating the thin layer of Radix Bupleuri in (3) side of being differentiates
We serve as that Study on Identification is carried out in contrast with the Radix Bupleuri control medicinal material, make negative control simultaneously, and the result shows: negative control is not seen interference, in the test sample chromatograph with contrast chromatograph corresponding position on, show the speckle of same color.And examine entirely three batches all up to specification, so this discriminating is listed in this product quality standard.
14.2.1.4 other
Once the method on the reference literature in the identification experiment of the Radix Aucklandiae, adopted multiple extraction solvents such as chloroform to handle sample with different sample treatments, screened different developing solvents, but all do not occur and the corresponding speckle of control medicinal material in the gained test sample chromatograph, and disturb very big, so we do not include its discriminating in this product quality standard in temporarily.The Radix Paeoniae Alba carries out the assay item because of it, so do not consider to do qualitative identification.
14.2.2 check
14.2.2.1 content uniformity
Check that according to content uniformity inspection technique under the granule item (2000 editions appendix IC of Chinese Pharmacopoeia) result is all up to specification.
14.2.2.2 granularity
Check that according to granularity inspection technique under the granule item (2000 editions appendix IC of Chinese Pharmacopoeia) result is all up to specification.
14.2.2.3 moisture
Check that according to moisture inspection technique under the granule item (2000 editions appendix IC of Chinese Pharmacopoeia) and (2000 editions appendix IXH of Chinese Pharmacopoeia) result is all up to specification
14.2.2.4 heavy metal
Checked 3 batch samples by heavy metal inspection technique (2000 editions one appendix IXE second method of Chinese Pharmacopoeia), the result all surpasses 10/1000000ths, so quality standard is not included in an inspection temporarily in.
14.2.2.5 arsenic salt
Checked 3 batch samples according to arsenic salt inspection technique [2000 editions one appendix IXF first method of Chinese Pharmacopoeia], the result all surpasses 2/1000000ths, so quality standard is not included in an inspection temporarily in.
14.2.2.6 limit test of microbe
Press 2000 editions appendix XIIIC of Chinese Pharmacopoeia " microbial limit standard " regulation, the bacterial population of granule must not be crossed 1000/g, and mycete, yeast count must not be crossed 100/g, and live demodicid mite and colibacillus should detect.Several batches of testing results of this preparation are all up to specification.
14.2.3 assay
The research of content of paeoniflorin assay method in the Radix Paeoniae Alba
1, instrument and reagent
High performance liquid chromatograph: Waters 2996 types, quaternary pump
Detector: DAD diode array detector
Chromatographic column: YMC 5 μ m C18 150mm * 6.4mm
Peoniflorin reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute, 110736-200423 uses for assay).
Acetonitrile is a chromatographically pure, and other reagent is analytical pure, and water is ultra-pure water.
2, chromatographic condition and system suitability test
Immobile phase: octadecylsilane chemically bonded silica
Mobile phase: acetonitrile-0.1% phosphoric acid solution (14: 86)
Detect wavelength: 230nm
Column temperature: 25 ℃
Flow velocity: 1.0ml/min
It is an amount of that the preparation precision of reference substance solution takes by weighing the peoniflorin reference substance, makes the reference substance solution that every 1ml contains peoniflorin 0.1mg with methanol
The negative sample that lacks white Peony Root is got in the preparation of negative sample solution, makes with method by the preparation method under the test sample item.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
In the above conditions, the adjacent component with other of peoniflorin all can reach baseline separation, and separating degree is greater than 1.5, and number of theoretical plate calculates by the peoniflorin peak should be not less than 5000.And under identical retention time, there is not absworption peak with the negative control of scarce white Peony Root.
3, the investigation of the preparation of need testing solution and method
(1) comparison of extracting method: accurate claim random sample product (lot number: 20040713) an amount of, put the 50ml measuring bottle, it is an amount of to add methanol, ultrasonic 30 minutes, put coldly, add methanol and be diluted to scale, filtration; Other gets 1 part and puts in the 100ml conical flask and measure, and precision is measured methanol 50ml, claims decide weight, and reflux 30 minutes is put coldly, and it is fixed to claim, and supplies the weight of loss, and above two measured in solution are got in filtration respectively, the results are shown in Table 14-3.
