DK2630954T3 - Pulmonal indgivelse af levodopa - Google Patents
Pulmonal indgivelse af levodopa Download PDFInfo
- Publication number
- DK2630954T3 DK2630954T3 DK13161929.8T DK13161929T DK2630954T3 DK 2630954 T3 DK2630954 T3 DK 2630954T3 DK 13161929 T DK13161929 T DK 13161929T DK 2630954 T3 DK2630954 T3 DK 2630954T3
- Authority
- DK
- Denmark
- Prior art keywords
- particles
- dopa
- levodopa
- administration
- oral
- Prior art date
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- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000003746 surface roughness Effects 0.000 description 1
- NJGWOFRZMQRKHT-UHFFFAOYSA-N surfactin Natural products CC(C)CCCCCCCCCC1CC(=O)NC(CCC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)O1 NJGWOFRZMQRKHT-UHFFFAOYSA-N 0.000 description 1
- NJGWOFRZMQRKHT-WGVNQGGSSA-N surfactin C Chemical compound CC(C)CCCCCCCCC[C@@H]1CC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)O1 NJGWOFRZMQRKHT-WGVNQGGSSA-N 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229920001664 tyloxapol Polymers 0.000 description 1
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 1
- 229960004224 tyloxapol Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
-
- 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
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (8)
1. Partikelmasse, der indbefatter L-Dopa, et phospholipid og et salt, hvor L-Dopa udgør 75 vægt-% eller mere af massen.
2. Partikelmasse ifølge krav 1, hvor saltet er et kraftigt elektrolytsalt.
3. Anvendelse af partikler, der omfatter et salt, et phospholipid og 75 vægt-% eller mere levodopa i fremstillingen af et medikament til administration til en patients luftveje, hvor partiklerne indgives til lungesystemet for behandling af Parkinsons sygdom.
4. Anvendelse ifølge krav 3, hvor phospholipidet er dipalmitoylphosphatidylcholin.
5. Anvendelse ifølge krav 3 eller 4, hvor partiklerne indbefatter 90 vægtprocent eller mere Levodopa.
6. Anvendelse ifølge krav 5, hvor partiklerne består af 90 vægtprocent levodopa, mindre end 10 vægtprocent dipalmitoylphosphatidylcholin og mindre end 5 vægtprocentsalt.
7. Anvendelse ifølge krav 3, hvor administration af partiklerne omfatter co-administration af partiklerne med oral levodopa, oral carbidopa eller både oral levodopa og oral carbidopa til kronisk levodopaterapi.
8. Anvendelse ifølge krav 3 eller krav 4, hvor saltet er et kraftigt elektrolytsalt.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36647102P | 2002-03-20 | 2002-03-20 | |
| EP12170237.7A EP2494962B1 (en) | 2002-03-20 | 2003-03-19 | Pulmonary delivery for levodopa |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2630954T3 true DK2630954T3 (da) | 2017-01-23 |
Family
ID=28454804
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK13161929.8T DK2630954T3 (da) | 2002-03-20 | 2003-03-19 | Pulmonal indgivelse af levodopa |
| DK03714302.1T DK1531798T3 (da) | 2002-03-20 | 2003-03-19 | Pulmonal frigørelse af Levodopa |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK03714302.1T DK1531798T3 (da) | 2002-03-20 | 2003-03-19 | Pulmonal frigørelse af Levodopa |
Country Status (13)
| Country | Link |
|---|---|
| US (7) | US7879358B2 (da) |
| EP (3) | EP2494962B1 (da) |
| JP (1) | JP4384503B2 (da) |
| AU (1) | AU2003218307B8 (da) |
| CA (1) | CA2478980C (da) |
| CY (1) | CY1118517T1 (da) |
| DK (2) | DK2630954T3 (da) |
| ES (3) | ES2389156T3 (da) |
| HU (1) | HUE031167T2 (da) |
| LT (1) | LT2630954T (da) |
| PT (3) | PT2630954T (da) |
| SI (1) | SI2630954T1 (da) |
| WO (1) | WO2003079992A2 (da) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4384503B2 (ja) * | 2002-03-20 | 2009-12-16 | アルカーメス，インコーポレイテッド | レボドパの肺送達 |
