CN102240291A - Imatinib-containing composition and preparation method thereof - Google Patents
Imatinib-containing composition and preparation method thereof Download PDFInfo
- Publication number
- CN102240291A CN102240291A CN2011101294691A CN201110129469A CN102240291A CN 102240291 A CN102240291 A CN 102240291A CN 2011101294691 A CN2011101294691 A CN 2011101294691A CN 201110129469 A CN201110129469 A CN 201110129469A CN 102240291 A CN102240291 A CN 102240291A
- Authority
- CN
- China
- Prior art keywords
- imatinib
- compositions
- microcrystalline cellulose
- preparation
- lactose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an imatinib-containing composition and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The imatinib-containing composition disclosed by the invention is composed of imatinib, a diluent, a disintegrating agent, an adhesive and a lubricant, wherein the imatinib is imatinib mesylate alpha crystal; the diluent is a mixture of microcrystalline cellulose and lactose; the disintegrating agent is cross-linked polyvidone; the adhesive is polyvidone K30; and the lubricant is a mixture of magnesium stearate, talc powder and silica micropowder. The preparation method is simple and efficient in process, and can be used for industrial mass production, and the problem that the imatinib mesylate alpha crystal has strong hydroscopicityis and is not easy to form preparation is completely solved.
Description
Technical field
The present invention relates to technical field of medicine, be specifically related to a kind of composition and method of making the same that comprises the imatinib mesylate alpha-crystal form.
Background technology
Imatinib mesylate chemically is called 4-[(4-methyl isophthalic acid-piperazinyl) methyl]-N-[4-methyl-3-[[4-(3-pyridine radicals)-2-pyrimidine radicals] amino]-phenyl] the Benzoylamide mesylate, molecular formula is C
29H
31N
7O.CH
4SO
3, molecular weight is 589.7.
The chemical structural formula of imatinib mesylate is as follows:
Imatinib mesylate (Imatinib Mesylate) be Switzerland Novartis Co.,Ltd research and development a specific tyrosine kinase inhibitor (tyrosine kinases inhibitos, TKI).On May 10 calendar year 2001, imatinib enters the U.S. FDA express train and examines passage to have breakthrough antitumor mechanism, is used for α-interferon administration failure blastocyte crisis stadium, chronic stadium, quickens the granulocyte leukemia medicine for treatment of stadium.
After clinical verification widely, imatinib mesylate has obtained the high evaluation of global medical circle, on February 1st, 2002, FDA ratified its 2nd indication again---be used for the treatment of the treatment of gastrointestinal tract Leydig's cell tumor, at present as the first-line treatment medicine of chronic myelocytic leukemia.
Imatinib mesylate has multiple crystal formation, and as alpha-crystal form, beta crystal etc., wherein FDA approval listing is beta crystal.The beta crystal stable in properties is made preparation easily.Patent WO 2006048890(
IMATINIB MESYLATE CRYSTAL FORM AND PROCESS FOR PREPARATION THEREOF) alpha-crystal form that is not subjected to patent protection has been described, because of its strong hygroscopicity, flowability is very bad, is unsuitable for general oral solid formulation preparation technology, particularly wet granulation technology.If use dry granulation, rise easily after the active ingredient moisture absorption and glue, on the dry granulation machine, gather blocking channel easily, need shut down cleaning when occurring these problems in the production process, both influenced production efficiency, also can reduce the finished product yield.If the use technique of direct powder compression not only to production equipment performance requirement height, requires also high, very unfavorable to the control of product cost like this to employed adjuvant.
Summary of the invention
The objective of the invention is to overcome in the prior art and the imatinib mesylate alpha-crystal form (hereinafter can't not indicated if having, " imatinib " all refers to this active ingredient) preparation of industrialization becomes the technological deficiency of preparation, a kind of preparation nature stable oral preparation is provided, provide a kind of advantages of simplicity and high efficiency technology for preparing this stability property preparation simultaneously, to be fit to industrialized great production.
The present invention adopts rational supplementary material ratio, solved the problem that imatinib strong hygroscopicity is difficult for preparation, the imatinib compositions, the advantages of simplicity and high efficiency preparation technology that have good stability are provided, can have required lower, the basic wet method preparation process widely of industrialized great production to produce the imatinib oral solid formulation that has remarkable clinical efficacy equally by equipment and technology.
