CN102749413B - Quality detection method of traditional Chinese medicine composition for treating headache - Google Patents
Quality detection method of traditional Chinese medicine composition for treating headache Download PDFInfo
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- CN102749413B CN102749413B CN201210212011.7A CN201210212011A CN102749413B CN 102749413 B CN102749413 B CN 102749413B CN 201210212011 A CN201210212011 A CN 201210212011A CN 102749413 B CN102749413 B CN 102749413B
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides a traditional Chinese medicine composition for treating headache and its preparation method and quality control method. The traditional Chinese medicine composition comprises cassia seed, szechuan lovage rhizome, dahurian angelica root, prepared aconite root and gambir plant. The traditional Chinese medicine composition can be added with auxiliary materials and be prepared into clinically acceptable tablets, capsules, an oral liquid, dropping pills, soft capsules and granules by conventional processes. The quality control method of the traditional Chinese medicine composition comprises the following steps of carrying out qualitative detection of szechuan lovage rhizome and dahurian angelica root, carrying out qualitative amount-limited detection of aconitine, carrying out quantitative detection of alcohol soluble extract, carrying out detection of nitrogen content, and carrying out quantitative detection of ferulic acid. The traditional Chinese medicine composition has an obvious effect of treating headache.
Description
The present invention is divisional application, and original bill application number is 200810057967.8, and the original bill applying date is on February 22nd, 2008, and original bill name is called Chinese medicine composition for the treatment of headache and preparation method thereof and method of quality control.
Technical field
The present invention relates to a kind of pharmaceutical composition, relate in particular to a kind of Chinese medicine composition for the treatment of headache and preparation method thereof and method of quality control, belong to technical field of traditional Chinese medicines.
Background technology
Headache is common clinically illness, is found in fever caused by infection disease, the diseases such as high blood pressure, Intracranial Diseases, neurosis, cerebral concussion and antimigraine at present taking headache as primary symptom person.
All diseases caused by external factors six external factors which cause diseases, interior viscerotrauma, cause yang-energy to block, on turbid pathogenic factor, saw, liver-yang hyperactivity, marrow deficiency of vital energy and blood, the not normal person of channels and collaterals running, all can have a headache.Divide by the cause of disease, headache has diseases caused by external factors, internal injury not.Exogenous headache, has cold, wind-heat, rheumatism, hinders heat, fire-evil induced pain and cold headache etc.Beadache with internal injury, has the deficiency of vital energy, the deficiency of blood, the deficiency of yang, the deficiency of Yin, liver-yang, gets ill from overeating, hemostasis induced pain etc.Divide from channels and collaterals, have three-yang headache (taiyang headache, yangming headache, shaoyang headache), headache of triple yin (taiyin headache, shaoyin headache, jueyin headache) etc.Divide by state of an illness weight, course of disease length, rule of onset and painful area, have unendurable headache a, wind, antimigraine, thunder headache, brain wind, parietal headache, chronic headache etc.
Headache is to produce abnormal nerve impulse and be communicated to due to brain because incidence pain sensation tip receptor is upset.Cranium is organized outward except skull itself, from periosteum until face, oral cavity all to pain sensitivity; Intracranial tissue only has venous sinus and reflux veins, the hard brain of basis cranii and arteria basilaris to pain sensitivity, and brain remaining tissue is all insensitive to the pain sensation.The encephalic pain sensation is through V, IV, X to cranial nerve and 2nd～3 pairs of cervical nerve conduction, and the outer pain sensation of cranium, except above-mentioned nerve, still can be conducted through sympathetic nerve.
First treatment is active prevention and the various protopathy for the treatment of.Symptomatic treatment can use the analgesic drug product except morphine class, as various antipyretic analgesics, can according to the state of an illness pause clothes or 2-3 time/d of short-term take, severe patient can be taken codeine, Rotundine or dihydroetorphine etc. on a small quantity.But above these medicines are taken for a long time and are not only had habituation, and tolerance is poor, cannot fundamentally solve patient's headache problem.Treatment by Chinese herbs headache not only can reach the effect for the treatment of both principal and secondary aspect of disease, and can effectively treat various protopathy, and can not produce dependence, has improved the security that patient uses.
Summary of the invention
The object of the present invention is to provide a kind of Chinese medicine composition for the treatment of headache; Another object of the present invention is to provide the preparation method of this Chinese medicine composition; The 3rd object of the present invention is to provide the method for quality control of this Chinese medicine composition.
The present invention seeks to be achieved through the following technical solutions:
The bulk drug of the Chinese medicine composition for the treatment of headache of the present invention consists of:
Goat's horn 1300-1500 weight portion, Ligusticum wallichii 200-400 weight portion, root of Dahurain angelica 300-500 weight portion, aconiti preparata,radix 100-300 weight portion.
Above-mentioned raw materials optimum ratio is:
Goat's horn 1350-1450 weight portion, Ligusticum wallichii 200-300 weight portion, root of Dahurain angelica 400-500 weight portion, aconiti preparata,radix 100-200 weight portion.
The Chinese medicine composition for the treatment of headache of the present invention also can be made up of the bulk drug of following weight ratio:
Goat's horn 1300-1500 weight portion, Ligusticum wallichii 200-400 weight portion, root of Dahurain angelica 300-500 weight portion, aconiti preparata,radix 100-300 weight portion, yncaria stem with hooks 100-300 weight portion.
Above-mentioned raw materials optimum ratio is:
Goat's horn 1350-1450 weight portion, Ligusticum wallichii 200-300 weight portion, root of Dahurain angelica 400-500 weight portion, aconiti preparata,radix 100-200 weight portion, yncaria stem with hooks 150-250 weight portion.
Above-mentioned raw materials optimum ratio is:
Goat's horn 1400 weight portions, Ligusticum wallichii 250 weight portions, the root of Dahurain angelica 450 weight portions, aconiti preparata,radix 150 weight portions, yncaria stem with hooks 200 weight portions.
In the invention described above traditional Chinese medicinal composition raw materials:
Goat's horn can be substituted by mother-of-pearl, raddle, oyster, tribulus terrestris or fresh rhizoma Gastrodiae; The root of Dahurain angelica can be substituted by windproof, notopterygium root or the achene of Siberian cocklebur.
Composition of the present invention routinely technique adds auxiliary material to make the clinical acceptable formulations such as tablet, capsule, oral liquid, pill, soft capsule, granule; Described auxiliary material comprises solvent, disintegrant, flavouring, antiseptic, colorant, bonding agent, lubricant, matrix etc.
The preparation method of the tablet of the Chinese medicine composition for the treatment of headache of the present invention is:
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, merging filtrate, the thick paste that while being concentrated into 50 DEG C, relative density is 1.32～1.35; All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, the thick paste that while being concentrated into 50 DEG C, relative density is 1.32～1.35, mixes with goat's horn cream and dextrin 100～150g, granulates, dry, be pressed into 1000, dressing, to obtain final product.
Goat's horn pound sheet refers to scleroid goat's horn raw medicinal material, becomes superfine medicine materical crude slice according to traditional processing procedure with special pound cutter pound.
