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A kind of ir-780 iodide-chitosan stearic acid graft and its preparation and application

A technology of IR-780 and chitosan, which is applied in the direction of drug combinations, preparations for in vivo tests, medical preparations of non-active ingredients, etc., can solve problems such as drug leakage, reduce leakage, improve curative effect, and increase concentration Effect

Active Publication Date: 2020-08-04
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the environmental parameters of tumor mitochondria and cytoplasm are too similar, and it is difficult to avoid drug leakage before the drug delivery system reaches the mitochondria

Method used

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  • A kind of ir-780 iodide-chitosan stearic acid graft and its preparation and application
  • A kind of ir-780 iodide-chitosan stearic acid graft and its preparation and application
  • A kind of ir-780 iodide-chitosan stearic acid graft and its preparation and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] (1) Preparation of low molecular weight chitosan

[0039] Take 50g of chitosan with a molecular weight of 450kDa and a degree of deacetylation of 95%, add it to 1500mL of hydrochloric acid aqueous solution with a volume ratio of 1.2%, and stir for 2 hours at 55°C to fully swell the chitosan, then slowly add 2% chitosan enzyme solution, chitosan enzymolysis reaction is carried out under the condition of 55 ℃, and the degradation degree of chitosan is controlled by gel permeation chromatography. After the reaction is finished, stir at 80°C for 0.5 hour, add 0.3% active carbon in a weight / volume ratio, dilute the reaction solution, filter it with a Buchner funnel, and process the filtrate with a 0.45 μm microporous membrane, freeze-dry to a low Molecular weight chitosan, the weight average molecular weight of the obtained chitosan is 5-20kDa.

[0040] (2) Synthesis of chitosan stearic acid graft

[0041] Take the above-mentioned chitosan with a molecular weight of 5-20 k...

Embodiment 2

[0046] (1) Preparation of low molecular weight chitosan

[0047] Take 50g of chitosan with a molecular weight of 450kDa and a degree of deacetylation of 95%, add it to 1500mL of hydrochloric acid aqueous solution with a volume ratio of 1.2%, and stir for 2 hours at 55°C to fully swell the chitosan, then slowly add 2% chitosan enzyme solution, chitosan enzymolysis reaction is carried out under the condition of 55 ℃, and the degradation degree of chitosan is controlled by gel permeation chromatography. After the reaction is finished, stir at 80°C for 0.5 hour, add 0.3% active carbon in a weight / volume ratio, dilute the reaction solution, filter it with a Buchner funnel, and process the filtrate with a 0.45 μm microporous membrane, freeze-dry to a low Molecular weight chitosan, the weight average molecular weight of the obtained chitosan is 5-20kDa.

[0048] (2) Synthesis of chitosan stearic acid graft

[0049] Take the above-mentioned chitosan with a molecular weight of 5-20 k...

Embodiment 3

[0054] (1) Preparation of low molecular weight chitosan

[0055] Take 50g of chitosan with a molecular weight of 450kDa and a degree of deacetylation of 95%, add it to 1500mL of hydrochloric acid aqueous solution with a volume ratio of 1.2%, and stir for 2 hours at 55°C to fully swell the chitosan, then slowly add 2% chitosan enzyme solution, chitosan enzymolysis reaction is carried out under the condition of 55 ℃, and the degradation degree of chitosan is controlled by gel permeation chromatography. After the reaction is finished, stir at 80°C for 0.5 hour, add 0.3% active carbon in a weight / volume ratio, dilute the reaction solution, filter it with a Buchner funnel, and process the filtrate with a 0.45 μm microporous membrane, freeze-dry to a low Molecular weight chitosan, the weight average molecular weight of the obtained chitosan is 5-20kDa.

[0056] (2) Synthesis of chitosan stearic acid graft

[0057] Take the above-mentioned chitosan with a molecular weight of 5-20 k...

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Abstract

The invention provides an IR-780 iodide-chitosan stearic acid grafted substance. Triethylamine is used as an acid-binding agent, IR-780 iodide is grafted to the chitosan stearic acid grafted substance, and the IR-780 iodide-chitosan stearic acid grafted substance with a mitochondrial targeting function is obtained. An antitumor drug adriamycin is encapsulated through a dialysis method, and a mitochondrial targeting IR-780 iodide-chitosan stearic acid grafted substance drug-carrying micelle is obtained. The drug-carrying micelle provided by the invention has a mitochondrial high-efficiency targeting function, the encapsulated drug adriamycin can be rapidly released in a tumor cell mitochondria after being subjected to near infrared laser radiation, leakage of adriamycin in a normal tissue and a non-targeting part is reduced, the toxic and side effects of adriamycin are decreased, the concentration of adriamycin in the tumor cell mitochondria is increased, a tumor cell is induced to be apoptotic, and thus the anti-tumor efficacy is improved.

Description

technical field [0001] The invention belongs to the field of pharmacy and relates to the construction of a mitochondrial targeting and photothermal response release drug delivery system, in particular to an IR-780 iodide-chitosan stearic acid graft with mitochondrial targeting and photothermal response release properties Construction of drug-loaded micelles and their application in antitumor drugs. Background technique [0002] Tumor cells are characterized by unlimited proliferative potential, insensitivity to growth inhibitory signals, inhibition of apoptosis, persistent proliferative signals, induction of angiogenesis, invasion and metastasis to other locations through capillary walls and basement membrane. Currently, chemotherapeutic agents with the potential to kill tumor cells also produce nonspecific toxicity to normal tissues. [0003] Drug molecules can act on the receptors, enzymes, and ion channels of the lesion cells through the occupying effect. The cell membr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/08A61K41/00A61K49/00A61K9/107A61K47/36A61K31/704A61P35/00
CPCA61K9/1075A61K31/704A61K41/0028A61K41/0052A61K47/36A61K49/0032C08B37/003A61K2300/00
Inventor 胡富强谭亚南孟廷廷袁弘
Owner ZHEJIANG UNIV
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