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Environmentally responsive tumor targeted combined administration transfer system

An environment-responsive, tumor-targeting technology, applied in the field of environment-responsive tumor-targeting combined drug delivery system and its preparation, can solve problems such as low drug loading, achieve good environment responsiveness, rapid systemic circulation stability, Avoiding the effect of disintegration and drug leakage

Active Publication Date: 2016-06-29
武汉博诚恒瑞医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The application of polymer materials to prepare nanoparticles for the delivery of anti-tumor drugs has been a hot spot in the research of drug delivery systems in recent years, but there are defects such as low drug loading. Combined administration can make up for the defects of low drug loading, and at the same time exert the synergistic effect of drugs. effect

Method used

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  • Environmentally responsive tumor targeted combined administration transfer system
  • Environmentally responsive tumor targeted combined administration transfer system
  • Environmentally responsive tumor targeted combined administration transfer system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1. Preparation of High Molecular Polymer

[0032] (1) Synthesis of DOX-DSP-CMCS

[0033] Take doxorubicin hydrochloride, accurately weighed, dissolve in pure water, add triethylamine (the molar ratio of doxorubicin hydrochloride to triethylamine is 1:2) and stir overnight in the dark, and put the reaction solution in a dialysis bag for pure Water is protected from light and dialyzed, refrigerated and centrifuged, and the retentate is lyophilized to obtain base doxorubicin (DOX).

[0034] Take 40 mg of DSP, accurately weighed, dissolve in 2.0 mL of dimethyl sulfoxide, and add 0.1 mL of 0.1% triethylamine dimethyl sulfoxide solution. Take another 54 mg of DOX, weigh it accurately, dissolve it in 2.7 mL of dimethyl sulfoxide solution, slowly add it dropwise to the above DSP solution (the molar ratio of DOX to DSP is 1:0.9), and stir at room temperature for 2 hours to obtain the intermediate DOX- DSP.

[0035] Accurately weigh DOX-DSP and dissolve in dimethyl sulfoxide s...

Embodiment 2

[0060] 1. Preparation of DOX-DSP-CMCS

[0061] Same as the method of Example 1.

[0062] 2. Preparation of polymers with surface-coupled targeting molecules

[0063] Add 10 mg of ammoniated folic acid to 2 mg / mL DOX-DSP-CMCS aqueous solution (25 ml), add 8 mg of EDC to react for 12 hours, dialyze with deionized water for 48 hours, and freeze-dry to obtain a high molecular weight polymer with surface-coupled targeting molecules.

[0064] 3. Preparation of environment-responsive tumor-targeted drug delivery system

[0065] Get 20 mg of the high molecular polymer obtained in step 2 and disperse it in 10 mL of water, add 2 mg of curcumin, stir in the dark for 3 days, ultrasonic the probe for 30 times, then dialyze with deionized water for 24 hours, remove excess curcumin, freeze-dry, that is have to.

[0066] 3. Tumor cytotoxicity test

[0067] Test method is identical with embodiment 1, and test result sees the following table.

[0068]

[0069] 4. In vitro release experi...

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Abstract

The invention discloses an environmentally responsive tumor targeted combined administration transfer system.Adriamycin amycin and carboxymethyl chitosan are connected through a disulfide bond, and therefore an adriamycin amycin macromolecular prodrug is synthesized.The other chemotherapy drug is ingeniously encapsulated in the adriamycin amycin macromolecular prodrug, and therefore the combined administration nano transfer system is prepared.The system has good systemic circulation stability and intelligent drug release performance, few drug ingredients are released in simulated blood, the release quantity of the drug ingredients in a cancer cell environment is very large, and meanwhile high applicability is achieved.

Description

technical field [0001] The invention belongs to the field of pharmaceuticals, and in particular relates to an environment-responsive tumor-targeting combined drug delivery system and a preparation method thereof. Background technique [0002] Chemotherapy, as the main means of tumor treatment, has always had the problems of poor therapeutic effect and large side effects. Clinical experiments and research have shown that it is difficult for a single drug to have a significant therapeutic effect on tumors, and it is easy to produce drug resistance and reduce the curative effect. Therefore, combined drug administration has become a development direction for tumor treatment. [0003] Doxorubicin and cisplatin are two drugs with different anti-tumor mechanisms. They are often used in combination to treat tumors clinically. Clinical results show that the combination of the two has a synergistic effect. Doxorubicin is an antitumor antibiotic that can inhibit the synthesis of RNA a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/704A61K33/24A61K47/48A61P35/00A61K31/12
CPCA61K31/12A61K31/704A61K33/24A61K2300/00
Inventor 刘诗久张政张雪琼
Owner 武汉博诚恒瑞医药科技有限公司
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