CN1193752C - 含有四氢一制胰脂菌素的组合物 - Google Patents
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Abstract
本发明涉及含有作为活性成分的四氢一制胰脂菌素和药学可接受赋形剂的产物,特征在于,其是直径为0.25mm至2mm的微粒形式;并且涉及含有该产物的口服药物制剂或组合物。
Description
四氢一制胰脂菌素(“THL”)是一种胰脂肪酶抑制剂,并且已知其通用名称为orlistat。美国专利No.4,598,089公开了THL用作药物,特别是用作抗肥胖药剂,以及含有THL作为活性剂的药物组合物。
由于其大约44℃的低熔点,特别是当在湿空气或者高于35℃的干空气中贮存时,THL即发生水解降解和热降解。此外,象美国专利No.4,598,089中描述的常规剂量形式,例如,片剂或硬明胶胶囊,不容易从粉末混合物配制或者通过常规湿造粒方法制备,因为在压片或制胶囊过程中出现粘连和粘结现象。因此,存在对于含有THL的产物和在生产和贮存期间对湿和热稳定的剂量形式的需要。
一方面,本发明涉及含有作为活性成分的THL、稳定剂、药学可接受赋形剂的产物,特征在于,其是直径范围为大约0.25mm至大约2mm的微粒形式。
这样的微粒一般是颗粒或小丸形式。优选的小丸形式需要存在微晶纤维素。优选的是,小丸的直径范围是大约0.5mm至大约1.5mm。
惊奇地发现,含有THL的微粒不发生粘结和粘连现象,并且显示出优越的THL稳定性。
现在通过其优选实施方案描述本发明。给出这些实施方案是为了有助于理解本发明而不是以此为限。
本发明提供用于制备药物组合物例如单位剂量形式的微粒,例如颗粒和小丸。应用小丸形式的微粒是优选的。
令人惊奇地发现含有THL的微粒(也称为多单位)使在压片或制胶囊过程中所遇到的粘结和粘连现象降低到最小程度。一方面,本发明涉及含有许多直径范围为0.25-2mm的小丸的单位剂量形式,其中每一个微粒含有四氢一制胰脂菌素、稳定剂和至少一种药学可接受赋形剂。当微粒是小丸形式时,关键是使用微晶纤维素。
术语“稳定剂”是指水分摄入速度大于对于THL的水分摄入速度的试剂。这样的稳定剂的作用是阻止THL的水解降解。优选的是,该稳定剂在百分之五十(50%)相对湿度时具有大于百分之五(5%)的含湿量。阅读本说明书后对于具有上述质量的稳定剂的选择在本领域技术人员的技术范围内。这样的稳定剂的例子包括但不限于羟基丙基甲基纤维素,羟基丙基纤维素,聚乙烯吡咯烷酮和乳糖。
优选的是,微粒平均直径范围是0.5-1.5mm。本说明书自始至终直径是指平均直径。尽管优选所有微粒是在所述范围内,但是存在非常少的或痕量的过大或过小的微粒是可以接受的。
本发明又一个目的是如上所述含有THL与稳定剂的特定组合,和赋形剂的产物,特别是含有聚乙烯吡咯烷酮和/或乳糖为稳定剂的产物。
优选的是,该产物含有或者(a)乳糖,和至少该产物重量的3%是聚乙烯吡咯烷酮,或者(b)至少该产物重量的5%是聚乙烯吡咯烷酮。
优选的组合物一般含有大约20%至大约75%重量的THL,和大约3%至大约60%重量的稳定剂。优选的小丸另外含有大约10%至大约60%重量的微晶纤维素。更优选的是,这样的小丸含有大约25%至大约75%重量的THL;大约20%至大约60%重量的微晶纤维素;大约1%至大约10%重量的羟基乙酸淀粉钠;大约1%至大约8%重量的十二烷基硫酸钠;大约1%至大约10%重量的聚乙烯吡咯烷酮;和大约0%至大约1%重量的滑石。
最优选的是,这样的小丸含有大约50%重量的THL;大约39%重量的微晶纤维素;大约3%重量的羟基乙酸淀粉钠;大约3%重量的十二烷基硫酸钠;大约5%重量的聚乙烯吡咯烷酮;和大约0.1%重量的滑石。
这样的产物是化学稳定的,并且能在快速运转的制胶囊机器中填充而不存在粘结和粘连现象。
除优选的稳定剂,聚乙烯吡咯烷酮和/或乳糖外,本发明产物(微粒)含有其他赋形剂,例如稀释剂,例如蔗糖或优选微晶纤维素(本发明小丸所必须用的);粘合剂,例如淀粉糊;表面活性剂,例如十二烷基硫酸钠或二辛基磺基琥珀酸钠;和/或崩解剂,例如羟基乙酸淀粉钠、交联的聚乙烯吡咯烷酮、内交联的羧甲基纤维素钠或者低取代的羟基丙基纤维素。小丸还可以含有玉米淀粉作为稀释剂和崩解剂,和三酸甘油酯。
小丸优选通过挤压湿物质之后球化来制备。也可以通过在流化床设备中的旋转底板上粒化,通过在斜式盘设备上,或者在高剪切混合器中团聚粒化来制备。
制备小丸的方法实质上是已知的。参见,例如J.W.Conine和H.R.Hadley,D & CI,1970年4月,p.38-41:小固体药物球;A.D.Reynold,Manufacturing Chemist & Aerosol News,1970年6月,p.40-43:生产球状颗粒的新技术;C.W.Woodruff和N.O.Nuessle,医药科学杂志(J.Pharm.Sci.)
