CN1903325A - Blood-sugar lowering A prepn. for treating diabetes, its prepn. method and quality-control method - Google Patents
Blood-sugar lowering A prepn. for treating diabetes, its prepn. method and quality-control method Download PDFInfo
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Abstract
A hypoglycemic medicine A in the form of capsule, particles, or pill for treating diabetes is prepared from 5 Chinese-medicinal materials including astragalus root, rehmannia root, pseudostellaria root, trichosanthes root, etc. Its preparing process and quality control method are also disclosed.
Description
Technical field: the present invention relates to a kind of blood sugar lowering medicine A for the treatment of diabetes and preparation method thereof and method of quality control, belong to the technical field of herbal pharmaceutical.
Background technology: blood sugar lowering first sheet records in Drug Standard of Ministry of Public Health of the Peoples Republic of China, clinical practice for many years, prescription is rigorous, compatibility is reasonable, taken in national essential drugs catalogue in 2004, clinical practice obtains the approval and the welcome of extensive patients, has solid clinical basis, have no side effect determined curative effect.By market survey, blood sugar lowering first sheet cooperates antidiabetic drug gliclazide sheet to sell, and can remedy the symptom of quenching one's thirst that Western medicine can not be alleviated, and market potential is bigger.But the quality control standard of blood sugar lowering first sheet is simple, and product quality is wayward, and tablet is through operations such as granulation, tablettings in addition, and the medicine absorption in vivo will be passed through processes such as disintegrate, granule dissolving, and drug absorption is slow.
Summary of the invention:
The objective of the invention is to: a kind of blood sugar lowering medicine A for the treatment of diabetes and preparation method thereof and method of quality control are provided, the present invention studies and improves on the basis of existing blood sugar lowering first sheet, it is prepared into capsule, granule, the watered pill or drop pill, drug absorption is rapid, and each dose reduces; Supplementary product consumption is few, and production process is simplified, and has reduced production cost; And improved quality control standard.
The present invention constitutes like this: it is to process capsule, granule, the watered pill or the drop pill that Rhizoma Polygonati 642.6g, Radix Rehmanniae 642.6g, Radix Pseudostellariae 642.6g and Radix Trichosanthis 642.6g make with Radix Astragali 642.6g, wine.
The preparation method of the blood sugar lowering medicine A of treatment diabetes is: get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add for the first time 10 times of water gagings, decocted 2 hours, add for the second time 8 times of water gagings, decocted 1 hour, and added 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, add the Radix Pseudostellariae fine powder, mixing, drying, be ground into fine powder, add suitable adjuvant and make different preparations.
Blood sugar lowering nail gelatin wafer is preparation like this: get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add for the first time 10 times of water gagings, decocted 2 hours, add for the second time 8 times of water gagings, decocted 1 hour, and added 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, adds ethanol and makes that to contain that alcohol measures be 75%, stirs evenly, left standstill 48 hours, and filtered, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, adds the Radix Pseudostellariae fine powder, mixing, drying is ground into fine powder, the dress enteric coated capsule, promptly.
The agent of blood sugar lowering Jia Keli is preparation like this: get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add for the first time 10 times of water gagings, decocted 2 hours, add for the second time 8 times of water gagings, decocted 1 hour, and added 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, adds the Radix Pseudostellariae fine powder, the dextrin of 1～4 times of amount, an amount of protein sugar or cyclamate, an amount of essence, the system granule, drying, packing, promptly.
The blood sugar lowering first watered pill is preparation like this: get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add 10 times of water gagings for the first time, decocted 2 hours, and added 8 times of water gagings for the second time, decocted 1 hour, add 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, adds the Radix Pseudostellariae fine powder, mixing, drying is ground into fine powder, with the general ball of making of suitable quantity of water, drying, promptly.
Blood sugar lowering first drop pill prepares like this: get the Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis and decoct with water three times, add 10 times of water gagings for the first time, decocted 2 hours, add 8 times of water gagings for the second time, decocted 1 hour, add 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1200ml, adds ethanol and makes that to contain that alcohol measures be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, add PEG6000 and PEG4000 500g～600g, drip and make ball, promptly.
The method of quality control of blood sugar lowering medicine A mainly comprise in character, discriminating, inspection and the assay project partly or entirely, wherein differentiate to comprise microexamination and the thin layer chromatography of the Radix Astragali, Rhizoma Polygonati, Radix Pseudostellariae, Radix Trichosanthis in the preparation is differentiated; Assay is the assay to the contained astragaloside of the Radix Astragali in the preparation.
The discrimination method of the Radix Astragali is to be contrast with Radix Astragali control medicinal material, and with chloroform: methanol=8.5: 0.5 is the thin layer chromatography of developing solvent; The discrimination method of Rhizoma Polygonati is to be contrast with the Rhizoma Polygonati control medicinal material, and with chloroform: methanol: acetic acid=5: 4: 1 is the thin layer chromatography of developing solvent; The discrimination method of Radix Pseudostellariae is to be contrast with the Radix Pseudostellariae control medicinal material, and with chloroform: methanol: 14% ammonia spirit=2: 3: 1 is the thin layer chromatography of developing solvent; The discrimination method of Radix Trichosanthis is to be contrast with the Radix Trichosanthis control medicinal material, and with n-butyl alcohol: ethanol: glacial acetic acid: water=8: 2: 2: 3 is the thin layer chromatography of developing solvent.
Concrete discrimination method comprises the part or all of of following project:
(1) get this preparation, put microscopically and observe: starch grain is numerous, simple grain five similar rounds and semicircle diameter 4～20 μ m, and omphalion is slit-like, and accidental composite grain is integrated by 2～3; The conduit master is screw thread and reticulate vessel, diameter 10～22 μ m;
(2) get this preparation or its content 1.5g under the content uniformity item, add ethyl acetate 20ml, reflux 1 hour filters, and filtrate is concentrated into about 1ml, as need testing solution; Other gets Radix Astragali control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=8.5: 0.5 is developing solvent, launch, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with the sodium carbonate test solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get this preparation or its content 2g under the content uniformity item, add ethanol 20ml, reflux 2 hours filters, and filtrate evaporate to dryness, residue add acetone 10ml makes dissolving, filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Rhizoma Polygonati control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: acetic acid=5: 4: 1 is developing solvent, launch, take out, dry, spray is with 5% phosphomolybdic acid ethanol solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(4) get this preparation or its content 3g under the content uniformity item, add methanol 30ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add 30 milliliters of heating for dissolving of water, with ether extraction 3 times, and each 30ml; Water layer is flung to ether, with water saturated n-butanol extraction 3 times, is followed successively by 40,30,20ml, merges n-butyl alcohol, adds 0.5 milliliter of ammonia, again with n-butyl alcohol saturated be washed to neutrality, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Pseudostellariae control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: 14% ammonia spirit=2: 3: 1 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, 105 ℃ to be heated to speckle colour developing clear, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(5) get this preparation or its content 2g under the content uniformity item, add methanol 25ml, supersound process 30 minutes filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Radix Trichosanthis control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with n-butyl alcohol: ethanol: glacial acetic acid: water=8: 2: 2: 3 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, and 105 ℃ to be heated to the speckle colour developing clear; Put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
The content assaying method of astragaloside is to be contrast with the astragaloside reference substance in the Radix Astragali, and with acetonitrile: water=36: 64 is the high performance liquid chromatography of mobile phase.
Concrete content assaying method is:
According to an appendix VI of Chinese Pharmacopoeia version in 2000 D high effective liquid chromatography for measuring:
The suitable application test of system is a filler with the carbon octadecylsilane chemically bonded silica; Acetonitrile: water=36: 64 is mobile phase; Detect with evaporative light scattering detector; Theoretical cam curve should be not less than 6000 by the astragaloside peak;
It is an amount of that the preparation precision of reference substance solution takes by weighing the astragaloside reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 0.40mg, promptly;
This preparation or its content 6g under the content uniformity item got in the preparation of need testing solution, the accurate title, decide, put in the tool plug conical flask, precision adds methanol 50ml, claims to decide weight, supersound process is 1 hour under 250W, 29～34kHz condition, put coldly, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 25ml that draws, evaporate to dryness, residue is with adding water saturated n-butyl alcohol 50ml dissolving, wash with ammonia solution 20ml, divide and get n-butyl alcohol liquid, evaporate to dryness, residue is with dissolve with methanol and be settled to 5ml, shake up, promptly;
Accurate reference substance solution each 10 μ l, the 20 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, with external standard two-point method natural logrithm Equation for Calculating, promptly;
Every of this capsule contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.13mg.Granule contains the Radix Astragali with astragaloside C for every bag
41H
68O
14Meter must not be less than 0.2～0.4mg; The every 1g of the watered pill contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.3mg; The every 1g of drop pill contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.13mg.
