CN100585401C

CN100585401C - Detection method for orally administered formulation for reducing fat and expelling toxins

Info

Publication number: CN100585401C
Application number: CN200610201323A
Authority: CN
Inventors: 叶湘武; 江帆; 徐裕彬; 韦莹
Original assignee: Guizhou Yibai Pharmaceutical Co Ltd
Current assignee: Guizhou Yibai Pharmaceutical Co Ltd
Priority date: 2006-12-19
Filing date: 2006-12-19
Publication date: 2010-01-27
Anticipated expiration: 2026-12-19
Also published as: CN1970070A

Abstract

The invention relates to an oral pharmaceutical preparation for antihyperglycemic and toxin expelling, its preparing process and quality control method, wherein the preparation is made mainly from rhubarb horsetails, cassia seed, haw, oriental wormwood, cape jasmine, oriental water plantain rhizome, fleece-flower root, zedoary, thorowax root and right amount of adjuvant. The preparation can be effectively used for the treatment of hyperlipoidemia.

Description

The detection method of defatting and poison expelling oral formulations

Technical field:

The present invention relates to a kind of defatting and poison expelling oral formulations and preparation method thereof and method of quality control, belong to technical field of traditional Chinese medicine pharmacy.

Background technology:

Hyperlipidemia belongs to that traditional Chinese medical science phlegm is turbid more, the phlegm stasis of blood, qi depression to blood stasis category, be meant a kind of state that dyslipidemias increases in the blood, mostly occur the elderly, obesity crowd and greasy food of long-term happiness edible oil or heavy drinker have the medical history person of hyperlipidemia family easily to send out the crowd especially.Hyperlipidemia can cause obesity, fatty liver, atherosclerotic and cardiovascular and cerebrovascular disease.Defatting and poison expelling capsule just was disclosed in as far back as in 2002 during " national standard for traditional Chinese medicines compilation " internal medicine feels concerned about, and is clearing heat and detoxicating, the stagnation resolvation lipopenicillinase.Be used for the treatment of turbid stasis of blood mutual resistance, hyperlipemia is clinically received good effect.Form by rheum officinale, oriental wormwood, rhizoma alismatis, the fleece-flower root, cassia seed, hawthorn etc. in the side.Rheum officinale is a monarch drug in a prescription in the side, and nature and flavor hardship, cold is returned spleen, stomach, large intestine, liver, pericardium channel, the function logical intestines that purge heat, removing pattogenic heat from the blood and toxic material from the body is stimulated the menstrual flow by the stasis of blood, decorporation just, protect the liver, hemostasis, reducing blood lipid, anti-infective, improve immunologic function.Oriental wormwood property hardship, suffering are slightly cold, and return spleen, stomach, liver, gallbladder channel, clearing away damp-heat, removing jaundice subcutaneous ulcer.Rhizoma alismatis property is sweet, cold, returns kidney, urinary bladder channel, diuresis, clearing away damp-heat.Fleece-flower root hardship, sweet, puckery, temperature is returned liver, the heart, kidney channel, detoxifcation, the carbuncle that disappears relaxes bowel.Cassia seed is sweet, bitter, salty, is slightly cold, and returns liver, large intestine channel, and removing heat to brighten vision relaxes bowel.In calendar year 2001 the patented claim of defatting and poison expelling capsule is just arranged, but original preparation formulation is single, can not satisfy market demand; And defatting and poison expelling preparation function cures mainly and is stagnation resolvation lipopenicillinase, the defaecation Cuo that disappears, and is used for the simple obesity due to the stagnation of turbidity and stasis, hyperlipidemia, and acne, thereby a large amount of sugar should not arranged in the auxiliary material.In addition, in the existing quality standard, the discrimination method feminine gender of rheum officinale, the fleece-flower root has interference, and the assay of Gardenoside becomes swarming to separate also incomplete with other, the quality of defatting and poison expelling preparation be can not effectively control, thereby production and the quality and the clinical efficacy thereof of product influenced.

Summary of the invention:

The objective of the invention is to: a kind of defatting and poison expelling oral formulations and preparation method thereof and method of quality control are provided, and this oral formulations comprises tablet and granule.The present invention is directed to the deficiencies in the prior art, auxiliary material, preparation technology and the method for quality control of defatting and poison expelling oral formulations carried out research and preferred, satisfied requirement of different patients, and can effectively control the quality of said preparation, thereby guaranteed its clinical efficacy.

The present invention constitutes like this: calculate according to composition by weight: it is made by rheum officinale 30-300 part, cassia seed 100-500 part, hawthorn 100-500 part, oriental wormwood 100-500 part, cape jasmine 50-200 part, rhizoma alismatis 100-400 part, fleece-flower root 100-400 part, curcuma zedoary 100-400 part, radix bupleuri 50-300 part and appropriate amount of auxiliary materials.

Specifically, it is made by rheum officinale 150g, cassia seed 300g, hawthorn 300g, oriental wormwood 300g, cape jasmine 100g, rhizoma alismatis 250g, fleece-flower root 250g, curcuma zedoary 250g, radix bupleuri 150g and appropriate amount of auxiliary materials.

Described oral formulations is tablet or granule.

The preparation method of defatting and poison expelling oral formulations of the present invention is: get rheum officinale, cassia seed, the fleece-flower root, rhizoma alismatis and add alcohol extract, merge extract, leave standstill, filter, filtrate is condensed into thick paste, and drying is ground into fine powder, and is standby; Cape jasmine, radix bupleuri, curcuma zedoary, hawthorn, oriental wormwood boiling filter, and collecting decoction is got supernatant concentration and become thick paste, and drying is ground into fine powder, with above-mentioned fine powder mixing, adds appropriate amount of auxiliary materials then and makes different preparations.

Specifically, get rheum officinale, cassia seed, the fleece-flower root, rhizoma alismatis and add 5～12 times of amount 30～85% alcohol extracts 1～5 time, 2～6 hours for the first time, 1～5 hour for the second time, 0.5～3 hour for the third time, fourth, fifth time each 0.5～2 hour.Merge extract, leave standstill, filter, filtrate is condensed into thick paste, and drying is ground into fine powder, and is standby; Cape jasmine, radix bupleuri, curcuma zedoary, hawthorn, oriental wormwood add 3～15 times of water gagings and decoct 1～5 time, and 1～4 hour for the first time, second and third time each 0.5～3 hour, fourth, fifth time each 0.5～2 hour, filter, collecting decoction is got supernatant concentration and is become thick paste, drying is ground into fine powder, with above-mentioned fine powder mixing; The pregelatinized starch that adds medicinal powder total amount 15～40%, mixing, dry pressing is granulated, whole grain, it is an amount of to add 0.1～0.6% dolomol and pregelatinized starch again, and making general assembly (TW) is 280g, mix, compressing tablet, the bag film-coating promptly gets tablet; Add dextrin in the mixed powder: sweet mellow wine=1: 2 is an amount of, mixing, and packing promptly gets granule.