Pharmaceutical composition method of quality control of the present invention comprises one or more in following qualitative checking method and/or quantitative detecting method:
(1) qualitative detection of Ligusticum wallichii
Get pharmaceutical composition content of the present invention, porphyrize, the ultrasonic processing that adds diethyl ether, filters, filtrate evaporate to dryness, residue adds ethanol to be made to dissolve, as need testing solution;
Get Ligusticum wallichii control medicinal material, add the ultrasonic processing of ethanol and be prepared into control medicinal material solution;
According to thin-layered chromatography test, draw need testing solution, control medicinal material solution, put respectively on same silica gel g thin-layer plate, taking cyclohexane-ethyl acetate as developping agent, launch, take out, dry, put under ultraviolet lamp and inspect; In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color;
(2) qualitative detection of the root of Dahurain angelica
Get pharmaceutical composition content of the present invention, porphyrize, adds absolute ethyl alcohol, and ultrasonic processing filters, filtrate evaporate to dryness, and residue adds absolute ethyl alcohol and disperses, and gets supernatant as need testing solution;
Get root of Dahurain angelica control medicinal material, be prepared into control medicinal material solution according to need testing solution preparation method;
According to thin-layered chromatography test, draw above-mentioned two kinds of solution each, put respectively on same silica gel g thin-layer plate, taking methenyl choloride-methyl alcohol-formic acid as developping agent, launch, take out, dry, put under ultraviolet lamp and inspect; In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color;
(3) the qualitative limit examine of aconitine
Get pharmaceutical composition content of the present invention, be ground into fine powder, precision takes, and adds ammonia solution, places, and adds diethyl ether, and jolting, places, filter, and filtrate evaporate to dryness, residue anhydrous alcohol solution, as need testing solution;
Get aconitine reference substance, add absolute ethyl alcohol and make reference substance solution;
According to thin-layered chromatography test, draw above-mentioned two kinds of solution points on same silica G plate, taking cyclohexane-ethyl acetate-diethylamine as developping agent, launch, airing, spray is with rare bismuth potassium iodide test solution; In test sample chromatogram, with the corresponding position of reference substance chromatogram on the spot colors that occurs should be shallower than reference substance spot or not occur spot;
(4) the quantitative detection of forulic acid:
According to high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: with octadecylsilane chemically bonded silica be filling agent; Taking acetonitrile-water-glacial acetic acid as mobile phase; Detection wavelength is 322nm; Number of theoretical plate calculates and should be not less than 1500 by forulic acid peak;
The preparation of reference substance solution: precision takes forulic acid reference substance, puts in measuring bottle, dissolves and is diluted to scale with methyl alcohol, shakes up, and to obtain final product;
The preparation of need testing solution: get pharmaceutical composition content of the present invention, porphyrize, accurately weighed, add methyl alcohol, add hot reflux, let cool. filter, residue is washed 2 times with methyl alcohol, filters merging filtrate, evaporate to dryness, the gradation of add water-ammoniacal liquor of residue is dissolved, and puts in separating funnel, wash 2 times with ether, discard ether solution, water liquid is adjusted pH with watery hydrochloric acid, by extracted with diethyl ether 4 times, merge ether solution, wash with water, discard water liquid, ether solution evaporate to dryness, residue adds methyl alcohol and dissolves, be transferred in measuring bottle, be diluted to scale with methyl alcohol, shake up, filter, get subsequent filtrate, to obtain final product;
Determination method: accurate reference substance solution and the need testing solution drawn respectively, injection liquid chromatography, measures, and to obtain final product.
Pharmaceutical composition method of quality control of the present invention comprises one or more in following preferred qualitative checking method and/or quantitative detecting method:
(1) qualitative detection of Ligusticum wallichii
Pharmaceutical composition content of the present invention is equivalent to crude drug 49g, porphyrize, and the ultrasonic processing of the 30ml that adds diethyl ether 30 minutes, filters, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, as need testing solution; Separately get Ligusticum wallichii control medicinal material 1g, add the ultrasonic processing of ethanol 30ml 30 minutes, filter, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, medicinal material solution in contrast; According to thin-layered chromatography test, draw need testing solution 8 μ l, control medicinal material solution 2 μ l, put respectively on same silica gel g thin-layer plate, taking the cyclohexane-ethyl acetate of 7:3 ratio as developping agent, launch, take out, dry, put under the ultraviolet lamp that wavelength is 365nm and inspect; In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color;
(2) qualitative detection of the root of Dahurain angelica
Pharmaceutical composition content of the present invention is equivalent to crude drug 15g, and porphyrize adds absolute ethyl alcohol 30ml, and ultrasonic processing 30 minutes filters, filtrate evaporate to dryness, and residue adds absolute ethyl alcohol 2ml and disperses, and gets supernatant as need testing solution; Separately get root of Dahurain angelica control medicinal material 1g, with the standby one-tenth of legal system control medicinal material solution; According to thin-layered chromatography test, draw the each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, taking the methenyl choloride-methyl alcohol-formic acid of 9:1:0.1 ratio as developping agent, launch, take out, dry, put under the ultraviolet lamp that wavelength is 365nm and inspect; In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color;
(3) the qualitative limit examine of aconitine
Pharmaceutical composition content of the present invention, is ground into fine powder, and precision takes 5g, adds ammonia solution 5ml, place 2 hours, and the 100ml that adds diethyl ether, jolting 1 hour, places 24 hours, filters, filtrate evaporate to dryness, residue dissolves with absolute ethyl alcohol 2ml, as need testing solution; Separately get aconitine reference substance appropriate, add absolute ethyl alcohol and make the reference substance solution of every 1ml containing 2mg; According to thin-layered chromatography test, draw the each 2 μ l points of above-mentioned two kinds of solution on same silica G plate, taking the cyclohexane-ethyl acetate-diethylamine of 7:2:0.5 ratio as developping agent, launch, airing, spray is with rare bismuth potassium iodide test solution; In test sample chromatogram, with the corresponding position of reference substance chromatogram on the spot colors that occurs should be shallower than reference substance spot or not occur spot;
(4) the quantitative detection of forulic acid:
According to high effective liquid chromatography for measuring;
Chromatographic condition and system suitability: with octadecylsilane chemically bonded silica be filling agent; Taking the acetonitrile-water-glacial acetic acid of 20:80:1 ratio as mobile phase; Detection wavelength is 322nm; Number of theoretical plate calculates and should be not less than 1500 by forulic acid peak;
The preparation of reference substance solution: precision takes forulic acid reference substance 3mg, puts in 100ml measuring bottle, dissolves and is diluted to scale with methyl alcohol, shakes up, and makes in every 1ml containing forulic acid 30 μ g, to obtain final product;
The preparation of need testing solution: get pharmaceutical composition content of the present invention appropriate, porphyrize, get 2.5 g, accurately weighed, add methyl alcohol 50ml, add hot reflux 1h, let cool. filter, residue is washed 2 times with the methyl alcohol of 5ml, filter, merging filtrate, evaporate to dryness, residue adds the water-ammonia water 20ml gradation dissolving of 20:2 ratio, put in separating funnel, wash 2 times with the ether of 20ml, discard ether solution, water liquid is adjusted pH to 2 with watery hydrochloric acid, by extracted with diethyl ether 4 times, each 20ml, merge ether solution, with the washing of 30ml, discard water liquid, ether solution evaporate to dryness, residue adds methyl alcohol and dissolves, be transferred in 10 ml measuring bottles, be diluted to scale with methyl alcohol, shake up, filter, get subsequent filtrate, obtain,
Determination method: accurate reference substance solution and the each 10 μ l of need testing solution of drawing respectively, injection liquid chromatography, measures, and to obtain final product.
In medicine of the present invention, the flat liver of goat's horn, relieving convulsion, is applicable to liver-yang hyperactivity, have a dizzy spell, and liver-fire flaming, red eye, swell pain, the diseases such as convulsion, are monarch drug in a prescription; Ligusticum wallichii, the root of Dahurain angelica, aconiti preparata,radix are dispelled rheumatism, and promoting qi circulation and relieving pain is ministerial drug; Yncaria stem with hooks heat-clearing, flat liver, breath wind, is adjutant; Each medicine share and plays altogether flat liver, the effect of analgesia, and for antimigraine, vascular headache, tension headache and nervous headache, effect is remarkable.
