Approach to antimicrobial host defense with molecular shields with EPA and DHA analogs

• US 7,741,368 B2
• Filed: 02/14/2006
• Issued: 06/22/2010
• Est. Priority Date: 12/18/2001
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Colgan, Sean P., Serhan, Charles N.
• Primary Examiner(s): Wang; Shengjun
• Application Number:
  US11/353,436
• Publication Number:
  US 20060128804A1
• Time in Patent Office: 1,589 Days
• Field of Search: 514/560, 514/549, 514/552
• US Class Current: 514/560
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61P 31/04 Antibacterial agents

Abstract

Methods to cause tissue, such as mucosal cells, to express increased amounts of bactericidal permeability increasing protein (BPI) are described. Various BPI inducing agents include icosapentanoic acid (EPA) analogs and docosahexaenoic acid (DHA) analogs.

Claims

1. A method for the stimulation of bactericidal permeability increasing protein (BPI) in a subject, comprising administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of a pharmaceutical composition comprising an eicosapentaenoic acid (EPA) analog or docosahexaenoic acid (DHA) analog and a pharmaceutically acceptable carrier, such that cells in the subject express increased levels of BPI, wherein the EPA analog is:

2. A method for treating a bacterial infection in a subject, comprising administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of a pharmaceutical composition comprising an eicosapentaenoic acid (EPA) analog or docosahexaenoic acid (DHA) analog and a pharmaceutical carrier, such that cells in the subject express increased levels of BPI, thereby treating the BPI sensitive bacterial infection, wherein the EPA analog is:

3. A method for treating invasion by bacteria in a subject, comprising administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of a pharmaceutical composition comprising an eicosapentaenoic acid (EPA) analog or docosahexaenoic acid (DHA) analog and a pharmaceutical carrier, such that cells in the subject express increased levels of BPI, thereby treating the BPI sensitive bacterial invasion in the subject, wherein the EPA analog is:

4. A method for the stimulation of bactericidal permeability increasing protein (BPI) in a subject, comprising administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog or docosahexaenoic acid (DHA) analog, such that the cells in the subject express increased levels of BPI, wherein the EPA analog is:

5. A method for treating a bacterial infection in a subject, comprising administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog or docosahexaenoic acid (DHA) analog, such that cells in the subject express increased levels of BPI, thereby treating the infection by the BPI sensitive bacteria, wherein the EPA analog is:

6. A method for treating invasion by bacteria in a subject, comprising administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog or a docosahexaenoic acid (DHA) analog, such that invasion by the BPI sensitive bacteria in a subject is treated, or such that mucosal cells in the subject express increased levels of BPI, thereby treating the invasion of the BPI sensitive bacteria, wherein the EPA analog is: