CN1165297C - 透皮给药组合物 - Google Patents
透皮给药组合物 Download PDFInfo
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- CN1165297C CN1165297C CNB961984651A CN96198465A CN1165297C CN 1165297 C CN1165297 C CN 1165297C CN B961984651 A CNB961984651 A CN B961984651A CN 96198465 A CN96198465 A CN 96198465A CN 1165297 C CN1165297 C CN 1165297C
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Classifications
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/01—Aerosol hair preparation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/02—Resin hair settings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
一种通过从喷雾罐中喷出的可在皮肤上形成一透皮给药活性成分的膜的组合物,其中包括:a)一种亲脂性活性成分b)0.5-25%(重量),优选5-25%(重量)的硅氧烷基粘性聚合物成分c)0-25%(重量)的吸收促进剂d)25-95%(重量)的包括挥发性硅氧烷的挥发性溶剂,和e)0.5-50%(重量)的压缩喷射推进剂气体。
Description
本发明涉及一种新的透皮给药活性成分的组合物。
应用于局部皮肤、被用作一种或多种活性成分的赋形剂或载体、释放并透过皮肤屏障后通常产生全身作用的透皮给药系统发展于八十年代。
通常被称为“透皮贴剂”的这些系统与普通皮肤科剂型,如油膏剂、药膏、凝胶、溶液和洗剂相比具有以下几种优点:
-直接和持续进入体循环,
-抑制肝脏首过效应和/或在消化道中的降解,由此降低副作用,
-延长作用时间,
-维持血浆中活性成分的恒定水平,
-透过降低给药频率,提高对处方说明的顺应性,
-降低个体差异,
-透过储库的膜或基质系统控制给药剂量,
-在整个应用过程中获得恒定浓度的活性成分。
尽管这些系统提供了一定程度的革新,但目前这些形式的药物仍只有极少数的几种。这是由于这些系统要求:
·高度复杂的制造技术,
·仅有属于处垄断地位的几家大公司的少数生产点,
·这导致较高的制造成本及较高的成本价和零售价。总之,这些系统被作为昂贵产品。
本发明提供透皮给药活性成分的新组合物,
-其用法简便,不需庞大、复杂和昂贵的工业设备,
-无论在制剂还是在使用期间的作用方式上它们都具有多重目的,
-降低产品成本,具有经济优势。
为此,本发明的主题是一种通过从喷雾罐中喷出的可在皮肤上形成一透皮给药活性成分的膜的组合物,该组合物包括:
a)一种亲脂性活性成分
b)0.5-25%(重量),优选5-25%(重量)的硅氧烷基粘性聚合物成分
c)0-25%(重量)的吸收促进剂
d)25-95%(重量)的包括挥发性硅氧烷的挥发性溶剂,和
e)0.5-50%(重量)的压缩喷射推进气体。
本发明的主题还是:
-一种组合物通过从喷雾罐中喷出在患者皮肤上形成一透皮给药活性成分的膜的用途,该组合物包括:
a)一种亲脂性活性成分
b)0.5-25%(重量),优选5-25%(重量)的硅氧烷基粘性聚合物成分
c)0-25%(重量)的吸收促进剂
d)25-95%(重量)的包括挥发性硅氧烷的挥发性溶剂,和
e)0.5-50%(重量)的压缩喷射推进气体。
-一种向患者透皮给药活性成分的方法,该方法包括通过从喷雾罐中向患者皮肤喷雾一种组合物,在该患者皮肤上形成一层膜,所述组合物包括:
a)一种亲脂性活性成分
b)0.5-25%(重量),优选5-25%(重量)的硅氧烷基粘性聚合物成分
c)0-25%(重量)的吸收促进剂
d)25-95%(重量)的包括挥发性硅氧烷的挥发性溶剂,和
e)0.5-50%(重量)的压缩喷射推进气体。
本发明中,术语活性成分主要指药品或有治疗作用的物质。
这些药品尤其是亲脂性维生素如维生素D和E及其衍生物、激素如降钙素、甾族化合物如雌二醇及其酯和强的松、尼古丁、类皮质激素、视黄酸衍生物、抗真菌剂如酮康唑、麻醉剂、镇痛剂如利多卡因或皮肤用抗癌药。
不言而喻,本发明组合物中活性成分的百分比取决于活性成分的性质。通常,该百分比为0.01-10%(重量)。
依据本发明,硅氧烷基聚合物成分应理解为是指包含硅氧烷基聚合物和硅氧烷基共聚物的成分。
这些硅氧烷,将按CTFA(Cosmetic,Toiletry and FragranceAssociation)字典中命名,它们尤其包括聚二甲基硅氧烷油或用离子或非离子有机基团改性的聚二甲基硅氧烷油。
作为聚二甲基硅氧烷油的实例可例举下式的二甲聚硅氧烷:
其中n是小于5000的整数,
和二甲聚硅氧烷醇,它们是带有末端羟基的二甲基硅氧烷。
作为改性聚二甲基硅氧烷的实例可例举二甲聚硅氧烷共聚聚醇,它们是含有聚氧乙烯和/或聚氧丙烯侧链的二甲基硅氧烷聚合物。
硅氧烷基的粘性聚合物成分优选占该组合物重量的5-25%。
吸收促进剂尤其可选自丙二醇、己二醇、二壬酸丙二醇酯、甘油单乙基醚、二甘醇、甘油单酸酯、乙氧化甘油一油酸酯(含8-10个环氧乙烷单位)、azone(1-十二烷基氮杂环庚-2-酮)、2-(正壬基)-1,3-二氧戊环、肉豆蔻酸异丙酯、肉豆蔻酸辛酯、肉豆蔻酸十二烷基酯、肉豆蔻醇、月桂醇、月桂酸、乳酸月桂基酯、萜品油、1-薄荷醇、D-苎烯、β-环糊精及其衍生物或表面活性剂如聚山梨酯(Polysorbate)、山梨醇酯、蔗糖酯、脂肪酸和胆汁烷酸盐,或者亲脂性和/或亲水性和/或两性产品如聚甘油、N-甲基吡咯烷酮、聚糖基甘油酯和乳酸鲸蜡基酯。
