CN101125131A - Method for preparing flupentixol and melitracen capsule - Google Patents
Method for preparing flupentixol and melitracen capsule Download PDFInfo
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- CN101125131A CN101125131A CNA200710045583XA CN200710045583A CN101125131A CN 101125131 A CN101125131 A CN 101125131A CN A200710045583X A CNA200710045583X A CN A200710045583XA CN 200710045583 A CN200710045583 A CN 200710045583A CN 101125131 A CN101125131 A CN 101125131A
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- flupentixol
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- melitracen
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Abstract
The present invention relates to a preparation method of flupentixol - melitracen capsules, which is characterized in that the present invention adopts a ball milling machine to mix and grind the prescription dose of flupentixol dihydrochloride and the diluents to the powder, the preparation technique does not use the ethanol or solvent media, which can not only introduce no other organic impurities, but can also improve the bioavailability of the drug, so the present invention is more safe and effective for the human body.
Description
Technical field
The present invention relates to a kind of preparation method of flupentixol and melitracen capsule, belong to technical field of medicine.
Background technology
The compound preparation that the flupentixol and melitracen capsule agent is made up of flupentixol and two kinds of very effective chemical compounds of melitracen, flupentixol have and rouse oneself and activation, play antipsycholic action by the blocking-up d2 dopamine receptor simultaneously; Sedation and less to the inhibitory action of motion.Be applicable to acute and chronic schizophrenia, melancholia and depressive neurosis, especially to apathy, the symptom of shrinking back is effective.Low dose of medication has stabilizing the emotions, anxiety and anti-slight depressed effect.Melitracen is the two-phase antidepressant, during low dose applications, has excited characteristic, has been proved to be effective antidepressant, anxiety agent.
Flupentixol and melitracen share does not influence its independent pharmaco-kinetic properties.
Disclosed patent, number of patent application is 200510043966.4, name is called " compound recipe melitracen flupentixol capsule ", it is quoted organic solvent and comes the hydrotropy Flupenthixol Hydrochloride in preparation technology, dissolution is on the low side like this, and dispersing uniformity is relatively poor, and the drug effect of preparation is brought certain influence, and may introduce organic impurities.
Summary of the invention
The preparation method that the purpose of this invention is to provide a kind of flupentixol and melitracen capsule safely and effectively.
For realizing above purpose, technical scheme of the present invention provides a kind of preparation method of flupentixol and melitracen capsule, it is characterized in that, takes the blended mode of ball mill, and its preparation method is:
The first step. pre-treatment
1.1 take by weighing 1 part of Flupenthixol Hydrochloride, U-24973A 18-22 part and polyvinylpyrrolidone K30
0.5-1 part, magnesium stearate 1-2 part, cross-linking sodium carboxymethyl cellulose 3-5 part, micropowder silica gel 1-2 part;
1.2 with 1: the ratio of 3.5-4.5 is used ball mill ball milling 22-26 hour with Flupenthixol Hydrochloride and mixing diluents;
1.3 with 1: the ratio of 1-2 is mixed U-24973A and disintegrating agent, mixes sieve with 40 orders and sieves;
1.4 the preparation of serosity
Polyvinylpyrrolidone K30 is dissolved in the purified water of boiling, being cooled to room temperature, is mixed with the 3%K30 aqueous solution;
Second step. granulate
2.1 the mixed sieve powder of the ball milling powder of Flupenthixol Hydrochloride, diluent and U-24973A, disintegrating agent is placed wet granulator, do and mixed 5 minutes-15 minutes, the slow rib of stirring blade stirs the limit and adds the 3%K30 aqueous solution, slowly retaining stirred 1-2 minute, change up retaining 1-2 minute again, sieve with 20 order nylon mesh behind the soft material beading shape;
2.2 the soft material particulate that sieves is put into oven drying, baking temperature≤55 ℃, dry 3 hours-6 hours;
2.3 with the crushing and pelletizing machine dried granulate of exsiccant soft material particulate with 1.2 apertures, rotating speed is 10-20 rev/min, the time is minute 10-20 minute;
Always mix 2.4 put into magnesium stearate, cross-linking sodium carboxymethyl cellulose and micropowder silica gel again, incorporation time is 5 minutes-15 minutes;
2.5 capsule is dressed up in filling, theoretical loading amount: 0.2552g/ grain, content uniformity: ± 10%.