More precisely, get rheum officinale, cassia seed, the fleece-flower root, rhizoma alismatis and add 8 times of amount 65% alcohol extracts three times, 4 hours for the first time, 3 hours for the second time, 2 hours for the third time, merge extract, leave standstill, filter, filtrate is condensed into thick paste, and drying is ground into fine powder, and is standby; Cape jasmine, radix bupleuri, curcuma zedoary, hawthorn, oriental wormwood add 10 times of water gagings and decoct three times, and 3 hours for the first time, second and third time each 2 hours filtered, and collecting decoction is got supernatant concentration and become thick paste, and drying is ground into fine powder, with above-mentioned fine powder mixing; The pregelatinized starch that adds medicinal powder total amount 26%, mixing, dry pressing is granulated, whole grain, it is an amount of to add 0.3% dolomol and pregelatinized starch again, and making general assembly (TW) is 280g, mix, compressing tablet, the bag film-coating promptly gets tablet; Add dextrin in the mixed powder: sweet mellow wine=1: 2 is an amount of, mixing, and packing promptly gets granule.

The method of quality control of defatting and poison expelling tablet of the present invention and granule is: described method of quality control mainly comprise in proterties, discriminating, inspection and the assay project partly or entirely; Wherein differentiate the thin-layer chromatography discriminating that comprises rheum officinale, hawthorn, cape jasmine and rhizoma alismatis in the preparation; Assay is that the contained Gardenoside of cape jasmine in the preparation is carried out assay.

The discrimination method of rheum officinale is to be contrast with the rheum officinale control medicinal material, is the thin-layered chromatography of developping agent with the upper solution of 30～60 ℃ sherwood oils-formic acid second fat-formic acid=5-25: 1-10: 0.1-2; The discrimination method of hawthorn is to be contrast with the ursolic acid reference substance, is the thin-layered chromatography of developping agent with sherwood oil-benzene-glacial acetic acid-ethyl acetate=5-15: 10-30: 0.1-1: 1-10; The discrimination method of cape jasmine is to be contrast with the Gardenoside reference substance, is the thin-layered chromatography of developping agent with ethyl acetate-acetone-formic acid-water=5-15: 1-12: 0.5-5: 0.1-1; The discrimination method of rhizoma alismatis is to be contrast with the rhizoma alismatis control medicinal material, is the thin-layered chromatography of developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8.

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

(1) get tablet or granule, fine ground, add methyl alcohol, close plug soaks, and filters, get the filtrate evaporate to dryness, residue is dissolved in water, and adds hydrochloric acid again, reflux, cooling immediately, extract with the ether jolting, divide and get ether solution, evaporate to dryness, residue add the methenyl choloride dissolving, as need testing solution; Other gets the rheum officinale control medicinal material, shines medicinal material solution in pairs with legal system; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw above-mentioned need testing solution and control medicinal material solution, put respectively in same be on the silica gel H thin layer plate of binder with the sodium carboxymethyl cellulose, upper solution with 30～60 ℃ sherwood oils-formic acid second fat-formic acid=5-25: 1-10: 0.1-2 is a developping agent, launch, take out, dry, put under the 200-500nm ultraviolet light and inspect; In the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence principal spot of same color;

(2) get tablet or granule, pulverize, add ether, reflux filters, and filtrate volatilizes, and residue adds ethanol, as need testing solution; Other gets the ursolic acid reference substance, adds ethanol and makes reference substance solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, draw above-mentioned need testing solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with sherwood oil-benzene-glacial acetic acid-ethyl acetate=5-15: 10-30: 0.1-1: 1-10 is developping agent, launches, and takes out, dry, spray is with sulfuric acid ethanol liquid, and it is clear to be heated to the spot colour developing at 90～120 ℃, puts under the 200-500nm ultraviolet lamp and inspects; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical fluorescence spot;

(3) get tablet or granule, porphyrize, the jolting that adds diethyl ether discards ether solution, and residue volatilizes, and adds ethyl acetate, and reflux filters, and filtrate volatilizes, and residue adds ethanol makes dissolving, as need testing solution; Other gets the Gardenoside reference substance, adds ethanol and makes reference substance solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid-water=5-15: 1-12: 0.5-5: 0.1-1 is developping agent, launches, and takes out, dry, spray is with ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;

(4) get tablet or granule, porphyrize is dissolved in water, and transferring PH with NaOH is 12～13, add ether and saturated aqueous common salt and fully vibrate, divide and get ether layer, water layer repeats once combined ether layer according to last method again, volatilize, residue adds ethyl acetate makes dissolving, as need testing solution; Other gets the rhizoma alismatis control medicinal material, adds water boil, filters, and filtrate concentrates, and transferring PH with NaOH is 12～13, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, drawing above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8, room temperature condition launches down, take out, dry, spray is with ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color.

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

(1) get 2～8 in tablet or granule 2～8g, fine ground, add methyl alcohol 10～40ml, close plug soaked 0.5～2 hour, filtered, get filtrate 2～8ml, evaporate to dryness, residue add water 5～20ml makes dissolving, add hydrochloric acid 0.5～2ml again, reflux 15～60 minutes, cooling immediately, divide 2 joltings to extract with ether, each 10～40ml merges ether solution, evaporate to dryness, residue add methenyl choloride 0.5～3ml dissolving, as need testing solution; Other gets rheum officinale control medicinal material 0.1g, shines medicinal material solution in pairs with legal system; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel H thin layer plate of binder with the sodium carboxymethyl cellulose, upper solution with 30～60 ℃ sherwood oils-formic acid second fat-formic acid=5-25: 1-10: 0.1-2 is a developping agent, launches, and takes out, dry, put under the 365nm ultraviolet light and inspect; In the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence principal spot of same color;

(2) get 2～8 in tablet or granule 2～8g, pulverize, the 10～40ml that adds diethyl ether, reflux 0.5～2 hour filters, and filtrate volatilizes, and residue adds ethanol 0.5～5ml makes dissolving, as need testing solution; Other gets the ursolic acid reference substance, adds ethanol and makes 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-layered chromatography, draw need testing solution 5 μ l, reference substance solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with sherwood oil-benzene-glacial acetic acid-ethyl acetate=5-15: 10-30: 0.1-1: 1-10 is developping agent, launches, and takes out, dry, spray is with 10% sulfuric acid ethanol liquid, and it is clear to be heated to the spot colour developing at 90～120 ℃, puts under the 365nm ultraviolet lamp and inspects; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical fluorescence spot;

(3) get 2～8 in tablet or granule 2～8g, porphyrize, the 5～30ml that adds diethyl ether, jolting 5～20 minutes, discard ether solution, residue volatilizes, and adds ethyl acetate 5～30ml, reflux 0.5～2 hour, filter, filtrate volatilizes, and residue adds ethanol 0.5～2ml makes dissolving, as need testing solution; Other gets the Gardenoside reference substance, adds ethanol and makes 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-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid-water=5-15: 1-12: 0.5-5: 0.1-1 is developping agent, launches, and takes out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;

(4) get 10～40 in tablet or granule 10～50g, porphyrize, add water 20～60ml, it is 12～13 that the NaOH with 15% is transferred PH, adds ether 20～60ml and saturated aqueous common salt 2～6ml and fully vibrates, divide and get ether layer, water layer repeats once according to last method again, and combined ether layer volatilizes, residue adds ethyl acetate 0.2～2ml makes dissolving, as need testing solution; Other gets rhizoma alismatis control medicinal material 1～3g, adds water 20～90ml, boils 15～60min, filters, and filtrate is concentrated into about 30ml, and it is 12～13 that the NaOH with 15% is transferred PH, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8, room temperature condition launches down, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color.

