Approach to anti-microbial host defense with molecular shields with EPA and DHA analogs

• US 7,030,159 B2
• Filed: 12/18/2002
• Issued: 04/18/2006
• 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: Serhan, Charles N., Colgan, Sean P.
• Primary Examiner(s): Wang, Shengjun
• Application Number:
  US10/323,867
• Publication Number:
  US 20030191184A1
• Time in Patent Office: 1,217 Days
• Field of Search: 514/560, 514/552, 514/549
• 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'"'"'s tissue, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog, such that the subject'"'"'s tissues express increased levels of BPI to treat the BPI sensitive infection, wherein the EPA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

2. A method for the simulation of bactericidal permeability increasing protein (BPI) in a subject'"'"'s tissue, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of a docosahexaenoic acid (DHA) analog, such that the subject'"'"'s tissues express increased levels of BPI to treat the BPI sensitive infection, wherein the DHA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

3. A method for the stimulation of bactericidal permeability increasing protein (BPI) in mucosal cells, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog, such that the mucosal cells express increased levels of BPI to treat the BPI sensitive infection, wherein the EPA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

4. A method for the stimulation of bactericidal permeability increasing protein (BPI) in mucosal cells, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount o f a docosahexaenoic acid (DHA) analog, such that the mucosal cells express increased levels of BPI to treat the BPI sensitive infection, wherein the DHA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

5. A method for treating a bacterial infection in a subject, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog, such that infection by the BPI sensitive bacteria in a subject is treated, wherein the EPA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

6. A method for treating a bacterial infection in subject, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of a docosahexaenoic acid (DHA) analog, such that infection by the BPI sensitive bacteria in a subject is treated, wherein the DHA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

7. A method for treating a bacterial infection in a subject, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog to the subject suitable to cause mucosal cells in the subject to express increased levels of BPI, such that infection by the BPI sensitive bacteria in the subject is treated, wherein the EPA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

8. A method for treating a bacterial infection in a subject, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of a docosahexaenoic acid (DHA) analog to the subject suitable to cause mucosal cells in the subject to express increased levels of BPI, such that infection by the BPI sensitive bacteria in the subject is treated, wherein the DHA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

9. A method for treating invasion by bacteria in a subject, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog, such that invasion by the BPI sensitive bacteria in a subject is treated, wherein the EPA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

10. A method for treating invasion by bacteria in a subject, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of a docosahexaenoic acid (DHA) analog, such that invasion by the BPI sensitive bacteria in a subject is treated, wherein the DHA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

11. A method for treating invasion by bacteria in a subject, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of an eicosapentaenoic acid (EPA) analog to the subject suitable to cause mucosal cells in the subject to express increased levels of BPI, such that invasion by the BPI sensitive bacteria in the subject is treated, wherein the EPA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.

12. A method for treating invasion by bacteria in a subject, comprising the step of administering to a subject infected with BPI sensitive bacteria a therapeutically effective amount of a docosahexaenoic acid (DHA) analog to the subject suitable to cause mucosal cells in the subject to express increased levels of BPI, such that invasion by the BPI sensitive bacteria in the subject is treated, wherein the DHA analog is selected from the group consisting of:

wherein each P, independently, is a hydrogen atom and R is a hydrogen atom, an alkyl group or a pharmaceutically acceptable salt.