CN1973897A - Quality control method for puerperal blood clot dispersing tablet - Google Patents

Abstract

The present invention is quality control method for puerperal blood clot dispersing tablet. The quality control method includes partial or complete character identification and content measurement. The character identification includes the microscopic examination and the thin-layer chromatographic identification on motherwort, angelica and Chuanxiong rhizome; and the content measurement is to measure the content of cadabine hydrochloride in motherwort Compared with available technology, the present invention has the advantages of high precision, high repeatability, high recovering rate, accurate measurement result and capacity of raising the quality of puerperal blood clot dispersing tablet.

Description

The method of quality control of puerperal blood clot dispersing tablet

Technical field: the present invention relates to a kind of method of quality control of puerperal blood clot dispersing tablet, belong to the technical field of medicine being carried out quality control.

Background technology: puerperal blood clot dispersing tablet just was disclosed in as far back as 1998 in " Chinese traditional patent formulation preparation promulgated by the ministries or commissions of the Central Government ", mainly was made up of Herba Leonuri, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Zingiberis Preparatum, had promoting blood flow to regulate menstruation, blood stasis removing analgesic effect.This medicine is used for the treatment of postnatal blood stasis retention in clinical practice for many years, and young married woman's stomachache is evident in efficacy.But find after deliberation, puerperal blood clot dispersing preparation initial quality control criterion is too simple, only with character, microscopical identification and routine examination project as evaluation index, both do not had thin layer and differentiated not have assay yet, shortcomings such as it is backward to exist method of quality control, and product quality is wayward.Herba Leonuri is a monarch drug in the side, promoting blood flow to regulate menstruation, promoting the circulation of blood dissipating blood stasis.Do not differentiate do not have the assay index and both it has been carried out thin layer chromatography in the existing quality standard yet,, thereby will influence production and the quality assurance and the clinical efficacy thereof of this product so existing quality standard can not effectively be controlled the quality of puerperal blood clot dispersing preparation.

Summary of the invention:

The objective of the invention is to: the method for quality control that a kind of puerperal blood clot dispersing tablet is provided.The present invention is directed to the deficiency of existing quality control standard, method of quality control to puerperal blood clot dispersing tablet is studied, replenish that the thin layer chromatography set up Herba Leonuri and Radix Angelicae Sinensis, Rhizoma Chuanxiong is differentiated and Determination of Contents of Hydrochloric Stachydrine is measured, improve the quality control standard of puerperal blood clot dispersing tablet, thereby guaranteed the quality and the clinical efficacy of this medicine.

Puerperal blood clot dispersing tablet of the present invention is to constitute like this: it mainly is prepared from by Herba Leonuri 1000-1500g, Radix Angelicae Sinensis 100-200g, Rhizoma Chuanxiong 120-230g and Rhizoma Zingiberis Preparatum 40-100g.Its preparation method is: get Herba Leonuri, Radix Angelicae Sinensis, each 20g of Rhizoma Chuanxiong and be ground into fine powder, standby, residue Radix Angelicae Sinensis, Rhizoma Chuanxiong and Rhizoma Zingiberis Preparatum extract volatile oil, and medicinal residues decoct with water secondary with the residue Herba Leonuri, 2 hours for the first time, 1 hour for the second time, filter, filtrate merges, and is condensed into thick paste, adds above-mentioned fine powder, mixing, oven dry, system granule, oven dry again adds volatile oil such as Radix Angelicae Sinensis, mixing, be pressed into 1000, the bag film-coat, promptly.

Method of quality control of the present invention mainly comprise in character, discriminating, inspection and the assay project partly or entirely; Wherein differentiate the thin layer chromatography discriminating that comprises microexamination, Herba Leonuri and Radix Angelicae Sinensis, Rhizoma Chuanxiong; Assay is that the contained stachydrine hydrochloride of Herba Leonuri in the preparation is carried out assay.

Wherein the discrimination method of Herba Leonuri is to be contrast with the stachydrine hydrochloride reference substance, is the thin layer chromatography of developing solvent with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2; The discrimination method of Radix Angelicae Sinensis, Rhizoma Chuanxiong is to be contrast with Radix Angelicae Sinensis, Rhizoma Chuanxiong control medicinal material, is the thin layer chromatography of developing solvent with normal hexane-ethyl acetate=1-15: 0.2-2.

