CN1785293A - Quality control method of heart pulse free flow oral preparation - Google Patents
Quality control method of heart pulse free flow oral preparation Download PDFInfo
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Abstract
A quality control method for the orally taken Chinese medicine 'Xinmaitong' includes such steps as examining its characteristics, identifying the Chinese angelica root, rhubarb, pueraria root, cassia seed, notoginseng, etc, and measuring the content of lutin.
Description
Technical field: the present invention relates to a kind of method of quality control of heart pulse free flow oral preparation, belong to the technical field of medicine being carried out quality control.
Technical background: along with The development in society and economy, and people's growth in the living standard, the increasing of work, ambient pressure, the variation of dietary structure, hypertension, hyperlipemia sickness rate rise appreciably in recent years, are seriously threatening human life security, become one of principal disease that increases family and social economy's burden, yet up to the present, the new Chinese medicine kind of treatment hypertension, hyperlipemia can not be met the need of market far away.Heart beniol preparation is by Radix Angelicae Sinensis, Semen Cassiae, Ramulus Uncariae Cum Uncis, Radix Achyranthis Bidentatae, Radix Salviae Miltiorrhizae, Radix Puerariae, Flos Sophorae, Radix Ilicis Pubescentis, Spica Prunellae and Radix Notoginseng are formed, has blood circulation promoting and blood stasis dispelling, freeing vessels and nourishing heart, the hypertension and hyperlipemia function, wherein " xinmaitong tablet " publication is the 6th of Drug Standard of Ministry of Public Health of the Peoples Republic of China, and this tablet is used for many years clinically, in treatment hypertension, obtain satisfied therapeutic effect on the hyperlipemia, but discover through us, " xinmaitong tablet " exists quality control standard simple, the uppity shortcoming of product quality, in process of producing product, the quality of heart beniol preparation can not be effectively controlled with this method of quality control, thereby the clinical efficacy of heart beniol preparation will be influenced.
Summary of the invention: the objective of the invention is to: the method for quality control that a kind of heart pulse free flow oral preparation is provided.This solid preparation comprises capsule, granule and tablet.It is simple to the present invention is directed to original preparation xinmaitong tablet quality control standard, shortcomings such as product quality is wayward, method of quality control to this preparation is studied, method of quality control has increased the assay of rutin and the TLC thin layer of Radix Angelicae Sinensis, Semen Cassiae, Radix Puerariae and four medical materials of Radix Notoginseng is differentiated, improve the quality control standard of heart beniol preparation, thereby guaranteed the clinical efficacy of this preparation.
Heart pulse free flow oral preparation described in the present invention is according to the described technology of ministry standard xinmaitong tablet and extracts, add preparation behind the adjuvant again and get, its prescription calculates according to composition by weight, form by Radix Angelicae Sinensis 100-250, Semen Cassiae 100-250, Ramulus Uncariae Cum Uncis 50-200, Radix Achyranthis Bidentatae 50-200, Radix Salviae Miltiorrhizae 50-150, Radix Puerariae 50-150, Flos Sophorae 50-150, Radix Ilicis Pubescentis 50-150, Spica Prunellae 50-150, Radix Notoginseng 1-15, its preparation method is: Radix Notoginseng powder is broken into fine powder, sieves.Flos Sophorae decocts with water after boil, and transfers PH to 5-12 with lime cream, decocts 1-5 time, filter, and merging filtrate, with hydrochloric acid accent PH to 3-7, after the cooling, elimination precipitates, and drying is standby.Radix Angelicae Sinensis, Ramulus Uncariae Cum Uncis decoct with water 1-5 time, filter, and merging filtrate concentrates, and add ethanol and make and contain the alcohol amount and be 30-90%, leave standstill, and filter, and filtrate recycling ethanol is condensed into thick paste.Six-elements such as all the other Radix Salviae Miltiorrhizaes decoct with water 1-5 time, filter, and merging filtrate is condensed into thick paste, with above-mentioned thick paste and fine powder and appropriate amount of auxiliary materials mixing, is prepared into capsule, granule or tablet according to diverse ways again.
Described method of quality control mainly comprises character, inspection, and in the discriminating, two projects of assay one or two; Wherein differentiate comprise with Radix Angelicae Sinensis control medicinal material, chrysophanol reference substance, puerarin reference substance, Radix Notoginseng control medicinal material, panoxadiol's reference substance be the thin layer of contrast differentiate part or all of; Assay comprises the content assaying method with control substance of Rutin.
In this preparation, the content assaying method of rutin comprises with methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is the high-efficient liquid phase determining method of mobile phase.
The discrimination method of Radix Angelicae Sinensis comprises that with the Radix Angelicae Sinensis medical material be contrast in this preparation, and with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is the thin layer discrimination method of developing solvent.
The discrimination method of Semen Cassiae comprises that with the chrysophanol reference substance be contrast in this preparation, and with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is the thin layer discrimination method of developing solvent.
The discrimination method of Radix Puerariae comprises that with the puerarin reference substance be contrast in this preparation, and with ethyl acetate: chloroform: methanol or acetonitrile: water: glacial acetic acid or formic acid=3～15: 1～5: 1～5: 1～5: lower floor's solution of 0.02～0.1 is the thin layer discrimination method of developing solvent.
The discrimination method of Radix Notoginseng comprises that with Radix Notoginseng control medicinal material, panoxadiol's reference substance be contrast in this preparation, and with toluene: acetone=3-15: 1-5 solution is the thin layer discrimination method of developing solvent.
Described method of quality control comprises:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate:
(1) core beniol capsule, granule or tablet are put in the tool plug triangular flask, add ether, and supersound process makes dissolving fully, filter, and the filtrate water-bath is waved near and done, and residue adds methanol makes dissolving, as need testing solution; Other gets the Radix Angelicae Sinensis control medicinal material, shines medical material solution in pairs with legal system; Draw need testing solution and Radix Angelicae Sinensis control medicinal material solution respectively, point is on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
(2) core beniol capsule, granule or tablet add ethanol, and supersound process makes dissolving fully, filter, filtrate adds hydrochloric acid, heating and refluxing extraction, the extracting solution water-bath is waved to about 2-10ml, add water 5-20ml mixing, extract 1-5 time for 40～100 ℃, each 10-50ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Other gets the chrysophanol reference substance, adds dissolve with ethanol, product solution in contrast; Draw need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=2～10: 0.2～1: 0.05～0.5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
(3) core beniol capsule, granule or tablet, add the 30-95% alcoholic solution, heating and refluxing extraction filters the filtrate evaporate to dryness, add the fusion of water slight fever, filter, filtrate adds polyamide column, successively with 5-15% ethanol, 20-80% alcoholic solution difference eluting, collect last eluent, evaporate to dryness, residue add methanol makes dissolving, adds neutral alumina, mix thoroughly, be added on the neutral alumina post, use the 30-80% ethanol elution, the eluent evaporate to dryness, residue adds methanol makes dissolving, as need testing solution; Other gets the puerarin reference substance, uses dissolve with methanol, in contrast product solution; Draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: methanol or acetonitrile: water: glacial acetic acid or formic acid=3～15: 1～5: 1～5: 1～5: lower floor's solution of 0.02～0.1 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 1-10g, the 10-100 order, internal diameter 0.5-5cm is earlier with ethanol 20-100ml eluting, reuse water 50-500ml eluting; The neutral alumina post is 1-10g, 50-500 order, internal diameter 0.5-5cm.
