CN100500182C - Chinese medicinal composition, preparation and quality control thereof - Google Patents
Chinese medicinal composition, preparation and quality control thereof Download PDFInfo
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- CN100500182C CN100500182C CNB2004100480876A CN200410048087A CN100500182C CN 100500182 C CN100500182 C CN 100500182C CN B2004100480876 A CNB2004100480876 A CN B2004100480876A CN 200410048087 A CN200410048087 A CN 200410048087A CN 100500182 C CN100500182 C CN 100500182C
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- 239000000463 material Substances 0.000 claims abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 184
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 165
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- JEJFTTRHGBKKEI-OKILXGFUSA-N deoxyschizandrin Chemical compound C1[C@H](C)[C@H](C)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC JEJFTTRHGBKKEI-OKILXGFUSA-N 0.000 claims description 6
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- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A Chinese medicine for treating insomnia, disturbed sleep, dizziness, tinnitus, fidget, etc is prepared from 6 Chinese-medicinal materials including coptis root, rehmannia root, white peony root, wild jujube kernel, etc. Its preparing process and quality control method are also disclosed.
Description
Invention field
The present invention relates to a kind of Chinese medicine composition and preparation method thereof and method of quality control, particularly a kind of Chinese medicine composition that is used for the treatment of diseases such as the insomnia of syndrome of hyperactivity of fire due to deficiency of YIN finding, dreaminess and preparation method thereof and method of quality control.
Background technology
Motherland's medical science often claims insomnia to be " being insomnia ".Should at first distinguish deficiency and excess clinically, deficiency syndrome belong to deficiency of YIN-blood more, focus on heart spleen Liver and kidney; Excess syndrome is many because of pathogenic fire derived from stagnation of liver-QI, dyspepsia and retention of phlegm, and hyperactivity of heart-fire, in the treatment, its deficiency of nourishing for deficiency; The suitable reducing for the excess syndrome of reality person.Simulataneous insufficiency and excessive person when dividing the specimen weight, sets upright with eliminating evil again.
Insomnia often shows as three kinds of situations clinically, and the one, be difficult to fall asleep; The 2nd, be easy to wake up with a start; The 3rd, be shorter than normally (early awakening) length of one's sleep, or insomnia-middle.How inequality the characteristics of its insomnia of deficiency syndrome excess syndrome are.The fire derived from stagnation of liver-QI type of excess syndrome is because feelings will is not smooth, mechanism of qi retardance, and strongly fragrant and fire-transformation, fire is disturbed the mind and is caused, and shows as insomnia more, dreaming often and waking easily.The type of disturbing is because eating and drinking without temperance on the expectorant heat, and dyspepsia is stagnated, and leads to expectorant heat, disorder of stomach-QI, and disturbing the mind upwards and causing shows as sleep disorder more, sleeps less promptly to wake up or lie awake all night.Type of hyperactivity of heart-fire is that visceral-qi is become estranged owing to overaction of the five emotions, hyperactivity of heart-fire, and refreshing uneasiness is given up and is caused, and shows as more and ponders over dreaminess, dysphoria and insomnia.
The type of deficiency of both the heart and spleen of deficiency syndrome is because overstrain is pondered over too, injures heart spleen, blood failing to tonify the heart, mental derangement and causing.Show as dreaming often and waking easily more, like dream like waking up or sleeplessness whole night.Deficiency of YIN liver-fire type is because plain body innate deficiency, or excess of sexual intercourse, or obstinate disease causes the kidney yin consumption to be hindered, the not good fire of water, and heart-yang is solely high, shows as vexedly to sleep less more, and sleep slightly and promptly wake up, or emission.Type of failure of the heart and kidney integrating is that flaming of heart-fire in the interior can not meet at kidney down owing to overaction of the five emotions; Or various reasons causes kidney yin consumption to be hindered, hyperaction of mingmen fire, and heart monarch is disturbed and cause, show as fidgets due to deficiency and be insomnia, difficulty falling asleep is slept slightly and is promptly waken up, or nocturnal emission is arranged, and many body constitution of type of deficiency of heart-QI and gallbladder-QI weakness, heart and gallbladder is plain empty, frightened cruelly, undermine heart and gallbladder, refreshing uneasy the Tibetan, resolution is had no right and is caused, show as insomnia and dreamful sleep, in time, easily wake up with a start.
Syndrome of hyperactivity of fire due to deficiency of YIN is seen insomnia clinically, mainly is because deficiency of kidney-YIN, due to the hyperactivity of heart-fire, should focus on restoring normal coordination between the heart and kidney in the treatment, thereby the kidney invigorating water, clearing away liver-fire, falls heart-fire and reach regulation between water and fire, the effect of sleeping peacefully of YIN and YANG balancing.Fully excavate the rich experiences of diseases such as the insomnia of Chinese medicine syndrome of hyperactivity of fire due to deficiency of YIN finding, dreaminess, in conjunction with research and the Chinese medicine latest developments of modern medicine to primary disease, the Chinese patent medicine of diseases such as the treatment syndrome of hyperactivity of fire due to deficiency of YIN finding insomnia that develop a kind of determined curative effect, cheap, suitable China's national situation, carry taking convenience, has no side effect, dreaminess has important theoretical meaning and value for clinical application.
Summary of the invention
One object of the present invention is to disclose a kind of Chinese medicine composition; Another object of the present invention is to disclose a kind of Chinese medicine composition that is used for the treatment of diseases such as the insomnia of syndrome of hyperactivity of fire due to deficiency of YIN finding, dreaminess; The 3rd purpose of the present invention is to disclose a kind of preparation method of Chinese medicine composition; The object of the invention also is to disclose a kind of method of quality control of Chinese medicine composition.
The crude drug of pharmaceutical composition of the present invention is formed and proportioning following (by weight):
Rhizoma Coptidis 30-60 weight portion Radix Rehmanniae 200-250 weight portion Radix Scutellariae 120-150 weight portion
Radix Paeoniae Alba 200-250 weight portion Fructus Schisandrae Chinensis 120-150 weight portion Semen Ziziphi Spinosae 400-500 weight portion
It is (by weight) that the crude drug of pharmaceutical composition of the present invention is formed optimum ratio:
Rhizoma Coptidis 45 weight portion Radix Rehmanniae 225 weight portion Radix Scutellariaes 135 weight portions
The Radix Paeoniae Alba 225 weight portion Fructus Schisandrae Chinensis 135 weight portion Semen Ziziphi Spinosae (parched)s 450 weight portions
It is (by weight) that the crude drug of pharmaceutical composition of the present invention is formed optimum ratio:
Rhizoma Coptidis 35 weight portion Radix Rehmanniae 245 weight portion Radix Scutellariaes 125 weight portions
The Radix Paeoniae Alba 245 weight portion Fructus Schisandrae Chinensis 125 weight portion Semen Ziziphi Spinosaes 480 weight portions
It is (by weight) that the crude drug of pharmaceutical composition of the present invention is formed optimum ratio:
Rhizoma Coptidis 55 weight portion Radix Rehmanniae 210 weight portion Radix Scutellariaes 145 weight portions
The Radix Paeoniae Alba 205 weight portion Fructus Schisandrae Chinensis 145 weight portion Semen Ziziphi Spinosae (parched)s 420 weight portions
This preparation of drug combination method:
Above Six-element, Rhizoma Coptidis, the Radix Paeoniae Alba, Fructus Schisandrae Chinensis add 6-10 and doubly measure 60-80% ethanol, reflux, extract, 1-3 time, and each 1-2 hour, merge alcohol extract, decompression recycling ethanol is condensed into thick paste, is dried to driedly, is ground into fine powder; Radix Rehmanniae, Radix Scutellariae, Semen Ziziphi Spinosae (parched) add 8-12 times of water gaging, decoct each 1-3 hour 1-3 time, gradation filters, merging filtrate, and being concentrated into relative density 60 ℃ of filtrates is 1.10 clear paste, add ethanol and make and contain alcohol amount and reach 50-60%, stir evenly cold preservation 24 hours, filter, reclaim ethanol, be condensed into thick paste, be dried to driedly, be ground into fine powder, merge above-mentioned two kinds of fine powders, get this pharmaceutical composition, this pharmaceutical composition can be made into clinical acceptable forms, comprises tablet, capsule, granule etc.
Selecting micropowder silica gel and dextrin is molding adjuvant of the present invention, and usage ratio is dextrin: micropowder silica gel=1-3:2-5.