61(5),p.787-790(1972):加工变量对通过挤压-球化方法获得的颗粒的影响;和H. J.Malinowski和W.E.Smith,J.Pharm.Sci.
64(10),p.1688-1692(1975):应用因子设计评价通过球化作用制备的颗粒。
一般情况下,通过挤压和球化进行的制丸过程包括下面的单元操作:
-- 湿润并捏和含有活性物质THL和附加的赋形剂的粉末物质与适当粘合剂的一种合适的、通常是含水的溶液,得到湿润的糊状物质。或者,粘合剂可以在湿润和捏和之前包含在粉末混合物中;
-- 利用合适的设备(挤出机)迫使湿润的物质通过孔板的小孔,得到象通心粉一样的湿润的股。孔的直径可以在宽范围内变化,例如,根据要得到的具体产物,可以在0.4-1.0mm之间。
-- 将股破碎成短段,同时在一个立式圆筒中(球化器),通过快速旋转的、通常是结构化的板形成大体上球状的微粒。
-- 利用任何合适的干燥设备,例如,流化床干燥器或盘架干燥器来干燥湿球。
-- 任选地,干燥的球可以被分成合适大小的等级,或者可以通过适当的筛选或筛分方法将主要材料和过小或过大材料分开。优选的是,在整个过程中,温度保持在35℃以下。
本发明的又一方面是含有该微粒的用于口服的药物制剂或组合物。可以将其简单地装入PVC容器中,可以用剂量勺从中取出微粒。其它口服剂量形式是袋剂,其中单独装入微粒,或者微粒与合适的赋形剂,例如脱脂奶粉,微晶纤维素,羧甲基纤维素钠和滑石一起装入,形成用于再配制的粉剂。另一个可能性是将微粒包埋在基质赋形剂中,例如微晶纤维素中,接着压制成片,特别是可咀嚼片剂。该微粒也可以装入胶囊,例如硬明胶胶囊中。
下面的实施例是详细说明而不是限制本发明。
实施例1
制备小丸
下面适用于4.0kg批量的小丸。
a)搅拌下,将120g十二烷基硫酸钠和200g聚乙烯吡咯烷酮(Povidone)溶解于适量软化水中。将溶液冷却到10-15℃(溶液A)。
b)将2000g THL、1560g微晶纤维素和120g羟基乙酸淀粉钠装入高速混合器(DIOSNA,P50型),并且预混1分钟,混合器和切碎机处于低速位置“I”(预混物B)。
c)将溶液A加入到预混物B中,并在混合器和切碎机置“I”处捏和2.5分钟,然后将切碎机置于位置“II”。3分钟后,将切碎机位置又回到“I”持续1分钟,然后通过出口阀排出材料;其温度处于20和25℃之间。
d)将材料送入挤出机(NICA Lab,E-140型)。挤出机装备有0.8mm公称筛目尺寸且厚度1.0mm的筛;该筛周围是冷却装置。将材料挤成合适长度的通心粉。挤出物温度和挤出机筛的温度低于35℃(挤出物D)。
e)以大约800g次批量将挤出物D转移给球化器(NICA Lab,S-320型),并以700rpm球化3/4-2分钟(湿丸E)。
f)圆筒形的湿丸E被转移给流化床干燥器(AEROMATC,MP-1型),该流化床干燥器装有干燥空气源,并且在低于35℃的进料空气温度下干燥,得到低的最终含湿量的小丸(F)。
g)利用筛卡盘为0.50mm和1.25mm筛目尺寸的方筛筛选干燥过的小丸;弃除过小或过大级分;在密闭容器中收集0.5-1.25mm级分作为THL小丸。参见下面表1中的小丸A。
实施例2
制备小丸
下面适用于6.0kg批量的小丸
a)利用搅拌器,将180g十二烷基硫酸钠和300g Povidone溶解于适量软化水中。通过将烧杯放入冰和水的混合物中来将溶液冷却到大约10-15℃(A)。
b)将1800g THL、3120g微晶纤维素和600g羟基乙酸淀粉钠装入高速混合器(DIOSNA,P50型),并且预混1分钟,混合器和切碎机处于低速位置“I”(B)。
c)将溶液A加入到预混物B中,并在混合器和切碎机置“I”处捏和2.5分钟,然后将切碎机置于位置“II”。3分钟后,将切碎机位置又回到“I”持续1分钟,然后通过出口阀排出材料;其温度处于20和25℃之间(C)。
d)将该材料送入挤出机,并且根据实施例1d)处理。
e)以大约800g次批量将得到的挤出物转移到流化床干燥器(AEROMATC,MP-1型),该液化床干燥器装有旋转造粒装置和干燥空气源,并且以500rpm球化3分钟(E)。
f)圆筒形的湿丸E然后在相同的设备中干燥,进料空气温度低于35℃,得到低的最终含湿量的小丸(F)。
g)利用筛卡盘为0.50mm和1.25mm筛目尺寸的方筛筛选干燥过的小丸F;弃除过小或过大级分;在密闭容器中收集0.5-1.25mm级分作为THL小丸。参见下面的小丸B。
表1给出了小丸A和小丸B的组成:
表1
小丸制剂(重量百分比%) | A | B |
活性药剂 | ||
磨细的THL | 50.0 | 30.0 |
赋形剂 | ||
微晶纤维素 | 39.0 | 52.0 |
羟基乙酸淀粉钠 | 3.0 | 10.0 |
十二烷基硫酸钠 | 3.0 | 3.0 |
聚乙烯吡咯烷酮 | 5.0 | 5.0 |
总计 | 100.0 | 100.0 |
实施例3
装备小丸
以类似于小丸A和B的方法制备具有下面组成的小丸:
表2
小丸制剂(重量百分比%) | F1 | F2 | F3 | F4 | F5 | F6 |
THL | 29.1 | 30.2 | 50 | 50 | 50 | 50 |
乳糖 | 33.5 | 34.0 | 7 | 21 | 12 | |
微晶纤维素 | 23.6 | 20.8 | 36 | 19.5 | 21 | 41 |
羟基乙酸淀粉钠 | 9.1 | 9.4 | 3 | 3 | 9.5 | 3 |
十二烷基硫酸钠 | 1.1 | 1.1 | 1 | 1 | 3 | 1 |
(Povidone)聚乙烯吡咯烷酮 | 3.6 | 4.5 | 3 | 3 | 4.5 | 5 |
中链三酸甘油酯 | 2.5 |
实施例4
制备最终剂量形式
将小丸A或B(来自上述实施例1和2)与滑石混合并在装有小丸装填台的设备上制胶囊(制剂C,E);
