CN101336967A - Tongbianling preparation and quality control method - Google Patents

Abstract

The invention relates to a Tongbianling Preparation and a quality control method thereof. The preparation is prepared from Folium Sennae (Cassia angustifolia and/or Cassia acutifolia) 1,200 g, Angelica sinensis 150 g and Cistanche deserticola 150 g by the steps of ultrasonic immersing, percolating, concentrating under reduced pressure, spray drying, spray granulating, and other low-temperature extracting and drying techniques. Compared with the original ministerial standards, the preparation maximally extracts and retains effective ingredients and has stable therapeutic effect. The quality control method comprising identification with thin layer chromatography and content determination ensures stable product quality.

Description

Tongbianling preparation and method of quality control

Technical field

The present invention relates to a kind of preparation technology and method of quality control of medicine, particularly relate to Tongbianling preparation and method of quality control.

Background technology

The TONGBIAN LING capsule records in the 7th in the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation, writes out a prescription to be Folium Sennae 1200g, Radix Angelicae Sinensis 150g, Herba Cistanches 150g; Method for making is to get Radix Angelicae Sinensis 75g to be ground into fine powder; Two flavors such as remaining Radix Angelicae Sinensis and all the other Folium Sennae decoct with water 1.5 hours, filter, and filtrate is condensed into thick paste, adds Chinese Angelica Root, mixing, and cold drying is pulverized, and sieves, and mixing incapsulates and makes 1000, promptly.Folium Sennae contains the Senna fruit glycoside) A, B C, D, chrysophanol, emodin, physcione.The water-soluble portion of Radix Angelicae Sinensis contains ferulic acid, succinic acid, Yan acid, uracil, adenine, scopoletin, umbelliferone, vanillic acid and choline.The chemical analysis of Herba Cistanches is mainly chylocaulous and contains boschnialoside A, B, C, H, foreign eugenol glycoside, and 2-acetyl group ocean eugenol glycoside, seven kinds of phenethanol glycosides of echinacosid composition also contains the Liriodendron glycoside, the acid of 8-table Semen Strychni glycoside, daucosterol, betanin, cupreol.Because the thermal instability of sennoside adopts extractions such as decocting, boiling water immersion, alcohol reflux, concentrates, the method for oven dry obtains the effective ingredient of Folium Sennae, exists extraction rate low, and heated time is long, the problem of effective ingredient thermally labile loss.

Summary of the invention

The objective of the invention is to adopt the extract at low temperature drying process to prepare Tongbianling preparation, effective ingredient is proposed to greatest extent and keep, make therapeutic effect stable.Setting up thin layer simultaneously differentiates and content assaying method.

The present invention is made of following technology contents:

Getting the prescription ratio is Folium Sennae 1200g, Radix Angelicae Sinensis 150g, the medical material combination of Herba Cistanches 150g, the Folium Sennae coarse powder is according to the percolation (an appendix I of Chinese Pharmacopoeia version in 2005 O) under fluid extract and the extractum item, water or 2～4 times of amounts of 20～90% ethanol are made solvent supersonic and are handled after 15～60 minutes or soak after 12～36 hours and carry out percolation, collect the percolate of 6～12 times of amounts of medical material amount, concentrate under reduced pressure at low temperature to relative density is that the ointment of 1.05～1.15 (60 ℃) is spray dried to extract powder, 50% of Radix Angelicae Sinensis is ground into fine powder, all the other Radix Angelicae Sinensis and Herba Cistanches add 6～10 times of decoctings and boil 2 times, each 1～2 hour, filter, it is that the extractum spray drying of 1.15～1.24 (80 ℃) is made extract powder that filtrate is condensed into relative density, Radix Angelicae Sinensis powder mixing with above-mentioned Black Draught powder and pulverizing, add pharmacy acceptable right amount of auxiliary materials in case of necessity, through pill, granulate, dry, tabletting, capsule is filled, and the pharmaceutical formulations technology that packing etc. are necessary is made the acceptable micropill of galenic pharmacy, granule, capsule, ordinary tablet, effervescent tablet, dosage forms such as chewable tablet, promptly.

