CN108379669B - Medical catheter with copper-containing coating and preparation method thereof - Google Patents
Medical catheter with copper-containing coating and preparation method thereof Download PDFInfo
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- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
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- 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
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- 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
- A61L29/148—Materials at least partially resorbable by the body
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- 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
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- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/02—Use of inorganic materials
- A61L33/022—Metal or alloys
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
- A61L2300/424—Anti-adhesion agents
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- 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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
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- 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
Abstract
The invention discloses a medical catheter with a copper-containing coating. The copper-carrying microspheres with different concentrations are fixed/dispersed in the polymer carrier on the surface of the medical catheter in a gradient manner in a certain way, so that the biological functionalization of the medical catheter can be realized. The fixing mode of the functionalized copper-loaded microspheres comprises chemical grafting, physical blending, electrostatic interaction and the like. The medical catheter with the biological functional copper-containing coating can play a role in reducing platelet adhesion, anticoagulation, antibacterial proliferation and anti-fibrous tissue adhesion after being implanted into a body, so that adverse events such as thrombus, infection or catheter and tissue adhesion after the medical catheter is implanted are avoided.
Description
Technical Field
The invention relates to the field of medical instruments of implantation/intervention catheters, in particular to a medical catheter with a copper coating, which can maintain the circulation of body fluid (body fluid, blood and the like) or maintain the supply of nutrition to human bodies from the outside and has a biological function.
Background
Medical catheters are commonly used in the fields of infusion, tumor chemotherapy, total parenteral nutrition, urinary drainage and the like. However, catheters embedded in the body of a patient for a long time, such as peripheral central venous catheters, are common complications, such as catheter-related infection, related thrombosis, phlebitis, lumen blockage and the like. In clinic, once infection and blockage occur, the catheter needs to be discarded and re-intubated, which causes great burden to the body of the patient. Therefore, there is a great deal of interest in reducing the incidence of related complications following catheter placement.
The application of antimicrobial agents, including antibiotics, disinfectants, and metal-containing agents, to the surface of catheters is one way to inhibit catheter-related infections in blood vessels. Chaftari et al placed minocycline/rifampin surface coated catheters into the central venous catheters of patients with staphylococcus aureus-associated bloodstream infections, with significantly less mortality than the common catheters. Rouse et al compared the formation of bacterial biofilms on the surfaces of silver-coated and uncoated endotracheal tubes and found that the colonization rates of the inner and outer surfaces of silver-coated catheters were lower than those of uncoated catheters. In addition, the low ampere current carbon coated catheter treated by a physical mechanical method also has the function of repelling microorganisms, and the catheter is combined with antibiotics to play an important role in improving the antibacterial activity of the antibiotics. Hazan et al inserted the mechanically surface treated Foley catheter into the urethra of male rabbits to maintain urine sterility for 9 days, while the control catheter set was only 2 days. Although the coating surface treatment mode can effectively improve the antibacterial capacity of the surface of the catheter, the action time is short, and when the catheter is kept in place for a long time, the coating is easy to elute due to poor binding force between the coating and the catheter matrix, and further the catheter fails. Anticoagulant treatment of the surface of a medical catheter also has the same technical drawbacks. The heparin is bonded to the surface of the catheter by coating or ionic bonding, which can effectively inhibit coagulation, but because heparin gradually dissolves in blood, the anticoagulant property of heparin is gradually lost, and the heparin is only suitable for short-time anticoagulation.
In order to solve the problems, the application provides a copper-containing coating with multiple biological functions, which has good anti-infection, anti-thrombosis and anti-adhesion functions, and can exist in a human body in a stable and durable combination mode so as to play a role for a long time. Copper is a trace metal element essential to the human body. Studies have demonstrated that 10-6The copper ion with the concentration of M can show a powerful sterilization function, and when the concentration reaches 10-4The M has no influence on normal tissue cells of a human body, so that a larger applicable concentration range is provided for copper ions, and the basic biological safety is achieved while the biological function of the copper ions is ensured. In addition, copper ions also have a certain inhibitory effect on blood coagulation. Johnson et al have shown that copper ions affect the movement of calcium in platelets, stimulate thrombin, affect the activity of copper superoxide dismutase, reduce the production of thromboxane and lipid peroxide in platelets, and thus inhibit thrombosis. Therefore, the copper-containing coating is prepared on the surface of the medical catheter, the biological effect of copper can be exerted for a long time, and multiple biological functions of infection resistance, thrombus resistance, tissue adhesion resistance and the like after the catheter is placed are realized, so that the medical catheter is reducedProbability of occurrence of clinical complications.
Aiming at the medical catheter, the invention provides a copper-containing coating with multiple biological functions of resisting infection, thrombus, fibrous adhesion and the like on the surface of the medical catheter in order to solve the problems of infection, thrombus and the like caused in the body after the medical catheter is indwelling for a long time, and the occurrence probability of complications after the medical catheter is indwelling is reduced on the premise of ensuring the existing safety and functionality of the catheter.
Disclosure of Invention
The invention aims to prepare a copper-containing coating with biological functions on the surface of a catheter on the basis of ensuring that a lumen of the medical catheter is kept smooth after the medical catheter is placed, so that multiple biological functions of anticoagulation, bacterial infection resistance, tissue adhesion prevention and the like of the medical catheter after the medical catheter is placed are realized.
The technical scheme of the invention is as follows:
a medical catheter having a copper-containing coating, characterized by: the surface of the medical catheter is coated with a copper-containing polymer coating, and the coating contains copper element.
As a preferred technical scheme:
the medical catheter with the copper-containing coating is characterized by comprising a central venous catheter, a peripheral central venous catheter, an interventional catheter, an infusion indwelling catheter, a stomach tube, an esophagus, a trachea, a catheter, a dialysis catheter and the like.
The medical catheter with the copper-containing coating is characterized in that: the copper element is added through copper-carrying microspheres, and the copper-carrying microspheres are degradable polymer coating microspheres with the diameter of 50-500 nm.
The medical catheter with the copper-containing coating is characterized in that: the microsphere matrix material of the copper-carrying microsphere is a polymer with good film forming property, biocompatibility and degradability, such as one or more of polytrimethylene carbonate (PTMC), Polycyanoacrylate (PACA), polyhydroxyalkyl alcohol ester (PHAs), PHB (poly-3-hydroxybutyrate), polyglycolide-lactide copolymer (PLGA), Polycaprolactone (PCL), polyacrylic acid, cellulose, chitosan and the like, and the carried copper-containing substance is one or more of nano-scale metal copper powder, inorganic copper ions and copper-containing organic substances.
The medical catheter with the copper-containing coating is characterized in that: the size of the nano-scale metal copper powder is within the range of 10-200nm, inorganic copper ions are one or more of basic copper sulfate, copper oxychloride and copper hydroxide, and copper-containing organic matters are one or more of copper acetate, copper amino acid and copper quinoline.
The medical catheter with the copper-containing coating is characterized in that: the molar ratio of the matrix material to the copper-containing substance in the copper-carrying microspheres is in the range of 100:1 to 2: 1.
The medical catheter with the copper-containing coating is characterized in that: the copper element concentration is distributed in the coating polymer in a gradient manner; the polymer is synthetic polymer and natural polymer such as chitosan and its derivatives, polyurethane, cyclodextrin, starch, cellulose, sodium alginate, collagen, polylactic acid, polyethylene glycol, polycarbonate, etc.
The medical catheter with the copper-containing coating is characterized in that: the thickness of the copper-containing polymer coating is less than or equal to 5 mu m.
The preparation method of the medical catheter is characterized by comprising the following steps: the distribution mode of the copper element in the orthopedic implant surface coating polymer is as follows: the copper-loaded microspheres are dispersed in the polymer coating in a gradient manner by a layered preparation method in the form of copper-loaded microspheres.
The preparation method of the medical catheter is characterized by comprising the following steps:
the method comprises the following steps: the copper-carrying microspheres are prepared by a microemulsion method.
Step two: preparing copper-carrying microsphere polymer solutions with different proportions, and preparing the polymer coating with the copper-carrying microspheres layer by a leaching or spraying method.
