CN100396282C - Slow released doxazosin mesilate capsule and its prepn process - Google Patents
Slow released doxazosin mesilate capsule and its prepn process Download PDFInfo
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- CN100396282C CN100396282C CNB2006100455568A CN200610045556A CN100396282C CN 100396282 C CN100396282 C CN 100396282C CN B2006100455568 A CNB2006100455568 A CN B2006100455568A CN 200610045556 A CN200610045556 A CN 200610045556A CN 100396282 C CN100396282 C CN 100396282C
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- slow
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- capsule
- carclura
- doxazosin
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Abstract
The present invention relates to slow released doxazosin mesilate preparation, and is especially slow released doxazosin mesilate capsule. The slow released doxazosin mesilate capsule has filler comprising doxazosin mesilate 1.0-4.0 wt%, blank pill core 70-95 wt%, adhesive 0.5-3.0 wt%, slow releasing material polyacrylic resin and/or ethyl cellulose 1.0-10.0 wt%, plasticizer 0.2-3.0 wt% and anti-sticking agent 2.0-10.0 wt%. The preparation process includes: preparing medicine-containing coating liquid, coating the medicine-containing layer, preparing slow releasing coating liquid, coating the slow releasing film and encapsulating. The slow released doxazosin mesilate preparation of the present invention can maintain effective and stable blood medicine concentration for 24 hr and less side effects.
Description
Technical field
The present invention relates to the oral slow-releasing preparation of Carclura, particularly slow released doxazosin mesilate capsule, oral back generation rule, stable blood concentration.
Background technology
Carclura is selectivity α
1Adrenergic receptor blocker reaches blood vessel dilating, reduces vascular resistance, brings high blood pressure down by retardance α receptor; By the alpha adrenergic receptor of selective exclusion prostate smooth muscle substrate, tunicle and neck of bladder, improve the symptom of Benign Prostatic Hypertrophy.Its structural formula is as follows:
This product absorbs rapidly mainly in gastrointestinal absorption, and age and sex do not have influence to absorbing.Carclura was the product of being developed by Britain Pfizer, obtained the chemical compound patent in 1978.Doxazosin mesilate tablets in 1988 is in Denmark's Initial Public Offering, and this product is again in country's listings such as Britain, the U.S., Japan and China subsequently.At present commercially available Carclura has ordinary preparation such as tablet, capsule, and controlled release preparation such as doxazosin-mesylate controlled-releasing tablet.The administering mode of Carclura ordinary preparation is initial dose 1mg, and every day 1 time, 1-2 adjusts dosage according to clinical setting after week.Maintenance dose is 1-8mg, every day 1 time.This administering mode has brought inconvenience to the patient, and side effect is bigger.
The patent of doxazosin mesylate sustained-release preparation has at present: (application number: CN03133367.2), this patent has been described the preparation method of matrix type doxazosin mesylate sustained-release sheet to the doxazosin mesylate sustained-release preparation.
US 4,765,989 and the doxazosin-mesylate controlled-releasing tablet of Pfizer listing be to adopt laser boring, coating membrane controlled-release technology, preparation technology is loaded down with trivial details, complicated, working condition requires high, needs special installation.
Summary of the invention
The purpose of this invention is to provide a kind of slow released doxazosin mesilate capsule, the present invention can slowly discharge Carclura in 24 hours, treatment benign prostatic hyperplasia and hypertension.
Another object of the present invention provides a kind of preparation method of slow released doxazosin mesilate capsule, and it has, and preparation technology is simple, easy to operate, high repeatability and other advantages.
Technical scheme of the present invention is, employing coats the Carclura medicine on blank piller surface, coats the polymer release membranes clothing with semi-transparent performance again, makes the doxazosin mesylate sustained-release piller, by the capsule of packing into No. 3 of the weight after calculating, promptly get slow released doxazosin mesilate capsule.The doxazosin mesylate sustained-release piller is with after external medium or human body fluid contact, moisture enters piller inside by the polymer release membranes clothing with semi-transparent performance, active constituents of medicine is dissolved, in the inner supersaturation concentration medicine-active ingredient solution that forms of slow-release pill, the supersaturation concentration active constituents of medicine forms equivalent release in the unit interval by the slow release layer of semi-transparent performance.Multiple polymers can be used as the sustained release coating material, mainly be Eudragit, ethyl cellulose etc., the particularly a kind of arbitrarily or combination of choosing two or more wantonly in them among Eudragit RS100, Eudragit RL100, ethyl cellulose, Aquacoat, EudragitRS10030D, Eud ragit RL10030D, the Eudragit NE30D.The present invention adopts the polymer of different classes of or proportioning, to reach accurate control drug release.
Slow released doxazosin mesilate capsule of the present invention, the implant in the capsule by Carclura, celphere, adhesive, slow-release material, plasticizer, antiplastering aid form slow-release pill, the percentage by weight of each composition is:
Carclura 1.0-4.0%
Celphere 70-95%
Adhesive 0.5-3.0%
Slow-release material 1.0-10.0%
Plasticizer 0.2-3.0%
Antiplastering aid 2.0-10.0%
Slow-release material is meant a kind of arbitrarily or combination of choosing two or more wantonly in them among Eudragit RS100, Eudragit RL100, ethyl cellulose, Aquacoat, Eudragit RS10030D, Eudragit RL10030D, the Eudragit NE30D in the slow released doxazosin mesilate capsule of the present invention; Adhesive is meant any one in 30 POVIDONE K 30 BP/USP 30 or the hypromellose; Plasticizer is meant any one in triethyl citrate, diethyl phthalate, the Polyethylene Glycol-6000; Antiplastering aid is meant Pulvis Talci.
The preparation method of slow released doxazosin mesilate capsule of the present invention is through following step: comprise the preparation of pastille coating liquid, the preparation that coats pastille slow-release film, the outer release-controlled coated liquid of medicine layer, the outer release membranes of coating medicine layer and fill capsule.The pastille coating liquid adopts 30 POVIDONE K 30 BP/USP 30 or hypromellose as adhesive, the ball core is the neutral spherical piller of particle diameter 0.6-0.9mm, the outer release membranes of medicine layer with one of Eudragit RS100, Eudragit RL100, ethyl cellulose, Aquacoat, Eudragit RS10030D, Eudragit RL10030D, Eudragit NE30D or they optional two or more be slow-release material, with the triethyl citrate is plasticizer, with the Pulvis Talci is antiplastering aid, and concrete steps are:
(1) 30 POVIDONE K 30 BP/USP 30 or hypromellose are slowly joined in 75% ethanol, stirring and dissolving becomes settled solution;
(2) Carclura is joined in the ethanol under lucifuge, until being dissolved into settled solution;
(3) (1) and (2) liquid is merged, use atomizing lance evenly to be injected on the celphere, get Carclura pastille piller after the drying;
(4) slow-release material is joined in the ethanol, until being dissolved into settled solution;
(5) triethyl citrate, Pulvis Talci are joined in (4), make the release membranes coating solution;
(6) with atomizing lance set by step (5) coating solution of making be ejected on the Carclura pastille piller that step (3) makes, the coating process should intermittently and stir the spray coating solution, after the drying the doxazosin mesylate sustained-release piller;
(7) during the doxazosin mesylate sustained-release piller that step (6) is made incapsulates, make slow released doxazosin mesilate capsule.
The celphere that implant in the slow released doxazosin mesilate capsule of the present invention is used is commercially available or makes neutral spherical piller by oneself that particle diameter is 0.6-0.9mm.The ball core is answered the tool modular size, helps forming stable technological parameter.Carclura content is 1.0-4.0% in the doxazosin mesylate sustained-release piller.Slow-release material uses Eudragit RS100, Eudragit RL100, ethyl cellulose, Aquacoat, Eudragit RS10030D, Eudragit RL10030D, Eudragit NE30D as semi-permeable polymer sustained release coating material, use atomizing lance that release membranes clothing solution is ejected into pastille piller surface, dry back forms the sustained release coating film of even compact, this sustained release coating film has stable semi-permeable performance, and Carclura was slowly discharged in 24 hours.
Slow released doxazosin mesilate capsule of the present invention and ordinary preparation are relatively, ordinary preparation produces the blood drug level peak value after the patient takes medicine, slow releasing preparation does not have the blood drug level peak value, medicine slowly discharges at absorption site, blood drug level is steadily reached and remain within the treatment concentration range, can make side effects of pharmaceutical drugs reduce to minimum degree and reduce administration number of times.Improve the safety and the effectiveness of medicine, made things convenient for patient's medication.Slow releasing preparation of the present invention can be remained valid in 24 hours, stable blood concentration, reduced side effect.Slow released doxazosin mesilate capsule preparation method of the present invention has that preparation technology is simple, easy to operate, high repeatability and other advantages.
Description of drawings
Fig. 1 is a Carclura fast-release tablet dissolution curve
Fig. 2 is a doxazosin-mesylate controlled-releasing tablet release curve
Fig. 3 is by being painted the slow released doxazosin mesilate capsule release profiles according to the invention process method 1-3.
The specific embodiment
Prescription:
Carclura 4g
Celphere 200g
Hypromellose 2g
Eudragit RL100 4.0g
Triethyl citrate 0.66g
Pulvis Talci 2.2g
Preparation method:
The preparation method of doxazosin mesylate sustained-release piller is as follows: get the 2g hypromellose and slowly join in 90ml 60% ethanol that has agitating device, constantly stir until being dissolved into settled solution.The 4g Carclura is joined under lucifuge in the anhydrous 200ml ethanol, until dissolving.Above-mentioned two liquid are merged as coating solution.220g places coating pan with celphere, setting the peristaltic pump rotating speed is 20 ± 5 rev/mins, stream pressure 0.5 ~ 0.65Mpa, 45 ~ 50 ℃ of material bed tempertaures, spouting velocity 5ml/ minute, using atomizing lance will contain medicinal liquid evenly is ejected on the ball core, intermittently operated, spray ten thousand coating solutions after, in coating pan dry 10 minutes earlier, in 40 ℃ of dryings 2 hours, promptly get Carclura pastille piller then.The gained piller is crossed the 18-24 mesh sieve, collect piller and put in the coating pan, standby.Eudragit RS1004.0g is dissolved in the 45ml ethanol, stirs until dissolving.Add triethyl citrate 0.66g, Pulvis Talci 2.2g and ethanol 200ml, adopt the high-speed mixer mix homogeneously, promptly be made into the release membranes coating solution.Repeat above-mentioned coating operation, in the coating process, should continue to stir coating solution, sprayed until coating solution.In coating pan dry 10 minutes earlier, in 40 ℃ of dryings 8 hours, the gained slow-release pill is crossed the 18-24 mesh sieve then, collect piller and promptly get the doxazosin mesylate sustained-release piller.Calculate the capsule of packing into No. 3 after the loading amount, promptly get slow released doxazosin mesilate capsule.According to present embodiment gained slow released doxazosin mesilate capsule content is 99.6%, and the release in vitro degree was respectively 25%, 63% and 94% at 4 hours, 8 hours and 12 hours.
Prescription:
Carclura 4g
Celphere 200g
Hypromellose 2g
Eudragit RS100 4.5g
Triethyl citrate 0.66g
Pulvis Talci 2.2g
Preparation method:
The preparation method of doxazosin mesylate sustained-release piller is with embodiment 1.
Prescription:
Carclura 4g
Celphere 200g
Hypromellose 2g
Eudragit RL100 2.0g
Eudragit RS100 2.0g
Triethyl citrate 0.66g
Pulvis Talci 2.2g
Preparation method:
The preparation method of doxazosin mesylate sustained-release piller is with embodiment 1.
Prescription:
Carclura 4g
Celphere 200g
Hypromellose 2g
Eudragit RL100 1.33g
Eudragit RS100 2.67g
Triethyl citrate 0.66g
Pulvis Talci 2.2g
Preparation method:
The preparation method of doxazosin mesylate sustained-release piller is with embodiment 1.
Prescription:
Carclura 4g
Celphere 200g
Hypromellose 2g
Eudragit RL100 2.67g
Eudragit RS100 1.33g
Triethyl citrate 0.66g
Pulvis Talci 2.2g
Preparation method:
The preparation method of doxazosin mesylate sustained-release piller is with embodiment 1.
Prescription:
Carclura 4g
Celphere 200g
Hypromellose 2g
Eudragit RL100 1.0g
Eudragit RS100 1.0g
Ethyl cellulose 1.0g
Triethyl citrate 0.66g
Pulvis Talci 2.2g
Preparation method:
The preparation method of doxazosin mesylate sustained-release piller is with embodiment 1.
The dissolution medium of Carclura preparation is 0.01mol/L hydrochloric acid solution 900ml, and rotating speed 100 changes blue method.The release limit is as follows: 4h:10-40% 8h:40-70% 12h: 〉=75%.
The commercially available Carclura ordinary tablet dissolution of table 1-time data table
| Time (h) | 0.083 | 0.167 | 0.25 | 0.5 | 0.75 | 1 |
| Dissolution (%) | 37 | 75 | 94 | 99 | 100 | 98 |
Table 2 doxazosin-mesylate controlled-releasing tablet dissolution-time data table
| Time (h) | 2 | 4 | 6 | 8 | 10 | 12 | 15 | 24 |
| Dissolution (% | 6 | 32 | 41 | 56 | 77 | 93 | 103 | 101 |
Table 3 slow released doxazosin mesilate capsule dissolution-time data table
Claims (2)
1. a slow released doxazosin mesilate capsule is characterized in that the slow-release pill that the implant in the capsule is made up of Carclura, celphere, adhesive, slow-release material, plasticizer, antiplastering aid, and the percentage by weight of each composition is:
Carclura 1.0-4.0%
Celphere 70-95%
Adhesive 0.5-3.0%
Slow-release material 1.0-10.0%
Plasticizer 0.2-3.0%
Antiplastering aid 2.0-10.0%
Described slow-release material is meant a kind of arbitrarily or combination of choosing two or more wantonly in them in Eudragit RS100, Eudragit RL100, the ethyl cellulose; Described adhesive is meant any one in 30 POVIDONE K 30 BP/USP 30 or the hypromellose; Described plasticizer is meant any one in triethyl citrate, diethyl phthalate, the Polyethylene Glycol-6000; Described antiplastering aid is meant Pulvis Talci.