Discrimination method comprises the part or all of of following project:

(1) get this preparation, put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get this preparation, remove film-coat, porphyrize adds ethanol, and reflux is put coldly, filters, and filtrate concentrates, and adds on active carbon-alumina column, use ethanol elution, the collection eluent, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make solution, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, 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 carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2 is developing solvent, launch, take out, dry, spray is to improve bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1-10: the mixed solution of 0.2-2 is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation, remove film-coat, porphyrize is put in the tool plug conical flask, and the supersound extraction twice that adds diethyl ether merges ether solution, filter, and the filtrate evaporate to dryness, residue adds acetic acid ethyl dissolution, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10 μ l of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1-15: 0.2-2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color.

Concrete discrimination method comprises the part or all of of following project:

(1) get this preparation, put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get 5～15 in this preparation, remove film-coat, porphyrize, add ethanol 20～80ml, reflux 0.5～3 hour is put cold, filter, filtrate is concentrated into about 2～8ml, adds to contain on the active carbon alumina column of active carbon 1g, 100～200 purpose neutral aluminas, 2～3g, internal diameter 1.5～2cm, with ethanol 20～80ml eluting, collect eluent, evaporate to dryness, residue add ethanol 0.5～3ml makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, 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 carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2 is developing solvent, launch, take out, dry, spray is to improve bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1-10: the mixed solution of 0.2-2 is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation 2～10g, remove film-coat, porphyrize is put in the tool plug conical flask, the 10～30ml supersound extraction twice that adds diethyl ether, and each 2～8 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 0.5～3ml dissolving, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10 μ l of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1-15: 0.2-2 is developing solvent, launch, take out, dry, put under ultra-violet lamp 200～300nm and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color.

The Determination of Contents of Hydrochloric Stachydrine assay method is to be contrast with the stachydrine hydrochloride reference substance in the Herba Leonuri, is the high performance liquid chromatography of mobile phase with acetonitrile-water=50-150: 5-20.

The Determination of Contents of Hydrochloric Stachydrine assay method is:

According to Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50-150: 5-20 is mobile phase; Flow velocity: 0.2-2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0-3.0L/min; Drift tube temperature: 50-120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

This preparation is got in the preparation of need testing solution, removes coating, porphyrize, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol that adds, claim to decide weight, supersound process under power 150W, frequency 50kHz condition is put cold, supply the weight that subtracts mistake with ethanol, filter, measure subsequent filtrate in evaporating dish, put evaporate to dryness on the water-bath, residue dissolve with methanol standardize solution shakes up, use membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri with stachydrine hydrochloride C ₇H ₁₃NO ₂The HCl meter must not be less than 1.5mg.

The stachydrine hydrochloride content assaying method is more specifically:

According to Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50-150: 5-20 is mobile phase; Flow velocity: 0.2-2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0-3.0L/min; Drift tube temperature: 50-120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

5～15 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.2～0.8g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 20～80ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with being less than or equal to 0.45 μ m membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri with stachydrine hydrochloride C ₇H ₁₃N0 ₂The HCl meter must not be less than 1.5mg.

Method of quality control of the present invention comprises:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of;

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get this preparation, remove film-coat, porphyrize adds ethanol, and reflux is put coldly, filters, and filtrate concentrates, and adds on the active carbon alumina column, use ethanol elution, the collection eluent, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make solution, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, 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 carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2 is developing solvent, launch, take out, dry, spray is to improve bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1-10: the mixed solution of 0.2-2 is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation, remove film-coat, porphyrize is put in the tool plug conical flask, and the supersound extraction twice that adds diethyl ether merges ether solution, filter, and the filtrate evaporate to dryness, residue adds acetic acid ethyl dissolution, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10 μ l of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1-15: 0.2-2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color;

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item;

Assay: shine Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50-150: 5-20 is mobile phase; Flow velocity: 0.2-2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0-3.0L/min; Drift tube temperature: 50-120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

This preparation is got in the preparation of need testing solution, removes coating, porphyrize, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol that adds, claim to decide weight, supersound process under power 150W, frequency 50kHz condition is put cold, supply the weight that subtracts mistake with ethanol, filter, measure subsequent filtrate in evaporating dish, put evaporate to dryness on the water-bath, residue dissolve with methanol standardize solution shakes up, use membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri with stachydrine hydrochloride C ₇H ₁₃NO ₂The HCl meter must not be less than 1.5mg.