Method of quality control of the present invention comprises:
Character: capsule is an enteric coated capsule, and its content is a brown ceramic powder; Feeble QI perfume (or spice), sweet-bitter flavor;
For granule, medicine is a brown particle; Feeble QI perfume (or spice), sweet-bitter flavor;
For the watered pill, medicine is the brownish black ball; Feeble QI perfume (or spice), sweet-bitter flavor;
For drop pill, medicine is the dark-brown ball; Feeble QI perfume (or spice), sweet-bitter flavor;
Differentiate: (1) gets this preparation, and put microscopically and observe: starch grain is numerous, simple grain five similar rounds and semicircle diameter 4～20 μ m, and omphalion is slit-like, and accidental composite grain is integrated by 2～3; The conduit master is screw thread and reticulate vessel, diameter 10～22 μ m;
(2) get this preparation or its content 1.5g under the content uniformity item, add ethyl acetate 20ml, reflux 1 hour filters, and filtrate is concentrated into about 1ml, as need testing solution; Other gets Radix Astragali control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=8.5: 0.5 is developing solvent, launch, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with the sodium carbonate test solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get this preparation or its content 2g under the content uniformity item, add ethanol 20ml, reflux 2 hours filters, and filtrate evaporate to dryness, residue add acetone 10ml makes dissolving, filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Rhizoma Polygonati control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: acetic acid=5: 4: 1 is developing solvent, launch, take out, dry, spray is with 5% phosphomolybdic acid ethanol solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(4) get this preparation or its content 3g under the content uniformity item, add methanol 30ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add 30 milliliters of heating for dissolving of water, with ether extraction 3 times, and each 30ml; Water layer is flung to ether, with water saturated n-butanol extraction 3 times, is followed successively by 40,30,20ml, merges n-butyl alcohol, adds 0.5 milliliter of ammonia, again with n-butyl alcohol saturated be washed to neutrality, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Pseudostellariae control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: 14% ammonia spirit=2: 3: 1 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, 105 ℃ to be heated to speckle colour developing clear, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(5) get this preparation or its content 2g under the content uniformity item, add methanol 25ml, supersound process 30 minutes filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Radix Trichosanthis control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with n-butyl alcohol: ethanol: glacial acetic acid: water=8: 2: 2: 3 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, and 105 ℃ to be heated to the speckle colour developing clear; Put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
Check: should meet relevant every regulation under each preparation item of appendix I of Chinese Pharmacopoeia version in 2000;
Assay: shine an appendix VI of Chinese Pharmacopoeia version in 2000 D high effective liquid chromatography for measuring:
The suitable application test of system is a filler with the carbon octadecylsilane chemically bonded silica; Acetonitrile: water=36: 64 is mobile phase; Detect with evaporative light scattering detector; Theoretical cam curve should be not less than 6000 by the astragaloside peak;
It is an amount of that the preparation precision of reference substance solution takes by weighing the astragaloside reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 0.40mg, promptly;
This preparation or its content 6g under the content uniformity item got in the preparation of need testing solution, the accurate title, decide, put in the tool plug conical flask, precision adds methanol 50ml, claims to decide weight, supersound process is 1 hour under 250W, 29～34kHz condition, put coldly, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 25ml that draws, evaporate to dryness, residue is with adding water saturated n-butyl alcohol 50ml dissolving, wash with ammonia solution 20ml, divide and get n-butyl alcohol liquid, evaporate to dryness, residue is with dissolve with methanol and be settled to 5ml, shake up, promptly;
Accurate reference substance solution each 10 μ l, the 20 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, with external standard two-point method natural logrithm Equation for Calculating, promptly;
Every of this capsule contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.13mg.Granule contains the Radix Astragali with astragaloside C for every bag
41H
68O
14Meter must not be less than 0.2～0.4mg; The every 1g of the watered pill contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.3mg; The every 1g of drop pill contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.13mg.
Among the we, Radix Astragali sweet in the mouth, tepor is returned lung, spleen channel.Have invigorating QI to consolidate the body surface resistance, the diuresis poison holding, evacuation of pus, the effect of expelling pus and promoting granulation, diuretic cures mainly diseases such as deficient qi and blood, spontaneous perspiration, chronic diarrhea proctoptosis, uterine prolapse, nephritis edema, albuminuria, diabetes, chronic ulcer.The Rhizoma Polygonati sweet in the mouth, slightly warm in nature is returned spleen, lung, kidney channel.Boosting qi and nourishing yin, spleen invigorating, lung moistening, kidney tonifying.Has good tonifying the lung, bone and muscle strengthening, blood sugar lowering, replenishing essence marrow, the effect of delaying human body caducity.Radix Rehmanniae is cold in nature, sweet in the mouth.GUIXIN, liver, kidney channel.Clearing away heat and cooling blood, yin nourishing is promoted the production of body fluid; Be used for the calentura excessive thirst, send out speckle dermexanthesis, interior-heat caused by deficiency of YIN, haematemesis, epistaxis, diabetes, infectious hepatitis.Radix Pseudostellariae is flat, sweet in the mouth, little hardship.Return spleen, lung meridian.Function with replenishing QI to invigorate the spleen, promoting the production of body fluid for nourishing the lung.Be used for that insufficiency of the spleen body is tired, inappetence, weakness, deficiency of both vital energy and Yin, thirsty, the dryness of the lung dry cough of spontaneous perspiration after being ill.The Radix Trichosanthis cold nature, sweet in the mouth, little hardship.Attach to the lung and stomach meridians.Function with clearing away heat and promoting production of body fluid, detumescence and apocenosis.Be used for that calentura excessive thirst, lung-heat type cough, interior-heat are quenched one's thirst, sore swollen toxin.More than all medicines share, play invigorating the spleen and replenishing QI altogether, the merit of YIN nourishing and the production of body fluid promoting.Be used for type of deficiency of both QI and YIN diabetes (non-insulin-dependent diabetes mellitus).
Compared with prior art, drug absorption of the present invention is rapid, and each dose reduces, and hygroscopicity is little, good stability; Production process is simplified, and has reduced production cost; The thin layer chromatography that has increased the assay of astragaloside and Rhizoma Polygonati, Radix Pseudostellariae, Radix Trichosanthis medical material in the quality standard is differentiated, has improved the quality control standard of blood sugar lowering medicine A, thereby has effectively guaranteed the clinical efficacy of said preparation.
The applicant has carried out a series of experimental study, with preparation technology and method of quality control preferred, checking pharmaceutical preparation of the present invention, makes it reach optimum efficiency.
Experimental example 1: Study on Preparation
Process conditions preferred:
Four Chinese medicine material such as Radix Astragali decocts with water extraction in the former tablet technology, has stipulated the decoction number of times, decocting time, but not clear and definite amount of water.Under the constant situation of extraction time extraction time, the applicant makes single factor experiment to amount of water, medical material water absorption rate etc. and investigates, and be evaluation index with the astragaloside rate of transform and total solid matters yield, decocting is boiled process conditions research, to determine optimum extraction process.
1. decocting process research
1.1 the medical material moisture content test takes by weighing 4 parts of 1/15 recipe quantity medical materials in the prescription ratio, every part of 205.6g adds 6 times of amounts of water (1233.6ml) submergence respectively, leaches soak in different time, till water absorption no longer increases, the results are shown in Table 1.
Table 1 medical material water absorption test result
| Soak time (h) | 1 | 2 | 3 | 4 |
| Filtrable volume (ml) | 1005 | 919 | 904 | 897 |
| Water absorption (ml) | 228.6 | 314.6 | 329.6 | 336.6 |
| Water absorption rate (%) | 111 | 153 | 160 | 164 |
The result shows that water absorption rate is about 200% of medical material weight, so decoct the water of adding about 2 times of amounts for the first time.
1.2 determining of amount of water
Feed intake by prescription 1/10, decoct simmer down to 105ml according to the requirement under each tested number.Carry out single factor with amount of water and investigate, and be evaluation index, filter out best amount of water, the results are shown in Table 2 with Astragaloside content, total solid matters yield.
1.2.1 Astragaloside content is measured: analyzing the effective ingredient of monarch, ministerial drug in the prescription, is index with the rate of transform of astragaloside in the monarch drug Radix Astragali, and amount of water is investigated.The Astragaloside content assay method is measured according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 D).
The sample treatment extracting sample solution is an amount of, puts to concentrate near doing in the tool plug conical flask, and precision adds methanol 50ml, claims to decide weight, supersound process (250W, 29～34kHz) 1 hours, put coldly, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 25ml that draws, evaporate to dryness, residue washs with ammonia solution 20ml with adding water saturated n-butyl alcohol 50ml dissolving, divide and get n-butyl alcohol liquid, evaporate to dryness, residue is with 5% dissolve with methanol and be settled to 5ml, shake up, filter, promptly get need testing solution with 0.45 μ m filter membrane
Chromatographic condition chromatographic column: enlightening horse SB-C
18(5 μ m, 150 * 4.6 i.d.mm), product serial number: 8011091; Mobile phase of acetonitrile and water (36: 64); Flow velocity: 0.7ml/min; Temperature: 30 ℃; Evaporation photodetector condition: air 1.6L/min; Drift tube temperature: 41 ℃; Signal gain (Gain) 1; Rush and hit device (Impactor) and open (ON).
The system suitability test is a filler with the carbon octadecylsilane chemically bonded silica; Acetonitrile-water (36: 64) is a mobile phase; Detect with evaporative light scattering detector.Theoretical cam curve should be not less than 6000 by the astragaloside peak.
Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, promptly.
1.2.2 total solid matters is measured the accurate medical material decocting and concentrating liquid 50ml that draws, and puts in the evaporating dish that is dried to constant weight, volatilizes, and in 105 ℃ of dryings 3 hours, moves in the exsiccator, cool off 30 minutes, accurately rapidly claims to decide weight, calculating, promptly.
Table 2 amount of water is investigated the result
| Tested number | Amount of water (doubly) | Astragaloside | Total solid matters | ||||
| Content (mg/ml) | Quality (mg) | The rate of transform (%) | Content (g/50ml) | Quality (g) | Yield (%) | ||
| 1 | 12，10，8 | 0.2148 | 10.74 | 65 | 58.3692 | 17.6625 | 30.26 |
| 2 | 10，8，6 | 0.2214 | 11.07 | 67 | 56.3615 | 16.7934 | 29.80 |
| 3 | 8，6，4 | 0.1916 | 9.58 | 58 | 53.3054 | 14.5658 | 27.33 |
The 50ml concentrated solution is equivalent to medical material amount: 146.86g, contains Milkvetch Root: 30.60g, medical material contain astragaloside 0.054%.
From table 2 result as seen, decoct three times, each time amount of water is respectively 12,10, and 8 times and 10,8,6 times are not had obvious influence to the astragaloside rate of transform and total solid matters yield.From saving man-hour, the angle that cuts down the consumption of energy is selected the amount of water scheme tested for No. 2, and promptly medical material decocts with water three times, for the first time add 10 times of amounts of water, decoct 2 hours (adding 2 times of water gagings for the first time), add 8 times of amounts of water for the second time, decocted 1 hour, and added 6 times of amounts of water for the third time, decocted 1 hour.Filter, merging filtrate is concentrated into 1050ml, and is standby.
1.3 yield of extract and technology stability are investigated
Get three parts of 1,2,3 times of recipe quantity Radixs Astragali, Rhizoma Polygonati (wine is processed), Radix Rehmanniae, Radix Pseudostellariae, Radix Trichosanthis respectively, extract by preferred technology, concentrate, drying is investigated the astragaloside rate of transform, is received cream rate and stability.Result of the test shows that astragaloside mean transferred rate is 67.17%, RSD=3.92%; Yield of extract is 10.24%, RSD=3.50%.Illustrate that selected extraction process stablizes feasiblely, the results are shown in Table 3.
Table 3 technology stability demonstration test
| Tested number | Medical material inventory (kg) | Receive cream amount (kg) | Receive cream rate (%) | Astragaloside content in the cream (%) | Astragaloside amount (mg) | The astragaloside rate of transform (%) |
| 1 | 3.084 | 0.306 | 9.92 | 0.077 | 234.37 | 67.54 |
| 2 | 6.168 | 0.621 | 10.06 | 0.072 | 446.74 | 64.37 |
| 3 | 9.252 | 0.994 | 10.74 | 0.073 | 724.54 | 69.60 |
| Meansigma methods (%) | 10.24 | 67.17 | ||||
| RSD(％) | 4.28 | 3.92 |
Medical material contains astragaloside 0.054%, and the medical material that feeds intake contains the Radix Astragali: 20.84%, and contain the astragaloside theoretical amount and be respectively: 0.347g, 0.694g, 1.041g.
2. Radix Pseudostellariae disintegrating process
2.1 the medical material pre-treatment is got the Radix Pseudostellariae selection and is removed impurity, takes by weighing the prescription proportional quantities.
2.2 the crushing screening pulverizing medicinal materials becomes fine powder (refer to and can all sieve by No. five, and contain and can be no less than 95% powder by No. six sieves), the triage after the screening (" chieftain ") pulverize, sieve after 80 ℃ of dryings, and is standby.
3. drying process research
Get the four Chinese medicine materials such as the Radix Astragali of 1 times of recipe quantity, extract, concentrate by the decocting process of working out, precipitate with ethanol, being concentrated into relative density is 1.28 (50 ℃ of heat are surveyed), is divided into 4 parts.Add Radix Pseudostellariae fine powder 32.25g respectively, mixing is put drying under the different condition, pulverizes.The sampling and measuring Astragaloside content the results are shown in Table 4.
The comparison of the different drying conditions of table 4
| Drying condition | Dry thing heavy (g) | Astragaloside content (%) | Astragaloside amount (g) | The astragaloside rate of transform (%) | Drying time (h) |
| Vacuum drying (60 ℃) | 115.24 | 0.0481 | 0.0554 | 63.86 | 12 |
| Vacuum drying (80 ℃) | 114.75 | 0.0487 | 0.0559 | 64.44 | 8 |
| Constant pressure and dry (80 ℃) | 112.98 | 0.0470 | 0.0531 | 61.21 | 21 |
| Constant pressure and dry (100 ℃) | 112.07 | 0.0451 | 0.0505 | 58.21 | 10 |
Total medical material: 3213g, decocting herbs amount: 3084g, fine powder: 129g, 1/4=32.25g.
Dry extract yield 10.76%, 10.70%, 10.47%, 10.35%, dry extract heavy 82.99g, 82.50g, 80.73g, 79.82g.
Medical material contains astragaloside 0.054%, and every part contains Radix Astragali 160.65g, astragaloside theoretical amount 0.0868g.
Result of the test shows that except that 100 ℃ of constant pressure and dry astragaloside loss rates were higher, all the other drying conditions did not have obvious influence to astragaloside.The vacuum drying time is short, and the sample quality is loose, is easy to pulverize.So select 60～80 ℃ of vacuum dryings for use.
Experimental example 2: Study on Forming
One, capsule moulding process
(1) preparation technology is four Chinese medicine material decoction extractions such as the Radix Astragali in the side, and Radix Pseudostellariae part medical material fine powder is received cream, pulverizes the back filled capsules.The flowability of content is filled with influence to capsular.By measuring powder angle of repose, the result shows that the flowability of powder is all better, and directly filled capsules need not to granulate.According to making total amount, add again that an amount of (5g～10g) starch is regulated total amount, to guarantee the unanimity of crude drug day dose behind the sample drying.Be to add crude drug fine powder receipts cream after medicinal liquid is concentrated into thick paste, mix that 60～80 ℃ of drying under reduced pressure are pulverized, and adjust total amount to 450g with appropriate amount of starch, mixing incapsulates, and makes 1000, promptly.
(2) recipe quantity, daily dose, loading amount, specification determines
1 recipe quantity calculates: the process data that goes out according to the formulation and technology conditional filtering calculates recipe quantity, and compares with former tablet formulation amount.
1.1 blood sugar lowering first tablet recipe contains crude drug 2142g altogether, makes 1000, per 1 contains crude drug 2.142g.1 time 6,3 times on the 1st, take crude drug amount 38.556g every day.
1.2 blood sugar lowering nail gelatin capsule prescription contains crude drug 3213g altogether, makes 1000, every contains crude drug 3.213g.4 of doses 1 time 3 times on the 1st, are taken crude drug amount 38.556g every day.
Two-form is at every turn with to take the crude drug amount every day identical.
1.3 dry extract: according to result of the test, this preparation dry extract average yield is 10.24%, and powder gets dry extract: 3084 * 10.24%=315.80g
2 preparation prescriptions
Dry extract 315.8g
Crude drug fine powder 129g
Add starch 5～10g
Make 1000 (0.45g/ grains) altogether
The actual addition of starch can be adjusted according to the actual recovery of extractum, and making total preparation amount is 450g, constant with the crude drug amount that guarantees to take every day.
(3) the powder hygroscopicity is investigated
Place exsiccator to be sealed in 25 ℃ of thermostatic drying chambers placements 24 hours the sulfuric acid solution of variable concentrations, can obtain the experiment condition of different constant temperature and humidities.Precision takes by weighing through 3 hours blood sugar lowering nail gelatin capsule content (every part of about 2g) of 80 ℃ of freeze-day with constant temperature in the weighing botle of constant weight, weighing botle is placed the exsiccator of above-mentioned constant temperature and humidity condition to place 3 days again, takes out, and precision is weighed, and calculates hydroscopicity, the results are shown in Table 5.
Table 5 sample hydroscopicity
| Relative humidity | 50 | 55 | 60 | 65 | 70 | 75 | 80 |
| Hydroscopicity | 2.4 | 3.9 | 9.1 | 16.0 | 21.6 | 23.1 | 24.3 |
With the hydroscopicity is vertical coordinate, and relative humidity is the abscissa mapping, gets the hydroscopicity curve.
From the hydroscopicity curve as can be known, blood sugar lowering nail gelatin capsule critical relative humidity (CRH) is about 55%.Can determine the storage requirement of this preparation thus.
(4) pilot scale
By prescription and method for making that the present invention works out, 10 times of recipe quantities feed intake, and every index in the production technology is detected, reasonability with further this preparation process thereof of investigation, result of the test shows that preparation were established is reasonable, and process conditions meet the plant produced requirement.
