Time-temperature double-sensitive degradable polymer hydrogel and preparation method thereof

Abstract

The invention relates to a time-temperature double-sensitive degradable polymer hydrogel and a preparation method thereof. The time-temperature double-sensitive degradable polymer hydrogel is mainly composed of a degradable polymer and a medium; the degradable polymer is a triblock multipolymer, and is prepared via steps of material preparation, polymerization, refining, sol preparation, and gelatinization; the time-temperature double-sensitive degradable polymer hydrogel based on the degradable polymer has time and temperature double sensitivity because of a unique structure and a synthetic method, and is extremely suitable for injection; syringe needle blocking is not caused in injection processes; after injection, it is beneficial for free and full distribution of drug-containing hydrogel in infection cavities in the body, and is beneficial for improving adaptive capacity of the hydrogel on body local characteristics, so that drug controlled release effect and disease treatment effect are improved. The time-temperature double-sensitive degradable polymer hydrogel is suitable to be taken as a controlled release carrier of drugs, DNA, cells, functional nanoparticles, and tissue chips, and is capable of satisfying requirements on diagnosis, treatment, and health care in the field of biomedicine.

Description

technical field

[0001] The invention relates to a hydrogel and a preparation method thereof, and belongs to the field of manufacture and application of biomedical polymer materials, in particular to a degradable polymer hydrogel with double sensitivity to time and temperature and a preparation method thereof. Background technique

[0002] With the progress of synthesis technology, screening technology, separation technology and the development of biomedicine, the speed of drug development is accelerating, and the connotation and types of drugs are constantly expanding. In addition to traditional drug therapy, gene therapy, protein therapy, cell therapy, stem cell therapy and other new The concept of treatment has also been continuously proposed and applied to the practice of treatment, making human beings' ability to fight against diseases stronger and stronger. In order to obtain the best therapeutic effect, in addition to the need for high-efficiency drugs and advanced tre...

Examples

Embodiment 1

[0025] Weigh 100g of poly(ethylene oxide-co-butylene oxide) with a number average molecular weight of 1300 and a mass ratio of butylene oxide to ethylene oxide of 0.35:1, 150g of 2-hexylcaprolactone, and 0.8g of aluminum isooctanoate , Add 0.2g of stannous octoate into the reactor, replace the air in the reactor with high-purity nitrogen, raise the temperature of the reaction system to 130°C, and react at this temperature for 30h, add 300mL of ethyl acetate after the reaction system is cooled to room temperature , heated and oscillated at 50°C to dissolve, then added 500mL of petroleum ether, removed the upper liquid after shaking, then added 300mL of petroleum ether, removed the upper liquid after shaking, dried the product at 3Pa, 80°C for 48h, added 1L of deionized water , the hydrosol is prepared by heating, shaking, cooling and other methods. The hydrosol can form a gel at 27°C during the heating process, and the gel time at 27°C is 30min.

Embodiment 2

[0027] Weigh 100g of poly(ethylene oxide-co-butylene oxide) with a number average molecular weight of 3000 and a mass ratio of butylene oxide to ethylene oxide of 0.1:1, 200g of 2-propyl caprolactone, and 0.8g of isooctanoic acid Add aluminum to the reactor, replace the air in the reactor with high-purity argon, raise the temperature of the reaction system to 140°C, and react at this temperature for 25h, add 350mL ethyl acetate after the reaction system is cooled to room temperature, and heat at 50°C Shake to dissolve, then add 500mL petroleum ether, remove the upper liquid after shaking, then add 300mL petroleum ether, remove the upper liquid after shaking, dry the product at 3Pa, 100°C for 10h, add 2.5L phosphate buffer solution with a pH of 7.4 , the hydrosol is prepared by heating, shaking, cooling and other methods. The hydrosol can form a gel at 30°C during the heating process, and the gel time at 30°C is 42min.

Embodiment 3

[0029] Weigh 100g of poly(oxyethylene-co-butylene oxide) with a number average molecular weight of 2000 and a mass ratio of butylene oxide to ethylene oxide of 0.05:1, 100g of caprolactone, and 5g of 2-methylcaprolactone , 15g2-ethylcaprolactone, 20g2-propylcaprolactone, 25g2-butylcaprolactone, 10g2-pentylcaprolactone, 15g2-hexylcaprolactone, 0.4g aluminum isooctanoate, 0.5g suboctanoate Add tin into the reactor, replace the air in the reactor with high-purity nitrogen, raise the temperature of the reaction system to 140°C, and react at this temperature for 30h, add 400mL ethyl acetate after the reaction system is cooled to room temperature, and heat and shake at 50°C Dissolve, then add 450mL of petroleum ether, remove the upper liquid after shaking, then add 250mL of petroleum ether, remove the upper liquid after shaking, dry the product at 100Pa, 80°C for 48h, add 1.7L of phosphate buffer solution with a pH of 7.4, The hydrosol is prepared by heating, shaking, cooling and ot...

technical field

[0001] The invention relates to a hydrogel and a preparation method thereof, and belongs to the field of manufacture and application of biomedical polymer materials, in particular to a degradable polymer hydrogel with double sensitivity to time and temperature and a preparation method thereof. Background technique

[0002] With the progress of synthesis technology, screening technology, separation technology and the development of biomedicine, the speed of drug development is accelerating, and the connotation and types of drugs are constantly expanding. In addition to traditional drug therapy, gene therapy, protein therapy, cell therapy, stem cell therapy and other new The concept of treatment has also been continuously proposed and applied to the practice of treatment, making human beings' ability to fight against diseases stronger and stronger. In order to obtain the best therapeutic effect, in addition to the need for high-efficiency drugs and advanced tre...

Examples

Embodiment 1

[0025] Weigh 100g of poly(ethylene oxide-co-butylene oxide) with a number average molecular weight of 1300 and a mass ratio of butylene oxide to ethylene oxide of 0.35:1, 150g of 2-hexylcaprolactone, and 0.8g of aluminum isooctanoate , Add 0.2g of stannous octoate into the reactor, replace the air in the reactor with high-purity nitrogen, raise the temperature of the reaction system to 130°C, and react at this temperature for 30h, add 300mL of ethyl acetate after the reaction system is cooled to room temperature , heated and oscillated at 50°C to dissolve, then added 500mL of petroleum ether, removed the upper liquid after shaking, then added 300mL of petroleum ether, removed the upper liquid after shaking, dried the product at 3Pa, 80°C for 48h, added 1L of deionized water , the hydrosol is prepared by heating, shaking, cooling and other methods. The hydrosol can form a gel at 27°C during the heating process, and the gel time at 27°C is 30min.

Embodiment 2

[0027] Weigh 100g of poly(ethylene oxide-co-butylene oxide) with a number average molecular weight of 3000 and a mass ratio of butylene oxide to ethylene oxide of 0.1:1, 200g of 2-propyl caprolactone, and 0.8g of isooctanoic acid Add aluminum to the reactor, replace the air in the reactor with high-purity argon, raise the temperature of the reaction system to 140°C, and react at this temperature for 25h, add 350mL ethyl acetate after the reaction system is cooled to room temperature, and heat at 50°C Shake to dissolve, then add 500mL petroleum ether, remove the upper liquid after shaking, then add 300mL petroleum ether, remove the upper liquid after shaking, dry the product at 3Pa, 100°C for 10h, add 2.5L phosphate buffer solution with a pH of 7.4 , the hydrosol is prepared by heating, shaking, cooling and other methods. The hydrosol can form a gel at 30°C during the heating process, and the gel time at 30°C is 42min.

Embodiment 3

[0029] Weigh 100g of poly(oxyethylene-co-butylene oxide) with a number average molecular weight of 2000 and a mass ratio of butylene oxide to ethylene oxide of 0.05:1, 100g of caprolactone, and 5g of 2-methylcaprolactone , 15g2-ethylcaprolactone, 20g2-propylcaprolactone, 25g2-butylcaprolactone, 10g2-pentylcaprolactone, 15g2-hexylcaprolactone, 0.4g aluminum isooctanoate, 0.5g suboctanoate Add tin into the reactor, replace the air in the reactor with high-purity nitrogen, raise the temperature of the reaction system to 140°C, and react at this temperature for 30h, add 400mL ethyl acetate after the reaction system is cooled to room temperature, and heat and shake at 50°C Dissolve, then add 450mL of petroleum ether, remove the upper liquid after shaking, then add 250mL of petroleum ether, remove the upper liquid after shaking, dry the product at 100Pa, 80°C for 48h, add 1.7L of phosphate buffer solution with a pH of 7.4, The hydrosol is prepared by heating, shaking, cooling and ot...