CN1728984A - 以卵磷脂为表面活性剂的可控制剂量的气雾剂 - Google Patents
以卵磷脂为表面活性剂的可控制剂量的气雾剂 Download PDFInfo
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Abstract
一种包含至少一种医学药物、用作推进剂的加压液化异丁烷和用作表面活性剂的卵磷脂的可控制剂量的气雾剂。
Description
技术领域
本发明的主题是一种包含至少一种医学药物以及由作为推进剂的加压液化异丁烷和作为表面活性剂的卵磷脂组成的混合物的可控制剂量的气雾剂。
本发明更具体地涉及包含至少一种具有抗哮喘作用的选自糖皮质激素类的组的医学药物以及由作为推进剂的加压液化异丁烷和卵磷脂组成的混合物的可控制剂量的气雾剂。
背景技术
通过使用液化加压气体或压缩气体作为推进剂而制备和应用的气溶胶式压缩气体包装(aerosol pressurized gas packs)，也被简称为可控制剂量的气雾剂或量化气雾剂，早已为人所知。通常，这种量化气雾剂包含具有用于抽出其内含物的阀门结构的优选为金属或玻璃的压力容器，和通常包含活性物质溶液以及气态或以压力作用下被液化的气体混合物形式的推进剂的要喷出的实际药剂。加压液化的气体或加压液化气体混合物应该可以理想地与活性物质以任意比例混溶从而形成单一液相。另一种选择是，加压液化气体或气体混合物可以与活性物质形成悬浮物，该活性物质可以被轻易地摇散并在其上方形成气相。根据所含的药剂，这些量化的气雾剂被用于化妆品和医药领域，或作为室内喷雾剂、驱虫喷雾剂等。
可控制剂量的气雾剂中的推进剂必须满足特定要求。其一定不能与活性药剂溶液的组分反应。同时，推进剂必须是非刺激性和无毒性的。氟氯化烃类已被证明是特别适合的。然而，由于其臭氧损耗效应，因此需要开发替代的推进剂。然而，这些替代推进剂的品质必须能与氟氯化烃类相当；首先，它们必须既不能对健康有危害还要有生态相容性。开始，部分卤化氟氯化烃被常常认为是替代品，但是其仍然具有不可接受的高臭氧损耗能力。
DE4132176公开了用于异丙肾上腺素衍生物、所谓的β-类交感神经药剂、或非类固醇类抗发炎药剂DNCG的给药的可控制剂量的气雾剂，其中异丁烷被用作推进剂。
DE19911064公开了包含选自糖皮质激素类的组的支气管扩张药(broncholytic agent)和/或抗发炎药剂、以异丁烷作为推进剂并以油酸或以Span85作为表面活性物质的可控制剂量的气雾剂。然而，这些剂量气雾剂具有不令人满意的再悬浮性和活性物质在推进剂中沉降太快的缺点。
发明内容
因而本发明的目的之一是提供一种用于医学药物、尤其是用于选自糖皮质激素类的组的抗哮喘药剂的可控制剂量的气雾剂，该可控制剂量的气雾剂没有DE19911064所公开的控制剂量气雾剂的缺点。
惊讶地发现，辅剂卵磷脂会造成医学药物、尤其是糖皮质激素类药物在异丁烷中再悬浮性的显著提高。
卵磷脂为由脂肪酸、丙三醇、磷酸和胆碱构成的磷酸甘油酯类。天然存在的卵磷脂为1，2-二酰基-sn-丙三醇-3-磷酸的衍生物。从生物材料中提取获得的卵磷脂通常是由于不同的脂肪酸酯而彼此不同的卵磷脂的混合物。
根据本发明，优选的卵磷脂为已经在医药工业中被广泛用作乳化剂的大豆卵磷脂。
通过在加入大豆卵磷脂或各种抗哮喘药的量化气雾剂的制备中常规使用的表面活性剂的情况下，对比药物悬浮液在异丁烷中的沉降行为可以看出，以及从下面的实施例也可看出，使用大豆卵磷脂的药物悬浮液的沉降时间比使用油酸的药物悬浮液的沉降时间长10倍，并比使用Span85的药物悬浮液的沉降时间长5倍。
在进一步的试验中，在药物与大豆卵磷脂的比例为1∶2、1∶1或1∶0.5时，沉降时间方面没有发现不同，所以可以有利地选择使用药物与大豆卵磷脂的比例为1∶0.5。
具体实施方式
实施例
使用各种表面活性剂的药物悬浮液在异丁烷中的悬浮行为的对比。
| 相对沉降 | |
| 糖皮质激素∶油酸(100∶1)糖皮质激素∶Span85(1∶1)糖皮质激素∶大豆卵磷脂(1∶2)糖皮质激素∶大豆卵磷脂(1∶1)糖皮质激素∶大豆卵磷脂(1∶0.5) | 12101010 |
在进一步的试验中，下面的配方被证明是尤其有利的：
配方1： 糖皮质激素 0.1％～0.2％
卵磷脂 0.05％～0.4％
异丁烷 99.85％～99.4％
配方2： 糖皮质激素 0.5％～1.0％
卵磷脂 0.25％～4.0％
异丁烷 99.75％～95.0％
对于糖皮质激素二丙酸倍氯米松(beclomethasone dipropionate)，下面的配方被发现是有用的。
配方3： 倍氯米松 0.1％～2.5％
大豆卵磷脂 0.05％～5.0％