The applicant finds after deliberation, adopts the quality of following method of quality control with easier control puerperal blood clot dispersing tablet, is more conducive to guarantee the clinical efficacy of said preparation.So described method of quality control also can comprise:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of;

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get 5～15 in this preparation, remove film-coat, porphyrize, add ethanol 20～80ml, reflux 0.5～3 hour is put cold, filter, filtrate is concentrated into about 2～8ml, adds to contain on the active carbon alumina column of active carbon 1g, 100～200 purpose neutral aluminas, 2～3g, internal diameter 1.5～2cm, with ethanol 20～80ml eluting, collect eluent, evaporate to dryness, residue add ethanol 0.5～3ml makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, 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 carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2 is developing solvent, launch, take out, dry, spray is to improve bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1-10: the mixed solution of 0.2-2 is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation 2～10g, remove film-coat, porphyrize is put in the tool plug conical flask, the 10～30ml supersound extraction twice that adds diethyl ether, and each 2～8 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 0.5～3ml dissolving, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10 μ l of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1-15: 0.2-2 is developing solvent, launch, take out, dry, put under ultra-violet lamp 200～300nm and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color;

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item;

Assay: shine Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50-150: 5-20 is mobile phase; Flow velocity: 0.2-2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0-3.0L/min; Drift tube temperature: 50-120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

5～15 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.2～0.8g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 20～80ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with being less than or equal to 0.45 μ m membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri with stachydrine hydrochloride C ₇H ₁₃N0 ₂The HCl meter must not be less than 1.5mg.

Find that after deliberation following method of quality control is an optimal choice, the quality of easier control puerperal blood clot dispersing tablet guarantees its clinical efficacy.So described method of quality control can also comprise:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of;

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get 10 in this preparation, remove film-coat, porphyrize, add ethanol 50ml, reflux 1 hour is put cold, filter, filtrate is concentrated into about 5ml, adds to contain on the active carbon alumina column of active carbon 1g, 100～200 purpose neutral aluminas, 2～3g, internal diameter 1.5～2cm, with ethanol 50ml eluting, collect eluent, evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, 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 carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=10: 6: 1 was developing solvent, launch, take out, dry, spray is heated to clear spot with the mixed solution of improvement bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=5: 1; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation 5g and remove film-coat, porphyrize is put in the tool plug conical flask, the 20ml supersound extraction twice that adds diethyl ether, and each 5 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 1ml dissolving, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10 μ l of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=9: 1 was developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color;

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item;

Assay: stachydrine hydrochloride shines Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=88: 12 was mobile phase; Flow velocity: 1.0ml/min; Detector: evaporative light scattering detector; Gas flow: 2.0L/min; Drift tube temperature: 90 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

10 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.5g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 50ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with being less than or equal to 0.45 μ m membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri with stachydrine hydrochloride C ₇H ₁₃NO ₂The HCl meter must not be less than 1.5mg.

Method of quality control of the present invention is the preferred plan that obtains through a large amount of screening tests, and following experimentation is a preferred process of the present invention:

The research of stachydrine hydrochloride content assaying method:

