CN100346778C - Nimesulide sustained release medicinal composition - Google Patents
Nimesulide sustained release medicinal composition Download PDFInfo
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- CN100346778C CN100346778C CNB2005100508429A CN200510050842A CN100346778C CN 100346778 C CN100346778 C CN 100346778C CN B2005100508429 A CNB2005100508429 A CN B2005100508429A CN 200510050842 A CN200510050842 A CN 200510050842A CN 100346778 C CN100346778 C CN 100346778C
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- nimesulide
- ethyl cellulose
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Abstract
The present invention discloses a nimesulide slow release composition. 1000 granules of nimesulide slow release composition mainly contain the following raw material according to the weight compounding ratio: 200g of nimesulide, 40g of hydroxypropyl methyl cellulose whose methoxy content is from 19.0% to 24.0%, 10 to 20g of hydroxypropyl methyl cellulose whose methoxy content is from 28.0% to 30.0%, 0 to 10g of ethyl cellulose, 2.5g of lactose, 1.5g of magnesium stearate and a right amount of ethyl cellulose ethanol liquid of 2%. The present invention leads proper auxiliary material and the nimesulide to be combined, the release of nimesulide medicine is delayed, the present invention has the good slow release effect, and a preparation once a day can be prepared.
Description
Technical field
The present invention relates to a kind of Nimesulide sustained release medicinal composition, said composition relates to utilizes suitable adjuvant and nimesulide combination, delays disengaging of nimesulide medicine, can be made into dosage form once a day.
Background technology
Nimesulide is a NSAID (non-steroidal anti-inflammatory drug), has analgesic and analgesic activities.Therapeutical effect mainly is that it can suppress the synthetic of prostaglandin by suppressing cyclo-oxygenase.But this effect also suppresses the prostaglandin of stomach protectiveness, thereby causes the gastrointestinal intolerance.The nimesulide sheet specification of clinical practice at present is the 100mg/ sheet, takes every day 2 times, each 100mg.For this class insoluble drug of nimesulide, this tablet instability occurs discharging under the condition in vivo easily, and changes easily.
Publication number is that the application for a patent for invention of CN1399543A discloses a kind of controlled release composition that contains nimesulide.It contains the nimesulide that accounts for compositions 5-95%w/w as active medicine, the pharmaceutical excipient that accounts for one or more slow-release materials of compositions 2-95%w/w and account for compositions 0-90%w/w.Its compositions is made up of bilayer tablet, and wherein can there be wherein one deck or two-layer in activating agent.This controlled release composition can be controlled the medicine active ingredient at regular time and quantity by zero level speed constant speed release medicine, processed complex, cost height.
Summary of the invention
The invention provides a kind of Nimesulide sustained release medicinal composition, its composition sustained-release effect is obvious, easy to process, and cost is low.
A kind of Nimesulide sustained release medicinal composition, in 1000, mainly form by following materials of weight proportions:
Nimesulide 200g
Methoxyl content is the hydroxypropyl emthylcellulose 40g of 19.0%-24.0%
Methoxyl content is the hydroxypropyl emthylcellulose 10-20g of 28.0%-30.0%
Ethyl cellulose 0-10g
Lactose 2.5g
Magnesium stearate 1.5g
2% ethyl cellulose ethanol liquid is an amount of
Most preferred scheme is:
A kind of Nimesulide sustained release medicinal composition, 1000 meters, mainly form by following materials of weight proportions:
Nimesulide 200g
Methoxyl content is the hydroxypropyl emthylcellulose 40g of 19.0%-24.0%
Methoxyl content is the hydroxypropyl emthylcellulose 10g of 28.0%-30.0%
Ethyl cellulose 10g
Lactose 2.5g
Magnesium stearate 1.5g
2% ethyl cellulose ethanol liquid is an amount of
The preparation technology of above-mentioned composition is:
1, takes by weighing supplementary material by proportional quantity and cross 80 mesh sieve mixings.
2, it is an amount of to take by weighing ethyl cellulose, adds dissolve with ethanol, is made into 2% ethyl cellulose ethanol liquid.
3, drip an amount of 2% ethyl cellulose ethanol liquid in the supplementary material of mixing, the system soft material is crossed 20 mesh sieve system granules.
4, granule is in 60 ℃ of dryings 4 hours, surveys content after taking out granulate, irritates No. 0 capsule.
