CN102058834B

CN102058834B - Traditional Chinese medicine composition dispersible tablet capable of lowering blood pressure, reducing heat and resisting inflammation and preparation method thereof

Info

Publication number: CN102058834B
Application number: CN2009102375699A
Authority: CN
Inventors: 刘丽颖; 郑松涛
Original assignee: 刘丽颖
Current assignee: Harbin Pugongying Pharmaceutical Co., Ltd.
Priority date: 2009-11-12
Filing date: 2009-11-12
Publication date: 2012-07-25
Anticipated expiration: 2029-11-12
Also published as: CN102058834A

Abstract

The invention discloses a traditional Chinese medicine composition dispersible tablet capable of lowering blood pressure, reducing heat and resisting inflammation and a preparation method thereof. The traditional Chinese medicine composition comprises the following 15 bulk pharmaceutical chemicals: calculus bovis artifactus, pulvis fellis suis, Scutellaria baicalensis, radix curcumae, gardenia, borneol, Coptis chinensis, pearl, ochre, realgar, cinnabar, menthol, gypsum, buffalo horn concentrated powder and pearl shell, and comprises the following the auxiliary materials: disintegrating agent, adhesive and lubricant, and other common medical auxiliary materials can be added. The preparation technology of the medicine composition dispersible tablet comprises: grouping the bulk pharmaceutical chemicals; respectively preparing an intermediate and medical powder; and after mixing, preparing the dispersible table by adding the auxiliary materials according to a normal technology. The pharmacodynamics experiment indicates that the medicine composition dispersible tablet has effects of reducing heat, resisting inflammation and thrombosis and reducing pressure.

Description

A kind of blood pressure lowering, antipyretic and anti-inflammatory Chinese medicine composition composition dispersible tablets and preparation method thereof

Technical field

The present invention relates to a kind of medicament combination dispersible tablet and preparation method thereof, particularly a kind of blood pressure lowering, antipyretic and anti-inflammatory Chinese medicine composition composition dispersible tablets and preparation method thereof.

Background technology

Annaowan bolus is the prescriptions of Chinese medicine that is recorded in the 13 77 pages in the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation; Standard is numbered WS3-B-2517-97, and the prescription of having put down in writing Annaowan bolus in the standard comprises: artificial Calculus Bovis, Pulvis Fellis Suis, Cinnabaris, Borneolum Syntheticum, Pulvis Cornus Bubali Concentratus, Margarita, Radix Scutellariae, Rhizoma Coptidis, Fructus Gardeniae, Realgar, Radix Curcumae, Gypsum Fibrosum, Haematitum, Concha Margaritifera and Mentholum; The patent No. is the prescription consumption proportion relation that 93100258.3 patent applications disclose Annaowan bolus, and conventional preparation technology; The open Annaowan bolus of available data has heat-clearing and toxic substances removing, refreshment and tranquilization, eliminates phlegm for resuscitation, the relieving convulsion effect that relieves dizziness, high fever, infantile convulsions, epilepsy, etc., and nowadays is hyperpyrexia, the delirious clinical application that a kind of treatment acute inflammation commonly used causes.

Yet; Annaowan bolus has existed for many years as the honeyed pill dosage form; By the simple and regular preparation technology that pulverizing, water fly, step such as refined honey is formed can't solve this prescription products all the time and have that potential toxic and side effects, wastage of material are more, dosage form originally causes fully being absorbed by human body, bioavailability is not high; There is untoward reaction; Take problems such as inconvenience, the problems referred to above exert an influence to the market prospect of this prescription products in the environment that nowadays tradition is write out a prescription and high-tech is combined closely, and simplifying prescription, improveing dosage form, improve preparation technology all is problem demanding prompt solutions that Annaowan bolus faces.

Summary of the invention

The objective of the invention is to disclose a kind of blood pressure lowering, antipyretic and anti-inflammatory Chinese medicine composition composition dispersible tablets, the present invention also aims to disclose the method for preparing of this dispersible tablet.

The present invention seeks to realize through following scheme.

The crude drug of dispersible tablet of the present invention consists of:

Artificial Calculus Bovis 0.5-2 weight portion Pulvis Fellis Suis 7-20 weight portion Rhizoma Coptidis 5-15 weight portion

Radix Scutellariae 5-15 weight portion Margarita 1-5 weight portion Fructus Gardeniae 5-15 weight portion

Radix Curcumae 5-15 weight portion Haematitum 2-6 weight portion Realgar 3-9 weight portion

Cinnabaris 2-6 weight portion Mentholum 0.5-2 weight portion Gypsum Fibrosum 5-12 weight portion

Borneolum Syntheticum 0.5-4 weight portion Pulvis Cornus Bubali Concentratus 7-20 weight portion

Concha Margaritifera 2-8 weight portion.

The crude drug composition of dispersible tablet of the present invention is preferably:

Artificial Calculus Bovis's 1 weight portion Pulvis Fellis Suis 13 weight portion Rhizoma Coptidis 10 weight portions

Radix Scutellariae 10 weight portion Margaritas 3 weight portion Fructus Gardeniaes 10 weight portions

Radix Curcumae 10 weight portion Haematitums 4 weight portion Realgars 6 weight portions

Cinnabaris 4 weight portion Mentholums 1 weight portion Gypsum Fibrosum 8 weight portions

Borneolum Syntheticum 2 weight portion Pulvis Cornus Bubali Concentratuss 13 weight portion Concha Margaritiferas 5 weight portions.

Artificial Calculus Bovis's 0.7 weight portion Pulvis Fellis Suis 18 weight portion Rhizoma Coptidis 6 weight portions

Radix Scutellariae 14 weight portion Margaritas 2 weight portion Fructus Gardeniaes 14 weight portions

Radix Curcumae 6 weight portion Haematitums 5 weight portion Realgars 4 weight portions

Cinnabaris 5 weight portion Mentholums 0.7 weight portion Gypsum Fibrosum 11 weight portions

Borneolum Syntheticum 1 weight portion Pulvis Cornus Bubali Concentratus 18 weight portion Concha Margaritiferas 3 weight portions.

Artificial Calculus Bovis's 1.8 weight portion Pulvis Fellis Suiss 9 weight portion Rhizoma Coptidis 14 weight portions

Radix Scutellariae 6 weight portion Margaritas 4 weight portion Fructus Gardeniaes 6 weight portions

Radix Curcumae 14 weight portion Haematitums 3 weight portion Realgars 8 weight portions

Cinnabaris 3 weight portion Mentholums 1.8 weight portion Gypsum Fibrosum 6 weight portions

Borneolum Syntheticum 3.5 weight portion Pulvis Cornus Bubali Concentratuss 9 weight portion Concha Margaritiferas 7 weight portions.

