Title:
NONAQUEOUS SOLUTIONS AND SUSPENSIONS OF MACROMOLECULES FOR PULMONARY DELIVERY
Document Type and Number:
WIPO Patent Application WO/2000/042993
Kind Code:
A2
Abstract:
Methods and formulations for delivery of macromolecules, such as proteins, polysaccharides, and nucleic acids, are disclosed, where the macromolecule is dissolved or dispersed in a low toxicity organic solvent which can be aerosolized for delivery to a patient's lungs by inhalation. Optionally, appropriate solubility enhancers are also present in the formulations composition.
Inventors:
KLIBANOV ALEXANDER M
Application Number:
PCT/US2000/000957
Publication Date:
July 27, 2000
Filing Date:
January 14, 2000
Export Citation:
Assignee:
MASSACHUSETTS INST TECHNOLOGY (US)
International Classes:
A61K9/00; A61K9/14; A61K9/72; A61K31/00; A61K38/00; A61K48/00; A61L9/04; A61P11/00; (IPC1-7): A61K9/72
Domestic Patent References:
| WO1994008599A1 | 1994-04-28 | |||
| WO1990009167A1 | 1990-08-23 |
Foreign References:
| US3632743A | 1972-01-04 | |||
| US5536444A | 1996-07-16 |
Attorney, Agent or Firm:
Pabst, Patrea L. (LLP 2800 One Atlantic Center 1201 West
Peachtree Street Atlanta, GA, US)
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Claims:
What is claimed is:
| 1. | A formulation for pulmonary delivery of a bioactive agent comprising a solution or suspension of a bioactive agent to be delivered in a biocompatible organic solvent suitable for aerosolization of the bioactive molecule. |
| 2. | The formulation of claim 1 wherein the bioactive agent is a therapeutic, diagnostic or prophylactic agent. |
| 3. | The composition of claim 1 wherein the bioactive agent is a macromolecule selected from the group consisting of proteins, peptides, polysaccharides, oligosaccharides, and nucleic acid molecules. |
| 4. | The formulation of claim 2 wherein the biological agent is selected from the group consisting of vasoactive agents, neuroactive agents, hormones, anticoagulants, immunomodulating agents, cytotoxic agents, prophylactic agents, antibiotics, antivirals, antisense, antigens, and antibodies. |
| 5. | The formulation of claim 1 wherein the bioactive agent is for the treatment of a pulmonary disease or disorder. |
| 6. | The formulation of claim 1 wherein the bioactive agent is selected from the group consisting of insulin, calcitonin, human growth hormone, EPO, DNAse, gonadotropinreleasing hormone, granulocyte colonystimulating factor, parathyroid hormonerelated peptide, somatostatin, testosterone, progesterone, and estradiol, nicotine, fentanyl, norethisterone, clonidine, scopolomine, salicylate, cromolyn sodium, salmeterol, formeterol, albuterol, and valium. |
| 7. | The formulation of claim 1 wherein the solvent is selected from the group consisting of ethanol, acetone, ethyl acetate, tetrahydofuran, ethyl ether, and propanol. |
| 8. | The formulation of claim 1 wherein the bioactive agent is present in solution or suspension at a concentration up to about 500 mg/ml. |
| 9. | The formulation of claim 8 wherein the bioactive agent is present as a suspension. |
| 10. | The formulation of claim 1 further comprising an agent selected from the group consisting of surfactants which enhance solubility of the bioactive agent, inorganic salts and viscosity modifying agents. |
| 11. | A method of delivery of a bioactive agent comprising administering to a patient an aerosol formulation of a solution or suspension of the bioactive agent in a biocompatible organic solvent. |
| 12. | A method of manufacture of a composition comprising a bioactive agent dissolved or suspended in an organic solvent wherein the method comprises: (a) selecting the bioactive agent to be delivered, (b) mixing the bioactive agent with a biocompatible organic solvent suitable for aerosol formation of the composition, and (c) forming an aerosol of the bioactive agent composition. |
| 13. | The method of claim 12 wherein the bioactive agent is lysophilized prior to mixing with the solvent. |
Description:
INTERNATIONALSEARCHREPORT <----------------- Ins. tional ApplicationNo PCT/US00/00957 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category Citationofdocument,withindication,whereappropriate,oftherele
vantpassagesRelevanttoclaimNo. AUS5536444A(H.HETTCHEETAL.)1-13 16July1996(1996-07-16) claims1,16,19 column5,line35-line66 column6,line16-line24 example1 AWO9009167A(CALIFORNIABIOTECHNOLOGY1-13 INC.,U.S.A.)23August1990(1990-08-23) claims 1 INTERNATIONALSEARCHREPORT ! nh. tiona) ApplicationNo Information on patent family members PCT/US 00/00957 PatentdocumentPublicabon Patent family Publicaton citedinsearchreportdate member(s)date US3632743A04-01-1972BE 717820 A 09-01-1969 DE 1767927 A 30-09-1971 FR 8155 M 24-08-1970 FR 8156 M 24-08-1970 GB 1230472 A 05-05-1971 IE 32559 B 19-09-1973 MY 21074 A 31-12-1974 NL 6809695 A 14-01-1969 WO9408599A28-04-1994AU 5171293 A 09-05-1994 US 5981474 A 09-11-1999 US 5770559 A 23-06-1998 US5536444A16-07-1996DE 4322703 A 12-01-1995 AT 183077 T 15-08-1999 DE 59408608 D 16-09-1999 EP 0633019 A 11-01-1995 ES 2136680 T 01-12-1999 JP 7070557 A 14-03-1995 WO9009167A23-08-1990US 5011678 A 30-04-1991 AU 5159490 A 05-09-1990
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