CN108478843B - Medical dressing with copper-containing coating and preparation method thereof - Google Patents
Medical dressing with copper-containing coating and preparation method thereof Download PDFInfo
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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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/18—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
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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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
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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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/62—Compostable, hydrosoluble or hydrodegradable 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
- 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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- 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
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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
- A61L2300/412—Tissue-regenerating or healing or proliferative 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
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
Abstract
The invention discloses a medical dressing 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 dressing in a gradient manner in a certain way, so that the biological functionalization of the medical dressing can be realized. The fixing mode of the functionalized copper-loaded microspheres comprises chemical grafting, physical blending, electrostatic interaction and the like. After the dressing with the biological functional copper-containing coating is attached to a wound, the dressing can play a role in resisting bacterial proliferation, promoting wound healing, promoting angiogenesis and resisting tissue adhesion, so that the problems of infection or difficult healing and the like caused by the fact that the dressing is attached to the wound are solved.
Description
Technical Field
The invention relates to the field of dressing medical instruments, in particular to a medical dressing applied to a wound part difficult to heal, which is a copper-containing medical dressing capable of isolating and preventing bacteria from invading and propagating, promoting the healing speed of the wound, promoting the generation of new vessels and preventing adhesion
Background
The dressing, even if used as a covering outside a wound, can replace damaged skin to play a temporary role in protecting the damaged skin during the wound healing process, avoid or control wound infection and provide a proper healing environment for the surface of the wounded body. Traditional dressings can play a role in monitoring and covering wounds, cannot be used for infectious wounds, have no promotion effect on wound healing, have limited exudate management capacity, adhere wounds, re-damage new epithelial tissues and cause bleeding, and are painful for patients after dressing change. In order to provide a good wound healing environment, reduce scarring, and improve user comfort, new medical dressings have gradually replaced traditional dressings that provide only the simplest barrier protection in recent years.
With the proposal of the theory of moist healing of wounds, a plurality of novel dressings are continuously developed, and the novel medical dressings mainly comprise alginate dressings, polyurethane dressings, hydrogel dressings, film dressings and the like. Although the types of the dressings are various, the novel dressings can provide a wet environment for wounds and can effectively promote the healing of the wounds. In addition to providing a moist environment for the wound to promote wound healing, antimicrobial dressings have also been created to address infection issues that may be encountered during the wound healing process.
Since the beginning of the use of Silver Sulfa Diazine (SSD) in burn wounds, Silver ions in the SSD are slowly released, and the SSD plays an antibacterial role. The silver ion can promote the healing of the wound to a certain extent, and the silver-containing dressing is widely applied to burn and scald patients and other patients with a series of wounds. A large number of clinical results prove the effectiveness of the silver-containing dressing in the aspect of antibiosis, but many researches prove that the antibacterial performance of pure silver ions is stronger than that of a silver compound, the compound is easy to generate cell toxicity, and the nano silver dressing developed at the later stage also has the risk that nano silver particles can penetrate through cell walls to enter blood, enter blood circulation and deposit in certain organs, and threaten the health of a human body.
Accordingly, the present application provides a copper-containing medical dressing having biological functionality. Copper, as an essential trace metal element in the human body, plays an important role in the maintenance of cardiovascular health. Medical research has found that copper deficiency may lead to the development of a range of cardiovascular diseases, such as coronary heart disease, hypertension, arrhythmia, etc. Studies have demonstrated that copper can affect the expression of growth factors associated with angiogenesis. After a proper amount of copper is added into the existing biomedical materials, the discovery shows that the sustained release of trace copper ions can promote the proliferation and migration of endothelial cells and increase the expression of vascular growth factors in the endothelial cells, thereby accelerating the healing of wounds. A great deal of research proves that the release of the trace copper ions can have the functions of resisting bacterial proliferation, promoting wound healing, promoting angiogenesis and resisting tissue adhesion. Therefore, the copper-containing coating is prepared on the surface of the medical dressing or is directly added into the dressing body, so that multiple biological functions of resisting infection, promoting wound healing, promoting angiogenesis, resisting tissue adhesion and the like after the dressing is pasted on a wound can be realized, and the pain and the economic burden of a patient are reduced.
Disclosure of Invention
The invention aims to add a copper-containing coating with biological functions on the surface of a dressing on the basis of ensuring the basic functions of a medical dressing, so that multiple biological functions of resisting bacterial infection, promoting wound healing, promoting angiogenesis, preventing tissue adhesion and the like of the medical dressing after being applied to a wound are realized.
The technical scheme of the invention is as follows:
a medical dressing having a copper-containing coating, characterized by: the surface of the medical dressing is coated with a copper-containing polymer coating, and the coating contains copper element.
As a preferred technical scheme:
the copper-containing medical dressing with the biological function is characterized in that the medical dressing comprises natural gauze, synthetic fiber dressings, polymeric film dressings, foaming polymeric dressings, hydrocolloid dressings, alginate dressings and the like.
The medical dressing 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 5-500 nm.
The medical dressing 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 dressing 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 dressing 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 dressing 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 dressing 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 dressing is characterized by comprising the following steps: the distribution mode of the copper element in the surface coating polymer of the medical dressing 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 dressing 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 dressing 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 2-120 mg/mL;
(2) preparing a microsphere matrix solution with the mass volume concentration of 2-800mg/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 2-12 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 dressing, and the coating is uniformly distributed at each position of the dressing so as to ensure that the medical dressing 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 dressing layer by using copper-bearing microspheres with different concentrations through a physical blending, chemical grafting or electrostatic adsorption method, 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 dressing is not damaged, so that the basic functions of the medical dressing, infection resistance, wound healing promotion, angiogenesis promotion, tissue adhesion resistance and other biological functions are realized.