In the present composition, the hydroxypropyl emthylcellulose of two kinds of different methoxyl contents and ethyl cellulose are the skeleton of slow releasing preparation, and lactose is a porogen, and 2% ethyl cellulose ethanol liquid is binding agent, and magnesium stearate is lubricant and fluidizer.The present invention selects the hydroxypropyl emthylcellulose material and the ethyl cellulose cellulosic material of best methoxyl content by the combination of different slow-release materials, and the compositions medical instrument of formation has the good slow release performance, and is easy to process.
The specific embodiment
1. be that hydroxypropyl emthylcellulose (its methoxyl content is 19.0%-24.0%), the trade mark of K4M is E by nimesulide 200g, the trade mark
50Hydroxypropyl emthylcellulose (methoxyl content is 28.0%-30.0%), three kinds of sustained-release matrix materials of ethyl cellulose according to the form below shown in tested number, lactose 2.5g, magnesium stearate 1.5g take by weighing supplementary material and cross 80 mesh sieve mixings.
2. it is an amount of to take by weighing ethyl cellulose, adds dissolve with ethanol, is made into 2% ethyl cellulose ethanol liquid.
3, drip an amount of 2% ethyl cellulose ethanol liquid in the supplementary material of mixing, the system soft material is crossed 20 mesh sieve system granules.
4, granule is in 60 ℃ of dryings 4 hours, surveys content after taking out granulate, irritates No. 0 capsule.
Sustained-release matrix material to Nimesulide sustained release medicinal composition is tested, and mainly considers following three factors: consumption (2) hydroxypropyl emthylcellulose (E of (1) hydroxypropyl emthylcellulose (K4M)
50) consumption (3) ethyl cellulose consumption.We are with the foundation of every group of release of 2 hours, 4 hours, 8 hours as judge prescription quality.By 3 factors, 3 levels of each factor are used L
93
3Orthogonal table is carried out orthogonal test, and the result sees table 5-1,5-2 for details:
Table 5-1 factor level table (by 1000 calculating)
Table 5-2 Nimesulide sustained release medicinal composition orthogonal test (L
93
3) catalog as a result
| NO | A (g) | B (g) | C (g) | Release | Remarks | ||
| 2 hours | 4 hours | 8 hours | |||||
| 1 2 3 4 5 6 7 8 9 | 1 1 1 2 2 2 3 3 3 | 1 2 3 1 2 3 1 2 3 | 1 2 3 2 3 1 3 1 2 | 81.2 62.6 58.1 45.7 32.5 22.4 18.4 12.9 8.8 | 100.4 86.1 76.8 70.2 66.5 46.3 40.1 24.4 15.5 | 101.4 101.0 95.2 92.3 93.8 71.4 68.2 59.1 33.8 | Slightly slow release medicine slow release medicine slow release medicine is slow for the desirable release of the release slightly fast drug release rate of the too fast fast drug release rate of release of too fast release |
By orthogonal test, the result shows embodiment 5 release data the bests, and preferred plan is A
2B
2C
3, promptly hydroxypropyl emthylcellulose (K4M) is 40g, hydroxypropyl emthylcellulose (E
50) be 10g, ethyl cellulose is 10g.For verification experimental verification, this composition sustained-release is respond well through animal drugs.
To the preferred plan compositions, promptly nimesulide 200g, hydroxypropyl emthylcellulose (K4M) are 40g, hydroxypropyl emthylcellulose (E
50) be 10g, ethyl cellulose is that Nimesulide sustained-release capsule that 10g, lactose 2.5g, magnesium stearate 1.5g, 2% ethyl cellulose ethanol liquid make in right amount carries out the human-body biological equivalence and relative bioavailability is tested, the result is:
Nimesulide sustained-release capsule (the 200mg/ grain of 20 men's health trial volunteers self intersection singles and repeatedly oral the present invention preparation, test preparation) and nimesulide sheet (the 100mg/ grain produced of Guangdong JIANLIBAO pharmaceutcal corporation, Ltd, reference preparation) after, measure blood drug level over time, the main pharmacokinetic parameter of trying to achieve single-dose test preparation and reference preparation is respectively AUC
0-24AUC
0-2491.90 ± 8.14h μ g/ml and 90.81 ± 10.90h μ g/ml; AUC
0-∞95.14 ± 8.68h μ g/ml and 91.65 ± 11.06h μ g/ml; Cmax7.28 ± 0.72 μ g/ml and 12.19 ± 2.02 μ g/ml; Tmax5.0 ± 1.3h and 3.0 ± 1.0h; MRT9.55 ± 0.57h and 7.01 ± 0.58h; Cl/F2.12 ± 0.21L/h and 2.21 ± 0.26L/h.