Table 14-3
| Extracting method | Ultrasonic | Reflux |
| Content (mg/g) | 2.54 | 2.53 |
Conclusion: above result shows ultrasonic and reflow method is more or less the same, and is energy-conservation because of ultrasonic easy than reflux operation, so adopt supersound extraction as giving birth to particulate extracting method.
(2) extract the investigation of solvent: accurate claim random sample product (lot number: 20040713), intending with ethanol, Diluted Alcohol, methanol is to extract solvent, ultrasonic 30 minutes, put coldly, and be diluted to scale, filtration, mensuration the results are shown in Table 14-4.
Table 14-4
| Extract solvent | Ethanol | Diluted Alcohol | Methanol |
| Content (mg/g) | 1.35 | 2.45 | 2.54 |
Conclusion: above result shows with the methanol supersound extraction better, is to extract solvent so select methanol for use.
(3) extraction time is relatively: accurate claim random sample product (lot number: 20040713), intending with methanol is to extract solvent, ultrasonic 20,30,40,50 minutes respectively, put coldly, and be diluted to scale, filtration, mensuration the results are shown in Table 14-5.
Table 14-5
| Extraction time (minute) | 20 | 30 | 40 | 50 |
| Content (mg/g) | 2.54 | 2.58 | 2.56 | 2.56 |
Conclusion: by above data relatively more as broad as long with 40 and 50 minutes when extracting 30 minutes, extract substantially complete, so definite extraction time is 30 minutes.
In sum, the preparation method of need testing solution is as follows:
Get the content under this product content uniformity item, mixing, porphyrize is got about 2.0g, accurate claims surely, puts in the 50ml measuring bottle, and it is an amount of to add methanol, and supersound process 30 minutes is put coldly, adds methanol and is diluted to scale, shakes up, and filters, promptly.
4, linear relationship is investigated
Get concentration and be 0.0416,0.1041,0.2082,0.4164, the peoniflorin reference substance solution 10 μ l of 1.041mg/ml, sample introduction is measured peak area successively, the drawing standard curve the results are shown in Table 14-6.
Table 14-6 linear relationship
| Reference substance concentration | 0.0416 | 0.1041 | 0.2082 | 0.4164 | 1.041 |
| Peak area | 510369 | 1243014 | 2508691 | 5012769 | 12822091 |
With concentration is abscissa, and peak area is a vertical coordinate drawing standard curve, calculates regression equation.
Regression equation is: Y=1.23e+007x-5.00e+004, R
2=0.9999, illustrate: the concentration of peoniflorin all is linear in the 0.0416-1.041mg/ml scope.
5, precision test
(concentration: 0.4164mg/ml), press text [assay] method operation down, continuous sample introduction 5 times is measured peak area value to get the peoniflorin reference substance solution.Measurement result sees Table 14-7.
The test of table 14-7 precision
| No | The peoniflorin peak area | RSD％ |
| 1 2 3 4 5 | 5019720 5023061 5030628 5026617 5031123 | 0.10 |
6, stability test
The stability of reference substance solution: (concentration: 0.2082mg/ml), respectively at following time point sample introduction, reference substance solution is stable in 12 hours as a result to get the peoniflorin reference substance solution.(seeing Table 14-8)
The stability of table 14-8 reference substance solution
| Time (h) | The peoniflorin peak area | RSD％ |
| 0 2 4 8 12 | 2527103 2525132 2514659 2517892 2514850 | 0.23 |
The stability of need testing solution: precision take by weighing test sample (lot number: 20040713) 2.1041g, press under the text content assaying method item preparation need testing solution, respectively at following time point sample introduction, need testing solution is stable in 12 hours as a result.(seeing Table 14-9)
The stability of table 14-9 need testing solution
| Time (h) | The peoniflorin peak area | RSD％ |
| 0 2 4 8 12 | 1240155 1302193 1221022 1272628 1232160 | 2.65 |
7, replica test
Precision take by weighing test sample (lot number: 20040713) 5 parts, press under the text content assaying method item preparation need testing solution respectively, calculate paeoniflorin content, the results are shown in Table 14-10.