The invention has the characteristics and beneficial effects that:
1. the medical dressing containing the copper coating with the biological function, provided by the invention, has multiple biological functions of resisting infection, promoting wound healing, resisting tissue adhesion and the like.
2. The copper-containing coating with biological function can replace the antibiotic medicine coating adopted by the existing medical dressing. 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 cycle of the medical dressing.
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 dressing 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 CuCl2The aqueous solution is slowly dripped into the PACA organic solutionUniformly mixing, adding the mixed solution into a PVA aqueous solution, magnetically stirring at the revolution of 500rpm for 8 hours; 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 dressing by an extraction method, the thickness of the coating is about 0.8 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 dressing layer by layer. The total thickness of the coating is controlled within 5 mu m.
(3) Animal experiments
Attaching the gradient copper-containing medical dressing to a rabbit wound model, taking the copper-free medical dressing as a control group, observing the wound healing condition and the tissue adhesion degree in 15 days, and observing the wound surface after dressing treatment. The experimental result shows that the wound of the medical dressing containing copper is basically completely healed after 15 days of use, and the wound treated by the dressing of the control group still shows red swelling and scabbing phenomena; when the copper-containing medical dressing is separated from the wound, a patient does not feel pain, and the surface of the copper-containing medical dressing does not have the tissue adhesion phenomenon; the surface of the medical dressing of the control group is adhered to the new fiber tissue, and when the dressing is peeled from the wound, the patient feels pain. Therefore, the medical dressing containing copper with biological function of the invention has the characteristics of antibiosis, tissue healing acceleration, tissue adhesion resistance and the like.
Example 2
Preparing a coating with gradient copper-loaded microspheres on the medical dressing 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 dressing by an extraction method;
(2) preparation of copper-loaded microspheres
Weighing 0.20g of chitosan into a 250mL single-neck round-bottom flask, adding 250mL of 2% (mass fraction) acetic acid solution, 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 a 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 (the pH 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 the microspheres is 0.2g and 0.5g respectively, and microspheres with gradient concentration are obtained.
(3) Preparation of gradient copper-loaded polymer coating
The medical dressing 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 medical dressing with the copper-containing coating is observed through a scanning electron microscope, and the surface of the copper-containing coating prepared by the leaching method keeps the original surface morphology of the original dressing. The scanning electron microscope energy spectrum analysis result proves that the copper exists in the coating.
The medical dressing with the copper-containing coating is soaked in normal saline (0.9% NaCl), and leaching liquor is respectively taken 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 medical dressing containing the copper coating with the biological function has good biocompatibility and shows multiple biological functions of antibiosis, wound healing promotion, 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 actual use condition.
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 the prevention of bacterial infection after the dressing is placed through the initial release of copper ions and promotes the healing of tissues. In the later stage, fibrin adhesion is inhibited through the release of trace copper ions, so that the function of resisting tissue adhesion is realized.
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 dressing containing gradient copper is attached to a rabbit wound model, the medical dressing which is prepared by the applied patent and does not have copper ion gradient release is used as a control group, the wound healing condition and the tissue adhesion degree are observed in 15 days, and the wound surface after dressing treatment is observed. The experimental result shows that the wound of the medical dressing containing the copper in the gradient state is basically completely healed after 15 days of use, while the wound treated by the dressing in the control group still shows slight red swelling and scabbing phenomena; when the copper-containing medical dressing is separated from the wound, a patient does not feel pain, and the surface of the copper-containing medical dressing does not have the tissue adhesion phenomenon; the surface of the medical dressing of the control group is adhered to the new fiber tissue, and when the dressing is peeled from the wound, the patient feels pain. Therefore, the gradient copper-containing medical dressing has the characteristics of antibiosis, tissue healing acceleration, tissue adhesion resistance and the like, and is effectively used as a common copper-containing medical dressing.
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 (9)
1. A medical dressing having a copper-containing coating, characterized by: coating a copper-containing polymer coating on the surface of the medical dressing, wherein the coating contains copper element; the copper element is added through copper-carrying microspheres; the copper element concentration is distributed in the coating polymer in a gradient manner, and the polymer is one or more of chitosan and derivatives thereof, polyurethane, cyclodextrin, starch, cellulose, sodium alginate, collagen, polylactic acid, polyethylene glycol and polycarbonate.
2. The medical dressing having a copper-containing coating of claim 1, wherein the medical dressing is one or more of a natural gauze dressing, a synthetic fiber dressing, a polymeric film dressing, a foamed polymeric dressing, a hydrocolloid dressing, and an alginate dressing.
3. The medical dressing having a copper-containing coating according to claim 1, wherein: the copper-carrying microspheres are degradable polymer coating microspheres with the diameter of 5-500 nm.
4. A medical dressing having a copper-containing coating according to claim 3, 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 inorganic copper ions and copper-containing organic substances, 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.
5. A medical dressing having a copper-containing coating according to claim 3, wherein: 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.
6. The medical dressing having 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.
7. A method of making the medical dressing of claim 1, wherein: the distribution mode of the copper element in the surface coating polymer of the medical dressing 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.
8. A method of making a medical dressing according to claim 7, comprising the steps of:
the method comprises the following steps: preparing copper-carrying microspheres 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.
9. The preparation method of the medical dressing according to claim 8, wherein the step one of preparing the copper-loaded microspheres by using a microemulsion method comprises the following steps:
(1) preparing a copper salt aqueous solution with the mass volume concentration of 2-120 mg/mL;
(2) preparing a microsphere matrix solution with the mass volume concentration of 2-800mg/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 2-12 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.
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| CN113398064A (en) * | 2021-07-07 | 2021-09-17 | 福建宸润生物科技有限公司 | Medical copper oxide spray and manufacturing method thereof |
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