(4) the beniol capsule of coring, granule or tablet add methanol, reflux, extract,, filter, filtrate evaporate to dryness, residue add the fusion of water slight fever, filter, the saturated n-butanol extraction of filtrate water 1-5 time, each 10-50ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 1-3 time, each 10-50ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 1-3 time, each 10-50ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain the vitriolic 30-80% dissolve with ethanol solution of 4-10%, heating and refluxing extraction, cooling, with petroleum ether 40-100 ℃ of extraction 1-5 time, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol makes dissolving, as need testing solution; Other gets the Radix Notoginseng control medicinal material, add and contain the vitriolic 30-80% dissolve with ethanol solution of 4-10%, heating and refluxing extraction, cooling is with 40-100 ℃ of petroleum ether) extract 1-5 time, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add dissolve with methanol, in contrast product solution; Draw above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=3-15: 1-5 solution is developing solvent, launch, take out, dry, spray is with the 5-20% ethanol solution of sulfuric acid, be heated to clear spot at 100-120 ℃, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Assay:
Rutin is adopted high performance liquid chromatography, and chromatographic column is C18 or C4 or C8 post, and with methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is a mobile phase, and the detection wavelength is 200～500nm; Precision takes by weighing in the control substance of Rutin of 100-150 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, shakes up, and promptly gets reference substance solution; Core beniol capsule, granule or tablet accurately claim surely, put in the tool plug triangular flask, and the accurate methanol that adds claims decide weight, supersound process, cold after, add methanol and supply the weight that subtracts mistake, shake up, filtration promptly gets need testing solution; Accurate respectively reference substance solution and the need testing solution drawn, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
We find after deliberation, adopt the quality of following method of quality control with easier control heart pulse free flow oral preparation, are more conducive to guarantee the clinical efficacy of this preparation.So described method of quality control also can comprise:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate:
(1) core beniol capsule, granule or tablet 3-20g put in the tool plug triangular flask, add ether 10-100ml, supersound process 5-30min makes dissolving fully, filters, and filtrate is put 30-80 ℃ of water-bath and waved near dried, residue adds methanol 0.2-2ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.05-0.5g, shines medical material solution in pairs with legal system; Draw each 5-20 μ l of need testing solution and Radix Angelicae Sinensis control medicinal material solution respectively, on the same silica gel g thin-layer plate of idea, with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
(2) core beniol capsule, granule or tablet 1-5g add ethanol 10-50ml, and supersound process 5-30min makes dissolving fully, filter, filtrate adds hydrochloric acid 0.5-5ml, heating and refluxing extraction 0.5-3 hour, the extracting solution water-bath is waved to about 2-10ml, add water 5-20ml mixing, extract 1-5 time for 40～100 ℃, each 10-50ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol 0.5-3ml makes dissolving, as need testing solution.Other gets the chrysophanol reference substance, adds ethanol and makes the solution that every 1ml contains 0.1-0.5mg, in contrast product solution; Draw each 5-20 μ l of need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=2～10: 0.2～1: 0.05～0.5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
(3) the beniol capsule of coring, granule or tablet 1-8g, add 30-95% alcoholic solution 10-50ml, reflux 10-80min filters the filtrate evaporate to dryness, add the fusion of water 10-50ml slight fever, filter, filtrate adds polyamide column, uses 5-15% ethanol 10-50ml successively, 20-80% alcoholic solution 10-50ml is eluting respectively, collect second ethanol elution, evaporate to dryness, residue add methanol 1-5ml makes dissolving, adds neutral alumina 1-5g, mix thoroughly, be added on the neutral alumina post, with 30-80% ethanol 20-150ml eluting, eluent evaporate to dryness, residue adds methanol 0.5-3ml makes dissolving, as need testing solution; Other gets the puerarin reference substance, makes the solution that every 1ml contains 0.2-2mg with methanol, in contrast product solution; Draw need testing solution and each 5-20 μ l of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: methanol or acetonitrile: water: glacial acetic acid or formic acid=3～15: 1～5: 1～5: 1～5: lower floor's solution of 0.02～0.1 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 1-10g, the 10-100 order, internal diameter 0.5-5cm is earlier with ethanol 20-100ml eluting, reuse water 50-500ml eluting; The neutral alumina post is 1-10g, 50-500 order, internal diameter 0.5-5cm.
(4) the beniol capsule of coring, granule or tablet 3-20g add methanol 10-100ml, heating and refluxing extraction 0.5-3 hour, filter, filtrate evaporate to dryness, residue add the fusion of water 20-100ml slight fever, filter, the saturated n-butanol extraction of filtrate water 1-5 time, each 10-50ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 1-3 time, each 10-50ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 1-3 time, each 10-50ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain the vitriolic 30-80% alcoholic solution of 4-10% 10-60ml dissolving, heating and refluxing extraction 0.5-3 hour, cooling, with petroleum ether 40-100 ℃ of extraction 1-5 time, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue add methanol 0.5-3ml makes dissolving, as need testing solution; Other gets Radix Notoginseng control medicinal material 0.1-0.5g, add and contain the vitriolic 30-80% alcoholic solution of 4-10% 10-50ml dissolving, heating and refluxing extraction 0.5-3 hour, cooling was extracted 1-5 time for 40-100 ℃ with petroleum ether, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol 0.5-3ml makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add methanol and make the solution that every 1ml contains 0.1-0.5mg, in contrast product solution; Draw each 5-20 μ l of above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=3-15: 1-5 solution is developing solvent, launches, and takes out, dry, spray is heated to clear spot with the 5-20% ethanol solution of sulfuric acid at 100-120 ℃.Put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Assay: rutin is adopted high performance liquid chromatography, and chromatographic column is C18 or C4 or C8 post, and with methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is a mobile phase, and the detection wavelength is 200～500nm; Precision takes by weighing in the control substance of Rutin of 100-150 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, makes the solution that every 1ml contains 50 μ g, shakes up, and promptly gets reference substance solution; Core beniol capsule, granule or 10/sheet/bag of tablet are got the content mixing, and precision takes by weighing 0.5g, put in the tool plug triangular flask, precision adds methanol 50ml, claims to decide weight, supersound process 10 minutes, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 5ml that draws puts in the 25ml volumetric flask, adds methanol and is diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 5-20 μ l of need testing solution of drawing, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
Among the present invention, contained Flos Sophorae has pharmacological actions such as heart tonifying, coronary artery dilating, blood pressure lowering, antiinflammatory, antiviral, spasmolytic, antiulcer in the heart beniol preparation, it is one of main medicine of heart beniol treatment high blood pressure disease, because rutin content is higher in this preparation, has small artery, the blood capillary sphincter of contraction, improve capillary fragility and permeability, effects such as antiinflammatory, antiviral.For this reason, we study the content assaying method of rutin in the Flos Sophorae, " content assaying method of rutin is a spectrophotography in Flos Sophorae of Chinese pharmacopoeia version in 2000, but we find in product research, when rutin adopted spectrophotography to carry out assay in this preparation, its result was accurate inadequately.Though " assay of rutin is a high performance liquid chromatography in Flos Sophorae of Chinese pharmacopoeia version in 2005, and we find, when used chromatographic condition detected this preparation in this method, the gained chromatographic peak can not separate fully, and the peak type is bad, and testing result is inaccurate.We find after deliberation, adopt high performance liquid chromatography that rutin content is measured in this preparation, and adopt methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is a mobile phase, and its result is accurate, and precision, repeatability and stability all can reach requirement.
Radix Angelicae Sinensis has the effect of enriching blood and invigorating blood circulation, and is one of medicine of playing a major role in this preparation.We find after deliberation, in the thin layer discrimination method of Radix Angelicae Sinensis medical material, because Radix Angelicae Sinensis mainly contains compositions such as volatile oil, organic acid, still be the composition that extractant extracts Radix Angelicae Sinensis in the preparation with the ether, and with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 be developing solvent, thin layer result demonstration, this method specificity is strong, good separating effect, it is clear to develop the color, and can well differentiate the Radix Angelicae Sinensis medical material in this preparation.
