Bioadhesive temperature-sensitive material, preparation method thereof and application of drug carrier

A bioadhesive, temperature-sensitive material technology, used in drug combination, drug delivery, medical preparations with inactive ingredients, etc. Strong adhesive effect

Active Publication Date: 2020-05-08
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Catechol residues in the gel skeleton can undergo reversible chemical combination with amino groups on the surface of the cavity mucosa, resulting in high-strength mucoadhesion, increasing the residence time of sulfasalazine in the colon, and improving the therapeutic effect of ulcerative colitis (see Acta Biomater:2017,48:247-257), but the adhesive material needs to be pre-added with a cross-linking agent to gel, and it takes a long time to gel, and the application in the cavity still has the defect of easy loss

Method used

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  • Bioadhesive temperature-sensitive material, preparation method thereof and application of drug carrier
  • Bioadhesive temperature-sensitive material, preparation method thereof and application of drug carrier
  • Bioadhesive temperature-sensitive material, preparation method thereof and application of drug carrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Catechol-terminated polyoxyethylene-polyoxypropylene-polyoxyethylene copolymer

[0042] Weigh 1 part of polyoxyethylene-polyoxypropylene-polyoxyethylene copolymer and dissolve it in dichloromethane, add 5 parts of 4-nitrophenyl chloroformate into the above solution, and add 0.5 parts after it is completely dissolved Triethylamine, after reacting at room temperature for 4 hours, add 5 parts of ethylenediamine to the reaction system, continue stirring at room temperature for 24 hours, remove dichloromethane by rotary evaporation, add 10 parts of distilled water to dissolve the residue, and centrifuge at 5000rpm / min for 5min to remove the precipitate. The supernatant was dialyzed against deionized water with a dialysis membrane (molecular weight cut-off of 3500Da) for 3-5 days, and then freeze-dried for 24 hours to obtain an amino-terminated polyoxyethylene-polyoxypropylene-polyoxyethylene copolymer;

[0043] Weigh 1 part of polyoxyethylene-polyoxypropylene-polyo...

Embodiment 2

[0048] Example 2 Bioadhesive Determination

[0049] Catechol-terminated polyoxyethylene-polyoxypropylene-polyoxyethylene copolymers are dispersed in cold water, left overnight to dissolve completely, and a solution with a concentration of 20% is prepared, and gelled in a water bath at 37°C for 30 minutes to prepare Bioadhesive gel. Maintaining a temperature of 37°C, the bioadhesive gel was placed between two POM (polyoxymethylene or polyoxymethylene) discs, and the adhesion force of the bioadhesive thermosensitive gel was measured using a universal tester.

[0050] As can be seen from Table 1, the polyoxyethylene-polyoxypropylene-polyoxyethylene copolymer of catechol-terminated polyoxyethylene-polyoxypropylene-polyoxyethylene copolymer compared with the polyoxyethylene-polyoxypropylene-polyoxyethylene in the control group-1 or the control group-2 The copolymer has stronger bioadhesive force, and with the increase of the caffeic acid percentage in the polymer, the bioadhesive ...

Embodiment 3

[0051] Embodiment 3 Determination of gelation temperature

[0052] Catechol-terminated polyoxyethylene-polyoxypropylene-polyoxyethylene copolymers are dispersed in cold water, left overnight to dissolve completely, and a solution with a concentration of 20% is prepared, put into a vial, and incubated in a constant temperature oven for 30 minutes. Tilt the vial upside down until the temperature at which no flowable liquid is observed is the gelation temperature.

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Abstract

The invention discloses a bioadhesive temperature-sensitive material, a preparation method thereof and application of a drug carrier. The material does not need to be additionally provided with a cross-linking agent or subjected to other treatment, an aqueous solution of the material is dehydrated and gelled by polyoxyethylene-polyoxypropylene-polyoxyethylene chains along with temperature rise, the material has good temperature sensitivity, and meanwhile, catechol terminal groups of the material can be spontaneously and chemically cross-linked with one another or can be spontaneously and chemically cross-linked with amino on the surface of a living body to generate super-strong bioadhesive force. The bioadhesive temperature-sensitive material is combined with a temperature-sensitive gel matrix and a stabilizer and can be used as a delivery carrier of bioactive factors. Bioadhesive temperature-sensitive drug-loaded hydrogel can be directly used for perfusion and administration in a cavity, can quickly respond to body temperature change for gelling, meanwhile can be uniformly adhered to the surface of mucosa of the cavity, slowly releases the bioactive factors and promotes repair ofthe ulcerative mucosa.

Description

technical field [0001] The invention relates to the field of polymer biomaterials, in particular to bioadhesive temperature-sensitive materials, bioadhesive temperature-sensitive drug-loaded hydrogels and preparation methods thereof. Background technique [0002] Mucosal damage occurs in the oral cavity, tongue, vagina, uterus, and anal mucosa, with mucosal inflammation and ulceration as the main pathological features. Its pathogenesis is not very clear at present, and it is believed to be related to the mucosal barrier damage caused by comprehensive factors such as genetics and environment. Sustained or recurrent mucosal inflammation can easily lead to fibrosis and narrowing of the lumen mucosa, and even mucosal cancer. It has been reported that a variety of growth factors such as vascular endothelial growth factor, keratinous growth factor, epidermal growth factor, vasoactive intestinal peptide, and fibroblast growth factor can effectively promote mucosal repair. Compare...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/18A61K9/06A61K38/18A61P1/04A61P17/02C08G65/332
CPCA61K47/18A61K9/06A61K9/0031A61K9/006A61K9/0043A61K9/0034A61P17/02A61P1/04A61K38/18C08G65/3326C08G2650/04Y02A50/30
Inventor 徐荷林王丽芬薛鹏鹏赵应征诸葛得力
Owner WENZHOU MEDICAL UNIV
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