WO1990009781A1 - Compositions aerosol therapeutiques - Google Patents
Compositions aerosol therapeutiques Download PDFInfo
- Publication number
- WO1990009781A1 WO1990009781A1 PCT/US1990/000928 US9000928W WO9009781A1 WO 1990009781 A1 WO1990009781 A1 WO 1990009781A1 US 9000928 W US9000928 W US 9000928W WO 9009781 A1 WO9009781 A1 WO 9009781A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
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- leu
- ser
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- gln
- Prior art date
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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
- A61K9/0012—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
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/23—Calcitonins
-
- 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
- A61K9/0043—Nose
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
Definitions
- the present invention relates to a novel therapeutic self-propelled aerosol formulation for inhalation. More particularly, it relates to a therapeutic formulation of the dispersion or suspension type comprising: a physiologically active solid drug and a solid extender or carrier for the drug suspended in a chlorofluorocarbon propellant mixture.
- the present invention also relates to a process for the preparation of self-propelled aerosol formulation intended for inhalation wherein the preparative steps include: dissolving a solid drug and a solid extender or carrier in a solvent; lyophilizing the solution to obtain a powder; micronizing and suspending the powder in a propellant mixture.
- the preferred embodiment of the present invention relates to a self-propelled aerosol formulation for inhalation wherein the active drug is a polypeptide having calcitonin activity for the treatment of bone diseases.
- Inhalation therapy involves direct deposition of medication onto the airway of a patient by the nasal or oral routes.
- This method of delivery of medication is therapeutically sound and is well accepted in the prior art.
- the benefits of the method are: the rapid medication effects essential in the treatment of life threatening afflictions, such as certain allergic and asthmatic conditions; the reduction of systemic side effects; convenience and cost as compared to, for example, intravenous or intramuscular administration; and self-administration of certain drugs such as the pharmaceutically active peptides that cannot be taken orally for reason of decomposition in the gastrointestinal tract.
- Inhalation therapy can be used for the treatment of a variety of diseases requiring physiologically active drugs such as insulin, calcitonin, interferons, vaccines, decongestants, antiasth atics and the like.
- physiologically active drugs such as insulin, calcitonin, interferons, vaccines, decongestants, antiasth atics and the like.
- Particle penetration and deposition are believed to maximized by the use of a particle size range of from about 2 to about lO ⁇ . Particles less than 2 ⁇ , although reach the alveoli, deposit minimally and are likely to be exhaled. Particles lO ⁇ or greater do not enter the respiratory tract and are deposited in the oropharynx. Comminuting solid drugs to obtain the desired particle size range poses no problem in the prior art. However, the requirements of particle stability, precise dosage and non-irritation have not been, in general, quite satisfactorily met. Generally described, the heretofore proposed and/or utilized aerosol formulations, are micronized drug particles suspended in a propellant mixture.
- the formulations also contain a surfactant, a solvent or a dispersing agent to prevent agglomeration or sedimentation of the suspended particles.
- a surfactant e.g., sodium bicarbonate
- a solvent or a dispersing agent e.g., sodium bicarbonate
- the drug particles tend to form agglomerates, floating flocculants or sedimentary precipitations during extended shelf-life resulting in destruction or clogging of the dispensing mechanism, and when administered, uneven distribution and non-uniform dosage of the drug in the tracheobronchial tree of the patient.
- certain solvents and surfactants tend to cause irritation on extended use of the formulations.
- a self-propelled therapeutic aerosol formulation for oral and/or intranasal application comprising:
- said homogeneous complex is insoluble in said propellant mixture and is present in the form of micronized solid particles of which at least 90% w/w has an effective particle diameter of about 2 to about lO ⁇ and having a density of about 1.33 to about 1.40 gm/cc.
- the active drug and the pharmaceutically acceptable extender are dissolved in water, the resultant solution is lyophilized forming a homogeneous complex wherein the drug and extender molecules are in intimate contact with each other.
- the so obtained powder is comminuted to the desired particle size, then combined with a small amount of solvent and/or surfactant, followed by metering into aerosol containers and adding the propellant mixture thereto.
- the desired, self-propelled therapeutic formulations can be obtained as described above and as will be further explained and exemplified in detail.