The preparation method of the medical catheter is characterized in that the step two of preparing the copper-loaded microspheres by adopting a microemulsion method comprises the following steps:
(1) preparing a copper salt aqueous solution with the mass volume concentration of 3-180 mg/mL;
(2) preparing a microsphere matrix solution with the mass volume concentration of 8-900mg/mL, wherein the solvent is chloroform: acetone is 1: 4-4: 1;
(3) preparing PVA water solution with the mass volume concentration of 1-200 mg/mL;
(4) adding a copper salt aqueous solution into a microsphere matrix solution, uniformly stirring, and adding a mixed solution into a PVA aqueous solution;
(5) preparing microspheres with different particle sizes by adopting a mechanical stirring or ultrasonic oscillation method, wherein the stirring revolution is within the range of 500-5000rpm, and the stirring time is 2.5-10 h; the ultrasonic power is within the range of 50-100W, and the ultrasonic time is 5-25 min;
(6) collecting the microspheres prepared by the reaction by using a centrifugal or rotary evaporation method, wherein:
the rotation number adopted by the centrifugation method is 500-;
the rotary evaporation method adopts rotation speed of 10-50rpm, settling solution for a certain time, removing supernatant, adding lower layer reaction solution into rotary evaporator at 30-45 deg.C for 30min-2 h.
The design idea of the invention is as follows:
the copper-containing coating with biological functions is prepared on the surface of the medical catheter, and the coating is uniformly distributed at each position of the catheter so as to ensure that the medical catheter has biological functions of anticoagulation, infection resistance, tissue adhesion resistance and the like after being placed. Copper-bearing coating is prepared on the surface of the medical catheter layer by using copper-bearing microspheres with different concentrations through physical blending, chemical grafting or electrostatic adsorption, so that the copper content of the coating has the characteristic of gradient, and the coating carrier is a medical-grade degradable high polymer material (the schematic diagram of the copper-bearing coating is shown in figure 2). When the copper-carrying microsphere is prepared, the microsphere shell material is a high polymer material which is biodegradable, has good film-forming property and good biocompatibility. In the preparation process of the coating, the gradient copper-containing coating is constructed by adjusting the copper content in the microspheres or the content of the microspheres contained in the coating. In the preparation process of the coating, the structure of the medical catheter is not damaged, so that the smoothness of the medical catheter and biological functions of anticoagulation, infection resistance, tissue adhesion resistance and the like are realized.
The invention has the characteristics and beneficial effects that:
1. the medical catheter with the copper-containing coating and the biological function, provided by the invention, has multiple biological functions of anticoagulation, infection resistance, tissue adhesion resistance and the like.
2. The copper-containing coating with biological function can replace the antibiotic medicine coating adopted by the prior medical catheter. The copper-containing coating has the anti-infection characteristic, and can avoid the problem of bacterial drug resistance caused by the drug coating.
3. The invention not only can be used as a biological functional drug coating, but also has the functions of anticoagulation and tissue adhesion resistance, thereby reducing the risk of thrombosis and tissue adhesion and prolonging the service life of the medical catheter.
Drawings
FIG. 1 is a schematic diagram of the morphology of copper-loaded microspheres.
FIG. 2 is a schematic representation of a biofunctionalized copper-containing coating with graded copper-loaded microspheres.
Detailed Description
The following examples further illustrate the invention but are not intended to limit the invention thereto.
Example 1
Preparing a coating with gradient copper-loaded particles on the medical catheter by a layer-by-layer chemical grafting method:
the copper-loaded microspheres with active functional groups such as hydroxyl, carboxyl and the like are fixed on a natural degradable chitosan polymer with amino and hydroxyl by adopting a layer-by-layer chemical grafting method, the amount of copper loaded on each layer is graded, copper ions are released in a gradient manner through the coating, and the biological functionalization regulation and control of the copper-containing coating are realized.
(1) Preparation of copper-loaded microspheres
Weighing 0.05g, 0.2g and 0.5g of CuCl2And are respectively dissolved in 5mL of distilled water to prepare three homogeneous solutions;
dissolving 1.0g of PACA in a mixed solution of trichloromethane and acetone (wherein the volume ratio of trichloromethane to acetone is 3:2) to prepare an organic PACA solution with the mass volume concentration of 100 mg/mL;
③ weighing 1.0g of PVA0, dissolving the PVA1.0g of PVAin distilled water, preparing PVA aqueous solution with the mass volume concentration of 20mg/mL, and uniformly mixing the PVA aqueous solution for later use;
fourthly, mixing CuCl2Slowly dripping the aqueous solution into the PACA organic solution, uniformly mixing, adding the mixed solution into the PVA aqueous solution, and stirring for 8 hours at the rotation speed of 500rpm by magnetic stirring; the ultrasonic power is within the range of 50-100W, and the ultrasonic time is 5 min;
fifthly, standing the reaction solution for 2 hours, removing supernatant, transferring the lower-layer precipitate into a rotary evaporator, and performing rotary evaporation for 30 minutes at 30 ℃ to obtain a large amount of microsphere powder.