异丁烷 99.85％～92.5％
对于布地缩松(budesonide)，下面的配方被发现是有用的。
配方4： 布地缩松 0.1％～2.5％
大豆卵磷脂 0.05％～5.0％
异丁烷 99.85％～92.5％
所有量均为重量百分比。
本发明的气雾剂可以通过在推进剂和表面活性剂为液态且活性药剂存在于固相中的条件下混和各种组分制得。
药物悬浮液在压力作用下通过阀门填充到密闭的罐体中，该罐体在填充过程开始时为室温。悬浮液的温度约为-10～+10℃。然后，用推进剂填充罐体，从而同时清洗了阀门。
根据本发明的可控制剂量的气雾剂可以用于人和动物的治疗，特别是用于例如哮喘或过敏性鼻炎(干草热)的呼吸道过敏性疾病的治疗，优选通过由口腔或鼻腔吸入。
Claims (10)
1、一种包含至少一种医学药物、作为推进剂的加压液化异丁烷和作为表面活性剂的卵磷脂的可控制剂量的气雾剂。
2、根据权利要求1的可控制剂量的气雾剂，其特征在于，所说的医学药物为糖皮质激素，所说的糖皮质激素优选为选自包含皮质醇、泼尼松、氢化泼尼松、甲泼尼松、去炎松、泼尼立定、氟考龙、帕拉米松、地塞米松、倍他米松、氟尼缩松、氟替卡松、倍氯米松、布地缩松和/或其抗哮喘活性衍生物和/或其混合物的组。
3、根据权利要求1或2的可控制剂量的气雾剂，其特征在于，对应的配方为：
糖皮质激素 0.1％～0.2％
卵磷脂 0.05％～0.4％
异丁烷 99.85％～99.4％
4、根据权利要求1或2的可控制剂量的气雾剂，其特征在于，对应的配方为：
糖皮质激素 0.5％～1.0％
卵磷脂 0.25％～4.0％
异丁烷 99.75％～95.0％
5、根据前面任意一项权利要求的可控制剂量的气雾剂，其特征在于，所述卵磷脂为大豆卵磷脂。
6、根据权利要求1或2的可控制剂量的气雾剂，其特征在于，对应的配方为：
倍氯米松 0.1％～2.5％
大豆卵磷脂 0.05％～5.0％
异丁烷 99.85％～92.5％
7、根据权利要求1或2的可控制剂量的气雾剂，其特征在于，对应的配方为：
布地缩松 0.1％～2.5％
大豆卵磷脂 0.05％～5.0％
异丁烷 99.85％～92.5％
8、根据前面任意一项权利要求的可控制剂量的气雾剂，其特征在于，糖皮质激素与大豆卵磷脂的比例为1∶2，优选为1∶1，并且特别优选为1∶0.5。
9、根据前面任意一项权利要求的可控制剂量的气雾剂，用于治疗人和动物的过敏性疾病、优选地用于呼吸道的过敏性疾病的吸入治疗。
10、根据权利要求1至8的任意一项权利要求的可控制剂量的气雾剂，用于治疗哮喘或过敏性鼻炎。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10260882.2 | 2002-12-24 | ||
| DE10260882A DE10260882B4 (de) | 2002-12-24 | 2002-12-24 | Dosieraerosole mit Sojalecithin als oberflächenaktiver Substanz und dessen Verwendung |
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| CN1728984A true CN1728984A (zh) | 2006-02-01 |
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| US (1) | US20060073103A1 (zh) |
| EP (1) | EP1575559B1 (zh) |
| JP (1) | JP2006517190A (zh) |
| CN (1) | CN1728984A (zh) |
| AT (1) | ATE335467T1 (zh) |
| AU (1) | AU2003300230A1 (zh) |
| DE (2) | DE10260882B4 (zh) |
| DK (1) | DK1575559T3 (zh) |
| ES (1) | ES2270166T3 (zh) |
| IL (1) | IL169356A0 (zh) |
| TW (1) | TW200423969A (zh) |
| WO (1) | WO2004058221A1 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US5292499A (en) * | 1990-09-11 | 1994-03-08 | University Of Wales College Of Cardiff | Method of preparing medical aerosol formulations including drug dissolved in reverse micelles |
