CN1395929A - Slow-releasing maclobemide capsule - Google Patents
Slow-releasing maclobemide capsule Download PDFInfo
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- CN1395929A CN1395929A CN 02129439 CN02129439A CN1395929A CN 1395929 A CN1395929 A CN 1395929A CN 02129439 CN02129439 CN 02129439 CN 02129439 A CN02129439 A CN 02129439A CN 1395929 A CN1395929 A CN 1395929A
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Abstract
A slow-releasing maclobemide caspule for treating depression, phobia, dysphoria, senile dementia, etc. is prepared from maclobemide, empty core, slow-releasing agent, plasticizer and antisticking agent through proportioning, preparing medicine core, drying, coating slow-releasing agent layer, drying and loading in capsule. Its advantages are high concentration of medicine in blood, durable acting, and low toxic by-effect.
Description
Affiliated technical field
The invention belongs to medical technology, particularly a kind of slow-releasing maclobemide capsule is used for senile dementia disease therapeutic medicine, can slowly discharge and keep comparatively stable blood concentration and longer action time, has toxic and side effects and reduces, takes convenient.
Background technology
Depression is a kind of common mental disease, because clinical tricyclic antidepressant side effect commonly used at present is many and serious, causes about 1/2nd depressive patients partner treatment well, and these all directly affect patient's rehabilitation.It with the moclobemide appearance of the strong reversibility oxidase inhibitor (RIMA) of the selectivity of representative, indicate the important breakthrough of this research field, these product have brand-new chemical constitution, compare with traditional antidepressant, be characterized in: (one) good effect, this product curative effect at least quite or be better than second filial generation antidepressants maprotiline, the curative effect of mianserin and fluvoxamine, also obviously be better than reversibility but non-selective monoamine oxidase, MAO (MAO-A) inhibitor Toloxatone, with the therapeutic equivalence of fluoxetine (fluoxetine), act on then faster; (2) except that antidepressant effect, also effective to phobia, anxiety neurosis, can improve cognitive function, can be used for the senile dementia disease therapeutic; (3) this medicine few side effects is safe and reliable, and patient is to its better tolerance, and the anti-choline that seldom other antidepressant occurs after patient's medication and produced can effect.As blurred vision, xerostomia, constipation, dysuria, tachycardia, hyperhidrosis, tremble etc.This medicine is particularly useful for long-term after treatment and elderly patients.
In the 8th world's psychiatry conference that hold in Athens in October, 1989, experts and scholars have given high evaluation to this medicine, think that it is widely used in clinical as a kind of up-and-coming antidepressant one line medicine.China does not still have this type of representative drugs at present, therefore researchs and develops this product, will produce good society and economic benefit.
Moclobemide is by Switzerland Luo Shi (Roche) company exploitation, and in nineteen ninety at first in Sweden's listing, country's listing surplus 50 successively so far, China is not imported raw material and preparation as yet at present.
Summary of the invention
The invention provides a kind of slow-releasing maclobemide capsule, it is efficiently, can be used for senile dementia disease therapeutic medicine, has toxic and side effects and reduces, takes convenient advantage.
Weight of the present invention is formed and is comprised:
100 parts of moclobemides
107 parts of celphere
0.9～90 part of slow releasing agent
0～4.3 part of plasticizer
0～17.1 part of antiplastering aid
Above-mentioned slow releasing agent be meant one of ethyl cellulose (EC), stearic acid, cellulose acetate, Eudragit RS (acrylic resin) 100, Eudragit RL 100, Surelease (Aquacoat), Eudragit RS 30D, EudragitRL30D, Eudragit RS 30D, Eudragit NE 30D or they optional two or more.
Above-mentioned plasticizer is meant Polyethylene Glycol-6000, diethyl phthalate or triethyl citrate.
Above-mentioned antiplastering aid be meant Pulvis Talci (if join slurry with ethanol, antiplastering aid be ethanol heavy 1%, otherwise without antiplastering aid).
The capsular preparation of moclobemide divided for two steps, and the first step is that the raw material fine powder is adhered on the celphere by suitable adhesive, made to contain pill core, and second step was to containing pill core bag extended release coatings film, controlling principal agent and discharge.
Slow-releasing maclobemide capsule of the present invention is taken twice every day, each 1, compare with the moclobemide capsule, because the characteristics that this dosage form slowly discharges, can continue release in 8 hours, thereby keep comparatively stable blood concentration and longer action time, have toxic and side effects and reduce, take convenient advantage.Therefore, develop this product and will obtain social benefit and economic benefit widely.
Description of drawings
Fig. 1: the cumulative in vitro release profiles of prescription A; Fig. 2: the cumulative in vitro release profiles of prescription B; Fig. 3: the cumulative in vitro release profiles of prescription C; Fig. 4: the cumulative in vitro release profiles of prescription D; Fig. 5: the cumulative in vitro release profiles of prescription E; Fig. 6: the cumulative in vitro release profiles of prescription F; Fig. 7: the cumulative in vitro release profiles of prescription G; Fig. 8: the cumulative in vitro release profiles of prescription H.
