The present invention is based, in part, on the unexpected discovery that particles for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent that comprise a phospholipid and a sufficient amount of leucine can produce sustained effect of the agent. Specifically, particles for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent that contain a phospholipid or combination of phospholipids, wherein the phospholipid or combination of phospholipids is present in the particles in an amount of about 1 to 46 weight percent; and leucine, wherein leucine is present in the particles in an amount of at least 46 weight percent, can contribute to sustained effect of the agent. Particles that comprise at least 46 weight percent leucine but that do not contain phospholipids do not exhibit these same sustained effect properties.
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 9/00 - Medicinal preparations characterised by special physical form
2.
RESPIRABLE POLYNUCLEOTIDE POWDER FORMULATIONS FOR INHALATION
The invention provides respirable dry powder particle formulations comprising polynucleotides preferably prepared by spray drying for delivery to the pulmonary system via inhalation. Preferably, the polynucleotide is RNA.
The present invention is directed respirable, dry powder particle formulations of lung surfactants that optionally comprise surfactant proteins and that are formulated for delivery to the pulmonary system via inhalation.
A61J 3/07 - Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
A61K 9/72 - Medicinal preparations characterised by special physical form for smoking or inhaling
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present invention is directed respirable, dry powder particle formulations of lung surfactants that optionally comprise surfactant proteins and that are formulated for delivery to the pulmonary system via inhalation.
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present invention is directed respirable, dry powder particle formulations of lung surfactants that optionally comprise surfactant proteins and/or polypeptide and that are formulated for delivery to the pulmonary system via inhalation.
The present invention is directed respirable, dry powder particle formulations of lung surfactants that optionally comprise surfactant proteins and that are formulated for delivery to the pulmonary system via inhalation.
A61P 11/00 - Drugs for disorders of the respiratory system
A61K 31/685 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
The invention provides stable, spray-dried, particle formulations containing a triptan, preferably sumatriptan, or a pharmaceutically acceptable salt thereof, which are useful for pulmonary administration to the respiratory tract of a patient for the treatment of disease.
The invention provides stable, spray-dried, particle formulations containing a triptan, preferably sumatriptan, or a pharmaceutically acceptable salt thereof, which are useful for pulmonary administration to the respiratory tract of a patient for the treatment of disease.
The invention provides powder formulations containing zolmitriptan, or a pharmaceutically acceptable salt thereof, which are useful for pulmonary administration to the respiratory tract of a patient for the treatment of disease.
The invention provides stable, spray- dried, particle formulations containing rapamycin, or pharmaceutically acceptable salts of rapamycin, which are useful for pulmonary administration to the respiratory tract of a patient for the treatment of disease.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
The invention provides stable, spray- dried, particle formulations containing rapamycin, or pharmaceutically acceptable salts of rapamycin, which are useful for pulmonary administration to the respiratory tract of a patient for the treatment of disease.
A61K 9/72 - Medicinal preparations characterised by special physical form for smoking or inhaling
A61K 31/436 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
12.
RAPID RELIEF OF MOTOR FLUCTUATIONS IN PARKINSON'S DISEASE
The present invention provides methods for treating OFF episodes in a Parkinson's Disease patient comprising administering levodopa to the pulmonary system of a patient wherein after administration, the patient's Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 score is improved by, for example, at least about 5 points as compared to placebo control and/or as compared to the patient's UDPRS Part 3 score prior to administration. The invention also provides methods of reducing mean daily OFF time in a Parkinson's patient.
A device (100) for puncturing a capsule (219) to release a powdered medicament therefrom includes a chamber (210) for receiving the capsule. The capsule includes opposing domes and a cylindrical wall portion defined by a capsule wall radius r. The device further includes a mechanism (230) for puncturing at least one hole in at least one dome. A center of each hole is located within an annular puncture region situated at no less than 0.4r, and a total surface area of all puncture holes is between about 0.5% and about 2.2% of a total surface area of the capsule. The annular puncture region may, for example, be situated between about 0.4r and about 0.8r, or between about 0.4r and about 0.6r.
