CN100526878C - Method for detecting oral disintegration tablet for treating coronary heart disease - Google Patents
Method for detecting oral disintegration tablet for treating coronary heart disease Download PDFInfo
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Abstract
The invention relates to an orally-disintegrating tablet for treating coronary diseases, the process for preparation and method for quality control, wherein the tablet is prepared from liquidambar orientalis mill 25g, borneol 52.5g, frankincense 52.5g, sandalwood 105g, banksia rose 105g and right amount of auxiliary materials.
Description
Technical field:
The present invention relates to a kind of detection method of oral disintegration tablet for treating coronary heart disease, belong to technical field of Chinese medicine.
Background technology:
Angiocardiopathy is one of principal disease of present harm humans health, and storax pill for treating coronary heart disease and storax capsule for treating coronary heart disease have the effects such as wide chest, pain relieving of regulating the flow of vital energy, and can treat and prevent angina pectoris attacks, aspect the treatment angiocardiopathy sure curative effect is being arranged.And novel solid quick releasing formulation-oral disnitegration tablet of researching and developing in recent years, water assisting deglutition not when taking, can be in the oral cavity in the 1min rapidly disintegration become fine grained, by swallowing power, can finish drug administration process, compare with conventional tablet, its absorption is faster, bioavilability is higher, and the gastrointestinal mucosal spread effect is little, and helps industrialized production.In addition, in order to investigate and control the quality of product comprehensively, need to formulate rational preparation technology and stabilizing effective detection method.
Summary of the invention:
The objective of the invention is to: the detection method that a kind of oral disintegration tablet for treating coronary heart disease is provided, the present invention on the basis of existing technology, the novel solid quick releasing formulation of a kind of good effect, taking convenience is provided, and studied and defined scientific and reasonable process and detection method, with effective control with improve the quality of products.
The present invention constitutes like this: it is prepared from by storax 25g, borneol 52.5g, frankincense 52.5g, santal 105g, elecampane 105g and microcrystalline cellulose 100g, crospolyvinylpyrrolidone 200g, low-substituted hydroxypropyl cellulose 100g, aspartame 10g, dolomol 5g.
The preparation method of oral disintegration tablet for treating coronary heart disease is: takes by weighing frankincense, santal, elecampane, pulverizes, cross 80 mesh sieves, and standby; Take by weighing microcrystalline cellulose, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, aspartame, mix with above-mentioned crude drug powder, make wetting agent system softwood with 95% ethanol that is dissolved with storax, 20 eye mesh screens are granulated, in 60 ± 5 ℃ of dryings, dried particle is with the whole grain of 20 eye mesh screens, add the borneol and the dolomol of 80 mesh sieves in the particle behind the whole grain, mixed, be pressed into 1000, packing, promptly.
The detection method of oral disintegration tablet for treating coronary heart disease: described detection method mainly comprise in proterties, inspection, discriminating, the assay project partly or entirely; Wherein discriminating is that the thin-layer chromatography of storax is differentiated; Assay is the assay to borneol in the preparation and alantolactone.
The discrimination method of storax is to be contrast with the storax control medicinal material, and with 30～60 ℃ of sherwood oils: normal hexane: ethyl formate: formic acid=10: 30: 15: 1 is the thin-layer chromatography discrimination method of developping agent.
Concrete discrimination method is:
Get 2 in preparation of the present invention, porphyrize, 50ml adds diethyl ether, sonicated 20 minutes, filter, filtrate evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, be added on the neutral alumina post of 100～200 orders, 8g, internal diameter 1.5cm, with ether 80ml wash-out, collect eluent, put evaporate to dryness in the water-bath, residue adds 60～90 ℃ of sherwood oil 1ml makes dissolving, as need testing solution; Other gets the storax control medicinal material, adds 60～90 ℃ of sherwood oils and makes the solution that every 1ml contains 25 μ l, in contrast medicinal material solution; According to " each 5 μ l of above-mentioned two kinds of solution are drawn in the test of 2005 editions one appendix VIB thin-layered chromatography of Chinese pharmacopoeia, put respectively in same be the high-efficient silica gel GF of binder with the sodium carboxymethyl cellulose
254On the thin layer plate, with 30～60 ℃ of sherwood oils: normal hexane: ethyl formate: formic acid=10: 30: 15: 1 is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to spot colour developing at 105 ℃, puts under the 365nm ultraviolet lamp and inspects, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence spot of same color.
The content assaying method of borneol is to be the vapor-phase chromatography of contrast with the borneol reference substance; The content assaying method of alantolactone is to be the vapor-phase chromatography of contrast with the alantolactone reference substance.
Concrete content assaying method comprises the part or all of of following project:
(1) borneol is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-INNOWAX fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.53mm * 0.32 μ m; Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000;
It is an amount of that correction factor mensuration is got gaultherolin, and accurate the title decides, and adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.20mg, as inner mark solution; It is an amount of that other gets the borneol reference substance, and accurate the title decides, and adds the inner mark solution dissolving and be diluted to the solution that every 1ml contains 0.25mg, draws 2 μ l inject gas chromatographs, the calculation correction factor;
Determination method is got 10 in preparation of the present invention, and accurate the title decided porphyrize, precision takes by weighing the fine powder that contains borneol 12.5mg, and in the flask, precision adds inner mark solution 50ml at the bottom of the horizontalization, water-bath refluxed 15 minutes, put coldly, filtered, get subsequent filtrate, as need testing solution, get 2 μ l inject gas chromatographs, measure, calculate by internal standard method, promptly;
Every in preparation of the present invention contains borneol C
10H
18O is 40.0mg～60.0mg;
(2) alantolactone is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000;
The preparation of the reference substance solution constuslactone reference substance that fetches earth is an amount of, accurately claims surely, adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.2mg, promptly;
10 in preparation of the present invention is got in the preparation of need testing solution, and accurate the title decided porphyrize, get 2g, accurate claim fixed, at the bottom of the horizontalization in the flask, add sherwood oil 50ml, reflux 2 hours is put cold, filter,, merge sherwood oil liquid with sherwood oil 20ml gradation washing filter residue and container, reclaim sherwood oil to doing, the residue anhydrous alcohol solution is transferred in the 10ml volumetric flask, add absolute ethyl alcohol and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 2 μ l of need testing solution of drawing of determination method, inject gas chromatograph is measured, promptly;
Every in preparation of the present invention contains elecampane with alantolactone C
15H
20O
2Meter must not be less than 0.50mg.