The invention provides a kind of compositions that contains imatinib, by weight percentage, comprising:
(a) imatinib 25～70%;
(b) diluent 20～60%;
(c) disintegrating agent 5～15%;
(d) binding agent 0.5～3%;
(e) lubricant 2.5～5%;
Wherein said diluent can be selected any or any two the above mixture in microcrystalline Cellulose, lactose, pregelatinized Starch, calcium carbonate, tricalcium orthophosphate, mannitol, xylitol, sorbitol, glucose, erithritol or the starch; The mixture of preferably microcrystalline cellulose and lactose is more preferably with the mixture of the ratio of weight 1:4～4:1.
Wherein said disintegrating agent is selected from any or any two the above mixture in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone or the starch; Preferred polyvinylpolypyrrolidone.
Wherein said binding agent is selected from any or any two above mixture of starch slurry, gelatin, sodium carboxymethyl cellulose or 30 POVIDONE K 30 BP/USP 30; Preferred 30 POVIDONE K 30 BP/USP 30, more preferably 1～5% ethanol solution.。
Wherein said lubricant is selected from magnesium stearate, micropowder silica gel, Pulvis Talci, Polyethylene Glycol, stearic any or any two above mixture; The mixture of preferred magnesium stearate, Pulvis Talci and micropowder silica gel, more preferably the three is with the mixture of weight ratio 2:2:1 or 2:1:1 ratio.
In the prescription screening process, the inventor drips the alcoholic solution of pure water, concentration 50%, the alcoholic solution of concentration 70%, the alcoholic solution and the dehydrated alcohol of concentration 85% respectively in the imatinib raw material of equivalent, observes the variation of imatinib raw material.The imatinib that wherein drips the alcoholic solution of pure water, concentration 50 all becomes faint yellow vicidity object by original white powder immediately; And the imatinib of alcoholic solution that has dripped alcoholic solution, the concentration 85% of concentration 70% has become pale yellow powder by original immediately white powder; Have only the imatinib that drips dehydrated alcohol that significant change does not take place.This has also confirmed in imatinib preparation of compositions process can not use aqueous solvent.
The inventor has contrasted and has used microcrystalline Cellulose, lactose respectively separately and and unite the dissolution test of the imatinib oral solid formulation that the imatinib preparation of compositions of using microcrystalline Cellulose and milk-sugar mixture to do diluent goes out.Presentation of results is united in the prescription and is used a certain proportion of microcrystalline Cellulose and lactose to have the effect that promotes the imatinib drug release, makes drug releasing rate faster.The optimal proportion that the present invention obtains microcrystalline Cellulose and lactose coupling in this compositions is: 1:4～4:1.
The inventor has also investigated the concentration of binding agent, and presentation of results binding agent 30 POVIDONE K 30 BP/USP 30 ethanol solution optium concentrations are 1%-5% (w/w).
The inventor has investigated the consumption of lubricant, the result shows to unite and uses Pulvis Talci, magnesium stearate and silicon dioxide to make lubricant can effectively to solve compositions and become sticking, mobile bad problem in preparation process, and result according to the present embodiment, the inventor has also further carried out screening test to the use amount of Pulvis Talci, magnesium stearate and silicon dioxide, according to final The selection result, profit compositions lubrication prescription magnesium stearate, Pulvis Talci and micropowder silica gel optimum weight ratio that the present invention obtains are: 2:2:1 or 2:1:1.
The inventor screens imatinib composition component and consumption thereof as investigating index with coherent detection projects such as the mouldability of imatinib compositions, flowability, stability, and finishing screen is selected optimal set compound of the present invention.
The present invention also provides preparation to contain the imatinib method for compositions, carries out according to the following steps:
A. supplementary material is crossed 80 mesh sieves respectively;
B. with the microcrystalline Cellulose of imatinib, 4/7 total recipe quantity, the polyvinylpolypyrrolidone mix homogeneously of 1/2 total recipe quantity, add binding agent and carry out wet granulation, dry under 45～60 ℃ of conditions, granulate;
C. add remaining microcrystalline Cellulose, polyvinylpolypyrrolidone and lactose, Pulvis Talci, micropowder silica gel and magnesium stearate, mix homogeneously is made granule, capsule or tablet.
Specifically, carry out according to the following steps:
A. supplementary material is prepared, sieved: except that polyvidone, imatinib, microcrystalline Cellulose, lactose, polyvinylpolypyrrolidone, Pulvis Talci, silicon dioxide, magnesium stearate are crossed 80 mesh sieves, standby respectively; 30 POVIDONE K 30 BP/USP 30 ethanol solutions preparations: get 30 POVIDONE K 30 BP/USP 30, it is an amount of to add dehydrated alcohol, and stirring and dissolving is to clear, makes concentration and be 1～5%(w/w) 30 POVIDONE K 30 BP/USP 30 ethanol solutions, promptly.
B. mix, granulate: take by weighing the imatinib of recipe quantity, the microcrystalline Cellulose of 4/7 total recipe quantity, the polyvinylpolypyrrolidone of 1/2 total recipe quantity and put quick granulator, mixing adds above-mentioned 30 POVIDONE K 30 BP/USP 30 ethanol solutions and carries out wet granulation; The above-mentioned wet granular of making is taken out, and about 45～60 ℃ are dried to pellet moisture＜5%, 24 mesh sieve granulate.
C. add, mix: the granule of above-mentioned drying, granulate adds remaining microcrystalline Cellulose, polyvinylpolypyrrolidone and lactose, Pulvis Talci, micropowder silica gel and magnesium stearate, and mix homogeneously is made granule, capsule or tablet.
Imatinib composition and method of making the same of the present invention, its technique effect is mainly reflected in: (1) prepared preparation has under the situation of same clinical efficacy with external listing product (Gleevec), stability is very good, in temperature is that 25 ℃, relative humidity are naked putting 10 days under 75% the condition, the invariant color of imatinib medicine, and related substance increases less; (2) adopt rational supplementary material ratio, make the imatinib that does not possess the wet method preparation condition requiring carrying out suitability for industrialized production under low, the basic good wet method preparation process of industrialized great production to equipment and technology, cost is low.
Specific embodiment
By specific embodiment given below, can further clearly understand the present invention, but they not limitation of the invention.
Embodiment 1
Prescription:
The employed 30 POVIDONE K 30 BP/USP 30 of remarks: compositions 1-3 is an ethanol solution, concentration is 3% (w/w), compositions 4 employed 30 POVIDONE K 30 BP/USP 30 ethanol solution concentration are 1% (w/w), and the employed 30 POVIDONE K 30 BP/USP 30 dehydrated alcohol concentration of compositions 4-7 are 5% (w/w).
Preparation method: except that polyvidone, imatinib, microcrystalline Cellulose, lactose, polyvinylpolypyrrolidone, Pulvis Talci, silicon dioxide, magnesium stearate are crossed 80 mesh sieves, standby respectively.
Take by weighing the imatinib of recipe quantity, the microcrystalline Cellulose of 4/7 total recipe quantity, the polyvinylpolypyrrolidone of 1/2 total recipe quantity and put quick granulator, mixing adds above-mentioned 30 POVIDONE K 30 BP/USP 30 ethanol solutions and carries out wet granulation.Extremely about 55 ℃ are dried to pellet moisture＜5%, 24 mesh sieve granulate.Add remaining microcrystalline Cellulose, polyvinylpolypyrrolidone and lactose, Pulvis Talci, silicon dioxide and magnesium stearate, mix homogeneously is made tablet, film coating.
In the present embodiment, in compositions 1-3 we contrasted use separately respectively microcrystalline Cellulose, lactose and and unite and use microcrystalline Cellulose and milk-sugar mixture to do the imatinib compositions of diluent; We have investigated the ratio of microcrystalline Cellulose and lactose and the concentration of binding agent in compositions 4-5; We have investigated the concentration of imatinib in compositions 6-7.
Compositions 1-7 is shone dissolution determination method (two appendix XC second methods of Chinese Pharmacopoeia version in 2010), measure 7 groups of different components gained thin membrane coated tablets respectively under 0.1mol/L hydrochloric acid solution, PH4.5 acetate buffer, purified water, four kinds of media of PH6.8 phosphate buffer, dissolution in the time of 15 minutes the results are shown in following table 1.
Stripping contrast (sample point: 15min) under the table 1:7 group different components different medium
Comparing result by watch 1 contains a certain proportion of microcrystalline Cellulose and lactose in the compositions when only containing microcrystalline Cellulose or lactose as can be known simultaneously, and the rate of release of medicine is faster.The optimal proportion of microcrystalline Cellulose and lactose coupling in this compositions is as can be drawn from Table 1: 1:4～4:1; Binding agent can be 30 POVIDONE K 30 BP/USP 30 ethanol solutions of 1%-5%; Principal agent imatinib optimal proportion by weight is 25～70%.
