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Carboxymethyl chitosan microcapsule for jointly loading chemotherapeutic drug and thermal therapy sensitizer to slowly release novel embolic agent, and preparation method and application of carboxymethyl chitosan microcapsule

A technology of carboxymethyl chitosan microcapsules and carboxymethyl chitosan, applied in the field of medicine, can solve the problems of slow metabolism, local accumulation, high tissue toxicity, etc., so as to reduce pain, reduce toxic side effects, and reduce drug dosage Effect

Inactive Publication Date: 2020-12-25
SICHUAN KANGCHENG BIOLOGICAL SCI & TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there are still problems such as local accumulation, slow metabolism and excessive tissue toxicity in drug-loaded systems such as indocyanine green, and carboxymethyl chitosan has not been seen to be loaded with chemotherapeutic drugs and indocyanine green. Microcapsules of sensitizers and their application in photothermal therapy and chemotherapy of tumors

Method used

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  • Carboxymethyl chitosan microcapsule for jointly loading chemotherapeutic drug and thermal therapy sensitizer to slowly release novel embolic agent, and preparation method and application of carboxymethyl chitosan microcapsule
  • Carboxymethyl chitosan microcapsule for jointly loading chemotherapeutic drug and thermal therapy sensitizer to slowly release novel embolic agent, and preparation method and application of carboxymethyl chitosan microcapsule
  • Carboxymethyl chitosan microcapsule for jointly loading chemotherapeutic drug and thermal therapy sensitizer to slowly release novel embolic agent, and preparation method and application of carboxymethyl chitosan microcapsule

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Dissolve carboxymethyl chitosan in 5mL of aqueous solution to a concentration of 0.1g / mL, and stir at 500r / min to form a water phase; 20mL of soybean oil and 0.5mL of Span80 emulsifier are stirred at 500r / min An oil phase is formed; the water phase is added dropwise to the oil phase, and emulsified at a room temperature of 25° C. and 500 r / min for 60 min.

[0041] The reaction solution was placed in a hot water bath at 70° C., 0.5 mL of 50% glutaraldehyde was added, and stirred and solidified at 500 r / min for 1 h. After reaction finishes, wash with water, Virahol respectively, dry to obtain microcapsules, the size of the microcapsules of gained is about 5 μm (see image 3 ).

Embodiment 2

[0043] Dissolve carboxymethyl chitosan and chemotherapeutic drug doxorubicin in 10mL of aqueous solution to make the concentrations respectively 0.02g / mL and 100μg / mL, and stir at 1400r / min to form an aqueous phase; 100mL of olive oil, Span60 Emulsifier 1.5mL, stirred at 1400r / min to form an oil phase; water phase was added dropwise to the oil phase, stirred at 35°C and 1400r / min to emulsify for 40min.

[0044] The reaction solution was placed in a hot water bath at 60° C., 0.5 mL of 50% formaldehyde was added, and stirred and solidified at 1400 r / min for 2 hours. After the reaction, wash with water and isopropanol respectively, and dry to obtain microcapsules, and the size of the obtained microcapsules is about 500nm.

[0045] Prepare a mixed solution containing 0.05mol / L NHS and 0.025mol / L EDC with DMSO as a solvent, take 50mg of microcapsules and 1.0mg of folic acid and add 0.1mL of the above mixed solution respectively, and stir it overnight by magnetic force at room tempe...

Embodiment 3

[0047] Dissolve carboxymethyl chitosan, chemotherapeutic drug doxorubicin, and photothermal sensitizer indocyanine green in 10 mL of aqueous solution to make the concentrations 0.1 g / mL, 10 μg / mL, and 0.05 mg / mL, respectively. Stir at 800r / min to form a water phase; stir 80mL of linseed oil and 0.8mL of triglyceride emulsifier at 800r / min to form an oil phase; add the water phase to the oil phase drop by drop, Min under stirring for emulsification 45min.

[0048] The reaction solution was placed in a hot water bath at 70°C, 0.8 mL of glutaraldehyde was added, and stirred and solidified at 800 r / min for 0.5 h. After the reaction, wash with water and isopropanol respectively, and dry to obtain microcapsules. The size of the obtained microcapsules is about 20 μm.

[0049] Prepare a mixed solution containing 0.01mol / L NHS and 0.005mol / L EDC with DMSO as a solvent, take 20mg of microcapsules and 0.3mg of folic acid and add 0.2mL of the above mixed solution respectively, and stir m...

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Abstract

The invention discloses a microcapsule with a chemotherapeutic drug and a thermal therapy sensitizer, and a preparation method of the microcapsule. The diameter of the microcapsule is 0.5-250 mu m; and the thickness of a shell of the microcapsule is 0.05-30 mu m. The microcapsule with the chemotherapeutic drug and the thermal therapy sensitizer in the invention comprises the shell and a core material; the shell is carboxymethyl chitosan; the core material is wrapped in the shell; the core material comprises a photothermal sensitizer and the chemotherapeutic drug; and targeting molecules are coupled to the outer surface of the shell. The microcapsule in the invention is prepared according to the following steps: emulsification, interfacial polymerization, folic acid coupling and washing, soas to obtain a material for coating photo-thermal temperature rise and tumour embolic agents. The microcapsule prepared by the method in the invention is simple in process, good in repeatability andhigh in production efficiency; and large-scale production is easy to realize. The particle size, the size and the thickness of the microcapsule prepared by the method in the invention are controllable. The shell material contains a large amount of amino groups, so that the drug can be endowed with the functions of controlled release, antibody coupling and the like. The microcapsule is a carboxymethyl chitosan microcapsule carrier with photo-thermal sensitization, chemotherapeutic drug sustained and controlled release, targeting and good biocompatibility, and has a good application prospect inbreast cancer treatment as an embolic agent.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to a slow-release novel embolization carboxymethyl chitosan microcapsule co-carrying chemotherapeutic drugs and thermotherapy sensitizers and its preparation method and application. Background technique [0002] Breast cancer is one of the main malignant tumors that threaten the health of women in my country. At present, the clinical treatment methods for primary breast cancer mainly use surgical resection, embolization, radiotherapy and chemotherapy, etc., but these methods have certain limitations. However, such as high surgical risk, high side effects, lack of tumor specificity and drug resistance in the course of treatment, the purpose of treatment cannot be achieved. Traditional treatment methods have extremely limited effects on metastatic tumors, which is also a major reason why the mortality rate of malignant tumors is difficult to be effectively controlled. Co...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K45/06A61K47/06A61K47/36A61K47/44A61K47/54A61K47/69A61L24/00A61L24/08A61P15/14A61P35/00
CPCA61K41/0052A61K45/06A61K47/06A61K47/36A61K47/44A61L24/0015A61L24/08A61L2430/36A61K47/545A61K47/6925A61P15/14A61P35/00A61K2300/00C08L5/08
Inventor 杜奇军肖凯钟治晖
Owner SICHUAN KANGCHENG BIOLOGICAL SCI & TECH
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