Method for making can also be that to get the prescription ratio be Folium Sennae 1200g, Radix Angelicae Sinensis 150g, the medical material combination of Herba Cistanches 150g, the Folium Sennae coarse powder is according to the percolation (an appendix I of Chinese Pharmacopoeia version in 2005 O) under fluid extract and the extractum item, water or 2～4 times of amounts of 20～90% ethanol are made solvent supersonic and are handled after 15～60 minutes or soak after 12～36 hours and carry out percolation, collect the percolate of 6～12 times of amounts of medical material amount, concentrate under reduced pressure at low temperature to relative density is that the ointment of 1.05～1.15 (60 ℃) is spray dried to extract powder, 50% of Radix Angelicae Sinensis is ground into fine powder, all the other Radix Angelicae Sinensis and Herba Cistanches add 6～10 times of decoctings and boil 2 times, each 1～2 hour, filter, filtrate is condensed into the extractum that relative density is 1.20～1.26 (80 ℃); Get the Radix Angelicae Sinensis powder of Black Draught powder and pulverizing, add pharmacy acceptable right amount of auxiliary materials in case of necessity, mixing, make adhesive with Radix Angelicae Sinensis Herba Cistanches extractum,, granulate through pill, drying, tabletting, capsule is filled, the pharmaceutical formulations technology that packing etc. are necessary is made the acceptable micropill of galenic pharmacy, granule, capsule, ordinary tablet, effervescent tablet, dosage forms such as chewable tablet, promptly.

The Folium Sennae extraction concentration technique of optimizing is: get Folium Sennae coarse powder (20～30 order) according to the percolation (an appendix I of Chinese Pharmacopoeia version in 2005 O) under fluid extract and the extractum item, do the solvent supersonic processing with triplication 50% ethanol and carry out percolation after 30 minutes, collect the percolate of 8 times of amounts of medical material, concentrate under reduced pressure at low temperature to relative density is the clear paste of 1.05～1.15 (60 ℃), spray drying (150～170 ℃ of inlet temperature, 100～105 ℃ of leaving air temps), make extract powder.

This product quality standard mainly comprise following one or more, be applicable to that all pharmacy of this product can accept the quality control of dosage form:

(1) gets this product an amount of (being equivalent to Folium Sennae 0.5g approximately), add methanol 20ml, supersound process 30 minutes, centrifugal, draw supernatant, evaporate to dryness, residue adds water 10ml makes dissolving, puts in the round-bottomed flask of 100ml, adds 10.5% liquor ferri trichloridi 20ml, shake up, connect condensing tube, put in the water-bath reflux after 20 minutes, should keep the water-bath liquid level on the flask liquid level, add hydrochloric acid 1ml immediately, continue to reflux 20 minutes, jolting constantly is to precipitation dissolving fully, put cold, mixed liquor is moved in the separatory funnel, extract 3 times, each 25ml with the ether jolting, combined ether liquid, tepor is evaporated to dried, and residue adds methanol 1ml makes dissolving, as need testing solution.Other gets Folium Sennae control medicinal material 0.5g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 B), draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel H lamellae of adhesive with the sodium carboxymethyl cellulose, upper solution with petroleum ether (30～60 ℃)-Ethyl formate-formic acid (15: 5: 1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color; Put in the ammonia steam smoked after, under daylight, inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.

(2) get this 6g, put in the apparatus,Soxhlet's, add methanol 100ml, extracted 1 hour, boil off methanol, residue adds water 50ml, and heating makes dissolving, puts cold, with ether extraction three times, each 15ml, combined ether liquid is with 20% sodium carbonate liquor extraction three times, each 15ml divides and gets alkali liquor, adds hydrochloric acid and regulates pH value 2～3, adds benzene 15ml, extract once, discard benzene liquid, add diethyl ether again and extract three times, each 15ml, ether liquid merges, and volatilizes, and residue adds methanol 1ml makes dissolving, as need testing solution.Other gets the ferulic acid reference substance, adds methanol and makes the solution that contains 1mg among every 1ml, in contrast product solution.Test according to thin layer chromatography (37 pages of appendix of Chinese Pharmacopoeia version in 1985), draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same and contain on the silica gel g thin-layer plate that 0.3% sodium carboxymethyl cellulose is a binding agent, with benzene-glacial acetic acid-methanol (30: 1: 3) is developing solvent, launch, take out, dry, under ultra-violet lamp (365nm), inspect.For look in the product chromatograph with the corresponding position of reference substance chromatograph on, the fluorescence speckle of apparent same color.