The content assaying method of Gardenoside is to be contrast with the Gardenoside reference substance in the cape jasmine, is the high performance liquid chromatography of moving phase with methanol-water=1540: 50-100.

The content assaying method of Gardenoside is:

According to an appendix VI of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring:

Chromatographic condition and system suitability test are filling agent with octadecylsilane chemically bonded silica; Methanol-water=15-40: 50-100 is a moving phase; The detection wavelength is 240nm; Number of theoretical plate must not calculate with the Gardenoside peak and is lower than 4000;

The preparation precision of reference substance solution takes by weighing the Gardenoside reference substance, adds dissolve with methanol, shakes up, promptly;

Tablet or the granule under the content uniformity item got in the preparation of need testing solution, accurate claims surely, and the accurate methyl alcohol that adds claims decide weight, and ultrasonic Extraction is put coldly, adds methyl alcohol and supplies weight, shakes up, and gets the supernatant filtration, promptly;

Accurate respectively reference substance solution and the need testing solution drawn of determination method injects liquid chromatograph, measures, promptly;

In this preparation, tablet contains cape jasmine with Gardenoside C ₁₇H ₂₄O ₁₀Meter must not be less than the 0.25mg/ sheet; Granule contains cape jasmine with Gardenoside C for every bag ₁₇H ₂₄O ₁₀Meter must not be less than 1.0mg.

Content assaying method is more specifically:

The preparation precision of reference substance solution takes by weighing the Gardenoside reference substance, adds methyl alcohol and makes the solution that every 1ml contains Gardenoside 60.0 μ g, shakes up, promptly;

Tablet or the granule 0.5-2g under the content uniformity item got in the preparation of need testing solution, the accurate title, decide, precision adds methyl alcohol 10-50ml, claim to decide weight, ultrasonic Extraction was put cold after 20～60 minutes under power 250W, frequency 50kHZ condition, add methyl alcohol and supply weight, shake up, get supernatant and filter, promptly with being less than or equal to 0.45 μ m miillpore filter;

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of determination method inject liquid chromatograph, measure, promptly;

In this preparation, tablet contains cape jasmine with Gardenoside C ₁₇H ₂₄0 ₁₀Meter must not be less than the 0.25mg/ sheet; Granule contains cape jasmine with Gardenoside C for every bag ₁₇H ₂₄O ₁₀Meter must not be less than 1.0mg.

Method of quality control of the present invention comprises:

Proterties: for tablet, product is a Film coated tablets, is pale brown look to sepia after removing film-coating; Bitter;

For granule, product is that pale brown look is to brown granular; It is sweet to distinguish the flavor of;

Differentiate: (1) gets tablet or granule, and is fine ground, adds methyl alcohol, and close plug soaks, and filters, get the filtrate evaporate to dryness, residue is dissolved in water, and adds hydrochloric acid again, reflux, cooling immediately, extract with the ether jolting, divide and get ether solution, evaporate to dryness, residue add the methenyl choloride dissolving, as need testing solution; Other gets the rheum officinale control medicinal material, shines medicinal material solution in pairs with legal system; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw above-mentioned need testing solution and control medicinal material solution, put respectively in same be on the silica gel H thin layer plate of binder with the sodium carboxymethyl cellulose, upper solution with 30～60 ℃ sherwood oils-formic acid second fat-formic acid=5-25: 1-10: 0.1-2 is a developping agent, launch, take out, dry, put under the 200-500nm ultraviolet light and inspect; In the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence principal spot of same color;

(4) get tablet or granule, porphyrize is dissolved in water, and transferring PH with NaOH is 12～13, add ether and saturated aqueous common salt and fully vibrate, divide and get ether layer, water layer repeats once combined ether layer according to last method again, volatilize, residue adds ethyl acetate makes dissolving, as need testing solution; Other gets the rhizoma alismatis control medicinal material, adds water boil, filters, and filtrate concentrates, and transferring PH with NaOH is 12～13, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, drawing above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8, room temperature condition launches down, take out, dry, spray is with ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color;

Check: should meet relevant every regulation under Chinese Pharmacopoeia appendix tablet of version in 2005 or the granule item;

Assay: Gardenoside shines an appendix VI of Chinese Pharmacopoeia version in 2005 D high effective liquid chromatography for measuring:

Through discovering of applicant, adopt the quality of following method of quality control with this defatting and poison expelling oral formulations of easier control, be more conducive to guarantee the clinical efficacy of said preparation.So described method of quality control also can comprise:

Differentiate: (1) gets 2～8 in tablet or granule 2～8g, and is fine ground, adds methyl alcohol 10～40ml, close plug soaked 0.5～2 hour, filtered, get filtrate 2～8ml, evaporate to dryness, residue add water 5～20ml makes dissolving, add hydrochloric acid 0.5～2ml again, reflux 15～60 minutes, cooling immediately, divide 2 joltings to extract with ether, each 10～40ml merges ether solution, evaporate to dryness, residue add methenyl choloride 0.5～3ml dissolving, as need testing solution; Other gets rheum officinale control medicinal material 0.1g, shines medicinal material solution in pairs with legal system; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel H thin layer plate of binder with the sodium carboxymethyl cellulose, upper solution with 30～60 ℃ sherwood oils-formic acid second fat-formic acid=5-25: 1-10: 0.1-2 is a developping agent, launches, and takes out, dry, put under the 365nm ultraviolet light and inspect; In the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence principal spot of same color;

(3) get 2～8 in tablet or granule 2～8g, porphyrize, the 5～30ml that adds diethyl ether, jolting 5～20 minutes, discard ether solution, residue volatilizes, and adds ethyl acetate 5～30ml, reflux 0.5～2 hour, filter, filtrate volatilizes, and residue adds ethanol 0.5～2ml makes dissolving, as need testing solution; Other gets the Gardenoside reference substance, adds ethanol and makes 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-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid water=5-15: 1-12: 0.5-5: 0.1-1 is developping agent, launches, and takes out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;

(4) get 10～40 in tablet or granule 10～50g, porphyrize, add water 20～60ml, it is 12～13 that the NaOH with 15% is transferred PH, adds ether 20～60ml and saturated aqueous common salt 2～6ml and fully vibrates, divide and get ether layer, water layer repeats once according to last method again, and combined ether layer volatilizes, residue adds ethyl acetate 0.2～2ml makes dissolving, as need testing solution; Other gets rhizoma alismatis control medicinal material 1～3g, adds water 20～90ml, boils 15～60min, filters, and filtrate is concentrated into about 30ml, and it is 12～13 that the NaOH with 15% is transferred PH, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8, room temperature condition launches down, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color;

The preparation method of preparation of the present invention and method of quality control are the preferred plan that obtains through a large amount of screenings, and following experimental study is a preferred process of the present invention.

Experiment 1: the screening of additive of tablet

Tablet is full medicinal extract sheet, needs to add suitable filling agent, binder, and disintegrant and lubricant consider that the hydroscopicity of extract powder is strong, and is mobile poor, need make a certain size particle before the compressing tablet.