Two, granule moulding process
(1) technical study is added an amount of dextrin and received cream by the clear paste that preparation technology extracts, and is easily dry, and the hygroscopicity of dry back dry extract is obviously improved.This preparation is a granule, needs to add an amount of sucrose, protein sugar or citric acid and makes correctives.Through test preparation 800～1500g granule, with add dextrin 300～1000g, 2% protein sugar 16～30g, citric acid 5～20g, essence 5～20ml are advisable.Adopt the different concentration ethanol wet granulation, the concentration of alcohol the when result granulates is lower than at 75% o'clock, is difficult to granulate, and granule easily lumps after the molding, and it is bad to be higher than 85% o'clock grain forming, and granularity is defective.So select 75% ethanol moistening to granulate, 80 ℃ of vacuum dryings, promptly.
(2) preparation prescription
Dry extract 414g
Protein sugar (2%) 16～30g
Dextrin 300～1000g
Citric acid 5～20g
Fructus Citri tangerinae essence 5～20ml
Make 800～1500g altogether
The actual addition of dextrin can be adjusted according to the actual recovery of extractum, and is constant with the crude drug amount that guarantees to take every day.
(3) the granule hygroscopicity is investigated
Result of the test shows: hygroscopicity is relevant with the relative humidity of environment.Relative humidity is not seen obvious moisture absorption 70% when following.Critical relative humidity is 70%.Therefore, relative humidity should be controlled at below 70% in process of production.
Table 6 sample hydroscopicity
| Relative humidity | 50 | 55 | 60 | 65 | 70 | 75 | 80 |
| Hydroscopicity | 1.58 | 1.64 | 2.13 | 3.54 | 5.48 | 12.75 | 16.62 |
(4) pilot scale
Produce three batches (10 times of recipe quantities) by the preparation technology who works out, every index in the production technology is detected, and with the reasonability of further this preparation process thereof of examination, result of the test shows, this preparation were established is reasonable, and process conditions meet the plant produced requirement.
Three, the applicant has carried out experimental study to the moulding process of the watered pill and drop pill equally, and the result shows, when the present invention makes the watered pill, does not add the better effects if of adjuvant; And when making drop pill, select for use PEG6000 and PEG4000 better, and its optimum amount is 500g～600g as the effect of substrate.
Experimental example 3: method of quality control research
1. differentiate
This preparation is formed through extraction by the Radix Astragali, Rhizoma Polygonati (wine is processed), Radix Rehmanniae, Radix Pseudostellariae, Radix Trichosanthis Chinese medicine of the five flavours.Proper mass standard Drug Standard of Ministry of Public Health of the Peoples Republic of China (the 8th 104 pages in Chinese traditional patent formulation preparation) " blood sugar lowering first sheet " (standard No.: differentiate WS3-B-1570-93) that (1) is the microscopical identification of Radix Pseudostellariae fecula, (2), (3) are respectively the thin layer discriminating of the Radix Astragali, Rhizoma Polygonati, for improving the quality standard of said preparation, all the other medical materials among applicant the other side have all carried out the thin layer chromatography Study on Identification.
1.1 instrument and reagent REPROSTAR3 thin layer chromatography imaging system (Switzerland GAMAG); Radix Astragali control medicinal material (lot number: 0974-200106), Rhizoma Polygonati control medicinal material (1341-200401), Radix Pseudostellariae control medicinal material (lot number: 1004-200203), Radix Trichosanthis control medicinal material (lot number: 1361-200401).Above control medicinal material is all purchased to Chinese pharmaceutical biological product and is identified institute; Ether, chloroform, glacial acetic acid, n-butyl alcohol, methanol, ethanol etc. are analytical pure; Silica gel G precoated plate (Haiyang Chemical Plant, Qingdao); Silica gel g thin-layer plate (self-control).
1.2 differentiate: (1) same primary standard.
(2) same primary standard.
(3) same primary standard.
(4) thin layer chromatography of Radix Pseudostellariae medical material is differentiated among the other side:
The preparation of need testing solution: get blood sugar lowering medicine A or its content 3g, added methanol 50ml supersound extraction 30 minutes, filter the filtrate evaporate to dryness.Residue adds water 50ml heating for dissolving, put cold after, be transferred in the separatory funnel.With ether extraction 5 times, each 30ml, water layer is flung to ether, with water saturated n-butanol extraction 3 times (40,30,20ml), merge n-butanol extracting liquid, add 0.5 milliliter of ammonia, again with n-butyl alcohol saturated be washed to neutrality, evaporate to dryness in the water-bath, residue add methanol makes dissolving for 1 milliliter, as need testing solution.
The preparation of control medicinal material solution: get control medicinal material 1g, shine medical material solution in pairs with legal system.
The preparation of negative control solution: remove negative preparation 3 grams, make negative control solution with method except that Radix Pseudostellariae.
The thin layer chromatography condition: the silica gel G plate, developing solvent: chloroform-methanol-14% ammonia spirit (2: 3: 1), launch, take out, to dry, spray is with 5% ninhydrin solution, and it is clear to be heated to the speckle colour developing in 105 ℃.Once (4: 1: 5: 0.5) the multiple ratio of development system was launched with n-butyl alcohol-ethyl acetate-water-methanol, take out, dry, respectively at inspecting under daylight and the 365nm uviol lamp, relatively through repetition test, with chloroform-methanol-14% ammonia spirit (2: 3: 1) is that developing solvent expansion effect is better, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, the speckle of displaing amaranth, negative control is noiseless, so quality standard of the present invention is listed in this discriminating in.
(5) thin layer chromatography of Radix Trichosanthis medical material is differentiated among the other side:
The preparation of need testing solution: get blood sugar lowering medicine A sample 2g, add methanol 25ml, supersound extraction 30 minutes filters, and filtrate is concentrated into 2ml, as need testing solution.
The preparation of control medicinal material solution: get Radix Trichosanthis control medicinal material 1g, shine medical material solution in pairs with legal system.
The preparation of negative control solution: remove negative preparation 2 grams, make negative control solution with method except that the Radix Trichosanthis medical material.
The thin layer chromatography condition: the silica gel G plate, developing solvent: (8: 2: 2: 3), developer: 5% ninhydrin solution, it was clear to be heated to speckle colour developing under 105 ℃ for n-butyl alcohol-dehydrated alcohol-glacial acetic acid-water.Once used the various ratios of this development system and different development system repetition tests, the result launches with above developing solvent, and chromatographic isolation is good, speckle colour developing is clear, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color, negative control is noiseless.So quality standard of the present invention is listed in this discriminating in.
2. check according to the pertinent regulations under each preparation item (" appendix I of Chinese pharmacopoeia version in 2000) and check.Check index, method and the results are shown in Table 7.
2.1 moisture is according to " correlation method detects under an appendix IL of Chinese pharmacopoeia version in 2000 the capsule item.
2.2 content uniformity is according to " correlation method detects under an appendix IL of Chinese pharmacopoeia version in 2000 the capsule item.
2.3 disintegration is according to " correlation method detects under an appendix IL of Chinese pharmacopoeia version in 2000 the capsule item.
2.4 microbial limit is according to " inspection method and the capsule microbial limit standard of an appendix XIIIC of Chinese pharmacopoeia version in 2000 are checked.
2.5 the heavy metal inspection is according to " heavy metal inspection technique (second method) is checked under an appendix IX of Chinese pharmacopoeia version in 2000 the E item.
Get this preparation or its content 2g, slowly blazing to fully carbonization, put coldly, add sulphuric acid 1ml, make moistening, after eliminating with low-temperature heat to sulphuric acid, add nitric acid 0.5ml, evaporate to dryness eliminates nitrogen oxide, puts coldly, blazingly makes complete ashing at 500～600 ℃, put coldly, add hydrochloric acid 2ml and put evaporate to dryness in the water-bath, add water 15ml, drip ammonia solution to instructions phenolphthalein solution and show neutral, add acetate buffer (pH3.5) 2ml again, the slight fever dissolving, in the dislocation nessler colorimetric tube, thin up becomes 25ml, gets sample cell.Other gets the reagent of preparation need testing solution, puts evaporate to dryness in the porcelain dish, adds acetate buffer (pH3.5) 2ml and water 15ml, after the slight fever dissolving, in the dislocation nessler colorimetric tube, add standard lead solution 2ml (every 1ml is equivalent to the Pb of 10 μ g), be diluted with water to 25ml again, get standard lead solution pipe.Check, promptly in accordance with the law.
Testing result: the color that the sample cell of three batch samples shows all is shallower than standard lead solution pipe color, illustrates that this preparation content of beary metal is lower than 10/1000000ths.So do not list quality standard of the present invention in.
2.6 the inspection of arsenic salt is according to " arsenic salt inspection technique (first method) is checked under an appendix IX of Chinese pharmacopoeia version in 2000 the F item.
Get this preparation or its content 1g, adding calcium hydroxide 0.5g, mixing adds water and stirs on a small quantity, drying, burning with little baked wheaten cake earlier makes carbonization, in 500～600 ℃ of blazing ashing extremely fully, adds hydrochloric acid 5ml again, and water 21ml gets sample cell.Check, promptly in accordance with the law.