| GB0321607D0 (en) | 2003-09-15 | 2003-10-15 | Vectura Ltd | Manufacture of pharmaceutical compositions |
| RU2007137121A (ru) * | 2005-03-09 | 2009-04-20 | Оно Фармасьютикал Ко., Лтд. (Jp) | Частица и препарат, содержащий указанную частицу |
| ECSP077628A (es) * | 2007-05-03 | 2008-12-30 | Smithkline Beechman Corp | Nueva composición farmacéutica |
| GB2454480A (en) * | 2007-11-07 | 2009-05-13 | Vectura Group Plc | Pulmonary inhalation of levodopa containing compositions in the treatment of Parkinsons disease and other central nervous system disorders |
| CA2754691C (en) | 2009-03-26 | 2019-07-30 | Pulmatrix, Inc. | Dry powder formulations and methods for treating pulmonary diseases |
| EP2464346A1 (en) | 2010-08-30 | 2012-06-20 | Pulmatrix, Inc. | Treatment of cystic fibrosis using calcium lactate, leucine and sodium chloride in a respiraple dry powder |
| AU2011296343B2 (en) | 2010-08-30 | 2015-12-10 | Pulmatrix Operating Company, Inc. | Dry powder formulations and methods for treating pulmonary diseases |
| EP3470057B1 (en) | 2010-09-29 | 2021-11-03 | Pulmatrix Operating Company, Inc. | Cationic dry powders comprising magnesium salt |
| RU2017144619A (ru) | 2010-09-29 | 2019-02-20 | Пулмэтрикс, Инк. | Катионы одновалентных металлов сухих порошков для ингаляций |
| CN107596518B (zh) | 2012-02-29 | 2021-04-23 | 普马特里克斯营业公司 | 可吸入干粉剂 |
| PT2908805T (pt) * | 2012-10-22 | 2021-09-10 | Civitas Therapeutics Inc | Formulações de levodopa para alívio rápido da doença de parkinson |
| KR102237007B1 (ko) * | 2012-10-22 | 2021-04-06 | 키비타스 테라퓨틱스, 인코포레이티드. | 레보도파 혈장 농도의 환자간 변산도의 감소 |
| US8545878B1 (en) * | 2012-11-09 | 2013-10-01 | Civitas Therapeutics, Inc. | Capsules containing high doses of levodopa for pulmonary use |
| BR112015010601B1 (pt) * | 2012-11-09 | 2022-07-19 | Civitas Therapeutics, Inc. | Composição farmacêutica e uso da composição |
| US20140150787A1 (en) | 2012-12-04 | 2014-06-05 | Civitas Therapeutics, Inc. | Devices and methods for puncturing a capsule to release a powdered medicament therefrom |
| JP6473738B2 (ja) | 2013-04-01 | 2019-02-20 | パルマトリックス，インコーポレイテッド | チオトロピウム乾燥粉末 |
| US20160317542A1 (en) | 2013-12-09 | 2016-11-03 | Respira Therapeutics, Inc. | Pde5 inhibitor powder formulations and methods relating thereto |
| TWI589308B (zh) * | 2014-03-25 | 2017-07-01 | 林信湧 | 一種用於治療帕金森氏症之吸入式醫藥組成物及其備製方法 |
| WO2015163840A1 (en) * | 2014-04-21 | 2015-10-29 | Civitas Therapeutics, Inc. | Rapid relief of motor fluctuations in parkinson's disease |
| MA40910A (fr) | 2014-11-07 | 2017-09-12 | Civitas Therapeutics Inc | Poudres de rapamycine pour administration pulmonaire |
| AU2016258179B2 (en) | 2015-05-06 | 2021-07-01 | Synagile Corporation | Pharmaceutical suspensions containing drug particles, devices for their administration, and methods of their use |
| AU2016287582B2 (en) | 2015-07-02 | 2020-03-12 | Civitas Therapeutics, Inc. | Triptan powders for pulmonary delivery |
| WO2018138581A1 (en) | 2017-01-30 | 2018-08-02 | Globalmed, Inc. | Heated respiratory hose assembly |
| US11517548B2 (en) * | 2018-07-19 | 2022-12-06 | Impel Pharmaceuticals Inc. | Respiratory tract delivery of levodopa and DOPA decarboxylase inhibitor for treatment of Parkinson's Disease |
| JP2019108379A (ja) * | 2019-03-05 | 2019-07-04 | サイヴィタス セラピューティックス，インコーポレイテッド | パーキンソン病の運動症状変動の迅速な緩和 |
| IT202000030437A1 (it) * | 2020-12-10 | 2022-06-10 | Zambon Spa | Metodo per la realizzazione di una polvere inalabile comprendente voriconazolo |
| US12005185B2 (en) * | 2021-12-17 | 2024-06-11 | Belhaven BioPharma Inc. | Medical counter measures including dry powder formulations and associated methods |
| WO2025007958A1 (zh) | 2023-07-05 | 2025-01-09 | 上海汉都医药科技有限公司 | 药物组合物、含其的制剂、套装及其制备方法和应用 |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3689643A (en) | 1971-01-27 | 1972-09-05 | Abbott Lab | Combination of l-dopa, 2-imino-5-phenyl-4-oxazolidinone and an aluminum or alkaline earth metal salt or base used to treat parkinson{40 s disease |
| US4069819A (en) | 1973-04-13 | 1978-01-24 | Societa Farmaceutici S.P.A. | Inhalation device |
| US4511258A (en) | 1983-03-25 | 1985-04-16 | Koflo Corporation | Static material mixing apparatus |
| JPS6122019A (ja) | 1984-07-06 | 1986-01-30 | Tomio Konno | 吸入細胞活性薬品とその使用方法 |
| GB8501015D0 (en) | 1985-01-16 | 1985-02-20 | Riker Laboratories Inc | Drug |
| DE3686025T2 (de) | 1985-05-22 | 1993-01-07 | Liposome Technology Inc | Verfahren und system zum einatmen von liposomen. |
| IT1228459B (it) | 1989-02-23 | 1991-06-19 | Phidea S R L | Inalatore con svuotamento regolare e completo della capsula. |
| US6048857A (en) | 1989-10-17 | 2000-04-11 | Ellinwood, Jr.; Everett H. | Dosing method of administering medicaments via inhalation administration |
| US5118494A (en) | 1990-03-23 | 1992-06-02 | Minnesota Mining And Manufacturing Company | Use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations |
| JPH05507090A (ja) | 1990-05-08 | 1993-10-14 | リポサーム テクノロジー インコーポレイテッド | 直接噴霧乾燥された薬剤／脂質粉末組成物 |
| US5166202A (en) | 1990-09-19 | 1992-11-24 | Trustees Of The University Of Pennsylvania | Method for the treatment of panic disorder |
| JPH0697804A (ja) * | 1991-01-08 | 1994-04-08 | Nec Corp | 論理回路 |
| GB9101592D0 (en) | 1991-01-24 | 1991-03-06 | Glaxo Group Ltd | Compositions |
| PT533268E (pt) | 1991-09-18 | 2002-02-28 | Glaxo Group Ltd | Derivados de benzanilida como antagonistas de 5-ht1d |
| US5457100A (en) | 1991-12-02 | 1995-10-10 | Daniel; David G. | Method for treatment of recurrent paroxysmal neuropsychiatric |
| US5756071A (en) | 1992-06-03 | 1998-05-26 | Arrowdean Limited | Method for nasally administering aerosols of therapeutic agents to enhance penetration of the blood brain barrier |
| US5284133A (en) | 1992-07-23 | 1994-02-08 | Armstrong Pharmaceuticals, Inc. | Inhalation device with a dose-timer, an actuator mechanism, and patient compliance monitoring means |
| AU5171293A (en) | 1992-10-14 | 1994-05-09 | Regents Of The University Of Colorado, The | Ion-pairing of drugs for improved efficacy and delivery |
| US5354885A (en) | 1992-12-24 | 1994-10-11 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Process for preparing ethyl ester of L-DOPA |
| NZ281112A (en) | 1994-03-07 | 1998-04-27 | Inhale Therapeutic Syst | Powdered insulin delivered as an aerosol |
| CA2152684A1 (en) | 1994-07-01 | 1996-01-02 | Richard Anthony Henry | Aerosol delivery of midazolam |
| US6019968A (en) | 1995-04-14 | 2000-02-01 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
| US6165463A (en) | 1997-10-16 | 2000-12-26 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
| US5654007A (en) | 1995-06-07 | 1997-08-05 | Inhale Therapeutic Systems | Methods and system for processing dispersible fine powders |
| GB9606677D0 (en) * | 1996-03-29 | 1996-06-05 | Glaxo Wellcome Inc | Process and device |
| US5875776A (en) | 1996-04-09 | 1999-03-02 | Vivorx Pharmaceuticals, Inc. | Dry powder inhaler |
| US6254854B1 (en) | 1996-05-24 | 2001-07-03 | The Penn Research Foundation | Porous particles for deep lung delivery |
| US5985309A (en) | 1996-05-24 | 1999-11-16 | Massachusetts Institute Of Technology | Preparation of particles for inhalation |
| US5874064A (en) | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