Method of quality control of the present invention comprises:
Proterties: medicine is that light brown is to brown; Gas perfume (or spice), bitter, cold;
Differentiate: get 2 in preparation of the present invention, porphyrize, 50ml adds diethyl ether, sonicated 20 minutes, filter, filtrate evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, be added on the neutral alumina post of 100～200 orders, 8g, internal diameter 1.5cm, with ether 80ml wash-out, collect eluent, put evaporate to dryness in the water-bath, residue adds 60～90 ℃ of sherwood oil 1ml makes dissolving, as need testing solution; Other gets the storax control medicinal material, adds 60～90 ℃ of sherwood oils and makes the solution that every 1ml contains 25 μ l, in contrast medicinal material solution; According to " each 5 μ l of above-mentioned two kinds of solution are drawn in the test of 2005 editions one appendix VIB thin-layered chromatography of Chinese pharmacopoeia, put respectively in same be the high-efficient silica gel GF of binder with the sodium carboxymethyl cellulose
254On the thin layer plate, with 30～60 ℃ of sherwood oils: normal hexane: ethyl formate: formic acid=10: 30: 15: 1 is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to spot colour developing at 105 ℃, puts under the 365nm ultraviolet lamp and inspects, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence spot of same color;
Check: get 10ml scale test tube disintegration time limited, the 2ml distilled water of packing into is put in 37 ℃ of water-baths, gets 1 in preparation of the present invention, puts in vitro, and timing immediately should disintegration in 1 minute, and the particle greater than No. two mesh sizes must not be arranged;
Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item;
Assay: (1) borneol is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-INNOWAX fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.53mm * 0.32 μ m; Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000;
It is an amount of that correction factor mensuration is got gaultherolin, and accurate the title decides, and adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.20mg, as inner mark solution; It is an amount of that other gets the borneol reference substance, and accurate the title decides, and adds the inner mark solution dissolving and be diluted to the solution that every 1ml contains 0.25mg, draws 2 μ l inject gas chromatographs, the calculation correction factor;
Determination method is got 10 in preparation of the present invention, and accurate the title decided porphyrize, precision takes by weighing the fine powder that contains borneol 12.5mg, and in the flask, precision adds inner mark solution 50ml at the bottom of the horizontalization, water-bath refluxed 15 minutes, put coldly, filtered, get subsequent filtrate, as need testing solution, get 2 μ l inject gas chromatographs, measure, calculate by internal standard method, promptly;
Every in preparation of the present invention contains borneol C
10H
18O is 40.0mg～60.0mg;
(2) alantolactone is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000;
The preparation of the reference substance solution constuslactone reference substance that fetches earth is an amount of, accurately claims surely, adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.2mg, promptly;
10 in preparation of the present invention is got in the preparation of need testing solution, and accurate the title decided porphyrize, get 2g, accurate claim fixed, at the bottom of the horizontalization in the flask, add sherwood oil 50ml, reflux 2 hours is put cold, filter,, merge sherwood oil liquid with sherwood oil 20ml gradation washing filter residue and container, reclaim sherwood oil to doing, the residue anhydrous alcohol solution is transferred in the 10ml volumetric flask, add absolute ethyl alcohol and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 2 μ l of need testing solution of drawing of determination method, inject gas chromatograph is measured, promptly;
Every in preparation of the present invention contains elecampane with alantolactone C
15H
20O
2Meter must not be less than 0.50mg.
Among the we storax hot temperature fragrance is arranged, have one's ideas straightened out ward off dirty, open the strongly fragrant turbid merit of dispelling, promoting the circulation of qi is reduced phlegm, the logical pain relieving of temperature, stimulating the menstrual flow reaches network, dissolves the stagnant effect of the strongly fragrant heap soil or fertilizer over and around the roots of phlegm in the body; Elecampane, santal can activating qi for lowering adverse qis, a surname's key is opened strongly fragrantly, and can manage it diffusing, the wide chest of sharp diaphragm, promoting qi circulation and relieving pain; Frankincense then can the promoting the circulation of qi homoiothermy, makes QI-blood circulation unobstructed, and general rule is not bitterly.Coronary disease Soviet Union close preparation cure mainly uncomfortable in chest, feel suffocated, have the effects such as wide chest, pain relieving of regulating the flow of vital energy, can treat and prevent angina pectoris attacks, and can play mitigation angina pectoris.
Compared with prior art, oral disnitegration tablet of the present invention can be in the oral cavity disintegration rapidly, taking convenience absorbs sooner, bioavilability is higher, the gastrointestinal mucosal spread effect is little, its preparation technology helps industrialized production; Change agent and become oral disnitegration tablet, can give full play to its formulation advantage, help patient's medication.In addition, method of quality control precision height of the present invention, favorable reproducibility, workable, improve coronary disease Soviet Union and closed the quality control standard of preparation, thereby guaranteed the clinical efficacy of said preparation.
The applicant has carried out preparation technology and the method for quality control that pharmaceutical preparation of the present invention is selected in a series of experiments, guaranteeing its science, reasonable, feasible, and has excellent curative.
One, Study on Preparation
1. preparation prescription craft screening
| Form | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 |
| Crude drug powder (g) | A recipe quantity | A recipe quantity | A recipe quantity | A recipe quantity |
| Microcrystalline cellulose (g) | 100 | 100 | 50 | 80 |
| Crospolyvinylpyrrolidone (g) | 250 | 200 | 150 | 220 |
| Low-substituted hydroxypropyl cellulose (g) | 150 | 100 | 150 | 80 |
| Superfine silica gel powder (g) | 50 | — | — | 50 |
| Aspartame (g) | 15 | 10 | 10 | 10 |
| Dolomol (g) | 3 | 5 | 5 | 5 |
| Disintegration | ＜30 seconds | ＜30 seconds | 50 seconds | Between 40～50 seconds |
| Taste | Generally | Suitable | Suitable | Suitable |
| Unilateral | Smooth, sheet is heavy higher | Smooth | Dry linting phenomenon slightly | Smooth |
| Compressibility | Suitable | Hardness is suitable | Relatively poor | Slightly poor |
Above test findings shows, adopts prescription 2 better, determines that finally oral disintegration tablet for treating coronary heart disease prescription and technology are as follows:
Storax 25g
Borneol 52.5g
Frankincense (system) 52.5g
Santal 105g
Elecampane 105g
Microcrystalline cellulose 100g
Crospolyvinylpyrrolidone 200g
Low-substituted hydroxypropyl cellulose 100g
Dolomol 5g
Aspartame 10g
Make 1000 altogether, every heavy 0.76g.
Preparation technology: the frankincense (system), santal, the elecampane that take by weighing recipe quantity, pulverize, cross 80 mesh sieves, standby, take by weighing microcrystalline cellulose, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, the aspartame of recipe quantity, mix with above-mentioned crude drug powder, make wetting agent system softwood with 95% ethanol that is dissolved with storax, 20 eye mesh screens are granulated, in 60 ± 5 ℃ of dryings, dried particle is with the whole grain of 20 eye mesh screens, add borneol (crossing 80 mesh sieves) and dolomol in the particle behind the whole grain, mix, be pressed into 1000, packing, promptly.