One, the screening of filling agent

Through data check, the filling agent of tablet has dextrin, sucrose, pregelatinized starch etc.With disintegration time, hydroscopicity, compressibility is that index is screened filling agent, the results are shown in Table 1.

The screening of table 1 filling agent kind

Filling agent	Dextrin	Sucrose	Pregelatinized starch
Filling agent	Dextrin	Sucrose	Pregelatinized starch	Hydroscopicity	Slower	Comparatively fast	Slower
Disintegration time (min)	56	47	40	Hydroscopicity	Slower	Comparatively fast	Slower
Disintegration time (min)	56	47	40	Compressibility	Relatively poor	Better	Good

From table 1 result as seen, it is comparatively suitable to make filling agent with pregelatinized starch.

Two, the selection of disintegrant

Pregelatinized starch is a multi-functional auxiliary material, can make filling agent, has good flowability, compressibility, self-lubricity and dry adhesive, and calving disaggregation is preferably arranged.

Aborning, the inside and outside addition of the general employing of disintegrant, can make the disintegration of tablet not only occur in granule interior but also occur between the particle, thereby reach good disintegration effect, usually add disintegration dosage and account for 25%～50% of disintegrant total amount, in add disintegration dosage and account for 75%～50% of disintegrant total amount, for the ratio that allows in the disintegrant, add more reasonable, with investigating its used ratio as index disintegration time limited, the results are shown in Table 2.

The screening of the inside and outside additional proportion of table 2 disintegrant

The inside and outside addition ratio of disintegrant	5∶5	6∶4	7∶3	8∶2
The inside and outside addition ratio of disintegrant	5∶5	6∶4	7∶3	8∶2	Disintegration time (min)	38	35	30	32

Evaluation of result: the amount of pregelatinized starch 70% adds with interior addition, and it is best that addition adds effect beyond 30% the amount.

Three, the selection of method of granulating

Because of this preparation is full medicinal extract sheet, the chance water viscosity is too big, so adopt the ethanol of high concentration to granulate and dry granulation as wetting agent, selects granulating process by investigating the yield of once making particle, the results are shown in Table 3.

The selection result of table 3 concentration of alcohol

Interpretation of result: 90% following ethanol is made wetting agent, medicinal powder conglomeration hardening, and color is profound, can not make softwood; 95% ethanol is made wetting agent and is granulated, and loose particles is inhomogeneous; Dry-pressing is granulated, particle is neat, of light color, because of the dry-pressing granulation need not add any wetting agent, particle just need not dried can be directly used in compressing tablet, can effectively keep contained heat-labile composition in the medicine, compare with wet processing, shortened process route, saved human and material resources and energy consumption, so preferred dry-pressing is granulated.

Four, the screening of lubricant

Lubricant can improve the flowability of particle, is convenient to compressing tablet.Conventional lubricants has talcum powder, dolomol, superfine silica gel powder etc., adds in the particle with same amount, surveys its angle of repose, investigates its influence to the compressing tablet process.The results are shown in Table 4.

The screening of table 4 lubricant kind

The lubricant kind	Talcum powder	Dolomol	Superfine silica gel powder
The lubricant kind	Talcum powder	Dolomol	Superfine silica gel powder	The angle of repose	38.3°	35.7°	35.0°

The result is as seen: the lubricant effect of dolomol and superfine silica gel powder is suitable, and all good than talcum powder, says from cost, selects dolomol to be more suitable for.To further investigate its consumption below, the results are shown in Table 5.

The screening of table 5 dolomol consumption

Consumption (%)	0.1	0.2	0.3	0.4	0.5
Consumption (%)	0.1	0.2	0.3	0.4	0.5	The angle of repose	36.8°	36.3°	34.1°	33.4°	32.5°
Disintegration time (minute)	＜30	＜30	＜30	＞30	＞30	The angle of repose	36.8°	36.3°	34.1°	33.4°	32.5°
Disintegration time (minute)	＜30	＜30	＜30	＞30	＞30	Hardness (kg)	3.7	3.6	3.9	3.2	2.9

Therefore, determine the amount of the consumption of dolomol for adding 0.3% in each prescription.

Experiment 2: the selection of granule auxiliary material

Defatting and poison expelling preparation function cures mainly and is stagnation resolvation lipopenicillinase, the defaecation Cuo that disappears.Be used for the simple obesity due to the stagnation of turbidity and stasis, hyperlipidemia, acne should not have a large amount of sugar in the auxiliary material.Mix the back respectively with starch+sweet mellow wine, dextrin+sweet mellow wine by dried cream powder and survey the melting experiment, selected auxiliary material is mainly dextrin+sweet mellow wine, as the examination index, selects the ratio between dextrin and the sweet mellow wine with flowability, melting, mouthfeel.The result is as follows:

Table 6 auxiliary material is selected experimental result

By above experiment, find that 2 and 3 result is more satisfactory, but the angle from reducing production costs determines that it is best that the dextrin and the ratio of sweet mellow wine are classified 1: 2 as.

Experiment 3: Gardenoside content assaying method research

1. need testing solution preparation method research

Method one: get this preparation 0.9g under the content uniformity item, the accurate title, decide, and places the 10ml measuring bottle, adds methyl alcohol and be diluted to scale, shakes up, and leaves standstill.Get supernatant with 0.45 μ m filtering with microporous membrane, accurately again draw subsequent filtrate 1ml and put in the 10ml measuring bottle, add methanol-water=be diluted to scale at 1: 1, shake up, as need testing solution.

Method two: get this preparation 0.9g under the content uniformity item, the accurate title, decide, precision adds methyl alcohol 25ml, claim to decide weight, ultrasonic Extraction was put cold after 45 minutes under power 250W, frequency 50kHZ condition, add methyl alcohol and supply weight, shake up, get supernatant and filter, promptly with being less than or equal to 0.45 μ m miillpore filter.

Method three: get this preparation 0.9g under the content uniformity item, put in the 100ml measuring bottle, adding distil water shakes up to scale, filters with being less than or equal to 0.45 μ m miillpore filter, gets subsequent filtrate, promptly.

Table 7

Sample	Method 1 (mg/g)	Method 2 (mg/g)	Method 3 (mg/g)
Sample	Method 1 (mg/g)	Method 2 (mg/g)	Method 3 (mg/g)	1	0.658	0.831	0.622
2	0.700	0.852	0.654	1	0.658	0.831	0.622
2	0.700	0.852	0.654	3	0.698	0.843	0.638

According to test findings table 7 as can be known, adopt method two to prepare need testing solution, Gardenoside extracts more complete.

2. the selection of moving phase

Moving phase 1: methanol-water=27: 73 is a moving phase

Moving phase 2: acetonitrile-water=10: 90 is a moving phase

Moving phase 3: water-methanol-phosphoric acid=85: 15: 0.1

The result: with methanol-water=27: 73 was moving phase, and defatting and poison expelling preparation good separation, Gardenoside separate fully (degree of separation＞1.5) with close impurity peaks, so optimal flow is mutually: methanol-water=27: 73.