2. the preparation method of a slow released doxazosin mesilate capsule is characterized in that preparation process is:
(1) prescription
Carclura 1.0-4.0%
Celphere 70-95%
Adhesive 0.5-3.0%
Slow-release material 1.0-10.0%
Plasticizer 0.2-3.0%
Antiplastering aid 2.0-10.0%
(2) preparation process:
1. adhesive 30 POVIDONE K 30 BP/USP 30 or hypromellose are slowly joined in 75% ethanol, stirring and dissolving becomes settled solution;
2. Carclura is joined in the ethanol under lucifuge, until being dissolved into settled solution;
3. incite somebody to action 1. and 2. liquid merging, use atomizing lance evenly to be injected on the celphere, get Carclura pastille piller after the drying;
4. slow-release material is joined in the ethanol, until being dissolved into settled solution, slow-release material can be selected a kind of arbitrarily or combination of choosing two or more wantonly in them in EudragitRS100, Eudragit RL100, the ethyl cellulose for use;
5. in joining plasticizer triethyl citrate, antiplastering aid Pulvis Talci 4., make the release membranes coating solution;
6. the coating solution that 5. makes set by step with atomizing lance is ejected on the Carclura pastille piller that 3. step make, and the coating process is hydrojet and stir the spray coating solution intermittently, after the drying the doxazosin mesylate sustained-release piller;
7. during the doxazosin mesylate sustained-release piller that 6. step is made incapsulates, make slow released doxazosin mesilate capsule.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100455568A CN100396282C (en) | 2006-07-25 | 2006-07-25 | Slow released doxazosin mesilate capsule and its prepn process |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100455568A CN100396282C (en) | 2006-07-25 | 2006-07-25 | Slow released doxazosin mesilate capsule and its prepn process |
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| CN1887278A CN1887278A (en) | 2007-01-03 |
| CN100396282C true CN100396282C (en) | 2008-06-25 |
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| CNB2006100455568A Expired - Fee Related CN100396282C (en) | 2006-07-25 | 2006-07-25 | Slow released doxazosin mesilate capsule and its prepn process |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102816154B (en) * | 2012-09-10 | 2015-08-19 | 刘庆彬 | A kind of non-crystalline state one hydration (-)-doxazosin mesylate, preparation method and application thereof |
| CN103705490B (en) * | 2013-10-31 | 2016-08-17 | 蚌埠丰原医药科技发展有限公司 | The slow releasing preparation of a kind of aspartic acid ornithine and preparation technology thereof |
| CN104983717A (en) * | 2015-06-04 | 2015-10-21 | 湖北生物医药产业技术研究院有限公司 | Sodium prasterone sulfate sustained-release capsule and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1215993A (en) * | 1995-11-21 | 1999-05-05 | 辉瑞研究开发公司 | Pharmaceutical formulations |
| JPH11506743A (en) * | 1995-06-06 | 1999-06-15 | ハンプシャー ケミカル コーポレイション | Preparation of alkali metal acylamino acids |
| CN1285353A (en) * | 1999-08-20 | 2001-02-28 | 广东康美药业股份有限公司 | Process for synthesizing doxazosin mesylate |
| CN1395929A (en) * | 2002-08-26 | 2003-02-12 | 鲁南制药股份有限公司 | Slow-releasing maclobemide capsule |
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2006
- 2006-07-25 CN CNB2006100455568A patent/CN100396282C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11506743A (en) * | 1995-06-06 | 1999-06-15 | ハンプシャー ケミカル コーポレイション | Preparation of alkali metal acylamino acids |
| CN1215993A (en) * | 1995-11-21 | 1999-05-05 | 辉瑞研究开发公司 | Pharmaceutical formulations |
| CN1285353A (en) * | 1999-08-20 | 2001-02-28 | 广东康美药业股份有限公司 | Process for synthesizing doxazosin mesylate |
| CN1395929A (en) * | 2002-08-26 | 2003-02-12 | 鲁南制药股份有限公司 | Slow-releasing maclobemide capsule |
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| CN1887278A (en) | 2007-01-03 |
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| C14 | Grant of patent or utility model | ||
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| CP02 | Change in the address of a patent holder |
Address after: Xinluo Avenue high tech Zone of Ji'nan City, Shandong province 250101 No. 989 Shandong Academy of Pharmaceutical Sciences Room 401 Patentee after: Medicine Industry Inst., Shandong Prov. Address before: 250100 Shandong Pharmaceutical Industry Research Institute, 52 Da Bei Road, Shandong, Ji'nan Patentee before: Medicine Industry Inst., Shandong Prov. |
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| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Zibo Shandong mountain Pharmaceutical Co., Ltd. Assignor: Medicine Industry Inst., Shandong Prov. Contract record no.: 2011370000035 Denomination of invention: Slow released doxazosin mesilate capsule and its prepn process Granted publication date: 20080625 License type: Exclusive License Open date: 20070103 Record date: 20110314 |
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Granted publication date: 20080625 Termination date: 20150725 |
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