CN1846730A - Chaihuang soft capsule preparing process and its quality control technology - Google Patents

Abstract

The present invention discloses the preparation process and quality control method for Chaihuang soft capsule. The Chaihuang soft capsule is prepared through extracting effective components of bupleurum root and skullcap root, adding soybean oil, beeswax and Span-80, and encapsulating. The quality control method includes qualitative identification of bupleurum saponin A and baicalin and quantitative measurement of baicalin content to ensure the curative effect of the medicine. The Chaihuang soft capsule has high bioavailability, accurate content, fast disintegration and other advantages.

Description

The preparation method of Chaihuang soft capsule and Quality Control Technology

Technical field

The present invention relates to a kind of novel form of Chinese medicine, specifically is the new capsule formulation and the Quality Control Technology of the yellow electuary of existing form of Chinese drug bavin.

Background technology

" yellow electuary (the WS of bavin ₃-B-2009-95) " be that office of State Food and Drug Administration issues the tenth in standard Chinese traditional patent formulation preparation (the tenth in former Ministry of Public Health ministry standard Chinese traditional patent formulation preparation) and records kind.This dosage form granule is taken inconvenience, and contains sugar in the granule, and diabetics can not use, and has influenced the performance of the purposes and the effectiveness of this medicine.

Summary of the invention

The preparation method and the Quality Control Technology that the purpose of this invention is to provide a kind of Chaihuang soft capsule are that the yellow electuary kind of bavin is carried out secondary development, and dosage changing form is a soft capsule, it has the bioavailability height, good airproof performance, and content is accurate, advantages such as disintegrate is rapid, and is aesthetic in appearance.

Technical scheme of the present invention is as follows:

The preparation method of Chaihuang soft capsule, raw material is made by Radix Bupleuri, Radix Scutellariae, it is characterized in that:

(1), behind the Radix Bupleuri extracting in water, its extracting solution reuse ethanol extraction obtains extractum through concentrating, drying under reduced pressure, it is standby to be ground into fine powder;

(2), get the Radix Scutellariae extracting in water after, filtrate adds sour adjust pH to 1～2, filters, taking precipitate is suspended in an amount of hot water, adds alkali again and regulates pH value to 7, adds alcoholic solution, fully stir, filter, filtrate adds acid for adjusting pH value to 1～2, filter, the collecting precipitation thing washes with water earlier, the reuse washing with alcohol, cold drying promptly gets Radix Scutellariae extract;

(3), each composition weight proportioning:

Radix Bupleuri 1250

Radix Scutellariae extract (baicalin (C ₂₁H ₁₈O ₁₁) be no less than 85%) 80～100

Soybean oil 280～325

Cera Flava 10～20

Arlacel-80 3～8

Get the soybean oil of above-mentioned weight, add Cera Flava, Arlacel-80, heating is dissolved it fully, is cooled to room temperature, adds Radix Scutellariae extract, Radix Bupleuri extractum powder, stirs, and mixing is prepared into capsule.

Above-mentioned preparation method, wherein the concrete grammar in (1), (2) step is:

(1), gets Radix Bupleuri and add 4～6 times of water gagings extractions 1～2 time, each 1～2 hour, extracting solution, filter, adding ethanol under stir the concentrated back of filtrate is 50～60% to containing pure amount, leaves standstill, filter, filtrate recycling ethanol and to be condensed into relative density be 1.30～1.33 clear paste, drying under reduced pressure, it is standby to be ground into fine powder;

(2), get Radix Scutellariae, decoct with water 1～2 time, each 0.5～1 hour, collecting decoction, filter, filtrate adds hydrochloric acid adjust pH to 1～2,80 ℃ of insulations 1 hour, filters, taking precipitate is suspended in an amount of hot water, regulates pH value to 7 with sodium hydroxide solution, adds equivalent ethanol, fully stirs, filter, filtrate adds hydrochloric acid and regulates pH value to 1～2, is heated to 80 ℃, the insulation back filters, and the collecting precipitation thing washes with water earlier, the reuse washing with alcohol, cold drying promptly gets Radix Scutellariae extract.