The adjuvant of dispersible tablet of the present invention comprises as follows:

Disintegrating agent 120-520 weight portion

Adhesive 50-280 weight portion

Lubricant 50-320 weight portion.

Disintegrating agent 320 weight portions

Adhesive 160 weight portions

Lubricant 180 weight portions.

Disintegrating agent 500 weight portions

Adhesive 60 weight portions

Lubricant 60 weight portions.

Disintegrating agent 150 weight portions

Adhesive 250 weight portions

Lubricant 300 weight portions.

The adjuvant of dispersible tablet of the present invention is formed can also add other conventional pharmaceutic adjuvants again on the basis of above-mentioned adjuvant.

Wherein, above-mentioned disintegrating agent is one or more in starch, dextrin, gel aluminum hydroxide, carboxymethyl starch sodium, low substituted hydroxy-propyl methylcellulose, crospolyvinylpyrrolidone, microcrystalline Cellulose, tween 80, cetab, sodium lauryl sulphate and the polyacrylic resin.

Wherein, above-mentioned adhesive is one or more in polyvinylpyrrolidone, methylcellulose, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl emthylcellulose, gelatin and the polyacrylic resin.

Wherein, above-mentioned lubricant is one or more in magnesium stearate, calcium stearate, hydrogenated vegetable oil, Polyethylene Glycol, Stepanol MG, micropowder silica gel, Pulvis Talci and the silicon dioxide.

The method for preparing of dispersible tablet of the present invention comprises the steps:

Get the above-mentioned raw materials medicine, add conventional adjuvant according to common process and process intermediate, add above-mentioned adjuvant again and process dispersible tablet of the present invention.

Wherein, the said crude drug method of processing intermediate can also be in the following method any one:

Technology 1: form by following steps A, B, C, D and E

Steps A: preparation intermediate compound I

A1: crude drug Radix Scutellariae, Rhizoma Coptidis, Fructus Gardeniae, Radix Curcumae and Gypsum Fibrosum are added hot water reflux, extract, 2-4 time jointly, each 0.5-2.5 hour, merge decocting liquid, be concentrated into thick paste; Add the 30-80% ethanol of 4-10 times of weight in the thick paste, left standstill 12-48 hour, get supernatant and reclaim ethanol, concentrate, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I;

Or A2: crude drug Radix Scutellariae, Rhizoma Coptidis, Fructus Gardeniae, Radix Curcumae and Gypsum Fibrosum are added hot water reflux, extract, 2-4 time jointly, each 0.5-2.5 hour, merge decocting liquid; Be concentrated into relative density 1-1.0～1.4, centrifugal, supernatant is crossed macroporous resin column; The 30-80% ethanol elution; Reclaim ethanol, concentrate, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I;

Or A3: Radix Curcumae is added hot water reflux, extract, 2-4 time earlier, and each 0.5-2.5 hour, volatile oil was subsequent use; Radix Curcumae medicinal residues and the common decocting of crude drug Radix Scutellariae, Rhizoma Coptidis, Gypsum Fibrosum and Fructus Gardeniae boil 2-4 time, and each 0.5-2.5 hour, merge decocting liquid, be concentrated into thick paste; Add the 30%-80% ethanol of 4-10 times of weight in the thick paste, left standstill 12-48 hour, get supernatant and reclaim ethanol, concentrate, spray into volatile oil, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I;

Or A4: Radix Curcumae is added hot water reflux, extract, 2-4 time earlier, and each 0.5-2.5 hour, volatile oil was subsequent use; Radix Curcumae medicinal residues and the common decocting of crude drug Radix Scutellariae, Rhizoma Coptidis, Gypsum Fibrosum and Fructus Gardeniae boil 2-4 time, each 0.5-2.5 hour, merge decocting liquid; Be concentrated into relative density 1-1.0～1.4, centrifugal, supernatant is crossed macroporous resin column; The 30-80% ethanol elution reclaims ethanol, concentrates; Spray into volatile oil, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I;

Step B: preparation intermediate II

B1: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add the 3-10% dilute hydrochloric acid, consumption is the 5-15 times of weight, makes into suspension, leaves standstill 12-48 hour, filters, and filtrating transfers pH value to 3-5 with 10-20% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 8-10 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II;

Or B2: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add the 3-10% dilute hydrochloric acid, consumption is the 5-15 times of weight, makes into suspension, leaves standstill 12-48 hour, filters, and filtrating transfers pH value to 3-5 with 10-20% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 8-10 times of weight in the concentrated solution, leaves standstill, and gets supernatant; Reclaim ethanol, be concentrated into relative density 1-1.0～1.4, centrifugal, supernatant is crossed macroporous resin column; The 30-80% ethanol elution reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II;

Or B3: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, add the 3-10% dilute hydrochloric acid respectively, consumption is the 5-15 times of weight; Make into suspension; Left standstill 12-48 hour, and filtered, filtrating transfers pH value to 3-5 with 10-20% sodium hydroxide (or other alkali liquor); Filtration, filtrating is concentrated into thick paste, adds the ethanol of 8-10 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and gets the extract of Pulvis Cornus Bubali Concentratus powder, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly gets intermediate II after the mixing; Or behind the combination drying the powder of intermediate II;

Or B4: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder,, add the 3-10% dilute hydrochloric acid respectively; Consumption is the 5-15 times of weight, makes into suspension, leaves standstill 12-48 hour; Filter, filtrating transfers pH value to 3-5 with 10-20% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 8-10 times of weight in the concentrated solution, leaves standstill; Get supernatant, reclaim ethanol, be concentrated into relative density 1-1.0～1.4, centrifugal; Supernatant is crossed macroporous resin column, and the 30-80% ethanol elution reclaims ethanol; Concentrate, get the extract of Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly get intermediate II after the mixing; Or behind the combination drying the powder of intermediate II;

Step C: preparation intermediate III

C1: get Pulvis Fellis Suis and Realgar is broken into fine powder, mix, add 3-5% sodium hydroxide 4-8 times of weight, left standstill 12-48 hour, filter, filtrating transfers pH value to 3-5, concentrates, and adds 30-80% ethanol 8-15 times of weight; Get supernatant, reclaim ethanol, concentrate, promptly get intermediate III; Or after the drying the powder of intermediate III;