| GB9118830D0 (en) * | 1991-09-03 | 1991-10-16 | Minnesota Mining & Mfg | Medical aerosol formulations |
| ATE219355T1 (de) * | 1997-02-05 | 2002-07-15 | Jago Res Ag | Medizinische aerosolformulierungen |
| US6017545A (en) * | 1998-02-10 | 2000-01-25 | Modi; Pankaj | Mixed micellar delivery system and method of preparation |
| ATE283033T1 (de) * | 1998-07-24 | 2004-12-15 | Jago Res Ag | Medizinische aerosolformulierungen |
| US6312665B1 (en) * | 1998-12-21 | 2001-11-06 | Generex Pharmaceuticals Incorporated | Aerosol formulations for buccal and pulmonary application |
| DE19911064A1 (de) * | 1999-03-12 | 2000-09-14 | Ig Spruehtechnik Gmbh | Dosieraerosole mit Isobutan als Treibmittel |
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2002
- 2002-12-24 DE DE10260882A patent/DE10260882B4/de not_active Expired - Fee Related
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2003
- 2003-12-18 TW TW092135946A patent/TW200423969A/zh unknown
- 2003-12-24 CN CNA2003801071841A patent/CN1728984A/zh active Pending
- 2003-12-24 EP EP03799507A patent/EP1575559B1/de not_active Expired - Lifetime
- 2003-12-24 ES ES03799507T patent/ES2270166T3/es not_active Expired - Lifetime
- 2003-12-24 AU AU2003300230A patent/AU2003300230A1/en not_active Abandoned
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Also Published As
| Publication number | Publication date |
|---|---|
| DE10260882B4 (de) | 2007-02-08 |
| DE50304615D1 (de) | 2006-09-21 |
| ATE335467T1 (de) | 2006-09-15 |
| AU2003300230A1 (en) | 2004-07-22 |
| EP1575559A1 (de) | 2005-09-21 |
| US20060073103A1 (en) | 2006-04-06 |
| DE10260882A1 (de) | 2004-09-30 |
| IL169356A0 (en) | 2007-07-04 |
| EP1575559B1 (de) | 2006-08-09 |
| ES2270166T3 (es) | 2007-04-01 |
| JP2006517190A (ja) | 2006-07-20 |
| WO2004058221A1 (de) | 2004-07-15 |
| TW200423969A (en) | 2004-11-16 |
| DK1575559T3 (da) | 2006-11-27 |
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