Owing to containing a large amount of volatile ingredients in prescription, in the preparation process of medicine of the present invention, select percolation effective component extracting, be the key that curative effect of medication is improved; And the extract powder containing in preparation has very strong hydroscopicity, if only make plain sheet, not only the easy moisture absorption, affects the dissolving of medicine, and the stability of distribution, absorption and preparation, makes coating tablet and can effectively avoid above problem.
By method of quality control of the present invention, not only qualitative detection Ligusticum wallichii, the root of Dahurain angelica, has also carried out content limit inspection to aconitine, and the content of forulic acid in quantitative pharmacy, quality and the curative effect of controlling significantly product, ensured the security of medicine of the present invention.
In order to make those skilled in the art understand better content of the present invention, below pharmaceutical composition of the present invention and preparation method thereof and method of quality control are described in detail.
beneficial effect
Following test example and embodiment are used for further illustrating the present invention but are not limited to the present invention.
Test example 1 process test research
1, diacolation speed trial:
Press three parts of medicinal materials of embodiment 1 prescription configuration, every part containing Ligusticum wallichii 250g, root of Dahurain angelica 450g, aconiti preparata,radix 150g, yncaria stem with hooks 200g add 30% ethanol and make solvent, cold soaking 24 hours, diacolation, is divided into five groups, diacolation speed is respectively: 100ml/min.kg, 120ml/min.kg, 150ml/min.kg, 180 ml/min.kg, 200 ml/min.kg, determine diacolation speed according to paste volume.The results are shown in Table 1.
Table 1: diacolation speed trial
According to above data, can find out, diacolation speed is 150ml/min.kg, and this is complete to go out cream base, and in actual production, diacolation speed is decided to be 150ml/min.kg.
2, the smashing fineness of grinding medicinal materials test
Press embodiment 1 recipe quantity configuration Ligusticum wallichii, the root of Dahurain angelica, aconiti preparata,radix.Divide respectively four groups to test: smashing fineness is respectively: 10 orders, 24 orders, 50 orders, 65 orders, determine smashing fineness taking pulverizing loss as index respectively.The results are shown in Table 2:
Table 2: pulverize test findings
Above result shows: when smashing fineness is 24 order, indices is better, therefore select 24 orders in producing.
3, amount of water test
Press three parts of medicinal materials of embodiment 1 prescription preparation, test first group of 6 times of amounts, 4 times of amount that amount of water is medicinal material for every part containing goat's horn pound sheet 1400g grouping; Second group of amount of water is 10 times of amounts of medicinal material, 8 times of amounts; The 3rd group of amount of water is 8 times of amounts of medicinal material, 6 times of amounts.Determine amount of water taking paste volume as leading indicator.In table 3:
Table 3: amount of water test
Above result shows: taking paste volume as 8 times of amounts of index amount of water, 6 times amount extract substantially complete, be defined as 8 times of amounts, 6 times of amounts according to needs of production amount of water.
4, the selection of auxiliary material:
In view of drug substance contents of the present invention is full medicinal extract, there is very strong viscosity and moisture absorption, be unfavorable for preparations shaping, need add suitable filling agent, respectively dextrin, starch, lactose to be examined or check, examination the results are shown in Table 4:
The examination result of table 4 filling agent
| ? | comprehensive Assessment result |
| dextrin | compressibility is strong, cheap. |
| starch | separately as filling agent, poor compressibility. |
| lactose | price is more expensive, and specification is also inconsistent. |
Therefore select dextrin, both can change the viscosity of sheet, be easy to again compressing tablet, select sugar coated tablet, there is certain protection against the tide, isolated air effect and can cover up bad smell, improve outward appearance and be easy to and swallow.
5, sugar coated tablet art for coating
5.1 separation layers: plain sheet is placed in to coating pan and rolls, add mixing slurry (35% peach gum: 70% syrup=1:5) to make evenly to adhere to unilateral upper (plain sheet: mix slurry=50 g:1 ml), blowing hot-air is dry, for preventing that tablet is inter-adhesive or sticking on coating pan, add talcum powder, dry at 40～50 DEG C of hot blasts, twice of repetitive operation.
5.2 sub coats: slice, thin piece continues to roll in coating pan, add 70% syrup, after making slice, thin piece surface uniform wetting, add talcum powder, make to adhere to sheet sub-surface, continue roll and dry dry (50～55 DEG C), repetitive operation, until slice, thin piece faceted pebble disappears, by plain sheet weight: 70% syrup: talcum powder=3:1.7:1 feeds intake.
5.3 sugarcoating layers: slice, thin piece rolls in coating pan, add 70% syrup (plain sheet: 70% syrup=15:1, syrup addition is descending successively decreases) sheet sub-surface slowly dry, form fine and smooth sugar crystal clothing layer, increase clothing layer fastness and sweet taste.
5.4 coloured sugarcoating layers: be diluted to the mill base of 2mg/ml with 70% syrup, mill base is diluted to not to concentration with 70% syrup, concentration is ascending, adds coating pan, dry layer by layer.Element sheet and pigment amount ratio are 7.5kg:1g.
5.5 polishings: for sugar coated tablet surface-brightening is attractive in appearance, have moisture-proof role concurrently, add insect wax, by plain sheet: insect wax=3kg:5g adds, rotate coating pan insect wax is wrapped on slice, thin piece uniformly, take out coating tablet, dry after 24 hours, to obtain final product.
Experimental example 2 quality determining method experimental studies
1, the thin layer of Ligusticum wallichii is differentiated
(1) preparation of need testing solution and reference substance solution
Get 20 totally four parts, the preparation prepared according to embodiment 1, remove sugar-coat, porphyrize, the ultrasonic processing of 30ml that adds diethyl ether respectively, filters, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, as need testing solution.
Get totally four parts of Ligusticum wallichii control medicinal material 1g, add the ultrasonic processing of ethanol 30ml, filter, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, medicinal material solution in contrast.
Prepare the negative sample that lacks Ligusticum wallichii according to embodiment 1 preparation method, then prepare negative control solution according to need testing solution preparation method.
According to thin-layered chromatography test, draw need testing solution and the each 8 μ l of negative control solution, control medicinal material solution 2 μ l, put respectively on same silica gel g thin-layer plate, taking cyclohexane-ethyl acetate (7:3) as developping agent, launch, take out, dry, put under ultraviolet lamp (365nm) and inspect.More different extraction times, need testing solution and the color developing effect of control medicinal material solution on thin layer plate, the results are shown in following table 5:
The comparison of ultrasonic extraction time of table 5
(2) selection of developping agent
Prepare need testing solution, reference substance solution and negative sample solution according to above-mentioned preferred method, test according to thin-layered chromatography, draw need testing solution and the each 8 μ l of negative control solution, control medicinal material solution 2 μ l, put respectively on same silica gel g thin-layer plate, with developping agent, launch, take out, dry, put under ultraviolet lamp (365nm) and inspect.More different developping agents, need testing solution and the control medicinal material solution expansion effect on thin layer plate, the results are shown in following table 6:
The selection of table 6 developping agent
As can be seen from the above table, selecting cyclohexane-ethyl acetate 7:3 is developping agent, launch effective, and negative noiseless, Pass Test requirement.By revision test repeatedly, prove that the method stability and reappearance are all good, therefore one of method of quality control using the qualitative detection of Ligusticum wallichii as pharmaceutical composition of the present invention.
2, the thin layer of the root of Dahurain angelica is differentiated
Get 6, the preparation prepared by embodiment 1, porphyrize, adds absolute ethyl alcohol 30ml, and ultrasonic processing 30 minutes filters, filtrate evaporate to dryness, and residue adds absolute ethyl alcohol 2ml and disperses, and gets supernatant as need testing solution.