Or C2: get Pulvis Fellis Suis and be broken into fine powder, add 3-5% sodium hydroxide 4-8 times of weight, left standstill 12-48 hour, filter, filtrating transfers pH value to 3-5, concentrates, and adds 30-80% ethanol 8-15 times of weight; Get supernatant, reclaim ethanol, concentrate, promptly get ketone ibuprofen extract, or get the ketone ibuprofen extract powder after the drying; Get Realgar powder and be broken into fine powder, add 4-8 times of weight 5-10% hydrochloric acid, left standstill 8-24 hour, filter, filtrating accent pH value concentrates to 3-5, adds washing to colourless, promptly gets Realgar extract, or gets the Realgar extract powder after the drying; Ketone ibuprofen extract is mixed with Realgar extract, intermediate III or the powder of intermediate III;

Step D: preparation medicated powder

D1: respectively Borneolum Syntheticum, Mentholum, Cinnabaris and Haematitum are prepared impalpable powder, mix medicated powder;

Or D2: Borneolum Syntheticum, Mentholum and Haematitum are prepared impalpable powder, Cinnabaris is added 5-8 times of weight water grind to pasty state, again by 1: 60--70 adds entry and stirs, and leaves standstill, and inclining suspension, and sediment grinds again; As above method is 3-6 time repeatedly, merges each time suspension, leaves standstill, and gets to be deposited in 25-45 ℃ of airing, and levigation promptly gets the Cinnabaris impalpable powder; With the impalpable powder of above-mentioned four kinds of crude drug mix medicated powder;

Step e: crude drug intermediate

The powder of intermediate compound I, II, III or intermediate compound I, II, III is mixed with medicated powder, get the crude drug intermediate.

The preferred following method of steps A wherein:

A1: crude drug Radix Scutellariae, Rhizoma Coptidis, Fructus Gardeniae, Radix Curcumae and Gypsum Fibrosum are added the hot water reflux, extract, 3 times jointly, each 1.5 hours, merge decocting liquid, be concentrated into thick paste; Add 50% ethanol of 7 times of weight in the thick paste, left standstill 24 hours, get supernatant and reclaim ethanol, concentrate, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I;

Or A2: crude drug Radix Scutellariae, Rhizoma Coptidis, Fructus Gardeniae, Radix Curcumae and Gypsum Fibrosum are added the hot water reflux, extract, 3 times jointly, each 1.5 hours, merge decocting liquid, be concentrated into relative density 1-1.2; Centrifugal, supernatant is crossed macroporous resin column, 50% ethanol elution; Reclaim ethanol, concentrate, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I;

Or A3: Radix Curcumae is added the hot water reflux, extract, earlier 3 times, and each 1.5 hours, volatile oil was subsequent use; Radix Curcumae medicinal residues and the common decocting of crude drug Radix Scutellariae, Rhizoma Coptidis, Gypsum Fibrosum and Fructus Gardeniae boil 3 times, and each 1.5 hours, merge decocting liquid, be concentrated into thick paste; Add 50% ethanol of 7 times of weight in the thick paste, left standstill 24 hours, get supernatant and reclaim ethanol, concentrate, spray into volatile oil, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I;

Or A4: Radix Curcumae is added the hot water reflux, extract, earlier 3 times, and each 1.5 hours, volatile oil was subsequent use; Radix Curcumae medicinal residues and the common decocting of crude drug Radix Scutellariae, Rhizoma Coptidis, Gypsum Fibrosum and Fructus Gardeniae boil 3 times, and each 1.5 hours, merge decocting liquid, be concentrated into relative density 1-1.2; Centrifugal, supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol; Concentrate, spray into volatile oil, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I.

The preferred following method of step B wherein:

B1: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add 6% dilute hydrochloric acid, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II;

Or B2: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add 6% dilute hydrochloric acid, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, is concentrated into relative density 1-1.2, and centrifugal, supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II;

Or B3: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, add 6% dilute hydrochloric acid respectively, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide (or other alkali liquor); Filtration, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and gets the extract of Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly gets intermediate II after the mixing; Or behind the combination drying the powder of intermediate II;

Or B4: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, add 6% dilute hydrochloric acid respectively, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill; Get supernatant, reclaim ethanol, be concentrated into relative density 1-1.2, centrifugal; Supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol; Concentrate, get the extract of Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly get intermediate II after the mixing; Or behind the combination drying the powder of intermediate II.

The preferred following method of step C wherein:

C1: get Pulvis Fellis Suis and Realgar is broken into fine powder, mix, add 4% sodium hydroxide, 6 times of weight, left standstill 24 hours, filter, filtrating is transferred pH value to 4, concentrates, and adds 50% ethanol, 12 times of weight; Get supernatant, reclaim ethanol, concentrate, promptly get intermediate III; Or after the drying the powder of intermediate III;

Or C2: get Pulvis Fellis Suis and be broken into fine powder, add 4% sodium hydroxide, 6 times of weight, left standstill 24 hours, filter, filtrating is transferred pH value to 4, concentrates, and adds 50% ethanol, 12 times of weight; Get supernatant, reclaim ethanol, concentrate, promptly get ketone ibuprofen extract, or get the ketone ibuprofen extract powder after the drying; Get Realgar powder and be broken into fine powder, add 6 times of weight, 8% hydrochloric acid, left standstill 24 hours, filter, filtrating accent pH value to 4 concentrates, and adds washing to colourless, promptly gets Realgar extract, or gets the Realgar extract powder after the drying; Ketone ibuprofen extract is mixed with Realgar extract, intermediate III or the powder of intermediate III.

The preferred following method of step D wherein:

Or D2: Borneolum Syntheticum, Mentholum and Haematitum are prepared impalpable powder, Cinnabaris is added 6 times of weight water grind to pasty state, added entry by 1: 65 again and stir, leave standstill, inclining suspension, and sediment grinds again; As above method is 4 times repeatedly, merges each time suspension, leaves standstill, and gets and is deposited in 35 ℃ of airings, and levigation promptly gets the Cinnabaris impalpable powder; With the impalpable powder of above-mentioned four kinds of crude drug mix medicated powder.

Wherein, above-mentioned any step all can be substituted by conventional method.

Wherein, above-mentioned macroporous resin column model is: YPR-II, X5, AB-8, HPD-100, DX-5, D101, DA201, DM130, WLD-3 or NKA-9.

