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Drug carrier system and preparation method thereof

A carrier system and drug technology, applied in the field of drug carrier system and its preparation, can solve the problems of normal tissue and organ side effects, difficult treatment, and reduced drug availability

Inactive Publication Date: 2013-06-26
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Chemotherapy is one of the traditional treatment methods for cancer, but at present, the drugs generally lack selectivity in clinical treatment. cause significant side effects
In addition, long-term use of chemotherapy drugs will also cause tumor cells to develop resistance to chemotherapy drugs, which will increase the difficulty of later treatment.

Method used

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  • Drug carrier system and preparation method thereof
  • Drug carrier system and preparation method thereof
  • Drug carrier system and preparation method thereof

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preparation example Construction

[0056] The invention provides a preparation method of a drug carrier system, comprising the following steps:

[0057] A) Mix and incubate the negatively charged drug with the cationic carrier to obtain a binary complex;

[0058] B) mixing the binary complex with a pH-sensitive masking system to obtain a drug carrier system;

[0059] The pH sensitive masking system is a copolymer of hyperbranched polyethyleneimine, lysine and glutamic acid, or a copolymer of hyperbranched polyethyleneimine, lysine and aspartic acid; The molecular weight of the copolymer of polyethyleneimine, lysine and glutamic acid is 2600~60000; The molecular weight of the copolymer of described hyperbranched polyethyleneimine, lysine and aspartic acid is 2600~ 60000; in the hyperbranched polyethyleneimine, lysine and glutamic acid copolymer, the molar ratio of glutamic acid to lysine is (1.5-50): 1; the hyperbranched In the copolymer of polyethyleneimine, lysine and aspartic acid, the molar ratio of aspart...

Embodiment 1～8

[0068] Dissolve polyethyleneimine (PEI) and lysine-N-endocarboxylic acid anhydride in a mixed solvent of dichloromethane and DMF, respectively, and the volume ratio of dichloromethane and DMF is 1:2. Both were mixed and reacted at 30° C. for 72 hours. Then add the mixed solution of ε-benzyloxycarbonyl-L-glutamic acid-N-internal carboxylic acid anhydride in dichloromethane and DMF, react at 35°C for 72 hours, settle with ether after the reaction, filter and dry, dissolve in trifluoro Add the acetic acid solution of hydrogen bromide to acetic acid, deprotect at room temperature for 2 hours, then settle with ether, dissolve in water after drying, dialyze with a 3500Da dialysis bag for 3 days, change the water 6 times, and obtain polyethylene glycol after freeze-drying. The block copolymer of amine-polylysine-polyglutamic acid is denoted as PEI-b-PLL-b-PGA.

[0069] PEI-b-PLL-b-PGA with different molecular weights and compositions can be obtained by changing the molar amounts of ...

Embodiment 9～16

[0074] According to the raw material ratio shown in Table 1, the random copolymer of polyethyleneimine-polylysine-polyglutamic acid was prepared according to the following method.

[0075] Dissolve polyethyleneimine (PEI) in a mixed solvent of dichloromethane and DMF, the volume ratio of dichloromethane and DMF is 1:2, add lysine-N-endocarboxylic acid anhydride and ε-benzyloxycarbonyl- L-glutamic acid-N-internal carboxylic acid anhydride, react at 35°C for 72 hours, settle with ether after the reaction, filter and dry, dissolve in trifluoroacetic acid, add hydrogen bromide in acetic acid solution, deprotect at room temperature 2 hours, then settled with ether, dried and dissolved in water, dialyzed with a 3500Da dialysis bag for 3 days, changed the water 6 times, and obtained a random copolymer of polyethyleneimine-polylysine-polyglutamic acid after freeze-drying the product , recorded as PEI-b-P (LL-ran-GA).

[0076] PEI-b-P (LL-ran-GA) with different molecular weights and c...

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Abstract

The invention provides a drug carrier system. The drug carrier system comprises a pH sensitive shielding system, a cation carrier and electronegative drugs, wherein the pH sensitive shielding system is a copolymer of hyperbranched polyethyleneimine, lysine and glutamic acid or the copolymer of hyperbranched polyethyleneimine, lysine and aspartic acid; in the copolymer of the hyperbranched polyethyleneimine, lysine and glutamic acid, the molar ratio of the glutamic acid to the lysine is (1.5-50):1; in the copolymer of the hyperbranched polyethyleneimine, lysine and aspartic acid, the molar ratio of the aspartic acid to the lysine is (1.5-50):1; and the weight ratio of the pH sensitive shielding system to the cation carrier is (0.5-100):1. The drug carrier system has pH value responsibility and obvious difference of cytotoxicity under different pH conditions and can be used for intelligently releasing drugs.

Description

technical field [0001] The invention relates to the field of biological materials, in particular to a drug carrier system and a preparation method thereof. Background technique [0002] At present, malignant tumors have become a major threat to human life. According to the World Health Organization, about 7.6 million people died of cancer in the world in 2008, and it is expected to exceed 13.1 million by 2030 (GLOBOCAN2008 (IARC) Section of Cancer Information (28 / 6 / 2012)). Therefore, anti-tumor therapy has received widespread attention from researchers. [0003] Chemotherapy is one of the traditional treatment methods for cancer, but at present, the drugs generally lack selectivity in clinical treatment. cause significant toxic side effects. In addition, long-term use of chemotherapy drugs will also cause tumor cells to develop resistance to chemotherapy drugs, which will increase the difficulty of later treatment. Therefore, how to improve the selectivity of drugs to tu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K47/34A61P35/00
Inventor 田华雨关秀文陈学思焦自学陈杰郭兆培林琳
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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