阅读说明：本技术 一种抗菌聚氨酯水凝胶医用敷料及其制备方法 (Antibacterial polyurethane hydrogel medical dressing and preparation method thereof ) 是由 孙复钱 张鹏 舒泉水 于 2020-04-26 设计创作，主要内容包括：本发明公开了一种抗菌聚氨酯水凝胶医用敷料及其制备方法,属于生物医用材料领域。材料是包含甲基丙烯酸封端的亲水聚氨酯单体、含两性离子结构的甲基丙烯酸酯、甲基丙烯酸酯类、交联剂、引发剂组成的混合物经过紫外光照固化或加热固化,然后在水中溶胀吸收水份后形成。本发明制备的抗菌聚氨酯水凝胶医用敷料具有良好的抗菌性能并长久保持材料抗菌性、制作工艺简单、效率高、组分配比可调、材料性能可控的特点,是一种新型功能性医用创伤敷料。(The invention discloses an antibacterial polyurethane hydrogel medical dressing and a preparation method thereof, belonging to the field of biomedical materials. The material is formed by curing a mixture consisting of a methacrylic acid end-capped hydrophilic polyurethane monomer, methacrylate containing a zwitterion structure, methacrylate, a cross-linking agent and an initiator by ultraviolet irradiation or heating, and then swelling in water to absorb water. The antibacterial polyurethane hydrogel medical dressing prepared by the invention has the characteristics of good antibacterial performance, long-term antibacterial property of the material, simple manufacturing process, high efficiency, adjustable component proportion and controllable material performance, and is a novel functional medical wound dressing.)

1. The antibacterial polyurethane hydrogel medical dressing is characterized by comprising the following raw materials in parts by mass: 50-80% of methacrylic acid end-capped hydrophilic polyurethane monomer, 5-10% of methacrylate containing a zwitterion structure, 8.9-41.5% of methacrylate, 1-3% of cross-linking agent and 0.1-0.5% of initiator.

2. The antibacterial polyurethane hydrogel medical dressing according to claim 1, wherein the methacrylic acid terminated hydrophilic polyurethane monomer comprises the following raw materials: polyethylene glycol, glycerol, isocyanate and methacrylate with hydroxyl.

3. The antibacterial polyurethane hydrogel medical dressing according to claim 2,the polyethylene glycol The molecular weight is 600-3000, and the methacrylate with hydroxyl comprises hydroxyethyl methacrylate and hydroxypropyl methacrylate One or a mixture of two of the esters.

4. The antimicrobial polyurethane hydrogel medical dressing of claim 1, wherein the methacrylate ester containing a zwitterionic structure comprises a mixture of one or more of phosphorylcholine methacrylate, sulfobetaine methacrylate and carboxybetaine methacrylate.

5. The antimicrobial polyurethane hydrogel medical dressing of claim 1, wherein the methacrylate ester comprises a mixture of one or more of methacrylic acid, N' N-dimethylamide methacrylate, and glycidyl methacrylate.

6. The antimicrobial polyurethane hydrogel medical dressing of claim 1, wherein the antimicrobial polyurethane hydrogel medical dressing comprises a dressing body having a first surface and a second surface, and wherein the first surface is substantially parallel to the second surfaceThe cross-linking agent package Comprises one or more of ethylene glycol dimethacrylate, butylene glycol dimethacrylate and glyceryl trimethacrylate Mixing; the initiator is an ultraviolet light initiator or an azo thermal initiator.

7. A preparation method of an antibacterial polyurethane hydrogel medical dressing is characterized by comprising the following steps:

(1) synthesis of isocyanate-terminated hydrophilic prepolymer: dehydrating hydrophilic polyethylene glycol, adding an initiator glycerol and isocyanate, and stirring at high speed at 40-70 ℃ under an anhydrous condition until the-NCO content reaches 7-10% to obtain an isocyanate-terminated hydrophilic prepolymer;

(2) methacrylic acid end-capped hydrophilic polyurethane monomer synthesis: mixing the isocyanate-terminated hydrophilic prepolymer and methacrylate with hydroxyl, stirring at a high speed at 40-70 ℃ under an anhydrous condition, and continuing to react to obtain a methacrylic acid-terminated hydrophilic polyurethane monomer;

(3) preparing a curing mixture: the antibacterial polyurethane hydrogel medical dressing according to any one of claims 1 to 6, wherein the raw materials are weighed and mixed uniformly to form a solidified mixture.

(4) Preparing the antibacterial polyurethane hydrogel medical dressing: and pouring the cured mixture into a container, reacting under 365nm ultraviolet illumination or at 90-110 ℃, and then immersing the cured product after reaction into the solution to swell to obtain the antibacterial polyurethane hydrogel medical dressing.