Technology 2: form by following steps A, B, C and D

Steps A: preparation intermediate compound I

Step B: preparation intermediate II

B1: crude drug Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita, Concha Margaritifera, Pulvis Fellis Suis and Realgar powder are broken into fine powder, mix, add the 30-80% ethanol of 4-10 times of weight; 40-60 ℃ warm macerating 12-48 hour, filter, get filtrating; Reclaim ethanol, concentrate, promptly get intermediate II; Or after the drying the powder of intermediate II;

Step C: preparation medicated powder

C1: respectively Borneolum Syntheticum, Mentholum, Cinnabaris and Haematitum are prepared impalpable powder, mix medicated powder;

Or C2: Borneolum Syntheticum, Mentholum and Haematitum are prepared impalpable powder, Cinnabaris is added 5-8 times of weight water grind to pasty state, again by 1: 60--70 adds entry and stirs, and leaves standstill, and inclining suspension, and sediment grinds again; As above method is 3-6 time repeatedly, merges each time suspension, leaves standstill, and gets to be deposited in 25-45 ℃ of airing, and levigation promptly gets the Cinnabaris impalpable powder; With the impalpable powder of above-mentioned four kinds of crude drug mix medicated powder;

Step D: crude drug intermediate

The powder of intermediate compound I, II or intermediate compound I, II is mixed with medicated powder, get the crude drug intermediate.

The preferred following method of steps A wherein:

The preferred following method of step B wherein:

B1: crude drug Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita, Concha Margaritifera, Pulvis Fellis Suis and Realgar powder are broken into fine powder, mix, add 50% ethanol of 7 times of weight, 50 ℃ of warm macerating 24 hours filter, and get filtrating, reclaim ethanol, concentrate, and promptly get intermediate II; Or after the drying the powder of intermediate II.

The preferred following method of step C wherein:

C1: respectively Borneolum Syntheticum, Mentholum, Cinnabaris and Haematitum are prepared impalpable powder, respectively or mix medicated powder;

Or C2: Borneolum Syntheticum, Mentholum and Haematitum are prepared impalpable powder, Cinnabaris is added 6 times of weight water grind to pasty state, added entry by 1: 65 again and stir, leave standstill, inclining suspension, and sediment grinds again; As above method is 4 times repeatedly, merges each time suspension, leaves standstill, and gets and is deposited in 35 ℃ of airings, and levigation promptly gets the Cinnabaris impalpable powder; With the impalpable powder of above-mentioned four kinds of crude drug mix medicated powder.

Through pharmacodynamic experiment, show that medicament combination dispersible tablet of the present invention has analgesic, antiinflammatory, antithrombotic forms and the effect of blood pressure lowering.

Following experimental example and embodiment are used to further specify but are not limited to the present invention.

The medicament combination dispersible tablet of the present invention that experimental example 1 embodiment of the invention 1-30 processes is to the hypertensive influence of rat experiment property

Laboratory animal: healthy male Waster rat, body weight 190g～210g;

Experiment equipment: RBP-1 type rat blood pressure meter;

Experimental drug and reagent: modeling agent: androlin; Get the medicament combination dispersible tablet of the present invention that embodiment of the invention 1-30 processes, pulverize, be mixed with 100mg/ml with normal saline, 4-5 ℃ of preservation.

Experimental technique: get healthy rat, be divided into 28 groups at random, 8 every group, survey normotensive value and continuous measurement 3 days.After the METHOD FOR CONTINUOUS DETERMINATION 3 days, subcutaneous injection androlin 25mg/kg/ day, each group is irritated clothes equivalent (1g/kg) medicament combination dispersible tablet of the present invention, continuous 10 days respectively.Measure animal blood pressure on time, observe its blood pressure, the result sees table 1.

Table 1 medicament combination dispersible tablet of the present invention is to the hypertensive influence of rat test property (n=8, mmHg, X ± S)

Table 1 shows that the medicament combination dispersible tablet that embodiment of the invention 1-30 prepares all has significant blood pressure reduction effect.The medicament combination dispersible tablet that experimental example 2 embodiment of the invention 1-30 prepare is to the analgesic and antiinflammatory action of inflammatory rat

Laboratory animal: healthy male Waster rat, body weight 190g～210g;

Experiment equipment: pointer electron temperature indicator.

Pyrogen: 1% carrageenin.

Experimental technique: take by weighing carrageenin 100mg, add sterile saline 10ml, mixing, in 4 ℃ of refrigerators, take out morning next day, is inverted to make suspension even for several times, subsequent use; Get the medicament combination dispersible tablet that embodiment of the invention 1-30 prepares, be mixed with 100mg/ml with normal saline respectively, 4 ℃ of preservations are subsequent use; Healthy rat every day is surveyed axil temperature 2 times (upper and lower noon each 1 time) with the electronics temperature indicator, continuous 3 days, chooses the body temperature rat that is no more than 0.3 ℃ of fluctuating and is divided into 28 groups at random, 10 every group.Irritate clothes medicament combination dispersible tablet 1g/kg of the present invention for every group, after this administration measures its axil temperature simultaneously in rat rear foot ripple plantar subcutaneous injection 1% carrageenin suspension 0.1ml/ pawl on time, and the result sees table 2.

The influence of rat fever due to the table 2 medicament combination dispersible tablet on Carrageenan of the present invention (℃, X ± S)

Table 2 shows that the medicament combination dispersible tablet that embodiment of the invention 1-30 prepares all has significant analgesic and antiphlogistic effect.

Following embodiment all can realize the described effect of above-mentioned experimental example.

The specific embodiment

Crude drug described in the following embodiment is formed 1 and is:

Artificial Calculus Bovis 1kg Pulvis Fellis Suis 13kg Rhizoma Coptidis 10kg

Radix Scutellariae 10kg Margarita 3kg Fructus Gardeniae 10kg

Radix Curcumae 10kg Haematitum 4kg Realgar 6kg

Cinnabaris 4kg Mentholum 1kg Gypsum Fibrosum 8kg

Borneolum Syntheticum 2kg Pulvis Cornus Bubali Concentratus 13kg Concha Margaritifera 5kg.

Described crude drug is formed 2 and is:

Artificial Calculus Bovis 0.7kg Pulvis Fellis Suis 18kg Rhizoma Coptidis 6kg

Radix Scutellariae 14kg Margarita 2kg Fructus Gardeniae 14kg

Radix Curcumae 6kg Haematitum 5kg Realgar 4kg

Cinnabaris 5kg Mentholum 0.7kg Gypsum Fibrosum 11kg

Borneolum Syntheticum 1kg Pulvis Cornus Bubali Concentratus 18kg Concha Margaritifera 3kg.

Described crude drug is formed 3 and is:

Artificial Calculus Bovis 1.8kg Pulvis Fellis Suis 9kg Rhizoma Coptidis 14kg

Radix Scutellariae 6kg Margarita 4kg Fructus Gardeniae 6kg

Radix Curcumae 14kg Haematitum 3kg Realgar 8kg

Cinnabaris 3kg Mentholum 1.8kg Gypsum Fibrosum 6kg

Borneolum Syntheticum 3.5kg Pulvis Cornus Bubali Concentratus 9kg Concha Margaritifera 7kg.