3. replica test

Get this preparation fine powder, the preparation method by test liquid under the assay item in the method for quality control of the present invention prepares 5 parts of test liquids respectively, and sample introduction is measured peak area, and the Gardenoside average content is 1.7027mg/g, and RSD is 0.59%.Show that repeatability is good, the results are shown in Table 8.

The replica test of Gardenoside in the table 8 preparation test sample

The sample introduction number of times	1	2	3	4	5	Mean value	RSD(％)
The sample introduction number of times	1	2	3	4	5	Mean value	RSD(％)	Peak area	1.7162	1.6956	1.7090	1.7012	1.6914	1.7027	0.59

4. stability test

Get this preparation fine powder, prepare test liquid by the preparation method of test liquid under the assay item in the method for quality control of the present invention, measure its Gardenoside peak area respectively at 0,2,4,6,8 hour, average peak area is 863144, and RSD is 0.27%.Show that Gardenoside is stable in 8 hours in the need testing solution, the results are shown in Table 9.

The stability test of Gardenoside in the table 9 preparation test sample

Time (hour)	0	2	4	6	8	Mean value	RSD(％)
Time (hour)	0	2	4	6	8	Mean value	RSD(％)	Peak area	860904	864441	866394	861600	862380	863144	0.27

5. recovery test

Adopt the application of sample absorption method, each is an amount of for accurate this preparation of absorption (average content is 1.7027mg/g) respectively, put in the tool plug conical flask, (with methyl alcohol is solvent to accurate adding Gardenoside reference substance, make that to contain Gardenoside be 30.6 μ g/ml) solution 25ml, make test liquid by the preparation method of test liquid under the assay item in the method for quality control of the present invention.The accurate respectively 10 μ l of absorption inject liquid chromatograph, and the record chromatogram is measured content, and calculate recovery rate sees Table 10.Average recovery rate is 99.07%, and RSD is 1.22%, proves that this method is feasible.

Gardenoside is measured recovery test in table 10 need testing solution

6. method of quality control contrast experiment

The defatting and poison expelling particle: one hundred pharmaceutical Co. Ltd provides by the Guizhou benefit; The defatting and poison expelling sheet: one hundred pharmaceutical Co. Ltd provides by the Guizhou benefit.By the method for quality control and the method for quality control of the present invention of original standard product is differentiated and assay respectively.The results are shown in following table:

Table 11 method of quality control result contrast

	Former method defatting and poison expelling granule	Former method defatting and poison expelling tablet	Granule of the present invention	Tablet of the present invention
	Former method defatting and poison expelling granule	Former method defatting and poison expelling tablet	Granule of the present invention	Tablet of the present invention	Rheum officinale is differentiated	Feminine gender has interference	Feminine gender has interference	Negative noiseless, the spot degree of separation is good, and reappearance is good	Negative noiseless, the spot degree of separation is good, and reappearance is good
Hawthorn is differentiated	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Rheum officinale is differentiated	Feminine gender has interference	Feminine gender has interference
Hawthorn is differentiated	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	The fleece-flower root is differentiated	Feminine gender has interference	Feminine gender has interference	Do not have	Do not have
Cape jasmine is differentiated	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	The fleece-flower root is differentiated	Feminine gender has interference	Feminine gender has interference	Do not have	Do not have
Cape jasmine is differentiated	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Negative noiseless, reappearance is good	Rhizoma alismatis is differentiated	Do not have	Do not have	The spot degree of separation is good, and negative noiseless, reappearance is good	The spot degree of separation is good, and negative noiseless, reappearance is good
Stability experiment RSD value (%)	0.58	0.62	0.27	0.26	Rhizoma alismatis is differentiated	Do not have	Do not have
Stability experiment RSD value (%)	0.58	0.62	0.27	0.26	Recovery experiment RSD value (%)	1.60	1.55	1.22	1.21

The result shows that by method of quality control of the present invention, the quality of easier control product, stability is better, and accuracy is higher.

Compared with prior art, the auxiliary material in the oral formulations provided by the present invention does not have and contains sugared composition, and preparation technology is reasonable, can more effectively treat hyperlipemia, has satisfied requirement of different patients.Method of quality control accuracy height of the present invention, favorable reproducibility, good stability, recovery height has improved the quality control standard of defatting and poison expelling oral formulations, can effectively guarantee the clinical efficacy of said preparation.

Embodiment:

Embodiments of the invention 1: rheum officinale 150g, cassia seed 300g, hawthorn 300g, oriental wormwood 300g, cape jasmine 100g, rhizoma alismatis 250g, fleece-flower root 250g, curcuma zedoary 250g, radix bupleuri 150g

Get rheum officinale, cassia seed, the fleece-flower root, rhizoma alismatis and add 8 times of amount 65% alcohol extracts three times, 4 hours for the first time, 3 hours for the second time, 2 hours for the third time, merge extract, leave standstill, filter, filtrate is condensed into thick paste, and drying is ground into fine powder, and is standby; Cape jasmine, radix bupleuri, curcuma zedoary, hawthorn, oriental wormwood add 10 times of water gagings and decoct three times, and 3 hours for the first time, second and third time each 2 hours filtered, and collecting decoction is got supernatant concentration and become thick paste, and drying is ground into fine powder, with above-mentioned fine powder mixing; The pregelatinized starch that adds medicinal powder total amount 26%, mixing, dry pressing is granulated, whole grain, it is an amount of to add 0.3% dolomol and pregelatinized starch again, and making general assembly (TW) is 280g, mix, compressing tablet, the bag film-coating is made 1000 altogether, promptly gets tablet of the present invention.

Embodiments of the invention 2: rheum officinale 30g, cassia seed 100g, hawthorn 100g, oriental wormwood 100g, cape jasmine 50g, rhizoma alismatis 100g, fleece-flower root 100g, curcuma zedoary 100g, radix bupleuri 50g

Get rheum officinale, cassia seed, the fleece-flower root, rhizoma alismatis and add 5 times of amount 30% alcohol extracts 6 hours, extract leaves standstill, and filters, and filtrate is condensed into thick paste, and drying is ground into fine powder, and is standby; Cape jasmine, radix bupleuri, curcuma zedoary, hawthorn, oriental wormwood add 3 times of water gagings and decocted 4 hours, filter, and collecting decoction is got supernatant concentration and become thick paste, and drying is ground into fine powder, with above-mentioned fine powder mixing; The pregelatinized starch that adds medicinal powder total amount 15%, mixing, dry pressing is granulated, whole grain, it is an amount of to add 0.1% dolomol and pregelatinized starch again, and making general assembly (TW) is 280g, mix, compressing tablet, the bag film-coating promptly gets tablet of the present invention.