吸收促进剂优选占组合物重量的5-25%。
挥发性硅氧烷或聚硅氧烷,尤其是聚二甲基环硅氧烷,即下式的化合物:
其中n平均为3-6,尤其是其中n=4或5的化合物以及线性聚硅氧烷如六甲基二硅氧烷或低分子量的二甲聚硅氧烷主要用作挥发性溶剂。
挥发性硅氧烷优选占组合物重量的50-85%。
此外,也可使用不超过25%,优选不超过20%不包括水在内的其他挥发性溶剂如乙醇、异丙醇、氯仿、庚烷或乙酸乙酯。在实际中应注意到水与使用的聚硅氧烷不相溶,故应避免使用。
喷射推进剂气体可以是任何用于喷雾存在于喷雾罐中的液体组合物的喷射推进剂气体。它尤其可以是HFC类喷射推进剂气体,如HFC134A(CH2F-CF3),该类喷射推进剂已发展用于代替CFC类,或者可以使用相对惰性的喷射推进剂气体如氮气和二氧化碳。
优选使用安装有计量阀门的、可定量喷雾压缩组合物的罐。这可将定量的活性成分释放于皮肤之上。
也可使用其喷嘴安装有锥形体的阀门,这可局限喷雾分散。这样在确定的皮肤表面就形成了可以受控方式释放定量活性成分的膜。
下面给出本发明组合物的实施例
实施例1:含视黄酸的组合物
将50毫克视黄酸溶于20克异丙醇中。加入与60克挥发性聚二甲基环硅氧烷预混的1克硅氧烷溶液(组成为13%二甲聚硅氧烷醇的挥发性聚二甲基环硅氧烷溶液)。
将获得的溶液以每罐10毫升的比例加到铝质喷雾罐中,用计量阀加以密封。
最后,加压下(约5-7×105帕)将喷射推进剂(CH2F-CH3)充填到罐中。
获得每罐中含有下述成分(重量%)的组合物:
视黄酸 0.05%
异丙醇 20%
挥发性硅氧烷(聚二甲基环硅氧烷) 60%
13%二甲聚硅氧烷的聚二甲基环硅氧烷溶液 1%
CH2-CF3 18.95%
通过加压计量阀门,将100微升该组合物以细小液滴形式喷雾到皮肤上,该液滴滞留在皮肤上形成含视黄酸的硅氧烷基质膜。
100微升剂量形成含50微克视黄酸的膜。
该膜逐渐释放视黄酸透过皮肤。
该组合物可用于治疗座疮。
实施例2:倍他米松组合物
按照实施例1的方法,制备含有下述成分的组合物:
二丙酸倍他米松(以倍他米松计) 0.05%
丙二醇 10%
挥发性硅氧烷(聚二甲基环硅氧烷) 60%
13%二甲聚硅氧烷醇的聚二甲基环硅氧烷溶液 2%
CH2F-CF3 27.95%
100微升剂量形成含50微克倍他米松的膜。
实施例3:利多卡因组合物
按照实施例1的方法,制备含有下述成分的组合物:
利多卡因 5%
硬脂酸乙二醇酯 10%
乙醇 10%
挥发性硅氧烷(聚二甲基环硅氧烷) 50%
13%二甲聚硅氧烷醇的聚二甲基环硅氧烷溶液 2%
CH2F-CF3 23%
100微升剂量形成含5毫克利多卡因的膜。
实施例4:酮康唑组合物
按照实施例1的方法,制备含有下述成分的组合物:
酮康唑 2%
丙二醇 10%
Polysorbate60 1%
挥发性硅氧烷(聚二甲基环硅氧烷) 60%
13%二甲聚硅氧烷醇的聚二甲基环硅氧烷溶液 1%
CH2F-CF3 26%
100微升剂量形成含2毫克酮康唑的膜。
Claims (7)
1.通过从喷雾罐中喷出的可在皮肤上形成透皮给药活性成分的膜的组合物,其中包括:
a)一种亲脂性活性成分
b)0.5-25%重量粘性聚硅氧烷
c)0-25%重量吸收促进剂
d)25-95%重量包括挥发性硅氧烷的挥发性溶剂和基于组合物总重多达25%重量除水以外的另一种挥发性溶剂,和
e)0.5-50%重量压缩喷射推进气体。
2.权利要求1的组合物,其中包括5-25%重量粘性聚硅氧烷。
3.权利要求1的组合物,其中所述挥发性硅氧烷是聚二甲基环硅氧烷。
4.权利要求1或3的组合物,其中包括50-85%重量挥发性硅氧烷。
5.权利要求1的组合物,其中包括0-20%重量所述另一种挥发性溶剂。
6.权利要求1的组合物,其中它存在于设有剂量阀门的喷雾罐中。
7.权利要求1~6中任一项的组合物在制备在患者皮肤上用于透皮给药活性成分的膜方面的用途。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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FR95/12393 | 1995-10-20 | ||
FR9512393A FR2740038B1 (fr) | 1995-10-20 | 1995-10-20 | Composition pour l'administration transdermique |
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CN1202819A CN1202819A (zh) | 1998-12-23 |
CN1165297C true CN1165297C (zh) | 2004-09-08 |
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US (1) | US6325990B1 (zh) |
EP (1) | EP0855907B1 (zh) |
JP (1) | JP2000500436A (zh) |
KR (1) | KR100447034B1 (zh) |
CN (1) | CN1165297C (zh) |
AT (1) | ATE220899T1 (zh) |
AU (1) | AU713474B2 (zh) |
DE (1) | DE69622574T2 (zh) |
DK (1) | DK0855907T3 (zh) |
ES (1) | ES2179213T3 (zh) |
