[發明專利]納米顆粒他克莫司制劑

無效

• 申請號: 200580047894.9
• 申請日: 2005-12-15
• 公開（公告）號: CN101132768A
• 公開（公告）日: 2008-02-27
• 發明（設計）人: S·詹金斯;G·利弗西奇;E·利弗西奇
• 申請（專利權）人: 伊蘭制藥國際有限公司
• 主分類號: A61K9/14
• 分類號: A61K9/14;A61K38/13;A61P37/06
• 代理公司: 中國專利代理(香港)有限公司
• 代理人: 關立新;范赤

技術領域

本發明涉及含有他克莫司的納米顆粒組合物。在本發明的兩個示例性的實施方案中，描述的是可注射的納米顆粒他克莫司組合物和腸溶口服納米顆粒他克莫司組合物，及其制備和使用方法。

背景技術

關于納米顆粒活性劑組合物的背景

納米顆粒組合物最早見于美國專利5,145,684(684專利)，是由溶解性差的治療或診斷劑的顆粒組成，在其表面上有吸附的或結合的一種非交聯的表面穩定劑。該684專利還描述了制備這種納米顆粒組合物的方法，但是沒有提到含有納米顆粒形式的他克莫司的組合物。在題為“Method?of?Grinding?Pharmaceutical?Substances”的美國專利5,518,187和5,862,999，題為“Continuous?Method?of?Grinding?PharmaceuticalSubstances”的美國專利5,718,388，和題為“Process?of?PreparingTherapeutic?Compositions?Containing?Nanoparticles”的美國專利5,510,118中，描述了制造納米顆粒組合物的方法。

