CN112007209A

CN112007209A - CS/QCS/zwitterion/epoxidized zwitterion antibacterial and release integrated gel dressing and preparation method thereof

Info

Publication number: CN112007209A
Application number: CN202010356646.9A
Authority: CN
Inventors: 鲍晓炯; 金晓强; 胡巧玲
Original assignee: Zhejiang University ZJU
Current assignee: Zhejiang University ZJU
Priority date: 2020-04-29
Filing date: 2020-04-29
Publication date: 2020-12-01
Anticipated expiration: 2040-04-29
Also published as: CN112007209B

Abstract

The invention discloses a CS/QCS/zwitterion/epoxidized zwitterion sterilization-resistant and release integrated gel dressing and a preparation method thereof, wherein the dressing has the functions of dual bacterium adhesion resistance, dual contact sterilization, and salt response release of dead bacteria, so that the formation of a bacterial biofilm is effectively resisted; firstly, preparing quaternized chitosan with a certain grafting degree through an epoxy ring-opening reaction, and preparing epoxidized zwitterions with a certain copolymerization ratio through a free radical copolymerization reaction; dissolving Chitosan (CS) in a water phase, sequentially adding quaternized chitosan, zwitterions, AAm, MBAA and APS, pouring after centrifugal defoaming, and carrying out one-pot reaction to obtain gel; finally, the gel is soaked in an epoxidized zwitter-ion solution, TEA is added, and the gel is reacted in an oven for a period of time to obtain the sterilization and release resistant integrated gel dressing which has the advantages of dual bacterial adhesion resistance, dual contact sterilization and salt response dead bacteria release, and is expected to be used for treating wound infection.

Description

CS/QCS/zwitterion/epoxidized zwitterion antibacterial and release integrated gel dressing and preparation method thereof

Technical Field

The invention belongs to the field of medical gel dressings, and particularly relates to a chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial and release integrated gel dressing and a preparation method thereof.

Background

Wounds such as scratch, bruise, burn and the like frequently occur in daily life, and the problem of bacterial infection caused by the wounds troubles the life of patients. Wound dressings that function as temporary skin barriers must have some function against bacterial infection during trauma. Dressings with a single anti-or bactericidal function against bacteria are nowadays increasingly inadequate for clinical use. The anti-killing integrated dressing can better exert the effect of resisting bacterial infection, simultaneously prolong the service time of the dressing, reduce the replacement frequency and reduce unnecessary secondary damage of an infected part. Even if the dressing has the anti-killing function, dead bacteria and substances secreted by the dead bacteria on the surface of the dressing are easy to prevent the dressing from being in full contact with the bacteria after a period of use, so that the anti-killing function of the dressing cannot be further continuously exerted, and a bacterial biofilm which is difficult to remove is easy to gradually form. Thus, the function of responding and releasing dead bacteria to the dressing is extremely important for the existing dressing.

Disclosure of Invention

The invention aims to solve the problem of wound interface bacterial infection and provides a chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial and release integrated gel dressing and a preparation method thereof.

The invention is realized by the following technical scheme:

a chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial and release integrated gel dressing is prepared by the following method:

preparing Quaternized Chitosan (QCS) through an epoxy ring-opening reaction, wherein the epoxy ring-opening reaction functional monomer is chlorinated glycidol trimethylamine, and the quaternized grafting degree is 2-60%;

preparing epoxidized zwitterions (ESBMA) through free radical copolymerization, wherein in the free radical copolymerization, functional monomers are [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide and glycidyl methacrylate, a copolymerization mixed solvent is water and other solvents, and the copolymerization ratio is regulated and controlled by regulating the proportion of the other solvents to the water; the other solvent is selected from dimethyl sulfoxide, acetonitrile, dimethylformamide, methanol, ethanol, isopropanol, acetone, tetrahydrofuran, ethyl acetate, diethyl ether, dichloromethane, chloroform and toluene;

dissolving Chitosan (CS) in a water phase, sequentially adding quaternized chitosan, zwitterion (SBMA), acrylamide (AAm), N-Methylene Bisacrylamide (MBAA) and initiator Ammonium Persulfate (APS), performing centrifugal deaeration, pouring in a mold, and performing one-pot reaction in an oven to obtain gel;

the prepared gel is soaked in an epoxidized zwitter-ion solution, Triethylamine (TEA) is added, and the gel is reacted in an oven for a period of time to prepare the antibacterial and release integrated gel dressing which has good mechanical property and biocompatibility, can resist bacterial adhesion in a double mode, kills bacteria in a double-contact mode, and releases dead bacteria in a salt response mode.

