CN1044591A - 一种水分散二甲苯氧庚酸组合物的制备方法 - Google Patents

一种水分散二甲苯氧庚酸组合物的制备方法 Download PDF

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Publication number
CN1044591A
CN1044591A CN90100780A CN90100780A CN1044591A CN 1044591 A CN1044591 A CN 1044591A CN 90100780 A CN90100780 A CN 90100780A CN 90100780 A CN90100780 A CN 90100780A CN 1044591 A CN1044591 A CN 1044591A
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gemfibrozil
wax
wetted material
mixture
water wetted
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艾萨克·吉布雷-塞尔拉西
乌马·艾耶
罗伯特·哈里·戈登
马迪·巴基尔·福齐
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Warner Lambert Co LLC
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Warner Lambert Co LLC
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract

一种制备水分散二甲苯氧庚酸组合物的方法，包括用蜡与至少一种亲水材料的混合物均匀地包覆纯二甲苯氧庚酸的磨细的颗粒，再用较少量的一种表面活性剂对上述被包覆的颗粒进行外包衣。

Description

本发明涉及一种水分散的二甲苯氧庚酸组合物。
二甲苯氧庚酸即5-（2，5-二甲苯氧基）-2，2-二甲基戊酸，是一种广泛地作为抗高脂蛋白血症的药剂，由于它需要大剂量，所以一般用多个胶囊的形式一天服用多次。虽然它需要以水分散制剂的形式服用，但是由于它在口腔粘膜中产生使人讨厌的灼烧回味，该方法到目前为止不能实现。
提供这种具有持续释放性质的这种水可分散的组合物来减少必须施用药物的次数是有好处的。
英国专利申请2，179，254公开了一些先用甲基丙烯酸-丙烯酸共聚物包衣，然后用甲基丙烯酸酯共聚物包衣，最后用多乙氧基醚80和羟丙基甲基纤维素的混合物包衣的止痛的丙酸衍生物（如异丁苯丙酸）的组合物。
Epo-A8600802公开了聚乙烯乙二醇和两亲化合物的缓释组合物。
法国专利申请2，554，717公开的缓释组合物使用乙烯基吡咯烷酮-乙烯基醋酸酯共聚物和用聚烯丙基蔗糖交联的丙烯酸聚合物作为基质（也可参见比利时申请901007）。
美国专利4，132，753公开了可控的释药颗粒，其中药物粉末被加热以陷入到很细的蜡类材料中。
美国专利4，195，084公开了一种用于降低高血胆甾醇的细微的妥尔油谷甾醇的液体混悬剂。
美国专利4，263，272公开了逐渐释药或分两个阶段释药的胆汁酸的三组分组合物。
美国专利4，291，016公开了具有用羟丙基甲基纤维素包裹的基质芯的药物组合物。
美国专利4，533，562公开了用成膜聚合物如羟丙基甲基纤维素和一种液体增塑剂，如聚乙二醇包衣的片剂。
美国专利4，661，162公开了一种肠溶性组合物，它含有肠溶聚合物，如（m）丙烯酸乙酯/甲基丙烯酸酯共聚物和多阴离子聚合物如藻酸及其盐类的混合物。
本发明提供一种水可分散的二甲苯氧庚酸组合物，它既能提供即时释放、持续释放，也能提供一种即时和持续结合的释放。具体地说，本发明使用了一种制剂，在该制剂中用蜡和至少一种亲水性材料的混合物均匀地包覆纯二甲苯氧庚酸磨细的颗粒。被包覆的颗粒再依次用较少量的表面活性剂，最好一起用矫味剂在外面包衣。
上述蜡成分是一种常规的药用微晶蜡。亲水材料通常是药用乙醇和酯类化合物，例如脂肪酸乙醇、脂肪酸酯、多元醇、纤维素衍生物和乙烯基衍生物。一种优选的亲水材料是十八烷醇。
蜡与亲水材料的比率是从约1∶0.1到约0.1∶1。推荐的范围是亲水材料∶蜡为约1∶1到约5∶1。
将蜡和亲水材料混合制备包衣组合物，最好加入少量的增塑剂，例如聚乙二醇。然后用该混合物均匀地包覆纯二甲苯氧庚酸磨细的颗粒。
对于用上述快速包衣材料处理基底的设备不是关键的。一般地说，只要能以足够量的上述包衣材料有效地包住该药物或其它可服用药剂以掩盖二甲苯氧庚酸的异味的任何设备均可。包覆装置的一个优选类型是一种流床设备。
包衣之后，被包覆的颗粒依次用少量的药用表面活性剂再包一次，例如溶解在含水载体中的十二烷硫酸钠或多乙氧基醚。上述表面活性剂外包层可以与适当的提供一种令人满意的味道、但是不影响上述组合物作用的矫味剂混合。上述外包层组合物能够简单地喷在被包好的颗粒上，然后去除多余的水份。
所得到的组合物外观是粉剂状的，并且在口服用的常水中是可口的和容易分散的。该包衣的组合物具有事实上在口中不溶解，而在胃液所提供的酸性环境中容易崩解的溶解特性。
在另一个实施方案中，该组合物包括用蜡和亲水材料（例如十八烷醇）的混合物均匀包覆的纯二甲苯氧庚酸磨细的颗粒的第一部分（以提供如上面所描述的相对的快速即时释放）和用蜡与疏水材料的混合物均匀包覆的纯二甲苯氧庚酸磨细的颗粒的第二部分，以提供相对的持续释放。一种优选的疏水材料是氢化的蓖麻油。
以下实例起进一步说明本发明的特征的作用，但是不应解释为对于本发明范围的限定，本发明的范围仅由权利要求书来限定。
实施例1
用下列的成份制备包衣组合物：
成份    重量份数
十八烷醇    3份
微晶蜡    1份
聚乙二醇400    0.16份
用上述组合物均匀地包覆磨细的二甲苯氧庚酸颗粒，然后用下列组合物的外包衣制剂喷覆：
十二烷基硫酸钠    3份
纯水    97份
将该外包衣了的颗粒干燥并包装。
实例2
由下列的成份中制备持续释放包衣组合物：
成份    重量份数
氢化蓖麻油    3份
微晶蜡    1份
聚乙二醇400    0.08份
用上述制剂均匀地包覆磨细的二甲苯氧庚酸颗粒，然后用下列组成的外包覆制剂喷覆：
十二烷基硫酸钠    3份
纯水    97份
将外包衣好的颗粒干燥，然后与按照实施例1制备的包覆颗粒等重量混合。