The method of quality control of this composite preparation contains one or more in following discriminating and/or the content assaying method, and discriminating in the method for quality control of the present invention and content assaying method are:
Discrimination method is selected from one or more in the following method:
A, get content 1g of the present invention, porphyrize is put in the tool plug conical flask, adds methanol 10ml, close plug, and supersound process 20-40 minute, filter, filtrate is as need testing solution; Other gets Rhizoma Coptidis control medicinal material 50mg, shines medical material solution in pairs with legal system; Get the berberine hydrochloride reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 2 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with benzene-ethyl acetate-methanol-isopropyl alcohol-strong ammonia solution (11-13:5-7:2-4:2-4:1-2) is developing solvent, put in the expansion cylinder of ammonia saturated with vapor, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect; In the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get the baicalin reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw need testing solution and each 5 μ l of baicalin reference substance solution under a item, put respectively on same silica gel g thin-layer plate, with ethyl acetate-butanone-formic acid-water (4-6:2-4:1-2:1-2) is developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
C, get content 6g of the present invention, add 60～90 ℃ petroleum ether 30ml, reflux 20-40 minute, filter, medicinal residues are standby, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets the deoxyschizandrin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica GF254 lamellae, upper solution with petroleum ether-Ethyl formates of 60-90 ℃-formic acid (12-18:4-6:1-2) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (254nm) and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
D, get under the c item medicinal residues behind 60-90 ℃ the Petroleum ether extraction, volatilize petroleum ether, put in the tool plug conical flask, add methanol 40ml, close plug supersound process 20-40 minute, filters, the filtrate evaporate to dryness, residue adds water 30ml makes dissolving, filters, and filtrate moves in the separatory funnel, add water saturated n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, and the ammonia (40ml strong aqua ammonia thin up to 100ml) saturated with n-butyl alcohol washs 3 times, each 10ml, discard washing liquid, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, residue adds dehydrated alcohol 2ml makes dissolving, filter, filtrate is as need testing solution; Other gets the peoniflorin reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 3 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform-ethyl acetate-methanol-formic acid (30-50:4-6:8-12:0.1-0.3) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulphuric acid liquid, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, get jujuboside A reference substance, add dehydrated alcohol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution and each 5 μ l of jujuboside A reference substance solution under the d item, put respectively on same silica gel g thin-layer plate, upper strata liquid with n-butyl alcohol-glacial acetic acid-water (3-5:1-2:4-6) is developing solvent, launch, take out, dry, spray is with vanillin ethanol solution of sulfuric acid (get vanillin 2g add 10% ethanol solution of sulfuric acid 100ml dissolving), and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Content assaying method is:
Measure according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000).
With octadecylsilane chemically bonded silica is that potassium dihydrogen phosphate-acetonitrile filler: 0.05mol/L, 47:53 is a mobile phase, and wherein every 1000ml mobile phase contains sodium lauryl sulphate 1.7g; The detection wavelength is 265nm; Number of theoretical plate calculates by the berberine hydrochloride peak should be not less than 4000; It is an amount of that precision takes by weighing the berberine hydrochloride reference substance, uses 50% dissolve with methanol, makes the solution that every 1ml contains 0.025mg, shakes up, and promptly gets reference substance solution; Get the content under the content uniformity, porphyrize is got about 0.3g, the accurate title, decide, and puts in the tool plug conical flask, the accurate 50% methanol 50ml that adds, claim to decide weight, reflux 20-40 minute, put cold, claim again to decide weight, supply the weight that subtracts mistake, shake up with 50% methanol, filter, get subsequent filtrate, filter, promptly get need testing solution with microporous filter membrane (0.45 μ m); Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and every of this product contains Rhizoma Coptidis with berberine hydrochloride (C
20H
18ClNO
4) meter, must not be less than 1.0mg.
Pharmaceutical composition mind calming of the present invention liver heat removing, nourishing YIN and benefiting blood is held back god and is slept peacefully.Cure mainly the insomnia of syndrome of hyperactivity of fire due to deficiency of YIN finding, vexed, dreaminess, dizziness and tinnitus, dry mouth and throat, diseases such as dysphoria with feverish sensation in the chest palms and soles.The preparation stabilization that the present invention realizes, quality controllable.
Press 0.984g crude drug/kg, 2.952g crude drug/kg and 8.856g crude drug/kg with capsule (sleep and the consider the peace capsule) rat that the present invention makes, mice presses 1.422g crude drug/kg, 4.265g crude drug/kg and 12.794g crude drug/kg (presses body surface area calculating, be equivalent to 1,3 and 9 times clinical people every day with the 10.935g crude drug) oral administration, result of the test is as seen: sleep consider that the peace capsule obviously prolongs stagnation of liver-QI rat model, insufficiency of heart-QI mice and pentobarbital sodium collaborative length of one's sleep, suspension transfixion time, forced swimming dead time, and can improve the memory of rat model; Also obviously prolong normal mouse and pentobarbital sodium and work in coordination with the length of one's sleep, hang quiescent time, forced swimming dead time, and can reduce autonomic activities; Can also suppress normal rat and seize the sexual assault behavior.Illustrating that the worry peace capsule of sleeping has the effect that the mind calming liver heat removing is calmed the nerves, and has the good curing effect to the insomnia.Following experimental example is used to further specify the present invention:
Experimental example 1 Rhizoma Coptidis, the Radix Paeoniae Alba, Fructus Schisandrae Chinensis alcohol extraction technology are investigated
1, alcohol extraction interference experiment test method
Take by weighing with batch medical material by table 1, add 10 times of amount 70% ethanol respectively, extract 2 times, each 2 hours, merge pure liquid, concentrate, be settled to 1000ml with 70% ethanol, be equipped with inspection.
The table 1 alcohol extraction interference experiment medical material amount of taking by weighing (g)
Adopt high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000) to measure berberine hydrochloride; Chromatographic condition: OPS-C18 post; Mobile phase: acetonitrile: 0.05mol/LKH2PO4 (transferring PH=5.0)=28:72 with 10%KOH, column temperature: room temperature: detect wavelength: 265nm; Flow velocity: 1.0ml/min.The preparation of reference substance solution: precision takes by weighing berberine hydrochloride 5mg after drying, puts to add methanol in the 50ml measuring bottle and be diluted to scale, shakes up, promptly.The preparation of need testing solution: the accurate sample solution 2ml that draws, put in the 25ml measuring bottle, add 50% methanol and be diluted to scale, shake up, promptly.The preparation of Rhizoma Coptidis medical material solution: precision takes by weighing Rhizoma Coptidis medicinal powder 0.3062g, puts in the 500ml round-bottomed flask, adds 50ml methanol, connect apparatus,Soxhlet's and be extracted into colourlessly, filter, and with an amount of methanol wash filtering residue and container, filtrate is transferred in the 50ml volumetric flask, to scale, shake up the accurate 2ml that draws with methanol constant volume, put in the 5ml volumetric flask,, shake up to scale with methanol constant volume, promptly.Measure: accurate respectively reference substance solution and the need testing solution drawn, each 10ul of Rhizoma Coptidis medical material solution injects chromatograph of liquid respectively, measures in accordance with the law, and Rhizoma Coptidis medical material content of berberine hydrochloride is 6.2%, and interference test the results are shown in Table 2.
Table 2 interference test berberine hydrochloride extracted amount
The above results shows Rhizoma Coptidis and the Radix Paeoniae Alba, the common alcohol extraction of Fructus Schisandrae Chinensis, disturbs lessly, can carry altogether.For preferred each parameter of alcohol extraction process better, adopt the orthogonal experiment test.
2, alcohol extraction process orthogonal test
The factor that influences alcohol extraction process mainly contains the ethanol multiple, concentration of alcohol, extraction time, extraction time four factors, adopt L9 (34) table to carry out, if four factors are all included in, then there is not error term, can have influence on the reliability of result of the test, if design error item, adopt L18 (37) orthogonal table, test number (TN) is too many, considers that the alcohol extraction number of times generally adopts 2 times in the industrialized great production, with reference to aforementioned interference test, extract 2 times, extraction efficiency is very high, for this reason the fixed extraction number of times, adopt the test of L9 (34) orthogonal table, can further investigate the feasibility of extraction time simultaneously in the preferred back of orthogonal test.So the design factor water-glass is as follows:
Table 3 alcohol extraction process orthogonal test factor level table
Take by weighing Rhizoma Coptidis 30g, totally 9 parts of Radix Paeoniae Alba 150g, Fructus Schisandrae Chinensis 90g, by orthogonal table L9 (34) test, every part of heating and refluxing extraction 2 times, merge extractive liquid, is concentrated into 100ml, is equipped with inspection.Adopt the content of high effective liquid chromatography for measuring berberine hydrochloride, condition, the same interference test of method; The preparation of need testing solution: get above-mentioned concentrated solution, shake up, supersound process 5 minutes, the accurate absorption extracted concentrated solution 1ml, and it is little to put the 50ml volumetric flask,, shakes up to scale with 50% methanol constant volume, promptly.Orthogonal test and result of the test see Table 4.