FR (1) | FR2740038B1 (zh) |
HU (1) | HU225105B1 (zh) |
NZ (1) | NZ320337A (zh) |
PT (1) | PT855907E (zh) |
WO (1) | WO1997015295A1 (zh) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5968919A (en) * | 1997-10-16 | 1999-10-19 | Macrochem Corporation | Hormone replacement therapy drug formulations for topical application to the skin |
PL346238A1 (en) | 1998-08-20 | 2002-01-28 | 3M Innovative Properties Co | Spray on bandage and drug delivery system |
US8263580B2 (en) * | 1998-09-11 | 2012-09-11 | Stiefel Research Australia Pty Ltd | Vitamin formulation |
NZ515953A (en) | 1999-07-02 | 2003-06-30 | Lts Lohmann Therapie System Ag | Microreservoir system on the basis of polysiloxanes and ambiphilic solvents |
US6337076B1 (en) * | 1999-11-17 | 2002-01-08 | Sg Licensing Corporation | Method and composition for the treatment of scars |
US6512072B1 (en) | 2000-06-12 | 2003-01-28 | Dow Corning Corporation | Fast cure film forming formulation |
US20040057907A1 (en) * | 2002-09-23 | 2004-03-25 | Leonard Mackles | Dri-nasal sprays |
FR2856301B1 (fr) * | 2003-06-23 | 2007-08-03 | Galderma Res & Dev | Composition sous forme de spray comprenant un actif pharmaceutique, au moins un silicone volatile et une phase non polaire non volatile |
RU2006121973A (ru) * | 2003-11-21 | 2007-12-27 | Галдерма Ресерч Энд Девелопмент, С.Н.С. (Fr) | Распыляемая композиция для введения производных витамина d |
FR2862540B1 (fr) * | 2003-11-21 | 2007-03-30 | Galderma Res & Dev | Composition sous forme de spray comprenant un actif pharmaceutique, au moins un silicone volatile et une phase non polaire non volatile |
FR2867682B1 (fr) * | 2004-03-22 | 2009-06-05 | Galderma Res & Dev | Composition pharmaceutique anhydre associant un agent silicone et un principe actif solubilise. |
DE602005003138T3 (de) * | 2004-06-17 | 2011-07-14 | Galderma S.A. | Zusammensetzung in sprayform mit einer kombination aus clobetasolpropionat und calcitriol, einer alkoholphase und ölphase |
FR2871697B1 (fr) * | 2004-06-17 | 2007-06-29 | Galderma Sa | Composition sous forme de spray comprenant une association d'actifs pharmaceutiques, une phase alcoolique, au moins un silicone volatile et une phase huileuse non volatile |
FR2871696B1 (fr) * | 2004-06-17 | 2006-11-10 | Galderma Sa | Composition topique pour le traitement du psoriasis |
FR2871700B1 (fr) * | 2004-06-17 | 2006-11-17 | Galderma Sa | Composition sous forme de spray comprenant une association d'actifs pharmaceutiques, une phase alcoolique, et une phase huileuse |