Get root of Dahurain angelica control medicinal material 1g, with the standby one-tenth of legal system control medicinal material solution.
Prepare the negative sample that lacks the root of Dahurain angelica according to embodiment 1 preparation method, then prepare negative control solution according to need testing solution preparation method.
(1) comparison of developping agent
Prepare test sample, control medicinal material solution and negative control product solution by above-mentioned method, draw the each 10 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, taking methenyl choloride-methyl alcohol-formic acid as developping agent, proportioning is respectively 7:3:0.2,8:2:0.1,9:1:0.2,9:1:0.1, launches, and takes out, dry, put under ultraviolet light (365nm) and inspect.Relatively need testing solution and the expansion effect of reference substance solution on thin layer plate, the results are shown in following table 7:
The selection of table 7 developping agent proportioning
As can be seen from the above table, taking methenyl choloride-methyl alcohol-formic acid 9:1:0.1, during as developping agent, it is best that need testing solution and reference substance solution are launched effect on thin layer plate, and negative noiseless, Pass Test requirement.
(2) selection of point sample amount
Prepare as stated above test sample and control medicinal material solution, draw need testing solution 2 μ l, 5 μ l, 8 μ l, 10 μ l, reference substance solution 10 μ l, put respectively on the same silica gel g thin-layer plate that is bonding agent containing sodium carboxymethyl cellulose, taking benzene-ethyl acetate (8:2) as developping agent, launch, take out, dry,, after smoked 3 minutes, put under ultraviolet light (365nm) and inspect with liquor ammoniae fortis.Relatively need testing solution and the color developing effect of reference substance solution on thin layer plate, the results are shown in following table 8:
The selection of table 8 test sample point sample amount
| Point sample amount | 2μl | 5μl | 8μl | 10μl |
| Color developing effect | Spot does not develop the color | Spot colour developing is very shallow | Spot colour developing is shallow | Spot colour developing is clear |
As can be seen from the above table, reference substance solution point sample amount is 10 μ l, need testing solution and reference substance solution thin layer plate relevant position, and spot colour developing is clear, Pass Test requirement, point of sample diameter is excessive to continue to strengthen point sample amount, has affected the quality of point sample.
3, the qualitative limit examine of aconitine
Inventor, determining before the qualitative limit examine of aconitine, is studied the content of medicine mesaconitine of the present invention.Result is as follows:
Assay is measured according to high performance liquid chromatography (annex VID).
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filling agent; Methyl alcohol-0.5% triethylamine (4:1) is mobile phase; Detection wavelength is 235nm; Flow velocity: 0.5ml/min; Column temperature: room temperature; Column type: Agilent, C18,150mm.
It is appropriate that the preparation precision of reference substance solution takes aconitine reference substance, adds methyl alcohol and make the solution of every 1ml containing 0.25mg, to obtain final product.
It is appropriate that the pharmaceutical preparation of the present invention of preparing according to embodiment 1 is got in the preparation of need testing solution, and desaccharification clothing, is ground into fine powder, precision takes powder 2g, adds the 25ml that adds methylene chloride after the wetting 5min of ammoniacal liquor 2ml, and 30min is extracted in jolting, incline and extract, divide and wash the dregs of a decoction and container, combined dichloromethane, water-bath (80 DEG C) evaporate to dryness for several times with 25ml methylene chloride again, residue dissolves with methyl alcohol, and being settled to 10ml, micro porous filtration, to obtain final product.
Result survey medicine mesaconitine content of the present invention lower than ten thousand/, and inferior separating effect, therefore detection method does not comprise the content detection of aconitine.
Although the quantitative detection to aconitine is not listed in method of quality control, but because aconitine belongs to toxic component, so to carrying out the detection of aconitine in the quality control of medicine of the present invention, then aconitine has been carried out to qualitative limit examine test, result is as follows:
It is appropriate that the pharmaceutical preparation of the present invention of preparing according to embodiment 1 is got in the preparation of need testing solution, and desaccharification clothing, is ground into fine powder, precision takes 5g, add ammonia solution 5ml, place 2 hours, 100ml adds diethyl ether, jolting 1 hour, place 24 hours, filter filtrate evaporate to dryness, residue dissolves with absolute ethyl alcohol 2ml, as need testing solution.
The preparation of reference substance solution, according to the regulation to aconiti preparata,radix mesaconitine limitation in 2005 editions pharmacopeia, is got aconitine reference substance appropriate, adds absolute ethyl alcohol and makes the reference substance solution of every 1ml containing 2mg.
According to thin-layered chromatography test, draw the each 2 μ l points of above-mentioned two kinds of solution on same silica G plate, taking the different proportionings of cyclohexane-ethyl acetate-diethylamine as developping agent, launch, airing, spray is with rare bismuth potassium iodide test solution.In test sample chromatogram, with the corresponding position of reference substance chromatogram on the spot colors that occurs should be shallower than reference substance spot or not occur spot.The results are shown in following table 9:
The selection of table 9 developping agent proportioning
As can be seen from the above table, taking cyclohexane-ethyl acetate-diethylamine 7:2:0.5 as developping agent, launch effective, and good stability, Pass Test requirement.
4, ferulic acid in Chuanxiong assay
Method one:
Detecting instrument: the SPD-10ATvp of Shimadzu company type high performance liquid chromatograph
Chromatographic column: (Zorbax C18 4.6 × 150 mm, 5 μ m) in Di Ma company
Mobile phase: methyl alcohol-2% glacial acetic acid (1:4) flow velocity: 0.800ml/min
Detect wavelength: 323nm column temperature: room temperature
Forulic acid reference substance is purchased from Nat'l Pharmaceutical & Biological Products Control Institute's lot number: 0773-9910
It is appropriate that the preparation precision of reference substance solution takes forulic acid reference substance, adds mobile phase and make the solution of every 1ml containing 25 μ g, product solution in contrast.
It is appropriate that the pharmaceutical preparation of the present invention of preparing according to embodiment 1 is got in the preparation of need testing solution, and desaccharification clothing is pulverized, get the about 1g of powder, accurately weighed, put in tool plug conical flask, precision adds mobile phase 25ml, precise weighing, ultrasonic processing 30 minutes, cool, weigh, supply the weight of less loss with mobile phase, shake up, filtering with microporous membrane, to obtain final product
Negative control solution lacks the blank sample of Ligusticum wallichii according to the method preparation of embodiment 1, then prepares negative controls by the preparation method of need testing solution.
With miillpore filter, (m), precision is drawn negative controls, reference substance solution and each 5～10 μ l of need testing solution to 0.45 μ respectively, and injection liquid chromatography, measures.
Result: forulic acid reference substance appearance time is 6.3min also has peak herein in test sample chromatogram and negative control chromatogram, and changing subsequently mobile phase is methyl alcohol-2% glacial acetic acid (32:68), feminine gender still have disturb and content very low.
Method two:
Instrument Shimadzu LC mono-10A high performance liquid chromatograph, detecting device: SPD-IOA UV-detector.Workstation: Yi Lite EC2003 chromatographic work station.
Reagent forulic acid reference substance (Nat'l Pharmaceutical & Biological Products Control Institute provides, lot number: 0773-9910); Medicine of the present invention (making by oneself according to embodiment 1); Methyl alcohol, second eyeball are chromatographically pure, and water is redistilled water, and all the other reagent are pure for analyzing.
Chromatographic condition chromatographic column: Hypesil C18(250 mm x4.6 mm, 5 μ m) are with preposition guard column; Acetonitrile-water-glacial acetic acid (20:80:1) is mobile phase; Flow velocity is 1.0 ml/min; Detecting wavelength is 322 nm.Number of theoretical plate is pressed forulic acid peak and is calculated, and should be not less than 1500.