Table 4 orthogonal test and result of the test
With R value intuitive analysis Rc〉RA〉RD〉RB, visible C factor affecting maximum, B factor affecting minimum, and A2〉A1〉A3, B2〉B1〉B3, C3〉C2〉should to select A2B2C3 be optimum level to C1, in order to optimize technological parameter better, The above results is carried out variance analysis, the results are shown in Table 5.
Table 5 alcohol extraction orthogonal test analysis of variance table
Fa＝0.01(2，2)＝99.0 Fa＝0.05(2，2)＝19
From last table as seen, B factor sum of sguares of deviation from mean minimum is carried out variance analysis with it as error term for this reason, Table A, each level of C factor have significant difference as a result, so select optimum level A2C3, the B factor can be chosen a level wantonly because of there was no significant difference, both considered operability in the production, consider again and save the cost and the energy, choose B2, promptly choose and use 70% ethanol, 8 times of amounts are extracted 2 times, and each 2 hours is alcohol extraction process.
3, the checking of alcohol extraction process
Because extraction time is a fixed factor in orthogonal test, do not carry out preferably, whether feasible, remain further to be verified.
Take by weighing two parts of Rhizoma Coptidis 30g, Radix Paeoniae Alba 150g, Fructus Schisandrae Chinensis 90g, carry out alcohol extraction by above-mentioned selection process respectively, merge pure liquid, medicinal residues continue to extract 2 hours with 8 times of amount 70% ethanol, and each 100ml that takes a sample detects, testing conditions and method are the same, being prepared as of need testing solution: preceding 2 extracting solution, the accurate 5ml that draws, put in the 25ml measuring bottle, add 50% methanol constant volume to scale, shake up, that is: the 3rd extracting solution, filter, promptly.Testing result sees Table 6.
Table 6 alcohol extraction demonstration test result
From the last table average extraction rate reached 95% of can seing before 2 times, the basic extraction fully, the 3rd time extraction ratio only is about 5%, and has rolled up man-hour and production cost, to extract 2 times be feasible so adopt.According to above-mentioned result of the test, alcohol extraction process is defined as: add 8 times of amount 70% ethanol, extract 2 times, each 2 hours, gradation filtered, and merges pure liquid.
Experimental example 2 alcohol extract ethanol reclaim, and concentration process is to the influence of content of berberine hydrochloride
In order to consider the influence of berberine hydrochloride at ethanol recovery and concentration process, alcohol extract that will be in confirmatory experiment, last pure liquid after sampling 100ml check, decompression recycling ethanol, and be concentrated into certain volume, get thick paste, sampling, measure content of berberine hydrochloride, the same interference test of assay method and condition.The preparation of need testing solution: precision is measured concentrated solution 1ml, puts in the 50ml measuring bottle, adds 50% methanol to scale, shakes up, promptly.Result of the test sees Table 7.
Table 7 alcohol extract ethanol reclaims, and concentration process is to the influence of content of berberine hydrochloride
From the average retention rate of the visible berberine hydrochloride of last table result ethanol recovery and concentration process is 94.14%; Illustrate that this process is less to the influence of berberine hydrochloride, on producing, adopt decompression recycling ethanol and high-efficiency evaporator to concentrate feasible.
Experimental example 3 alcohol extract thick paste dry runs are to the influence of berberine hydrochloride
After above-mentioned concentrated thick paste sampling, get 200ml respectively, put (85 ± 2 ℃ in electrically heated drying cabinet (85 ± 2 ℃) and vacuum drying oven,-0.1MPa) be dried to driedly, take by weighing weight, the sampling and measuring content of berberine hydrochloride, the same interference test of condition determination and method. need testing solution is prepared as: precision takes by weighing dried cream powder end 0.6g, add 50% methanol 50ml, supersound process 30min filters, precision is measured in subsequent filtrate 10ml to the 25ml measuring bottle, add 50% methanol constant volume to scale, shake up, promptly.Result of the test sees Table 8.
Table 8 alcohol extract thick paste in dry run to the influence of berberine hydrochloride
From last table as seen, dry run is less to the content of berberine hydrochloride influence, adopts direct heat drying and vacuum drying difference little, produces and can select drying room drying and vacuum drying according to manufacturing enterprise's physical condition.
The investigation of experimental example 4 Radix Scutellariaes, Radix Rehmanniae, Semen Ziziphi Spinosae (parched) extraction process by water
1, for the extraction process by water manufacturing parameter of preferred Radix Scutellariae, Radix Rehmanniae, Semen Ziziphi Spinosae (parched) better, adopt the orthogonal experiment test, select orthogonal table L9 (34) for use, the investigation index is a content of baicalin.Take by weighing Radix Scutellariae 45g, Radix Rehmanniae 75g, Semen Ziziphi Spinosae (parched) 150g, nine parts, soak after 1 hour earlier and test by the orthogonal table tested number, merge extractive liquid, suitably is concentrated into 200ml, and cold preservation is equipped with inspection.
2, content of baicalin assay method
Record radix scutellariae medicinal materials content of baicalin assay method with reference to Chinese Pharmacopoeia, adopt high performance liquid chromatography (2000 editions one appendix VI D of Chinese Pharmacopoeia) to measure.Chromatographic condition: ODS-C18 post, mobile phase: methanol-water-phosphoric acid (47:53:0.2); Column temperature: room temperature, detect wavelength: 280mm flow velocity: 1.0ml/min.The preparation of reference substance solution: precision takes by weighing and adds methanol in right amount through 4 hours baicalin reference substance of 60 ℃ of drying under reduced pressure and make the solution that every 1ml contains 60 μ g, promptly.The preparation of need testing solution: get concentrated solution, jolting, supersound process 10 minutes makes mixing, and precision is measured 1ml, puts in the 100ml measuring bottle, adds 70% ethanol and is settled to scale, shakes up, and precision is measured 2ml, puts in the 10ml measuring bottle, adds methanol constant volume to scale, shakes up, promptly.Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, calculate, promptly.Orthogonal test and result see Table 9
Water such as table 9 Radix Scutellariae are put forward orthogonal experiments
From the intuitive analysis of R value, RB〉RC〉RD〉RA, as seen factor B and C influence is bigger, and factor A influence is less, and A3〉A1〉A3, B3〉B2〉B1, C2〉C3〉C1, should select A3B3C2 is optimum level, in order to optimize technological parameter better, The above results is carried out variance analysis, the results are shown in Table 10.
Water such as table 10 Radix Scutellariae are carried the orthogonal test analysis of variance table
Fa＝0.01(2，2)＝99.0 Fa＝0.05(2，2)＝19
From the mean square minimum of the visible A factor of last table,, select A1 because of there was no significant difference from producing using water wisely and reducing energy consumption consideration A factor so with it as error term relatively, the result shows that B, C all have utmost point significant difference, should choose optimum level B3C2.Promptly choose and add 8 times of water gagings decoctions 3 times, each 2 hours.
Because above-mentioned orthogonal test B, C factor have utmost point significant difference, be necessary orthogonal experiments is carried out demonstration test, investigate the baicalin rate of transform, to judge the reliability of technological parameter.Test method: take by weighing totally 3 parts of Radix Scutellariae 90g, Radix Rehmanniae 150g, Semen Ziziphi Spinosae (parched) 300g, add 8 times of water gagings respectively, decoct 3 times, each 2 hours, filter respectively, merging filtrate shakes up, and measures volume, and each 200ml cold preservation of taking a sample is equipped with inspection.Content assaying method is with aforementioned baicalin condition determination method.The preparation of test solution: get extracting solution, shake up, supersound process 10 minutes, the accurate 1ml that draws puts in the 25ml measuring bottle,, shakes up to scale with methanol constant volume, promptly.The preparation of radix scutellariae medicinal materials solution: precision takes by weighing decides medical material fine powder 0.3g, adds 70% methanol 40ml, reflux 3 hours, filter, filtrate is to the 100ml measuring bottle, and with a small amount of 70% ethanol gradation washing container and residue, washing liquid is filtered in the measuring bottle, add 70% ethanol and be settled to scale, shake up, the accurate 1ml that draws puts in the 10ml measuring bottle, adds methanol constant volume to scale, shake up, promptly.Measurement result: radix scutellariae medicinal materials, content of baicalin is 14.32%, water is put forward the rate of transform and be the results are shown in Table 11.
Table 11 Radix Scutellariae water is put forward the demonstration test result
Above result shows, and is higher by the preferred extraction process by water of orthogonal test, baicalin mean transferred rate, about 90%, can adopt this technology to carry out water and carry.
