CN1823858A - Quality control method of andrographis oral preparation - Google Patents
Quality control method of andrographis oral preparation Download PDFInfo
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Abstract
A quality control method for the orally taken medicine of green chiretta includes such steps as checking its characteristics, determination including the color development reaction by sodium nitrite and aluminum nitrate and thin-layer determination, and measuring the content of andrographolide.
Description
Technical field: the present invention relates to a kind of method of quality control of andrographis oral preparation, belong to the technical field of medicine being carried out quality control.
Background technology: cold, fever, laryngopharynx swelling and pain, aphtha of the mouth and tongue are a kind of commonly encountered diseases in our daily life, and people health in serious threat.Creat formulation is prepared from by Herba Andrographis and adjuvant, has heat-clearing and toxic substances removing, the effect of removing heat from blood repercussive.Wherein " CHUANXINLIAN JIAONANG " and " andrographis tablet " published respectively on one one of 20 in ministry standard Chinese traditional patent formulation preparation and Chinese Pharmacopoeia version in 2000.This medicine is used for many years clinically, at the treatment cold, fever, laryngopharynx swelling and pain, aphtha of the mouth and tongue, pertussis chronic cough, dysentery, the puckery pain of pyretic stranguria, the carbuncle skin infection, the venom aspect obtains satisfied therapeutic effect, but through discovering that existing creat formulation all exists the irrational shortcoming of method of quality control.In the existing creat formulation, dehydrorographolide all adopts thin layer chromatography scanning to carry out assay, the data relative standard deviation of surveying big, the determination data unstable result.So existing method of quality control can not effectively be controlled the quality of this andrographis oral preparation, thereby will influence the clinical efficacy of said preparation.
Summary of the invention:
The objective of the invention is to: the method for quality control that a kind of andrographis oral preparation is provided, this oral formulations comprises granule, capsule and tablet, the present invention is directed to the existing irrational shortcoming of method of quality control, the content assaying method of dehydrorographolide and the thin layer discrimination method of Herba Andrographis are studied and screened, improve the quality control standard of creat formulation, thereby guaranteed the clinical efficacy of said preparation.
Andrographis oral preparation of the present invention is prepared from by Herba Andrographis and adjuvant, its preparation method is: get the Herba Andrographis coarse powder, extract 1-5 time with the hot dipping of 50-95% ethanol, merge extractive liquid, filters filtrate recycling ethanol, be condensed into the thick paste shape, be dried to dry extract, be ground into fine powder, add adjuvant and make capsule, tablet or granule according to conventional method.
Described method of quality control mainly comprise in character, inspection, discriminating, the assay project partly or entirely; Wherein differentiating the chromogenic reaction that comprises with sodium nitrite and aluminum nitrate, serves as the thin layer discriminating that the Herba Andrographis medical material is differentiated in contrast with Herba Andrographis control medicinal material and dehydrorographolide reference substance; Assay is the assay to andrographolide in the preparation.
The discrimination method of Herba Andrographis is to be contrast with Herba Andrographis control medicinal material and dehydrorographolide reference substance in this preparation, and with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is the thin layer discrimination method of developing solvent.
Discrimination method comprises the part or all of of following project:
(1) get content, tablet or granule in the capsule respectively, tablet is removed coating, porphyrize, add dehydrated alcohol, heating and refluxing extraction is put cold, filter, the filtrate evaporate to dryness, residue adds entry, regulate pH value to 0.5-2 with hydrochloric acid solution, in water-bath, heat, filter, get filtrate, add 5-20% sodium nitrite solution and 5-20% aluminum nitrate solution, shake up, repeated hydrogenation sodium oxide test solution, solution show orange red;
(2) get content, tablet or granule in the capsule respectively, tablet is removed coating, and porphyrize adds the ethanol supersound process, filters, and filtrate concentrates, as need testing solution; Other gets the Herba Andrographis control medicinal material, adds the ethanol supersound process, filters, and concentrates, in contrast medical material solution; Get the dehydrorographolide reference substance again, add dissolve with ethanol, in contrast product solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw above-mentioned three kinds of solution, put respectively in same be the silica gel G F of adhesive with the sodium carboxymethyl cellulose
254On the lamellae, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1-5%3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5-5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively.
Discrimination method comprises the part or all of of following project more specifically:
(1) gets capsule 2-10 grain, tablet 1-10 sheet or granule 0.5-2 bag respectively, tablet is removed coating, porphyrize, add dehydrated alcohol 20-200ml, reflux 0.5-5 hour, put coldly, filter, the filtrate evaporate to dryness, residue adds water 1-20ml, regulates pH value to 0.5-2 with the 0.5-10% hydrochloric acid solution, and heating is 10-100 minute in water-bath, filter, get filtrate, add the 5-20% sodium nitrite solution and each 1-20 of 5-20% aluminum nitrate solution drips, shake up, repeated hydrogenation sodium oxide test solution 0.1ml～5ml, solution show orange red;
(2) get capsule 2-10 grain, tablet 2-10 sheet or granule 0.5-2 bag respectively, tablet is removed coating, and porphyrize adds ethanol 10-100ml supersound process 10-100 minute, filters, and filtrate is concentrated into 1-10ml as need testing solution; Other gets Herba Andrographis control medicinal material 0.1-1g, adds ethanol 10-100ml supersound process 10-100 minute, filters, and is concentrated into 1-5ml, in contrast medical material solution; Get the dehydrorographolide reference substance again, add ethanol and make the solution that 1ml contains 0.5-5mg, in contrast product solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw each 3-20 μ l of above-mentioned three kinds of solution, put respectively in same be the silica gel G F of adhesive with the sodium carboxymethyl cellulose
254On the lamellae, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1-5%3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5-5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively.
The content assaying method of andrographolide is to be contrast with the dehydrorographolide reference substance in this preparation, is the high performance liquid chromatography of mobile phase with methanol or acetonitrile: water=1-9: 9-1.
