CN1122223A - 程控型透皮贴剂的制造方法 - Google Patents
程控型透皮贴剂的制造方法 Download PDFInfo
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Abstract
一种采用高稳定过饱和固溶液体系及释药量方便可调控释膜的膜控型程控制量透皮贴剂的新制造方法，其特征是：
1.能较长时间不断通过皮肤释放药物进入全身血液体系而保持药效。
2.随着病症不断减轻而自动按需要程序逐渐降低给药剂量以减少药物所引起的不必要的副作用。
3.特别适于可乐定类药物用于戒除依赖性药物(如对阿片类，尼古丁，酒精等脱瘾)等所产生的戒断综合症。
Description
本发明是涉及采用新的高稳定过饱和固溶体药库技术及释药量方便可调控释膜制备程控型透皮治疗系统(Programmed Transdermal Therapeuticsystem)，或程控型贴剂的方法。
自从80年代透皮治疗系统(Transdermal Therapeutic System TTS)或称透皮贴剂(以下简称贴剂)正式上市以来，由于该剂型具备传统剂型所没有的一系列优越性而得到迅速发展。这是由于贴剂能控制药物以病人需要的剂量恒速持久(一天乃至一周)地进入人的血液循环系统，避免常规给药出现的血药浓度峰谷现象、药物对肠胃的刺激及肝的首过作用，且使用方便。特别是采用先进膜控释技术的膜控型透皮贴剂，由于其能按照设定的给药剂量控释给药，而较少受皮肤渗透性影响，从而不同人员及不同皮肤部位均能按照设定剂量给药。
国际上已上市多年的Transderm-Nitro(硝化甘油贴剂)Transderm-Scop(东茛菪碱贴剂)，Estraderm(雌二醇贴剂)Catapres-TTS(可乐定贴剂)及1992年新上市的Nicoderm(尼古丁贴剂)等均为膜控型。
有效稳定给药时间较长(数日至一周)膜控型TTS如可乐定贴剂均采用可乐定固体微粒存在下的饱和高聚物固溶体药库体系，以便达到长时间内药库内药物溶液处于饱和状态，即有恒定的药物浓度或梯度，从而保证其恒定零级释药速率。如U.S，Pat.4,201,211所表述的。
但由于某些病症的治疗不仅需要较长的给药时间，而且要求随着病症不断减轻而自动按需要程序逐渐降低给药剂量以减少该药物所引起的不必要的副作用。如可乐定用于减轻戒毒时形成的戒断综合症。
要保持贴剂具有较大起始给药剂量，然后按需要或按预定程序随时间逐渐下降其给药剂量，首先要维持药库中较高的浓度。但由于药物在高聚物载体中的溶解度一般均较小，所以必须形成过饱和状态才能形成需要的高浓度。但要使以过饱和状态长期稳定，在液态情况下是不可能实现。只有在固态情况下，在特殊工艺条件下形成一定条件时才有可能实现。
本发明就用一系列特殊工艺条件以保证形成需要的高稳定过饱和固溶体。这样就创造了一个贴剂具有较大起始剂量但随时间剂量下降的基本条件。但要其剂量随时间下降的变化程序附合某一特定程序或要求，就必须采用一种在宽范围内易于调节其释放量的控释膜。这种控释膜可用中国专利公开号CN1079414(新型核径迹微孔膜及其制造方法)或已申请中国专利(用作透皮贴剂控释膜的改性EVA膜)提供的控释膜。然后采用CN1080524(膜控型透皮贴剂的新型制造方法)提供的方法制备透皮贴剂。当选择释放量大的控释膜时其剂量随时间下降的速度就快，反之就慢。
下面通过实施例对本发明作进一步详细说明。程控型可乐定戒毒贴剂制备工艺：
配方： 药库 接触粘胶层
可乐定 1.4g 0.20g
聚丙烯酸酯压敏胶 33.33g 33.33g
乙酸乙酯 60g 100g
共制1000片
控释膜：改性EVA膜(不同释放量系列化膜中选用)制备工艺：
按上述药库与接触粘胶层配方比例称取可乐定，然后溶于乙酸乙酯中。将此溶液与聚丙烯酸酯胶均匀混合，形成药库胶粘液和接触粘胶层胶粘液，密封于容器中待涂布成膜。
将上述两种涂膜溶液分别用涂布机涂成厚度均匀的薄膜，然后送入专门设计的温度逐步增大的烘道中，最高温度不超过80℃，整个干燥时间为1小时。在整个干燥过程中不应出现析晶及失透现象，否则说明过饱和状态已转变成饱和状态。在正常情况下两种涂膜液干燥后均形成过饱和固溶体系透明薄膜。
将此二层薄膜按背衬层、药库、控释膜、接触粘胶层、防粘层顺序复合成五层组成的叠片，然后冲切成面积为2.3cm2贴片。
制成程控型戒毒贴剂将随时间变化按下列程序改变其可乐定给药剂量：
第一天：0.17mg/天
第二天：0.13mg/天
第三天：0.09mg/天
第四天：0.06mg/天
第五天：0.04mg/天
第六天：0.02mg/天
Claims (3)
1、一种程序控制剂量的膜控型透皮贴剂的制造方法，其特征是：
(1)采用高稳定过饱和固溶液体系作为药库。
(2)采用方便可调释放量的控释膜。
(3)随着病症不断减轻而自动按预定程序逐渐降低给药剂量以减少药物所引起的不必要的副作用。
2、按照权力要求1方法，其中的有效药物是可乐定或其他药物。
3、按照权力要求1方法，其适应症是减轻对依赖性药物(如阿片类，尼古丁，洒精等)脱瘾时即戒毒，戒烟，戒洒时所产生的戒断综合症。
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95102854A CN1078460C (zh) | 1995-03-23 | 1995-03-23 | 程控型透皮贴剂 |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95102854A CN1078460C (zh) | 1995-03-23 | 1995-03-23 | 程控型透皮贴剂 |
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| Publication Number | Publication Date |
|---|---|
| CN1122223A true CN1122223A (zh) | 1996-05-15 |
| CN1078460C CN1078460C (zh) | 2002-01-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95102854A Expired - Lifetime CN1078460C (zh) | 1995-03-23 | 1995-03-23 | 程控型透皮贴剂 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103919755A (zh) * | 2013-01-15 | 2014-07-16 | 江苏康倍得药业有限公司 | 妥洛特罗透皮贴剂及其制备方法 |
| CN103933018A (zh) * | 2013-01-18 | 2014-07-23 | 江苏康倍得药业有限公司 | 一种透皮给药系统 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4201211A (en) * | 1977-07-12 | 1980-05-06 | Alza Corporation | Therapeutic system for administering clonidine transdermally |
| CN1080524A (zh) * | 1993-06-10 | 1994-01-12 | 北京市三喜化学新技术公司 | 膜控型透皮贴剂的新型制造方法 |
-
1995
- 1995-03-23 CN CN95102854A patent/CN1078460C/zh not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103919755A (zh) * | 2013-01-15 | 2014-07-16 | 江苏康倍得药业有限公司 | 妥洛特罗透皮贴剂及其制备方法 |
| CN103933018A (zh) * | 2013-01-18 | 2014-07-23 | 江苏康倍得药业有限公司 | 一种透皮给药系统 |
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| Publication number | Publication date |
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| CN1078460C (zh) | 2002-01-30 |
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