CN102008466A - Febuxostat medicament composition and preparation method thereof - Google Patents
Febuxostat medicament composition and preparation method thereof Download PDFInfo
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- CN102008466A CN102008466A CN 201010567463 CN201010567463A CN102008466A CN 102008466 A CN102008466 A CN 102008466A CN 201010567463 CN201010567463 CN 201010567463 CN 201010567463 A CN201010567463 A CN 201010567463A CN 102008466 A CN102008466 A CN 102008466A
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- febustat
- mannitol
- gelatin
- taste masking
- aspartame
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Abstract
The invention relates to a febuxostat medicament composition and a preparation method thereof. The febuxostat medicament composition is characterized in that: the flavoring agent in the febuxostat medicament composition is selected from gelatin, mannitol or aspartame; the medicament composition exists in a form of powder or granules; and the preparation has good stability, covers the bitter taste, has good mouthfeel, quick disintegration and quick absorption, and is convenient to carry.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains the Febustat pharmaceutical composition and preparation method thereof, Febustat is prepared into the taste masking compositions, add other adjuvant again and be prepared into Febuxostat dispersible tablet, it is scattered in rapidly in the water, covered the oral zest of Febustat.
Background technology
Febustat, its chemistry is by name: 2-(3-cyano-4-isobutoxy phenyl)-4-methyl-5-thiazole formic acid.Molecular formula: C16H16N2O3S, molecular weight: 316.37.Its structural formula is as follows:
The pharmacology type:A new generation's xanthine oxidase inhibitor.
Mechanism of action:Febustat is a 2-arylthiazole derivative, realizes its therapeutic effect by the selectivity inhibited oxidation enzyme that reduces serum uric acid level.
Indication:The Febustat sheet is a kind of xanthine oxidase (XO) inhibitor, is used for the long-term treatment of patient with gout hyperuricemia.Do not advise the Febustat sheet is used for the treatment of asymptomatic hyperuricemia.
Usage and dosage:Recommending the predose of Febustat sheet is 40mg/day.If use 40mg/day dosage after two weeks, patient's serum uric acid (sUA) content still is higher than 6mg/dL, then advises the dosage of Febustat sheet is increased to 80mg/day.
The former producer of grinding of Febustat is Japanese Teijin Ltd, the Adenuric of Ipsen company on the 5th obtained European Union approval and went on the market in France in May, 2008, the ULORIC of Japanese military field pharmacy on the 13rd February in 2009 obtains the drugs approved by FDA listing, is used for the treatment of the hyperuricemia (patient who comprises tophus deposition and gouty arthritis) that is caused by gout clinically.
The morbidity and the living standard of gout are closely related, and China's living standards of the people were lower in the past, and the animal food in the diet is less, thereby the prevalence of gout is lower, are considered to a kind of rare disease always, are called as " emperor's disease " in the past.China was in first report 2 routine gouts in 1948, raising along with living standards of the people, with the relevant food of gout morbidity, mainly be that various animal foods, high protein and the proportion of high purine food in dietary structure increase gradually, make original rare gout prevalence grow with each passing day, the gesture that directly chases after western countries even surmount is arranged.Especially easier morbidity in mid-aged population, chronic cardiovascular disease and diabetics.
Partial investigation that units concerned carry out finds, area, Shanghai each age group hematuria acid number of male is all obviously greater than the blood uric acid meansigma methods in Shanghai in 2006 and Beijing, Guangzhou, and the too high principal element that causes gout just of blood uric acid.The staple market that Beijing, 3 cities in Shanghai and Guangzhou are antigout drug, the antigout drug hospital market in these 3 cities in national antigout drug hospital market proportion by 2005 66.78% rise to 2007 80.64%.