- the extenders serve as carriers and diluents for the active drugs in the formulations and comprise about 75 to 99.9% of the drug/extender homogeneous complex.
- the extender must be a solid, water soluble, propellant insoluble, pharmaceutically acceptable material, so that it can be dissolved in an aqueous solution together with the active drug, lyophilized and the so obtained homogeneous complex comminuted to the desired particle size.
- a) other amino acids including D or L-Methionine, glycine, alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, serine, cystein, aspartic acid, glutamic acid, arginine, lysine, asparagine, histidine, tryptophan and proline;
- monosaccharides such as, D-allose, D-altrose, fructose, galactose, glucose, inositol, D-mannose and sorbose;
- disaccharides such as, sucrose, cellobiose, lactose, maltose, melibiose, trehalose and turanose;
- polysaccharides such as, dextrin, glycogen and starch
- peptides and proteins such as the widely used dipeptide, Aspartame.
- the present invention utilizes from about 0.1 to about 3.0% w/w of a solvent and/or surfactant to help maintain a stable suspension.
- the solvents used include alcohols, preferably ethyl alcohol; while the surfactants include nonionic, cationic and anionic surface active agents, the preferred being oleic acid.
- the propellant mixture comprises from about 92 to about 99.89% w/w of the total formulation having a density of about 1.33 to 1.40 gm/cc and consists of a 90/10 mixture of dichlorodifluoromethane and dichlorotetrafluoroethane, or a 90/10 mixture of dichlorodifluoromethane and trichlorofluoromethane, sold under the trade names Dymel 12, Dymel 114 and Dymel 11 respectively.
- the active drug comprises from about 0.1 to about 25.0% w/w of the drug/extender homogeneous complex.
- Drugs in solid form and drugs that can be made into a solid form and are soluble in aqueous solutions and insoluble in the hydrocarbon mixtures hereindescribed are contemplated for use in accordance with the present invention.
- bronchodilators such as:
- Ipratropium bromide 3-(3-hydroxy-l-oxo-2- phenylpropoxy)-8- methyl-8-(1-methylethyl)-3-azonicabicyclo[3.2.1]octane bromide;
- Metaproterenol sulfate 5-[l-hydroxy-2-[ (1-methylethyl) amino]ethyl]1,3-benzenediol sulfate;
- Terbutaline sulfate 5-[2-[(1,1-dimethylethyl)amino]-1- hydroxyethyl]-1,3-benzenediol sulfate;
- Bitolterol mesylate 4-methylbenzoic acid 4-[2-[(l,l- dimethylethyl)amino]-1-hydroxyethyl]-1,2-phenylene ester mesylate;
- Isoproterenol hydrochloride 4-[l-hydroxy-2-[ (1-methyl ⁇ ethyl)amino]ethyl]-1,2-benzenediol hydrochloride;
- Epinephrine hydrochloride 4-[l-hydroxy-2(methylamino)- ethyl]-1,2-benzenediol hydrochloride;
- Albuterol sulfate a•-[[(1,1- dimethylethyl)amino]methyl]- 4-hydroxy-l,3-benzenedimethanol sulfate;
- Theophylline 3,7-dihydro-l,3-dimethyl-lH-purine-2,6- dione.
