Claims
- 1. A method for preparing dispersible dry powders of biological macromolecules, said method comprising:
providing an evaporable liquid medium containing a predetermined concentration of the macromolecule and excipients; atomizing the liquid medium under conditions selected to form droplets having an average size below predetermined maximum; drying the droplets under conditions selected to form dispersible particles of the composite material containing the biological macromolecules, said particles having a moisture content below a predetermined moisture content, and collecting the particles with high yields.
- 2. A method as in claim 1, wherein the total solids content in the liquid medium is below 10% by weight.
- 3. A method as in claim 2, wherein the concentration of macromolecule is in the range from 1% to 5% by weight.
- 4. A method as in claim 1, wherein the liquid medium comprises an aqueous medium.
- 5. A method as in claim 1, wherein the maximum mean droplet size is 11 μm.
- 6. A method as in claim 5, wherein the atomizing step comprises flowing the liquid medium and an atomization gas stream through a two fluid nozzle at a predetermined gas:liquid mass flow ratio.
- 7. A method as in claim 6, wherein the gas:liquid mass flow ratio is above 5.
- 8. A method as in claim 7, wherein the fluid nozzle has a liquid orifice diameter in the range from 0.015 in.to 0.075 in.and wherein the air pressure upstream of the orifice is maintained above 25 psi.
- 9. A method as in claim 1, wherein the droplets are dried to form particles having a moisture content below 10% by weight.
- 10. A method as in claim 9, wherein the drying step comprises flowing the droplets in a heated gas stream.
- 11. A method as in claim 10, wherein the droplets are flowed concurrently with the gas stream and wherein the gas stream has an inlet temperature above 90° C.
- 12. A method as in claim 11, wherein the gas stream has an inlet temperature above 90° C. and an outlet temperature above 50° C.
- 13. A method as in claim 1, wherein the droplets are dried under conditions selected to provide particles having a rugosity measured by air permeability above 2.
- 14. A method as in claim 1, wherein the drying step produces a powder having at least 90% of the mass of particles in the size range from 0.4 μm to 5 μm and the particle collecting step comprises separating substantially the entire particle output of the drying step from the gas stream.
- 15. A method as in claim 14, further comprising packaging a portion of the separated particles in a container, wherein the particles have not been size classified prior to packaging.
- 16. A method as in claim 15, wherein the portion is packaged in a unit dosage container.
- 17. A method as in claim 1, wherein the particle separating step comprises passing substantially the entire gas stream through a separator which removes at least about 90% by weight of all particles having a size above 1 μm from said gas stream.
- 18. A method as in claim 17, wherein the separator is a sintered metal fiber filter.
- 19. A method as in claim 17, wherein the separator is a bag filter, cartridge filter, or cloth filter.
- 20. A method as in claim 17, wherein the separator is a high efficiency cyclone.
- 21. A method as in claim 1, wherein the macromolecule is selected from the list of macromolecules set forth in Table 1.
- 22. A macromolecule composition prepared by the method of claim 1.
- 23. A dispersible macromolecule composition for inhalation into the alveolar regions of the lung, said composition comprising particles having an average particle size below 5 μm and a rugosity measured by air permeametry above 2.
- 24. A dispersible macromolecule composition as in claim 23, wherein the macromolecule is a protein, a nucleic acid, or a high molecular weight polysaccharide.
- 25. A dispersible macromolecule composition as in claim 24, wherein the macromolecule is a protein selected from the group consisting of proteins set forth in Table 1.
- 26. A dispersible macromolecule composition as in claim 25, wherein the protein is insulin.
- 27. A dispersible macromolecule composition as in claim 23, wherein the particles further comprise a carrier.
- 28. A dispersible macromolecule composition as in claim 23, wherein the particles have a moisture content below 10% by weight.
- 29. A dispersible macromolecule composition as in claim 23, wherein over 90% by weight of the composition comprises particles having a particle size in the range from 0.1 μm to 7 μm.
- 30. A unit dose of a macromolecule comprising a unit dose receptacle having a therapeutically effective amount of a macromolecule composition as in claim 23 therein.
CROSS REFERENCES TO RELATED APPLICATIONS
[0001] The present application is a continuation of application number 08/644,681, filed on May 8, 1996, which is a continuation-in-part of application Ser. No. 08/423,515, filed on Apr. 14, 1995, and is also a continuation-in-part of application Ser. No. 08/383,475, filed on Feb. 1, 1995, which is a continuation-in-part of application Ser. No. 08/207,472, filed on Mar. 7, 1994, now abandoned. The full disclosures of each of these applications are incorporated herein by reference.
Continuations (2)
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09498397 |
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10007868 |
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08644681 |
May 1996 |
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09498397 |
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Continuation in Parts (3)
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08423515 |
Apr 1995 |
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08644681 |
May 1996 |
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08383475 |
Feb 1995 |
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08423515 |
Apr 1995 |
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08207472 |
Mar 1994 |
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08383475 |
Feb 1995 |
US |