Semen Cassiae has the effect of clearing away heat to improve acuity of vision in this preparation, is one of medicine of playing a major role in this preparation.We find after deliberation, in the thin layer discrimination method of Semen Cassiae medical material, because Semen Cassiae contains chemical compounds such as emodin, chrysophanol, in product research, we select the pool serves as that contrast is differentiated with emodin reference substance, chrysophanol reference substance, through repetition test, find that the interference of emodin discriminating is bigger, so differentiate the Semen Cassiae medical material with the chrysophanol reference substance.In the preparation method of need testing solution, we find after deliberation, and this preparation adopts the ethanol supersound process, and filtrate adds the hydrochloric acid reflux hydrolysis, hydrolyzed solution is waved in right amount, adds water, uses Petroleum ether extraction, petroleum ether liquid evaporate to dryness, residue adds dissolve with ethanol, and the gained need testing solution is noiseless; In the selection of developing solvent, respectively with the mixture of cyclohexane extraction, ethyl acetate and formic acid, the mixture of chloroform, methanol, acetone and glacial acetic acid, the mixture of benzene, acetone and acetic acid, the mixture of chloroform, methanol and formic acid is that developing solvent launches, the result is with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=2～10: 0.2～1: 0.05～0.5 is that the developing solvent separating effect is best, speckle separating degree height, it is clear to develop the color, the negative control test is noiseless, so in order to the thin layer discrimination method of last method as Semen Cassiae.
Radix Puerariae has the effect of expelling pathogenic factors from muscles for reducing heat in this preparation, is one of medicine of playing a major role in this preparation.Wherein puerarin is the main effective ingredient in the Radix Puerariae, we find in product research, when differentiating the Radix Puerariae medical material with the puerarin reference substance, but the result shows, puerarin to detect interference bigger, need carry out separation and purification to sample, we find after deliberation, this preparation is handled the back through polyamide and neutral alumina and can be accessed preferably on silica gel g thin-layer plate and separate, and it is clear that speckle develops the color, and can well differentiate the Radix Puerariae medical material in this preparation.
Radix Notoginseng has the effect of dissipating blood stasis hemostatic, is one of medicine of playing a major role in this preparation.Because Radix Notoginseng contains multiple and the similar composition of ginsenoside, is respectively ginsenoside Rb
1, Rd, Re, Rg
1, Rg
2, Rh
1, Panax Notoginseng saponin R
1, R
2, R
3, R
4, R
6Deng, in product research, among us once with Radix Notoginseng control medicinal material, ginsenoside Rb
1, Re, Rg
1, Panax Notoginseng saponin R
1In contrast, the saponins compound of Radix Notoginseng in the discriminating side, through repetition test, the chromatograph speckle is not obvious, and negative control has interference, finds through studying us repeatedly, be contrast with the Radix Notoginseng control medicinal material through ethanol extraction posthydrolysis processing with panoxadiol in test, chromatograph clear spot as a result, negative control is noiseless, so in order to the thin layer discrimination method of last method as pseudo-ginseng in this preparation.
For reasonability of verifying rutin content assay method among the present invention etc., carried out following experiment.
One, the preparation of need testing solution
The investigation of rutin extraction method in the test sample: because the Flos Sophorae medical material is to exist with form of extract in the preparation, easily be dissolved in the character of methanol, ethanol equal solvent according to rutin, in the test, the methanol of having investigated variable concentrations is solvent, the method of supersound process the results are shown in following table.
Rutin content measurement result in the variable concentrations methanol extraction preparation
| Methanol concentration (%) | 30 | 50 | 70 | 100 |
| Average content (%) | 1.54 | 2.66 | 3.01 | 3.13 |
As seen, with the methanol supersound process of variable concentrations 10 minutes, the result was that solvent is best with methanol, so extract solvent employing methanol from last table.
Two, precision test: the beniol of coring, by method of quality control test of the present invention, repeat sample introduction 5 times, measure peak area, the results are shown in following table:
The precision of rutin test in the heart beniol preparation need testing solution
| The sample introduction number of times | 1 | 2 | 3 | 4 | 5 | On average | RSD(％) |
| Peak area | 388408 | 390377 | 387689 | 390502 | 384899 | 388375 | 0.59 |
Three, repeatability test: the beniol of coring, by method of quality control test of the present invention, prepare 5 parts of test liquids, sample introduction is measured peak area respectively, the results are shown in following table:
The repeatability of rutin test in the heart beniol preparation test sample
| Sample number | 1 | 2 | 3 | 4 | 5 | On average | RSD(％) |
| Content (%) | 3.108 | 3.120 | 3.177 | 3.079 | 3.152 | 3.13 | 1.22 |
Four, stability test: in the last sample introduction test liquid of repeatability is zero hour, and the according to the form below official hour is got this test liquid mensuration again, and the result shows that rutin is stable in 8 hours in the need testing solution.
Rutin stability test in the test sample
| Time (h) | 0 | 1 | 2 | 4 | 8 | On average | RSD(％) |
| Peak area | 405519 | 406018 | 404385 | 406291 | 404036 | 405250 | 0.25 |
Five, the recovery test precision takes by weighing control substance of Rutin 81.2mg, put in the 500ml volumetric flask, with dissolve with methanol and be diluted to scale, shake up, get the reference substance methanol solution that every 1ml contains rutin 0.1624mg, with this liquid serves as to extract solvent, takes by weighing 5 parts in preparation (average content 3.13%) measuring content, accurately adds above-mentioned control substance of Rutin solution 50ml, press 5 parts of test liquids of preparation quality standard draft preparation, sample introduction is measured peak area respectively, and result of calculation sees the following form.
The recovery test of rutin in the preparation test sample
| Experiment number | Sample size (g) | Contain rutin (mg) | Add rutin (mg) | The amount of recording (mg) | The response rate (%) | Average recovery rate (%) | RSD (％) |
| 1 | 0.2612 | 8.176 | 8.12 | 16.03 | 96.72 | ||
| 2 | 0.2536 | 7.938 | 8.12 | 15.88 | 97.81 | ||
| 3 | 0.2553 | 7.991 | 8.12 | 16.12 | 100.1 | 98.7 | 1.45 |
| 4 | 0.2572 | 8.050 | 8.12 | 16.15 | 99.75 | ||
| 5 | 0.2515 | 7.872 | 8.12 | 15.94 | 99.36 |
Show according to above experimental result, among the present invention, in the heart pulse free flow oral preparation in the content assaying method of rutin, the solvent of need testing solution is selected rationally, and show according to precision test, repeatability test, stability test, recovery test result, the inventive method is reasonable, feasible, is control heart beniol quality of the pharmaceutical preparations method preferably.
Compared with the prior art, among the present invention, simple at original preparation xinmaitong tablet quality control standard, shortcomings such as product quality is wayward, method of quality control to this preparation is studied, the TLC thin layer that has increased the assay of rutin and Radix Angelicae Sinensis, Semen Cassiae, Radix Puerariae and four medical materials of Radix Notoginseng at quality standard is differentiated, has improved the quality control standard of heart beniol preparation, thereby has guaranteed the clinical efficacy of this preparation.
Wherein, in the content assaying method of rutin, we discover, when rutin adopts spectrophotography to carry out assay in this preparation, its result is accurate inadequately, as detecting with high performance liquid chromatography, has only the methanol of employing or acetonitrile: when 0.1-0.5% phosphoric acid solution=20-80: 80-20 is mobile phase, its testing result is just comparatively accurate, and precision, repeatability and stability all can reach requirement; In the discrimination method of Radix Angelicae Sinensis, we are the composition that extractant extracts Radix Angelicae Sinensis in the preparation with the ether, and with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is developing solvent, the thin layer result shows that this method specificity is strong, good separating effect, it is clear to develop the color, and naked eyes are observed easily, is easy to differentiate; In the discrimination method of Semen Cassiae, in the preparation method of need testing solution, the present invention is with preparation ethanol supersound process, filtrate adds the hydrochloric acid reflux hydrolysis, hydrolyzed solution is waved in right amount, adds water, uses Petroleum ether extraction, petroleum ether liquid evaporate to dryness, after residue added dissolve with ethanol, the gained need testing solution was noiseless, and with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=2～10: 0.2～1: 0.05～0.5 is developing solvent, the result shows, good separating effect, speckle separating degree height, it is clear to develop the color, the negative control test is noiseless, is easy to differentiate; In the discrimination method of Radix Puerariae, the present invention handles the back with this preparation through polyamide and neutral alumina and can access preferably on silica gel g thin-layer plate and separate, and it is clear that speckle develops the color, and can well differentiate the Radix Puerariae medical material in this preparation; In the discrimination method of Radix Notoginseng, among the present invention the Radix Notoginseng control medicinal material is handled and is contrast with panoxadiol through the ethanol extraction posthydrolysis, chromatograph clear spot as a result, negative control is noiseless, so in order to the thin layer discrimination method of last method as pseudo-ginseng in this preparation.So with the quality of the inventive method control heart pulse free flow oral preparation, not only the discrimination method specificity is strong, the content assaying method favorable reproducibility; Simultaneously, used discrimination method and assay project can be guaranteed the curative effect of medicine, have reached the goal of the invention of the quality of effective control medicine.
