CN108478843A - With the medical dressing and preparation method thereof containing copper coating - Google Patents

With the medical dressing and preparation method thereof containing copper coating Download PDF

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Publication number
CN108478843A
CN108478843A CN201810118474.4A CN201810118474A CN108478843A CN 108478843 A CN108478843 A CN 108478843A CN 201810118474 A CN201810118474 A CN 201810118474A CN 108478843 A CN108478843 A CN 108478843A
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copper
medical dressing
coating
dressing
microballoon
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CN108478843B (en
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陈姗姗
杨柯
张炳春
杨辉
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Institute of Metal Research of CAS
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Institute of Metal Research of CAS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/18Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/20Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/46Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/62Compostable, hydrosoluble or hydrodegradable materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/42Anti-thrombotic agents, anticoagulants, anti-platelet agents

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

There is the medical dressing containing copper coating the invention discloses a kind of.By the copper-loaded microballoon of various concentration it is by certain mode gradient distribution fixed/be dispersed in the polymer support on medical dressing surface, to realize the biological functional of medical dressing.Wherein, the fixed form of the copper-loaded microballoon of functionalization includes chemical graft, physical blending, electrostatic interaction etc..It is this to have after dressing of the biological functional containing copper coating is attached at wound, antibacterium proliferation can be played, promote wound healing, new vessels is promoted to generate and the effect of anti-tissue adhesion, the problems such as to which infection or difficult healing occur after avoiding dressing from being attached at wound.

Description

With the medical dressing and preparation method thereof containing copper coating
Technical field
The present invention relates to dressings medical instruments field more particularly to a kind of Medical coatings applied to Hard agglut wound position Material rises and completely cuts off and prevent bacterium intrusion, breeding, the cupric for promoting speed of wound healing, new vessels being promoted to generate and prevent adhesion Medical dressing
Background technology
Dressing, that is, the covering being used in outside wound, in wound healing process can substitute damaged skin plays temporarily Property protective effect, avoid or control wound infection, provide the body surface that is wound suitable healing environment.Traditional dressing can play The effect of supervision covering wound, it is impossible to be used in infected wound does not have facilitation, sepage managerial ability to have wound healing Limit, adhesion wound damage newborn epithelial tissue and cause bleeding again, pain after patient's more change dressings.It is good in order to provide Wound healing environment reduces scar and promotes the comfort level of user, and Medical dressing gradually replaces and is only capable of in recent years The traditional dressing of simplest insulation blocking effect is provided.
With the proposition of wound wet union theory, many new pattern compress are constantly developed the novel medical dressing of Include mainly alginates dressing, polyurethanes dressing, Hydrogels dressing, film class dressing etc..Although dressing type is numerous It is more, but these novel dressing can provide a moist environment for wound, can effectively facilitate wound healing.In addition to for Wound provides moist environment to promote outside wound healing, and anti-microbial type dressing is also directed to the infection that may be faced in wound healing process Problem and generate.
Since sulfanilamide (SN) silver Silver sulfadiazine (SSD) begin to use after burn wound, silver ion quilt therein It slowly releases, plays the role of antibacterial.Silver ion can promote the healing of wound, silver dressings quilt in certain degree It is widely used in burn and scald sufferer and a series of other sufferers for wound occur.A large amount of clinical effectiveness confirm silver dressings In the validity of antibiosis, but many studies demonstrate that, the anti-microbial property of fine silver ion is stronger than the compound of silver, and compound compared with Easy to produce the toxicity of cell, the Nanometer silver dressing that later stage hair is opened there is also nanometer-level silver particle can penetration cell wall enter blood Liquid into blood circulation and is deposited in certain organs, there is the risk for threatening health.