Said process 1 A1 is:

A1: crude drug Radix Scutellariae, Rhizoma Coptidis, Fructus Gardeniae, Radix Curcumae and Gypsum Fibrosum are added the hot water reflux, extract, 3 times jointly, each 1.5 hours, merge decocting liquid, be concentrated into thick paste; Add 50% ethanol of 7 times of weight in the thick paste, left standstill 24 hours, get supernatant and reclaim ethanol, concentrate, get the powder of intermediate compound I after the drying.

Said process 1 A2 is:

Crude drug Radix Scutellariae, Rhizoma Coptidis, Fructus Gardeniae, Radix Curcumae and Gypsum Fibrosum are added the hot water reflux, extract, 3 times jointly, each 1.5 hours, merge decocting liquid, be concentrated into relative density 1-1.2; Centrifugal, supernatant is crossed macroporous resin column, 50% ethanol elution; Reclaim ethanol, concentrate, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I.

Said process 1 A3 is:

Radix Curcumae is added the hot water reflux, extract, earlier 3 times, and each 1.5 hours, volatile oil was subsequent use; Radix Curcumae medicinal residues and the common decocting of crude drug Radix Scutellariae, Rhizoma Coptidis, Gypsum Fibrosum and Fructus Gardeniae boil 3 times, and each 1.5 hours, merge decocting liquid, be concentrated into thick paste; Add 50% ethanol of 7 times of weight in the thick paste, left standstill 24 hours, get supernatant and reclaim ethanol, concentrate, spray into volatile oil, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I.

Said process 1 A4 is:

Radix Curcumae is added the hot water reflux, extract, earlier 3 times, and each 1.5 hours, volatile oil was subsequent use; Radix Curcumae medicinal residues and the common decocting of crude drug Radix Scutellariae, Rhizoma Coptidis, Gypsum Fibrosum and Fructus Gardeniae boil 3 times, and each 1.5 hours, merge decocting liquid, be concentrated into relative density 1-1.2; Centrifugal, supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol; Concentrate, spray into volatile oil, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I.

Said process 1 B1 is:

Respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add 6% dilute hydrochloric acid, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II.

Said process 1 B2 is:

Respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add 6% dilute hydrochloric acid, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, is concentrated into relative density 1-1.2, and centrifugal, supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II.

Said process 1 B3 is:

Respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, add 6% dilute hydrochloric acid respectively, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide (or other alkali liquor); Filtration, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and gets the extract of Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly gets intermediate II after the mixing; Or behind the combination drying the powder of intermediate II.

Said process 1 B4 is:

Respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, add 6% dilute hydrochloric acid respectively, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide (or other alkali liquor); Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill; Get supernatant, reclaim ethanol, be concentrated into relative density 1-1.2, centrifugal; Supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol; Concentrate, get the extract of Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly get intermediate II after the mixing; Or behind the combination drying the powder of intermediate II.

Said process 1 C1 is:

Get Pulvis Fellis Suis and Realgar is broken into fine powder, mix, add 4% sodium hydroxide, 6 times of weight, left standstill 24 hours, filter, filtrating is transferred pH value to 4, concentrates, and adds 50% ethanol, 12 times of weight; Get supernatant, reclaim ethanol, concentrate, promptly get intermediate III; Or after the drying the powder of intermediate III.

Said process 1 C2 is:

Get Pulvis Fellis Suis and be broken into fine powder, add 4% sodium hydroxide, 6 times of weight, left standstill 24 hours, filter, filtrating is transferred pH value to 4, concentrates, and adds 50% ethanol, 12 times of weight; Get supernatant, reclaim ethanol, concentrate, promptly get ketone ibuprofen extract, or get the ketone ibuprofen extract powder after the drying; Get Realgar powder and be broken into fine powder, add 6 times of weight, 8% hydrochloric acid, left standstill 24 hours, filter, filtrating accent pH value to 4 concentrates, and adds washing to colourless, promptly gets Realgar extract, or gets the Realgar extract powder after the drying; Ketone ibuprofen extract is mixed with Realgar extract, intermediate III or the powder of intermediate III.

Said process 1 D1 is:

Respectively Borneolum Syntheticum, Mentholum, Cinnabaris and Haematitum are prepared impalpable powder, mix medicated powder.

Said process 1 D2 is:

Borneolum Syntheticum, Mentholum and Haematitum are prepared impalpable powder, Cinnabaris is added 6 times of weight water grind to pasty state, added entry by 1: 65 again and stir, leave standstill, inclining suspension, and sediment grinds again; As above method is 4 times repeatedly, merges each time suspension, leaves standstill, and gets and is deposited in 35 ℃ of airings, and levigation promptly gets the Cinnabaris impalpable powder; With the impalpable powder of above-mentioned four kinds of crude drug mix medicated powder.

Said process 2 A1 are:

Crude drug Radix Scutellariae, Rhizoma Coptidis, Fructus Gardeniae, Radix Curcumae and Gypsum Fibrosum are added the hot water reflux, extract, 3 times jointly, each 1.5 hours, merge decocting liquid, be concentrated into thick paste; Add 50% ethanol of 7 times of weight in the thick paste, left standstill 24 hours, get supernatant and reclaim ethanol, concentrate, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I.

Said process 2 A2 are:

Said process 2 A3 are:

Said process 2 A4 are:

Said process 2 B1 are:

Crude drug Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita, Concha Margaritifera, Pulvis Fellis Suis and Realgar powder are broken into fine powder, mix, add 50% ethanol of 7 times of weight, 50 ℃ of warm macerating 24 hours filter, and get filtrating, reclaim ethanol, concentrate, and promptly get intermediate II; Or after the drying the powder of intermediate II.

Said process 2 C1 are:

Respectively Borneolum Syntheticum, Mentholum, Cinnabaris and Haematitum are prepared impalpable powder, respectively or mix medicated powder.

Said process 2 C2 are:

Embodiment 1: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: starch 100kg microcrystalline Cellulose 100kg polyacrylic resin 120kg

Adhesive: polyvinylpyrrolidone 80kg methylcellulose 80kg

Lubricant: magnesium stearate 180kg;

Get the above-mentioned raw materials medicine, process intermediate, add above-mentioned adjuvant and process dispersible tablet through conventional technology.

