CN1292715A - 粉末吸入器 - Google Patents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
- A61M15/0033—Details of the piercing or cutting means
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/06—Solids
- A61M2202/064—Powder
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Abstract
本发明涉及单剂量干粉吸入器,其中药物贮存在胶囊中,并通过用涂布有聚合物的钢针将胶囊刺穿来释放药物。本发明还描述了制备涂布有聚合物的刺穿装置的方法,以及所述刺穿装置在将药物从胶囊中释放出来中的应用。
Description
本发明涉及单剂量干粉吸入器，其中药物在释放前是贮存在胶囊中。
在吸入器中用金属针或其它切割装置刺穿胶囊是众所周知的。例如DE 3927170和EP 528764中公开了胶囊切割装置。
粉末药物吸入器描述在US 3991761中(下文中称为吸入器A)。吸入器A包含接受胶囊的凹口，并提供了携带金属尖针的按钮，该按钮是通过偏置弹簧保持在适当的位置。在使用时，胶囊被弹簧负载的金属针刺穿，在松开按钮时，金属针从穿孔胶囊收缩回来，使得药物从胶囊中释出。
已知的胶囊刺穿装置所面临的问题是，切割装置例如金属针会粘附在胶囊壁上。这阻止了吸入药物的完全释放，并在使用者中引起挫折。
本申请人已经寻求解决该问题的方法，并且已经发现，涂在金属针上的聚合物涂层能够使得胶囊刺穿后药物完全释放。
因此，一方面，本发明提供了包含金属胶囊刺穿装置的吸入器，其中所述金属胶囊刺穿装置涂覆有聚合物。
另一方面，本发明提供了吸入器中涂覆有聚合物的金属胶囊刺穿装置在更快、更完全和更有效地释放药物中的应用。
本发明提供了刺穿装置，该刺穿装置具有至少一层惰性聚合物涂层，所述惰性聚合物的特征是，(ⅰ)具有优良的抗粘特性，即高润滑性，例如具有低磨擦系数的聚合物，例如在轻载条件下至少0．1的摩擦系数(定义为：以恒定速度使一个物体在另一物体上运动所需的力除以物体重量所获得的无量纲商数)，和(ⅱ)高的热和化学惰性。优选的聚合物包括任何惰性聚合物，例如包含-CF2-CF2-单元的碳氟聚合物，包括其共聚物，根据聚合物的生产方法，所述聚合物在聚合物链末端具有不同末端基团例如氢、卤素、卤代碳如三氯碳、羧酸、烷基或醇。尤其优选的是还称为TEFLON的聚四氟乙烯(PTFE)。用于涂覆本发明刺穿装置的聚合物的分子量为约2×103-约2×106道尔顿。这些聚合物优选以至多30％，例如5-30％的浓度均匀混合例如均匀分布在例如合金基质中。这些合金可含有铬和／或一种或多种元素周期表Ⅷ族元素例如铁、钴、镍、优选镍，和／或贵金属例如钌、铑、钯。特别优选的是其中优选含有约90-93％重量的镍和约7-10％重量的磷的镍磷合金。
通过在胶囊每一末端的一个或多个针可实现胶囊的共终点刺穿。涂层可覆盖至少针上面接触并刺穿胶囊的一部分，但是优选覆盖针的整个表面。可使用一种以上的合金来把一层以上的涂层涂覆在针上，特别优选具有两个涂层。聚合物涂层的总厚度一般为约1-约30微米，例如第一涂层的厚度可以为约5-约15微米，第二个涂层的厚度可以为约3-10微米。
因此，在本发明的一个实施方案中，刺穿装置可涂覆上PTFE或合金基质，例如铬或镍磷合金，或者含有PTFE颗粒的合金基质，例如含有PTFE的镍磷合金，该合金也称为CHENIFLONTM。
在本发明特别优选的实施方案中，将在吸入装置中使用的钢针例如不锈钢针涂覆上厚度为约5-约15微米的第一层镍磷合金例如NIPLOYTM，并可将含有均匀掺混在镍磷合金基质中的约20-30％体积(volume)PTFE的第二层以3-10微米的厚度涂覆到第一层上。
镀覆沉积物组成优选含有约80-95％、例如85％重量的镍，5-20％、例如6．6％重量的磷，和至多30％、例如8．4％重量的PTFE。复合材料中8．4％重量的PTFE含量可相当于沉积物中约25％体积的量。
可用适于形成均匀涂层的技术将聚合物涂覆在针例如钢针上。常规涂布技术一般包括(ⅰ)将聚合物优选以细分散液形式涂布上去，和(ⅱ)将液态介质蒸发以形成涂覆层。这类技术包括例如(ⅰ)将针浸渍到合金分散液中，并通过聚合物浓度、浸渍和取出的速度、以及涂布次数来控制涂层厚度；(ⅱ)将稀的合金分散液擦拭到或刷到针的表面上，该操作特别适于部分表面涂布；(ⅲ)用常规喷雾装置将分散在挥发性较低的溶剂中的合金进行喷涂，例如空气喷雾。使用稀释合金分散液的无气喷涂，或静电喷涂；(ⅳ)用气雾剂沉积涂层；(ⅴ)通过紫外线光致聚合；(ⅵ)通过RF溅射；或(ⅶ)通过电泳将这种分散液涂覆在针上。
用于形成分散液的合适液体介质包括水溶液，氟里昂，例如二氯二氟甲烷、二氯四氟乙烷等，还包括这些介质的混合物。分散液优选是细分散液，这样在弱搅拌或不搅拌情况下颗粒能保持均匀分布。然而，最优选的聚合物涂层是通过用镀覆方法沉积涂层来形成的，特别优选化学镀镍复合镀覆工艺。
将镍直接还原到表面上的化学镀镍方法一般可在能提供所需能量的还原剂例如次磷酸钠、硼化合物或肼存在下在溶液中进行。最优选的还原反应是通过次磷酸盐来进行的，这可导致少量磷，例如至多10％，如约7％-10％重量的磷共沉积。相应的复合工艺还包括在喷覆溶液中的颗粒，例如聚合物如PTFE。镀覆溶液的化学组成通常含有6g／l镍金属、30g／l次磷酸钠、3-6g／lPTFE粉末、10-30g／l有机酸和皮摩尔浓度的稳定剂。操作条件一般可包括约4．7-5．0的pH和约183-193F的温度。
因此，在特别优选的实施方案中，可通过化学镀镍或复合涂覆进行涂布，例如用来自意大利Argos公司的CheniflonTM进行涂布。
下述非限制性实施例用来举例说明本发明方法。测试1
