CN101057926A - Gynaecologic menstruation regulating preparation for treating gynecopathy and its preparation method and quality control method - Google Patents
Gynaecologic menstruation regulating preparation for treating gynecopathy and its preparation method and quality control method Download PDFInfo
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Abstract
The invention relates to a pharmaceutical preparation for treating gynaecologic diseases and regulating menstruation, its preparing process and quality control method, wherein the preparation is made mainly from Chinese angelica root, Ligusticum wallichii, prepared nutgrass flatsedge rhizome, white atractylodes rhizome, root of herbaceous peony and red peony root, and can be made into dispersible tablets, mini-pills, dripping pills, soft capsules and pharmacologically allowable dose forms. The invention also provides the method for determining and identifying contents of the preparation.
Description
Technical field
The present invention is a kind of gynecological's menstruation-regulating preparation for the treatment of gynaecopathia and preparation method thereof and method of quality control, belongs to technical field of Chinese medicine.
Technical background
Gynaecopathia such as menoxenia, abdominal pain in menstruation etc. all are to threaten the able-bodied common disease of women in the world today, have brought great misery for numerous women, prevent and treat purpose in order to reach, a large amount of research has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; As: gynecological's regulating menstruation granule, still, the dose of granule is big, and supplementary product consumption is many, the easy moisture absorption, unstable product quality.And the dosage form kind is abundant inadequately, is suitable for crowd's narrow range, and bioavailability, the medicine stability of conventional dosage forms are undesirable, and the problem that especially bioavailability of effective ingredient is not high is badly in need of solving; In view of such circumstances, improve the thing that technology or improvement dosage form have just become people to be badly in need of solving.
Summary of the invention
The objective of the invention is to: a kind of gynecological's menstruation-regulating preparation for the treatment of gynaecopathia and preparation method thereof is provided; The present invention is directed to prior art, the micropill that provides, dispersible tablet, disintegrative are good, and the bioavailability height is particularly suitable for the old people and swallow tablet or the inconvenient patient of capsule take; Soft capsule preparation provided by the invention forms drug blockage in soft gel coat, solved medicine and met damp and hot problem of unstable, can also cover the poor taste and the abnormal smells from the patient of medicine, can play the effect that increases stability, improves bioavailability; Drop pill good mouthfeel provided by the invention absorbs soon bioavailability height, taking convenience.
The present invention constitutes like this: calculate according to weight, it is with Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g all the acceptable dosage forms on the pharmaceutics that are made comprise: injection, the powder pin, freeze-dried powder, tablet, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, micropill, powder, drop pill, slow releasing preparation, controlled release preparation, gel, oral liquid, soft extract, extractum and membrane.Say accurately: described preparation is dispersible tablet, soft capsule, granule, micropill, gel, oral liquid, drop pill, sustained-release preparation, tablet, effervescent tablet or capsule.
The method for making of gynecological's menstruation-regulating preparation of described treatment gynaecopathia: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, makes different preparations then respectively.Drop pill in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 1～2.5 part of Macrogol 4000 adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip, drip speed 20～50d/min apart from 1～9cm, 60～90 ℃ of material temperature, drip and in 20～30 ℃ dimethicone, to become ball, collect drop pill, remove the methyl-silicone oil on surface, packing, promptly.Say accurately, drop pill in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate, be 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 2 parts of Macrogol 4000s adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip, drip speed 30～40d/min apart from 3～7cm, 70～80 ℃ of material temperature, drip and in 20～30 ℃ dimethicone, to become ball, collect drop pill, remove the methyl-silicone oil on surface, packing, promptly.
Pellet in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate, it when being evaporated to 80～85 ℃ of relative densities 1.18～1.20 clear paste, drying under reduced pressure is pulverized, and adds an amount of starch, with 70% ethanol and soybean oil system soft material, extruding-round as a ball pill or the general ball of making of employing coating pan, drying, promptly.
Dispersible tablet in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Get CMC-Na: PVPP: mannitol=add an amount of pigment mixing as pharmaceutical adjunct at 1: 2: 2, get 3/5 pharmaceutical adjunct and the medicated powder mix homogeneously that is equivalent to 8 times of amounts of CMC-Na approximately, PVP-K with 2%
30Anhydrous alcohol solution is made binding agent, and 40 order system material, granulate remain 2/5 pharmaceutical adjunct and an amount of caramel color mixing, be added on outward in the particle that makes, and tabletting, promptly.
Soft capsule in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure, pulverize, cross 80 mesh sieves, press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%, pelleting; The dry typing drying of rolling that adopts combined with two steps of tray dried, dry 2 hours of the typing of rolling, and 22 ℃ of baking temperatures, dry relative humidity should be lower than 40%, and drying time is at 24～48 hours, promptly.
The method of quality control of gynecological's menstruation-regulating preparation of described treatment gynaecopathia, its discrimination method comprise following part or all of content:
A. one or both thin layer chromatography discriminating in Rhizoma Cyperi medical material, the α-cyperone in the preparation
It is an amount of to get this product powder, is dissolved in water or extracts, and aqueous solution adds diethyl ether or ethyl acetate or chloroform jolting are extracted, and extracting solution concentrates or evaporate to dryness adds the appropriate solvent dissolving again, as need testing solution; Other gets the Rhizoma Cyperi control medicinal material, with reference to the need testing solution method for making, makes control medicinal material solution; Get α-cyperone, make reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-ethyl acetate-formic acid=6～8: be developing solvent at 4～6: 0.1～0.3, launch, take out, dry, spray is with the vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the same color speckle;
B. one or both thin layer chromatography discriminating in corydalis tuber medicinal material, the tetrahydropalmatine in the preparation
It is an amount of to get this product powder, adds methanol or ethanol supersound process, filters, and filtrate evaporate to dryness, residue add water makes dissolving, adds alkali liquor and transfers to alkalescence, extracts with ether or chloroform jolting, and extracting solution concentrates or evaporate to dryness adds the appropriate solvent dissolving again, as need testing solution; Other gets the Rhizoma Corydalis control medicinal material, with reference to the need testing solution method for making, makes control medicinal material solution; Get tetrahydropalmatine, make reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate with the sodium hydroxide solution preparation, with toluene-acetone=8～10: 1.5～2.5 is developing solvent, launch, take out, dry, put in the iodine steam smoked after, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the fluorescence speckle of same color;
C. one or more thin layer chromatography discriminating in Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, the ferulic acid in the preparation
It is an amount of to get this product, is dissolved in water or extracts, and water liquid extracts with the ether jolting, ether solution extracts with the alkali liquor jolting, and alkali liquor extracts with acid for adjusting pH value to 1～3, reuse ether or ethyl acetate jolting, extracting solution concentrates or evaporate to dryness adds the appropriate solvent dissolving again, as need testing solution; Other gets Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, add the alkaline solution supersound extraction respectively, extracting solution is with adding acid for adjusting pH value to 1～3, and reuse ether or ethyl acetate jolting are extracted, extracting solution concentrates or evaporate to dryness adds the appropriate solvent dissolving again, makes Radix Angelicae Sinensis control medicinal material solution, Rhizoma Chuanxiong control medicinal material solution respectively; Other gets the ferulic acid reference substance, makes reference substance solution; According to thin layer chromatography test, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively in same with silica gel G F
254On the plate, with benzene-methanol-glacial acetic acid=13～17: be developing solvent at 1～2: 0.8～1.2, launches, and takes out, and dries, and puts under the ultra-violet lamp 254nm and inspect; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color;
D. one or more thin layer chromatography discriminating in white Peony Root, Radix Paeoniae Rubra medical material, the peoniflorin in the preparation
It is an amount of to get this product, is dissolved in water or extracts, and water liquid extracts with water saturated n-butyl alcohol jolting, n-butyl alcohol liquid evaporate to dryness, and residue adds methanol or ethanol makes dissolving, as need testing solution; Other gets white Peony Root, Radix Paeoniae Rubra medical material, adds methanol or ethanol extraction, makes control medicinal material solution respectively; Get the peoniflorin reference substance, make every reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate, with chloroform-methanol=7～9: 1.5～2.5 is developing solvent, launch, take out, dry, spray is with the vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
Say accurately: discrimination method comprises following part or all of content:
A. one or both thin layer chromatography discriminating in Rhizoma Cyperi medical material, the α-cyperone in the preparation
It is an amount of to get this product, is dissolved in water or extracts, and the jolting that adds diethyl ether of water liquid is extracted, and ether solution volatilizes, and residue adds dissolve with methanol, as need testing solution; Other gets the Rhizoma Cyperi control medicinal material, adds the water heating extraction, filters, and the jolting that adds diethyl ether of water liquid is extracted, and ether solution volatilizes, and residue adds dissolve with methanol, in contrast medical material solution; Get α-cyperone, add methanol and make reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-ethyl acetate-formic acid=7: 5: 0.2 was developing solvent, launch, take out, dry, spray is with the vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the same color speckle;
B. one or both thin layer chromatography discriminating in corydalis tuber medicinal material, the tetrahydropalmatine in the preparation
It is an amount of to get this product powder, adds the methanol supersound process, filters, and filtrate evaporate to dryness, residue add water makes dissolving, adds strong ammonia solution and transfers to alkalescence, extracts with the ether jolting, and ether solution concentrates, as need testing solution; Other gets the Rhizoma Corydalis control medicinal material, shines medical material solution in pairs with legal system; Get tetrahydropalmatine, add methanol and make reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with toluene-acetone=9: 2 was developing solvent, launched, and took out, dry, put in the iodine cylinder after about 3 minutes and take out, wave the iodine that adsorbs on the most plate after, put under the ultra-violet lamp 365nm and inspect; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the fluorescence speckle of same color;
C. one or more thin layer chromatography discriminating in Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, the ferulic acid in the preparation
It is an amount of to get this product, is dissolved in water or extracts, and extracts with the ether jolting, ether solution extracts with 5% sodium bicarbonate solution jolting, and soda solution is regulated pH value to 2～3 with dilute hydrochloric acid, and the jolting of reuse ether is extracted, ether solution evaporate to dryness, residue add ethanol or methanol makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, add the sodium bicarbonate solution supersound extraction respectively, centrifugal, supernatant is regulated pH value to 2～3 with dilute hydrochloric acid, and the jolting of reuse ether is extracted, ether solution, evaporate to dryness, residue add ethanol or methanol makes dissolving, makes Radix Angelicae Sinensis control medicinal material solution, Rhizoma Chuanxiong control medicinal material solution respectively; Get the ferulic acid reference substance, add methanol or ethanol is made reference substance solution; According to thin layer chromatography test, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put in same silica gel G F respectively
254On the plate, be developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect with benzene-methanol-glacial acetic acid=15: 1.5: 1; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color;
D. one or more thin layer chromatography discriminating in white Peony Root, Radix Paeoniae Rubra medical material, the peoniflorin in the preparation
It is an amount of to get this product, is dissolved in water or extracts, extract with water saturated n-butyl alcohol jolting, and n-butyl alcohol liquid evaporate to dryness, residue adds methanol or ethanol makes dissolving, as need testing solution; Other gets white Peony Root, Radix Paeoniae Rubra medical material, adds methanol or ethanol extraction, and extracting solution concentrates, and makes control medicinal material solution respectively; Get the peoniflorin reference substance, add methanol or ethanol and make every reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate, with chloroform-methanol=8: 2 was developing solvent, launch, take out, dry, spray is with the vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
Content assaying method comprises following part or all of content:
A. the high performance liquid chromatography assay of peoniflorin in the preparation
It is an amount of to get this product powder, accurate claims surely, is dissolved in water or extracts, and aqueous solution extracts with the water-saturated n-butanol jolting, n-butyl alcohol liquid evaporate to dryness, and residue adds dissolve with methanol and standardize solution, filters, and gets subsequent filtrate, as need testing solution; It is an amount of to get the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes reference substance solution; Adopting high performance liquid chromatography, is filler with octadecylsilane chemically bonded silica; With acetonitrile-0.01～0.05mol/L sodium dihydrogen phosphate=13～17: 87～83 is mobile phase; The detection wavelength is 227～233nm, and number of theoretical plate calculates by the peoniflorin peak should be not less than 2000; Accurate respectively absorption reference substance solution and need testing solution are an amount of, inject chromatograph of liquid, measure, and calculate with one point external standard method or standard curve method; This product contained peoniflorin with dosage on 1st must not be less than 1.2mg;
B. the high performance liquid chromatography assay of ferulic acid in the preparation
It is an amount of to get this product powder, accurate claim fixed, the accurate acidic methanol aqueous solution that adds, supersound process is put coldly, supplies the solvent of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution; It is an amount of to get the ferulic acid reference substance, and accurate the title decides, and adds methanol aqueous solution and makes reference substance solution; The test of employing high performance liquid chromatography is a filler with octadecylsilane chemically bonded silica; Methanol-0.5～1.5% glacial acetic acid solution=25～29: 75～71 are mobile phase; The detection wavelength is 313～317nm; Number of theoretical plate calculates by the ferulic acid peak should be not less than 800; Each is an amount of for accurate respectively absorption reference substance solution and need testing solution, injects chromatograph of liquid, measures, and calculates with one point external standard method or standard curve method; This product contained ferulic acid with dosage on 1st must not be less than 0.25mg.
