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Application of chitosan oligosaccharide in preparation of medicines for preventing and treating endotoxemia/bacteremia

A technology of endotoxemia and chitosan oligosaccharide, applied in medicine or health food, the application field of chitosan oligosaccharide in the prevention and treatment of endotoxemia/bacteremia, can solve clinical application limitations, damage , toxic and side effects, etc.

Active Publication Date: 2011-06-08
DALIAN GLYCOBIO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although polymyxin B can chemically bind the lipid A part of endotoxin to neutralize or inactivate its toxicity, its toxic side effects are severe, especially to the nervous system and kidneys, which limits its clinical application.

Method used

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  • Application of chitosan oligosaccharide in preparation of medicines for preventing and treating endotoxemia/bacteremia
  • Application of chitosan oligosaccharide in preparation of medicines for preventing and treating endotoxemia/bacteremia
  • Application of chitosan oligosaccharide in preparation of medicines for preventing and treating endotoxemia/bacteremia

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Reference literature (Aoshiba, K., Onizawa, S., Tsuji, T., & Nagai, A. (2009). Therapeutic effects of erythropoietin in murine models of endotoxin shock. CRITICAL CARE MEDICINE, 37(3), 889-898 ), 24 mice (8 weeks, 18-22 g, half male and half male) were divided into one group, a total of 3 groups, and the drugs were injected intraperitoneally. Divided into simple chitooligosaccharide group (deacetylation degree ≥ 95%, molecular weight < 1000Da) (COS), endotoxin group (LPS), chitooligosaccharide (deacetylation degree ≥ 95%, molecular weight < 1000Da) treatment group, 100mg / kg Body weight (LPS+COS). Continuous observation for 7 days, every 6 hours for the first 3 days, and every 12 hours for the next 4 days.

[0024] figure 1 In the figure, the solid dots represent the endotoxin LPS group, the hollow dots represent the LPS+COS treatment group, and the inverted triangles represent the simple chitosan oligosaccharide group. It can be seen from the figure that 100 mg / kg bo...

Embodiment 2

[0026] More than 12 mice were divided into 3 groups, and the drugs were injected intraperitoneally. Simple chitosan oligosaccharide (deacetylation degree ≥ 95%, molecular weight < 1000Da) group, LPS group (LPS), chitosan oligosaccharide (deacetylation degree ≥ 95%, molecular weight < 1000Da) treatment group (100mg / kg body weight), respectively Blood was collected from 6 mice at 1.5 and 3 hours after LPS injection. Mouse serum was separated for TNF-α ELISA analysis. Briefly, 100 μl of diluted serum sample was added to the bottom of the well of the ELISA plate, incubated at 37°C for 2 hours, 350 μl of washing solution was manually washed 5 times, and 100 μl of enzyme-labeled antibody was added, incubated at 37°C for 2 hours, and the plate was washed manually with 350 μl of washing solution 5 times, add 100 μl of substrate working solution and incubate at 37°C for 30 minutes, then add 100 μl of stop solution, and read the plate at 450 nm on a microplate reader.

[0027] figur...

Embodiment 3

[0029]The mouse peritoneal cell line RAW264.7 was pressed at 0.1-10×10 6 pcs / mL (in this example, 1-2×10 6 seed / mL) in a 6-well plate, cultivated for 10-24h (this example uses 12h), then add chitosan oligosaccharide (deacetylation degree ≥ 95%, molecular weight < 1000Da) into the culture medium, the final concentration is respectively 100μg / mL, 200μg / mL, 400μg / mL, add LPS (100ng / ml) at the same time, continue to culture for 6h, discard culture medium, wash with PBS (pH7.4) for 3 times, add ELISA specimen diluent, liquid nitrogen repeatedly The cells were lysed by freezing and thawing, and the lysate was taken for ELISA to detect the expression of pro-IL-1β in the cells, and the steps were the same as above.

[0030] image 3 From left to right, respectively, blank group, LPS group, LPS+COS and COS concentration gradually increased. It can be seen from the figure that 400 μg / mL chitosan oligosaccharide can significantly inhibit LPS-mediated cell secretion of inflammatory fac...

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Abstract

The invention relates to biological medicines, in particular to an application of chitosan oligosaccharide in preparation of medicines for preventing and treating endotoxemia / bacteremia. The chitosan oligosaccharide can inhibit the secretion of inflammatory factors to prevent and treat endotoxin shock, i.e. the chitosan oligosaccharide can be further used for preparing medicines for preventing and treating endotoxemia. In the invention, the cell experiment shows that the chitosan oligosaccharide can inhibit the secretion of inflammatory cytokines caused by lipopolysaccharide (LPS). The animal experiment shows that the chitosan oligosaccharide can obviously improve the survival rate of a mouse with endotoxemia, inhibit the secretion of inflammatory factors TNF (tumor necrosis factor)-alpha of the mouse and inhibit the secretion of inflammatory factors IL-1beta of a macrophage strain RAW264.7 of the mouse.

Description

technical field [0001] The present invention relates to biomedicine, specifically the application of chitosan oligosaccharides in the prevention and treatment of endotoxemia / bacteremia; in the application. Background technique [0002] Systemic infection refers to the systemic inflammatory response syndrome caused by microorganisms invading the body after infection. Severe infection, septic shock and multiple organ dysfunction syndrome are the follow-up symptoms of systemic infection. At present, 30% to 45% of patients with endotoxemia still die due to failure to control the disease in time, and the incidence of endotoxemia continues to increase every year. According to the report of the US Centers for Disease Control and Prevention, the incidence of severe endotoxemia has increased by 139% in the last 10 years; there are at least 750,000 new cases in the United States every year; endotoxemia is the 11th cause of disease death , Some people even think that it is second onl...

Claims

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Application Information

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IPC IPC(8): A61K31/722A61P39/02A61P31/04A61P29/00
Inventor 杜昱光乔莹熊川男白雪芳
Owner DALIAN GLYCOBIO
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