Application of carbon monoxide releasing molecules in preparing medicines for inhibiting blood coagulation activation diseases

A technology for inhibiting blood coagulation and carbon monoxide, applied in blood diseases, drug combinations, extracellular fluid diseases, etc., can solve the problems of additional dosage, complex devices, high HbCO, etc., achieve concentration control and accuracy, meet clinical application, and easy concentration control Effect

Inactive Publication Date: 2012-12-12
AFFILIATED HOSPITAL OF JIANGSU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In the past, "inhalation of CO" was often used as the source of exogenous CO, but many disadvantages were found, such as complex devices, difficulty in controlling and maintaining the inhalation concentration, difficulty in increasing the dose when the experiment required, and easily leading to high HbCO (carbohemoglobin) hyperemia, etc.

Method used

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  • Application of carbon monoxide releasing molecules in preparing medicines for inhibiting blood coagulation activation diseases
  • Application of carbon monoxide releasing molecules in preparing medicines for inhibiting blood coagulation activation diseases
  • Application of carbon monoxide releasing molecules in preparing medicines for inhibiting blood coagulation activation diseases

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Embodiment 1

[0025] Inhibitory effects of exogenous carbon monoxide releasing molecules (CO-RMs) on platelet membrane glycoproteins and platelet activation in sepsis

[0026] experiment method:

[0027] 1 CLP animal model

[0028] 6-8 week old C 57 BL / 6 mice, weighing 20±2g, are all male. The mice were anesthetized by inhalation of 2% isoflurane, and a 1-1.5 cm incision was made below the midline of the abdominal wall to find the cecum, and a 3-0 thread was used to ligate 1 / 2 of the total length of the cecum, taking care not to cause intestinal obstruction. Do not damage the ileal artery. A single puncture is made in the cecal wall with a 20-gauge needle, and the cecum is gently squeezed so that a small amount of intestinal contents overflow at the puncture site to ensure complete perforation, paying close attention to maintaining continuity between the small and large intestines. Examination of mice in different parts of the gut after CLP did not reveal the presence of intestinal obst...

Embodiment 2

[0093] Effects of exogenous carbon monoxide releasing molecules (CO-RMs) on platelet HS1 phosphorylation in sepsis

[0094] The excessive activation of coagulation system in sepsis promotes the development of sepsis, which further develops into septic shock. Platelets play a very important role in this complex interaction process, which is mainly reflected in the excessive activation of platelets and the occurrence of massive Adhesion and aggregation, leading to pathological thrombus formation. The main platelet membrane glycoproteins GPⅡb / IIIa (ie CD41 / CD61), CD62p, etc. mediate the above pathological process. Hematopoietic cell-specific protein-1 (HS1) is a key signaling molecule in the activation process of platelets after stimulation, and the activation signals of the above-mentioned important platelet membrane glycoproteins are all transmitted through HS1. Therefore, inhibiting the expression of membrane glycoproteins, or blocking HS1 signal transduction, thereby inhibitin...

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Abstract

The invention discloses application of carbon monoxide releasing molecules in preparing medicines for inhibiting blood coagulation activation diseases. In vivo animal experiments and in vitro cell experiments show that exogenous carbon monoxide can significantly reduce the expression of blood coagulation factors FIB and D-D in sepsis, and reduce the expression of platelet membrane glycoprotein CD 61 and CD 62p in plasma, thereby down-regulating the adhesiveness and aggregation function of platelet, inhibiting the phosphorylation level of platelet HIS of sepsis mice and finally inhibiting over activation of the coagulation system in sepsis. When the carbon monoxide releasing molecules are adopted for inhibiting over activation diseases of the coagulation system in sepsis, the concentration control is relatively easy and accurate, adding is convenient for long-term use, and the requirement of clinical application can be satisfied.

Description

technical field [0001] The patent of the present invention relates to the new application of carbon monoxide releasing molecules in blood coagulation system, specifically, it relates to a method for early application of carbon monoxide releasing molecules to treat excessive activation of blood coagulation system in sepsis. Background technique [0002] Sepsis is a common complication after severe trauma, shock and infection. Even in the modern era of highly developed basic and clinical medical research and intensive care methods, clinical treatment still has little effect, and the mortality rate remains high! Statistics show that more than 10% of the dead patients in the world are closely related to sepsis. In the complicated pathogenesis of sepsis, the disorder of coagulation system is an important reason for the increased mortality. Abnormal coagulation system plays an important role in the occurrence and development of sepsis. In sepsis, due to the cascade release of cy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K33/00A61P7/00
Inventor 孙炳伟孙艳王旭
Owner AFFILIATED HOSPITAL OF JIANGSU UNIV
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