The investigation of experimental example 5 Radix Scutellariae water extracting liquid precipitate with ethanol processes
In order to reach purified purpose, reduce the single dose, adopt the alcohol deposition method roguing, adopt the preferred precipitate with ethanol technological parameter of orthogonal experiment.The factor that influences the precipitate with ethanol process is mainly the relative density of concentrated solution, and alcohol precipitation concentration and precipitate with ethanol time serve as to investigate index with the retention rate of baicalin, and the factor level table sees Table 12.
Table 12 precipitate with ethanol orthogonal test factor level table
The concentrated solution sample 1 (d=1.10) of water extract concentration processs such as above-mentioned Radix Scutellariae being investigated test divides 3 parts, every part of 200ml, and concentrated solution sample 2 (d=1.15) divides 3 parts, every part of 150ml, concentrated solution sample 3 (d=1.20) divides 3 parts, every part of 100ml, choose concentrated solution by the corresponding relative density of the tested number of orthogonal test table, test by tested number, behind the precipitate with ethanol, divide and get upper strata liquid, subnatant filters, filtrate and upper strata liquid merge, and sampling is equipped with inspection.
1, content of baicalin assay method
Adopt high effective liquid chromatography for measuring, condition and method are the same, the preparation of need testing solution: the pure liquid 1ml of accurate absorption, put in the 50ml measuring bottle, and add methanol constant volume to scale, shake up, promptly.
2, orthogonal test and result of the test see Table 13.
Table 13 orthogonal test and result
The visible RA of intuitive analysis The above results〉RB〉RC〉RD explanation influences baicalin rate of transform A〉B〉C, and A1 A2 A3, and B1〉B2〉B3, C2〉C1〉C3, optimum level is A1B1C2 for this reason.In order further to analyze each factor affecting degree, The above results is carried out variance analysis, the results are shown in Table 14.
The variance analysis of table 14 orthogonal test
Fa＝0.01(2，2)＝99.0 Fa＝0.05(2，2)＝19
Last table result shows that A, B factor all have significant difference, should choose optimum level first level, and simultaneously from precipitate with ethanol process retention rate, precipitate with ethanol is bigger to the baicalin influence.
3, test of precipitate with ethanol process verification and elongation test
Take by weighing Radix Scutellariae 90g, Radix Rehmanniae 150g, Semen Ziziphi Spinosae (parched) 300g, totally two parts, extract by extraction process by water respectively, extracting solution is concentrated into d=1.10 (60 ℃ of heat are surveyed) and measures volume, be respectively 700ml, 625ml, sampling is got 300ml2 part with the 1st part of concentrated solution after detecting, and carries out the precipitate with ethanol test by table 12-17 test 1 and 2, the 2nd part of concentrated solution got 300ml carry out the precipitate with ethanol test by table 12-17 test 3, get 250ml and adjust volume to being 1.05 to relative density, measuring volume is 580ml, carries out the precipitate with ethanol test by table 15 test 4, branch was got supernatant after each tested precipitate with ethanol, subnatant filters, and filtrate and supernatant merge, and measure volume, sampling detects, detection method and condition are the same, and extension rate is done suitable adjustment as required in the preparation process of test liquid, and result of the test sees Table 16.
Table 15 precipitate with ethanol demonstration test parameter
Table 16 precipitate with ethanol demonstration test result
Adopt 50% alcohol precipitation concentration precipitate with ethanol as seen from Table 16, do not reach the precipitate with ethanol effect, so that filtration difficulty, baicalin is adsorbed in the precipitate, and retention rate is very low, and is infeasible in the production, adopt the d=1.05 precipitate with ethanol, volume is big, and the ethanol consumption is big, and retention rate and d=1.10 are suitable, can not obviously improve retention rate, can not adopt for this reason, and d=1.10,60% alcohol precipitation concentration, retention rate can be greater than 80%, although illustrate that precipitate with ethanol is influential to baicalin,, still can adopt in order to satisfy purified needs.The alcohol precipitation process parameter is defined as for this reason: relative density is that 1.10 (60 ℃ of heat are surveyed) alcohol precipitation concentration is 60%, precipitate with ethanol 24 hours.
The influence of 6 pairs of stagnation of liver-QI rat models of experimental example pentobarbital sodium induced hypnotic time
Getting body weight is 60 of 200～220g male rats, be divided into normal group (waiting capacity) at random, model group (waiting capacity), positive group (8.10g/kg), sleep to consider little (the 0.984g crude drug/kg) of peace, in (the 2.952g crude drug/kg), (the 8.856g crude drug/kg) (press body surface area calculates heavy dose of group, be equivalent to clinical people and use 1 of 10.935g crude drug every day, 3 and 9 times) except that normal group, other are respectively organized rat and clamp afterbody with vascular forceps and enrage rat, make it to keep the fight state with other rats, once a day, each 45min, modeling is 30 days continuously, rat skin lower injection epinephrine 0.2mg/ weekly of while.After the modeling, according to dosage successive administration 4 days (1.0ml/100g body weight) behind last administration 30min, is pressed 40mg/kg lumbar injection pentobarbital sodium, and record rat sleep incubation period and righting reflex loss the results are shown in Table 17 to the length of one's sleep of recovering.
Table 17 sleep to be considered the peace capsule lures the different length of one's sleep to stagnation of liver-QI rat model pentobarbital sodium influence (x ± s)
With the normal group ratio
*P＜0.05,
*P＜0.01, with model group than Δ P＜0.05, Δ Δ P＜0.01
By table 17 as seen: after the rat modeling, the incubation period and the length of one's sleep obviously shorten, and the modeling success is described.Animal pattern obviously prolongs the length of one's sleep, shortens incubation period after considering the peace capsule with sleeping, and with the model group ratio significant difference is arranged.Illustrating that capsule is pacified in the worry of sleeping and pentobarbital sodium has certain synergism.The influence of 7 pairs of stagnation of liver-QI rat model memories of experimental example
Screening (time of arriving at platform in Y type water maze the is no more than 15 seconds) body weight of learning from else's experience is 60 of 200～220g rats, be divided into normal group (waiting capacity) at random, model group (waiting capacity), positive group (8.10g/kg), sleep to consider little (the 0.984g crude drug/kg) of peace, in (the 2.952g crude drug/kg), (the 8.856g crude drug/kg) (press body surface area calculates heavy dose of group, be equivalent to clinical people and use 1 of 10.935g crude drug every day, 3 and 9 times) the modeling administration is the same, and 24h trains twice in Y type water maze continuously before the last administration, 30min behind the last medicine measures the time that rat is correctly arrived at platform of respectively organizing.The results are shown in Table 18.
The influence that table 18 dormancy worry peace capsule is remembered the stagnation of liver-QI rat model (x ± s)
With normal group than * P＜0.05, * * P＜0.01, with model group than Δ P＜0.05, Δ Δ P＜0.01
By table 18 as seen: after the rat modeling, arrive at the platform time obviously to prolong, the modeling success is described, sleep and consider each group of peace capsule and all can obviously shorten rat model and arrive at the platform time, significant difference is arranged with the model group ratio.It is the most obvious wherein to organize effect in a large number, and illustrating sleeps considers the memory function that the peace capsule can obviously improve rat model.
The influence of 8 pairs of stagnation of liver-QI rat model forced swimming dead times of experimental example
Get body weight and be 60 of 160g-180g rat, grouping, modeling and administration are the same.Behind last administration 30min, rat put into the dark Plastic Drum that the depth of water is 35cm, after 25 ℃ of water temperatures are put into water 2min, begin to calculate the dead time in the 5min.The results are shown in Table 19.
Table 19 sleep to be considered the peace capsule to the stagnation of liver-QI rat model influence of forced swimming dead time (x ± s)
With normal group than * P＜0.05, with model group than Δ P＜0.05, Δ Δ P＜0.01
By table 19 as seen: after the rat modeling, non-swimming time obviously prolongs, and illustrates that modeling is successful, the obvious lengthening model rat forced swimming dead time of energy behind the application dormancy worry peace capsule, with the model group ratio significant differences is arranged.Illustrating sleeps considers the peace capsule certain sedation.