Embodiment 2: dispersible tablet of the present invention

Crude drug forms 2;

Disintegrating agent: crospolyvinylpyrrolidone 500kg

Adhesive: sodium carboxymethyl cellulose 60kg

Lubricant: Polyethylene Glycol 60kg;

Intermediates preparation is steps A 3, B2, C1, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 3: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: low substituted hydroxy-propyl methylcellulose 160kg cetab 160kg

Adhesive: methylcellulose 100kg gelatin 60kg

Lubricant: calcium stearate 100kg hydrogenated vegetable oil 80kg;

Intermediates preparation is steps A 4, B2, C1, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 4: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: gel aluminum hydroxide 80kg carboxymethyl starch sodium 80kg low substituted hydroxy-propyl methylcellulose 80kg sodium lauryl sulphate 80kg

Adhesive: low-substituted hydroxypropyl cellulose 80kg hydroxypropyl emthylcellulose 80kg

Lubricant: Polyethylene Glycol 180kg;

Intermediates preparation is steps A 3, B3, C1, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 5: dispersible tablet of the present invention

Crude drug forms 2;

Disintegrating agent: microcrystalline Cellulose 250kg tween 80 250kg

Adhesive: gelatin 60kg

Lubricant: Polyethylene Glycol 30kg micropowder silica gel 30kg;

Embodiment 6: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: starch 100kg gel aluminum hydroxide 100kg microcrystalline Cellulose 120kg

Adhesive: methylcellulose 100kg sodium carboxymethyl cellulose 60kg

Lubricant: hydrogenated vegetable oil 100kg micropowder silica gel 80kg;

Intermediates preparation is steps A 4, B3, C1, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 7: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: cetab 160kg sodium lauryl sulphate 160kg

Adhesive: polyvinylpyrrolidone 80kg methylcellulose 80kg

Lubricant: magnesium stearate 100kg Stepanol MG 80kg;

Intermediates preparation is steps A 1, B1, C1, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 8: dispersible tablet of the present invention

Crude drug forms 2;

Disintegrating agent: dextrin 80kg low substituted hydroxy-propyl methylcellulose 120kg crospolyvinylpyrrolidone 120kg

Adhesive: polyvinylpyrrolidone 80kg polyacrylic resin 80kg

Lubricant: magnesium stearate 100kg silicon dioxide 80kg;

Intermediates preparation is steps A 3, B1, C1, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 9: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: starch 200kg gel aluminum hydroxide 120kg

Adhesive: methylcellulose 100kg sodium carboxymethyl cellulose 60kg

Lubricant: Polyethylene Glycol 80kg Pulvis Talci 100kg;

Intermediates preparation is steps A 2, B2, C2, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 10: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: low substituted hydroxy-propyl methylcellulose 200kg tween 80 300kg

Adhesive: hydroxypropyl emthylcellulose 60kg

Lubricant: silicon dioxide 60kg;

Intermediates preparation is steps A 3, B2, C2, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 11: dispersible tablet of the present invention

Crude drug forms 2;

Disintegrating agent: microcrystalline Cellulose 200kg sodium lauryl sulphate 120kg

Lubricant: Polyethylene Glycol 100kg micropowder silica gel 80kg;

Intermediates preparation is steps A 1, B3, C1, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 12: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: gel aluminum hydroxide 100kg carboxymethyl starch sodium 100kg microcrystalline Cellulose 100kg tween 80 100kg sodium lauryl sulphate 100kg

Adhesive: hydroxypropyl emthylcellulose 60kg

Lubricant: Pulvis Talci 30kg silicon oxide 30kg;

Embodiment 13: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: microcrystalline Cellulose 100kg cetab 50kg

Adhesive: methylcellulose 200kg low-substituted hydroxypropyl cellulose 50kg

Lubricant: magnesium stearate 100kg Polyethylene Glycol 100kg Stepanol MG 100kg;

Intermediates preparation is steps A 4, B3, C1, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 14: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: crospolyvinylpyrrolidone 100kg polyacrylic resin 50kg

Adhesive: polyvinylpyrrolidone 200kg methylcellulose 50kg

Lubricant: Stepanol MG 100kg micropowder silica gel 200kg;

Intermediates preparation is steps A 2, B4, C2, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 15: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: dextrin 300kg gel aluminum hydroxide 200kg

Adhesive: polyvinylpyrrolidone 60kg

Lubricant: hydrogenated vegetable oil 60kg;

Intermediates preparation is steps A 4, B4, C2, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 16: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: carboxymethyl starch sodium 80kg microcrystalline Cellulose 150kg polyacrylic resin 90kg

Adhesive: hydroxypropyl emthylcellulose 100kg gelatin 60kg

Lubricant: Pulvis Talci 100kg silicon dioxide 80kg;

Intermediates preparation is steps A 1, B1, C2, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 17: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: sodium lauryl sulphate 50kg polyacrylic resin 50kg

Adhesive: methylcellulose 100kg polyacrylic resin 150kg

Lubricant: magnesium stearate 100kg Polyethylene Glycol 100kg micropowder silica gel 100kg;

Intermediates preparation is steps A 2, B1, C2, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 18: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: starch 200kg crospolyvinylpyrrolidone 120kg

Adhesive: polyvinylpyrrolidone 80kg hydroxypropyl emthylcellulose 50kg gelatin 30kg

Lubricant: Polyethylene Glycol 50kg Stepanol MG 60kg micropowder silica gel 70kg;

Intermediates preparation is steps A 3, B4, C2, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 19: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: starch 300kg dextrin 100kg low substituted hydroxy-propyl methylcellulose 100kg

Adhesive: hydroxypropyl emthylcellulose 60kg

Lubricant: Pulvis Talci 30kg silicon dioxide 30kg;

Intermediates preparation is steps A 4, B3, C2, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 20: dispersible tablet of the present invention

Crude drug forms 2;

Disintegrating agent: carboxymethyl starch sodium 130kg low substituted hydroxy-propyl methylcellulose 120kg tween 80 70kg

Adhesive: polyvinylpyrrolidone 100kg hydroxypropyl emthylcellulose 60kg

Lubricant: hydrogenated vegetable oil 90kg Polyethylene Glycol 90kg;

Intermediates preparation is steps A 1, B4, C1, the D2 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 21: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: gel aluminum hydroxide 200kg cetab 300kg

Adhesive: methylcellulose 20kg sodium carboxymethyl cellulose 20kg low-substituted hydroxypropyl cellulose 20kg

Lubricant: calcium stearate 60kg;

Intermediates preparation is steps A 1, B4, C2, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 22: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: carboxymethyl starch sodium 50kg crospolyvinylpyrrolidone 50kg cetab 50kg

Adhesive: polyvinylpyrrolidone 50kg methylcellulose 50kg sodium carboxymethyl cellulose 50kg low-substituted hydroxypropyl cellulose 50kg hydroxypropyl emthylcellulose 50kg