Preparing copper-carrying microspheres with different copper carrying amounts by the same method, wherein CuCl is weighed2The mass of the microspheres is 0.2g and 0.5g respectively, microspheres with gradient concentration are obtained, and the appearance of the microspheres is shown in figure 1.
(2) Preparation of gradient copper-loaded polymer coating
Firstly, preparing 1% acetic acid solution
Taking 1mL of glacial acetic acid reagent into a 100mL volumetric flask, slowly adding distilled water into the volumetric flask, and fixing the volume and uniformly mixing the solution for later use.
② preparing 1 percent chitosan solution
Accurately weighing 1g of chitosan powder, uniformly mixing 100ml of prepared acetic acid solution with the powder, standing for 24 hours, and removing bubbles for later use.
Preparation of single-layer copper-carrying coating
The chitosan coating is prepared on the medical catheter by an ultrasonic atomization spraying or leaching method, the thickness of the coating is about 1 mu m, and after the coating is dried, the low-concentration copper-loaded microspheres are grafted on the chitosan coating under the catalytic action of EDC/NHS.
Preparation of gradient copper-carried microsphere coating
The preparation method of the single-layer copper-carrying coating is repeated, and the copper-carrying microsphere coatings with different copper-carrying concentrations are prepared on the surface of the medical catheter layer by layer. The total thickness of the coating is controlled within 5 mu m.
(3) Animal experiments
The medical catheter containing the copper coating and having the biological function is placed into a rabbit urethra, the catheter without the copper coating is used as a control group, materials are taken after 15 days of implantation, and the appearance of a bacterial biofilm on the surface of the catheter is observed through a scanning electron microscope. The experimental result shows that the catheter with the copper-containing coating has no obvious bacterial biofilm formation after being implanted for 15 days, while the catheter of the control group is coated by a large-area bacterial biofilm; the catheter with the copper-containing coating has no resistance when taken out, and no tissue adhesion phenomenon occurs on the surface; while the surface of the catheter of the control group is coated with a certain amount of fibrous shell. Therefore, the copper-containing coating catheter with biological function has the characteristics of antibiosis, tissue adhesion resistance and the like.
Example 2
Preparing a coating with gradient copper-loaded microspheres on the medical catheter by a layer-by-layer electrostatic adsorption method:
(1) preparing an aqueous solution (with the concentration of 1-5%) of sodium hyaluronate with negative charges, and preparing a hyaluronic acid coating on the inner/outer surface of the medical catheter by an extraction method;
(2) preparation of copper-loaded microspheres
Weighing 0.20g of chitosan into a 250m L single-neck round-bottom flask, adding 2% (mass fraction) acetic acid solution 250m L, starting an electric stirring device, and slowly stirring until the chitosan is completely dissolved.
Secondly, adding Span-800.4 mL and Tween-800.6 mL while stirring, and continuously stirring for 30min to form uniform, transparent and stable microemulsion. Then adding 0.05g of copper sulfate powder, and stirring at a high speed to uniformly diffuse the copper sulfate powder;
thirdly, slowly dripping 1 mol.L-1Stirring the solution with NaOH at constant speed, and detecting the change of the pH value of the system at 25 ℃ by using a PHS-3B type precision pH meter (Shanghai Lei Magnetitum, China) until the pH value is slightly alkaline (p H value is 7.20);
fourthly, after the dropwise addition of the NaOH solution is finished, stirring at medium speed, adding 0.30g of trisodium citrate, continuously stirring for 3 hours to crosslink and solidify the chitosan microspheres formed in the emulsion, and centrifugally separating the obtained transparent emulsion by using a centrifugal machine;
transferring the lower layer precipitate into a rotary evaporator, and performing rotary evaporation for 30 minutes at 30 ℃ to obtain a large amount of microsphere powder.
Preparing copper-carrying microspheres with different copper carrying amounts by the same method, wherein CuSO is weighed4The mass of (a) is 0.2g and 0.5g respectively to obtain the micro-particles with gradient concentrationA ball.