The Quality Control Technology of Chaihuang soft capsule is characterized in that

(1), qualitative identification

A, to get this product Chinese medicine content an amount of, and it is an amount of to add the saturated ammonia solution of n-butyl alcohol, puts heating for dissolving in the water-bath, moves in the separatory funnel, adds Petroleum ether extraction, leaves standstill, and divides and gets petroleum ether liquid, discards; The alkali liquor layer adds water-saturated n-butanol and extracts, and leaves standstill, and divides and gets n-butyl alcohol liquid, merges, and adds the saturated water washing of n-butyl alcohol, leaves standstill, and discards water lotion, and n-butyl alcohol liquid is put evaporate to dryness in the water-bath, and residue adds an amount of heating of water makes dissolving, is chilled to room temperature, passes through D ₁₀₁Macroporous adsorptive resins (φ 1.8cm * 40cm, 50ml), add an amount of eluting of water, discard water lotion, continue with an amount of eluting of low-concentration ethanol, discard the low-concentration ethanol eluent, add an amount of eluting of high concentration ethanol again, collect the high concentration ethanol eluent, put evaporate to dryness in the water-bath, residue adds methanol makes dissolving in right amount, as need testing solution; Other gets the saikoside a reference substance, adds methanol and makes the saikoside a reference substance solution; Drawing need testing solution, each 5 μ l of reference substance solution, put respectively on same silica gel g thin-layer plate, is that ethyl acetate-alcohol-water of 8: 2: 1 is developing solvent with volume ratio, launch, take out, dry, spray is with the ethanol solution of sulfuric acid of paradime thylaminobenzaldehyde, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

B, get the baicalin reference substance, add methanol and make the baicalin reference substance solution; Draw subsequent filtrate, each 5 μ l of baicalin reference substance solution under the Radix Scutellariae extract quantitative assay, put respectively on same silica gel g thin-layer plate, be 5: 3: 1 with volume ratio: ethyl acetate-butanone of 1-formic acid-water is developing solvent, launch, take out, dry, spray is with the ferric chloride alcoholic solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

(2), quantitative assay

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-water-phosphoric acid (50: 50: 0.2) is a mobile phase; Detect wavelength 280nm, number of theoretical plate calculates by the baicalin peak should be not less than 2500; The preparation of reference substance solution: precision takes by weighing at 4 hours baicalin reference substance of 60 ℃ of drying under reduced pressure an amount of, adds methanol and makes the solution that every 1ml contains 80 μ g, promptly; The preparation of need testing solution: get the content under this product content uniformity, mixing is got 0.2g, the accurate title, decide, and puts in the 100ml tool plug conical flask, adds petroleum ether (60～90 ℃) 10ml supersound extraction 10 minutes, filter, discard petroleum ether extract, filtering residue, filter paper are flung to solvent, move in the lump in the same tool plug conical flask, the accurate methanol 50ml that adds, claim to decide weight, supersound extraction 30 minutes is put cold, claim to decide weight again, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 1ml that draws puts in the 10ml measuring bottle, add methanol to scale, shake up, promptly; Algoscopy: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly get the every 0.5g of this product Chinese medicine and contain baicalin (C ₂₁H ₁₈O ₁₁) must not be less than 90mg.

Every of this product contains baicalin (C ₂₁H ₁₈O ₁₁) must not be less than 90mg.

Function with cure mainly: heat clearing and inflammation relieving.Be used for respiratory tract infection, cat fever.

Usage and consumption: oral, one time 4,2 times on the one.

Specification: every dress 0.5g

Storage: sealing, put shady and cool dry place and preserve.

The specific embodiment

Prescription

Radix Bupleuri 1250g

Radix Scutellariae extract (in baicalin) 90g

Soybean oil 305g

Cera Flava 15g

Arlacel-80 5g

More than prepare 1000 capsules

Method for making

Get Radix Bupleuri and add 6 times of water gagings extraction secondaries, each 2 hours, merge extractive liquid, filters, and filtrate is concentrated into 250ml, stirring down, adding ethanol is 60% to containing the alcohol amount, left standstill 24 hours, and filtered, filtrate recycling ethanol and to be condensed into relative density be 1.30～1.33 clear paste, 80 ℃ of drying under reduced pressure, it is standby to be ground into fine powder; Get Radix Scutellariae, decoct with water secondary, each 1 hour, collecting decoction, filter, filtrate adds hydrochloric acid adjust pH to 1～2,80 ℃ of insulations 1 hour, filters, taking precipitate is suspended in an amount of hot water, regulates pH value to 7 with 40% sodium hydroxide solution, adds equivalent ethanol, fully stirs, filter, filtrate adds hydrochloric acid and regulates pH value to 1～2, is heated to 80 ℃, is incubated 30 minutes, filter, the collecting precipitation thing washes with water earlier, reuse washing with alcohol 1 time, cold drying gets promptly that (this product contains baicalin (C ₂₁H ₁₈O ₁₁) must not be less than 85%).Get soybean oil 305g, add Cera Flava 15g, Arlacel-80 5g, heating is dissolved it fully, is cooled to room temperature, adds Radix Scutellariae extract, Radix Bupleuri extractum powder, stirs, and mixing is pressed into 1000, promptly.

