因華:公告本公司安它可朋組成物取得歐亞專利組織﹝EAPO﹞ 專利獲證許可 鉅亨網新聞中心(來源：台灣證券交易所)2016-04-26第三十四條第42款1.事實發生日:105/04/262.公司名稱:因華生技製藥股份有限公司3.與公司關係(請輸入本公司或聯屬公司):本公司4.相互持股比例(若前項為本公司，請填不適用):不適用5.發生緣由: 本公司研發之安它可朋組成物，取得歐亞組織﹝EAPO﹞專利 發明名稱:A COMPOSITION OF ENTACOPONE6.因應措施:無。7.其他應敘明事項: 歐亞專利組織﹝EAPO﹞為一個類似歐盟的專利組織，會員國如下： 土庫曼、白俄羅斯、塔吉克斯坦、俄羅斯、哈薩克、亞塞拜然、吉爾吉斯 亞美尼亞、摩爾多瓦
Composition of entacopone US 20140120166 A1
摘要A composition of entacapone comprising entacapone or pharmaceutically acceptable salts, PVPK30 and SDS is disclosed in the present invention, wherein the mass ratio of entacapone: PVPK30: SDS is 1:0.05-0.6:0.06-0.1. The present invention also discloses preparative method and use of the composition of entacapone.
聲明所有權(20) What is claimed is: 1. A composition of entacapone, comprising entacapone or a pharmaceutically acceptable salt thereof, PVP K30 and SDS; wherein entacapone, PVP K30 and SDS are present at a weight ratio of 1:0.05-0.6:0.06-0.1, and the composition has a dissolution rate of more than 88%. 2. The composition of entacapone according to claim 1, wherein entacapone, PVP K30 and SDS are present at a weight of 1:0.05-0.2:0.06. 3. The composition of entacapone according to claim 2, wherein entacapone, PVP K30 and SDS are present at a weight of 1:0.2:0.06. 4. The composition of entacapone according to claim 1, wherein the dissolution rate is more than 90%. 5. The composition of entacapone according to claim 4, wherein the dissolution rate is more than 95%. 6. The composition of entacapone according to claim 1, further comprising at least one excipient, and said excipient is selected from povidone, crospovidone, carbohydrates, croscarmellose sodium, or combinations thereof. 7. The composition of entacapone according to claim 6, wherein the carbohydrates are selected from microcrystalline cellulose, mannitol, cellulose, hydroxypropyl methylcellulose, starch, or lactose. 8. A process for preparing the composition of entacapone according to claim 1, comprising the following steps: (a) mixing entacapone or a pharmaceutically acceptable salt thereof, PVP K30 and SDS, wherein entacapone, PVP K30 and SDS are present at a weight ratio of 1:0.05-0.6: 0.06-0.1; (b) sieving the mixture obtained in step (a) through a sieve, wherein the sieve has a mesh size smaller than 180 μm; (c) granulating the mixture obtained in step (b) to obtain granules; (d) drying the granules obtained in step (c) until the water content thereof is between 1% and 3%, obtaining the composition of entacapone according to claim 1; the process does not comprise any step of grinding, crushing or micronizing the mixture of entacapone or a pharmaceutically acceptable salt thereof, PVP K30 and SDS to make the particle size of the mixture less than 30 μm. 9. The process according to claim 8, wherein in step (a) entacapone, PVP K30 and SDS are present at a weight ratio of 1:0.05-0.2:0.06. 10. The process according to claim 9, wherein in step (a) entacapone, PVP K30 and SDS are present at a weight ratio of 1:0.2:0.06. 11. The process according to claim 8, wherein in step (c) the granulating step is wet granulation. 12. The process according to claim 8, which does not comprise any step of grinding, crushing or micronizing the mixture of entacapone or a pharmaceutically acceptable salt thereof, PVP K30 and SDS to make the particle size of the mixture less than 40 μm. 13. The process according to claim 8, wherein step (a) further comprises adding at least one excipient, and said excipient is selected from povidone, crospovidone, carbohydrates, croscarmellose sodium, or combinations thereof. 14. The process according to claim 13, wherein the carbohydrates are selected from microcrystalline cellulose, mannitol, cellulose, hydroxypropyl methylcellulose, starch, or lactose. 15. A pharmaceutical composition, comprising the composition of entacapone according to claim 1. 16. The pharmaceutical composition according to claim 15, which is a pharmaceutical composition for treating Parkinson's Disease. 17. The pharmaceutical composition according to claim 16, further comprising levodopa and benserazide, or further comprising levodopa and carbidopa. 18. Use of the composition of entacapone according to claim 1 for manufacturing a pharmaceutical composition. 19. The use according to claim 18, wherein said pharmaceutical composition is one for treating Parkinson's Disease. 20. The use according to claim 18, wherein said pharmaceutical composition further comprises levodopa and benserazide, or further comprising levodopa and carbidopa.
說明FIELD OF THE INVENTION [0001] The present invention relates to a composition of entacapone, comprising entacapone, PVP K30 and SDS. In addition, the present invention also relates to a process for preparing said composition of entacapone and uses thereof.