8. The method for preparing an antibacterial polyurethane hydrogel medical dressing according to claim 7, wherein in the step (1), the ratio of polyethylene glycol: the mass ratio of the glycerol to the isocyanate is 50:1-3: 10-20.

9. The method for preparing the antibacterial polyurethane hydrogel medical dressing as claimed in claim 7, wherein in the step (2), the mass ratio of the isocyanate-terminated hydrophilic prepolymer to the methacrylate with hydroxyl is 250:56-250: 77.

10. The method for preparing an antibacterial polyurethane hydrogel medical dressing as claimed in claim 7, wherein in the step (4), the water content of the antibacterial polyurethane hydrogel medical dressing is 20% -90%.

Technical Field

The invention belongs to the technical field of biomedical materials, and particularly relates to an antibacterial polyurethane hydrogel medical dressing and a preparation method thereof.

Background

The medical wound dressing covers the skin wound surface to protect the wound, avoids the skin from secondary damage, can provide a favorable environment for the healing of the wound, is mainly used for covering sores, wounds or other injuries, is an important biomedical material, and has been a hot problem in research and development.

The common dressing mainly comprises gauze, hydrogel and the like. The gauze is the dressing which is the earliest and the most widely used dressing, and the gauze dressing has the advantages of wound surface protection, bacteria invasion reduction, strong wound surface exudate absorption capacity, simple production and processing and low price, but the gauze has large pore diameter, poorer barrier effect and higher possibility of bacteria invasion, is easy to dehydrate and adhere the wound surface, causes secondary mechanical injury during replacement, ensures that granulation tissues of the wound surface are easy to grow into meshes of the gauze, and can damage new tissues during dressing change to cause pain.

Hydrogels are a class of polymers having a three-dimensional network structure that can absorb a large amount of water in water to swell and, after swelling, can continue to maintain their original structure without being dissolved. The modern wound healing theory considers that the wet healing is the basis of the wound healing, so that the guarantee of the wound surface wetting in the wound healing process is the necessary requirement of a functional dressing, and the hydrogel is very soft due to the fact that the hydrogel contains a large amount of moisture and can be used as an excellent biomedical material, particularly a novel wound dressing. When the hydrogel is used for wound dressing, the pollution of external bacteria and microorganisms to a wound can be reduced, the loss of body fluid is effectively prevented, oxygen can be transmitted to the wound, a certain wettability is kept, the healing of the wound is accelerated, the fibrinogen is dissolved, the self-dissolving debridement effect is achieved, gel is formed, the exposed nerve endings are protected, the pain is relieved, and the secondary mechanical injury is not easily caused.

Because of good mechanical properties, polyurethane is widely applied to the industrial field, and polyurethane hydrogel materials can be developed to be used as drug release systems, wound dressings, contact lenses, tissue engineering materials and the like. Particularly, polyurethane hydrogel wound dressings have the characteristics of softness and good elasticity, and research and products on polyurethane hydrogel wound dressings have been published, such as a PU wound dressing which is developed in patent EP1333788 and consists of a hydrophilic PU foam and a PU hydrogel two-layer structure. The hydrogel layer is laminated to the foam layer and bonded thereto by means of an adhesive or a radiation crosslinking reaction. Similar products are also available as the Hydrasorb PU dressing from Avitar corporation and the Hydro-foam dressing from Tyco corporation. Patent WO9817215 uses IPDI and polyhydric alcohol as raw materials to polymerize to obtain prepolymer, then reacts with polypropylene glycol (PPG), and is further mixed with propylene glycol and PPG to obtain PU hydrogel wound dressing, and antibacterial drugs such as bismuth tribromophenate (BT P), sulfadiazine (SSD) and the like can also be added in the preparation process to obtain PU hydrogel with antibacterial function. The product developed by Cardio Tech company is named as SpyroDerm PU hydrogel wound dressing, is transparent gel in appearance, can be used for skin ulcer, abrasion, wound and burn, can be directly coated on the wound, and is easy to remove and replace.

However, the existing polyurethane hydrogel wound dressing still has the defects of complex preparation process and single function and component, and cannot be used for wounds with much seepage, particularly wounds are easily infected by bacteria in the healing process, and the healing condition of the wounds is seriously influenced.

Therefore, the problem to be solved in the field is how to provide an antibacterial polyurethane hydrogel medical dressing which is simple in preparation process, durable in antibacterial property and adjustable in component proportion.