Experimental example 9 is slept and is considered the peace capsule hangs the transfixion time to the insufficiency of heart-QI model mice influence
Get body weight 18-22g male mice, be divided into normal group (waiting capacity), model group (waiting capacity), positive group (11.70g/kg) at random, sleep consider peace little (1.422g crude drug/kg), in (4.265g crude drug/g), a large amount of group (12.794g crude drug/g) (calculating by body surface area: be equivalent to clinical people and use 1,3 and 9 times of 10.935g crude drug every day).Under laboratory natural lighting condition, adopt small station platform water environment technology to deprive mice REM sleep.Model group mice small station platform diameter is 2cm, platform diameter side, matched group small station 6cm (mice can freely be slept), every day twice, each 30min, continuous 17 days, model group last lumbar injection pituitrin 0.2ml (50u/kg).Oral administration (0.2ml/10g body weight) according to dosage after modeling, continuous 4 days, 30min behind the last medicine hung on mice on the fixed stand upside down with cord.Record not when mice is movable occurs with the mice dead time in the stopwatch accumulative total 6min, the results are shown in Table 20 when motionless.
Table 20 sleep to be considered the peace capsule hangs the transfixion time to the insufficiency of heart-QI model mice influence (x ± s)
With normal group than * p＜0.05, with model group than Δ Δ P＜0.01
By table 20 as seen: after the mice modeling, the dead time obviously shortens, and with the normal group ratio, significant difference is arranged.Consider the peace capsule with sleeping after, each administration group obviously prolongs the insufficiency of heart-QI model mice and hangs the transfixion time, with the model group ratio significant difference is arranged.Illustrating sleeps considers the peace capsule certain sedation.The influence of 10 pairs of insufficiency of heart-QI model mices of experimental example pentobarbital sodium induced hypnotic time
Get 60 of 18～22g mices, male and female half and half, be divided into normal group, model group, positive group at random, sleep consider peace little, in, heavy dose of group.Modeling is the same, after the modeling, presses table 5 dosed administration, successive administration 4 days, and behind last administration 30min, lumbar injection pentobarbital sodium 40mg/kg, the results are shown in Table 21 at the record mice sleep incubation period and the length of one's sleep from righting reflex loss to recovery.
Table 21 sleep to be considered the peace capsule to the influence of insufficiency of heart-QI model mice pentobarbital sodium induced hypnotic time (x ± s)
With normal group than * P＜0.05, * * P＜0.01, with model group than Δ P＜0.05, Δ Δ P＜0.01
By table 21 as seen: after the mice modeling, the prolongation of latency of sleep, keeping time phase obviously shortens, and with the normal group ratio, significant difference is arranged.After using the worry peace capsule of sleeping, obviously prolong the length of one's sleep of each administration group model mice, with the model group ratio significant differences arranged.Illustrating that capsule is pacified in the worry of sleeping and pentobarbital sodium has certain synergism.
Experimental example 11 is slept and is considered the influence of peace capsule to the memory of insufficiency of heart-QI model mice
Get 60 of 18～22g mices (arrive at platform time be no more than 120s), male and female half and half, grouping modeling administration is the same, trains twice continuously in Y type water maze in preceding 24 hours in the last administration, 30min behind the last medicine, the time that the mensuration mice is correctly arrived at platform the results are shown in Table 22.
The influence that table 22 dormancy worry peace capsule is remembered the insufficiency of heart-QI model mice (x ± s)
With normal group than * P＜0.05, with model group than Δ P＜0.05, Δ Δ P＜0.01
By table 22 as seen: after the mice modeling, arrive at the platform time obviously to prolong, hypomnesis with the normal group ratio, has significant difference.After using the worry peace capsule of sleeping, obviously shorten model mice and arrive at the platform time, significant difference is arranged with the model group ratio.Illustrating sleeps considers the function that the peace capsule can obviously improve the memory of model mice.
Experimental example 12 is slept and is considered the peace capsules to the influence of forced swimming dead time of insufficiency of heart-QI model mice
The screening body weight of learning from else's experience is 60 of 18-22g mices, male and female half and half, and grouping, modeling and administration are the same.Behind last administration 30min, mice is put into the dark Plastic Drum that the depth of water is 16cm, put into the dead time that begins to calculate 5min after water 2min mice adapts to, the results are shown in Table 23.
Table 23 sleep to be considered the peace capsule has the time to insufficiency of heart-QI model mice forced swimming influence (x ± s)
With normal group than * P＜0.05, with model group than Δ P＜0.05, Δ Δ P＜0.01
By table 23 as seen: after the mice modeling, non-swimming time obviously shortens, and with the normal group ratio, significant difference is arranged.After using the worry peace capsule of sleeping, the non-swimming time of lengthening model mice, wherein a large amount of group effects are the most obvious, with the normal group ratio significant difference arranged, and with the model group ratio significant differences arranged.Illustrating sleeps considers the peace capsule certain sedation.
13 pairs of normal mouses of experimental example hang the influence of transfixion time
Get 50 of body weight 18～22g mices, male and female half and half, be divided into normal group (waiting capacity), positive group (11.70g/kg) at random, sleep consider the peace capsule little (1.422g crude drug/kg), in (4.265g crude drug/kg), a large amount of group (12.794g crude drug/kg), press body surface area and calculate, be equivalent to 1,3 and 9 times of clinical people's usefulness every day 10.935g crude drug.According to dosage oral administration (0.2ml/10g body weight) continuous 4 days, hangs on mice on the fixed stand with cord behind the 30min behind the last medicine upside down.Occur starting the mice dead time in the stopwatch accumulative total 6min when motionless writing time not when mice is movable, the results are shown in Table 24.
Table 24 sleep to be considered the peace capsule hangs the transfixion time to normal mouse influence (x ± s)
With normal group than * P＜0.05, * * P＜0.01
By table 24 as seen: the worry peace of sleeping capsule obviously prolongs mice; Hang the transfixion time, wherein a large amount of groups are the most obvious.With normal group than capable significant difference.Illustrating sleeps considers the peace capsule has certain sedation to normal mouse.
14 pairs of normal mouse pentobarbital sodiums of experimental example lure the influence of the different length of one's sleep
Getting body weight is 50 of 18～22g mices, male and female half and half, and grouping and dosage are the same, successive administration 4 days behind last administration 30min, is pressed 40mg/kg lumbar injection pentobarbital sodium, record mice incubation period and righting reflex loss the results are shown in Table 25 to the length of one's sleep of recovering.
Table 25 sleep to be considered the peace capsule to the normal mouse pentobarbital sodium influence of induced hypnotic time (x ± s)
With normal group than * P＜0.05, * * P＜0.01
By table 25 as seen: each administration group of the worry peace of sleeping capsule can obviously prolong holding time of normal mouse sleep, has compared significant differences with normal group.Illustrating sleeps considers the peace capsule has certain syngignoscism to normal mouse.
The influence of 15 pairs of normal mouse forced swimming dead times of experimental example
The screening body weight of learning from else's experience is 50 of 22～25g mices, and grouping and dosage are the same, and the ig administration is 4 days continuously, in last administration 30min, mice is put into the dark Plastic Drum that the depth of water is 16cm, puts into the dead time that begins to calculate 5min after water 2min adapts to.The results are shown in Table 26.
Table 26 sleep to be considered the peace capsule to the influence of normal mouse forced swimming dead time (x ± s)
With normal group than * P＜0.05
By table 26 as seen: sleep and consider the non-swimming time that the peace capsule can obviously prolong normal mouse, significant difference is arranged with the normal group ratio.Illustrating sleeps considers the peace capsule has certain sedation to normal mouse.16 pairs of normal rats of experimental example are seized the influence of sexual assault behavior
Get 50 of 200～220g male rats, be divided into normal group (waiting capacity), positive group (8.10g/kg) at random, sleep consider peace little (0.984g crude drug/kg), in (2.952g crude drug/kg), heavy dose of group (8.856g crude drug/kg), press body surface area and calculate, be equivalent to 1,3 and 9 times of clinical people's usefulness every day 10.935g crude drug.Behind rat isolation and fasting 24h, a mice is put into cage, rat bites the mice cervical vertebra broken deadly positive.Respectively with administration before, 0.5h, 1h survey incubation period (calculating by 10 minutes) and the positive rate that rat is attacked after the administration, the results are shown in Table 27.
Table 27 sleep to be considered the peace capsule is seized the sexual assault behavior to normal rat influence (x ± s)
With normal group than * P＜0.05
By table 27 as seen: sleep and consider a large amount of groups of sexual assault behaviors of seizing that can obviously suppress normal rat of peace capsule, significant difference is arranged with the normal group ratio.Illustrating sleeps considers the peace capsule has certain sedation to normal rat.
