Copolymer with temperature/PH dual-sensibility and preparation and application thereof

A dual-sensitive, copolymer technology, applied in the preparation of temperature-sensitive/pH double-sensitive gel drug delivery system and pH-sensitive micellar drug delivery system, temperature/pH double-sensitive copolymer field, can solve drug leakage, Inability to deliver drugs, insensitive response to pH changes, etc., to achieve the effect of increasing stability

Inactive Publication Date: 2009-09-23
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The above-mentioned pH-sensitive copolymer has the disadvantages of poor stability, prone to drug leakage in plasma, and insensitive response to small pH changes in the environment, which makes it unable to deliver the drug to the target site according to the design requirements during the administration process.

Method used

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  • Copolymer with temperature/PH dual-sensibility and preparation and application thereof
  • Copolymer with temperature/PH dual-sensibility and preparation and application thereof
  • Copolymer with temperature/PH dual-sensibility and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Synthesis of temperature / pH double-sensitive OLH-b-PLGA-b-PEG-b-PLGA-b-OLH

[0038] (1) Synthesis of temperature-sensitive PLGA-b-PEG-b-PLGA block copolymers

[0039] Take polyethylene glycol (PEG1000 or PEG1500) and lactide (LA), glycolide (GA) and catalyst stannous octanoate (Sn (Oct) 2), wherein the mass ratio of PEG to LA and GA mass sum 2:5, the molar ratio of LA to GA is 5:1, Sn(Oct)2 is 0.5% of the mass sum of all monomers, put it into a dry polymerization tube, and after deoxygenation by nitrogen, seal the tube under vacuum, Reacted at 150°C for 8h to obtain a colorless and transparent semi-solid product. The resulting crude product is dissolved in cold water (less than 10°C), heated to 80°C to precipitate the copolymer, and the low molecular weight water-soluble copolymer and unreacted monomer compounds are removed. After three repetitions, the isolated copolymer is decompressed at room temperature Dry to obtain purified PLGA-PEG-PLGA terpolymer wi...

Embodiment 2

[0063] Embodiment 2: Phase transition temperature (PIT) is measured

[0064]Weigh two proportions of appropriate copolymers, dissolve them in pH7.4 PBS solution, prepare a copolymer solution with a concentration of 20%, transfer the solution to a glass container, adjust the magnetic stirring speed to 200rpm, and keep the water bath slowly warming up , the heating rate was 1°C / min, and the temperature at which the clear solution formed a gel was recorded. The phase transition temperature of the copolymer used for injection of sustained-release materials is 36°C, and the phase transition pH is 7.0-7.4, which ensures that it exists in a gel state in a physiological environment and can release drugs slowly. The phase transition temperature of the material used in the micellar targeted drug delivery system is 59°C, which ensures that it exists in a solution state in a physiological environment and can be used for intravenous injection.

Embodiment 3

[0065] Embodiment 3: Preparation of OLH-PLGA-PEG-PLGA-OLH blank micelles

[0066] Take 10mg of OLH-PLGA-PEG-PLGA-OLH into a small vial, add 20ml of deionized water, and stir magnetically for 5 hours to prepare blank micelles. The micelles have light blue opalescence, and the particle size is about 90nm. The distribution is narrow.

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PUM

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Abstract

The invention relates to a novel temperature/PH dual-sensibility self-assembly segmented copolymer, i.e. polyhistidine-polylactic-co-glycolic acid-polyethyleneglycol-polylactic-co-glycolic acid-polyhistidine (OLH-b-PLGA-b-PEG-b-PLGA-b-OLH), belonging to the technical field of medicine. The self-assembly segmented copolymer accords with the structural features of a temperature/PH unika polymer, and a molecular structure of the self-assembly segmented copolymer respectively comprises a polylactic-co-glycolic acid-polyethyleneglycol-polylactic-co-glycolic acid (PLGA-b-PEG-b-PLGA) chain link which responds to temperature change and a low polyhistidine chain link which responds to PH change; copolymers can be dissolved into water under room temperature to form a free-pouring micellar solution,and when the temperature and the PH of an external environment change, the copolymers with different structural proportions are respectively expressed as follows: (1) the phase variation of solution-gelatin, and (2) the response action of the dissociation of a micellar structure, wherein the copolymer with the response action of the (1) can be taken as a carrier of an injection type sustained controlled-release drug delivery system, and the copolymer with the response action of the (2) can be taken as a carrier of a micellar target drug delivery system.

Description

technical field [0001] The invention belongs to the technical field of medical materials, and in particular relates to a novel temperature / pH dual-sensitive copolymer. The invention also relates to the preparation of temperature-sensitive / pH dual-sensitive gel drug delivery system and pH-sensitive micelles by using the polymer drug delivery system. Background technique [0002] In recent years, driven by the rapid development of biomaterials and polymer chemistry, various functional polymer materials have emerged, which has prompted the rapid development of research on pharmaceutical dosage forms and preparations and has entered the era of drug delivery system (DDS) , the development of long-acting, high-efficiency, targeted and other new drug delivery systems represents the development direction of the pharmaceutical sciences. [0003] Environmentally sensitive polymers (Environmentally sensitive polymers) are a new class of functional polymer materials that can sense and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/00C08G63/08C08G63/85C08G65/48C08G63/91C08G69/10A61K47/34
Inventor 乔明曦古建春陈大为胡海洋赵秀丽
Owner SHENYANG PHARMA UNIVERSITY
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