Anti-gout drugs mainly is clinical application, sales volume and consumption sum from present hospital gout preparation, the sale of nearly 2 years these class medicines all presents skyrocketing trend, and present seasonal characteristics occurred frequently summer and autumn, this and the temporal analysis basically identical of epidemiology onset peak.The present kind of antigout drug is few, and clinical treatment is mainly based on colchicine, nonsteroidal antiinflammatory drug, hormone, (as probenecid, sulphur than ketone and benzbromarone) with suppress uric acid synthetic drug (allopurinol).Acute period of disease is mainly used colchicine, nonsteroidal antiinflammatory drug, hormone, and the catabasis is mainly used and promotes urate excretion medicine, inhibition uric acid synthetic drug.These medicines are defectiveness all in treatment.Weak curative effect, side effect become the bottleneck of its clinical practice greatly.Look back nearly 2 years gout treatment medicine market, be not difficult to find out in this field to be difficult to see the new product listing, market is still based on allopurinol and benzbromarone.These two kinds of medicines all are to alleviate medication, and the former is to suppress uricopoiesis, and the latter is to promote drainage.The same with allopurinol, Febustat forms by the blocking-up uric acid and plays a role, and uric acid crystal causes painful swelling in patient with gout intraarticular precipitation.But allopurinol suppresses the enzyme of a series of participation uric acid paths, and Febustat only suppresses xanthine oxidase, so Febustat is a kind of specific medicine that has more.Based on these characteristics, Febustat has more safety than similar medicine.
From absolute number, in fact also there is a huge patient crowd in China, adds that the sickness rate of gout constantly rises, and present the trend that spreads to youngster, so the market potential of developing new drug Febustat is quite big.
Patent CN101780073A discloses Febuxostat dispersible tablet drug and preparation method.This medicine is that the active drug composition is formed jointly with acceptable auxiliary element in dispersible tablet formulation with the Febustat, it is characterized in that containing in the said auxiliary element and comprise at least a as the solubilizing agent composition in the poly-hydrocarbon oxygen esters composition of Myrj 45 constituents, polyoxyethylene ether castor oil constituents, castor oil hydrogenated, consumption is 0.1 ~ 5 times of Febustat weight.
Patent CN101773498A provides a kind of oral sustained-release preparation that contains Febustat and preparation method thereof, Febustat is prepared into long lasting oral sustained-release preparation, can solve the ordinary preparation that prior art exists very fast because of stripping, have burst effect, increase the problem of adverse reaction rate.Technical scheme is: a kind of oral sustained-release preparation that contains Febustat, comprise following component and weight percentage thereof: Febustat 5% ~ 60%, slow controlled-release material 10% ~ 50% is filled adjuvant 20% ~ 80%, binding agent 0.3% ~ 20%, lubricant or fluidizer 0.1% ~ 7%.
Patent CN101474175 relates to a kind of high bioavailability Febustat oral solid formulation and preparation method thereof, it is characterized in that comprising: a) Febustat is C, H, I or J crystal formation; B) mean diameter of Febuxostat crystal form is preferably 3.5 ~ 7 μ m at 3.5 ~ 10 μ m.Preferred oral solid formulation is a tablet, and this tablet producing technology is simple, and cost is low, and relative bioavailability is higher, can be used for the treatment of and the too high diseases associated of uric acid, as gout, is used for reducing the uric acid of blood.
Patent CN101296696 pharmaceutical composition and application in the medicine of preparation treatment gout thereof that is used for the treatment of gout, this pharmaceutical composition comprises Febustat or its pharmaceutical salts or its solvate and the uricosuric eccritic for the treatment of effective dose.
Patent CN101658520 relates to the pharmaceutical composition that is used for the treatment of hyperuricemia, and said composition comprises Febustat or derivatives thereof and probenecid and pharmaceutically acceptable pharmaceutical carrier; Febustat or derivatives thereof wherein: probenecid: the ratio of weight and number of pharmaceutically acceptable pharmaceutical carrier is 1: 10 ~ 200: 0.5 ~ 100.