The preparation precision of reference substance solution takes forulic acid reference substance 3mg, puts in 100ml measuring bottle, dissolves and is diluted to scale with methyl alcohol, shakes up, and obtains (in every 1ml containing forulic acid 30 μ g).
It is appropriate that this product is got in the preparation of need testing solution, porphyrize, get 2.5 g, accurately weighed, add methyl alcohol 50ml, add hot reflux 1h, let cool. filter, residue is washed 2 times with the methyl alcohol of 5ml, filter, merging filtrate, evaporate to dryness, add water-ammoniacal liquor of residue (20:2) 20ml gradation is dissolved, put in separating funnel, wash 2 times with the ether of 20ml, discard ether solution, water liquid is adjusted pH to 2 with watery hydrochloric acid, by extracted with diethyl ether 4 times, each 20ml, merge ether solution, with the washing of 30ml, discard water liquid, ether solution evaporate to dryness, residue adds methyl alcohol and dissolves, be transferred in 10 ml measuring bottles, be diluted to scale with methyl alcohol, shake up, filter, get subsequent filtrate, obtain.
The preparation of negative control solution is removed Ligusticum wallichii by embodiment 1 recipe quantity, makes negative control preparation, and by need testing solution, preparation method makes negative control solution.
Determination method is accurate reference substance solution and the each 10 μ l of need testing solution of drawing respectively, and injection liquid chromatography, measures, and to obtain final product.
Result: the chromatographic peak of forulic acid separates good, and in preparation,, without the interference of other compositions, retention time is 11min.Through methodological study, detection method linearity of the present invention, precision, stability, reappearance and the recovery are all good, can Accurate Determining medicine in the content of forulic acid.
According to the investigation result of above two kinds of methods, determine the detection method of content taking method two forulic acid in medicine of the present invention.
5, the assay of root of Dahurain angelica Imperatorin
Detecting instrument: the SPD-10ATvp of Shimadzu company type high performance liquid chromatograph
Chromatographic column: (Zorbax C18 4.6 × 150 mm, 5 μ m) in Di Ma company
Mobile phase: methanol-water (55:45) flow velocity: 1.000ml/min
Detect wavelength: 300nm column temperature: room temperature
Imperatorin reference substance is purchased from Nat'l Pharmaceutical & Biological Products Control Institute's lot number: 11826-200410
It is appropriate that the preparation precision of reference substance solution takes Imperatorin reference substance, adds mobile phase and make the solution of every 1ml containing 10 μ g, product solution in contrast.
It is appropriate that the pharmaceutical preparation of the present invention of preparing according to embodiment 1 is got in the preparation of need testing solution, and desaccharification clothing is pulverized, get the about 1g of powder, accurately weighed, put in tool plug conical flask, precision adds methyl alcohol 25ml, precise weighing, ultrasonic processing 30 minutes, cool, weigh, supply the weight of less loss with methyl alcohol, shake up, filtering with microporous membrane, to obtain final product.
Negative control solution lacks the blank sample of the root of Dahurain angelica according to the method preparation of embodiment 1, then prepares negative controls by the preparation method of need testing solution.
With miillpore filter, (m), precision is drawn negative controls, reference substance solution and each 5～10 μ l of need testing solution to 0.45 μ respectively, and injection liquid chromatography, measures.
Result: Imperatorin reference substance appearance time is 8.5min, in test sample chromatogram and negative control chromatogram, do not have peak to occur herein, get subsequently part angelica root powder and prepare sample according to the preparation method of patent medicine, obtain single angelica root need testing solution by test sample preparation method place again, result fails to detect Imperatorin equally, illustrates in 30% ethanol extract of the root of Dahurain angelica and there is no Imperatorin.
According to above experimental result, therefore the assay of Imperatorin is not listed in the method for quality control of medicine of the present invention.
6, the quantitative detection of ethanol soluble extractives:
By the research of the detection method of content to medicine mesaconitine of the present invention, forulic acid, Imperatorin, but because above three kinds of component contents are too low, therefore fail to set up the detection method of content of aconitine, forulic acid, Imperatorin in the method for quality control of medicine of the present invention.Inventor is studied extract content again, drafts as follows: with methyl alcohol be solvent, measure according to the hot dipping under ethanol soluble extractives determination method item.The three batches of extract testing results are in table 10:
Table 10: extract testing result
| Lot number | Extract result |
| 1701 | 27.5％ |
| 1802 | 26.8％ |
| 1903 | 28.4％ |
As can be seen from the above table, use the method can stably control total active constituent content in medicine, ensure curative effect of medication.
7, the mensuration of nitrogen content:
In medicine of the present invention, goat's horn contains a large amount of keratin, after hydrolysis, it is several amino acids class material, therefore can more effectively control the quality of medicine of the present invention to the mensuration of nitrogen content, ensure security, validity that medicine uses, improve the science of drug standard.
Get 3 batches of the medicinal tablets of the present invention prepared according to embodiment 1, remove sugar-coat, be ground into fine powder, precision takes 0.4g, adopts annex IXL first method of Chinese Pharmacopoeia version in 2005 to measure, and result is as follows:
Table 11: nitrogen content testing result
| Lot number | Nitrogen content |
| 1701 | 5.9％ |
| 1802 | 6.1％ |
| 1903 | 6.2％ |
As can be seen from the above table, use nitrogen content stability in the method control medicine, reappearance all better.
Test example 3 pharmacodynamics test researchs
1, test material
1.1 medicine medicine I of the present invention, II are respectively according to the tablet of embodiment 1,2 preparations;
Positive control medicine is compound cavel sheet, and by Heilungkiang, Jiang Bao pharmaceutical factory produces;
The above medicine used time grinds and is made into 20% suspension oral gavage.
1.2 animal Kunming mouses and Wistar kind rat, provided by experimental animal chamber, the court.
2, method and result
2.1 analgesic activity
2.1.1 hot plate method: choose 40 of 20 ± 2g female mices, be divided at random 4 groups, administration group gavage is given and medicine I of the present invention, II, III 5.3g/kg (contained crude drug amount), positive control medicine (compound cavel sheet) 3.9g/kg (contained crude drug amount), negative control group is to consubstantiality ponding, every day 1 time, continuous 7 days, 1h after last administration, animal is placed on 55 ± 1 DEG C of hot plates, record animal from putting into the time that starts to lick metapedes (being pain threshold), measure 1 time every 1h, survey altogether 3 times.The results are shown in Table 12.
The impact (X ± SD) of table 12 on thermostimulation pain threshold
With relatively ##P < 0.01 of negative control group, # P < 0.05; With relatively * P < 0.05. of positive drug control group
As can be seen from the above results, medicine of the present invention and positive control medicine all can significantly improve the pain threshold of mouse to thermostimulation, and wherein the effect of medicine I of the present invention is significantly better than positive control medicine.
2.1.2 acetic acid twisting method: Kunming mouse male and female half and half, grouping and the same 2.1.1 of administration, 30min after last administration, mouse peritoneal is injected 1% acetum 0.1ml/10g, and the writhing number of times that records animal in 10min the results are shown in Table 13.
The impact (X ± SD) of table 13 Dichlorodiphenyl Acetate writhing response
| Group | Dosage (g/kg*d) | Writhing number of times |
| Negative control group (10) | 0*7 | 39.8±4.8 |
| Positive control medicine group (10) | 3.9*7 | 33.6±6.9# |
| Medicine I of the present invention (10) | 5.3*7 | 27.8±7.3##* |
| Medicine II of the present invention (10) | 5.3*7 | 29.7±6.8## |
With relatively ##P < 0.01 of negative control group, # P < 0.05; With relatively * P < 0.05. of positive drug control group
As can be seen from the above results, medicine of the present invention all can significantly reduce with positive control medicine the number of times that mouse acetic acid twisting reacts, and the effect of medicine I of the present invention is significantly better than positive control medicine.
