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A t-peptide immunomodulator for sepsis treatment

A two-way regulation and reagent technology, applied in the field of biomedicine, can solve the problems of increased mortality, inability to clear pathogens, secondary infection of latent viruses, etc.

Active Publication Date: 2016-05-11
FIRST HOSPITAL AFFILIATED TO GENERAL HOSPITAL OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The specific manifestation is that pathogens cannot be eliminated, and it is easy to cause secondary infection and resurrection of latent virus, etc., and even exist for a period of time after the recovery of sepsis patients, resulting in a decline in quality of life and an increase in mortality after discharge [WintersBD, EberleinM, LeungJ, etal.Long-termmortalityandqualityoflifeinsepsis:asystematicreview.CritCareMed, 2010, 38(5): 1276-1283]

Method used

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  • A t-peptide immunomodulator for sepsis treatment
  • A t-peptide immunomodulator for sepsis treatment
  • A t-peptide immunomodulator for sepsis treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1: Effect of T peptide on survival rate of mouse sepsis model

[0060] 1. Experimental animals and main reagents

[0061] Male BALB / c mice, 6-8w, 20+2g, were purchased from the Institute of Experimental Animals, Chinese Academy of Medical Sciences (animal certificate number: SCXK Beijing 2009-0007). Adaptive feeding for 1 week, free access to food and water, room temperature 25°C, 12h circadian rhythm.

[0062] Ketamine Hydrochloride Injection (Shanghai First Biochemical Pharmaceutical Company, China): Sumianxin II Injection (developed by Military Veterinary Research Institute, Academy of Military Medical Sciences, China): 0.9% normal saline (Shandong Luxin Pharmaceutical Group, China) by volume The ratio is 2:2.5:4.5. T-peptide: 1mg / cartridge, ① Dissolve 4mg T-peptide in 10ml of 0.9% normal saline, mix thoroughly, and use it in the 4mg / kg group; kg group; ③Take 2.5ml of the solution in ②, dilute to 10ml, and use it in the 0.25mg / kg group. The corresponding ...

Embodiment 2

[0072] Example 2: Effect of T peptide on the activity of effector T lymphocytes

[0073] 1. Experimental animals and main reagents

[0074] Male BALB / c mice, 6-8w, 20±2g, were purchased from the Institute of Experimental Animals, Chinese Academy of Medical Sciences (animal certificate number: SCXK Beijing 2009-0007). Adaptive feeding for 1 week, free access to food and water, room temperature 25°C, 12h circadian rhythm.

[0075] T-peptide: 1 mg / cartridge, ① Dissolve 1 mg of T-peptide in RPMI-1640 medium (Beijing Suo Laibao Company, China) containing 10% fetal bovine serum (FBS, Hyclone Company, USA), mix well, and use for 100μg / ml group; ②Take 100μl of ① solution and dilute to 1ml for the 10μg / ml group; ③Take 100μl of ② solution and dilute to 1ml for the 1μg / ml group. According to the needs of each group, use RPMI-1640 medium containing 10% fetal bovine serum to further dilute to the required concentration.

[0076] Purified anti-mouse-CD3 / CD28: eBioscience Company, USA: Pr...

Embodiment 3

[0090] Example 3: Effect of T peptide on regulatory T cell activity

[0091] 1. Experimental animals and main reagents

[0092] Male BALB / c mice, 6-8w, 20±2g, were purchased from the Institute of Experimental Animals, Chinese Academy of Medical Sciences (animal certificate number: SCXK Beijing 2009-0007). Adaptive feeding for 1 week, free access to food and water, room temperature 25°C, 12h circadian rhythm.

[0093] T-peptide: 1 mg / branch, ①Dissolve 1 mg of T-peptide in RPMI-1640 medium (Beijing Suo Laibao Company, China) containing 10% fetal bovine serum (FBS, Hyclone Company, U.S.), mix well, and use In the 100μg / ml group; ②take 100μl of the solution of ①, dilute to 1ml, and use it in the 10μg / ml group; ③take 100μl of the solution of ②, dilute to 1ml, and use it in the 1μg / ml group. According to the needs of each group, use RPMI-1640 medium containing 10% fetal bovine serum to further dilute to the required concentration.

[0094] Purified anti-mouse-CD3 / CD28: eBioscienc...

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Abstract

The invention relates to a T-peptide immunomodulator for treating sepsis. The immunomodulator adopts the structure of (Thr-Lys-Pro-Arg-AAN)4-(Lys-AAN)2-Lys-AAN, wherein N is a natural number. According to the immunomodulator, through animal experiment researches, the fact that T-peptide has functions of modulating proliferation and secretion of effector T cells and can relieve the negative immunoregulationeffect of regulatory T cells through combination of Nrp-1 (neuropilin-1) of surface molecules of the regulatory T cells is discovered. The T-peptide can relieve the immunosuppression state caused by the sepsis through the mechanism, particularly the cellular immunosuppression, so that the survival rate of sepsis mice can be increased, sepsis symptoms can be improved, and the T-peptide immunomodulator can be used for treating the sepsis.

Description

technical field [0001] The present invention relates to the technical field of biomedicine, in particular to T-peptides and applications thereof, more specifically, to the application of T-peptides in the preparation of drugs for the treatment of sepsis, wherein the T-peptides negatively regulate immune regulation by inhibiting regulatory T cells , Relieve the mechanism of cellular immunosuppression, increase the survival rate of sepsis organisms and improve the symptoms of sepsis. Background technique [0002] Sepsis is a systemic inflammatory response syndrome induced by infection. Sepsis is not simply an uncontrolled inflammatory response, but also severe and progressive immunosuppression, especially cellular immunosuppression. The specific manifestation is that pathogens cannot be eliminated, and it is easy to cause secondary infection and resurrection of latent virus, etc., and even exist for a period of time after the recovery of sepsis patients, resulting in a declin...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/16A61P29/00A61P37/04
Inventor 姚咏明高玉雷祝筱梅韩苏
Owner FIRST HOSPITAL AFFILIATED TO GENERAL HOSPITAL OF PLA
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