Content assaying method is:
Andrographolide adopts high performance liquid chromatography, chromatographic column is C18 or C4 or C8 post, with methanol or acetonitrile: water=1-9: 9-1 is mobile phase, flow velocity: 0.8-1.2ml/min, column temperature: 40 ℃, detect wavelength 200-500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, with methanol or dissolve with ethanol, promptly gets reference substance solution; Get content, tablet or granule in the capsule respectively, tablet is removed coating, and accurate the title decided porphyrize, add ethanol, merceration, supersound extraction is put cold again, supply the weight that subtracts mistake with ethanol, shake up, use microporous filter membrane to filter, promptly get need testing solution less than 0.65 μ m; Accurate respectively reference substance solution and the need testing solution drawn injects hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Content assaying method is more specifically:
Andrographolide adopts high performance liquid chromatography, chromatographic column is C18 or C4 or C8 post, with methanol or acetonitrile: water=1-9: 9-1 is mobile phase, flow velocity: 0.8-1.2ml/min, column temperature: 40 ℃, detect wavelength 200-500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, with methanol or dissolve with ethanol, makes the solution that every 1ml contains dehydrorographolide 0.05-0.3mg, promptly gets reference substance solution; Get capsule 20-50 grain, tablet 20-60 sheet or granule 5-10 bag respectively, tablet is removed coating, the accurate title, decide, and porphyrize is got capsule 0.3g, tablet 0.3g or granule 1g, the accurate title, decide, the accurate 25ml ethanol that adds claims to decide weight, merceration 0.5-3 hour, supersound process 10-100 minute, put coldly, claim again to decide weight, supply the weight that subtracts mistake with ethanol, shake up, use the microporous filter membrane less than 0.65 μ m to filter, precision is got filtrate 5ml and is put in the 10ml volumetric flask, adds ethanol and is diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 3-20 μ l of need testing solution of drawing injects hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Described method of quality control comprises:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Differentiate: (1) gets content, tablet or the granule in the capsule respectively, and tablet is removed coating, porphyrize, add dehydrated alcohol, heating and refluxing extraction is put cold, filter, the filtrate evaporate to dryness, residue adds entry, regulate pH value to 0.5-2 with hydrochloric acid solution, in water-bath, heat, filter, get filtrate, add 5-20% sodium nitrite solution and 5-20% aluminum nitrate solution, shake up, repeated hydrogenation sodium oxide test solution, solution show orange red;
(2) get content, tablet or granule in the capsule respectively, tablet is removed coating, and porphyrize adds the ethanol supersound process, filters, and filtrate concentrates, as need testing solution; Other gets the Herba Andrographis control medicinal material, adds the ethanol supersound process, filters, and concentrates, in contrast medical material solution; Get the dehydrorographolide reference substance again, add dissolve with ethanol, in contrast product solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw above-mentioned three kinds of solution, put respectively in same be the silica gel G F of adhesive with the sodium carboxymethyl cellulose
254On the lamellae, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1-5%3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5-5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively;
Check:
Capsule of the present invention, tablet or granule should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item;
Assay:
Andrographolide adopts high performance liquid chromatography, chromatographic column is C18 or C4 or C8 post, with methanol or acetonitrile: water=1-9: 9-1 is mobile phase, flow velocity: 0.8-1.2ml/min, column temperature: 40 ℃, detect wavelength 200-500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, with methanol or dissolve with ethanol, promptly gets reference substance solution; Get content, tablet or granule in the capsule respectively, tablet is removed coating, and accurate the title decided porphyrize, add ethanol, merceration, supersound extraction is put cold again, supply the weight that subtracts mistake with ethanol, shake up, use microporous filter membrane to filter, promptly get need testing solution less than 0.65 μ m; Accurate respectively reference substance solution and the need testing solution drawn injects hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Find after deliberation, adopt the quality of following method of quality control, be more conducive to guarantee the clinical efficacy of this preparation easier control preparation of the present invention.So described method of quality control also can comprise:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Differentiate: (1) gets capsule 2-10 grain, tablet 1-10 sheet or granule 0.5-2 bag respectively, tablet is removed coating, porphyrize, add dehydrated alcohol 20-200ml, reflux 0.5-5 hour, put coldly, filter, the filtrate evaporate to dryness, residue adds water 1-20ml, regulates pH value to 0.5-2 with the 0.5-10% hydrochloric acid solution, and heating is 10-100 minute in water-bath, filter, get filtrate, add the 5-20% sodium nitrite solution and each 1-20 of 5-20% aluminum nitrate solution drips, shake up, repeated hydrogenation sodium oxide test solution 0.1ml～5ml, solution show orange red;
(2) get capsule 2-10 grain, tablet 2-10 sheet or granule 0.5-2 bag respectively, tablet is removed coating, and porphyrize adds ethanol 10-100ml supersound process 10-100 minute, filters, and filtrate is concentrated into 1-10ml as need testing solution; Other gets Herba Andrographis control medicinal material 0.1-1g, adds ethanol 10-100ml supersound process 10-100 minute, filters, and is concentrated into 1-5ml, in contrast medical material solution; Get the dehydrorographolide reference substance again, add ethanol and make the solution that 1ml contains 0.5-5mg, in contrast product solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw each 3-20 μ l of above-mentioned three kinds of solution, put respectively in same be the silica gel G F of adhesive with the sodium carboxymethyl cellulose
254On the lamellae, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, launch, take out, dry, put under the ultra-violet lamp 200-500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1-5%3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5-5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively;
Check:
Capsule of the present invention, tablet or granule should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item;
Assay:
Andrographolide adopts high performance liquid chromatography, chromatographic column is C18 or C4 or C8 post, with methanol or acetonitrile: water=1-9: 9-1 is mobile phase, flow velocity: 0.8-1.2ml/min, column temperature: 40 ℃, detect wavelength 200-500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, with methanol or dissolve with ethanol, makes the solution that every 1ml contains dehydrorographolide 0.05-0.3mg, promptly gets reference substance solution; Get capsule 20-50 grain, tablet 20-60 sheet or granule 5-10 bag respectively, tablet is removed coating, the accurate title, decide, and porphyrize is got capsule 0.3g, tablet 0.3g or granule 1g, the accurate title, decide, the accurate 25ml ethanol that adds claims to decide weight, merceration 0.5-3 hour, supersound process 10-100 minute, put coldly, claim again to decide weight, supply the weight that subtracts mistake with ethanol, shake up, use the microporous filter membrane less than 0.65 μ m to filter, precision is got filtrate 5ml and is put in the 10ml volumetric flask, adds ethanol and is diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 3-20 μ l of need testing solution of drawing injects hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Mainly contain a large amount of bitter principles, andrographolide, dehydrorographolide and flavone compound etc. in the Herba Andrographis medical material.We find in product research, the Herba Andrographis medical material is after alcohol extraction, when reclaiming alcohol extract to extractum, andrographolide content reduces, dehydrorographolide content increases, total lactone content changes and reduces, concentrate drying becomes dried cream, it is zero that the andrographolide content loss is close to, the corresponding minimizing of dehydrorographolide content, total lactone content changes and reduces, as seen, the examination index that can not measure as formulation content with total lactone content of andrographolide and dehydrorographolide is so examine or check the preparation index with dehydrorographolide among the present invention.In addition, the content assaying method of Herba Andrographis has thin layer chromatography scanning, high performance liquid chromatography etc.The inventor is respectively according to the content assaying method of dehydrorographolide in the Chinese traditional patent formulation preparation promulgated by the ministries or commissions of the Central Government 20 " CHUANXINLIAN JIAONANG ", the content assaying method of " andrographis tablet " middle dehydrorographolide of Chinese Pharmacopoeia version in 2000 is measured the content of dehydrorographolide, found that, above-mentioned two kinds of methods are to big with the content data relative standard deviation that records under a collection of medical material, the identical conditions, the determination data unstable result is so the inventor adopts high performance liquid chromatography that the content of dehydrorographolide in the Herba Andrographis medical material is measured.Show that through experimental result repeatedly adopt the method to measure, relative standard deviation is less, favorable reproducibility.
Method of quality control of the present invention is the preferred plan that obtains through a large amount of screenings, and following experimentation is a preferred process of the present invention.
One, dehydrorographolide content assaying method research
1, through evidence, adopt thin layer chromatography scanning that dehydrorographolide in the creat formulation is carried out assay, its specificity is not strong, error is big, the measurement result instability, relative standard deviation more efficient liquid chromatography is big, so the present invention adopts the content of high effective liquid chromatography for measuring creat formulation, below is the comparison that preparation of the present invention adopts high performance liquid chromatography, tlc scanning determination result:
| Sample | 1 | 2 | 3 | |
| High performance liquid chromatography | Content (%) | 4.23 | 4.55 | 4.17 |
| RSD(％) | 0.87 | 1.01 | 0.93 | |
| Thin layer chromatography scanning 1 | Content (%) | 4.21 | 4.51 | 4.13 |
| RSD(％) | 3.52 | 3.53 | 4.15 | |
| Thin layer chromatography scanning 2 | Content (%) | 4.14 | 4.25 | 4.00 |
| RSD(％) | 2.15 | 2.78 | 3.42 | |
In the said method, thin layer chromatography scanning 1 is measured according to the content assaying method of 20 " CHUANXINLIAN JIAONANG " middle dehydrorographolide of Chinese traditional patent formulation preparation promulgated by the ministries or commissions of the Central Government; Thin layer chromatography scanning 2 is measured according to the content assaying method of " andrographis tablet " middle dehydrorographolide of Chinese Pharmacopoeia version in 2000.
2, need testing solution preparation method research:
2.1 Study on Extraction Method
Method 1: the thing of getting it filled, accurate claim surely, add ethanol, claim decide weight, heating and refluxing extraction is put coldly, claims to decide weight again, supplies the weight that subtracts mistake with ethanol, shake up, filtration, promptly;
Method 2: the thing of getting it filled, accurate claim surely, add ethanol, claim decide weight, merceration, supersound process is then put coldly, claims to decide weight again, supplies the weight that subtracts mistake with ethanol, shake up, filtration, promptly;
| Extracting method | Heating and refluxing extraction (mg/g is average) | Supersound process is extracted (mg/g is average) |
| Dehydrorographolide content RSD (%) | 21.91 2.81 | 21.94 0.91 |
Reflux method and supersound extraction are relatively, result and dehydrorographolide that the result that andrographis tablet powder reflux is measured measures than the method for supersound process are approaching, but because reflux measurement result relative deviation is than factors such as big and supersound process comparatively save trouble, therefore, adopt the method for supersound process better.
2.2 extract the easy solution and methanol of choice of Solvent dehydrorographolide, dehydrated alcohol, ethanol equal solvent, use methanol, dehydrated alcohol, alcohol solvent respectively, soaked 1 hour, carried out supersound process 30 minutes, supply ultrasonic back weight, 0.45 μ m filters, and the sampling and measuring dehydrorographolide is total lactone content, through test of many times, measure the dehydrorographolide content results and see the following form.
The different solvents supersound process is measured the content results (n=2) of total andrographolides
| Extract solvent | Methanol (mg/g is average) | Dehydrated alcohol (mg/g is average) | Ethanol (mg/g is average) |
| Dehydrorographolide RSD (%) | 20.4 1.7 | 20.5 1.3 | 21.8 1.1 |
Extracting solvent as seen from the table selects ethanol better.