在20℃，在具有未涂覆钢针的吸入器A中连续使用50个Beclometason 400 Cyclocaps。每一胶囊刺穿后，松开按钮，发现钢针保留在15个胶囊中，或从15个胶囊中不完全抽出。采用具有涂覆有NiployTM和ChenirlonTM的钢针的吸入器A进行重复操作，发现没有针保留在任一胶囊中。测试2
在20℃，在具有未涂覆钢针的吸入器A中连续使用50个Salbutanol 200 Cyclocaps。每一胶囊刺穿后，松开按钮，发现钢针保留在18个胶囊中，或从18个胶囊中不完全抽出。采用具有涂布有NiployTM和CheniflonTM的钢针的吸入器A进行重复操作，发现没有针保留在任一胶囊中。
Claims (9)
1．涂覆有聚合物的金属胶囊刺穿装置在吸入器装置中的应用。
2．权利要求的应用，其中所述聚合物是在合金基质中的聚四氟乙烯。
3．权利要求1或2的应用，其中所述胶囊刺穿装置是尖锐的钢针。
4．包含钢制胶囊刺穿装置的吸入器，其中所述刺穿装置涂覆有聚合物。
5．权利要求4的吸入器，其中所述钢制胶囊刺穿装置涂覆有镍磷合金的第一涂层和含有PTFE颗粒的镍磷合金的第二涂层。
6．权利要求4或5的吸入器，其中所有聚合物涂层的总厚度为5-30微米。
7．化学镀镍复合镀覆工艺在将PTFE／镍合金复合层涂覆到吸入器用胶囊刺穿装置上的应用。
8．基本上如本说明书所述的涂的胶囊刺穿装置。
9．制备吸入器用涂覆有聚合物的刺穿装置的方法，包括将刺穿装置涂覆上第一层镍磷合金涂层和第二层含PTFE颗粒的镍磷合金涂层。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9805102.2A GB9805102D0 (en) | 1998-03-10 | 1998-03-10 | Device |
| GB9805102.2 | 1998-03-10 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1292715A true CN1292715A (zh) | 2001-04-25 |
| CN1212868C CN1212868C (zh) | 2005-08-03 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB998037435A Expired - Lifetime CN1212868C (zh) | 1998-03-10 | 1999-03-08 | 粉末吸入器 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US6488027B1 (zh) |
| EP (1) | EP1061979B1 (zh) |
| JP (2) | JP3094437U (zh) |
| KR (1) | KR100585483B1 (zh) |
| CN (1) | CN1212868C (zh) |
| AT (1) | ATE283083T1 (zh) |
| AU (1) | AU750844B2 (zh) |
| BR (2) | BR9908626A (zh) |
| CA (1) | CA2322575C (zh) |
| CO (1) | CO5080779A1 (zh) |
| DE (2) | DE69922175T2 (zh) |
| ES (1) | ES2232119T3 (zh) |
| GB (1) | GB9805102D0 (zh) |
| HK (1) | HK1035151A1 (zh) |
| IL (1) | IL138121A (zh) |
| NZ (1) | NZ506645A (zh) |
| PL (1) | PL187578B1 (zh) |
| PT (1) | PT1061979E (zh) |
| WO (2) | WO1999045986A1 (zh) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060165606A1 (en) | 1997-09-29 | 2006-07-27 | Nektar Therapeutics | Pulmonary delivery particles comprising water insoluble or crystalline active agents |
| DE19835346A1 (de) * | 1998-08-05 | 2000-02-10 | Boehringer Ingelheim Pharma | Zweiteilige Kapsel zur Aufnahme von pharmazeutischen Zubereitungen für Pulverinhalatoren |
| GB9928311D0 (en) | 1999-11-30 | 2000-01-26 | Novartis Ag | Organic compounds |
| US7871598B1 (en) | 2000-05-10 | 2011-01-18 | Novartis Ag | Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use |
| WO2003041776A1 (en) | 2001-11-14 | 2003-05-22 | Nektar Therapeutics | Aerosolization apparatus comprising connectable body and endpiece |
| TWI324518B (en) | 2001-12-19 | 2010-05-11 | Nektar Therapeutics | Pulmonary delivery of aminoglycosides |
| US20040173211A1 (en) * | 2003-01-14 | 2004-09-09 | Boehringer Ingelheim International Gmbh | Powder inhaler |
