Summary of the invention
The objective of the invention is for top described defective, the preparation method of the shenkangning capsules of the higher and energy-saving and environmental protection of a kind of active constituent content is provided.
The objective of the invention is to be achieved by the following technical programs.
A kind of preparation method of shenkangning capsules, comprise the following raw materials according medical material: the Radix Astragali 380~340g, Herba Leonuri 470~430g, Herba Cynomorii 320~280g, Rhizoma Alismatis 200~160g, RADIX ACONITI LATERALIS PREPARATA 200~160g, Radix Salviae Miltiorrhizae 110~90g, Poria 85~65g, Rhizoma Dioscoreae 60~40g, it is characterized in that: in turn include the following steps: 1. with the Radix Astragali, Herba Leonuri, Herba Cynomorii, Rhizoma Alismatis, RADIX ACONITI LATERALIS PREPARATA, Radix Salviae Miltiorrhizae, Poria, Rhizoma Dioscoreae eight flavor pulverizing medicinal materials, by 60~80 mesh sieve holes, extract take ethanol as the solvent supersonic ripple, get ethanol extraction extractum; 2. the medicinal residues behind the ethanol extraction take water as the solvent ultrasonic extraction, get water extract extractum again; 3. ethanol extraction extractum is mixed with water extract extractum and be concentrated into thick paste, vacuum drying gets compound Chinese medicine extract; 4. extract adds the starch mixing, granulate, and drying, granulate incapsulates, corning, and get final product.
Described step is 1. middle to be that the extraction of solvent supersonic ripple refers to eight flavor medical material fine powders with ethanol, in being 70% ethanol, concentration soaked 1.5~2 hours, then extract 2 times at 35~40kHz with ultrasonic extractor, each 30~50min, filter afterwards to get medicinal residues and extracting solution, extracting solution is through Recycled ethanol, at vacuum 0.85~0.95Mpa, 60~70 ℃ of relative densities when being evaporated to 50 ℃ are 1.20~1.30 extractum, get ethanol extraction extractum.
The medicinal residues that described step refers to ethanol extraction is crossed with ultrasonic extraction take water as solvent in 2. are take water as solvent, extract 2 times at 35~40kHz with ultrasonic extractor at 70~80 ℃, each 50~70min, filter afterwards, extracting solution is at vacuum 0.85~0.95Mpa, 60~70 ℃ of relative densities when being evaporated to 50 ℃ are 1.20~1.30 extractum, get water extract extractum.
Described step is 3. at vacuum 0.85~0.95Mpa, 60~70 ℃ ethanol extraction extractum and water extract extractum mixture dried to water content≤5%, and the compound Chinese medicine extract extraction ratio is 15.3~18.0%.
Described step 1. in every 1g Radix Astragali, Herba Leonuri, Herba Cynomorii, Rhizoma Alismatis, RADIX ACONITI LATERALIS PREPARATA, Radix Salviae Miltiorrhizae, Poria and Rhizoma Dioscoreae medical material powder add 8~10ml ethanol.
Described step 2. in every 1g Radix Astragali, Herba Leonuri, Herba Cynomorii, Rhizoma Alismatis, RADIX ACONITI LATERALIS PREPARATA, Radix Salviae Miltiorrhizae, Poria and Rhizoma Dioscoreae medical material powder add 10~12ml water.
Described step 4. in every capsules contain compound Chinese medicine extract 0.280~0.320g.
The invention has the beneficial effects as follows: the present invention adopts supersonic extracting method, can make the rapid stripping of effective ingredient in the crude drug cell, and remove the destruction of medical material effective ingredient under the violent condition such as heating and decoction etc. from, reach the advantages such as effective component extraction rate height, extraction time weak point, energy-conserving and environment-protective.All medical materials are all through solvent extraction in preparation, have avoided crude drug to join in the preparation in the mode of fine powder, and it is thick, large, black and absorb slowly situation to have improved Chinese medicine compound preparation.And owing to adopt two kinds of solvent systems to extract, improved the content of preparation active ingredients from traditional Chinese medicinal, reduced the dose of medicine, made things convenient for the patient.
The specific embodiment
Embodiment one.
Radix Astragali 380g, Herba Leonuri 470g, Herba Cynomorii 320g, Rhizoma Alismatis 200g, RADIX ACONITI LATERALIS PREPARATA 200g, Radix Salviae Miltiorrhizae 110g, Poria 85g, Rhizoma Dioscoreae 60g.Eight flavor pulverizing medicinal materials are crossed 60 mesh sieve holes, adding concentration is 70% ethanol 14600ml, soak 120min, then extract 2 times under 40kHz with ultrasonic extractor, each 50min filters to get filtering residue and extracting solution, with the extracting solution Recycled ethanol, at vacuum 0.95Mpa, 60 ℃ are evaporated to relative density is 1.25(50 ℃) extractum, get ethanol extraction extractum.
