CN115068697A

CN115068697A - Antibacterial composite material based on hyperbranched polyquaternary ammonium salt

Info

Publication number: CN115068697A
Application number: CN202210463961.0A
Authority: CN
Inventors: 朱宝库; 王楚瑶; 薛云云; 方立峰; 赵自豪; 田华
Original assignee: Zhejiang University ZJU
Current assignee: Zhejiang University ZJU
Priority date: 2022-04-27
Filing date: 2022-04-27
Publication date: 2022-09-20
Anticipated expiration: 2042-04-27
Also published as: CN115068697B

Abstract

The invention discloses an antibacterial composite material based on hyperbranched polyquaternary ammonium salt, which comprises hyperbranched polyquaternary ammonium salt and a matrix polymer, wherein the mass content of the matrix polymer is 90-99.5%, and the mass content of the hyperbranched polyquaternary ammonium salt is 0.5-10%; the hyperbranched polyquaternary ammonium salt simultaneously contains phase-separated quaternary ammonium salt groups, hydrophobic long-chain alkyl groups and one of anionic groups or zwitterionic groups; the antibacterial composite material can be processed and prepared into catheter medical products, non-woven fabrics, films and other medical products through melt extrusion, melt-blowing or solution coating and other routes. The preparation method of the antibacterial composite material and the medical equipment thereof is simple and has wide application range; the prepared medical materials such as catheters, non-woven fabrics and films not only have efficient and stable antibacterial and antiviral functions, but also have the characteristics of good adhesion resistance, low toxicity, biocompatibility and the like, and have great application value in a plurality of medical instruments.

Description

Antibacterial composite material based on hyperbranched polyquaternary ammonium salt

Technical Field

The invention belongs to the field of biomedical materials, and particularly relates to an antibacterial composite material based on hyperbranched polyquaternary ammonium salt.

Background

The medical appliance in the forms of various catheters, film dressings, non-woven fabrics and the like is implanted or externally used and is mainly prepared from high polymer materials, and has important functions in the fields of medical treatment and health. At present, the medical polymer materials have three common problems: firstly, common medical polymer materials mostly have no antibacterial performance, and are easy to cause serious infection and inflammation reactions in the application process or the infection of pathogenic microorganisms such as bacteria and the like; secondly, in order to deal with pathogenic infection caused by medical high polymer materials, antibiotics or antibacterial agents are often used for treatment, and the substances are dissolved out of the polymer materials, so that new risks and injuries are caused by side effects such as cytotoxicity, teratogenesis, gene mutation and the like; third, these materials tend to have strong cell adhesion and poor biocompatibility, including but not limited to cytotoxicity, hemocompatibility and histocompatibility, which are prone to adhesion, hemolysis, and other problems. These common problems also become the main reason for few antibacterial medical devices at home and abroad, so the problem of the lack of the machinable medical polymer material which has the functions of antibacterial, antiviral, nontoxic and biocompatible and does not affect the basic physical properties of material mechanics, thermal property and the like is urgently needed to be solved.

The antibacterial property is the property of killing bacteria by adopting a chemical or physical method or hindering the growth and the reproduction of the bacteria and the activity thereof, namely the antibacterial property and the antibacterial property are divided into two degrees, wherein the bactericidal effect can reduce the concentration of the living bacteria, and the antibacterial property can slow down the propagation and the growth speed of the bacteria, namely the concentration of the living bacteria is increased more slowly than that of a blank control. The antibacterial property of the material can be characterized by measuring the number of live bacteria in bacterial liquid after the material is contacted with the material. The antibacterial adhesion refers to the performance of inhibiting the fixed growth of bacteria on the surface of the material, does not influence the increase of the concentration of the live bacteria, and can be characterized by measuring the number of bacteria adhered to the surface of the material before and after the material is contacted with bacterial liquid.

The polymer materials for antibacterial medical instruments reported at present are mainly prepared by adding various antibacterial agents into a polymer matrix material and carrying out molding processing by methods such as melt extrusion, melt blowing, solution spinning and the like, so that the polymer materials for antibacterial medical instruments have to have good antibacterial property, biocompatibility and moldability at the same time, and any one of the three properties is not satisfied, so that the polymer materials cannot be used as the materials for antibacterial medical instruments.

The quaternary ammonium salt compound has broad-spectrum high-efficiency bactericidal property and is widely applied to antibacterial materials. The quaternary ammonium salt compounds can be divided into small molecular quaternary ammonium salt, non-hyperbranched high molecular polyquaternium and hyperbranched high molecular (hyperbranched) polyquaternium. The molecular chain structure of the non-hyperbranched polymer is a long straight chain or has a small amount of side groups, but the molecular chain still takes a linear main chain as a main chain. Hyperbranched Polymer molecules have highly branched three-dimensional spherical structures (C.Gao, D.Yan, Hyperbranched polymers: from synthesis to applications in Polymer Science,2004,29: 183-. The hyperbranched polymer is one of dendritic polymers, and the difference is that the dendritic polymer has very regular branching, so the problems of complicated synthesis process and high cost and is difficult to carry out large-scale industrial production and application exist. It is well known to those skilled in the art that the name of hyperbranched structured polymers must have a naming prefix for hyperbranched.

For the micromolecular quaternary ammonium salt antibacterial polymer material, the antibacterial component is a cationic quaternary ammonium salt group, and the antibacterial mechanism is that the positively charged quaternary ammonium group destroys the bacterial cell membrane after contacting bacteria and leads protein in the bacterial cell membrane to be denatured or destroys the cell structure so as to kill the bacteria. For example, patent CN113736200A discloses an antibacterial resin composite material prepared by adding a small molecular quaternary ammonium salt antibacterial agent into a super absorbent resin. However, the small molecular quaternary ammonium salt antibacterial agent is soluble in water, similar to a metal ion or metal nanoparticle antibacterial agent, has low compatibility with a high molecular matrix material, is easy to dissolve out, has high electropositivity to cause a membrane rupture killing effect on mammalian cells, and has biocompatibility problems of high cytotoxicity, high hemolysis rate, strong protein adhesion and the like caused by dissolution out. Therefore, the organic micromolecule-based antibacterial polymer material cannot meet the requirements of medical instruments.

Non-hyperbranched polyquaternary ammonium salt antibacterial polymer material, for example, inventive patent CN112646110A further synthesizes polyurethane by synthesizing diol monomer containing gemini quaternary ammonium salt to obtain gemini quaternary ammonium salt polyurethane coating material with antibacterial property; the invention patent CN105999406A obtains the antibacterial quaternary ammonium salt chitosan composite gel coating by modifying the surface of the chitosan/polyvinyl alcohol composite gel coating with 1-bromoheptane. The polyquaternium sterilization mechanism is material contact sterilization, bacteria are attracted to the surface of the material through strong positive charge of a large number of quaternary ammonium salt groups on the surface of the material, the structure of a cell membrane is damaged through strong attraction of the quaternary ammonium salt groups and negatively charged phospholipid of the cell membrane of the bacteria, the permeability of the cell membrane is changed, and death such as cytoplasm leakage is caused. However, compared with the small molecular quaternary ammonium salt, the polyquaternium has higher cation concentration on the surface of the material, so that the long-term antibacterial effect and the service performance are easily influenced by the reduction of biocompatibility and the adhesion of bacteria to the surface of the material due to the excessively strong electrostatic attraction effect generated between the polyquaternium and the substances such as bacteria, cells, proteins and the like. There are also high molecular materials obtained by crosslinking non-hyperbranched polyquaternium, but the network crosslinked polymer itself has already become a three-dimensional structure, does not have the continuous molding processability, and cannot be used as an antibacterial medical instrument material. For example, in patent CN111675789A, quaternary ammonium salt and acrylamide are copolymerized and crosslinked to prepare an antibacterial hydrogel, so that the existing antibacterial materials based on non-hyperbranched high molecular polymers have the disadvantages of low biocompatibility, easy generation of adhesive contamination on the material surface, and the like, and cannot be used as antibacterial medical device materials.

Aiming at the problems of insufficient biocompatibility or easy generation of adhesion pollution of proteins, bacteria and the like of a high-molecular antibacterial material, the method adopts a mode of introducing zwitterions, mixed charge polymers or responsive switching groups as a modified substance, and has the property of effectively inhibiting the surface adhesion of the proteins, the bacteria and the like by enabling the surface to be rich in positive and negative charges to generate hydrogen bond interaction with water molecules to generate a hydration layer. For example, patent CN105199070A introduces zwitterions into the polyurethane backbone to achieve antibacterial adhesion properties; the invention patent US10905796B2 proposes to introduce a zwitterionic betaine structure into a thermoplastic elastomeric supramolecular polymer to improve the adhesion resistance and biocompatibility; fan et al polymerize vinyl monomers containing quaternary ammonium salt, carboxyl group and n-butyl group, and synergistically prepare a Coating material having antibacterial property and blood compatibility by using Mixed charges (Xiao-li Fan, Mihu, Zhui-hui Qin, et al, bacterial and compatible Coating of the Mixed-Charged Copolymer [ J ] ACS Applied Materials & Interfaces,2018,10:10428 10436.); the patent CN112007209A achieves salt response of the antibacterial and antibacterial integrated gel dressing by introducing epoxidized zwitterion into quaternized chitosan. However, the material containing only the zwitterionic polymer has weak sterilization capability and limited application scenes.

