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Medicine composition, application and antineoplastic medicine

A drug and tumor technology, applied in the field of anti-tumor drugs and drug combinations

Inactive Publication Date: 2019-07-26
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although VDAs induce extensive necrosis in the tumor center, highly vascularized tumor cells at the tumor margins survive

Method used

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  • Medicine composition, application and antineoplastic medicine
  • Medicine composition, application and antineoplastic medicine
  • Medicine composition, application and antineoplastic medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Anti-tumor results and survival analysis of combined drug therapy of vascular blocker nanomedicine CA4-NPs and angiogenesis inhibitor SRF.

[0056] Inoculate H22 cells subcutaneously in Balb / c mice, when the subcutaneous tumor volume grows to about 140mm 3 , the mice were randomly divided into 4 groups: PBS, CA4-NPs (20mg·kg -1 ), SRF, SRF+CA4-NPs (20mg·kg -1 ), 7 in each group. The doses of CA4-NPs were equal to the doses of CA4. The treatment started on the 7th day after tumor implantation and ended on the 20th day, a total of 14 days. Sorafenib administration method is as follows: 30mg·kg -1 , intraperitoneal injection once a day, a total of 14 days; CA4-NPs administration method is as follows: 20mg·kg -1 , on the first day of administration by tail vein injection, a total of 1 time; the PBS group was given 200 μL PBS tail vein injection on the first day, and 200 μL PBS intraperitoneal injection once a day, a total of 14 days. The doses of CA4-NPs men...

Embodiment 2

[0062] Example 2 Tumor H&E pathological results after combined treatment of vascular blocker nanomedicine CA4-NPs and angiogenesis inhibitor SRF.

[0063] The subcutaneous H22 tumor model, grouping of tumor-bearing mice, and drug administration methods were the same as those in Example 1. After the treatment, the mice were sacrificed, the subcutaneous tumors were peeled off, fixed with 4% paraformaldehyde, embedded in paraffin, and stained with H&E. The H&E staining results were observed and photographed under an inverted phase-contrast microscope, and semi-quantitative analysis was performed with Image-J software. The result is as figure 2 (scale bar = 50 μm).

[0064] Depend on figure 2 It can be seen that a large number of tumor cells survived in the control group, and the CA4-NPs combined with sorafenib group could cause tumor necrosis after treatment, while the combined treatment group caused the largest area of ​​tumor necrosis.

Embodiment 3

[0065] Example 3 The pathological results of tumor Ki-67 after combined treatment of the vessel-blocking agent nanomedicine CA4-NPs and the angiogenesis inhibitor SRF.

[0066]The subcutaneous H22 tumor model, grouping of tumor-bearing mice, and drug administration methods were the same as those in Example 1. After the treatment, the mice were sacrificed, the subcutaneous tumors were peeled off, fixed with 4% paraformaldehyde, embedded in paraffin, immunohistochemically stained for Ki-67, and photographed under an inverted phase-contrast microscope with Image J or Image-Pro Plus6.0 software A semi-quantitative analysis was carried out, and the results were as follows image 3 (scalebar = 20 μm).

[0067] Depend on image 3 It can be seen that after the treatment, the expression of the proliferation index Ki-67 of the tumors in the four groups was the highest in the PBS group, followed by the Sorafenib group and the CA4-NPs group, and the lowest expression in the combined adm...

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Abstract

The invention provides a medicine composition, which comprises a vascular disrupting agent and an angiogenesis inhibitor. The medicine composition provided by the invention comprises an effective amount of the vascular disrupting agent and an effective amount of the angiogenesis inhibitor. The inventor discovers that the vascular disrupting agent can destroy the internal blood vessels of a tumor and give rise to tumor hypoxia, and the vascular disrupting agent and the angiogenesis inhibitor can have a synergistic effect and further enhance inhibition to the tumor when the vascular disrupting agent is in combined medication with the angiogenesis inhibitor. The combination of the vascular disrupting agent and the angiogenesis inhibitor provided by the invention can synergistically enhance aninhibiting effect on the tumor, and has a broad application prospect in the cancer treatment field.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a drug combination, application and anti-tumor drug. Background technique [0002] With increasing population and age, changes in human lifestyle have increased cancer risk, and cancer cases and deaths are expected to increase rapidly. Cancer has become one of the main causes of human death and seriously threatens human health. Tumor cell cycle instability leads to rapid cell proliferation and inhibition of apoptosis, forming an abnormal tumor microenvironment. The tumor microenvironment plays an important role in tumor therapy. Tumors need blood vessels to provide them with oxygen and nutrients as they grow, and to take away waste products from cell metabolism. In 1982, Denekamp proposed a new strategy to cause tumor cell death by collapsing or occluding tumor blood vessels. [0003] Vascular disrupting agents (VDAs for short) can destroy the formed tumor blood vessels and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61P35/00
CPCA61K45/06A61P35/00
Inventor 汤朝晖王雅琳于海洋宋万通陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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