Say accurately: content assaying method comprises following part or all of content:
A. the high performance liquid chromatography assay of peoniflorin in the preparation
It is an amount of to get this product powder, accurate claims surely, is dissolved in water or extracts, and aqueous solution extracts 4 times with the water-saturated n-butanol jolting, merges n-butyl alcohol liquid, and evaporate to dryness, residue add dissolve with methanol and standardize solution, filter, and get subsequent filtrate, as need testing solution; It is an amount of to get the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes reference substance solution; Adopting high performance liquid chromatography, is filler with octadecylsilane chemically bonded silica; With acetonitrile-0.02mol/L sodium dihydrogen phosphate=15: 85 was mobile phase; The detection wavelength is 230nm, and number of theoretical plate calculates by the peoniflorin peak should be not less than 3000; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and calculate with one point external standard method; This product contained peoniflorin with dosage on 1st must not be less than 2.4mg;
B. the high performance liquid chromatography assay of ferulic acid in the preparation
It is an amount of to get this product powder, accurate claim fixed, the accurate acidic methanol aqueous solution that adds, supersound process is put coldly, supplies the solvent of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution; It is an amount of to get the ferulic acid reference substance, and accurate the title decides, and adds methanol aqueous solution and makes reference substance solution; The test of employing high performance liquid chromatography is a filler with octadecylsilane chemically bonded silica; Methanol-1% glacial acetic acid solution=27: 73 is a mobile phase; The detection wavelength is 315nm; Number of theoretical plate calculates by the ferulic acid peak should be not less than 1000; Each is an amount of for accurate respectively absorption reference substance solution and need testing solution, injects chromatograph of liquid, measures, and calculates with one point external standard method; This product contained ferulic acid with dosage on 1st must not be less than 0.5mg.Compared with prior art, micropill disintegrative of the present invention is good, and the bioavailability height is particularly suitable for the old people and swallow tablet or the inconvenient patient of capsule take; Medicine tablet formulation provided by the invention, the mode of taking is more, can swallow, buccal and sucking take, and it is convenient to use more than other oral solid formulations, and simultaneously, this product chance water disintegrate rapidly forms homodisperse aqueous solution; Drop pill provided by the invention has solved the not high problem of bioavailability of effective ingredient; Soft capsule of the present invention is that drug blockage is formed in soft gel coat, has solved medicine and has met damp and hot problem of unstable, can also cover adverse drug taste, abnormal smells from the patient, plays the effect that increases stability, improves bioavailability.
The applicant finds that in development process for guaranteeing product quality, the screening of adjuvant, process conditions is just most important.The applicant has carried out a series of experiments, with the supplementary product kind of the preparation technology that selects pharmaceutical preparation provided by the invention, use and consumption, ratio etc.; Guarantee its science, reasonable, feasible; The preparation that obtains has effective therapeutic effect.
Technology advanced person of the present invention, simple; The preparation that obtains is for gynaecopathia such as menoxenia, and abdominal pain in menstruation etc. have reasonable prevention effect; But and the little patients life-time service of preparation untoward reaction provided by the invention.
Experimental example 1: technical studies such as extraction
1.1 extraction process
In the prior art, the part medical material is a water extraction, but not clear and definite to amount of water, therefore adopts the single factor experiment method, with the content of paeoniflorin is to investigate index to carry out preferably, and test method and result are as follows:
Take by weighing Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi 88.9g, Rhizoma Atractylodis Macrocephalae 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4 g, totally 6 minutes, decoct with water secondary respectively, 3 hours for the first time, 2 hours for the second time, collecting decoction filters, and filtrate decompression concentrates, dry, it is heavy to claim to decide cream, and measures content of paeoniflorin in the extractum, and result of the test sees the following form.
| The investigation of amount of water | ||||
| Tested number | Amount of water (doubly) | Extractum recovery rate (%) | Paeoniflorin content (mg/g) | |
| For the first time | For the second time | |||
| 1 2 3 4 5 6 | 6 8 10 10 10 8 | 6 8 10 8 6 6 | 7.68 9.24 11.69 11.63 9.47 8.94 | 1.57 1.83 2.89 2.87 1.94 1.78 |
As seen from the above table: extractum recovery rate and paeoniflorin content were higher when amount of water was 10,10 times and 10,8 times amount, and not significantly difference between the two, guaranteeing under the sufficient prerequisite of extracts active ingredients, in order to save cost and to shorten man-hour, determine to extract amount of water 10 times of amounts for the first time, for the second time 8 times of amounts.
In order to verify determined preparation technology's feasibility, we have carried out confirmatory experiment three times to these process conditions.
Test method: take by weighing Radix Angelicae Sinensis 64g, Rhizoma Chuanxiong 7.2g, Rhizoma Cyperi 177.8g, Rhizoma Atractylodis Macrocephalae 10.2g, Radix Paeoniae Alba 5.2g, Radix Paeoniae Rubra 5.2g, Rhizoma Corydalis 14.2g, Radix Rehmanniae Preparata 21.4g, Fructus Jujubae 35.6g, Radix Glycyrrhizae 4.8g in the prescription ratio, totally 6 minutes, decoct with water secondary respectively, 3 hours for the first time, 2 hours for the second time, collecting decoction filters, and filtrate decompression concentrates, dry, it is heavy to claim to decide cream, and measures content of paeoniflorin in the extractum, and result of the test sees the following form.
| The extraction process confirmatory experiment | ||||
| Tested number | Medical material amount (g) | Cream heavy (g) | Extractum recovery rate (%) | Paeoniflorin content (mg/g) |
| 1 2 3 | 345.6 345.6 345.6 | 39.46 41.37 40.37 | 11.42 11.61 11.67 | 2.91 2.94 2.90 |
Extract by visible this condition of the result of confirmatory experiment that extractum recovery rate and paeoniflorin content are more stable as a result, illustrate this extraction process condition be rationally, stablize feasible.
1.2 separation, concentration technology research
Separate and select: all adopt 200 order filter clothes to filter.
The concentration technology condition: in conjunction with factory's current production devices, filtrate adopts the triple effect concentration tank to concentrate, and is concentrated into the thick paste that relative density is about 1.30 (60 ℃), and is standby.Concentrated condition is: temperature is 84 ℃ of effects, two 80 ℃ of effects, 69 ℃ of triple effects, and vacuum is that an effect 0.025Mpa, two is imitated 0.046Mpa, triple effect 0.068Mpa.
Experimental example 2: Study on Forming
2.1 dispersible tablet
Dispersible tablet meet water rapidly disintegrate form the water dispersion tablet of uniform sticky suspension, it is poor to have solved former dosage form disintegrative, stripping is shortcoming slowly, and the dispersible tablet that the applicant makes is disintegrate fully in the 3min in 19 ℃～21 ℃ water, and suspension ability is good, bioavailability is high, dispersed homogeneous degree.
2.1.1 adjuvant screening
| Prescription | CMC-Na(g) | PPVP(g) | Mannitol (g) | K30(％) | Disintegration time/s |
| 1 2 3 4 5 6 | 10 10 20 20 30 30 | 10 20 20 30 10 20 | 10 20 10 20 20 10 | 2 2 1.5 1.5 1 1 | 131 65 96 120 126 202 |
2.1.2 check disintegration
Adopting changes the basket method, and lift disintegration tester, tablet are got 6, observes the situation by screen cloth.Percent of pass height then disintegrative is good, more pleasant bulk absorption.
| Group | Disintegration (s) | |||||
| Tablet ordinary tablet of the present invention | 1 | 2 | 3 | 4 | 5 | 6 |
| 60 1134 | 63 1298 | 59 1567 | 61 1520 | 52 1531 | 53 1153 | |
The result shows that the dispersible tablet product of the inventive method preparation is easy to disintegrate.
2.2 pellet Study on Forming
The micropill diameter is less than 2.5mm, and class is in particle properties, the bioavailability height, and the applicant is when development product micropill of the present invention, and maximum difficulty is exactly that hygroscopicity is strong and mobile poor, and poor plasticity is difficult to molding.The micropill manufacturing technology and the adjuvant that adopt the applicant's screening to obtain make product be easy to disintegrate, and the bioavailability height is well-behaved.
2.2.1 supplementary product kind and consumption are selected
Wettability test: get two parts of extract powders, a starch that adds, mixing is put respectively in the flat weighing bottle of having weighed, and accurate the title, decide, and is to measure its hygroscopic capacity under 75.0% condition at 25 ℃ of temperature, relative humidity, the results are shown in Table.
| The wettability test result | |||
| Sample | Pure extract powder | Extract powder+starch | |
| The weighing bottle numbering | 1 | 2 | |
| Weight of material (g) | 0.9879 | 0.9856 | |
| Moisture absorption blanking time percentage (%) | 1h 2h 3h 4h 6h 8h 10h 12h 24h 36h 48h 72h 84h 96h | 1.45 3.58 5.11 6.98 8.38 11.24 12.97 15.68 18.20 25.32 31.08 39.75 42.34 45.80 | 1.08 2.75 4.40 6.12 7.08 8.35 10.02 13.11 14.98 18.71 20.79 25.65 37.21 40.78 |
The result shows that it is rationally feasible to adopt starch to make adjuvant.
2.2.2 system soft material
Get extractum fine powder and starch, soybean oil and ethanol and make soft material with wet granulation process in right amount, make it to reach and hold agglomeratingly, that pinches can loose, standby.Research emphasis concentration of alcohol and soybean oil consumption influence pill, and experimental result sees Table.
| Concentration of alcohol is investigated | ||
| Tested number | Concentration of alcohol | System soft material situation |
| 1 2 3 | 65% ethanol, 70% ethanol, 75% ethanol | The moderate soft material of the not enough soft material of soft material viscosity easily bonds |
| The soybean oil consumption is investigated | ||
| Tested number | The soybean oil consumption | The pill situation |
| 1 2 3 | 70% ethanol, 1.5% soybean oil, 70% ethanol, 1.8% soybean oil, 70% ethanol, 2.0% soybean oil | Soft material viscosity is not enough, and is can't the pill soft material moderate, and suitable pill soft material easily bonds the pill difficulty |
The result as seen, it is more satisfactory to adopt 70% ethanol, 1.8% soybean oil to be that adhesive is granulated, otherwise is difficult to molding.
2.2.3 pill
The soft material that makes is with micropill mechanism ball, and wet feed pushed the 0.8mm sieve aperture, and the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 16～20 mesh sieves and selected ball.
2.3 soft capsule
Soft capsule disintegrate in gastrointestinal tract is fast, and after softgel shell broke, medicine disperseed rapidly, so the drug release stripping is fast, produce effects is rapid, the bioavailability height; Semi-transparent soft capsule can protect medicine not to be subjected to the effect of oxygen, light in dampness and the air with packaging material preferably, thereby improves the stability of labile elements such as andrographolide; So capsular stability and moulding process are very crucial technology.