1, need testing solution preparation method research

Method 1: get 10 in this preparation, remove coating, porphyrize is got about 0.5g, and accurate the title decides, and puts in the 100ml boiling flask.Add dehydrated alcohol 30ml, 3h is extracted in hot reflux, filters, and with absolute ethanol washing filtering residue 3 times, each 5ml merges washing liquid and filtrate, evaporated under reduced pressure, and residue adds 20ml 0.1molL ^-1Dissolve with hydrochloric acid solution adds freshly prepared 2% sulfur hydracid chromium ammonium salt solution 5ml, puts and places 1h in the ice bath, filter,, discard filtrate with frozen water gradation washing container and precipitation, with 15ml acetone solution precipitation, in acetone soln, drip 0.5% silver sulfate solution and produce to no longer including precipitation, place.Natural filtration, with 70% ethanol 15ml gradation washing precipitation, merge washing liquid and filtrate, put and be concentrated into about 1ml in the water-bath, put coldly, add 1% barium chloride solution with the silver sulfate equivalent, water quantitatively is transferred in the 100ml measuring bottle and is diluted to scale, shake up, filter, promptly get need testing solution with 0.45 μ m filter membrane.

Method 2: get 10 in this preparation, remove coating, porphyrize, get about 0.5g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 50ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with 0.45 μ m membrane filtration, promptly.

Table 1

Sample	Method 1 (mg/g)	Method 2 (mg/g)
			1	4.995	5.896
2	4.752	5.988
			3	4.831	6.012

According to result of the test table 1 as can be known, employing method 2 preparation need testing solutions, stachydrine hydrochloride extracts more complete.

2, the selection of mobile phase:

Respectively following mobile phase is selected:

Mobile phase 1: with the acetonitrile-water different proportion is mobile phase

Mobile phase 2: with methanol-0.05mol/L potassium dihydrogen phosphate different proportion is mobile phase

Mobile phase 3:0.1molL ^-1The mixed solution of sodium radio-phosphate,P-32 solution-water different proportion is a mobile phase

The result: with acetonitrile-water=50-150: 5-20 is mobile phase; The negative sample chromatogram is at noiseless peak, stachydrine hydrochloride position, and stachydrine hydrochloride separates fully (separating degree＞1.5) with close impurity peaks, and promptly stachydrine hydrochloride separates with other components fully under this condition.Optimal flow is mutually: acetonitrile-water=88: 12.

3, replica test

Get same batch sample (051103), precision takes by weighing 6 parts respectively, every part of about 0.5g, the accurate title, decide, according to the preparation method preparation of above-mentioned need testing solution, the accurate respectively 10 μ l sample introductions of drawing, the record chromatogram calculates content, and 6 duplicate samples stachydrine hydrochloride assay meansigma methodss are 6.57mg/g, RSD% is 1.0%, illustrates that this method repeatability is good.The results are shown in Table 2.

Table 2 replica test is table as a result

Numbering	Sample weighting amount (g)	Stachydrine hydrochloride content (mg/g)	Meansigma methods (mg/s)	RSD (％)
					1	0.5098	6.61	6.57	1.0
2	0.5092	6.55
			3	0.5068	6.66
4	0.5143	6.53

5	0.5155	6.57
					6	0.5148	6.48

4, recovery test

Adopting application of sample to reclaim tests.Get and 6 parts in repeated same lot number 051103 sample, every part of 0.25g, the accurate title, decide, add stachydrine hydrochloride reference substance 1.798mg respectively, the preparation method of shining above-mentioned need testing solution prepares solution, the accurate respectively 10 μ l sample introductions of drawing, the record chromatogram, the calculate recovery rate meansigma methods is 98.2%, and RSD% is 1.8%, illustrates that this method response rate is good.The results are shown in Table 3.

Table 3 recovery test is table as a result

Numbering	Sample weighting amount (g)	Sample size (mg)	Reference substance addition (mg)	Record total amount (mg)	The response rate (%)	Average recovery rate (%)	RSD (％)
								1	0.2304	1.5137	1.833	3.3172	0.984	98.2	1.8
2	0.2345	1.5407	1.833	3.3282	0.975
						3	0.2279	1.4973	1.833	3.3140	0.991
4	0.2369	1.5564	1.833	3.3293	0.967
						5	0.2243	1.4737	1.833	3.3289	1.012
6	0.2377	1.5617	1.833	3.3284	0.964

The initial quality standard and the quality standard of the present invention of puerperal blood clot dispersing tablet are compared, specifically see the following form:

		Primary standard	Standard of the present invention
				Method for making		Method for making does not have material alterations
Differentiate	(1)	Microscopical identification	Microscopical identification
				(2)	Do not have	Detect Herba Leonuri
	(3)	Do not have	Detect Radix Angelicae Sinensis
				(4)	Do not have	Detect Rhizoma Chuanxiong
	Check		The tablet general rule				The tablet general rule
Assay				Do not have	Stachydrine hydrochloride HPLC assay

Compared with prior art, method of quality control precision height of the present invention, favorable reproducibility, response rate height, measurement result is accurate, has improved the quality control standard of puerperal blood clot dispersing tablet, can control product quality effectively, thereby has definitely guaranteed its clinical efficacy.