[assay] Sennoside A and Sennoside B are measured according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D).

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Contain 0.25mmol/L four heptyl ammonium bromide and the 0.25mmol/L sodium hydrogen phosphate is a mobile phase with methanol-acetonitrile-0.1% phosphoric acid (40: 15: 45); The detection wavelength is 344nm.Number of theoretical plate is pressed the Sennoside B peak and is calculated, and should be not less than 6500, and the separating degree of Sennoside A, B peak and adjacent impurity peaks should be greater than 2.

Learn from else's experience 12 hours Sennoside As of drying under reduced pressure and Sennoside B reference substance of the preparation of reference substance solution is an amount of, accurately claims surely, puts in the brown bottle, adds 50% methanol solution and makes every 1ml to contain Sennoside A be that 80 μ g and Sennoside B are the solution of 0.35mg, promptly.

This product under the weight differential item is got in the preparation of need testing solution, and porphyrize is got an amount of (being equivalent to sennoside B 18mg approximately), and accurate the title decides, put in the conical flask, the accurate 50% methanol solution 50ml that adds, supersound process 15 minutes (30～40 ℃) is put cold, filter, get subsequent filtrate, promptly.

Accurate each the 10 μ l of above-mentioned two kinds of solution that draw of algoscopy inject chromatograph of liquid, measure, promptly.

The pharmacy personnel can make improvement and raising without prejudice to essence of the present invention to the present invention, belong to category of the present invention.

The specific embodiment:

The present invention is described in more detail below in conjunction with embodiment, but the invention is not restricted to these embodiment.

Embodiment 1 granule (Sugarless type)

[prescription] Folium Sennae 7200g Radix Angelicae Sinensis 900g Herba Cistanches 900g

[method for making] gets Folium Sennae coarse powder (20～30 order) according to the percolation (an appendix I of Chinese Pharmacopoeia version in 2005 O) under fluid extract and the extractum item, do the solvent supersonic processing with triplication 50% ethanol and carry out percolation after 30 minutes, collect the percolate of 8 times of amounts of medical material, concentrate under reduced pressure at low temperature to relative density is the clear paste of 1.05～1.15 (60 ℃), spray drying (150～170 ℃ of inlet temperature, 100～105 ℃ of leaving air temps), make extract powder; Radix Angelicae Sinensis 450g is ground into fine powder, and all the other Radix Angelicae Sinensis and Herba Cistanches add 8 times of decoctings and boil 2 times, and each 1.5 hours, filter, filtrate is condensed into the extractum that relative density is 1.20～1.26 (80 ℃); Get the Black Draught powder, the Radix Angelicae Sinensis powder of pulverizing, dextrin 1200g, stevioside 120g, starch 150g, mixing is made adhesive with Radix Angelicae Sinensis Herba Cistanches extractum, and boiling granulating adds magnesium stearate 12g, mixing, packing is made 1000 bags, promptly.

Embodiment 2 tablets

[prescription] Folium Sennae 1200g Radix Angelicae Sinensis 150g Herba Cistanches 150g

[method for making] gets Folium Sennae coarse powder (20 order powder), according to the percolation under fluid extract and the extractum item (an appendix I of Chinese Pharmacopoeia version in 2005 O), do the solvent supersonic processing with 30% ethanol triplication and carry out percolation after 30 minutes, collect the percolate of 8 times of amounts of medical material, concentrate under reduced pressure at low temperature to relative density is the ointment of 1.16～1.22 (60 ℃), spray drying (160～170 ℃ of inlet temperature, 50～60 ℃ of leaving air temps) becomes extract powder.Radix Angelicae Sinensis 75g is ground into fine powder, and all the other Radix Angelicae Sinensis and Herba Cistanches add 8 times of water gagings and decoct 2 times, and each 1.5 hours, filter, filtrate is condensed into the extractum that relative density is 1.20～1.26 (80 ℃); Get the Radix Angelicae Sinensis powder of Black Draught powder and pulverizing, mixing is made adhesive with Radix Angelicae Sinensis Herba Cistanches extractum, and boiling granulating adds magnesium stearate 2g, mixing, and tabletting is made 1000, promptly.

