CN110343284B - Preparation method of antibacterial and anticoagulant coating on surface of polyurethane interventional catheter - Google Patents
Preparation method of antibacterial and anticoagulant coating on surface of polyurethane interventional catheter Download PDFInfo
- Publication number
- CN110343284B CN110343284B CN201910627602.2A CN201910627602A CN110343284B CN 110343284 B CN110343284 B CN 110343284B CN 201910627602 A CN201910627602 A CN 201910627602A CN 110343284 B CN110343284 B CN 110343284B
- Authority
- CN
- China
- Prior art keywords
- polyurethane
- pamam
- peg
- reaction
- catheter
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/04—Macromolecular materials
- A61L29/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/10—Inorganic materials
- A61L29/106—Inorganic materials other than carbon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F228/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a bond to sulfur or by a heterocyclic ring containing sulfur
- C08F228/02—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a bond to sulfur or by a heterocyclic ring containing sulfur by a bond to sulfur
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
- C08J7/14—Chemical modification with acids, their salts or anhydrides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
- C08J7/16—Chemical modification with polymerisable compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
- A61L2300/104—Silver, e.g. silver sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/04—Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2375/00—Characterised by the use of polyureas or polyurethanes; Derivatives of such polymers
- C08J2375/04—Polyurethanes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention relates to the field of medical instruments, in particular to a preparation method of an antibacterial and anticoagulant coating on the surface of a polyurethane interventional catheter. According to the invention, the cross-linking reaction of the propylene sulfonic acid and the vinyl acetate on the surface of the polyurethane pipe is utilized, so that the adhesion of the coating on the surface of the pipe is enhanced, and a sulfonic acid group with an anticoagulation effect is introduced. After hydroxyl is introduced in the saponification reaction, the saponification reaction is further reacted with PEG-PAMAM, and a PEG fragment with strong hydrophilicity and anticoagulation effect is introduced. Due to the introduction of PAMAM, the PAMAM can be coordinated with Ag with antibacterial effect+Complexing can realize better antibacterial effect. The raw materials used by the invention have low cost, the coating has the dual effects of antibiosis and anticoagulation, and the coating forms a network structure through a crosslinking reaction and is fixed on the surface of the pipe, so that the durability of the coating is ensured.
Description
Technical Field
The invention relates to the field of medical instruments, in particular to a preparation method of an antibacterial and anticoagulant coating on the surface of a polyurethane interventional catheter.
Background
An intravascular interventional catheter is one of the main instruments for intravascular interventional techniques. Intravascular interventional catheters can be classified into contrast interventional catheters, drug administration interventional catheters, angioplasty interventional catheters, and the like according to the use. In recent years, the successful clinical application of the intravascular interventional diagnosis and treatment technology greatly relieves the pain of patients, relieves the working difficulty of medical workers, and the interventional diagnosis and treatment catheter is increasingly widely applied. The manufacturing technology of the catheter is relatively mature, and the performance is gradually improved. As a medical apparatus in contact with blood, an intravascular interventional catheter must have good biocompatibility and blood compatibility, certain mechanical properties, surface smoothness and the like.
Polyurethanes (PU) are a class of block copolymers containing-NHCOO-repeat structural units in the backbone. The main chain of the polyurethane is composed of rigid chain segments (hard segments) and flexible chain segments (soft segments) alternately, and the formed microphase separation structure enables the polyurethane to have better biocompatibility (including blood compatibility and tissue compatibility) than other high polymer materials, and simultaneously has excellent fatigue resistance, wear resistance, high elasticity and high strength, so the polyurethane is widely used as an interventional catheter material. The polyurethane interventional catheter has the excellent performance and causes a plurality of complications, wherein the initiation of blood coagulation and infection is a troublesome problem which troubles medical staff, so that research on the modification of the anticoagulant property, the hydrophilicity, the antibacterial property and the lubricity of the surface of the polyurethane catheter has become a research hotspot in the field.