3, the selection of mobile phase:
Mobile phase 1: the mixed solution with methanol, water different proportion is a mobile phase.
Mobile phase 2: the mixed solution with acetonitrile, water different proportion is a mobile phase.
Mobile phase 3: with the mixed solution of methanol, water different proportion, and to transfer the solution of pH to 4.5 with hydrochloric acid be mobile phase.
Mobile phase 4: the mixed solution with methanol, 0.1% phosphoric acid solution different proportion is a mobile phase.
The result: with methanol or acetonitrile: water=1-9: 9-1 is mobile phase; The negative sample chromatogram is at non-false positive peak, dehydrorographolide position, and dehydrorographolide separates fully (separating degree＞1.5) with close impurity peaks, and promptly dehydrorographolide separates with other components fully under this condition.Optimal flow is mutually: methanol: water=55: 45.
4, replica test
The thing powder of getting it filled accurately claims surely, and by 5 parts of test liquids of preparation method preparation of test liquid under the assay item in the method for quality control of the present invention, sample introduction is measured peak area respectively, and result of calculation is listed following table in, and average content is the 21.66mg/g powder, and RSD is 0.52%.
The repeatability of dehydrorographolide test in the andrographis tablet test sample
| The sample introduction number of times | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Dehydrorographolide content (mg/g) | 21.35 | 21.60 | 21.94 | 21.76 | 21.66 | 21.66 | 0.52 |
The result shows that this method repeatability is good.
5, recovery test:
Adopt the application of sample absorption method, get 5 parts and remove coating, porphyrize, measured each 0.15g of sample powder (average content is 21.89mg/g) of content, the accurate title, decide, accurate 25ml dehydrorographolide reference substance (0.1312mg/ml) alcoholic solution that adds, claim to decide weight, soaked 1 hour, supersound process 30 minutes is put cold, claim to decide weight again, supply the weight that subtracts mistake with ethanol, shake up, filter with microporous filter membrane 0.45 μ m, precision is got filtrate 5ml and is put in the 10ml volumetric flask, add ethanol and be diluted to scale, shake up promptly, make test liquid.Accurate respectively each the 5 μ l of above-mentioned 5 duplicate samples that draw inject chromatograph of liquid, and the record chromatograph is measured content, calculate recovery rate.Average recovery rate is 99.22%, and RSD is 2.16%.
The recovery test of dehydrorographolide in the preparation test sample
| Test number (TN) | Sample size (g) | Contain dehydrorographolide (mg) | Add dehydrorographolide (mg) | The amount of recording (mg) | The response rate (%) | Average recovery rate (%) | RSD (％) |
| 1 2 3 4 5 | 0.1386 0.1574 0.1504 0.1473 0.1491 | 3.0343 3.4453 3.2927 3.2254 3.2645 | 3.2800 | 6.2241 6.6895 6.5540 6.5644 6.5674 | 97.25 98.91 99.43 101.8 100.7 | 99.62 | 1.74 |
Two, Herba Andrographis thin layer Study on Identification
Need testing solution preparation method one: the thing of getting it filled, porphyrize adds the ethanol supersound process, filters, and filtrate concentrates, promptly; Lack the Herba Andrographis negative controls with the method preparation.
Need testing solution preparation method two: the thing of getting it filled, porphyrize adds ethyl acetate 20ml, and supersound process filters, evaporate to dryness ethyl acetate extraction liquid, residue adds dissolve with methanol, promptly; Lack the Herba Andrographis negative controls with the method preparation.
Need testing solution preparation method three: the thing of getting it filled, porphyrize adds diethyl ether, and heating and refluxing extraction filters, and evaporate to dryness, residue add ethanol makes dissolving, promptly; Lack the Herba Andrographis negative controls with the method preparation.
Need testing solution preparation method four: the thing of getting it filled, porphyrize adds water and makes dissolving, uses ethyl acetate extraction 2 times, merges ethyl acetate extraction liquid, and evaporate to dryness, residue add methanol makes dissolving, promptly; Lack the Herba Andrographis negative controls with the method preparation.
Need testing solution preparation method five: the thing of getting it filled, porphyrize accurate claims surely, adds methanol, claim decide weight, merceration 1 hour, supersound process 30 minutes is put coldly, claims to decide weight again, supplies the weight that subtracts mistake with methanol, shake up, filtration, promptly; Lack the Herba Andrographis negative controls with the method preparation.
Developing solvent is selected: respectively with the mixed solution of toluene, ethyl acetate, methanol, glacial acetic acid different proportion; The mixed solution of chloroform, methanol, acetone, formic acid different proportion; The mixed solution of petroleum ether (60～90 ℃), ethyl acetate, acetone, glacial acetic acid different proportion; The mixed solution of chloroform, ethyl acetate, acetonitrile different proportion; The mixed solution of chloroform, ethyl acetate, methanol different proportion is developing solvent.
The result: selecting method one, employing method one preparation need testing solution, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, and separating degree is good, and the method favorable reproducibility.Other gets the middle test agent that the andrographis tablet of commercially available different manufacturers production or CHUANXINLIAN JIAONANG and the applicant provide, and differentiates comparative study by method one respectively, and show through test of many times and result: selecting method one, the method specificity is strong, favorable reproducibility.Best developing solvent is: chloroform: ethyl acetate: methanol=20: 15: 2.Adopt additive method to prepare need testing solution, it is bad that identification result all exists separating degree, speckle unsharp shortcoming that develops the color.
Compared with prior art, the present invention is directed to the deficiencies in the prior art, the content assaying method of dehydrorographolide and the thin layer discrimination method of Herba Andrographis are studied and screened, and selected method specificity is strong, favorable reproducibility, response rate height, measurement result is stable, and relative standard deviation is little, has improved the quality control standard of creat formulation, can effectively control the quality of andrographis oral preparation, thereby guarantee the clinical efficacy of said preparation.