The specific embodiment:
The embodiment of the invention 1:
Character: for capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate: (1) core beniol capsule, granule or tablet content 6g, put in the tool plug triangular flask, add ether 30ml, supersound process 15min makes dissolving fully, filters, and filtrate is put 40-50 ℃ of water-bath and waved near dried, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.1g, shines medical material solution in pairs with legal system; Draw each 10 μ l of need testing solution and Radix Angelicae Sinensis control medicinal material solution respectively, point is on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate=10: 1 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 365nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
(2) core beniol capsule, granule or tablet content 2g add ethanol 20ml, and supersound process 10min makes dissolving fully, filter, filtrate adds hydrochloric acid 1ml, heating and refluxing extraction 1 hour, the extracting solution water-bath is waved to about 5ml, add water 10ml mixing, extract 2 times for 60～90 ℃, each 20ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets the chrysophanol reference substance, adds ethanol and makes the solution that every 1ml contains 0.2mg, in contrast product solution; Draw each 15 μ l of need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=5: 0.5: 0.3 are developing solvent, launch, take out, dry, put under the ultra-violet lamp 360nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
(3) core beniol capsule, granule or tablet content 3g, add 75% alcoholic solution 30ml, reflux 30min filters the filtrate evaporate to dryness, add the fusion of water 40ml slight fever, filter, filtrate adds polyamide column, successively with 10% ethanol 30ml, 40% alcoholic solution 30ml difference eluting, collect 40% ethanol elution, evaporate to dryness, residue add methanol 2ml makes dissolving, adds neutral alumina 2g, mix thoroughly, be added on the neutral alumina post, with 50% ethanol 100ml eluting, eluent evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution; Other gets the puerarin reference substance, makes the solution that every 1ml contains 1mg with methanol, in contrast product solution; Draw each 10 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: methanol: water: glacial acetic acid=6: 2: 2: lower floor's solution of 2: 0.05 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 365nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 5g, the 30-60 order, internal diameter 1-1.5cm is earlier with ethanol 50ml eluting, reuse water 200ml eluting; The neutral alumina post is 4g, 100-200 order, internal diameter 1-1.5cm.
(4) the beniol capsule of coring, granule or tablet content 6g add methanol 50ml, heating and refluxing extraction 1 hour, filter, filtrate evaporate to dryness, residue add the fusion of water 40ml slight fever, filter, the saturated n-butanol extraction of filtrate water 3 times, each 20ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 2 times, each 20ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 2 times, each 20ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain 7% vitriolic 50% alcoholic solution 30ml dissolving, heating and refluxing extraction 1 hour, cooling, with petroleum ether 60-90 ℃ of extraction 3 times, each 20ml, petroleum ether liquid washes with water 3 times, each 20ml, petroleum ether liquid evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets Radix Notoginseng control medicinal material 0.2g, add and contain 7% vitriolic 50% alcoholic solution 30ml dissolving, heating and refluxing extraction 1 hour, cooling is extracted 3 times for 60-90 ℃ with petroleum ether, each 20ml, petroleum ether liquid washes with water 3 times, each 20ml, petroleum ether liquid evaporate to dryness, residue adds methanol 1ml makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add methanol and make the solution that every 1ml contains 0.2mg, in contrast product solution; Draw each 10 μ l of above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=10: 3 solution is developing solvent, launches, and takes out, and dries, and spray is heated to clear spot with 10% ethanol solution of sulfuric acid at 105 ℃.Put under the ultra-violet lamp 365nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Assay: according to high effective liquid chromatography for measuring.
Chromatographic condition and system suitability test: chromatographic column is the C18 post; Acetonitrile: 0.3% phosphoric acid solution=40: 60 is a mobile phase; The detection wavelength is 360nm, and theoretical cam curve should be not less than 3500 in the rutin peak.
The preparation of reference substance solution: precision takes by weighing in the control substance of Rutin of 120 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, makes the solution that every 1ml contains 50 μ g, shakes up, promptly;
The preparation of need testing solution: the beniol capsule of coring, granule or 10/sheet/bag of tablet, get the content mixing, precision takes by weighing 0.5g, put in the tool plug triangular flask, precision adds methanol 50ml, claims to decide weight, supersound process 10 minutes, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 5ml that draws puts in the 25ml volumetric flask, adds methanol and is diluted to scale, shake up, promptly;
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
Embodiments of the invention 2:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate: the beniol capsule of coring, granule or tablet 1g, add ethanol 10ml, supersound process 5min makes dissolving fully, filter, filtrate adds hydrochloric acid 0.5ml, heating and refluxing extraction 0.5 hour, the extracting solution water-bath is waved to about 2ml, add water 5ml mixing, extract 1 time for 40-70 ℃, each 10ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol 0.5ml makes dissolving, as need testing solution.Other gets the chrysophanol reference substance, adds ethanol and makes the solution that every 1ml contains 0.1mg, in contrast product solution; Draw each 20 μ l of need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: formic acid=2: 1: 0.05 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Assay: according to high effective liquid chromatography for measuring.
Chromatographic condition and system suitability test: chromatographic column is the C18 post; Methanol: 0.2% phosphoric acid solution=70: 30 is a mobile phase; The detection wavelength is 265nm, and theoretical cam curve should be not less than 3000 in the rutin peak.
The preparation of reference substance solution: precision takes by weighing in the control substance of Rutin of 120 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, makes the solution that every 1ml contains 50 μ g, shakes up, promptly;
The preparation of need testing solution: the beniol capsule of coring, granule or 10/sheet/bag of tablet, get the content mixing, precision takes by weighing 0.5g, put in the tool plug triangular flask, precision adds methanol 50ml, claims to decide weight, supersound process 10 minutes, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 5ml that draws puts in the 25ml volumetric flask, adds methanol and is diluted to scale, shake up, promptly;
Algoscopy: accurate respectively reference substance solution and each 15 μ l of need testing solution of drawing, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
Embodiments of the invention 3:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate: the beniol capsule of coring, granule or tablet 1g, add 30% alcoholic solution 10ml, reflux 10min filters the filtrate evaporate to dryness, add the fusion of water 10ml slight fever, filter, filtrate adds polyamide column, successively with 5% ethanol 50ml, 20% alcoholic solution 50ml difference eluting, collect 20% ethanol elution, evaporate to dryness, residue add methanol 1ml makes dissolving, adds neutral alumina 1g, mix thoroughly, be added on the neutral alumina post, with 30% ethanol 150ml eluting, eluent evaporate to dryness, residue adds methanol 0.5ml makes dissolving, as need testing solution; Other gets the puerarin reference substance, makes the solution that every 1ml contains 0.2mg with methanol, in contrast product solution; Draw each 20 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: acetonitrile: water: glacial acetic acid=3: 5: 1: lower floor's solution of 5: 0.02 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 200nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 1g, the 10-50 order, internal diameter 0.5-3cm is earlier with ethanol 20ml eluting, reuse water 50ml eluting; The neutral alumina post is 1g, 50-200 order, internal diameter 0.5-3cm.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Assay: according to high effective liquid chromatography for measuring.