| JP4542090B2 (ja) | 2003-04-09 | 2010-09-08 | ネクター セラピューティクス | カプセル穿刺整合ガイドを有するエアロゾル化装置 |
| US20090285900A1 (en) * | 2003-07-31 | 2009-11-19 | Robinson Cynthia B | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a beta-agonist bronchodilator for treatment of asthma or chronic obstructive pulmonary disease |
| US20050026884A1 (en) * | 2003-07-31 | 2005-02-03 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a beta-agonist bronchodilator for treatment of asthma or chronic obstructive pulmonary disease |
| US20050113318A1 (en) * | 2003-07-31 | 2005-05-26 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a beta-agonist bronchodilator for treatment of asthma or chronic obstructive pulmonary disease |
| US7861712B2 (en) * | 2004-04-23 | 2011-01-04 | Manta Product Development | Sealed capsule including an integrated puncturing mechanism |
| DE102005001332A1 (de) * | 2005-01-11 | 2006-07-20 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Zweiteilige Kapsel mit Vorverschluss zur Aufnahme von pharmazeutischen Zubereitungen für Pulverinhalatoren |
| DE102006009637A1 (de) | 2005-10-28 | 2007-05-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Inhalator mit Mundstück mit mikrobiologischer Schutzfunktion |
| DE102005054383B4 (de) | 2005-11-15 | 2013-10-31 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Nadel zum Lochen von Pulverkapseln für die Inhalation |
| US7987845B2 (en) * | 2006-01-31 | 2011-08-02 | Oriel Therapeutics, Inc. | Dry powder inhalers having spiral travel paths, unit dose microcartridges with dry powder, related devices and methods |
| US8360057B2 (en) * | 2006-03-10 | 2013-01-29 | Dose One, Llc | Medication inhaler for dispensing multiple capsules |
| US8464712B2 (en) * | 2006-03-10 | 2013-06-18 | Dose One, Llc | Medication inhaler |
| US7832399B2 (en) * | 2006-03-10 | 2010-11-16 | One Dose, Llc | Medication inhaler |
| DE102006016904A1 (de) | 2006-04-11 | 2007-10-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Inhalator |
| DE102006016901A1 (de) | 2006-04-11 | 2007-10-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Mundstück für einen Inhalator |
| DE102006016903A1 (de) | 2006-04-11 | 2007-10-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Inhalator |
| NL1033047C2 (nl) * | 2006-12-13 | 2008-06-16 | Pharmachemie Bv | Capsule, gevuld met een medicijn, in het bijzonder een inhaleerbaar medicijn. |
| DE102007033860A1 (de) | 2007-07-20 | 2009-01-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Prüfvorrichtung |