The PU modified by the sulfonic acid group has certain anticoagulation performance. End sulfonic polyoxyethylene (PEO-SO)3) Grafted on the surface of polyurethane, and the results of platelet adhesion experiments show that PU-PEO-SO3The surface has better anti-platelet adhesion capability, the surface can greatly improve the adsorption of albumin while resisting the adsorption of other proteins, and the PU-PEO surface only shows the non-specific anti-protein adhesion performance and proves the anticoagulation performance of sulfonic acid groups. Polyethylene glycol (PEG) is a representative anticoagulant polymer material. PEG is soluble in water and various organic solvents, is non-toxic, and has been approved by the FDA in the United states for use in humans. An important property of PEG is that it can be attached to other molecules or cell surfaces, providing a biocompatible protective layer that can reduce adsorption of proteins, cells and bacteria. Therefore, in the research and development of anticoagulant materials, PEG has been selected as a modified material, and is introduced to other macromolecules or grafted to the surface of the material through various methods to reduce the plasma protein adsorption and the platelet adhesion on the surface of the material.
The PAMAM dendrimer is an artificially synthesized spherical and highly branched high-molecular polymer, and has the structural characteristics that a central core molecule is taken as a starting point and is diffused outwards, a large number of surface functional groups are provided, cavities exist in the molecule, the relative molecular mass is controllable, the molecular weight distribution can reach monodispersity, the molecule has the characteristics of nanometer size and the like. The structural features of Polyamidoamine (PAMAM) dendrimers give them unique properties: good compatibility and easy modification, good permeability and stability, can be used for drug loading technology, and the Polyamidoamine (PAMAM) dendrimer also has good prospects in the aspects of gene vectors, nano composite materials and the like.
As a commonly used antibacterial group, Ag + is firmly adsorbed to a cell membrane by coulomb attraction, and then breaks down the cell wall to enter the cell to coagulate bacterial proteins, so that the cell loses its ability to divide and proliferate and dies. In addition, Ag + can also destroy the electronic transmission system, the respiratory system and the material transmission system of microorganisms, and when the bacteria lose activity, the Ag + is dissociated from the bacteria and is repeatedly sterilized, so that the antibacterial effect is durable. Antibacterial properties are imparted to a material by introducing antibacterial groups into the material. The methods for introducing Ag + are various, including fixation by coordination bonds, and complexing of resin with triethyltetramine or thiol groups with Ag +, Cu2+, Zn2+ and the like by Takamasa and the like to prepare the material with antibacterial property.
At present, thrombus and infection still represent two major complications with high incidence in application of a polyurethane catheter, so how to endow the polyurethane catheter with antibacterial and anticoagulant properties is a problem to be solved urgently in clinical application at present. According to the invention, the cross-linked structure is formed on the surface of the catheter, so that the catheter and the coating are effectively combined, and meanwhile, the surface of the catheter is subjected to antibacterial and anticoagulant modification by combining other technologies, thereby providing a new technical approach for obtaining the high-performance antibacterial and anticoagulant polyurethane medical interventional catheter.
Disclosure of Invention
The invention provides a preparation method and an application method of an antibacterial and anticoagulant coating aiming at improving the antibacterial and anticoagulant performance of a polyurethane catheter, and the coating can effectively realize antibacterial and anticoagulant functions.
1. A preparation method of a polyurethane interventional catheter surface antibacterial and anticoagulant coating is characterized by comprising the following steps:
(1) cleaning the surface of the polyurethane conduit by using deionized water or distilled water, drying and cooling for later use;
(2) taking n parts of propylene sulfonic acid, adding DMSO, stirring for dissolving, adding m parts of refined vinyl acetate into a round-bottom flask, adding a small amount of azodiisobutyronitrile catalyst under stirring, soaking a polyurethane catheter in the solution, taking out for reaction, washing with DMSO after the reaction is finished, washing away residual monomers, washing with acetone, removing residual solvent to obtain PVAc (SO) with the surface containing vinyl acetate and propylene sulfonic acid copolymer polyvinyl sodium acetate3) A polyurethane catheter of Na is dried to constant weight;
(3) immersing a polyurethane catheter containing a copolymer of vinyl acetate and acrylic sulfonic acid PVAc (SO3) Na on the surface thereof in a methanol solution, taking out the catheter, and performing saponification to obtain PVA (SO)3) Na, and drying at room temperature to remove methanol;
(4) dissolving PEG-PAMAM in 0.2mol/L PBS buffer solution, and adding PVA (SO) on the surface3) Soaking the Na polyurethane catheter in a PBS (phosphate buffer solution) of PEG-PAMAM (polyethylene glycol-polyamidoamine), taking out for reaction, washing with acetone for multiple times, removing excessive unreacted substances, and drying;
(5) surface of the mixture contains PAMAM-PEG-PVA (SO)3) Soaking Na polyurethane conduit in AgNO3In the water solution, the obtained surface contains Ag-PAMAM-PEG-PVA (SO) after the reaction is finished3) Na polyurethane catheter Ag-PAMAM-PEG-PVA (SO)3) Na @ PU was dried in vacuo at room temperature.