納米顆粒組合物還描述于例如以下專利中：

美國專利5,298,262″Use?of?Ionic?Cloud?Point?Modifiers?to?Prevent?ParticleAggregation?During?Sterilization；″美國專利5,302,401″Method?toReduce?Particle?Size?Growth?During?Lyophilization；″美國專利5,318,767″X-Ray?Contrast?Compositions?Useful?in?Medical?Imaging；″美國專利5,326,552″Novel?Formulation?For?Nanoparticulate?X-Ray?Blood?PoolContrast?Agents?Using?High?Molecular?Weight?Non-ionic?Surfactants；″美國專利5,328,404for″Method?of?X-Ray?Imaging?Using?Iodinated?AromaticPropanedioates；″美國專利5,336,507″Use?of?Charged?Phospholipids?toReduce?Nanoparticle?Aggregation；″美國專利5,340,564″FormulationsComprising?Olin?10-G?to?Prevent?Particle?Aggregation?and?Increase?Stability；″美國專利5,346,702″Use?of?Non-Ionic?Cloud?Point?Modifiers?toMinimize?Nanoparticulate?Aggregation?During?Sterilization；″美國專利5,349,957″Preparation?and?Magnetic?Properties?of?Very?Small?Magnetic-Dextran?Particles；″美國專利5,352,459″Use?of?Purified?SurfaceModifiers?to?Prevent?Particle?Aggregation?During?Sterilization；″美國專利5,399,363和5,494,683，″Sufface?Modified?Anticancer?Nanoparticles；″美國專利5,401,492″Water?Insoluble?Non-Magnetic?Manganese?Particlesas?Magnetic?Resonance?Enhancement?Agents；″美國專利5,429,824″Useof?Tyloxapol?as?a?Nanoparticulate?Stabilizer；″美國專利5,447,710″Method?for?Making?Nanoparticulate?X-Ray?Blood?Pool?Contrast?Agents?UsingHigh?Molecular?Weight?Non-ionic?Surfactants；″美國專利5,451,393″X-Ray?Contrast?Compositions?Useful?in?Medical?Imaging；″美國專利5,466,440″Formulations?of?Oral?Gastrointestinal?Diagnostic?X-Ray?Contrast?Agents?inCombination?with?Pharmaceutically?Acceptable?Clays；″美國專利5,470,583″Method?of?Preparing?Nanoparticle?Compositions?Containing?ChargedPhospholipids?to?Reduce?Aggregation；″美國專利5,472,683″Nanoparticulate?Diagnostic?Mixed?Carbamic?Anhydrides?as?X-Ray?ContrastAgents?for?Blood?Pool?and?Lymphatic?System?Imaging；″美國專利5,500,204″Nanoparticulate?Diagnostic?Dimers?as?X-Ray?Contrast?Agents?for?BloodPool?and?Lymphatic?System?Imaging；″美國專利5,518,738″Nanoparticulate?NSAID?Formulations；″美國專利5,521,218″Nanoparticulate?Iododipamide?Derivatives?for?Use?as?X-Ray?Contrast?Agents；″美國專利5,525,328″Nanoparticulate?Diagnostic?Diatrizoxy?Ester?X-RayContrast?Agents?for?Blood?Pool?and?Lymphatic?System?Imaging；″美國專利5,543,133″Process?of?Preparing?X-Ray?Contrast?Compositions?ContainingNanoparticles；″美國專利5,552,160″Surface?Modified?NSAIDNanoparticles；″美國專利5,560,931″Formulations?of?Compounds?asNanoparticulate?Dispersions?in?Digestible?Oils?or?Fatty?Acids；″美國專利5,565,188″Polyalkylene?Block?Copolymers?as?Surface?Modifiers?forNanoparticles；″美國專利5,569,448″Sulfated?Non-ionic?BlockCopolymer?Surfactant?as?Stabilizer?Coatings?for?Nanoparticle?Compositions；″美國專利5,571,536″Formulations?of?Compounds?as?NanoparticulateDispersions?in?Digestible?Oils?or?Fatty?Acids；″美國專利5,573,749″Nanoparticulate?Diagnostic?Mixed?Carboxylic?Anydrides?as?X-Ray?ContrastAgents?for?Blood?Pool?and?Lymphatic?System?Imaging；″美國專利5,573,750″Diagnostic?Imaging?X-Ray?Contrast?Agents；″美國專利5,573,783″Redispersible?Nanoparticulate?Film?Matrices?With?Protective?Overcoats；″美國專利5,580,579″Site-specific?Adhesion?Within?the?GI?Tract?UsingNanoparticles?Stabilized?by?High?Molecular?Weight,Linear?Poly(ethylene?Oxide)Polymers；″美國專利5,585,108″Formulations?of?Oral?GastrointestinalTherapeutic?Agents?in?Combination?with?Pharmaceutically?Acceptable?Clays；″美國專利5,587,143″Butylene?Oxide-Ethylene?Oxide?Block?CopolymersSurfactants?as?Stabilizer?Coatings?for?Nanoparticulate?Compositions；″美國專利5,591,456″Milled?Naproxen?with?Hydroxypropyl?Cellulose?as?DispersionStabilizer；″美國專利5,593,657″Novel?Barium?Salt?FormulationsStabilized?by?Non-ionic?and?Anionic?Stabilizers；″美國專利5,622,938″Sugar?Based?Surfactant?for?Nanocrystals；″美國專利5,628,981″Improved?Formulations?of?Oral?Gastrointestinal?Diagnostic?X-Ray?ContrastAgents?and?Oral?Gastrointestinal?Therapeutic?Agents；″美國專利5,643,552″Nanoparticulate?Diagnostic?Mixed?Carbonic?Anhydrides?as?X-Ray?ContrastAgents?for?Blood?Pool?and?Lymphatic?System?Imaging；″美國專利5,718,388″Continuous?Method?of?Grinding?Pharmaceutical?Substances；″美國專利5,718,919″Nanoparticles?Containing?the?R(-)Enantiomer?of?Ibuprofen；″美國專利5,747,001″Aerosols?Containing?Beclomethasone?NanoparticleDispersions；″美國專利5,834,025″Reduction?of?IntravenouslyAdministered?Nanoparticulate?Formulation?Induced?Adverse?PhysiologicalReactions；″美國專利6,045,829″Nanocrystalline?Formulations?of?HumanImmunodeficiency?Virus(HIV)Protease?Inhibitors?Using?Cellulosic?SurfaceStabilizers；″美國專利6,068,858″Methods?of?Making?NanocrystallineFormulations?of?Human?Immunodeficiency?Virus(HIV)Protease?InhibitorsUsing?Cellulosic?Surface?Stabilizers；″美國專利6,153,225″InjectableFormulations?of?Nanoparticulate?Naproxen；″美國專利6,165,506″NewSolid?Dose?Form?of?Nanoparticulate?Naproxen；″美國專利6,221,400″Methods?of?Treating?Mammals?Using?Nanocrystalline?Formulations?of?HumanImmunodeficiency?Virus(HIV)Protease?Inhibitors；″美國專利6,264,922″Nebuulized?Aerosols?Containing?Nanoparticle?Dispersio；″美國專利6,267,989″Methods?for?Preventing?Crystal?Growth?and?Particle?Aggregationin?Nanoparticle?Compositions；″美國專利6,270,806″Use?of?PEG-Derivatized?Lipids?as?Surface?Stabilizers?for?Nanoparticulate?Compositions；″美國專利6,316,029″Rapidly?Disintegrating?Solid?Oral?Dosage?Form，″美國專利6,375,986″Solid?Dose?Nanoparticulate?CompositionsComprising?a?Synergistic?Combination?of?a?Polymeric?Surface?Stabilizer?andDioctyl?Sodium?Sulfosuccinate；″美國專利6,428,814″BioadhesiveNanoparticulate?Compositions?Having?Cationic?Surface?Stabilizers；″美國專利6,431,478″Small?Scale?Mill；″美國專利6,432,381″Methods?forTargeting?Drug?Delivery?to?the?Upper?and/or?Lower?Gastrointestinal?Tract；″美國專利6,582,285″Apparatus?for?Sanitary?Wet?Milling；″和美國專利6,592,903″Nanoparticulate?Dispersions?Comprising?a?SynergisticCombination?of?a?Polymeric?Surface?Stabilizer?and?Dioctyl?SodiumSulfosuccinate；″美國專利6,656,504“Nanoparticulate?Compositions?ComprisingAmorphous?Cyclosporine；”美國專利6,742,734“System?and?Method?for?MillingMaterials；”美國專利6,745,962“Small?Scale?Mill?and?Method?Thereof；”美國專利6,811,767“Liquid?droplet?aerosols?of?nanoparticulate?drugs；”和美國專利6,908,626“Compositions?having?a?combination?of?immediate?release?and?controlled?releasecharacteristics；”