| DE102007052871A1 (de) | 2007-11-02 | 2009-05-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Kapsel zur Aufnahme von pharmazeutischen Wirkstoffformulierungen |
| US8668972B2 (en) * | 2008-10-24 | 2014-03-11 | Gvd Corporation | Coating methods and coated syringe |
| DE202008015493U1 (de) | 2008-11-21 | 2009-02-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Faltschachtel |
| US20150010527A1 (en) | 2012-02-01 | 2015-01-08 | Protalix Ltd. | Dnase i polypeptides, polynucleotides encoding same, methods of producing dnase i and uses thereof in therapy |
| US20170304459A1 (en) | 2014-10-10 | 2017-10-26 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for inhalation delivery of conjugated oligonucleotide |
| BR112021021775A2 (pt) | 2019-04-29 | 2022-01-04 | Insmed Inc | Composições de pó seco de pró-fármacos de treprostinil e métodos de uso destas |
| WO2023150747A1 (en) | 2022-02-07 | 2023-08-10 | Insmed Incorporated | Dry powder compositions of bedaquiline and salts and methods of use thereof |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2814296A (en) | 1954-04-15 | 1957-11-26 | S & R J Everett & Co Ltd | Surgical needles |
| NL123398C (zh) | 1959-12-31 | |||
| US3209754A (en) | 1961-08-10 | 1965-10-05 | Ernest C Wood | Surgical clip |
| US3203829A (en) | 1962-09-25 | 1965-08-31 | Eversharp Inc | Razor blades |
| US3379552A (en) | 1963-11-15 | 1968-04-23 | Sutures Inc | Impregnation of stretched multifilament polyester suture with polytetrafluoroethylene |
| US3518110A (en) | 1964-07-23 | 1970-06-30 | Gillette Co | Razor blade and method of making same |
| US3652342A (en) | 1967-06-07 | 1972-03-28 | Gillette Co | Razor blades and processes for the preparation thereof |
| US3949751A (en) * | 1970-03-03 | 1976-04-13 | Fisons Limited | Method and device for dispensing medicament to the body |
| US3700489A (en) | 1970-07-30 | 1972-10-24 | Ethicon Inc | Process for applying a thin coating of polytetrafluoroethylene |
| GB1352241A (en) | 1971-04-13 | 1974-05-08 | Wilkinson Sword Ltd | Razor blades |
| DE2354428C2 (de) | 1972-11-03 | 1985-06-13 | Ethicon, Inc., Somerville, N.J. | Mehrfädiges chirurgisches Nahtmaterial |
| US4012551A (en) | 1974-02-05 | 1977-03-15 | Warner-Lambert Company | Coated razor blade |
| IT1016489B (it) | 1974-03-18 | 1977-05-30 | Isf Spa | Inalatore |
| US3958570A (en) * | 1974-09-03 | 1976-05-25 | Vogelman Joseph H | Syringes and syringe capsules |
| US4275813A (en) | 1979-06-04 | 1981-06-30 | United States Surgical Corporation | Coherent surgical staple array |