The medicinal residues that ethanol extraction is crossed add water 18250ml, extract 2 times each 70min at 40kHz at 80 ℃ of lower ultrasonic extractors of using, filter afterwards, extracting solution is at vacuum 0.95Mpa, and 60 ℃ are evaporated to relative density is 1.25(50 ℃) extractum, get water extract extractum.
At vacuum 0.95Mpa, 60 ℃ ethanol extraction extractum and water extract extractum mixture dried to water content≤5.0%, get compound Chinese medicine extract 292.4g.
Compound Chinese medicine extract is added 57.6g starch mixing, granulate, capsule is loaded in oven dry, and the 0.35g/ grain is made 1000, and be get final product.
Detect finished product according to former preparation process quality standard.
Differentiate:(1) gets this product content 13g, add chloroform 50ml, reflux 30 minutes filters, discard filtrate, medicinal residues add methanol 50ml, and reflux 30 minutes filters, the filtrate evaporate to dryness, residue adds water 15ml makes dissolving, adds the water-saturated n-butanol jolting and extracts 3 times (20ml, 20ml, 10ml), merges n-butyl alcohol liquid, with 1% sodium hydroxide solution washing 2 times, each 20ml discards alkali liquor, again with n-butyl alcohol saturated be washed to neutrality, discard water liquid, n-butyl alcohol liquid evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets the astragaloside 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 2005 B), draw need testing solution 3ul, reference substance solution 2ul, put respectively on same silica gel g thin-layer plate take sodium carboxymethyl cellulose as binding agent, lower floor's solution of placing below 10 ℃ take chloroform-methanol-water (13: 7: 2) launches as developing solvent, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 100 ℃.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of aobvious same color.
(2) get this product content 10g, add methanol 100ml, reflux 1 hour filters, filtrate evaporate to dryness, residue add water 40ml to be made and leaches, with chloroform extraction 3 times, and each 50ml, merge chloroform liquid, evaporate to dryness, residue add methanol 0.5ml makes dissolving, as need testing solution.Other gets Rhizoma Dioscoreae control medicinal material 3g, adds methanol 50ml, and reflux 1 hour filters, and filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, in contrast medical material solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw need testing solution 5ul, control medicinal material solution 4ul, put respectively on same silica gel g thin-layer plate take sodium carboxymethyl cellulose as binding agent, take toluene-ethyl acetate-formic acid (6: 4: 0.3) as developing solvent, launch, take out, dry, spray is with 5% vanillin sulfuric acid solution, and 100 ℃ to be heated to speckle colour developing clear.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, the speckle of aobvious same color.
(3) get this product content 10g, add warm the making of water 40ml and leach, add hydrochloric acid and regulate pH value to 1~2, supersound process 10 minutes, centrifugal, get supernatant, be added on the strong acid cation exchange resin column [001 * 7 type (732) Na-type, internal diameter 1.5cm, column length 13cm], closely colourless to be washed to effluent, discard water liquid, again with 2mol/L ammonia solution 100ml eluting, collect eluent, water bath method, residue add methanol 20ml makes dissolving, centrifugal, get supernatant, add active carbon 0.5g, water-bath was boiled 10 minutes, let cool, filter, filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets the stachydrine hydrochloride reference substance, adds methanol and makes the solution that every 1ml contains 2mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw need testing solution 3ul, reference substance solution 2ul, put respectively on same silica gel g thin-layer plate take sodium carboxymethyl cellulose as binding agent, take n-butyl alcohol-hydrochloric acid-water (8: 2: 1) as developing solvent, launch, take out, hot blast drying, spray is with improvement bismuth potassium iodide test solution (face and use new system).In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of aobvious same color.
Check.
Aconitine limit checks:Get this product content 40g, put in the tool plug conical flask, the 150ml that adds diethyl ether, jolting 10 minutes adds ammonia solution 10ml, and jolting 30 minutes was placed 1~2 hour, divided and got the ether layer, and evaporate to dryness, residue add dehydrated alcohol 2ml makes dissolving, as need testing solution.Other gets the aconitine reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 2mg, in contrast product solution.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 B), draw need testing solution 6ul, reference substance solution 5ul, put respectively on same silica gel g thin-layer plate take sodium carboxymethyl cellulose as binding agent, take normal hexane-ethyl acetate (1: 1) as developing solvent, put in the expansion cylinder of ammonia saturated with vapor, launch below 25 ℃, take out, dry, spray with potassium iodide iodine test solution and bismuth potassium iodide test solution etc. the appearance mixed liquor.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on speckle does not appear.
Should meet every regulation relevant under the capsule item (an appendix I of Chinese Pharmacopoeia version in 2005 L).
Assay:According to high effective liquid chromatography for measuring (an appendix VI of Chinese Pharmacopoeia version in 2005 D).
Chromatographic condition and system suitability: take octadecylsilane chemically bonded silica as filler; Take methanol-1% glacial acetic acid solution (12:88) as mobile phase, the detection wavelength is 280nm.Number of theoretical plate calculates by the danshensu peak should be not less than 1200.
