CN1799591A - Preparation method of 'Xue Fu Zhu Yu' capsule and quality standard thereof - Google Patents

Abstract

Disclosed is a preparation method of 'Xue Fu Zhu Yu' capsule and quality standard, wherein in the quality standard, identification items for peach kernel, fruit of citron and extractum glycyrrhizae liquidum are arranged. Calculated on peony glycosides (C23H28011), each unit of the capsule should contain no less than 2.20mg. The method of inspection and quality improvement, the optimized process and technological conditions are also disclosed.

Description

A kind of preparation method of XUEFU ZHUYU JIAONANG and quality standard thereof

Technical field

The present invention relates to derive from the technical field of medicinal preparation (international Patent classificating number 35/79) of the product that contains not clear structure of plant, specifically is the preparation method and the quality standard thereof of a kind of XUEFU ZHUYU JIAONANG of making of raw material with the Chinese crude drug extract.

Background technology

XUEFU ZHUYU JIAONANG (Xuefu Zhuyu Jiaonang) is a kind of classical Chinese patent medicine, Ministry of Public Health standard WS ₃-B-0928-91 record prescription and quality standard:

Semen Persicae (stir-fry) Radix Angelicae Sinensis Fructus Aurantii (parched with bran) Rhizoma Chuanxiong

Radix Bupleuri Flos Carthami Radix Achyranthis Bidentatae Radix Paeoniae Rubra

Radix Rehmanniae Radix Platycodonis Radix Glycyrrhizae

[character] this product is a capsule, and content is tan powder; The gas suffering, mildly bitter flavor.

This product is got in [discriminating] (1), puts microscopically and observes: the stone cell yellow, and shell-like, the wall one side is thicker, and laminated striation is fine and closely woven.Parenchyma cell spindle, wall are slightly thick, and atomic thin oblique cross lamination is arranged.Oil pipe contains yellow or pale brown color secretions.Spiral duct diameter 8～23 μ m, thickened wall is interconnection, and like netted spiral duct, prism of calcium oxalate is present in the parenchyma in flakes.

(2) get this product 5g, add methanol 20ml, merceration spends the night, and filters, and filtrate is concentrated into 2ml, as need testing solution.Other gets the hesperidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB), draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with ethyl acetate-alcohol-water (8: 2: 1) is developing solvent, launches, and takes out, dry, spray is with 5% magnesium acetate methanol solution, treat that methanol volatilizes after, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.

[inspection] should meet every regulation relevant under the capsule item (appendix IL).

[assay] measured according to high performance liquid chromatography (appendix VID).

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; With acetonitrile-water-glacial acetic acid (16: 84: 1) is mobile phase; The detection wavelength is 230nm.Number of theoretical plate calculates by the paeoniflorin peak should be not less than 2500.Separating degree should be up to specification.

The preparation of reference substance solution is taken at 80 ℃ of paeoniflorin reference substance 2mg that are dried to constant weight, and accurate the title decides, and puts in the 10ml volumetric flask, adds dehydrated alcohol to scale, shakes up, and promptly gets (containing paeoniflorin 0.2mg among every 1ml).

The content under this product content uniformity item is got in the preparation of need testing solution, and accurate the title decides, and mixing takes by weighing about 3g, the accurate title, decide, and puts in the conical flask, accurate dehydrated alcohol 50ml, the close plug of adding, claim to decide weight, reflux, extract, is after 4 hours in water-bath, and supersound extraction is 1 hour again, takes out, put coldly, claim to decide weight, supply the dehydrated alcohol amount of loss, filter, get subsequent filtrate 25ml and put and be concentrated into 2ml in the water-bath, and change molten to the 10ml measuring bottle, add dehydrated alcohol to scale, shake up, as need testing solution.

Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, and calculate the content of paeoniflorin in the test sample by external standard method.

Every of this product contains paeoniflorin (C ₂₃H ₂₈O ₁₁) must not be lower than 0.24mg.

[function with cure mainly] blood circulation promoting and blood stasis dispelling, promoting the circulation of QI to relieve pain.Be used for blood-stasis internal-depression, chest pain or headache, interior-heat blurring of vision accompanied with oppressive feeling, insomnia and dreamful sleep, severe palpitation, impatience and irascibility.

[usage and consumption] is oral, one time 6,2 times on the one, one month is a course of treatment.

The hot cold drinks and snachs thing of [attention] diet.Be not taken by pregnant women.

[specification] every dress 0.4g

Shady and cool dry place is put in [storage] sealing.

Original preparation technology: Semen Persicae 100g, Radix Angelicae Sinensis, Radix Paeoniae Rubra, Fructus Aurantii, Rhizoma Chuanxiong, Radix Bupleuri are ground into fine powder, sieve, mixing, the five tastes such as all the other Flos Carthamis and Semen Persicae 100g decoct with water three times, filter merging filtrate, being condensed into relative density is the thick paste of 1.15～1.25 (65～70 ℃), with above-mentioned powder mixing, make granule, oven dry, pulverize, sieve, encapsulated, promptly.

Other has applying date 2001.1.5, the patent of publication number CN1362075A " nano blood stasis dispersing preparation medicine and preparation method thereof "

The record prescription:

Nanometer Semen Persicae 10-50 part nano Chinese angelica 8-60 part nanometer Fructus Aurantii 10-70 part nanometer Rhizoma Chuanxiong 8-60 part

Nano bupleurum 10-60 part nano safflower 8-60 part nanometer Radix Achyranthis Bidentatae 8-50 part nanometer Radix Paeoniae Rubra 8-60 part

Nanometer Radix Rehmanniae 10-60 part nanometer Radix Platycodonis 5-50 part nanometer Radix Glycyrrhizae 5-30 part

The preparation method of record nano blood stasis dispersing preparation medicine, function with cure mainly: can be used for treatment of conditions such as headache, dizzy, brain injury sequela, angina pectoris.

Pharmacology and Clinics of Chinese Materia Medica, 1990,6 (6), the 1-4 page or leaf, Peng Kang, Zheng Youshun work " side's of tearing open research of decoction for removing blood stasis---to microcirculatory pharmacological action " prove can microcirculation improvement, and the hypertension that causes because of the increase of blood capillary resistance is had certain inhibitory action.

More than also have discriminating project, discriminating means, content assaying method imperfection in the disclosed XUEFU ZHUYU JIAONANG quality standard prior art, on preparation method, exist the preparation method of nano blood stasis dispersing preparation medicine not obtain drug effect proof and production cost height as yet, the preparation method of original capsule type, 6 of each doses, taking dose absorbs slowly greatly in vivo, take shortcomings such as inconvenience, do not meet three little, triple effect and five standard easily.

Summary of the invention

The preparation method and the quality standard thereof that the purpose of this invention is to provide a kind of XUEFU ZHUYU JIAONANG are made every effort to make and are developed the XUEFU ZHUYU JIAONANG of improving after the technology and meet three little, triple effect and five standard easily.

For the quality of strictness control medicine, guarantee curative effect, formulated quality standard

1. in the research of the qualitative identification of this product, design is to Semen Persicae in the prescription, Fructus Aurantii, and Radix Glycyrrhizae, Radix Achyranthis Bidentatae, Radix Platycodonis carry out qualitative identification, at first adopt the bibliographical information method test, and formulation samples is undesirable as a result, and developing solvent is repeatedly changed in serious hangover, separates still relatively poor.Adopt the development system of different sample treatments and opposed polarity to separate, especially Radix Achyranthis Bidentatae, Radix Platycodonis disturb big, with reference substance same position speckle in an overlapping, and feminine gender has interference.After improving on the sample treatment, put plate again and differentiate, Semen Persicae, Radix Glycyrrhizae, Fructus Aurantii flavour of a drug separate better as a result, with the reference substance same position on be same blob, and negative noiseless, favorable reproducibility.So set up the thin layer discrimination method of Semen Persicae, Radix Glycyrrhizae, Fructus Aurantii in the prescription.

2. this product has at first been carried out the experiment of component analysis with ministerial drug Radix Paeoniae Rubra in the prescription in the design of quantitative analysis.According to reported in literature, contain the peoniflorin composition in the Radix Paeoniae Rubra, measure so adopt high performance liquid chromatography to carry out content of paeoniflorin.Select to detect wavelength X=230nm test by the pharmacopeia method, and carried out methodological study, sample pre-treatments adopts extracting of different ultrasonic times, and selected 50% methanol that adds extracted in ultrasonic 10 minutes, and effective ingredient extracts substantially.The ratio of adjusting mobile phase is: second eyeball-water (16: 84), flow velocity is 1.0ml/min, the isochromatic spectrum condition, investigate through test precision, repeatability, stability, the response rate, determined to adopt the HPLC method to measure content with the peoniflorin reference substance, favorable reproducibility can detect the quality of medicine fast and accurately.

Technical scheme of the present invention is: increased the discriminating of Semen Persicae in existing quality standard: get this product content 1g, add water 20ml dissolving, add ether 20ml extraction 2 times, discard ether solution, aqueous solution reuse ethyl acetate 30ml extraction 2 times, collect ethyl acetate liquid and volatilize, add 2ml methanol and promptly get need testing solution.Other gets the naringin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography (" appendix VIB of Chinese pharmacopoeia version in 2000) test, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, the subnatant of placing 12 hours with chloroform-methanol-water (45: 17: 5) launches, take out, dry, spray is put under the ultra-violet lamp (365nm) with the aluminum chloride methanol solution and is inspected.In the test sample chromatograph, with the corresponding position of reference substance on, show identical bright fluorescence speckle.

