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Pharmaceutical composition treating tumors

A composition and drug technology, applied in the fields of biology and medicine, can solve problems such as tumors that have not yet been seen

Inactive Publication Date: 2014-08-20
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] So far, there is no report on the combination or sequential administration of autophagy-modulating drugs and monoclonal antibody drugs to make pharmaceutical compositions or compound drugs to treat tumors

Method used

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  • Pharmaceutical composition treating tumors
  • Pharmaceutical composition treating tumors
  • Pharmaceutical composition treating tumors

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0039] Preparation of monoclonal antibody master solution: Weigh 10 mg of chLym-1 monoclonal antibody freeze-dried powder and dissolve it in 1 ml of 0.02M PBS solution with pH=7.4. Stir well and filter through a 0.1 μm sterile filter. Divide into 10 tubes for storage. Diluted to 10μg / ml for in vitro tests.

[0040] Preparation of rituximab stock solution: Weigh 10mg of rituximab freeze-dried powder and dissolve it in 1ml of 0.02M PBS solution with pH=7.4. Stir well and filter through a 0.1 μm sterile filter. Divide into 10 tubes for storage. Diluted to 10μg / ml for in vitro tests.

[0041] Preparation of trastuzumab stock solution: Weigh 10mg of lyophilized powder of trastuzumab and dissolve in 1ml of 0.02M PBS solution with pH=7.4. Stir well and filter through a 0.1 μm sterile filter. Divide into 10 tubes for storage. Diluted to 10μg / ml for in vitro tests.

[0042] Autophagy inhibitor drug configuration

[0043] (1) Preparation of chloroquine solution: Dissolv...

Embodiment 1

[0052] Example 1 chLym-1 monoclonal antibody induces up-regulation of LC3-II expression in Raji cells

[0053] The Raji cells treated with 10 μg / ml chLym-1 monoclonal antibody for 24 hours and the control group Raji were lysed with Western Blot and IP lysate to extract the total protein of the cells for protein quantification, and 50 μg of protein per well was loaded for protein electrophoresis and analyzed. Transfer membrane for Western blot, and use ECL chemiluminescence kit for chemiluminescence, the results are as follows figure 1 As shown: the expression of autophagy-related protein LC3Ⅱ in Raji cells treated with 10 μg / ml chLym-1 monoclonal antibody for 24 hours was higher than that of the control group, and the grayscale processing software IQuentTL analysis found that there was a very significant difference between the two ( p <0.01), due to the positive correlation between the expression of LC3Ⅱ and the number of autophagosomes, the higher the expression of LC3Ⅱ, the ...

Embodiment 2

[0056] Example 2 chLym-1 monoclonal antibody induces autophagosome aggregation in Raji cells

[0057] Raji cells intervened by chLym-1 monoclonal antibody for 24 hours were collected, fixed, embedded, sectioned, and stained, and then their ultrastructure was observed under an electron microscope. 10μg / ml chLym-1 monoclonal antibody intervened for 24 hours, and the nucleus of Raji cells was severely deformed. Under the magnification of 8000×, many vacuole-like structures were found in the extranuclear area, and under the magnification of 50000×, a large number of Obvious bilayer membrane structure (such as image 3 shown), according to literature reports, the diameter of autophagosomes is generally between more than 300 nanometers and several microns, which is consistent with the size of the double-membrane structure vacuoles shown in the figure of this example. The analysis confirms that the arrow points to The double-membrane-like vacuoles were autophagosomes. Compared wit...

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Abstract

The invention relates to the technical field of medicines and biology, and concretely relates to a pharmaceutical composition treating tumors. The pharmaceutical composition consists of one or a plurality of autophagy adjusting medicines and a monoclonal antibody medicine. The autophagy adjusting medicine(s) and the monoclonal antibody medicine in the pharmaceutical composition are administrated in a combined administration manner or in a sequential administration manner. By adjusting cell autophagy, the curative effect of the monoclonal antibody medicine on various tumors is enhanced. By utilizing the cell autophagy adjusting medicines to activate / inhibit autophagy, the curative effects of a plurality of monoclonal antibody medicines on lymphoma, stomach cancer, breast cancer, lung cancer, ovarian cancer and brain tumor are enhanced, and especially the curative effects on lymphoma, stomach cancer and breast cancer are enhanced.

Description

technical field [0001] The present invention relates to the fields of medicine and biotechnology, and to antitumor drugs, in particular to a pharmaceutical composition for treating tumors, especially to a pharmaceutical composition composed of one or more autophagy-regulating drugs and a monoclonal antibody drug . Background technique [0002] Chemotherapy is still the main method for tumor treatment at present. However, the side effects of chemotherapy are large, which makes monoclonal drugs have a huge market and demand. In recent years, monoclonal antibody (McAb, referred to as monoclonal antibody) therapeutic drugs have developed rapidly, and some have been used clinically or made into diagnostic kits and detection reagents. Among them, Rituximab, chLym-1 monoclonal antibody and Trastuzumab are more prominent [Bozhkov B. Monoclonal antibodies--their clinical and diagnostic importance. Vutr Boles. 1987;26( 6): 1-9.]; For example, rituximab is used in clinical treatment ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61P35/00
Inventor 鞠佃文范佳君曾贤王绍飞李玉彬王子玉
Owner FUDAN UNIV
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