The specific embodiment:
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiments of the invention 1:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Differentiate: (1) gets 5 of capsules, 3 in tablet or granule 1 bag respectively, and tablet is removed coating, porphyrize, add dehydrated alcohol 25ml, reflux 1 hour is put cold, filter, filtrate evaporate to dryness, residue add water 5ml, regulate pH value to 1.0 with 2% hydrochloric acid solution, heating is 30 minutes in water-bath, filters, get filtrate, add each 3 of 10% sodium nitrite solution and 10% aluminum nitrate solutions, shake up, repeated hydrogenation sodium oxide test solution 0.5ml～1ml, solution show orange red;
(2) get 5 of capsules, 5 in tablet or granule 1 bag respectively, tablet is removed coating, and porphyrize adds ethanol 30ml supersound process 30 minutes, filters, and filtrate is concentrated into 2ml as need testing solution; Other gets Herba Andrographis control medicinal material 0.2g, adds ethanol 30ml supersound process 30 minutes, filters, and is concentrated into 2ml, in contrast medical material solution; Get the dehydrorographolide reference substance again, add ethanol and make the solution that 1ml contains 1mg, in contrast product solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw each 5 μ l of above-mentioned three kinds of solution, put respectively in same be the silica gel G F of adhesive with the sodium carboxymethyl cellulose
254On the lamellae, with chloroform: ethyl acetate: methanol=20: 15: 2 is developing solvent, launches, take out, dry, put under the ultra-violet lamp 254nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 2%3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 2mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively;
Check:
Capsule of the present invention, tablet or granule should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item;
Assay: andrographolide adopts high performance liquid chromatography, and chromatographic column is the C18 post, and with methanol: water=55: 45 is mobile phase, flow velocity: 1.0ml/min, column temperature: 40 ℃, detect wavelength 251nm, theoretical cam curve should be not less than 3000 in the dehydrorographolide peak; Precision takes by weighing dehydrorographolide reference substance 10mg, puts in the 100ml volumetric flask, adds dissolve with ethanol and is diluted to scale, shakes up, and makes the solution that every 1ml contains dehydrorographolide 0.1mg, promptly gets reference substance solution; Get 30 of capsules, 40 in tablet or granule 8 bags respectively, tablet is removed coating, and accurate the title decided porphyrize, get capsule 0.3g, tablet 0.3g or granule 1g, the accurate title, decide, the accurate 25ml ethanol that adds, claim to decide weight, merceration 1 hour, supersound process 30 minutes, put coldly, claim again to decide weight, supply the weight that subtracts mistake with ethanol, shake up, with the microporous filter membrane filtration of 0.45 μ m, precision is got filtrate 5ml and is put in the 10ml volumetric flask, add ethanol and be diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 5 μ l of need testing solution of drawing inject hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Embodiments of the invention 2:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Differentiate: get 2 of capsules, 1 in tablet or granule 0.5 bag respectively, tablet is removed coating, porphyrize, add dehydrated alcohol 20ml, reflux 0.5 hour is put cold, filter, filtrate evaporate to dryness, residue add water 1ml, regulate pH value to 0.5 with 0.5% hydrochloric acid solution, heating is 10 minutes in water-bath, filters, get filtrate, add each 20 of 5% sodium nitrite solution and 5% aluminum nitrate solutions, shake up, repeated hydrogenation sodium oxide test solution 0.1ml～3ml, solution show orange red;
Check:
Capsule of the present invention, tablet or granule should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item;
Assay: andrographolide adopts high performance liquid chromatography, and chromatographic column is the C4 post, and with acetonitrile: water=1: 9 is mobile phase, flow velocity: 0.8ml/min, column temperature: 40 ℃, detect wavelength 200nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, uses dissolve with methanol, makes the solution that every 1ml contains dehydrorographolide 0.05mg, promptly gets reference substance solution; Get 20 of capsules, 20 in tablet or granule 5 bags respectively, tablet is removed coating, and accurate the title decided porphyrize, get capsule 0.3g, tablet 0.3g or granule 1g, the accurate title, decide, the accurate 25ml ethanol that adds, claim to decide weight, merceration 0.5 hour, supersound process 10 minutes, put coldly, claim again to decide weight, supply the weight that subtracts mistake with ethanol, shake up, with the microporous filter membrane filtration of 0.35 μ m, precision is got filtrate 5ml and is put in the 10ml volumetric flask, add ethanol and be diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 3 μ l of need testing solution of drawing inject hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Embodiments of the invention 3:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Differentiate: get 2 of capsules, 2 in tablet or granule 0.5 bag respectively, tablet is removed coating, and porphyrize adds ethanol 10ml supersound process 10 minutes, filters, and filtrate is concentrated into 1ml as need testing solution; Other gets Herba Andrographis control medicinal material 0.1g, adds ethanol 10ml supersound process 10 minutes, filters, and is concentrated into 1ml, in contrast medical material solution; Get the dehydrorographolide reference substance again, add ethanol and make the solution that 1ml contains 0.5mg, in contrast product solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw each 3 μ l of above-mentioned three kinds of solution, put respectively in same be the silica gel G F of adhesive with the sodium carboxymethyl cellulose
254On the lamellae, with chloroform: ethyl acetate: acetonitrile=30: 10: 0.5 is developing solvent, launches, take out, dry, put under the ultra-violet lamp 200nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1%3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively;