The discriminating of Fructus Aurantii: get this product content 1g, adding methanol 15ml supersound process 10min filters, filtrate evaporated under reduced pressure adds brick glue (100-160 order) 0.5g, mixing to small size, evaporate to dryness, add on the silicagel column (column diameter 1cm column length 25cm, silica gel 100 ~ 160 order 5g, dry column-packing) with chloroform: ethyl acetate: methanol: (15: 40: 22: 10) 5～10 ℃ of lower floors of placing 12 hours were eluent to water, eluting is collected 16～21ml liquid and is promptly got need testing solution.Other gets the amygdaloside reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography (" appendix VIB of Chinese pharmacopoeia version in 2000) test, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with the eluant is that developing solvent launches, take out, dry, spray immediately with phosphorus molybdenum acid solution (phosphomolybdic acid 2g, add water 20ml and make dissolving, slowly add sulphuric acid 30ml mixing again.) put about 10 minutes of 105 ℃ of heating colour developings, in the test sample chromatograph, with the corresponding position of reference substance on, show identical navy blue speckle.

The discriminating of Radix Glycyrrhizae: get this product content 2g, the 30ml that adds diethyl ether, supersound process 10min, filter, discard ether solution, residue adds methanol 30ml, supersound process 10min, filtrate evaporated under reduced pressure adds water 40ml dissolving to doing, and uses n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, be decompressed to driedly, add methanol 5ml dissolving, promptly get need testing solution.Extracting liquorice acid mono-ammonium reference substance adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution in addition.According to thin layer chromatography (" appendix VIB of Chinese pharmacopoeia version in 2000) test, draw each 2～4 μ l of above-mentioned two kinds of solution, put respectively in same high-efficient silica gel GF ₂₅₄On the lamellae, be that developing solvent launches, take out, dry, put under the ultra-violet lamp (254nm) and inspect with n-butyl alcohol-20% ammonia-methanol (5: 2: 1.5), in the test sample chromatograph, with the corresponding position of reference substance on, show identical black-and-blue speckle.

Improved content assaying method and improved Radix Paeoniae Rubra with peoniflorin (C ₂₃H ₂₈O ₁₁) meter standard as follows

[assay] measured according to high performance liquid chromatography (appendix VID)

Chromatographic condition and system suitability test are filler with the octadecyl silane; With second eyeball-water (16: 84) is mobile phase; The detection wavelength is 230nm.Number of theoretical plate calculates by the peoniflorin peak should be not less than 4300.

It is an amount of that the preparation of reference substance solution takes by weighing the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes the solution that every 1ml contains 0.1mg, promptly.

This product content 0.3g is got in the preparation of need testing solution, porphyrize, and accurate the title, decide.Insert in the 25ml measuring bottle and to add methanol 24ml, ultrasonic 10min is put coldly, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate and puts in the brown bottle, promptly.

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Every of this product contains Radix Paeoniae Rubra with peoniflorin (C ₂₃H ₂₈O ₁₁) meter, must not be less than 2.20mg.

The quality standard research data

[discriminating]

One. differentiate this prescription of object totally ten Herba indigoferae Pseudotinctoriae, Semen Persicae, Fructus Aurantii, Radix Glycyrrhizae, Radix Achyranthis Bidentatae, Radix Platycodonis five tastes medical material are set up discrimination method among design the other side.In experimental study, adopt the development system of different sample treatments and opposed polarity to separate chromatography respectively, because the prescription taste of Chinese medicine is more, complicated component disturbs greatly, the result has set up the thin layer discrimination method to Semen Persicae, Radix Glycyrrhizae, Fructus Aurantii three flavor medical materials in the prescription.Two qualitative identification have been increased than former technology capsule.

Two, reference substance source: the used reference substance of this product is all purchased in Chinese biological goods calibrating institute

Three., discrimination method

1, the discriminating of Semen Persicae

This product content 1g is got in the preparation of need testing solution, adds methanol 15ml, supersound process 10min, filter, filtrate evaporated under reduced pressure adds silica gel (100-160 order) 0.5g, mixing to small size, evaporate to dryness, (15: 40: 22: 10) 5～10 ℃ of lower floors of placing 12 hours were eluent with chloroform-ethyl acetate-methanol-water to add on the silicagel column (column diameter 1cm column length 25cm, silica gel 100 ~ 160 order 5g, dry column-packing), eluting is collected 16-21ml liquid and is promptly got need testing solution.

The amygdaloside reference substance is got in the preparation of reference substance solution, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography (" appendix VIB of Chinese pharmacopoeia version in 2000) test, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be that developing solvent launches with the eluant,

The preparation of feminine gender blank solution is formed deal by prescription, gets all the other flavour of a drug except that Semen Persicae, makes negative sample by technological requirement, takes by weighing 1g, presses the method operation under the need testing solution preparation, gets negative sample liquid.

Thin layer chromatography:

Adsorbent silica gel G plate (10 * 10cm) Haiyang Chemical Plant, Qingdao

Point sample amount 5--10 μ l

(15: 40: 22: 10) 5～10 ℃ of lower floors of placing 12 hours were eluent to developing solvent chloroform-ethyl acetate-methanol-water

Exhibition is apart from 8cm

The result takes out, and dries, and sprays immediately that (phosphomolybdic acid 2g adds water 20ml and makes dissolving, slowly adds sulphuric acid 30ml mixing again with phosphorus molybdenum acid solution.) put about 10 minutes of 105 ℃ of heating colour developings, in the test sample chromatograph, with the corresponding position of reference substance on, show identical navy blue speckle.Negative sample does not have this speckle.

2, the discriminating of Fructus Aurantii

This product content 1g is got in the preparation of need testing solution, adds water 20ml dissolving, adds ether 20ml extraction 2 times, discards ether solution, and aqueous solution reuse ethyl acetate 30ml extraction 2 times is collected ethyl acetate liquid and volatilized, and adds 2ml methanol and promptly gets need testing solution.

The naringin reference substance is got in the preparation of reference substance solution, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.

The preparation of feminine gender blank solution is formed deal by prescription, gets all the other flavour of a drug except that Fructus Aurantii, makes negative sample by technological requirement, takes by weighing 1g, presses the method operation under the need testing solution preparation, gets negative sample liquid.

Thin layer chromatography:

Adsorbent silica gel G plate (10 * 10cm) Haiyang Chemical Plant, Qingdao

Point sample amount 5～10 μ l

Developing solvent chloroform-methanol-water (32: 17: 5) lower floor launches,

Exhibition is apart from 8cm

The result takes out, and dries, and spray is put under the ultra-violet lamp (365nm) with the aluminum chloride methanol solution and inspected.In the test sample chromatograph, with the corresponding position of reference substance on, show identical bright fluorescence speckle.Negative sample liquid does not have this speckle.

3. the discriminating of Radix Glycyrrhizae

This product content 2g, the 30ml that adds diethyl ether, supersound process 10min are got in the preparation of need testing solution, filter, discard ether solution, residue adds methanol 30ml, supersound process 10min, filtrate evaporated under reduced pressure adds water 40ml dissolving to doing, and uses n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, be decompressed to driedly, add methanol 5ml dissolving, promptly get need testing solution.

The preparation extracting liquorice acid mono-ammonium reference substance of reference substance solution adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.

The preparation of feminine gender blank solution is formed deal by prescription, gets all the other flavour of a drug except that Radix Glycyrrhizae, makes negative sample by technological requirement, takes by weighing 1g, presses the method operation under the need testing solution preparation, gets negative sample liquid.

Thin layer chromatography:

Adsorbent high-efficient silica gel GF ₂₅₁Lamellae, (10 * 10cm) Haiyang Chemical Plant, Qingdao

Point sample amount 2-5 μ l

Developing solvent n-butyl alcohol-20% ammonia-methanol (5: 2: 1.5)

Exhibition is apart from 8cm

The result takes out, and dries, put under the ultra-violet lamp (254nm) and inspect, in the test sample chromatograph, with the corresponding position of reference substance on, show identical black-and-blue speckle.Negative sample liquid does not have this speckle.

[assay] assay object with become the component selections foundation: this product Radix Paeoniae Rubra mainly contains peoniflorin, be chosen in have specificity among the we peoniflorin as component target, measure content, can control drug quality preferably.

One. instrument and reagent

The HP1100 high performance liquid chromatograph, detector: G1314A, Als:1313A, Colcomp:G1316A, pump: G1310A

Methanol, fine analytical pure and the chromatographically pure of being of second

Peoniflorin reference substance: purchase in Nat'l Pharmaceutical ﹠ Biological Products Control Institute

XUEFU ZHUYU JIAONANG: 3 batches, provide by XUEFU ZHUYU JIAONANG special topic group.

Two. high-efficient liquid phase chromatogram condition

Chromatographic column: YWG-C ₁₈(250 * 4.6mm) 5 μ m

Detect wavelength: λ=230nm column temperature: 30 ℃

Mobile phase: second is fine-water (16: 84),

Flow velocity: 1.0ml/min

Three. the purity of reference substance peoniflorin is determined

Source: Nat'l Pharmaceutical ﹠ Biological Products Control Institute

Purity: reference substance is made into the methanol solution of 0.92mg/ml, injects 11 μ l, parallel injection methanol 11 μ l, the record chromatogram, the peak area normalization method is calculated content, content 98.10%.

Four. reference substance, sample, negative liquid chromatogram and peoniflorin theoretical cam curve are calculated according to operating under the assay item.

1. reference substance peoniflorin liquid chromatogram

2. Yin Xing liquid chromatogram

3. positive medical material liquid chromatogram

4. the liquid chromatogram of test sample

5. the theoretical cam curve of peoniflorin is calculated: N=5.54 * (t _R/ W _1/2h) ²

＝5.54×(9.989/0.3589) ²＝4291

Theoretical cam curve is 4291

Five. assay

(1) method is investigated

The sample extraction method is a water soluble ingredient according to the composition peoniflorin of contained mensuration, with reference to pharmacopeia Radix Paeoniae Rubra content assaying method, sample pre-treatments is investigated with the comparison of supersound extraction and the selection of mobile phase.