Embodiments of the invention 3: rheum officinale 300g, cassia seed 500g, hawthorn 500g, oriental wormwood 500g, cape jasmine 200g, rhizoma alismatis 400g, fleece-flower root 400g, curcuma zedoary 400g, radix bupleuri 300g

Get rheum officinale, cassia seed, the fleece-flower root, rhizoma alismatis and add 12 times of amount 85% alcohol extracts 5 times, 2 hours for the first time, 1 hour for the second time, third and fourth, five times each 0.5 hour, merge extract, leave standstill, filter, filtrate is condensed into thick paste, drying is ground into fine powder, and is standby; Cape jasmine, radix bupleuri, curcuma zedoary, hawthorn, oriental wormwood add 15 times of water gagings and decoct 5 times, 1 hour for the first time, second and third, four, five times each 0.5 hour, filter, collecting decoction is got supernatant concentration and is become thick paste, drying is ground into fine powder, with above-mentioned fine powder mixing; The pregelatinized starch that adds medicinal powder total amount 40%, mixing, dry pressing is granulated, whole grain, it is an amount of to add 0.6% dolomol and pregelatinized starch again, and making general assembly (TW) is 280g, mix, compressing tablet, the bag film-coating promptly gets tablet of the present invention.

Embodiments of the invention 4: rheum officinale 100g, cassia seed 200g, hawthorn 200g, oriental wormwood 200g, cape jasmine 80g, rhizoma alismatis 200g, fleece-flower root 200g, curcuma zedoary 200g, radix bupleuri 100g

Get rheum officinale, cassia seed, the fleece-flower root, rhizoma alismatis and add 10 times of amount 50% alcohol extracts twice, 6 hours for the first time, 5 hours for the second time, merge extract, leave standstill, filter, filtrate is condensed into thick paste, and drying is ground into fine powder, and is standby; Cape jasmine, radix bupleuri, curcuma zedoary, hawthorn, oriental wormwood add 8 times of water gagings and decoct twice, and 4 hours for the first time, 3 hours for the second time, filter, collecting decoction is got supernatant concentration and is become thick paste, and drying is ground into fine powder, with above-mentioned fine powder mixing; Add dextrin: sweet mellow wine=1: 2 is an amount of, and mixing is made about 1000g, and packing promptly gets granule of the present invention.

Embodiments of the invention 5: the method for quality control of defatting and poison expelling tablet comprises:

Proterties: for tablet, product is a Film coated tablets, is pale brown look to sepia after removing film-coating; Bitter.

Differentiate: (1) gets 4 in tablet, and is fine ground, adds methyl alcohol 20ml, close plug soaked 1 hour, filtered, get filtrate 5ml, evaporate to dryness, residue add water 10ml makes dissolving, add hydrochloric acid 1ml again, reflux 30 minutes, cooling immediately, divide 2 joltings to extract with ether, each 20ml merges ether solution, evaporate to dryness, residue add methenyl choloride 1ml dissolving, as need testing solution.Other gets rheum officinale control medicinal material 0.1g, shines medicinal material solution in pairs with legal system.Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel H thin layer plate of binder with the sodium carboxymethyl cellulose, upper solution with 30～60 ℃ sherwood oils-formic acid second fat-formic acid=15: 5: 1 is a developping agent, launch, take out, dry, put under the ultraviolet light 365nm and inspect.In the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence principal spot of same color.

(2) get 4 in tablet, pulverize, the 30ml that adds diethyl ether, reflux 1 hour filters, and filtrate volatilizes, and residue adds ethanol 2ml makes dissolving, as need testing solution.Other gets the ursolic acid reference substance, adds ethanol and makes 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-layered chromatography, draw need testing solution 5 μ l, reference substance solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with sherwood oil-benzene-glacial acetic acid-ethyl acetate=10: 20: 0.5: 5 was developping agent, launches, and takes out, dry, spray is with 10% sulfuric acid ethanol liquid, and it is clear to be heated to the spot colour developing at 110 ℃, puts under the 365nm ultraviolet lamp and inspects.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical fluorescence spot.

(3) get 4 in tablet, porphyrize, the 15ml that adds diethyl ether, jolting 10 minutes discards ether solution, and residue volatilizes, and adds ethyl acetate 15ml, and reflux 1 hour filters, and filtrate volatilizes, and residue adds ethanol 1ml makes dissolving, as need testing solution.Other gets the Gardenoside reference substance, adds ethanol and makes 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-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid-water=10: 7: 2: 0.5 was developping agent, launches, and takes out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.

(4) get 24 in tablet, porphyrize, add water 40ml, it is 12～13 that the NaOH with 15% is transferred PH, adds ether 40ml and saturated aqueous common salt 4ml and fully vibrates, divide and get ether layer, water layer repeats once according to last method again, and combined ether layer volatilizes, residue adds ethyl acetate 1ml makes dissolving, as need testing solution.Other gets rhizoma alismatis control medicinal material 2g, adds water 60ml, boils 30min, filters, and filtrate is concentrated into about 30ml, and it is 12～13 that the NaOH with 15% is transferred PH, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=10: 3: 0.3, room temperature condition launches down, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color.

Check: should meet relevant every regulation under an appendix tablet of Chinese Pharmacopoeia version in 2005 item.

Chromatographic condition and system suitability test are filling agent with octadecylsilane chemically bonded silica; Methanol-water=27: 73 is a moving phase; The detection wavelength is 240nm.Number of theoretical plate must not calculate with the Gardenoside peak and is lower than 4000.

The preparation precision of reference substance solution takes by weighing the Gardenoside reference substance, adds methyl alcohol and makes the solution that every 1ml contains Gardenoside 60.0 μ g, shakes up, promptly.

The tablet 0.9g under the content uniformity item is got in the preparation of need testing solution, and accurate the title decides, and precision adds methyl alcohol 25ml, claims to decide weight, ultrasonic Extraction is after 45 minutes under power 250W, frequency 50kHZ condition, puts coldly, adds methyl alcohol and supplies weight, shake up, get supernatant with 0.45 μ m filtering with microporous membrane, promptly.

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of determination method inject liquid chromatograph, measure, promptly.

Every in this preparation contains cape jasmine with Gardenoside (C ₁₇H ₂₄O ₁₀) must not count and be less than 0.25mg.

Embodiments of the invention 6: the method for quality control of defatting and poison expelling granule comprises:

Proterties: for granule, product is that pale brown look is to brown granular; It is sweet to distinguish the flavor of.

Differentiate: (1) gets granule 2g, and is fine ground, adds methyl alcohol 10ml, close plug soaked 0.5 hour, filtered, get filtrate 2ml, evaporate to dryness, residue add water 5ml makes dissolving, add hydrochloric acid 0.5ml again, reflux 15 minutes, cooling immediately, divide 2 joltings to extract with ether, each 10ml merges ether solution, evaporate to dryness, residue add methenyl choloride 0.5ml dissolving, as need testing solution.Other gets rheum officinale control medicinal material 0.1g, shines medicinal material solution in pairs with legal system.Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel H thin layer plate of binder with the sodium carboxymethyl cellulose, upper solution with 30～60 ℃ sherwood oils-formic acid second fat-formic acid=5: 10: 0.1 is a developping agent, launch, take out, dry, put under the 365nm ultraviolet light and inspect.In the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence principal spot of same color.

(2) get granule 2g, pulverize, the 10ml that adds diethyl ether, reflux 0.5 hour filters, and filtrate volatilizes, and residue adds ethanol 0.5ml makes dissolving, as need testing solution.Other gets the ursolic acid reference substance, adds ethanol and makes 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-layered chromatography, draw need testing solution 5 μ l, reference substance solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with sherwood oil-benzene-glacial acetic acid-ethyl acetate=5: 30: 0.1: 10 was developping agent, launches, and takes out, dry, spray is with 10% sulfuric acid ethanol liquid, and it is clear to be heated to the spot colour developing at 90 ℃, puts under the 365nm ultraviolet lamp and inspects.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical fluorescence spot.

(3) get granule 2g, porphyrize, the 5ml that adds diethyl ether, jolting 5 minutes discards ether solution, and residue volatilizes, and adds ethyl acetate 5ml, and reflux 0.5 hour filters, and filtrate volatilizes, and residue adds ethanol 0.5ml makes dissolving, as need testing solution.Other gets the Gardenoside reference substance, adds ethanol and makes 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-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid-water=5: 12: 0.5: 1 was developping agent, launches, and takes out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.

(4) get granule 10g, porphyrize, add water 20ml, it is 12～13 that the NaOH with 15% is transferred PH, adds ether 20ml and saturated aqueous common salt 2ml and fully vibrates, divide and get ether layer, water layer repeats once according to last method again, and combined ether layer volatilizes, residue adds ethyl acetate 0.2ml makes dissolving, as need testing solution.Other gets rhizoma alismatis control medicinal material 1g, adds water 20ml, boils 15min, filters, and filtrate is concentrated into about 30ml, and it is 12～13 that the NaOH with 15% is transferred PH, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5: 5: 0.1, room temperature condition launches down, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color.

Check: should meet relevant every regulation under an appendix granule of Chinese Pharmacopoeia version in 2005 item.

Chromatographic condition and system suitability test are filling agent with octadecylsilane chemically bonded silica; Methanol-water=15: 100 is a moving phase; The detection wavelength is 240nm; Number of theoretical plate must not calculate with the Gardenoside peak and is lower than 4000.

The granule 0.5g under the content uniformity item is got in the preparation of need testing solution, the accurate title, decide, precision adds methyl alcohol 10ml, claim to decide weight, ultrasonic Extraction was put cold after 20 minutes under power 250W, frequency 50kHZ condition, add methyl alcohol and supply weight, shake up, get supernatant and filter, promptly with 0.30 μ m miillpore filter.

This particle contains cape jasmine with Gardenoside C for every bag ₁₇H ₂₄O ₁₀Meter must not be less than 1.0mg.

Embodiments of the invention 7: the method for quality control of defatting and poison expelling oral formulations of the present invention can comprise:

For granule, product is that pale brown look is to brown granular; It is sweet to distinguish the flavor of.

Differentiate: (1) gets 8 in tablet or granule 8g, and is fine ground, adds methyl alcohol 40ml, close plug soaked 2 hours, filtered, get filtrate 8ml, evaporate to dryness, residue add water 20ml makes dissolving, add hydrochloric acid 2ml again, reflux 60 minutes, cooling immediately, divide 2 joltings to extract with ether, each 40ml merges ether solution, evaporate to dryness, residue add methenyl choloride 3ml dissolving, as need testing solution.Other gets rheum officinale control medicinal material 0.1g, shines medicinal material solution in pairs with legal system.Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw need testing solution 10 μ l, control medicinal material solution 5 μ l, put respectively in same be on the silica gel H thin layer plate of binder with the sodium carboxymethyl cellulose, upper solution with 30～60 ℃ sherwood oils-formic acid second fat-formic acid=25: 1: 2 is a developping agent, launch, take out, dry, put under the 365nm ultraviolet light and inspect.In the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence principal spot of same color.

(2) get 8 in tablet or granule 8g, porphyrize, the 30ml that adds diethyl ether, jolting 20 minutes discards ether solution, and residue volatilizes, and adds ethyl acetate 30ml, and reflux 2 hours filters, and filtrate volatilizes, and residue adds ethanol 2ml makes dissolving, as need testing solution.Other gets the Gardenoside reference substance, adds ethanol and makes 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-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid-water=15: 1: 5: 0.1 was developping agent, launches, and takes out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color.

(3) get 40 in tablet or granule 50g, porphyrize, add water 60ml, it is 12～13 that the NaOH with 15% is transferred PH, adds ether 60ml and saturated aqueous common salt 6ml and fully vibrates, divide and get ether layer, water layer repeats once according to last method again, and combined ether layer volatilizes, residue adds ethyl acetate 2ml makes dissolving, as need testing solution.Other gets rhizoma alismatis control medicinal material 3g, adds water 90ml, boils 60min, filters, and filtrate is concentrated into about 30ml, and it is 12～13 that the NaOH with 15% is transferred PH, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system.Test according to an appendix VI of Chinese Pharmacopoeia version in 2005 B thin-layered chromatography, drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=15: 0.5: 0.8, room temperature condition launches down, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color.

Check: should meet relevant every regulation under Chinese Pharmacopoeia appendix tablet of version in 2005 or the granule item.

Embodiments of the invention 8: the method for quality control of defatting and poison expelling oral formulations can comprise:

Differentiate: get 8 in tablet or granule 8g, pulverize, the 40ml that adds diethyl ether, reflux 2 hours filters, and filtrate volatilizes, and residue adds ethanol 5ml makes dissolving, as need testing solution.Other gets the ursolic acid reference substance, adds ethanol and makes 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-layered chromatography, draw need testing solution 5 μ l, reference substance solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with sherwood oil-benzene-glacial acetic acid-ethyl acetate=15: 10: 1: 1 was developping agent, launches, and takes out, dry, spray is with 10% sulfuric acid ethanol liquid, and it is clear to be heated to the spot colour developing at 120 ℃, puts under the 365nm ultraviolet lamp and inspects.In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical fluorescence spot.

Chromatographic condition and system suitability test are filling agent with octadecylsilane chemically bonded silica; Methanol-water=40: 50 is a moving phase; The detection wavelength is 240nm; Number of theoretical plate must not calculate with the Gardenoside peak and is lower than 4000.

Tablet or the granule 2g under the content uniformity item got in the preparation of need testing solution, the accurate title, decide, precision adds methyl alcohol 50ml, claim to decide weight, ultrasonic Extraction was put cold after 60 minutes under power 250W, frequency 50kHZ condition, add methyl alcohol and supply weight, shake up, get supernatant and filter, promptly with 0.40 μ m miillpore filter.

In this preparation, tablet contains cape jasmine with Gardenoside C ₁₇H ₂₄O ₁₀Meter must not be less than the 0.25mg/ sheet; This particle contains cape jasmine with Gardenoside C for every bag ₁₇H ₂₄O ₁₀Meter must not be less than 1.0mg.