Assay: andrographolide adopts high performance liquid chromatography, chromatographic column C8 post, and with methanol: water=9: 1 is mobile phase, flow velocity: 1.2ml/min, column temperature: 40 ℃, detect wavelength 500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, uses dissolve with ethanol, makes the solution that every 1ml contains dehydrorographolide 0.3mg, promptly gets reference substance solution; Get 50 of capsules, 60 in tablet or granule 10 bags respectively, tablet is removed coating, and accurate the title decided porphyrize, get capsule 0.3g, tablet 0.3g or granule 1g, the accurate title, decide, the accurate 25ml ethanol that adds, claim to decide weight, merceration 3 hours, supersound process 100 minutes, put coldly, claim again to decide weight, supply the weight that subtracts mistake with ethanol, shake up, with the microporous filter membrane filtration of 0.25 μ m, precision is got filtrate 5ml and is put in the 10ml volumetric flask, add ethanol and be diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 20 μ l of need testing solution of drawing inject hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Embodiments of the invention 4:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Differentiate: (1) gets 10 of capsules, 10 in tablet or granule 2 bags respectively, and tablet is removed coating, porphyrize, add dehydrated alcohol 200ml, reflux 5 hours is put cold, filter, filtrate evaporate to dryness, residue add water 20ml, regulate pH value to 2 with 10% hydrochloric acid solution, heating is 100 minutes in water-bath, filters, get filtrate, add each 1 of 20% sodium nitrite solution and 20% aluminum nitrate solution, shake up, repeated hydrogenation sodium oxide test solution 3ml～5ml, solution show orange red;
(2) get 10 of capsules, 10 in tablet or granule 2 bags respectively, tablet is removed coating, and porphyrize adds ethanol 100ml supersound process 100 minutes, filters, and filtrate is concentrated into 10ml as need testing solution; Other gets Herba Andrographis control medicinal material 1g, adds ethanol 100ml supersound process 100 minutes, filters, and is concentrated into 5ml, in contrast medical material solution; Get the dehydrorographolide reference substance again, add ethanol and make the solution that 1ml contains 5mg, in contrast product solution; According to Chinese Pharmacopoeia thin layer chromatography test, draw each 20 μ l of above-mentioned three kinds of solution, put respectively in same be the silica gel G F of adhesive with the sodium carboxymethyl cellulose
254On the lamellae, with chloroform: ethyl acetate: methanol=10: 30: 5 is developing solvent, launches, take out, dry, put under the ultra-violet lamp 500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 5%3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively;
Check:
Capsule of the present invention, tablet or granule should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item.
The present invention sends out embodiment 5:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Check:
Capsule of the present invention, tablet or granule should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item;
Assay: andrographolide adopts high performance liquid chromatography, and chromatographic column is the C18 post, and with acetonitrile: water=7: 3 is mobile phase, flow velocity: 1.0ml/min, column temperature: 40 ℃, detect wavelength 365nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, uses dissolve with methanol, makes the solution that every 1ml contains dehydrorographolide 0.2mg, promptly gets reference substance solution; Get 40 of capsules, 50 in tablet or granule 6 bags respectively, tablet is removed coating, and accurate the title decided porphyrize, get capsule 0.3g, tablet 0.3g or granule 1g, the accurate title, decide, the accurate 25ml ethanol that adds, claim to decide weight, merceration 2 hours, supersound process 60 minutes, put coldly, claim again to decide weight, supply the weight that subtracts mistake with ethanol, shake up, with the microporous filter membrane filtration of 0.50 μ m, precision is got filtrate 5ml and is put in the 10ml volumetric flask, add ethanol and be diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Claims (9)
1. the method for quality control of an andrographis oral preparation, this oral formulations comprises granule, capsule and tablet, it is characterized in that: described method of quality control mainly comprise in character, inspection, discriminating, the assay project partly or entirely; Wherein differentiating the chromogenic reaction that comprises with sodium nitrite and aluminum nitrate, serves as the thin layer discriminating that the Herba Andrographis medical material is differentiated in contrast with Herba Andrographis control medicinal material and dehydrorographolide reference substance; Assay is the assay to andrographolide in the preparation.
2. according to the method for quality control of the described andrographis oral preparation of claim 1, it is characterized in that: the discrimination method of Herba Andrographis is to be contrast with Herba Andrographis control medicinal material and dehydrorographolide reference substance in this preparation, and with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is the thin layer discrimination method of developing solvent.
3. according to the method for quality control of claim 1 or 2 described andrographis oral preparations, it is characterized in that: discrimination method comprises the part or all of of following project:
(1) get content, tablet or granule in the capsule respectively, tablet is removed coating, porphyrize, add dehydrated alcohol, heating and refluxing extraction is put cold, filter, the filtrate evaporate to dryness, residue adds entry, regulate pH value to 0.5-2 with hydrochloric acid solution, in water-bath, heat, filter, get filtrate, add 5-20% sodium nitrite solution and 5-20% aluminum nitrate solution, shake up, repeated hydrogenation sodium oxide test solution, solution show orange red;
(2) get content, tablet or granule in the capsule respectively, tablet is removed coating, and porphyrize adds the ethanol supersound process, filters, and filtrate concentrates, as need testing solution; Other gets the Herba Andrographis control medicinal material, adds the ethanol supersound process, filters, and concentrates, in contrast medical material solution; Get the dehydrorographolide reference substance again, add dissolve with ethanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned three kinds of solution, put respectively in same be on the silica GF254 lamellae of adhesive with the sodium carboxymethyl cellulose, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, launches, take out, dry, put under the ultra-violet lamp 200-500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1-5% 3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5-5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively.