2. the test findings of three batches of pilot products
| Lot number | 050401 | 050402 | 050403 |
| Raw medicinal herbs input amount (kg) | 3.40 | 3.40 | 3.40 |
| Microcrystalline cellulose (kg) | 1.00 | 1.00 | 1.00 |
| Low-substituted hydroxypropyl cellulose (kg) | 1.00 | 1.00 | 1.00 |
| Crospolyvinylpyrrolidone (kg) | 2.00 | 2.00 | 2.00 |
| Aspartame (kg) | 0.10 | 0.10 | 0.10 |
| Dolomol (kg) | 0.05 | 0.05 | 0.05 |
| Theoretical yield (sheet) | 10000 | 10000 | 10000 |
| Actual output (sheet) | 9048 | 9168 | 9264 |
| Yield rate (%) | 90.48 | 91.68 | 92.64 |
Conclusion: three batches of pilot product trial results show that this preparation process is reasonable, stable, and the finished product recovery rate is higher, and the gained finished product is through quality inspection, and the result shows all up to specification.
Two, pharmacodynamic study
On the Model Rats with Acute Myocardial Ischemia due to the pituitrin, observe the effect that preparation and nifedipine group are closed by coronary disease Soviet Union, the result is as follows:
(1) medicine to the influence of ECG to blank group rat iv. pituitrin (pituitrin Pit) after, ECG the ST section occurs and obviously raises in 30s,〉0.2mV, slightly descend during 1min, but still higher than giving before the pit, show the indication of myocardial damage.Coronary disease Soviet Union closes after preparation and nifedipine group rat give pit, though the ST section is raised, raises amplitude＜0.1mV.Compare with the control group with the time, administration group ST section changes obviously and reduces, P＜0.01.Blank group rat is after giving pit, and ventricular arrhythmia appears in ECG, and administration group rat is not found the arrhythmia cordis phenomenon.
(2) after medicine is given pit to the influence of rat blood serum LDH activity, two groups of active equal highly significant, P＜0.01 of improving of rat blood serum LDH.But the preparation group is closed by coronary disease Soviet Union and nifedipine rat blood serum LDH level is compared with control group, and there is the reduction of highly significant P＜0.01.No significant difference then between two administration groups, P〉0.05.
(3) medicine acute myocardial ischemia rat that the influence of rat blood serum MDA is caused by pit, Content of MDA significantly improves, P＜0.01.And give the rat that preparation and nifedipine processing are closed by coronary disease Soviet Union in advance, and behind iv pit, Content of MDA is not found obvious raising, P〉0.05.
The result shows: preparation closes in coronary disease Soviet Union and nifedipine all can significantly improve the ischemic cardiogram, reduces serum lactic acid dehydrogenase activity, the treating myocardial ischemia damage that the antagonism pituitrin causes, and preparation closes in coronary disease Soviet Union can make mda content reduction in the rats with myocardial ischemia blood.
Three, method of quality control research
(1) sample and contrast medicine source
Sample: our company's self-control, lot number is: 050401,050402,050403.
Alantolactone provides (lot number: 110760-200204) by Nat'l Pharmaceutical ﹠ Biological Products Control Institute;
The borneol reference substance provides (lot number: 110743-200303) by Nat'l Pharmaceutical ﹠ Biological Products Control Institute;
(2) content limit
This preparation specification is 0.76g, and it all is to adopt gas chromatography determination that oral disintegration tablet for treating coronary heart disease needs two quantitative content's index, and every in this preparation contains borneol (C
10H
18O) be 40.0mg～60.0mg; Every contains elecampane with alantolactone (C
15H
20O
2) meter, must not be less than 0.50mg.
(3) proterties
This preparation medicinal powder of making a living adds appropriate amount of auxiliary materials, forms through mixing, granulation, compressing tablet, and through many batch samples trial-productions, the result shows and is light brown to brown; Gas perfume (or spice), bitter, cold.Therefore the proterties item is defined as in the oral disintegration tablet for treating coronary heart disease quality standard: medicine is that light brown is to brown; Gas perfume (or spice), bitter, cold.
(4) differentiate
With reference to " storax pill for treating coronary heart disease of Chinese pharmacopoeia version in 2005 is differentiated item content down, with the method for thin-layer chromatography our main ingredient storax is differentiated.
(1) get 2 in this preparation, porphyrize, 50ml adds diethyl ether, sonicated 20 minutes filters the filtrate evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, is added in neutral alumina post (100～200 orders, 8g, internal diameter 1.5cm) on, with ether 80ml wash-out, collect eluent, put evaporate to dryness in the water-bath, residue adds sherwood oil (60～90 ℃) 1ml makes dissolving, as need testing solution.Other gets the storax control medicinal material, adds sherwood oil (60～90 ℃) and makes the solution that every 1ml contains 25 μ l, medicinal material solution in contrast.According to thin-layered chromatography (" appendix VIB of Chinese pharmacopoeia version in 2005) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively in same be the high-efficient silica gel GF of binder with the sodium carboxymethyl cellulose
254On the thin layer plate, with sherwood oil (30～60 ℃)-normal hexane-ethyl formate-formic acid (10: 30: 15: 1) be developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to spot colour developing at 105 ℃, puts under the ultraviolet lamp (365nm) and inspects, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence spot of same color.
(2) selection of point sample amount
Through experimental selection need testing solution and reference substance solution each point sample 2 μ l, 5 μ l, 10 μ l, spot is better when found that need testing solution and reference substance solution point sample 5 μ l and 10 μ l, comparatively clear, spot is unintelligible during 2 μ l, so this standard reference material solution and need testing solution select for use 5 μ l as the point sample amount.
(3) specificity experiment
Get the negative sample 0.6g that lacks storax, make negative need testing solution, launch the back and do not have corresponding spot, illustrate that negative sample is noiseless to this experiment at the reference substance place with extracting the operation of a item method.
(5) check
1, get 10ml scale test tube disintegration time limited, the 2ml distilled water of packing into is put in 37 ℃ of water-baths, gets 1 in this preparation, puts in vitro, and timing immediately should be molten diffusing in 1 minute, and the particle greater than No. two mesh sizes must not be arranged.
Table 1 is investigated the result disintegration time limited
| Lot number | 050401 | 050402 | 050403 |
| Time (second) | 30 | 28 | 31 |
2, arsenic salt checks that by an appendix IX of Chinese Pharmacopoeia version in 2000 F arsenic salt inspection technique first method result is up to specification.
Table 2 arsenic salt measurement result
| Lot number | 050401 | 050402 | 050403 |
| Arsenic salt | <2ppm | <2ppm | <2ppm |
3, heavy metal checks that by an appendix IX of Chinese Pharmacopoeia version in 2000 E heavy metal inspection technique second method result is up to specification.
Table 3 determining heavy metals result
| Lot number | 050401 | 050402 | 050403 |
| Heavy metal | <5ppm | <5ppm | <5ppm |
4, weight differential
This preparation sheet is great in 0.3g, should get 20 inspections of this preparation three batch samples in ± 5% by a regulation of version Chinese Pharmacopoeia in 2000 tablet weight variation, the results are shown in following table 5.