Table 14-10 replica test
| NO | Sample weighting amount (g) | The peoniflorin peak area | Paeoniflorin content (mg/g) | RSD％ |
| 1 2 3 4 5 | 2.0542 2.0348 2.0327 2.0294 2.0913 | 1215906 1208510 1206799 1207657 1259662 | 2.48 2.49 2.49 2.50 2.53 | 0.68 |
8, average recovery test
Get known content sample (lot number: 20040713) 1.0g, accurate claim surely, put in the 50mL volumetric flask.The accurate peoniflorin reference substance solution (concentration: 0.242mg/ml) 10ml that adds; Press sample [assay] item method mensuration down, with the following formula calculate recovery rate, measurement result sees Table 14-11.
The test of table 14-11 average recovery
| NO | Sample weighting amount (g) | Content in the sample (mg) | Reference substance addition (mg) | Measured quantity (mg) | The response rate (%) | Average recovery rate (%) | RSD％ |
| 1 2 3 | 1.0118 1.0421 1.0152 | 2.51 2.59 2.52 | 2.42 2.42 2.42 | 4.96 5.00 4.92 | 101.14 99.74 99.11 | 100.76 | 1.08 |
| 4 5 6 | 1.0134 1.0014 1.0018 | 2.52 2.49 2.49 | 2.42 2.42 2.42 | 4.96 4.93 4.95 | 101.32 101.31 101.94 |
The result: test to such an extent that its average recovery rate is 100.76% through sample is carried out average recovery, RSD is 1.08%, and the result shows that this method has the response rate preferably.
Above-mentioned experimental results show that: through content assaying method being carried out the experiment of precision, repeatability, stability and the response rate, RSD is all less than 3.0%, and this method is more easy to operate, can control the quality of product preferably, so definite [assay] is as described in the text.
9,10 batches give birth to particle content measuring
Press text [assay] method, measure ten batches give birth to the content of Radix Paeoniae in the granule, the results are shown in Table 14-16.
10 crowdes of 14-16 of table give birth to particulate content results
| Lot number | Paeoniflorin content (mg/ bag) | Meansigma methods (mg/ bag) | |
| 20040713 20040714 20040715 20041101 20041102 20041103 20041104 20051214 20051215 20051216 | 11.3 11.6 11.7 8.4 8.4 8.6 8.5 12.5 12.5 12.0 | 11.6 11.4 11.5 8.4 8.3 8.9 8.6 12.6 12.6 12.1 | 10.6 |
The formulation of content limit: calculating its meansigma methods more than the process is the 10.6mg/ bag, if decide content limit 8.5mg/ bag with 80% of its average content, for more effective, reasonably formulate content limit, to calculate according to the rate of transform of content, formula: content of paeoniflorin limit * rate of transform % in every bag of amount * Radix Paeoniae Alba that contains white Peony Root, wherein every bag to contain the white Peony Root amount be the 0.753g/ bag, the content of paeoniflorin limit is 1.6% in the white Peony Root, the rate of transform is about about 60%, result of calculation is the 7.2mg/ bag, carrying out with 80% of content more quantitatively is the 6.0mg/ bag, so tentative this product contains the Radix Paeoniae Alba with peoniflorin (C for every bag
23H
28O
11) meter, must not be less than 6.0mg.
More than this product described in the method for quality control of the present invention, be meant according to prepared of the present invention must give birth to granule, when other dosage forms are measured, refer to corresponding other dosage forms.
The invention has the advantages that: method of quality control of the present invention has guaranteed that the quality inspection standard of preparation of the present invention can be than the qualitative character of effectively controlling preparation comprehensively, have accuracy and advance, can be used as the effective technology means of the stability of quality control and investigation technology.Be of great importance to improving the quality of products.
The specific embodiment:
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1 must give birth to particulate quality control
Method of quality control of the present invention may further comprise the steps:
The observation of character, step is:
[character] this product is yellow to filemot granule; It is sweet to distinguish the flavor of.