4. according to the method for quality control of the described andrographis oral preparation of claim 3, it is characterized in that: concrete discrimination method comprises the part or all of of following project:
(1) gets capsule 2-10 grain, tablet 1-10 sheet or granule 0.5-2 bag respectively, tablet is removed coating, porphyrize, add dehydrated alcohol 20-200ml, reflux 0.5-5 hour, put coldly, filter, the filtrate evaporate to dryness, residue adds water 1-20ml, regulates pH value to 0.5-2 with the 0.5-10% hydrochloric acid solution, and heating is 10-100 minute in water-bath, filter, get filtrate, add the 5-20% sodium nitrite solution and each 1-20 of 5-20% aluminum nitrate solution drips, shake up, repeated hydrogenation sodium oxide test solution 0.1ml～5ml, solution show orange red;
(2) get capsule 2-10 grain, tablet 2-10 sheet or granule 0.5-2 bag respectively, tablet is removed coating, and porphyrize adds ethanol 10-100ml supersound process 10-100 minute, filters, and filtrate is concentrated into 1-10ml as need testing solution; Other gets Herba Andrographis control medicinal material 0.1-1g, adds ethanol 10-100ml supersound process 10-100 minute, filters, and is concentrated into 1-5ml, in contrast medical material solution; Get the dehydrorographolide reference substance again, add ethanol and make the solution that 1ml contains 0.5-5mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 3-20 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica GF254 lamellae of adhesive with the sodium carboxymethyl cellulose, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, launches, take out, dry, put under the ultra-violet lamp 200-500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1-5% 3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5-5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively.
5. according to the method for quality control of the described andrographis oral preparation of claim 1, it is characterized in that: the content assaying method of andrographolide is to be contrast with the dehydrorographolide reference substance in this preparation, is the high performance liquid chromatography of mobile phase with methanol or acetonitrile: water=1-9: 9-1.
6. according to the method for quality control of claim 1 or 5 described andrographis oral preparations, it is characterized in that: content assaying method is:
Andrographolide adopts high performance liquid chromatography, and chromatographic column is C18 or C4 or C8 post, is mobile phase with methanol or acetonitrile: water=1-9: 9-1, flow velocity: 0.8-1.2ml/min, column temperature: 40 ℃, detect wavelength 200-500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, with methanol or dissolve with ethanol, promptly gets reference substance solution; Get content, tablet or granule in the capsule respectively, tablet is removed coating, and accurate the title decided porphyrize, add ethanol, merceration, supersound extraction is put cold again, supply the weight that subtracts mistake with ethanol, shake up, use microporous filter membrane to filter, promptly get need testing solution less than 0.65 μ m; Accurate respectively reference substance solution and the need testing solution drawn injects hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
7. according to the method for quality control of the described andrographis oral preparation of claim 6, it is characterized in that: concrete content assaying method is:
Andrographolide adopts high performance liquid chromatography, chromatographic column is C18 or C4 or C8 post, with methanol or acetonitrile: water=1-9: 9-1 is mobile phase, flow velocity: 0.8-1.2ml/min, column temperature: 40 ℃, detect wavelength 200-500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, with methanol or dissolve with ethanol, makes the solution that every 1ml contains dehydrorographolide 0.05-0.3mg, promptly gets reference substance solution; Get capsule 20-50 grain, tablet 20-60 sheet or granule 5-10 bag respectively, tablet is removed coating, the accurate title, decide, and porphyrize is got capsule 0.3g, tablet 0.3g or granule 1g, the accurate title, decide, the accurate 25ml ethanol that adds claims to decide weight, merceration 0.5-3 hour, supersound process 10-100 minute, put coldly, claim again to decide weight, supply the weight that subtracts mistake with ethanol, shake up, use the microporous filter membrane less than 0.65 μ m to filter, precision is got filtrate 5ml and is put in the 10ml volumetric flask, adds ethanol and is diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 3-20 μ l of need testing solution of drawing injects hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
8. according to the method for quality control of the described andrographis oral preparation of claim 1, it is characterized in that: described method of quality control comprises:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Differentiate: (1) gets content, tablet or the granule in the capsule respectively, and tablet is removed coating, porphyrize, add dehydrated alcohol, heating and refluxing extraction is put cold, filter, the filtrate evaporate to dryness, residue adds entry, regulate pH value to 0.5-2 with hydrochloric acid solution, in water-bath, heat, filter, get filtrate, add 5-20% sodium nitrite solution and 5-20% aluminum nitrate solution, shake up, repeated hydrogenation sodium oxide test solution, solution show orange red;
(2) get content, tablet or granule in the capsule respectively, tablet is removed coating, and porphyrize adds the ethanol supersound process, filters, and filtrate concentrates, as need testing solution; Other gets the Herba Andrographis control medicinal material, adds the ethanol supersound process, filters, and concentrates, in contrast medical material solution; Get the dehydrorographolide reference substance again, add dissolve with ethanol, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw above-mentioned three kinds of solution, put respectively in same be on the silica GF254 lamellae of adhesive with the sodium carboxymethyl cellulose, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, launches, take out, dry, put under the ultra-violet lamp 200-500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1-5% 3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5-5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively;
Check:
Capsule of the present invention, tablet or granule should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item;
Assay: andrographolide adopts high performance liquid chromatography, chromatographic column is C18 or C4 or C8 post, with methanol or acetonitrile: water=1-9: 9-1 is mobile phase, flow velocity: 0.8-1.2ml/min, column temperature: 40 ℃, detect wavelength 200-500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, with methanol or dissolve with ethanol, promptly gets reference substance solution; Get content, tablet or granule in the capsule respectively, tablet is removed coating, and accurate the title decided porphyrize, add ethanol, merceration, supersound extraction is put cold again, supply the weight that subtracts mistake with ethanol, shake up, use microporous filter membrane to filter, promptly get need testing solution less than 0.65 μ m; Accurate respectively reference substance solution and the need testing solution drawn injects hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
9. according to the method for quality control of the described andrographis oral preparation of claim 8, it is characterized in that: described method of quality control comprises:
Character:
For capsule: content is that taupe is to tan powder, bitter in the mouth;
For tablet: product is a Film coated tablets, shows taupe to sepia after removing coated tablet; Bitter in the mouth;
For granule: product is that taupe is to tan granule;
Differentiate: (1) gets capsule 2-10 grain, tablet 1-10 sheet or granule 0.5-2 bag respectively, tablet is removed coating, porphyrize, add dehydrated alcohol 20-200ml, reflux 0.5-5 hour, put coldly, filter, the filtrate evaporate to dryness, residue adds water 1-20ml, regulates pH value to 0.5-2 with the 0.5-10% hydrochloric acid solution, and heating is 10-100 minute in water-bath, filter, get filtrate, add the 5-20% sodium nitrite solution and each 1-20 of 5-20% aluminum nitrate solution drips, shake up, repeated hydrogenation sodium oxide test solution 0.1ml～5ml, solution show orange red;
(2) get capsule 2-10 grain, tablet 2-10 sheet or granule 0.5-2 bag respectively, tablet is removed coating, and porphyrize adds ethanol 10-100ml supersound process 10-100 minute, filters, and filtrate is concentrated into 1-10ml as need testing solution; Other gets Herba Andrographis control medicinal material 0.1-1g, adds ethanol 10-100ml supersound process 10-100 minute, filters, and is concentrated into 1-5ml, in contrast medical material solution; Get the dehydrorographolide reference substance again, add ethanol and make the solution that 1ml contains 0.5-5mg, in contrast product solution; Test according to the Chinese Pharmacopoeia thin layer chromatography, draw each 3-20 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica GF254 lamellae of adhesive with the sodium carboxymethyl cellulose, with chloroform: ethyl acetate: methanol or acetonitrile=10-30: 10-30: 0.5-5 is developing solvent, launches, take out, dry, put under the ultra-violet lamp 200-500nm and inspect, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color; Spray is with 1-5% 3, and the equivalent mixed liquor of 5-dinitrobenzoic acid alcoholic solution and 0.5-5mol/L potassium hydroxide solution is faced the time spent configuration; Observe under fluorescent light immediately, in the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the speckle of same color respectively;
Check:
Capsule of the present invention, tablet or granule should meet Chinese Pharmacopoeia about the pertinent regulations under capsule, tablet or the granule item;
Assay: andrographolide adopts high performance liquid chromatography, chromatographic column is C18 or C4 or C8 post, with methanol or acetonitrile: water=1-9: 9-1 is mobile phase, flow velocity: 0.8-1.2ml/min, column temperature: 40 ℃, detect wavelength 200-500nm, theoretical cam curve should be not less than 2000 in the dehydrorographolide peak; Precision takes by weighing the dehydrorographolide reference substance, with methanol or dissolve with ethanol, makes the solution that every 1ml contains dehydrorographolide 0.05-0.3mg, promptly gets reference substance solution; Get capsule 20-50 grain, tablet 20-60 sheet or granule 5-10 bag respectively, tablet is removed coating, the accurate title, decide, and porphyrize is got capsule 0.3g, tablet 0.3g or granule 1g, the accurate title, decide, the accurate 25ml ethanol that adds claims to decide weight, merceration 0.5-3 hour, supersound process 10-100 minute, put coldly, claim again to decide weight, supply the weight that subtracts mistake with ethanol, shake up, use the microporous filter membrane less than 0.65 μ m to filter, precision is got filtrate 5ml and is put in the 10ml volumetric flask, adds ethanol and is diluted to scale, shake up, promptly get need testing solution; Accurate respectively reference substance solution and each 3-20 μ l of need testing solution of drawing injects hplc determination content, promptly; In this oral formulations, contain dehydrorographolide in the capsule and must not be less than and contain dehydrorographolide in 4mg/ grain, the tablet and must not be less than and contain dehydrorographolide in 3.5mg/ sheet, the granule and must not be less than the 8mg/ bag; Wherein every or every in capsule or tablet contain Herba Andrographis dry extractum 0.105g; Granule contains Herba Andrographis dry extractum 0.210g for every bag.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510200877 CN1823858A (en) | 2005-12-28 | 2005-12-28 | Quality control method of andrographis oral preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510200877 CN1823858A (en) | 2005-12-28 | 2005-12-28 | Quality control method of andrographis oral preparation |
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| Publication Number | Publication Date |
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| CN1823858A true CN1823858A (en) | 2006-08-30 |
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| CN 200510200877 Pending CN1823858A (en) | 2005-12-28 | 2005-12-28 | Quality control method of andrographis oral preparation |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013071461A1 (en) * | 2011-11-16 | 2013-05-23 | 广州白云山和记黄埔中药有限公司 | Andrographis paniculata and testing method for preparation thereof |
| CN105738552A (en) * | 2016-04-25 | 2016-07-06 | 广西壮族自治区梧州食品药品检验所 | Method for determining dehydrated andrographolide content in common andrographis herb tablets based on liquid-mass series process |
| CN105954457A (en) * | 2016-06-24 | 2016-09-21 | 广西灵峰药业有限公司 | Production quality control method for Jinxiang capsule |
| CN111189944A (en) * | 2020-03-11 | 2020-05-22 | 济南广盛源生物科技有限公司 | Method for simultaneously identifying radix sophorae flavescentis and common andrographis herb in three-flavor bistort rhizome oral liquid |
-
2005
- 2005-12-28 CN CN 200510200877 patent/CN1823858A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013071461A1 (en) * | 2011-11-16 | 2013-05-23 | 广州白云山和记黄埔中药有限公司 | Andrographis paniculata and testing method for preparation thereof |
| CN105738552A (en) * | 2016-04-25 | 2016-07-06 | 广西壮族自治区梧州食品药品检验所 | Method for determining dehydrated andrographolide content in common andrographis herb tablets based on liquid-mass series process |
| CN105954457A (en) * | 2016-06-24 | 2016-09-21 | 广西灵峰药业有限公司 | Production quality control method for Jinxiang capsule |
| CN111189944A (en) * | 2020-03-11 | 2020-05-22 | 济南广盛源生物科技有限公司 | Method for simultaneously identifying radix sophorae flavescentis and common andrographis herb in three-flavor bistort rhizome oral liquid |
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