Embodiment 3 capsules

[prescription] Folium Sennae 1200g Radix Angelicae Sinensis 150g Herba Cistanches 150g

[method for making] gets Folium Sennae coarse powder (20 order powder), according to the percolation under fluid extract and the extractum item (appendix I0 of Chinese Pharmacopoeia version in 2005), adding triplication water is that the solvent supersonic processing was carried out percolation after 30 minutes, collect the percolate of 8 times of amounts of medical material, concentrate under reduced pressure at low temperature to relative density is the ointment of 1.16～1.22 (60 ℃), spray drying (160～170 ℃ of inlet temperature, 50～60 ℃ of leaving air temps) becomes extract powder.Radix Angelicae Sinensis 75g is ground into fine powder, and all the other Radix Angelicae Sinensis and Herba Cistanches add 8 times of water gagings and decoct 2 times, and each 1.5 hours, filter, filtrate is condensed into the extractum that relative density is 1.20～1.26 (80 ℃); Get the Radix Angelicae Sinensis powder of Black Draught powder and pulverizing, mixing is made adhesive with Radix Angelicae Sinensis Herba Cistanches extractum, and boiling granulating adds magnesium stearate 2g, mixing, and capsule is filled, and makes 1000, promptly.

The capsule that embodiment 4 gets the foregoing description 3 carries out the quality standard test

(1) be the thin layer discriminating of Folium Sennae, get this product content 0.15g, warp and scarce Folium Sennae negative sample, the contrast of Folium Sennae control medicinal material, it is clear to develop the color, and negative sample is noiseless, can adopt.Folium Sennae control medicinal material Nat'l Pharmaceutical ﹠ Biological Products Control Institute lot number: 120996-200504.

[assay] Sennoside A and Sennoside B are measured according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D).

Instrument and reagent

High performance liquid chromatograph PII 200II type high pressure constant flow pump LabAlliance UV, visible light wavelength detecting

The characteristic spectrum data workstation chromatographic column Yi Lite HypersilODS C18 5um 4.6 * 200mm of Erie

Chromatograph acetonitrile, chromatograph methanol Tian Jinsi friend biomedical technology company limited

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Contain 0.25mmol/L four heptyl ammonium bromide and the 0.25mmol/L sodium hydrogen phosphate is a mobile phase with methanol-acetonitrile-0.1% phosphoric acid (40: 15: 45); The detection wavelength is 344nm.Number of theoretical plate is pressed the Sennoside B peak and is calculated, and should be not less than 6500, and the separating degree of Sennoside A, B peak and adjacent impurity peaks should be greater than 2.

Learn from else's experience 12 hours Sennoside As of drying under reduced pressure and Sennoside B reference substance of the preparation of reference substance solution is an amount of, accurately claims surely, puts in the brown bottle, adds 50% methanol solution and makes every 1ml to contain Sennoside A be that 80 μ g and Sennoside B are the solution of 0.35mg, promptly.

This product content under the weight differential item is got in the preparation of need testing solution, and porphyrize is got 0.25g, accurate claims surely, put in the conical flask, and the accurate 50% methanol solution 100ml that adds, supersound process 15 minutes (30～40 ℃) is put coldly, filters, and gets subsequent filtrate, promptly.

Accurate each the 10 μ l of above-mentioned two kinds of solution that draw of algoscopy inject chromatograph of liquid, measure, promptly.

Standard curve

The preparation of reference substance solution:

Learn from else's experience 12 hours Sennoside As of drying under reduced pressure and Sennoside B reference substance is an amount of, accurately claims surely, puts in the brown bottle, add 50% methanol solution make every 1ml to contain Sennoside B be 2320 μ g for and Sennoside A be the solution of 600 μ g, promptly.