The hyperbranched polyquaternary ammonium salt is a polymer with a highly branched three-dimensional spherical structure, and is prepared by grafting or quaternizing quaternary ammonium salt groups of the hyperbranched polymer or directly polymerizing monomers containing the quaternary ammonium salt groups. The hyperbranched polyquaternary ammonium salt powder, solution or coating material is used and has no independent molding processability, so the hyperbranched polyquaternary ammonium salt powder, solution or coating material has less application in the aspect of solid materials and is mainly applied to the fields of antistatic agents, dye adsorption in wastewater treatment, demulsifiers and the like. Hyperbranched polyquaternium is studied for Antibacterial purposes, mainly for material surface coatings (Lia A.T.W.Ash, Mihalea Crismaru, Steven Roest, et al, A Shape-Adaptive, Antibacterial-Coating of Immobilized Quaternary Ammonium-Ammonium complex and Materials Mechanism of Action [ J ]. Advanced Functional Materials,2013,24:346-355.) and textile Antibacterial modification (chemical, Xingdong Zhou, Xnging Wang, Ku et al, Synthesis and Application of waterborne polyurethane Quaternary Ammonium salt, so that it is difficult to satisfy the compatibility of hyperbranched polyquaternium with non-biodegradable Quaternary Ammonium salt, so that the compatibility of hyperbranched polyquaternium with non-biodegradable Quaternary Ammonium salt, such as bacterial inhibition 1088, still cannot be satisfied with the requirements of medical instruments.

In conclusion, the prior art is difficult to satisfy the requirements of the biomedical material with simple operation, low cost, durable effect, excellent performance and controllability on good antibacterial property, biocompatibility and formability and processability.

Disclosure of Invention

Aiming at the defects of the prior art, the technical problems to be solved by the invention are as follows: the polymer material for the medical instrument has the characteristics of good antibacterial property, biocompatibility and formability and processability, is simple and convenient in preparation method, low in cost, excellent in performance and durable in effect, overcomes the defects that the antibacterial property and the biocompatibility are difficult to achieve simultaneously and the formability and processability are difficult to achieve in the prior art, and solves the problem that the growth of a biological film and the bacterial infection on the surface of the medical polymer material are harmful to the health of a human body due to bacterial adhesion.

The invention adopts the following technical scheme:

the invention provides an antibacterial composite material based on hyperbranched polyquaternary ammonium salt, which comprises the hyperbranched polyquaternary ammonium salt and a matrix polymer, wherein the mass content of the matrix polymer is 90-99.5%, and the mass content of the hyperbranched polyquaternary ammonium salt is 0.5-10%, wherein the hyperbranched polyquaternary ammonium salt has the following structural formula:

in the formula, R ₁ The hyperbranched polymer is preferably selected from any one of hyperbranched polyamide-amine, hyperbranched polyethyleneimine, hyperbranched polyester and hyperbranched polyurethane; preferably, the hyperbranched polymer has a structure selected fromAny one of the following structures:

R ₂ containing a quaternary ammonium salt group, preferably, the R ₂ The structure is selected from any one of the following structures:

R ₃ the alkyl group is a long-chain alkyl group, the carbon atom number of the long-chain alkyl group is more than or equal to 6, and preferably, the carbon atom number of the long-chain alkyl group is 6-18;

R ₄ comprises an anionic group or a zwitterionic group; preferably, the anionic group is selected from at least one of a sulfonic acid group, a carboxylic acid group, and a phosphoric acid group; preferably, the zwitterion group is selected from at least one of anion and cation coexisting structures in sulfobetaine, carboxyl betaine and phosphorylcholine structures, wherein the sulfobetaine structure is

The carboxyl betaine has the structure of

The phosphorylcholine has a structure of

Preferably, the matrix polymer is selected from any one or more of polyurethane, polyether amide, polyester, polyvinyl chloride and polypropylene;

preferably, the element mole ratio of the nitrogen positive ions on the surface of the antibacterial composite material is 0.40-2%;

preferably, the antibacterial composite material based on the hyperbranched polyquaternary ammonium salt has bactericidal property and biocompatibility, wherein the bactericidal rate of escherichia coli reaches 99%, the cell survival rate reaches 85%, and the hemolysis rate is less than 2%. Wherein, the sterilization rate in the invention refers to the Escherichia coli killing rate.

Preferably, when the hyperbranched polyquaternium in the antibacterial composite material is hyperbranched polyamide-amine polyquaternium, the matrix polymer is polyurethane, the mass content of the hyperbranched polyquaternium is 0.5-3%, and the mass content of the matrix polymer is 97-99.5%, the molar ratio of the elements of nitrogen positive ions in quaternary ammonium salt groups on the surface of the antibacterial composite material is 0.50-0.70%; preferably, the sterilization rate of the escherichia coli is more than 99.9%, and the long-term sterilization rate is more than 90%; preferably, the cell survival is > 90%, the long-term cell survival is > 95%, and the hemolysis rate is < 0.5%.

Preferably, the antibacterial composite material comprises any one of the following components:

1) the matrix polymer is polyurethane, and the hyperbranched polyquaternary ammonium salt is any one of hyperbranched polyurethane polyquaternary ammonium salts and hyperbranched polyamide-amine polyquaternary ammonium salts;

2) the matrix polymer is polyester, and the hyperbranched polyquaternary ammonium salt is hyperbranched polyester polyquaternary ammonium salt;

3) the matrix polymer is polypropylene, and the hyperbranched polyquaternary ammonium salt is hyperbranched polyester polyquaternary ammonium salt;

4) the substrate polymer is polyether amide, and the hyperbranched polyquaternary ammonium salt is any one of hyperbranched polyamide-amine polyquaternary ammonium salt and hyperbranched polyethyleneimine polyquaternary ammonium salt;

5) the matrix polymer is polyvinyl chloride, and the hyperbranched polyquaternary ammonium salt is selected from any one of hyperbranched polyamide-amine polyquaternary ammonium salt and hyperbranched polyester polyquaternary ammonium salt.

Preferably, the hyperbranched polyquaternary ammonium salt is hyperbranched polyamide-amine polyquaternary ammonium salt;

preferably, the preparation method comprises the following steps: dissolving hyperbranched polyamide-amine in a solvent, and adding the solution containing R ₂ Compounds of the group, containing R ₃ Compounds containing radicals, or obtained by chemical reaction ₄ Of radicalsThe compound reacts with hyperbranched polyamide-amine, and then the solvent is removed to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt;

more preferably, the compound containing quaternary ammonium salt groups is selected from any one or more of 2, 3-epoxypropyltrimethylammonium chloride, 2, 3-epoxypropyltriethylammonium chloride, 3-chloro-2-hydroxypropyltrimethylammonium chloride, 2-chloroethyltrimethylammonium chloride and dimethylaminoethylmethacrylate quaternary ammonium salt;

more preferably, the compound containing long-chain alkyl is selected from any one or more of 1-iodo, 1-bromo, 1-chloro, and linear alkanes containing 6 to 18 carbon atoms of 1-acyl chloride structure;

more preferably, the compound containing or formed by chemical reaction to contain an anionic group is selected from any one or more of 1, 3-propane sultone, chlorosulfonic acid, chloroacetic acid, and carboxyl-containing acrylate compounds;

more preferably, the compound containing the zwitterion group is selected from any one or more of sulfobetaine methacrylate, carboxyl betaine methacrylate and 2-methacryloyloxyethyl phosphorylcholine;

more preferably, said compound contains or is obtained by chemical reaction ₂ ，R ₃ ，R ₄ All components of the compound of the group account for hyperbranched polyamide-amine and contain or obtain R after chemical reaction ₂ ，R ₃ ，R ₄ 40-80% of the total mass of all components of the compound of the group; namely, it is

Wherein the content of the first and second substances,

the mass of the hyperbranched polyamide-amine is,

to contain R ₂ The mass of the compound of the group,

to contain R ₃ The mass of the compound of the group,

is a compound containing or obtained by chemical reaction of R ₄ A compound of group (I);

further preferably, R is obtained after said containing or by chemical reaction ₂ ，R ₃ ，R ₄ In the three compound components of the group, the molar content of the quaternary ammonium salt group is 40-60%, the molar content of the long-chain alkyl group is 20-40%, and the molar content of the anionic or zwitterionic group is 20-40%;

preferably, the solvent is selected from any one of methanol, ethanol, N-dimethylformamide and N, N-dimethylacetamide; more preferably, the reaction conditions are at a temperature of 60 ℃ and a reaction time of 6 to 10 hours.

Preferably, the hyperbranched polyquaternary ammonium salt is hyperbranched polyethyleneimine polyquaternary ammonium salt;

preferably, the preparation method comprises the following steps: dissolving hyperbranched polyethyleneimine in a solvent, and respectively adding the hyperbranched polyethyleneimine containing R ₂ Compounds of the group, containing R ₃ Compounds containing radicals, or obtained by chemical reaction ₄ Reacting a compound of the group with hyperbranched polyethyleneimine, and removing a solvent to obtain the hyperbranched polyethyleneimine polyquaternary ammonium salt;

more preferably, said compound contains or is obtained by chemical reaction ₂ ，R ₃ ，R ₄ All components of the compound of the group account for hyperbranched polyethyleneimine and R is obtained by containing or through chemical reaction ₂ ，R ₃ ，R ₄ 40-80% of the total mass of all components of the compound of the group; namely, it is

Wherein the content of the first and second substances,

the mass of the hyperbranched polyethyleneimine is shown in the specification,

to contain R ₂ The mass of the compound of the group,

to contain R ₃ The mass of the compound of the group,

preferably, the solvent is selected from any one of methanol and ethanol; more preferably, the reaction conditions are 60 ℃ and the reaction time is 6-10 h.