The specific embodiment:

Further specify the present invention by the following examples, but not as limitation of the present invention.

Embodiments of the invention 1: the method for quality control of puerperal blood clot dispersing tablet comprises:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of.

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell.

(2) get 10 in this preparation, remove film-coat, porphyrize, add ethanol 50ml, reflux 1 hour is put cold, filter, filtrate is concentrated into about 5ml, adds active carbon-alumina column (active carbon 1g, neutral alumina 100～200 orders, 2～3g are on the internal diameter 1.5～2cm), with ethanol 50ml eluting, collect eluent, evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, 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 carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=10: 6: 1 was developing solvent, launch, take out, dry, spray is heated to clear spot with the mixed solution of improvement bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=5: 1.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color.

(3) get this preparation 5g and remove film-coat, porphyrize is put in the tool plug conical flask, the 20ml supersound extraction twice that adds diethyl ether, and each 5 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 1ml dissolving, as need testing solution.Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10 μ l of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=9: 1 was developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color.

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item.

Assay: stachydrine hydrochloride shines Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=88: 12 was mobile phase; Flow velocity: 1.0ml/min; Detector: evaporative light scattering detector; Gas flow: 2.0L/min; Drift tube temperature: 90 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000.

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly.

10 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.5g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 50ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with 0.45 μ m membrane filtration, promptly.

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly.

Every in this preparation contains Herba Leonuri with stachydrine hydrochloride C ₇H ₁₃NO ₂The HCl meter must not be less than 1.5mg.

Embodiments of the invention 2: the method for quality control of puerperal blood clot dispersing tablet can comprise:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of.

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell.

(2) get 5 in this preparation, remove film-coat, porphyrize, add ethanol 20ml, reflux 0.5 hour is put cold, filter, filtrate is concentrated into about 2ml, adds active carbon alumina column (active carbon 1g, neutral alumina 100～200 orders, 2～3g are on the internal diameter 1.5～2cm), with ethanol 20ml eluting, collect eluent, evaporate to dryness, residue add ethanol 0.5ml makes dissolving, as need testing solution.It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, 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 carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5: 10: 0.5 was developing solvent, launch, take out, dry, spray is heated to clear spot with the mixed solution of improvement bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1: 2.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color.

Assay: stachydrine hydrochloride shines Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50: 20 was mobile phase; Flow velocity: 0.2ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0L/min; Drift tube temperature: 50 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000.

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly.

5 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.2g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 20ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with 0.40 μ m membrane filtration, promptly.

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly.

Every in this preparation contains Herba Leonuri with stachydrine hydrochloride C ₇H ₁₃NO ₂The HCl meter must not be less than 1.5mg.

Embodiments of the invention 3: the method for quality control of puerperal blood clot dispersing tablet can comprise:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of.

Differentiate: get this preparation 2g, remove film-coat, porphyrize is put in the tool plug conical flask, the 10ml supersound extraction twice that adds diethyl ether, and each 2 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 0.5ml dissolving, as need testing solution.Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10 μ l of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1: 2 was developing solvent, launch, take out, dry, put under the ultra-violet lamp 200nm and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color.

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item.

Assay: stachydrine hydrochloride shines Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=150: 5 was mobile phase; Flow velocity: 2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 3.0L/min; Drift tube temperature: 120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000.

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly.

15 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.8g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 80ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with 0.30 μ m membrane filtration, promptly.

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly.

Every in this preparation contains Herba Leonuri with stachydrine hydrochloride C ₇H ₁₃NO ₂The HCl meter must not be less than 1.5mg.