Chromatographic condition and system suitability test: chromatographic column is the C8 post; Acetonitrile: 0.5% phosphoric acid solution=80: 80 is a mobile phase; The detection wavelength is 500nm, and theoretical cam curve should be not less than 1500 in the rutin peak.
The preparation of reference substance solution: precision takes by weighing in the control substance of Rutin of 150 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, makes the solution that every 1ml contains 50 μ g, shakes up, promptly;
The preparation of need testing solution: the beniol capsule of coring, granule or 10/sheet/bag of tablet, get the content mixing, precision takes by weighing 0.5g, put in the tool plug triangular flask, precision adds methanol 50ml, claims to decide weight, supersound process 10 minutes, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 5ml that draws puts in the 25ml volumetric flask, adds methanol and is diluted to scale, shake up, promptly;
Algoscopy: accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
Embodiments of the invention 4:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate: the beniol capsule of coring, granule or tablet 3g add methanol 10ml, heating and refluxing extraction 0.5 hour, filter, filtrate evaporate to dryness, residue add the fusion of water 20ml slight fever, filter, the saturated n-butanol extraction of filtrate water 1 time, each 10ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 1 time, each 10ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 1 time, each 10ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain 4% vitriolic 30% alcoholic solution 10ml dissolving, heating and refluxing extraction 0.5 hour, cooling, with petroleum ether 40-70 ℃ of extraction 1 time, each 5ml, petroleum ether liquid washes with water 1 time, each 10ml, petroleum ether liquid evaporate to dryness, residue add methanol 0.5ml makes dissolving, as need testing solution; Other gets Radix Notoginseng control medicinal material 0.1g, add and contain 4% vitriolic 30% alcoholic solution 10ml dissolving, heating and refluxing extraction 0.5 hour, cooling is extracted 1 time for 40-70 ℃ with petroleum ether, each 5ml, petroleum ether liquid washes with water 1 time, each 10ml, petroleum ether liquid evaporate to dryness, residue adds methanol 0.5ml makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add methanol and make the solution that every 1ml contains 0.1mg, in contrast product solution; Draw each 20 μ l of above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=3: 5 solution is developing solvent, launches, and takes out, and dries, and spray is heated to clear spot with 5% ethanol solution of sulfuric acid at 120 ℃.Put under the ultra-violet lamp 200nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Embodiments of the invention 5:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate:
(1) core beniol capsule, granule or tablet 20g put in the tool plug triangular flask, add ether 100ml, and supersound process 30min makes dissolving fully, filter, and filtrate is put 30-50 ℃ of water-bath and waved near and do, and residue adds methanol 2ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.5g, shines medical material solution in pairs with legal system; Draw each 5 μ l of need testing solution and Radix Angelicae Sinensis control medicinal material solution respectively, point is on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate=20: 0.5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 600nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
(2) core beniol capsule, granule or tablet 8g, add 95% alcoholic solution 50ml, reflux 80min filters the filtrate evaporate to dryness, add the fusion of water 50ml slight fever, filter, filtrate adds polyamide column, successively with 15% ethanol 10ml, 80% alcoholic solution 10ml difference eluting, collect 80% ethanol elution, evaporate to dryness, residue add methanol 5ml makes dissolving, adds neutral alumina 5g, mix thoroughly, be added on the neutral alumina post, with 80% ethanol 20ml eluting, eluent evaporate to dryness, residue adds methanol 3ml makes dissolving, as need testing solution; Other gets the puerarin reference substance, makes the solution that every 1ml contains 2mg with methanol, in contrast product solution; Draw each 5 μ l of need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: acetonitrile: water: formic acid=15: 1: 5: lower floor's solution of 1: 0.1 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 10g, the 50-100 order, internal diameter 3-5cm is earlier with ethanol 100ml eluting, reuse water 500ml eluting; The neutral alumina post is 10g, 200-500 order, internal diameter 3-5cm.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Embodiments of the invention 6:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate:
(1) core beniol capsule, granule or tablet 5g add ethanol 50ml, and supersound process 30min makes dissolving fully, filter, filtrate adds hydrochloric acid 5ml, heating and refluxing extraction 3 hours, the extracting solution water-bath is waved to about 10ml, add water 20ml mixing, extract 5 times for 70-100 ℃, each 50ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol 3ml makes dissolving, as need testing solution.Other gets the chrysophanol reference substance, adds ethanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution; Draw each 5 μ l of need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: glacial acetic acid=10: 0.2: 0.5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
(2) the beniol capsule of coring, granule or tablet 20g add methanol 100ml, heating and refluxing extraction 3 hours, filter, filtrate evaporate to dryness, residue add the fusion of water 100ml slight fever, filter, the saturated n-butanol extraction of filtrate water 5 times, each 50ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 3 times, each 50ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 3 times, each 50ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain 10% vitriolic 80% alcoholic solution 60ml dissolving, heating and refluxing extraction 3 hours, cooling, with petroleum ether 70-100 ℃ of extraction 5 times, each 40ml, petroleum ether liquid washes with water 5 times, each 50ml, petroleum ether liquid evaporate to dryness, residue add methanol 3ml makes dissolving, as need testing solution; Other gets Radix Notoginseng control medicinal material 0.5g, add and contain 10% vitriolic 80% alcoholic solution 50ml dissolving, heating and refluxing extraction 3 hours, cooling is extracted 5 times for 70-100 ℃ with petroleum ether, each 40ml, petroleum ether liquid washes with water 5 times, each 50ml, petroleum ether liquid evaporate to dryness, residue adds methanol 3ml makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Draw each 5 μ l of above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=15: 1 solution is developing solvent, launches, and takes out, and dries, and spray is heated to clear spot with 20% ethanol solution of sulfuric acid at 100 ℃.Put under the ultra-violet lamp 600nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Assay: according to high effective liquid chromatography for measuring.
Chromatographic condition and system suitability test: chromatographic column is the C4 post; Methanol: 0.1% phosphoric acid solution=20: 80 is a mobile phase; The detection wavelength is 200nm, and theoretical cam curve should be not less than 4000 in the rutin peak.
The preparation of reference substance solution: precision takes by weighing in the control substance of Rutin of 100 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, makes the solution that every 1ml contains 50 μ g, shakes up, promptly;
The preparation of need testing solution: the beniol capsule of coring, granule or 10/sheet/bag of tablet, get the content mixing, precision takes by weighing 0.5g, put in the tool plug triangular flask, precision adds methanol 50ml, claims to decide weight, supersound process 10 minutes, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 5ml that draws puts in the 25ml volumetric flask, adds methanol and is diluted to scale, shake up, promptly;
Algoscopy: accurate respectively reference substance solution and each 5 μ l of need testing solution of drawing, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
Embodiments of the invention 7:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Differentiate: the beniol capsule of coring, granule or tablet 3g, put in the tool plug triangular flask, adding ether 10ml, supersound process 5min makes dissolving fully, filters, and filtrate is put 50-80 ℃ of water-bath and is waved near dried, and residue adds methanol 0.2ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.05g, shines medical material solution in pairs with legal system; Draw each 20 μ l of need testing solution and Radix Angelicae Sinensis control medicinal material solution respectively, point is on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate=4: 2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200nm 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 every regulation relevant under the Chinese Pharmacopoeia capsule item.
Embodiments of the invention 8:
Character:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery.
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery.
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery.
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item.
Assay: according to high effective liquid chromatography for measuring.
Chromatographic condition and system suitability test: chromatographic column is the C8 post; Acetonitrile: 0.3% phosphoric acid solution=50: 50 is a mobile phase; The detection wavelength is 400nm, and theoretical cam curve should be not less than 3500 in the rutin peak.
