CN101015536A - 一种含有西洛他唑的缓释制剂及其制备方法 - Google Patents
一种含有西洛他唑的缓释制剂及其制备方法 Download PDFInfo
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- CN101015536A CN101015536A CN 200710020473 CN200710020473A CN101015536A CN 101015536 A CN101015536 A CN 101015536A CN 200710020473 CN200710020473 CN 200710020473 CN 200710020473 A CN200710020473 A CN 200710020473A CN 101015536 A CN101015536 A CN 101015536A
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- 229960004588 cilostazol Drugs 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 230000001476 alcoholic effect Effects 0.000 claims description 9
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- 229920001249 ethyl cellulose Polymers 0.000 claims description 8
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Abstract
本发明涉及药物制剂领域，具体涉及西洛他唑的缓释制剂，本发明的西洛他唑缓释制剂由含35～60％西洛他唑，10～60％缓释材料及余量的其它药用辅料组成，本发明的缓释西洛他唑制剂进入体内后药物缓慢释放，可以一天服用一次。
Description
技术领域
本发明涉及药物制剂领域，具体涉及一种含有西洛他唑的缓释制剂及其制备方法。
背景技术
西洛他唑(cilostazol)化学名为6-[4-(1-环己基-1H-戊四唑(5’)]丁氧基-3，4-二氢-1H喹诺酮(2’)，是一种新型抗血小板聚集药物，通过抑制血小板及血管平滑肌内磷酸二酯酶活性，从而增加血小板及平滑肌内cAMP浓度、发挥抗血小板作用及血管扩张作用。本品抑制ADP、肾上腺素、胶原及花生四烯酸诱导的血小板初期、二期聚集和释放反应，且呈剂量相关性。西洛他唑口服100mg对血小板体外聚集的抑制较相应量阿司匹林强7～78倍(阿司匹林对血小板初期聚集无效)。本品不干扰血管内皮细胞合成血管保护性前列环素，对慢性动脉闭塞患者，采用体积描记法显示本品能增加足、腓肠肌部位的组织血流量，使下肢血压指数上升、皮肤血流增加及四肢皮温升高，并改善间歇跛行。
目前在临床使用的主要是西洛他唑普通片，另外，也有其它剂型的报道，如：CN1562018A公开了西洛他唑的固体分散体；CN1403083A公开了西洛他唑的速崩片。这些速释制剂口服后迅速崩解，在短时间内在体内释放出大量多余的西洛他唑，因此会产生诸如头痛、严重的头部不适和疼痛感的副作用。为了克服这些缺陷，CN1168102A公开了一种能在一段长时间内在体内连续地释放出所需量的西洛他唑的树脂微粒，它通过将西洛他唑掺入乙烯乙烯醇共聚物中以实现持续释放的目的，它主要采用熔融法制备，但是熔融法制备时需要用到氯仿等有机溶剂，这些溶剂的残留会对患者造成副作用，另外，熔融和成形过程中西洛他唑和共聚物易被氧化，这些不利因素都制约了它的生产和使用。
发明内容
本发明公开了一种西洛他唑的缓释制剂，它含有作为活性成分的西洛他唑和缓释材料，本发明的西洛他唑缓释制剂服用后药物在体内缓慢释放，药物在体内较长时间保持有效药物浓度，从而达到减少药物剂量，提高药效，延长药物作用时间和减少药物不良反应的积极效果。
本发明的西洛他唑缓释制剂由含35～60％西洛他唑，10～60％缓释材料及余量的其它药用辅料组成，上述百分比为重量百分比。
更优选的重量百分比是西洛他唑45～60％，缓释材料15～50％，余量为其它药用辅料。
上述所述缓释材料优选卡波普、乙基纤维素、甲基纤维素、羟丙基纤维素、羟丙甲基纤维素、羧甲基纤维素、硬脂酸、单硬脂酸甘油酯、十八醇、聚乙烯、聚丙烯、聚硅氧烷中的一种或几种。
缓释材料更优选卡波普、羟丙甲基纤维素、乙基纤维素中的一种或几种。
上述所述其它药用辅料优选自填充剂、崩解剂、粘合剂、润滑剂等药剂学常用辅料中的一种或几种。
上述填充剂优选糖、蔗糖、淀粉、预胶化淀粉、纤维素、糖粉、糊精、葡萄糖、甘露醇、硫酸钙、碳酸氢钙中的一种或几种；崩解剂优选甲基淀粉钠、低取代羟丙基纤维素、交联聚维酮、交联羧甲基纤维素钠中的一种或几种；粘合剂优选醇、聚乙烯吡咯烷酮、乙基纤维素的醇溶液、淀粉浆、纤维素醚类的水或醇溶液、胶浆中的一种或几种；润滑剂优选硬脂酸镁、滑石粉、微粉硅胶、十二烷基硫酸钠或十二烷基硫酸镁中的一种或几种。
本发明的缓释制剂，优选的剂型是片剂或胶囊。
本发明的缓释制剂制备工艺简单，具体方法为：将西洛他唑、缓释材料、其它药用辅料混匀后制粒，再压片或灌装入胶囊。
本发明缓释制剂改变了原有剂型的释药形式，在服药二小时内释放10-30％，服药八小时内释放45～75％，从而产生持续药效。本发明提供了一种药物库形式，使含有西洛他唑的药物能缓慢释放。本发明的缓释药物可以一天服用一次。
具体实施方式
实施例1