1, supersound extraction test, different ultrasonic times are handled behind the adding solvent in sample.Measure content and see Table 6

The different ultrasonic times of table 6 extract the assay result

Time	10 minutes	20 minutes	30 minutes	40 minutes
					Content (mg/g)	8.285	8.275	8.350	8.340

Result of the test shows: the content size that different ultrasonic extracting methods are measured is approximate substantially, and ultrasonic basic extraction was complete at 10 minutes.So having selected ultrasonic time is 10 minutes.

2, the selection of mobile phase: mobile phase is selected with reference to pharmacopeia Radix Paeoniae Rubra content assaying method, its mobile phase is methanol-potassium dihydrogen phosphate 0.05M (40: 65), it is tested, and single medicinal material test sample chromatogram is all right, and sample chromatogram figure is then undesirable, main peak separates bad, so mobile phase is adjusted, through repetition test, determine at last optimal flow reach mutually ratio be second fine-water (16: 84), main peak separates better, and is stable.

3, detect wavelength and select to detect peoniflorin wavelength X=230nm, it is tested with reference to official method.The result shows: negative noiseless at 230nm wavelength place,, sample has identical maximum to inhale absworption peak with reference substance, and the result is more satisfactory, is λ=230nm so adopt the detection wavelength.

(2) system suitability experiment chromatographic column YWG-C ₁₈(250 * 4.6mm) 5 μ m; Mobile phase second eyeball-water (16: 84); Detect wavelength X=230nm.Theoretical cam curve is calculated by peoniflorin and is not less than 4300

(3) an amount of content porphyrize is got in the preparation of need testing solution, claims 0.3g, and accurate the title decides.Insert in the 25ml measuring bottle the accurate 50% methanol 24ml of adding, ultrasonic 10min is put coldly, adds methanol to scale, shakes up, and microporous filter membrane filters, and promptly gets need testing solution.

(4) Radix Paeoniae Rubra coarse powder 0.1g is got in the preparation of positive solution, and accurate the title decides, and gets positive solution with the Radix Paeoniae Rubra preparation method.

(5) the peoniflorin reference substance is got in the preparation of reference substance solution, adds methanol and makes solution that 1ml contains 0.5072mg product storing solution in contrast.

(6) preparation of negative solution is got and is lacked Radix Paeoniae Rubra extract 23g, gets negative solution with (two) legal system.

(7) assay

1. the investigation of linear relationship: draw reference substance storing solution 0.6,0.8,1.0,1.2,1.4,1.6ml,

Insert respectively in the 5.0ml measuring bottle, add methanol, shake up, promptly to scale.Each injects 10 μ l, is abscissa with the injection rate, and peak area is a vertical coordinate, the drawing standard curve chart, handle regression equation, see Table 7, Fig. 1.

Table 7 peoniflorin standard curve

Concentration (μ g)	0.60864	0.81152	1.01440	1.21728	1.42016	1.62304
							Peak area	809.7949	1108.939	1400.748	1692.776	1950.427	2250.17

Result: in 0.60864～1.62304 μ g scope, be good linear relationship.

2. blank assay: get the prescription drugs that lacks Radix Paeoniae Rubra, make negative sample by the preparation method of sample.Handle with need testing solution method under the assay item, and record chromatogram, confirm noiseless

3. stability test: the sample liquid (040907) that will treat sample introduction is placed different time, injects chromatograph of liquid and measures, record peak area integrated value.See Table 8

Table 8 stability test result

Time (h)	0	4	8	12	24
						Content (mg/g)	9.00	8.96	8.96	8.98	9.07

RSD＝0.51％

4. precision test: get sample liquid (040907) the 10 μ l under the assay item, sample introduction five times writes down the peak area integrated value respectively.The results are shown in Table 9

Table 9 Precision test result

The sample introduction number of times	1	2	3	4	5
						Content (mg/g)	9.00	8.98	8.93	8.94	8.96

RSD＝0.32％

5. repeatability test: according to the operation down of content assaying method item, precision takes by weighing 5 parts in 040907 sample respectively, carries out assay.The results are shown in Table 10

Table 10 reproducible test results

The NO of sample introduction	1	2	3	4	5
						Content (mg/g)	9.00	8.98	8.98	8.99	8.99

RSD＝0.08％

6. recovery test: get 040907 batch sample 0.15g, accurately claim surely, add reference substance 1.268mg in finished product, handle by preparation need testing solution method, according to measuring under the content assaying method item.Content results sees Table 11

Table 11 recovery test result

RSD＝2.7％

7. sample determination: the chromatographic condition of drafting by determination, with need testing solution and reference substance solution each

10 μ l inject chromatograph of liquid, measure the paeoniflorin content result.The assay of three batch samples the results are shown in Table 12

Table 12 sample determination result

It is 8.03mg/g that the content average is surveyed in this experiment, is equivalent to Radix Paeoniae Rubra 0.24g in the prescription, and the content of Radix Paeoniae Rubra is 33.45mg/g in the conversion prescription, and it is 75.7% that preparation is compared its extraction ratio with single medicinal material Radix Paeoniae Rubra mensuration content (44.20mg/g).Consider practice in factory, regulation this product is with peoniflorin (C ₂₃H ₂₈O ₁₁) meter content should not be lower than 4.80mg/g.Every capsules is not less than 2.20mg.

'Xue Fu Zhu Yu ' (former dosage form is a capsule) is the compound Chinese medicinal preparation that Tianjin Hong Rentang pharmaceutical factory produces.This medicine has been widely used in clinical, and has obtained effect preferably.Because clinical large usage quantity has been carried out process modification for guaranteeing and improve the quality of XUEFU ZHUYU JIAONANG to 'Xue Fu Zhu Yu ', technical scheme of the present invention is: a kind of preparation method of XUEFU ZHUYU JIAONANG is characterized in that with following weight proportion Chinese crude drug be raw material

Radix Angelicae Sinensis 162g Semen Persicae 216g Flos Carthami 162g Radix Achyranthis Bidentatae 162g

Radix Rehmanniae 162g Radix Paeoniae Rubra 108g Fructus Aurantii 108g Radix Platycodonis 81g

Rhizoma Chuanxiong 81g Radix Bupleuri 54g Radix Glycyrrhizae 54g,

Preparation method is: get ten Herba indigoferae Pseudotinctoriae water extraction 1-3 times such as Radix Angelicae Sinensis, water consumption 6-10 doubly, each 0.5-1.5h, filter, collect filtrate, being evaporated to relative density is 1.07-1.35,60-70 ℃ of mensuration, treat cold placement room temperature, add ethanol and make and contain the alcohol amount and be 60-80%, stir evenly, leave standstill (5-25h) and make precipitation, getting supernatant, to be evaporated to relative density be 1.30-1.50, and 60-70 ℃ of mensuration adds the starch of extractum amount 10-15%, dry 5-12h in drying baker, T=65-80 ℃, get dry thing, dried cream rate 20-28%, the silicon dioxide that adds dry thing weight 2%-8%, incapsulate, pulverized the 24-60 mesh sieve, every gram capsule is equivalent to crude drug 3.10 ~ 3.38g.

The preparation method of described XUEFU ZHUYU JIAONANG is characterized in that with following weight proportion Chinese crude drug be raw material

Radix Angelicae Sinensis 162g Semen Persicae 216g Flos Carthami 162g Radix Achyranthis Bidentatae 162g

Radix Rehmanniae 162g Radix Paeoniae Rubra 108g Fructus Aurantii 108g Radix Platycodonis 81g

Rhizoma Chuanxiong 81g Radix Bupleuri 54g Radix Glycyrrhizae 54g

The preferred for preparation method is: get ten Herba indigoferae Pseudotinctoriae water extraction 2 times such as Radix Angelicae Sinensis, 8 times of each water consumptions, each extraction time 1h, filter, collect filtrate, being evaporated to relative density is 1.16-1.19,60 ℃ of mensuration are treated cold placement room temperature, add ethanol and make that to contain the alcohol amount be 70%, stir evenly, leave standstill and make precipitation, getting supernatant, to be evaporated to relative density be 1.35-1.43,60 ℃ of mensuration, the starch that adds extractum amount 15%, dry 9h in drying baker, gets dry thing by T=70-75 ℃, dried cream rate 23-25%, the silicon dioxide that adds dry thing weight 6% was pulverized 40 mesh sieves, incapsulated, make 1000, every gram capsule is equivalent to crude drug 3.375g.

XUEFU ZHUYU JIAONANG Research on Process data:

Former dosage form is a capsule, 6 of each doses.Owing to the reason of dose with in the limitation of market coverage rate, can not satisfy the needs of extensive patients.Make the mentality of designing that reduces taking dose be the original capsule process modification: to XUEFU ZHUYU JIAONANG technology, quality, pharmacology, etc. carry out systematic research, to guarantee and to improve the capsular curative effect of improvement technology is purpose, with quality standard control technology and drug effect is index, determine best process flow and process conditions, make and have the little absorption in vivo of taking dose soon, characteristics such as taking convenience.Make every effort to make and develop the XUEFU ZHUYU JIAONANG of improving after the technology and meet three little, triple effect and five standard easily.

One. prescription is formed:

Radix Angelicae Sinensis 162g Semen Persicae 216g Flos Carthami 162g Radix Achyranthis Bidentatae 162g

Radix Rehmanniae 162g Radix Paeoniae Rubra 108g Fructus Aurantii 108g Radix Platycodonis 81g

Rhizoma Chuanxiong 81g Radix Bupleuri 54g Radix Glycyrrhizae 54g

Two. best preparation technology

1. get ten Herba indigoferae Pseudotinctoriae water extraction 2 times such as Radix Angelicae Sinensis, 8 times of each water consumptions, each extraction time 1h, filter, collect filtrate, being evaporated to relative density is 1.16-1.19 (60 ℃), treat cold placement room temperature, add ethanol and make that to contain the alcohol amount be 70%, stir evenly, leave standstill and make precipitation, getting supernatant, to be evaporated to relative density be 1.35-1.43 (60 ℃), the starch that adds extractum amount 15%, dry 9h in drying baker (T=70-75 ℃) gets dry thing (dried cream rate 23-25%), the silicon dioxide that adds dry thing weight 6%, pulverize 40 mesh sieves, incapsulated, made 1000.(every gram capsule is equivalent to crude drug 3.375g), best preparation technology's flow process was seen Fig. 2.