The preparation of reference substance solution: precision takes by weighing in the control substance of Rutin of 120 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, makes the solution that every 1ml contains 50 μ g, shakes up, promptly;
The preparation of need testing solution: the beniol capsule of coring, granule or 10/sheet/bag of tablet, get the content mixing, precision takes by weighing 0.5g, put in the tool plug triangular flask, precision adds methanol 50ml, claims to decide weight, supersound process 10 minutes, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 5ml that draws puts in the 25ml volumetric flask, adds methanol and is diluted to scale, shake up, promptly;
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
Claims (12)
1. the method for quality control of a heart pulse free flow oral preparation, described oral formulations comprises capsule, granule and tablet, it is characterized in that: described method of quality control mainly comprises character, inspection, and in the discriminating, two projects of assay one or two; Wherein differentiate comprise with Radix Angelicae Sinensis control medicinal material, chrysophanol reference substance, puerarin reference substance, Radix Notoginseng control medicinal material, panoxadiol's reference substance be the thin layer of contrast differentiate part or all of; Assay comprises the content assaying method with control substance of Rutin.
2. according to the method for quality control of the described heart pulse free flow oral preparation of claim 1, it is characterized in that: in this preparation, the content assaying method of rutin comprises with methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is the high-efficient liquid phase determining method of mobile phase.
3. according to the method for quality control of claim 1 or 2 described heart pulse free flow oral preparations, it is characterized in that: content assaying method comprises:
Rutin is adopted high performance liquid chromatography, and chromatographic column is C18 or C4 or C8 post, and with methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is a mobile phase, and the detection wavelength is 200～500nm; Precision takes by weighing in the control substance of Rutin of 100-150 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, shakes up, and promptly gets reference substance solution; Core beniol capsule, granule or tablet accurately claim surely, put in the tool plug triangular flask, and the accurate methanol that adds claims decide weight, supersound process, cold after, add methanol and supply the weight that subtracts mistake, shake up, filtration promptly gets need testing solution; Accurate respectively reference substance solution and the need testing solution drawn, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
4. according to the method for quality control of the described heart pulse free flow oral preparation of claim 3, it is characterized in that: content assaying method comprises:
Rutin is adopted high performance liquid chromatography, and chromatographic column is C18 or C4 or C8 post, and with methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is a mobile phase, and the detection wavelength is 200～500nm; Precision takes by weighing in the control substance of Rutin of 100-150 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, makes the solution that every 1ml contains 50 μ g, shakes up, and promptly gets reference substance solution; Core beniol capsule, granule or 10/sheet/bag of tablet are got the content mixing, and precision takes by weighing 0.5g, put in the tool plug triangular flask, precision adds methanol 50ml, claims to decide weight, supersound process 10 minutes, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 5ml that draws puts in the 25ml volumetric flask, adds methanol and is diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 5-20 μ l of need testing solution of drawing, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
5. according to the method for quality control of the described heart pulse free flow oral preparation of claim 1, it is characterized in that: the discrimination method of Radix Angelicae Sinensis comprises that with the Radix Angelicae Sinensis medical material be contrast in this preparation, and with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is the thin layer discrimination method of developing solvent.
6. according to the method for quality control of the described heart pulse free flow oral preparation of claim 1, it is characterized in that: the discrimination method of Semen Cassiae comprises that with the chrysophanol reference substance be contrast in this preparation, and with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is the thin layer discrimination method of developing solvent.
7. according to the method for quality control of the described heart pulse free flow oral preparation of claim 1, it is characterized in that: the discrimination method of Radix Puerariae comprises that with the puerarin reference substance be contrast in this preparation, and with ethyl acetate: chloroform: methanol or acetonitrile: water: glacial acetic acid or formic acid=3～15: 1～5: 1～5: 1～5: lower floor's solution of 0.02～0.1 is the thin layer discrimination method of developing solvent.
8. according to the method for quality control of the described heart pulse free flow oral preparation of claim 1, it is characterized in that: the discrimination method of Radix Notoginseng comprises that with Radix Notoginseng control medicinal material, panoxadiol's reference substance be contrast in this preparation, and with toluene: acetone=3-15: 1-5 solution is the thin layer discrimination method of developing solvent.
9. according to the method for quality control of claim 1,5,6,7 or 8 described heart pulse free flow oral preparations, it is characterized in that: discrimination method comprises the part or all of of following project:
(1) core beniol capsule, granule or tablet are put in the tool plug triangular flask, add ether, and supersound process makes dissolving fully, filter, and the filtrate water-bath is waved near and done, and residue adds methanol makes dissolving, as need testing solution; Other gets the Radix Angelicae Sinensis control medicinal material, shines medical material solution in pairs with legal system; Draw need testing solution and Radix Angelicae Sinensis control medicinal material solution respectively, point is on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(2) core beniol capsule, granule or tablet add ethanol, and supersound process makes dissolving fully, filter, filtrate adds hydrochloric acid, heating and refluxing extraction, the extracting solution water-bath is waved to about 2-10ml, add water 5-20ml mixing, extract 1-5 time for 40～100 ℃, each 10-50ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Other gets the chrysophanol reference substance, adds dissolve with ethanol, product solution in contrast; Draw need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=2～10: 0.2～1: 0.05～0.5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
(3) core beniol capsule, granule or tablet, add the 30-95% alcoholic solution, heating and refluxing extraction filters the filtrate evaporate to dryness, add the fusion of water slight fever, filter, filtrate adds polyamide column, successively with 5-15% ethanol, 20-80% alcoholic solution difference eluting, collect last eluent, evaporate to dryness, residue add methanol makes dissolving, adds neutral alumina, mix thoroughly, be added on the neutral alumina post, use the 30-80% ethanol elution, the eluent evaporate to dryness, residue adds methanol makes dissolving, as need testing solution; Other gets the puerarin reference substance, uses dissolve with methanol, in contrast product solution; Draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: methanol or acetonitrile: water: glacial acetic acid or formic acid=3～15: 1～5: 1～5: 1～5: lower floor's solution of 0.02～0.1 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 1-10g, the 10-100 order, internal diameter 0.5-5cm is earlier with ethanol 20-100ml eluting, reuse water 50-500ml eluting; The neutral alumina post is 1-10g, 50-500 order, internal diameter 0.5-5cm;
(4) the beniol capsule of coring, granule or tablet add methanol, reflux, extract,, filter, filtrate evaporate to dryness, residue add the fusion of water slight fever, filter, the saturated n-butanol extraction of filtrate water 1-5 time, each 10-50ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 1-3 time, each 10-50ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 1-3 time, each 10-50ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain the vitriolic 30-80% dissolve with ethanol solution of 4-10%, heating and refluxing extraction, cooling, with petroleum ether 40-100 ℃ of extraction 1-5 time, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol makes dissolving, as need testing solution; Other gets the Radix Notoginseng control medicinal material, add and contain the vitriolic 30-80% dissolve with ethanol solution of 4-10%, heating and refluxing extraction, cooling is extracted 1-5 time for 40-100 ℃ with petroleum ether, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add dissolve with methanol, in contrast product solution; Draw above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=3-15: 1-5 solution is developing solvent, launch, take out, dry, spray is with the 5-20% ethanol solution of sulfuric acid, be heated to clear spot at 100-120 ℃, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
