Injectable block copolymer hydrogel of temperature sensibility(epsi - caprolactone - glycolide)- polyethyleneglycol

A copolymer and temperature-sensitive technology, applied in the direction of organic active ingredients, medical preparations of non-active ingredients, peptide/protein ingredients, etc., can solve problems such as limited application, adverse tissue reactions and side effects, and slow degradation rate

Inactive Publication Date: 2007-05-09
CHENGDU ORGANIC CHEM CO LTD CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the extremely slow degradation rate of poly(ε-caprolactone), the reported hydrogel is not absorbed in the human body for a long time, which is prone to adverse tissue reactions and side effects, which limits its application in the field of injectable drug-loaded hydrogels. application in

Method used

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  • Injectable block copolymer hydrogel of temperature sensibility(epsi - caprolactone - glycolide)- polyethyleneglycol
  • Injectable block copolymer hydrogel of temperature sensibility(epsi - caprolactone - glycolide)- polyethyleneglycol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Synthesis of P(ε-CL-GA)-PEG-P(ε-CL-GA) Triblock Copolymer

[0022] In a 100 ml reaction vessel equipped with a magnetic stirrer, add 20 grams of polyethylene glycol with a molecular weight of 1540, 40 grams of ε-caprolactone, and 4 grams of glycolide, and then inject 0.5 ml of caprylic acid with a micro syringe Stannous solution (0.1g / ml concentration). The reaction system was decompressed and evacuated at room temperature, and the system was replaced with high-purity nitrogen every half an hour, and this was repeated several times. Polymerization was carried out in an oil bath at 120°C with stirring for 12 hours. After the reaction, the obtained polymer was dissolved in dichloromethane, and then precipitated with a large amount of frozen ether, and the purified polymer was dried in a vacuum oven at 70° C. for 24 hours.

Embodiment 2

[0024] Thermal Transition Properties of P(ε-CL-GA)-PEG-P(ε-CL-GA) Triblock Copolymer

[0025] The sol-gel thermal transition behavior of the triblock copolymer aqueous solution in Example 1 was measured at different concentrations. Aqueous solutions of triblock copolymers with different concentrations were prepared at low temperature, and their viscosity changes between 20-50°C were observed. Gel is defined as the state in which the solution does not flow when the aqueous solution containing the triblock copolymer is inverted. FIG. 1 is a phase diagram showing the sol-gel transition of the triblock copolymer aqueous solution in Example 1. FIG. It can be seen from the phase diagram that when the concentration is above 25wt%, the aqueous solution of the triblock copolymer is a flowable liquid at or below room temperature, but exists in a stable gel state at human body temperature.

Embodiment 3

[0027] Thermosensitivity of ABA Type P(ε-CL-GA)-PEG-P(ε-CL-GA) Triblock Copolymers with Different Compositions

[0028] Using the synthesis method in Example 1, a series of tri-block copolymers with different compositions were synthesized using polyethylene glycol with a molecular weight of 1540 as the hydrophilic segment. The raw material composition ratio of P(ε-CL-GA)-PEG-P(ε-CL-GA) triblock copolymer with reversible thermal transition behavior is shown in the following table:

[0029] Sample No.

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Abstract

An injectable temp-sensitive hydrogel with high affinity to both hydrophobic and hydrophilic medicines is a poly (epsilon-caprolactone-glycolide)-polyethylene glycol block copolymer or poly (epsilon-caprolactone-paradioxy hexacyclone)- polyethylene glycol block copolymer, which is composed of poly (epsilon- caprolactone-glycolide) [P(epsilon-CL-GA)] or poly (epsilon-caprolactone- paradioxyhexacyclone) [P(epsilon-CL-PDO)] as hydrophobic chain and the polyethylene glycol as hydrophilic chain. It appears as liquid at room temp or gel at the temp of human body.

Description

technical field [0001] The present invention relates to injectable thermosensitive poly(ε-caprolactone-glycolide)-polyethylene glycol, poly(ε-caprolactone-p-dioxanone)-polyethylene glycol block copolymer Hydrogel and its drug controlled release system. It is based on poly(ε-caprolactone-glycolide) [P(ε-CL-GA)] or poly(ε-caprolactone-p-dioxanone) [P(ε-CL-PDO) ] is a hydrophobic segment (A) and polyethylene glycol (PEG) is an ABA or BAB triblock copolymer composed of a hydrophilic segment (B), and its aqueous solution of a certain concentration exists in liquid form at room temperature or below room temperature, It turns into a gel at body temperature. The invention belongs to the field of biodegradable materials and drug controlled release. Background technique [0002] The purpose of studying controlled-release preparations is to seek a method that can maintain the activity of the drug, maintain an effective blood drug concentration in the affected area for a long time du...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K45/00A61K39/39A61K38/28A61K38/21A61K38/18A61K31/517A61K31/496A61K31/485A61K31/337C08G81/00
Inventor 郝建原蒋志强邓先模叶友全张良辅夏雨
Owner CHENGDU ORGANIC CHEM CO LTD CHINESE ACAD OF SCI
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