Three. preparation technology's research

(1) the technology drug effect relatively

According to this medical instrument the effect of blood circulation promoting and blood stasis dispelling is arranged, above two kinds of technologies have been carried out the pharmacodynamics test of hemorheology and two models of carotid artery thrombosis.The result is as follows:

1. provide by the court's 'Xue Fu Zhu Yu ' seminar for the reagent thing:

No. 1 technology sample of 'Xue Fu Zhu Yu ': light brown powder, every gram powder are equivalent to crude drug 3.38 grams, lot number 0513.

No. 2 technology samples of 'Xue Fu Zhu Yu ': dark-brown powder, every gram powder are equivalent to crude drug 2.87 grams, lot number 0514.

XUEFU ZHUYU JIAONANG: dark-brown powder, every gram powder are equivalent to crude drug 1.69 grams, every capsules dress 0.675g medicated powder.Produce by Tianjin Hong Rentang pharmaceutical factory.Lot number D03022.

FUFANG DANSHEN PIAN: Shijiazhuang City China imperial Pharmaceutical limited company, lot number 040504.

10% macromolecule right rotary glycoside injection: Chinese Academy of Medical Sciences's Blood Research Institute product, molecular weight 300,000.

Aspirin: white crystals, 99.5%, synthesis pharmaceutical factory in northwest provides.

2. for examination animal Wistar kind mice, male and female dual-purpose, body weight 200 ~ 250g; Above animal provides by the court animal housing, the quality certification " No. the 001st, Tianjin kinoplaszm word ".

3. instrument BR2-500E type cone-plate year counts: Tokyo gauge Co., Ltd. product

The experimental thrombus in vivo of BT87-3 type forms analyzer: the development of packet header medical college

4. test method and result

1) to the influence of hemorheology of rat due to the macromolecule right rotary glycoside

Choose above-mentioned healthy rat, be divided into normal group, model control group, No. 2 sample sets, No. 1 sample sets, former dosage form group, positive drug FUFANG DANSHEN PIAN group at random by sex, body weight.No. 1 sample sets of 'Xue Fu Zhu Yu ', No. 2 sample sets, former dosage form matched group all by 1.5,3,6g crude drug/kg gastric infusion, the positive drug control group FUFANG DANSHEN PIAN is pressed 2.0g medicated powder/kg gastric infusion, the administration volume is 1ml/100g, model control group, normal control group such as give at capacity 0.5%CMC, once a day, continuous 10 days.Each organized rat all after the last administration 1 hour, pentobarbital sodium (40mg/kg), and tail vein injection 10% macromolecule right rotary glycoside injection 1ml/kg causes the blood high viscosity syndrome model.Quiet notes from abdominal aortic blood, with 3.8% sodium citrate anticoagulant (anticoagulant is 1: 9 with the ratio of whole blood), were measured 4 whole blood viscosity of cutting under the speed after 10 minutes on cone-plate type viscometer.In the hematocrit pipe, measure packed cell volume and erythrocyte sedimentation rate.3000 rev/mins centrifugal 10 minutes, get blood plasma and on capillary viscosimeter, measure plasma viscosity.See Table 1

Result of the test adopts two groups of mean statistical analysiss-t value method to carry out significance test, and the result shows, compares with the normal control group, and whole blood viscosity, the plasma viscosity under the speed respectively cut in the obvious rising of model control group, shows the moulding success.No. 1 sample 6g crude drug of 'Xue Fu Zhu Yu '/kg dosage group compares with model control group, and obviously the whole blood viscosity under the speed is respectively cut in reduction, obviously reduces plasma viscosity.The former dosage form of 'Xue Fu Zhu Yu ', positive control drug FUFANG DANSHEN PIAN also have obvious effect.No. 2 samples of 'Xue Fu Zhu Yu ' only reduce the whole blood viscosity under the low shear rate.Each dosage group does not all have obvious influence to erythrocyte erythrocyte sedimentation rate, packed cell volume.

2) No. 1, No. 2 samples of 'Xue Fu Zhu Yu ' are to the thrombotic influence of carotid artery

Choose above-mentioned healthy rat, be divided into normal group, No. 2 sample sets, No. 1 sample sets, former dosage form group, positive drug aspirin matched group at random by sex, body weight.No. 1 sample sets of 'Xue Fu Zhu Yu ', No. 2 sample sets, former dosage form group all by 1.5,3,6g crude drug/kg gastric infusion, once a day, continuous 10 days, the positive drug control group aspirin is pressed the 150mg/kg gastric infusion, once a day, continuous 5 days, the administration volume was 1ml/100g, and the normal control group waits capacity 0.5%CMC.Each organized rat all after the last administration 1 hour, pentobarbital sodium intraperitoneal anesthesia (40mg/kg), separate the about 15mm of a bilateral common carotid artery, with BT-87-3 type thrombosis instrument stimulating electrode and temperature sensor hook on carotid artery, electric current with 1.5mA continues to stimulate blood vessel wall 7 minutes, detect the blood vessel surface variation of temperature by temperature sensor simultaneously, work as thrombosis, during plug flow, blood vessel distal end temperature bust, instrument are reported to the police, from stimulation begin to time of fire alarming as thrombus formation time (OT value), result of the test adopts two groups of mean statistical analysis t-value methods to carry out test of significance, sees Table 2

No. 1, No. 2 technology samples of table 1 'Xue Fu Zhu Yu ' are to the influence of hemorheology of rat due to the high molecular dextran (X ± SD)

Group	Dosage	Number of animals	Whole blood viscosity (mpa.s)				Plasma viscosity	Erythrocyte sedimentation rate	Hematocrit
											(the g crude drug/kg)	(only)	7.5S′	18.8 S′	37.5 S′	75S′		(cm/h)	(％)
Normal control		1 0	7.14± 1.95	3.38± 0.80	3.08± 0.55	2.80± 0.40	1.06± 0.15	0.20± 0.08	42.4± 4.19
										The model contrast		1 0	13.56± 2.53^^	7.32± 1.66^^	6.12± 1.30^^	5.29± 1.06^^	1.46± 0.11^^	0.21± 0.10	45.6± 4.09
No. 1 technology	6	1 0	10.50± 2.12**	5.71± 1.23*	4.86± 0.88*	4.24± 0.66*	1.26± 0.14**	0.22± 0.09	43.7± 3.34
											3	8	10.95± 1.46*	6.21± 1.11	5.07± 0.85	4.37± 0.71*	1.34± 0.14	0.25± 0.08	43.5± 3.16
	1.5	8	12.30± 2.33	7.41± 1.57	5.55± 1.35	4.70± 1.25	1.38± 0.06	0.24± 0.11	43.3± 3.62
										No. 2 technologies	6	1 0	11.28± 2.09*	6.00± 1.44	5.04± 1.00	4.44± 0.88	1.31± 0.18*	0.27± 0.11	43.7± 3.53
	3	8	12.68± 2.32	7.35± 2.27	5.96± 1.78	4.83± 1.37	1.41± 0.12	0.24± 0.05	43.8± 7.80
											1.5	8	13.65± 3.54	7.29± 2.01	5.84± 1.51	4.83± 1.15	1.45± 0.09	0.26± 0.11	45.6± 5.63
Former dosage form	6	1 0	10.14± 3.07*	5.50± 1.51*	4.84± 1.02*	4.17± 0.79*	1.24± 0.14**	0.22± 0.09	42.0± 4.76
											3	8	10.50± 2.63*	5.46± 1.45	4.40± 0.85*	3.56± 0.75**	1.31± 0.11*	0.24± 0.09	41.8± 7.11
	1.5	8	11.88± 3.33	6.48± 1.12	5.22± 0.93	4.43± 0.96	1.39± 0.10	0.25± 0.12	43.5± 11.78
										FUFANG DANSHEN PIAN	2g medicated powder	8	10.80± 2.70**	5.28± 2.04*	4.53± 1.59*	4.02± 1.28*	1.25± 0.21*	0.24± 0.07	42.5± 8.54

^{The Δ Δ}: * p＜0.05, p＜0.01 (comparing), * * p＜0.01 (comparing) with model control group with the normal control group

No. 1, No. 2 technology samples of table 2 'Xue Fu Zhu Yu ' to the thrombotic influence of carotid artery (± SD)

Group	Dosage (the g crude drug/kg)	Number of animals (only)	OT value (branch)
				No. 2 former formulation aspirin of the former formulation of the former formulation of technology of No. 2 technologies of No. 2 technologies of No. 1 technology of No. 1 technology of No. 1 technology of normal control	6 3 1.5 6 3 1.5 6 3 1.5 150mg/kg	8 8 8 8 8 8 8 8 8 8 8	16.29±4.90 26.33±9.85* 23.55±9.30 18.57±4.64 19.42±8.99 20.50±4.52 16.95±5.76 28.40±5.87** 22.62±6.25* 18.64±4.37 28.79±5.47**

*:: P＜0.05 * *:: P＜0.01 (comparing) with the normal control group

The result shows, compares No. 1 sample 6g crude drug of the 'Xue Fu Zhu Yu '/obvious prolong rats carotid artery of kg dosage group thrombus formation time with the normal control group.The former dosage form of 'Xue Fu Zhu Yu ', positive control drug aspirin also have obvious effect.No. 2 samples of 'Xue Fu Zhu Yu ' do not have obvious effect.

