CN-115554389-B - Rectal gel based on hydroxybutyl chitosan and graphene oxide, and preparation method and application thereof

Abstract

The invention relates to the field of preparation of rectal administration systems, in particular to a preparation method and application of a novel rectal gel based on hydroxybutyl chitosan and graphene oxide. Firstly, preparing HBC by a homogeneous synthesis method, then preparing GO by a modified Hummers method, carrying an anticancer model drug PYM on the surface of the GO to obtain GO@PYM, and finally, crosslinking the GO@PYM with the HBC to obtain the HBC/GO@PYM. According to the invention, the nano material GO is introduced, so that the defect of in-situ temperature-sensitive gel is overcome, the drug loading and the mechanical strength are improved, the drug release amount and the bioavailability are improved, and the sustained release effect is obvious. The invention provides a novel method for solving the problems of insufficient mechanical strength, low drug loading, low bioavailability and the like of a rectal administration in-situ temperature-sensitive gel.

Inventors

• LI LI
• LIU YU
• YAO LUYANG
• XIAO HAN
• LI XURUI

Assignees

• 辽宁大学

Dates

Publication Date

20260505

Application Date

20221020

Claims (6)

1. 1. The rectal gel based on the hydroxybutyl chitosan and the graphene oxide is characterized in that HBC is prepared by a homogeneous synthesis method, GO is prepared by an improved Hummers method, an anticancer model drug X is carried on the surface of GO to obtain GO@X, and finally, the GO@X and the HBC are crosslinked to obtain HBC/GO@X; The preparation method of the rectal gel based on the hydroxybutyl chitosan and the graphene oxide comprises the following steps: 1) Sequentially adding KOH, urea, distilled water and CS into a container, uniformly mixing, refrigerating for a certain time, recovering to room temperature, adding 1, 2-epoxybutane, reacting under the protection of nitrogen, and then regulating pH, dialyzing and freeze-drying to obtain HBC; 2) Sequentially adding concentrated sulfuric acid, graphite powder, sodium nitrate and potassium permanganate into a container, reacting for a period of time at a certain temperature, ending the reaction, standing, adding hydrogen peroxide solution until the color of the reaction solution turns yellow, centrifuging, washing and freeze-drying the product to obtain GO; 3) Adding a certain amount of GO dispersion liquid into the GO obtained in the step 2) by an ultrasonic stripping method, carrying out shading reaction, centrifuging the product after the reaction is finished, and freeze-drying the lower layer precipitate to obtain GO@X; 4) Adding a proper amount of HBC and bletilla striata polysaccharide obtained in the step 1) into the GO@X obtained in the step 3), and ending the reaction after a period of time to obtain HBC/GO@X; Drug X is pingyangmycin; According to the mass ratio, GO@X and HBC, bletilla striata polysaccharide=1:18-22:0.08-0.16.
2. 2. The rectal gel based on hydroxybutyl chitosan and graphene oxide according to claim 1, wherein in the step 1), the refrigerating time is 2 hours, and the reaction time is 48 hours.
3. 3. The rectal gel based on hydroxybutyl chitosan and graphene oxide according to claim 1, wherein in the step 2), the reaction is carried out for a period of time at a certain temperature of 1h at 5 ℃,30 min at 35 ℃,30 min at 65 ℃ and 30min at 85 ℃.
4. 4. The rectal gel based on hydroxybutyl chitosan and graphene oxide according to claim 1, wherein in the step 3), according to the mass ratio, GO is drug X=5:1-3.
5. 5. The rectal gel based on hydroxybutyl chitosan and graphene oxide according to claim 1, wherein in the step 3), the shading reaction time is 10-120 min, and the shading reaction temperature is 20-120 ℃.
6. 6. Use of a hydroxybutyl chitosan and graphene oxide based rectal gel according to claim 1 for the preparation of a rectal drug delivery vehicle.