Preferably, deionized water or distilled water is adopted to carry out ultrasonic washing on the surface of the polyurethane conduit in the step (1), the temperature of an oven is 30-45 ℃, and the drying time is 1-2 h;
preferably, the molar ratio n to m of the reaction of acrylic acid and vinyl acetate in the step (2) is (2-7): 1;
preferably, the polyurethane catheter in the step (2) is soaked in the reactant solution for 1-3min, the reaction temperature is 60-75 ℃, and the reaction time is 5-10 h;
preferably, the temperature of the methanol solution in which the polyurethane conduit in the step (3) is immersed is 40-60 ℃ and the time is 30-60 s;
preferably, the polyurethane conduit in the step (3) is taken out from the methanol solution, the reaction temperature is room temperature, and the reaction time is 2-5 h;
preferably, the polyurethane catheter obtained in the step (3) in the step (4) is soaked in the PBS buffer solution of PEG-PAMAM for 1-2min and then taken out, and the reaction temperature with the PEG-PAMAM is 60-80 ℃, and the reaction time is 3-6 h;
preferably, the drying temperature after washing in the step (4) is 20-40 ℃, and the drying time is 12-48 h;
preferably, the surface of the polyurethane catheter in the step (5) is PAMAM-PEG-PVA (SO)3) Na and AgNO3The reaction temperature of the aqueous solution is room temperature, and the reaction time is 12-36h under stirring;
preferably, AgNO used in step 93The concentration of the aqueous solution is 0.001-0.01 mol/L.
The reaction process is as follows:
according to the invention, the cross-linking reaction of the propylene sulfonic acid and the vinyl acetate on the surface of the polyurethane pipe is utilized, so that the adhesion of the coating on the surface of the pipe is enhanced, and a sulfonic acid group with an anticoagulation effect is introduced. After hydroxyl is introduced in the saponification reaction, the saponification reaction is further reacted with PEG-PAMAM, and a PEG fragment with strong hydrophilicity and anticoagulation effect is introduced. The PAMAM can be complexed with Ag + with antibacterial effect through coordination, so that a better antibacterial effect can be realized. The raw materials used by the invention have low cost, the coating has the dual effects of antibiosis and anticoagulation, and the coating forms a network structure through crosslinking reaction and is fixed on the surface of the pipe, so that the durability of the coating is ensured.
The molecular formulas of the polymers are respectively as follows:
PVAc(SO3)Na：
PAMAM-PEG:
PAMAM-PEG-PVA(SO3)Na:
Ag-PAMAM-PEG-PVA(SO3)Na:
drawings
Fig. 1 is a schematic structural diagram of the product of the present invention.
Detailed Description
In order to better illustrate the present invention, the following embodiments of the present invention are used to clearly and completely describe the technical solutions in the present invention:
examples 1
(1) And cleaning the surface of the polyurethane conduit by using deionized water or distilled water.
(2) Taking 5 parts of propylene sulfonic acid, adding DMSO, stirring and dissolving, taking 1 part of refined vinyl acetate, adding a small amount of azodiisobutyronitrile catalyst into a round-bottom flask under stirring, soaking a polyurethane catheter in the solution for 2min, taking out, and reacting for 4h at 65 ℃. Washing with DMSO after the reaction is finished, washing to remove residual monomers, washing with acetone, removing residual solvent to obtain PVAc (SO) with surface containing vinyl acetate and propylene sulfonic acid copolymer3) Na polyurethane catheter, dried to constant weight.
(3) The surface of the material contains a copolymer PVAc (SO) of vinyl acetate and propylene sulfonic acid3) Soaking Na polyurethane conduit in 50 deg.C methanol solution for 60s, reacting at room temperature for 3 hr, and saponifying to obtain PVA (SO)3) Na, dried at room temperature to remove methanol.
