Isolated algal lipopolysaccharides and use of same to inhibit endotoxin-initiated sepsis

• US 6,534,648 B1
• Filed: 11/19/1999
• Issued: 03/18/2003
• Est. Priority Date: 01/21/1997
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Nebraska
• Original Assignee: Board of Regents of the University of Nebraska
• Inventors: Shnyra, Alex, Morrison, David C., Pardy, R. L., Royce, Clare L.
• Primary Examiner(s): Barts, Samuel
• Assistant Examiner(s): Khare, Devesh
• Application Number:
  US09/443,674
• Time in Patent Office: 1,215 Days
• Field of Search: 514/54, 514/53, 514/23, 514/75, 536/128, 536/123.13, 424/195.1
• US Class Current: 536/128
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P

Abstract

The isolation and purification of lipopolysaccharides from several related strains of eukaryotic algae is disclosed. These lipopolysaccharides have been shown to be structurally and functionally similar to the lipopolysaccharides of gram negative bacteria, or endotoxins, which have been shown to be a cause of sepsis or septic shock. The present invention also relates to the use of these algal lipopolysaccharides to inhibit the release of TNF-a from macrophages, which has been associated with the initiation and escalation of sepsis as a result of bacterial endotoxins.

Claims

1. Algal lipopolysaccharide isolated from ATCC Accession No. 209592.

2. Purified algal lipopolysaccharide isolated from ATCC Accession No. 209592.

3. A method of inhibiting endotoxin-initiated sepsis in a host comprising providing the host with a quantity of algal lipopolysaccharide.

4. A compound for inhibiting endotoxin-initiated sepsis comprising algal lipopolysaccharide.

5. A method of inhibiting the onset of sepsis caused by endotoxins comprising administering to a mammal an algal lipopolysaccharide in an amount effective for inhibiting the onset of sepsis.

6. An isolated chlorella lipopolysaccharide comprising a 2-keto-3-deoxyoctulosonic acid moiety and a β

-OH-myristic acid moiety.

7. An isolated eukaryotic algal lipopolysaccharide comprising a 2-keto-3-deoxyoctulosonic acid moiety and a β

-OH-myristic acid moiety.

8. A method of inhibiting the onset of sepsis caused by endotoxins comprising administering to a mammal a compound in an amount effective for inhibiting the onset of sepsis, wherein the compound is isolated from ATCC Accession No. 209592, and further comprises a 2-keto-3-deoxyoctulosonic acid moiety and a β

-OH-myristic acid moiety.

9. A compound isolated from ATCC Accession No. 209592, said compound comprising a 2-keto-3-deoxyoctulosonic acid moiety, a sugar associated with an inner core, a β

-OH-myristic acid moiety, and a lipid A moiety, wherein said compound tests positive for LAL activity controlled for β

-D-glucans.

10. A method of inhibiting a bacterial endotoxin initiated release of TNF-a comprising introducing to a host an amount of lipopolysaccharide isolated from ATCC Accession No. 209592.