FR2871698B1 (fr) * | 2004-06-17 | 2008-07-04 | Galderma Sa | Composition sous forme de spray comprenant une association d'actifs pharmaceutiques et une phase huileuse |
MXPA06014397A (es) * | 2004-06-17 | 2007-02-15 | Galderma Sa | Composicion en forma de aerosol que comprende una combinacion de un corticoide y un derivado de la vitamina d en una fase aceitosa. |
JP4723899B2 (ja) * | 2005-04-26 | 2011-07-13 | 日光ケミカルズ株式会社 | 皮膚外用組成物 |
CA2611147C (en) | 2005-06-01 | 2013-04-09 | Stiefel Research Australia Pty Ltd. | Topical emulsion formulation |
FR2887150B1 (fr) * | 2005-06-17 | 2007-08-03 | Galderma Res & Dev | Composition pharmaceutique comprenant un elastomere organopolysiloxane et un principe actif solubilise |
EP1928415A2 (en) * | 2005-08-13 | 2008-06-11 | Collegium Pharmaceutical, Inc. | Topical delivery with a carrier fluid |
GB0518769D0 (en) * | 2005-09-14 | 2005-10-19 | Medpharm Ltd | Topical formulations |
CN101478973B (zh) | 2006-05-23 | 2013-08-28 | 陶氏康宁公司 | 用于递送活性成分的新型硅氧烷成膜剂 |
EP2124907B1 (en) | 2007-03-19 | 2018-05-30 | Vita Sciences, Llc | Transdermal patch and method for delivery of vitamin b12 |
WO2008128280A1 (en) * | 2007-04-20 | 2008-10-30 | Acrux Dds Pty Ltd | Method and system for transdermal administration of volatile active |
GB0919650D0 (en) * | 2009-11-10 | 2009-12-23 | Futura Medical Developments Ltd | Pharmaceutical composition |
WO2011061155A1 (en) | 2009-11-17 | 2011-05-26 | Bayer Consumer Care Ag | Antifungal formulations and their use |
WO2012150891A1 (en) * | 2011-05-02 | 2012-11-08 | Lipidor Ab | Composition for administration of a pharmacologically or cosmetically active agent onto a surface of a living organism |
KR101858835B1 (ko) * | 2016-10-17 | 2018-05-17 | 이제후 | 에어로졸 제형의 스프레이 밴드용 조성물 및 그 제조방법 |
BR112023020576A2 (pt) * | 2021-04-15 | 2023-12-05 | Philip Morris Products Sa | Substrato para distribuição de uma substância biologicamente ativa |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3836647A (en) * | 1970-10-22 | 1974-09-17 | Dow Corning | Wash-resistant skin preparation |
DE3682953D1 (de) * | 1985-06-06 | 1992-01-30 | Procter & Gamble | Frisierschaum und verfahren. |
US4902499A (en) * | 1986-04-04 | 1990-02-20 | The Procter & Gamble Company | Hair care compositions containing a rigid silicone polymer |
JP2627750B2 (ja) * | 1987-09-17 | 1997-07-09 | 株式会社資生堂 | エアゾール化粧料 |
JPH01230514A (ja) * | 1987-11-25 | 1989-09-14 | Osaka Aerosol Ind Corp | エアゾール型外用貼付剤 |