Testing result: the arsenic speckle color that sample cell produced of three batch samples all is shallower than standard arsenic speckle color, illustrates that this preparation arsenic salt content all is lower than 2/1000000ths.So do not list quality standard of the present invention in.
Table 7 blood sugar lowering medicine A inspection item result of study
As shown in Table 7, the inspection item of above-mentioned batch of blood sugar lowering medicine A sample is all " within the scope of an appendix I of Chinese pharmacopoeia version in 2000 defined.
3. assay is according to the chemical composition analysis of the medical material of respectively distinguishing the flavor of among the other side, the applicant in test among the other side the content of the contained astragaloside of the Radix Astragali measure, and assay method is studied.
3.1 instrument Agilent 1100 high performance liquid chromatographs comprise the Agilent-G1312A binary pump, the 61315B diode array detector, the G1313 automatic sampler, the G1316A column oven, G1322A vacuum degassing machine, Agilent-A.08.03[847] chem workstation; Evaporative light scattering detector (U.S. safe ELSD 2000 difficult to understand); Ultrasonic washing unit (250W, 29～34kHz; Beijing ultrasonic device factory).
3.2 reagent acetonitrile (chromatographically pure); Water is redistilled water; Astragaloside reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute, assay usefulness, lot number: 0781-200109).
3.3 chromatographic condition chromatographic column: enlightening horse SB-C
18(5 μ m, 150 * 4.6 i.d.mm), product serial number: 8011091; Mobile phase: acetonitrile-water (36: 64); Flow velocity: 0.7ml/min; Temperature: 30 ℃; Evaporation photodetector condition: air 1.6L/min; Drift tube temperature: 41 ℃; Signal gain (Gain) 1; Rush and hit device (Impactor) and open (ON).
3.4 the system suitability test is got astragaloside reference substance solution, preparation need testing solution respectively and is lacked the negative control solution of Milkvetch Root, blank solvent injection chromatograph of liquid, record chromatogram.As seen, the retention time t of astragaloside
RBe about 10.0 minutes, promptly astragaloside separates with other components fully under this experimental condition.Theoretical cam curve is calculated as 6000 with the astragaloside peak, astragaloside with and the separating degree of other component peaks greater than 1.5.So decide number of theoretical plate in the astragaloside peak, should be not less than 5000.
3.5 the selection of detector parameters is according to mobile phase kind and ratio, by observing signal intensity at different drift tube temperatures astragaloside during with different air velocity sample introduction, again in conjunction with the situation of baseline noise, determine that at last drift tube temperature is 41 ℃, air velocity is 1.6L/min, and signal gain (Gain) is 1.
3.6 it is an amount of that astragaloside reference substance purity test takes by weighing the astragaloside reference substance, be mixed with the reference substance solution that every 1ml contains 1mg with methanol, draw this solution 20 μ l, inject chromatograph of liquid, measure, calculating Astragaloside content with peak area normalization is 100.0%.
3.7 linear relationship is investigated
3.7.1 the preparation precision of reference substance solution takes by weighing astragaloside reference substance 10.10mg, puts in the 25ml volumetric flask, adds dissolve with methanol and is diluted to scale, shakes up, and promptly gets the reference substance solution that concentration is 0.404mg/ml.
3.7.2 the above-mentioned reference substance solution 4 of the accurate respectively absorption of the drafting of standard curve, 8,12,16,20,25 μ l, inject chromatograph of liquid, the record chromatograph, with the peak area is abscissa, sample size is a vertical coordinate, found that, linear relationship bad (γ=0.99479), and carry out linear regression calculating with the natural logrithm (lnA) of peak area and the natural logrithm (lnM) of sample size, get equation of linear regression: lnM=0.679825lnA-2.797564 (r=0.999955), because this regression equation is not by zero, text adopts external standard two-point method natural logrithm Equation for Calculating content.The range of linearity: 1.616～10.100 μ g.
3.8 the preparation of need testing solution
The contained free cpds of astragaloside of Milkvetch Root in the preparation for having extracted, this compounds only need use methanol, the dissolving of ethanol equal solvent to get final product, in the test, adopt ultrasonic extraction, and to have investigated respectively with variable concentrations methanol serve as to extract solvent, supersound process time, purification method etc., the result is solvent with methanol, and 1 hour method of supersound process is the most effective.
3.8.1 test sample astragaloside extraction choice of Solvent is a solvent with the methanol of variable concentrations, adopts the method for supersound process 60min to extract astragaloside in the formulation samples, the results are shown in Table 8.
Table 8 preparation compares with the result of Different Extraction Method
| Methanol concentration | 30 | 50 | 70 | 100 |
| Astragaloside content (mg/g) | 0.5681 | 0.8492 | 0.8312 | 0.8375 |
From table 8, as seen,,, be to extract solvent so select methanol for use because extracting solution needs evaporate to dryness in purified treatment with the basically identical as a result behind 50～100% methanol supersound process 50min.
3.8.2 it is solvent that the supersound process time is investigated with methanol, investigates the result of different supersound process times, sees Table 9.
The result of different supersound process times of table 9 relatively
| Ultrasonic time (min) | 20 | 30 | 60 | 90 |
| Average content (mg/g) | 0.5378 | 0.6750 | 0.8528 | 0.8490 |
Supersound process 60 minutes and 90 minutes basically identicals as a result as a result are so selected supersound process for use 60 minutes.
3.8.3 the investigation of purification method is because the preparation complicated component, directly measure with the methanol extract liquid sample introduction, disturb the separation of astragaloside, behind the methanol extract liquid evaporate to dryness, residue dissolves with water saturated n-butyl alcohol, with ammonia solution washing n-butyl alcohol liquid, remove interfering material, need testing solution after investigate, washing once with the 20ml ammonia solution does not disturb the mensuration of astragaloside, and the response rate is good.
3.8.4 this preparation or its content 6.0g under the content uniformity item are got in the preparation of need testing solution, the accurate title, decide, and puts in the tool plug conical flask, and precision adds methanol 50ml, claim to decide weight, supersound process 1 hour, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 25ml that draws, evaporate to dryness, residue is with adding water saturated n-butyl alcohol 50ml dissolving, with ammonia solution 20ml washing, divide and get n-butyl alcohol liquid, evaporate to dryness, residue is with dissolve with methanol and be settled to 5ml, shakes up, promptly.
3.8.5 the negative control product that lack Milkvetch Root are got in the preparation of negative controls, prepare negative control product solution by the preparation method of need testing solution.
3.9 reference substance solution (0.404mg/ml) 10 μ l are got in the precision test, repeat sample introduction 5 times, measure peak area (the results are shown in Table 10), RSD=1.05%.
The precision test of table 10 astragaloside
| The sample introduction number of times | 1 | 2 | 3 | 4 | 5 | RSD％ |
| Peak area | 450.879 | 453.682 | 456.001 | 451.948 | 450.980 | 0.48 |
3.10 replica test is got test sample (20040701), preparation method by need testing solution in the quality standard of the present invention, prepare each 3 parts of 3 variable concentrations need testing solutions, the accurate respectively 10 μ l sample introductions of drawing are measured peak area, calculate (the results are shown in Table 11), average content 0.829mg/g, RSD=0.99%, result show that repeatability is good.
The replica test of astragaloside in the table 11 preparation test sample
| Concentration | Sequence number | Sample size (g) | Peak area | Content (mg/g) | Meansigma methods | RSD％ |
| 80％ | 1 | 4.8239 | 477.302 | 0.8369 | 0.829 | 0.99 |
| 2 | 4.8123 | 470.636 | 0.8309 | |||
| 3 | 4.8092 | 456.219 | 0.8139 | |||
| 100 ％ | 4 | 6.0048 | 651.198 | 0.8323 | ||
| 5 | 6.0059 | 649.314 | 0.8305 | |||
| 6 | 6.0079 | 657.801 | 0.8376 | |||
| 120 ％ | 7 | 7.2169 | 828.328 | 0.8169 | ||
| 8 | 7.2114 | 845.850 | 0.8294 | |||
| 9 | 7.2068 | 850.373 | 0.8330 |
3.11 stability test is got a test sample (20040701), preparation method by need testing solution in the quality standard of the present invention prepares need testing solution, time in accordance with regulations, the accurate 10 μ l sample introductions of drawing are measured (table 12), and the result shows that astragaloside is stable in 8 hours in the preparation need testing solution.
Astragaloside stability test in table 12 test sample
| Time (h) | 0 | 2 | 4 | 6 | 8 | RSD％ |
| Peak area A | 651.198 | 661.773 | 659.358 | 645.292 | 663.079 | 1.16 |
3.11 recovery test takes by weighing 9 parts in preparation (average content 0.829mg/g) measuring content, the accurate astragaloside reference substance that adds of according to the form below is an amount of respectively, prepare need testing solution by quality standard of the present invention, the accurate respectively 10 μ l sample introductions of drawing, measure peak area (the results are shown in Table 13), calculate, the average recovery rate of astragaloside is 100.42%, RSD=1.70%.