Preferably, the hyperbranched polyquaternary ammonium salt is hyperbranched polyester polyquaternary ammonium salt or hyperbranched polyurethane polyquaternary ammonium salt;

preferably, the preparation method comprises the following steps: dissolving hyperbranched polyester or hyperbranched polyurethane in a solvent, and respectively adding a solvent containing R ₂ Compounds of the group, containing R ₃ Compounds containing radicals, or obtained by chemical reaction ₄ Reacting the compound of the group with hyperbranched polyester or hyperbranched polyurethane, and removing the solvent to obtain hyperbranched polyester polyquaternium or hyperbranched polyurethane polyquaternium; more preferably, the compound containing quaternary ammonium salt groups is selected from any one or more of 2, 3-epoxypropyltrimethylammonium chloride and 2, 3-epoxypropyltriethylammonium chloride;

more preferably, the compound containing long-chain alkyl is selected from any one or more of 1-acyl chloride, and linear alkane containing 6-18 carbon atoms of 1, 2-epoxy structure;

more preferably, the compound containing or formed by chemical reaction to contain an anionic group is selected from any one or more of 1, 3-propane sultone and chlorosulfonic acid;

more preferably, said compound contains or is obtained by chemical reaction ₂ ，R ₃ ，R ₄ All components of the compound of the group account for hyperbranched polyester or hyperbranched polyurethane and contain or obtain R through chemical reaction ₂ ，R ₃ ，R ₄ 40-80% of the total mass of all components of the compound of the group; namely, it is

Wherein the content of the first and second substances,

is the quality of hyperbranched polyester or hyperbranched polyurethane,

to contain R ₂ The mass of the compound of the group,

to contain R ₃ The mass of the compound of the group,

further preferably, R is obtained after said containing or by chemical reaction ₂ ，R ₃ ，R ₄ In the three compound components of the group, the molar content of the quaternary ammonium salt group is 40-60%, the molar content of the long-chain alkyl group is 20-40%, and the molar content of the anionic group is 20-40%;

preferably, the solvent is selected from any one of tetrahydrofuran, N-dimethylformamide and N, N-dimethylacetamide; more preferably, the reaction temperature is 70 ℃, the reaction time is 8-10h respectively, and the reaction is catalyzed by sodium hydride.

Preferably, the antibacterial composite material is prepared by blending hyperbranched polyquaternary ammonium salt and a matrix polymer.

The invention also provides an antibacterial composite, which comprises the antibacterial composite material and at least one additive; preferably, the additive is selected from any one or more of synthetic macromolecular compounds, modified macromolecular polysaccharides, pigments, reinforcing agents, plasticizers, antioxidants, mildewproofing agents, antibiotics, anti-inflammatory agents, analgesics and antihistamines; preferably, the synthetic polymer compound is selected from one or more of a polymer compound obtained by addition polymerization, a polymer compound obtained by polycondensation, a polyamide-based polymer compound, and a synthetic rubber-based polymer compound; preferably, the antibiotic is selected from any one or more of quinolone antibiotics, beta-lactam antibiotics, macrolides and aminoglycoside antibiotics; preferably, the modified high molecular polysaccharide is selected from one or more of carboxyl modified high molecular polysaccharide, amino modified high molecular polysaccharide and sulfhydryl modified high molecular polysaccharide; preferably, the high molecular polysaccharide is selected from any one or more of cellulose, lignin, starch, chitosan and agarose.

The invention also provides an antibacterial high polymer material for medical appliances, which is prepared from the antibacterial composite material or the antibacterial composite material; preferably, the preparation method of the antibacterial polymer material comprises the following steps: the antibacterial composite material or the antibacterial composite is processed and molded by a melting, high-speed mixing or solution route.

The invention also provides a medical appliance, which is prepared by processing the antibacterial high polymer material;

preferably, the medical apparatus is a medical tube, a film, a sheet, a medical non-woven fabric or a medical composite coating material; preferably, the forming preparation method of the medical tube, the film and the sheet comprises the following steps: preparing medical pipes, films or sheets by melt line extrusion, calendering, curtain coating or solution line;

preferably, the forming preparation method of the medical non-woven fabric comprises the following steps: preparing a porous non-woven fabric material through a melting or solution spinning route;

preferably, the preparation method of the medical composite coating material comprises the following steps: after the solution is dissolved, coating and drying the surface of the matrix polymer to prepare the antibacterial composite coating material;

more preferably, the medical device is subjected to a molding preparation process, then is soaked in pure water at the temperature of 40-60 ℃ for 10-24h, and is dried at the temperature of 50 ℃ for 24h, and then is treated to realize the enhancement of the antibacterial property and the biocompatibility.

According to the invention, the quaternary ammonium salt, the long-chain alkyl, the anion or the zwitterion functional group (each functional group is on different terminal groups of the hyperbranched polymer) is simultaneously introduced into the hyperbranched polymer to prepare the hyperbranched polyquaternary ammonium salt, and the hyperbranched polyquaternary ammonium salt is compounded with various matrix polymers, so that the obtained composite material has good antibacterial property, even bactericidal property, biocompatibility and formability processability under the conditions of the ratio of the quaternary ammonium salt, the long-chain alkyl, the anion or the zwitterion functional group and the ratio of the hyperbranched polyquaternary ammonium salt to the matrix polymer in a specific range, and different balance between the antibacterial property and the biocompatibility is obtained, thereby greatly widening the application range of the material. In the process of preparing medical instruments from the hyperbranched polyquaternium antibacterial composite material, the material forms of pipes, films, non-woven fabrics, coatings and the like can be selected at will according to actual requirements, and the hyperbranched polyquaternium antibacterial composite material has a wide application scene. The invention has the advantages that the cost of the adopted raw materials is lower, the reactivity is better, the cost, the energy consumption and the pollution in the actual production are greatly reduced:

(1) the method of the antibacterial composite material based on the hyperbranched polyquaternary ammonium salt is simple and feasible, and the final product not only has efficient and stable antibacterial and antiviral functions, but also has the characteristics of good anti-adhesion property, low toxicity, biocompatibility, formability, processing and the like.

(2) The synthesized hyperbranched polymer polyquaternary ammonium salt is compounded with the matrix polymer, has simple preparation process and can stably exist in the matrix polymer so as to solve the problem of dissolution of metal ions, small molecular bactericides and traditional linear high molecular antibacterial agents in materials.

(3) The hyperbranched polymer has a large number of reactive end groups, has the advantages of simple synthesis, good solubility, high chemical reactivity, good biocompatibility and the like, and different hyperbranched polymers have different types and numbers of end group reactive groups and physicochemical properties, can be variously selected according to requirements such as actual performance, compatibility with a matrix polymer and the like, change the types, molecular weights, end group reactive groups and the like of the hyperbranched polymer, and are favorable for functional modification and performance regulation.

(4) The separated quaternary ammonium group, the hydrophobic long-chain alkyl group, the anion or the zwitterion group are matched, so that the excellent synergistic effect is achieved, and the optimal balance effect among antibacterial property, anti-adhesion property and biocompatibility can be achieved through regulation and control of the grafting proportion and the grafting rate of the three functional groups.

(5) The invention discloses a polyquaternium biomedical composite material, which is based on the compounding of polyquaternium hyperbranched polymer and matrix polymer, has no special requirements on the type and the form of the matrix polymer, can be prepared into various forms such as catheters, films, non-woven fabrics, coatings and the like in various matrix polymers, and can also be prepared into various forms such as catheters, films, non-woven fabrics, coatings and the like by melt extrusion, tape casting, melt blowing, solution coating and the like, thereby having wide application range in the field of biomedicine.

(6) Through the water soaking process after the composite material is formed, the composite material can obtain excellent surface sterilization and anti-adhesion performance under the condition of containing few hyperbranched polymer polyquaternary ammonium salts, the problem that a large amount of bactericides are required to be added in the traditional sterilization material is solved, and the social value and the economic benefit can be considered.

(7) The polyquaternary ammonium salt biomedical composite material disclosed by the invention is simple and feasible in manufacturing process, mild in reaction condition and processing condition, less in energy consumption, low in raw material cost, wide in application range and suitable for industrial mass production and application.

Drawings

FIG. 1 is a schematic view of the surface structure of an antibacterial composite material based on hyperbranched polyquaternium;

FIG. 2 is a schematic diagram of the structure of the hyperbranched polyamide-amine polyquaternium and a diagram of the process for preparing the hyperbranched polyamide-amine polyquaternium polyurethane composite film in example 13;

FIG. 3 is the IR and NMR spectra of the hyperbranched polyamidoamine and the hyperbranched polyamidoamine polyquaternium of example 13;

FIG. 4 is a surface potential diagram of the hyperbranched polyamide-amine polyquaternium polyurethane composite film of example 13 and the polyurethane film of comparative example 10;

FIG. 5 is a graph showing the results of mechanical property tests of the hyperbranched polyamide-amine polyquaternium polyurethane composite film of example 13 and the polyurethane film of comparative example 10;

FIG. 6 is a DSC graph of the hyperbranched polyamide-amine polyquaternium polyurethane composite film of example 13 and the polyurethane film of comparative example 10;

FIG. 7 is a graph showing the bactericidal effect of the hyperbranched polyamide-amine polyquaternium polyurethane composite film of example 13 and the polyurethane film of comparative example 10;

FIG. 8 is a graph showing the long-term antibacterial effect of the hyperbranched polyamide-amine polyquaternium polyurethane composite film in example 13;

FIG. 9 is a graph showing the adsorption of fluorescent proteins and the hemolysis ratio of the hyperbranched polyamide-amine polyquaternium polyurethane composite film of example 13 and the polyurethane film of comparative example 10;

fig. 10 is a graph of the short-term and long-term cell viability of the hyperbranched polyamide-amine polyquaternium polyurethane composite film in example 13.

Detailed Description

The following will describe in detail the polyquaternium composite material of the present invention and its application in medical devices with specific examples. The implementation steps of all the examples are the same as those described in the summary of the invention. It should be noted that the embodiments described are not intended to limit the invention, and all modifications that can be derived or suggested by those skilled in the art from the disclosure of the present invention should be considered within the scope of the present invention.

The following examples and comparative examples show the results of the performance tests of the antibacterial composite material in table 2.