With every 1ml to contain Sennoside B be 2320 μ g for and Sennoside A be that the solution of 600 μ g is that mother solution is mixed with the solution product solution in contrast that contains sennoside B 1160 μ g/ml and Sennoside A 300 μ g/ml, sennoside B 580 μ g/ml and Sennoside A 150 μ g/ml, sennoside B 232 μ g/ml and Sennoside A 60 μ g/ml, sennoside B 116 μ g/ml and Sennoside A 30 μ g/ml respectively.

Accurate each the 20 μ l of above-mentioned reference substance solution that draw inject chromatograph of liquid, measure.

Sennoside B concentration is respectively 2320 μ g/ml, 1160 μ g/ml, 580 μ g/ml, 232 μ g/ml, 116 μ g/ml.Corresponding peak area is respectively 14145.01,6873.12,3479.12,1350.41,695.33.

The sennoside B regression curve is Y (peak area)=6.10083X (concentration)-69.8964 r=0.99991

Sennoside A concentration is respectively 600 μ g/ml, 300 μ g/ml, 150 μ g/ml, 60 μ g/ml, 30 μ g/ml.Corresponding peak area is respectively 3487.87,1751.86,869.68,331.31,170.22.

The Sennoside A regression curve is Y (peak area)=5.83390X (concentration)-7.9411 r=0.99998

The range of linearity of sennoside B is that the range of linearity of 116～2320 μ g/ml, Sennoside A is 30～600 μ g/ml, and standard curve all was similar to initial point, adopts one point external standard method quantitative.

The selection of need testing solution preparation method:

List of references, the test sample preparation method: get this product content under the weight differential item, porphyrize is respectively got 0.25g, the accurate title, decide, put in the conical flask accurate respectively 50% methanol, methanol, 70% methanol, 0.1% sodium bicarbonate solution 50ml, the supersound process 15 minutes (30～40 ℃) of adding, put cold, filter, get subsequent filtrate, promptly.

Prepare test sample with above-mentioned test sample preparation method, measure through sample introduction, good with 0.1% sodium bicarbonate solution and 50% methanol result, consider facile hydrolysis under the sennoside alkali condition, select 50% methanol to make the preparation solvent, the peak shape separating degree is suitable, and is negative noiseless.

Precision

Same sample continuous sample introduction is measured 5 times, sennoside B peak area (mv.sec) is respectively: 2653.6,2638.86,2704.02,2738.14,2693.96, Sennoside A peak area (mv.sec) is respectively: 776.56,769.86,790.03,795.68,784.74, the relative standard deviation of sennoside B, Sennoside A is respectively 1.51%, 1.32%, less than 3.0%.

Stability

Same sample, measure respectively after back 30 minutes, 2 hours, 4 hours, 8 hours, 12 hours in preparation, sennoside B peak area (mv.sec) is respectively: 2467.28,2512.9,2466.27,2486.63,2506.59, Sennoside A peak area (mv.sec) is respectively: 719.60,728.58,712.19,751.02,736.67, sennoside B, Sennoside A relative standard deviation are respectively 0.87%, 2.07%, less than 5.0%, show the sample solution good stability.

Repeatability

Same sample is got 5 parts, each about 0.25g, and accurate the title, decide, and prepares need testing solution by the need testing solution preparation method under the assay item, and accurate each the 20 μ l of above-mentioned need testing solution that draw inject chromatograph of liquid, mensuration.Sampling amount is respectively: 0.2737,0.2562g, 0.2513g, 0.2507g, 0.2501g, the Sennoside A peak area is respectively: 776.34,728.31,665.08,695.94,695.98, Sennoside A content (mg/g) content is respectively: 5.17,5.17,4.82,5.06,5.06, average 5.06mg/g, sennoside B peak area (mv.sec) is respectively: 2631.99,2497.87,2478.79,2552.09,2526.27, sennoside B content (mg/g) is respectively: 19.80,20.08,20.30,20.95,20.80, average 20.39mg/g, Sennoside A and sennoside B relative standard deviation are respectively 2.79%, 2.37%, less than 5.0%.

