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Application of uridine phosphorylase inhibitor and composition containing the same

A technology of uridine phosphorylase and inhibitors, which can be used in drug combinations, carbohydrate active ingredients, anti-toxins, etc., and can solve problems such as discomfort and infection

Inactive Publication Date: 2005-07-20
PRO NEURON INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Parenteral administration of uridine requires the use of a central venous catheter (discomfort and risk of infection), but since phlebitis was a problem in early clinical trials of uridine administered via an arm venous catheter (VanGroeningen et al., Cancer Treat Rep, 1986, 70:745-50)

Method used

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  • Application of uridine phosphorylase inhibitor and composition containing the same
  • Application of uridine phosphorylase inhibitor and composition containing the same
  • Application of uridine phosphorylase inhibitor and composition containing the same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0200] Triacetyluridine and uridine increase the survival of mice treated with dead E. coli

[0201] Purpose:

[0202] Sepsis can be caused by G - Bacteria trigger, even in G - In near nonviable cases, because the main trigger is endotoxin (a component of the bacterial cell wall). The purpose of the study in this Example was to examine the effect of oral administration of triacetyluridine and parenteral administration of uridine on the survival of mice treated with lethal doses of dead E. coli.

[0203] method:

[0204] Eighteen female Balb / c mice (8 weeks old) were divided into groups of 6 animals. All mice were given 500 ug of sonicated E. Coli (serotype 0111:B4) in acetone powder suspended in 0.2 ml saline. One group of mice was injected intraperitoneally with uridine (2000 mg / kg in 0.2 ml saline) 2 hours before administration of E. coli. Another group of mice was given triacetyluridine (6000 mg / kg in a 1:1 corn oil / water vehicle containing 2.5% Tween 80) via laryngea...

Embodiment 2

[0211] A Dose-Response Study of Uridine in Protecting Tissues from Endotoxin Damage

[0212] Purpose:

[0213] The purpose of this study was to determine the dose-response profile of uridine in preventing inflammatory tissue damage caused by endotoxin (LPS).

[0214] method:

[0215] Female Balb / c mice (8 weeks old) were divided into 6 groups of 6 animals each. One group of animals was left untreated to provide baseline serum chemistry values ​​indicative of tissue damage. The remaining five groups of mice were given 100 μg of S. typhimurium endotoxin in 0.2 ml saline by intraperitoneal injection. Two hours before endotoxin administration, the five groups of mice were given uridine at 0.500, 1000, 2000 and 4000 mg / kg (in 0.2 ml saline) by intraperitoneal injection, respectively. Eighteen hours after endotoxin administration, blood samples were collected for determination of serum chemical indicators of tissue damage.

[0216] result:

[0217] Uridine produced dose-depend...

Embodiment 3

[0233] Oral administration of triacetyluridine increases survival in mice treated with lethal doses of Salmonella typhimurium endotoxin

[0234] Purpose:

[0235] by G - The sepsis syndrome caused by bacteria is mediated by endotoxin, a lipopolysaccharide component of the bacterial wall. The aim of this experiment was to determine the effect of oral administration of technical uridine (triacetyluridine; TAU) on the survival of mice treated with lethal doses of purified Salmonella typhimurium endotoxin (LPS).

[0236] method:

[0237] Twenty female Balb / c mice (8 weeks old) were divided into two groups, 10 in each group. All mice were injected intraperitoneally with 100 ug of S. typhimurium endotoxin dissolved in 0.2 ml of saline. One group of mice was intragastrically administered triacetyluridine (6000 mg / kg in a 1:1 corn oil / water vehicle containing 2.5% Tween 80). Survival was monitored for one week.

[0238] result:

[0239] All 10 animals given endotoxin only died ...

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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.

Description

[0001] This application is a divisional application of an invention patent application with an application date of December 7, 1993, an application number of 93121700.8, and an invention title of "Pyrimidine Nucleotide Precursor for Treating Systemic Inflammation and Inflammatory Hepatitis". technical field [0002] The present invention relates to the preparation of uridine phosphorylase inhibitors for the treatment or prevention of sepsis, the toxicity of therapeutic cytokines or inflammatory stimuli in animals, cancer, inflammatory hepatitis, liver damage in animals receiving total parenteral nutrition As well as the application of drugs in the treatment of liver damage in animals receiving liver transplantation. The present invention also relates to compositions containing inhibitors of uridine phosphorylase. Background technique [0003] Sepsis (also known as sepsis syndrome) is the result of a serious infection caused by ...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/00A61K31/505A61K31/513A61K31/515A61K31/70A61K31/7042A61K31/7052A61K31/706A61K31/7064A61K31/7068A61K31/7072A61K31/7076A61K31/708A61K31/715A61K38/00A61K45/06A61P1/16A61P17/00A61P29/00A61P31/00A61P31/04A61P35/00A61P37/02A61P37/06A61P39/02A61P43/00C07D239/54C07HC07H19/06C07H19/10
CPCA61K31/505A61K31/515C07H19/06A61K31/7088A61K31/70A61K31/513A61K31/715A61K45/06A61K31/7068A61K31/7072A61K31/00A61P1/16A61P17/00A61P29/00A61P31/00A61P31/02A61P31/04A61P35/00A61P37/02A61P37/06A61P39/02A61P43/00A61K2300/00
Inventor R·W·冯波斯特尔M·K·巴马特B·M·希尔特布兰德
Owner PRO NEURON INC
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