ES2618457T3 - Liposoma transpulmonar para controlar la llegada del fármaco - Google Patents
Liposoma transpulmonar para controlar la llegada del fármaco Download PDFInfo
- Publication number
- ES2618457T3 ES2618457T3 ES08739274.2T ES08739274T ES2618457T3 ES 2618457 T3 ES2618457 T3 ES 2618457T3 ES 08739274 T ES08739274 T ES 08739274T ES 2618457 T3 ES2618457 T3 ES 2618457T3
- Authority
- ES
- Spain
- Prior art keywords
- liposome
- drug
- arrival
- control
- transpulmonary
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- 239000002502 liposome Substances 0.000 title abstract description 15
- 239000003814 drug Substances 0.000 title description 2
- 229940079593 drug Drugs 0.000 title description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 abstract description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 230000002685 pulmonary effect Effects 0.000 abstract 1
- 229940126585 therapeutic drug Drugs 0.000 abstract 1
- 229920000642 polymer Polymers 0.000 description 8
- 210000004072 lung Anatomy 0.000 description 7
- 229920001661 Chitosan Polymers 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 241000700159 Rattus Species 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1277—Preparation processes; Proliposomes
-
- 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
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2810/00—Vectors comprising a targeting moiety
- C12N2810/10—Vectors comprising a non-peptidic targeting moiety
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- Biotechnology (AREA)
- Pulmonology (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Otolaryngology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Un liposoma para su uso en fármaco terapéutico o administración génica por administración pulmonar, en el que la superficie del liposoma está modificada con un poli(alcohol vinílico) hidrofobizado terminal.
Description
Ejemplo 2 (Ejemplo de referencia)
Preparación de liposoma modificado con quitosano
Se preparó un liposoma modificado con quitosano de la misma manera que en el Ejemplo 1, excepto que se usó quitosano (peso molecular: 150.000, grado de desacetilación: 85 %) en lugar del poli(alcohol vinílico) hidrofobizado
5 terminal. Sin embargo, el diámetro de partícula aumentó mezclando una cantidad igual de una suspensión de liposomas y tampón que contenía quitosano disuelto en el mismo, y por lo tanto se realizó un tratamiento ultrasónico después de mezcla.
Ejemplo de prueba 1
Evaluación del comportamiento intrapulmonar en ratas
10 El liposoma modificado con polímero del Ejemplo 1 o 2 (Ejemplo de referencia) se administró por vía transbronquial ((15,63 µg de CA/rata) a ratas Wistar macho (7 semanas de edad). Cinco horas después de la administración, se calculó la relación residual de dosificación (% de dosis) midiendo la concentración de CA en tejido pulmonar, fluido de lavado broncoalveolar (BALF) y células de lavado broncoalveolar (BALC) usando un espectrofluorómetro (HITACHI F3010). Para comparación, se realizó una prueba de la misma manera a la anteriormente descrita,
15 excepto que se usó un liposoma que no está modificado con un polímero (la composición de membrana y el contenido de CA son los mismos que en el Ejemplo 1) en lugar del liposoma modificado con polímero (Ejemplo comparativo 1). Los resultados se muestran en la Fig. 1.
Como es evidente a partir de los resultados mostrados en la Fig.1, en el liposoma modificado con polímero del Ejemplo 1, se detectó una fluorescencia más fuerte derivada de CA en BALF en comparación con el Ejemplo
20 comparativo 1. Así, se confirmó que el liposoma modificado con polímero del Ejemplo 1 es útil para ejercer una acción farmacológica en la superficie o las células de superficie de tejido pulmonar, ya que son capaces de retenerse en la superficie de tejido pulmonar durante un largo periodo de tiempo.
En el liposoma modificado con polímero del Ejemplo 2 (Ejemplo de referencia), se mostró que se transfirió más liposoma en el tejido pulmonar debido a que se observó una fluorescencia más fuerte derivada de CA en el liposoma
25 modificado con polímero del Ejemplo 2 (Ejemplo de referencia) en comparación con el Ejemplo comparativo 1. Por lo tanto, se reveló que el liposoma modificado con polímero del Ejemplo 2 (Ejemplo de referencia) puede ser transferido de manera eficiente en tejidos pulmonares en un corto tiempo, y así es posible administrar de manera eficiente en tejido pulmonar fármacos que, por ejemplo, no son fácilmente transferidos en el tejido pulmonar.
