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Pharmaceutical composition for treating non-small cell lung cancer

A technology of non-small cell lung cancer and its composition, applied in the field of medicine, can solve the problems that cannot fundamentally solve the drug resistance mechanism of non-small cell lung cancer

Inactive Publication Date: 2020-10-27
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The abnormality of PI3K / AKT / mTOR signaling pathway often occurs in lung cancer. Related to the loss of the tumor suppressor gene PTEN, these phenomena occur more frequently in NSCLC squamous cell carcinoma; currently, this signaling pathway is used as a target to treat related inhibitors of NSCLC, including mTORC1 inhibitors, PI3K specific inhibitors, mTOR catalytic targets Inhibitors, PI3K-mTOR dual inhibitors and Akt inhibitors[13,14]; both preclinical and clinical, the above inhibitors have played a certain effect on the treatment of NSCLC, especially in combination with other anticancer drugs However, practice has shown that the inhibitors can only partially enhance the curative effect of platinum and TKI, and cannot fundamentally solve the drug resistance mechanism of non-small cell lung cancer

Method used

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  • Pharmaceutical composition for treating non-small cell lung cancer
  • Pharmaceutical composition for treating non-small cell lung cancer
  • Pharmaceutical composition for treating non-small cell lung cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Preparation and preservation of embodiment 1 pharmaceutical composition

[0062] (1) Preparation of Vismodegib and chloroquine pharmaceutical composition: first hydroxypropyl-β-cyclodextrin (HP-β-CD) is dissolved in water and is prepared into a 25% aqueous solution, then Vismodegib is dissolved in dimethyl sulfoxide (DMSO) was prepared into a 200mg / mL solution; the prepared Vismodegib dimethyl sulfoxide solution was slowly added to the HP-β-CD aqueous solution, and the final concentration of DMSO was 5%, and an appropriate amount of CQ was added to make it 10mg / mL Mix the solution by inverting slowly at room temperature until the solution becomes a clear drug sol suspension, and store it at 4°C;

[0063] (2) Preparation of GANT61 and chloroquine pharmaceutical composition: first dissolve hydroxypropyl-β-cyclodextrin (HP-β-CD) in water to prepare a 25% aqueous solution, then weigh GANT61 and dissolve it in dimethyl sulfoxide (DMSO) was prepared into a 135mg / mL solution;...

Embodiment 2

[0067] Hedgehog pathway inhibitor alone cannot inhibit the growth of non-small cell lung cancer subcutaneous xenografts in nude mice

[0068] By inoculating 1*10 subcutaneously in nude mice 7 A549 or NCI-H1975 non-small cell lung cancer cells were used to construct a subcutaneous tumor model of non-small cell lung cancer in nude mice. When the tumor grows to an average of 75cm 3 Give Vismodegib suspension treatment (dose is 50mg / kg) once every two days afterward, observe 28 days, measure tumor volume during, put to death experimental nude mice after experiment finishes, record tumor weight, the result shows, two Vismodegib treats 30 days after nude Compared with the control group, there was no significant difference (P>0.05) between the mouse subcutaneous tumors, (such as figure 1 shown).

Embodiment 3

[0070] After administration of Hedgehog pathway inhibitors, the expression of Gli2 in the subcutaneous xenografts of non-small cell lung cancer nude mice was not significantly changed, and the level of autophagy-related protein LC3-II was significantly increased:

[0071] In this experiment, the reason why non-small cell lung cancer is not sensitive to Vismodegib treatment was investigated. The Hedgehog-related genes Gli1 and Gli2 in the tumor before and after treatment were detected, and the autophagy-related protein LC3-II was detected at the same time; the results showed that, After treatment, the expression level of Hedgehog-related gene Gli1 decreased significantly. The results showed that Vismodegib inhibited the activity of Hedgehog signaling pathway in tumors. However, the expression level of the most critical prognostic factor Gli2 did not change significantly. It is speculated that there may be other mechanisms affecting Gli2 activity of Vismodegib, resulting in poor ...

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Abstract

The invention belongs to the technical field of medicines, and relates to a pharmaceutical composition for treating the non-small cell lung cancer, in particular to a pharmaceutical composition composed of a Hedgehog inhibitor and a cell autophagy inhibitor or a preparation method. The Hedgehog inhibitor in the pharmaceutical composition cannot effectively inhibit proliferation of non-small cell lung cancer tumors when being used alone, and after the Hedgehog inhibitor is used in combination with the autophagy inhibitor, the tumor burden of a mouse can be rapidly relieved, and the expression of a key prognostic protein molecule GLI2 of the mouse can be inhibited; meanwhile, the pharmaceutical composition also has a remarkable treatment effect on wild EGFR type tumors; the pharmaceutical composition has no obvious influence on the weight of the mouse, so that the pharmaceutical composition is proved to have no obvious drug toxicity in an experiment period; and the pharmaceutical composition has the characteristics of high targeting property, stable curative effect and the like, and is expected to become a new generation of medicine for non-small cell lung cancer treatment.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a pharmaceutical composition used for the treatment of non-small cell lung cancer, in particular to the characteristics, composition and preparation method of a pharmaceutical composition used for the treatment of non-small cell lung cancer, and its effect on EGFR mutants and EGFR wild-type application in the treatment of non-small cell lung cancer. Background technique [0002] The existing technology discloses the current research status of non-small cell lung cancer. The results show that lung cancer is one of the most malignant tumors with the highest morbidity and mortality in the world. In 2018, there were 2.1 million new lung cancer cases and 1.8 million deaths , accounting for approximately one-fifth (18.4%) of cancer deaths [1]. Lung cancer is usually divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC); among them, non-small cell lung cancer...

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 鞠佃文范佳君戴诗瑄章旭耀陈伟王一辰孙夕林申宝忠
Owner FUDAN UNIV
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