(4) Dissolving PEG-PAMAM in 0.2mol/L PBS buffer solution, and adding PVA (SO) on the surface3) Soaking the Na polyurethane catheter in PBS buffer solution of PEG-PAMAM for 1-2min, taking out, reacting at 70 deg.C for 4 hr, washing with acetone for several times, removing excessive unreacted material, and oven drying at 40 deg.C for 24 hr.
(5) Surface of the mixture contains PAMAM-PEG-PVA (SO)3) Soaking Na polyurethane conduit in 0.005mol/L AgNO3Stirring the mixture in water solution at room temperature for reaction for 24 hours, and drying the catheter in a vacuum container at 25 ℃ for 24 hours to obtain the modified polyurethane catheter Ag-PAMAM-PEG-PVA (SO)3)Na@PU。
EXAMPLES example 2
(1) And cleaning the surface of the polyurethane conduit by using deionized water or distilled water.
(2) Taking 6 parts of propylene sulfonic acid, adding DMSO, stirring and dissolving, taking 1 part of refined vinyl acetate, adding a small amount of azodiisobutyronitrile catalyst into a round-bottom flask under stirring, soaking a polyurethane catheter in the solution for 3min, taking out, and reacting for 2h at 65 ℃. Washing with DMSO after the reaction is finished, washing to remove residual monomers, washing with acetone, removing residual solvent to obtain PVAc (SO) with surface containing vinyl acetate and propylene sulfonic acid copolymer3) Na polyurethane catheter, dried to constant weight.
(3) The surface of the material contains a copolymer PVAc (SO) of vinyl acetate and propylene sulfonic acid3) Soaking Na polyurethane conduit in 50 deg.C methanol solution for 30s, reacting at room temperature for 3 hr, and saponifying to obtain PVA (SO)3) Na, dried at room temperature to remove methanol.
(4) Dissolving PEG-PAMAM in 0.2mol/L PBS buffer solution, and coating PVA (SO) on the surface3) Soaking the Na polyurethane catheter in PBS buffer solution of PEG-PAMAM for 1-2min, taking out, reacting at 70 deg.C for 6h, washing with acetone for several times, removing excessive unreacted substances, and oven drying at 40 deg.C for 24 h.
(5) Surface of the mixture contains PAMAM-PEG-PVA (SO)3) Soaking the polyurethane conduit of Na in 0.001mol/L AgNO3Stirring the mixture in water solution at room temperature for reaction for 24 hours, and drying the catheter in a vacuum container at 25 ℃ for 24 hours to obtain the modified polyurethane catheter Ag-PAMAM-PEG-PVA (SO)3)Na@PU。
EXAMPLE 3
(1) And cleaning the surface of the polyurethane conduit by using deionized water or distilled water.
(2) Taking 7 parts of propylene sulfonic acid, adding DMSO, stirring and dissolving, taking 1 part of refined vinyl acetate, adding a small amount of azodiisobutyronitrile catalyst into a round-bottom flask under stirring, soaking a polyurethane catheter in the solution for 1min, taking out, and reacting for 6h at 60 ℃. Washing with DMSO after the reaction is finished, washing to remove residual monomers, washing with acetone, removing residual solvent to obtain PVAc (SO) with surface containing vinyl acetate and propylene sulfonic acid copolymer3) Na polyurethane catheter, dried to constant weight.
(3) The surface of the material contains a copolymer PVAc (SO) of vinyl acetate and propylene sulfonic acid3) Soaking Na polyurethane conduit in 50 deg.C methanol solution for 40s, reacting at room temperature for 3 hr, and saponifying to obtain PVA (SO)3) Na, dried at room temperature to remove methanol.
(4) Dissolving PEG-PAMAM in 0.2mol/L PBS buffer solution, and adding PVA (SO) on the surface3) Soaking the Na polyurethane catheter in a PBS (phosphate buffer solution) solution of PEG-PAMAM for 2min, taking out, reacting for 3h at 60 ℃, washing with acetone for multiple times, removing excessive unreacted substances, and drying for 24h at 40 ℃.
(5) Surface of the mixture contains PAMAM-PEG-PVA (SO)3) Soaking Na polyurethane conduit in 0.01mol/L AgNO3Stirring the mixture in water solution at room temperature for reaction for 24 hours, and drying the catheter in a vacuum container at 25 ℃ for 24 hours to obtain the modified polyurethane catheter Ag-PAMAM-PEG-PVA (SO)3)Na@PU。
EXAMPLE 4
(1) And cleaning the surface of the polyurethane conduit by using deionized water or distilled water.