Embodiment 2
Prescription:
Remarks: employed 30 POVIDONE K 30 BP/USP 30 is an ethanol solution, and concentration is 5% (w/w).
Preparation method: with embodiment 1.
In the present embodiment, the inventor has contrasted respectively when containing different classes of lubricant in the compositions, and compositions compression forming situation and flowability thereof are seen compositions 8-10.Presentation of results is united and is used Pulvis Talci, magnesium stearate and silicon dioxide to make lubricant can effectively to solve compositions and become sticking, mobile bad problem in preparation process.The inventor has also further carried out screening test to the use amount and the disintegrating agent polyvinylpolypyrrolidone of Pulvis Talci, magnesium stearate and silicon dioxide, sees compositions 11.Presentation of results, the optimum weight ratio of profit compositions lubrication prescription magnesium stearate, Pulvis Talci and micropowder silica gel that the present invention obtains be 2:2:1 or 2:1:1 disintegrating agent polyvinylpolypyrrolidone by weight optimal proportion be 5%-15%.The tabletting situation the results are shown in Table 2.
Table 2: the compositions tabletting situation that contains different classes of lubricant
Embodiment 3 pilot scales
Prescription:
Preparation technology:
(1) supplementary material is prepared, sieved: except that 30 POVIDONE K 30 BP/USP 30, imatinib, microcrystalline Cellulose, lactose, polyvinylpolypyrrolidone, Pulvis Talci, silicon dioxide, magnesium stearate are crossed 80 mesh sieves, standby respectively.
(2) 30 POVIDONE K 30 BP/USP-30 ethanol solution preparation: take by weighing an amount of 30 POVIDONE K 30 BP/USP-30, add an amount of dehydrated alcohol, stirring and dissolving is added an amount of dehydrated alcohol to clear, and making concentration is 1%(g/g) 30 POVIDONE K 30 BP/USP-30 ethanol solution, promptly.
(3) mix, granulate: take by weighing the microcrystalline Cellulose of recipe quantity imatinib, 4/7 total recipe quantity and the polyvinylpolypyrrolidone of 1/2 total recipe quantity and put quick granulator, mixing adds above-mentioned 30 POVIDONE K 30 BP/USP 30 ethanol solutions and carries out wet granulation.
(4) dry, granulate: the above-mentioned wet granular of making is taken out, and about 55 ℃ are dried to pellet moisture＜5%, 24 order granulate.
(5) add, always mix: the microcrystalline Cellulose of the granule adding residue recipe quantity of above-mentioned drying, granulate and polyvinylpolypyrrolidone and Pulvis Talci, silicon dioxide, magnesium stearate, mix homogeneously detects granule content.
(6) tabletting, coating: heavily carry out tabletting according to granule content, balance theory of computation sheet.It is heavy that plain sheet is controlled average sheet according to granule content.
The qualified on inspection back of plain sheet coating.With Opadry coating powder 295B620010 concentration is the coating solution coating of 80% ethanol water configuration into about 8% concentration, and coating increases weight about 3%.
(7) check, packing: sample carries out preliminary test according to quality standard, the two aluminum packings in qualified back.
The stripping contrast test of embodiment 4 various different dissolution mediums
Dissolution is got embodiment 3 and is sample, according to dissolution determination method (two appendix X of Chinese Pharmacopoeia version in 2010 C, second method), with 0.1mol/L hydrochloric acid solution 1000ml is solvent, and Revolution Per Minute 50 changes, in accordance with the law operation, in the time of 15 minutes, it is an amount of to get solution, filters through 0.45 μ m microporous filter membrane, and precision is measured filtrate 5ml, put the 50ml(100mg specification) add the 0.1mol/l hydrochloric acid solution in the measuring bottle and be diluted to scale, shake up.It is an amount of that other gets imatinib mesylate (the Gleevec Imatinib Mesylate Tablets) reference substance of import listing, makes the solution that every 1ml contains 12 μ g with the 0.1mol/l hydrochloric acid solution.Get above-mentioned two kinds of solution,, measure trap, calculate every stripping quantity at 264nm wavelength place according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2010 A).
According to " oral solid formulation dissolution experimental technique guideline ", measure Gleevec and embodiment 3 samples respectively under 0.1mol/L hydrochloric acid solution, PH4.5 acetate buffer, purified water, four kinds of media of PH6.8 phosphate buffer, dissolution in the time of 15 minutes the results are shown in following table 3.