或者将小丸A或B与脱脂奶粉,微晶纤维素和滑石的混合物装填成袋剂(制剂D)。
将类似的混合物压制成可咀嚼片剂(制剂F)。
表3给出了最终剂量形式C,D,E,F的组成。
表3:最终剂量形式的组成(mg/剂)
制剂 | C | D | E | F | |
最终活性药剂含量 | 120.0 | 60.0 | 30.0 | 30.0 | mg |
小丸形式的活性药剂 | |||||
小丸A | 240.0 | 120.0 | -- | -- | mg |
小丸B | -- | -- | 100.0 | 100.0 | mg |
赋形剂 | |||||
脱脂奶粉(粒化的) | 3875.0 | mg | |||
微晶纤维素+羧甲基纤维素钠(AVICEL RC-型) | 1000.0 | mg | |||
微晶纤维素 | 1888.0 | mg | |||
滑石 | 0.24 | 5.0 | 0.1 | 2.0 | mg |
硬脂酸镁 | 10.0 | mg | |||
总硬明胶胶囊填充重量 | 240.24 | 100.1 | mg | ||
总袋剂填充重量 | 5000.0 | mg | |||
可咀嚼片剂重量 | 2000.0 | mg |
表4给出了用小丸A装填的胶囊制剂C的详细组成:
表4:生产批量大小=160.160kg=666,666胶囊
填充重量=240.24mg
成分 | 量,mg/胶囊 | 666,666个胶囊含有(kg) |
THL | 120.00 | 80.000 |
微晶纤维素(AVICEL PH-101) | 93.60 | 62.400 |
羟基乙酸淀粉钠(PRIMOJEL) | 7.20 | 4.800 |
十二烷基硫酸钠 | 7.20 | 4.800 |
聚乙烯吡咯烷酮(Povidone)(K-30) | 12.00 | 8.000 |
滑石 | 0.24 | 0.160 |
总计 | 240.24mg | 160.160kg |
实施例5
制备含有THL的颗粒和制剂
成分 | mg/胶囊 |
1.THL | 120 |
2.微晶纤维素 | 93.6 |
3.羟基乙酸淀粉钠 | 7.2 |
4.聚乙烯吡咯烷酮 | 12.0 |
5.十二烷基硫酸钠 | 7.2 |
总计 | 240.00 |
1.将聚乙烯吡咯烷酮和十二烷基硫酸钠溶解于水中。
2.将THL、微晶纤维素和羟基乙酸淀粉钠混合10分钟并与第1步的溶液一起造粒。
3.将颗粒在30℃或低于30℃干燥并通过#20目筛。
4.将颗粒填入#1硬明胶胶囊。
实施例6
制备含有THL的颗粒和制剂
成分 | mg/胶囊 |
1.THL | 120 |
2.无水乳糖 | 93.6 |
3.羟基乙酸淀粉钠 | 7.2 |
4.聚乙烯吡咯烷酮 | 12.0 |
5.十二烷基硫酸钠 | 7.2 |
总计 | 240.00 |
1.将聚乙烯吡咯烷酮和十二烷基硫酸钠溶解于水中。
2.将THL、无水乳糖和羟基乙酸淀粉钠混合10分钟并与第1步的溶液一起造粒。
3.将颗粒在30℃或低于30℃于燥并通过#20目筛。
4.将颗粒填入#1硬明胶胶囊。
本发明以其优选实施方案的形式进行了描述。通过阅读本说明书,本领域技术人员将理解各种各样的改变的实施方案。认为这些变化在本发明范围和精神内,本发明只受下面的权利要求书及其等同范围限制。
Claims (19)
1.一种药物组合物,其含有平均直径为0.25mm至2mm的许多微粒,每个微粒含有四氢一制胰脂菌素、稳定剂和至少一种药学可接受赋形剂,条件是当微粒是小丸形式时,每个小丸含有微晶纤维素。
2.权利要求1的组合物,其中微粒是小丸或颗粒。
3.权利要求2的组合物,其中小丸或颗粒具有0.5mm至1.5mm的平均直径。
4.权利要求2的组合物,其中稳定剂选自聚乙烯吡咯烷酮、乳糖、聚乙烯吡咯烷酮和乳糖的组合、羟基丙基甲基纤维素和羟基丙基纤维素。
5.权利要求4的组合物,其中至少组合物重量的5%是聚乙烯吡咯烷酮。
6.权利要求4的组合物,其中稳定剂是乳糖和聚乙烯吡咯烷酮的组合,其中至少组合物重量的3%是聚乙烯吡咯烷酮。
7.权利要求2的组合物,其中药学可接受赋形剂是表面活性剂,稀释剂或崩解剂。
8.权利要求7的组合物,其中药学可接受赋形剂是表面活性剂。
9.权利要求8的组合物,其中表面活性剂是十二烷基硫酸钠或二辛基磺基琥珀酸钠。
10.权利要求7的组合物,其中药学可接受赋形剂是稀释剂。
11.权利要求10的组合物,其中稀释剂是微晶纤维素、蔗糖或玉米淀粉。
12.权利要求7的组合物,其中赋形剂是崩解剂。
13.权利要求12的组合物,其中崩解剂是羟基乙酸淀粉钠,交联的聚乙烯吡咯烷酮,内交联的羧甲基纤维素钠或低取代的羟基丙基纤维素。
14.权利要求2的组合物,其含有20%至75%重量的四氢一制胰脂菌素;3%至60%重量的稳定剂;和10%至60%重量的微晶纤维素。
15.权利要求14的组合物,其含有25%至75%重量的四氢一制胰脂菌素;20%至60%重量的微晶纤维素;1%至10%重量的羟基乙酸淀粉钠;1%至8%重量的十二烷基硫酸钠;1%至10%重量的聚乙烯吡咯烷酮;和0%至1%重量的滑石。
16.权利要求15的组合物,其含有50%重量的四氢一制胰脂菌素;39%重量的微晶纤维素;3%重量的羟基乙酸淀粉钠;3%重量的十二烷基硫酸钠;5%重量的聚乙烯吡咯烷酮;和0.1%重量的滑石。
17.权利要求1,2和14-16中任一项的组合物,其是单位剂量形式。
18.权利要求1的药物组合物,其含有120mg四氢一制胰脂菌素;93.6mg微晶纤维素;7.2mg羟基乙酸淀粉钠;7.2mg十二烷基硫酸钠;和12mg聚乙烯吡咯烷酮;和0.24mg滑石。
19.权利要求18的组合物,其是单位剂量形式。
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US3738497P | 1997-02-05 | 1997-02-05 | |