2.3.1 disperse medium (or claiming substrate) is selected
At fill material and substrate energy mix homogeneously, and under the prerequisite of unobstructed defeated material of energy and pelleting, reduce substrates quantity as far as possible.By test of many times, determine medication amount (g): substrate amount (g)=be advisable at 1: 1.2, experimental result sees Table.
| Substrates quantity is investigated | |||
| Medication amount (g): substrate amount (g) | 1∶1 | 1∶1.2 | 1∶2 |
| Quality of liquid medicine | Viscosity is big, mobile poor | Viscosity, flowability are all good | Differences in viscosity is mobile big |
2.3.2 opacifier is selected
The transparent adhesive tape softgel shell easily causes instability, so need to add a certain amount of opacifier.Select titanium dioxide (titanium dioxide) to make opacifier through investigation and can reach effective shaded effect, and steady quality, not with rubber cement and fill material generation chemical change.Its consumption is through investigating with gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g is advisable, and little to the rubber quality influence, the results are shown in Table.
| The opacifier consumption is selected | |||
| Usage ratio | The rubber transparency | Rubber cement viscosity (Mpas) | Overall merit |
| Gelatin 100g: glycerol 45g: water 100g: titanium dioxide 1g gelatin 100g: glycerol 45g: water 100g: titanium dioxide 2g gelatin 100g: glycerol 45g: water 100g: titanium dioxide 2.5g gelatin 100g: glycerol 45g: water 100g: titanium dioxide 3g | Translucent opaque | 3.12 3.35 3.58 3.61 | The big viscosity of the good inadequately viscosity of consumption is bigger |
Quality is more stable after adding opacifier in the capsule formula.
2.3.3 batchingization glue is investigated
By aforementioned preferred prescription is gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: the 2g weigh batching with different temperatures glue, the results are shown in Table.
| Changing the glue temperature investigates | ||
| Temperature (℃) | Change the glue time (H) | The rubber quality |
| 50 60 70 80 90 | 7 5 5 5 4 | Good have bubble than the ebonite skin carefully, harder |
By the table prompting, it is the most suitable with 60～70 ℃ to change the glue temperature.So batchingization adhesive tape part is: weigh batching, in the inputizations glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirs 5 hours also the while evacuation except that bubble, treat sizing material even after blowing, incapsulate after the filtration in the sizing material bucket of machine.
2.4 drop pill
4.1 preparation prescription design and screening
Drop pill substrate Macrogol 4000 and polyethylene glycol 6000 are compared test.The Polyethylene Glycol of different model is put in the small beaker, be heated to 80-90 ℃, after treating whole fusions, add extract powder, investigate substrate and extract powder the fusion situation, select fusion situation dripping system (the system condition: expect warm 75 ℃ of writing out a prescription preferably, coolant is a dimethicone, drip apart from 3～7cm, drip 30～40 droplets/minute of speed), the results are shown in following table.
| The fusion situation of substrate and principal agent relatively | ||||||||
| The prescription number | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 | Prescription 7 | Prescription 8 |
| Extract powder (g) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
| Macrogol 4000 (g) | 10 | 15 | 20 | 25 | --------- | --------- | --------- | --------- |
| Polyethylene glycol 6000 (g) | --------- | --------- | --------- | --------- | 10 | 15 | 20 | 25 |
| Principal agent: substrate | 1∶1 | 1∶1.5 | 1∶2 | 1∶2.5 | 1∶1 | 1∶1.5 | 1∶2 | 1∶2.5 |
| The fusion situation of principal agent and substrate | Principal agent can merge with substrate, but system does not have flowability | Principal agent can merge with substrate, but the system flowability is relatively poor | Principal agent can merge with substrate, and the system flowability is fine | Principal agent can merge with substrate, and the system flowability is fine | Principal agent and substrate merge relatively poor | Principal agent can merge with substrate, but system does not have flowability | Principal agent can merge with substrate, and the system flowability is relatively poor | Principal agent can merge with substrate, and system is better mobile |
| The drop pill outward appearance | --------- | Roundness is poor, hangover | Smooth, roundness is good | Smooth, roundness is good | --------- | Roundness is poor, serious hangover | Roundness is poor, hangover | Roundness is poor slightly, and hangover is arranged slightly |
| Drop pill hardness | --------- | Hardness is better | Hardness is better | Hardness is better | --------- | Hardness is better | Hardness is better | Hardness is better |
| The ball method of double differences is different | 6.5％ | 7.5％ | 8.0％ | --------- | 23％ | 18％ | ||
| Dissolve scattered time limit (min) | --------- | 5～8 | 6～9 | 6～9 | --------- | --------- | 10～15 | 10～15 |
The above results shows, the good fluidity of the 3 fusion medicinal liquids of writing out a prescription, and the drop pill good moldability, smooth, mellow and full, the ball method of double differences is different little, and molten loosing comparatively fast is so select prescription No. 3.
4.2 dripping the system condition selects
4.2.1 coolant is selected
Get extract powder 10g, Macrogol 4000 20g, mix homogeneously is heated to 80-90 ℃, treat whole fusions after, get in right amount, splash into respectively in simethicone and the liquid paraffin coolant, observe drop pill molding situation, the results are shown in following table.
| Coolant is selected | |||||
| The cold agent kind of getting | Coolant temperature | Drip distance | Drip speed | The material temperature | Drop pill molding situation |
| The dimethicone liquid paraffin | 30℃ 30℃ | 3cm 3cm | 30～40d/min 30～40d/min | 75℃ 75℃ | Roundness is good, the hangover of forming drop pill, and shape is relatively poor |
Last table shows, is that coolant drop pill roundness is good with the simethicone, forming.
4.2.2 coolant temperature is selected
Get extract powder 10g, Macrogol 4000 2.0g, mix homogeneously is heated to 80-90 ℃, treat whole fusions after, get in right amount, splash into respectively in the simethicone coolant of different temperatures, observe drop pill molding situation, the results are shown in following table.
| Coolant temperature is selected | ||||
| Coolant temperature | Drip distance | Drip speed | The material temperature | Drop pill molding situation |
| 20 ℃ of 30 ℃ of gradients coolings | 3cm 3cm 3cm | 30～40d/min 30～40d/min 30～40d/min | 75℃ 75℃ 75℃ | Roundness is good, and the forming roundness is good, and the forming roundness is good, forming |
Annotate: the gradient cooling means is: 30～40 ℃ on top, middle part are 15～30 ℃, and the bottom is 5～15 ℃.
Last table shows that under above-mentioned three kinds of chilling temperatures, the mouldability of this product is all good, is easy operation, is 20～30 ℃ so select coolant temperature.
4.2.3 the water dropper bore is selected
Get extract powder 10g, Macrogol 4000 20g makes the fusion medicinal liquid by method for making, and the water dropper with different bores drips system respectively, and the average ball of investigating the gained drop pill weighs the degree of closeness that weighs (60mg/ ball) with the target ball, the results are shown in following table.
| The water dropper bore is selected | |||||
| Water dropper bore (inside/outside mm/mm) | 2.7/3.1 | 3.3/4.1 | 3.6/4.8 | 4.3/5.1 | 4.9/5.8 |
| Heavy (mg) ball method of double differences (mg) of heavy (mg) target ball of average ball | 30.6 -29.4 | 39.7 -20.3 | 48.5 60mg -11.5 | 59.1 -0.9 | 68.3 8.3 |
The above results shows that the water dropper bore is that the drop pill ball of the water dropper of 4.3/5.1 (inside/outside mm/mm) system of dripping overlaps reason, is 4.3/5.1 (inside/outside mm/mm) so select the water dropper bore.
4.2.4 drip apart from selecting
Get extract powder 10g, Macrogol 4000 20g makes the fusion medicinal liquid by method for making, with different dripping apart from the system of dripping, investigates the different and face shaping of the ball method of double differences of gained drop pill respectively, the results are shown in following table.
| Drip apart from selecting | ||
| Drip apart from (cm) | Weight differential | The drop pill outward appearance |
| 1 3 5 7 9 | ------ 10％ 9.1％ 8.7％ 26％ | The drop pill adhesion, roundness difference drop pill outward appearance rounding, smooth surface drop pill outward appearance rounding, smooth surface drop pill outward appearance rounding, smooth surface drop pill outward appearance rounding, smooth surface |
Last table shows, when dripping apart from the time at 3～7cm, and drop pill outward appearance rounding, smooth surface, weight differential is little, is 3～7cm so select to drip a distance.
4.2.5 fusion fluid temperature (material temperature), a system speed are selected
Get extract powder 10g, Macrogol 4000 20g makes the fusion medicinal liquid by method for making, and gentle system speed (all the other conditions are by the method for making) system of dripping of dripping of the material of according to the form below the results are shown in following table.
| Fusion fluid temperature (material temperature), a system speed are selected | ||||||
| Sequence number | Drip speed (d/min) | The material temperature (℃) | Weight differential coefficient (%) | Average ball heavy (mg) | Average heavy-60 (mg) of ball | The drop pill outward appearance |
| 1 2 3 4 5 6 7 8 9 | 20~30 20~30 20~30 30~40 30~40 30~40 40~50 40~50 40~50 | 60~70 70~80 80~90 60~70 70~80 80~90 60~70 70~80 80~90 | 8.1 7.4 8.2 7.1 6.8 7.3 9.6 9.4 9.3 | 56.7 57.2 55.6 63.5 60.8 61.8 70.5 68.7 66.5 | -3.3 -2.8 -4.4 3.5 0.8 1.8 10.5 8.7 6.5 | Rounding, rounding attractive in appearance, rounding attractive in appearance, rounding attractive in appearance, rounding attractive in appearance, rounding attractive in appearance, the poor slightly roundness of the poor slightly roundness of roundness attractive in appearance is poor slightly |
From table as can be known, when selecting for use when dripping 70～80 ℃ of speed 30～40d/min, material temperature, the gained ball is heavy heavy the most approaching with the target ball, simultaneously little, the drop pill outward appearance rounding, attractive in appearance of weight differential.So select to drip 70～80 ℃ of speed 30～40d/min, material temperature.
Experimental example 3 analgesic activities (to the inhibitory action of mouse writhing reaction)
Experimental technique: mice is divided into 7 groups at random, continuous irrigation stomach 8 days, the last administration after 90 minutes mouse peritoneal inject 0.7% glacial acetic acid 0.1ml/10 gram body weight, observe the counting mice and turn round the body number of times in 15 minutes.
| Group | Dosage (g/kg) | Animal (only) | Turn round the body number of times | Suppression ratio (%) |
| Control group hydrocortisone group Fuke Tiaojing Granules group dispersing tablet group of the present invention micropill group of the present invention soft capsule group of the present invention dripping pill group of the present invention | 20ml/kg 0.04 2.0 2.0 2.0 2.0 2.0 | 10 10 10 10 10 10 10 | 30.5±2.2 12.3±1.9 20.1±4.7 18.5±3.4 18.7±2.3 19.0±6.5 18.0±2.4 | - 65.29 30.24 34.17 32.15 31.17 34.50 |
The result shows that preparation of the present invention has the reagentia of obvious suppression mouse writhing, illustrates that it has good analgesic activity, and effect is better than commercially available gynecological regulating menstruation granule.
The thin layer chromatography of Rhizoma Cyperi medical material, α-cyperone is differentiated in experimental example 4 drop pills
For the feature of outstanding Rhizoma Cyperi, selected α-cyperone as its principal character composition, but owing to had composition, for example liposoluble constituent in Radix Angelicae Sinensis, the Rhizoma Chuanxiong like the more or polar phase close in the preparation with α-cyperone structure.Have only the interference of getting rid of these compositions, could obtain ideal chromatograph effect.The key factor of thin layer chromatography effect quality is the composition of unfolding condition, particularly developing solvent.Therefore, test is an immobile phase with the silica gel g thin-layer plate, has screened multiple developing solvent, and part developing solvent and result are as follows:
| The thin layer chromatography of Rhizoma Cyperi medical material, α-cyperone is differentiated in the drop pill | |
| Developing solvent | The result |
| Benzinum (30～60 ℃)-chloroform=9: 1 chloroform-acetone-methyl alcohol=10: 1: 1 n-hexane-ethyl acetate=9: 1 ethyl acetate-acetone=5: 2 chloroform-ethyl acetate-ethanol=8: 3: 4 cyclohexane-ethyl acetate-formic acid=8: 4: 0.1 cyclohexane-ethyl acetate-formic acid=6: 6: 0.3 cyclohexane-ethyl acetate-formic acid=7: 5: 0.2 | Separating unintelligible feminine gender has the speckle of interference hangover feminine gender to have the interference separation poor separation clear, Rf value is low slightly, negative noiseless separation is clear, Rf value is high slightly, negative noiseless separation is the most clear, Rf value is moderate, and is negative noiseless |
Through screening, determined optimum condition: with the silica gel g thin-layer plate immobile phase, cyclohexane extraction-ethyl acetate-formic acid=be developing solvent at 7: 5: 0.2, with this understanding, the Rf value of α-cyperone feature speckle is moderate, and it is the most clear to separate with other speckle, negative noiseless.