Average recovery

Get 5 parts in the sample (about 0.25g) of known content, The accurate title, decide, and the every 1ml of accurate adding contains Sennoside A 3.48mg, sennoside B 12.84mgEach 1.5ml of reference substance solution, evaporate to dryness prepares need testing solution by the need testing solution preparation method under the assay item, accurate each the 20 μ l of above-mentioned need testing solution that draw inject chromatograph of liquid, measure.The average average recovery of sennoside B, Sennoside A is respectively 98.93%, 99.18%.

Average recovery Sennoside A determination data

Average recovery sennoside B determination data

Sample determination

Adopt high performance liquid chromatography to measure to three batches of pilot products.

[assay] Sennoside A and Sennoside B are measured according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D).

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Contain 0.25mmol/L four heptyl ammonium bromide and the 0.25mmol/L sodium hydrogen phosphate is a mobile phase with methanol-acetonitrile-0.1% phosphoric acid (40: 15: 45); The detection wavelength is 344nm.Number of theoretical plate is pressed the Sennoside B peak and is calculated, and should be not less than 6500, and the separating degree of Sennoside A, B peak and adjacent impurity peaks should be greater than 2.

Learn from else's experience 12 hours Sennoside As of drying under reduced pressure and Sennoside B reference substance of the preparation of reference substance solution is an amount of, accurately claims surely, puts in the brown bottle, adds 50% methanol solution and makes every 1ml to contain Sennoside A be that 80 μ g and Sennoside B are the solution of 0.35mg, promptly.

This product content under the weight differential item is got in the preparation of need testing solution, and porphyrize is got 0.25g, accurate claims surely, put in the conical flask, and the accurate 50% methanol solution 50ml that adds, supersound process 15 minutes (30～40 ℃) is put coldly, filters, and gets subsequent filtrate, promptly.

Accurate each the 10 μ l of above-mentioned two kinds of solution that draw of algoscopy inject chromatograph of liquid, measure, promptly.

Three batch sample assay tables of data

Lot number	Sampling amount (g)	The Sennoside A peak area	The sennoside B peak area	Sennoside A (mg/ sheet)	Sennoside B (mg/ sheet)	Total content (mg/ sheet)
							0709001	0.2564	714.20	2471.51	4.86	21.07	25.93

0709002	0.2575	724.89	2471.88	4.92	20.99	25.91
							0709003	0.2578	654.52	2465.51	4.44	20.93	25.37

Prescription consumption and three batches of pilot scale determination datas according to Folium Sennae in this product determine that every of this product contains Folium Sennae with sennoside B (C ₁₅H ₁₀O ₅And Sennoside A (C ₁₅H ₁₀O ₄) the total amount meter, must not be less than 22mg.

Embodiment 5: the capsule of getting the foregoing description 3 carries out stability test

1, main test apparatus: high performance liquid chromatograph (the special scientific instrument company limited of Erie), Tianjin, analytical balance AY120 island

2, medicine: supply test agent: TONGBIAN LING capsule self-control lot number is: 0709001,0709002,0709003, Sennoside A and sennoside B reference substance (self-control) content is all greater than 98%, Folium Sennae control medicinal material Nat'l Pharmaceutical ﹠ Biological Products Control Institute lot number: 120996-200504.

3, accelerated stability test method: TONGBIAN LING capsule (0709001,0709002,0709003) aluminium-plastic panel packing (listing packing), 40 ± 2 ℃ of temperature, placed 6 months under the condition of relative humidity 75% ± 5% (saturated aqueous common salt), respectively at 0 month, 1 the end of month, 2 the end of month, 3 the end of month, sampling in 6 months once, detect by stable high spot reviews project (character, discriminating, inspection, content).

4, long-term stable experiment method: TONGBIAN LING capsule (0709001,0709002,0709003) aluminium-plastic panel packing (listing packing) 25 ± 2 ℃ of temperature, is placed under the condition of relative humidity 60% ± 10%.Respectively at 0 month, 3 the end of month, 6 the end of month, detect by stable high spot reviews project (character, discriminating, inspection, content).