Outward appearance of the present invention: should be clean and tidy, bonding, distortion or fracture phenomena must not be arranged, and should not have foreign odor.
Described diluent is a lactose; Described disintegrating agent is a microcrystalline Cellulose.
The present invention takes the blended mode of ball mill, farthest ensures the safe and effective of human body medication.
Advantage of the present invention is that preparation technology does not adopt ethanol, avoids introducing organic impurities, adopts the mode of ball mill to replace the organic solvent material, has improved the safety of medicine, the bioavailability height.
The specific embodiment
The invention will be further described below in conjunction with embodiment.
Contrast technology: with U-24973A (with C
21H
25N meter) 20 parts, 150 parts of lactose, 30 parts of abundant mixings of microcrystalline Cellulose, with Flupenthixol Hydrochloride (with C
23H
25F
3N
2OS meter) 1 part with behind the dissolve with ethanol.Evenly be added in the mixing powder of front 60 ℃ of dryings.Use 3% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution an amount of afterwards, wet method 28 orders are granulated, 60 ℃ of dryings, 26 order granulate.Add 2 parts of magnesium stearate, total mixing.Incapsulate, make 1000.
The embodiment of the invention
Get flupentixol (with C
23H
25F
3N
2The OS meter) 1 part, 400 parts of abundant mixings of lactose are clayed into power with ball mill; U-24973A is (with C
21H
25The N meter) 20 parts and 25 parts of mixed sieves of microcrystalline Cellulose are dissolved in 0.5 part of polyvinylpyrrolidone K30 in the purified water of boiling, being cooled to room temperature, are mixed with the 3%K30 aqueous solution; The mixed sieve powder of the ball milling powder of Flupenthixol Hydrochloride, diluent and U-24973A, disintegrating agent is placed wet granulator, do and mixed 10 minutes, the slow rib of stirring blade stirs the limit and adds 3%K
30Aqueous solution, retaining stirred 2 minutes slowly, changed up retaining 1 minute again, sieved with 20 order nylon mesh behind the soft material beading shape; The soft material particulate that sieves is put into oven drying, 50 ℃ of baking temperatures, dry 4 hours; With the crushing and pelletizing machine dried granulate of exsiccant soft material particulate with 1.2 apertures, rotating speed is 10-20 rev/min, and the time is 15 minutes; Add 2 parts of magnesium stearate, 4 parts of cross-linking sodium carboxymethyl celluloses, 1 part of micropowder silica gel always mixed 10 minutes, incapsulated, and the 0.2552g/ grain is made 1000.
The capsule that two technologies make is measured respectively, result such as following table:
| Composition | Technology | Uniformity of dosage units (RSD%) | Dissolution (%) 20m sampling | Related substance (%) |
| Flupenthixol Hydrochloride | Existing technology | 6.27 | 81.4 | 4.5 |
| Technology of the present invention | 2.35 | 96.1 | 0.8 | |
| U-24973A | Existing technology | ---- | 88.3 | 3.2 |
| Technology of the present invention | ---- | 97.4 | 0.7 |
Every investigation index of capsule of the present invention all obviously is better than the capsule of existing prepared, being uniformly dispersed of capsule of the present invention, and related substance is low, the dissolution height; Advantages such as it is few to have impurity, safe and effective, capsule is easy to utilize, has obvious social and economic benefit.