(3) Preparation of gradient copper-loaded polymer coating
The medical catheter with the electronegative hyaluronic acid coating is immersed into the water solution with electropositive low-concentration copper-loaded microspheres, and the microspheres are fixed on the hyaluronic acid coating through electrostatic action.
The preparation method of the single-layer coating is repeated to construct the polymer coating with the copper-loaded microspheres in a gradient mode (the copper content is gradually increased layer by layer).
(4) Preparation of the hydrophilic outer layer
And preparing a polyethylene glycol coating layer with the diameter less than 1 mu m by an ultrasonic atomization spraying method outside the polymer coating layer loaded with the gradient copper-loaded microspheres.
(5) Characterization of copper-containing coatings
The surface appearance of the tracheal catheter with the copper-containing coating is observed through a scanning electron microscope, which shows that the surface of the copper-containing coating prepared by the leaching method is smooth and compact. The scanning electron microscope energy spectrum analysis result proves that the copper exists in the coating.
Soaking the tracheal catheter with the copper-containing coating in normal saline (0.9% NaCl), and collecting the leaching solution after 1, 7, 14 and 28 days. The concentration of copper ions in the leaching solution is tested by plasma inductively coupled atomic absorption spectrometry (ICP-AAS), and the result shows that the copper in the coating is dissolved out in an ion form in the soaking process, and the dissolution amount is in ppb order of magnitude.
The copper-coated endotracheal tube with biological function of the invention has good biocompatibility and shows multiple biological functions of antibiosis, tissue adhesion resistance and the like.
Comparative example 3
The preparation method of the copper-containing coating with the gradient copper-loaded microspheres prepared in the example 2 is compared with the method for plating the copper ion coating on the surface provided in the patent of the invention of ' a biodegradable copper-containing coating pure magnesium anastomosis nail and the preparation thereof ' (the patent publication number is CN 103110977A '), and the safety and the effectiveness of the copper-containing coatings prepared by the two methods are evaluated by comparing the ion dissolution performance of the coatings prepared by the two methods in vitro and the implantation condition in vivo.
From example 2, it can be seen that the copper-containing coating with the copper-loaded microspheres of the invention can realize that the concentration of copper ions sufficient for expressing biological functions is released from the coating at the initial stage of device implantation, and the release amount of the copper ions is ensured within the biological safety range by the coating design and the fine adjustment of the copper-loaded amount of the copper-loaded microspheres; the coating realizes antibiosis and anticoagulation through copper ions released in the initial stage, thereby avoiding thrombus and bacterial infection after the catheter is placed. In the later period of implantation, the generation of fibrin shell is inhibited through the release of trace copper ions, so as to realize the function of resisting tissue adhesion.
While the copper ion-coated coatings provided in the previously filed patent do not have the effect of a gradient release of copper ions, the amount of copper ions released depends only on the nature of the coated carrier, e.g., with carriers that are water soluble or degrade at a rapid rate, the copper in the coating may have been released during implantation and not enough copper ions are available to act on the surrounding tissue when the target site is reached; if a carrier with a slow degradation rate is used, there is not enough copper ion release to achieve its multiple biological functionality in the early post-implantation period.
The medical catheter with the gradient copper-containing coating prepared according to example 2 was implanted into the jugular vein of a rabbit, and an animal experiment comparison was performed by using the medical catheter without gradient release of copper ions prepared in the applied patent as a control group. The materials are taken after being implanted for 15 days, and the appearance of the bacterial biofilm on the surface of the medical catheter is observed through a scanning electron microscope. The experimental result shows that the medical catheter with the copper-containing coating has no bacterial biofilm formation after being implanted for 15 days, while the catheter of the control group is partially coated by the bacterial biofilm; the medical catheter with the copper-containing coating has no resistance when being taken out, and no tissue adhesion phenomenon occurs on the surface; the surface of the medical catheter of the control group is coated with a certain amount of fiber shell. Therefore, the medical catheter with the gradient copper-containing coating has the characteristics of antibiosis, tissue adhesion resistance and the like.
The experimental results and analysis show that the coating with the gradient copper-loaded microspheres and the preparation method thereof, which are claimed in the claims, have obvious excellent effects.
