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Details for Patent: 5,691,320

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Details for Patent: 5,691,320

Title: Acylated pyrimidine nucleosides for treatment of systemic inflammation and inflammatory hepatitis
Abstract:Pyrimidine nucleotide precursors including acyl derivatives of cytidine, uridine, and orotate, and uridine phosphorylase inhibitors, and their use in enhancing resistance to sepsis or systemic inflammation are disclosed.
Inventor(s): von Borstel; Reid W. (Potomac, MD), Bamat; Michael K. (Potomac, MD), Hiltbrand; Bradley M. (Columbia, MD)
Assignee: Pro-Neuron, Inc. (Rockville, MD)
Filing Date:Jun 05, 1995
Application Number:08/465,454
Claims:1. A method for treating tissue damage due to systemic inflammatory response syndrome comprising administering to an animal a therapeutically effective amount of uridine, cytidine, orotic acid, acylated uridine, acylated cytidine, or acylated orotic acid, or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 wherein said acylated uridine is triacetyluridine.

3. The method of claim 1 further comprising administering an inhibitor of uridine phosphorylase.

4. A method for preventing tissue damage due to systemic inflammatory response syndrome comprising identifying an animal at risk for developing tissue damage due to systemic inflammatory response syndrome, and then administering to said animal a prophylactically effective mount of uridine, cytidine, orotic acid, acylated uridine, acylated cytidine, acylated orotic acid, or a pharmaceutically acceptable salt thereof.

5. The method of claim 4 wherein said acylated uridine is triacetyluridine.

6. The method of claim 4 further comprising administering an inhibitor of uridine phosphorylase.

7. A method for treating sepsis comprising administering to an animal a therapeutically effective amount of uridine, cytidine, orotic acid, acylated uridine, acylated cytidine, or acylated orotic acid.

8. The method of claim 7 wherein said acylated uridine is triacetyluridine.

9. The method of claim 7 further comprising administering an inhibitor of uridine phosphorylase.

10. A method for preventing sepsis comprising identifying an animal at risk for developing sepsis, and then administering to said animal aprophylactically effective amount of uridine, cytidine, orotic acid, acylated uridine, acylated cytidine, or acylated orotic acid.

11. The method of claim 10 wherein said acylated uridine is triacetyluridine.

12. The method of claim 10 further comprising administering an inhibitor of uridine phosphorylase.

13. A method for treating sepsis comprising administering to an animal a therapeutically effective amount of an inhibitor of uridine phosphorylase.

14. A method for preventing sepsis comprising identifying an animal at risk for developing sepsis, and then administering to said animal a prophylactically effective amount of an inhibitor of uridine phosphorylase.

15. A method for reducing toxicity of a therapeutic cytokine or inflammatory stimulus comprising administering to a animal a therapeutically effective mount of uridine, cytidine, orotic acid, acylated uridine, acylated cytidine, acylated orotic acid, or a pharmaceutically acceptable salt thereof, prior to, during, or after administration of said cytokine or said stimulus.

16. The method of claim 15 wherein said acylated uridine is triacetyluridine.

17. The method of claim 15 further comprising administering an inhibitor of uridine phosphorylase.

18. The method of claim 15 wherein said cytokine or said stimulus is selected from the group consisting of interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor, endotoxin, fungal polysaccharides, and double-stranded RNA.

19. The method of claim 18 wherein said cytokine or said stimulus is selected from the group consisting of interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor, endotoxin, fungal polysachharides, and double-stranded RNA.

20. A method for reducing toxicity of a therapeutic cytokine or inflammatory stimulus comprising administering to an animal a therapeutically effective amount of an inhibitor of uridine phosphorylase prior to, during, or after administering said cytokine or said stimulus.
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