10. according to the method for quality control of claim 1,5,6,7 or 8 described heart pulse free flow oral preparations, it is characterized in that: discrimination method comprises the part or all of of following project:
(1) core beniol capsule, granule or tablet 3-20g put in the tool plug triangular flask, add ether 10-100ml, supersound process 5-30min makes dissolving fully, filters, and filtrate is put 30-80 ℃ of water-bath and waved near dried, residue adds methanol 0.2-2ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.05-0.5g, shines medical material solution in pairs with legal system; Draw each 5-20 μ l of need testing solution and Radix Angelicae Sinensis control medicinal material solution respectively, point is on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(2) core beniol capsule, granule or tablet 1-5g add ethanol 10-50ml, and supersound process 5-30min makes dissolving fully, filter, filtrate adds hydrochloric acid 0.5-5ml, heating and refluxing extraction 0.5-3 hour, the extracting solution water-bath is waved to about 2-10ml, add water 5-20ml mixing, extract 1-5 time for 40～100 ℃, each 10-50ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol 0.5-3ml makes dissolving, as need testing solution; Other gets the chrysophanol reference substance, adds ethanol and makes the solution that every 1ml contains 0.1-0.5mg, in contrast product solution; Draw each 5-20 μ l of need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=2～10: 0.2～1: 0.05～0.5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
(3) the beniol capsule of coring, granule or tablet 1-8g, add 30-95% alcoholic solution 10-50ml, reflux 10-80min filters the filtrate evaporate to dryness, add the fusion of water 10-50ml slight fever, filter, filtrate adds polyamide column, uses 5-15% ethanol 10-50ml successively, 20-80% alcoholic solution 10-50ml is eluting respectively, collect second ethanol elution, evaporate to dryness, residue add methanol 1-5ml makes dissolving, adds neutral alumina 1-5g, mix thoroughly, be added on the neutral alumina post, with 30-80% ethanol 20-150ml eluting, eluent evaporate to dryness, residue adds methanol 0.5-3ml makes dissolving, as need testing solution; Other gets the puerarin reference substance, makes the solution that every 1ml contains 0.2-2mg with methanol, in contrast product solution; Draw need testing solution and each 5-20 μ l of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: methanol or acetonitrile: water: glacial acetic acid or formic acid=3～15: 1～5: 1～5: 1～5: lower floor's solution of 0.02～0.1 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 1-10g, the 10-100 order, internal diameter 0.5-5cm is earlier with ethanol 20-100ml eluting, reuse water 50-500ml eluting; The neutral alumina post is 1-10g, 50-500 order, internal diameter 0.5-5cm;
(4) the beniol capsule of coring, granule or tablet 3-20g add methanol 10-100ml, heating and refluxing extraction 0.5-3 hour, filter, filtrate evaporate to dryness, residue add the fusion of water 20-100ml slight fever, filter, the saturated n-butanol extraction of filtrate water 1-5 time, each 10-50ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 1-3 time, each 10-50ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 1-3 time, each 10-50ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain the vitriolic 30-80% alcoholic solution of 4-10% 10-60ml dissolving, heating and refluxing extraction 0.5-3 hour, cooling, with petroleum ether 40-100 ℃ of extraction 1-5 time, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue add methanol 0.5-3ml makes dissolving, as need testing solution; Other gets Radix Notoginseng control medicinal material 0.1-0.5g, add and contain the vitriolic 30-80% alcoholic solution of 4-10% 10-50ml dissolving, heating and refluxing extraction 0.5-3 hour, cooling was extracted 1-5 time for 40-100 ℃ with petroleum ether, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol 0.5-3ml makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add methanol and make the solution that every 1ml contains 0.1-0.5mg, in contrast product solution; Draw each 5-20 μ l of above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=3-15: 1-5 solution is developing solvent, launches, and takes out, dry, spray is heated to clear spot with the 5-20% ethanol solution of sulfuric acid at 100-120 ℃; Put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
11. the method for quality control according to the described heart pulse free flow oral preparation of claim 1 is characterized in that: the character in the described method of quality control is:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery;
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery;
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery;
Discriminating is:
(1) core beniol capsule, granule or tablet are put in the tool plug triangular flask, add ether, and supersound process makes dissolving fully, filter, and the filtrate water-bath is waved near and done, and residue adds methanol makes dissolving, as need testing solution; Other gets the Radix Angelicae Sinensis control medicinal material, shines medical material solution in pairs with legal system; Draw need testing solution and Radix Angelicae Sinensis control medicinal material solution respectively, point is on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(2) core beniol capsule, granule or tablet add ethanol, and supersound process makes dissolving fully, filter, filtrate adds hydrochloric acid, heating and refluxing extraction, the extracting solution water-bath is waved to about 2-10ml, add water 5-20ml mixing, extract 1-5 time for 40～100 ℃, each 10-50ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol makes dissolving, as need testing solution; Other gets the chrysophanol reference substance, adds dissolve with ethanol, product solution in contrast; Draw need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=2～10: 0.2～1: 0.05～0.5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
(3) core beniol capsule, granule or tablet, add the 30-95% alcoholic solution, heating and refluxing extraction filters the filtrate evaporate to dryness, add the fusion of water slight fever, filter, filtrate adds polyamide column, successively with 5-15% ethanol, 20-80% alcoholic solution difference eluting, collect last eluent, evaporate to dryness, residue add methanol makes dissolving, adds neutral alumina, mix thoroughly, be added on the neutral alumina post, use the 30-80% ethanol elution, the eluent evaporate to dryness, residue adds methanol makes dissolving, as need testing solution; Other gets the puerarin reference substance, uses dissolve with methanol, in contrast product solution; Draw need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: methanol or acetonitrile: water: glacial acetic acid or formic acid=3～15: 1～5: 1～5: 1～5: lower floor's solution of 0.02～0.1 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 1-10g, the 10-100 order, internal diameter 0.5-5cm is earlier with ethanol 20-100ml eluting, reuse water 50-500ml eluting; The neutral alumina post is 1-10g, 50-500 order, internal diameter 0.5-5cm;
(4) the beniol capsule of coring, granule or tablet add methanol, reflux, extract,, filter, filtrate evaporate to dryness, residue add the fusion of water slight fever, filter, the saturated n-butanol extraction of filtrate water 1-5 time, each 10-50ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 1-3 time, each 10-50ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 1-3 time, each 10-50ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain the vitriolic 30-80% dissolve with ethanol solution of 4-10%, heating and refluxing extraction, cooling, with petroleum ether 40-100 ℃ of extraction 1-5 time, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol makes dissolving, as need testing solution; Other gets the Radix Notoginseng control medicinal material, add and contain the vitriolic 30-80% dissolve with ethanol solution of 4-10%, heating and refluxing extraction, cooling is with 40-100 ℃ of petroleum ether) extract 1-5 time, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add dissolve with methanol, in contrast product solution; Draw above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=3-15: 1-5 solution is developing solvent, launch, take out, dry, spray is with the 5-20% ethanol solution of sulfuric acid, be heated to clear spot at 100-120 ℃, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
Inspection is: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item;
Assay is: rutin is adopted high performance liquid chromatography, and chromatographic column is C18 or C4 or C8 post, and with methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is a mobile phase, and the detection wavelength is 200～500nm; Precision takes by weighing in the control substance of Rutin of 100-150 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, shakes up, and promptly gets reference substance solution; Core beniol capsule, granule or tablet accurately claim surely, put in the tool plug triangular flask, and the accurate methanol that adds claims decide weight, supersound process, cold after, add methanol and supply the weight that subtracts mistake, shake up, filtration promptly gets need testing solution; Accurate respectively reference substance solution and the need testing solution drawn, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