Claims (5)

1、一种制备二甲苯氧庚酸的水可分散组合物的方法，其中包括用蜡和至少一种亲水材料的混合物均匀包覆磨细的纯二甲苯氧庚酸颗粒，亲水材料选自于脂肪酸醇、脂肪酸酯、多元醇、纤维素衍生物，和乙烯基衍生物中进行选择，所述的被包覆颗粒再用较少量的表面活性剂进行外包衣。
2、权利要求1所述的方法，其中蜡与亲水材料的比率是从约1∶0.1到约0.1∶1。
3、权利要求2所述的方法，其中亲水材料是十八烷醇。
4、权利要求1到3所述的方法，其中表面活性剂是十二烷基硫酸钠。
5、权利要求1到3所述的方法，其中用蜡和十八烷醇的混合物均匀包覆的纯二甲苯氧庚酸的磨细颗粒的第一部分提供了相对即时的释放，以及用蜡与氢化蓖麻油的混合物均匀包覆的纯二甲苯氧庚酸的磨细的颗粒的第二部分提供了相对持续的释放。
CN90100780A 1989-02-02 1990-02-02 一种水分散二甲苯氧庚酸组合物的制备方法 Pending CN1044591A (zh)

Applications Claiming Priority (2)

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US305,081 1981-09-24
US07/305,081 US4971804A (en) 1989-02-02 1989-02-02 Water dispersible gemfibrozil compositions

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CN1044591A true CN1044591A (zh) 1990-08-15

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US (1) US4971804A (zh)
EP (1) EP0381220B1 (zh)
JP (1) JPH02240016A (zh)
CN (1) CN1044591A (zh)
AT (1) ATE89720T1 (zh)
AU (1) AU623731B2 (zh)
CA (1) CA2009136A1 (zh)
DE (1) DE69001682T2 (zh)
DK (1) DK0381220T3 (zh)
ES (1) ES2055178T3 (zh)
FI (1) FI900490A0 (zh)
HU (1) HU204193B (zh)
IE (1) IE900370L (zh)
IL (1) IL92993A (zh)
NO (1) NO900482L (zh)
NZ (1) NZ232323A (zh)
PH (1) PH26014A (zh)
PT (1) PT93027A (zh)
ZA (1) ZA90773B (zh)

Cited By (1)

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CN101081213B (zh) * 2007-06-26 2010-10-06 中山大学 丁二酸(5-雄甾烯-17-酮-3β-羟基)二酯固体分散体及其制备方法与应用

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ES2055178T3 (es) 1994-08-16
CA2009136A1 (en) 1990-08-02
AU4899390A (en) 1990-08-09
EP0381220A3 (en) 1990-12-05
NO900482D0 (no) 1990-02-01
DE69001682T2 (de) 1993-09-16
ZA90773B (en) 1991-10-30
US4971804A (en) 1990-11-20
PH26014A (en) 1992-01-29
IL92993A0 (en) 1990-09-17
EP0381220B1 (en) 1993-05-26
AU623731B2 (en) 1992-05-21
IE900370L (en) 1990-08-02
HUT52951A (en) 1990-09-28
HU900639D0 (en) 1990-04-28
IL92993A (en) 1994-04-12
NZ232323A (en) 1992-04-28
NO900482L (no) 1990-08-03
HU204193B (en) 1991-12-30
FI900490A0 (fi) 1990-01-31
DE69001682D1 (de) 1993-07-01
DK0381220T3 (da) 1993-06-14
EP0381220A2 (en) 1990-08-08
JPH02240016A (ja) 1990-09-25
ATE89720T1 (de) 1993-06-15
PT93027A (pt) 1990-08-31

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