2.2 form and the impact of blood viscosity external thrombus:
2.2.1 on the thrombotic impact of rats in vitro: 40 of adult rats, male and female half and half, grouping and the same 2.1.1 of administration, after last administration, 30min extracting vein blood is surveyed thrombus length, weight in wet base and dry weight.The results are shown in Table 14:
Table 14 is on the thrombotic impact of rats in vitro (X ± SD)
With relatively ##P < 0.01 of negative control group, # P < 0.05; With relatively * P < 0.05. of positive drug control group
Medicine of the present invention and positive control medicine all can significantly suppress rats in vitro thrombosis, and thrombus length, weight in wet base, dry weight all have obvious reduction, and the inhibiting effect of medicine of the present invention is better than positive control medicine, especially thrombus length is had to remarkable inhibiting effect.
2.2.2 the impact on mouse whole blood viscosity: the same 2.1.1 of mice group and administration, last administration 30min extracts the bottle that eyeball gets blood and be placed in heparinize and shakes up, and then surveys its whole blood viscosity (ratio).The results are shown in Table 15.
The impact (X ± SD) of table 15 on mouse whole blood viscosity
Medicine of the present invention and positive control medicine all can reduce mouse whole blood viscosity, and the effect of medicine of the present invention is better than positive control medicine.
Following examples are used for further illustrating the present invention.
Embodiment 1
Goat's horn 1400g Ligusticum wallichii 250g root of Dahurain angelica 450g aconiti preparata,radix 150g yncaria stem with hooks 200g
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix with goat's horn cream and 100g dextrin, granulate, dry, be pressed into 1000, sugar coating, to obtain final product.
Embodiment 2
Goat's horn 1400g Ligusticum wallichii 250g root of Dahurain angelica 450g aconiti preparata,radix 150g
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix with goat's horn cream and 116g dextrin, granulate, dry, be pressed into 1000, sugar coating, to obtain final product.
Embodiment 3
Goat's horn 1300g Ligusticum wallichii 400g root of Dahurain angelica 300g aconiti preparata,radix 300g yncaria stem with hooks 100g
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.32 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.32 thick paste (50 DEG C), mix with goat's horn cream and 105g dextrin, granulate, dry, be pressed into 1000, sugar coating, to obtain final product.
Embodiment 4
Goat's horn 1500g Ligusticum wallichii 200g root of Dahurain angelica 500g aconiti preparata,radix 100g yncaria stem with hooks 300g
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix with goat's horn cream and 135g dextrin, granulate, dry, be pressed into 1000, sugar coating, to obtain final product.
Embodiment 5
Goat's horn 1350g Ligusticum wallichii 200g root of Dahurain angelica 400g aconiti preparata,radix 100g yncaria stem with hooks 150g
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix with goat's horn cream and 118g dextrin, granulate, dry, be pressed into 1000, film coating, to obtain final product.
Embodiment 6
Goat's horn 1450g Ligusticum wallichii 300g root of Dahurain angelica 500g aconiti preparata,radix 200g yncaria stem with hooks 250g
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix with goat's horn cream and 100g dextrin, granulate, dry, be pressed into 1000, film coating, to obtain final product.
Embodiment 7 capsules
Mother-of-pearl 1400g Ligusticum wallichii 250g root of Dahurain angelica 450g aconiti preparata,radix 150g yncaria stem with hooks 200g
Mother-of-pearl boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix with goat's horn cream and 100g dextrin, granulate, dry, whole grain, packs 1000 capsules into, to obtain final product.
Embodiment 8 granules
Fresh rhizoma Gastrodiae 1400g Ligusticum wallichii 250g notopterygium root 450g aconiti preparata,radix 150g yncaria stem with hooks 200g
Fresh rhizoma Gastrodiae boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix with goat's horn cream and 200g dextrin, 400g sucrose, granulate, dry, whole grain, granulation 800g, to obtain final product.
Embodiment 9 oral liquids
The windproof 450g aconiti preparata,radix of oyster 1400g Ligusticum wallichii 250g 150g yncaria stem with hooks 200g
Oyster boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.15 ~ 1.20 clear cream (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, carry out diacolation with the speed of 150ml/min*kg, to the liquid of filtering till colourless or inanimate object alkali reaction, the collection liquid of filtering, reclaim ethanol, be condensed into 1.15 ~ 1.20 clear cream (50 DEG C), mix with the clear cream of goat's horn, separately get sucrose 650g and add water boil, after dissolving, filter the concentrated syrup of making, mix with above-mentioned concentrated clear cream, boil, let cool, add antiseptic and essence, and be diluted to 1000ml with cold boiling water, to obtain final product.
Embodiment 10 dripping pills
Raddle 1400g Ligusticum wallichii 250g achene of Siberian cocklebur 450g aconiti preparata,radix 150g yncaria stem with hooks 200g
Raddle boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix vacuum drying with the clear cream of goat's horn, dried cream powder is broken to 150 orders, mix according to the ratio of 3:7 with the Macrogol 4000 of melting, make dripping pill, to obtain final product.
Embodiment 11 soft capsules
Word puncture vine 1400g Ligusticum wallichii 250g root of Dahurain angelica 450g aconiti preparata,radix 150g yncaria stem with hooks 200g
Tribulus terrestris boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix vacuum drying with the clear cream of goat's horn, dried cream powder is broken to 150 orders, mix according to the ratio of 1:2 with soybean oil, be pressed into soft capsule, to obtain final product.
The method of quality control of medicinal tablet of the present invention prepared by embodiment 12 embodiment 1-6
Differentiate:
(1) get 20 of this product, porphyrize, the ultrasonic processing of the 30ml that adds diethyl ether 30 minutes, filters, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, as need testing solution.Separately get Ligusticum wallichii control medicinal material 1g, add the ultrasonic processing of ethanol 30ml 30 minutes, filter, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, medicinal material solution in contrast.According to thin-layered chromatography (" Chinese Pharmacopoeia 2005 version annex VI B) test, draw need testing solution 8 μ l, control medicinal material solution 2 μ l, put respectively on same silica gel g thin-layer plate, taking cyclohexane-ethyl acetate (7:3) as developping agent, launch, take out, dry, put under ultraviolet lamp (365nm) and inspect.In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color.
(2) get 6 of this product, porphyrize, adds absolute ethyl alcohol 30ml, and ultrasonic processing 30 minutes filters, filtrate evaporate to dryness, and residue adds absolute ethyl alcohol 2ml and disperses, and gets supernatant as need testing solution.Separately get root of Dahurain angelica control medicinal material 1g, with the standby one-tenth of legal system control medicinal material solution.According to thin-layered chromatography (" Chinese Pharmacopoeia 2005 version annex VI B) test, draw the each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, taking methenyl choloride-methyl alcohol-formic acid (9:1:0.1) as developping agent, launch, take out, dry, put under ultraviolet lamp (365nm) and inspect.In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color.