Description

Rectal gel based on hydroxybutyl chitosan and graphene oxide, and preparation method and application thereof Technical Field The invention relates to the field of preparation of rectal administration systems, in particular to a rectal gel based on hydroxybutyl chitosan and graphene oxide, and a preparation method and application thereof. Background The rectal administration system is a drug delivery system for allowing the drug to enter the whole body circulation through the rectal mucosa, has the characteristics of high safety, quick drug absorption, high bioavailability and the like, and is particularly suitable for the old, children and other patients inconvenient for oral administration. After the drug is administrated through rectum, about 50-75% of the drug can be directly absorbed into the systemic circulation through the rectal mucosa, so that the occurrence of the first pass effect of liver is reduced, and the drug can be applied to local treatment and systemic treatment, such as ulcerative colitis, chronic prostatitis, chronic pelvic inflammatory disease, tumor and the like. At present, rectal administration preparations are mainly divided into enemas, suppositories and rectal gels, wherein the enemas have poor compliance of patients in the use process and risk of leakage in the administration process, the suppositories have limited drug distribution in the use process to cause the insufficient drug effect of most suppositories, and the traditional rectal gels have certain difficulty in the administration process because of overlarge viscosity, so that the in-situ temperature-sensitive gels are used as novel rectal administration preparations and are increasingly attracting wide attention of people. The in-situ temperature-sensitive gel is a temperature-sensitive gel preparation which is in a sol state at room temperature, can be converted into a semisolid gel state from the sol state when the temperature rises to a gel point, has the characteristics of good biocompatibility, strong permeability, reduced toxic and side effects of medicines and the like, and can be widely applied to various administration routes such as injection administration, oral administration, rectal administration, mucous membrane administration and the like. The novel rectal gel based on the gel reduces the administration difficulty at room temperature, and can be converted into a semisolid gel state after the temperature rises to the rectal temperature exceeding the gel point temperature, thereby being beneficial to being fixed at the pathological change part of the rectum and playing the role of positioning and administration. Hydroxybutyl chitosan (HBC) is an excellent matrix of in-situ thermosensitive hydrogel, but the effects of rectal administration are limited by the defects of low drug loading, low mechanical strength, poor stability and the like. Graphene Oxide (GO) is a biomedical nanomaterial with excellent performance, has the characteristics of large specific surface area, high mechanical strength, good biocompatibility and the like, is continuously researched and developed in the fields of biosensors, drug delivery, tissue engineering, antibacterial materials and the like, and is found from a plurality of related documents at home and abroad that the mechanical property and drug loading capacity of the graphene oxide are improved to a great extent by introducing the graphene oxide into an in-situ temperature-sensitive hydrogel, and the graphene oxide is expected to further improve the bioavailability, change the drug dissolution characteristics, improve the antibacterial capability and the like by introducing the graphene oxide into the in-situ temperature-sensitive hydrogel due to the characteristics of large specific surface area, high mechanical strength and the like. Based on the preparation method, the invention provides a preparation method and application of a novel rectal gel based on hydroxybutyl chitosan and graphene oxide. Disclosure of Invention The invention aims to provide a novel rectal gel based on hydroxybutyl chitosan and graphene oxide. The graphene oxide is introduced into the hydroxybutyl chitosan in-situ temperature sensitive hydrogel, so that the problems of low mechanical property, low drug loading and the like of the hydroxybutyl chitosan in-situ temperature sensitive hydrogel can be effectively solved, the bioavailability of the drug can be improved, and a slow release effect is generated, so that the novel rectal gel is obtained. In order to achieve the purpose, the technical scheme of the invention is that HBC is prepared through a homogeneous synthesis method based on hydroxybutyl chitosan and graphene oxide rectal gel, GO is prepared through an improved Hummers method, an anti-cancer model drug X is carried on the surface of GO to obtain GO@X, and finally, the GO@X and the HBC are crosslinked to obtain HBC/GO@X. The preparation method of the rectal gel based on the hydroxybutyl ch