초록 ▼

Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cm3and a ma

Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cm3and a mass mean diameter between 5 μm and 30 μm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear α-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 μm, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

대표청구항 ▼

1. A mass of biocompatible particles, suitable for pulmonary delivery, comprising particles having therapeutic, prophylactic or diagnostic agent, and having a mass mean diameter of at least 6.5 μm and an aerodynamic diameter of less than 4 μm, wherein at least 46% of the mass of particles are deposi

1. A mass of biocompatible particles, suitable for pulmonary delivery, comprising particles having therapeutic, prophylactic or diagnostic agent, and having a mass mean diameter of at least 6.5 μm and an aerodynamic diameter of less than 4 μm, wherein at least 46% of the mass of particles are deposited after the first bifurcation of the lungs. 2. The particles of claim 1 wherein the particles have a mass mean diameter between 6.5 μm and 30 μm. 3. The particles of claim 1 wherein the particles have an aerodynamic diameter of less than 3 μm. 4. The particles of claim 1 wherein the agent is selected from the group consisting of proteins, polysaccharides, lipids, nucleic acids, beta agonists and combinations thereof. 5. The particles of claim 1 wherein the agent is selected from the group consisting of insulin, calcitonin, leuprolide, LHRH, granulocyte colony stimulating factor, parathyroid hormone-related peptide, somatostatin, testosterone, progesterone, estradiol, nicotine, fentanyl, norethisterone, clonidine, scopolomine, salicylate, cromolyn sodium, salmeterol, formeterol, albuterol, and vallium. 6. The particles of claim 1 wherein the particles further comprise a biodegradable material. 7. The particles of claim 6 wherein the biodegradable material is a polymeric material. 8. The particles of claim 6 wherein the biodegradable material is a non-polymeric material. 9. The particles of claim 1 wherein the particles have a tap density of less than about 0.4 g/cm3. 10. The particles of claim 9 wherein the particles have a tap density of less than about 0.1 g/cm3. 11. A method for delivery of a therapeutic, prophylactic or diagnostic agent to the pulmonary system comprising: administering to the respiratory tract of a patient in need of treatment, prophylaxis or diagnosis an effective amount of biocompatible particles, wherein the particles comprising a therapeutic, prophylactic or diagnostic agent, and have a mass mean diameter of at least 6.5 μm and an aerodynamic diameter of less than 4 μm, wherein 46% of the mass of said particles delivered are deposited after the first bifurcation of the lungs. 12. The method of claim 11 wherein the particles have a mass mean diameter between 6.5 μm and 30 μm. 13. The method of claim 11 wherein the particles have an aerodynamic diameter of less than 3 μm. 14. The method of claim 11 wherein the agent is selected from the group consisting of proteins, polysaccharides, lipids, nucleic acids, beta agonists and combinations thereof. 15. The method of claim 11 wherein the agent is selected from the group consisting of insulin, calcitonin, leuprolide, LHRH, granulocyte colony stimulating factor, parathyroid hormone-related peptide, somatostatin, testosterone, progesterone, estradiol, nicotine, fentanyl, norethisterone, clonidine, scopolomine, salicylate, cromolyn sodium, salmeterol, formeterol, albuterol, and vallium. 16. The method of claim 11 wherein the particles further comprise a biodegradable material. 17. The method of claim 16 wherein the biodegradable material is a polymeric material. 18. The method of claim 16 wherein the biodegradable material is a non-polymeric material. 19. The method of claim 11 wherein the particles have a tap density of less than about 0.4 g/cm3. 20. The method of claim 19 wherein the particles have a tap density of less than about 0.1 g/cm3. 21. The method of claim 11 wherein the agent is delivered to the deep lung. 22. The method of claim 11 wherein the agent is delivered to the central airways. 23. A particulate composition suitable for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent, comprising particles having a tap density less than 0.4 g/cm3,wherein more than 50% of the particles are respirable.