Conclusion: No. 1 technology sample of 'Xue Fu Zhu Yu ' 6g crude drug/kg dosage group, obviously reduce the blood high viscosity syndrome rat respectively cut speed under whole blood viscosity, plasma viscosity.Obvious prolong rats carotid artery thrombus formation time.No. 2 sample sets 6g crude drugs of 'Xue Fu Zhu Yu '/kg dosage group only reduces the hemorheology under the blood high viscosity syndrome rat low shear rate, and rat carotid artery thrombosis does not have obvious effect.

(2) Study on extraction process

According to above-mentioned pharmacodynamic experiment result, and consider the practical operation of the big production of factory, determine process route No. 1, i.e. aqueous extraction-alcohol precipitation technology, and this process route investigated water extraction and precipitate with ethanol condition respectively.

1. the investigation of water extraction process: select different amounts, extraction time, extraction time three factors, the testing program of three levels.Factor level sees Table 3, is component target to survey paeoniflorin content, carries out orthogonal test, and extraction process by water optimization is studied.

Table 3 factor level table L ₉(3 ³)

Level	Factor
				Water consumption A (doubly)	Extraction time B (h)	Extraction time C
	1 2 3	6 8 10	30 60 90				1 2 3

The preparation of orthogonal experiment sample: take by weighing 9 parts of recipe quantity 100g medical materials, consumption, extraction time, the extraction time with different water extracts respectively respectively, gets extracting solution.Carry out the pre-treatment of sample and measure content of paeoniflorin by content assaying method, select L for use ₉(3 ³) orthogonal design table tests, and the results are shown in Table 4

Table 4 water extraction process is investigated L ₉(3 ³) test card

R value: RC＞RA＞RB

As shown in Table 4, three factors all have certain influence to paeoniflorin content.The influence degree of each factor is followed successively by C＞A＞B, wherein A factor A ₃＞A ₂＞A ₁, B factor B ₃＞B ₂＞B ₁, C factor C ₃＞C ₂＞C ₁. in factors, among the data ABC among K2 and the ABC K3 approximate substantially, consider that energy consumption and cost are low, save time, suitable big production adopted A ₂, B ₂, C ₂Factor.Determine extraction process by water condition: A ₂B ₂C ₂, promptly adopt 8 times of water gagings to extract twice, each 60 minutes optimum condition extracts.And carried out three batches of verification experimental verifications, by the operation of said extracted method, measure content.Calculate rate of transform result such as following table 5:

Three batches of tests of table 5 rate of transform result

	Sample

1	Sample 2	Sample 3
			The content rate of transform (%) X	76.77	82.94 77.8	73.64

Three crowdes of checking results show: content rate of transform average is 77.8%.Improved stable process conditions, good reproducibility can be operated.

2. the investigation of aqueous extraction-alcohol precipitation technology

Behind the water extraction, its impurity is more in technology, and dose is excessive, directly influencing the foundation of dosage form, carry out precipitate with ethanol after having selected water to carry, serves as to investigate index to measure content, get recipe quantity 900g medical material, press the water extraction process condition and extract twice of water extraction, each 1 hour, measure relative density when its aqueous extract is concentrated into the medical material different proportion, add ethanol respectively, make it reach the alcohol amount that contains of variable concentrations, the precipitate with ethanol different time is investigated its content.Select L for use ₉(3 ³) orthogonal design table tests, and the results are shown in Table 6, table 7, table 8

Table 6 factor level table

Factor level	Concentrated solution relative density A	Alcohol precipitation concentration (%) B	Precipitate with ethanol time (h) C
				1 2 3	1.07 1.16 1.35	60 70 80	5 15 25

Table 7 aqueous extraction-alcohol precipitation technology is investigated L ₉(3 ³) test computer chart result

R：A＞B＞C

Table 8 analysis of variance table

Soruces of variation	Quadratic sum	Degree of freedom	Mean square	F	Factor affecting
						Water dope density A alcohol precipitation concentration B extraction time C sum of the deviations	7410.383 26.233 8.834 120.547 7565.997	2 2 2 2 8	3705.192 13.117 4.417 60.274	61.472 0.218 0.073	Significantly or not remarkable

The results of analysis of variance shows: orthogonal test A factor has remarkable influence, and B, C factor affecting are not remarkable.

Orthogonal experiments shows: the relative density of water extracting liquid has certain influence to content, and the relative density of R value explanation water dope is a principal element, and alcohol precipitation concentration and precipitate with ethanol time are secondary causes.The degree of each factor affecting is followed successively by RA＞RB＞RC, and A in the A factor ₁Approximate substantially with A2 numerical value, but A2 saves one times low with alcohol amount cost than A1, adopts A2.The B factor adopts B ₂, C factor numerical value is approximate substantially, considers from operability, adopts C ₂So determine A ₂B ₂C ₂Condition is promptly: water extraction concentrated solution to relative density is 1.16, and precipitate with ethanol makes and reaches that to contain the alcohol amount be 70%, precipitate with ethanol time 15h.

Above-mentioned technology has been carried out three batches of checkings,, measured the rate of transform result such as the following table 9 of content by the operation of said extracted method

Three batches of checkings of table 9 precipitate with ethanol content rate of transform result

	Sample

1	Sample 2	Sample 3
			The content rate of transform (%) X	78.31	76.95 76.5	74.43

Content rate of transform meansigma methods is 76.5% as a result.Illustrate that this test technology condition is reliable.

3, the dry thing content rate of transform is investigated the result

Press above-mentioned aqueous extraction-alcohol precipitation technology extraction, get the concentrated clear paste of extracting solution, add adjuvant, put drying in the drying baker, temperature gets dry thing at 70-75 ℃, and mensuration content is tested content rate of transform result such as table 10 for three batches

The dry thing content of table 10 rate of transform is investigated the result

NO.	Sample 1	Sample 2	Sample 3	Average
					Content rate of transform %	73.79	73.19	71.21	72.73

The result shows that the content rate of transform of extracting solution concentrated dry thing is 73.4%, is 97.7% of the water extract-alcohol precipitation liquid hold-up rate of transform.Illustrate that this drying condition is feasible.

(3) investigation of preparations shaping technology

The purpose of improving technology according to this product is to reduce taking dose, and the condition of its preparations shaping is investigated:

1. the selection that adds amount of starch has been selected above-mentioned technology according to drug effect, is prepared into the technology extract stable

Capsule 's content need add starch makes better molding, and respectively with 10%, 15%, 30% amount of starch joins in the extract, investigates its molding situation and sees Table 11

Table 11 adds the investigation of supplementary product starch amount

Add amount of starch %	10	15	30
				The molding situation	Mobile bad	Good fluidity	Good fluidity

The result shows that the said preparation content is with 15%, 30% forming, and flowability is also good, considers taking dose, has selected to add the content molding that 15% amount of starch makes preparation.But find that in study on the stability content has caking phenomenon, consider to increase supplementary product starch, add fluidizer silicon dioxide for this reason again and investigate from dosage form dosage.

2. the selection that adds silica volume: in content, add with 2%, 4% 6%, 8% difference respectively

The silicon dioxide of ratio 25 ℃ of room temperatures, under the condition of humidity 45%, to measure the flowability of investigating its content angle of repose, the results are shown in Table 12

Table 12 adds the not investigation of commensurability silica volume

Add silica volume %	2	4	6	8
					Mobile situation	68°	50°	40°	30°

The result shows, its good fluidity of the addition with 6%, 8%, and room temperature placement nothing caking moisture absorption phenomenon show stable.Consider the each side factor, selected 6% for the silicon dioxide addition be feasible.

(4), change the technology post dose and determine foundation

The former capsular dosage of 'Xue Fu Zhu Yu ': oral 6/time, every day secondary, (each the suitable crude drug 4.05g of dose).This product dosage is to determine according to the taking dose of former XUEFUZHUYU JIAONANG: the dosage that improves the XUEFU ZHUYU JIAONANG after the technology: oral 3/time, every day secondary.(each suitable crude drug 4.05g of dose).It is consistent that former XUEFUZHUYU JIAONANG contains the crude drug amount with the oral dose of the XUEFU ZHUYU JIAONANG of improving technology.

XUEFU ZHUYU JIAONANG and former technology XUEFU ZHUYU JIAONANG after the improvement technology compare, and the results are shown in following table:

New technology capsule and the capsular comparison of former technology

Above-mentioned data show that new capsule is better than former capsule, and technology is reasonable, and is quality controllable, technology advanced person, and drug effect is remarkable, and taking dose is little, and clinical dosage is safely and effectively.

The 'Xue Fu Zhu Yu ' pharmacodynamics test:

This medicine of 'Xue Fu Zhu Yu ' (former dosage form is a capsule) has been widely used in clinical, and has obtained effect preferably.Because clinical large usage quantity, 'Xue Fu Zhu Yu ' has been carried out process modification, we have carried out the pharmacodynamic study of hemorheology, platelet aggregation and 3 test models of microcirculation to the new technology sample, and and former dosage form compare.The result is as follows:

Rheology test: choose above-mentioned healthy rat, male and female dual-purpose, body weight 200 ~ 250g.Be divided into normal control group, model control group, 'Xue Fu Zhu Yu ' 1.5,3,6g crude drug/kg dosage group at random by sex, body weight, ((the dosage group of 3g medicated powder/kg), totally 7 groups, every group is 10 to former dosage form for the dosage group of 6g crude drug/kg), positive drug compound Salviae Miltiorrhizae.Gastric infusion, once a day, continuous 10 days, to irritate the stomach volume and be the 1ml/100g body weight, normal control group and model control group are all irritated stomach and are waited capacity 0.5%CMC.After the last administration 1 hour, except that the normal control group, all the other respectively organized the equal tail vein injection 10% high molecular dextran injection 1ml/kg of rat, cause the blood high viscosity syndrome model.Quiet notes from abdominal aortic blood, with 3.8% sodium citrate anticoagulant (anticoagulant is 1: 9 with the ratio of whole blood), were measured 4 whole blood and plasma viscosities of cutting under the speed after 10 minutes on the LG-R-80C viscometer.In the hematocrit pipe, measure packed cell volume and erythrocyte sedimentation rate.Result of the test adopts two groups of mean statistical analysiss-t value method to carry out significance test, compares with the normal control group, and whole blood viscosity, the plasma viscosity under the speed respectively cut in the obvious rising of model control group, and packed cell volume obviously reduces erythrocyte sedimentation rate, shows the moulding success.Compare with model control group, 'Xue Fu Zhu Yu ' 1.5,3,6g crude drug/kg dosage group all obviously reduce the whole blood viscosity of blood high viscosity syndrome rat, and 6g crude drug/kg dosage carefully also obviously reduces plasma viscosity and packed cell volume.Each dosage group is to the equal no significant difference of erythrocyte sedimentation rate.The former dosage form of 'Xue Fu Zhu Yu ', positive control drug FUFANG DANSHEN PIAN also have similar action.