The recovery test of astragaloside in the table 13 preparation test sample
| Sample size (g) | Content (mg) | Addition | Peak area | The amount of recording | Response rate % | Meansigma methods | RSD％ | |
| 1 | 3.0256 | 2.5082 | 1.4910 | 466.215 | 3.9728 | 98.22 | 100.42 | 1.70 |
| 2 | 3.0212 | 2.5046 | 1.4910 | 476.365 | 4.0318 | 102.43 | ||
| 3 | 3.0199 | 2.5035 | 1.4910 | 468.024 | 3.9832 | 99.24 | ||
| 4 | 3.0109 | 2.4960 | 2.4850 | 661.618 | 5.0523 | 102.87 | ||
| 5 | 3.0210 | 2.5044 | 2.4850 | 658.210 | 5.0344 | 101.81 | ||
| 6 | 3.0218 | 2.6051 | 2.4850 | 655.215 | 5.0187 | 101.15 | ||
| 7 | 3.0154 | 2.4998 | 3.7280 | 886.000 | 6.1745 | 98.57 | ||
| 8 | 3.0212 | 2.5046 | 3.7280 | 897.604 | 6.2299 | 99.93 | ||
| 9 | 3.0230 | 2.5061 | 3.7280 | 894.807 | 6.2166 | 99.53 |
3.12 sample determination prepares blood sugar lowering medicine A need testing solution and reference substance solution by quality standard of the present invention, accurate respectively need testing solution 10 μ l, reference substance solution 10 μ l, the 20 μ l sample introductions drawn, and the record chromatograph is measured peak area, calculates content.
The assay of astragaloside the results are shown in Table 14 in ten batch samples.
Astragaloside content measurement result in the table 14 blood sugar lowering medicine A
| Lot number | Sampling amount (g) | Peak area | Astragaloside content (mg/g) | Average content (mg/g) | Grand mean (mg/g) | |||
| 1 | 2 | 1 | 2 | 1 | 2 | |||
| 1 | 6.0123 | 6.0136 | 683.216 | 679.415 | 0.8591 | 0.8558 | 0.8574 | |
| 2 | 6.0226 | 6.0214 | 394.052 | 386.594 | 0.5877 | 0.5801 | 0.5839 | |
| 3 | 6.0108 | 6.0118 | 643.596 | 628.008 | 0.8248 | 0.8109 | 0.8178 | |
| 4 | 6.0127 | 6.0101 | 578.260 | 584.448 | 0.7661 | 0.7720 | 0.7690 | |
| 5 | 6.0086 | 6.0115 | 385.348 | 375.564 | 0.5801 | 0.5697 | 0.5749 | 0.6682 |
| 6 | 6.0104 | 6.0079 | 377.904 | 377.743 | 0.5722 | 0.5723 | 0.5722 | |
| 7 | 6.0208 | 6.0157 | 436.291 | 454.686 | 0.6304 | 0.6491 | 0.6398 | |
| 8 | 6.0103 | 6.0092 | 443.210 | 443.877 | 0.6384 | 0.6392 | 0.6388 | |
| 9 | 6.0208 | 6.0175 | 452.962 | 453.716 | 0.6469 | 0.6480 | 0.6474 | |
| 10 | 6.0143 | 6.0152 | 387.137 | 386.744 | 0.5814 | 0.5809 | 0.5811 |
3.14 sample Astragaloside content limit is from 10 crowdes of blood sugar lowering nail gelatin capsule pilot scale sample determination results as seen, in each lot number sample the astragaloside extraction ratio all more than 50%, so in the preparation astragaloside extraction ratio by being not less than 50%.The Astragaloside content limit is calculated as follows in per 1 seed lac wafer: Astragaloside content limit=preparation contains Milkvetch Root (g) * Milkvetch Root and contains heavy (the g)/preparation amount (g) of astragaloside limit * extraction ratio * sheet=642.6g * 0.04% * 50% * 0.45g * 1000/450g=0.129mg/ grain, so tentative every of this capsule contains the Radix Astragali with astragaloside (C
41H
68O
14) meter, must not be less than 0.13mg.Same calculating can get, and granule contains the Radix Astragali with astragaloside C for every bag
41H
68O
14Meter must not be less than 0.2～0.4mg; The every 1g of the watered pill contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.3mg; The every 1g of drop pill contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.13mg.
The specific embodiment:
Embodiments of the invention 1: Radix Astragali 642.6g, Rhizoma Polygonati (wine is processed) 642.6g, Radix Rehmanniae 642.6g, Radix Pseudostellariae 642.6g, Radix Trichosanthis 642.6g
Get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add 10 times of water gagings for the first time, decoct 2 hours, add 8 times of water gagings for the second time, decoct 1 hour, add 6 times of water gagings for the third time, decoct 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, adds the Radix Pseudostellariae fine powder, mixing, 60～80 ℃ of drying under reduced pressure are pulverized, adjust total amount to 450g with appropriate amount of starch, mixing, dress enteric coated capsule, make 1000 (0.45g/ grains), promptly get capsule.This preparation oral, one time 4,3 times on the one.
Embodiments of the invention 2: Radix Astragali 642.6g, Rhizoma Polygonati (wine is processed) 642.6g, Radix Rehmanniae 642.6g, Radix Pseudostellariae 642.6g, Radix Trichosanthis 642.6g
Get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add 10 times of water gagings for the first time, decoct 2 hours, add 8 times of water gagings for the second time, decoct 1 hour, add 6 times of water gagings for the third time, decoct 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, adds Radix Pseudostellariae fine powder, the dextrin of 2 times of amounts and 2% protein sugar 20g, with 75% ethanol moistening system granule, 80 ℃ of vacuum dryings, packing, every packed 8g～15g promptly gets granule.This preparation oral, one time 1～2 bag, 3 times on the one.
Embodiments of the invention 3: Radix Astragali 642.6g, Rhizoma Polygonati (wine is processed) 642.6g, Radix Rehmanniae 642.6g, Radix Pseudostellariae 642.6g, Radix Trichosanthis 642.6g
Get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add 10 times of water gagings for the first time, decoct 2 hours, add 8 times of water gagings for the second time, decoct 1 hour, add 6 times of water gagings for the third time, decoct 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1060ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, adds the Radix Pseudostellariae fine powder, mixing, drying is ground into fine powder, with the general ball of making of suitable quantity of water, drying is made 400g～500g, promptly gets the watered pill.This preparation oral, a 1～2g, 3 times on the one.
Embodiments of the invention 4: Radix Astragali 642.6g, Rhizoma Polygonati (wine is processed) 642.6g, Radix Rehmanniae 642.6g, Radix Pseudostellariae 642.6g, Radix Trichosanthis 642.6g
Get the Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis and decoct with water three times, add 10 times of water gagings for the first time, decocted 2 hours, add 8 times of water gagings for the second time, decocted 1 hour, add 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction, filter, filtrate is concentrated into about 1200ml, adds ethanol and makes that to contain that alcohol measures be 75%, stir evenly, left standstill 48 hours, and filtered, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, add PEG6000 and PEG4000 500g～600g, drip and make ball, make 1000g, promptly get drop pill.This preparation oral, one time 10～20,3 times on the one.
Embodiments of the invention 5: the method for quality control of blood sugar lowering medicine A comprises:
Character: capsule is an enteric coated capsule, and its content is a brown ceramic powder; Feeble QI perfume (or spice), sweet-bitter flavor;
For granule, medicine is a brown particle; Feeble QI perfume (or spice), sweet-bitter flavor;
For the watered pill, medicine is the brownish black ball; Feeble QI perfume (or spice), sweet-bitter flavor;
For drop pill, medicine is the dark-brown ball; Feeble QI perfume (or spice), sweet-bitter flavor.