Embodiments of the invention 4: the method for quality control of puerperal blood clot dispersing tablet can comprise:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of.

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell.

(2) get 15 in this preparation, remove film-coat, porphyrize, add ethanol 80ml, reflux 3 hours is put cold, filter, filtrate is concentrated into about 8ml, adds active carbon alumina column (active carbon 1g, neutral alumina 100～200 orders, 2～3g are on the internal diameter 1.5～2cm), with ethanol 80ml eluting, collect eluent, evaporate to dryness, residue add ethanol 3ml makes dissolving, as need testing solution.It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, 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 carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=15: 2: 2 was developing solvent, launch, take out, dry, spray is heated to clear spot with the mixed solution of improvement bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=10: 0.2.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color.

(3) get this preparation 10g, remove film-coat, porphyrize is put in the tool plug conical flask, the 30ml supersound extraction twice that adds diethyl ether, and each 8 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 3ml dissolving, as need testing solution.Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10 μ l of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=15: 0.2 was developing solvent, launch, take out, dry, put under the ultra-violet lamp 300nm and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color.

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item.

Claims (10)

1. the method for quality control of a puerperal blood clot dispersing tablet is characterized in that: described method of quality control mainly comprise in character, discriminating, inspection and the assay project partly or entirely; Wherein differentiate the thin layer chromatography discriminating that comprises microexamination, Herba Leonuri and Radix Angelicae Sinensis, Rhizoma Chuanxiong; Assay is that the contained stachydrine hydrochloride of Herba Leonuri in the preparation is carried out assay.

2. according to the method for quality control of the described puerperal blood clot dispersing tablet of claim 1, it is characterized in that: the discrimination method of Herba Leonuri is to be contrast with the stachydrine hydrochloride reference substance, is the thin layer chromatography of developing solvent with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2; The discrimination method of Radix Angelicae Sinensis, Rhizoma Chuanxiong is to be contrast with Radix Angelicae Sinensis, Rhizoma Chuanxiong control medicinal material, is the thin layer chromatography of developing solvent with normal hexane-ethyl acetate=1-15: 0.2-2.

3. according to the method for quality control of claim 1 or 2 described puerperal blood clot dispersing tablets, it is characterized in that: discrimination method comprises the part or all of of following project:

(1) get this preparation, put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get this preparation, remove film-coat, porphyrize adds ethanol, and reflux is put coldly, filters, and filtrate concentrates, and adds on active carbon-alumina column, use ethanol elution, the collection eluent, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make solution, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2 is developing solvent, launch, take out, dry, spray is to improve bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1-10: the mixed solution of 0.2-2 is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation, remove film-coat, porphyrize is put in the tool plug conical flask, and the supersound extraction twice that adds diethyl ether merges ether solution, filter, and the filtrate evaporate to dryness, residue adds acetic acid ethyl dissolution, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10ul of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1-15: 0.2-2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color.

4. according to the method for quality control of the described puerperal blood clot dispersing tablet of claim 3, it is characterized in that: concrete discrimination method comprises the part or all of of following project:

(1) get this preparation, put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get 5～15 in this preparation, remove film-coat, porphyrize, add ethanol 20～80ml, reflux 0.5～3 hour is put cold, filter, filtrate is concentrated into about 2～8ml, adds to contain on the active carbon alumina column of active carbon 1g, 100～200 purpose neutral aluminas, 2～3g, internal diameter 1.5～2cm, with ethanol 20～80ml eluting, collect eluent, evaporate to dryness, residue add ethanol 0.5～3ml makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2 is developing solvent, launch, take out, dry, spray is to improve bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1-10: the mixed solution of 0.2-2 is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation 2～10g, remove film-coat, porphyrize is put in the tool plug conical flask, the 10～30ml supersound extraction twice that adds diethyl ether, and each 2～8 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 0.5～3ml dissolving, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10ul of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1-15: 0.2-2 is developing solvent, launch, take out, dry, put under ultra-violet lamp 200～300nm and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color.