(2) Taking 4 parts of propylene sulfonic acid, adding DMSO, stirring and dissolving, taking 1 part of refined vinyl acetate, adding a small amount of azodiisobutyronitrile catalyst into a round-bottom flask under stirring, and soaking a polyurethane catheter in the solution for 3miAnd taking out the mixture after n, and reacting for 6 hours at the temperature of 60 ℃. Washing with DMSO after the reaction is finished, washing to remove residual monomers, washing with acetone, removing residual solvent to obtain PVAc (SO) with surface containing vinyl acetate and propylene sulfonic acid copolymer3) Na polyurethane catheter, dried to constant weight.
(3) The surface of the material contains a copolymer PVAc (SO) of vinyl acetate and propylene sulfonic acid3) Soaking Na polyurethane conduit in 50 deg.C methanol solution for 30s-60s, reacting at room temperature for 2h, and saponifying to obtain PVA (SO)3) Na, dried at room temperature to remove methanol.
(4) Dissolving PEG-PAMAM in 0.2mol/L PBS buffer solution, and coating PVA (SO) on the surface3) Soaking the Na polyurethane catheter in a PBS (phosphate buffer solution) solution of PEG-PAMAM for 2min, taking out, reacting at 70 ℃ for 8h, washing with acetone for multiple times, removing excessive unreacted substances, and drying at 40 ℃ for 24 h.
(5) Surface of the mixture contains PAMAM-PEG-PVA (SO)3) Soaking the polyurethane conduit of Na in 0.008mol/L AgNO3Stirring the mixture in water solution at room temperature for reaction for 24 hours, and drying the catheter in a vacuum container at 25 ℃ for 24 hours to obtain the modified polyurethane catheter Ag-PAMAM-PEG-PVA (SO)3)Na@PU。
EXAMPLE 5
Taking the concentration as 106The number of bacteria on the surface of the medical polyurethane catheter prepared in examples 1 to 4 was measured by culturing cfu/mL of Staphylococcus aureus in LB medium for 24 hours, diluting the Staphylococcus aureus for 24 hours, spreading a certain amount of the diluted sample solution on a plate, and culturing the sample solution for 48 hours, and the average of the results of 3 tests is shown in Table 1.
| Sample (I) | Unmodified catheter | Example 1 | Example 2 | Example 3 | Example 4 |
| Number of bacteria | 9.4×108 | 8.9×104 | 2.6×105 | 5.4×105 | 6.6×105 |
As can be seen from the data in the table, when the surface of the medical polyurethane catheter is modified, the number of bacteria on the surface of the catheter is obviously lower than that on the surface of the unmodified catheter.
Claims (9)
1. A preparation method of a polyurethane interventional catheter surface antibacterial and anticoagulant coating is characterized by comprising the following steps:
(1) cleaning the surface of the polyurethane conduit by using deionized water or distilled water, drying and cooling for later use;
(2) taking n parts of propylene sulfonic acid, adding DMSO, stirring and dissolving, taking m parts of refined vinyl acetate, and adding into a round-bottom flask, wherein the mol ratio n: m of the propylene sulfonic acid to the vinyl acetate is (2-7): 1, adding a small amount of catalyst azodiisobutyronitrile under stirring, soaking the polyurethane catheter in the solution, taking out for reaction, washing with DMSO after the reaction is finished, washing away residual monomers, washing with acetone, and removing residual solvent to obtain PVAc (SO) with the surface containing vinyl acetate and propylene sulfonic acid copolymer polyvinyl sodium acetate3) A polyurethane catheter of Na is dried to constant weight;
(3) the surface of the material contains a copolymer PVAc (SO) of vinyl acetate and propylene sulfonic acid3) Na polyurethane catheter immersed in methanolTaking out the solution, and performing saponification reaction to obtain PVA (SO)3) Na, and drying at room temperature to remove methanol;
(4) dissolving PEG-PAMAM in 0.2mol/L PBS buffer solution, and allowing the surface to contain PVAc (SO)3) Soaking the Na polyurethane catheter in a PBS (phosphate buffer solution) of PEG-PAMAM (polyethylene glycol-polyamidoamine), taking out for reaction, washing with acetone for multiple times, removing excessive unreacted substances, and drying;
(5) surface of the mixture contains PAMAM-PEG-PVA (SO)3) Soaking the polyurethane conduit in AgNO3In water solution, the obtained Ag-PAMAM-PEG-PVA (SO) is obtained after the reaction is finished3) Na @ PU was dried in vacuo at room temperature.
2. The preparation method according to claim 1, wherein the surface of the polyurethane conduit is ultrasonically washed by deionized water or distilled water in the step (1), the temperature of an oven is 30-45 ℃, and the drying time is 1-2 h.
3. The method according to claim 1, wherein the polyurethane catheter in the step (2) is soaked in the reactant solution for 1-3min at a reaction temperature of 60-75 ℃ for 5-10 h.
4. The manufacturing method according to claim 1, wherein the temperature of the methanol solution in which the polyurethane catheter of the step (3) is immersed is 40 to 60 ℃ for 30 to 60 seconds.
5. The method according to claim 1, wherein the reaction temperature of the polyurethane tube in step (3) is room temperature after the polyurethane tube is removed from the methanol solution, and the reaction time is 2-5 hours.
6. The method according to claim 1, wherein the polyurethane catheter obtained in step (3) in step (4) is soaked in PBS buffer solution of PEG-PAMAM for 1-2min, and reacted with PEG-PAMAM at 60-80 deg.C for 3-6 h.
7. The method according to claim 1, wherein the drying temperature after washing in step (4) is 20-40 ℃ and the drying time is 12-48 h.
8. The method of claim 1, wherein the surface of the polyurethane catheter is PAMAM-PEG-PVA (SO)3) Na and AgNO3The reaction temperature of the aqueous solution is room temperature, and the reaction time is 12-36h under stirring.
9. The method of claim 8, wherein the AgNO is3The concentration of the aqueous solution is 0.001-0.01 mol/L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910627602.2A CN110343284B (en) | 2019-07-12 | 2019-07-12 | Preparation method of antibacterial and anticoagulant coating on surface of polyurethane interventional catheter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910627602.2A CN110343284B (en) | 2019-07-12 | 2019-07-12 | Preparation method of antibacterial and anticoagulant coating on surface of polyurethane interventional catheter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110343284A CN110343284A (en) | 2019-10-18 |
| CN110343284B true CN110343284B (en) | 2021-09-14 |
Family
ID=68175665
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910627602.2A Active CN110343284B (en) | 2019-07-12 | 2019-07-12 | Preparation method of antibacterial and anticoagulant coating on surface of polyurethane interventional catheter |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110343284B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112022010381A2 (en) * | 2019-11-30 | 2022-09-13 | Smart Reactors Service Ltd | COATING FOR MEDICAL DEVICES |
| CN114558174A (en) * | 2021-12-22 | 2022-05-31 | 山东百多安医疗器械股份有限公司 | Preparation method of polyurethane catheter with hydrophilic anticoagulant surface |
| CN117159813A (en) * | 2023-09-08 | 2023-12-05 | 浙江海圣医疗器械股份有限公司 | Medical catheter with hydrophilic coating and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10328293A (en) * | 1997-06-04 | 1998-12-15 | Unitika Ltd | Medical instrument and manufacture therefor |
| CN101011605A (en) * | 2006-11-28 | 2007-08-08 | 武汉理工大学 | Anticoagulant polyurethane material, and preparation and usage thereof |
| CN102357265A (en) * | 2011-07-29 | 2012-02-22 | 中山大学 | Surface modification polyurethane central venous catheter and preparation method thereof |
| CN102380130A (en) * | 2011-07-29 | 2012-03-21 | 中山大学 | Nano-silver surface modified polyurethane central venous catheter and preparation method thereof |
| CN107537069A (en) * | 2017-09-05 | 2018-01-05 | 泉州市科茂利通智能科技有限公司 | Nano Silver polyurethane medical material that a kind of polyethylene glycol surface is modified and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6852353B2 (en) * | 2000-08-24 | 2005-02-08 | Novartis Ag | Process for surface modifying substrates and modified substrates resulting therefrom |
| WO2005115490A2 (en) * | 2004-05-25 | 2005-12-08 | Surmodics, Inc. | Natural biodegradable polysaccharide coatings for meical articles |
| WO2009085096A2 (en) * | 2007-12-05 | 2009-07-09 | Semprus Biosciences Corporation | Non-leaching, non-fouling antimicrobial coatings |
-
2019