The specific embodiment
Embodiment: (one) contains the preparation of pill core
Moclobemide 280g
Celphere 300g
7%PVP solution (solvent is 85% ethanol) 300g preparation technology:
Moclobemide is crossed 160 mesh sieves, and recipe quantity takes by weighing, and pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, CYL 3bar, CAP1 0.9bar pours celphere into, pelletize, blanking velocity 4rpm, the pump 10% of wriggling, rotary speed 150rpm, 60 ℃ of oven dry, discharging 600g.(2) eight kinds of concrete prescriptions are as follows: (determining slow releasing agent kind and quantity) prescription A:
Contain pill core 500g
Ethyl cellulose 7.5g
Stearic acid 25g
Polyethylene Glycol-6000 0.75g
Pulvis Talci 10g
95% ethanol 1000g preparation technology: recipe quantity takes by weighing and contains pill core, pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, CYL3bar, CAP1 0.9bar, rotary speed 180rpm, the pump 7% of wriggling sprays into ethyl cellulose and stearic 95% ethanol, 40 ℃ of oven dry.Coating finishes, discharging 520g.Prescription B:
Contain pill core 500g
Ethyl cellulose 60g
Stearic acid 125g
Polyethylene Glycol-6000 6g
Pulvis Talci 20g
95% ethanol 2000g preparation technology is with prescription A.Prescription C:
Contain pill core 500g
Ethyl cellulose 7.5g
Eudragit?RS?100?????????????????????????10g
Citrin triethyl 1g
Pulvis Talci 10g
95% ethanol 1000g preparation technology: recipe quantity takes by weighing and contains pill core, pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, CYL3bar, CAP1 0.9bar, 30 ℃ of inlet air temperature, rotary speed 180rpm, the pump 7% of wriggling sprays into 95% alcoholic solution of ethyl cellulose and Eudragit RS 100.Coating finishes, discharging 510g.Prescription D:
Contain pill core 500g
Ethyl cellulose 60g
Eudragit?RS?100?????????????????????????80g
Citrin triethyl 8g
Pulvis Talci 20g
95% ethanol 2000g preparation technology is with prescription C.Prescription E:
Contain pill core 500g
Eudragit?RS?100?????????????????????????10g
Eudragit?RL?100?????????????????????????2g
Polyethylene Glycol-6000 1.7g
Pulvis Talci 10g
95% ethanol 1000g preparation technology: recipe quantity takes by weighing and contains pill core, pours in the hopper.Drive the granulating and coating machine, go into wind pressure 0.5bar, CYL3bar, CAP1 0.9bar, 30 ℃ of inlet air temperature, rotary speed 180rpm, the pump 7% of wriggling sprays into 95% alcoholic solution of Eudragit RS 100 and Eudragit RL 100.Coating finishes, discharging 510g.Prescription F:
Contain pill core 500g
Eudragit?RS?100?????????????????????????80g
Eudragit?RL?100?????????????????????????20g
Polyethylene Glycol-6000 10g
Pulvis Talci 20g
95% ethanol 2000g preparation technology is with prescription E.Prescription G:
Contain pill core 500g
Surelease???????????????????????????????70g
Pure water 70g preparation technology: recipe quantity takes by weighing and contains pill core, pours in the hopper.Drive the granulating and coating machine, go into wind pressure 1.0bar, CYL3bar, CAP1 1.5bar, 55 ℃ of inlet air temperature, rotary speed 180rpm, the pump 10% of wriggling sprays into the pure water solution of Surelease.Coating finishes, discharging 530g.Prescription H:
Contain pill core 500g
Surelease???????????????????????????210g
Pure water 210g preparation technology is with prescription G.(3) slow-releasing maclobemide capsule dissolution determination
Slow-releasing maclobemide capsule (prescription A-H), its extracorporeal releasing experiment method is as follows: get this product according to drug release determination method (two appendix XD first methods of Chinese Pharmacopoeia version in 2000), utilize dissolution determination device (two appendix XC first methods of Chinese Pharmacopoeia version in 2000), 1000ml is a solvent with hydrochloric acid solution (9 → 1000), rotating speed 50 changes, in accordance with the law operation.Got solution 10ml (and instant replenish equivalent solvent) at 1,4 and 8 hour respectively, filter, precision is measured subsequent filtrate 3ml, put in the 50ml volumetric flask, with same solvent dilution to scale, as need testing solution; Other the moclobemide reference substance that is dried to constant weight of learning from else's experience 105 ℃ is an amount of, accurate claim fixed, add hydrochloric acid solution (9 → 1000) dissolving and quantitatively dilution make the solution that contains 10 μ g among every 1ml, product solution in contrast.Respectively according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), measure the trap of need testing solution and reference substance solution at the wavelength place of 240nm, calculate according to external standard method, draw every burst size of this product and should be respectively more than 10%～30%, 40%～70% and 75% of labelled amount at 1,4,8 hour, all should be up to specification.See table 1-8 and accompanying drawing 1-8 for details.