Claims (5)
1. A medical catheter having a copper-containing coating, characterized by: the surface of the medical catheter is coated with a copper-containing polymer coating, the coating contains copper element, the copper element is added through copper-carrying microspheres, the copper-carrying microspheres are degradable polymer coated microspheres with the diameter of 50-500nm, and the molar ratio of microsphere matrix materials to copper element-containing substances in the copper-carrying microspheres is within the range of 100:1-2: 1; the copper element concentration is distributed in the coating polymer in a gradient manner;
the preparation method of the medical catheter is to disperse the copper-loaded microspheres in the polymer coating in a gradient manner by a layered preparation method, and comprises the following specific steps:
the method comprises the following steps: preparing copper-carrying microspheres by a microemulsion method;
(1) preparing a copper salt aqueous solution with the mass volume concentration of 3-180 mg/mL;
(2) preparing a microsphere matrix solution with the mass volume concentration of 8-900mg/mL, wherein a solvent is a mixed solution of trichloromethane and acetone, and the volume ratio of the trichloromethane to the acetone is as follows: acetone is 1: 4-4: 1;
(3) preparing PVA water solution with the mass volume concentration of 1-200 mg/mL;
(4) adding a copper salt aqueous solution into a microsphere matrix solution, uniformly stirring, and adding a mixed solution into a PVA aqueous solution;
(5) preparing microspheres with different particle sizes by adopting a mechanical stirring or ultrasonic oscillation method, wherein the stirring revolution is within the range of 500-5000rpm, and the stirring time is 2.5-10 h; the ultrasonic power is within the range of 50-100W, and the ultrasonic time is 5-25 min;
(6) collecting the microspheres prepared by the reaction by using a centrifugal or rotary evaporation method, wherein:
the rotation number adopted by the centrifugation method is 500-;
the rotation speed adopted by the rotary evaporation method is 10-50rpm, supernatant liquid of the settled solution is removed, and lower layer reaction liquid is added into a rotary evaporator at the temperature of 30-45 ℃ for 30min-2 h;
step two: preparing copper-carrying microsphere polymer solutions with different proportions, and preparing the polymer coating with the copper-carrying microspheres layer by a leaching or spraying method.
2. The medical catheter with a copper-containing coating according to claim 1, wherein the medical catheter is one or more of a central venous catheter, a peripheral central venous catheter, a gastric tube, an esophagus, a trachea, a urinary catheter, a dialysis catheter.
3. The medical catheter with a copper-containing coating according to claim 1, wherein: the microsphere matrix material of the copper-carrying microsphere is one or more of polytrimethylene carbonate (PTMC), Polycyanoacrylate (PACA), polyhydroxyalkyl alcohol ester (PHAs), PHB (poly-3-carboxybutyrate), polyglycolide-lactide copolymer (PLGA), Polycaprolactone (PCL), polyacrylic acid, cellulose and chitosan, the carried copper-containing substance is one or more of nano-scale metal copper powder, inorganic copper ions and copper-containing organic substances, the size of the nano-scale metal copper powder is within the range of 10-200nm, the inorganic copper ions are one or more of basic copper sulfate, copper oxychloride and copper hydroxide, and the copper-containing organic substances are one or more of copper acetate, copper amino acid and copper quinoline.
4. The medical catheter with a copper-containing coating according to claim 1, wherein: the polymer is one or more of chitosan and derivatives thereof, polyurethane, cyclodextrin, starch, cellulose, sodium alginate, collagen, polylactic acid, polyethylene glycol and polycarbonate.
5. The medical catheter with a copper-containing coating according to claim 1, wherein: the thickness of the copper-containing polymer coating is less than or equal to 5 mu m.
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| CN114177359B (en) * | 2021-11-24 | 2023-03-24 | 广东省科学院健康医学研究所 | Antibacterial coating and preparation method and application thereof |
| CN116808311B (en) * | 2023-01-10 | 2024-04-12 | 亿科吉互联网科技(南京)有限公司 | Preparation method of medical catheter with anticoagulation antibacterial coating |
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| CN105688276A (en) * | 2008-02-29 | 2016-06-22 | 史密夫和内修有限公司 | Gradient coating for biomedical applications |
| CN107427354A (en) * | 2015-03-30 | 2017-12-01 | C·R·巴德股份有限公司 | Apply antimicrobial to medical treatment device |
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| CN105688276A (en) * | 2008-02-29 | 2016-06-22 | 史密夫和内修有限公司 | Gradient coating for biomedical applications |
| CN107427354A (en) * | 2015-03-30 | 2017-12-01 | C·R·巴德股份有限公司 | Apply antimicrobial to medical treatment device |
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