Aconitine limit checks:
Get this product desaccharification clothing, be ground into fine powder, precision takes 5g, add ammonia solution 5ml, place 2 hours, 100ml adds diethyl ether, jolting 1 hour, place 24 hours, filter filtrate evaporate to dryness, residue dissolves with absolute ethyl alcohol 2ml, as need testing solution, separately get aconitine reference substance appropriate, add absolute ethyl alcohol and make the reference substance solution of every 1ml containing 2mg.According to thin-layered chromatography test (" Chinese Pharmacopoeia 2005 version annex VIB), draw the each 2 μ l points of above-mentioned two kinds of solution on same silica G plate, taking cyclohexane-ethyl acetate-diethylamine (7:2:0.5) as developping agent, launch, airing, spray is with rare bismuth potassium iodide test solution.In test sample chromatogram, with the corresponding position of reference substance chromatogram on the spot that occurs should be less than reference substance spot or not occur spot.
Extract content is measured:
Measure according to the hot dipping under ethanol soluble extractives determination method item, make solvent with methyl alcohol, must not be less than 18.0%.
Nitrogen analysis:
Get this product appropriate, remove sugar-coat, be ground into fine powder, precision takes 0.4g, measures (annex IX L first method of Chinese Pharmacopoeia version in 2005) according to n2 method, and this product nitrogen content must not be less than 4.0%.
Ferulaic acid content is measured
Measure according to high performance liquid chromatography (" Chinese Pharmacopoeia 2005 version annex VI D).
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filling agent; Acetonitrile-water-glacial acetic acid (20:80:1) is mobile phase; Detection wavelength is 322nm.Number of theoretical plate calculates and should be not less than 1500 by forulic acid peak.
The preparation precision of reference substance solution takes forulic acid reference substance 3mg, puts in 100ml measuring bottle, dissolves and is diluted to scale with methyl alcohol, shakes up, and obtains (in every 1ml containing forulic acid 30 μ g).
It is appropriate that this product is got in the preparation of need testing solution, remove sugar-coat, porphyrize, get 2.5 g, accurately weighed, add methyl alcohol 50ml, add hot reflux 1h, let cool. filter, residue is washed 2 times with the methyl alcohol of 5ml, filter, merging filtrate, evaporate to dryness, add water-ammoniacal liquor of residue (20:2) 20ml gradation is dissolved, put in separating funnel, wash 2 times with the ether of 20ml, discard ether solution, water liquid is adjusted pH to 2 with watery hydrochloric acid, by extracted with diethyl ether 4 times, each 20ml, merge ether solution, with the washing of 30ml, discard water liquid, ether solution evaporate to dryness, residue adds methyl alcohol and dissolves, be transferred in 10 ml measuring bottles, be diluted to scale with methyl alcohol, shake up, filter, get subsequent filtrate, obtain.
Determination method is accurate reference substance solution and the each 10 μ l of need testing solution of drawing respectively, and injection liquid chromatography, measures, and to obtain final product.
Every of this product contains Ligusticum wallichii with forulic acid (C
10h
10o
4) meter, must not be less than 0.08mg.
Embodiment 13
Goat's horn 1400g Ligusticum wallichii 250g root of Dahurain angelica 450g aconiti preparata,radix 150g
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, and merging filtrate, is condensed into 1.35 thick paste (50 DEG C); All the other Ligusticum wallichiis etc. are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, be condensed into 1.35 thick paste (50 DEG C), mix with goat's horn cream and 116g dextrin, granulate, dry, be pressed into 1000, sugar coating, to obtain final product.
[proterties] this product is sugar coated tablet, removes aobvious sepia after sugar-coat; Taste is micro-puckery.
20 of this product are got in [discriminating] (1), remove sugar-coat, porphyrize, and the ultrasonic processing of the 30ml that adds diethyl ether 30 minutes, filters, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, as need testing solution.Separately get Ligusticum wallichii control medicinal material 1g, add the ultrasonic processing of ethanol 30ml 30 minutes, filter, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, medicinal material solution in contrast.According to thin-layered chromatography (" Chinese Pharmacopoeia 2005 version annex VI B) test, draw need testing solution 8 μ l, control medicinal material solution 2 μ l, put respectively on same silica gel g thin-layer plate, taking cyclohexane-ethyl acetate (7:3) as developping agent, launch, take out, dry, put under ultraviolet lamp (365nm) and inspect.In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color.
(2) get 6 of this product, remove sugar-coat, porphyrize, adds absolute ethyl alcohol 30ml, and ultrasonic processing 30 minutes filters, filtrate evaporate to dryness, and residue adds absolute ethyl alcohol 2ml and disperses, and gets supernatant as need testing solution.Separately get root of Dahurain angelica control medicinal material 1g, with the standby one-tenth of legal system control medicinal material solution.According to thin-layered chromatography (" Chinese Pharmacopoeia 2005 version annex VI B) test, draw the each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, taking methenyl choloride-methyl alcohol-formic acid (9:1:0.1) as developping agent, launch, take out, dry, put under ultraviolet lamp (365nm) and inspect.In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color.
[inspection] should meet every regulation relevant under tablet item (" Chinese Pharmacopoeia 2005 version annex I D page).
This product desaccharification clothing is got in aconitine limit inspection, is ground into fine powder, and precision takes 5g, add ammonia solution 5ml, place 2 hours, 100ml adds diethyl ether, jolting 1 hour, place 24 hours, filter filtrate evaporate to dryness, residue dissolves with absolute ethyl alcohol 2ml, as need testing solution, separately get aconitine reference substance appropriate, add absolute ethyl alcohol and make the reference substance solution of every 1ml containing 2mg.According to thin-layered chromatography test (" Chinese Pharmacopoeia 2005 version annex VIB), draw the each 2 μ l points of above-mentioned two kinds of solution on same silica G plate, taking cyclohexane-ethyl acetate-diethylamine (7:2:0.5) as developping agent, launch, airing, spray is with rare bismuth potassium iodide test solution.In test sample chromatogram, with the corresponding position of reference substance chromatogram on the spot that occurs should be less than reference substance spot or not occur spot.
[extract] measured according to the hot dipping (Chinese Pharmacopoeia version annex X A in 2005) under ethanol soluble extractives determination method item, makes solvent with methyl alcohol, must not be less than 18.0%.
[assay] photograph high performance liquid chromatography (" Chinese Pharmacopoeia 2005 version annex VI D) measure.
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filling agent; Acetonitrile-water-glacial acetic acid (20:80:1) is mobile phase; Detection wavelength is 322nm.Number of theoretical plate calculates and should be not less than 1500 by forulic acid peak.
The preparation precision of reference substance solution takes forulic acid reference substance 3mg, puts in 100ml measuring bottle, dissolves and is diluted to scale with methyl alcohol, shakes up, and obtains (in every 1ml containing forulic acid 30 μ g).
It is appropriate that this product is got in the preparation of need testing solution, remove sugar-coat, porphyrize, get 2.5g, accurately weighed, add methyl alcohol 50ml, add hot reflux 1h, let cool. filter, residue is washed 2 times with the methyl alcohol of 5ml, filter, merging filtrate, evaporate to dryness, add water-ammoniacal liquor of residue (20:2) 20ml gradation is dissolved, put in separating funnel, wash 2 times with the ether of 20ml, discard ether solution, water liquid is adjusted pH to 2 with watery hydrochloric acid, by extracted with diethyl ether 4 times, each 20ml, merge ether solution, with the washing of 30ml, discard water liquid, ether solution evaporate to dryness, residue adds methyl alcohol and dissolves, be transferred in 10 ml measuring bottles, be diluted to scale with methyl alcohol, shake up, filter, get subsequent filtrate, obtain.
Determination method is accurate reference substance solution and the each 10 μ l of need testing solution of drawing respectively, and injection liquid chromatography, measures, and to obtain final product.
Every of this product contains Ligusticum wallichii with forulic acid (C
10h
10o
4) meter, must not be less than 0.08mg.
[function with cure mainly] flat liver, analgesia.For antimigraine, vascular headache, tension headache and nervous headache.
