New uses of lymphotoxin derivatives

A technology of lymphotoxins and derivatives, which is applied in the direction of medical preparations containing active ingredients, anti-toxins, drug combinations, etc., and can solve problems such as incomplete application research, lack of protective means and treatment methods, capillary leakage, etc.

Active Publication Date: 2020-08-21
苏州华测生物技术有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, protecting and restoring bone marrow function is one of the key factors related to the prognosis of patients with radiation damage, but there is still no effective means of protection and treatment for bone marrow damage caused by nuclear radiation
[0003] As early as 1996, Genentech Corporation of the United States discovered that wild-type lymphotoxin α (Lymphotoxinα, LTα) had a protective effect on the bone marrow injury of mice caused by nuclear radiation. Adverse reactions, such as severe capillary leakage, hypotension, and chills and fever, have prevented the application research of LTα from being carried out in depth

Method used

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  • New uses of lymphotoxin derivatives
  • New uses of lymphotoxin derivatives
  • New uses of lymphotoxin derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Preparation of LT008

[0039] It is prepared according to the process of Example 1 of the patent document with the publication number CN101084238B, and its amino acid sequence (SEQID NO:1) is:

[0040] MHSTLKPAAHLIGDPSKQNSLLWRANTDRAFLQDGFSLSNNSLLVPTSGIYFVYSQVVFSGKAYSPKATSSPLYLAHEVQLFSSEYPFHVPLLSSQKMVYPGLQEPWLHSMYHGAAFQLTQGDQLSTHTDGIPHLVLSPSTVFFGAFAL.

Embodiment 2

[0041] Example 2 LT008 can promote the recovery of wild-type C57BL / 6 mice from nuclear radiation damage in vivo

[0042] 2.1 Research methods

[0043] Wild C57BL / 6 mice were quarantined and reared in the SPF animal room for 3 weeks after they were purchased. After weighing them with a BS124 balance before grouping, they were numbered and marked by the ear tag method and randomly grouped according to their body weight. Divided into PBS control group (W1) and LT008 group (W2), each with 20 animals, half of the male and the female, for the survival rate determination. In addition, PBS control group (W3) and LT008 group (W4) were used, each with 60 animals, half male and female, for the study of blood picture, bone marrow cytology, bone marrow pathology and related mechanisms.

[0044] All mice in the LT group were given 250μg / kg LT008 via tail vein injection for three consecutive days after 75% alcohol disinfection two days before and on the day of irradiation. The administration conc...

Embodiment 3

[0059] Example 3 The protective effect of LT008 on human monocyte THP-1 damage caused by nuclear radiation in vitro

[0060] 3.1 LT008 can promote the proliferation of THP-1 cells and promote the survival of THP-1 cells under irradiation

[0061] (1) Method: Different concentrations of LT008 (0, 0.1, 1, 10 and 50μg / mL) were treated with THP-1 cells for different times (0, 1, 4, 8, 24, 48 and 72 hours) and then counted To make the cell proliferation curve; after the above-mentioned different concentrations of LT008 are applied to the cells, the total amount of 6Gy 60Co-γ irradiation (1.63Gy / min) is performed immediately, and the cells are processed for 0, 1, 4, 8, 24, 48, 72h Count and make cell proliferation curve. See the result Figure 13 .

[0062] (2) Test result: the result is as Figure 13 As shown in A, compared with the control group, the cell number of cells treated with 0-10μg / mL LT008 did not change significantly at different times, but the number of THP-1 cells began to...

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Abstract

The invention discloses a new application of a lymphotoxin derivative LT008 (another name LTa-55) in preparation of drugs for preventing and treating a nuclear radiation injury, and particularly discloses a new application in preparation of drugs for treating radiation-induced acute and chronic tissue injuries or even severe organ dysfunction. Through a plurality of researches and drug screening tests, the results prove that the LT008 has a good effect in prevention and treatment of nuclear radiation diseases, especially radiation-induced acute and chronic tissue injuries or even severe organ dysfunction, and can be prepared into a new drug applied to the aspect.

Description

Technical field [0001] The invention relates to a new use of the lymphotoxin derivative LT008, and belongs to the technical field of new uses of medicine. Background technique [0002] The nuclear radiation mentioned in the present invention refers to the flow of microscopic particles released during the transformation of atomic nuclei from one structure or one energy state to another structure or another energy state. Due to the current environmental pollution and energy shortage, nuclear energy, as an efficient and clean energy source, is widely used worldwide. However, the potential safety hazards caused by nuclear leaks have a huge impact on human survival. Nuclear radiation can cause acute and chronic tissue damage and even severe organ dysfunction, especially damage to tissues composed of cells that proliferate and renew rapidly. The main reason for the death of patients after radiation is the hematopoietic dysfunction caused by bone marrow suppression and the decline of ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/19A61P39/00A61P17/16
CPCA61K38/191
Inventor 陆国才宗英沈毅珺杨彤夏玉叶陈永春高婷婷
Owner 苏州华测生物技术有限公司
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