The thin layer chromatography of corydalis tuber medicinal material, tetrahydropalmatine is differentiated in experimental example 5 drop pills
For the feature of outstanding Rhizoma Corydalis, selected tetrahydropalmatine as its principal character composition, but owing to had composition, for example compositions such as ligustrazine in the Rhizoma Chuanxiong like the more or polar phase close in the preparation with the tetrahydropalmatine structure.Have only the interference of getting rid of these compositions, could obtain ideal chromatograph effect.The key factor of thin layer chromatography effect quality is the composition of unfolding condition, particularly developing solvent.Therefore, test is an immobile phase with the silica gel g thin-layer plate, has screened multiple developing solvent, and part developing solvent and result are as follows:
| The thin layer chromatography of corydalis tuber medicinal material, tetrahydropalmatine is differentiated in the drop pill | |
| Developing solvent | The result |
| Benzene-chloroform=9: 1 n-hexane-acetone-methyl alcohol=10: 1: 1 benzene-ethyl acetate=9: 1 chloroform-acetone=5: 2 ethyl acetate-ethanol=11: 3 toluene-acetone=10: 1.5 toluene-acetone=8: 2.5 toluene-acetone=9: 2 | Separating unintelligible feminine gender has the unintelligible feminine gender of interference separation to have the interference separation poor separation clear, Rf value is low slightly, negative noiseless separation is clear, Rf value is high slightly, negative noiseless separation is the most clear, Rf value is moderate, and is negative noiseless |
Through screening, determined optimum condition: with the silica gel g thin-layer plate immobile phase, toluene-acetone=be developing solvent at 9: 2, with this understanding, the Rf value of tetrahydropalmatine feature speckle is moderate, and it is the most clear to separate with other speckle, negative noiseless.
The thin layer chromatography of Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, ferulic acid is differentiated in experimental example 6 dispersible tablets
For the feature of outstanding Radix Angelicae Sinensis, Rhizoma Chuanxiong, selected ferulic acid as its principal character composition, but owing to there is composition like the more or polar phase close in the preparation, the peoniflorin in the Radix Paeoniae Alba, the Radix Paeoniae Rubra for example, compositions such as the glycyrrhizic acid in the Radix Glycyrrhizae with the ferulic acid structure.Have only the interference of getting rid of these compositions, could obtain ideal chromatograph effect.The key factor of thin layer chromatography effect quality is the composition of unfolding condition, particularly developing solvent.Therefore, experiment sieving multiple unfolding condition, part unfolding condition and result are as follows:
| The thin layer chromatography of Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, ferulic acid is differentiated | |
| Unfolding condition | The result |
| Benzene-methanol=5: 1 is developing solvent, silica gel G F 254Plate is an immobile phase.Normal hexane-acetone-methanol=be developing solvent at 10: 1: 1, the silica gel G plate is an immobile phase.Benzene-ethyl acetate=be developing solvent at 9: 1, the silica gel G plate is an immobile phase.Chloroform-acetone=be developing solvent at 5: 2, the silica gel G plate is an immobile phase.Benzene-methanol-glacial acetic acid=be developing solvent at 13: 1: 1.2, the silica gel G plate is an immobile phase.Benzene-methanol-glacial acetic acid=18: 1.5: 1 is developing solvent, silica gel G F 254Plate is an immobile phase.Benzene-methanol-glacial acetic acid=17: 2: 0.8 is developing solvent, silica gel G F 254Plate is an immobile phase.Benzene-methanol-glacial acetic acid=13: 1: 1.2 is developing solvent, silica gel G F 254Plate is an immobile phase.Benzene-methanol-glacial acetic acid=15: 1.5: 1 is developing solvent, silica gel G F 254Plate is an immobile phase. | Separating unintelligible feminine gender has the unintelligible feminine gender of interference separation to have the feminine gender of interference to have the interference separation poor separation clear, negative noiseless separation is clear, negative noiseless separation is the most clear, Rf value is moderate, and is negative noiseless |
Through screening, determined optimum condition: with silica gel G F
254Lamellae is an immobile phase, benzene-methanol-glacial acetic acid=be developing solvent at 15: 1.5: 1, and with this understanding, the Rf value of ferulic acid feature speckle is moderate, and it is the most clear to separate with other speckle, negative noiseless.
The thin layer chromatography of white Peony Root, Radix Paeoniae Rubra medical material, peoniflorin is differentiated in experimental example 7 pellets
For the feature of the outstanding Radix Paeoniae Alba, Radix Paeoniae Rubra, selected peoniflorin as its principal character composition, but owing to had composition, for example ferulic acid in Rhizoma Chuanxiong, the Radix Angelicae Sinensis, the compositions such as glycyrrhizic acid in the Radix Glycyrrhizae like the more or polar phase close in the preparation with the peoniflorin structure.Have only the interference of getting rid of these compositions, could obtain ideal chromatograph effect.The key factor of thin layer chromatography effect quality is the composition of unfolding condition, particularly developing solvent.Therefore, test is an immobile phase with the silica gel g thin-layer plate, has screened multiple developing solvent, and part developing solvent and result are as follows:
| The thin layer chromatography of white Peony Root, Radix Paeoniae Rubra medical material, peoniflorin is differentiated in the pellet | |
| Developing solvent | The result |
| Benzinum-methyl alcohol=9: 1 n-hexane-acetone-methyl alcohol=10: 1: 1 benzene-ethyl acetate=9: 1 chloroform-acetone=5: 2 chloroform-methyl alcohol=10: 1.5 chloroform-methyl alcohol=9: 1.5 chloroform-methyl alcohol=7: 2.5 chloroform-methyl alcohol=8: 2 | Separating unintelligible feminine gender has the unintelligible feminine gender of interference separation to have the interference separation poor separation clear, Rf value is low slightly, negative noiseless separation is clear, Rf value is high slightly, negative noiseless separation is the most clear, Rf value is moderate, and is negative noiseless |
Through screening, determined optimum condition: with the silica gel g thin-layer plate immobile phase, chloroform-methanol=be developing solvent at 8: 2, with this understanding, the Rf value of peoniflorin feature speckle is moderate, and it is the most clear to separate with other speckle, negative noiseless.
The high performance liquid chromatography assay of peoniflorin in experimental example 8 drop pills
1 instrument and reagent
1.1 key instrument
Tianjin, high performance liquid chromatograph 10A island
The general all purpose instrument company limited of analysing in ultraviolet spectrophotometer TU-1800SPC Beijing
Electronic analytical balance AE240 SARTORIUS
Ultrasonic washing unit KQ250B Kunshan Ultrasonic Instruments Co., Ltd.
1.2 reagent
Peoniflorin: Nat'l Pharmaceutical ﹠ Biological Products Control Institute
Methanol analytical pure Beijing Chemical Plant
Acetonitrile chromatographic grade Di Ma company
Sodium dihydrogen phosphate analytical pure Beijing chemical reagents corporation
It is an amount of that the 2 selection precisions that detect wavelength take by weighing the peoniflorin reference substance, adds methanol and make the solution that every 1ml contains 15 μ g, in the interscan of 200～400nm wave-length coverage.The result shows that peoniflorin has absorption maximum at the 230nm place, therefore selects 230nm as the detection wavelength of measuring paeoniflorin content in gynecological's regulating menstruation drop pill.
3 chromatographic conditions
Chromatographic column: Diamonsil ODS 250mm * 4.6mm 5 μ m
Mobile phase: acetonitrile-0.02mol/L sodium dihydrogen phosphate (15: 85)
Flow velocity: 1.0ml/min
Column temperature: 30 ℃
Sample size: 10 μ l
Detect wavelength: 230nm
Test and Selection peoniflorin as its index components, but owing to have composition example, for example ferulic acid in Rhizoma Chuanxiong, the Radix Angelicae Sinensis, the compositions such as glycyrrhizic acid in the Radix Glycyrrhizae like the more or polar phase close in the preparation with the peoniflorin structure.Have only the interference of getting rid of these compositions, could obtain ideal chromatograph effect.The key factor of high performance liquid chromatography effect quality is the composition of elution requirement, particularly mobile phase.Therefore, test is an immobile phase with the octadecylsilane chemically bonded silica, has screened multiple mobile phase, and part mobile phase and result are as follows:
| The investigation of chromatographic condition | |
| The mobile phase condition | The result |
| Methanol-water=50: 50 methanol-water=15: 85 acetonitrile-water=15: 85 acetonitrile-water=60: 20 acetonitrile-0.05mol/L sodium dihydrogen phosphate=10: 90 acetonitrile-0.02mol/L sodium dihydrogen phosphate=20: 80 acetonitrile-0.01mol/L sodium dihydrogen phosphate=17: 83 acetonitrile-0.05mol/L sodium dihydrogen phosphate=13: 87 acetonitrile-0.02mol/L sodium dihydrogen phosphate=15: 85 | Separate not exclusively to separate not exclusively and divide, it is clear that the long separation of the incomplete appearance time of the asymmetric separation of the asymmetric peak shape of peak shape not exclusively separates, negative noiseless retention time is long slightly, it is clear to separate, negative noiseless retention time is moderate, it is the most clear to separate, negative noiseless |
Through screening, determined with the octadecylsilane chemically bonded silica to be immobile phase, acetonitrile-0.02mol/L sodium dihydrogen phosphate=15: 85 is a mobile phase, with this understanding, the peoniflorin retention time is moderate, and the peak is capable sharp-pointed, symmetry, it is the most clear to separate with adjacent peak, negative noiseless.
4 algoscopys
Get this product, porphyrize is got about 0.6g, the accurate title, decide, and adds water 15ml and make dissolving, extracts 4 times with the water-saturated n-butanol jolting, each 15ml merges n-butyl alcohol liquid, evaporate to dryness, residue add methanol make in right amount the dissolving and be transferred in the 5ml measuring bottle, add methanol to scale, shake up, microporous filter membrane (0.45 μ m) filters, get subsequent filtrate, as need testing solution.It is an amount of to get the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes the reference substance solution that every 1ml contains 0.1mg.Accurate respectively each the 10 μ l of above-mentioned two kinds of solution that draw inject chromatograph of liquid, measure, and calculate with one point external standard method.
The investigation precision of 5 linear relationships is measured peoniflorin reference substance solution (0.6272mg/ml) 1.0ml, 1.5m, 2.0ml, 2.5ml, 3.0ml, split in the 10ml measuring bottle, add methanol and be diluted to scale, shake up, be mixed with the reference substance solution of 0.06272mg/ml, 0.09408mg/ml, 0.12544mg/ml, 0.15680mg/ml, 0.18816mg/ml, the therefrom accurate respectively 10 μ l that draw inject chromatograph of liquid, according to high effective liquid chromatography for measuring.With the peak area is abscissa, and the sample size of peoniflorin (μ g) is figure for vertical coordinate, the drawing standard curve.The result is as follows:
| The peoniflorin linear relationship | ||
| Numbering | Peak area | Peoniflorin sample size (μ g) |
| 1 2 3 4 5 | 403528 611854 804516 1012519 1218477 | 0.6272 0.9408 1.2544 1.5680 1.8816 |
Regression equation: Y=0.0000015X+0.0033426
Correlation coefficient: γ=0.9999
The result shows that peoniflorin linear relationship between 0.6272 μ g～1.8816 μ g is good.
Through calculating, the peoniflorin standard curve is one to cross the straight line of initial point, therefore selects one point external standard method to measure content of paeoniflorin in gynecological's regulating menstruation drop pill.
The test of 6 precision is accurate draws with a peoniflorin reference substance solution 10 μ l, injects chromatograph of liquid, and replication 5 times is investigated reference substance solution precision, and measurement result is as follows:
| The precision test | |||||||
| Test number (TN) | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Peak area | 762514 | 763957 | 759833 | 772015 | 780031 | 767670 | 1.08 |
The result shows that reference substance solution precision is good.
