Method of complexing a protein by the use of a dispersed system and proteins thereof

• US 20020127635A1
• Filed: 11/30/2001
• Published: 09/12/2002
• Est. Priority Date: 11/30/2000
• Status: Abandoned Application

• Current Assignee: The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: The Research Foundation for The State University of New York (State University of New York)
• Inventors: Straubinger, Robert M., Balasubramanian, Sathyamangalam V.
• Application Number:
  US10/000,226
• Publication Number:
  US 20020127635A1
• Time in Patent Office: Days
• US Class Current: 435/68.1
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 9/127 Liposomes

Abstract

A method for complexing a protein in a dispersed medium, includes: a) providing a protein, b) altering the conformational state of the protein to expose hydrophobic domains therein, c) binding a stabilizer to the exposed hydrophobic domains, and d) at least partially reversing the alteration to associate at least a portion of the protein with the stabilizer. A pharmaceutically effective stabilized protein dosage wherein from less than about 1% to greater than about 90% of the protein is associated by a stabilizer is also provided.

Claims

1. A method for complexing a protein in a dispersed medium, comprising:

a) providing a protein,

b) altering the conformational state of said protein to expose hydrophobic domains therein,

c) binding a stabilizer to said exposed hydrophobic domains, and

d) at least partially reversing said alteration to associate at least a portion of said protein with said stabilizer.

2. The method of claim 1, wherein said altering comprises contacting said protein with at least one of a chemical and physical perturabant.

3. The method of claim 2, wherein said chemical perturabant comprises organic solvent, urea, buffer having an acidic pH, or guandinium hydrochloride.

4. The method of claim 2, wherein said organic solvent comprises methanol, ethanol, glycerol, or ethylene glycol.

5. The method of claim 1, wherein said altering comprises contacting said protein with an ethanol-water mixture of from about 3% to about 80%.

6. The method of claim 1, wherein said protein comprises lysozome.

7. The method of claim 2, wherein said physical perturbant comprises thermal or pressure changes.

8. The method of claim 1, wherein said stabilizer comprises liposome.

9. The method of claim 1, wherein said reversing comprises cooling.

10. The method of claim 1, wherein said reversing comprises solvent removal.

11. The method of claim 1, wherein said reversing comprises dialysis.

12. The method of claim 1, wherein said altering comprises unfolding said protein.

13. The method of claim 1, wherein said reversing comprises refolding said protein.

14. The method of claim 1, wherein said association comprises encapsulation.

15. An associated protein produced by the method of claim 1.

17. The product of claim 16, further comprising a dispersed system medium.

18. The product of claim 16, wherein said stabilizer comprises liposome.

19. The product of claim 16, wherein greater than about 1% of the protein is associated.

20. The product of claim 16, wherein from greater than about 3% of the protein is associated.

21. The product of claim 16, wherein from about 80% to about 90% of the protein is associated.

22. The product of claim 16, wherein said association comprises encapsulation.

23. The product of claim 19, wherein said association comprises encapsulation.

24. The product of claim 20, wherein said association comprises encapsulation.

25. The product of claim 21, wherein said association comprises encapsulation.

16. A pharmaceutically effective stabilized protein dosage wherein from less than about 1% to greater than about 90% of the protein is associated with a stabilizer.