Table 4 weight differential check result
| Heavy (g) sheet of sheet number | 050401 | 050402 | 050403 |
| 1 | 0.7459 | 0.7617 | 0.7596 |
| 2 | 0.7527 | 0.7657 | 0.7412 |
| 3 | 0.7786 | 0.7438 | 0.7415 |
| 4 | 0.7815 | 0.7526 | 0.7422 |
| 5 | 0.7415 | 0.7786 | 0.7430 |
| 6 | 0.7437 | 0.7801 | 0.7821 |
| 7 | 0.7500 | 0.7809 | 0.7800 |
| 8 | 0.7628 | 0.7535 | 0.7766 |
| 9 | 0.7701 | 0.7606 | 0.7825 |
| 10 | 0.7829 | 0.7439 | 0.7617 |
| 11 | 0.7725 | 0.7526 | 0.7528 |
| 12 | 0.7688 | 0.7488 | 0.7463 |
| 13 | 0.7659 | 0.7651 | 0.7399 |
| 14 | 0.7438 | 0.7655 | 0.7457 |
| 15 | 0.7720 | 0.7435 | 0.7521 |
| 16 | 0.7933 | 0.7442 | 0.7480 |
| 17 | 0.7615 | 0.7487 | 0.7426 |
| 18 | 0.7509 | 0.7527 | 0.7835 |
| 19 | 0.7483 | 0.7596 | 0.7652 |
| 20 | 0.7527 | 0.7630 | 0.7827 |
| Average sheet heavy (g) | 0.7620 | 0.7583 | 0.7585 |
| The heavy scope (%) of sheet | -2.69％～+4.11％ | -1.95％～+2.98％ | -2.45％～+3.30％ |
This preparation three batch sample measurement results show that tablet weight variation is all within specialized range.
5, microbial limit
Check that according to microbial limit test (appendix XIII of Chinese Pharmacopoeia version in 2000) check result of three batch samples sees the following form.
Table 5 limit test of microbe result
| Lot number | 050401 | 050402 | 050403 |
| Bacterial population (individual/g) | Up to specification | Up to specification | Up to specification |
| Fungi count (individual/g) | Up to specification | Up to specification | Up to specification |
| Escherichia coli (individual/g) | Do not detect | Do not detect | Do not detect |
| Mite (individual/g) | Do not detect | Do not detect | Do not detect |
(6) assay
The checking of oral disintegration tablet for treating coronary heart disease content of bornyl alcohol assay method
1, instrument and reagent
Instrument: HP6890 gas chromatograph
The borneol reference substance: provide (lot number 110743-200303) by Nat'l Pharmaceutical ﹠ Biological Products Control Institute, it is pure that reagent is analysis.
2, the selection of extraction conditions:
Adopt to add inner mark solution, the water-bath refluxing extraction the results are shown in Table 6.
The examination of table 6 return time
The result shows when adopting the absolute ethyl alcohol reflow method to extract, when return time greater than 30 minutes, along with the increase of return time, content has downtrending, according to test findings, adopts and refluxes 15 minutes as extracting method.
3, chromatographic condition and system suitability test: HP-INNOWAX fused-silica capillary column (30m * 0.53mm * 0.32 μ m); Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Split sampling, split ratio: 50: 1.Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000.
Borneol under this chromatographic condition in the borneol and isoborneol and internal standard compound gaultherolin chromatographic peak degree of separation all meet the requirements.
4, the preparation of reference substance solution and need testing solution is seen below and is stated the content of bornyl alcohol assay method.
5, linear relationship is investigated: precision takes by weighing borneol reference substance 20.80mg and puts in the 25ml measuring bottle, adds the inner mark solution dissolving and is diluted to scale, and precision is measured this solution 1,2,3,4 respectively, 5ml puts in the 10ml measuring bottle, adds inner mark solution and is diluted to scale, shakes up.Get 2 μ l inject gas chromatographs respectively, ratio with the borneol peak in the borneol reference substance and isoborneol peak area summation and interior mark peak area is ordinate, borneol concentration (mg/ml) is horizontal ordinate (seeing Table 7), gets regression equation: Y=7.6678X+0.0277, r=0.9999; Borneol concentration has good linear relationship at 0.0832mg～0.4160mg in the scope.
Table 7 borneol linear relationship is investigated the result
| Numbering | 1 | 2 | 3 | 4 | 5 |
| Borneol concentration (mg/ml) | 0.0832 | 0.1644 | 0.2496 | 0.3328 | 0.4160 |
| Borneol and isoborneol peak area sum and interior mark peak area ratio | 0.6154 | 1.2501 | 1.8733 | 2.5239 | 3.1683 |
6, specificity test: get scarce borneol negative test sample, press the content assaying method sample introduction, the result shows that not having the chromatographic peak appearance with borneol and isoborneol same position negative control is noiseless.
7, precision: get with a reference substance solution, press the chromatographic condition under the assay, continuous sample introduction 5 times, mark and isoborneol, borneol peak area in measuring, calculate the ratio of both isoborneols and borneol peak area sum and interior mark peak area, RSD is 0.29% as a result, sees Table 8.
Table 8 Precision test result
| Numbering | 1 | 2 | 3 | 4 | 5 | Mean value | RSD％ |
| Isoborneol and borneol peak area sum and interior mark peak area ratio | 1.8808 | 1.8906 | 1.8836 | 1.8924 | 1.8923 | 1.8879 | 0.29 |
8, stability: get with a reference substance solution, press the assay chromatographic condition, at interval the certain hour sample introduction, mark and borneol, isoborneol peak area in measuring, calculate the ratio of borneol and isoborneol peak area sum and interior mark peak area, the result shows that need testing solution is stable in 8 hours, sees Table 9.
Table 9 stability test result
| Time (hour) | 0 | 2 | 4 | 6 | 8 | Mean value | RSD(％) |
| Isoborneol and borneol peak area sum and interior mark peak area ratio | 1.8882 | 1.9137 | 1.9321 | 1.8972 | 1.9054 | 1.9073 | 0.88 |
9, repeatability: (lot number: 050401) sample is 6 parts, opens the calculating content of bornyl alcohol by containing measurement foot ten thousand methods mensuration, and the borneol average content is the 54.6mg/ sheet as a result, and RSD is 0.69% (n=6), sees Table 10 to get same lot number.
Table 10 replica test result
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Mean value | RSD％ |
| Content of bornyl alcohol (mg/g) | 54.1 | 54.8 | 54.5 | 54.7 | 55.0 | 54.5 | 54.6 | 0.62 |
10, the recovery: because of borneol is that full medicine adds, and limit about having formulated, so the recovery adopts simulation prescription determination of recovery rates method, take by weighing 80%, 100%, 120% of about borneol amount in the prescription respectively, each three parts, and add other component and auxiliary material by prescription, and press that content assaying method is measured and calculating content, the result shows that average recovery rate is 99.8%, RSD is 0.91% (seeing Table 11).
Table 11 recovery test result
11, content of bornyl alcohol is measured in the sample: measure according to vapor-phase chromatography (2005 editions one appendix VI E of Chinese Pharmacopoeia).
Chromatographic condition and system suitability test HP-INNOWAX fused-silica capillary column (30m * 0.53mm * 0.32 μ m); Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000.
It is an amount of that correction factor mensuration is got gaultherolin, and accurate the title decides, and adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.20mg, as inner mark solution.It is an amount of that other gets the borneol reference substance, and accurate the title decides, and adds the inner mark solution dissolving and be diluted to the solution that every 1ml contains 0.25mg, draws 2 μ l inject gas chromatographs, is the borneol peak area with borneol and isoborneol peak area sum, the calculation correction factor.