- Cardiovascular drugs such as:
- Clonidine hydrochloride 2,6-dichloro-N-2- imidazolidinyli- denebenzeneamine hydrochloride
- Terazosin hydrochloride l-(4-amino-6,7-dimethoxy-2- quina- zolinyl)-4[ (tetrahydro-2-furanyl)carbonyl) ]piperazine hydrochloride;
- Prazosin hydrochloride l-(4-amino-6,7-dimethoxy-2- quina- zolinyl)-4-(2-furoyl)piperazine hydrochloride;
- Tolazoline hydrochloride 4,5-dihydro-2-(phenylmethyl)- lH-imidazole monohydrochloride
- Labetalol hydrochloride 5-[l-hydroxy-2-[ (l-methyl-3- phenylpropyl)amino]ethyl]salicylamide monohydrochloride;
- Captopril 1-[ (2S)-3-mercapto-2-methylpropionyl]-L- proline;
- Verapamil hydrochloride ⁇ -[3-[[2-(3,4-dimethoxyphenyl)- ethyl]-methylamino]propy1]-3,4-dimethoxy- ⁇ (1- methylethyl)benzene-acetonitrile hydrochloride;
- Diltiazem hydrochloride 3-(acetyloxy)-5-[2-(dimethyl- mino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5- benzothiazepin-4(5H)-one hydrochloride;
- Propranolol hydrochloride l-(isopropylamino)-3-(l- napthyl-oxy)-2-propanol hydrochloride;
- Bretylium tosylate (o-bromobenzyl) ethyl dimethylammonium p-toluene solfonate;
- Lidocaine hydrochloride 2-(diethylamino)-2• ,6'- acetoxyl-idide monohydrochloride;
- Mexilitine hydrochloride l-methyl-2-(2,6-xylyloxy)- ethyl-amine hydrochloride;
- Disopyramide phosphate ⁇ -[2-diisopropylamino)ethyl]-c_- phenyl-2-pyridineacetamide phosphate;
- Procainamide hydrochloride p-amino-N-[2-(diethylamino)- ethyl]-benzamide hydrochloride;
- Flecainide acetate N-(2-piperidinylmethyl)-2,5- bis(2,2,2-trifluoroethoxy)benzamide monoacetate;
- Tocainide hydrochloride 2-amino-N-(2,6-dimethylphenyl)- propanamide hydrochloride
- Methoxamine hydrochloride ⁇ -(l-aminoethyl)-2,5- dimethoxy-benzenemethanol hydrochloride;
- Minoxidil 6-(l-piperidinyl)-2,4-pyrimidinediamine-3- oxide
- Metoprolol tartrate l-(isopropylamino)-3-[p-(2-methoxy- ethyl)phenoxy]-2-propanol (2:1) dextro-tatrate salt;
- Hydroflumethiazide 3,4-dihydro-6-(trifluoromethyl)-2H- 1,2,4-benzothiadiazine-7-sulfonamide-l,1-dioxide;
- Amrinone lactate 5-amino[3,4*-bipyridine]-6(lH)-one 1actate;
- Ethaverine hydrochloride l-[(3,4- diethoxyphenyl)methyl]-6,7-diethoxyisoquinoline hydrochloride;
- Papaverine hydrochloride l-[(3,4- dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline hydrochloride.
- the preferred embodiment of the invention utilizes calcitonin as the active polypeptide for the treatment of bone diseases.
- Calcitonin is a polypeptide hormone involved in the control of calcium metabolism in the body. All known natural calcitonin peptides contain an amino acid sequence of 32 amino acids, of which the seven at the amino terminal end of the peptide chain are held in a cyclic configuration by a sulphur or carbon bridge and the carboxyl terminal residue consists of proline amide.
- the natural calcitonins include the salmon, eel, bovin, porcine, ovine, rat and human calcitonin.
- salmon calcitonin is of special interest in view of its relatively hydrophilic character and its stability. Salmon calcitonin has the following formula:
- the level of hypocalcemic activity of calcitonin varies from species to species.
- Salmon and chicken calcitonin have a potency of about 4,000 to 6,000 MCR (Medical Research Council) ⁇ /mg peptide; eel calcitonin about 2,000 to 4,000 MRC U/mg peptide; rat 400 MRC ⁇ /mg; while beef, sheep, hog and man about 100 to 200 MRC ⁇ /mg peptide.
- Calcitonin used by the present invention may be obtained from Armour Pharmaceutical Co. , from natural sources, or by synthetic routes known in the art. The synthesis can be performed by classical peptide synthesis as well as by solid phase synthesis.
- the present invention encompasses synthetic calcitonin peptides having biological activity of the same type as those above- described.
- synthetic calcitonin are disclosed, along with processes for preparation thereof in the following U.S. Pat. Nos.
- Synthetic calcitonin analogues disclosed in these patents are incorporated herein by reference as if set out in full herein. This list is not intended to be exhaustive of all U.S. Patents covering synthetic calcitonin analogues, but is representative of the analogues useful in the present invention; nor is the invention limited to the compounds disclosed in the listed patents.