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US09/003,137 | 1998-01-06 | ||
US09/003,137 US6004996A (en) | 1997-02-05 | 1998-01-06 | Tetrahydrolipstatin containing compositions |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104740637A (zh) * | 2013-12-31 | 2015-07-01 | 北京科信必成医药科技发展有限公司 | 一种稳定的奥利司他口服制剂及其制备方法 |
Families Citing this family (96)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
YU34199A (sh) * | 1997-02-05 | 2002-08-12 | F. Hoffmann-La Roche Ag. | Primena inhibitora gastrointestinalne lipaze |
BR9912980B1 (pt) * | 1998-08-14 | 2013-10-22 | Composição farmacêutica administrável oralmente, tablete de mascar contendo a mesma e utilização da mesma | |
WO2000013667A1 (en) * | 1998-09-08 | 2000-03-16 | Smithkline Beecham Corporation | Lipstatin derivative-soluble fiber tablets |
AR025587A1 (es) * | 1999-09-13 | 2002-12-04 | Hoffmann La Roche | Formulaciones en dispersion que contienen inhibidores de lipasa |
AR025609A1 (es) * | 1999-09-13 | 2002-12-04 | Hoffmann La Roche | Formulaciones lipidas solidas |
EP1132389A1 (en) | 2000-03-06 | 2001-09-12 | Vernalis Research Limited | New aza-indolyl derivatives for the treatment of obesity |
DE10021618A1 (de) * | 2000-05-04 | 2001-11-15 | Volker Helmstaedter | Präparat für Darmerkrankungen und dessen Verwendung |
CN1236764C (zh) * | 2000-06-27 | 2006-01-18 | 霍夫曼-拉罗奇有限公司 | 制备组合物的方法 |
NZ523684A (en) * | 2000-07-28 | 2005-04-29 | F | New pharmaceutical composition |
AU2001289696B2 (en) * | 2000-07-28 | 2006-07-06 | Cheplapharm Arzneimittel Gmbh | New use of lipase inhibitors |
KR100494245B1 (ko) | 2000-08-09 | 2005-06-13 | 에프. 호프만-라 로슈 아게 | 리파제 억제제의 용도 |
US6900226B2 (en) * | 2000-09-06 | 2005-05-31 | Hoffman-La Roche Inc. | Neuropeptide Y antagonists |
KR100545435B1 (ko) | 2000-10-16 | 2006-01-24 | 에프. 호프만-라 로슈 아게 | 인돌린 유도체 및 5-ht2 수용체 리간드로서의 이들의 용도 |
GB0030710D0 (en) * | 2000-12-15 | 2001-01-31 | Hoffmann La Roche | Piperazine derivatives |
CA2432085C (en) | 2000-12-27 | 2009-02-24 | F. Hoffmann-La Roche Ag | Indole derivatives and their use as 5-ht2b and 5-ht2c receptor ligands |
GB0106177D0 (en) * | 2001-03-13 | 2001-05-02 | Hoffmann La Roche | Piperazine derivatives |
WO2002094789A1 (en) | 2001-05-21 | 2002-11-28 | F. Hoffmann-La Roche Ag | Quinoline derivatives as ligands for the neuropeptide y receptor |
US20030027786A1 (en) * | 2001-06-06 | 2003-02-06 | Karsten Maeder | Lipase inhibiting composition |
US6787558B2 (en) | 2001-09-28 | 2004-09-07 | Hoffmann-La Roche Inc. | Quinoline derivatives |