A device (100) for puncturing a capsule (219) to release a powdered medicament therefrom includes a chamber (210) for receiving the capsule. The capsule includes opposing domes and a cylindrical wall portion defined by a capsule wall radius r. The device further includes a mechanism (230) for puncturing at least one hole in at least one dome. A center of each hole is located within an annular puncture region situated at no less than 0.4r, and a total surface area of all puncture holes is between about 0.5% and about 2.2% of a total surface area of the capsule. The annular puncture region may, for example, be situated between about 0.4r and about 0.8r, or between about 0.4r and about 0.6r.
The present invention provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L. The invention further provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L wherein the capsule's shell comprises hydroxypropylmethylcellulose (HPMC) and titanium dioxide.
The invention provides pharmaceutical compositions for pulmonary delivery comprising particles containing a pharmaceutical agent and having a geometric size of greater than about 5 µm and a tap density of less than about 0.075 g/cm3. The invention also provides methods for delivering the pharmaceutical compositions of the invention to the respiratory tract of a patient.
The present invention provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L. The invention further provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L wherein the capsule's shell comprises hydroxypropylmethylcellulose (HPMC) and titanium dioxide.
The invention provides pharmaceutical compositions for pulmonary delivery comprising particles containing a pharmaceutical agent and having a geometric size of greater than about 5 μm and a tap density of less than about 0.075 g/cm3. The invention also provides methods for delivering the pharmaceutical compositions of the invention to the respiratory tract of a patient.
The present invention provides a dosator apparatus and methods for dispensing low density, high flowing powders into capsules at high target fill weights with accuracy and repeatability.
B65B 1/04 - Methods of, or means for, filling the material into the containers or receptacles
B65B 31/00 - Packaging articles or materials under special atmospheric or gaseous conditionsAdding propellants to aerosol containers
B65B 43/42 - Feeding or positioning bags, boxes, or cartons in the distended, opened, or set-up stateFeeding preformed rigid containers, e.g. tins, capsules, glass tubes, glasses, to the packaging positionLocating containers or receptacles at the filling positionSupporting containers or receptacles during the filling operation
20.
LEVODOPA FORMULATIONS FOR RAPID RELIEF OF PARKINSON'S DISEASE
The present invention provides methods of providing rapid relief of motor fluctuations in a Parkinson's disease patient. The methods of the invention comprise pulmonary administration of levodopa by inhalation at therapeutically effective concentrations such that the patient's plasma levodopa concentration increases by at least about 200 ng/ml within 10 minutes or less post inhalation as compared to the concentration of levodopa in the patient's plasma prior to inhalation of the levodopa and wherein the patient's plasma concentration remains increased by at least about 200 ng/ml for a time period of at least 15 minutes after inhalation. The methods of the invention are particularly useful for treatment of motor fluctuations which arise as a result of poorly controlled levodopa plasma levels in a patient.
The present invention provides methods of providing rapid relief of motor fluctuations in a Parkinson's disease patient. The methods of the invention comprise pulmonary administration of levodopa by inhalation at therapeutically effective concentrations such that the patient's plasma levodopa concentration increases by at least about 200 ng/ml within 10 minutes or less post inhalation as compared to the concentration of levodopa in the patient's plasma prior to inhalation of the levodopa and wherein the patient's plasma concentration remains increased by at least about 200 ng/ml for a time period of at least 15 minutes after inhalation. The methods of the invention are particularly useful for treatment of motor fluctuations which arise as a result of poorly controlled levodopa plasma levels in a patient.
The present invention provides methods of reducing the inter-patient variability of levodopa plasma concentrations in a population of Parkinson's disease patients. The methods of the invention comprise pulmonary administration of levodopa at therapeutically effective concentrations such that the inter-patient variability of levodopa plasma concentrations at time periods ranging from about 10 minutes post inhalation to about 60 minutes or more post inhalation have less than a 50% coefficient variation. The methods of the invention are particularly useful for treatment of motor fluctuations which arise as a side effect of L-Dopa therapy.
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