Polymer with tumor organization pH responsiveness and micelle thereof

A tumor tissue and polymer glue technology, applied in the field of biological materials, polymer materials, and pharmaceutical preparations, can solve problems such as side effects and hinder the clinical application of drugs, and achieve good biocompatibility.

Inactive Publication Date: 2010-07-28
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the vast majority of anticancer drugs have seriou

Method used

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  • Polymer with tumor organization pH responsiveness and micelle thereof
  • Polymer with tumor organization pH responsiveness and micelle thereof
  • Polymer with tumor organization pH responsiveness and micelle thereof

Examples

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Example Embodiment

[0032] Example 1

[0033] Add 30g of dihydroxy polyethylene glycol (1500) into a 500ml three-necked flask, remove water under vacuum at 130°C for 4 hours, cool to 70°C with argon, add 60g lactide, 26mg stannous octoate (with a small amount of toluene), 100 Vacuum at °C for 30 minutes, argon gas, and heat to 130 °C to react for 12 hours. After the reaction is completed, the product is poured out while it is hot, and after cooling, the product is dissolved in dichloromethane and precipitated with ether to obtain a BAB block polymer. Take 15g of BAB block polymer, add 3.0g of N-Boc-histidine, 3.5g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl), 4 -Dimethylaminopyrimidine (DMAP) 2.6g, dichloromethane 150ml, react for 48 hours at room temperature. Suspend evaporation to remove part of the solvent, precipitate with ether, and further wash at 80°C to remove residual unreacted materials and catalyst, and freeze-dry. Synthesis diagram such as figure 1 Shown.

Example Embodiment

[0034] Example 2

[0035] The product obtained in Example 1 was made into a 1 wt% solution with a phosphate buffer solution, pH was adjusted, and filtered with a 0.8 micron filter to obtain the desired blank micelle solution. The prepared micelles can be degraded, see figure 2 . Dissolve 1 mg of doxorubicin hydrochloride and triethylamine in methanol / chloroform (volume ratio 1:1, the same below), add the polymer-containing methanol / chloroform solution (2ml, 5mg / ml) dropwise, spin Dry the film, add phosphate buffer solution for hydration, filter with a 0.8 micron filter, and dialyze to remove free adriamycin to obtain micelles containing adriamycin. The release rate of drug-loaded micelles is different between normal pH (7.4) of human body and pH (6.2) of extracellular fluid in tumor tissue, see image 3 . After culturing for 24 hours in a six-well cell culture plate containing human breast cancer cell line MDA-MB-435 and cell culture medium, change the medium, add new culture ...

Example Embodiment

[0036] Example 3

[0037] Add 30g dihydroxy polyethylene glycol (1500) into a 500ml three-necked flask, remove water under vacuum at 130°C for 4 hours, cool to 70°C with argon, add 50g lactide, 10g glycolide, and 26mg stannous octoate (solubilized) In toluene), vacuum at 100°C for 30 minutes, argon gas, and heat to 130°C to react for 12 hours. After the reaction is completed, the product is poured out while it is hot, and after cooling, the product is dissolved in dichloromethane and precipitated with ether to obtain a BAB block polymer. Take 10g of BAB block polymer, add 1.8g of N-Boc-histidine, 1.7g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl), 4 -Dimethylaminopyrimidine (DMAP) 1.3g, dichloromethane 150ml, react for 48 hours at room temperature. Suspend evaporation to remove part of the solvent, precipitate with ether, and further wash at 80°C to remove residual unreacted materials and catalyst, and freeze-dry. The obtained product is made into a 1 ...

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Abstract

The invention belongs to the technical field of pharmaceutical preparations and high molecular materials, in particular to a polymer with tumor organization pH responsiveness, a micelle and a preparation method thereof. In the invention, an amphipathic block polymer is firstly synthesized, and histidine with pH-sensitive groups or a derivate thereof is introduced to the both ends of the amphipathic block polymer. The materials are dissolved in an aqueous solvent in definite proportion to form the micelle by self-assembly; or the materials and medicines are dissolved in an organic solvent together to form a membrane by rotation, and then the membrane is dispersed in water to form a medicine-carrying micelle. The size of the micelle can be controlled by the pH adjustment. The medicine-carrying micelle has different medicine releasing rates for the tumor organization pH and the normal physiologic pH of a human body. The polymer and the micelle thereof are well-behaved carrier materials for the slow release of the medicines.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, biomaterials and polymer materials, and in particular relates to a degradable polymer and micelles thereof for accelerated drug release in tumor sites, and a preparation method of the polymers and micelles. Background technique [0002] With the development of science and technology, a series of anticancer drugs have been synthesized or isolated from nature. However, most anticancer drugs have serious side effects, which hinder the clinical application of drugs. In order to solve this problem, scientists use nanoparticles as drug carriers, such as nanomicelles to encapsulate drugs, improve the therapeutic effect of drugs, and reduce toxic and side effects. Among them, nanomicelles with a diameter of 20-200 nanometers can effectively enhance the penetration and retention (EPR effect) of particles in tumor tissues, thereby enhancing the drug efficacy. Nanoparticles with intell...

Claims

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Application Information

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IPC IPC(8): C08G65/48C08G63/91C08G63/664C08G69/44C08G69/40C08G69/10C08L71/08C08L67/04C08L77/04A61K47/34A61K9/00A61P35/00
Inventor 丁建东常广涛陆伟跃李翀
Owner FUDAN UNIV
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