Example 1

The preparation process of the hyperbranched polyurethane polyquaternium antibacterial composite pipe (1) comprises the following steps: 20 parts by mass of hyperbranched polyurethane with the molecular weight of 5200 and the hydroxyl value of 520mg KOH/g is dissolved in 80 parts of tetrahydrofuran to be stirred, nitrogen is introduced into a reaction system for 15min to exhaust air, 8 parts of sodium hydride is added, the temperature is raised to 70 ℃, 9 parts of 2, 3-epoxypropyltrimethylammonium chloride, 12 parts of 1-acyl dodecane and 7 parts of 1, 3-propane sultone are sequentially added at intervals of 3 hours to react. And filtering the reaction system to obtain the polyquaternary ammonium salt hyperbranched polyurethane. Melting and blending the medical polyurethane base material and the polyquaternary ammonium salt hyperbranched polymer at 200 ℃, then extruding to prepare a pipe, and then soaking in water for 15h to obtain the hyperbranched polyurethane polyquaternary ammonium salt antibacterial composite pipe (1). Wherein the hyperbranched polyurethane polyquaternary ammonium salt accounts for 5 percent of the total mass fraction.

The performance evaluation of the prepared hyperbranched polyquaternary ammonium salt antibacterial composite material is mainly characterized by the following characteristic parameters, namely the sterilization rate and the biocompatibility of the material, wherein the biocompatibility is characterized by cytotoxicity and hemolysis rate.

And (3) testing the sterilization rate: coli as a model bacterium, the surface of the test material (2.5X 2.5 cm) ² ) And 50 μ L of 10 ⁷ The killing effect of escherichia coli of Colony Forming Unit (CFU)/mL is 24h after contact culture, bacterial liquid is diluted in a gradient manner, and the bacterial CFU number is calculated after the escherichia coli is coated on an agar plate and cultured for 16 h.

The antibacterial ratio BR is defined as: BR ═ 100% (1-c2/c1), c1 and c2 are bacterial CFU counts of blank and test samples, respectively.

Cytotoxicity test: taking mouse fibroblast L929 as a model cell, and taking the sample to be detected at a distance of 3cm ² Leach ratio/mL test leach solution at 24h for 10h after leaching in MEM medium ⁴ The influence of the growth of each L929 cell is quantitatively calculated by the absorbance at 450nm of the CCK-8 reagent on the cell survival rate. Cell survival CV is defined as: CV is (As-Ab)/(Ac-Ab) × 100%, As, Ab, Ac are absorbance of the sample to be tested, blank, negative control, respectively.

The hemolysis rate: the sample to be tested (1X 1 cm) was determined from porcine anticoagulated whole blood ² ) The time of contact with blood was 1h, and then the absorbance of the supernatant at 545nm was measured after centrifugation at 3500 rpm for 5 min. The hemolysis rate HR is defined as: HR ═ As-Anc)/(Apc-Anc) × 100%, As, Anc, Apc are absorbance at 545nm of the sample to be tested, negative control (saline), positive control (deionized water), respectively.

The results are shown in table 2, which shows that the antibacterial performance of the material is significantly improved to 98.8% by blending and compounding the polyquaternium hyperbranched polyurethane and the polyurethane base material, and the biocompatibility is still good.

Comparative example 1

The medical polyurethane base material is melted and blended at 200 ℃ and then extruded to prepare a pipe, and then the pipe is soaked in water for 15 hours to obtain the polyurethane pipe (comparative example 1).

The characterization method of the prepared polyurethane pipe is the same as that of example 1, and the sterilization rate, the cell survival rate and the hemolysis rate are shown in table 2.

The result shows that compared with the pure polyurethane pipe, the hyperbranched polyurethane polyquaternium polyurethane-based antibacterial composite pipe has the advantages that the antibacterial performance is obviously improved, and the biocompatibility is excellent.

Example 2

The preparation process of the hyperbranched polyamide-amine polyquaternium polyether amide antibacterial composite membrane material (2) comprises the following steps: dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g (obtained by acid-base titration) in 80 parts of methanol, introducing nitrogen into a reaction system for 15min to remove air, adding 7 parts of 3-chloro-2-hydroxypropyl trimethyl ammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 5 parts of sodium hydroxide was added to the reaction system, 2 parts of chlorosulfonic acid dissolved in 10 parts of methanol was added and the mixture was reacted for 3 hours while stirring and heating at 60 ℃.4 parts of 1-iodododecane dissolved in 20 parts of methanol are then added and the reaction is carried out for 3h at 60 ℃ with stirring and heating. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Melting and blending the medical polyether amide substrate and the hyperbranched polyamide-amine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15h to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite film material (2-1). Wherein the hyperbranched polyamide-amine polyquaternary ammonium salt accounts for 3 percent of the total mass fraction.

Dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 4 parts of 2, 3-epoxypropyltrimethylammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 6 parts of sodium hydroxide was added to the reaction system, 5 parts of chlorosulfonic acid dissolved in 10 parts of methanol was added and the mixture was reacted for 3 hours while stirring and heating at 60 ℃.4 parts of 1-iodododecane dissolved in 20 parts of methanol are then added and the reaction is carried out for 3h at 60 ℃ with stirring and heating. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Melting and blending the medical polyether amide substrate and the hyperbranched polyamide-amine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15h to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite film material (2-2). Wherein the hyperbranched polyamide-amine polyquaternary ammonium salt accounts for 3 percent of the total mass fraction.

Dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 3 parts of 3-chloro-2-hydroxypropyl trimethyl ammonium chloride dissolved in 10 parts of alcohol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 8 parts of sodium hydroxide was added to the reaction system, 7 parts of chlorosulfonic acid dissolved in 10 parts of methanol was added and the mixture was reacted for 3 hours while stirring and heating at 60 ℃.4 parts of 1-iodododecane dissolved in 20 parts of methanol are then added and the reaction is carried out for 3h at 60 ℃ with stirring and heating. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Melting and blending the medical polyether amide substrate and the hyperbranched polyamide-amine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15h to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite film material (2-3). Wherein the hyperbranched polyamide-amine polyquaternary ammonium salt accounts for 3 percent of the total mass fraction.

The characterization method of the prepared hyperbranched polyamide-amine polyquaternium polyether amide antibacterial composite membrane material is the same as that of example 1, and the bactericidal rate, the cell survival rate and the hemolysis rate are shown in table 2.

The result shows that along with the gradual reduction of the content of the quaternary ammonium salt in the hyperbranched polyquaternary ammonium salt, the content of the sulfonic acid group is gradually increased, the positive electricity of the surface charge is gradually weakened, the sterilization performance is gradually weakened, but the level of the sterilization performance is still maintained to be more than 95 percent, the biocompatibility is gradually increased, the overall performance is excellent, and the hyperbranched polyquaternary ammonium salt has practical application prospects such as medical implants or wound dressings and the like.

Comparative example 2

The medical polyether amide base material is melted and blended at 200 ℃, then cast into a film, and then soaked in water for 15 hours to obtain the polyether amide film material (comparative example 2).

The characterization method of the prepared polyether amide membrane material is the same as that of example 1, and the bactericidal rate, the cell survival rate and the hemolysis rate are shown in table 2.

The result shows that compared with a pure polyether amide membrane material, the antibacterial performance of the hyperbranched polyurethane polyquaternium polyurethane-based antibacterial composite material is obviously improved, the biocompatibility is excellent, and the key of the material with antibacterial and biocompatibility is shown when hyperbranched polyquaternium is used.

Comparative example 3

Dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 4 parts of 2, 3-epoxypropyltrimethylammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Melting and blending the medical polyether amide substrate and the hyperbranched polyamide-amine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15h to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite film (comparative example 3). Wherein the hyperbranched polyamide-amine polyquaternary ammonium salt accounts for 3 percent of the total mass fraction.

Compared with the example 2-2, the result shows that the hyperbranched polyquaternium antibacterial composite material only containing quaternary ammonium salt groups has slightly poor antibacterial performance and low biocompatibility, and cannot meet the requirements of both antibacterial property and biocompatibility.

Comparative example 4

Dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 4 parts of 2, 3-epoxypropyltrimethylammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 6 parts of sodium hydroxide was added to the reaction system, 4 parts of 1-iodododecane dissolved in 20 parts of methanol was added, and the mixture was reacted for 3 hours with stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Melting and blending the medical polyether amide substrate and the hyperbranched polyamide-amine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15h to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite film (comparative example 4). Wherein the hyperbranched polyamide-amine polyquaternary ammonium salt accounts for 3 percent of the total mass fraction.

Compared with the example 2-2, the result shows that the hyperbranched polyquaternium antibacterial composite material simultaneously containing the quaternary ammonium salt groups and the long-chain alkyl groups introduced into different hyperbranched end groups has excellent antibacterial performance, but the biocompatibility is low, which indicates that the alkyl chains have obvious antibacterial effect, but the biocompatible groups are required to be added for biocompatibility modification.

Comparative example 5

Dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 4 parts of 2, 3-epoxypropyltrimethylammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 6 parts of sodium hydroxide was added to the reaction system, 5 parts of chlorosulfonic acid dissolved in 10 parts of methanol was added and the mixture was reacted for 3 hours while stirring and heating at 60 ℃. Then, 3 parts of 1-iodobutane dissolved in 20 parts of methanol was added thereto, and the mixture was reacted for 3 hours while stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Melting and blending the medical polyether amide substrate and the hyperbranched polyamide-amine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15h to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite film (comparative example 5). Wherein the hyperbranched polyamide-amine polyquaternary ammonium salt accounts for 3 percent of the total mass fraction.

Compared with the comparative example 2-2, the result shows that the hyperbranched polyquaternium antibacterial composite material simultaneously containing the quaternary ammonium salt groups, the long-chain alkyl groups and the anionic groups introduced into different hyperbranched end groups has good antibacterial performance, but the composite material does not have excellent antibacterial performance due to the short alkyl chains, and the important effect of the long-chain alkyl groups on the antibacterial effect is shown.

Comparative example 6

Dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 9 parts of 2, 3-epoxypropyldimethyldodecylammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Melting and blending the medical polyether amide base material and the hyperbranched polyamide-amine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15 hours to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite film material (comparative example 6). Wherein the hyperbranched polyamide-amine polyquaternary ammonium salt accounts for 3 percent of the total mass fraction.

The selection of the raw material 2, 3-epoxypropyl dimethyl dodecyl ammonium chloride in the preparation process ensures that the quaternary ammonium salt group and the long-chain alkyl group in the synthesized hyperbranched polyquaternary ammonium salt exist in the same hyperbranched end group, compared with the comparative example 2-2, the result shows that the hyperbranched polyquaternary ammonium salt antibacterial composite material obtained by connecting the quaternary ammonium salt group and the long-chain alkyl group has better antibacterial effect than the hyperbranched polyquaternary ammonium salt antibacterial composite material obtained by separating and grafting the quaternary ammonium salt group and the long-chain alkyl group, and the separation of the quaternary ammonium salt group and the long-chain alkyl group is an important structure of the hyperbranched polyquaternary ammonium salt, so that the hyperbranched polyquaternary ammonium salt has important significance for the performances of both antibacterial property, biocompatibility and machinability of the material.

Example 3

The preparation process of the hyperbranched polyamide-amine polyquaternium polyether amide antibacterial composite pipe (3) comprises the following steps: dissolving 20 parts of hyperbranched polyamide-amine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 100 parts of N, N-dimethylformamide, introducing nitrogen into a reaction system for 15min to remove air, adding 5 parts of sodium hydroxide into the reaction system, adding 7 parts of dimethylaminoethyl methacrylate trimethyl ammonium chloride, 7 parts of sulfobetaine methacrylate and 4 parts of 1-iodododecane, and reacting for 8h at the temperature of 60 ℃ under the condition of stirring and heating. And filtering the solution to obtain the hyperbranched polyamide-amine polyquaternium precipitate. The medical polyether amide base material and the hyperbranched polyamide-amine polyquaternary ammonium salt are melted and blended at 200 ℃, then extruded to prepare a pipe, and then soaked in water for 15 hours to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite film. Wherein the polyquaternary ammonium salt hyperbranched polymer accounts for 1 percent of the total mass fraction to obtain a hyperbranched polyamide-amine polyquaternary ammonium salt polyether amide antibacterial composite pipe (3-1); the polyquaternium hyperbranched polymer accounts for 5 percent of the total mass fraction to obtain a hyperbranched polyamide-amine polyquaternium polyether amide antibacterial composite pipe (3-2); the polyquaternium hyperbranched polymer accounts for 10 percent of the total mass fraction, and the hyperbranched polyamide-amine polyquaternium polyether amide antibacterial composite pipe (3-3) is obtained.

The hyperbranched polyamide-amine polyquaternium polyether amide antibacterial composite pipe has the same characterization method as the example 1, and the sterilization rate, the cell survival rate and the hemolysis rate are shown in the table 2.

The result shows that the hyperbranched polyamide-amine polyquaternium polyether amide antibacterial composite film has excellent performances, the surface charge electropositivity is gradually enhanced along with the gradual increase of the addition amount of the polyquaternium hyperbranched polymer, the bactericidal performance is gradually increased to be more than 99.9 percent, the biocompatibility is slightly reduced, but the overall effect is excellent, and the hyperbranched polyamide-amine polyquaternium polyether amide antibacterial composite film has practical application prospects of in-vitro wound dressings, in-vivo implanted catheters, wound healing promotion hydrogel and the like.

Example 4

The preparation process of the hyperbranched polyester polyquaternium polyester-based antibacterial composite non-woven fabric (4) comprises the following steps: dissolving 20 parts of hyperbranched aliphatic polyester with the molecular weight of 5200 and the hydroxyl value of 520mg KOH/g in 80 parts of tetrahydrofuran, stirring, introducing nitrogen into a reaction system for 15min to discharge air, adding 8 parts of sodium hydride, heating to 70 ℃, and sequentially adding 15 parts of 2, 3-epoxypropyltriethylammonium chloride, 15 parts of 1-acyl chloride octadecane and 7 parts of 1, 3-propane sultone at intervals of 3 hours to react. And filtering the reaction system to obtain the hyperbranched polyester polyquaternium. The medical polyester base material and the hyperbranched polyester polyquaternium are melted and blended at 250 ℃ and then are subjected to melt-blown spinning to prepare the porous non-woven fabric, wherein the hyperbranched polyester polyquaternium accounts for 5% of the total mass fraction. Then soaking the fabric in water for 10 hours to obtain the hyperbranched polyester polyquaternium polyester based antibacterial composite non-woven fabric (4-1).

Dissolving 20 parts of hyperbranched aliphatic polyester with the molecular weight of 5200 and the hydroxyl value of 520mg KOH/g in 80 parts of tetrahydrofuran, stirring, introducing nitrogen into a reaction system for 15min to exhaust air, adding 8 parts of sodium hydride, heating to 70 ℃, and sequentially adding 15 parts of 2, 3-epoxypropyltriethylammonium chloride, 12 parts of 1-dodecane chloride and 7 parts of 1, 3-propane sultone at intervals of 3 hours to react. And filtering the reaction system to obtain the hyperbranched polyester polyquaternium. The medical polyester base material and the hyperbranched polyester polyquaternium are melted and blended at 250 ℃ and then are subjected to melt-blown spinning to prepare the porous non-woven fabric, wherein the hyperbranched polyester polyquaternium accounts for 5% of the total mass fraction. Then soaking the fabric in water for 10 hours to obtain the hyperbranched polyester polyquaternium polyester based antibacterial composite non-woven fabric (4-2).

Dissolving 20 parts of hyperbranched aliphatic polyester with the molecular weight of 5200 and the hydroxyl value of 520mg KOH/g in 80 parts of tetrahydrofuran, stirring, introducing nitrogen into a reaction system for 15min to discharge air, adding 8 parts of sodium hydride, heating to 70 ℃, and sequentially adding 15 parts of 2, 3-epoxypropyltriethylammonium chloride, 9 parts of 1-acyl chloride hexane and 7 parts of 1, 3-propane sultone at intervals of 3 hours to react. And filtering the reaction system to obtain the hyperbranched polyester polyquaternium. The medical polyester base material and the hyperbranched polyester polyquaternium are melted and blended at 250 ℃ and then are subjected to melt-blown spinning to prepare the porous non-woven fabric, wherein the hyperbranched polyester polyquaternium accounts for 5% of the total mass fraction. Then soaking the fabric in water for 10 hours to obtain the hyperbranched polyester polyquaternium polyester based antibacterial composite non-woven fabric (4-3).

The characterization method of the hyperbranched polyester polyquaternium polyester based antibacterial composite non-woven fabric is the same as that of example 1, and the sterilization rate, the cell survival rate and the hemolysis rate are shown in table 2.

The result shows that compared with pure polyester non-woven fabric, the hyperbranched polyester polyquaternium polyester-based antibacterial composite non-woven fabric has obviously improved antibacterial performance, and the long-chain alkyl containing 12 carbons has the best bactericidal effect in the long-chain alkyl with different lengths. The hyperbranched polyester polyquaternium polyester-based antibacterial composite non-woven fabric has excellent biocompatibility, and has practical application prospect in direct contact with medical instruments by human bodies.

Comparative example 7

The polyester nonwoven fabric (comparative example 7) was prepared by melt-blowing and spinning a medical polyester substrate after melt-blending at 250 ℃.

The polyester nonwoven fabric was characterized in the same manner as in example 1, and the bactericidal rate, cell survival rate and hemolytic rate were as shown in Table 2.

Example 5

The preparation process of the hyperbranched polyester polyquaternium polyester-based antibacterial composite coating material (5) comprises the following steps: dissolving 20 parts of hyperbranched aliphatic polyester with the molecular weight of 5200 and the hydroxyl value of 520mg KOH/g in 80 parts of tetrahydrofuran, stirring, introducing nitrogen into a reaction system for 15min to discharge air, adding 8 parts of sodium hydride, heating to 70 ℃, and sequentially adding 9 parts of 2, 3-epoxypropyltrimethylammonium chloride, 10 parts of 1-acyl chloride hexane and 5 parts of 1, 3-propane sultone at intervals of 3 hours to react. And filtering the reaction system to obtain the hyperbranched polyester polyquaternium. The hyperbranched polyester polyquaternary ammonium salt is uniformly dissolved in an ethanol solution, then coated on the surface of a polyester material and dried at 60 ℃. And soaking the dried material in water for 15h to obtain the hyperbranched polyester polyquaternium polyester-based antibacterial composite coating material (5).

The characterization method of the hyperbranched polyester polyquaternium polyester-based antibacterial composite coating material is the same as that of example 1, and the sterilization rate, the cell survival rate and the hemolysis rate are shown in table 2.

The result shows that the hyperbranched polyester polyquaternium polyester-based antibacterial composite coating material has relatively excellent antibacterial performance and biocompatibility and has application prospect as a medical appliance product.

Example 6

The preparation process of the hyperbranched polyester polyquaternium polyester-based antibacterial composite coating material (6) comprises the following steps: dissolving 20 parts of hyperbranched aliphatic polyester with the molecular weight of 5200 and the hydroxyl value of 520mg KOH/g in 80 parts of tetrahydrofuran, stirring, introducing nitrogen into a reaction system for 15min to discharge air, adding 8 parts of sodium hydride, heating to 70 ℃, and sequentially adding 15 parts of 2, 3-epoxypropyltrimethylammonium chloride, 10 parts of 1-chlorohexane and 7 parts of 1, 3-propanesultone at intervals of 3 hours to react. And filtering the reaction system to obtain the hyperbranched polyester polyquaternium. The hyperbranched polyester polyquaternary ammonium salt is uniformly dissolved in an ethanol solution, then coated on the surface of a polyester material and dried at 60 ℃. And soaking the dried material in water for 15h to obtain the hyperbranched polyester polyquaternium polyester-based antibacterial composite coating material (6).