Embodiment 1:Capsule of the present invention
Rhizoma Coptidis 45g Radix Rehmanniae 225g Radix Scutellariae 135g
Radix Paeoniae Alba 225g Fructus Schisandrae Chinensis 135g Semen Ziziphi Spinosae (stir-fry) 450g
Above Six-element, Rhizoma Coptidis, the Radix Paeoniae Alba, Fructus Schisandrae Chinensis add 8 times of amount 70% ethanol, reflux, extract, 2 times, and each 2 hours, merge alcohol extract, decompression recycling ethanol is condensed into thick paste, is dried to driedly, is ground into fine powder; Radix Rehmanniae, Radix Scutellariae, Semen Ziziphi Spinosae (parched) add 8 times of water gagings, decoct each 2 hours 3 times, gradation filters, merging filtrate, and filtrate is concentrated into the clear paste that relative density is 1.10 (60 ℃ of heat are surveyed), adding ethanol makes and contains alcohol amount and reach 60%, stir evenly, cold preservation 24 hours filters, reclaim ethanol, be condensed into thick paste, be dried to driedly, be ground into fine powder.Get above-mentioned two kinds of extractum fine powders, add an amount of dextrin, micropowder silica gel, mixing adds an amount of ethanol and granulates, and drying incapsulates, and makes 1000.Oral, one time 3,3 times on the one.
Embodiment 2:Tablet of the present invention
Rhizoma Coptidis 35g Radix Rehmanniae 245g Radix Scutellariae 125g
Radix Paeoniae Alba 245g Fructus Schisandrae Chinensis 125g Semen Ziziphi Spinosae (stir-fry) 480g
Above Six-element, Rhizoma Coptidis, the Radix Paeoniae Alba, Fructus Schisandrae Chinensis add 6 times of amount 80% ethanol, reflux, extract, 3 times, and each 2 hours, merge alcohol extract, decompression recycling ethanol is condensed into thick paste, is dried to driedly, is ground into fine powder; Radix Rehmanniae, Radix Scutellariae, Semen Ziziphi Spinosae (parched) add 10 times of water gagings, decoct each 1 hour 2 times, gradation filters, merging filtrate, and filtrate is concentrated into the clear paste that relative density is 1.10 (60 ℃ of heat are surveyed), add ethanol and make and contain alcohol amount and reach 50%, stir evenly cold preservation 24 hours, filter, reclaim ethanol, be condensed into thick paste, be dried to dried, be ground into fine powder, get above-mentioned two kinds of extractum fine powders and make 1000 in tablet according to conventional method.Oral, one time 3,3 times on the one.
Embodiment 3:Granule of the present invention
Rhizoma Coptidis 55g Radix Rehmanniae 210g Radix Scutellariae 145g
Radix Paeoniae Alba 205g Fructus Schisandrae Chinensis 145g Semen Ziziphi Spinosae (stir-fry) 420g
Above Six-element, Rhizoma Coptidis, the Radix Paeoniae Alba, Fructus Schisandrae Chinensis add 8 times of amount 60% ethanol, reflux, extract, 1 time, and each 1 hour, merge alcohol extract, decompression recycling ethanol is condensed into thick paste, is dried to driedly, is ground into fine powder; Radix Rehmanniae, Radix Scutellariae, Semen Ziziphi Spinosae (parched) add 12 times of water gagings, decoct 2 hours time 1 time, get filtrate, filtrate is concentrated into relative density be 1.10 clear paste of (60 ℃ of heat are surveyed), adds ethanol and makes and contain the alcohol amount and reach 60%, stirs evenly, cold preservation 24 hours, filter, reclaim ethanol, be condensed into thick paste, be dried to driedly, be ground into fine powder.Get above-mentioned extractum fine powder, make granule according to conventional method.
Embodiment 4The discrimination method of this pharmaceutical composition:
Get this pharmaceutical composition 1g, porphyrize is put in the tool plug conical flask, adds methanol 10ml, close plug, and supersound process 30 minutes filters, and filtrate is as need testing solution; Other gets Rhizoma Coptidis control medicinal material 50mg, shines medical material solution in pairs with legal system; Get the berberine hydrochloride reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 2 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with benzene-ethyl acetate-methanol-isopropyl alcohol-strong ammonia solution (12:6:3:3:1) is developing solvent, put in the expansion cylinder of ammonia saturated with vapor, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect; In the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
Embodiment 5The discrimination method of this pharmaceutical composition:
1, gets the baicalin reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution and each 5 μ l of baicalin reference substance solution under a item, put respectively on same silica gel g thin-layer plate, with ethyl acetate-butanone-formic acid-water (5:3:1:1) is developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
2, get this pharmaceutical composition 6g, add 60～90 ℃ petroleum ether 30ml, reflux 30 minutes filters, and medicinal residues are standby, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets the deoxyschizandrin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica GF254 lamellae, upper solution with petroleum ether (60-90 ℃)-Ethyl formate-formic acid (15:5:1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (254nm) and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Embodiment 6The discrimination method of this pharmaceutical composition:
1, get this pharmaceutical composition 1g, porphyrize is put in the tool plug conical flask, adds methanol 10ml, close plug, and supersound process 30 minutes filters, and filtrate is as need testing solution; Other gets Rhizoma Coptidis control medicinal material 50mg, shines medical material solution in pairs with legal system; Get the berberine hydrochloride reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 2 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with benzene-ethyl acetate-methanol-isopropyl alcohol-strong ammonia solution (12:6:3:3:1) is developing solvent, put in the expansion cylinder of ammonia saturated with vapor, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect; In the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
2, get the baicalin reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution and each 5 μ l of baicalin reference substance solution under a item, put respectively on same silica gel g thin-layer plate, with ethyl acetate-butanone-formic acid-water (5:3:1:1) is developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
3, get this pharmaceutical composition 6g, add 60～90 ℃ petroleum ether 30ml, reflux 30 minutes filters, and medicinal residues are standby, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets the deoxyschizandrin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica GF254 lamellae, upper solution with petroleum ether (60-90 ℃)-Ethyl formate-formic acid (15:5:1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (254nm) and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
4, get the medicinal residues after petroleum ether under the c item (60～90 ℃) extracts, volatilize petroleum ether, put in the tool plug conical flask, add methanol 40ml, close plug, supersound process 30 minutes filters, the filtrate evaporate to dryness, residue adds water 30ml makes dissolving, filters, and filtrate moves in the separatory funnel, add water saturated n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, and the ammonia (40ml strong aqua ammonia thin up to 100ml) saturated with n-butyl alcohol washs 3 times, each 10ml, discard washing liquid, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, residue adds dehydrated alcohol 2ml makes dissolving, filter, filtrate is as need testing solution; Other gets the peoniflorin reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 3 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform-ethyl acetate-methanol-formic acid (40:5:10:0.2) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulphuric acid liquid, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
5, get jujuboside A reference substance, add dehydrated alcohol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B), draw need testing solution and each 5 μ l of jujuboside A reference substance solution under the embodiment 7, put respectively on same silica gel g thin-layer plate, upper strata liquid with n-butyl alcohol-glacial acetic acid-water (4:1:5) is developing solvent, launch, take out, dry, spray is with vanillin ethanol solution of sulfuric acid (get vanillin 2g add 10% ethanol solution of sulfuric acid 100ml dissolving), and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
Embodiment 7The content assaying method of this medicament composition capsule agent:
Measure according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000).
With octadecylsilane chemically bonded silica is that potassium dihydrogen phosphate-acetonitrile filler: 0.05mol/L, 47:53 is a mobile phase, and wherein every 1000ml mobile phase contains sodium lauryl sulphate 1.7g; The detection wavelength is 265nm; Number of theoretical plate calculates by the berberine hydrochloride peak should be not less than 4000; It is an amount of that precision takes by weighing the berberine hydrochloride reference substance, uses 50% dissolve with methanol, makes the solution that every 1ml contains 0.025mg, shakes up, and promptly gets reference substance solution; Get the content under the content uniformity, porphyrize is got about 0.3g, the accurate title, decide, and puts in the tool plug conical flask, the accurate 50% methanol 50ml that adds, claim to decide weight, reflux 30 minutes is put cold, claim again to decide weight, supply the weight that subtracts mistake, shake up with 50% methanol, filter, get subsequent filtrate, filter, promptly get need testing solution with microporous filter membrane (0.45 μ m); Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and every of this pharmaceutical composition contains Rhizoma Coptidis with berberine hydrochloride (C
20H
18ClNO
4) meter, must not be less than 1.0mg.
Embodiment 8The method of quality control of this medicament composition capsule agent:
1, get this pharmaceutical composition 1g, porphyrize is put in the tool plug conical flask, adds methanol 10ml, close plug, and supersound process 30 minutes filters, and filtrate is as need testing solution; Other gets Rhizoma Coptidis control medicinal material 50mg, shines medical material solution in pairs with legal system; Get the berberine hydrochloride reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 2 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with benzene-ethyl acetate-methanol-isopropyl alcohol-strong ammonia solution (12:6:3:3:1) is developing solvent, put in the expansion cylinder of ammonia saturated with vapor, launch, take out, dry, put under the ultra-violet lamp (365nm) and inspect; In the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.