Patent CN101658519 relates to the pharmaceutical composition that is used for the treatment of hyperuricemia, and said composition comprises Febustat or derivatives thereof and benzbromarone and pharmaceutically acceptable pharmaceutical carrier; Febustat or derivatives thereof wherein: benzbromarone: the ratio of weight and number of pharmaceutically acceptable pharmaceutical carrier is 1: 1 ~ 4: 0.5 ~ 100.
The Pharmaceutical composition of the Febustat taste masking compositions of the present invention's preparation, correctives in the Febustat taste masking compositions is selected from gelatin, mannitol, aspartame, this pharmaceutical composition exists with powder or particulate form, can make better stability of preparation and cover bitterness, mouthfeel is better, disintegrate is fast, absorbs fast, easy to carry.
Therefore, the inventor has solved the oral zest problem of Febustat, adopts special preparation technology to cover its pained mouthfeel, adopts proper auxiliary materials to be prepared into the dispersion sheet, has overcome Febustat and has absorbed the slow shortcoming of slow metabolism.
Summary of the invention
The purpose of this invention is to provide a kind of new Febustat combination of oral medication, it is characterized in that: contain Febustat taste masking compositions, filler, disintegrating agent, correctives and lubricant, Febustat taste masking compositions have been covered the oral pained mouthfeel that causes of Febustat on mouthfeel.
Another object of the present invention provides a kind of method of utilizing described preparation of compositions Febustat pharmaceutical composition.
According to an aspect of the present invention, described filler is selected from microcrystalline Cellulose, and described disintegrating agent is selected from cross-linking sodium carboxymethyl cellulose, and described correctives is selected from mannitol and fragrant citrus essence, and described lubricant is selected from magnesium stearate.
According to an aspect of the present invention, Febustat taste masking compositions is provided, described Febustat taste masking compositions is selected from mannitol, gelatin, aspartame and Febustat, and preparation makes and is uniformly dispersed through special process, shelter the zest mouthfeel of Febustat,, the weight proportion of described Febustat and mannitol, gelatin, aspartame is: 1:4:5:0.1 or 1:5:3:0.1.
According to another aspect of the present invention, the described special process of Febustat taste masking compositions is: with gelatin,
Mannitol and aspartame are crossed 60 mesh sieves respectively, add an amount of distilled water in gelatin, make the gelatin dissolving, under agitation add Febustat, mannitol and aspartame respectively, put in 70 ~ 80 ℃ of water-baths and mix evaporate to dryness, pulverize, and cross 50 mesh sieves, promptly.
According to another aspect of the present invention, provide a kind of preparation to contain the method for the pharmaceutical composition of Febustat taste masking compositions, may further comprise the steps:
1) gelatin, mannitol and aspartame are crossed 60 mesh sieves respectively, in gelatin, add an amount of distilled water, make the gelatin dissolving, under agitation add Febustat, mannitol and aspartame respectively, put in 70 ~ 80 ℃ of water-baths and mix evaporate to dryness, pulverize, cross 50 mesh sieves, standby;
2) microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, mannitol, fragrant citrus essence, magnesium stearate are sieved respectively, standby;
3) with 1) in the Febustat taste masking compositions and 2 that makes) in the adjuvant mix homogeneously, tabletting, promptly.
Advantage of the present invention is technical maturity, and is simple to operate, is fit to industrial large-scale production.
Advantage of the present invention is to adopt special process to prepare Febustat taste masking compositions, has overcome the oral zest mouthfeel of bringing of Febustat.
Advantage of the present invention is to adopt Febustat taste masking preparation of compositions dispersible tablet, makes its disintegrate rapid, has overcome to absorb the slow shortcoming of slow metabolism.
The specific embodiment
Below in conjunction with embodiment the present invention is described in further detail, but should understands the non-scope that only limits to these embodiment of scope of the present invention.