7 stability tests
Draw with a peoniflorin reference substance solution 10 μ l 7.1 the reference substance stability test is accurate, inject chromatograph of liquid, measure at 0,2,6,8,24 hour sample introduction respectively, measurement result is as follows:
| Reference substance stability test result | |||||||
| Time (h) | 0 | 2 | 6 | 8 | 24 | Meansigma methods | RSD(％) |
| Peak area | 762514 | 763957 | 759833 | 772015 | 780031 | 767670 | 1.08 |
The result shows that reference substance solution is good at 24 hours internal stabilities.
Draw with a need testing solution 10 μ l 7.2 the need testing solution stability test is accurate, inject chromatograph of liquid, measure at 0,2,4,8,24 hour sample introduction respectively, measurement result is as follows:
| Need testing solution stability test result | |||||||
| Testing time (h) | 0 | 2 | 4 | 8 | 24 | Meansigma methods | RSD(％) |
| Peak area | 812362 | 823064 | 822697 | 830141 | 822233 | 822099 | 0.77 |
The result shows that need testing solution is good at 24 hours internal stabilities.
8 replica tests are got this product of same lot number, and porphyrize is got about 0.6g (totally 5 parts), and accurate the title decides, and press operation under chromatographic condition and the algoscopy item.The result is as follows:
| Replica test | |||||||
| Numbering | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Content (μ g/ grain) | 62.333 | 61.722 | 62.778 | 62.444 | 60.333 | 61.922 | 1.56 |
The result shows that repeatability is good.
The application of sample absorption method is adopted in the test of 9 average recoveries, this product of getting same lot number, and porphyrize is got about 0.3g (totally 6 parts), and accurate the title, decide, and splits in the tool plug conical flask; Precision is measured peoniflorin reference substance solution (0.6272mg/ml) 0.5ml, splits in the above-mentioned tool plug conical flask, volatilizes methanol; Add water 15ml and make dissolving, extract 4 times, each 15ml with the water-saturated n-butanol jolting, merge n-butyl alcohol liquid, evaporate to dryness, residue add methanol make the dissolving and move in the 5ml measuring bottle, add methanol and be diluted to scale, shake up, microporous filter membrane (0.45 μ m) filters, and the accurate subsequent filtrate 10 μ l that draw inject chromatograph of liquid, measure, promptly.Measurement result is as follows:
| The test of peoniflorin average recovery | |||||
| Numbering | Weighing (g) | Peoniflorin amount (mg) in the test sample | Peoniflorin addition (mg) | Measured value (mg) | The response rate (%) |
| 1 2 3 4 5 6 | 0.34240 0.35187 0.36584 0.30628 0.36881 0.33096 | 0.3513 0.3610 0.3754 0.3142 0.3784 0.3396 | 0.3136 0.3136 0.3136 0.3136 0.3136 0.3136 | 0.6671 0.6678 0.6941 0.6239 0.6959 0.6619 | 100.70 97.83 101.63 98.76 101.24 102.77 |
Average recovery rate=100.49%, RSD=1.85%.
10 sample sizes are measured and are pressed chromatographic condition and the operation down of algoscopy item, measure ten batch samples, and the result is as follows:
| Content of paeoniflorin in gynecological's regulating menstruation drop pill | |
| Lot number | Peoniflorin average content (μ g/ grain) |
| 1 2 3 4 5 6 7 8 9 10 | 59.222 56.722 63.778 69.444 60.500 67.611 71.667 62.444 66.778 65.944 |
High performance liquid chromatography assay in experimental example 9 dispersible tablets
1 instrument and reagent
1.1 key instrument
High performance liquid chromatograph 1100 Aglient
The general all purpose instrument company limited of analysing in ultraviolet spectrophotometer TU-1800SPC Beijing
Electronic analytical balance AE240 SARTORIUS
Ultrasonic washing unit KQ250B Kunshan Ultrasonic Instruments Co., Ltd.
1.3 reagent
Ferulaic acid content is measured and is used Nat'l Pharmaceutical ﹠ Biological Products Control Institute
Methanol analytical pure Beijing Chemical Plant
Acetonitrile chromatographic grade Di Ma company
Sodium dihydrogen phosphate analytical pure Beijing chemical reagents corporation
It is an amount of that the 2 selection precisions that detect wavelength take by weighing the ferulic acid reference substance, adds methanol and make the solution that every 1ml contains 30 μ g, in the interscan of 200～400nm wave-length coverage.The result shows that ferulic acid has absorption maximum at the 315nm place, therefore selects 315nm as the detection wavelength of measuring ferulaic acid content in gynecological's regulating menstruation dispersible tablet.
3 chromatographic conditions
Chromatographic column: Diamonsil ODS 250mm * 4.6mm 5 μ m
Mobile phase: methanol-1% glacial acetic acid solution=27: 73
Flow velocity: 1.0ml/min
Column temperature: 30 ℃
Sample size: 10 μ l
Detect wavelength: 315nm
Test and Selection ferulic acid as its index components, but owing to have composition example, for example ferulic acid in the Radix Paeoniae Alba, the Radix Paeoniae Rubra, the compositions such as glycyrrhizic acid in the Radix Glycyrrhizae like the more or polar phase close in the preparation with the ferulic acid structure.Have only the interference of getting rid of these compositions, could obtain ideal chromatograph effect.The key factor of high performance liquid chromatography effect quality is the composition of elution requirement, particularly mobile phase.Therefore, test is an immobile phase with the octadecylsilane chemically bonded silica, has screened multiple mobile phase, and part mobile phase and result are as follows:
| The investigation of chromatographic condition | |
| The mobile phase condition | The result |
| Methanol-water=40: 60 methanol-water=15: 85 acetonitrile-water=60: 20 methyl alcohol-1% glacial acetic acid solution=20: 80 methyl alcohol-1% glacial acetic acid solution=30: 70 methyl alcohol-1.5% glacial acetic acid solution=29: 71 methyl alcohol-0.5% glacial acetic acid solution=25: 75 methyl alcohol-1% glacial acetic acid solution=27: 73 | Not exclusively separation is clear to separate the long separation of the incomplete appearance time of the asymmetric separation of incomplete peak shape, negative noiseless retention time is long slightly, it is clear to separate, negative noiseless retention time is moderate, it is the most clear to separate, negative noiseless |
Through screening, determined with the octadecylsilane chemically bonded silica to be immobile phase, methanol-1% glacial acetic acid solution=27: 73 is a mobile phase, with this understanding, the ferulic acid retention time is moderate, and the peak is capable sharp-pointed, symmetry, it is the most clear to separate with adjacent peak, negative noiseless, and number of theoretical plate calculates by the ferulic acid peak and is not less than 1000.
4 algoscopys
Get this product powder 3g, accurate claim fixed, the accurate 80% methanol aqueous solution 25ml that contains 1% glacial acetic acid that adds, supersound process is put coldly, supplies the solvent of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution.It is an amount of to get the ferulic acid reference substance, accurate claims surely, adds 80% methanol and makes every ml and contain 30 μ g reference substance solution.Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and calculate with one point external standard method.
The investigation precision of 5 linear relationships is measured the ferulic acid reference substance solution 10 μ l of variable concentrations, injects chromatograph of liquid, according to high effective liquid chromatography for measuring.Sample size (ng) with ferulic acid is an abscissa, and peak area is that vertical coordinate is figure, the drawing standard curve.The result is as follows:
| The ferulic acid linear relationship | ||
| Numbering | Ferulic acid sample size (ng) | Peak area |
| 1 2 3 4 5 | 150.456 225.684 300.912 376.140 451.368 | 782.905 1174.74 1564.63 1968.58 2345.06 |
Regression equation: y=5.2084x-0.0727
Correlation coefficient: γ=0.9999
The result shows that ferulic acid linear relationship between 150.456ng～451.368ng is good.
Through calculating, the ferulic acid standard curve is one to cross the straight line of initial point, therefore selects one point external standard method to measure content of ferulic acid in gynecological's regulating menstruation dispersible tablet.
The test of 6 precision is accurate draws with a ferulic acid reference substance solution 10 μ l, injects chromatograph of liquid, and replication 5 times is investigated reference substance solution precision, and measurement result is as follows:
| The precision test | |||||||
| Test number (TN) | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Peak area | 1659.1 | 1667.2 | 1658.8 | 1649.5 | 1643.3 | 1655.6 | 0.50 |
The result shows that reference substance solution precision is good.
7 stability tests
Draw with a ferulic acid reference substance solution 10 μ l 7.1 the reference substance stability test is accurate, inject chromatograph of liquid, measure at 0,2,6,8,24 hour sample introduction respectively, measurement result is as follows:
| Reference substance stability test result | |||||||
| Time (h) | 0 | 2 | 6 | 8 | 24 | Meansigma methods | RSD(％) |
| Peak area | 1659.4 | 1649.8 | 1675.6 | 1663.8 | 1678.2 | 1665.4 | 0.63 |
The result shows that reference substance solution is good at 24 hours internal stabilities.
Draw with a need testing solution 10 μ l 7.2 the need testing solution stability test is accurate, inject chromatograph of liquid, measure at 0,2,4,8,24 hour sample introduction respectively, measurement result is as follows:
| Need testing solution stability test result | |||||||
| Testing time (h) | 0 | 2 | 4 | 8 | 24 | Meansigma methods | RSD(％) |
| Peak area | 1536.4 | 1558.9 | 1546.3 | 1581.7 | 1553.6 | 1555.4 | 0.98 |
The result shows that need testing solution is good at 24 hours internal stabilities.
8 replica tests are got this product of same lot number, and porphyrize is got about 3.0g (totally 5 parts), and accurate the title decides, and press operation under chromatographic condition and the algoscopy item.The result is as follows:
| Replica test | |||||||
| Numbering | 1 | 2 | 3 | 4 | 5 | Meansigma methods | RSD(％) |
| Content (μ g/ sheet) | 54.6 | 55.7 | 57.4 | 55.1 | 56.2 | 55.8 | 1.73 |
The result shows that repeatability is good.
Application of sample absorption method, this product of getting same lot number, porphyrize are adopted in the test of 9 average recoveries, get 1.5g, the accurate title, decide, and the accurate ferulic acid reference substance solution that adds is an amount of, make in the ferulic acid of adding and the sample content suitable, the accurate 80% methanol aqueous solution 25ml that contains 1% glacial acetic acid, the supersound process of adding, put cold, supply the solvent of loss, shake up, filter, get subsequent filtrate, as need testing solution.Press operation under chromatographic condition and the algoscopy item, measure.Average recovery rate=99.7% as a result, RSD=1.34% shows that the response rate is good.
10 sample sizes are measured and are pressed chromatographic condition and the operation down of algoscopy item, measure ten batch samples, and the result is as follows:
| Content of ferulic acid in gynecological's regulating menstruation dispersible tablet | |
| Lot number | Ferulic acid average content (μ g/ sheet) |
| 1 2 3 4 5 6 7 8 9 10 | 55.8 60.2 53.4 64.7 70.5 55.4 54.6 60.8 59.7 57.0 |
Concrete embodiment
Embodiments of the invention 1: Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g
Get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 2 parts of Macrogol 4000s adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip apart from 5cm, drip fast 35d/min, 75 ℃ of material temperature are dripped become ball in 25 ℃ dimethicones, collect drop pill, remove the methyl-silicone oil on surface, packing, promptly get drop pill, oral, three times on the one, 14g/ time.
Embodiments of the invention 2: Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g
Get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter merging filtrate, it when being evaporated to 80～85 ℃ of relative densities 1.18～1.20 clear paste, drying under reduced pressure is pulverized, and adds an amount of starch, with 70% ethanol and soybean oil system soft material, extruding-round as a ball pill or the general ball of making of employing coating pan, drying promptly gets pellet.
Embodiments of the invention 3: Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g
Get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Get CMC-Na: PVPP: mannitol=add an amount of pigment mixing as pharmaceutical adjunct at 1: 2: 2, get 3/5 pharmaceutical adjunct and the medicated powder mix homogeneously that is equivalent to 8 times of amounts of CMC-Na approximately, PVP-K with 2%
30Anhydrous alcohol solution is made binding agent, and 40 order system material, granulate remain 2/5 pharmaceutical adjunct and an amount of caramel color mixing, are added on outward in the particle that makes, and tabletting promptly gets dispersible tablet.