The main pharmacokinetic parameter of multiple dosing test preparation and reference preparation is AUC 101.77 ± 8.65h μ g/ml and 49.16 ± 5.39h μ g/ml; Cmax7.86 ± 0.86 μ g/ml and 8.33 ± 1.06 μ g/ml; Cmin1.34 ± 0.48 μ g/ml and 1.14 ± 0.27 μ g/ml; Cav4.24 ± 0.36 μ g/ml and 4.10 ± 0.45 μ g/ml; Tmax4.9 ± 1.5h and 3.1 ± 0.9h.
Behind the single-dose, by AUC
0-24The relative bioavailability of the test preparation of estimation is 102.3% ± 12.9%; Cmax obviously reduces, and Tmax significantly postpones, and MRT numerical value prolongs, and shows that test preparation has sustained releasing character.Behind the multiple dosing, be 104.3% ± 11.3% by the relative bioavailability of the slow releasing preparation of AUC estimation; The Cmax of slow releasing preparation, Cmin and Cav and ordinary tablet are close, and Tmax significantly postpones, and the coefficient of variation of two preparations is respectively DF (%) 1.54 ± 0.12 and 1.77 ± 0.31.The AUC of the reference preparation of test preparation (dosage proofread and correct back) and Cmin, Cav, Cmax to number conversion after, show through variance analysis: there was no significant difference; Show through two one-side t checks: two kinds of preparation bioequivalences.Above-mentioned test structure shows that once-a-day taking slow releasing capsule is not worse than the clinical effectiveness of taking ordinary tablet for twice on the one.
Claims (1)
1. Nimesulide sustained release medicinal composition, in 1000, mainly form by following materials of weight proportions:
Nimesulide 200g
Methoxyl content is the hydroxypropyl emthylcellulose 40g of 19.0%-24.0%
Methoxyl content is the hydroxypropyl emthylcellulose 10g of 28.0%-30.0%
Ethyl cellulose 10g
Lactose 2.5g
Magnesium stearate 1.5g
2% ethyl cellulose ethanol liquid is an amount of.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100508429A CN100346778C (en) | 2005-07-22 | 2005-07-22 | Nimesulide sustained release medicinal composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100508429A CN100346778C (en) | 2005-07-22 | 2005-07-22 | Nimesulide sustained release medicinal composition |
Publications (2)
| Publication Number | Publication Date |
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| CN1723883A CN1723883A (en) | 2006-01-25 |
| CN100346778C true CN100346778C (en) | 2007-11-07 |
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| CNB2005100508429A Active CN100346778C (en) | 2005-07-22 | 2005-07-22 | Nimesulide sustained release medicinal composition |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188386B (en) * | 2010-03-02 | 2013-09-04 | 海南葫芦娃制药有限公司 | Nimesulide sustained-release pellets and preparation method thereof |
| CN102232928A (en) * | 2010-04-20 | 2011-11-09 | 广州艾格生物科技有限公司 | Nimesulide sustained-release suspension and preparation method thereof |
| CN102485220A (en) * | 2010-12-03 | 2012-06-06 | 沈阳药科大学 | Nimesulide monolayer osmotic pump controlled release tablet |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2340751A (en) * | 1998-08-12 | 2000-03-01 | Edko Trading Representation | Nimesulide topical formulations |
| CN1399543A (en) * | 1999-09-28 | 2003-02-26 | 灵药生物技术有限公司 | Controlled release composition comprising nimesulide |
| US6599529B1 (en) * | 1997-09-11 | 2003-07-29 | Nycomed Danmark A/S | Modified release multiple-units compositions of non-steroid anti-inflammatory drug substances (NSAIDs) |
-
2005
- 2005-07-22 CN CNB2005100508429A patent/CN100346778C/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6599529B1 (en) * | 1997-09-11 | 2003-07-29 | Nycomed Danmark A/S | Modified release multiple-units compositions of non-steroid anti-inflammatory drug substances (NSAIDs) |
| GB2340751A (en) * | 1998-08-12 | 2000-03-01 | Edko Trading Representation | Nimesulide topical formulations |
| CN1399543A (en) * | 1999-09-28 | 2003-02-26 | 灵药生物技术有限公司 | Controlled release composition comprising nimesulide |
Non-Patent Citations (1)
| Title |
|---|
| 尼美舒利缓释片的研制和体外溶出度 郭曙刚等.中国医院药学杂志，第20卷第7期 2000 * |
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