| US4307984A (en) * | 1979-11-19 | 1981-12-29 | Patterson James A | Cutting elements |
| US4484988A (en) | 1981-12-09 | 1984-11-27 | Richmond Metal Finishers, Inc. | Process for providing metallic articles and the like with wear-resistant coatings |
| US4621026A (en) * | 1981-12-09 | 1986-11-04 | Richmond Metal Finishers, Inc. | Process for providing metallic articles and the like with wear-resistant coatings, and improved coated metallic articles and the like |
| DK103483A (da) | 1982-04-15 | 1983-10-16 | Ethicon Inc | Siliconebelagt kirurgisk haefteklamme |
| DE3927170A1 (de) | 1989-08-17 | 1991-02-21 | Boehringer Ingelheim Kg | Inhalator |
| US5266359A (en) * | 1991-01-14 | 1993-11-30 | Becton, Dickinson And Company | Lubricative coating composition, article and assembly containing same and method thereof |
| US5197962A (en) * | 1991-06-05 | 1993-03-30 | Megadyne Medical Products, Inc. | Composite electrosurgical medical instrument |
| ATE139130T1 (de) | 1991-08-16 | 1996-06-15 | Sandoz Ag | Inhalator zur verabreichung von pulverförmigen substanzen |
| US5685961A (en) | 1992-03-27 | 1997-11-11 | P & D Medical Coatings, Inc. | Method for fabrication of metallized medical devices |
| US5352378A (en) | 1993-05-27 | 1994-10-04 | Minnesota Mining And Manufacturing Company | Nonflammable lubricious composition |
| JPH11500938A (ja) | 1995-03-02 | 1999-01-26 | サノフィ ファーマシューティカルズ，インコーポレイテッド | カートリッジシールキャップ用の低摩擦被膜 |
| US6026809A (en) * | 1996-01-25 | 2000-02-22 | Microdose Technologies, Inc. | Inhalation device |
| US5743251A (en) * | 1996-05-15 | 1998-04-28 | Philip Morris Incorporated | Aerosol and a method and apparatus for generating an aerosol |
| US5919172A (en) * | 1996-07-17 | 1999-07-06 | Becton, Dickinson And Company | Hypodermic needle having a differential surface finish |
| US6159233A (en) * | 1997-01-07 | 2000-12-12 | Mani, Inc. | Surgical needle device |
| JP3303288B2 (ja) * | 1997-05-12 | 2002-07-15 | ニプロ株式会社 | 穿刺針 |
| DE19722880C1 (de) * | 1997-05-24 | 1998-11-19 | Ethicon Gmbh | Verfahren zum Beschichten von chirurgischen Nadeln |
| US6298256B1 (en) * | 1999-09-10 | 2001-10-02 | Frank-Egbert Meyer | Device and method for the location and catheterization of the surroundings of a nerve |
-
1998
- 1998-03-10 GB GBGB9805102.2A patent/GB9805102D0/en not_active Ceased
-
1999
- 1999-03-05 CO CO99013725A patent/CO5080779A1/es unknown
- 1999-03-08 PT PT99911753T patent/PT1061979E/pt unknown
- 1999-03-08 WO PCT/EP1999/001486 patent/WO1999045986A1/en active Search and Examination
- 1999-03-08 PL PL99342825A patent/PL187578B1/pl unknown