Influence test to " blood stasis " rat platelet aggregation function: select healthy male Wistar kind rat for use, body weight 250g～300g is divided into 6 groups at random by body weight, 10 every group.'Xue Fu Zhu Yu ' administration group irritates respectively that stomach gives 1.5,3,6g crude drug/kg, the former dosage form group of 'Xue Fu Zhu Yu ' irritate that stomach gives 6g crude drug/kg, the positive drug group is irritated stomach and given aspirin 150mg/kg, irritate the stomach volume and be the 1ml/100g body weight, model control group is irritated stomach and is waited capacity 0.5%CMC, once a day, continuous 10 days.Each dosage group rat is all in the adrenalin hydrochloride 0.08ml/100g body weight of preceding 1 day subcutaneous injection 1mg/ml of test, and totally twice, 6 hours at interval, (about 3 hours) put into frozen water swimming 5 minutes with rat therebetween, and fasting then (can't help water) is spent the night.Behind the next day gastric infusion 1 hour, pentobarbital sodium (40mg/kg) intraperitoneal anesthesia, abdominal aortic blood, with 3.8% sodium citrate anticoagulant (anticoagulant is 1: 9 with the ratio of whole blood), centrifugal, preparation platelet rich plasma (PRP) and platelet poor plasma (PPP), (platelet count is about 300,000/mm to transfer PRP with PPP ³).Adopt turbidimetry, as derivant, carry out PAgT,, calculate the maximum percentage rate of assembling of platelet, observe the effect of 'Xue Fu Zhu Yu ' according to tracing curve at PAM-3 type dual pathways platelet aggregation instrument with ADP, AA, collagen.The result adopts two groups of mean statistical analysiss-t value method to carry out significance test, 'Xue Fu Zhu Yu ' 1.5,3,6g crude drug/kg dosage group and model control group are relatively, obviously suppress platelet aggregation by ADP, AA (removing 1.5g crude drug/kg dosage group), collagen (removing 1.5g crude drug/kg dosage group) inductive " blood stasis " rat, and increase with dosage, effect strengthens, and shows that 'Xue Fu Zhu Yu ' has tangible antiplatelet aggregative activity.The former dosage form of 'Xue Fu Zhu Yu ', positive drug aspirin also have obvious inhibitory action.

Influence is tested to the microcirculation disturbance microcirculation of mouse auricle: select healthy Kunming mouse for use, body weight 18 ~ 22g is divided into 7 groups at random, and 11 every group, equal male and female dual-purpose.Normal control group, model control group, 'Xue Fu Zhu Yu ' 3,6,12g crude drug/kg dosage group, the former dosage form 6g crude drug of 'Xue Fu Zhu Yu '/kg dosage group, positive drug FUFANG DANSHEN PIAN 4g medicated powder/kg dosage group are established in experiment.Gastric infusion, once a day, continuous 10 days, to irritate the stomach volume and be the 0.2ml/10g body weight, normal control group and model control group are all irritated stomach and are waited capacity 0.5%CMC.After the last administration 1 hour, lumbar injection pentobarbital sodium 50mg/kg after the anesthesia, dripped olive oil on microscope slide, and mice left side ear is open and flat, fixing.Observation and the microvascular fluidised form of record Mice Auricle, erythrocyte aggregation degree, point of intersect of the capillary network number under 50 power microscopes are as numerical value before the moulding.Tail vein injection 10% high molecular dextran (except the normal control group) 0.1ml/10g body weight then, back 5 minutes, 10 minutes, 20 minutes, 30 minutes microvascular fluidised forms in same position of record injection, erythrocyte aggregation degree, point of intersect of the capillary network number, relatively the effect of 'Xue Fu Zhu Yu ' is observed in the variation before and after the moulding.Fluidised form and erythrocyte aggregation degree adopt grade preface value method to carry out significance test, the point of intersect of the capillary network number adopts pairing t-value method to carry out significance test, result of the test shows: compare with the normal control group, the model control group mice is before the moulding of injection high molecular dextran, the blood fluidised form, the erythrocyte aggregation degree, point of intersect of the capillary network number average no significant difference, after the moulding 5,10,20,30 minutes, blood flow obviously slows down, erythrocyte aggregation obviously increases, the point of intersect of the capillary network number obviously reduces (30 minutes no significant differences), show to form microcirculation disturbance the model copy success.Compare with model control group, each dosage group blood fluidised form, erythrocyte aggregation degree, point of intersect of the capillary network number average no significant difference before the moulding, after the moulding 5,10,20,30 minutes, 'Xue Fu Zhu Yu ' 6,12g crude drug/kg and former dosage form 6g crude drug/kg dosage group all can obviously reduce blood fluidised form rank and erythrocyte aggregation (5 minutes, 10 minutes and 20 minutes), obviously increases point of intersect of the capillary network number (5 minutes, 10 minutes and 20 minutes).FUFANG DANSHEN PIAN 4g medicated powder/kg dosage group also has obvious effect.

Microcirculatory influence is tested to the rabbit conjunctive bulbi: select healthy big ear white race rabbit for use, and the male and female dual-purpose, body weight 2 ~ 2.6kg is divided into 7 groups at random by sex, body weight, and every group is 8.Normal control group, model control group, 'Xue Fu Zhu Yu ' 0.75,1.5,3g crude drug/kg dosage group, the former dosage form 3g crude drug of 'Xue Fu Zhu Yu '/kg dosage group, positive drug FUFANG DANSHEN PIAN 2g medicated powder/kg dosage group are established in experiment.Gastric infusion, once a day, continuous 7 days, to irritate the stomach volume and be the 5ml/kg body weight, normal control group and model control group are all irritated stomach and are waited capacity 0.5%CMC.After the last administration 1 hour, intravenous injection pentobarbital sodium 30mg/kg, after the anesthesia, (20 * 2.5 times) are observed and the microvascular red cell velocity of record rabbit conjunctive bulbi, fluidised form and point of intersect of the capillary network number under anatomic microscope, as numerical value before the moulding.Auricular vein is injected 10% high molecular dextran (except the normal control group) 1ml/kg body weight then, cause the rabbit microcirculation disturbance, back 20 minutes microvascular red cell velocity in same position of record injection, fluidised form, point of intersect of the capillary network number, relatively the effect of 'Xue Fu Zhu Yu ' is observed in the variation before and after the moulding.Fluidised form adopts grade preface value method to carry out significance test, flow velocity and point of intersect of the capillary network number adopt pairing t-value method to carry out significance test, result of the test shows: compare with the normal control group, the model control group rabbit before injection high molecular dextran moulding, the microvascular blood fluidised form of conjunctive bulbi, flow velocity, point of intersect of the capillary network number average no significant difference; After the moulding 20 minutes, velocity of blood flow obviously slowed down, the fluidised form rank obviously increases, the point of intersect of the capillary network number obviously reduces, and showed to form microcirculation disturbance the model copy success.Compare the microvascular blood fluidised form of each dosage group conjunctive bulbi, flow velocity, point of intersect of the capillary network number average no significant difference before the moulding with model control group; After the moulding 20 minutes, 'Xue Fu Zhu Yu ' 1.5,3g crude drug/kg and former dosage form 3g crude drug/kg dosage group all can obviously increase velocity of blood flow and point of intersect of the capillary network number, obviously reduces blood fluidised form rank.Positive drug FUFANG DANSHEN PIAN 2g medicated powder/kg dosage group also has obvious effect.

Conclusion (of pressure testing):

1. (the 6g crude drug/kg) group all obviously reduces the whole blood viscosity of blood high viscosity syndrome rat, and 6g crude drug/kg dosage group also obviously reduces plasma viscosity and packed cell volume for 'Xue Fu Zhu Yu ' 1.5,3,6g crude drug/kg dosage group and former dosage form.

2. 'Xue Fu Zhu Yu ' 1.5,3,6g crude drug/kg dosage group and former dosage form group all obviously suppress " blood stasis " rat by ADP, AA (removing 1.5g crude drug/kg dosage group), the inductive platelet aggregation of collagen (removing 1.5g crude drug/kg dosage group).

3. 'Xue Fu Zhu Yu ' 6,12g crude drug/kg dosage group and former dosage form group all obviously reduce rank, the erythrocyte aggregation degree of microcirculation disturbance Mice Auricle blood capillary blood fluidised form, obviously increase the point of intersect of the capillary network number.

4. 'Xue Fu Zhu Yu ' 1.5,3g crude drug/kg dosage group and former dosage form group all obviously reduce the rank of microcirculation disturbance rabbit conjunctive bulbi blood capillary blood fluidised form, obviously increasing blood flow speed and point of intersect of the capillary network number.