Therefore, the application proposes a kind of cupric medical dressing with biological function.Copper is as required one kind in human body Minor metallic element plays an important role in terms of safeguarding cardiovascular health.Medical research is it has been found that the shortage of copper may It can lead to a series of generation of angiocardiopathies, such as coronary heart disease, hypertension, arrhythmia cordis.Research has shown that, copper can influence with The expression of the growth factor of associated angiogenesis.It is found after adding copper in right amount into existing bio-medical material, micro copper ion Sustained release can promote proliferation and the migration of endothelial cell, increase the expression of endothelial cell medium vessels growth factor, thus Accelerate the healing of wound.The release that numerous studies have had proven to micro copper ion can have antibacterium proliferation, wound is promoted to be cured Close, promote the function of new vessels generation and anti-tissue adhesion.Therefore, copper coating will be contained and be prepared in medical dressing surface or direct Be added in dressing ontology, it can be achieved that dressing be pasted on after wound it is anti-infective, promote wound healing, new vessels promoted to generate And the multi-biological functionals such as anti-tissue adhesion, to reduce pain and the financial burden of sufferer.
Invention content
The purpose of the present invention is on the basis of ensureing medical dressing basic function, having life in dressing surface addition one kind Object function contains copper coating, realize bacterial-infection resisting of the medical dressing after being pasted on wound, promote wound healing, promote it is newborn The multi-biological functionals such as angiogenesis and preventing tissue adhesion.
Technical solution of the present invention is as follows:
It is a kind of that there is the medical dressing containing copper coating, it is characterised in that:It is coated on medical dressing surface and contains copper polymer Coating contains copper in the coating.
As preferred technical solution:
The cupric medical dressing with biological function, which is characterized in that the type of medical dressing includes natural yarns Cloth, the dressing of synthetic fibers class, the dressing of poly film class, the dressing of foaming multi-cluster, the dressing of hydrocolloid class, alginate dressing etc..
It is described that there is the medical dressing containing copper coating, it is characterised in that:The copper is added by copper-loaded microballoon, copper-loaded Microballoon is degradable polymer coated microsphere of the diameter in 5-500nm.
It is described that there is the medical dressing containing copper coating, it is characterised in that:The microsphere matrices material of copper-loaded microballoon is with good The polymer of good film forming, biocompatibility and degradability, such as polytrimethylene carbonate (PTMC), polybutylcyanoacrylate (PACA), poly- hydroxy alkyl alcohol ester (PHAs), PHB (poly- 3- carboxyls butyrate), polymeric polyglycolide-polylactide copolymer (PLGA), Polycaprolactone (PCL), polyacrylic acid, cellulose, chitosan etc. it is one or more, contained copper-containing substance be nano level metal copper Powder, inorganic copper ion, cupric organic matter it is one or more.
It is described that there is the medical dressing containing copper coating, it is characterised in that:The size of the nano level metal copper powder is in 10- In the range of 200nm, inorganic copper ion from basic copper sulfate, copper oxychloride, Kocide SD it is one or more, cupric is organic Object be copper acetate, amino acid copper, copper 8-hydroxyquinolinate it is one or more.
It is described that there is the medical dressing containing copper coating, it is characterised in that:In copper-loaded microballoon, host material and copper-containing substance Molar ratio is 100:1-2:In the range of 1.
It is described that there is the medical dressing containing copper coating, it is characterised in that:The copper concentration in gradient is distributed in painting In one polymer;The polymer is chitosan and its derivative, polyurethane, cyclodextrin, starch, cellulose, sodium alginate, glue The synthetic polymers such as original, polylactic acid, polyethylene glycol, makrolon and natural polymer.
It is described that there is the medical dressing containing copper coating, it is characterised in that:The cupric polymer coating thickness is less than or equal to 5 μm。
The preparation method of the medical dressing, it is characterised in that:Copper is in medical dressing surface coating polymerization object Distribution mode is:In the form of copper-loaded microballoon, copper-loaded microballoon gradient is dispersed in polymer coating by being layered the preparation method.
The preparation method of the medical dressing, which is characterized in that include the following steps:
Step 1:Copper-loaded microballoon is prepared using microemulsion method.