2, get the baicalin reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution and each 5 μ l of baicalin reference substance solution under a item, put respectively on same silica gel g thin-layer plate, with ethyl acetate-butanone-formic acid-water (5:3:1:1) is developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
3, get this pharmaceutical composition 6g, add 60～90 ℃ petroleum ether 30ml, reflux 30 minutes filters, and medicinal residues are standby, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets the deoxyschizandrin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica GF254 lamellae, upper solution with petroleum ether (60-90 ℃)-Ethyl formate-formic acid (15:5:1) is developing solvent, launch, take out, dry, put under the ultra-violet lamp (254nm) and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
4, get the medicinal residues after petroleum ether under the c item (60～90 ℃) extracts, volatilize petroleum ether, put in the tool plug conical flask, add methanol 40ml, close plug, supersound process 30 minutes filters, the filtrate evaporate to dryness, residue adds water 30ml makes dissolving, filters, and filtrate moves in the separatory funnel, add water saturated n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, and the ammonia (40ml strong aqua ammonia thin up to 100ml) saturated with n-butyl alcohol washs 3 times, each 10ml, discard washing liquid, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, residue adds dehydrated alcohol 2ml makes dissolving, filter, filtrate is as need testing solution; Other gets the peoniflorin reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 3 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform-ethyl acetate-methanol-formic acid (40:5:10:0.2) is developing solvent, launch, take out, dry, spray is with 5% vanillin sulphuric acid liquid, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
5, get jujuboside A reference substance, add dehydrated alcohol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution and each 5 μ l of jujuboside A reference substance solution under the embodiment 7, put respectively on same silica gel g thin-layer plate, upper strata liquid with n-butyl alcohol-glacial acetic acid-water (4:1:5) is developing solvent, launch, take out, dry, spray is with vanillin ethanol solution of sulfuric acid (get vanillin 2g add 10% ethanol solution of sulfuric acid 100ml dissolving), and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
6, measure according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000).
With octadecylsilane chemically bonded silica is that potassium dihydrogen phosphate-acetonitrile filler: 0.05mol/L, 47:53 is a mobile phase, and wherein every 1000ml mobile phase contains sodium lauryl sulphate 1.7g; The detection wavelength is 265nm; Number of theoretical plate calculates by the berberine hydrochloride peak should be not less than 4000; It is an amount of that precision takes by weighing the berberine hydrochloride reference substance, uses 50% dissolve with methanol, makes the solution that every 1ml contains 0.025mg, shakes up, and promptly gets reference substance solution; Get the content under the content uniformity, porphyrize is got about 0.3g, the accurate title, decide, and puts in the tool plug conical flask, the accurate 50% methanol 50ml that adds, claim to decide weight, reflux 30 minutes is put cold, claim again to decide weight, supply the weight that subtracts mistake, shake up with 50% methanol, filter, get subsequent filtrate, filter, promptly get need testing solution with microporous filter membrane (0.45 μ m); Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and every of this pharmaceutical composition contains Rhizoma Coptidis with berberine hydrochloride (C
20H
18ClNO
4) meter, must not be less than 1.0mg.
Claims (13)
1, a kind of Chinese medicine composition that improves sleep is characterized in that this Chinese medicine composition made by following raw material medicaments:
Rhizoma Coptidis 30-60 weight portion Radix Rehmanniae 200-250 weight portion Radix Scutellariae 120-150 weight portion
Radix Paeoniae Alba 200-250 weight portion Fructus Schisandrae Chinensis 120-150 weight portion
Semen Ziziphi Spinosae 400-500 weight portion.
2, Chinese medicine composition as claimed in claim 1 is characterized in that this Chinese medicine composition made by following raw material medicaments:
Rhizoma Coptidis 45 weight portion Radix Rehmanniae 225 weight portion Radix Scutellariaes 135 weight portions
The Radix Paeoniae Alba 225 weight portion Fructus Schisandrae Chinensis 135 weight portion Semen Ziziphi Spinosae (parched)s 450 weight portions.
3, Chinese medicine composition as claimed in claim 1 is characterized in that this Chinese medicine composition made by following raw material medicaments:
Rhizoma Coptidis 35 weight portion Radix Rehmanniae 245 weight portion Radix Scutellariaes 125 weight portions
The Radix Paeoniae Alba 245 weight portion Fructus Schisandrae Chinensis 125 weight portion Semen Ziziphi Spinosaes 480 weight portions.
4, Chinese medicine composition as claimed in claim 1 is characterized in that this Chinese medicine composition made by following raw material medicaments:
Rhizoma Coptidis 55 weight portion Radix Rehmanniae 210 weight portion Radix Scutellariaes 145 weight portions
The Radix Paeoniae Alba 205 weight portion Fructus Schisandrae Chinensis 145 weight portion Semen Ziziphi Spinosae (parched)s 420 weight portions.
5, as claim 1,2,3 or 4 described Chinese medicine compositions, it is characterized in that this Chinese medicine composition adds micropowder silica gel and dextrin is the molding adjuvant, dextrin: the ratio of micropowder silica gel is 1-3:2-5.
6, the preparation method of Chinese medicine composition as claimed in claim 5 is characterized in that this method is:
Above Six-element, Rhizoma Coptidis, the Radix Paeoniae Alba, Fructus Schisandrae Chinensis add 6-10 and doubly measure 60-80% ethanol, reflux, extract, 1-3 time, and each 1-2 hour, merge alcohol extract, decompression recycling ethanol is condensed into thick paste, is dried to driedly, is ground into fine powder; Radix Rehmanniae, Radix Scutellariae, Semen Ziziphi Spinosae (parched) add 8-12 times of water gaging, decoct each 1-3 hour 1-3 time, gradation filters, merging filtrate, and being concentrated into relative density 60 ℃ of filtrates is 1.10 clear paste, add ethanol and make and contain alcohol amount and reach 50-60%, stir evenly cold preservation 24 hours, filter, reclaim ethanol, be condensed into thick paste, be dried to driedly, be ground into fine powder, merge above-mentioned two kinds of fine powders, get this Chinese medicine compositions, this Chinese medicine compositions can be made into the dosage form of clinical acceptance.
7, the preparation method of Chinese medicine composition as claimed in claim 6 is characterized in that this method is:
Above Six-element, Rhizoma Coptidis, the Radix Paeoniae Alba, Fructus Schisandrae Chinensis add 8 times of amount 70% ethanol, reflux, extract, 2 times, and each 2 hours, merge alcohol extract, decompression recycling ethanol is condensed into thick paste, is dried to driedly, is ground into fine powder; Radix Rehmanniae, Radix Scutellariae, Semen Ziziphi Spinosae (parched) add 8 times of water gagings, decoct 3 times, and each 2 hours, gradation filtered, it is 1.10 clear paste that merging filtrate, filtrate are concentrated into relative density, adds ethanol and makes and contain the alcohol amount and reach 60%, stirs evenly, cold preservation 24 hours filters, and reclaims ethanol, is condensed into thick paste, be dried to driedly, be ground into fine powder, get above-mentioned two kinds of extractum fine powders, add an amount of dextrin, micropowder silica gel, mixing, add an amount of ethanol and granulate, drying incapsulates.