The result shows that the hyperbranched polyester polyquaternium polyester-based antibacterial composite coating material has relatively excellent antibacterial performance, but relatively weaker biocompatibility, and has application prospect as an in-vitro medical antibacterial material.

Example 7

The preparation process of the hyperbranched polyester polyquaternium polypropylene-based antibacterial composite non-woven fabric (7) comprises the following steps: dissolving 20 parts of hyperbranched aliphatic polyester with the molecular weight of 5200 and the hydroxyl value of 520mg KOH/g in 80 parts of tetrahydrofuran, stirring, introducing nitrogen into a reaction system for 15min to discharge air, adding 8 parts of sodium hydride, heating to 70 ℃, and sequentially adding 15 parts of 2, 3-epoxypropyltriethylammonium chloride, 16 parts of 1-acyl chloride octadecane and 5 parts of 1, 3-propane sultone at intervals of 3 hours to react. And filtering the reaction system to obtain the hyperbranched polyester polyquaternium. The medical polypropylene and the hyperbranched polyester polyquaternium are melt-blended at 200 ℃ and then melt-blown and spun to prepare the porous non-woven fabric, wherein the hyperbranched polyester polyquaternium accounts for 5 percent of the total mass. And then soaking in water for 20h to obtain the hyperbranched polyester polyquaternium polypropylene-based antibacterial composite non-woven fabric (7).

The hyperbranched polyester polyquaternium based polypropylene based antibacterial composite non-woven fabric is characterized by the same method as the example 1, and the sterilization rate, the cell survival rate and the hemolysis rate are shown in the table 2.

The result shows that the hyperbranched polyester polyquaternium polyester-based antibacterial composite film material has obviously improved antibacterial performance after being added with the polyquaternium hyperbranched polyester, but has relatively weak biocompatibility, and has application prospect as in-vitro antibacterial materials (such as mask materials and the like).

Comparative example 8

The medical polypropylene was melt-blended at 200 ℃ and then melt-blown spun to prepare a polypropylene nonwoven fabric (comparative example 8).

The polypropylene-based nonwoven fabric was characterized in the same manner as in example 1, and the bactericidal rate, cell survival rate and hemolytic rate were as shown in Table 2.

Example 8

The preparation process of the hyperbranched polyester polyquaternium polyvinyl chloride based antibacterial composite coating material (8) comprises the following steps: dissolving 20 parts of hyperbranched aliphatic polyester with the molecular weight of 5000 and the hydroxyl value of 520mg KOH/g in 80 parts of tetrahydrofuran, stirring, introducing nitrogen into a reaction system for 15min to discharge air, adding 8 parts of sodium hydride, heating to 70 ℃, and sequentially adding 12 parts of 2, 3-epoxypropyltrimethylammonium chloride, 18 parts of 1-acyl dodecane and 6 parts of 1, 3-propane sultone at intervals of 3 hours to react. And filtering the reaction system to obtain the hyperbranched polyester polyquaternium. The hyperbranched polyester polyquaternary ammonium salt is uniformly dissolved in an ethanol solution, then coated on the surface of a polyvinyl chloride material and dried at 60 ℃. And soaking the dried material in water for 15h to obtain the hyperbranched polyester polyquaternium polyvinyl chloride based antibacterial composite coating material (8).

The hyperbranched polyester polyquaternium polyvinyl chloride based antibacterial composite coating material has the same characterization method as the example 1, and the sterilization rate, the cell survival rate and the hemolysis rate are shown in the table 2.

The result shows that the antibacterial performance of the surface of the material is obviously improved to more than 99.9 percent by coating the hyperbranched polyester polyquaternium hyperbranched polyurethane on the polyvinyl chloride material, but the biocompatibility of the material is relatively weaker, and the material is suitable for the application of medical appliances which are not in direct contact with human tissues.

Comparative example 9

Pure polyvinyl chloride material was used as comparative example 9, which was characterized in the same manner as in example 1, and the sterilization rate, cell survival rate and hemolysis rate were shown in Table 2.

Example 9

The preparation process of the hyperbranched polyethyleneimine polyquaternium polyether amide antibacterial composite pipe (9) comprises the following steps: 20 parts of hyperbranched polyethyleneimine with the molecular weight of 20000 and the ammonia value of 0.009mol/g (obtained by acid-base titration) are dissolved in 80 parts of methanol, nitrogen is introduced into the reaction system for 15min to remove air, 9 parts of 2-chloroethyltrimethyl ammonium chloride dissolved in 10 parts of methanol is added, and the mixture is stirred and heated at 60 ℃ for reaction for 3 h. After 12 parts of sodium hydroxide was added to the reaction system, 7 parts of 1, 3-propanesultone dissolved in 10 parts of methanol was added and reacted for 3 hours with stirring. Then, 10 parts of 1-chlorododecane dissolved in 20 parts of methanol was added thereto, and the mixture was reacted for 3 hours while stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyethyleneimine polyquaternary ammonium salt. Melting and blending the medical polyether amide base material and the hyperbranched polyethylene imine polyquaternium at 200 ℃, extruding to prepare a pipe, and soaking in water for 15 hours to obtain the hyperbranched polyethylene imine polyquaternium polyether amide antibacterial composite pipe (9), wherein the hyperbranched polyethylene imine polyquaternium accounts for 5 percent of the total mass.

The hyperbranched polyethyleneimine polyquaternium polyether amide based antibacterial composite pipe has the same characterization method as example 1, and the bactericidal rate, cell survival rate and hemolytic rate are shown in table 2.

The result shows that the hyperbranched polyethyleneimine polyquaternium polyether amide antibacterial composite pipe has relatively excellent antibacterial performance and biocompatibility, and has an application prospect as a medical appliance product.

Example 10

The preparation process of the hyperbranched polyethyleneimine polyquaternium polyether amide antibacterial composite pipe (10) comprises the following steps: 20 parts of hyperbranched polyethyleneimine with the molecular weight of 20000 and the ammonia value of 0.009mol/g is dissolved in 80 parts of methanol, nitrogen is introduced into the reaction system for 15min to remove air, 9 parts of 2-chloroethyltrimethylammonium chloride dissolved in 10 parts of methanol is added, and the mixture is stirred and heated at the temperature of 60 ℃ for reaction for 3 h. After 12 parts of sodium hydroxide was added to the reaction system, 24 parts of carboxybetaine methacrylate dissolved in 10 parts of methanol was added and reacted for 3 hours with stirring. Then, 10 parts of 1-chlorododecane dissolved in 20 parts of methanol was added thereto, and the mixture was reacted for 3 hours while stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyethyleneimine polyquaternary ammonium salt. The medical polyether amide base material and the hyperbranched polyethyleneimine polyquaternary ammonium salt are melted and blended at 200 ℃ and then extruded to prepare a pipe, and then the pipe is soaked in water for 15 hours to obtain the hyperbranched polyethyleneimine polyquaternary ammonium salt polyether amide antibacterial composite pipe (10), wherein the hyperbranched polyethyleneimine polyquaternary ammonium salt accounts for 5% of the total mass fraction.

The result shows that the hyperbranched polyethyleneimine polyquaternium polyether amide antibacterial composite pipe has relatively excellent antibacterial performance and biocompatibility, and has application prospect as a medical appliance product.

Example 11

The preparation process of the hyperbranched polyethyleneimine polyquaternary ammonium salt polyvinyl chloride based antibacterial composite membrane material (11) comprises the following steps: 10 parts of hyperbranched polyethyleneimine with the molecular weight of 20000 and the ammonia value of 0.008mol/g is dissolved in 80 parts of methanol, nitrogen is introduced into the reaction system for 15min to remove air, then 15 parts of dimethylaminoethyl methacrylate trimethyl ammonium chloride dissolved in 10 parts of methanol is added, and the mixture is stirred and heated at the temperature of 60 ℃ for reaction for 3 h. After 12 parts of sodium hydroxide was added to the reaction system, 7 parts of 1, 3-propanesultone dissolved in 10 parts of methanol was added and reacted for 3 hours with stirring. Then 12 parts of 1-bromododecane dissolved in 20 parts of methanol were added and the reaction was carried out for 3 hours while stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyethyleneimine polyquaternary ammonium salt. Melting and blending medical polyvinyl chloride and hyperbranched polyethyleneimine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15h to obtain the hyperbranched polyethyleneimine polyquaternium polyvinyl chloride-based antibacterial composite film (11), wherein the hyperbranched polyethyleneimine polyquaternium accounts for 8% of the total mass fraction.

The hyperbranched polyethyleneimine polyquaternium polyvinyl chloride based antibacterial composite membrane material has the same characterization method as example 1, and the bactericidal rate, cell survival rate and hemolytic rate are shown in table 2.

The result shows that the hyperbranched polyethyleneimine polyquaternary ammonium salt polyvinyl chloride based antibacterial composite membrane has excellent antibacterial performance, but relatively weaker biocompatibility, and has application prospect as an in-vitro medical antibacterial material.

Example 12

The preparation process of the hyperbranched polyamide-amine polyquaternium polyvinyl chloride based antibacterial composite membrane material (12) comprises the following steps: dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 8 parts of dimethylaminoethyl methacrylate trimethyl ammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 5 parts of sodium hydroxide was added to the reaction system, 5 parts of 1, 3-propanesultone dissolved in 10 parts of methanol was added and reacted for 3 hours with stirring. Then 6 parts of 1-bromododecane dissolved in 20 parts of methanol were added and the reaction was carried out for 3 hours with stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Melting and blending medical polyvinyl chloride and hyperbranched polyamide-amine polyquaternary ammonium salt at 200 ℃, casting to prepare a film, and soaking in water for 15h to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyvinyl chloride-based antibacterial composite film material (12), wherein the hyperbranched polyamide-amine polyquaternary ammonium salt accounts for 8% of the total mass fraction.