Claims

1. the detection method of a defatting and poison expelling oral formulations, this defatting and poison expelling oral formulations is to constitute like this: calculate tablet or the granule of being made by rheum officinale 30-300 part, cassia seed 100-500 part, hawthorn 100-500 part, oriental wormwood 100-500 part, cape jasmine 50-200 part, rhizoma alismatis 100-400 part, fleece-flower root 100-400 part, curcuma zedoary 100-400 part, radix bupleuri 50-300 part and appropriate amount of auxiliary materials according to composition by weight, test item is proterties detection, discriminating and assay; It is characterized in that: discrimination method is:

(2) get tablet or granule, pulverize, add ether, reflux filters, and filtrate volatilizes, and residue adds ethanol, as need testing solution; Other gets the ursolic acid reference substance, adds ethanol and makes reference substance solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw above-mentioned need testing solution and reference substance solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with sherwood oil-benzene-glacial acetic acid-ethyl acetate=5-15: 10-30: 0.1-1: 1-10 is developping agent, launches, and takes out, dry, spray is with sulfuric acid ethanol liquid, and it is clear to be heated to the spot colour developing at 90～120 ℃, puts under the 200-500nm ultraviolet lamp and inspects; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical fluorescence spot;

(3) get tablet or granule, porphyrize, the jolting that adds diethyl ether discards ether solution, and residue volatilizes, and adds ethyl acetate, and reflux filters, and filtrate volatilizes, and residue adds ethanol makes dissolving, as need testing solution; Other gets the Gardenoside reference substance, adds ethanol and makes reference substance solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid-water=5-15: 1-12: 0.5-5: 0.1-1 is developping agent, launches, and takes out, dry, spray is with ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;

(4) get tablet or granule, porphyrize is dissolved in water, and transferring PH with NaOH is 12～13, add ether and saturated aqueous common salt and fully vibrate, divide and get ether layer, water layer repeats once combined ether layer according to last method again, volatilize, residue adds ethyl acetate makes dissolving, as need testing solution; Other gets the rhizoma alismatis control medicinal material, adds water boil, filters, and filtrate concentrates, and transferring PH with NaOH is 12～13, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, drawing above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8, room temperature condition launches down, take out, dry, spray is with ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color.

2. according to the detection method of the described defatting and poison expelling oral formulations of claim 1, it is characterized in that: concrete discrimination method is:

(2) get 2～8 in tablet or granule 2～8g, pulverize, the 10～40ml that adds diethyl ether, reflux 0.5～2 hour filters, and filtrate volatilizes, and residue adds ethanol 0.5～5ml makes dissolving, as need testing solution; Other gets the ursolic acid reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw need testing solution 5 μ l, reference substance solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with sherwood oil-benzene-glacial acetic acid-ethyl acetate=5-15: 10-30: 0.1-1: 1-10 is developping agent, launches, and takes out, dry, spray is with 10% sulfuric acid ethanol liquid, and it is clear to be heated to the spot colour developing at 90～120 ℃, puts under the 365nm ultraviolet lamp and inspects; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical fluorescence spot;

(3) get 2～8 in tablet or granule 2～8g, porphyrize, the 5～30ml that adds diethyl ether, jolting 5～20 minutes, discard ether solution, residue volatilizes, and adds ethyl acetate 5～30ml, reflux 0.5～2 hour, filter, filtrate volatilizes, and residue adds ethanol 0.5～2ml makes dissolving, as need testing solution; Other gets the Gardenoside reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid-water=5-15: 1-12: 0.55: 0.1-1 is a developping agent, launches, and takes out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;

(4) get 10～40 in tablet or granule 10～50g, porphyrize, add water 20～60ml, it is 12～13 that the NaOH with 15% is transferred PH, adds ether 20～60ml and saturated aqueous common salt 2～6ml and fully vibrates, divide and get ether layer, water layer repeats once according to last method again, and combined ether layer volatilizes, residue adds ethyl acetate 0.2～2ml makes dissolving, as need testing solution; Other gets rhizoma alismatis control medicinal material 1～3g, adds water 20～90ml, boils 15～60min, filters, and filtrate is concentrated into about 30ml, and it is 12～13 that the NaOH with 15% is transferred PH, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8, room temperature condition launches down, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color.

3. according to the detection method of the described defatting and poison expelling oral formulations of claim 1, it is characterized in that: content assaying method is:

According to an appendix VID of Chinese Pharmacopoeia version in 2005 high effective liquid chromatography for measuring:

4. according to the detection method of the described defatting and poison expelling oral formulations of claim 3, it is characterized in that: content assaying method is more specifically:

5. according to the detection method of the described defatting and poison expelling oral formulations of claim 1, it is characterized in that: described detection method is:

(4) get tablet or granule, porphyrize is dissolved in water, and transferring PH with NaOH is 12～13, add ether and saturated aqueous common salt and fully vibrate, divide and get ether layer, water layer repeats once combined ether layer according to last method again, volatilize, residue adds ethyl acetate makes dissolving, as need testing solution; Other gets the rhizoma alismatis control medicinal material, adds water boil, filters, and filtrate concentrates, and transferring PH with NaOH is 12～13, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, drawing above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8, room temperature condition launches down, take out, dry, spray is with ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color;

Assay: Gardenoside shines an appendix VID of Chinese Pharmacopoeia version in 2005 high effective liquid chromatography for measuring:

6. according to the detection method of the described defatting and poison expelling oral formulations of claim 5, it is characterized in that: described detection method is:

(2) get 2～8 in tablet or granule 2～8g, pulverize, the 10～40ml that adds diethyl ether, reflux 0.5～2 hour filters, and filtrate volatilizes, and residue adds ethanol 0.5～5ml makes dissolving, as need testing solution; Other gets the ursolic acid reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw need testing solution 5 μ l, reference substance solution 2 μ l, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with sherwood oil-benzene-glacial acetic acid-ethyl acetate=515: 10-30: 0.1-1: 1-10 is developping agent, launches, and takes out, dry, spray is with 10% sulfuric acid ethanol liquid, and it is clear to be heated to the spot colour developing at 90～120 ℃, puts under the 365nm ultraviolet lamp and inspects; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show identical fluorescence spot;

(3) get 2～8 in tablet or granule 2～8g, porphyrize, the 5～30ml that adds diethyl ether, jolting 5～20 minutes, discard ether solution, residue volatilizes, and adds ethyl acetate 5～30ml, reflux 0.5～2 hour, filter, filtrate volatilizes, and residue adds ethanol 0.5～2ml makes dissolving, as need testing solution; Other gets the Gardenoside reference substance, adds ethanol and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binder with the sodium carboxymethyl cellulose, with ethyl acetate-acetone-formic acid-water=5-15: 1-12: 0.5-5: 0.1-1 is developping agent, launches, and takes out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the spot colour developing at 110 ℃, inspects under the daylight; In the test sample chromatogram, with the corresponding position of reference substance chromatogram on, show the spot of same color;

(4) get 10～40 in tablet or granule 10～50g, porphyrize, add water 20～60ml, it is 12～13 that the NaOH with 15% is transferred PH, adds ether 20～60ml and saturated aqueous common salt 2～6ml and fully vibrates, divide and get ether layer, water layer repeats once according to last method again, and combined ether layer volatilizes, residue adds ethyl acetate 0.2～2ml makes dissolving, as need testing solution; Other gets rhizoma alismatis control medicinal material 1～3g, adds water 20～90ml, boils 15～60min, filters, and filtrate is concentrated into about 30ml, and it is 12～13 that the NaOH with 15% is transferred PH, adds diethyl ether and saturated aqueous common salt, shines medicinal material solution in pairs with legal system; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin-layered chromatography, drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with toluene-ethyl acetate-formic acid=5-15: 0.5-5: 0.1-0.8, room temperature condition launches down, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear that hot blast blows to the spot colour developing, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the spot of same color;