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 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à cinq chaînons avec un azote comme seul hétéro-atome d'un cycle, p. ex. sulpiride, succinimide, tolmétine, buflomédil
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
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 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.
A61K 47/24 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite contenant des atomes autres que des atomes de carbone, d'hydrogène, d'oxygène, d'halogènes, d'azote ou de soufre, p. ex. cyclométhicone ou phospholipides
A61K 9/72 - Préparations médicinales caractérisées par un aspect particulier à fumer ou inhaler
A61K 47/42 - ProtéinesPolypeptidesLeurs produits de dégradationLeurs dérivés p. ex. albumine, gélatine ou zéine
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
C07K 14/785 - Peptides du surfactif alvéolairePeptides du surfactif pulmonaire
A61J 3/07 - Dispositifs ou procédés spécialement conçus pour donner à des produits pharmaceutiques une forme physique déterminée ou une forme propre à leur administration la forme de capsules ou de petits conteneurs similaires à absorber par voie buccale
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.
A61K 47/24 - Composés organiques, p. ex. hydrocarbures naturels ou synthétiques, polyoléfines, huile minérale, gelée de pétrole ou ozocérite contenant des atomes autres que des atomes de carbone, d'hydrogène, d'oxygène, d'halogènes, d'azote ou de soufre, p. ex. cyclométhicone ou phospholipides
A61K 9/72 - Préparations médicinales caractérisées par un aspect particulier à fumer ou inhaler
C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères
C07K 14/785 - Peptides du surfactif alvéolairePeptides du surfactif pulmonaire
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.
A61K 38/00 - Préparations médicinales contenant des peptides
C07K 14/435 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains
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 - Médicaments pour le traitement des troubles du système respiratoire
A61K 31/685 - Diesters d'acide du phosphore avec deux composés hydroxyle, p. ex. phosphatidylinositols un des composés hydroxylés ayant des atomes d'azote, p. ex. phosphatidylsérine, lécithine
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.
A61K 31/685 - Diesters d'acide du phosphore avec deux composés hydroxyle, p. ex. phosphatidylinositols un des composés hydroxylés ayant des atomes d'azote, p. ex. phosphatidylsérine, lécithine
A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
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 - Préparations médicinales caractérisées par un aspect particulier
A61K 31/436 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle condensés en ortho ou en péri avec des systèmes hétérocycliques le système hétérocyclique contenant un cycle à six chaînons ayant l'oxygène comme hétéro-atome du cycle, p. ex. rapamycine
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 - Préparations médicinales caractérisées par un aspect particulier à fumer ou inhaler
A61K 9/00 - Préparations médicinales caractérisées par un aspect particulier
A61K 9/14 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres
A61K 31/436 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle condensés en ortho ou en péri avec des systèmes hétérocycliques le système hétérocyclique contenant un cycle à six chaînons ayant l'oxygène comme hétéro-atome du cycle, p. ex. rapamycine
15.
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.
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 for puncturing a capsule to release a powdered medicament therefrom includes a chamber 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 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.
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 - Procédés ou moyens pour remplir les réceptacles ou les récipients avec le matériau
B65B 1/00 - Emballage de matériaux solides fluents, p. ex. de poudres, de matériaux fibreux granulés ou en vrac, de masses en vrac de petits objets, dans des réceptacles ou récipients individuels, p. ex. sacs ou sachets, boîtes, cartons, bidons ou pots
B65B 31/00 - Emballage d'objets ou de matériaux dans des conditions atmosphériques ou gazeuses particulièresAddition de propergols à des réceptacles pour aérosols
B65B 43/42 - Alimentation ou positionnement des sacs, boîtes ou cartons en position dilatée, ouverte ou deboutAlimentation des réceptacles préformés rigides, p. ex. boîtes en fer-blanc, capsules, tubes en verre, flacons, vers la position d'empaquetageMise en place des réceptacles ou récipients au poste de remplissageMaintien des réceptacles ou récipients pendant le remplissage
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 - Procédés ou moyens pour remplir les réceptacles ou les récipients avec le matériau
B65B 31/00 - Emballage d'objets ou de matériaux dans des conditions atmosphériques ou gazeuses particulièresAddition de propergols à des réceptacles pour aérosols
B65B 43/42 - Alimentation ou positionnement des sacs, boîtes ou cartons en position dilatée, ouverte ou deboutAlimentation des réceptacles préformés rigides, p. ex. boîtes en fer-blanc, capsules, tubes en verre, flacons, vers la position d'empaquetageMise en place des réceptacles ou récipients au poste de remplissageMaintien des réceptacles ou récipients pendant le remplissage
26.
REDUCING INTER-PATIENT VARIABILITY OF LEVODOPA PLASMA CONCENTRATIONS
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.
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.
brevets
