A degradable polymer hydrogel sensitive to time and temperature and its preparation method

Abstract

The invention relates to a time- and temperature-sensitive degradable polymer hydrogel and a preparation method thereof. The hydrogel is mainly composed of a degradable polymer and a medium. , polymerization, refining, sol preparation, gelation and other steps, the unique structure and synthesis method make the hydrogel based on the degradable polymer have both time and temperature sensitivity, very suitable for injection use, not There will be a problem of clogging the needle during the injection process. After injection, it is also conducive to the free and sufficient distribution of the drug-containing sol in the body lesion cavity, which is conducive to improving the adaptability of the gel to the local characteristics of the body, thereby improving the controlled release of drugs and disease treatment. Effect. The hydrogel of the present invention is suitable for use as a controlled release carrier for drugs, DNA, cells, functional nanoparticles, tissue debris, etc., and meets the needs of diagnosis, treatment, health care, etc. 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 isooctanoic acid Add aluminum and 0.2g 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, then add 300mL of ethyl acetate after the reaction system is cooled to room temperature Dissolve the ester by heating and shaking at 50°C, 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, 80°C for 48h, add 1L deionized Water, 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 30 minutes.

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 0.1:1 of butylene oxide to ethylene oxide, 200g of 2-propylcaprolactone, 0.8g of iso Add aluminum octanoate into 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, Heat and oscillate to dissolve, then add 500mL of petroleum ether, remove the upper liquid after shaking, then add 300mL of petroleum ether, remove the upper liquid after shaking, dry the product at 3Pa, 100°C for 10h, add 2.5L of phosphoric acid with a pH of 7.4 The buffer solution 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, 5g of 2-methylcaprolactone Esters, 15g 2-ethylcaprolactone, 20g 2-propylcaprolactone, 25g 2-butylcaprolactone, 10g 2-pentylcaprolactone, 15g 2-hexylcaprolactone, 0.4g isooctanoic acid Add aluminum and 0.5g stannous octoate 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 Dissolve the ester by heating and shaking at 50°C, then add 450mL petroleum ether, remove the upper liquid after shaking, then add 250mL petroleum ether, remove the upper liquid after shaking, dry the product at 100Pa, 80°C for 48h, add 1.7L pH It is a phosphate buffer solution of 7.4, and the hydrosol is prepared by heating, ...

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 isooctanoic acid Add aluminum and 0.2g 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, then add 300mL of ethyl acetate after the reaction system is cooled to room temperature Dissolve the ester by heating and shaking at 50°C, 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, 80°C for 48h, add 1L deionized Water, 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 30 minutes.

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 0.1:1 of butylene oxide to ethylene oxide, 200g of 2-propylcaprolactone, 0.8g of iso Add aluminum octanoate into 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, Heat and oscillate to dissolve, then add 500mL of petroleum ether, remove the upper liquid after shaking, then add 300mL of petroleum ether, remove the upper liquid after shaking, dry the product at 3Pa, 100°C for 10h, add 2.5L of phosphoric acid with a pH of 7.4 The buffer solution 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, 5g of 2-methylcaprolactone Esters, 15g 2-ethylcaprolactone, 20g 2-propylcaprolactone, 25g 2-butylcaprolactone, 10g 2-pentylcaprolactone, 15g 2-hexylcaprolactone, 0.4g isooctanoic acid Add aluminum and 0.5g stannous octoate 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 Dissolve the ester by heating and shaking at 50°C, then add 450mL petroleum ether, remove the upper liquid after shaking, then add 250mL petroleum ether, remove the upper liquid after shaking, dry the product at 100Pa, 80°C for 48h, add 1.7L pH It is a phosphate buffer solution of 7.4, and the hydrosol is prepared by heating, ...