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Application of saturated amine compound in preparing medicament for treating ischemic diseases

A technology for ischemic diseases and drugs, applied in the field of chemical compounds, can solve problems such as poor therapeutic effect of internal medicine drugs and low tolerance of patients

Active Publication Date: 2013-07-24
FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] At present, there are few drug studies on the treatment of ischemic diseases by mobilizing stem / progenitor cells. Conventional medical drug treatment is not effective, and surgical operations cannot withstand vascular bypass due to low tolerance of patients. Granulocyte colonies are found clinically. Stimulatory factor (G-CSF) and AMD3100 (trade name Plerixafor, which is entering clinical phase III trials) have certain functions of mobilizing hematopoietic stem cells and endothelial progenitor cells, but the administration time before G-CSF mobilization is generally one week and needs to be repeated AMD3100 is a specific antagonist of CXCR4, and studies have found that it can quickly mobilize bone marrow hematopoietic stem cells, and also has a certain effect on mobilizing endothelial progenitor cells

Method used

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  • Application of saturated amine compound in preparing medicament for treating ischemic diseases
  • Application of saturated amine compound in preparing medicament for treating ischemic diseases
  • Application of saturated amine compound in preparing medicament for treating ischemic diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] The synthesis of embodiment 1, TA01

[0038] Such as figure 1 In the process shown, TA01 was synthesized with reference to the existing method. References ①Mei Guangquan. Improved Synthesis of β, β′, β″-Triaminotriethylamine. Journal of Gannan Normal University, 2002, 3:55-56; ②Nie Guochao. Phase Transfer Catalysis and Microwave Radiation Synthesis Tris(2-cyanoethyl)amine. Photosensitive Science and Photochemistry, 2004, 22(4): 293-297; ③Silvia Del Piero, Andrea Melchior, Davide Menotti, Marilena Tolazzi, Anders Solvent effect on the thermodynamics of Ag(I)coordination to tripodal polypyridine ligands. J Therm Anal Calorim, DOI 10.1007 / s 10973-009-0341-8; ④Silvia Del Piero, Rosalisa Fedele, Andrea Melchior, Pierluigi Polese, Roberto Portnanova, Marile Tolazzi. Affinity of Tripodal and Linear Tetraamines for Silver(I) in DimethylSulfoxide. J Solution Chem, 2008, 37: 543-551.

[0039] 1. Synthesis of TA01, the saturated amine compound tris(2-(dimethylamino)ethyl)amine...

Embodiment 2

[0055] Example 2, TA01 Mobilization of Endothelial Progenitor Cell Pharmacodynamics Detection

[0056]6 male C57 mice in the test group were subcutaneously administered TA01, and the injection volume was calculated according to 5 mg / kg body weight for each mouse (the solvent could be TE buffer solution with pH 7.5-8.5, normal saline, PBS or sterilized distilled water). According to the time points of 0h, 1.5h, 3h, 6h, 12h, 24h, 36h, 48h, and 72h, 100ul blood was cut from the tail respectively, and red blood cell lysate (purchased from Zhengsibai Biotechnology Co., Ltd.) was added at a ratio of 1:10, and mixed. Mix well, let stand at room temperature for 10-15min, centrifuge at 1500rpm / min for 6min, discard the supernatant, add 100ul PBS containing 1% BSA, mix by pipetting, add 1.25ul primary antibody anti-mouse Flk-1 (abcam company) ultra-clean Operate in Taichung, mix well, and incubate at 4°C for 40min. Supplement PBS containing 1% BSA to 1.5mL, centrifuge at 1500rpm / min fo...

Embodiment 3

[0057] Embodiment 3, TA01 improves the detection of white blood cell (WBC) content in mouse peripheral blood

[0058] 18 male C57 mice were randomly divided into 3 groups (PBS group, AMD3100 group, TA01 group), 6 in each group, and the injection volume was calculated according to 5 mg / kg body weight of each mouse (the solvent was TE buffer solution with pH 7.5-8.5, Normal saline, PBS or sterile distilled water are acceptable). After 2 hours of subcutaneous injection of AMD3100 and 12 hours of subcutaneous injection of TA01, 10 μl of blood was taken by clipping the tail, and 2 mL of the imported diluent matched with the instrument was added, and the content of WBC was detected by a hematology analyzer (ABX PENTRA, France). The results are shown in Table 1. It can be seen that the saturated amine compound TA01 of the present invention can increase the content of WBC in the peripheral blood of mice; the number of white blood cells in the control group did not change significantly...

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Abstract

The invention discloses new application of a saturated amine compound, namely application of the saturated amine compound in preparing a medicament for treating ischemic diseases. Experiments prove that: the compound tri(2-(dimethylamino)ethyl)amine (code name TA01) can effectively participate repairing of lower limb ischemia by mobilizing endothelial progenitor cells in bone marrow. The application plays an important role in researching and developing the medicament for treating ischemic diseases, and has wide application prospect.

Description

technical field [0001] The present invention relates to new applications of compounds, in particular to the application of a saturated amine compound tris(2-(dimethylamino)ethyl)amine (code name TA01) in the preparation of drugs for treating ischemic diseases. Background technique [0002] Ischemic disease is clinically a serious health hazard, reduces the quality of life, and has a high rate of death and disability. It is divided into chronic and acute ischemic diseases. With the improvement of people's living standards and the aging of the population, the incidence of chronic ischemic diseases such as cardiovascular and cerebrovascular infarction and retinal ischemic lesions is on the rise. For example, the incidence of peripheral arterial disease is 3%-7%, and those over 70 years old The crowd incidence rate is as high as 15%-20%. Acute ischemic disease The ischemic injury of the lower extremity is one of the common clinical diseases. If it is not diagnosed in time and t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/132
Inventor 裴雪涛李艳华陈海旭师伟任祥亮张静张锐姚海雷何丽娟
Owner FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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