Determination method is got 10 in this preparation, and accurate the title decided porphyrize, precision takes by weighing fine powder an amount of (containing borneol 0.25g approximately), and in the flask, precision adds inner mark solution 50ml at the bottom of the horizontalization, water-bath refluxed 15 minutes, put coldly, filtered, get subsequent filtrate, as need testing solution, get 2 μ l inject gas chromatographs, measure, calculate by internal standard method, promptly.
Every in this preparation contains borneol (C
10H
18O) be 40.0mg～60.0mg.
Measure three batch samples as stated above, the results are shown in Table 12.
Table 12 sample determination result
| Numbering | Lot number | Content (mg/ sheet) |
| 1 | 050401 | 54.6 |
| 2 | 050402 | 53.9 |
| 3 | 050403 | 53.9 |
| 4 | Lab scale 1 | 56.2 |
| 5 | Lab scale 2 | 53.0 |
| 6 | Lab scale 3 | 51.2 |
| 7 | Lab scale 4 | 48.6 |
According to measurement result and this preparation prescription, with reference to content of bornyl alcohol limit in the storax pill for treating coronary heart disease of 2005 editions one one of Chinese Pharmacopoeia, temporarily limit being decided to be every in this preparation, to contain borneol be 40.0mg～60.0mg.
The checking of oral disintegration tablet for treating coronary heart disease elecampane content assaying method
12, instrument and reagent
Instrument: HP6890 gas chromatograph
Reference substance: alantolactone by Nat'l Pharmaceutical ﹠ Biological Products Control Institute provide (lot number: 110760-200204), reagent be analyze pure.
13, the selection of extraction conditions: carried out banksia rose medicinal material extract method for the durability of ensuring method and investigated, to determine extraction conditions, can't determine the power and the frequency of existing ultrasonic oscillator down because of experiment condition, so wouldn't examine or check sonicated, and adopt the sherwood oil heating and refluxing extraction, the results are shown in Table 13.
Table 13 return time is selected experiment
The result shows when adopting the sherwood oil reflow method to extract that refluxed 30 minutes to 2 hours, along with the increase of return time, the constuslactone content is all in one of percentage.According to test findings, consider the medicinal material that may use the different places of production in the future producing, for guaranteeing the durability of this method, adopt temporarily and reflux 2 hours as return time.
14, chromatographic condition and system suitability test: HP-1 fused-silica capillary column (30m * 0.32mm * 0.25 μ m); Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Split sampling, split ratio: 50: 1.Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000.
Alantolactone and other assorted peak degree of separation are good under this chromatographic condition, and number of theoretical plate meets the requirements.
15, the preparation of reference substance solution and need testing solution is seen below and is stated content assaying method.
16, linear relationship is investigated: precision takes by weighing alantolactone reference substance 20.50mg and puts in the 25ml measuring bottle, add anhydrous alcohol solution and be diluted to scale, precision is measured this solution 1,2,3,4 respectively, 5ml puts in the 10ml measuring bottle, adds absolute ethyl alcohol and is diluted to scale, shakes up.Getting 2 μ l inject gas chromatographs respectively, is ordinate with the alantolactone peak area, and alantolactone concentration (mg/ml) is horizontal ordinate (seeing Table 14), gets regression equation: Y=4210.8X+113.8, r=0.9998; Alantolactone concentration has good linear relationship in 0.102mg/ml～0.510mg/ml scope.
Table 14 alantolactone linear relationship is investigated the result
| Numbering | 1 | 2 | 3 | 4 | 5 |
| Alantolactone concentration (mg/ml) | 0.102 | 0.204 | 0.306 | 0.408 | 0.510 |
| The alantolactone peak area | 4294 | 8486 | 12840 | 17040 | 21071 |
17, specificity test: get scarce alantolactone negative test sample, press assay ten thousand method sample introductions, the result shows that not having the chromatographic peak appearance with the alantolactone same position negative control is noiseless.
18, precision: get with a reference substance solution, press the chromatographic condition under the assay, continuous sample introduction 5 times is measured the alantolactone peak area, and RSD is 0.47% as a result, sees Table 15.
Table 15 Precision test result
| Numbering | 1 | 2 | 3 | 4 | 5 | Mean value | RSD(％) |
| The alantolactone peak area | 8341 | 8286 | 8294 | 8342 | 8251 | 8303 | 0.47 |
19, stability: get with a reference substance solution, press the assay chromatographic condition, the certain hour sample introduction is measured the alantolactone area at interval, shows that need testing solution is stable in 8 hours, sees Table 16.
Table 16 stability test result
| Time (hour) | 0 | 2 | 5 | 7 | 8 | Mean value | RSD(％) |
| The alantolactone area | 8246 | 8310 | 8276 | 8327 | 8228 | 8277 | 0.50 |
20, repeatability: (lot number: 050401) sample is 6 parts, presses content assaying method mensuration and calculates alantolactone content, and the alantolactone average content is the 0.800mg/ sheet as a result, and RSD is 1.10%, sees Table 17 to get same lot number.
Table 17 replica test result
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Mean value | RSD％ |
| Alantolactone content (mg/ sheet) | 0.806 | 0.802 | 0.787 | 0.793 | 0.804 | 0.811 | 0.800 | 1.10 |
21, the recovery: the sample fine powder (lot number: 050401) an amount of (totally 9 parts) that takes by weighing known content respectively, the accurate reference substance that adds is an amount of, press that content assaying method is measured and calculate content, the result shows that average recovery rate is 99.8%, RSD is 0.91% (seeing Table 18).
Table 18 recovery test result
22, assay: measure according to vapor-phase chromatography (2005 editions one appendix VI E of Chinese Pharmacopoeia).
Chromatographic condition and system suitability test HP-1 fused-silica capillary column (30m * 0.25mm * 0.32 μ m); Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000.
The preparation of the reference substance solution constuslactone reference substance that fetches earth is an amount of, accurately claims surely, adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.2mg.
It is fixed that 10 accurate titles of this preparation are got in the preparation of need testing solution, and porphyrize is got 2g, the accurate title, decide, and in the flask, adds sherwood oil 50ml at the bottom of the horizontalization, reflux 2 hours is put coldly, filters, with sherwood oil 20ml gradation washing filter residue and container, merge sherwood oil liquid, reclaim sherwood oil to doing, the residue anhydrous alcohol solution is transferred in the 10ml volumetric flask, adds absolute ethyl alcohol and is diluted to scale, shake up, promptly.
Accurate respectively reference substance solution and each 2ul of need testing solution of drawing of determination method, inject gas chromatograph is measured, promptly.
Every in this preparation contains elecampane with alantolactone (C
15H
20O
2) meter, must not be less than 0.50mg.
Measure three batch samples as stated above, the results are shown in Table 19.
