Claims
- 1. A method for delivery via the pulmonary system comprising:
administering to the respiratory tract of a patient in need of treatment, prophylaxis or diagnosis an effective amount of particles comprising: a bioactive agent in association with a charged lipid wherein the charged lipid has an overall net positive charge, the agent has an overall net negative charge upon association and wherein release of the agent is sustained.
- 2. The method of claim 1, wherein association of the agent and charged lipid comprises an ionic complexation.
- 3. The method of claim 2, wherein association of the lipid and agent further comprises hydrogen bonding.
- 4. The method of claim 1, wherein the charge ratio of lipid to bioactive agent is from about 0.25:1 to about 1:0.25.
- 5. The method of claim 4, wherein the charge ratio of lipid to bioactive agent is from about 0.5:1 to about 1:0.5.
- 6. The method of claim 5, wherein the charge ratio of lipid to bioactive agent is about 1:1.
- 7. The method of claim 1, wherein the bioactive agent is a protein.
- 8. The method of claim 7, wherein the protein is insulin.
- 9. The method of claim 8, wherein the sustained release is at least about 6 hours post administration.
- 10. The method of claim 1, wherein the lipid is a 1,2-diacyl-sn-glycero-3-alkylphosphocholine or a 1,2-diacyl-sn-glycero-3-alkyllphosphoalkanolamine.
- 11. The method of claim 10 wherein the 1,2-diacyl-sn-glycero-3-alkylphosphocholine lipid is represented by Formula III:
- 12. The method of claim 10, wherein the 1,2-diacyl-sn-glycero-3-alkylphosphocholine is 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine(DPePC), 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine(DMePC), 1,2-distearoyl-sn-glycero-3-ethylphosphocholine(DSePC), 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine (DLePC), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine(DOePC) or any combination thereof.
- 13. The method of claim 10, wherein the 1,2-diacyl-sn-glycero-3-alkylphosphoalkanolamine is represented by Formula IV:
- 14. The method of claim 10, wherein the 1,2-diacyl-sn-glycero-3-alkylphosphoalkanolamine is 1,2-dipalmitoyl-sn-glycero-3-ethylethanolamine(DPePE), 1,2-dimyristoyl-sn-glycero-3-ethylphosphoethanolamine(DMePE), 1,2-distearoyl-sn-glycero-3-ethylphosphoethanolamine(DSePE), 1,2-dilauroyl-sn-glycero-3-ethylphosphoethanolamine (DLePE), 1,2-dioleoyl-sn-glycero-3-ethylphosphoethanolamine(DOePE) or any combination thereof.
- 15. The method of claim 1 wherein the particles have a tap density less than about 0.4 g/cm3.
- 16. The method of claim 15, wherein the particles have a tap density less than about 0.1 g/cm3.
- 17. The method of claim 1, wherein the particles have a median geometric diameter of from about 5 micrometers and about 30 micrometers.
- 18. The method of claim 1, wherein the particles have an aerodynamic diameter of from about 1 to about 5 microns.
- 19. The method of claim 18, wherein the particles have an aerodynamic diameter of from about 1 to about 3 microns.
- 20. The method of claim 18, wherein the particles have an aerodynamic diameter of from about 3 to about 5 microns.
- 21. The method of claim 1, wherein delivery to the pulmonary system includes delivery to the deep lung.
- 22. The method of claim 1, wherein delivery to the pulmonary system includes delivery to the central airways.
- 23. The method of claim 1, wherein delivery to the pulmonary system includes delivery to the upper airways.
- 24. The method of claim 1, wherein the particles further comprise a lipid having no overall net charge.
- 25. The method of claim 1 wherein the particles further comprise a carboxylic acid or salt thereof.
- 26. The method of claim 25, wherein the carboxylic acid includes at least two carboxyl groups.
- 27. The method of claim 1, wherein the particles further comprise a multivalent metal salt or ionic components thereof.
- 28. The method of claim 27, wherein the multivalent salt is a salt of an alkaline earth metal.
