Preservation of bioactive materials by freeze dried foam

Abstract

This invention provides methods and compositions to preserve bioactive materials in a dried foam matrix. Methods provide non-boiling foam generation and penetration of preservative agents at temperatures near the phase transition temperature of the membranes.

What is claimed is: 
     
         1 - 40 . (canceled) 
     
     
         41 . A method for preparing a dry foam composition comprising a bioactive material, which method comprises:
 preparing a formulation comprising the bioactive material in a solvent, which solvent comprises a polyol or polymer;   reducing pressure on the formulation to a pressure between about 200 Torr and 25 Torr, whereby the formulation is expanded into a foam; and,   drying the foam by evaporating or sublimating the solvent from the foam;   
       thereby preparing a dry foam composition. 
     
     
         42 . The method of  claim 41 , wherein the bioactive material is selected from the group consisting of peptides, proteins, hormones, nucleic acids, antibodies, vaccines, bacteria, viruses, liposomes, platelets, and cell suspensions. 
     
     
         43 . The method of  claim 41 , wherein the bioactive material is live viruses selected from the group consisting of influenza virus, parainfluenza virus, AA V, adenovirus, respiratory syncytial virus, herpes simplex virus, cytomegalovirus, SARS virus, corona virus family members, human metapneumovirus, and Epstein-Barr virus. 
     
     
         44 . The method of  claim 41 , wherein the bioactive material comprises a lipid membrane, and wherein the method further comprises cooling the formulation to a phase transition temperature of the lipid membrane. 
     
     
         45 . The method of  claim 41 , wherein the polyol is present in an amount ranging from about 20 weight percent to about 45 weight percent. 
     
     
         46 . The method of  claim 41 , wherein the polymer is present in an amount ranging from about 1 weight percent to about 10 weight percent. 
     
     
         47 . The method of  claim 41 , wherein the polyol is selected from sucrose, trehalose, sorbose, melezitose, sorbitol, stachyose, raffinose, fructose, mannose, maltose, lactose, arabinose, xylose, ribose, rhamnose, galactose, glucose, mannitol, xylitol, erythritol, threitol, sorbitol, glycerol, or L-gluconate. 
     
     
         48 . The method of  claim 41 , wherein the polymer is selected from hydrolyzed gelatin, unhydrolyzed gelatin, collagen, chondroitin sulfate, a sialated polysaccharide, water soluble polymers, polyvinyl pyrrolidone, actin, myosin, microtubules, dynein, kinetin, or human serum albumin. 
     
     
         49 . (canceled) 
     
     
         50 . The method of  claim 41 , wherein the formulation comprises a surfactant or a buffer. 
     
     
         51 . The method of  claim 41 , wherein the bioactive material comprises a lipid membrane, and wherein the method further comprises cooling the formulation to a phase transition temperature of the lipid membrane. 
     
     
         52 . The method of  claim 51 , further comprising holding the formulation at the phase transition temperature for from about 10 minutes to about 60 minutes. 
     
     
         53 . The method of  claim 41 , further comprising increasing the temperature of the formulation to a drying temperature that is less than or about the glass transition temperature of the dry foam. 
     
     
         54 . The method of  claim 53 , further comprising holding the pressure below about 100 mTorr while the formulation is at the drying temperature. 
     
     
         55 . The method of  claim 41 , further comprising grinding the dry foam to a powder with an average particle size from about 0.1 μm to about 100 μm. 
     
     
         56 . The method of  claim 55 , wherein the powder comprises an average particle size from about 50 μm to about 100 μm. 
     
     
         57 . Use of the dry foam composition prepared by the method of  claim 41  in the preparation of a medicament to be administered to a mammal as a reconstituted liquid or as a ground powder. 
     
     
         58 . (canceled) 
     
     
         59 . A method for preparing a dry foam composition comprising a bioactive material, which method comprises:
 preparing a formulation comprising the bioactive material, a foaming agent, and a polyol or polymer in a solvent;   expanding the formulation into a foam by action of the foaming agent; and,   
       stabilizing or drying the foam by evaporating or sublimating the solvent from the foam; 
       thereby preparing a dry foam composition. 
     
     
         60 - 154 . (canceled)