Stripping contrast (sample point: 15min) under table 3 embodiment 3 samples and the import listing sample different medium
Presentation of results, the dissolution of oral solid formulation under multiple medium that contains imatinib of the present invention is the same good with the imatinib mesylate oral solid formulation of import listing, even outline hurry up.
Embodiment 5 influence factors test
Get embodiment 3 samples, carry out influence factor's test by two appendix medicine stabilities of Chinese Pharmacopoeia version in 2010 guideline.Test as follows: sample thief is uncovered respectively to be placed under the condition of illumination (4500 ± 500) lx, high temperature (60 ± 2) ℃ and relative humidity 75% and tested 10 days, in the 5th day and sampling sampling in the 10th day and sample contrast in 0 day, indexs of correlation such as test sample content, related substance, character outward appearance, dissolution.Influence factor's result of the test sees Table 4-6.
Result of the test under table 4 illumination illumination (4500 ± 500) the lx condition
Result of the test under table 5 high temperature (60 ± 2) ℃ condition
Result of the test under table 6 high humidity 75% condition
The result of consolidated statement 4-6 as can be known, the composition quality that contains imatinib of the present invention is stable.
Claims (2)
1. one kind contains the imatinib compositions, by weight percentage, comprising:
(a) imatinib 25～70%;
(b) diluent 20～60%;
(c) disintegrating agent 5～15%;
(d) binding agent 0.5～3%;
(e) lubricant 2.5～5%;
Wherein said imatinib is the imatinib mesylate alpha-crystal form; Diluent is the mixture of microcrystalline Cellulose and lactose; Disintegrating agent is a polyvinylpolypyrrolidone; Binding agent is a 30 POVIDONE K 30 BP/USP 30; Lubricant is the mixture of magnesium stearate, Pulvis Talci and micropowder silica gel.
2. the imatinib compositions that contains as claimed in claim 1 is characterized in that the weight ratio of described diluents microcrystalline cellulose and lactose is: 1:4～4:1.
3, the imatinib compositions that contains as claimed in claim 1 is characterized in that described binding agent 30 POVIDONE K 30 BP/USP 30 is 1～5%(w/w) ethanol solution.
4, the imatinib compositions that contains as claimed in claim 1, the weight ratio that it is characterized in that described magnesium stearate lubricant, Pulvis Talci and micropowder silica gel is 2:2:1 or 2:1:1.
5, a kind of preparation contains the imatinib method for compositions according to claim 1, comprising: a. supplementary material is crossed 80 mesh sieves respectively;
B. the polyvinylpolypyrrolidone mix homogeneously of the microcrystalline Cellulose of imatinib, 4/7 total recipe quantity, 1/2 total recipe quantity, add binding agent and carry out wet granulation, dry under 45～60 ℃ of conditions, granulate;
C. add remaining microcrystalline Cellulose, polyvinylpolypyrrolidone and lactose, Pulvis Talci, micropowder silica gel and magnesium stearate, mix homogeneously is made granule, capsule or tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101294691A CN102240291A (en) | 2011-05-18 | 2011-05-18 | Imatinib-containing composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101294691A CN102240291A (en) | 2011-05-18 | 2011-05-18 | Imatinib-containing composition and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102240291A true CN102240291A (en) | 2011-11-16 |
Family
ID=44958656
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011101294691A Pending CN102240291A (en) | 2011-05-18 | 2011-05-18 | Imatinib-containing composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102240291A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103405393A (en) * | 2013-08-02 | 2013-11-27 | 浙江华海药业股份有限公司 | Imatinib mesylate pill and preparation method thereof |
| CN103800334A (en) * | 2012-11-07 | 2014-05-21 | 北大方正集团有限公司 | Pharmaceutical composition of imatinib mesylate, and preparation method thereof |
| CN104288115A (en) * | 2014-10-30 | 2015-01-21 | 江苏豪森药业股份有限公司 | Medicinal preparation containing imatinib mesylate, and preparation method thereof |
| CN107233325A (en) * | 2017-06-23 | 2017-10-10 | 南京优科生物医药研究有限公司 | A kind of composition containing Imatinib and preparation method thereof |