In the technical scheme, further, different from a conventional method for changing the feed ratio, the method provided by the invention changes the copolymerization ratio of glycidyl methacrylate and SBMA by adjusting the ratio of other solvents to water, can effectively solve the problems of poor monomer solubility and low reaction efficiency caused by simply changing the feed ratio, and adjusts the copolymerization ratio to be 1: 9-9: 1 so as to adjust the hydrophilicity and hydrophobicity of a chain segment and the density and thickness of ESBMA riveted on the surface of the gel dressing to be in a proper range.

Further, the chitosan is dissolved in the water phase to prepare 0.1-10 wt% of CS acetic acid solution, and QCS, SBMA, AAm, MBAA and APS are sequentially added, wherein the addition amounts are 0.1-10 wt%, 0.25-6.25 wt%, 1-25 wt%, 0.001-0.1 wt% and 0.01-1 wt%, respectively.

Furthermore, the temperature of the oven is 40-80 ℃ during the one-pot reaction, and the reaction lasts for 4-10 hours.

Further, the epoxidized zwitterionic solution is 0.001-0.1 wt% ESBMA aqueous solution.

Further, the amount of TEA added is 0.1-10 vt% of the epoxidized zwitterionic solution.

Further, TEA is added and then transferred into an oven, the temperature is set to be 40-80 ℃, and the reaction lasts 12-24 hours.

According to the invention, an interpenetrating network which is formed by CS, QCS, SBMA and ESBMA in a water phase in a one-pot method and has excellent mechanical property and can resist killing and release, and the copolymerization proportion is creatively regulated and controlled by regulating and controlling the proportion of other solvents to water in a copolymerization mixed solution during the preparation of ESBMA, so that the hydrophilicity and hydrophobicity of the gel dressing and the density and thickness of the ESBMA riveted on the surface of the gel dressing reach a proper range, and the prepared anti-killing integrated gel dressing can also have excellent bacteria release performance. The following problems can be effectively solved: after the dressing is used for a period of time, dead bacteria and substances secreted by the dead bacteria on the surface of the dressing are extremely easy to prevent the dressing from being in full contact with the following bacteria, so that the anti-killing function of the dressing cannot be further continuously exerted, and bacterial biofilms which are difficult to remove are extremely easy to gradually form. Thus, the function of responding and releasing dead bacteria to the dressing is extremely important for the existing dressing.

Drawings

FIG. 1 is a schematic drawing of GO @ DA/sodium alginate/P (AAc-co-AAm) hydrogel stretching;

FIG. 2 is a schematic diagram of the conductivity of GO @ DA/sodium alginate/P (AAc-co-AAm) hydrogel;

FIG. 3 is a schematic of GO @ DA/sodium alginate/P (AAc-co-AAm) hydrogel adhesion capability;

Detailed Description

The invention is further illustrated below with reference to examples.

Example 1:

1) the ESBMA was first prepared: preparing dimethylformamide, wherein the volume ratio of water is 1: 5 dimethyl200mL of dimethylformamide aqueous solution, 0.1mol of glycidyl methacrylate and 0.1mol of SBMA are added in sequence, and the mixture is dissolved for 15min respectively and N is introduced₂Adding a little initiator AlBN, heating at 60 ℃ for 24h for reaction, stopping in ice water bath for 3h, carrying out rotary evaporation, recrystallizing, washing for three times, and freeze-drying to obtain the product.

And the following solutions were prepared: 0.1 wt% CS acetic acid solution, 0.001 wt% ESBMA water solution;

2) sequentially adding 10 wt% of QCS, 0.25 wt% of SBMA, 1 wt% of AAm, 0.1 wt% of MBAA and 1 wt% of APS into the CS acetic acid solution in the step (1), fully and uniformly stirring, performing centrifugal defoaming, and pouring in a mold;

3) transferring the mould in the step (2) into an oven, setting the temperature at 40 ℃, and reacting for 10 hours to obtain gel;

4) and (3) soaking the gel obtained in the step (3) in an ESBMA aqueous solution, adding 10 vt% TEA, transferring into an oven, setting the temperature at 40 ℃, and reacting for 24 hours to obtain the required CS/QCS/SBMA/ESBMA antibacterial integrated gel dressing.

