Patent EA-005025-B1 (EA)
Title: Dry power inhalation system transpulmonary administration
Inventor: YAMASHITA CHIKAMASA
IPC: A61K9/19
Filed: 2002-06-14
Abstract: 1. A dry powder inhalation system for transpulmonary administration, using a combination of: (1) a vessel housing a freeze-dried composition that contains a single dose of an active ingredient, and has: (i) a non-powder cake-like form, (ii) a disintegration index of 0.015 or more, and (iii) a property of becoming fine particles having a mean particle diameter of 10 microns or less or a fine particle fraction of 10% or more upon receiving an air impact having an air speed of at least 1 m/sec and an air flow rate of at least 17 ml/sec; and (2) a device comprising means capable of applying said air impact to the freeze-dried composition in said vessel, and means for discharging the powder-form freeze-dried composition that has been made into fine particles. 2. The dry powder inhalation system for transpulmonary administration according to claim 1, wherein the vessel and the device are used in combination at the time of inhalation. 3. The dry powder inhalation system for transpulmonary administration according to claim 1, wherein the disintegration index of the freeze-dried composition is 0.02 or more. 4. The dry powder inhalation system for transpulmonary administration according to claim 1, wherein the air impact of (iii) is generated by air having an air speed of at least 2 m/sec and an air flow rate of at least 17 ml/sec. 5. The dry powder inhalation system for transpulmonary administration according to claim 1, wherein the air impact of (iii) is generated by air having an air speed of at least 1 m/sec and an air flow rate of at least 20 ml/sec. 6. The powder inhalation system for transpulmonary administration according to claim 1, wherein the freeze-dried composition has a property of becoming fine particles having a mean particle diameter of 5 microns or less or a fine particle fraction of 20% or more upon receipt of an air impact. 7. The dry powder inhalation system for transpulmonary administration according to claim 1, wherein the freeze-dried composition contains a synthetic low-molecular-weight drug as the active ingredient. 8. The dry powder inhalation system for transpulmonary administration according to claim 1, wherein the freeze-dried composition contains a hight-molecular-weight drug as the active ingredient. 9. The dry powder inhalation system for transpulmonary administration according to claim 1, wherein the device is: i) a dry powder inhaler for transpulmonary administration, being a device used for making a freeze-dried composition that has been housed in non-powder form in a vessel into fine particles, and administering the resulting fine particles to a user by inhalation, comprising a needle part having an air jet flow path, a needle part having a discharge flow path, air pressure-feeding means for feeding air into the air jet flow path of said needle part, and an inhalation port that communicates with the discharge flow path of said needle part, and characterized by being constituted such that a stopper that seals up said vessel is pierced by said needle parts, thus communicating the air jet flow path and the discharge flow path with the inside of said vessel, and air is jetted into said vessel through said air jet flow path using said air pressure-feeding means, thus pulverizing said freeze-dried composition into fine particles by the impact of the jetted air, and discharging the fine particles obtained from the inhalation port via said discharge flow path, or ii) a dry powder inhaler for transpulmonary administration, being a device used for making a freeze-dried composition that has been housed in non-powder form in a vessel into fine particles, and administering the resulting fine particles to a user by inhalation, comprising a needle part having a suction flow path, a needle part having an air introduction flow path, and an inhalation port that communicates with said suction flow path, and characterized by being constituted such that, in a state in which a stopper sealing up said vessel has been pierced by said needle parts, through the inhalation pressure of the user, air in said vessel is inhaled from said inhalation port, and at the same time outside air flows into said vessel, at a negative pressure, through said air introduction flow path, and as a result said freeze-dried composition is pulverized into fine particles by the impact of the air flowing in, and the fine particles obtained are discharged from the inhalation port through said suction flow path. 10. The dry powder inhalation system for transpulmonary administration according to claim 1, using a combination of: (1) a vessel housing a freeze-dried composition that contains a single dose of an active ingredient, and has: (i) a non-powder cake-like form, (ii) a disintegration index in a range of 0.015 to 1.5, and (iii) a property of becoming fine particles having a mean particle diameter of 10 microns or less or a fine particle fraction of 10% or more upon receiving an air impact having an air speed in a range of 1 to 300 m/sec and an air flow rate in a range of 17 ml/sec to 15L/sec; and (2) a device comprising means capable of applying said air impact to the freeze-dried composition in said vessel, and means for discharging the powder-form freeze-dried composition that has been made into fine particles. 