Above result of the test shows that the new technology 'Xue Fu Zhu Yu ' has significantly " blood circulation promoting and blood stasis dispelling " effect.Cure mainly substantially with the function of this medicine and to conform to.Suitable with the former dosage form effect of same dose 'Xue Fu Zhu Yu '.The former capsular dosage of mansion removing blood stasis: oral 6/time, every day secondary, (each the suitable crude drug 4.05g of dose).This product dosage is to determine according to the taking dose of former XUEFUZHUYU JIAONANG: the dosage that improves the XUEFU ZHUYU JIAONANG after the technology: oral 3/time, every day secondary.(each suitable crude drug 4.05g of dose).It is consistent that former XUEFUZHUYU JIAONANG contains the crude drug amount with the oral dose of the XUEFU ZHUYU JIAONANG of improving technology.

The invention beneficial effect: the discriminating project of Semen Persicae, Fructus Aurantii, Radix Glycyrrhizae is set in the quality standard, and every capsules contains Radix Paeoniae Rubra with peoniflorin (C ₂₃H ₂₈O ₁₁) meter, must not be less than the quantitative target and the method for inspection of 2.20mg, improve the quality of products, and definite best process flow and process conditions, it is little to make XUEFU ZHUYU JIAONANG have a taking dose, absorb in vivo fast, characteristics such as taking convenience.

Description of drawings

Fig. 1 is the peoniflorin canonical plotting.

Fig. 2 is the best processing route figure.

The specific embodiment

XUEFU ZHUYU JIAONANG quality standard after embodiment 1 improves

1. title: XUEFU ZHUYU JIAONANG

2. write out a prescription:

Semen Persicae (stir-fry) Radix Angelicae Sinensis Fructus Aurantii (parched with bran) Rhizoma Chuanxiong

Radix Bupleuri Flos Carthami Radix Achyranthis Bidentatae Radix Paeoniae Rubra

Radix Rehmanniae Radix Platycodonis Radix Glycyrrhizae

[character] this product is a capsule, and content is tan powder; The gas suffering, mildly bitter flavor.

[method for making] gets ten Herba indigoferae Pseudotinctoriae water extraction 1-3 times such as Radix Angelicae Sinensis, water consumption 6-10 doubly, each 0.5-1.5h, filter, collect filtrate, being evaporated to relative density is 1.07-1.35 (60-70 ℃), treats cold placement room temperature, adds ethanol and makes and contain the alcohol amount and be 60-80%, stir evenly, leave standstill (5-25h) and make precipitation, get supernatant and be evaporated to the starch that relative density is 1.30-1.50 (60-70 ℃) adding extractum amount 10-15%, dry 5-12h in drying baker (T=65-80 ℃), get dry thing (dried cream rate 20-28%), add the silicon dioxide of dry thing weight 2%-8%, incapsulate, pulverized the 24-60 mesh sieve.(every gram capsule is equivalent to crude drug 3.10 ~ 3.38g)

[discriminating]

1, microscopical identification

Get this product, put microscopically and observe: parenchyma cell spindle, wall are slightly thick, and atomic thin oblique cross lamination is arranged.Oil pipe contains yellow or pale brown color secretions.Spiral duct diameter 8～23 μ m, thickened wall is interconnection, and like netted spiral duct, prism of calcium oxalate is present in the parenchyma in flakes.

2, hesperidin is differentiated

Get this product 5g, add methanol 20ml, merceration spends the night, and filters, and filtrate is concentrated into 2ml, as need testing solution.Other gets the hesperidin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB), draw each 2 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with ethyl acetate-alcohol-water (8: 2: 1) is developing solvent, launches, and takes out, dry, spray is with 5% magnesium acetate methanol solution, treat that methanol volatilizes after, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the fluorescence speckle of same color.

3, Radix Paeoniae Rubra is differentiated

Finished product powder 10g is got in the preparation of need testing solution, adds 70% ethanol 50ml dissolving, and placement is spent the night.Filter, filtrate is waved most ethanol, adds water to 20ml, uses ethyl acetate extraction 2 times, each 20ml.Combining extraction liquid with anhydrous sodium sulfate 2g dehydration, is concentrated into about 2ml, as need testing solution after the filtration.

Radix Paeoniae Rubra fine powder 2g is got in the preparation of control medicinal material solution, add 70% ethanol 30ml dissolving after, make Radix Paeoniae Rubra control medicinal material solution by the method under the need testing solution preparation.

The preparation of blank solution is removed Radix Paeoniae Rubra with the prescription of XUEFU ZHUYU JIAONANG, makes the blank product according to production technology, makes blank product solution by the method under the need testing solution preparation again.

Tlc analysis is got each 10 μ l of above-mentioned 3 kinds of solution, puts respectively on same high-efficient silica gel G plate, and (40: 5: 10: 0.2) be developing solvent, exhibition was apart from about 15cm with chloroform-ethyl acetate-methanol-formic acid.Take out, dry.Spray is with 5% vanillin sulfuric acid solution, and hot blow wind to speckle manifests.Test sample chromatograph and control medicinal material chromatograph have the speckle of same color on corresponding position, blank is noiseless.

4, the discriminating of Semen Persicae: get this product content 1g, add water 20ml dissolving, add ether 20ml extraction 2 times, discard ether solution, aqueous solution reuse ethyl acetate 30ml extraction 2 times is collected ethyl acetate liquid and is volatilized, and adds 2ml methanol and promptly gets need testing solution.Other gets the naringin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography (" appendix VIB of Chinese pharmacopoeia version in 2000) test, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, the subnatant of placing 12 hours with chloroform-methanol-water (45: 17: 5) launches, take out, dry, spray is put under the ultra-violet lamp (365nm) with the aluminum chloride methanol solution and is inspected.In the test sample chromatograph, with the corresponding position of reference substance on, show identical bright fluorescence speckle.

5, the discriminating of Fructus Aurantii: get this product content 1g, adding methanol 15ml supersound process 10min filters, filtrate evaporated under reduced pressure adds silica gel (100-160 order) 0.5g, mixing to small size, evaporate to dryness, add on the silicagel column (column diameter 1cm column length 25cm, silica gel 100 ~ 160 order 5g, dry column-packing) with chloroform: ethyl acetate: methanol: (15: 40: 22: 10) 5～10 ℃ of lower floors of placing 12 hours were eluent to water, eluting is collected 16～21ml liquid and is promptly got need testing solution.Other gets the amygdaloside reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography (" appendix VIB of Chinese pharmacopoeia version in 2000) test, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with the eluant is that developing solvent launches, take out, dry, spray immediately with phosphorus molybdenum acid solution (phosphomolybdic acid 2g, add water 20ml and make dissolving, slowly add sulphuric acid 30ml mixing again.) put about 10 minutes of 105 ℃ of heating colour developings, in the test sample chromatograph, with the corresponding position of reference substance on, show identical navy blue speckle.

6, the discriminating of Radix Glycyrrhizae: get this product content 2g, the 30ml that adds diethyl ether, supersound process 10min, filter, discard ether solution, residue adds methanol 30ml, supersound process l0min, filtrate evaporated under reduced pressure adds water 40ml dissolving to doing, and uses n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, be decompressed to driedly, add methanol 5ml dissolving, promptly get need testing solution.Extracting liquorice acid mono-ammonium reference substance adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution in addition.According to thin layer chromatography (" appendix VIB of Chinese pharmacopoeia version in 2000) test, draw each 2～4 μ l of above-mentioned two kinds of solution, put respectively in same high-efficient silica gel GF ₂₅₄On the lamellae, be that developing solvent launches, take out, dry, put under the ultra-violet lamp (254nm) and inspect with n-butyl alcohol-20% ammonia-methanol (5: 2: 1.5), in the test sample chromatograph, with the corresponding position of reference substance on, show identical black-and-blue speckle.

[inspection] content uniformity: get test sample, according to, " the content uniformity method is measured under an appendix IL of Chinese pharmacopoeia version in 2005 the capsule item, every loading amount is compared with the standard loading amount, should be ± 10.0% with interior (statutory standards should in ± 10.0%), what exceed the content uniformity limit must not be more than 2, and one times of 1 overrun must not be arranged.

Moisture: get the test sample content, according to " an appendix IX of Chinese pharmacopoeia version in 2005 H aquametry is measured, and should cross 8.0% (statutory standards should cross 9.0%).

Disintegration: according to " an appendix XII of Chinese pharmacopoeia version in 2005 A inspection technique disintegration is measured, and is medium with water, must not spend 20 minutes disintegration (legal must not spend 30 minutes).

Limit test of microbe: according to " an appendix XIII of Chinese pharmacopoeia version in 2005 C checks, should meet down

Row regulations: bacterial population must not cross 10000/g (statutory standards must not cross 10000/g).Mycete and yeast count

Must not cross 100/g (statutory standards must not cross 100/g).The escherichia coli and the demodicid mite that lives must not detect.Coliform

A group of mean people in 100/g (statutory standards less than 100/g).

[assay] measured according to high performance liquid chromatography (appendix VID)

Chromatographic condition and system suitability test are filler with the octadecyl silane; With second eyeball-water (16: 84) is mobile phase; The detection wavelength is 230nm.Number of theoretical plate calculates by the peoniflorin peak should be not less than 4300.

It is an amount of that the preparation of reference substance solution takes by weighing the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes the solution that every 1ml contains 0.1mg, promptly.

This product content 0.3g is got in the preparation of need testing solution, porphyrize, and accurate the title, decide.Insert in the 25ml measuring bottle and to add methanol 24ml, ultrasonic 10min is put coldly, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate and puts in the brown bottle, promptly.

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Every of this product contains Radix Paeoniae Rubra with peoniflorin (C ₂₃H ₂₈O ₁₁) meter, must not be less than 2.20mg.