Qualitative identification

This product is a soft capsule, and content is contain a small amount of suspendible solid extract faint yellow to brown xanchromatic oily liquids; Feeble QI perfume (or spice), bitter in the mouth.

Differentiate

(1), get this product content 2g, add the saturated ammonia solution 30ml of n-butyl alcohol, put in the water-bath heating and make dissolving, move in the separatory funnel, add petroleum ether (30～60 ℃) and extract 2 times, each 15ml leaves standstill, and divides and gets petroleum ether liquid, discards.The alkali liquor layer adds water-saturated n-butanol and extracts 3 times, and each 15ml leaves standstill, and divides and gets n-butyl alcohol liquid, merges, add the saturated water washing of n-butyl alcohol 2 times, each 15ml leaves standstill, and discards water lotion, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, and residue adds water 5ml heating makes dissolving, is chilled to room temperature, passes through D ₁₀₁Macroporous adsorptive resins (φ 1.8cm * 40cm, 50ml), add water 50ml eluting, discard water lotion, continue with 40% pure 50ml eluting, discard 40% ethanol elution, add 70% ethanol 100ml eluting again, collect 70% ethanol elution, put evaporate to dryness in the water-bath, residue adds methanol 2ml makes dissolving, as need testing solution.Other gets the saikoside a reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate-alcohol-water (8: 2: 1) is developing solvent, launch, take out, dry, spray is with 40% ethanol solution of sulfuric acid of 2% paradime thylaminobenzaldehyde, and 60 ℃ to be heated to the speckle colour developing clear.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

(2), get the baicalin reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw subsequent filtrate, each 5 μ l of baicalin reference substance solution under [assay] item, put respectively on same silica gel g thin-layer plate, with ethyl acetate-butanone-formic acid-water (5: 3: 1: 1) be developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

Check

Should meet every regulation relevant under the capsule item (an appendix I of Chinese Pharmacopoeia version in 2000 L).

Assay

Measure according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 D).

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Methanol-water-phosphoric acid (50: 50: 0.2) is a mobile phase; Detect wavelength 280nm.Number of theoretical plate calculates by the baicalin peak should be not less than 2500.

The preparation precision of reference substance solution takes by weighing at 4 hours baicalin reference substance of 60 ℃ of drying under reduced pressure an amount of, adds methanol and makes the solution that every 1ml contains 80 μ g, promptly.

The content under this product content uniformity is got in the preparation of need testing solution, and mixing is got 0.2g, the accurate title, decide, and puts in the 100ml tool plug conical flask, adds petroleum ether (60～90 ℃) 10ml supersound extraction 10 minutes, filter, discard petroleum ether extract, filtering residue, filter paper are flung to solvent, move in the lump in the same tool plug conical flask, the accurate methanol 50ml that adds, claim to decide weight, supersound extraction 30 minutes is put cold, claim to decide weight again, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 1ml that draws puts in the 10ml measuring bottle, add methanol to scale, shake up, promptly.

Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Claims (3)

1, the preparation method of Chaihuang soft capsule, raw material is made by Radix Bupleuri, Radix Scutellariae, it is characterized in that:

(1), behind the Radix Bupleuri extracting in water, its extracting solution reuse ethanol extraction obtains extractum through concentrating, drying under reduced pressure, it is standby to be ground into fine powder;

(2), get the Radix Scutellariae extracting in water after, filtrate adds sour adjust pH to 1～2, filters, taking precipitate is suspended in an amount of hot water, adds alkali again and regulates pH value to 7, adds alcoholic solution, fully stir, filter, filtrate adds acid for adjusting pH value to 1～2, filter, the collecting precipitation thing washes with water earlier, the reuse washing with alcohol, cold drying promptly gets Radix Scutellariae extract;

(3), each composition weight proportioning:

Radix Bupleuri 1250

Radix Scutellariae extract (baicalin (C ₂₁H ₁₈O ₁₁) be no less than 85%) 80～100

Soybean oil 280～325

Cera Flava 10～20

Arlacel-80 3～8

Get the soybean oil of above-mentioned weight, add Cera Flava, Arlacel-80, heating is dissolved it fully, is cooled to room temperature, adds Radix Scutellariae extract, Radix Bupleuri extractum powder, stirs, and mixing is prepared into capsule.