11. A freeze-dried composition for transpulmonary administration having the following properties (i) to (iii): (i) has a non-powder cake-like form, (ii) has a disintegration index of 0.015 or more, and (iii) becomes fine particles having a mean particle diameter of 10 microns or less or a fine particle fraction of 10% or more upon receipt of an air impact having an air speed of at least 1 m/sec and an air flow rate of at least 17 ml/sec. 12. The freeze-dried composition according to claim 11, wherein the disintegration index is 0.02 or more. 13. The freeze-dried composition according to claim 11, wherein the disintegration index is 0.015 to 1.5. 14. The freeze-dried composition according to claim 11, becoming fine particles having a mean particle diameter of 10 microns or less or a fine particle fraction of 10% or more upon receipt of an air impact having an air speed of at least 2 m/sec and an air flow rate of at least 17 ml/sec. 15. The freeze-dried composition according to claim 11, becoming fine particles having a mean particle diameter of 10 microns or less or a fine particle fraction of 10% or more upon receipt of an air impact having an air speed of at least 1 m/sec and an air flow rate of at least 20 ml/sec. 16. The freeze-dried composition according to claim 11, becoming fine particles having a mean particle diameter of 5 microns or less or a fine particle fraction of 20% or more upon receipt of the air impact. 17. The freeze-dried composition according to claim 11, containing a synthetic low-molecular-weight drug as an active ingredient. 18. The freeze-dried composition according to claim 11, containing a hight-molecular-weight drug as an active ingredient. 19. The freeze-dried composition according to claim 18, containing a hight-molecular-weight drug as the active ingredient, and at least one selected from the group consisting of amino acids, dipeptides, tripeptides, and saccharides as a carrier. 20. The freeze-dried composition according to claim 11, being a freeze-dried composition for transpulmonary administration having the following properties (i) to (iii): (i) has a non-powder cake-like form, (ii) has a disintegration index in a range of 0.015 to 1.5, and (iii) becomes fine particles having a mean particle diameter of 10 microns or less or a fine particle fraction of 10% or more upon receipt of an air impact having an air speed in a range of 1 to 300m/sec and an air flow rate in a range of 17 ml/sec to 15L/sec. 21. A dry powder inhaler for transpulmonary administration used for making a freeze-dried composition that has been housed in non-powder form in a vessel into fine particles by an air impact, and administering the resulting fine particles to a user by inhalation. 22. The dry powder inhaler for transpulmonary administration according to claim 21, being a device used for making a freeze-dried composition that has been housed in non-powder form in a vessel into fine particles, and administering the resulting fine particles to a user by inhalation, comprising a needle part having an air jet flow path, a needle part having a discharge flow path, air pressure-feeding means for feeding air into the air jet flow path of said needle part, and an inhalation port that communicates with the discharge flow path of said needle part, and being constituted such that a stopper that seals up said vessel is pierced by said needle parts, thus communicating the air jet flow path and the discharge flow path with the inside of said vessel, and air is jetted into said vessel through said air jet flow path using said air pressure-feeding means, thus making said freeze-dried composition into fine particles by the impact of the jetted air, and discharging the fine particles from the inhalation port via said discharge flow path. 23. The dry powder inhaler for transpulmonary administration according to claim 21, being a device used for pulverizing a freeze-dried composition that has been housed in non-powder form in a vessel into fine particles, and administering the resulting fine particles to a user by inhalation, comprising a needle part having a suction flow path, a needle part having an air introduction flow path, and an inhalation port that communicates with said suction flow path, and characterized by being constituted such that, in a state in which a stopper sealing up said vessel has been pierced by said needle parts, through the inhalation pressure of the user, air in said vessel is inhaled from said inhalation port, and at the same time outside air flows into said vessel, at a negative pressure, through said air introduction flow path, and as a result said freeze-dried composition is pulverized into fine particles