US7357891B2 (en) | 2001-10-12 | 2008-04-15 | Monosol Rx, Llc | Process for making an ingestible film |
US20110033542A1 (en) | 2009-08-07 | 2011-02-10 | Monosol Rx, Llc | Sublingual and buccal film compositions |
US8900498B2 (en) | 2001-10-12 | 2014-12-02 | Monosol Rx, Llc | Process for manufacturing a resulting multi-layer pharmaceutical film |
US8900497B2 (en) | 2001-10-12 | 2014-12-02 | Monosol Rx, Llc | Process for making a film having a substantially uniform distribution of components |
US10285910B2 (en) | 2001-10-12 | 2019-05-14 | Aquestive Therapeutics, Inc. | Sublingual and buccal film compositions |
US11207805B2 (en) | 2001-10-12 | 2021-12-28 | Aquestive Therapeutics, Inc. | Process for manufacturing a resulting pharmaceutical film |
US8603514B2 (en) | 2002-04-11 | 2013-12-10 | Monosol Rx, Llc | Uniform films for rapid dissolve dosage form incorporating taste-masking compositions |
US20190328679A1 (en) | 2001-10-12 | 2019-10-31 | Aquestive Therapeutics, Inc. | Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions |
US20070281003A1 (en) | 2001-10-12 | 2007-12-06 | Fuisz Richard C | Polymer-Based Films and Drug Delivery Systems Made Therefrom |
US8765167B2 (en) | 2001-10-12 | 2014-07-01 | Monosol Rx, Llc | Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions |
EP1448169A1 (en) * | 2001-11-07 | 2004-08-25 | Fujisawa Pharmaceutical Co., Ltd. | Method for improving dissolution of poorly dispersible medicaments |
US20050118258A1 (en) * | 2001-12-20 | 2005-06-02 | Federico Shroppolo | Pharmaceutical composition comprising skim milk powder |
GB0202015D0 (en) * | 2002-01-29 | 2002-03-13 | Hoffmann La Roche | Piperazine Derivatives |
ATE392897T1 (de) * | 2002-02-04 | 2008-05-15 | Hoffmann La Roche | Chinolinderivate als npy antagonisten |
RU2004129285A (ru) | 2002-02-28 | 2005-10-27 | Ф.Хоффманн-Ля Рош Аг (Ch) | Производные тиазола в качестве антагонистов рецептора npy |
EP1501498B1 (en) * | 2002-04-26 | 2009-12-30 | F. Hoffmann-La Roche Ag | Pharmaceutical composition comprising a lipase inhibitor and glucomannan |
RU2296757C2 (ru) * | 2002-07-05 | 2007-04-10 | Ф.Хоффманн-Ля Рош Аг | Производные хиназолина |
EP1539722A1 (en) * | 2002-08-07 | 2005-06-15 | F. Hoffmann-La Roche Ag | Thiazole derivatives |
BR0314261A (pt) * | 2002-09-12 | 2005-07-26 | Hoffmann La Roche | Compostos, processo de preparação de um composto, composição farmacêutica que compreende o mesmo, utilização de um composto, método para tratamento e/ou profilaxia de enfermidades e utilização e/ou método de tratamento |
