New application of lymphotoxin derivative

A technology of lymphotoxin and derivatives, which can be used in medical preparations containing active ingredients, antidote, drug combinations, etc., and can solve problems such as lack of protective measures and treatment methods, in-depth application research, and adverse reactions.

Active Publication Date: 2017-09-29
苏州华测生物技术有限公司
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  • Summary
  • 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, American Genentech Company discovered that wild-type Lymphotoxin α (Lymphotoxin α, LTα) had a protective effect on the bone marrow injury of mice caused by nuclear radiation, but it was found in subsequent preclinical animal experiments that wild-type LTα could cause obvious adverse reactions such as severe capillary leakage, hypotension and chills and fever, etc., so that the application research of LTα has not been carried out in depth

Method used

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  • New application of lymphotoxin derivative
  • New application of lymphotoxin derivative
  • New application of lymphotoxin derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] The preparation of embodiment 1 LT008

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

[0040] MHSTLKPAAHLIGDPSKQNSLLWRANTDRAFLQDGFSLSNNSLLVPTSGIYFVYSQVVFSGKAYSPKATSSPLYLAHEVQLFSSEYPFHVPLLSSQKMVYPGLQEPWLHSMYHGAAFQLTQGDQLSTHTDGIPHLVLSPSTVFFGAFAL.

Embodiment 2

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

[0042] 2.1 Research Methods

[0043] Wild C57BL / 6 mice were quarantined and raised in the SPF animal room for 3 weeks after purchase. Before grouping, the mice were weighed with BS124 balance, numbered and marked by ear tag method, and randomly grouped according to body weight. They were divided into PBS control group (W1) and LT008 group (W2), with 20 rats in each group, half male and half male, for the determination of survival rate. In addition, PBS control group (W3) and LT008 group (W4) were used, with 60 rats in each group, half male and half male, for the study of hemogram, bone marrow cytology, bone marrow pathology and related mechanisms.

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

Embodiment 3

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

[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: THP-1 cells were treated with different concentrations of LT008 (0, 0.1, 1, 10 and 50 μg / mL) for different times (0, 1, 4, 8, 24, 48 and 72 hours) and then the cells were processed. The cell proliferation curve was counted; the cells were irradiated with a total of 6 Gy 60Co-γ immediately after the above-mentioned different concentrations of LT008 (1.63 Gy / min), 0, 1, 4, 8, 24, 48, 72 h for cell counting and cell proliferation curves. see results Figure 13 .

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

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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 application of lymphotoxin derivative LT008, which belongs to the technical field of new application 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, is widely used around the world. However, the potential safety hazards caused by nuclear leaks have had a huge impact on human existence. Nuclear radiation can cause acute and chronic tissue damage and even severe organ dysfunction, especially for tissues composed of rapidly proliferating and renewing cells. The main reason for the death of patients after radiation is the hematopoietic dysfunction and the decrease of peripheral blood...

Claims

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Application Information

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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