The discriminating of content, step is:
This product 5g is got in [discriminating] (1), adds ethanol 30ml, and ultrasonic 30 minutes, put coldly, filter, filtrate is concentrated into about 5ml, is added on active carbon-alumina column (active carbon 0.5g; Neutral alumina 100～120 orders, 2g, internal diameter 10mm) on, with ethanol 30ml eluting, collect eluent, evaporate to dryness, residue add ethanol 0.5ml makes dissolving, as need testing solution.Other gets the stachydrine hydrochloride reference substance, adds ethanol and becomes every 1ml to contain the solution of 5mg, product solution in contrast.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with acetone-dehydrated alcohol-hydrochloric acid (10: 6: 1) is developing solvent, launches, and takes out, dry, 105 ℃ the heating 10 minutes, put cold, the spray with rare bismuth potassium iodide test solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
(2) get this product 10g, the 30ml that adds diethyl ether, ultrasonic 30 minutes, filter, filtrate evaporate to dryness, residue add ethyl acetate 1ml makes dissolving, as need testing solution.Get Rhizoma Chuanxiong, each 0.5g of Radix Angelicae Sinensis control medicinal material respectively in addition, shine medical material solution in pairs with legal system.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned 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 normal hexane-ethyl acetate (9: 1) is developing solvent, launches, and takes 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 two same colors.
(3) get this product 10g, add water 30ml and make its dissolving, with water saturated n-butanol extraction twice, each 30ml merges n-butyl alcohol liquid, extracts with isopyknic ammonia solution, gets n-butyl alcohol liquid, and evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Radix Bupleuri control medicinal material 1g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), 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 chloroform-methanol-water (65: 32: 10) below 10 ℃, lower floor's solution that placement is spent the night is developing solvent, launch, take out, dry, spray is dried by the fire to clear spot at 105 ℃ to contain 40% sulfuric acid solution of 4% paradime thylaminobenzaldehyde, puts under the ultra-violet lamp (365nm) and inspects.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the principal spot of same color.
The inspection of content, step is:
[inspection] should meet every regulation relevant under the granule item (Chinese Pharmacopoeia version one in 2005 is produced appendix IC).
The composition that contains is carried out assay, and step is:
[assay] measured according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2005).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Acetonitrile-0.1% phosphoric acid solution (14: 86) is a mobile phase; The detection wavelength is 230nm.Number of theoretical plate calculates by the peoniflorin peak should be not less than 3000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the peoniflorin reference substance, adds methanol and make the solution that every 1ml contains 0.1mg, promptly.
The content that the preparation of need testing solution is got under this product content uniformity item is an amount of, mixing, and porphyrize is got about 2.0g, and accurate the title, decide, put in the 50ml measuring bottle, it is an amount of to add methanol, and ultrasonic place 30 minutes puts coldly, is diluted to scale with methanol, shake up, filter, get subsequent filtrate, promptly with 0.45 μ m microporous filter membrane.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
This product contains the Radix Paeoniae Alba with peoniflorin (C for every bag
23H
28O
11) meter, must not be less than 6.0mg.
Embodiment 2 must give birth to granule
[prescription]
Herba Leonuri 451.8g Radix Bupleuri 75.3g Radix Angelicae Sinensis 150.6g
Rhizoma Chuanxiong 37.6g Radix Paeoniae Alba 150.6g Radix Aucklandiae 37.6g
Must give birth to the granule method for making: above Six-element, Herba Leonuri decocts with water secondary, and 2 hours for the first time, 1 hour for the second time; Radix Bupleuri boils back warm macerating secondary, and 2 hours for the first time, 1 hour for the second time, collecting decoction and warm macerating liquid were condensed into cream; Radix Angelicae Sinensis is made solvent with 95% ethanol for the first time, and 60% ethanol is made solvent for the second time, according to percolation (appendix IO of Chinese Pharmacopoeia version in 2000) under fluid extract and the extractum item, percolation secondary; Rhizoma Chuanxiong, the Radix Paeoniae Alba, the Radix Aucklandiae are made solvent with 60% ethanol, carry out percolation.The liquid of filtering more than the merging reclaims ethanol, is condensed into thick paste, merges with above-mentioned condensed cream, adds right amount of auxiliary materials, and mixing is granulated, drying, and granulate is made 1000g, promptly.
Claims (8)
1, a kind of method of quality control of 'Desheng ' is characterized in that, comprises the observation of character, the discriminating of content, and the step of assay is carried out in the inspection of content to the composition that contains.
2, the method for claim 1 is characterized in that, described 'Desheng ' is an oral solid formulation.