Table 19 sample determination result
| Numbering | Lot number | Content (mg/ sheet) |
| 1 | 050401 | 0.804 |
| 2 | 050402 | 0.800 |
| 3 | 050403 | 0.798 |
| 4 | Lab scale 1 | 0.777 |
| 5 | Lab scale 2 | 0.759 |
| 6 | Lab scale 3 | 0.813 |
| 7 | Lab scale 4 | 0.828 |
According to measurement result and this preparation prescription,, temporarily limit is decided to be every in this preparation and contains elecampane with alantolactone (C with reference to alantolactone content limit in the storax pill for treating coronary heart disease of 2005 editions one one of Chinese Pharmacopoeia
15H
20O
2) meter, must not be less than 0.50mg.
Conclusion:
Borneol adopts vapor-phase chromatography, selects the polarity capillary column for use, adopts gaultherolin to do interior mark, and borneol and isoborneol retention time are close in internal standard compound and the borneol under this chromatographic condition, and degree of separation meets the requirements.Content limit is tentative to contain borneol (C for every
10H
18O) 40.0mg～60.0mg.
Alantolactone adopts vapor-phase chromatography, selects nonpolar capillary column for use, external standard method, and under this chromatographic condition, alantolactone peak and other assorted peak degree of separation are good, and can obtain very high number of theoretical plate.Limit is tentative to contain elecampane with alantolactone (C for every
15H
20O
2) meter, must not be less than 0.50mg.
Embodiment:
Embodiments of the invention 1: storax 25g, borneol 52.5g, frankincense 52.5g, santal 105g, elecampane 105g, microcrystalline cellulose 100g, crospolyvinylpyrrolidone 200g, low-substituted hydroxypropyl cellulose 100g, aspartame 10g, dolomol 5g
Take by weighing frankincense, santal, elecampane, pulverize, cross 80 mesh sieves, standby; Take by weighing microcrystalline cellulose, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, aspartame, mix with above-mentioned crude drug powder, make wetting agent system softwood with 95% ethanol that is dissolved with storax, 20 eye mesh screens are granulated, in 60 ± 5 ℃ of dryings, dried particle is with the whole grain of 20 eye mesh screens, add the borneol and the dolomol of 80 mesh sieves in the particle behind the whole grain, mixed, be pressed into 1000, packing, promptly.This product oral, one time 2,1～3 time on the one.
Embodiments of the invention 2: described method of quality control comprises following content:
Proterties: medicine is that light brown is to brown; Gas perfume (or spice), bitter, cold;
Differentiate: get 2 in preparation of the present invention, porphyrize, 50ml adds diethyl ether, sonicated 20 minutes, filter, filtrate evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, be added on the neutral alumina post of 100～200 orders, 8g, internal diameter 1.5cm, with ether 80ml wash-out, collect eluent, put evaporate to dryness in the water-bath, residue adds 60～90 ℃ of sherwood oil 1ml makes dissolving, as need testing solution; Other gets the storax control medicinal material, adds 60～90 ℃ of sherwood oils and makes the solution that every 1ml contains 25 μ l, in contrast medicinal material solution; According to " each 5 μ l of above-mentioned two kinds of solution are drawn in the test of 2005 editions one appendix VIB thin-layered chromatography of Chinese pharmacopoeia, put respectively in same be the high-efficient silica gel GF of binder with the sodium carboxymethyl cellulose
254On the thin layer plate, with 30～60 ℃ of sherwood oils: normal hexane: ethyl formate: formic acid=10: 30: 15: 1 is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to spot colour developing at 105 ℃, puts under the 365nm ultraviolet lamp and inspects, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence spot of same color;
Check: get 10ml scale test tube disintegration time limited, the 2ml distilled water of packing into is put in 37 ℃ of water-baths, gets 1 in preparation of the present invention, puts in vitro, and timing immediately should disintegration in 1 minute, and the particle greater than No. two mesh sizes must not be arranged;
Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item;
Assay: (1) borneol is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-INNOWAX fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.53mm * 0.32 μ m; Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000;
It is an amount of that correction factor mensuration is got gaultherolin, and accurate the title decides, and adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.20mg, as inner mark solution; It is an amount of that other gets the borneol reference substance, and accurate the title decides, and adds the inner mark solution dissolving and be diluted to the solution that every 1ml contains 0.25mg, draws 2 μ l inject gas chromatographs, the calculation correction factor;
Determination method is got 10 in preparation of the present invention, and accurate the title decided porphyrize, precision takes by weighing the fine powder that contains borneol 12.5mg, and in the flask, precision adds inner mark solution 50ml at the bottom of the horizontalization, water-bath refluxed 15 minutes, put coldly, filtered, get subsequent filtrate, as need testing solution, get 2 μ l inject gas chromatographs, measure, calculate by internal standard method, promptly;
Every in preparation of the present invention contains borneol C
10H
18O is 40.0mg～60.0mg;
(2) alantolactone is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000;
The preparation of the reference substance solution constuslactone reference substance that fetches earth is an amount of, accurately claims surely, adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.2mg, promptly;
10 in preparation of the present invention is got in the preparation of need testing solution, and accurate the title decided porphyrize, get 2g, accurate claim fixed, at the bottom of the horizontalization in the flask, add sherwood oil 50ml, reflux 2 hours is put cold, filter,, merge sherwood oil liquid with sherwood oil 20ml gradation washing filter residue and container, reclaim sherwood oil to doing, the residue anhydrous alcohol solution is transferred in the 10ml volumetric flask, add absolute ethyl alcohol and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 2 μ l of need testing solution of drawing of determination method, inject gas chromatograph is measured, promptly;
Every in preparation of the present invention contains elecampane with alantolactone C
15H
20O
2Meter must not be less than 0.50mg.
Embodiments of the invention 3: method of quality control can comprise following content:
Proterties: medicine is that light brown is to brown; Gas perfume (or spice), bitter, cold;
Differentiate: get 2 in preparation of the present invention, porphyrize, 50ml adds diethyl ether, sonicated 20 minutes, filter, filtrate evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, be added on the neutral alumina post of 100～200 orders, 8g, internal diameter 1.5cm, with ether 80ml wash-out, collect eluent, put evaporate to dryness in the water-bath, residue adds 60～90 ℃ of sherwood oil 1ml makes dissolving, as need testing solution; Other gets the storax control medicinal material, adds 60～90 ℃ of sherwood oils and makes the solution that every 1ml contains 25 μ l, in contrast medicinal material solution; According to " each 5 μ l of above-mentioned two kinds of solution are drawn in the test of 2005 editions one appendix VIB thin-layered chromatography of Chinese pharmacopoeia, put respectively in same be the high-efficient silica gel GF of binder with the sodium carboxymethyl cellulose
254On the thin layer plate, with 30～60 ℃ of sherwood oils: normal hexane: ethyl formate: formic acid=10: 30: 15: 1 is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to spot colour developing at 105 ℃, puts under the 365nm ultraviolet lamp and inspects, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence spot of same color;
Assay: borneol is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-INNOWAX fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.53mm * 0.32 μ m; Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000;
It is an amount of that correction factor mensuration is got gaultherolin, and accurate the title decides, and adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.20mg, as inner mark solution; It is an amount of that other gets the borneol reference substance, and accurate the title decides, and adds the inner mark solution dissolving and be diluted to the solution that every 1ml contains 0.25mg, draws 2 μ l inject gas chromatographs, the calculation correction factor;
Determination method is got 10 in preparation of the present invention, and accurate the title decided porphyrize, precision takes by weighing the fine powder that contains borneol 12.5mg, and in the flask, precision adds inner mark solution 50ml at the bottom of the horizontalization, water-bath refluxed 15 minutes, put coldly, filtered, get subsequent filtrate, as need testing solution, get 2 μ l inject gas chromatographs, measure, calculate by internal standard method, promptly;
Every in preparation of the present invention contains borneol C
10H
18O is 40.0mg～60.0mg.