8
Claims (1)
-
imagen1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007090874 | 2007-03-30 | ||
| JP2007090874 | 2007-03-30 | ||
| PCT/JP2008/056156 WO2008120736A1 (ja) | 2007-03-30 | 2008-03-28 | 薬物送達制御用経肺投与リポソーム |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2618457T3 true ES2618457T3 (es) | 2017-06-21 |
Family
ID=39808316
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08739274.2T Active ES2618457T3 (es) | 2007-03-30 | 2008-03-28 | Liposoma transpulmonar para controlar la llegada del fármaco |
| ES13178179.1T Active ES2643938T3 (es) | 2007-03-30 | 2008-03-28 | Liposoma transpulmonar para controlar la llegada del fármaco |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13178179.1T Active ES2643938T3 (es) | 2007-03-30 | 2008-03-28 | Liposoma transpulmonar para controlar la llegada del fármaco |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US8658204B2 (es) |
| EP (2) | EP2656858B1 (es) |
| JP (2) | JP5191478B2 (es) |
| KR (2) | KR101476167B1 (es) |
| CN (2) | CN103356482A (es) |
| AR (1) | AR065865A1 (es) |
| AU (2) | AU2008233656B2 (es) |
| BR (1) | BRPI0809852A2 (es) |
| CA (2) | CA2885621C (es) |
| CO (1) | CO6260108A2 (es) |
| ES (2) | ES2618457T3 (es) |
| IL (1) | IL201172A0 (es) |
| MX (1) | MX2009010479A (es) |
| NZ (1) | NZ579881A (es) |
| PH (1) | PH12014502430A1 (es) |
| RU (1) | RU2493874C2 (es) |
| TW (1) | TW200902085A (es) |
| UA (1) | UA100375C2 (es) |
| WO (1) | WO2008120736A1 (es) |
| ZA (1) | ZA200906742B (es) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2748520C (en) * | 2008-12-26 | 2013-12-17 | Se-Ho Kim | Pharmaceutical composition containing an anionic drug, and a production method therefor |
| JP2011246464A (ja) * | 2010-04-28 | 2011-12-08 | Wakamoto Pharmaceutical Co Ltd | ジクロフェナクナトリウムを封入した後眼部到達用ポリマーコーティングリポソーム |
| KR101601035B1 (ko) | 2013-02-28 | 2016-03-08 | 주식회사 종근당 | 키토산 및 액상결정 형성 물질을 포함하는 유전자 전달용 조성물 |
| CN105579582A (zh) | 2013-07-25 | 2016-05-11 | 埃克西奎雷股份有限公司 | 用于预防和治疗用途的作为免疫刺激剂的基于球形核酸的构建体 |
| AU2015269412B2 (en) | 2014-06-04 | 2020-03-12 | Exicure Operating Company | Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications |
| CA2963931A1 (en) | 2014-10-06 | 2016-04-14 | Exicure, Inc. | Anti-tnf compounds |
| CN104922068B (zh) * | 2015-05-22 | 2017-10-13 | 江苏凯基生物技术股份有限公司 | 一种Decoy核酸阳离子脂质体载体及其制备方法 |
| SI3350222T1 (sl) | 2015-09-18 | 2022-01-31 | Technische Universitaet Muenchen | Ligandi za integrin avbeta6, sinteza in uporaba le-teh |
| US9732303B2 (en) | 2016-01-06 | 2017-08-15 | The Procter & Gamble Company | Microcapsules formed from phosphate esters and compositions containing same |
| US9730867B2 (en) | 2016-01-06 | 2017-08-15 | The Procter & Gamble Company | Methods of forming a slurry with microcapsules formed from phosphate esters |
| US10154947B2 (en) | 2016-01-06 | 2018-12-18 | The Procter & Gamble Company | Antiperspirant composition |
| US20200297867A1 (en) * | 2016-02-01 | 2020-09-24 | Exicure, Inc. | Surface functionalization of liposomes and liposomal spherical nucleic acids (snas) |
| EP3452598A4 (en) | 2016-05-06 | 2020-04-29 | Exicure, Inc. | LIPOSOMAL SPHERICAL NUCLEIC ACID (ANS) CONSTRUCTS HAVING ANTISENSE OLIGONUCLEOTIDES (ASO) FOR THE SPECIFIC INACTIVATION OF INTERLEUKIN 17 RECEPTOR RNA |
| TWI754659B (zh) * | 2016-08-08 | 2022-02-11 | 台灣微脂體股份有限公司 | 用於製備含有弱酸性劑之微脂體組合物的傳輸載體、方法及套組 |
| US11332498B2 (en) | 2017-03-17 | 2022-05-17 | Technische Universitat Munchen | Ligands for integrin αVβ8, synthesis and uses thereof |
| US11696954B2 (en) | 2017-04-28 | 2023-07-11 | Exicure Operating Company | Synthesis of spherical nucleic acids using lipophilic moieties |
| TWI734987B (zh) * | 2019-05-23 | 2021-08-01 | 國立陽明交通大學 | 單醣標記之奈米脂質體藥物遞送系統，其製法及其作為藥物靶定遞送載體之應用 |
