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Pharmaceutical composition with synergistic anti-osteosarcoma effect and application thereof

A composition and drug technology, applied in the field of medicine, can solve the problem of lack of osteosarcoma treatment drugs, etc., and achieve the effect of inhibiting the growth of osteosarcoma cells, less usage, and good anti-tumor effect

Active Publication Date: 2018-06-22
徐州维康生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, the treatment of osteosarcoma has encountered a bottleneck, especially for the treatment of some metastatic osteosarcoma and chemotherapy-resistant patients. We lack effective drugs for the treatment of osteosarcoma, and we need to develop new drugs and treatment strategies

Method used

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  • Pharmaceutical composition with synergistic anti-osteosarcoma effect and application thereof
  • Pharmaceutical composition with synergistic anti-osteosarcoma effect and application thereof
  • Pharmaceutical composition with synergistic anti-osteosarcoma effect and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Apatinib (purchased from sel leck, product number S2221) and GSK-J4 (purchased from sel leck, product number S7070) were prepared according to different concentrations before use.

[0028] The effects of different concentrations of drugs on the proliferation of human osteosarcoma cells 143B and SJSA1 were detected by the method of MTT experiment. 143B (ATCC number CRL-8303TM, human source, epithelial-like adherent growth) and SJSA1 cells (ATCC number CRL-2098TM, human source, epithelial-like adherent growth) in the exponential growth phase were digested with trypsin and blown Disperse into a single cell suspension, count, and inoculate into a 96-well culture plate. Cultivate in the incubator for 24 hours. After the cells adhere to the wall, add different concentrations of test drugs and stop the culture after acting for 48 hours respectively. Add 20 μl MTT (5 mg / mL) to each well and incubate at 37°C for 4 hours in the dark. Then discard the liquid in each well, add 150...

Embodiment 2

[0033] Furthermore, the inhibitory effect of apatinib and GSK-J4 on the proliferation of 143B and SJSA1 cells was investigated, and the drug interaction index CI was obtained by calculation.

[0034] Determination by MTT method

[0035] Inhibitory effect of apatinib and GSK-J4 single drug and the combination of the above two drugs on the proliferation of 143B and SJSA1 cells.

[0036] Experimental grouping: Experimental grouping 143B and SJSA1 cell lines were treated as follows: 1) blank control group: without any drug treatment; 2) each single drug group: apatinib group: at 40, 20, 10, 5, 2.5, 1.25, 0.625μmol / L apatinib for 48h; GSK-J4 group: 20, 10, 5, 2.5, 1.25, 0.625, 0.3125μmol / LGSK-J4 for 48h; 3) combined drug group: Apatinib+GSK-J4 group: 40, 20, 10, 5, 2.5, 1.25, 0.625μmol / L apatinib and 20, 10, 5, 2.5, 1.25, 0.625, 0.3125μmol / LGSK-J4 Under the action of culture for 48h; each group set 3 duplicate wells, the experiment was repeated 3 times, and the average value was ...

Embodiment 3

[0045] The osteosarcoma cells 143B and SJSA1 cells were cultured. When the cells were in the exponential growth phase, they were digested with trypsin, and the cells were collected and made into 1×10 cells with sterile saline. 7 cells / mL cell suspension, subcutaneously injected into the left armpit of male nude mice, each 0.2 mL. Observe the condition of the mice every day, measure the long diameter (a) and short diameter (b) of the tumor with a vernier caliper, according to the formula V(mm 3 )=(a×b 2 ) / 2 to calculate tumor volume. When the tumor volume reaches 80-100mm 3 , the animals were randomly divided into 4 groups, 5 animals in each group. They are: ①control group: normal saline; ②apatinib group: 100mg / kg; ③GSK-J4 group: 50mg / kg; ④combination group: apatinib 100mg / kg+GSK-J4 50mg / kg. The control group, the apatinib group, the GSK-J4 group and the combination group were intraperitoneally administered every other day for 5 consecutive administrations. After 27 days, ...

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Abstract

Provided are a pharmaceutical composition with a synergistic anti-osteosarcoma effect and application thereof. The invention discloses the pharmaceutical composition containing a VEGFR2 selective inhibitor Apatinib and a histone demethylase inhibitor GSK-J4 and the application thereof. Apatinib and GSK-J4 are used in combination to achieve the synergistic anti-osteosarcoma effect, the osteosarcomacell growth can be obviously inhibited, and the pharmaceutical composition is used for treatment of tumors like osteosarcoma.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a pharmaceutical composition with synergistic antitumor effect and application thereof. Background technique [0002] Osteosarcoma is a primary malignant bone tumor originating from bone mesenchymal cells, characterized by the direct formation of immature bone or osteoid tissue by proliferating tumor cells. Typical osteosarcoma is clinically rare, with an incidence rate of about 0.3 / 10,000, accounting for about 0.2% of malignant tumors and 15% of primary bone tumors. Typical osteosarcoma is more likely to occur in males, and the age of onset is mostly 8 to 25 years old. It is rare before the age of 6 and after the age of 60. The predilection site is the long bone, usually the distal femur or proximal tibia, followed by the proximal humerus, and other parts less common. Its hematogenous metastasis occurs early and has a high incidence rate, and progresses rapidly. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/506A61K31/4545A61P35/00
CPCA61K31/4545A61K31/506A61K2300/00
Inventor 赵蔚邹昌业
Owner 徐州维康生物科技有限公司
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