12. the method for quality control according to the described heart pulse free flow oral preparation of claim 11 is characterized in that: the character in the described method of quality control is:
For capsule: the product content thing is that pale brown color is to brown powder or granule; Mildly bitter flavor, puckery;
For tablet: medicine shows pale brown color to sepia; Mildly bitter flavor, puckery;
For granule: product is that pale brown color is to brown granule; Mildly bitter flavor, puckery;
Differentiate: (1) core beniol capsule, granule or tablet 3-20g, put in the tool plug triangular flask, add ether 10-100ml, supersound process 5-30min makes dissolving fully, filters, and filtrate is put 30-80 ℃ of water-bath and waved near dried, residue adds methanol 0.2-2ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 0.05-0.5g, shines medical material solution in pairs with legal system; Draw need testing solution and each 5-20 μ 1 of Radix Angelicae Sinensis control medicinal material solution respectively, point is on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate=4～20: 0.5～2 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
(2) core beniol capsule, granule or tablet 1-5g add ethanol 10-50ml, and supersound process 5-30min makes dissolving fully, filter, filtrate adds hydrochloric acid 0.5-5ml, heating and refluxing extraction 0.5-3 hour, the extracting solution water-bath is waved to about 2-10ml, add water 5-20ml mixing, extract 1-5 time for 40～100 ℃, each 10-50ml with petroleum ether, merge petroleum ether liquid, evaporate to dryness, residue add ethanol 0.5-3ml makes dissolving, as need testing solution; Other gets the chrysophanol reference substance, adds ethanol and makes the solution that every 1ml contains 0.1-0.5mg, in contrast product solution; Draw each 5-20 μ l of need testing solution and reference substance solution respectively, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction: ethyl acetate: formic acid or glacial acetic acid=2～10: 0.2～1: 0.05～0.5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
(3) the beniol capsule of coring, granule or tablet 1-8g, add 30-95% alcoholic solution 10-50ml, reflux 10-80min filters the filtrate evaporate to dryness, add the fusion of water 10-50ml slight fever, filter, filtrate adds polyamide column, uses 5-15% ethanol 10-50ml successively, 20-80% alcoholic solution 10-50ml is eluting respectively, collect second ethanol elution, evaporate to dryness, residue add methanol 1-5ml makes dissolving, adds neutral alumina 1-5g, mix thoroughly, be added on the neutral alumina post, with 30-80% ethanol 20-150ml eluting, eluent evaporate to dryness, residue adds methanol 0.5-3ml makes dissolving, as need testing solution; Other gets the puerarin reference substance, makes the solution that every 1ml contains 0.2-2mg with methanol, in contrast product solution; Draw need testing solution and each 5-20 μ l of reference substance solution, put respectively on same silica gel g thin-layer plate, with ethyl acetate: chloroform: methanol or acetonitrile: water: glacial acetic acid or formic acid=3～15: 1～5: 1～5: 1～5: lower floor's solution of 0.02～0.1 is developing solvent, launches, and takes out, dry, put in the ammonia steam smoked after, put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color; More than used polyamide column be 1-10g, the 10-100 order, internal diameter 0.5-5cm is earlier with ethanol 20-100ml eluting, reuse water 50-500ml eluting; The neutral alumina post is 1-10g, 50-500 order, internal diameter 0.5-5cm;
(4) the beniol capsule of coring, granule or tablet 3-20g add methanol 10-100ml, heating and refluxing extraction 0.5-3 hour, filter, filtrate evaporate to dryness, residue add the fusion of water 20-100ml slight fever, filter, the saturated n-butanol extraction of filtrate water 1-5 time, each 10-50ml merges n-butyl alcohol liquid, ammonia solution with the saturated mistake of n-butyl alcohol washs 1-3 time, each 10-50ml discards ammonia solution, the saturated water washing of n-butyl alcohol liquid reuse n-butyl alcohol 1-3 time, each 10-50ml, n-butyl alcohol liquid evaporate to dryness, residue add and contain the vitriolic 30-80% alcoholic solution of 4-10% 10-60ml dissolving, heating and refluxing extraction 0.5-3 hour, cooling, with petroleum ether 40-100 ℃ of extraction 1-5 time, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue add methanol 0.5-3ml makes dissolving, as need testing solution; Other gets Radix Notoginseng control medicinal material 0.1-0.5g, add and contain the vitriolic 30-80% alcoholic solution of 4-10% 10-50ml dissolving, heating and refluxing extraction 0.5-3 hour, cooling was extracted 1-5 time for 40-100 ℃ with petroleum ether, each 5-40ml, petroleum ether liquid washes with water 1-5 time, each 10-50ml, petroleum ether liquid evaporate to dryness, residue adds methanol 0.5-3ml makes dissolving, in contrast medical material solution; Get panoxadiol's reference substance again, add methanol and make the solution that every 1ml contains 0.1-0.5mg, in contrast product solution; Draw each 5-20 μ l of above-mentioned three kinds of solution respectively, put on same silica gel g thin-layer plate respectively, make into ribbon, with toluene: acetone=3-15: 1-5 solution is developing solvent, launches, and takes out, dry, spray is heated to clear spot with the 5-20% ethanol solution of sulfuric acid at 100-120 ℃; Put under the ultra-violet lamp 200-600nm and inspect, in the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
Check: should meet every regulation relevant under the Chinese Pharmacopoeia capsule item;
Assay: rutin is adopted high performance liquid chromatography, and chromatographic column is C18 or C4 or C8 post, and with methanol or acetonitrile: 0.1-0.5% phosphoric acid solution=20-80: 80-20 is a mobile phase, and the detection wavelength is 200～500nm; Precision takes by weighing in the control substance of Rutin of 100-150 ℃ of drying under reduced pressure to constant weight, adds dissolve with methanol, makes the solution that every 1ml contains 50 μ g, shakes up, and promptly gets reference substance solution; Core beniol capsule, granule or 10/sheet/bag of tablet are got the content mixing, and precision takes by weighing 0.5g, put in the tool plug triangular flask, precision adds methanol 50ml, claims to decide weight, supersound process 10 minutes, cold after, add methanol and supply the weight that subtracts mistake, shake up, filter, the accurate subsequent filtrate 5ml that draws puts in the 25ml volumetric flask, adds methanol and is diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 5-20 μ l of need testing solution of drawing, inject hplc determination content, in this heart pulse free flow oral preparation, contain Flos Sophorae in the capsule in rutin, must not be less than in 25mg/g, the tablet and contain Flos Sophorae in rutin, must not be less than in 9mg/ sheet, the granule and contain Flos Sophorae, must not be less than 5mg/g in rutin.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102879518A (en) * | 2012-11-02 | 2013-01-16 | 广西万寿堂药业有限公司 | Quality detection method of blood pressure-lowering and lipid-lowering drugs |
| CN104510813A (en) * | 2015-01-10 | 2015-04-15 | 江西济民可信药业有限公司 | Preparation method for Xinmaitong capsules |
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| CN106896180A (en) * | 2015-12-21 | 2017-06-27 | 九芝堂股份有限公司 | A kind of detection method of Bushen Tianjing oral liquid |
| CN108956845A (en) * | 2018-07-27 | 2018-12-07 | 河北中医学院 | One kind three changes one plate of soup freeze-dried powder, four medicinal material multi information thin-layer identification method |
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2005
- 2005-10-17 CN CNB2005102006183A patent/CN100475239C/en active Active
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| CN102879518A (en) * | 2012-11-02 | 2013-01-16 | 广西万寿堂药业有限公司 | Quality detection method of blood pressure-lowering and lipid-lowering drugs |
| CN102879518B (en) * | 2012-11-02 | 2014-07-09 | 广西万寿堂药业有限公司 | Quality detection method of blood pressure-lowering and lipid-lowering drugs |
| CN104510813A (en) * | 2015-01-10 | 2015-04-15 | 江西济民可信药业有限公司 | Preparation method for Xinmaitong capsules |
| CN104510813B (en) * | 2015-01-10 | 2017-09-15 | 江西济民可信药业有限公司 | A kind of preparation method of heart maitong capsule |
| CN105277648A (en) * | 2015-09-29 | 2016-01-27 | 河北中医学院 | Multi-information gradient thin layer discriminating method of Radix Puerariae medicinal material and water extract product thereof |
| CN106896180A (en) * | 2015-12-21 | 2017-06-27 | 九芝堂股份有限公司 | A kind of detection method of Bushen Tianjing oral liquid |
| CN108956845A (en) * | 2018-07-27 | 2018-12-07 | 河北中医学院 | One kind three changes one plate of soup freeze-dried powder, four medicinal material multi information thin-layer identification method |
| CN108956845B (en) * | 2018-07-27 | 2020-07-31 | 河北中医学院 | One-plate four-medicine multi-information thin-layer identification method for three-ingredient decoction freeze-dried powder |
| CN111718384A (en) * | 2019-06-13 | 2020-09-29 | 贵州益佰女子大药厂有限责任公司 | Method for extracting rutin from sophora flower buds |
| CN111398471A (en) * | 2020-04-10 | 2020-07-10 | 山东中大千方制药有限公司 | Identification method of sophora japonica-scutellaria ointment |
| CN114113509A (en) * | 2021-11-16 | 2022-03-01 | 国药集团同济堂（贵州）制药有限公司 | Quality detection method of sophora japonica branch medicinal material |
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