Embodiments of the invention 4: Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g
Get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure, pulverize, cross 80 mesh sieves, press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%, pelleting; The dry typing drying of rolling that adopts combined with two steps of tray dried, dry 2 hours of the typing of rolling, and 22 ℃ of baking temperatures, dry relative humidity should be lower than 40%, and promptly got soft capsule at 24～48 hours drying time.
Embodiments of the invention 5: Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, the Radix Paeoniae Alba 2.6 g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g
Get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 2 parts of Macrogol 4000s adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip, drip fast 30d/min apart from 3cm, 70 ℃ of material temperature, drip and in 20 ℃ dimethicone, to become ball, collect drop pill, remove the methyl-silicone oil on surface, packing promptly gets drop pill.
Embodiments of the invention 6: Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g
Get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 2 parts of Macrogol 4000s adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip, drip fast 40d/min apart from 7cm, 80 ℃ of material temperature, drip and in 30 ℃ dimethicone, to become ball, collect drop pill, remove the methyl-silicone oil on surface, packing promptly gets drop pill.
Embodiments of the invention 7: Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g
Get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 1 part of Macrogol 4000 adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip, drip fast 20d/min apart from 1cm, 60 ℃ of material temperature, drip and in 20 ℃ dimethicone, to become ball, collect drop pill, remove the methyl-silicone oil on surface, packing promptly gets drop pill.
Embodiments of the invention 8: Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g
Get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 2.5 parts of Macrogol 4000s adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip, drip fast 50d/min apart from 9cm, 90 ℃ of material temperature, drip and in 30 ℃ dimethicone, to become ball, collect drop pill, remove the methyl-silicone oil on surface, packing promptly gets drop pill.
The thin layer chromatography of Rhizoma Cyperi medical material, α-cyperone is differentiated in embodiment 9 drop pills
Get this product powder 2g, add water 50ml and make dissolving, the jolting that adds diethyl ether is extracted 3 times, and each 30ml merges ether solution, volatilizes, and residue adds methanol 1ml makes dissolving, as need testing solution; Other gets Rhizoma Cyperi control medicinal material 3g, adds water 50ml, and reflux 1 hour filters, and shines medical material solution in pairs with legal system.Get α-cyperone, add ethyl acetate and make the reference substance solution that every ml contains 1mg.According to the thin layer chromatography test, draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-ethyl acetate-formic acid (7: 5: 0.2) is developing solvent, launches, and takes out, dry, spray is with 1% vanillin sulfuric acid solution, and 105 ℃ to be heated to speckle colour developing clear.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the same color speckle.
The thin layer chromatography of Rhizoma Cyperi medical material, α-cyperone is differentiated in embodiment 10 dispersible tablets
Get this product powder 3g, add water 30m supersound extraction, filter, filtrate adds the ethyl acetate jolting extracts 2 times, and each 30ml merges ether solution, volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Rhizoma Cyperi control medicinal material 1g, adds water 30ml, and reflux 1 hour filters, and filtrate adds the ethyl acetate jolting extracts 2 times, each 30ml, and combined ethyl acetate liquid volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution.Get α-cyperone, add ethyl acetate and make the reference substance solution that every ml contains 2mg.According to the thin layer chromatography test, draw each 3 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-ethyl acetate-formic acid (8: 4: 0.3) is developing solvent, launches, and takes out, dry, spray is with 2% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the same color speckle.
The thin layer chromatography of Rhizoma Cyperi medical material is differentiated in embodiment 11 pellets
Get this product powder 2g, add water 30m supersound extraction, filter, filtrate adds the chloroform jolting extracts 2 times, and each 30ml merges chloroform liquid, volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Rhizoma Cyperi control medicinal material 1g, adds water 30ml, and reflux 1 hour filters, and the filtrate jolting that adds diethyl ether is extracted 2 times, and each 30ml merges ether solution, volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution.Get α-cyperone, add ethyl acetate and make the reference substance solution that every ml contains 2mg.According to the thin layer chromatography test, draw each 4 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-ethyl acetate-formic acid (6: 6: 0.1) is developing solvent, launches, and takes out, dry, spray is with 2% vanillin sulfuric acid solution, and it is clear to be heated to speckle colour developing.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the same color speckle.
The thin layer chromatography of corydalis tuber medicinal material, tetrahydropalmatine is differentiated in embodiment 12 drop pills
Get this product powder 3g, add methanol 50ml, supersound process 30 minutes filters the filtrate evaporate to dryness, residue adds water 10ml makes dissolving, adds strong ammonia solution and transfers to alkalescence, extracts 3 times with the ether jolting, each 10ml, merge ether solution, evaporate to dryness, the residue 1ml that adds diethyl ether makes dissolving, as need testing solution.Other gets Rhizoma Corydalis control medicinal material 0.5g, shines medical material solution in pairs with legal system.Get tetrahydropalmatine, add methanol and make the reference substance solution that every ml contains 2mg.Test according to thin layer chromatography, draw each 15～20 μ l of above-mentioned three kinds of solution, put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with toluene-acetone (9: 2) is developing solvent, launches, and takes out, dry, put in the iodine cylinder after about 3 minutes and take out, wave the iodine that adsorbs on the most plate after, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the fluorescence speckle of same color.
The thin layer chromatography of corydalis tuber medicinal material, tetrahydropalmatine is differentiated in embodiment 13 microcapsules
Get this product powder 2g, add ethanol 30ml, supersound process 15 minutes filters the filtrate evaporate to dryness, residue adds water 10ml makes dissolving, adds strong ammonia solution and transfers to alkalescence, extracts 3 times with the chloroform jolting, each 10ml, merge ether solution, evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution.Other gets Rhizoma Corydalis control medicinal material 0.5g, shines medical material solution in pairs with legal system.Get tetrahydropalmatine, add methanol and make the reference substance solution that every ml contains 2mg.Test according to thin layer chromatography, draw each 5 μ l of above-mentioned three kinds of solution, put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with toluene-acetone (8: 2.5) is developing solvent, launches, and takes out, dry, put in the iodine cylinder after about 3 minutes and take out, wave the iodine that adsorbs on the most plate after, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the fluorescence speckle of same color.
The thin layer chromatography of corydalis tuber medicinal material is differentiated in embodiment 14 pellets
Get this product powder 2g, add methanol 30ml, supersound process 15 minutes filters the filtrate evaporate to dryness, residue adds water 10ml makes dissolving, adds strong ammonia solution and transfers to alkalescence, extracts 3 times with the ether jolting, each 10ml, merge ether solution, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Rhizoma Corydalis control medicinal material 1g, shines medical material solution in pairs with legal system.According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with toluene-acetone (10: 1.5) is developing solvent, launches, and takes out, dry, put iodine steam smoked after, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the fluorescence speckle of same color.
The thin layer chromatography of Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, ferulic acid is differentiated and is got this product powder 2g in embodiment 15 pellets, adds water 30ml supersound extraction, filters, filtrate is extracted 2 times with the ether jolting, and each 20ml merges ether solution, extract 2 times with 5% sodium bicarbonate solution jolting, each 20ml merges soda solution, regulate pH value to 2～3 with dilute hydrochloric acid, the jolting of reuse ether is extracted 2 times, each 20ml, merge ether solution, evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis medical material 3g, Rhizoma Chuanxiong medical material 3g, add 1% sodium bicarbonate solution 50ml supersound extraction 10 minutes respectively, centrifugal, supernatant is regulated pH value to 2～3 with dilute hydrochloric acid, the jolting of reuse ether is extracted 2 times, each 20ml merges ether solution, evaporate to dryness, residue adds ethanol 1ml makes dissolving, makes Radix Angelicae Sinensis control medicinal material solution, Rhizoma Chuanxiong control medicinal material solution respectively.Get the ferulic acid reference substance, add ethanol and make the reference substance solution that every ml contains 2mg.According to the thin layer chromatography test, draw each 2～5 μ l of above-mentioned control medicinal material solution, reference substance solution and need testing solution, put in same silica gel G F respectively
254On the plate, be developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect with benzene-methanol-glacial acetic acid=15: 1.5: 1.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
The thin layer chromatography of Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, ferulic acid is differentiated in embodiment 16 drop pills
Get this product powder 2g, add water 30ml dissolving, filter, filtrate is extracted 2 times with the ethyl acetate jolting, and each 20ml merges ether solution, extract 2 times with 1% sodium hydroxide solution jolting, each 20ml merges caustic lye of soda, regulate pH value to 2～3 with dilute hydrochloric acid, the jolting of reuse ethyl acetate is extracted 2 times, each 20ml, merge ether solution, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis medical material 3g, Rhizoma Chuanxiong medical material 3g, add 1% sodium bicarbonate solution 50ml supersound extraction 10 minutes respectively, centrifugal, supernatant is regulated pH value to 2～3 with dilute hydrochloric acid, the jolting of reuse ether is extracted 2 times, each 20ml merges ether solution, evaporate to dryness, residue adds methanol 1ml makes dissolving, makes Radix Angelicae Sinensis control medicinal material solution, Rhizoma Chuanxiong control medicinal material solution respectively.Get the ferulic acid reference substance, add ethanol and make the reference substance solution that every ml contains 2mg.Other gets the ferulic acid reference substance, adds methanol and makes the reference substance solution that every ml contains 2mg.According to the thin layer chromatography test, draw each 2～10 μ l of above-mentioned control medicinal material solution, reference substance solution and need testing solution, put in same silica gel G F respectively
254On the plate, be developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect with benzene-methanol-glacial acetic acid=13: 2: 1.2.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
The thin layer chromatography of ferulic acid is differentiated in embodiment 17 microcapsules
Get this product powder 2g, add water 30ml supersound extraction, filter, filtrate is extracted 2 times with the ether jolting, and each 20ml merges ether solution, extract 2 times with 5% sodium bicarbonate solution jolting, each 20ml merges soda solution, regulate pH value to 2～3 with dilute hydrochloric acid, the jolting of reuse ether is extracted 2 times, each 20ml, merge ether solution, evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets the ferulic acid reference substance, adds ethanol and makes the reference substance solution that every ml contains 2mg.According to the thin layer chromatography test, draw each 2～5 μ l of above-mentioned reference substance solution and need testing solution, put in same silica gel G F respectively
254On the plate, be developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect with benzene-methanol-glacial acetic acid=17: 1: 0.8.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
The thin layer chromatography of white Peony Root, Radix Paeoniae Rubra medical material, peoniflorin is differentiated in embodiment 18 dispersible tablets
Get this product powder 2g, add water 30ml supersound extraction, centrifugal, supernatant extracts 2 times with water saturated n-butyl alcohol jolting, and each 30ml merges n-butyl alcohol, and liquid evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets white Peony Root 0.5g, Radix Paeoniae Rubra medical material 0.5g, adds methanol 30ml and extracts, and filters, and filtrate is concentrated into 1ml, makes Radix Paeoniae Alba control medicinal material solution, Radix Paeoniae Rubra control medicinal material solution respectively; Get the peoniflorin reference substance, add methanol and make the reference substance solution that every ml contains 1mg.Test according to thin layer chromatography, draw each 2～5 μ l of above-mentioned control medicinal material solution, reference substance solution and need testing solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol=8: 2 was developing solvent, launch, take out, dry, spray is with 1% vanillin sulfuric acid solution, and 105 ℃ to be heated to the speckle colour developing clear.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
The thin layer chromatography of peoniflorin is differentiated in embodiment 19 pellets
Get this product powder 2g, add water 30ml supersound extraction, centrifugal, supernatant extracts 2 times with water saturated n-butyl alcohol jolting, and each 30ml merges n-butyl alcohol, and liquid evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Get the peoniflorin reference substance, add methanol and make the reference substance solution that every ml contains 1mg.According to the thin layer chromatography test, draw each 2～5 μ l of above-mentioned reference substance solution and need testing solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol=7: 2.5 was developing solvent, launched, and took out, dry, spray is with 1% vanillin sulfuric acid solution, and 105 ℃ to be heated to speckle colour developing clear.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
The thin layer chromatography of white Peony Root, Radix Paeoniae Rubra medical material, peoniflorin is differentiated in embodiment 20 soft capsules
Get this product content 3g, add water 50ml supersound extraction, centrifugal, supernatant extracts 2 times with water saturated n-butyl alcohol jolting, and each 30ml merges n-butyl alcohol, and liquid evaporate to dryness, residue add ethanol 1ml makes dissolving, as need testing solution.Other gets white Peony Root 0.5 g, Radix Paeoniae Rubra medical material 0.5g, adds ethanol 30ml and extracts, and filters, and filtrate is concentrated into 1ml, makes Radix Paeoniae Alba control medicinal material solution, Radix Paeoniae Rubra control medicinal material solution respectively; Get the peoniflorin reference substance, add methanol and make the reference substance solution that every ml contains 2mg.Test according to thin layer chromatography, draw each 2～5 μ l of above-mentioned control medicinal material solution, reference substance solution and need testing solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol=9: 1.5 was developing solvent, launch, take out, dry, spray is with 1% vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing.In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
The high performance liquid chromatography assay of peoniflorin in embodiment 21 drop pills
This product, porphyrize is got about 0.6g, the accurate title, decide, and adds water 15ml and make dissolving, extracts 4 times with the water-saturated n-butanol jolting, each 15ml merges n-butyl alcohol liquid, evaporate to dryness, residue add methanol make in right amount the dissolving and be transferred in the 5ml measuring bottle, add methanol to scale, shake up, microporous filter membrane (0.45 μ m) filters, get subsequent filtrate, as need testing solution.It is an amount of to get the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes the reference substance solution that every 1ml contains 0.1mg.Adopting high performance liquid chromatography, is filler with octadecylsilane chemically bonded silica; With acetonitrile-0.02mol/L sodium dihydrogen phosphate=15: 85 was mobile phase; The detection wavelength is 230nm, and number of theoretical plate calculates by the peoniflorin peak should be not less than 3000.Accurate respectively each the 10 μ l of above-mentioned two kinds of solution that draw inject chromatograph of liquid, measure, and calculate with one point external standard method.This product contained peoniflorin with dosage on 1st must not be less than 2.4mg.
The high performance liquid chromatography assay of peoniflorin in embodiment 22 dispersible tablets
This product powder 1g, the accurate title, decide, and adds water 20ml supersound extraction, centrifugal, supernatant extracts 4 times with the water-saturated n-butanol jolting, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add methanol make in right amount the dissolving and be transferred in the 5ml measuring bottle, add methanol to scale, shake up, filter, get subsequent filtrate, as need testing solution.It is an amount of to get the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes the reference substance solution that every 1ml contains 0.1mg.Adopting high performance liquid chromatography, is filler with octadecylsilane chemically bonded silica; With acetonitrile-0.05mol/L sodium dihydrogen phosphate=13: 87 was mobile phase; The detection wavelength is 227nm, and number of theoretical plate calculates by the peoniflorin peak should be not less than 2000.Accurate respectively each the 5 μ l of above-mentioned two kinds of solution that draw inject chromatograph of liquid, measure, and calculate with one point external standard method.This product contained peoniflorin with dosage on 1st must not be less than 2.0mg.
The high performance liquid chromatography assay of peoniflorin in embodiment 23 pellets
This product powder 1g, the accurate title, decide, and adds water 20ml supersound extraction, centrifugal, supernatant extracts 4 times with the water-saturated n-butanol jolting, each 20ml, merge n-butyl alcohol liquid, evaporate to dryness, residue add methanol make in right amount the dissolving and be transferred in the 5ml measuring bottle, add methanol to scale, shake up, filter, get subsequent filtrate, as need testing solution.It is an amount of to get the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes the reference substance solution that every 1ml contains 0.05mg.Adopting high performance liquid chromatography, is filler with octadecylsilane chemically bonded silica; With acetonitrile-0.01mol/L sodium dihydrogen phosphate=17: 83 was mobile phase; The detection wavelength is 233nm, and number of theoretical plate calculates by the peoniflorin peak should be not less than 3000.Accurate respectively each the 15 μ l of above-mentioned two kinds of solution that draw inject chromatograph of liquid, measure, and calculate with standard curve method.This product contained peoniflorin with dosage on 1st must not be less than 1.2mg.
The high performance liquid chromatography assay of ferulic acid in embodiment 24 microcapsules
Get this product powder 3g, accurate claim fixed, the accurate 80% methanol aqueous solution 25ml that contains 1% glacial acetic acid that adds, supersound process is put coldly, supplies the solvent of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution.It is an amount of to get the ferulic acid reference substance, accurate claims surely, adds 80% methanol and makes every ml and contain 30 μ g reference substance solution.The test of employing high performance liquid chromatography is a filler with octadecylsilane chemically bonded silica; Methanol-1% glacial acetic acid solution=27: 73 is a mobile phase; The detection wavelength is 315nm.Number of theoretical plate calculates by the ferulic acid peak should be not less than 1000; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and calculate with one point external standard method.This product contained ferulic acid with dosage on 1st must not be less than 0.5mg.
The high performance liquid chromatography assay of ferulic acid in embodiment 25 drop pills
Get this product powder 2g, accurate claim fixed, the accurate 60% methanol aqueous solution 25ml that contains 1% glacial acetic acid that adds, supersound process is put coldly, supplies the solvent of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution.It is an amount of to get the ferulic acid reference substance, accurate claims surely, adds 60% methanol and makes every ml and contain 30 μ g reference substance solution.The test of employing high performance liquid chromatography is a filler with octadecylsilane chemically bonded silica; Methanol-0.5% glacial acetic acid solution=25: 75 is a mobile phase; The detection wavelength is 313nm.Number of theoretical plate calculates by the ferulic acid peak should be not less than 800; Accurate respectively reference substance solution and each 5 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and calculate with one point external standard method.This product contained ferulic acid with dosage on 1st must not be less than 0.25mg.
The high performance liquid chromatography assay of ferulic acid in embodiment 25 dispersible tablets
Get this product powder 2g, accurate claim fixed, the accurate 70% methanol aqueous solution 25ml that contains 0.3% hydrochloric acid that adds, supersound process is put coldly, supplies the solvent of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution.It is an amount of to get the ferulic acid reference substance, accurate claims surely, adds 70% methanol and makes every ml and contain 30 μ g reference substance solution.The test of employing high performance liquid chromatography is a filler with octadecylsilane chemically bonded silica; Methanol-1.5% glacial acetic acid solution=29: 71 is a mobile phase; The detection wavelength is 317nm.Number of theoretical plate calculates by the ferulic acid peak should be not less than 1000; Accurate respectively reference substance solution and each 15 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and calculate with one point external standard method.This product contained ferulic acid with dosage on 1st must not be less than 0.40mg.
Claims (12)
1, a kind of gynecological's menstruation-regulating preparation for the treatment of gynaecopathia, it is characterized in that: calculate according to weight, it is with Radix Angelicae Sinensis 32g, Rhizoma Chuanxiong 3.6g, Rhizoma Cyperi (processed with vinegar) 88.9g, Rhizoma Atractylodis Macrocephalae (parched with bran) 5.1g, Radix Paeoniae Alba 2.6g, Radix Paeoniae Rubra 2.6g, Rhizoma Corydalis (processed with vinegar) 7.1g, Radix Rehmanniae Preparata 10.7g, Fructus Jujubae 17.8g, Radix Glycyrrhizae 2.4g all the acceptable dosage forms on the pharmaceutics that are made comprise: injection, the powder pin, freeze-dried powder, tablet, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, micropill, powder, drop pill, slow releasing preparation, controlled release preparation, gel, oral liquid, soft extract, extractum and membrane.
2, according to gynecological's menstruation-regulating preparation of the described treatment gynaecopathia of claim 1, it is characterized in that: described preparation is dispersible tablet, soft capsule, granule, micropill, gel, oral liquid, drop pill, sustained-release preparation, tablet, effervescent tablet or capsule.
3, according to the method for making of gynecological's menstruation-regulating preparation of claim 1 or 2 described treatment gynaecopathias, it is characterized in that: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter merging filtrate, be 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, make different preparations then respectively.
4, according to the method for making of gynecological's menstruation-regulating preparation of the described treatment gynaecopathia of claim 3, it is characterized in that: the drop pill in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate, be 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 1～2.5 part of Macrogol 4000 adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip, drip speed 20～50d/min apart from 1～9cm, 60～90 ℃ of material temperature, drip and in 20～30 ℃ dimethicone, to become ball, collect drop pill, remove the methyl-silicone oil on surface, packing, promptly.
5, according to the method for making of gynecological's menstruation-regulating preparation of the described treatment gynaecopathia of claim 4, it is characterized in that: the drop pill in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate, be 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Ratio in 1 part in medicated powder, 2 parts of Macrogol 4000s adds Macrogol 4000, mix homogeneously, heating and melting, stir, be transferred to the drop pill machine, drip, drip speed 30～40d/min apart from 3～7cm, 70～80 ℃ of material temperature, drip and in 20～30 ℃ dimethicone, to become ball, collect drop pill, remove the methyl-silicone oil on surface, packing, promptly.
6, method for making according to gynecological's menstruation-regulating preparation of the described treatment gynaecopathia of claim 3, it is characterized in that: the pellet in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate is 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure, pulverize, add an amount of starch,, push a round as a ball pill or adopt the general ball of making of coating pan with 70% ethanol and soybean oil system soft material, drying, promptly.
7, according to the method for making of gynecological's menstruation-regulating preparation of the described treatment gynaecopathia of claim 3, it is characterized in that: the dispersible tablet in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate, be 1.18～1.20 clear paste when being evaporated to 80～85 ℃ of relative densities, drying under reduced pressure is pulverized; Get CMC-Na: PVPP: mannitol=add an amount of pigment mixing as pharmaceutical adjunct at 1: 2: 2, get 3/5 pharmaceutical adjunct and the medicated powder mix homogeneously that is equivalent to 8 times of amounts of CMC-Na approximately, PVP-K with 2%
30Anhydrous alcohol solution is made binding agent, and 40 order system material, granulate remain 2/5 pharmaceutical adjunct and an amount of caramel color mixing, be added on outward in the particle that makes, and tabletting, promptly.
8, according to the method for making of gynecological's menstruation-regulating preparation of the described treatment gynaecopathia of claim 3, it is characterized in that: the soft capsule in the described preparation prepares like this: get Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi (processed with vinegar), Rhizoma Atractylodis Macrocephalae (parched with bran), the Radix Paeoniae Alba, Radix Paeoniae Rubra, Rhizoma Corydalis (processed with vinegar), Radix Rehmanniae Preparata, Fructus Jujubae, Radix Glycyrrhizae, decoct with water secondary, 3 hours for the first time, 2 hours for the second time, filter, merging filtrate, it when being evaporated to 80～85 ℃ of relative densities 1.18～1.20 clear paste, drying under reduced pressure is pulverized, and crosses 80 mesh sieves, press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%, pelleting; The dry typing drying of rolling that adopts combined with two steps of tray dried, dry 2 hours of the typing of rolling, and 22 ℃ of baking temperatures, dry relative humidity should be lower than 40%, and drying time is at 24～48 hours, promptly.
9, according to the method for quality control of gynecological's menstruation-regulating preparation of any described treatment gynaecopathia in the claim 1～8, it is characterized in that: discrimination method comprises following part or all of content:
A. one or both thin layer chromatography discriminating in Rhizoma Cyperi medical material, the α-cyperone in the preparation
It is an amount of to get this product powder, is dissolved in water or extracts, and aqueous solution adds diethyl ether or ethyl acetate or chloroform jolting are extracted, and extracting solution concentrates or evaporate to dryness adds the appropriate solvent dissolving again, as need testing solution; Other gets the Rhizoma Cyperi control medicinal material, with reference to the need testing solution method for making, makes control medicinal material solution; Get α-cyperone, make reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-ethyl acetate-formic acid=6～8: be developing solvent at 4～6: 0.1～0.3, launch, take out, dry, spray is with the vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the same color speckle;
B. one or both thin layer chromatography discriminating in corydalis tuber medicinal material, the tetrahydropalmatine in the preparation
It is an amount of to get this product powder, adds methanol or ethanol supersound process, filters, and filtrate evaporate to dryness, residue add water makes dissolving, adds alkali liquor and transfers to alkalescence, extracts with ether or chloroform jolting, and extracting solution concentrates or evaporate to dryness adds the appropriate solvent dissolving again, as need testing solution; Other gets the Rhizoma Corydalis control medicinal material, with reference to the need testing solution method for making, makes control medicinal material solution; Get tetrahydropalmatine, make reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate with the sodium hydroxide solution preparation, with toluene-acetone=8～10: 1.5～2.5 is developing solvent, launch, take out, dry, put in the iodine steam smoked after, put under the ultra-violet lamp and inspect; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the fluorescence speckle of same color;
C. one or more thin layer chromatography discriminating in Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, the ferulic acid in the preparation
It is an amount of to get this product, is dissolved in water or extracts, and water liquid extracts with the ether jolting, ether solution extracts with the alkali liquor jolting, and alkali liquor extracts with acid for adjusting pH value to 1～3, reuse ether or ethyl acetate jolting, extracting solution concentrates or evaporate to dryness adds the appropriate solvent dissolving again, as need testing solution; Other gets Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, add the alkaline solution supersound extraction respectively, extracting solution is with adding acid for adjusting pH value to 1～3, and reuse ether or ethyl acetate jolting are extracted, extracting solution concentrates or evaporate to dryness adds the appropriate solvent dissolving again, makes Radix Angelicae Sinensis control medicinal material solution, Rhizoma Chuanxiong control medicinal material solution respectively; Other gets the ferulic acid reference substance, makes reference substance solution; According to thin layer chromatography test, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively in same with silica gel G F
254On the plate, with benzene-methanol-glacial acetic acid=13～17: be developing solvent at 1～2: 0.8～1.2, launches, and takes out, and dries, and puts under the ultra-violet lamp 254nm and inspect; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color;
D. one or more thin layer chromatography discriminating in white Peony Root, Radix Paeoniae Rubra medical material, the peoniflorin in the preparation
It is an amount of to get this product, is dissolved in water or extracts, and water liquid extracts with water saturated n-butyl alcohol jolting, n-butyl alcohol liquid evaporate to dryness, and residue adds methanol or ethanol makes dissolving, as need testing solution; Other gets white Peony Root, Radix Paeoniae Rubra medical material, adds methanol or ethanol extraction, makes control medicinal material solution respectively; Get the peoniflorin reference substance, make every reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate, with chloroform-methanol=7～9: 1.5～2.5 is developing solvent, launch, take out, dry, spray is with the vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
10, according to the method for quality control of gynecological's menstruation-regulating preparation of the described treatment gynaecopathia of claim 9, it is characterized in that: discrimination method comprises following part or all of content:
A. one or both thin layer chromatography discriminating in Rhizoma Cyperi medical material, the α-cyperone in the preparation
It is an amount of to get this product, is dissolved in water or extracts, and the jolting that adds diethyl ether of water liquid is extracted, and ether solution volatilizes, and residue adds dissolve with methanol, as need testing solution; Other gets the Rhizoma Cyperi control medicinal material, adds the water heating extraction, filters, and the jolting that adds diethyl ether of water liquid is extracted, and ether solution volatilizes, and residue adds dissolve with methanol, in contrast medical material solution; Get α-cyperone, add methanol and make reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate, with cyclohexane extraction-ethyl acetate-formic acid=7: 5: 0.2 was developing solvent, launch, take out, dry, spray is with the vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the same color speckle;
B. one or both thin layer chromatography discriminating in corydalis tuber medicinal material, the tetrahydropalmatine in the preparation
It is an amount of to get this product powder, adds the methanol supersound process, filters, and filtrate evaporate to dryness, residue add water makes dissolving, adds strong ammonia solution and transfers to alkalescence, extracts with the ether jolting, and ether solution concentrates, as need testing solution; Other gets the Rhizoma Corydalis control medicinal material, shines medical material solution in pairs with legal system; Get tetrahydropalmatine, add methanol and make reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on the silica gel g thin-layer plate of same usefulness 1% sodium hydroxide solution preparation, with toluene-acetone=9: 2 was developing solvent, launched, and took out, dry, put in the iodine cylinder after about 3 minutes and take out, wave the iodine that adsorbs on the most plate after, put under the ultra-violet lamp 365nm and inspect; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the fluorescence speckle of same color;
C. one or more thin layer chromatography discriminating in Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, the ferulic acid in the preparation
It is an amount of to get this product, is dissolved in water or extracts, and extracts with the ether jolting, ether solution extracts with 5% sodium bicarbonate solution jolting, and soda solution is regulated pH value to 2～3 with dilute hydrochloric acid, and the jolting of reuse ether is extracted, ether solution evaporate to dryness, residue add ethanol or methanol makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis medical material, Rhizoma Chuanxiong medical material, add the sodium bicarbonate solution supersound extraction respectively, centrifugal, supernatant is regulated pH value to 2～3 with dilute hydrochloric acid, and the jolting of reuse ether is extracted, ether solution, evaporate to dryness, residue add ethanol or methanol makes dissolving, makes Radix Angelicae Sinensis control medicinal material solution, Rhizoma Chuanxiong control medicinal material solution respectively; Get the ferulic acid reference substance, add methanol or ethanol is made reference substance solution; According to thin layer chromatography test, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put in same silica gel G F respectively
254On the plate, be developing solvent, launch, take out, dry, put under the ultra-violet lamp 254nm and inspect with benzene-methanol-glacial acetic acid=15: 1.5: 1; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color;
D. one or more thin layer chromatography discriminating in white Peony Root, Radix Paeoniae Rubra medical material, the peoniflorin in the preparation
It is an amount of to get this product, is dissolved in water or extracts, extract with water saturated n-butyl alcohol jolting, and n-butyl alcohol liquid evaporate to dryness, residue adds methanol or ethanol makes dissolving, as need testing solution; Other gets white Peony Root, Radix Paeoniae Rubra medical material, adds methanol or ethanol extraction, and extracting solution concentrates, and makes control medicinal material solution respectively; Get the peoniflorin reference substance, add methanol or ethanol and make every reference substance solution; Test according to thin layer chromatography, one or both and the need testing solution drawn in above-mentioned control medicinal material solution, the reference substance solution are an amount of, put respectively on same silica gel g thin-layer plate, with chloroform-methanol=8: 2 was developing solvent, launch, take out, dry, spray is with the vanillin sulfuric acid solution, and it is clear to be heated to the speckle colour developing; In the test sample chromatograph, with contrast chromatograph corresponding position on, show the speckle of same color.
11, according to the method for quality control of gynecological's menstruation-regulating preparation of any described treatment gynaecopathia in the claim 1～8, it is characterized in that: content assaying method comprises following part or all of content:
A. the high performance liquid chromatography assay of peoniflorin in the preparation
It is an amount of to get this product powder, accurate claims surely, is dissolved in water or extracts, and aqueous solution extracts with the water-saturated n-butanol jolting, n-butyl alcohol liquid evaporate to dryness, and residue adds dissolve with methanol and standardize solution, filters, and gets subsequent filtrate, as need testing solution; It is an amount of to get the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes reference substance solution; Adopting high performance liquid chromatography, is filler with octadecylsilane chemically bonded silica; With acetonitrile-0.01～0.05mol/L sodium dihydrogen phosphate=13～17: 87～83 is mobile phase; The detection wavelength is 227～233nm, and number of theoretical plate calculates by the peoniflorin peak should be not less than 2000; Accurate respectively absorption reference substance solution and need testing solution are an amount of, inject chromatograph of liquid, measure, and calculate with one point external standard method or standard curve method; This product contained peoniflorin with dosage on 1st must not be less than 1.2mg;
B. the high performance liquid chromatography assay of ferulic acid in the preparation
It is an amount of to get this product powder, accurate claim fixed, the accurate acidic methanol aqueous solution that adds, supersound process is put coldly, supplies the solvent of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution; It is an amount of to get the ferulic acid reference substance, and accurate the title decides, and adds methanol aqueous solution and makes reference substance solution; The test of employing high performance liquid chromatography is a filler with octadecylsilane chemically bonded silica; Methanol-0.5～1.5% glacial acetic acid solution=25～29: 75～71 are mobile phase; The detection wavelength is 313～317nm; Number of theoretical plate calculates by the ferulic acid peak should be not less than 800; Each is an amount of for accurate respectively absorption reference substance solution and need testing solution, injects chromatograph of liquid, measures, and calculates with one point external standard method or standard curve method; This product contained ferulic acid with dosage on 1st must not be less than 0.25mg.
12, according to the method for quality control of gynecological's menstruation-regulating preparation of the described treatment gynaecopathia of claim 11, it is characterized in that: content assaying method comprises following part or all of content:
A. the high performance liquid chromatography assay of peoniflorin in the preparation
It is an amount of to get this product powder, accurate claims surely, is dissolved in water or extracts, and aqueous solution extracts 4 times with the water-saturated n-butanol jolting, merges n-butyl alcohol liquid, and evaporate to dryness, residue add dissolve with methanol and standardize solution, filter, and get subsequent filtrate, as need testing solution; It is an amount of to get the peoniflorin reference substance, and accurate the title decides, and adds methanol and makes reference substance solution; Adopting high performance liquid chromatography, is filler with octadecylsilane chemically bonded silica; With acetonitrile-0.02mol/L sodium dihydrogen phosphate=15: 85 was mobile phase; The detection wavelength is 230nm, and number of theoretical plate calculates by the peoniflorin peak should be not less than 3000; Accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing inject chromatograph of liquid, measure, and calculate with one point external standard method; This product contained peoniflorin with dosage on 1st must not be less than 2.4mg;
B. the high performance liquid chromatography assay of ferulic acid in the preparation
It is an amount of to get this product powder, accurate claim fixed, the accurate acidic methanol aqueous solution that adds, supersound process is put coldly, supplies the solvent of loss, shakes up, and filters, and gets subsequent filtrate, as need testing solution; It is an amount of to get the ferulic acid reference substance, and accurate the title decides, and adds methanol aqueous solution and makes reference substance solution; The test of employing high performance liquid chromatography is a filler with octadecylsilane chemically bonded silica; Methanol-1% glacial acetic acid solution=27: 73 is a mobile phase; The detection wavelength is 315nm; Number of theoretical plate calculates by the ferulic acid peak should be not less than 1000; Each is an amount of for accurate respectively absorption reference substance solution and need testing solution, injects chromatograph of liquid, measures, and calculates with one point external standard method; This product contained ferulic acid with dosage on 1st must not be less than 0.5mg.
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| CN102805796A (en) * | 2012-08-29 | 2012-12-05 | 北京亚东生物制药有限公司 | Traditional Chinese medicine composition for treating abnormal menstruation and preparation method thereof |
| CN102988665A (en) * | 2012-10-08 | 2013-03-27 | 卞毓平 | Method for preparing gynecological menstruation regulating tablets and application |
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| CN102426212A (en) * | 2010-11-02 | 2012-04-25 | 河北以岭医药研究院有限公司 | Enhanced fluorescence thin layer identification method for Cyperus Rotundus L |
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| CN102988665A (en) * | 2012-10-08 | 2013-03-27 | 卞毓平 | Method for preparing gynecological menstruation regulating tablets and application |
| CN103394013A (en) * | 2013-07-19 | 2013-11-20 | 苏州市天灵中药饮片有限公司 | Traditional Chinese medicine containing corydalis tuber and preparation method thereof |
| CN106466396A (en) * | 2015-08-19 | 2017-03-01 | 贵州益佰女子大药厂有限责任公司 | A kind of Fuke Tiaojing sustained-release dropping pill and preparation method thereof |
| CN106466396B (en) * | 2015-08-19 | 2020-01-10 | 贵州益佰女子大药厂有限责任公司 | Gynaecologic menstruation regulating sustained-release dropping pill and preparation method thereof |
| CN106706825A (en) * | 2015-11-17 | 2017-05-24 | 天士力制药集团股份有限公司 | Method used for measuring content of tetrahydropalmatine in rhizoma cyperi-tangerine leaf capsule used for treating breast hyperplasia |
| CN106198835A (en) * | 2016-06-24 | 2016-12-07 | 广西灵峰药业有限公司 | A kind of quality of production control method of day wingceltis wine |
| CN106198835B (en) * | 2016-06-24 | 2018-06-01 | 广西灵峰药业有限公司 | A kind of quality of production control method of day wingceltis wine |
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| CN101057926B (en) | 2010-08-25 |
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