| CN107648237A (en) * | 2016-07-26 | 2018-02-02 | 江苏豪森药业集团有限公司 | Pharmaceutical composition of amino-metadiazine compound and preparation method thereof |
| CN114209671A (en) * | 2021-12-30 | 2022-03-22 | 苏州高迈药业有限公司 | Imatinib preparation and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7943172B2 (en) * | 2005-08-15 | 2011-05-17 | Siegfried Generics International Ag | Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound |
-
2011
- 2011-05-18 CN CN2011101294691A patent/CN102240291A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7943172B2 (en) * | 2005-08-15 | 2011-05-17 | Siegfried Generics International Ag | Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103800334A (en) * | 2012-11-07 | 2014-05-21 | 北大方正集团有限公司 | Pharmaceutical composition of imatinib mesylate, and preparation method thereof |
| CN103800334B (en) * | 2012-11-07 | 2016-12-21 | 北大方正集团有限公司 | pharmaceutical composition of imatinib mesylate and preparation method thereof |
| CN103405393A (en) * | 2013-08-02 | 2013-11-27 | 浙江华海药业股份有限公司 | Imatinib mesylate pill and preparation method thereof |
| CN104288115A (en) * | 2014-10-30 | 2015-01-21 | 江苏豪森药业股份有限公司 | Medicinal preparation containing imatinib mesylate, and preparation method thereof |
| CN104288115B (en) * | 2014-10-30 | 2016-02-24 | 江苏豪森药业股份有限公司 | Pharmaceutical preparation containing imatinib mesylate and preparation method thereof |
| CN107648237A (en) * | 2016-07-26 | 2018-02-02 | 江苏豪森药业集团有限公司 | Pharmaceutical composition of amino-metadiazine compound and preparation method thereof |
| CN107233325A (en) * | 2017-06-23 | 2017-10-10 | 南京优科生物医药研究有限公司 | A kind of composition containing Imatinib and preparation method thereof |
| CN114209671A (en) * | 2021-12-30 | 2022-03-22 | 苏州高迈药业有限公司 | Imatinib preparation and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105055359B (en) | (S) pyrrolidine acetamide sustained release tablets of 4 hydroxyl, 2 oxo 1 and preparation method thereof | |
| CN101647797B (en) | Pharmaceutical composition containing Amlodipine besilate and valsartan and preparation method thereof | |
| CN102240291A (en) | Imatinib-containing composition and preparation method thereof | |
| CN101273973B (en) | Pharmaceutical combination containing Mosapride citrate | |
| CN103156819A (en) | Benzoic acid alogliptin composition troche and preparation method thereof | |
| CN106176653A (en) | A kind of pharmaceutical composition of sitagliptin | |
| CN102846625A (en) | Stable valsartan, amlodipine and hydrochlorothiazide pharmaceutical composition and preparation method thereof | |
| CN104997744A (en) | High-stability capecitabine tablets and preparation method thereof | |
| CN106539777A (en) | A kind of methanesulfonic acid Da Lafeini slow releasing tablet and preparation method thereof | |
| CN102846575A (en) | Nifedipine sustained release tablet and preparation method thereof | |
| CN106018618B (en) | Escitalopram oxalate tablet composition and quality control method | |
| CN103127010A (en) | Stable candesartan cilexetil tablet combination | |
| CN102309482A (en) | Clopidogrel hydrogensulfate composition and preparation method thereof | |
| CN105395506B (en) | A kind of clonidine hydrochloride sustained release tablets | |
| CN112294770A (en) | Isosorbide mononitrate compound preparation and application and preparation method thereof | |
| CN104473892A (en) | Faropenem sodiumcomposition for direct tabletcompression and preparation method of faropenem sodiumcomposition | |
| CN103933005A (en) | Pantoprazole sodium-containing enteric-coated tablet and preparation method thereof | |
| CN106344531A (en) | Nifedipine controlled-release tablet composition and preparation method thereof | |
| CN104069082B (en) | A kind of aspartic acid piece and preparation method thereof | |
| CN105596341B (en) | A kind of amber love song Ge Lieting solid pharmaceutical preparations and preparation method | |
| CN104840460A (en) | Pharmaceutical composition containing valsartan and amlodipine | |
| CN104274422B (en) | A kind of pharmaceutical composition containing imidafenacin | |
| CN103356497A (en) | Benzenesulfonate amlodipine tablet and preparation method thereof | |
| CN104055741A (en) | Montelukast sodium tablet and preparation method thereof | |
| CN104414988B (en) | A kind of Dasatinib tablet and its preparation process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20111116 |