Animal drug disposition dynamic metabolism experimental technique of the present invention is as follows: experiment is divided into two groups, every group of 6 Canis familiaris L.s; Matched group gives oral common moclobemide tablet (100mg/ sheet), every day three times, each 1; Experimental group gives oral the present invention (prescription A-H, 150mg/ grain), every day twice, each 1; Respectively in administration after 1,2,3,4,5,6,7 days, get the blood drug level of determination of serum moclobemide, the result shows: matched group and experimental group all do not have marked difference at the area under the drug-time curve (AUC) of each time point, prompting the present invention is according to twice of every day, each 1 oral administration can reach ideal blood drug level, has excellent curative.
Table 1: prescription A cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????28 | ????31 | ????55 | ????60 | ????78 | ????82 | ????90 | ????97 |
Table 2: prescription B cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????13 | ????26 | ????37 | ????42 | ????55 | ????67 | ????71 | ????83 |
Table 3: prescription C cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????27 | ????39 | ????51 | ????64 | ????69 | ????81 | ????88 | ????94 |
Table 4: prescription D cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????12 | ????23 | ????34 | ????45 | ????50 | ????66 | ????72 | ????86 |
Table 5: prescription E cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????24 | ????40 | ????50 | ????64 | ????72 | ????78 | ????86 | ????94 |
Table 6: prescription F cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????15 | ????22 | ????37 | ????45 | ????51 | ????66 | ????79 | ????85 |
Table 7: prescription G cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????23 | ????40 | ????58 | ????64 | ????72 | ????81 | ????90 | ????98 |
Table 8: prescription H cumulative in vitro release
| Time (hour) | ????1 | ????2 | ????3 | ????4 | ????5 | ????6 | ????7 | ????8 |
| Release (%) | ????13 | ????25 | ????39 | ????45 | ????56 | ????69 | ????74 | ????86 |
Claims (6)
1, a kind of slow-releasing maclobemide capsule is characterized in that its weight composition comprises:
100 parts of moclobemides
107 parts of celphere
0.9～90 part of slow releasing agent
0～4.3 part of plasticizer
0～17.1 part of antiplastering aid
Above-mentioned slow releasing agent be meant ethyl cellulose (EC), stearic acid, cellulose acetate, Eudragit (acrylic resin) RS 100, Eudragit RL 100, Surelease (basic cellulose aqueous dispersion), Eudragit RS 30D, EudragitRL30D, one of Eudragit RS 30D, Eudragit NE 30D or they optional two or more;
Described plasticizer is meant Polyethylene Glycol-6000 or triethyl citrate;
Described antiplastering aid is a Pulvis Talci.
2. slow-releasing maclobemide capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of moclobemides
10.7～53.6 parts of stearic acid
2.1～10.7 parts of Pulvis Talci.
3. slow-releasing maclobemide capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of moclobemides
3.2～25.7 parts of ethyl celluloses
0.3～2.6 part of Polyethylene Glycol-6000
2.1～17.1 parts of Pulvis Talci.
4. slow-releasing maclobemide capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of moclobemides
100 4.3～34.3 parts of acrylic resin RS
0.4～3.4 part of citrin triethyl
0.9～6.9 part of Pulvis Talci.
5. slow-releasing maclobemide capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of moclobemides
100 0.9～8.6 parts of acrylic resin RL
0.7～4.3 part of Polyethylene Glycol-6000
0.9～5.1 part of Pulvis Talci.
6. slow-releasing maclobemide capsule according to claim 1 is characterized in that its weight composition comprises:
100 parts of moclobemides
30～90 parts of Aquacoats.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021294399A CN1194694C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing maclobemide capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021294399A CN1194694C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing maclobemide capsule |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1395929A true CN1395929A (en) | 2003-02-12 |
| CN1194694C CN1194694C (en) | 2005-03-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021294399A Expired - Fee Related CN1194694C (en) | 2002-08-26 | 2002-08-26 | Slow-releasing maclobemide capsule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1194694C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100396282C (en) * | 2006-07-25 | 2008-06-25 | 山东省医药工业研究所 | Slow released doxazosin mesilate capsule and its prepn process |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101125134B (en) * | 2006-08-16 | 2010-09-15 | 常州市第四制药厂有限公司 | Hydrochloric tamsulosin sustained-release capsule and its preparation method |
-
2002
- 2002-08-26 CN CNB021294399A patent/CN1194694C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100396282C (en) * | 2006-07-25 | 2008-06-25 | 山东省医药工业研究所 | Slow released doxazosin mesilate capsule and its prepn process |
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| Publication number | Publication date |
|---|---|
| CN1194694C (en) | 2005-03-30 |
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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: LUNAN PHARMACEUTICAL GROUP CO., LTD. Free format text: FORMER NAME OR ADDRESS: LUNAN PHARMACY CO. LTD. |
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| CP03 | Change of name, title or address |
Address after: 276005 No. 209 Hongqi Road, Shandong, Linyi Patentee after: Lunan Pharmaceutical Group Co., Ltd. Address before: 276003 No. 107, No. 1, Linxi, Shandong, Linyi Patentee before: Lunan Pharmacy Co., Ltd. |
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| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20050330 Termination date: 20200826 |