Claims (7)
1. treat a quality determining method for the Chinese medicine composition of headache, it is characterized in that the method comprises following qualitative checking method:
(1) qualitative detection of Ligusticum wallichii
Get described Chinese medicine composition content, porphyrize, the ultrasonic processing that adds diethyl ether, filters, filtrate evaporate to dryness, residue adds ethanol to be made to dissolve, as need testing solution:
Get Ligusticum wallichii control medicinal material, add the ultrasonic processing of ethanol and be prepared into control medicinal material solution;
According to thin-layered chromatography test, draw need testing solution, control medicinal material solution, put respectively on same silica gel g thin-layer plate, taking cyclohexane-ethyl acetate as developping agent, launch, take out, dry, put under ultraviolet lamp and inspect; In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color;
(2) qualitative detection of the root of Dahurain angelica
Get described Chinese medicine composition content, porphyrize, adds absolute ethyl alcohol, and ultrasonic processing filters, filtrate evaporate to dryness, and residue adds absolute ethyl alcohol and disperses, and gets supernatant as need testing solution;
Get root of Dahurain angelica control medicinal material, be prepared into control medicinal material solution according to need testing solution preparation method;
According to thin-layered chromatography test, draw above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, taking methenyl choloride-methyl alcohol-formic acid as developping agent, launch, take out, dry, put under ultraviolet lamp and inspect; In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color;
(3) limit examine of aconitine
Get described Chinese medicine composition content, be ground into fine powder, precision takes, and adds ammonia solution, places, and adds diethyl ether, and jolting, places, filter, and filtrate evaporate to dryness, residue anhydrous alcohol solution, as need testing solution;
Get aconitine reference substance, add absolute ethyl alcohol and make reference substance solution;
According to thin-layered chromatography test, draw above-mentioned two kinds of solution points on same silica G plate, taking cyclohexane-ethyl acetate-diethylamine as developping agent, launch, airing, spray is with rare bismuth potassium iodide test solution; In test sample chromatogram, with the corresponding position of reference substance chromatogram on the spot colors that occurs should be shallower than reference substance spot or not occur spot;
Wherein, described Chinese medicine composition is the tablet of preparing as follows:
Bulk drug composition:
Goat's horn 1300-1500 weight portion, Ligusticum wallichii 200-400 weight portion, root of Dahurain angelica 300-500 weight portion, aconiti preparata,radix 100-300 weight portion;
Preparation method:
Goat's horn pound sheet, boiling secondary, adds for the first time 8 times of water gagings and decocts 3 hours, adds for the second time 6 times of water gagings and decocts 3 hours, and gradation filters, merging filtrate, the thick paste that while being concentrated into 50 DEG C, relative density is 1.32～1.35; All the other bulk drugs are crushed to 24 orders, according to the percolation under liquid extract and extract item, taking 30% ethanol as solvent, speed with 150ml/min*kg is carried out diacolation, till colourless or inanimate object alkali reaction, collects the liquid of filtering to the liquid of filtering, reclaim ethanol, the thick paste that while being concentrated into 50 DEG C, relative density is 1.32～1.35, mixes with goat's horn cream and dextrin 100～150g, granulates, dry, be pressed into 1000, dressing, to obtain final product.
2. quality determining method as claimed in claim 1, is characterized in that described traditional Chinese medicinal composition raw materials consists of:
Goat's horn 1350-1450 weight portion, Ligusticum wallichii 200-300 weight portion, root of Dahurain angelica 400-500 weight portion, aconiti preparata,radix 100-200 weight portion.
3. quality determining method as claimed in claim 1, is characterized in that described traditional Chinese medicinal composition raw materials consists of:
Goat's horn 1300-1500 weight portion, Ligusticum wallichii 200-400 weight portion, root of Dahurain angelica 300-500 weight portion, aconiti preparata,radix 100-300 weight portion, yncaria stem with hooks 100-300 weight portion.
4. quality determining method as claimed in claim 1, is characterized in that described traditional Chinese medicinal composition raw materials consists of:
Goat's horn 1350-1450 weight portion, Ligusticum wallichii 200-300 weight portion, root of Dahurain angelica 400-500 weight portion, aconiti preparata,radix 100-200 weight portion, yncaria stem with hooks 150-250 weight portion.
5. quality determining method as claimed in claim 1, is characterized in that described traditional Chinese medicinal composition raw materials consists of:
Goat's horn 1400 weight portions, Ligusticum wallichii 250 weight portions, the root of Dahurain angelica 450 weight portions, aconiti preparata,radix 150 weight portions, yncaria stem with hooks 200 weight portions.
6. the detection method as described in claim 1-5 any one, is characterized in that in described traditional Chinese medicinal composition raw materials:
Goat's horn can be substituted by mother-of-pearl, raddle, oyster, tribulus terrestris or fresh rhizoma Gastrodiae; The root of Dahurain angelica can be substituted by windproof, notopterygium root or the achene of Siberian cocklebur.
7. the quality determining method as described in as arbitrary in claim 1-5, is characterized in that the method comprises in following qualitative checking method:
(1) qualitative detection of Ligusticum wallichii
Get described Chinese medicine composition content and be equivalent to crude drug 49g, porphyrize, the ultrasonic processing of the 30ml that adds diethyl ether 30 minutes, filters, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, as need testing solution; Separately get Ligusticum wallichii control medicinal material 1g, add the ultrasonic processing of ethanol 30ml 30 minutes, filter, filtrate evaporate to dryness, residue adds ethanol 1ml to be made to dissolve, medicinal material solution in contrast; According to thin-layered chromatography test, draw need testing solution 8 μ l, control medicinal material solution 2 μ l, put respectively on same silica gel g thin-layer plate, taking the cyclohexane-ethyl acetate of 7: 3 ratios as developping agent, launch, take out, dry, put under the ultraviolet lamp that wavelength is 365nm and inspect; In test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color;
(2) qualitative detection of the root of Dahurain angelica
Get described Chinese medicine composition content and be equivalent to crude drug 15g, porphyrize, adds absolute ethyl alcohol 30ml, and ultrasonic processing 30 minutes filters, filtrate evaporate to dryness, and residue adds absolute ethyl alcohol 2ml and disperses, and gets supernatant as need testing solution; Separately get root of Dahurain angelica control medicinal material 1g, with the standby one-tenth of legal system control medicinal material solution; Test according to thin-layered chromatography, draw the each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, taking the methenyl choloride-methyl alcohol-formic acid of 9: 1: 0.1 ratios as developping agent, launch, take out, dry, put under the ultraviolet lamp that wavelength is 365nm and inspect, in test sample chromatogram, with the corresponding position of control medicinal material chromatogram on, the fluorescence spot of aobvious same color;
(3) the qualitative limit examine of aconitine
Get described Chinese medicine composition content, be ground into fine powder, precision takes 5g, adds ammonia solution 5ml, place 2 hours, and the 100ml that adds diethyl ether, jolting 1 hour, places 24 hours, filters, filtrate evaporate to dryness, residue dissolves with absolute ethyl alcohol 2ml, as need testing solution; Separately get aconitine reference substance appropriate, add absolute ethyl alcohol and make the reference substance solution of every 1ml containing 2mg; According to thin-layered chromatography test, draw the each 2 μ l points of above-mentioned two kinds of solution on same silica gel g thin-layer plate, taking the cyclohexane-ethyl acetate-diethylamine of 7: 2: 0.5 ratios as developping agent, launch, airing, spray is with rare bismuth potassium iodide test solution; In test sample chromatogram, with the corresponding position of reference substance chromatogram on the spot colors that occurs should be shallower than reference substance spot or not occur spot.
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