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Application of carbon monoxide release molecules in preparing medicament for treating early sepsis

A carbon monoxide and sepsis technology, used in the treatment of sepsis, the early application of carbon monoxide release molecules, can solve the problems of exogenous CO administration mode and concentration control difficulties, unfavorable long-term observation of experimental results, etc., to achieve concentration control and correct , to meet the clinical application, the effect of easy concentration control

Inactive Publication Date: 2009-12-02
AFFILIATED HOSPITAL OF JIANGSU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few studies on the intervention of exogenous carbon monoxide on SIRS or Sepsis, mainly because the administration method and concentration control of exogenous CO are difficult, which is not conducive to long-term observation of experimental results.

Method used

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  • Application of carbon monoxide release molecules in preparing medicament for treating early sepsis
  • Application of carbon monoxide release molecules in preparing medicament for treating early sepsis
  • Application of carbon monoxide release molecules in preparing medicament for treating early sepsis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] 1. By measuring the carbon monoxide hemoglobin (COHb) in the blood, the binding degree of carbon monoxide (CO) and Hb can be judged. The method specified in the literature of Steina AB et al. (J Mol Cell Cardiol 38: 127-34, 2005) was used to measure the COHb detection results after using CORM-2 in animals (see Table 1).

[0025] Table 1 COHb detection results after use of CORM-2 in animals

[0026]

[0027] 2. The dosage of CORM-2 in this animal experiment study is 8 mg / kg bw.

Embodiment 2

[0029] Dissolve the carbon monoxide releasing molecule in DMSO solvent, and use the following method to test:

[0030] (1) In cell experiments, the final concentration of CORM-2 is 10M, 50M, and 100M solutions; in animal experiments, the dose of CORM-2 is 8mg / kg bw;

[0031] (2) Effects of different working concentrations of CORM-2 on LPS-induced oxidative stress (DHR 123) and NO production (DAF-FM) in HUVEC cells;

[0032] (3) The effect of different working concentrations of CORM-2 on the expression of LPS-induced HUVEC cell adhesion molecule ICAM-1;

[0033] experiment method:

[0034] Cells: human umbilical cord endothelial cells (passage 3-8), stimulated with LPS (final concentration 10g / ml) for 4 hours, and collected cells;

[0035] Extraction of nuclear and cytoplasmic proteins: Grind tissue samples in liquid nitrogen, then place in 300 l of buffer E (10mmol / L HEPES (pH7.9), 10mmol / L KCl, 1.5mmol / L MgCl2, 1% NP -40, 0.5mmol / L DTT, 0.5mmol / L PMSF, 10g / ml aprotinin, 10...

Embodiment 3

[0041] Inhibitory effect of CORM-2 on hepatic inflammatory response in septic mice.

[0042] experiment method:

[0043] (1) Animal and CLP sepsis model

[0044] Male C57BL / 6 mice, 6-8 weeks old, weighing 18±2 grams, were raised in a general laboratory (commercial dry block feed, free access to water). The experimental animals were divided into five groups according to the random number table method: Sham group (n=9), Sham+CORM-2 group (n=9), CLP group (n=9), CLP plus CORM-2 group (n=9) and CLP+DMSO group (n=9). Under isoflurane inhalation anesthesia, the mice in the CLP group were subjected to cecal ligation and perforation, and 1.5 ml of normal saline was injected intraperitoneally after injury to resist shock; the mice in the CLP plus CORM-2 group were injected with CORM-2 (8 mg / kg) into the tail vein after CLP. ). All animals were sacrificed with isoflurane inhalation 24 hours after injury and collected specimens.

[0045] (2) Detection indicators

[0046] Detection ...

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Abstract

The invention discloses an application of carbon monoxide release molecules in preparing a medicament for treating early sepsis. The invention discovers, according to massive cell and animal tests, that when the carbon monoxide release molecules are dissolved in DMSO solvent and then positioned in cell supernatant or a biological body, CO can be sustainedly released, therefore, the carbon monoxide release molecules can be used as an exogenous CO supplier; in addition, an inflammation model and a mouse CLP sepsis model which are stimulated by cells LPS are adopted for early intervention, and after tests, the carbon monoxide release molecules are dissolved to be capable of serving as a medicament for inhibiting the early sepsis. If the carbon monoxide release molecules are used for inhibiting the sepsis, the control of the concentration thereof is relatively easy and correct, and the superaddition is convenient if the carbon monoxide release molecules are used for a long time. The carbon monoxide release molecules can meet the requirements of clinical application.

Description

technical field [0001] The patent of the present invention relates to the new application of carbon monoxide releasing molecules, specifically, relates to a method for early application of carbon monoxide releasing molecules to treat sepsis. Background technique [0002] Sepsis is a common complication after severe trauma, shock and infection. Further development can lead to septic shock and multiple organ dysfunction syndrome (MODS). Clinical treatment still has little effect, and the mortality rate remains high. Studies have shown that vital organ failure after severe sepsis, especially multiple organ failure, has a high mortality rate. Once multiple organ failure occurs, existing treatment measures are difficult to reverse it, so it is particularly important to prevent or reduce early organ damage in sepsis. The change of liver function in the early stage after sepsis is closely related to the degree of liver inflammation. Whether the inflammatory response can be effect...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K33/00A61P31/00
Inventor 孙炳伟刘东明陈曦
Owner AFFILIATED HOSPITAL OF JIANGSU UNIV
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