Embodiments of the invention 4: method of quality control can comprise following content:
Proterties: medicine is that light brown is to brown; Gas perfume (or spice), bitter, cold;
Check: get 10ml scale test tube disintegration time limited, the 2ml distilled water of packing into is put in 37 ℃ of water-baths, gets 1 in preparation of the present invention, puts in vitro, and timing immediately should disintegration in 1 minute, and the particle greater than No. two mesh sizes must not be arranged;
Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item;
Assay: (1) borneol is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-INNOWAX fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.53mm * 0.32 μ m; Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000;
It is an amount of that correction factor mensuration is got gaultherolin, and accurate the title decides, and adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.20mg, as inner mark solution; It is an amount of that other gets the borneol reference substance, and accurate the title decides, and adds the inner mark solution dissolving and be diluted to the solution that every 1ml contains 0.25mg, draws 2 μ l inject gas chromatographs, the calculation correction factor;
Determination method is got 10 in preparation of the present invention, and accurate the title decided porphyrize, precision takes by weighing the fine powder that contains borneol 12.5mg, and in the flask, precision adds inner mark solution 50ml at the bottom of the horizontalization, water-bath refluxed 15 minutes, put coldly, filtered, get subsequent filtrate, as need testing solution, get 2 μ l inject gas chromatographs, measure, calculate by internal standard method, promptly;
Every in preparation of the present invention contains borneol C
10H
18O is 40.0mg～60.0mg;
(2) alantolactone is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000;
The preparation of the reference substance solution constuslactone reference substance that fetches earth is an amount of, accurately claims surely, adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.2mg, promptly;
10 in preparation of the present invention is got in the preparation of need testing solution, and accurate the title decided porphyrize, get 2g, accurate claim fixed, at the bottom of the horizontalization in the flask, add sherwood oil 50ml, reflux 2 hours is put cold, filter,, merge sherwood oil liquid with sherwood oil 20ml gradation washing filter residue and container, reclaim sherwood oil to doing, the residue anhydrous alcohol solution is transferred in the 10ml volumetric flask, add absolute ethyl alcohol and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 2 μ l of need testing solution of drawing of determination method, inject gas chromatograph is measured, promptly;
Every in preparation of the present invention contains elecampane with alantolactone C
15H
20O
2Meter must not be less than 0.50mg.
Embodiments of the invention 5: method of quality control can comprise following content:
Proterties: medicine is that light brown is to brown; Gas perfume (or spice), bitter, cold;
Differentiate: get 2 in preparation of the present invention, porphyrize, 50ml adds diethyl ether, sonicated 20 minutes, filter, filtrate evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, be added on the neutral alumina post of 100～200 orders, 8g, internal diameter 1.5cm, with ether 80ml wash-out, collect eluent, put evaporate to dryness in the water-bath, residue adds 60～90 ℃ of sherwood oil 1ml makes dissolving, as need testing solution; Other gets the storax control medicinal material, adds 60～90 ℃ of sherwood oils and makes the solution that every 1ml contains 25 μ l, in contrast medicinal material solution; According to " each 5 μ l of above-mentioned two kinds of solution are drawn in the test of 2005 editions one appendix VIB thin-layered chromatography of Chinese pharmacopoeia, put respectively in same be the high-efficient silica gel GF of binder with the sodium carboxymethyl cellulose
254On the thin layer plate, with 30～60 ℃ of sherwood oils: normal hexane: ethyl formate: formic acid=10: 30: 15: 1 is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to spot colour developing at 105 ℃, puts under the 365nm ultraviolet lamp and inspects, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence spot of same color;
Check: get 10ml scale test tube disintegration time limited, the 2ml distilled water of packing into is put in 37 ℃ of water-baths, gets 1 in preparation of the present invention, puts in vitro, and timing immediately should disintegration in 1 minute, and the particle greater than No. two mesh sizes must not be arranged;
Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item;
Assay: alantolactone is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determination
The HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000;
The preparation of the reference substance solution constuslactone reference substance that fetches earth is an amount of, accurately claims surely, adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.2mg, promptly;
10 in preparation of the present invention is got in the preparation of need testing solution, and accurate the title decided porphyrize, get 2g, accurate claim fixed, at the bottom of the horizontalization in the flask, add sherwood oil 50ml, reflux 2 hours is put cold, filter,, merge sherwood oil liquid with sherwood oil 20ml gradation washing filter residue and container, reclaim sherwood oil to doing, the residue anhydrous alcohol solution is transferred in the 10ml volumetric flask, add absolute ethyl alcohol and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 2 μ l of need testing solution of drawing of determination method, inject gas chromatograph is measured, promptly;
Every in preparation of the present invention contains elecampane with alantolactone C
15H
20O
2Meter must not be less than 0.50mg.
Claims (3)
- The detection method of [claim 1] a kind of oral disintegration tablet for treating coronary heart disease, oral disintegration tablet for treating coronary heart disease is prepared from by storax 25g, borneol 52.5g, frankincense 52.5g, santal 105g, elecampane 105g and microcrystalline cellulose 100g, crospolyvinylpyrrolidone 200g, low-substituted hydroxypropyl cellulose 100g, aspartame 10g and dolomol 5g, and described detection method is proterties, inspection, discriminating and assay project; Assay is the assay to borneol in the preparation and alantolactone; It is characterized in that: discrimination method is: get 2 in this preparation, and porphyrize, 50ml adds diethyl ether, sonicated 20 minutes, filter, filtrate evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, be added on the neutral alumina post of 100～200 orders, 8g, internal diameter 1.5cm, with ether 80ml wash-out, collect eluent, put evaporate to dryness in the water-bath, residue adds 60～90 ℃ of sherwood oil 1ml makes dissolving, as need testing solution; Other gets the storax control medicinal material, adds 60～90 ℃ of sherwood oils and makes the solution that every 1ml contains 25 μ l, in contrast medicinal material solution; According to " each 5 μ 1 of above-mentioned two kinds of solution are drawn in the test of 2005 editions one appendix VIB thin-layered chromatography of Chinese pharmacopoeia, put respectively in same be the high-efficient silica gel GF of binder with the sodium carboxymethyl cellulose 254On the thin layer plate, with 30～60 ℃ of sherwood oils: normal hexane: ethyl formate: formic acid=10: 30: 15: 1 is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to spot colour developing at 105 ℃, puts under the 365nm ultraviolet lamp and inspects, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence spot of same color.