CN100343250C (zh) * | 2002-11-25 | 2007-10-17 | 霍夫曼-拉罗奇有限公司 | 吲哚衍生物 |
US20040178058A1 (en) * | 2003-03-10 | 2004-09-16 | Hsueh-Chung Chen | Electro-chemical deposition apparatus and method of preventing cavities in an ECD copper film |
GB0314967D0 (en) * | 2003-06-26 | 2003-07-30 | Hoffmann La Roche | Piperazine derivatives |
CN100393718C (zh) * | 2003-08-12 | 2008-06-11 | 霍夫曼-拉罗奇有限公司 | 作为npy拮抗剂的噻唑衍生物 |
MXPA06001570A (es) * | 2003-08-12 | 2006-05-15 | Hoffmann La Roche | Antagonistas del receptor de neuropeptido y (npy) 2-amino-5-benzoiltiazol. |
WO2006110809A2 (en) * | 2005-04-12 | 2006-10-19 | Elan Pharma International, Limited | Nanoparticulate lipase inhibitor formulations |
CN101171252B (zh) * | 2005-05-03 | 2011-06-01 | 霍夫曼-拉罗奇有限公司 | 作为5-ht2配体的四环氮杂吡嗪并二氢吲哚类化合物 |
KR100910000B1 (ko) * | 2005-05-13 | 2009-07-29 | 씨제이제일제당 (주) | 리파아제 저해제 함유 약학 조성물 |
DK1897558T3 (da) * | 2005-06-09 | 2013-12-09 | Norgine Bv | Fast præparat af 2-hexadecyloxy-6-methyl-4h-3,1-benzoxazin-4-on |
BRPI0614834A2 (pt) * | 2005-08-18 | 2011-04-19 | Hoffmann La Roche | compostos, processo para a sua manufatura, composições farmacêuticas que os compreendem e usos destas |
WO2007041643A1 (en) * | 2005-10-03 | 2007-04-12 | University Of Tennessee Research Foundation | Dietary calcium for reducing the production of reactive oxygen species |
CN101316838B (zh) * | 2005-11-30 | 2013-01-30 | 霍夫曼-拉罗奇有限公司 | 用作h3调节剂的1,1-二氧代-硫代吗啉基吲哚基甲酮衍生物 |
KR20080076987A (ko) * | 2005-11-30 | 2008-08-20 | 에프. 호프만-라 로슈 아게 | 5-치환된 인돌-2-카복스아미드 유도체 |
CA2630314A1 (en) * | 2005-11-30 | 2007-06-07 | F. Hoffmann-La Roche Ag | 1,5-substituted indol-2-yl amide derivatives |
ES2333672T3 (es) * | 2005-12-09 | 2010-02-25 | F. Hoffmann-La Roche Ag | Derivados de amida triciclica para tratamiento de obesidad. |
CA2631694A1 (en) * | 2005-12-15 | 2007-06-21 | F. Hoffmann-La Roche Ag | Pyrrolo[2,3-c]pyridine derivatives |
CA2631695A1 (en) * | 2005-12-16 | 2007-06-21 | F. Hoffmann-La Roche Ag | Pyrrolo[2,3-b]pyridine derivatives as h3 receptor modulators |
EP1803714A1 (en) * | 2005-12-27 | 2007-07-04 | KRKA, tovarna zdravil, d.d., Novo mesto | Process for preparing crystalline forms of orlistat |
KR20080085031A (ko) * | 2006-01-13 | 2008-09-22 | 에프. 호프만-라 로슈 아게 | 사이클로헥실 피페라지닐 메탄온 유도체 및 히스타민 h3수용체 조절제로서의 이의 용도 |
EP1979322B1 (en) * | 2006-01-23 | 2010-09-01 | F. Hoffmann-La Roche AG | Cyclohexyl sulfonamide derivatives having h3 receptor activity |
US7432255B2 (en) * | 2006-05-16 | 2008-10-07 | Hoffmann-La Roche Inc. | 1H-indol-5-yl-piperazin-1-yl-methanone derivatives |