8,, it is characterized in that comprising in this method in the following discrimination method one or more as the method for quality control of claim 1,2,3 or 4 described Chinese medicine compositions:
A, get this Chinese medicine compositions 1g, porphyrize is put in the tool plug conical flask, adds methanol 10ml, close plug, and supersound process 20-40 minute, filter, filtrate is as need testing solution; Other gets Rhizoma Coptidis control medicinal material 50mg, shines medical material solution in pairs with legal system; Get the berberine hydrochloride reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 2 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, benzene-ethyl acetate-methanol-isopropyl alcohol-strong ammonia solution with the 11-13:5-7:2-4:2-4:1-2 ratio is developing solvent, put in the expansion cylinder of ammonia saturated with vapor, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get the baicalin reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution and each 5 μ l of baicalin reference substance solution under a item, put respectively on same silica gel g thin-layer plate, ethyl acetate-butanone-formic acid-water with the 4-6:2-4:1-2:1-2 ratio is developing solvent, launch, take out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
C, get this Chinese medicine compositions 6g, add 60～90 ℃ petroleum ether 30ml, reflux 20-40 minute, filter, medicinal residues are standby, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets the deoxyschizandrin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica GF254 lamellae, with 60-90 ℃, the 12-18:4-6:1-2 ratio the upper solution of petroleum ether-Ethyl formate-formic acid be developing solvent, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
D, get under the c item medicinal residues behind 60-90 ℃ the Petroleum ether extraction, volatilize petroleum ether, put in the tool plug conical flask, add methanol 40ml, close plug supersound process 20-40 minute, filters, the filtrate evaporate to dryness, residue adds water 30ml makes dissolving, filters, and filtrate moves in the separatory funnel, add water saturated n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, uses the saturated ammonia scrubbing of n-butyl alcohol 3 times, each 10ml, discard washing liquid, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, residue adds dehydrated alcohol 2ml makes dissolving, filter, filtrate is as need testing solution; Other gets the peoniflorin reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 2mg, in contrast product solution; Test according to thin layer chromatography according to an appendix VI of Chinese Pharmacopoeia version in 2000 B, draw each 3 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, chloroform-ethyl acetate-methanol-formic acid with the 30-50:4-6:8-12:0.1-0.3 ratio is developing solvent, launch, take out, dry, spray is with 5% vanillin sulphuric acid liquid, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, get jujuboside A reference substance, add dehydrated alcohol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution and each 5 μ l of jujuboside A reference substance solution under the d item, put respectively on same silica gel g thin-layer plate, upper strata liquid with the n-butyl alcohol-glacial acetic acid-water of 3-5:1-2:4-6 ratio is developing solvent, launch, take out, dry, spray is with the vanillin ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
9, method of quality control as claimed in claim 8 is characterized in that comprising in this method as follows
In the discrimination method one or more:
A, get this Chinese medicine compositions 1g, porphyrize is put in the tool plug conical flask, adds methanol 10ml, close plug, and supersound process 30 minutes filters, and filtrate is as need testing solution; Other gets Rhizoma Coptidis control medicinal material 50mg, shines medical material solution in pairs with legal system; Get the berberine hydrochloride reference substance again, add methanol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw each 2 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, benzene-ethyl acetate-methanol-isopropyl alcohol-strong ammonia solution with the 12:6:3:3:1 ratio is developing solvent, put in the expansion cylinder of ammonia saturated with vapor, launch, take out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with control medicinal material chromatograph and the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color;
B, get the baicalin reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw need testing solution and each 5 μ l of baicalin reference substance solution under a item, put respectively on same silica gel g thin-layer plate, ethyl acetate-butanone-formic acid-water with the 5:3:1:1 ratio is developing solvent, launches, and takes out, dry, spray is with 1% ferric chloride alcoholic solution; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
C, get this Chinese medicine compositions 6g, add 60～90 ℃ petroleum ether 30ml, reflux 30 minutes filters, and medicinal residues are standby, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets the deoxyschizandrin reference substance, adds ethyl acetate and makes the solution that every 1ml contains 1mg, in contrast product solution; According to the thin layer chromatography test, draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica GF254 lamellae, with 60-90 ℃, the upper solution of the petroleum ether-Ethyl formate-formic acid of 15:5:1 ratio is developing solvent, launches, and takes out, dry, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
D, get under the c item medicinal residues behind 60～90 ℃ the Petroleum ether extraction, volatilize petroleum ether, put in the tool plug conical flask, add methanol 40ml, close plug, supersound process 30 minutes filters, the filtrate evaporate to dryness, residue adds water 30ml makes dissolving, filters, and filtrate moves in the separatory funnel, add water saturated n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, uses the saturated ammonia scrubbing of n-butyl alcohol 3 times, each 10ml, discard washing liquid, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, residue adds dehydrated alcohol 2ml makes dissolving, filter, filtrate is as need testing solution; Other gets the peoniflorin reference substance, adds dehydrated alcohol and makes the solution that every 1ml contains 2mg, in contrast product solution; According to the thin layer chromatography test, draw each 3 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, chloroform-ethyl acetate-methanol-formic acid with the 40:5:10:0.2 ratio is developing solvent, launches, and takes out, dry, spray is with 5% vanillin sulphuric acid liquid, and it is clear to be heated to speckle colour developing; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E, get jujuboside A reference substance, add dehydrated alcohol and make the solution that every 1ml contains 0.5mg, in contrast product solution; Test according to thin layer chromatography, draw need testing solution and each 5 μ l of jujuboside A reference substance solution under the d item, put respectively on same silica gel g thin-layer plate, upper strata liquid with the n-butyl alcohol-glacial acetic acid-water of 4:1:5 ratio is developing solvent, launch, take out, dry, spray is with the vanillin ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 100 ℃; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
10,, it is characterized in that comprising in this method following content assaying method as the method for quality control of claim 1,2,3 or 4 described Chinese medicine compositions:
According to high performance liquid chromatography; With octadecylsilane chemically bonded silica is that potassium dihydrogen phosphate-acetonitrile filler: 0.05mol/L, 47:53 is a mobile phase, and wherein every 1000ml mobile phase contains sodium lauryl sulphate 1.7g; The detection wavelength is 265nm; Number of theoretical plate calculates by the berberine hydrochloride peak should be not less than 4000; It is an amount of that precision takes by weighing the berberine hydrochloride reference substance, uses 50% dissolve with methanol, makes the solution that every 1ml contains 0.025mg, shakes up, and promptly gets reference substance solution; Get the content under the content uniformity, porphyrize is got 0.3g, the accurate title, decide, and puts in the tool plug conical flask, the accurate 50% methanol 50ml that adds, claim to decide weight, reflux 20-40 minute, put cold, claim again to decide weight, supply the weight that subtracts mistake, shake up with 50% methanol, filter, get subsequent filtrate, filter, promptly get need testing solution with microporous filter membrane; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and every of this Chinese medicine compositions contains Rhizoma Coptidis with berberine hydrochloride C
20H
18ClNO
4Meter must not be less than 1.0mg.
11, method of quality control as claimed in claim 10 is characterized in that comprising in this method following content assaying method:
According to high effective liquid chromatography for measuring; With octadecylsilane chemically bonded silica is that potassium dihydrogen phosphate-acetonitrile filler: 0.05mol/L, 47:53 is a mobile phase, and wherein every 1000ml mobile phase contains sodium lauryl sulphate 1.7g; The detection wavelength is 265nm; Number of theoretical plate calculates by the berberine hydrochloride peak should be not less than 4000; It is an amount of that precision takes by weighing the berberine hydrochloride reference substance, uses 50% dissolve with methanol, makes the solution that every 1ml contains 0.025mg, shakes up, and promptly gets reference substance solution; Get the content under the content uniformity, porphyrize is got 0.3g, the accurate title, decide, and puts in the tool plug conical flask, the accurate 50% methanol 50ml that adds, claim to decide weight, reflux 30 minutes is put cold, claim again to decide weight, supply the weight that subtracts mistake, shake up with 50% methanol, filter, get subsequent filtrate, the microporous filter membrane filtration with 0.45 μ m promptly gets need testing solution; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and the every measurement unit of this Chinese medicine compositions contains Rhizoma Coptidis with berberine hydrochloride C
20H
18ClNO
4Meter must not be less than 1.0mg.
12, as claim 1,2, the application of 3 or 4 described Chinese medicine compositions in the medicine of the insomnia of preparation treatment syndrome of hyperactivity of fire due to deficiency of YIN finding, dreaminess disease.
13, as claim 1,2,3 or 4 described Chinese medicine compositions have sedation in preparation, improve memory effect, application in the medicine of syngignoscism.
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| CN102727646B (en) * | 2011-04-02 | 2014-04-16 | 张意明 | Medicine for treating insomnia |
| CN103063767A (en) * | 2012-12-21 | 2013-04-24 | 邯郸摩罗丹药业股份有限公司 | Quality standard of sanhuang dispersible tablets and detection method thereof |
| CN103630648B (en) * | 2013-10-15 | 2015-04-01 | 滨州医学院附属医院 | Method for detecting anti-infective drug |
| CN104208387A (en) * | 2014-09-29 | 2014-12-17 | 洛阳御平国生物科技有限公司 | Chinese medicinal formula for treating neurasthenia |
| CN105021762B (en) * | 2015-07-23 | 2017-06-16 | 河北中医学院 | A kind of quick multi information thin-layer identification method of spina date seed water extract |
| CN107621517B (en) * | 2016-07-14 | 2020-02-21 | 天津同仁堂集团股份有限公司 | Detection method of kechuanjing syrup |
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Effective date of registration: 20160204 Address after: 710119, No. 70, West Avenue, new industrial zone, Changan District hi tech Development Zone, Shaanxi, Xi'an Patentee after: Shaanxi Buchang Hi-Tech Pharmaceutical Co.,Ltd. Address before: 100101 Chaoyang District Academy of Sciences Beijing south wind forest oasis F05-32C Patentee before: Chen Yongtai |
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