- [claim 2] is characterized in that according to the detection method of the described oral disintegration tablet for treating coronary heart disease of claim 1: the content assaying method of borneol is to be the vapor-phase chromatography of contrast with the borneol reference substance; The content assaying method of alantolactone is to be the vapor-phase chromatography of contrast with the alantolactone reference substance; Concrete content assaying method is:(1) borneol is according to 2005 editions one appendix VIE gas chromatography determination of Chinese PharmacopoeiaThe HP-INNOWAX fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.53mm * 0.32 μ m; Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000;It is an amount of that correction factor mensuration is got gaultherolin, and accurate the title decides, and adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.20mg, as inner mark solution; It is an amount of that other gets the borneol reference substance, and accurate the title decides, and adds the inner mark solution dissolving and be diluted to the solution that every 1ml contains 0.25mg, draws 2 μ l inject gas chromatographs, the calculation correction factor;Determination method is got 10 in this preparation, and accurate the title decided porphyrize, precision takes by weighing the fine powder that contains borneol 12.5mg, and in the flask, precision adds inner mark solution 50ml at the bottom of the horizontalization, water-bath refluxed 15 minutes, put coldly, filtered, get subsequent filtrate, as need testing solution, get 2 μ l inject gas chromatographs, measure, calculate by internal standard method, promptly;Every in this preparation contains borneol C 10H 18O is 40.0mg～60.0mg;(2) alantolactone is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determinationThe HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000;The preparation of the reference substance solution constuslactone reference substance that fetches earth is an amount of, accurately claims surely, adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.2mg, promptly;10 in this preparation is got in the preparation of need testing solution, and accurate the title decided porphyrize, get 2g, accurate claim fixed, at the bottom of the horizontalization in the flask, add sherwood oil 50ml, reflux 2 hours is put cold, filter,, merge sherwood oil liquid with sherwood oil 20ml gradation washing filter residue and container, reclaim sherwood oil to doing, the residue anhydrous alcohol solution is transferred in the 10ml volumetric flask, add absolute ethyl alcohol and be diluted to scale, shake up, promptly;Accurate respectively reference substance solution and each the 2 μ l of need testing solution of drawing of determination method, inject gas chromatograph is measured, promptly;Every in this preparation contains elecampane with alantolactone C 15H 20O 2Meter must not be less than 0.50mg.
- [claim 3] is characterized in that according to the detection method of the described oral disintegration tablet for treating coronary heart disease of claim 1: described detection method is:Proterties: medicine is that light brown is to brown; Gas perfume (or spice), bitter, cold;Differentiate: get 2 in this preparation, porphyrize, 50ml adds diethyl ether, sonicated 20 minutes, filter, filtrate evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, be added on the neutral alumina post of 100～200 orders, 8g, internal diameter 1.5cm, with ether 80ml wash-out, collect eluent, put evaporate to dryness in the water-bath, residue adds 60～90 ℃ of sherwood oil 1ml makes dissolving, as need testing solution; Other gets the storax control medicinal material, adds 60～90 ℃ of sherwood oils and makes the solution that every 1ml contains 25 μ l, in contrast medicinal material solution; According to " each 5 μ l of above-mentioned two kinds of solution are drawn in the test of 2005 editions one appendix VIB thin-layered chromatography of Chinese pharmacopoeia, put respectively in same be the high-efficient silica gel GF of binder with the sodium carboxymethyl cellulose 254On the thin layer plate, with 30～60 ℃ of sherwood oils: normal hexane: ethyl formate: formic acid=10: 30: 15: 1 is developping agent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to spot colour developing at 105 ℃, puts under the 365nm ultraviolet lamp and inspects, in the test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, show the fluorescence spot of same color;Check: get 10ml scale test tube disintegration time limited, the 2ml distilled water of packing into is put in 37 ℃ of water-baths, gets 1 in this preparation, puts in vitro, and timing immediately should disintegration in 1 minute, and the particle greater than No. two mesh sizes must not be arranged;Other should meet " relevant every regulation under 2005 editions one appendix ID tablet of the Chinese pharmacopoeia item;Assay: (1) borneol is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determinationThe HP-INNOWAX fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.53mm * 0.32 μ m; Temperature programme: initial 140 ℃, kept 7 minutes, rise to 220 ℃ with 50 ℃ of per minutes and kept 2 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the gaultherolin peak and is calculated, and should be not less than 5000;It is an amount of that correction factor mensuration is got gaultherolin, and accurate the title decides, and adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.20mg, as inner mark solution; It is an amount of that other gets the borneol reference substance, and accurate the title decides, and adds the inner mark solution dissolving and be diluted to the solution that every 1ml contains 0.25mg, draws 2 μ l inject gas chromatographs, the calculation correction factor;Determination method is got 10 in this preparation, and accurate the title decided porphyrize, precision takes by weighing the fine powder that contains borneol 12.5mg, and in the flask, precision adds inner mark solution 50ml at the bottom of the horizontalization, water-bath refluxed 15 minutes, put coldly, filtered, get subsequent filtrate, as need testing solution, get 2 μ l inject gas chromatographs, measure, calculate by internal standard method, promptly;Every in this preparation contains borneol C 10H 18O is 40.0mg～60.0mg;(2) alantolactone is according to 2005 editions one appendix VI E of Chinese Pharmacopoeia gas chromatography determinationThe HP-1 fused-silica capillary column of chromatographic condition and system suitability test 30m * 0.25mm * 0.25 μ m; Temperature programme: 100 ℃ of initial temperatures, kept 5 minutes, rise to 220 ℃ with 10 ℃ of per minutes and kept 3 minutes; Flow rate of carrier gas: per minute 1.5ml; Number of theoretical plate is pressed the alantolactone peak and is calculated, and should be not less than 40000;The preparation of the reference substance solution constuslactone reference substance that fetches earth is an amount of, accurately claims surely, adds absolute ethyl alcohol and makes the solution that every 1ml contains 0.2mg, promptly;10 in this preparation is got in the preparation of need testing solution, and accurate the title decided porphyrize, get 2g, accurate claim fixed, at the bottom of the horizontalization in the flask, add sherwood oil 50ml, reflux 2 hours is put cold, filter,, merge sherwood oil liquid with sherwood oil 20ml gradation washing filter residue and container, reclaim sherwood oil to doing, the residue anhydrous alcohol solution is transferred in the 10ml volumetric flask, add absolute ethyl alcohol and be diluted to scale, shake up, promptly;Accurate respectively reference substance solution and each the 2 μ l of need testing solution of drawing of determination method, inject gas chromatograph is measured, promptly;Every in this preparation contains elecampane with alantolactone C 15H 20O 2Meter must not be less than 0.50mg.
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| 中华人民共和国卫生部 药品标准 中药成方制剂. 中华人民共和国卫生部药典委员会，158，中华人民共和国卫生部药典委员会. 1998 中华人民共和国药典. 国家药典委员会，551，国家药典委员会. 2005 |
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