- 29. The method of claim 1, wherein the particles further comprise an amino acid.
- 30. The method of claim 29, wherein the amino acid is hydrophobic.
- 31. The method of claim 30, wherein the hydrophobic amino acid is leucine, isoleucine, alanine, valine, phenylalanine or any combination thereof.
- 32. A method for delivery via the pulmonary system comprising:
administering to the respiratory tract of a patient in need of treatment an effective amount of particles comprising: insulin in association with a charged lipid wherein the charged lipid has an overall net positive charge which is opposite to the overall net negative charge of the insulin upon association and wherein release of the insulin is sustained.
- 33. The method of claim 32, wherein the lipid is a 1,2-diacyl-sn-glycero-3-alkylphosphocholine or a 1,2-diacyl-sn-glycero-3-alkyllphosphoalkanolamine.
- 34. The method of claim 33, wherein the 1,2-diacyl-sn-glycero-3-alkylphosphocholine is 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine(DPePC), 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine(DMePC), 1,2-distearoyl-sn-glycero-3-ethylphosphocholine(DSePC), 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine (DLePC), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine(DOePC) or any combination thereof.
- 35. The method of claim 33, wherein the 1,2-diacyl-sn-glycero-3-alkyllphosphoalkanolamine is 1,2-dipalmitoyl-sn-glycero-3-ethylethanolamine(DPePE), 1,2-dimyristoyl-sn-glycero-3-ethylphosphoethanolamine(DMePE), 1,2-distearoyl-sn-glycero-3-ethylphosphoethanolamine(DSePE), 1,2-dilauroyl-sn-glycero-3-ethylphosphoethanolamine (DLePE), 1,2-dioleoyl-sn-glycero-3-ethylphosphoethanolamine(DOePE) or any combination thereof.
- 36. The method of claim 32, wherein association of the agent and charged lipid comprises an ionic complexation.
- 37. The method of claim 36, wherein association of the lipid and agent further comprises hydrogen bonding.
- 38. The method of claim 32, wherein the charge ratio of lipid to bioactive agent is from about 0.25:1 to about 1:0.25.
- 39. The method of claim 38, wherein the charge ratio of lipid to bioactive agent is from about 0.5:1 to about 1:0.5.
- 40. The method of claim 39, wherein the charge ratio of lipid to bioactive agent is about 1:1.
- 41. The method of claim 32, wherein the particles further comprise a carboxylic acid.
- 42. The method of claim 32, wherein the particles further comprise an amino acid.
- 43. The method of claim 32, wherein the particles further comprise a lipid with no overall net charge.
- 44. The method of claim 32, wherein the particles further comprise a multivalent metal salt or ionic components thereof.
- 45. The method of claim 32, wherein delivery to the pulmonary system includes delivery to the deep lung.
- 46. The method of claim 32, wherein delivery to the pulmonary system includes delivery to the central airways.
- 47. The method of claim 32, wherein delivery to the pulmonary system includes delivery to the upper airways.
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser. No. 09/752,109, filed Dec. 29, 2000, which relates to application Ser. Nos. 09/337,245, filed on Jun. 22, 1999, 09/383,054, filed on Aug. 25, 1999, 09/382,959, filed on Aug. 25, 1999, 09/644,320, filed on Aug. 23, 2000, 09/665,252 filed on Sep. 19, 2000, 09/644,105, filed on Aug. 23, 2000, 09/644,736 filed on Aug. 23, 2000 and 09/591,307 filed on Jun. 9, 2000.
[0002] This application also relates to application Ser. No. 09/394,233 filed on Sep. 13, 1999, which is a continuation of application Ser. No. 08/971,791 filed on Nov. 17, 1997, now U.S. Pat. No. 5,985,309.
[0003] The entire contents of the above-reference applications are hereby incorporated by reference.
Continuations (1)
|
Number |
Date |
Country |
Parent |
09752109 |
Dec 2000 |
US |
Child |
10202616 |
Jul 2002 |
US |