The preparation of reference substance solution: precision takes by weighing the danshensu sodium reference substance, adds methanol and makes the solution (be equivalent to every 1ml and contain danshensu 72 μ g) that every 1ml contains 80 μ g, and get final product.
The preparation of need testing solution: get the content of this product, porphyrize is got about 0.5g, and is accurately weighed, puts in the 25ml measuring bottle, add the about 20ml of methanol, supersound process (power 80W, frequency 40KHz) 45 minutes lets cool, and adds methanol and is diluted to scale, shake up, filter, get subsequent filtrate, and get final product.Precision is drawn reference substance solution and each 10 μ l of need testing solution respectively, and the injection liquid chromatography is measured, and be get final product.
Every contains Radix Salviae Miltiorrhizae with danshensu (C
9H
10O
5) meter, be 1.07mg.
Embodiment two.
Get Radix Astragali 360g, Herba Leonuri 450g, Herba Cynomorii 300g, Rhizoma Alismatis 180g, RADIX ACONITI LATERALIS PREPARATA 180g, Radix Salviae Miltiorrhizae 100g, Poria 75g, Rhizoma Dioscoreae 50g.Eight flavor pulverizing medicinal materials are crossed 70 mesh sieve holes, adding concentration is 70% ethanol 15255ml, soak 90min, then extract 2 times under 35kHz with ultrasonic extractor, each 40min filters to get filtering residue and extracting solution, with the extracting solution Recycled ethanol, at vacuum 0.85Mpa, 70 ℃ are evaporated to relative density is 1.20(50 ℃) extractum, get ethanol extraction extractum.
The medicinal residues that ethanol extraction is crossed add water 18645ml, extract 2 times each 60min at 35kHz at 70 ℃ of lower ultrasonic extractors of using, filter afterwards, extracting solution is at vacuum 0.85Mpa, and 70 ℃ are evaporated to relative density is 1.20(50 ℃) extractum, get water extract extractum.
At vacuum 0.85Mpa, 70 ℃ ethanol extraction extractum and water extract extractum mixture dried to water content≤5.0%, get compound Chinese medicine extract 288.2g.
Compound Chinese medicine extract is added 61.8g starch mixing, granulate, capsule is loaded in oven dry, and the 0.35g/ grain is made 1000, and be get final product.
Detect(detection method is identical with embodiment one).
(1) astragaloside detects:In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of aobvious same color.
(2) Rhizoma Dioscoreae control medicinal material check:In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of aobvious same color.
(3) stachydrine hydrochloride check:In the test sample chromatograph, with reference substance chromatograph relevant position on, the speckle of aobvious same color.
Check.
Aconitine limit checks:In the test sample chromatograph, with the corresponding position of reference substance chromatograph on speckle does not appear.
Assay: every contains Radix Salviae Miltiorrhizae with danshensu (C
9H
10O
5) meter, be 0.97mg.
Embodiment three.
Get Radix Astragali 340g, Herba Leonuri 430g, Herba Cynomorii 280g, Rhizoma Alismatis 160g, RADIX ACONITI LATERALIS PREPARATA 160g, Radix Salviae Miltiorrhizae 90g, Poria 65g, Rhizoma Dioscoreae 40g.Eight flavor pulverizing medicinal materials are crossed 80 mesh sieve holes, adding concentration is 70% ethanol 15650ml, soak 90min, then extract 2 times under 35kHz with ultrasonic extractor, each 30min filters to get filtering residue and extracting solution, with the extracting solution Recycled ethanol, at vacuum 0.9Mpa, 50 ℃ are evaporated to relative density is 1.30(50 ℃) extractum, get ethanol extraction extractum.
The medicinal residues that ethanol extraction is crossed add water 18780ml, extract 2 times each 50min at 35kHz at 75 ℃ of lower ultrasonic extractors of using, filter afterwards, extracting solution is at vacuum 0.9Mpa, and 50 ℃ are evaporated to relative density is 1.30(50 ℃) extractum, get water extract extractum.
At vacuum 0.9Mpa, 60 ℃ ethanol extraction extractum and water extract extractum mixture dried to water content≤5.0%, get compound Chinese medicine extract 281.7g.
Compound Chinese medicine extract is added 68.3g starch mixing, granulate, capsule is loaded in oven dry, and the 0.35g/ grain is made 1000, and be get final product.
Detect(detection method is identical with embodiment one).
(1) astragaloside detects:In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of aobvious same color.
(2) Rhizoma Dioscoreae control medicinal material check:In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of aobvious same color.
(3) stachydrine hydrochloride check:In the test sample chromatograph, with reference substance chromatograph relevant position on, the speckle of aobvious same color.
Check.
Aconitine limit checks:In the test sample chromatograph, with the corresponding position of reference substance chromatograph on speckle does not appear.
Assay: every contains Radix Salviae Miltiorrhizae with danshensu (C
9H
10O
5) meter, be 0.94 mg.
The former handicraft product quality of this technique comparison sheet.
Learn that from upper table result the product of the present invention's preparation is compared every test item with former handicraft product and all reached requirement, and the index components content of Danshensu is higher than former technique.