Differentiate: (1) gets this preparation, and put microscopically and observe: starch grain is numerous, simple grain five similar rounds and semicircle diameter 4～20 μ m, and omphalion is slit-like, and accidental composite grain is integrated by 2～3; The conduit master is screw thread and reticulate vessel, diameter 10～22 μ m;
(2) get this preparation or its content 1.5g under the content uniformity item, add ethyl acetate 20ml, reflux 1 hour filters, and filtrate is concentrated into about 1ml, as need testing solution; Other gets Radix Astragali control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=8.5: 0.5 is developing solvent, launch, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with the sodium carbonate test solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get this preparation or its content 2g under the content uniformity item, add ethanol 20ml, reflux 2 hours filters, and filtrate evaporate to dryness, residue add acetone 10ml makes dissolving, filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Rhizoma Polygonati control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: acetic acid=5: 4: 1 is developing solvent, launch, take out, dry, spray is with 5% phosphomolybdic acid ethanol solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(4) get this preparation or its content 3g under the content uniformity item, add methanol 30ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add 30 milliliters of heating for dissolving of water, with ether extraction 3 times, and each 30ml; Water layer is flung to ether, with water saturated n-butanol extraction 3 times, is followed successively by 40,30,20ml, merges n-butyl alcohol, adds 0.5 milliliter of ammonia, again with n-butyl alcohol saturated be washed to neutrality, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Pseudostellariae control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: 14% ammonia spirit=2: 3: 1 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, 105 ℃ to be heated to speckle colour developing clear, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(5) get this preparation or its content 2g under the content uniformity item, add methanol 25ml, supersound process 30 minutes filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Radix Trichosanthis control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with n-butyl alcohol: ethanol: glacial acetic acid: water=8: 2: 2: 3 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, and 105 ℃ to be heated to the speckle colour developing clear; Put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
Check: should meet relevant every regulation under each preparation item of appendix I of Chinese Pharmacopoeia version in 2000;
Assay: shine an appendix VI of Chinese Pharmacopoeia version in 2000 D high effective liquid chromatography for measuring:
The suitable application test of system is a filler with the carbon octadecylsilane chemically bonded silica; Acetonitrile: water=36: 64 is mobile phase; Detect with evaporative light scattering detector; Theoretical cam curve should be not less than 6000 by the astragaloside peak;
It is an amount of that the preparation precision of reference substance solution takes by weighing the astragaloside reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 0.40mg, promptly;
This preparation or its content 6g under the content uniformity item got in the preparation of need testing solution, the accurate title, decide, put in the tool plug conical flask, precision adds methanol 50ml, claims to decide weight, supersound process is 1 hour under 250W, 29～34kHz condition, put coldly, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 25ml that draws, evaporate to dryness, residue is with adding water saturated n-butyl alcohol 50ml dissolving, wash with ammonia solution 20ml, divide and get n-butyl alcohol liquid, evaporate to dryness, residue is with dissolve with methanol and be settled to 5ml, shake up, promptly;
Accurate reference substance solution each 10 μ l, the 20 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, with external standard two-point method natural logrithm Equation for Calculating, promptly;
Every of this capsule contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.13mg; Granule contains the Radix Astragali with astragaloside C for every bag
41H
68O
14Meter must not be less than 0.2～0.4mg; The every 1g of the watered pill contains the Radix Astragali with astragaloside C
41H
680
14Meter must not be less than 0.3mg; The every 1g of drop pill contains the Radix Astragali with astragaloside C
41H
68O
14Meter must not be less than 0.13mg.
Claims (12)
1. blood sugar lowering medicine A for the treatment of diabetes, it is characterized in that: it is to process capsule, granule, the watered pill or the drop pill that Rhizoma Polygonati 642.6g, Radix Rehmanniae 642.6g, Radix Pseudostellariae 642.6g and Radix Trichosanthis 642.6g make with Radix Astragali 642.6g, wine.
2. treat the preparation method of the blood sugar lowering medicine A of diabetes according to claim 1, it is characterized in that: get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add for the first time 10 times of water gagings, decocted 2 hours, and added 8 times of water gagings for the second time, decocted 1 hour, add 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, add the Radix Pseudostellariae fine powder, mixing, drying, be ground into fine powder, add suitable adjuvant and make different preparations.
3. according to the preparation method of the blood sugar lowering medicine A of the described treatment diabetes of claim 2, it is characterized in that: blood sugar lowering nail gelatin wafer is preparation like this: get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add for the first time 10 times of water gagings, decocted 2 hours, and added 8 times of water gagings for the second time, decocted 1 hour, add 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, adds ethanol and makes that to contain that alcohol measures be 75%, stirs evenly, left standstill 48 hours, and filtered, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, adds the Radix Pseudostellariae fine powder, mixing, drying is ground into fine powder, the dress enteric coated capsule, promptly.
4. according to the preparation method of the blood sugar lowering medicine A of the described treatment diabetes of claim 2, it is characterized in that: the agent of blood sugar lowering Jia Keli is preparation like this: get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add for the first time 10 times of water gagings, decocted 2 hours, and added 8 times of water gagings for the second time, decocted 1 hour, add 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, add the dextrin of Radix Pseudostellariae fine powder, 1～4 times of amount, an amount of protein sugar or cyclamate, an amount of essence, system granule, drying, packing, promptly.
5. according to the preparation method of the blood sugar lowering medicine A of the described treatment diabetes of claim 2, it is characterized in that: the blood sugar lowering first watered pill is preparation like this: get Radix Pseudostellariae 129g and be ground into fine powder, the remaining Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis decoct with water three times, add for the first time 10 times of water gagings, decocted 2 hours, and added 8 times of water gagings for the second time, decocted 1 hour, add 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1050ml, add ethanol and make that to contain alcohol amount be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, adds the Radix Pseudostellariae fine powder, mixing, drying is ground into fine powder, with the general ball of making of suitable quantity of water, drying, promptly.
6. treat the preparation method of the blood sugar lowering medicine A of diabetes according to claim 1, it is characterized in that: blood sugar lowering first drop pill prepares like this: get the Radix Pseudostellariae and the Radix Astragali, Rhizoma Polygonati, Radix Rehmanniae and Radix Trichosanthis and decoct with water three times, add for the first time 10 times of water gagings, decocted 2 hours, add for the second time 8 times of water gagings, decocted 1 hour, and added 6 times of water gagings for the third time, decocted 1 hour; Collecting decoction filters, and filtrate is concentrated into about 1200ml, adds ethanol and makes that to contain that alcohol measures be 75%, stir evenly, left standstill 48 hours, filter, filtrate is concentrated into 50 ℃ of heat, and to survey relative densities be 1.25～1.30 thick paste, add PEG6000 and PEG4000 500g～600g, drip and make ball, promptly.
7. treat the method for quality control of the blood sugar lowering medicine A of diabetes as claimed in claim 1 or 2, it is characterized in that: described method of quality control mainly comprise in character, discriminating, inspection and the assay project partly or entirely, wherein differentiate to comprise microexamination and the thin layer chromatography of the Radix Astragali, Rhizoma Polygonati, Radix Pseudostellariae, Radix Trichosanthis in the preparation is differentiated; Assay is the assay to the contained astragaloside of the Radix Astragali in the preparation.
8. according to the method for quality control of the blood sugar lowering medicine A of the described treatment diabetes of claim 7, it is characterized in that: the discrimination method of the Radix Astragali is to be contrast with Radix Astragali control medicinal material, and with chloroform: methanol=8.5: 0.5 is the thin layer chromatography of developing solvent; The discrimination method of Rhizoma Polygonati is to be contrast with the Rhizoma Polygonati control medicinal material, and with chloroform: methanol: acetic acid=5: 4: 1 is the thin layer chromatography of developing solvent; The discrimination method of Radix Pseudostellariae is to be contrast with the Radix Pseudostellariae control medicinal material, and with chloroform: methanol: 14% ammonia spirit=2: 3: 1 is the thin layer chromatography of developing solvent; The discrimination method of Radix Trichosanthis is to be contrast with the Radix Trichosanthis control medicinal material, and with n-butyl alcohol: ethanol: glacial acetic acid: water=8: 2: 2: 3 is the thin layer chromatography of developing solvent.
9. according to the method for quality control of the blood sugar lowering medicine A of claim 7 or 8 described treatment diabetes, it is characterized in that: concrete discrimination method comprise following project partly or entirely:
(1) get this preparation, put microscopically and observe: starch grain is numerous, simple grain five similar rounds and semicircle diameter 4～20 μ m, and omphalion is slit-like, and accidental composite grain is integrated by 2～3; The conduit master is screw thread and reticulate vessel, diameter 10～22 μ m;
(2) get this preparation or its content 1.5g under the content uniformity item, add ethyl acetate 20ml, reflux 1 hour filters, and filtrate is concentrated into about 1ml, as need testing solution; Other gets Radix Astragali control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=8.5: 0.5 is developing solvent, launch, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with the sodium carbonate test solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get this preparation or its content 2g under the content uniformity item, add ethanol 20ml, reflux 2 hours filters, and filtrate evaporate to dryness, residue add acetone 10ml makes dissolving, filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Rhizoma Polygonati control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: acetic acid=5: 4: 1 is developing solvent, launch, take out, dry, spray is with 5% phosphomolybdic acid ethanol solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(4) get this preparation or its content 3g under the content uniformity item, add methanol 30ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add 30 milliliters of heating for dissolving of water, with ether extraction 3 times, and each 30ml; Water layer is flung to ether, with water saturated n-butanol extraction 3 times, is followed successively by 40,30,20ml, merges n-butyl alcohol, adds 0.5 milliliter of ammonia, again with n-butyl alcohol saturated be washed to neutrality, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Pseudostellariae control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: 14% ammonia spirit=2: 3: 1 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, 105 ℃ to be heated to speckle colour developing clear, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(5) get this preparation or its content 2g under the content uniformity item, add methanol 25ml, supersound process 30 minutes filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Radix Trichosanthis control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with n-butyl alcohol: ethanol: glacial acetic acid: water=8: 2: 2: 3 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, and 105 ℃ to be heated to the speckle colour developing clear; Put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
10. according to the method for quality control of the blood sugar lowering medicine A of the described treatment diabetes of claim 7, it is characterized in that: the content assaying method of astragaloside is to be contrast with the astragaloside reference substance in the Radix Astragali, and with acetonitrile: water=36: 64 is the high performance liquid chromatography of mobile phase.