BACKGROUND OF THE INVENTION [0002] Entacapone, also known as (E)-2-cyano-3-(3,4-dihydroxy-5-nitro-phenyl)-N,N-diethyl-2-propenamide, is a medicine presently known for treating Parkinson's Disease. [0003] Since entacapone has a low dissolution rate and low bio-availability, presently known compositions of entacapone are mostly made to be smaller-sized granules by grinding or crushing so as to increase its dissolution rate and bio-availability. For example, US 2010/0104634 A1 made 90% of entacapone granules have a particle size of less than 40 μm, while WO 2009098661 A1 made granules of entacapone and sugar alcohols go through a micronization process so that the particle size is less than 30 μm. [0004] However, techniques such as grinding or micronization usually generate high heat and thus make the drugs deteriorate. In addition, these techniques still have problems like low productivity and high costs. Therefore, a pressing problem to be solved in the art is how to prepare a composition of entacapone with a high dissolution rate or high bio-availability without utilizing techniques like grinding, crushing or micronization.
BRIEF SUMMARY OF THE INVENTION [0005] To solve the aforementioned problems, the inventors have developed an improved process which can increase the dissolution rate of entacapone without utilizing techniques like grinding, crushing or micronization, and also increase productivity and reduce production costs by simplifying the process. [0006] One of the objectives of the present invention is to provide a composition of entacapone, comprising entacapone or a pharmaceutically acceptable salt thereof, PVP K30 (polyvinylpyrrolidone K30), SDS (sodium dodecyl sulfate), and at least one pharmaceutically acceptable excipient. [0007] To achieve the above objective, the present invention provides a composition of entacapone comprising entacapone or a pharmaceutically acceptable salt thereof, PVP K30 and SDS; wherein entacapone, PVP K30 and SDS are present at a weight ratio of 1:0.05-0.6:0.06-0.1, and the composition has a dissolution rate of more than 88%. [0008] In a preferred embodiment of the present invention, in said composition of entacapone, entacapone, PVP K30 and SDS are present at a weight ratio of 1:0.05-0.2:0.06; more preferably, 1:0.2:0.06. [0009] In a preferred embodiment of the present invention, said composition of entacapone has a dissolution rate of more than 90%; more preferably, the dissolution rate is more than 95%. [0010] In a preferred embodiment of the present invention, said composition of entacapone further comprises at least one excipient, and said excipient is selected from povidone, crospovidone, carbohydrates, croscarmellose sodium, or combinations thereof. Said carbohydrate can be selected from, for example, microcrystalline cellulose (MCC), mannitol, cellulose, hydroxypropyl methylcellulose, starch, or lactose. [0011] The present invention also provides a process for preparing the composition of entacapone as described above, comprising the following steps: (a) mixing entacapone or a pharmaceutically acceptable salt thereof, PVP K30 and SDS, wherein entacapone, PVP K30 and SDS are present at a weight ratio of 1:0.05-0.6: 0.06-0.1; (b) sieving the mixture obtained in step (a) through a sieve, wherein the sieve has a mesh size smaller than 180 μm, more preferably smaller than 150 μm; (c) granulating the mixture obtained in step (b) to obtain granules; (d) drying the granules obtained in step (c) until the water content thereof is between 1% and 3%, obtaining said composition of entacapone; the process does not comprise any step of grinding, crushing or micronizing the mixture of entacapone or a pharmaceutically acceptable salt thereof, PVP K30 and SDS to make the particle size of the mixture less than 30 μm. [0016] In a preferred embodiment of the present invention, in step (a) of said process, entacapone, PVP K30 and SDS are present at a weight ratio of 1:0.05-0.2:0.06; more preferably, 1:0.2:0.06. [0017] In a preferred embodiment of the present invention, in step (c) of said process, the granulating step is wet granulation. [0018] In a preferred embodiment of the present invention, said process does not comprise any step of grinding, crushing or micronizing the mixture of entacapone, PVP K30 and SDS to make the particle size of the mixture less than 40 μm. [0019] In a preferred embodiment of the present invention, step (a) of said process further comprises at least one excipient, and said excipient is selected from povidone, crospovidone, carbohydrates, croscarmellose sodium, or combinations thereof. Said carbohydrate can be selected from, for example, microcrystalline cellulose, mannitol, cellulose, hydroxypropyl methylcellulose, starch, or lactose. [0020] The present invention further provides a pharmaceutical composition, comprising the aforementioned composition of entacapone; preferably a pharmaceutical composition for treating Parkinson's Disease. [0021] In a preferred embodiment of the present invention, said pharmaceutical composition further comprises levodopa and benserazide, or further comprises levodopa and carbidopa. [0022] The present invention further provides use of the aforementioned composition of entacapone for preparing pharmaceutical compositions; preferably, for preparing pharmaceutical compositions for treating Parkinson's Disease. [0023] In a preferred embodiment of the present invention, pharmaceutical compositions in said use further comprise levodopa and benserazide, or further comprise levodopa and carbidopa. [0024] In view of the above, the composition of entacapone provided in the present invention can increase the dissolution rate of entacapone to more than 88% without utilizing techniques like grinding, crushing or micronization. Compared to known processes, the present invention can not only simplify the process by preventing steps associated with grinding, but also avoid the risk of deterioration of entacapone induced by the high heat resulted from the grinding-associated steps. The present invention can also increase productivity and reduce costs.
DETAILED DESCRIPTION OF THE INVENTION [0025] The following examples are merely illustrations of the best embodiments but not intended to limit the scope of the present invention. Based on the disclosure of the present invention, those skilled in the art may make appropriate changes and modifications without violating the spirit of the present invention.
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