Embodiment 1
(1) Febustat taste masking preparation of compositions
Febustat 10g
Mannitol 40g
Gelatin 50g
Aspartame 0.1g
Make 1000
Preparation technology: gelatin, mannitol and aspartame are crossed 60 mesh sieves respectively, in gelatin, add an amount of distilled water, make the gelatin dissolving, under agitation add Febustat, mannitol and aspartame respectively, put in 70 ~ 80 ℃ of water-baths and mix evaporate to dryness, pulverize, cross 50 mesh sieves, standby;
(2) preparation of Febustat oral cavity disintegration tablet
Febustat masked composition 100.1g
Microcrystalline Cellulose 70g
Cross-linking sodium carboxymethyl cellulose 14g
Mannitol 13.5g
Fragrant citrus essence 0.5g
Magnesium stearate 4g
Make 1000
Preparation technology: check weighing by above-mentioned supplementary material amount through double, mix homogeneously, tabletting, hardness is at 5-7kg, promptly.
Embodiment 2
(1) Febustat taste masking preparation of compositions
Febustat 10g
Mannitol 50g
Gelatin 30g
Aspartame 0.1g
Make 1000
Preparation technology: gelatin, mannitol and aspartame are crossed 60 mesh sieves respectively, in gelatin, add an amount of distilled water, make the gelatin dissolving, under agitation add Febustat, mannitol and aspartame respectively, put in 70 ~ 80 ℃ of water-baths and mix evaporate to dryness, pulverize, cross 50 mesh sieves, standby;
(2) preparation of Febustat oral cavity disintegration tablet
Febustat masked composition 90.1g
Microcrystalline Cellulose 63g
Cross-linking sodium carboxymethyl cellulose 12.6g
Mannitol 12.2g
Fragrant citrus essence 0.45g
Magnesium stearate 3.6g
Make 1000
Preparation technology: check weighing by above-mentioned supplementary material amount through double, mix homogeneously, tabletting, hardness is at 5-7kg, promptly.
Embodiment 3(comparative example)
Febustat 10g
Mannitol 40g
Gelatin 50g
Aspartame 0.1g
Microcrystalline Cellulose 70g
Cross-linking sodium carboxymethyl cellulose 14g
Mannitol 13.5g
Fragrant citrus essence 0.5g
Magnesium stearate 3.6g
Make 1000
Preparation technology: check weighing by above-mentioned supplementary material amount through double, mix homogeneously, water is granulated, tabletting, hardness is at 5-7kg, promptly.
Test example 1
Select the volunteer that the sample of the foregoing description is carried out mouthfeel and dispersing uniformity time detecting, comprehensively its structure is averaged, and mouthfeel and dispersing uniformity testing result see Table 1.
The mouthfeel of each embodiment of table 1 and dispersing uniformity
[notes] +++: fabulous ++: good+: general-: relatively poor--: poor---: extreme difference
Conclusion: after Febustat and mannitol, gelatin, aspartame be prepared into the taste masking compositions by special process, covered the zest of medicine effectively, and disperse the dispersing uniformity of sheet not have influence to using said composition to be prepared into, its preparation method is simple and easy to do simultaneously, cost is low, has proved that this taste masking compositions has excellent characteristic.
Claims (4)
1. Pharmaceutical composition that contains Febustat taste masking compositions, it is characterized in that: contain Febustat taste masking compositions, filler, disintegrating agent, correctives and lubricant, described Febustat taste masking compositions is selected from mannitol, gelatin, aspartame and the preparation of Febustat process special process make and are uniformly dispersed, shelter the zest mouthfeel of Febustat, described filler is selected from microcrystalline Cellulose, described disintegrating agent is selected from cross-linking sodium carboxymethyl cellulose, described correctives is selected from mannitol and fragrant citrus essence, described lubricant is selected from magnesium stearate, described Febustat and mannitol, gelatin, the weight proportion of aspartame is: 1:4:5:0.1 or 1:5:3:0.1, described Febustat taste masking compositions special process is: with gelatin, mannitol and aspartame are crossed 60 mesh sieves respectively, in gelatin, add an amount of distilled water, make the gelatin dissolving, under agitation add Febustat respectively, mannitol and aspartame, put in 70 ~ 80 ℃ of water-baths and mix evaporate to dryness, pulverize, cross 50 mesh sieves, promptly.