[function with cure mainly]

Blood circulation promoting and blood stasis dispelling, promoting the circulation of QI to relieve pain.Be used for blood-stasis internal-depression, chest pain or headache, interior-heat blurring of vision accompanied with oppressive feeling, insomnia and dreamful sleep, severe palpitation, impatience and irascibility; Angina pectoris, blood vessel and traumatic headache belong to above-mentioned disease person.

[usage and consumption] is oral, one time 3,2 times on the one, one month is a course of treatment.

The hot cold drinks and snachs thing of [points for attention] diet.Be not taken by pregnant women.

Every dress of [points for attention] specification 0.4g

Shady and cool dry place is put in [storage] sealing.

[expiry date] 3 years.

Embodiment 2

Get ten Herba indigoferae Pseudotinctoriae 1.35kg such as Radix Angelicae Sinensis, with water extraction 2 times, 8 times of each water consumptions, each extraction time 1h filters, collect filtrate, being evaporated to relative density is 1.16 (60 ℃), treats cold placement room temperature, adds ethanol and makes that to contain the alcohol amount be 70%, stir evenly, leave standstill and make precipitation, getting supernatant, to be evaporated to relative density be 1.402 (60 ℃), adds the starch of 61.5g, dry 9h in drying baker (T=70-75 ℃), get dry thing 378g, add the silicon dioxide of 22.68g, pulverized 40 mesh sieves, incapsulate, make 1000.(every gram capsule is equivalent to crude drug 3.375g)

Embodiment 3

Get ten Herba indigoferae Pseudotinctoriae 1.35kg such as Radix Angelicae Sinensis, with water extraction 3 times, 6 times of each water consumptions, each extraction time 0.5h filters, collect filtrate, being evaporated to relative density is 1.08 (60 ℃), treats cold placement room temperature, adds ethanol and makes that to contain the alcohol amount be 60%, stir evenly, leave standstill and make precipitation, getting supernatant, to be evaporated to relative density be 1.43 (60 ℃), adds the starch of 64.8g, dry 9h in drying baker (T=65-70 ℃), get dry thing 375g, add the silicon dioxide of 25.53g, pulverized 24 mesh sieves, incapsulate, make 1000.(every gram capsule is equivalent to crude drug 3.215g)

Embodiment 4

Get ten Herba indigoferae Pseudotinctoriae 1.35kg such as Radix Angelicae Sinensis, with water extraction 1 time, 10 times of each water consumptions, each extraction time 1.5h filters, collect filtrate, being evaporated to relative density is 1.21 (60 ℃), treats cold placement room temperature, adds ethanol and makes that to contain the alcohol amount be 80%, stir evenly, leave standstill and make precipitation, getting supernatant, to be evaporated to relative density be 1.38 (60 ℃), adds the starch of 67.9g, dry 9h in drying baker (T=75-80 ℃), get dry thing 371g, add 29.82 silicon dioxide, pulverized 24 mesh sieves, incapsulate, make 1000.(every gram capsule is equivalent to crude drug 3.185g)

Claims (4)

1, a kind of preparation method of XUEFU ZHUYU JIAONANG is characterized in that with following weight proportion Chinese crude drug be raw material:

Radix Angelicae Sinensis 162g Semen Persicae 216g Flos Carthami 162g Radix Achyranthis Bidentatae 162g

Radix Rehmanniae 162g Radix Paeoniae Rubra 108g Fructus Aurantii 108g Radix Platycodonis 81g

Rhizoma Chuanxiong 81g Radix Bupleuri 54g Radix Glycyrrhizae 54g,

Preparation method is: get ten Herba indigoferae Pseudotinctoriae water extraction 1-3 times such as Radix Angelicae Sinensis, water consumption 6-10 doubly, each 0.5-1.5h, filter, collect filtrate, being evaporated to relative density is 1.07-1.35,60-70 ℃ of mensuration, treat cold placement room temperature, add ethanol and make and contain the alcohol amount and be 60-80%, stir evenly, leave standstill 5-25h and make precipitation, getting supernatant, to be evaporated to relative density be 1.30-1.50, and 60-70 ℃ of mensuration adds the starch of extractum amount 10-15%, dry 5-12h in drying baker, T=65-80 ℃, get dry thing, dried cream rate 20-28%, the silicon dioxide that adds dry thing weight 2%-8%, incapsulate, pulverized the 24-60 mesh sieve, every gram capsule is equivalent to crude drug 3.10～3.38g.

2, the preparation method of XUEFU ZHUYU JIAONANG according to claim 1 is characterized in that with following weight proportion Chinese crude drug be raw material:

Radix Angelicae Sinensis 162g Semen Persicae 216g Flos Carthami 162g Radix Achyranthis Bidentatae 162g

Radix Rehmanniae 162g Radix Paeoniae Rubra 108g Fructus Aurantii 108g Radix Platycodonis 81g

Rhizoma Chuanxiong 81g Radix Bupleuri 54g Radix Glycyrrhizae 54g,

The preferred for preparation method is: get ten Herba indigoferae Pseudotinctoriae water extraction 2 times such as Radix Angelicae Sinensis, 8 times of each water consumptions, each extraction time 1h, filter, collect filtrate, being evaporated to relative density is 1.16-1.19,60 ℃ of mensuration are treated cold placement room temperature, add ethanol and make that to contain the alcohol amount be 70%, stir evenly, leave standstill and make precipitation, getting supernatant, to be evaporated to relative density be 1.35-1.43,60 ℃ of mensuration, the starch that adds extractum amount 15%, dry 9h in drying baker, gets dry thing by T=70-75 ℃, dried cream rate 23-25%, the silicon dioxide that adds dry thing weight 6% was pulverized 40 mesh sieves, incapsulated, make 1000, every gram capsule is equivalent to crude drug 3.375g.

3, a kind of quality standard of XUEFU ZHUYU JIAONANG is characterized in that being provided with in the quality standard discriminating project of Semen Persicae, Fructus Aurantii, Radix Glycyrrhizae, and every capsules contains Radix Paeoniae Rubra with peoniflorin C ₂₃H ₂₈O ₁₁Count, must not be less than the quantitative target of 2.20mg.

4, a kind of quality standard of XUEFU ZHUYU JIAONANG, it is characterized in that the method for inspection that is provided with in the quality standard is the discriminating of Semen Persicae: get this product content 1g, add water 20ml dissolving, add ether 20ml extraction 2 times, discard ether solution, aqueous solution reuse ethyl acetate 30ml extraction 2 times is collected ethyl acetate liquid and is volatilized, and adds 2ml methanol and promptly gets need testing solution.Other gets the naringin reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.According to appendix VIB test of thin layer chromatography " Chinese Pharmacopoeia " version in 2005, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, the subnatant of placing at 45: 17: 5 12 hours with chloroform-methanol-water launches, and takes out, and dries, spray is put under the ultra-violet lamp 365nm with the aluminum chloride methanol solution and is inspected, in the test sample chromatograph, with the corresponding position of reference substance on, show identical bright fluorescence speckle;

The discriminating of Fructus Aurantii: get this product content 1g, add methanol 15ml supersound process 10min, filter, filtrate evaporated under reduced pressure adds silica gel 100-160 order 0.5g, mixing to small size, evaporate to dryness, add column diameter 1cm column length 25cm on the silicagel column, silica gel 100～160 order 5g, dry column-packing, with chloroform: ethyl acetate: methanol: water 15: 40: 22: 10,5～10 ℃ of lower floors of placing 12 hours are eluent, and eluting is collected 16～21ml liquid and promptly got need testing solution; Other gets the amygdaloside reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution; According to appendix VIB test of thin layer chromatography " Chinese Pharmacopoeia " version in 2005, draw each 5-10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with the eluant is that developing solvent launches, and takes out, and dries, spray immediately with phosphorus molybdenum acid solution, phosphomolybdic acid 2g adds water 20ml and makes dissolving, slowly adds sulphuric acid 30ml mixing again; Put about 10 minutes of 105 ℃ of heating colour developings, in the test sample chromatograph, with the corresponding position of reference substance on, show identical navy blue speckle;

The discriminating of Radix Glycyrrhizae: get this product content 2g, the 30ml that adds diethyl ether, supersound process 10min, filter, discard ether solution, residue adds methanol 30ml, supersound process 10min, filtrate evaporated under reduced pressure adds water 40ml dissolving to doing, and uses n-butanol extraction 3 times, each 20ml merges n-butyl alcohol liquid, be decompressed to driedly, add methanol 5ml dissolving, promptly get need testing solution; Extracting liquorice acid mono-ammonium reference substance adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution in addition; According to appendix VIB of thin layer chromatography " Chinese Pharmacopoeia " version in 2005) test, draw each 2～4 μ l of above-mentioned two kinds of solution, put respectively in same high-efficient silica gel GF ₂₅₄On the lamellae, be at 5: 2: 1.5 that developing solvent launches, take out, dry, put under the ultra-violet lamp 254nm and inspect with n-butyl alcohol-20% ammonia-methanol, in the test sample chromatograph, with the corresponding position of reference substance on, show identical black-and-blue speckle;

Assay: measure according to high performance liquid chromatography (appendix VI D), chromatographic condition and system suitability test: with the octadecyl silane is filler; With second eyeball-water is mobile phase at 16: 84; The detection wavelength is 230nm.Number of theoretical plate calculates by the peoniflorin peak should be not less than 4300.

The preparation of reference substance solution: it is an amount of to take by weighing the peoniflorin reference substance, accurately claims surely, adds methanol and makes the solution that every 1ml contains 0.1mg, promptly.

The preparation of need testing solution: get this product content 0.3g, porphyrize, the accurate title, decide.Insert in the 25ml measuring bottle and to add methanol 24ml, ultrasonic 10min is put coldly, adds methanol to scale, shakes up, and microporous filter membrane filters, and gets subsequent filtrate and puts in the brown bottle, promptly.

Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.

Images