US5658557A (en) * | 1989-08-07 | 1997-08-19 | The Procter & Gamble Company | Hair care compositions comprising silicone-containing copolymers |
FR2666962B1 (fr) * | 1990-09-26 | 1996-06-14 | Oreal | Composition antifongique sous forme de spray sec. |
FR2719220A1 (fr) * | 1994-04-29 | 1995-11-03 | Lafon Labor | Nouvelle forme galénique pour l'administration transdermique. |
JPH09512562A (ja) * | 1994-05-05 | 1997-12-16 | メルク フロスト カナダ インコーポレーテツド | 局所性ポリマー薬物供給システム |
-
1995
- 1995-10-20 FR FR9512393A patent/FR2740038B1/fr not_active Expired - Fee Related
-
1996
- 1996-10-17 CN CNB961984651A patent/CN1165297C/zh not_active Expired - Fee Related
- 1996-10-17 HU HU9802983A patent/HU225105B1/hu not_active IP Right Cessation
- 1996-10-17 ES ES96934932T patent/ES2179213T3/es not_active Expired - Lifetime
- 1996-10-17 DK DK96934932T patent/DK0855907T3/da active
- 1996-10-17 AT AT96934932T patent/ATE220899T1/de not_active IP Right Cessation
- 1996-10-17 AU AU73063/96A patent/AU713474B2/en not_active Ceased
- 1996-10-17 JP JP9516345A patent/JP2000500436A/ja active Pending
- 1996-10-17 US US09/051,719 patent/US6325990B1/en not_active Expired - Fee Related
- 1996-10-17 KR KR10-1998-0702839A patent/KR100447034B1/ko not_active IP Right Cessation
- 1996-10-17 DE DE69622574T patent/DE69622574T2/de not_active Expired - Fee Related
- 1996-10-17 NZ NZ320337A patent/NZ320337A/xx unknown
- 1996-10-17 EP EP96934932A patent/EP0855907B1/fr not_active Expired - Lifetime
- 1996-10-17 WO PCT/FR1996/001628 patent/WO1997015295A1/fr active IP Right Grant
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Also Published As
Publication number | Publication date |
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CN1202819A (zh) | 1998-12-23 |
KR100447034B1 (ko) | 2004-12-23 |
KR19990064336A (ko) | 1999-07-26 |
AU7306396A (en) | 1997-05-15 |
FR2740038A1 (fr) | 1997-04-25 |
DE69622574T2 (de) | 2002-12-19 |
AU713474B2 (en) | 1999-12-02 |
EP0855907B1 (fr) | 2002-07-24 |
DK0855907T3 (da) | 2002-11-11 |
HU225105B1 (en) | 2006-06-28 |
JP2000500436A (ja) | 2000-01-18 |
DE69622574D1 (de) | 2002-08-29 |
EP0855907A1 (fr) | 1998-08-05 |
ES2179213T3 (es) | 2003-01-16 |
PT855907E (pt) | 2002-11-29 |
NZ320337A (en) | 1998-12-23 |
HUP9802983A2 (hu) | 1999-06-28 |
ATE220899T1 (de) | 2002-08-15 |
HUP9802983A3 (en) | 2000-06-28 |
FR2740038B1 (fr) | 1998-01-02 |
US6325990B1 (en) | 2001-12-04 |
WO1997015295A1 (fr) | 1997-05-01 |
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