Claims (3)
1. the preparation method of a flupentixol and melitracen capsule is characterized in that, takes the blended mode of ball mill, and its preparation method is:
The first step. pre-treatment
1.1 take by weighing 1 part of Flupenthixol Hydrochloride, U-24973A 18-22 part and polyvinylpyrrolidone K300.5-1 part, magnesium stearate 1-2 part, cross-linking sodium carboxymethyl cellulose 3-5 part, micropowder silica gel 1-2 part;
1.2 with 1: the ratio of 3.5-4.5 is used ball mill ball milling 22-26 hour with Flupenthixol Hydrochloride and mixing diluents;
1.3 with 1: the ratio of 1-2 is mixed U-24973A and disintegrating agent, mixes sieve with 40 orders and sieves;
1.4 the preparation of serosity
Polyvinylpyrrolidone K30 is dissolved in the purified water of boiling, being cooled to room temperature, is mixed with the 3%K30 aqueous solution;
Second step. granulate
2.1 the mixed sieve powder of the ball milling powder of Flupenthixol Hydrochloride, diluent and U-24973A, disintegrating agent is placed wet granulator, to do and mixed 10 minutes, the slow rib of stirring blade stirs the limit and adds 3%K
30Aqueous solution, retaining stirred 1-2 minute slowly, changed up retaining 1-2 minute again, sieved with 20 order nylon mesh behind the soft material beading shape;
2.2 the soft material particulate that sieves is put into oven drying, baking temperature≤55 ℃, dry 3 hours-6 hours;
2.3 with the crushing and pelletizing machine dried granulate of exsiccant soft material particulate with 1.2 apertures, rotating speed is 10-20 rev/min, the time is 10 minutes-15 minutes;
Always mix 2.4 put into magnesium stearate, cross-linking sodium carboxymethyl cellulose and micropowder silica gel again, incorporation time is 5 minutes-15 minutes;
2.5 capsule is dressed up in filling, theoretical loading amount: 0.2552g/ grain, content uniformity: ± 10%.
2. according to the preparation method of the described a kind of flupentixol and melitracen capsule of claim 1, it is characterized in that described diluent is a lactose.
3. according to the preparation method of the described a kind of flupentixol and melitracen capsule of claim 1, it is characterized in that described disintegrating agent is a microcrystalline Cellulose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200710045583XA CN100560064C (en) | 2007-09-04 | 2007-09-04 | A kind of preparation method of flupentixol and melitracen capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200710045583XA CN100560064C (en) | 2007-09-04 | 2007-09-04 | A kind of preparation method of flupentixol and melitracen capsule |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101125131A true CN101125131A (en) | 2008-02-20 |
| CN100560064C CN100560064C (en) | 2009-11-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB200710045583XA Expired - Fee Related CN100560064C (en) | 2007-09-04 | 2007-09-04 | A kind of preparation method of flupentixol and melitracen capsule |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2374450A1 (en) * | 2010-04-06 | 2011-10-12 | H. Lundbeck A/S | Flupentixol compositions |
| CN103877088A (en) * | 2012-12-19 | 2014-06-25 | H.隆德贝克有限公司 | Melitracen pharmaceutical composition with high security |
| CN105663062A (en) * | 2016-02-17 | 2016-06-15 | 南京卓泰医药科技有限公司 | Flupentixol and melitracen medicine composition and preparation method thereof |
| CN103804347B (en) * | 2012-11-09 | 2017-10-03 | H.隆德贝克有限公司 | The method for preparing the pharmaceutical composition containing Flupentixol |
| CN108659001A (en) * | 2018-07-16 | 2018-10-16 | 陕西科技大学 | A kind of Flupentixol derivative and preparation method thereof |
-
2007
- 2007-09-04 CN CNB200710045583XA patent/CN100560064C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2374450A1 (en) * | 2010-04-06 | 2011-10-12 | H. Lundbeck A/S | Flupentixol compositions |
| CN103804347B (en) * | 2012-11-09 | 2017-10-03 | H.隆德贝克有限公司 | The method for preparing the pharmaceutical composition containing Flupentixol |
| CN103877088A (en) * | 2012-12-19 | 2014-06-25 | H.隆德贝克有限公司 | Melitracen pharmaceutical composition with high security |
| CN105663062A (en) * | 2016-02-17 | 2016-06-15 | 南京卓泰医药科技有限公司 | Flupentixol and melitracen medicine composition and preparation method thereof |
| CN105663062B (en) * | 2016-02-17 | 2019-01-29 | 南京卓康医药科技有限公司 | A kind of flupentixol and melitracen pharmaceutical composition and preparation method thereof |
| CN108659001A (en) * | 2018-07-16 | 2018-10-16 | 陕西科技大学 | A kind of Flupentixol derivative and preparation method thereof |
| CN108659001B (en) * | 2018-07-16 | 2020-01-31 | 陕西科技大学 | flupentixol derivatives and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100560064C (en) | 2009-11-18 |
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Granted publication date: 20091118 Termination date: 20160904 |
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| CF01 | Termination of patent right due to non-payment of annual fee |