- 1999-03-08 DE DE69922175T patent/DE69922175T2/de not_active Expired - Lifetime
- 1999-03-08 BR BR9908626-3A patent/BR9908626A/pt unknown
- 1999-03-08 DE DE29923581U patent/DE29923581U1/de not_active Expired - Lifetime
- 1999-03-08 IL IL13812199A patent/IL138121A/xx not_active IP Right Cessation
- 1999-03-08 CN CNB998037435A patent/CN1212868C/zh not_active Expired - Lifetime
- 1999-03-08 JP JP2000600054U patent/JP3094437U/ja not_active Expired - Lifetime
- 1999-03-08 WO PCT/EP1999/001487 patent/WO1999045987A1/en active IP Right Grant
- 1999-03-08 BR BR9908587-9A patent/BR9908587A/pt not_active IP Right Cessation
- 1999-03-08 NZ NZ506645A patent/NZ506645A/en not_active IP Right Cessation
- 1999-03-08 AT AT99911753T patent/ATE283083T1/de active
- 1999-03-08 EP EP99911753A patent/EP1061979B1/en not_active Expired - Lifetime
- 1999-03-08 AU AU30323/99A patent/AU750844B2/en not_active Expired
- 1999-03-08 ES ES99911753T patent/ES2232119T3/es not_active Expired - Lifetime
- 1999-03-08 JP JP2000535398A patent/JP4082864B2/ja not_active Expired - Lifetime
- 1999-03-08 CA CA002322575A patent/CA2322575C/en not_active Expired - Lifetime
- 1999-03-08 KR KR1020007009055A patent/KR100585483B1/ko not_active IP Right Cessation
-
2000
- 2000-09-08 US US09/657,967 patent/US6488027B1/en not_active Expired - Lifetime
-
2001
- 2001-06-20 HK HK01104311A patent/HK1035151A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HK1035151A1 (en) | 2001-11-16 |
| DE69922175T2 (de) | 2005-11-03 |
| IL138121A0 (en) | 2001-10-31 |
| GB9805102D0 (en) | 1998-05-06 |
| PL187578B1 (pl) | 2004-08-31 |
| CN1212868C (zh) | 2005-08-03 |
| KR20010041023A (ko) | 2001-05-15 |
| KR100585483B1 (ko) | 2006-06-02 |
| DE29923581U1 (de) | 2001-02-08 |
| AU3032399A (en) | 1999-09-27 |
| EP1061979B1 (en) | 2004-11-24 |
| JP3094437U (ja) | 2003-06-20 |
| BR9908587A (pt) | 2000-11-14 |
| AU750844B2 (en) | 2002-08-01 |
| CA2322575A1 (en) | 1999-09-16 |
| ATE283083T1 (de) | 2004-12-15 |
| EP1061979A1 (en) | 2000-12-27 |
| CO5080779A1 (es) | 2001-09-25 |
| IL138121A (en) | 2005-06-19 |
| CA2322575C (en) | 2008-02-05 |
| PT1061979E (pt) | 2005-02-28 |
| NZ506645A (en) | 2002-06-28 |
| WO1999045987A1 (en) | 1999-09-16 |
| BR9908626A (pt) | 2000-11-14 |
| DE69922175D1 (de) | 2004-12-30 |
| ES2232119T3 (es) | 2005-05-16 |
| PL342825A1 (en) | 2001-07-02 |
| JP4082864B2 (ja) | 2008-04-30 |
| WO1999045986A1 (en) | 1999-09-16 |
| JP2002505922A (ja) | 2002-02-26 |
| US6488027B1 (en) | 2002-12-03 |
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