The hyperbranched polyamide-amine polyquaternium polyvinyl chloride based antibacterial composite membrane material has the same characterization method as the example 1, and the bactericidal rate, the cell survival rate and the hemolysis rate are shown in the table 2.

The result shows that the hyperbranched polyamide-amine polyquaternium polyvinyl chloride antibacterial composite film has excellent antibacterial performance, but relatively weaker biocompatibility, and has application prospect as an in-vitro medical antibacterial material.

Example 13

The preparation process of the hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite membrane material (13) is shown in figure 2: dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 7 parts of 2, 3-epoxypropyltrimethylammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 5 parts of sodium hydroxide was added to the reaction system, 2 parts of 1, 3-propanesultone dissolved in 10 parts of methanol was added, and the reaction was carried out for 3 hours while stirring and heating at 60 ℃.4 parts of 1-iodododecane dissolved in 20 parts of methanol are then added and the reaction is carried out for 3h at 60 ℃ with stirring and heating. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Uniformly blending the medical polyurethane substrate and the hyperbranched polyamide-amine polyquaternium in N, N-dimethylformamide at 60 ℃, then casting and scraping the mixture into a film, and then soaking the film in water for 10 hours to obtain the hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite film material. Wherein the hyperbranched polyquaternary ammonium salt accounts for 0.5 percent of the total mass fraction to obtain a hyperbranched polyamide-amine polyquaternary ammonium salt polyurethane-based antibacterial composite film material (13-1); the hyperbranched polyquaternary ammonium salt accounts for 1 percent of the total mass fraction to obtain a hyperbranched polyamide-amine polyquaternary ammonium salt polyurethane-based antibacterial composite film material (13-2); the hyperbranched polyquaternary ammonium salt accounts for 1 percent of the total mass fraction, and the hyperbranched polyamide-amine polyquaternary ammonium salt polyurethane-based antibacterial composite film material (13-3) is obtained.

The characterization methods of the sterilization rate, the cytotoxicity and the hemolysis rate of the hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite membrane material are the same as those in example 1, wherein the sterilization rate takes escherichia coli and staphylococcus aureus as model bacteria.

In addition, the structural composition of the hyperbranched polyamide-amine polyquaternary ammonium salt is determined by infrared spectroscopy (FTIR) and nuclear magnetic hydrogen spectrum (FTIR) ¹ H-NMR). Hyperbranched polyamidoamine polyquaterniumsThe surface element composition of the salt polyurethane-based antibacterial composite film material is obtained by scanning and peak-splitting calculation through X-ray photoelectron spectroscopy (XPS), the surface potential and isoelectric point (IEP) are measured through an electric analyzer, the mechanical property is characterized by measuring the tensile modulus and the elongation at break through a universal tester, and the thermal property is obtained by measuring the glass transition temperature and the melting temperature through a Differential Scanning Calorimeter (DSC). The anti-protein adsorption performance of the hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite membrane material is obtained by measuring the adsorption amount of fluorescent labeled bovine serum albumin (FITC-BSA) within 12 hours, measuring the fluorescence intensity by a Confocal Laser Scanning Microscope (CLSM), and comparing the fluorescence intensity with the adsorption result of pure polyurethane membrane protein for semi-quantitative calculation; the long-term sterilization rate is characterized by testing the sterilization rate of the sample on Escherichia coli by the same method as in example 1 after oscillating the sample in deionized water at 37 ℃ for 24, 72 and 120 h; long-term cell viability was characterized by testing the cell viability of the test sample extract and L929 cells in the same manner as in example 1 after 24, 48, 72 and 120h of co-culture.

Comparative example 10

Dissolving the medical polyurethane base material in N, N-dimethylformamide at 60 ℃, then carrying out tape casting and scraping to form a film, and then quickly putting the film into water for soaking for 10 hours to obtain the hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite film material.

The properties were characterized as in example 13.

FTIR and comparative example 10 according to the characterization results of example 13 ¹ The H-NMR spectrum (figure 3) proves the successful synthesis of the hyperbranched polyamide-amine polyquaternary ammonium salt; XPS test results (Table 1) show the content of nitrogen positive ions in quaternary ammonium salt groups on the surface of the material and the surface enrichment phenomenon of the hyperbranched polyamide-amine polyquaternary ammonium salt in the polyurethane film; according to the experimental result of the surface potential (fig. 4), the increase of the isoelectric point indicates the existence of the hyperbranched polyamide-amine polyquaternary ammonium salt on the surface of the polyurethane composite membrane material; the results of mechanical property tests (figure 5) show that the introduction of the hyperbranched polyamide-amine polyquaternium leads the mechanical property of the polyurethane film not to be damaged, but leads the tensile film amount due to chain entanglement and hydrogen bond interactionEven slightly increases the elongation at break, and has excellent effect; the DSC curve (fig. 6) also demonstrates that the introduction of the hyperbranched polyamidoamine polyquaternium has no negative influence on the thermal properties of the polyurethane film. In example 13, the antibacterial composite film with hyperbranched polyamide-amine polyquaternium and polyurethane base has excellent effect of killing escherichia coli and staphylococcus aureus (fig. 7), and the antibacterial effect is better along with the increase of the content of the hyperbranched polyamide-amine polyquaternium in the composite material, while the long-term antibacterial effect (fig. 8) is respectively 91.2% (example 13-1), 94.0 (example 13-2) and 96.8 (example 13-3), and still maintains higher level(s) (fig. 8)>90 percent), the antibacterial performance is proved to be efficient and stable; the result of fluorescent protein adsorption (fig. 9) also proves that the introduction of the hyperbranched polyamide-amine polyquaternary ammonium salt endows the polyurethane film with the capability of resisting protein adsorption, and the biocompatibility of the polyurethane film is improved laterally; the hemolysis rate of the hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite membrane (figure 9) is kept at a very low level<0.2 percent) proves that the introduction of the hyperbranched polyamide-amine polyquaternary ammonium salt is beneficial to the improvement of the blood compatibility of the polyurethane film; the results of short-term and long-term cytotoxicity experiments (fig. 10) prove that the hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite membrane has very high cell survival rates, and the cell survival rates after 120h culture are 85.3% (comparative example 10), 91.9% (example 13-1), 98.3% (example 13-2) and 96.3% (example 13-3), respectively, and the tissue compatibility is excellent. In conclusion, the hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite film introduced with the hyperbranched polyamide-amine polyquaternium has long-acting antibacterial property and biocompatibility.

TABLE 1 analysis of surface elements of hyperbranched polyamidoamine polyquaternium polyurethane-based composite film in example 13

Comparative example 11

Dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 7 parts of 2, 3-epoxypropyltrimethylammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 5 parts of sodium hydroxide was added to the reaction system, 2 parts of chloroacetic acid dissolved in 10 parts of methanol was added and the reaction was carried out for 3 hours while stirring and heating at 60 ℃.4 parts of 1-iodododecane dissolved in 20 parts of methanol are then added and the reaction is carried out for 3h at 60 ℃ with stirring and heating. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Uniformly blending the medical polyurethane substrate and the hyperbranched polyamide-amine polyquaternary ammonium salt in N, N-dimethylformamide at 60 ℃, then casting and scraping the mixture into a film, and then soaking the film in water for 10 hours to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyurethane-based antibacterial composite film material. Wherein the hyperbranched polyquaternary ammonium salt accounts for 0.1 percent of the total mass fraction, and the hyperbranched polyamide-amine polyquaternary ammonium salt polyurethane-based antibacterial composite membrane material (comparative example 11) is obtained.

The hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite membrane material has the same characterization method as that of the example 1, and the bactericidal rate, the cell survival rate and the hemolysis rate are shown in table 2. The results show that when the mass content of the hyperbranched polyquaternary ammonium salt in the composite material is too low (< 0.5%), the hyperbranched polyquaternary ammonium salt does not have good antibacterial performance.

Comparative example 12

Dissolving 20 parts of hyperbranched polyamidoamine with the molecular weight of 30000 and the ammonia value of 0.01mol/g in 80 parts of methanol, introducing nitrogen into the reaction system for 15min to remove air, adding 7 parts of 2, 3-epoxypropyltrimethylammonium chloride dissolved in 10 parts of methanol, and reacting for 3h under the condition of stirring and heating at 60 ℃. After 5 parts of sodium hydroxide was added to the reaction system, 2 parts of chloroacetic acid dissolved in 10 parts of methanol was added and the reaction was carried out for 3 hours while stirring and heating at 60 ℃.4 parts of 1-iodododecane dissolved in 20 parts of methanol are then added and the reaction is carried out for 3h with stirring and heating at 60 ℃. And concentrating and cooling the solution to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt. Uniformly blending the medical polyurethane substrate and the hyperbranched polyamide-amine polyquaternary ammonium salt in N, N-dimethylformamide at 60 ℃, then casting and scraping the mixture into a film, and then soaking the film in water for 10 hours to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt polyurethane-based antibacterial composite film material. Wherein the hyperbranched polyquaternary ammonium salt accounts for 12 percent of the total mass fraction, and the hyperbranched polyamide-amine polyquaternary ammonium salt polyurethane-based antibacterial composite membrane material (comparative example 12) is obtained.

The hyperbranched polyamide-amine polyquaternium polyurethane-based antibacterial composite membrane material has the same characterization method as that of the example 1, and the bactericidal rate, the cell survival rate and the hemolysis rate are shown in table 2. The results show that when the mass content of the hyperbranched polyquaternary ammonium salt in the composite material is too high (> 10%), the hyperbranched polyquaternary ammonium salt does not have good biocompatibility.