Intermediates preparation is steps A 1, B1, the C1 in the technology 2, the powder of intermediate compound I, II is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 23: dispersible tablet of the present invention

Crude drug forms 2;

Disintegrating agent: crospolyvinylpyrrolidone 100kg microcrystalline Cellulose 100kg sodium lauryl sulphate 120kg

Adhesive: methylcellulose 40kg sodium carboxymethyl cellulose 40kg polyacrylic resin 80kg

Lubricant: magnesium stearate 50kg hydrogenated vegetable oil 50kg Stepanol MG 80kg;

Intermediates preparation is steps A 2, B1, the C1 in the technology 2, the powder of intermediate compound I, II is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 24: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: crospolyvinylpyrrolidone 150kg

Adhesive: hydroxypropyl emthylcellulose 250kg

Lubricant: Liquid Macrogol kg;

Intermediates preparation is steps A 3, B1, the C1 in the technology 2, the powder of intermediate compound I, II is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 25: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: starch 200kg microcrystalline Cellulose 120kg

Adhesive: polyvinylpyrrolidone 80kg methylcellulose 80kg

Lubricant: magnesium stearate 90kg Pulvis Talci 90kg;

Intermediates preparation is steps A 4, B1, the C1 in the technology 2, the powder of intermediate compound I, II is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 26: dispersible tablet of the present invention

Crude drug forms 2;

Disintegrating agent: crospolyvinylpyrrolidone 100kg sodium lauryl sulphate 50kg

Adhesive: hydroxypropyl emthylcellulose 200kg gelatin 50kg

Lubricant: hydrogenated vegetable oil 100kg Polyethylene Glycol 100kg Stepanol MG 100kg;

Intermediates preparation is steps A 1, B1, the C2 in the technology 2, the powder of intermediate compound I, II is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 27: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: crospolyvinylpyrrolidone 50kg sodium lauryl sulphate 50kg polyacrylic resin 50kg

Adhesive: methylcellulose 50kg low-substituted hydroxypropyl cellulose 50kg hydroxypropyl emthylcellulose 50kg

Lubricant: magnesium stearate 300kg;

Intermediates preparation is steps A 2, B1, the C2 in the technology 2, the powder of intermediate compound I, II is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 28: dispersible tablet of the present invention

Crude drug forms 1;

Disintegrating agent: microcrystalline Cellulose 150kg

Adhesive: polyvinylpyrrolidone 100kg gelatin 150kg

Lubricant: micropowder silica gel 100kg Pulvis Talci 100kg silica 1 00kg;

Intermediates preparation is steps A 3, B1, the C2 in the technology 2, the powder of intermediate compound I, II is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 29: dispersible tablet of the present invention

Crude drug forms 2;

Disintegrating agent: cetab 150kg

Adhesive: polyacrylic resin 250kg

Lubricant: silicon dioxide 300kg;

Intermediates preparation is steps A 4, B1, the C2 in the technology 2, the powder of intermediate compound I, II is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Embodiment 30: dispersible tablet of the present invention

Crude drug forms 3;

Disintegrating agent: crospolyvinylpyrrolidone 150kg

Adhesive: polyvinylpyrrolidone 100kg sodium carboxymethyl cellulose 150kg

Lubricant: Polyethylene Glycol 100kg 200kg;

Intermediates preparation is steps A 3, B3, C1, the D1 in the technology 1, the powder of intermediate compound I, II, III is mixed with medicated powder, the crude drug intermediate, add above-mentioned adjuvant and process dispersible tablet of the present invention.

Claims

1. the method for preparing of a medicament combination dispersible tablet is characterized in that this method is one or more in the following method:

Technology 1: form by following steps A, B, C, D and E

Steps A: preparation intermediate compound I

Step B: preparation intermediate II

B1: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add the 3-10% dilute hydrochloric acid, consumption is the 5-15 times of weight, makes into suspension, leaves standstill 12-48 hour, filters, and filtrating transfers pH value to 3-5 with 10-20% sodium hydroxide or other alkali liquor; Filter, filtrating is concentrated into thick paste, adds the ethanol of 8-10 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II;

Or B2: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add the 3-10% dilute hydrochloric acid, consumption is the 5-15 times of weight, makes into suspension, leaves standstill 12-48 hour, filters, and filtrating transfers pH value to 3-5 with 10-20% sodium hydroxide or other alkali liquor; Filter, filtrating is concentrated into thick paste, adds the ethanol of 8-10 times of weight in the concentrated solution, leaves standstill, and gets supernatant; Reclaim ethanol, be concentrated into relative density 1-1.0～1.4, centrifugal, supernatant is crossed macroporous resin column; The 30-80% ethanol elution reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II;

Or B3: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, add the 3-10% dilute hydrochloric acid respectively, consumption is the 5-15 times of weight; Make into suspension; Left standstill 12-48 hour, and filtered, filtrating transfers pH value to 3-5 with 10-20% sodium hydroxide or other alkali liquor; Filtration, filtrating is concentrated into thick paste, adds the ethanol of 8-10 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and gets the extract of Pulvis Cornus Bubali Concentratus powder, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly gets intermediate II after the mixing; Or behind the combination drying the powder of intermediate II;

Or B4: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, add the 3-10% dilute hydrochloric acid respectively, consumption is the 5-15 times of weight; Make into suspension; Left standstill 12-48 hour, and filtered, filtrating transfers pH value to 3-5 with 10-20% sodium hydroxide or other alkali liquor; Filter, filtrating is concentrated into thick paste, adds the ethanol of 8-10 times of weight in the concentrated solution, leaves standstill; Get supernatant, reclaim ethanol, be concentrated into relative density 1-1.0～1.4, centrifugal; Supernatant is crossed macroporous resin column, and the 30-80% ethanol elution reclaims ethanol; Concentrate, get the extract of Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly get intermediate II after the mixing; Or behind the combination drying the powder of intermediate II;

Step C: preparation intermediate III

Step D: preparation medicated powder

Step e: crude drug intermediate

The powder of intermediate compound I, II, III or intermediate compound I, II, III is mixed with medicated powder, get the crude drug intermediate;

Technology 2: form by following steps A, B, C and D

Steps A: preparation intermediate compound I

Step B: preparation intermediate II

Step C: preparation medicated powder

Step D: crude drug intermediate

The powder of intermediate compound I, II or intermediate compound I, II is mixed with medicated powder, get the crude drug intermediate;

Wherein, above-mentioned macroporous resin column model is: YPR-II, X5, AB-8, HPD-100, DX-5, D101, DA201, DM130, WLD-3 or NKA-9;

The raw material of this medicament combination dispersible tablet consists of:

Concha Margaritifera 2-8 weight portion;

Adjuvant is formed:

Disintegrating agent 120-520 weight portion

Adhesive 50-280 weight portion

Lubricant 50-320 weight portion;

Wherein, above-mentioned disintegrating agent is one or more in starch, dextrin, gel aluminum hydroxide, carboxymethyl starch sodium, low substituted hydroxy-propyl methylcellulose, crospolyvinylpyrrolidone, microcrystalline Cellulose, tween 80, cetab, sodium lauryl sulphate and the polyacrylic resin;

Wherein, above-mentioned adhesive is one or more in polyvinylpyrrolidone, methylcellulose, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl emthylcellulose, gelatin and the polyacrylic resin;

Get above-mentioned raw materials medicine intermediate, add above-mentioned adjuvant according to common process and process dispersible tablet.

2. the method for preparing of dispersible tablet as claimed in claim 1 is characterized in that this method is one or more in the following method:

Technology 1: form by following steps A, B, C, D and E

Steps A: preparation intermediate compound I

Or A4: Radix Curcumae is added the hot water reflux, extract, earlier 3 times, and each 1.5 hours, volatile oil was subsequent use; Radix Curcumae medicinal residues and the common decocting of crude drug Radix Scutellariae, Rhizoma Coptidis, Gypsum Fibrosum and Fructus Gardeniae boil 3 times, and each 1.5 hours, merge decocting liquid, be concentrated into relative density 1-1.2; Centrifugal, supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol; Concentrate, spray into volatile oil, promptly get intermediate compound I; Or after the drying the powder of intermediate compound I;

Step B: preparation intermediate II

B1: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add 6% dilute hydrochloric acid, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide or other alkali liquor; Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II;

Or B2: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, mix; Add 6% dilute hydrochloric acid, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide or other alkali liquor; Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, is concentrated into relative density 1-1.2, and centrifugal, supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol, concentrates, and promptly gets intermediate II; Or after the drying the powder of intermediate II;

Or B3: respectively Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera are ground into fine powder, add 6% dilute hydrochloric acid respectively, consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is transferred pH value to 4 with 15% sodium hydroxide or other alkali liquor; Filtration, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill, and gets supernatant, reclaims ethanol, concentrates, and gets the extract of Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly gets intermediate II after the mixing; Or behind the combination drying the powder of intermediate II;

Or B4. is ground into fine powder with Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, adds 6% dilute hydrochloric acid respectively, and consumption is 10 times of weight, makes into suspension, leaves standstill 24 hours, filters, and filtrating is with 15% sodium hydroxide or other alkali liquor accent pH value to 4; Filter, filtrating is concentrated into thick paste, adds the ethanol of 9 times of weight in the concentrated solution, leaves standstill; Get supernatant, reclaim ethanol, be concentrated into relative density 1-1.2, centrifugal; Supernatant is crossed macroporous resin column, and 50% ethanol elution reclaims ethanol; Concentrate, get the extract of Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita and Concha Margaritifera respectively, promptly get intermediate II after the mixing; Or behind the combination drying the powder of intermediate II;

Step C: preparation intermediate III

Or C2: get Pulvis Fellis Suis and be broken into fine powder, add 4% sodium hydroxide, 6 times of weight, left standstill 24 hours, filter, filtrating is transferred pH value to 4, concentrates, and adds 50% ethanol, 12 times of weight; Get supernatant, reclaim ethanol, concentrate, promptly get ketone ibuprofen extract, or get the ketone ibuprofen extract powder after the drying; Get Realgar powder and be broken into fine powder, add 6 times of weight, 8% hydrochloric acid, left standstill 24 hours, filter, filtrating accent pH value to 4 concentrates, and adds washing to colourless, promptly gets Realgar extract, or gets the Realgar extract powder after the drying; Ketone ibuprofen extract is mixed with Realgar extract, intermediate III or the powder of intermediate III;

Step D: preparation medicated powder

Or D2: Borneolum Syntheticum, Mentholum and Haematitum are prepared impalpable powder, Cinnabaris is added 6 times of weight water grind to pasty state, added entry by 1: 65 again and stir, leave standstill, inclining suspension, and sediment grinds again; As above method is 4 times repeatedly, merges each time suspension, leaves standstill, and gets and is deposited in 35 ℃ of airings, and levigation promptly gets the Cinnabaris impalpable powder; With the impalpable powder of above-mentioned four kinds of crude drug mix medicated powder;

Step e: crude drug intermediate

Technology 2: form by following steps A, B, C and D

Steps A: preparation intermediate compound I

Step B: preparation intermediate II

B1: crude drug Pulvis Cornus Bubali Concentratus, artificial Calculus Bovis, Margarita, Concha Margaritifera, Pulvis Fellis Suis and Realgar powder are broken into fine powder, mix, add 50% ethanol of 7 times of weight, 50 ℃ of warm macerating 24 hours filter, and get filtrating, reclaim ethanol, concentrate, and promptly get intermediate II; Or after the drying the powder of intermediate II;

Step C: preparation medicated powder

Or C2: Borneolum Syntheticum, Mentholum and Haematitum are prepared impalpable powder, Cinnabaris is added 6 times of weight water grind to pasty state, added entry by 1: 65 again and stir, leave standstill, inclining suspension, and sediment grinds again; As above method is 4 times repeatedly, merges each time suspension, leaves standstill, and gets and is deposited in 35 ℃ of airings, and levigation promptly gets the Cinnabaris impalpable powder; With the impalpable powder of above-mentioned four kinds of crude drug mix medicated powder;

Step D: crude drug intermediate

3. according to claim 1 or claim 2 the method for preparing of dispersible tablet is characterized in that wherein crude drug consists of in this method:

Borneolum Syntheticum 2 weight portion Pulvis Cornus Bubali Concentratuss 13 weight portion Concha Margaritiferas 5 weight portions;

Or

Borneolum Syntheticum 1 weight portion Pulvis Cornus Bubali Concentratus 18 weight portion Concha Margaritiferas 3 weight portions;

Or

4. according to claim 1 or claim 2 the method for preparing of dispersible tablet is characterized in that wherein adjuvant consists of in this method:

Disintegrating agent 320 weight portions

Adhesive 160 weight portions

Lubricant 180 weight portions;

Or

Disintegrating agent 500 weight portions

Adhesive 60 weight portions

Lubricant 60 weight portions;

Or

Disintegrating agent 150 weight portions

Adhesive 250 weight portions

Lubricant 300 weight portions;