US7902184B2 (en) * | 2006-05-30 | 2011-03-08 | Hoffmann-La Roche Inc. | Piperazinyl pyrimidine derivatives |
EP1872777A1 (en) * | 2006-06-27 | 2008-01-02 | LEK Pharmaceuticals D.D. | Pharmaceutical composition comprising tetrahydrolipstatin |
US7514433B2 (en) | 2006-08-03 | 2009-04-07 | Hoffmann-La Roche Inc. | 1H-indole-6-yl-piperazin-1-yl-methanone derivatives |
US20080146559A1 (en) | 2006-12-08 | 2008-06-19 | Li Chen | 4,5,6,7-Tetrahydro-Thieno [2,3-C] Pyridine Derivatives |
TR200607613A2 (tr) * | 2006-12-29 | 2008-07-21 | NOBEL İLAÇ SAN.ve TiC.A.Ş. | Lipaz inhibitörü içeren farmasötik formülasyonlar |
PL2002825T3 (pl) * | 2007-06-14 | 2013-12-31 | Krka | Kompozycje farmaceutyczne zawierające orlistat |
BRPI0817053A2 (pt) * | 2007-09-17 | 2015-03-24 | Reddys Lab Ltd Dr | Formulações farmacêuticas de orlistat |
WO2009044380A2 (en) | 2007-10-05 | 2009-04-09 | Ranbaxy Laboratories Limited | Formulations containing orlistat particles having controlled particle size |
US20100317642A1 (en) * | 2007-10-15 | 2010-12-16 | Inventis Dds Pvt Limited | Pharmaceutical composition of orlistat |
US8298583B2 (en) | 2007-10-19 | 2012-10-30 | Monosol Rx, Llc | Film delivery system for tetrahydrolipstatin |
US20090220593A1 (en) * | 2008-01-29 | 2009-09-03 | Gulati Inder | Extended release dosage forms of quetiapine |
PL216542B1 (pl) | 2008-03-20 | 2014-04-30 | Zakłady Farmaceutyczne POLPHARMA Spółka Akcyjna | Sposób wytwarzania stabilnej kompozycji orlistatu w postaci kapsułkowanego proszku |
US8309107B2 (en) * | 2008-10-06 | 2012-11-13 | Banner Pharmacaps, Inc. | Stable solutions of orlistat for pharmaceutical dosage forms |
BRPI0901602B8 (pt) * | 2009-04-03 | 2021-05-25 | Ems S/A | formulação farmacêuticas |
MX342962B (es) * | 2009-09-18 | 2016-06-07 | Teva Pharmaceuticals Holdings Mexico S A De C V | Composicion farmaceutica para bajar de peso y procedimiento para obtener la misma. |
UA107369C2 (en) | 2010-02-01 | 2014-12-25 | Lab Bago S A | Pharmaceutical composition with anti-obesity activity comprising a premixture of pure orlistat and preparation process |
US20120039999A1 (en) | 2010-08-11 | 2012-02-16 | Ashish Chatterji | Pharmaceutical compositions of metabotropic glutamate 5 receptor (mglu5) antagonists |
US20120040008A1 (en) | 2010-08-11 | 2012-02-16 | Ashish Chatterji | Pharmaceutical compositions of metabotropic glutamate 5 receptor (mglu5) antagonists |
US9149959B2 (en) | 2010-10-22 | 2015-10-06 | Monosol Rx, Llc | Manufacturing of small film strips |
KR101731155B1 (ko) * | 2011-06-15 | 2017-04-27 | 신톤 비.브이. | 안정화된 보리코나졸 조성물 |