In summary, the hyperbranched polyquaternium is prepared by simultaneously introducing quaternary ammonium salt, long-chain alkyl, anion or zwitterion functional groups (each functional group is on different hyperbranched polymer end groups) into the hyperbranched polymer, and is compounded with various matrix polymers, so that the hyperbranched polyquaternium has the unexpected effects of good antibacterial and even bactericidal properties, biocompatibility and formability and processability under the specific range of the ratio of the quaternary ammonium salt, the long-chain alkyl, the anion or zwitterion functional groups to the ratio of the hyperbranched polyquaternium to the matrix polymers. Wherein the infrared spectrum (FTIR) and nuclear magnetic hydrogen spectrum (b) are obtained ¹ H-NMR) combined with the chemical reaction principle, the quaternary ammonium salt, the long-chain alkyl, the anion or the zwitterion functional group can be judged to be respectively introduced into different end groups of the hyperbranched polymer, but not into the same end group.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that various changes and modifications can be made by those skilled in the art without departing from the spirit of the invention, and these changes and modifications are all within the scope of the invention. Therefore, the protection scope of the present invention should be subject to the appended claims.

TABLE 2 compositions and performance data of hyperbranched polyquaternary ammonium salt antibacterial composite materials in examples 1 to 13

Claims

1. The antibacterial composite material based on the hyperbranched polyquaternary ammonium salt is characterized by comprising the hyperbranched polyquaternary ammonium salt and a matrix polymer, wherein the mass content of the matrix polymer is 90-99.5%, and the mass content of the hyperbranched polyquaternary ammonium salt is 0.5-10%, wherein the hyperbranched polyquaternary ammonium salt has the following structural formula:

in the formula, R ₁ The hyperbranched polymer is preferably selected from any one of hyperbranched polyamide-amine (HPAMAM, namely hyperbranched polyamide with amino end groups), hyperbranched polyethyleneimine, hyperbranched polyester and hyperbranched polyurethane; preferably, the structure of the hyperbranched polymer is selected from any one of the following structures:

R ₄ comprises an anionic group or a zwitterionic group; preferably, the anionic group is at least one selected from the group consisting of a sulfonic acid group, a carboxylic acid group and a phosphoric acid groupSeed growing; preferably, the zwitterion group is selected from at least one of anion and cation coexisting structures in sulfobetaine, carboxyl betaine and phosphorylcholine structures, wherein the sulfobetaine structure is

The carboxyl betaine has the structure of

The phosphorylcholine has a structure of

preferably, the antibacterial composite material based on the hyperbranched polyquaternary ammonium salt has bactericidal property and biocompatibility, the bactericidal rate of escherichia coli reaches more than 99%, the cell survival rate reaches more than 85%, and the hemolysis rate is less than 2%. Wherein, the sterilization rate in the invention refers to the Escherichia coli killing rate.

2. The antibacterial composite material based on the hyperbranched polyquaternary ammonium salt according to claim 1, wherein when the hyperbranched polyquaternary ammonium salt in the antibacterial composite material is hyperbranched polyamide-amine polyquaternary ammonium salt, the matrix polymer is polyurethane, the mass content of the hyperbranched polyquaternary ammonium salt is 0.5% -3%, and the mass content of the matrix polymer is 97% -99.5%, the molar ratio of the elements of nitrogen positive ions in the quaternary ammonium salt groups on the surface of the antibacterial composite material is 0.50% -0.70%; preferably, the sterilization rate of escherichia coli of the antibacterial composite material is more than 99.9%, and the long-term sterilization rate is more than 90%; preferably, the antibacterial composite material has a cell survival rate of > 90%, a long-term cell survival rate of > 95% and a hemolysis rate of < 0.5%.

3. The antibacterial composite material based on hyperbranched polyquaternary ammonium salt according to claim 1, wherein the antibacterial composite material comprises any one of the following components:

4. The antibacterial composite material based on hyperbranched polyquaternium according to claim 1 or 2, wherein the hyperbranched polyquaternium is hyperbranched polyamide-amine type polyquaternium;

preferably, the preparation method comprises the following steps: dissolving hyperbranched polyamide-amine in a solvent, and adding the solution containing R ₂ Compounds of the group, containing R ₃ Compounds containing radicals, or obtained by chemical reaction ₄ Reacting a compound of the group with hyperbranched polyamide-amine, and removing the solvent to obtain the hyperbranched polyamide-amine polyquaternary ammonium salt;

more preferably, said compound contains or is obtained by chemical reaction ₂ ，R ₃ ，R ₄ All components of the compound of the group account for hyperbranched polyamide-amine and contain or obtain R after chemical reaction ₂ ，R ₃ ，R ₄ 40-80% of the total mass of all components of the compound of the group; further preferably, R is obtained after said containing or by chemical reaction ₂ ，R ₃ ，R ₄ In the three compound components of the group, the molar content of quaternary ammonium salt groups is 40-60%, the molar content of long-chain alkyl groups is 20-40%, and the molar content of anionic or zwitterionic groups is 20-40%;

preferably, the solvent is selected from any one of methanol, ethanol, N-dimethylformamide and N, N-dimethylacetamide.

5. The antibacterial composite material based on hyperbranched polyquaternium according to claim 1 or 2, wherein the hyperbranched polyquaternium is hyperbranched polyethyleneimine-based polyquaternium;

preferably, the preparation method comprises the following steps: dissolving hyperbranched polyethyleneimine in a solvent, and respectively adding the hyperbranched polyethyleneimine containing R ₂ Compounds of the group, containing R ₃ Compounds containing radicals, or obtained by chemical reaction ₄ Reacting the compound of the group with hyperbranched polyethyleneimine, and removing the solvent to obtain hyperbranched polyethyleneAn alkyleneimine polyquaternium;

more preferably, said compound contains or is obtained by chemical reaction ₂ ，R ₃ ，R ₄ All components of the compound of the group account for hyperbranched polyethyleneimine and R is obtained by containing or through chemical reaction ₂ ，R ₃ ，R ₄ 40-80% of the total mass of all components of the compound of the group; further preferably, R is obtained after said containing or by chemical reaction ₂ ，R ₃ ，R ₄ In the three compound components of the group, the molar content of quaternary ammonium salt groups is 40-60%, the molar content of long-chain alkyl groups is 20-40%, and the molar content of anionic or zwitterionic groups is 20-40%;

preferably, the solvent is selected from any one of methanol and ethanol.

6. The antibacterial composite material based on hyperbranched polyquaternium according to claim 1 or 2, wherein the hyperbranched polyquaternium is hyperbranched polyester polyquaternium or hyperbranched polyurethane polyquaternium;

it is preferable thatThe preparation method comprises the following steps: dissolving hyperbranched polyester or hyperbranched polyurethane in a solvent, and respectively adding a solvent containing R ₂ Compounds of the group, containing R ₃ Compounds containing radicals, or obtained by chemical reaction ₄ Reacting the compound of the group with hyperbranched polyester or hyperbranched polyurethane, and removing the solvent to obtain hyperbranched polyester polyquaternium or hyperbranched polyurethane polyquaternium; more preferably, the compound containing quaternary ammonium salt groups is selected from any one or more of 2, 3-epoxypropyltrimethylammonium chloride and 2, 3-epoxypropyltriethylammonium chloride;

more preferably, said compound contains or is obtained by chemical reaction ₂ ，R ₃ ，R ₄ All components of the compound of the group account for hyperbranched polyester or hyperbranched polyurethane and contain or obtain R through chemical reaction ₂ ，R ₃ ，R ₄ 40-80% of the total mass of all components of the compound of the group; further preferably, R is obtained after said containing or by chemical reaction ₂ ，R ₃ ，R ₄ In the three compound components of the group, the molar content of the quaternary ammonium salt group is 40-60%, the molar content of the long-chain alkyl group is 20-40%, and the molar content of the anionic group is 20-40%;

preferably, the solvent is selected from any one of tetrahydrofuran, N-dimethylformamide and N, N-dimethylacetamide.

7. The method for preparing the antibacterial composite material based on the hyperbranched polyquaternium of any one of claims 1 to 6, wherein the antibacterial composite material is prepared by blending the hyperbranched polyquaternium and a matrix polymer.

8. An antibacterial composite based on hyperbranched polyquaternary ammonium salt, characterized in that the antibacterial composite comprises the antibacterial composite material of any one of claims 1 to 6, and at least one additive; preferably, the additive is selected from any one or more of synthetic macromolecular compounds, modified macromolecular polysaccharides, pigments, reinforcing agents, plasticizers, antioxidants, mildewproofing agents, antibiotics, anti-inflammatory agents, analgesics and antihistamines; preferably, the synthetic polymer compound is selected from one or more of a polymer compound obtained by addition polymerization, a polymer compound obtained by polycondensation, a polyamide-based polymer compound, and a synthetic rubber-based polymer compound; preferably, the antibiotic is selected from any one or more of quinolone antibiotics, beta-lactam antibiotics, macrolides and aminoglycoside antibiotics; preferably, the modified high molecular polysaccharide is selected from one or more of carboxyl modified high molecular polysaccharide, amino modified high molecular polysaccharide and sulfhydryl modified high molecular polysaccharide; preferably, the high molecular polysaccharide is selected from any one or more of cellulose, lignin, starch, chitosan and agarose.

9. An antibacterial polymer material for medical equipment, wherein the antibacterial polymer material is prepared from the antibacterial composite material of any one of claims 1 to 6 or the antibacterial composite of claim 8; preferably, the preparation method of the antibacterial polymer material comprises the following steps: the antibacterial composite material or the antibacterial composite is processed and molded by a melting, high-speed mixing or solution route.

10. A medical appliance, which is characterized in that the medical appliance is prepared by processing the antibacterial polymer material according to claim 9;