| WO2026018889A1 (ja) * | 2024-07-19 | 2026-01-22 | 住友ファーマ株式会社 | ワクチンアジュバントを含むリポソーム製剤 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5006343A (en) * | 1988-12-29 | 1991-04-09 | Benson Bradley J | Pulmonary administration of pharmaceutically active substances |
| RU2130771C1 (ru) | 1998-06-01 | 1999-05-27 | Автушенко Сергей Сергеевич | Способ получения липосомальных препаратов |
| WO2000028969A2 (en) * | 1998-11-18 | 2000-05-25 | University Of Florida | Methods for preparing coated drug particles and pharmaceutical formulations thereof |
| JP2003504321A (ja) | 1999-07-08 | 2003-02-04 | オーランド・ハン | リポソーム被包カンナビノイドの肺送達 |
| JP2003528131A (ja) * | 2000-03-29 | 2003-09-24 | アラダイム コーポレーション | カチオン性リポソーム |
| US20030096774A1 (en) * | 2001-11-21 | 2003-05-22 | Igor Gonda | Compositions of nucleic acids and cationic aminoglycosides and methods of using and preparing the same |
| DE10214983A1 (de) | 2002-04-04 | 2004-04-08 | TransMIT Gesellschaft für Technologietransfer mbH | Vernebelbare Liposomen und ihre Verwendung zur pulmonalen Applikation von Wirkstoffen |
| AU2003237863A1 (en) * | 2002-05-20 | 2003-12-12 | Research Development Foundation | Aerosol drug inhibition of lung metastases |
| RU2238091C2 (ru) | 2002-12-15 | 2004-10-20 | Закрытое акционерное общество "АИП-Наука" | Способ лечения туберкулеза у человека |
| KR20060015265A (ko) | 2003-05-30 | 2006-02-16 | 알자 코포레이션 | 제제의 폐 투여 방법 |
| JP4503953B2 (ja) | 2003-08-11 | 2010-07-14 | テルモ株式会社 | プレフィルドシリンジの製造方法 |
| JP4669665B2 (ja) | 2004-04-12 | 2011-04-13 | 正彦 阿部 | 細胞毒性のないポリカチオン修飾リポソームおよびその製造方法 |
| CN100356919C (zh) * | 2004-05-31 | 2007-12-26 | 上海医药工业研究院 | 羟基喜树碱脂质体及其制备方法 |
| RU2007114068A (ru) * | 2004-09-15 | 2008-10-27 | Оцука Фармасьютикал Ко. | Композиция для введения через слизистую оболочку и способ улучшения всасывания через слизистую оболочку |
-
2008
- 2008-03-28 US US12/593,827 patent/US8658204B2/en not_active Expired - Fee Related
- 2008-03-28 CA CA2885621A patent/CA2885621C/en not_active Expired - Fee Related
- 2008-03-28 RU RU2009140058/15A patent/RU2493874C2/ru not_active IP Right Cessation
- 2008-03-28 ES ES08739274.2T patent/ES2618457T3/es active Active
- 2008-03-28 NZ NZ579881A patent/NZ579881A/xx not_active IP Right Cessation
- 2008-03-28 EP EP13178179.1A patent/EP2656858B1/en active Active
- 2008-03-28 TW TW097111328A patent/TW200902085A/zh unknown
- 2008-03-28 UA UAA200910942A patent/UA100375C2/ru unknown
- 2008-03-28 KR KR1020097021573A patent/KR101476167B1/ko not_active Expired - Fee Related
- 2008-03-28 AR ARP080101281A patent/AR065865A1/es unknown
- 2008-03-28 AU AU2008233656A patent/AU2008233656B2/en not_active Ceased
- 2008-03-28 KR KR1020147029191A patent/KR20140136047A/ko not_active Ceased
- 2008-03-28 EP EP08739274.2A patent/EP2133097B1/en not_active Not-in-force
- 2008-03-28 ES ES13178179.1T patent/ES2643938T3/es active Active
- 2008-03-28 BR BRPI0809852-2A patent/BRPI0809852A2/pt not_active IP Right Cessation
- 2008-03-28 WO PCT/JP2008/056156 patent/WO2008120736A1/ja not_active Ceased
- 2008-03-28 CA CA2682376A patent/CA2682376C/en not_active Expired - Fee Related
- 2008-03-28 CN CN2013103086090A patent/CN103356482A/zh active Pending
- 2008-03-28 MX MX2009010479A patent/MX2009010479A/es active IP Right Grant
- 2008-03-28 CN CN200880010670A patent/CN101646462A/zh active Pending
- 2008-03-28 JP JP2009507528A patent/JP5191478B2/ja active Active
-
2009
- 2009-09-24 IL IL201172A patent/IL201172A0/en unknown
- 2009-09-28 ZA ZA2009/06742A patent/ZA200906742B/en unknown
- 2009-10-30 CO CO09123134A patent/CO6260108A2/es not_active Application Discontinuation
-
2013
- 2013-01-23 JP JP2013010008A patent/JP5674831B2/ja active Active
- 2013-12-17 US US14/108,826 patent/US9750694B2/en not_active Expired - Fee Related
-
2014
- 2014-07-17 AU AU2014204483A patent/AU2014204483A1/en not_active Abandoned
- 2014-10-30 PH PH12014502430A patent/PH12014502430A1/en unknown
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