11. according to the method for quality control of the blood sugar lowering medicine A of claim 7 or 10 described treatment diabetes, it is characterized in that: concrete content assaying method is:
According to an appendix VI of Chinese Pharmacopoeia version in 2000 D high effective liquid chromatography for measuring:
The suitable application test of system is a filler with the carbon octadecylsilane chemically bonded silica; Acetonitrile: water=36: 64 is mobile phase; Detect with evaporative light scattering detector; Theoretical cam curve should be not less than 6000 by the astragaloside peak;
It is an amount of that the preparation precision of reference substance solution takes by weighing the astragaloside reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 0.40mg, promptly;
This preparation or its content 6g under the content uniformity item got in the preparation of need testing solution, the accurate title, decide, put in the tool plug conical flask, precision adds methanol 50ml, claims to decide weight, supersound process is 1 hour under 250W, 29～34kHz condition, put coldly, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 25ml that draws, evaporate to dryness, residue is with adding water saturated n-butyl alcohol 50ml dissolving, wash with ammonia solution 20ml, divide and get n-butyl alcohol liquid, evaporate to dryness, residue is with dissolve with methanol and be settled to 5ml, shake up, promptly;
Accurate reference substance solution each 10 μ l, the 20 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, with external standard two-point method natural logrithm Equation for Calculating, promptly;
Every of this capsule contains the Radix Astragali in astragaloside C41H68O14, must not be less than 0.13mg; Granule contains the Radix Astragali in astragaloside C41H68O14 for every bag, must not be less than 0.2～0.4mg; The every 1g of the watered pill contains the Radix Astragali in astragaloside C41H68O14, must not be less than 0.3mg; The every 1g of drop pill contains the Radix Astragali in astragaloside C41H68O14, must not be less than 0.13mg.
12. according to the method for quality control of the blood sugar lowering medicine A of the described treatment diabetes of claim 7, it is characterized in that: described method of quality control comprises:
Character: capsule is an enteric coated capsule, and its content is a brown ceramic powder; Feeble QI perfume (or spice), sweet-bitter flavor;
For granule, medicine is a brown particle; Feeble QI perfume (or spice), sweet-bitter flavor;
For the watered pill, medicine is the brownish black ball; Feeble QI perfume (or spice), sweet-bitter flavor;
For drop pill, medicine is the dark-brown ball; Feeble QI perfume (or spice), sweet-bitter flavor;
Differentiate: (1) gets this preparation, and put microscopically and observe: starch grain is numerous, simple grain five similar rounds and semicircle diameter 4～20 μ m, and omphalion is slit-like, and accidental composite grain is integrated by 2～3; The conduit master is screw thread and reticulate vessel, diameter 10～22 μ m;
(2) get this preparation or its content 1.5g under the content uniformity item, add ethyl acetate 20ml, reflux 1 hour filters, and filtrate is concentrated into about 1ml, as need testing solution; Other gets Radix Astragali control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol=8.5: 0.5 is developing solvent, launch, take out, dry, spray is put under the 365nm ultra-violet lamp and is inspected with the sodium carbonate test solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(3) get this preparation or its content 2g under the content uniformity item, add ethanol 20ml, reflux 2 hours filters, and filtrate evaporate to dryness, residue add acetone 10ml makes dissolving, filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Rhizoma Polygonati control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: acetic acid=5: 4: 1 is developing solvent, launch, take out, dry, spray is with 5% phosphomolybdic acid ethanol solution, and it is clear that hot blast blows to the speckle colour developing; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(4) get this preparation or its content 3g under the content uniformity item, add methanol 30ml, supersound process 30 minutes filters, and filtrate evaporate to dryness, residue add 30 milliliters of heating for dissolving of water, with ether extraction 3 times, and each 30ml; Water layer is flung to ether, with water saturated n-butanol extraction 3 times, is followed successively by 40,30,20ml, merges n-butyl alcohol, adds 0.5 milliliter of ammonia, again with n-butyl alcohol saturated be washed to neutrality, water bath method, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Pseudostellariae control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with chloroform: methanol: 14% ammonia spirit=2: 3: 1 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, 105 ℃ to be heated to speckle colour developing clear, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
(5) get this preparation or its content 2g under the content uniformity item, add methanol 25ml, supersound process 30 minutes filters, and filtrate is concentrated into 1ml, as need testing solution; Other gets Radix Trichosanthis control medicinal material 1g, shines medical material solution in pairs with legal system; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography, draw each 5～10 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of adhesive with the sodium carboxymethyl cellulose, with n-butyl alcohol: ethanol: glacial acetic acid: water=8: 2: 2: 3 is developing solvent, launch, take out, dry, spray is with 5% ninhydrin solution, and 105 ℃ to be heated to the speckle colour developing clear; Put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
Check: should meet relevant every regulation under each preparation item of appendix I of Chinese Pharmacopoeia version in 2000;
Assay: shine an appendix VI of Chinese Pharmacopoeia version in 2000 D high effective liquid chromatography for measuring:
The suitable application test of system is a filler with the carbon octadecylsilane chemically bonded silica; Acetonitrile: water=36: 64 is mobile phase; Detect with evaporative light scattering detector; Theoretical cam curve should be not less than 6000 by the astragaloside peak;
It is an amount of that the preparation precision of reference substance solution takes by weighing the astragaloside reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 0.40mg, promptly;
This preparation or its content 6g under the content uniformity item got in the preparation of need testing solution, the accurate title, decide, put in the tool plug conical flask, precision adds methanol 50ml, claims to decide weight, supersound process is 1 hour under 250W, 29～34kHz condition, put coldly, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 25ml that draws, evaporate to dryness, residue is with adding water saturated n-butyl alcohol 50ml dissolving, wash with ammonia solution 20ml, divide and get n-butyl alcohol liquid, evaporate to dryness, residue is with dissolve with methanol and be settled to 5ml, shake up, promptly;
Accurate reference substance solution each 10 μ l, the 20 μ l of drawing of algoscopy, need testing solution 10 μ l inject chromatograph of liquid, measure, with external standard two-point method natural logrithm Equation for Calculating, promptly;
Every of this capsule contains the Radix Astragali in astragaloside C41H68O14, must not be less than 0.13mg; Granule contains the Radix Astragali in astragaloside C41H68O14 for every bag, must not be less than 0.2～0.4mg; The every 1g of the watered pill contains the Radix Astragali in astragaloside C41H68O14, must not be less than 0.3mg; The every 1g of drop pill contains the Radix Astragali in astragaloside C41H68O14, must not be less than 0.13mg.
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| CN1903325A true CN1903325A (en) | 2007-01-31 |
| CN100594034C CN100594034C (en) | 2010-03-17 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102707011A (en) * | 2012-07-02 | 2012-10-03 | 涂瑶生 | Thin-layer chromatography identification method of white gourd kernel formula granules |
| CN102697909A (en) * | 2012-06-09 | 2012-10-03 | 卞毓平 | Traditional Chinese medicinal composition for treating hyperlipidaemia and diabetes mellitus |
| CN101551365B (en) * | 2009-05-18 | 2013-01-16 | 郑州市协和制药厂 | Method for detecting astragalus glucoside content in Chinese angelica tonifying blood oral liquid |
| CN103439449A (en) * | 2013-07-25 | 2013-12-11 | 广东远大药业有限公司 | Detection method of medicine used for nourishing lung and activating blood |
| CN105403654A (en) * | 2015-12-11 | 2016-03-16 | 陇西保和堂药业有限责任公司 | Method raising radix astragali thin-layer chromatographic identification |
| CN110187042A (en) * | 2018-12-24 | 2019-08-30 | 江苏辰星药业股份有限公司 | A kind of detection method of ocean blood-sugar lowering type health-care food function of blood sugar reduction |
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2006
- 2006-07-28 CN CN200610200757A patent/CN100594034C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101551365B (en) * | 2009-05-18 | 2013-01-16 | 郑州市协和制药厂 | Method for detecting astragalus glucoside content in Chinese angelica tonifying blood oral liquid |
| CN102697909A (en) * | 2012-06-09 | 2012-10-03 | 卞毓平 | Traditional Chinese medicinal composition for treating hyperlipidaemia and diabetes mellitus |
| CN102707011A (en) * | 2012-07-02 | 2012-10-03 | 涂瑶生 | Thin-layer chromatography identification method of white gourd kernel formula granules |
| CN102707011B (en) * | 2012-07-02 | 2014-03-26 | 涂瑶生 | Thin-layer chromatography identification method of white gourd kernel formula granules |
| CN103439449A (en) * | 2013-07-25 | 2013-12-11 | 广东远大药业有限公司 | Detection method of medicine used for nourishing lung and activating blood |
| CN103439449B (en) * | 2013-07-25 | 2015-07-29 | 广东远大药业有限公司 | A kind of detection method of medicine of invigorating blood circulation for tonifying lung |
| CN105403654A (en) * | 2015-12-11 | 2016-03-16 | 陇西保和堂药业有限责任公司 | Method raising radix astragali thin-layer chromatographic identification |
| CN110187042A (en) * | 2018-12-24 | 2019-08-30 | 江苏辰星药业股份有限公司 | A kind of detection method of ocean blood-sugar lowering type health-care food function of blood sugar reduction |
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|---|---|
| CN100594034C (en) | 2010-03-17 |
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