5, the stability test result: TONGBIAN LING capsule accelerated test is at (relative humidity 75% ± 5%, 40 ℃ ± 2 ℃ of temperature) test under the condition, long term test is at (relative humidity 60% ± 10%, 25 ℃ ± 2 ℃ of temperature) test under the condition, observed 6 months continuously respectively, therebetween to character, differentiate, check, projects such as content detect, and at 0 month, June, the foot couple microbial limit was investigated, the result has no significant change, the regulation that meets TONGBIAN LING capsule quality standard (draft), the TONGBIAN LING capsule quality is stable, and the expection stable phase of accelerated test is 24 months, and long-term stable experiment is still underway.Packaging material do not have influence to quality, tentative 24 months of effect duration.

Claims (4)

1 Tongbianling preparation and method of quality control, it is characterized by the prescription ratio is Folium Sennae 1200g, Radix Angelicae Sinensis 150g, the medical material combination of Herba Cistanches 150g, the Folium Sennae coarse powder is according to the percolation (an appendix I of Chinese Pharmacopoeia version in 2005 O) under fluid extract and the extractum item, water or 2～4 times of amounts of 20～90% ethanol are made solvent supersonic and are handled after 15～60 minutes or soak after 12～36 hours and carry out percolation, collect the percolate of 6～12 times of amounts of medical material amount, concentrate under reduced pressure at low temperature to relative density is that the ointment of 1.05～1.15 (60 ℃) is spray dried to extract powder, 50% of Radix Angelicae Sinensis is ground into fine powder, all the other Radix Angelicae Sinensis and Herba Cistanches add 6～10 times of decoctings and boil 2 times, each 1～2 hour, filter, it is that the extractum spray drying of 1.15～1.24 (80 ℃) is made extract powder that filtrate is condensed into relative density, Radix Angelicae Sinensis powder mixing with above-mentioned Black Draught powder and pulverizing, add pharmacy acceptable right amount of auxiliary materials in case of necessity, through pill, granulate, drying, tabletting, capsule is filled, the pharmaceutical formulations technology that packing etc. are necessary, make the acceptable micropill of galenic pharmacy, granule, capsule, ordinary tablet, effervescent tablet, dosage forms such as chewable tablet, promptly.

Described Tongbianling preparation of 2 claim 1 and method of quality control, it is characterized by method for making and can also be that to get the prescription ratio be Folium Sennae 1200g, Radix Angelicae Sinensis 150g, the medical material combination of Herba Cistanches 150g, the Folium Sennae coarse powder is according to the percolation (appendix IO of Chinese Pharmacopoeia version in 2005) under fluid extract and the extractum item, water or 2～4 times of amounts of 20～90% ethanol are made solvent supersonic and are handled after 15～60 minutes or soak after 12～36 hours and carry out percolation, collect the percolate of 6～12 times of amounts of medical material amount, concentrate under reduced pressure at low temperature to relative density is that the ointment of 1.05～1.15 (60 ℃) is spray dried to extract powder, 50% of Radix Angelicae Sinensis is ground into fine powder, all the other Radix Angelicae Sinensis and Herba Cistanches add 6～10 times of decoctings and boil 2 times, each 1～2 hour, filter, filtrate is condensed into the extractum that relative density is 1.20～1.26 (80 ℃); Get the Radix Angelicae Sinensis powder of Black Draught powder and pulverizing, add pharmacy acceptable right amount of auxiliary materials in case of necessity, mixing, make adhesive with Radix Angelicae Sinensis Herba Cistanches extractum,, granulate through pill, drying, tabletting, capsule is filled, the pharmaceutical formulations technology that packing etc. are necessary is made the acceptable micropill of galenic pharmacy, granule, capsule, ordinary tablet, effervescent tablet, dosage forms such as chewable tablet, promptly.

3 claim 1 or 2 described Tongbianling preparation and method of quality control, the Folium Sennae extraction concentration technique that it is characterized by optimization is: get Folium Sennae coarse powder (20～30 order) according to the percolation (an appendix I of Chinese Pharmacopoeia version in 2005 O) under fluid extract and the extractum item, do the solvent supersonic processing with triplication 50% ethanol and carry out percolation after 30 minutes, collect the percolate of 8 times of amounts of medical material, concentrate under reduced pressure at low temperature to relative density is the clear paste of 1.05～1.15 (60 ℃), spray drying (150～170 ℃ of inlet temperature, 100～105 ℃ of leaving air temps), make extract powder.