3, the method for claim 2 is characterized in that, described oral solid formulation be give birth to granule.
4, the method for claim 3 is characterized in that, described method step is as follows:
The observation of character, step is:
[character] this product is yellow to filemot granule; It is sweet to distinguish the flavor of;
The discriminating of content, step is:
This product 5g is got in [discriminating] (1), adds ethanol 30ml, and ultrasonic 30 minutes, put coldly, filter, filtrate is concentrated into about 5ml, is added on active carbon-alumina column (active carbon 0.5g; Neutral alumina 100～120 orders, 2g, internal diameter 10mm) on, with ethanol 30ml eluting, collect eluent, evaporate to dryness, residue add ethanol 0.5ml makes dissolving, as need testing solution; Other gets the stachydrine hydrochloride reference substance, adds ethanol and becomes every 1ml to contain the solution of 5mg, product solution in contrast; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with acetone-dehydrated alcohol-hydrochloric acid (10: 6: 1) is developing solvent, launches, and takes out, dry, 105 ℃ the heating 10 minutes, put cold, the spray with rare bismuth potassium iodide test solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
(2) get this product 10g, the 30ml that adds diethyl ether, ultrasonic 30 minutes, filter, filtrate evaporate to dryness, residue add ethyl acetate 1ml makes dissolving, as need testing solution; Get Rhizoma Chuanxiong, each 0.5g of Radix Angelicae Sinensis control medicinal material respectively in addition, shine medical material solution in pairs with legal system; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned 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 normal hexane-ethyl acetate (9: 1) is developing solvent, launches, and takes 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 two same colors;
(3) get this product 10g, add water 30ml and make its dissolving, with water saturated n-butanol extraction twice, each 30ml merges n-butyl alcohol liquid, extracts with isopyknic ammonia solution, gets n-butyl alcohol liquid, and evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Bupleuri control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), 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 chloroform-methanol-water (65: 32: 10) below 10 ℃, lower floor's solution that placement is spent the night is developing solvent, launch, take out, dry, spray is dried by the fire to clear spot at 105 ℃ to contain 40% sulfuric acid solution of 4% paradime thylaminobenzaldehyde, puts under the ultra-violet lamp (365nm) and inspects; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the principal spot of same color;
The inspection of content, step is:
[inspection] should meet every regulation relevant under the granule item (Chinese Pharmacopoeia version one in 2005 is produced appendix I C);
The composition that contains is carried out assay, and step is:
[assay] measured according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2005);
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Acetonitrile-0.1% phosphoric acid solution (14: 86) is a mobile phase; The detection wavelength is 230nm; Number of theoretical plate calculates by the peoniflorin peak should be not less than 3000;
It is an amount of that the preparation precision of reference substance solution takes by weighing the peoniflorin reference substance, adds methanol and make the solution that every 1ml contains 0.1mg, promptly;
The content that the preparation of need testing solution is got under this product content uniformity item is an amount of, mixing, porphyrize, get about 2.0g, the accurate title, decide, and puts in the 50ml measuring bottle, it is an amount of to add methanol, supersound process 30 minutes is put coldly, is diluted to scale with methanol, shake up, filter with 0.45 μ m microporous filter membrane, get subsequent filtrate, promptly;
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
This product contains the Radix Paeoniae Alba with peoniflorin (C for every bag
23H
28O
11) meter, must not be less than 6.0mg.
According to the method for claim 1, it is characterized in that 5, described 'Desheng ' is to be made by the raw material of Chinese medicine of following weight:
Herba Leonuri 451.8g Radix Bupleuri 75.3g Radix Angelicae Sinensis 150.6g
Rhizoma Chuanxiong 37.6g Radix Paeoniae Alba 150.6g Radix Aucklandiae 37.6g.
6, according to the method for claim 1, it is characterized in that, wherein said 'Desheng ' is by raw material of Chinese medicine is processed through extraction or other modes, make pharmaceutically active substance, subsequently, be raw material with this material, add the medicine acceptable carrier when needing, make according to the routine techniques of galenic pharmacy, described active substance obtains by the method that is selected from following mode: pulverize, squeeze, calcine, grind, sieve, percolation, extraction, water are carried, alcohol extraction, ester are carried, ketone is carried or chromatography.