CA2841748C (en) | 2011-07-15 | 2021-06-15 | Nusirt Sciences, Inc. | Compositions and methods for modulating metabolic pathways |
CN102362863B (zh) * | 2011-11-21 | 2013-06-12 | 山东新时代药业有限公司 | 一种含奥利司他的制剂及其制备方法 |
WO2013092786A1 (en) | 2011-12-23 | 2013-06-27 | Norgine B.V. | Compositions comprising cetilistat |
GB201122213D0 (en) * | 2011-12-23 | 2012-02-01 | Norgine Bv | Compositions |
NL2009995C2 (en) * | 2011-12-23 | 2013-09-18 | Norgine Bv | Compositions. |
US9198454B2 (en) | 2012-03-08 | 2015-12-01 | Nusirt Sciences, Inc. | Compositions, methods, and kits for regulating energy metabolism |
MX2014010926A (es) * | 2012-03-13 | 2015-04-10 | Piramal Entpr Ltd | Composicion herbaria para el tratamiento de transtornos metabolicos. |
JP6469015B2 (ja) | 2012-11-13 | 2019-02-13 | ニューサート サイエンシーズ, インコーポレイテッド | エネルギー代謝を増大させるための組成物および方法 |
DE202012104963U1 (de) | 2012-12-19 | 2013-01-14 | Norgine B.V. | Cetilistat aufweisende Zusammensetzungen |
CA2902879C (en) | 2013-03-15 | 2023-09-26 | Nusirt Sciences, Inc. | Leucine and nicotinic acid reduces lipid levels |
WO2015131152A1 (en) | 2014-02-27 | 2015-09-03 | Nusirt Sciences Inc. | Compositions and methods for the reduction or prevention of hepatic steatosis |
US10743813B2 (en) | 2014-09-11 | 2020-08-18 | Rattan Nath | Diabetes control using postprandial feedback |
KR20190005199A (ko) | 2016-05-05 | 2019-01-15 | 어퀘스티브 테라퓨틱스, 아이엔씨. | 강화된 전달 에프네프린 조성물 |
US11273131B2 (en) | 2016-05-05 | 2022-03-15 | Aquestive Therapeutics, Inc. | Pharmaceutical compositions with enhanced permeation |
CN108785272B (zh) * | 2018-09-04 | 2019-04-09 | 中山万汉制药有限公司 | 一种奥利司他软胶囊及其制备方法 |
CN115105476B (zh) * | 2021-03-23 | 2023-11-14 | 山东新时代药业有限公司 | 一种奥利司他冻干口服制剂及其制备工艺 |
CN115300479A (zh) * | 2022-08-23 | 2022-11-08 | 宁波高新区美诺华医药创新研究院有限公司 | 奥利司他胶囊制备方法 |
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CA1247547A (en) * | 1983-06-22 | 1988-12-28 | Paul Hadvary | Leucine derivatives |
JPH04198129A (ja) * | 1990-11-28 | 1992-07-17 | Sumitomo Pharmaceut Co Ltd | 活性型ビタミンd↓3類含有組成物 |
CA2098167C (en) * | 1992-06-24 | 2006-12-19 | Dorothea Isler | Foodstuffs and feedstuffs containing a lipase inhibitor |
TW381025B (en) * | 1993-08-05 | 2000-02-01 | Hoffmann La Roche | Pharmaceutical composition containing a glucosidase inhibitor and a lipase inhibitor |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN104740637A (zh) * | 2013-12-31 | 2015-07-01 | 北京科信必成医药科技发展有限公司 | 一种稳定的奥利司他口服制剂及其制备方法 |
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