Drug for treating bone marrow hematopoietic dysfunction

A technology of hematopoietic function and medicine, applied in the field of medicine

Active Publication Date: 2018-10-19
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the effect of ABC294640 on hemat

Method used

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  • Drug for treating bone marrow hematopoietic dysfunction
  • Drug for treating bone marrow hematopoietic dysfunction
  • Drug for treating bone marrow hematopoietic dysfunction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The SphK2 knockout mouse model was used to show that SphK2 knockout can increase the number of hematopoietic stem cells in the mouse bone marrow under normal physiological conditions.

[0033] SphK2 knockout mice were introduced from the National Institutes of Health (NIH) of the United States, and their background was C57BL / 6J, and they were raised in a specific pathogen-free (SPF) environment. First, we selected wild-type mice and SphK2 knockout mice, 6-8 weeks old, 6 in each, and killed them by neck dislocation, took their femurs and tibias, and flushed them out of the bone marrow cavity with a 1 ml syringe. The bone marrow was blown into a single cell suspension, and the red blood cell lysate was lysed for 2 minutes to remove the red blood cells, and filtered through a 70um filter to obtain a bone marrow single cell suspension. In order to calculate the number of hematopoietic stem cells in mice, the molecular marker system Lin-Sca-1+c-Kit+CD150+CD48- recognized in ...

Embodiment 2

[0036] Using the chemotherapy drug 5-fluorouracil to induce bone marrow hematopoietic system damage in mice, it was found that the damage repair ability of hematopoietic stem cells in SphK2 knockout mice was significantly enhanced.

[0037] The wild-type mice and SphK2 gene knockout mice in the feeding environment in Example 1 were selected respectively, 6-8 weeks old, and the number was 6. For intraperitoneal injection of 5-fluorouracil, the injection dose was 150 mg / kg, and after 12 days, the It was killed by neck dislocation, and its femur and tibia were taken, and the analysis process of other materials was the same as in Example 1. We used Graphpad6.0 for t-test analysis, and marked the significance of the difference with P<0.05.

[0038] The results showed that after 5-fluorouracil stimulation for 12 days, the number of hematopoietic stem cells in the bone marrow cells of the SphK2 gene knockout group was significantly more than that of the wild-type mouse group ( figu...

Embodiment 3

[0040] The survival period of SphK2 knockout mice is significantly longer than that of wild-type mice

[0041] The wild-type mice and the SphK2 gene knockout mice in the feeding environment in Example 1 were selected respectively, 8 weeks old, and the number was 10 each. For intraperitoneal injection of 5-fluorouracil, the injection dose was 150 mg / kg, once every 7 days , played continuously for 3 weeks, and observed the survival cycle of the mice ( image 3 ). We used Graphpad6.0 for t-test analysis, and marked the significance of the difference with P<0.05.

[0042] The results showed that the survival period of the SphK2 knockout mice group was significantly longer than that of the wild-type mice group under multiple 5-fluorouracil stimulations, indicating that the SphK2 knockout mice were more able to resist the chemotherapy damage induced by 5-fluorouracil, ** *P<0.001.

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Abstract

The invention provides application of a SphK2 inhibiting agent ABC294640 in improving hematopoietic stem cell functions and treating hematopoietic dysfunction. The ABC294640 can be used for treating essential hematopoietic dysfunction, or radiation and chemical drug irritated hematopoietic dysfunction, and is capable of improving hematopoietic stem cell functions to improve the recovery rate and the survive rate of hematopoietic function of a patient after chemotherapy is carried out for a plurality of times. According to the drug, a new drug source is provided to treat essential or induced hematopoietic dysfunction diseases.

Description

technical field [0001] The invention belongs to the field of medicine, and specifically relates to the application of ABC294640 in treating primary and hematopoietic dysfunction diseases caused by chemical drugs and radiation. Background technique [0002] Hematopoietic stem cells are a group of primitive hematopoietic cells that exist in hematopoietic tissues. Their main function is to differentiate and produce various blood immune cells such as red blood cells, platelets, and white blood cells, and support the renewal of the body's hematopoiesis and immune system. Hematopoietic stem cells play an important role in maintaining normal hematopoietic function and repairing damage. Primary lesions, radiation in the environment, chemical drugs in clinical treatment, and radiation all have serious damage to hematopoietic stem cells, leading to hematopoietic dysfunction, decreased blood count, decreased white blood cells, immune dysfunction, and even reduced survival rates. There...

Claims

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Application Information

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IPC IPC(8): A61K31/4409A61P7/00A61P35/02
CPCA61K31/4409A61P7/00A61P35/02
Inventor 赵萌
Owner SUN YAT SEN UNIV
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