5. according to the method for quality control of the described puerperal blood clot dispersing tablet of claim 1, it is characterized in that: the Determination of Contents of Hydrochloric Stachydrine assay method is to be contrast with the stachydrine hydrochloride reference substance in the Herba Leonuri, is the high performance liquid chromatography of mobile phase with acetonitrile-water=50-150: 5-20.

6. according to the method for quality control of claim 1 or 5 described puerperal blood clot dispersing tablets, it is characterized in that: the Determination of Contents of Hydrochloric Stachydrine assay method is:

According to Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50-150: 5-20 is mobile phase; Flow velocity: 0.2-2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0-3.0L/min; Drift tube temperature: 50-120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

This preparation is got in the preparation of need testing solution, removes coating, porphyrize, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol that adds, claim to decide weight, supersound process under power 150W, frequency 50kHz condition is put cold, supply the weight that subtracts mistake with ethanol, filter, measure subsequent filtrate in evaporating dish, put evaporate to dryness on the water-bath, residue dissolve with methanol standardize solution shakes up, use membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri in stachydrine hydrochloride C7H13NO2HCl, must not be less than 1.5mg.

7. according to the method for quality control of the described puerperal blood clot dispersing tablet of claim 6, it is characterized in that: concrete stachydrine hydrochloride content assaying method is:

According to Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50-150: 5-20 is mobile phase; Flow velocity: 0.2-2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0-3.0L/min; Drift tube temperature: 50-120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

5～15 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.2～0.8g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 20～80ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with being less than or equal to 0.45 μ m membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri in stachydrine hydrochloride C7H13NO2HCl, must not be less than 1.5mg.

8. according to the method for quality control of the described puerperal blood clot dispersing tablet of claim 1, it is characterized in that: described method of quality control comprises:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of;

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get this preparation, remove film-coat, porphyrize adds ethanol, and reflux is put coldly, filters, and filtrate concentrates, and adds on active carbon-alumina column, use ethanol elution, the collection eluent, and evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make solution, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2 is developing solvent, launch, take out, dry, spray is to improve bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1-10: the mixed solution of 0.2-2 is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation, remove film-coat, porphyrize is put in the tool plug conical flask, and the supersound extraction twice that adds diethyl ether merges ether solution, filter, and the filtrate evaporate to dryness, residue adds acetic acid ethyl dissolution, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10ul of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1-15: 0.2-2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color;

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item;

Assay: shine Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50-150: 5-20 is mobile phase; Flow velocity: 0.2-2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0-3.0L/min; Drift tube temperature: 50-120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

This preparation is got in the preparation of need testing solution, removes coating, porphyrize, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol that adds, claim to decide weight, supersound process under power 150W, frequency 50kHz condition is put cold, supply the weight that subtracts mistake with ethanol, filter, measure subsequent filtrate in evaporating dish, put evaporate to dryness on the water-bath, residue dissolve with methanol standardize solution shakes up, use membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri in stachydrine hydrochloride C7H13NO2HCl, must not be less than 1.5mg.

9. according to the method for quality control of claim 1 or 8 described puerperal blood clot dispersing tablets, it is characterized in that: described method of quality control comprises:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of;

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get 5～15 in this preparation, remove film-coat, porphyrize, add ethanol 20～80ml, reflux 0.5～3 hour is put cold, filter, filtrate is concentrated into about 2～8ml, adds to contain on the active carbon alumina column of active carbon 1g, 100～200 purpose neutral aluminas, 2～3g, internal diameter 1.5～2cm, with ethanol 20～80ml eluting, collect eluent, evaporate to dryness, residue add ethanol 0.5～3ml makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=5-15: 2-10: 0.5-2 is developing solvent, launch, take out, dry, spray is to improve bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=1-10: the mixed solution of 0.2-2 is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation 2～10g, remove film-coat, porphyrize is put in the tool plug conical flask, the 10～30ml supersound extraction twice that adds diethyl ether, and each 2～8 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 0.5～3ml dissolving, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10ul of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=1-15: 0.2-2 is developing solvent, launch, take out, dry, put under ultra-violet lamp 200～300nm and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color;

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item;

Assay: shine Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=50-150: 5-20 is mobile phase; Flow velocity: 0.2-2.0ml/min; Detector: evaporative light scattering detector; Gas flow: 1.0-3.0L/min; Drift tube temperature: 50-120 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

5～15 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.2～0.8g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 20～80ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with being less than or equal to 0.45 μ m membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri in stachydrine hydrochloride C7H13NO2HCl, must not be less than 1.5mg.

10. according to the method for quality control of the described puerperal blood clot dispersing tablet of claim 9, it is characterized in that: described method of quality control comprises:

Character: product is a Film coated tablets, remove coating after, show yellowish-brown; Gas perfume (or spice), little suffering of distinguishing the flavor of;

Differentiate: (1) gets this preparation, and put microscopically and observe: phloem parenchyma cell spindle, wall are slightly thick, and there is atomic thin oblique cross lamination on the surface; Rich in starch grain in the parenchyma cell, calcium oxalate crystals is present in the parenchyma cell, is similar round agglomerate or class cluster crystal shape; Glandular scale head 4,6 or 8 cells, handle is unicellular, nonglandular hair 1～4 cell;

(2) get 10 in this preparation, remove film-coat, porphyrize, add ethanol 50ml, reflux 1 hour is put cold, filter, filtrate is concentrated into about 5ml, adds to contain on the active carbon alumina column of active carbon 1g, 100～200 purpose neutral aluminas, 2～3g, internal diameter 1.5～2cm, with ethanol 50ml eluting, collect eluent, evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution; It is an amount of that other gets the stachydrine hydrochloride reference substance, adds ethanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned two kinds of each 10ul of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with carboxycellulose sodium, with acetone-dehydrated alcohol-hydrochloric acid=10: 6: 1 was developing solvent, launch, take out, dry, spray is heated to clear spot with the mixed solution of improvement bismuth potassium iodide test solution-1% ferric chloride anhydrous alcohol solution=5: 1; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color;

(3) get this preparation 5g and remove film-coat, porphyrize is put in the tool plug conical flask, the 20ml supersound extraction twice that adds diethyl ether, and each 5 minutes, merge ether solution, filter, filtrate evaporate to dryness, residue add ethyl acetate 1ml dissolving, as need testing solution; Other gets Radix Angelicae Sinensis, each 0.5g of Rhizoma Chuanxiong control medicinal material, handles as stated above and makes control medicinal material solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin layer chromatography, draw above-mentioned need testing solution, each 10ul of control medicinal material solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with normal hexane-ethyl acetate=9: 1 was developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the fluorescence speckle of same color;

Check: should meet relevant every regulation under Chinese Pharmacopoeia version appendix in 2005 the I D tablet item;

Assay: stachydrine hydrochloride shines Chinese Pharmacopoeia appendix VI D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filler with amino bonded silica gel; With acetonitrile-water=88: 12 was mobile phase; Flow velocity: 1.0ml/min; Detector: evaporative light scattering detector; Gas flow: 2.0L/min; Drift tube temperature: 90 ℃; Number of theoretical plate calculates with the stachydrine hydrochloride peak should be not less than 2000;

The preparation precision of reference substance solution takes by weighing at 3 hours stachydrine hydrochloride reference substance of 105 ℃ of dryings an amount of, adds the solution that methanol is made 0.35mg/ml, promptly;

10 in this preparation is got in the preparation of need testing solution, removes coating, porphyrize, get about 0.5g, the accurate title, decide, and puts in the tool plug conical flask, the accurate ethanol 50ml that adds claims to decide weight, supersound process 30min under power 150W, frequency 50kHz condition, put coldly, supply the weight that subtracts mistake, filter with ethanol, precision is measured subsequent filtrate 25ml in evaporating dish, puts evaporate to dryness on the water-bath, and residue is settled to 5ml with dissolve with methanol, shake up, with being less than or equal to 0.45 μ m membrane filtration, promptly;

Accurate reference substance solution 5 μ l, the 10 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, and calculate with external standard two-point method logarithmic equation, promptly;

Every in this preparation contains Herba Leonuri in stachydrine hydrochloride C7H13NO2HCl, must not be less than 1.5mg.