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A pharmaceutical composition of siramesine and snake venom cytotoxin-ctx1

A-CTX1, cytotoxin technology, applied in the field of medicine, can solve the problems of increasing the pH value of tumor cell lysosome, not getting curative effect in mentally ill patients, affecting the stability of mitochondrial membrane, etc., so as to improve the effect of killing tumor cells and reduce economic The effect of reducing the burden and reducing the cost of treatment

Active Publication Date: 2020-10-02
黄山市三祈生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some studies have pointed out that LMP is an early event of sigma2 receptor ligand-induced tumor cell death, and some studies have also found that Sira can increase the pH value of tumor cell lysosomes, resulting in increased ROS (Reactive oxygen species), affecting the stability of mitochondrial membranes, thereby Initiate programmed cell death
[0004] Sira was studied as an anti-anxiety and anti-depressant piperidine drug in the early stage. In clinical trials, Sira was found to have low toxicity and good tolerance, but it did not achieve corresponding curative effect on patients with mental illness.

Method used

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  • A pharmaceutical composition of siramesine and snake venom cytotoxin-ctx1
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  • A pharmaceutical composition of siramesine and snake venom cytotoxin-ctx1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1: Effects of CTX1 combined with Sira on the growth of MCF7 cells

[0034] After treating MCF7 cells with CTX1 combined with Sira for 12, 24, and 36 hours, the results showed that the combination group had a more obvious inhibitory effect on the proliferation of MCF7 cells than the CTX1 single drug group, and the inhibitory effect had obvious dose and time effects. There is a significant statistical difference (P﹤0.01), the results are shown in figure 1 .

Embodiment 2

[0035] Embodiment 2: CI value evaluates drug synergistic effect:

[0036] The synergy index CI value of CTX1 combined with Sira is between 0.3 and 0.7, showing strong synergy (+++). The results are shown in Table 1. The CI values ​​of the control drug Ixabepilone (IXA) combined with hydroxychloroquine (HCQ) are mainly concentrated between 0.85 and 3.3, showing weak or no synergistic effect (see Table 2, 3).

[0037]

[0038] Table 2.CI value of IXA combined with HCQ-30μM on MCF7 n=3)

[0039]

[0040] Table 3.CI value of IXA combined with HCQ-40μM on MCF7 n=3)

[0041]

Embodiment 3

[0042] Example 3: Effect of CTX1 combined with Sira on MCF7 cell death

[0043] Flow cytometry: CTX1 can significantly induce the death of MCF-7 cells. With the increase of CTX1 dose, the death rate of MCF7 cells was significantly increased; the death rate of the combination group was more significantly increased than that of the CTX1 single drug group (P figure 2 , 3 .

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Abstract

The invention relates to the technical field of medicines and in particular relates to a pharmaceutical composition of Siramesine and snake venom cytotoxin-CTX1 and application of the pharmaceutical composition to preparation of anti-tumor drugs. Sira is a sigma2 receptor stimulant; after the Sira is combined with a sigma2 receptor, the permeability of a lysosome membrane is increased and tumor cells are induced to die; the Sira also can improve the pH (Potential of Hydrogen) value of lysosome of the tumor cells so that ROS is raised and program death of the cells is started. The Sira is combined with CTX1 so that the effect of the CTX1 on the lysosome is enhanced; the dosage of the CTX1 in the pharmaceutical composition is only 1 / 3.6 to 1 / 2.3 of the single dosage; the composition has a relatively strong cooperative effect and a tumor cell killing effect is remarkably improved; the pharmaceutical composition also has a remarkable killing effect on the drug-resisting tumor cells. The dosage of the drug is relatively low, so that the side effect and the untoward effect rate in a drug utilization process are reduced, the treatment cost is reduced and the economic burden of patients isalleviated.

Description

technical field [0001] The invention relates to the technical field of drugs, in particular to a pharmaceutical composition of siramesine and snake venom cytotoxin-CTX1 and its application in the preparation of antitumor drugs. Background technique [0002] The snake venom secreted by Zhoushan cobra (Naja naja atra) contains a variety of cytotoxins (Cytotoxin, CTX). At least 5 to 7 different CTXs have been isolated from the Zhoushan cobra venom produced in mainland China and Taiwan, all of which are strong basic polypeptides with a large number of hydrophobic residues composed of 60 to 63 amino acid residues. It is 6000~7000Da. CTXs belong to the three-finger toxins family (three-finger toxins), and its four highly conserved disulfide bonds make the spatial structure of CTX a "three-finger" shape. Arginine and lysine, and it is believed that this amphipathic finger structure is conducive to the combination of CTXs and cell membranes. CTXs penetrate the cell membrane and en...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/17A61P35/00A61K31/438
CPCA61K31/438A61K38/1703A61K2300/00
Inventor 董伟华香永欣孔天翰王菡彭享汪胜松
Owner 黄山市三祈生物医药科技有限公司
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