Adjuvant formulation comprising a submicron oil droplet emulson

• US 20030147898A1
• Filed: 09/17/2002
• Published: 08/07/2003
• Est. Priority Date: 05/25/1989
• Status: Abandoned Application

• Current Assignee: Gail Barchfeld, Gary Ott, Gary Van Nest
• Original Assignee: Gail Barchfeld, Gary Ott, Gary Van Nest
• Inventors: Ott, Gary, Van Nest, Gary, Barchfeld, Gail
• Application Number:
  US10/246,195
• Publication Number:
  US 20030147898A1
• Time in Patent Office: Days
• US Class Current: 424/184.1
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 977/802 Virus-based particle
• CPC Class Codes: Y10S 977/918 Immunological

Abstract

An adjuvant composition, comprising a metabolizable oil and an emulsifying agent, wherein the oil and the detergent are present in the form of an oil-in-water emulsion having oil droplets substantially all of which are less than 1 micron in diameter. In preferred embodiments, the emulsifying agent is also an immunostimulating agent, such as a lipophilic muramyl peptide. Alternatively, an immunostimulating agent separate from the emulsifying agent can be used.

Claims

1. An adjuvant composition, comprising:

(1) a metabolizable oil and

(2) an emulsifying agent, wherein said oil and said emulsifying agent are present in the form of an oil-in-water emulsion having oil droplets substantially all of which are less than 1 micron in diameter and wherein said composition exists in the absence of any polyoxypropylene-polyoxyethylene block copolymer.

2. The composition of claim 1, wherein said oil is an animal oil.

3. The composition of claim 2, wherein said oil is an unsaturated hydrocarbon.

4. The composition of claim 1, wherein said oil is a terpenoid.

5. The composition of claim 1, wherein said oil is a vegetable oil.

6. The composition of claim 1, wherein said composition comprises 0.5 to 20% by volume of said oil in an aqueous medium.

7. The composition of claim 1, wherein said emulsifying agent comprises a non-ionic detergent.

8. The composition of claim 20, wherein said emulsifying agent comprises a polyoxyethylene sorbitan mono-, di-, or triester or a sorbitan mono-, di-, or triether.

9. The composition of claim 8, wherein said composition comprises 0.01 to 0.5% by weight of said emulsifying agent.

10. The composition of claim 9, wherein said composition further comprises a separate immunostimulating agent.

11. The composition of claim 8, wherein said immunostimulating agent comprises alum or a bacterial cell wall component.

12. The composition of claim 11, wherein said composition comprises 0.0001 to 1.0% by weight of said immunostimulating agent.

13. The composition of claim 11, wherein said immunostimulating agent comprises a muramyl peptide.

14. The composition of claim 1, wherein said emulsifying agent also functions as an immunostimulating agent.

15. The composition of claim 14, wherein said composition comprises 0.01 to 0.5% by weight of said immunostimulating agent.

16. The composition of claim 14, wherein said immunostimulating agent comprises a lipophilic muramyl peptide.

17. The composition of claim 16, wherein said peptide comprises a muramyl dipeptide or a muramyl tripeptide.

18. The composition of claim 17, wherein said peptide further comprises a phospholipid.

19. The composition of claim 18, wherein said phospholipid comprises a phosphoglyceride.

20. The composition of claim 14, wherein said peptide is a compound of the formula

21. The composition of claim 20, wherein R⁴ is methyl, X is alanyl, and Y is isoglutaminyl.

22. The composition of claim 20, wherein n is 1;

Z is alanyl;

R is acetyl; and

R¹, R², and R³ are all H.

23. The composition of claim 22, wherein L comprises a phospholipid moiety.

24. The composition of claim 23, wherein said phospholipid moiety comprises a diacylphosphoglyceride.

25. The composition of claim 20, wherein said peptide is N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-[1,2-dipalmitoyl-sn-glycero-3-(hydroxy-phosphoryloxy)]ethylamide.

26. The composition of claim 20, wherein at least one of R¹ and R² represents an acyl group containing from 1 to 22 carbons.

27. The composition of claim 20, wherein at least one of R¹, R², and R³ represents an acyl group containing from 14 to 22 carbons.

28. A vaccine composition, comprising:

(1) an immunostimulating amount of an antigenic substance, and

(2) an immunostimulating amount of the adjuvant of claim 1.

29. A method of stimulating an immune response in a host animal, comprising:

administering a protective antigen to said animal in the presence of an immunostimulating amount of submicron metabolizable oil droplets in a continuous aqueous phase and in the absence of any polyoxypropylene-polyoxyethylene block copolymer.

30. The method of claim 29, wherein said oil droplets further comprise an emulsifying agent.

31. The method of claim 30, wherein said oil droplets further comprise an immunostimulating agent separate from said oil and said emulsifying agent.

32. The method of claim 31, wherein said immuno-stimulating agent comprises alum or a bacterial cell wall component.

33. The method of claim 31, wherein said immuno-stimulating agent comprises a muramyl peptide.

34. The method of claim 30, wherein said emulsifying agent is also effective as an immunostimulating agent.

35. The method of claim 34, wherein said immuno-stimulating agent comprises a lipophilic muramyl peptide.