4 claim 1 or 2 described Tongbianling preparation and method of quality control, it is characterized by this product quality standard mainly comprise following one or more, be applicable to that all pharmacy of this product can accept the quality control of dosage form:

(1) gets this product an amount of (being equivalent to Folium Sennae 0.5g approximately), add methanol 20ml, supersound process 30 minutes, centrifugal, draw supernatant, evaporate to dryness, residue adds water 10ml makes dissolving, puts in the round-bottomed flask of 100ml, adds 10.5% liquor ferri trichloridi 20ml, shake up, connect condensing tube, put in the water-bath reflux after 20 minutes, should keep the water-bath liquid level on the flask liquid level, add hydrochloric acid 1ml immediately, continue to reflux 20 minutes, jolting constantly is to precipitation dissolving fully, put cold, mixed liquor is moved in the separatory funnel, extract 3 times, each 25ml with the ether jolting, combined ether liquid, tepor is evaporated to dried, and residue adds methanol 1ml makes dissolving, as need testing solution.Other gets Folium Sennae control medicinal material 0.5g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 B), draw each 10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel H lamellae of adhesive with the sodium carboxymethyl cellulose, upper solution with petroleum ether (30～60 ℃)-Ethyl formate-formic acid (15: 5: 1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color; Put in the ammonia steam smoked after, under daylight, inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.

(2) get this 6g, put in the apparatus,Soxhlet's, add methanol 100ml, extracted 1 hour, boil off methanol, residue adds water 50ml, and heating makes dissolving, puts cold, with ether extraction three times, each 15ml, combined ether liquid is with 20% sodium carbonate liquor extraction three times, each 15ml divides and gets alkali liquor, adds hydrochloric acid and regulates pH value 2～3, adds benzene 15ml, extract once, discard benzene liquid, add diethyl ether again and extract three times, each 15ml, ether liquid merges, and volatilizes, and residue adds methanol 1ml makes dissolving, as need testing solution.Other gets the ferulic acid reference substance, adds methanol and makes the solution that contains 1mg among every 1ml, in contrast product solution.Test according to thin layer chromatography (37 pages of appendix of Chinese Pharmacopoeia version in 1985), draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same and contain on the silica gel g thin-layer plate that 0.3% sodium carboxymethyl cellulose is a binding agent, with benzene-glacial acetic acid-methanol (30: 1: 3) is developing solvent, launch, take out, dry, under ultra-violet lamp (365nm), inspect.For look in the product chromatograph with the corresponding position of reference substance chromatograph on, the fluorescence speckle of apparent same color.

[assay] Sennoside A and Sennoside B are measured according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2005 D).

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Contain 0.25mmol/L four heptyl ammonium bromide and the 0.25mmol/L sodium hydrogen phosphate is a mobile phase with methanol-acetonitrile-0.1% phosphoric acid (40: 15: 45); The detection wavelength is 344nm.Number of theoretical plate is pressed the Sennoside B peak and is calculated, and should be not less than 6500, and the separating degree of Sennoside A, B peak and adjacent impurity peaks should be greater than 2.

Learn from else's experience 12 hours Sennoside As of drying under reduced pressure and Sennoside B reference substance of the preparation of reference substance solution is an amount of, accurately claims surely, puts in the brown bottle, adds 50% methanol solution and makes every 1ml to contain Sennoside A be that 80 μ g and Sennoside B are the solution of 0.35mg, promptly.

This product under the weight differential item is got in the preparation of need testing solution, and porphyrize is got an amount of (being equivalent to sennoside B 18mg approximately), and accurate the title decides, put in the conical flask, the accurate 50% methanol solution 50ml that adds, supersound process 15 minutes (30～40 ℃) is put cold, filter, get subsequent filtrate, promptly.

Accurate each the 10 μ l of above-mentioned two kinds of solution that draw of algoscopy inject chromatograph of liquid, measure, promptly.