| US5855913A (en) | 1997-01-16 | 1999-01-05 | Massachusetts Instite Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
| US6103270A (en) | 1996-06-07 | 2000-08-15 | Inhale Therapeutic Systems | Methods and system for processing dispersible fine powders |
| DE69732306T2 (de) | 1997-01-16 | 2006-01-12 | Massachusetts Institute Of Technology, Cambridge | Zubereitung von partikelhaltigen arzneimitteln zur inhalation |
| US6193954B1 (en) | 1997-03-21 | 2001-02-27 | Abbott Laboratories | Formulations for pulmonary delivery of dopamine agonists |
| US5958902A (en) | 1997-04-16 | 1999-09-28 | Wisconsin Alumni Research Foundation | Method and composition for treating sleep apnea |
| CA2371836C (en) | 1999-05-27 | 2006-01-31 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
| US6858199B1 (en) | 2000-06-09 | 2005-02-22 | Advanced Inhalation Research, Inc. | High efficient delivery of a large therapeutic mass aerosol |
| US6461631B1 (en) * | 1999-11-16 | 2002-10-08 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
| US6514482B1 (en) | 2000-09-19 | 2003-02-04 | Advanced Inhalation Research, Inc. | Pulmonary delivery in treating disorders of the central nervous system |
| US6613308B2 (en) | 2000-09-19 | 2003-09-02 | Advanced Inhalation Research, Inc. | Pulmonary delivery in treating disorders of the central nervous system |
| JP4384503B2 (ja) * | 2002-03-20 | 2009-12-16 | アルカーメス，インコーポレイテッド | レボドパの肺送達 |
| US10156302B1 (en) | 2016-02-09 | 2018-12-18 | Blox, Llc | Mechanical electrical plumbing rack device |
-
2003
- 2003-03-19 JP JP2003577824A patent/JP4384503B2/ja not_active Expired - Lifetime
- 2003-03-19 WO PCT/US2003/008659 patent/WO2003079992A2/en not_active Ceased
- 2003-03-19 SI SI200332506T patent/SI2630954T1/sl unknown
- 2003-03-19 PT PT131619298T patent/PT2630954T/pt unknown
- 2003-03-19 ES ES03714302T patent/ES2389156T3/es not_active Expired - Lifetime
- 2003-03-19 HU HUE13161929A patent/HUE031167T2/hu unknown
- 2003-03-19 AU AU2003218307A patent/AU2003218307B8/en not_active Expired
- 2003-03-19 CA CA002478980A patent/CA2478980C/en not_active Expired - Lifetime
- 2003-03-19 ES ES12170237.7T patent/ES2487816T3/es not_active Expired - Lifetime
- 2003-03-19 ES ES13161929.8T patent/ES2609482T3/es not_active Expired - Lifetime
- 2003-03-19 LT LTEP13161929.8T patent/LT2630954T/lt unknown
- 2003-03-19 PT PT121702377T patent/PT2494962E/pt unknown
- 2003-03-19 DK DK13161929.8T patent/DK2630954T3/da active
- 2003-03-19 EP EP12170237.7A patent/EP2494962B1/en not_active Expired - Lifetime
- 2003-03-19 EP EP03714302A patent/EP1531798B1/en not_active Expired - Lifetime
- 2003-03-19 US US10/392,342 patent/US7879358B2/en not_active Ceased
- 2003-03-19 EP EP13161929.8A patent/EP2630954B1/en not_active Expired - Lifetime
- 2003-03-19 PT PT03714302T patent/PT1531798E/pt unknown
- 2003-03-19 DK DK03714302.1T patent/DK1531798T3/da active
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2010
- 2010-12-20 US US12/972,824 patent/US8404276B2/en not_active Expired - Fee Related
-
2011
- 2011-10-17 US US13/274,787 patent/USRE43711E1/en active Active
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2013
- 2013-02-21 US US13/773,054 patent/US8586093B2/en not_active Expired - Fee Related
- 2013-10-17 US US14/055,959 patent/US9155699B2/en not_active Expired - Fee Related
-
2015
- 2015-09-10 US US14/849,950 patent/US20160058727A1/en not_active Abandoned
-
2016
- 2016-12-30 CY CY20161101363T patent/CY1118517T1/el unknown
-
2017
- 2017-04-06 US US15/480,956 patent/US20180055800A1/en not_active Abandoned
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