- analogues of calcitonin constitute specific active ingredients used in the various suppository formulations of the present invention:
- Des-2-Serine, 3-Asparagine Calcitonin having the following structures:
- G-Serine, Des-19-Leucine Calcitonin having the following structures:
- Salmon Calcitonin having the following structures:
- Des-Leu 16 -Calcitonin having the following structures:
- Leucine 22 - Calcitonin having the following structures:
- Glycine - 8 Calcitonin having the following structures:
- Glycine 8 -D-Arginine 24 Calcitonin having the following structures:
- L-Tyrosine 21 Calcitonin having the following structures
- D-Arginine 24 Calcitonin having the following structures:
- N ⁇ -Propionyl, l,7-Di-Alanine, Des-19-Leucine Calcitonin having the following structure:
- the active drug and the extender both being in a solid form, are dissolved in water by means of mechanical mixing, followed by lyophilization and comminution to the desired particle size, using well-known technique employed in the prior art.
- the drug/extender complex at least 90% of which possess an effective particle diameter of about 2 to 10 ⁇ is combined with a solvent or surfactant by means of blending and metered into a suitable aerosol container.
- the desired amount of the 90/10 dichlorodifluoromethane/ dichlorotetrafluoroethane is charged into the container to complete the process in making the self-propelled formulation.
- micronized calcitonin/DL-Methione complex was then combined with oleic acid and a 90/10 blend of Dymel 12/Dymel 114 in a suitable container.
- the so prepared formulation was found to contain:
- Dose delivery was found to contain an average of 7.32 ⁇ g of calcitonin and 1063 ⁇ g DL-Methionine per actuation, while content uniformity was found to be an average of 1.795 ⁇ g/unit of calcitonin and 259.2 ⁇ g/unit DL-Methionine.
- Particle size measurement showed an M50 of 4.4 ⁇ and an M90 of 13.5 ⁇ .
- a calcitonin/DL-Methionine complex was prepared and processed as in Example 1.
- the final formulation contained 0.125 grams of calcitonin/DL-Methionine, 0.095 grams of oleic acid and 16.148 grams of 90/10 mixture of Dymel 12/Dymel 114.
- Dose delivery was found to be 22.5 ⁇ g of calcitonin and 477.5 ⁇ g of DL-Methionine per actuation.
- a slurry was prepared consisting of 20.0 grams of DL- Methionine/SCT, 40.0 grams of absolute ethanol, and 40.0 grams of oleic acid. 250 ml of the slurry was then combined with 9.75 ml of 90/10 of Dymel 12/Dymel 114 propellant blend to produce the following self-propelled aerosol suspension:
- the formulation provides 200 IU/50 ⁇ L per actuation.
- a slurry was then prepared using the micronized powder, 15 grams of SPAN 85 and 120 grams of ethanol. The slurry was then combined with a propellant mixture containing 3,000 grams of Dymel 114 and 12,000 grams of Dymel 12.
