Method of treating and preventing infectious diseases

• US 20070212376A1
• Filed: 04/12/2007
• Published: 09/13/2007
• Est. Priority Date: 06/29/2000
• Status: Abandoned Application

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Cham, Bill
• Application Number:
  US11/786,649
• Publication Number:
  US 20070212376A1
• Time in Patent Office: Days
• US Class Current: 424/208.100
• CPC Class Codes: A61K 2039/5252 inactivated (killed)
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/29 Hepatitis virus
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: A61M 1/3486 Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: C12N 2730/10134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2730/10163 : by chemical treatment
• CPC Class Codes: C12N 2770/24334 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/24363 : by chemical treatment
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention relates to a method for reducing the occurrence and severity of infectious diseases, especially infectious diseases in which lipid-containing infectious organisms are found in biological fluids, such as blood. The present invention employs solvents useful for extracting lipids from the lipid-containing infectious organism, thereby reducing the infectivity of the infectious organism. The present invention also provides a vaccine composition, comprising a lipid-containing infectious organism, treated with solvents to reduce the lipid content of the infectious organism, combined with a pharmaceutically acceptable carrier. The vaccine composition is administered to an animal or a human to provide protection against the lipid-containing infectious organism.

Claims

1. A method for reducing levels of a lipid-containing infectious organism in a fluid comprising:

contacting the fluid containing the lipid-containing infectious organism with a first organic solvent capable of extracting lipid from the lipid-containing infectious organism;

mixing the fluid and the first solvent;

permitting organic and aqueous phases to separate; and

collecting the aqueous phase containing the infectious organism with reduced lipid content.

2. The method of claim 1, further comprising:

contacting the aqueous phase with a de-emulsifying agent capable of removing the first organic solvent; and

,

separating the de-emulsifying agent containing the removed first organic solvent from the contacted aqueous phase.

12. The method of claim 1 wherein the lipid-containing infectious organism is a virus, bacterium, protozoan or fungus.

13. The method of claim 1 wherein the infectious organism is a virus and the virus is immunodeficiency virus, hepatitis or pestivirus.

14. The method of claim 1, wherein the first organic solvent is an alcohol, an ether, an amine, a hydrocarbon, or a combination thereof.

15. The method of claim 1, wherein the first organic solvent is an alcohol, an ether, or a combination thereof.

16. The method of claim 15 wherein the ether is C₄ to C₈ ether and the alcohol is a C₁ to C₅ alcohol.

17. The method of claim 2, wherein the de-emulsifying agent is an ether.

18. The method of claim 1, wherein the fluid is plasma, serum, peritoneal fluid, lymphatic fluid, pleural fluid, pericardial fluid, cerebrospinal fluid, or a fluid of the reproductive system.

3. A method for reducing levels of a lipid-containing infectious organism in an animal or a human comprising:

obtaining a fluid containing the lipid-containing infectious organism from the animal or the human;

contacting the fluid containing the lipid-containing infectious organism with a first organic solvent capable of extracting lipid from the lipid-containing infectious organism;

mixing the fluid and the first organic solvent;

permitting organic and aqueous phases to separate;

collecting the aqueous phase containing the infectious organism with reduced lipid content; and

introducing the aqueous phase containing the infectious organism with reduced lipid content into the animal or the human.

4. The method of claim 3, wherein after the aqueous phase is collected, the aqueous phase is contacted with a de-emulsifying agent capable of removing the first organic solvent, and the de-emulsifying agent containing the removed first organic solvent is removed from the aqueous phase before introducing the aqueous phase containing the infectious organism with reduced lipid content into the animal or the human.

5. A method for reducing levels of a lipid-containing infectious organism in animal or human plasma comprising:

removing blood containing the lipid-containing infectious organism from the animal or the human;

obtaining plasma from the blood, the plasma containing the lipid-containing infectious organism;

contacting the plasma containing the lipid-containing infectious organism with a first organic solvent capable of extracting lipid from the lipid-containing infectious organism;

mixing the plasma and the first organic solvent;

permitting organic and aqueous phases to separate;

collecting the aqueous phase containing the infectious organism with reduced lipid content; and

introducing the aqueous phase containing the infectious organism with reduced lipid content into the animal or the human.

6. The method of claim 5, wherein after the aqueous phase is collected, the aqueous phase is contacted with a de-emulsifying agent capable of removing the first organic solvent, and the de-emulsifying agent containing the removed first organic solvent from the contacted aqueous phase is separated and removed before introducing the aqueous phase containing the infectious organism with reduced lipid content into the animal or the human.

7. The method of claim 5, further comprising adding cells to the aqueous phase containing the infectious organism with reduced lipid content before introduction into the animal or the human.

8. A method for making a vaccine comprising:

contacting a lipid-containing infectious organism in a fluid with a first organic solvent capable of extracting lipid from the lipid- containing infectious organism;

mixing the fluid and the first organic solvent for a time sufficient to extract lipid from the lipid-containing infectious organism;

permitting organic and aqueous phases to separate; and

collecting the aqueous phase containing the infectious organism with reduced lipid content.

9. The method of claim 8, further comprising:

contacting the aqueous phase with a de-emulsifying agent capable of removing the first organic solvent; and

,

separating the de-emulsifying agent and the removed first organic solvent from the contacted aqueous phase.

10. A method of providing protection in an animal or a human against an infectious organism comprising:

administration to the animal or the human of an effective amount of a composition comprising the infectious organism with reduced lipid content of claim 8 in a pharmaceutically acceptable carrier, wherein the amount is effective to provide a protective effect against infection by the infectious organism in the animal or the human.

11. The method of claim 10 further comprising administration of an immunostimulant.

19. The method of claim 8, wherein the first organic solvent is an alcohol, an ether, an amine, a hydrocarbon, an ester, a surfactant or a combination thereof.

20. A vaccine composition, comprising a substantially delipidated infectious organism and a pharmaceutically acceptable carrier.

21. The composition of claim 20, further comprising an immunostimulant.

22. The composition of claim 20, wherein the infectious organism is a virus, a bacterium, a fungus, or a protozoan.

23. The composition of claim 22, wherein the virus is an immunodeficiency virus or hepatitis.

24-28. -28. (canceled)