- 2019-07-12 CN CN201910627602.2A patent/CN110343284B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10328293A (en) * | 1997-06-04 | 1998-12-15 | Unitika Ltd | Medical instrument and manufacture therefor |
| CN101011605A (en) * | 2006-11-28 | 2007-08-08 | 武汉理工大学 | Anticoagulant polyurethane material, and preparation and usage thereof |
| CN102357265A (en) * | 2011-07-29 | 2012-02-22 | 中山大学 | Surface modification polyurethane central venous catheter and preparation method thereof |
| CN102380130A (en) * | 2011-07-29 | 2012-03-21 | 中山大学 | Nano-silver surface modified polyurethane central venous catheter and preparation method thereof |
| CN107537069A (en) * | 2017-09-05 | 2018-01-05 | 泉州市科茂利通智能科技有限公司 | Nano Silver polyurethane medical material that a kind of polyethylene glycol surface is modified and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110343284A (en) | 2019-10-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110343284B (en) | Preparation method of antibacterial and anticoagulant coating on surface of polyurethane interventional catheter | |
| US4880883A (en) | Biocompatible polyurethanes modified with lower alkyl sulfonate and lower alkyl carboxylate | |
| US5017664A (en) | Biocompatible polyurethane devices wherein polyurethane is modified with lower alkyl sulfonate and lower alkyl carboxylate | |
| JP6373872B2 (en) | Medical tools | |
| JP2537580B2 (en) | Method for producing fluorinated polyurethane with improved blood compatibility | |
| JP4952578B2 (en) | Durability wet surface coating excellent in durability, surface coating method, and medical device having the surface coating | |
| CN116003692B (en) | Surface graft crosslinked zwitterionic polymer coating, and preparation method and application thereof | |
| CN113209394A (en) | Anticoagulation antibacterial coating and preparation method and application thereof | |
| Lee et al. | Platelet and bacterial repellence on sulfonated poly (ethylene glycol)-acrylate copolymer surfaces | |
| Aksoy et al. | Surface modification of polyurethanes with covalent immobilization of heparin | |
| Zhang et al. | Surface biocompatible modification of polyurethane by entrapment of a macromolecular modifier | |
| JPS61200114A (en) | Antithrombotic polyurethane compound and production thereof | |
| CN110028692A (en) | A kind of preparation method cooperateing with surface heparinization anticoagulation medical apparatus based on ionic bond-covalent bond | |
| CN114748703B (en) | Hydrophilic lubrication anticoagulant hydrogel film and preparation method and application thereof | |
| JP6195335B2 (en) | Polymer compound, composition using the same, and medical device | |
| You et al. | Microwave-assisted functionalization of polyurethane surface for improving blood compatibility | |
| Zhang et al. | Comparative studies on hydrophilic and hydrophobic segments grafted poly (vinyl chloride) | |
| WO2020181857A1 (en) | Medical tube and preparation method therefor | |
| Lim et al. | Effects of oligoethylene oxide monoalkyl (aryl) alcohol ether grafting on the surface properties and blood compatibility of a polyurethane | |
| CN115120785A (en) | Medical catheter with polysaccharide coating and preparation method thereof | |
| CN114984331A (en) | Ultra-smooth anticoagulant coating material and preparation method and application thereof | |
| Balakrishnan et al. | Chemical modification of poly (vinyl chloride) using poly (ethylene glycol) to improve blood compatibility | |
| Feng | Some advances in synthetic biomedical polymers | |
| JP3818684B2 (en) | Antithrombotic medical substrate and method for producing the same | |
| Park et al. | Sulfonated poly (ethylene glycol) containing methacrylate copolymer surfaces; preparation, characterization and in vitro biocompatibility |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: 251100 Shandong Qihe Dezhou high tech Development Zone, Bai Dian an biomedical science and Technology Park Applicant after: Shandong baiduoan Medical Equipment Co.,Ltd. Address before: 251100 Shandong Qihe Dezhou high tech Development Zone, Bai Dian an biomedical science and Technology Park Applicant before: Shandong Branden Medical Device Co.,Ltd. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |