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Application of EPO (erythropoietin) analogue in preparation of medicine for treating sepsis

A technique for sepsis and analogues, which is applied in the field of application of EPO analogues in the preparation of drugs for the treatment of sepsis, to achieve the effect of improving survival rate, reducing mortality rate and promoting expression

Inactive Publication Date: 2021-05-04
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether the small molecule polypeptide derived from EPO can promote the generation of endotoxin-resistant macrophages by activating EPOR, and its use in the preparation of drugs for treating sepsis-related diseases has not yet been reported or patented.

Method used

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  • Application of EPO (erythropoietin) analogue in preparation of medicine for treating sepsis
  • Application of EPO (erythropoietin) analogue in preparation of medicine for treating sepsis
  • Application of EPO (erythropoietin) analogue in preparation of medicine for treating sepsis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Effect of EPO polypeptide on promoting endotoxin-resistant macrophage production

[0033] 1. Animals:

[0034] C57 / BL6 mice, male, 10-12 weeks old, weighing 20-25 grams, were purchased from the Experimental Animal Center of the Army Military Medical University, and were normally raised in an SPF animal room.

[0035] 2. Cell acquisition and culture:

[0036]Bone marrow cells were obtained from femurs and tibias of wild-type C57BL / 6J mice aged 10-12 weeks, centrifuged and cultured in DMEM medium for 24 hours to collect non-adherent cells. After culturing in DMEM medium containing macrophage colony-stimulating factor (MCSF) for 4 days, add fresh DMEM medium containing MCSF to continue culturing for 3 days, and collect adherent cells as bone marrow-derived macrophages (BMDM). Flow cytometry The technology detects the expression of CD11b and F4 / 80, and the purity can reach more than 98%.

[0037] 3. Experimental method

[0038] BMDM was given LPS (100ng / ml) combined wit...

Embodiment 2

[0043] EPO peptide treatment inhibits gene expression of pro-inflammatory cytokines in septic mice

[0044] 1. Animals:

[0045] C57 / BL6 mice, male, 10-12 weeks old, weighing 20-25 grams, were purchased from the Experimental Animal Center of the Army Military Medical University, and were normally raised in an SPF animal room.

[0046] 2. Experimental method:

[0047] Wild-type C57BL / 6J mice aged 10-12 weeks were given intraperitoneal injection of PBS or EPO polypeptide (100 μmol / kg) combined with LPS (1 mg / kg). After 24 hours, the mice received a second LPS (10 mg / kg). / kg) intraperitoneally. Six hours after the second LPS injection, the peritoneal cavity of the mice was washed with normal saline, and centrifuged to collect the inflammatory cells in the peritoneal cavity; in addition, the mouse spleen, lung, liver, kidney and other tissues were taken, and the pro-inflammatory factor TNF in the above samples was detected by fluorescent quantitative PCR method -α, IL6, IL-1β ...

Embodiment 3

[0052] EPO peptide treatment promotes gene expression of antibacterial and tissue repair molecules in septic mice

[0053] 1. Animals:

[0054] C57 / BL6 mice, male, 10-12 weeks old, weighing 20-25 grams, were purchased from the Experimental Animal Center of the Army Military Medical University, and were normally raised in an SPF animal room.

[0055] 2. Experimental method:

[0056] Get 10-12 weeks old wild-type C57BL / 6J mice, use PBS or EPO polypeptide (100μmol / kg) combined with LPS (1mg / kg) to give mice intraperitoneal injection, 24 hours later, the mice received a second LPS (10mg / kg) kg) intraperitoneally. Six hours after the second LPS injection, the peritoneal cavity of the mice was washed with normal saline, and the inflammatory cells in the peritoneal cavity were collected by centrifugation; in addition, the mouse spleen, lung, liver, kidney and other tissues were taken, and the antibacterial genes MARCO and CNLP, and gene expression differences of the damage repair ...

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Abstract

The invention relates to the technical field of biological medicines, in particular to application of an EPO analogue in preparation of a medicine for treating sepsis. The EPO analogue is an EPO-sourced micro-molecule polypeptide, and the structural formula of the EPO analogue is as follows: Gln Glu GlnLeu Glu Arg Ala Leu Asn Ser Ser; the EPO-sourced micro-molecule polypeptide can be compounded with LPS (lipopolysaccharide) to treat sepsis, and can be used as an endotoxin-tolerant accelerant for macrophage generation, an inhibitor for gene expression of proinflammatory factor, an accelerant for gene expression of antibacterial and tissue repair molecules, an inhibitor of chemotactic factors CCL3 and CCL4, and an accelerant of CD64, MARCO, C-type lectin domain family 4 member A, CNLP, formyl peptide receptor 1, acyloxyacyl hydrolase and ribonuclease T2. By activating the macrophage EPOR, expression of inflammatory factors of the macrophage can be inhibited, expression of antibacterial and tissue repair genes of the macrophage can be promoted, the survival rate of sepsis can be increased, the death rate can be reduced, and a new treatment thought is provided for treating various sepsis-related diseases.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of an EPO analogue in the preparation of medicines for treating sepsis. Background technique [0002] The latest international definition of sepsis (sepsis version 3.0) believes that sepsis is a life-threatening organ dysfunction caused by an immune response disorder caused by infection. The incidence of sepsis is high. There are more than 18 million cases of severe sepsis every year in the world, and this number is also increasing at a rate of 1.5% to 8.0% per year. Sepsis is a dangerous condition with a high fatality rate. About 14,000 people worldwide die from its complications every day, and it has become the main cause of death of non-cardiac patients in the intensive care unit. In recent years, despite advances in anti-infection therapy and organ function support technology, the mortality rate of sepsis is still as high as 30% to 70%. Moreover, the cos...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61P31/04
CPCA61K38/1816A61P31/04
Inventor 罗邦伟张志仁张雪贺丹
Owner ARMY MEDICAL UNIV
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