Disclosure of Invention

The invention discloses an antibacterial polyurethane hydrogel medical dressing and a preparation method thereof. In order to achieve the purpose, the invention adopts the following technical scheme:

an antimicrobial polyurethane hydrogel medical dressing comprising: 50-80% of methacrylic acid end-capped hydrophilic polyurethane monomer, 5-10% of methacrylate containing a zwitterion structure, 8.9-41.5% of methacrylate, 1-3% of cross-linking agent and 0.1-0.5% of initiator;

the methacrylic acid end-capped hydrophilic polyurethane monomer comprises the following raw materials: polyethylene glycol, glycerol, isocyanate, methacrylate with hydroxyl;

the molecular weight of the polyethylene glycol is 600-3000, and the methacrylate with hydroxyl comprises one or a mixture of hydroxyethyl methacrylate and hydroxypropyl methacrylate;

preferably, the polymerization degree of the polyethylene glycol is between 1000 and 3000;

the methacrylate containing the zwitterion structure comprises one or more of phosphorylcholine methacrylate, sulfobetaine methacrylate and carboxybetaine methacrylate;

the methacrylate comprises one or more of methacrylic acid, N' N-dimethyl amide methacrylate and glycidyl methacrylate.

The cross-linking agent comprises one or more of ethylene glycol dimethacrylate, butylene glycol dimethacrylate and glyceryl trimethacrylate; the initiator is an ultraviolet light initiator or an azo thermal initiator;

preferably, the initiator includes ultraviolet initiators such as 1176, 184, TPO, etc., or azo thermal initiators such as AIBN, etc.;

a preparation method of an antibacterial polyurethane hydrogel medical dressing comprises the following steps:

(1) synthesis of isocyanate-terminated hydrophilic prepolymer: dehydrating hydrophilic polyethylene glycol, adding an initiator glycerol and isocyanate, and stirring at high speed at 40-70 ℃ under an anhydrous condition until the-NCO content reaches 7-10% to obtain an isocyanate-terminated hydrophilic prepolymer;

preferably, in the step (1), the reaction is carried out under the protection of inert gas;

preferably, in the step (1), the high-speed stirring rotating speed is 500-1500 r/min;

(2) methacrylic acid end-capped hydrophilic polyurethane monomer synthesis: mixing the isocyanate-terminated hydrophilic prepolymer and methacrylate with hydroxyl, stirring at a high speed at 40-70 ℃ under an anhydrous condition, and continuing to react to obtain a methacrylic acid-terminated hydrophilic polyurethane monomer;

preferably, in the step (2), the reaction is carried out under the protection of inert gas;

preferably, in the step (2), the mixing method of the reactants is as follows: slowly adding methacrylate with hydroxyl into the isocyanate-terminated hydrophilic prepolymer;

preferably, in the step (2), the high-speed stirring rotating speed is 500-1500 r/min;

(3) preparing a curing mixture: weighing the raw materials according to any one of the antibacterial polyurethane hydrogel medical dressing containing the methacrylic acid end-capped hydrophilic polyurethane monomer, the methacrylate containing a zwitterion structure, the methacrylate, the cross-linking agent and the initiator, and uniformly mixing and dissolving to form a curing mixture.

(4) Preparing the antibacterial polyurethane hydrogel medical dressing: pouring the cured mixture into a container, reacting under 365nm ultraviolet illumination or at 90-110 ℃, and then immersing the cured product after reaction into the solution to swell to obtain the antibacterial polyurethane hydrogel medical dressing;

in the step (1), the polyethylene glycol: the mass ratio of the glycerol to the isocyanate is 50:1-3: 10-20;

in the step (2), the mass ratio of the isocyanate-terminated hydrophilic prepolymer to the methacrylate with hydroxyl is 250:56-250: 77;

in the step (4), the water content of the antibacterial polyurethane hydrogel medical dressing is 20-90%.

In conclusion, the methacrylate with the zwitterionic structure is taken as an antibacterial molecule and is combined into the polyurethane hydrogel in a covalent bond form, so that the polyurethane hydrogel can have good antibacterial performance and keep the antibacterial property of the material for a long time; the antibacterial group is safe and nontoxic, has good biocompatibility and no harm to wound skin, and is safe and effective when added into polyurethane hydrogel as a dressing. The preparation method of the antibacterial polyurethane hydrogel medical dressing has simple preparation process, and overcomes the defects of complex preparation process and poor antibacterial property of the existing polyurethane hydrogel medical dressing; and has the characteristics of high efficiency, adjustable component proportion and controllable material performance, and is suitable for industrial mass production.

Detailed Description

The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.