2, preparation method according to claim 1 is characterized in that the concrete grammar in (1), (2) step is:

(1), gets Radix Bupleuri and add 4～6 times of water gagings extractions 1～2 time, each 1～2 hour, extracting solution, filter, adding ethanol under stir the concentrated back of filtrate is 50～60% to containing pure amount, leaves standstill, filter, filtrate recycling ethanol and to be condensed into relative density be 1.30～1.33 clear paste, drying under reduced pressure, it is standby to be ground into fine powder;

(2), get Radix Scutellariae, decoct with water 1～2 time, each 0.5～1 hour, collecting decoction, filter, filtrate adds hydrochloric acid adjust pH to 1～2,80 ℃ of insulations 1 hour, filters, taking precipitate is suspended in an amount of hot water, regulates pH value to 7 with sodium hydroxide solution, adds equivalent ethanol, fully stirs, filter, filtrate adds hydrochloric acid and regulates pH value to 1～2, is heated to 80 ℃, the insulation back filters, and the collecting precipitation thing washes with water earlier, the reuse washing with alcohol, cold drying promptly gets Radix Scutellariae extract.

3, the Quality Control Technology of Chaihuang soft capsule is characterized in that

(1), qualitative identification

A, to get this product Chinese medicine content an amount of, and it is an amount of to add the saturated ammonia solution of n-butyl alcohol, puts heating for dissolving in the water-bath, moves in the separatory funnel, adds Petroleum ether extraction, leaves standstill, and divides and gets petroleum ether liquid, discards; The alkali liquor layer adds water-saturated n-butanol and extracts, and leaves standstill, and divides and gets n-butyl alcohol liquid, merges, and adds the saturated water washing of n-butyl alcohol, leaves standstill, and discards water lotion, and n-butyl alcohol liquid is put evaporate to dryness in the water-bath, and residue adds an amount of heating of water makes dissolving, is chilled to room temperature, passes through D ₁₀₁Macroporous adsorptive resins (φ 1.8cm * 40cm, 50ml), add an amount of eluting of water, discard water lotion, continue with an amount of eluting of low-concentration ethanol, discard the low-concentration ethanol eluent, add an amount of eluting of high concentration ethanol again, collect the high concentration ethanol eluent, put evaporate to dryness in the water-bath, residue adds methanol makes dissolving in right amount, as need testing solution; Other gets the saikoside a reference substance, adds methanol and makes the saikoside a reference substance solution; Drawing need testing solution, each 5 μ l of reference substance solution, put respectively on same silica gel g thin-layer plate, is that ethyl acetate-alcohol-water of 8: 2: 1 is developing solvent with volume ratio, launch, take out, dry, spray is with the ethanol solution of sulfuric acid of paradime thylaminobenzaldehyde, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

B, get the baicalin reference substance, add methanol and make the baicalin reference substance solution; Draw subsequent filtrate, each 5 μ l of baicalin reference substance solution under the Radix Scutellariae extract quantitative assay, put respectively on same silica gel g thin-layer plate, be 5: 3: 1 with volume ratio: ethyl acetate-butanone of 1-formic acid-water is developing solvent, launch, take out, dry, spray is with the ferric chloride alcoholic solution.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

(2), quantitative assay

Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Methanol-water-phosphoric acid (50: 50: 0.2) is a mobile phase; Detect wavelength 280nm, number of theoretical plate calculates by the baicalin peak should be not less than 2500; The preparation of reference substance solution: precision takes by weighing at 4 hours baicalin reference substance of 60 ℃ of drying under reduced pressure an amount of, adds methanol and makes the solution that every 1ml contains 80 μ g, promptly; The preparation of need testing solution: get the content under this product content uniformity, mixing is got 0.2g, the accurate title, decide, and puts in the 100ml tool plug conical flask, adds petroleum ether (60～90 ℃) 10ml supersound extraction 10 minutes, filter, discard petroleum ether extract, filtering residue, filter paper are flung to solvent, move in the lump in the same tool plug conical flask, the accurate methanol 50ml that adds, claim to decide weight, supersound extraction 30 minutes is put cold, claim to decide weight again, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 1ml that draws puts in the 10ml measuring bottle, add methanol to scale, shake up, promptly; Algoscopy: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly get the every 0.5g of this product Chinese medicine and contain baicalin (C ₂₁H ₁₈O ₁₁) must not be less than 90mg.