- the formulation had the following composition:
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Abstract
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP90504385A JPH05508616A (ja) | 1989-02-23 | 1990-02-21 | 治療用エアロゾル剤 |
FI913899A FI913899A0 (fi) | 1989-02-23 | 1991-08-19 | Terapeutiska aerosolblandningar. |
NO91913298A NO913298L (no) | 1989-02-23 | 1991-08-22 | Terapeutisk aerosolpreparater. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US31460589A | 1989-02-23 | 1989-02-23 | |
US314,605 | 1989-02-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1990009781A1 true WO1990009781A1 (fr) | 1990-09-07 |
Family
ID=23220626
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1990/000928 WO1990009781A1 (fr) | 1989-02-23 | 1990-02-21 | Compositions aerosol therapeutiques |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0460064A4 (fr) |
JP (1) | JPH05508616A (fr) |
AU (1) | AU5194990A (fr) |
CA (1) | CA2050905A1 (fr) |
FI (1) | FI913899A0 (fr) |
WO (1) | WO1990009781A1 (fr) |
Cited By (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0562125A1 (fr) * | 1991-10-11 | 1993-09-29 | Toray Industries, Inc. | Composition a base d'anticorps |
US5354562A (en) * | 1992-01-21 | 1994-10-11 | Sri International | Process for preparing micronized polypeptide drugs |
WO1996031536A1 (fr) * | 1995-04-04 | 1996-10-10 | Zymogenetics, Inc. | Agents mimetiques synthetiques de la calcitonine |
WO1999007340A1 (fr) * | 1997-08-04 | 1999-02-18 | Boehringer Ingelheim Pharma Kg | Preparations d'aerosols aqueuses contenant des macromolecules biologiquement actives et procede de production des aerosols correspondants |
EP1123120A1 (fr) * | 1998-09-22 | 2001-08-16 | Aeropharm Technology Incorporated | Formulation d'aerosol medicinal |
WO2002005784A1 (fr) * | 2000-07-17 | 2002-01-24 | Aeropharm Technology, Inc. | Formulation medicinale d'aerosol |
US6464959B1 (en) | 2000-05-01 | 2002-10-15 | Aeropharm Technology Incorporated | Non-aqueous aerosol suspension comprising troglitazone, a fluid propellant, and an amino acid stabilizer |
US6468507B1 (en) | 2000-05-01 | 2002-10-22 | Aeropharm Technology, Inc. | Non-aqueous aerosol formulation comprising rosiglitazone maleate, a non-aqueous carrier, and an amino acid stabilizer |
US6540982B1 (en) | 2000-01-25 | 2003-04-01 | Aeropharm Technology Incorporated | Medical aerosol formulation |
US6540983B1 (en) | 2000-01-25 | 2003-04-01 | Aeropharm Technology Incorporated | Medical aerosol formulation |
US6548049B1 (en) | 2000-05-01 | 2003-04-15 | Aeropharm Technology Incorporated | Medicinal aerosol formulation |
US6565833B1 (en) | 2000-05-01 | 2003-05-20 | Aeropharm Technology Incorporated | Medicinal aerosol formulation |
US6585957B1 (en) | 2000-01-25 | 2003-07-01 | Aeropharm Technology Incorporated | Medicinal aerosol formulation |
WO2004020405A2 (fr) | 2002-08-30 | 2004-03-11 | Biorexis Pharmaceutical Corporation | Proteines de fusion de transferrine modifiees |
US6749845B2 (en) | 2001-02-15 | 2004-06-15 | Aeropharm Technology, Inc. | Modulated release particles for lung delivery |
EP1428524A1 (fr) * | 1995-04-14 | 2004-06-16 | Nektar Therapeutics | Administration pulmonaire de médicaments en aérosol |
US7481995B2 (en) * | 1998-04-03 | 2009-01-27 | University College Cardiff Consultants Limited | Aerosol composition |
WO2009015037A2 (fr) | 2007-07-21 | 2009-01-29 | Albany Molecular Research, Inc. | Indazoles substitués par du 5-pyridinone |
EP2088154A1 (fr) | 2004-03-09 | 2009-08-12 | Ironwood Pharmaceuticals, Inc. | Procédés et compositions pour le traitement de troubles gastro-intestinaux |
WO2010059836A1 (fr) | 2008-11-20 | 2010-05-27 | Decode Genetics Ehf | Composés bicycliques substitués à pont aza pour maladie cardiovasculaire et du système nerveux central |
WO2010084499A2 (fr) | 2009-01-26 | 2010-07-29 | Israel Institute For Biological Research | Composés spiro hétérocycliques bicycliques |
EP2476680A1 (fr) | 2008-01-11 | 2012-07-18 | Albany Molecular Research, Inc. | Pyridoindoles à substitution (1-azinone) |
EP2628727A2 (fr) | 2007-11-21 | 2013-08-21 | Decode Genetics EHF | Inhibiteurs de PDE4 biaryle pour le traitement de troubles pulmonaires et cardiovasculaires |
US9545487B2 (en) | 2012-04-13 | 2017-01-17 | Boehringer Ingelheim International Gmbh | Dispenser with encoding means |
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US9827384B2 (en) | 2011-05-23 | 2017-11-28 | Boehringer Ingelheim International Gmbh | Nebulizer |
US9943654B2 (en) | 2010-06-24 | 2018-04-17 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10004857B2 (en) | 2013-08-09 | 2018-06-26 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10011906B2 (en) | 2009-03-31 | 2018-07-03 | Beohringer Ingelheim International Gmbh | Method for coating a surface of a component |
US10016568B2 (en) | 2009-11-25 | 2018-07-10 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10099022B2 (en) | 2014-05-07 | 2018-10-16 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10124125B2 (en) | 2009-11-25 | 2018-11-13 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10124129B2 (en) | 2008-01-02 | 2018-11-13 | Boehringer Ingelheim International Gmbh | Dispensing device, storage device and method for dispensing a formulation |
US10195374B2 (en) | 2014-05-07 | 2019-02-05 | Boehringer Ingelheim International Gmbh | Container, nebulizer and use |
WO2019183245A1 (fr) | 2018-03-20 | 2019-09-26 | Icahn School Of Medicine At Mount Sinai | Composés inhibiteurs de kinase, compositions et procédés d'utilisation |
WO2020142485A1 (fr) | 2018-12-31 | 2020-07-09 | Icahn School Of Medicine At Mount Sinai | Composés inhibiteurs de kinase, compositions et procédés d'utilisation |
US10722666B2 (en) | 2014-05-07 | 2020-07-28 | Boehringer Ingelheim International Gmbh | Nebulizer with axially movable and lockable container and indicator |
US10966943B2 (en) | 2018-09-06 | 2021-04-06 | Innopharmascreen Inc. | Methods and compositions for treatment of asthma or parkinson's disease |
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GB9612297D0 (en) * | 1996-06-11 | 1996-08-14 | Minnesota Mining & Mfg | Medicinal aerosol formulations |
US8297305B2 (en) | 2008-01-28 | 2012-10-30 | Kohler Co. | Valve assembly having an improved flow path |
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US4690952A (en) * | 1984-11-26 | 1987-09-01 | Yamanouchi Pharmaceutical Co., Inc. | Pharmaceutical compositions for nasal administration comprising calcitonin and an absorption-promoting substance |
US4758550A (en) * | 1985-12-04 | 1988-07-19 | Sandoz Ltd. | Calcitonin derivatives |
US4895719A (en) * | 1985-05-22 | 1990-01-23 | Liposome Technology, Inc. | Method and apparatus for administering dehydrated liposomes by inhalation |
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BE556587A (fr) * | 1957-01-31 | 1957-04-11 | ||
US3169095A (en) * | 1962-10-30 | 1965-02-09 | Rexall Drug Chemical | Self-propelling powder-dispensing compositions |
JPS60161924A (ja) * | 1984-02-01 | 1985-08-23 | Fujisawa Pharmaceut Co Ltd | 肺吸収用組成物 |
US5059587A (en) * | 1987-08-03 | 1991-10-22 | Toyo Jozo Company, Ltd. | Physiologically active peptide composition for nasal administration |
-
1990
- 1990-02-21 JP JP90504385A patent/JPH05508616A/ja active Pending
- 1990-02-21 EP EP19900904101 patent/EP0460064A4/en not_active Withdrawn
- 1990-02-21 CA CA 2050905 patent/CA2050905A1/fr not_active Abandoned
- 1990-02-21 AU AU51949/90A patent/AU5194990A/en not_active Abandoned
- 1990-02-21 WO PCT/US1990/000928 patent/WO1990009781A1/fr not_active Application Discontinuation
-
1991
- 1991-08-19 FI FI913899A patent/FI913899A0/fi not_active Application Discontinuation
Patent Citations (5)
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WO1996031536A1 (fr) * | 1995-04-04 | 1996-10-10 | Zymogenetics, Inc. | Agents mimetiques synthetiques de la calcitonine |
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Also Published As
Publication number | Publication date |
---|---|
AU5194990A (en) | 1990-09-26 |
EP0460064A4 (en) | 1992-04-01 |
EP0460064A1 (fr) | 1991-12-11 |
CA2050905A1 (fr) | 1990-08-24 |
JPH05508616A (ja) | 1993-12-02 |
FI913899A0 (fi) | 1991-08-19 |
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