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A kind of methionine-polyester amide macromolecular polymer with ros responsiveness and its application

A high-molecular polymer and polyester amide technology, applied in the direction of organic active ingredients, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve problems that have not been published in the newspapers, and achieve good clinical application Potential, good biodegradability, good biocompatibility

Active Publication Date: 2021-12-10
SUN YAT SEN UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current research on the use of methionine-polyesteramide polymer materials as drug delivery carriers for encapsulating paclitaxel has not been reported.

Method used

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  • A kind of methionine-polyester amide macromolecular polymer with ros responsiveness and its application
  • A kind of methionine-polyester amide macromolecular polymer with ros responsiveness and its application
  • A kind of methionine-polyester amide macromolecular polymer with ros responsiveness and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] Polyester amide-based synthetic methionine Example 1

[0098] 1, Met-PEA polymer prepared in the following steps:

[0099] (1) Synthesis of monomer N-x (x denotes the number of methyl groups on ethylene dichloride)

[0100]1 here, take N-2 as an example. 0.0603 mol of triethylamine and 0.0603 mol were added to 100 mL of acetone, stirred mixed at room temperature, and then kept the acetone solution in -78 ° C with dry ice, then 0.03 mol (3.2 ml) Di two Acid chloride is added to 40 mL of acetone, and the mixed uniform is added dropwise to the frozen solution and stirred at -78 ° C for 2 h, and then transferred to room temperature and stir overnight.

[0101] 2 The mixed solution obtained by step 1 is poured into 800 mL of distilled water, precipitated the product, filtered it, thoroughly washed with distilled water, and then dried at 50 ° C, and finally crystallized from acetonitrile. Phenol esters, ie N-2 (x = 2) monomers.

[0102] 3 According to the method in the above step...

Embodiment 2

[0118] Example 2 Preparation and Screening of Nano - systems of PTX in PTX based on methionine-based polyester amine polymers

[0119] 1. Preparation of PTX @ Met-PEA nano-loading system by the following steps

[0120] (1) 12 Met-PEA prepared in Example 1 was dissolved in DMSO, respectively, and a solution of 25 mg / ml, 200 μl of spare; the stabilizer DSPE-PEG2000 is dissolved in dimethyl sulfoxide (DMSO) The solution was obtained into 15 mg / ml solution, and 100 μl of spare was taken; paclitaxel (PTX) was dissolved in DMSO, formulated with 5 mg / ml solution, and 100 μl of spare. At this time, the DSPE-PEG2000 is 30% (mass percentage) of Met-PEA, and PTX is 10% (mass percentage) of Met-PEA.

[0121] (2) The above solution was mixed to give 400 ul of mixed solution as an organic phase. At a speed of 1000 rpm, the organic phase was added dropwise to 10 ml of deionized water (the volume ratio of the organic phase and the aqueous phase was 1: 25), and after the drop was completed, ...

Embodiment 3

[0129] Example 3 PTX @ Met-PEA nanoparticles stability and drug release inquiry

[0130] 1, PTX @ Met-PEA nanoparticle stability inquiry

[0131] (1) Four kinds of pharmaceutical nanoparticles prepared in Example 2 (PTX @ N-2-Met-8 NPS, PTX @ N-4-Met-8NPS, PTX @ N-2-Met-10 NPS and PTX @ N-4-MET-10 NPS) Removal of the PBS buffer containing 10% (V / V) fetal bovine serum (FBS), at room temperature, and the corresponding particle size and PDI were determined daily, and the nano Long-term stability of the particles.

[0132] (2) Figure 5 As shown, PTX @ N-2-MET-8 NPS and PTX @ N-4-Met-8 NPS gradually becomes large in PBS buffer containing 10% FBS, indicating that it is destroyed in stability, it is difficult to Stable in vivo existence. However, PTX @ N-2-Met-10 NPS and PTX @ N-4-Met-10 NPS can stably exist more than 7 days in the same environment, and can extend the cycle time of PTX to a certain extent. Therefore, the two materials of PTX @ N-2-Met-10 NPS and PTX @ N-4-Met-10 NPS an...

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Abstract

The invention discloses a ROS-responsive methionine-polyesteramide polymer and its application. The structural formula of the methionine-polyester amide macromolecular polymer is shown in formula (I). The present invention uses methionine, diacids and diols containing different numbers of methylene groups as raw materials, and synthesizes methionine-based polyester amide polymer materials through melt polycondensation reaction. The method has good repeatability and is easy to operate. The raw materials used are non-toxic, Economical and easy to obtain, the obtained high molecular polymer material has excellent biosafety and biodegradability, and can be used as a drug carrier. 2 o 2 Under the environment, it can be controlled release, which effectively solves the problems of poor stability, poor biological safety and weak targeting of nano-drugs, and has a good prospect in biomedical applications such as tumor treatment.

Description

Technical field [0001] The present invention relates to the field of nano-drug carriers, and more particularly to a methionine-polyester amide polymer polymer having a ROS-responsive. Background technique [0002] According to WHO's "Global Cancer Report", 2018 cancer deaths 9.6 million, adding 18.1 million cases, and the global cancer burden is further aggravated. At present, the most important treatment for cancer is surgical resection, but the local tumor residue makes the cancer recurrence chance increase. Total residues are also common radiotherapy and chemotherapy for the treatment of tumors. However, radiotherapy will cause damage to normal cells, and chemotherapy can cause drug resistance of tumor cells. The drug delivery system (DDS) passes through solid tumors (EPR effect, ie ENHANCED PERMEABILITY AND RETENTIONEFFECT) can accurately targeting the tumor site, improving the utilization and stability of the drug, bringing cancer treatment new Hope. [0003] The drug carrie...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G69/44A61K9/51A61K47/34A61K31/337A61P35/00
CPCC08G69/44A61K9/5146A61K31/337A61P35/00
Inventor 吴钧刘杰顾志鹏
Owner SUN YAT SEN UNIV
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