Claims for Patent: 7,556,798

Summary for Patent: 7,556,798

Title:	Highly efficient delivery of a large therapeutic mass aerosol
Abstract:	A method for delivering an agent to the pulmonary system, in a single, breath-activated step or a single breath, comprises administering from a receptacle enclosing a mass of particles, to a subject's respiratory tract, particles which have a tap density of less than 0.4 g/cm.sup.3 and deliver at least about 50% of the mass of particles. The particles are capable of carrying agents. The agent is (1) part of the spray-drying pre-mixture and thereby incorporated into the particles, (2) added to separately-prepared particles so that the agent is in chemical association with the particles or (3) blended so that the agent is mixed with, and co-delivered with the particles. Respirable compositions comprising carrier particles having a tap density of less than 0.4 g/cm.sup.3 and a composition comprising an agent are also disclosed. Methods of delivering these respirable compositions are also included.
Inventor(s):	Edwards; David A. (Boston, MA), Batycky; Richard P. (Newton, MA), Johnston; Lloyd (Belmont, MA)
Assignee:	Alkermes, Inc. (Cambridge, MA)
Application Number:	09/878,146
Patent Claims:	1. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the particles have a tap density of about 0.1 g/cm.sup.3 or less. 2. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the particles have a geometric diameter about 5 .mu.m or more. 3. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the receptacle has a volume of about 0.37 cm.sup.3 or more. 4. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the receptacle has a volume of about 0.48 cm.sup.3 or more. 5. The method of claim 4 wherein the receptacle has a volume of about 0.67 cm.sup.3 or more. 6. The method of claim 5 wherein the receptacle has a volume of about 0.95 cm.sup.3 or more. 7. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the agent is a bioactive agent and wherein administration to the respiratory tract is by a dry powder inhaler. 8. The method of claim 7 wherein the bioactive agent is albuterol sulfate. 9. The method of claim 7 wherein the bioactive agent is insulin. 10. The method of claim 7 wherein the bioactive agent is growth hormone. 11. The method of claim 7 wherein the bioactive agent is ipratropium bromide. 12. The method of claim 7 wherein the bioactive agent is fluticasone. 13. The method of claim 7 wherein the bioactive agent is salmeterol. 14. The method of claim 7 wherein the bioactive agent is L-Dopa. 15. The method of claim 7 wherein the bioactive agent is a hydrophobic drug. 16. The method of claim 7 wherein the bioactive agent is a hydrophilic drug. 17. The method of claim 7 wherein the bioactive agent is a monoclonal antibody. 18. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the particles are spray-dried particles. 19. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the particles are in the form of a dry powder. 20. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein administration to the respiratory tract is by a dry powder inhaler. 21. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the particles are non-polymeric and wherein administration to the respiratory tract is by a dry powder inhaler. 22. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the particles have a dynamic bulk density greater than 0.1 g/cm.sup.3 and wherein administration to the respiratory tract is by a dry powder inhaler. 23. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the agent is non-crystalline and wherein administration to the respiratory tract is by a dry powder inhaler. 24. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the agent is incorporated into the particles and wherein administration to the respiratory tract is by a dry powder inhaler. 25. The method of claim 24 wherein the agent is incorporated into the particles by a spray drying process. 26. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the agent adheres to the surface of the particles and wherein administration to the respiratory tract is by a dry powder inhaler. 27. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the agent adsorbs to the surface of the particles and wherein administration to the respiratory tract is by a dry powder inhaler. 28. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein at least one additional agent is administered with the particles and wherein administration to the respiratory tract is by a dry powder inhaler. 29. The method of claim 28 wherein the at least one additional agent is incorporated into the particles, adheres to the surface of the particles or adsorbs on to the surface of the particles. 30. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein at least 50% of the particles have a fine particle fraction less than 4.0 .mu.m and wherein administration to the respiratory tract is by a dry powder inhaler. 31. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; wherein the particles have a tap density of less than 0.4 g/cm.sup.3 and wherein administration to the respiratory tract is by a dry powder inhaler. 32. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; and ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; and iii) at least 75% of the particles have a fine particle fraction less than 6.8 .mu.m. 33. A method of delivering an agent to the pulmonary system, in a single, breath-activated step, comprising administering particles comprising an agent from a receptacle having a mass consisting of said particles to a subject's respiratory tract, wherein: i) about 50% or more of the mass of particles stored in the receptacle is delivered to the pulmonary system of the subject; ii) about 5 milligrams or more of the agent is delivered to the pulmonary system of the subject; iii) at least 50% of the particles have a fine particle fraction less than 4.0 .mu.m; and iv) at least 75% of the particles have a fine particle fraction less than 6.8 .mu.m.