西洛他唑缓释片，按1000片计
组分 重量(g)
西洛他唑 200
羟丙基甲基纤维素K4M 70
乳糖 100
硬脂酸镁 3.5
聚乙烯基吡咯烷酮乙醇溶液K-30 q.s
制备方法：
原辅料粉碎过筛，混匀后与润滑剂混合，压片。
实施例2
西洛他唑缓释片：按1000片计
组分 重量(g)
西洛他唑 200
羟丙基甲基纤维素Methocl K4M 40
羟丙基甲基纤维素Methocl 100cp 40
乳糖 100
硬脂酸镁 3.5
聚乙烯基吡咯烷酮乙醇溶液 q.s
制备方法：
原辅料粉碎过筛，按上述处方量分别混匀，制成颗粒，烘干，过筛，然后与润滑剂混合压片。
实施例3
西洛他唑缓释片：按1000片计
组分 重量(g)
西洛他唑 200
羟丙基甲基纤维素Methocl K4M 120
微晶纤维素PH101 30
乳糖 50
硬脂酸镁 4
羟丙甲纤维素乙醇溶液(100cp) q.s
制备方法同实施例2。
实施例4
西洛他唑缓释胶囊：按1000颗胶囊计
组分 重量(g)
西洛他唑 200
羟丙基甲基纤维素K10M 120
乳糖 30
淀粉水溶液 q.s
制备方法：
原辅料粉碎过筛，按上述处方量分别混匀，制成颗粒，烘干，整粒，灌注于胶囊中。
实施例5
西洛他唑缓释胶囊：按1000颗胶囊计
组分 重量(g)
西洛他唑 200
羟丙基甲基纤维素 120
乙基纤维素 30
乙基纤维素乙醇溶液 q.s
制备方法同实施例4。
实施例6
西洛他唑缓释胶囊：按1000颗胶囊计
组分 重量(g)
西洛他唑 200
羟丙基甲基纤维素 120
卡波姆934 20
乳糖 20
聚乙烯基吡咯烷酮乙醇溶液 q.s
制备方法同实施例4。
实施例7
体外溶出试验
溶出介质：0.45％十二烷基硫酸钠水溶液，100转/分转篮法
实施例1至6中所制备的西洛他唑缓释制剂的不同时间体外累积溶出值见表：
| 时间 | 实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 实施例6 |
| 2h | 24.5 | 26.07 | 14.29 | 14.75 | 19.47 | 18.93 |
| 4h | 40.26 | 42.23 | 29.61 | 26.42 | 42.17 | 36.78 |
| 8h | 70.83 | 69.44 | 55.39 | 48.57 | 65.97 | 52.74 |
| 12h | 83.67 | 88.85 | 74.81 | 70.44 | 80.56 | 74.58 |
| 24h | 95.64 | 92.49 | 95.79 | 87.56 | 92.68 | 98.39 |
上表可见，本发明的西洛他唑缓释制剂能缓慢释放，达到了理想的释放效果。
Claims (8)
1、一种西洛他唑的缓释制剂，其特征是：由含35～60％西洛他唑，10～60％缓释材料及余量的其它药用辅料组成，为重量百分比。
2、权利要求1的缓释制剂，其中含西洛他唑45～60％、缓释材料15～50％及余量的其它药用辅料。
3、权利要求1或2的缓释制剂，其中缓释材料选自卡波普、乙基纤维素、甲基纤维素、羟丙基纤维素、羟丙甲基纤维素、羧甲基纤维素、硬脂酸、单硬脂酸甘油酯、十八醇、聚乙烯、聚丙烯、聚硅氧烷中的一种或几种。
4、权利要求3的缓释制剂，其中缓释材料选自卡波普、羟丙甲基纤维素、乙基纤维素中的一种或几种。
5、权利要求1或2的缓释制剂，其中其它药用辅料选自填充剂、崩解剂、粘合剂、润滑剂中的一种或几种。
6、权利要求5的缓释制剂，其中填充剂选自糖、蔗糖、淀粉、预胶化淀粉、纤维素、糖粉、糊精、葡萄糖、甘露醇、硫酸钙、碳酸氢钙中的一种或几种；崩解剂选自甲基淀粉钠、低取代羟丙基纤维素、交联聚维酮、交联羧甲基纤维素钠中的一种或几种；粘合剂选自醇、聚乙烯吡咯烷酮、乙基纤维素的醇溶液、淀粉浆、纤维素醚类的水或醇溶液、胶浆中的一种或几种；润滑剂选自硬脂酸镁、滑石粉、微粉硅胶、十二烷基硫酸钠或镁中的一种或几种。
7、权利要求1或2的缓释制剂，其剂型是片剂或胶囊。
8、权利要求1至7中任一项的缓释制剂的制备方法，包括：将西洛他唑、缓释材料和其它药用辅料混匀后制粒，再压片或灌装入胶囊。
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| CN102548543A (zh) * | 2009-09-23 | 2012-07-04 | 韩国联合制药株式会社 | 具有改进的溶出率和最小的副作用的缓释的西洛他唑片剂 |
| EP2481398A1 (en) * | 2009-09-23 | 2012-08-01 | Korea United Pharm, Inc. | Slow-release cilostazol tablet having an improved elution rate and minimal side effects |
| EP2481398A4 (en) * | 2009-09-23 | 2013-03-06 | Korea United Pharm Inc | RETARD CILOSTA TOLL VEHICLE WITH IMPROVED ELUTION RATE AND MINIMAL SIDE EFFECTS |
| CN102548543B (zh) * | 2009-09-23 | 2014-02-12 | 韩国联合制药株式会社 | 具有改进的溶出率和最小的副作用的缓释的西洛他唑片剂 |
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