7, according to the method for claim 6, it is characterized in that, wherein said 'Desheng ' be give birth to granule.
According to the method for claim 7, it is characterized in that 8, the wherein said granule of must giving birth to is by preparing through following method: Herba Leonuri decocts with water secondary, 2 hours for the first time, 1 hour for the second time; Radix Bupleuri boils back warm macerating secondary, and 2 hours for the first time, 1 hour for the second time, collecting decoction and warm macerating liquid were condensed into cream; Radix Angelicae Sinensis is made solvent with 95% ethanol for the first time, and 60% ethanol is made solvent for the second time, according to percolation (an appendix I of Chinese Pharmacopoeia version in 2000 O) under fluid extract and the extractum item, percolation secondary; Rhizoma Chuanxiong, the Radix Paeoniae Alba, the Radix Aucklandiae are made solvent with 60% ethanol, carry out percolation; The liquid of filtering more than the merging reclaims ethanol, is condensed into thick paste, merges with above-mentioned condensed cream, adds right amount of auxiliary materials, and mixing is granulated, drying, and granulate is made 1000g, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100656497A CN1857445B (en) | 2006-03-23 | 2006-03-23 | Quality control method for Desheng preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100656497A CN1857445B (en) | 2006-03-23 | 2006-03-23 | Quality control method for Desheng preparation |
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| CN1857445A true CN1857445A (en) | 2006-11-08 |
| CN1857445B CN1857445B (en) | 2011-06-01 |
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| CN2006100656497A Expired - Fee Related CN1857445B (en) | 2006-03-23 | 2006-03-23 | Quality control method for Desheng preparation |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526229A (en) * | 2011-12-27 | 2012-07-04 | 陕西兴邦药业有限公司 | Chinese medicinal composition for regulating menstruation, nourishing blood, regulating flow of qi and dissipating blood stasis and preparation method thereof |
| CN102641361A (en) * | 2012-02-21 | 2012-08-22 | 常熟市方塔涂料化工有限公司 | Chinese herb preparation for treating abnormal menstruation |
| CN102998273A (en) * | 2012-08-23 | 2013-03-27 | 江苏苏南药业实业有限公司 | Quality controlling method for termitarium capsules |
| CN103908500A (en) * | 2014-03-20 | 2014-07-09 | 牛光明 | Traditional Chinese medicine prescription for treating gynecological disease |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1270822A (en) * | 2000-03-15 | 2000-10-25 | 杨志正 | Chinese medicine for treating puerperal diseases |
-
2006
- 2006-03-23 CN CN2006100656497A patent/CN1857445B/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526229A (en) * | 2011-12-27 | 2012-07-04 | 陕西兴邦药业有限公司 | Chinese medicinal composition for regulating menstruation, nourishing blood, regulating flow of qi and dissipating blood stasis and preparation method thereof |
| CN102526229B (en) * | 2011-12-27 | 2013-08-07 | 陕西兴邦药业有限公司 | Chinese medicinal composition for regulating menstruation, nourishing blood, regulating flow of qi and dissipating blood stasis and preparation method thereof |
| CN102641361A (en) * | 2012-02-21 | 2012-08-22 | 常熟市方塔涂料化工有限公司 | Chinese herb preparation for treating abnormal menstruation |
| CN102998273A (en) * | 2012-08-23 | 2013-03-27 | 江苏苏南药业实业有限公司 | Quality controlling method for termitarium capsules |
| CN102998273B (en) * | 2012-08-23 | 2015-02-18 | 江苏苏南药业实业有限公司 | Detecting method for termitarium capsules |
| CN103908500A (en) * | 2014-03-20 | 2014-07-09 | 牛光明 | Traditional Chinese medicine prescription for treating gynecological disease |
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|---|---|
| CN1857445B (en) | 2011-06-01 |
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Address after: 1266 No. 330052 Nanchang Huiren Jiangxi economic and Technological Development Zone Avenue. Patentee after: JIANGXI HUIREN PHARMACEUTICAL CO.,LTD. Address before: 330043 1189 Yingbin Avenue, Nanchang, Jiangxi Patentee before: Jiangxi Huiren Pharmaceutical Co.,Ltd. |
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