2. the Pharmaceutical composition that contains Febustat taste masking compositions according to claim 1 is characterized in that this compositions is a dispersible tablet.
3. the Pharmaceutical composition that contains Febustat taste masking compositions according to claim 1 is characterized in that each component is:
Weight ratio of constituents (%)
Febustat taste masking compositions 50%
Microcrystalline Cellulose 35%
Cross-linking sodium carboxymethyl cellulose 7%
Mannitol 6.75%
Fragrant citrus essence 0.25%
Magnesium stearate 1%.
4. the preparation method that contains the Pharmaceutical composition of Febustat taste masking compositions according to claim 1 is characterized in that comprising following preparation steps:
1) gelatin, mannitol and aspartame are crossed 60 mesh sieves respectively, in gelatin, add an amount of distilled water, make the gelatin dissolving, under agitation add Febustat, mannitol and aspartame respectively, put in 70 ~ 80 ℃ of water-baths and mix evaporate to dryness, pulverize, cross 50 mesh sieves, standby;
2) microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, magnesium stearate are sieved respectively, standby;
3) with 1) in the Febustat taste masking compositions and 2 that makes) in the adjuvant mix homogeneously, tabletting, promptly.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201010567463 CN102008466A (en) | 2010-11-29 | 2010-11-29 | Febuxostat medicament composition and preparation method thereof |
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| CN 201010567463 CN102008466A (en) | 2010-11-29 | 2010-11-29 | Febuxostat medicament composition and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104644580A (en) * | 2013-11-25 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Pharmaceutical composition of teneligliptin |
| CN106421744A (en) * | 2016-11-11 | 2017-02-22 | 上海雅本化学有限公司 | Pharmaceutical composition containing trandolapril taste masking composition |
| WO2023284426A1 (en) * | 2021-07-13 | 2023-01-19 | 北京天衡军威医药技术开发有限公司 | Anti-gout celery seed-flos sophorae immaturus extract and febuxostat pharmaceutical composition, and use thereof |
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| CN101632665A (en) * | 2009-09-01 | 2010-01-27 | 严洁 | Novel torasemide oral medicine composition |
| CN101697988A (en) * | 2009-10-30 | 2010-04-28 | 重庆科瑞制药有限责任公司 | Taste hiding composition and application thereof in Xuesaitong chewable tablet |
| CN101757603A (en) * | 2009-11-02 | 2010-06-30 | 严洁 | Medicinal composition containing trandolapril taste-masking composition |
| CN101780073A (en) * | 2009-01-21 | 2010-07-21 | 重庆圣华曦药业有限公司 | Febuxostat dispersible tablet drug and preparing method thereof |
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2010
- 2010-11-29 CN CN 201010567463 patent/CN102008466A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101780073A (en) * | 2009-01-21 | 2010-07-21 | 重庆圣华曦药业有限公司 | Febuxostat dispersible tablet drug and preparing method thereof |
| CN101632665A (en) * | 2009-09-01 | 2010-01-27 | 严洁 | Novel torasemide oral medicine composition |
| CN101697988A (en) * | 2009-10-30 | 2010-04-28 | 重庆科瑞制药有限责任公司 | Taste hiding composition and application thereof in Xuesaitong chewable tablet |
| CN101757603A (en) * | 2009-11-02 | 2010-06-30 | 严洁 | Medicinal composition containing trandolapril taste-masking composition |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104644580A (en) * | 2013-11-25 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | Pharmaceutical composition of teneligliptin |
| CN106421744A (en) * | 2016-11-11 | 2017-02-22 | 上海雅本化学有限公司 | Pharmaceutical composition containing trandolapril taste masking composition |
| WO2023284426A1 (en) * | 2021-07-13 | 2023-01-19 | 北京天衡军威医药技术开发有限公司 | Anti-gout celery seed-flos sophorae immaturus extract and febuxostat pharmaceutical composition, and use thereof |
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Application publication date: 20110413 |