Example 2:

1) firstly, preparing dimethyl sulfoxide, wherein the volume ratio of water is 1: 1 of 200mL of dimethyl sulfoxide aqueous solution, 0.1mol of glycidyl methacrylate and 0.1mol of SBMA are added in sequence, and the mixture is dissolved for 15min respectively and N is introduced₂Adding a little initiator AlBN, heating at 60 ℃ for 24h for reaction, stopping in ice water bath for 3h, carrying out rotary evaporation, recrystallizing, washing for three times, and freeze-drying to obtain the product. And the following solutions were prepared: 10 wt% CS acetic acid solution, 0.1 wt% ESBMA water solution;

2) sequentially adding 0.1 wt% of QCS, 6.25 wt% of SBMA, 25 wt% of AAm, 0.05 wt% of MBAA and 0.5 wt% of APS into the CS acetic acid solution in the step (1), fully and uniformly stirring, performing centrifugal defoaming, and pouring in a mold;

3) transferring the mould in the step (2) into an oven, setting the temperature to be 80 ℃, and reacting for 4 hours to obtain gel;

4) and (3) soaking the gel obtained in the step (3) in an ESBMA aqueous solution, adding 0.1 vt% TEA, transferring the solution into an oven, setting the temperature to be 80 ℃, and reacting for 12 hours to obtain the required CS/QCS/SBMA/ESBMA antibacterial integrated gel dressing.

Example 3:

1) firstly, preparing a methanol-water volume ratio of 5: 1 of 200mL of aqueous methanol solution, 0.1mol of glycidyl methacrylate and 0.1mol of SBMA are added in sequence, and the mixture is dissolved for 15min respectively and N is introduced₂Adding a little initiator AlBN, heating at 60 ℃ for 24h for reaction, stopping in ice water bath for 3h, carrying out rotary evaporation, recrystallizing, washing for three times, and freeze-drying to obtain the product. And the following solutions were prepared: 5 wt% CS acetic acid solution, 0.5 wt% ESBMA water solution;

2) sequentially adding 5 wt% of QCS, 3.12 wt% of SBMA, 12.5 wt% of AAm, 0.001 wt% of MBAA and 0.01 wt% of APS into the CS acetic acid solution in the step (1), fully and uniformly stirring, performing centrifugal defoaming, and pouring in a mold;

3) transferring the mould in the step (2) into an oven, setting the temperature at 60 ℃, and reacting for 8 hours to obtain gel;

4) and (3) soaking the gel obtained in the step (3) in an ESBMA aqueous solution, adding 5 vt% TEA, transferring to an oven, setting the temperature at 60 ℃, and reacting for 18 hours to obtain the required CS/QCS/SBMA/ESBMA antibacterial integrated gel dressing.

Claims

1. A chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial and release integrated gel dressing is characterized in that the dressing is prepared by the following method:

the molecular weight of the chitosan is 50w-200w, and the deacetylation degree is 75% -95%;

preparing epoxidized zwitterions (ESBMA) through free radical copolymerization, wherein in the free radical copolymerization, functional monomers are [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA) and glycidyl methacrylate, a copolymerization mixed solvent is water and other solvents, and the copolymerization ratio is regulated by regulating the proportion of the other solvents to the water; the other solvent is selected from dimethyl sulfoxide, acetonitrile, dimethylformamide, methanol, ethanol, isopropanol, acetone, tetrahydrofuran, ethyl acetate, diethyl ether, dichloromethane, chloroform and toluene;

dissolving Chitosan (CS) in a water phase, sequentially adding QCS, zwitterion SBMA, acrylamide (AAm), N-Methylene Bisacrylamide (MBAA) and initiator Ammonium Persulfate (APS), performing centrifugal deaeration, pouring in a mold, and performing one-pot reaction in an oven to obtain gel;

and soaking the prepared gel in an epoxidized zwitter ion ESBMA solution, adding Triethylamine (TEA), and reacting in an oven for a period of time to obtain the antibacterial and antibacterial integrated gel dressing.

2. The chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial integrated gel dressing of claim 1, wherein: regulating the volume ratio of other solvents to water to be 1: 5-5: 1, so that the copolymerization ratio is 1: 9-9: 1.

3. the chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial integrated gel dressing of claim 1, wherein the chitosan is dissolved in the aqueous phase to obtain a 0.1-10 wt% CS acetic acid solution, and QCS, SBMA, AAm, MBAA and APS are sequentially added, and the addition amounts are respectively 0.1-10 wt%, 0.25-6.25%, 1-25 wt%, 0.001-0.1 wt% and 0.01-1 wt%.

4. The chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial integrated gel dressing of claim 1, wherein the temperature of the oven during the one-pot reaction is 40-80 ℃, and the reaction lasts for 4-10 hours.

5. The chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion anti-bactericidal/antibacterial integrated gel dressing of claim 1, wherein the epoxidized zwitterion ESBMA solution is 0.001 to 0.1 wt% ESBMA aqueous solution.

6. The chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial integrated gel dressing of claim 1, wherein the TEA is added in an amount of 0.1 to 10 vt% of the epoxidized zwitterion solution.

7. The chitosan/quaternized chitosan/zwitterion/epoxidized zwitterion antibacterial integrated gel dressing of claim 1, wherein TEA is added and then transferred into an oven, the temperature is set at 40-80 ℃, and the reaction is carried out for 12-24 hours.