Step 2:The copper-loaded microsphere polymer solution for preparing different ratio, successively being prepared by extraction or spray coating method has The polymer coating of copper-loaded microballoon.
The preparation method of the medical dressing, which is characterized in that copper-loaded microballoon packet is prepared using microemulsion method in step 2 Include following steps:
(1) copper salt solution that mass-volume concentration is 2-120mg/mL is prepared;
(2) the microsphere matrices solution that mass-volume concentration is 2-800mg/mL is prepared, solvent is volume ratio chloroform:Third Ketone=1:4—4:1;
(3) the PVA aqueous solutions that mass-volume concentration is 1-200mg/mL are prepared;
(4) copper salt solution is added in microsphere matrices solution, mixed liquor is added in PVA aqueous solutions after stirring evenly;
(5) method of mechanical agitation or ultrasonic vibration is used to prepare varigrained microballoon, wherein agitation revolution is in 500- In the range of 5000rpm, mixing time 2-12h;Ultrasonic power is in the range of 50-100W, ultrasonic time 5-25min;
(6) reaction microballoon obtained is collected using the method for centrifugation or rotary evaporation, wherein:
The revolution that centrifugal process is taken is 500-2000rpm, removes supernatant after centrifugation, microballoon is deposited in distilled water Suspend cleaning, dry;
The rotating speed that rotary evaporation is taken is 10-50rpm, will settle the solution of certain time, removes supernatant, by lower layer Reaction solution is added in Rotary Evaporators, and it is 30-45 DEG C that temperature, which occurs, time 30min-2h.
The design philosophy of the present invention:
It is prepared on medical dressing surface and contains copper coating with biological function, coating should be evenly distributed in each position of dressing It sets, after ensuring medical dressing merging, plays the biological functions such as anticoagulation, anti-infective, anti-tissue adhesion.By the load of various concentration Copper microballoon is prepared in medical dressing surface layer-by-layer using the method for physical blending, chemical graft or Electrostatic Absorption and contains copper coating, made Coating copper content has the characteristics that gradient distribution, coated carrier are that medical grade degradable high polymer material (be shown in attached by schematic diagram containing copper coating Fig. 2).When prepared by copper-loaded microballoon, microballoon case material should be biodegradable, and film forming is good and has good biocompatibility High molecular material.In coating preparation process, by the amount of microballoon contained by copper content in adjusting microballoon or coating, gradient distribution is built Containing copper coating.In coating preparation process, medical dressing structure should not be damaged, to realize the basic training of medical dressing Energy and anti-infective, promotion wound healing promote the biological functions such as new vessels generation and anti-tissue adhesion.
The features of the present invention and advantageous effect are:
1. a kind of medical dressing containing copper coating with biological function provided by the invention makes dressing have anti-infective, rush Into multi-biological functionals such as wound healing, anti-tissue adhesions.
2. of the present invention contain copper coating with biological function, antibiotic used by alternative current medical dressing Medication coat.There is anti-infectious characteristic containing copper coating, can avoid caused by medication coat the problem of bacterial drug resistance.
3. the present invention can not only be used as a kind of biological functional " medication coat ", also there is anticoagulation, anti-tissue adhesion Function, to reduce occur thrombus and organize adhesion risk, extend the service life of medical dressing.
Description of the drawings
The copper-loaded microballoon pattern schematic diagrames of Fig. 1.
Fig. 2 has schematic diagram of the biological functional containing copper coating of the copper-loaded microballoon of gradient distribution.
Specific implementation mode
Following embodiment will be further described the present invention, but not thereby limiting the invention.
Embodiment 1
Successively chemical graft process prepares the coating with the copper-loaded particle of gradient distribution on medical dressing:
The copper-loaded microballoon with hydroxyl, carboxyl isoreactivity functional group is fixed on amino using successively chemical graft process On the natural degradable chitosan polymer of hydroxyl, every layer of copper-loaded amount is changed in gradient, discharges copper by coating gradientsization Ion realizes that the biological functional containing copper coating is controllable.
(1) preparation of copper-loaded microballoon
1. weighing 0.05g, 0.2g and 0.5gCuCl2, and it is dissolved separately in three kinds of uniform solutions of preparation in 5mL distilled water;
2. 1.0gPACA is dissolved in (wherein, chloroform in the mixed solution of chloroform and acetone again:The volume of acetone Than being 3:2) the PACA organic solutions that mass-volume concentration is 100mg/mL, are made;
3. weighing PVA1.0g, it is dissolved in distilled water, makes the PVA aqueous solutions that mass-volume concentration is 20mg/mL, Mixing is for use;
4. by CuCl2Aqueous solution is slowly dropped into PACA organic solutions, is uniformly mixed, then PVA is added in above-mentioned mixed liquor In aqueous solution, magnetic agitation, revolution 500rpm is stirred 8 hours;In the range of 50-100W, ultrasonic time is ultrasonic power 5min;
5. reaction solution stands 2 hours, supernatant is removed, lower sediment is transferred in Rotary Evaporators, under 30 degrees Celsius, rotation It steams 30 minutes, obtains a large amount of microsphere powders.
The copper-loaded microballoon that different copper-loaded amounts are prepared with method, the difference is that weighing CuCl2Quality be respectively 0.2g and 0.5g, The microballoon of gradient concentration is obtained, microballoon pattern is shown in attached drawing 1.
(2) preparation of the copper-loaded polymer coating of gradient distribution
1. preparing 1% acetum
It takes the glacial acetic acid reagent of 1mL in 100ml volumetric flasks, is slowly added to distilled water, and constant volume thereto, mixing waits for With.
2. preparing 1% chitosan solution
Chitosan powder 1g accurately is weighed, by the prepared acetums of 100ml and powder mixing, 24 hours is stood, removes Bubble is for use.
3. the preparation of the copper-loaded coating of single layer
Chitosan coat is prepared on medical dressing by extraction, about 0.8 μm of coating layer thickness, after drying to be coated, Under EDC/NHS catalytic action, the copper-loaded microballoon of low concentration is grafted on chitosan coat.
4. the preparation with the copper-loaded microballoon coating of gradient distribution
The preparation method for repeating the copper-loaded coating of single layer prepares the copper-loaded micro- of different copper-loaded concentration in medical dressing surface layer-by-layer Ball coating.Total coating thickness controls within 5 μm.
(3) zoopery
There to be gradient distribution cupric medical dressing to be attached in rabbit wound model, as a contrast with no cupric medical dressing Group, 15 days observation wound healing situations and tissue adhesion degree, to dressing, treated that wound surface is observed.Experimental result Show that wound heals completely substantially after using 15 days with cupric medical dressing, and uses the wound of control group dressing processing Still show red and swollen, incrustation phenomenon;When cupric medical dressing is with wound separation, sufferer is painless, and surface inorganization adhesion is existing As occurring;And control group medical dressing surface is then with newborn fibr tissue adhesion, when dressing and wound are removed, sufferer is felt to ache Bitterly.Therefore, there is the present invention cupric medical dressing of biological function to show antibacterial, acceleration organization healing, anti-tissue adhesion etc. Characteristic.
Embodiment 2
Successively Electrostatic Absorption method prepares the coating with the copper-loaded microballoon of gradient distribution on medical dressing:
(1) aqueous solution (concentration 1-5%) for preparing negatively charged Sodium Hyaluronate, by extraction in medical dressing Inside/outside surface prepares hyaluronic acid coatings;
(2) preparation of copper-loaded microballoon
1. weighing 0.20g chitosans in 250mL single necked round bottom flask, 2% (mass fraction) acetum is added 250mL opens electric mixing device and is slowly stirred until chitosan is completely dissolved.
2. Span-80 0.4mL and Tween-80 0.6mL are added while stirring, continue stirring 30min and be allowed to be formed Microemulsion that is even, transparent, stablizing.0.05g copper sulphate powders are subsequently added into, it is uniform that high-speed stirred is allowed to diffusion;
3. 1molL then, is slowly added dropwise-1NaOH solution, while at the uniform velocity stirring, with PHS-3B type precisions pH meter (in State's Shanghai thunder magnetic) variation of detection architecture pH value at 25 DEG C, until alkalescence (pH value 7.20);
4. after NaOH solution is added dropwise, simultaneously 0.30g trisodium citrates are added in moderate-speed mixer, continue to stir 3h, make lotion The chitosan micro-sphere crosslinked solidification of middle formation, obtained transparency emulsion are detached with centrifuge;
5. lower sediment is transferred in Rotary Evaporators, under 30 degrees Celsius, rotates 30 minutes, obtain a large amount of microsphere powders.
The copper-loaded microballoon that different copper-loaded amounts are prepared with method, the difference is that weighing CuSO4Quality be respectively 0.2g and 0.5g, Obtain the microballoon of gradient concentration.
(3) preparation of the copper-loaded polymer coating of gradient distribution
It is water-soluble with the copper-loaded microballoon of electropositive low concentration by being immersed with the medical dressing of elecrtonegativity hyaluronic acid coatings In liquid, microballoon will be fixed on by electrostatic interaction on hyaluronic acid coatings.
Repeat the preparation method of above signal layer coating, structure has the copper-loaded microballoon of gradient distribution (copper content successively increment mode) Polymer coating.
(4) preparation of hydrophily outer layer
Outside the polymer coating for being loaded with the copper-loaded microballoon of gradient distribution, it is poly- that one layer of 1 μm of < is prepared by Ultrasonic spraying method Ethylene glycol coating.
(5) characterization containing copper coating
The surface topography that the medical dressing containing copper coating is carried by scanning electron microscopic observation shows to prepare by extraction Surface containing copper coating keeps the initial surface form of former dressing.Sem energy spectrum analysis is as a result, it was confirmed that there is copper in coating In the presence of.
It will be immersed in physiological saline (0.9%NaCl) with the medical dressing containing copper coating, after 1,7,14,28 day respectively Take leaching liquor.By plasma inductive coupling-atomic absorption spectrography (AAS) (ICP-AAS) to the copper ion concentration in leaching liquor into Row test, the results showed that, in soaking process, the copper in coating dissolves out in the form of an ion, and stripping quantity is in the ppb orders of magnitude.
Containing copper coating medical dressing of the present invention with biological function can be with good biocompatibility, and shows to resist Bacterium promotes the multi-biological functionals such as wound healing and anti-tissue adhesion.
Comparative example 3
It will be prepared in embodiment 2 special with preparation method of the copper-loaded microballoon of gradient distribution containing copper coating and the invention applied (patent publication No. is profit " a kind of biodegradable copper-containing coating pure magnesium anastomosis staple and its preparation ":CN 103110977A) in carry The method of the Coating copper ion coating of confession is compared, molten by comparing the ion of the coating of two methods preparation in vitro Go out performance, and actual use situation, safety containing copper coating and validity prepared by two methods of evaluation.
By embodiment 2 it is found that the present invention have the copper-loaded microballoon of gradient distribution contain copper coating, it can be achieved that device be implanted into initial stage, Release is enough to express the copper ion concentration of biological function from coating, and by coating design, the copper-loaded amount of copper-loaded microballoon it is micro- It transfers to ensure amount of copper ions released within the scope of bio-safety;Coating avoids dressing from setting by the copper ion that initial stage discharges to realize Bacterium infection after entering occurs, and promotes organization healing.It is placed in the later stage, inhibits fibrin glutinous by the release of micro copper ion It is attached, to realize the function of anti-tissue adhesion.
And according to the coating copper ion coating provided in the patent applied, then do not have the effect of copper ion gradient release The burst size of fruit, copper ion only depends on the property of coated carrier, such as the carrier with water-soluble or degradation rate quickly, then is implanted into In the process, the copper in coating may discharge, and when reaching target location, not enough copper ions have acted on surrounding Tissue;Such as with the slow carrier of degradation rate, then initial stage, not enough copper ion discharged to realize its multi-biological work(after being implanted into It can property.
There is gradient distribution cupric medical dressing to be attached in rabbit wound model the present invention, it is standby with the patent system applied Do not have copper ion gradient release medical dressing as a control group, 15 days observation wound healing situations and tissue adhesion journey Degree, to dressing, treated that wound surface is observed.The experimental results showed that using 15 with gradient distribution cupric medical dressing Wound heals completely substantially after it, and the wound of control group dressing processing still shows mild redness, incrustation phenomenon;Cupric is medical When dressing is with wound separation, sufferer is painless, and surface inorganization adhesion phenomenon occurs;And control group medical dressing surface then with Newborn fibr tissue adhesion, when dressing is removed with wound, sufferer feels pain.Therefore, the present invention has gradient distribution cupric medical Dressing shows antibacterial, accelerates the characteristics such as organization healing, anti-tissue adhesion, effectively due to common cupric medical dressing.
The above experimental result and analysis shows, application protection there is the copper-loaded microballoon of gradient distribution to apply in the claims in the present invention Layer and preparation method thereof has apparent excellent effect.

Claims (10)

1. a kind of having the medical dressing containing copper coating, it is characterised in that:It is coated on medical dressing surface and is applied containing copper polymer Layer, contain copper in the coating.
2. the cupric medical dressing described in accordance with the claim 1 with biological function, which is characterized in that the type of medical dressing For natural gauze, the dressing of synthetic fibers class, the dressing of poly film class, the dressing of foaming multi-cluster, the dressing of hydrocolloid class, alginate dressing It is one or more.
3. according to having the medical dressing containing copper coating described in claim 1, it is characterised in that:The copper passes through copper-loaded micro- Ball adds, and copper-loaded microballoon is degradable polymer coated microsphere of the diameter in 5-500nm.
4. according to having the medical dressing containing copper coating described in claim 3, it is characterised in that:The microsphere matrices material of copper-loaded microballoon Material is polytrimethylene carbonate (PTMC), polybutylcyanoacrylate (PACA), poly- hydroxy alkyl alcohol ester (PHAs), PHB (poly- 3- carboxyls butyrate), polymeric polyglycolide-polylactide copolymer (PLGA), polycaprolactone (PCL), polyacrylic acid, cellulose, shell it is poly- Sugared is one or more, and contained copper-containing substance is one kind or more of nano level metal copper powder, inorganic copper ion, cupric organic matter Kind, the size of nano level metal copper powder in the range of 10-200nm, inorganic copper ion from basic copper sulfate, copper oxychloride, Kocide SD it is one or more, cupric organic matter be copper acetate, amino acid copper, copper 8-hydroxyquinolinate it is one or more.
5. according to having the medical dressing containing copper coating described in claim 3, it is characterised in that:In copper-loaded microballoon, host material Molar ratio with copper-containing substance is 100:1-2:In the range of 1.
6. according to having the medical dressing containing copper coating described in claim 1, it is characterised in that:The copper concentration in gradient Change be distributed in coated polymeric, the polymer be chitosan and its derivative, polyurethane, cyclodextrin, starch, cellulose, Sodium alginate, collagen, polylactic acid, polyethylene glycol, makrolon it is one or more.
7. according to having the medical dressing containing copper coating described in claim 1, it is characterised in that:The cupric polymer coating is thick Degree is less than or equal to 5 μm.
8. the preparation method of medical dressing described in a kind of claim 1, it is characterised in that:Copper is in medical dressing face coat Distribution mode in polymer is:In the form of copper-loaded microballoon, copper-loaded microballoon gradient is dispersed in polymerization by being layered the preparation method In object coating.
9. according to the preparation method of medical dressing described in claim 8, which is characterized in that include the following steps:
Step 1:Copper-loaded microballoon is prepared using microemulsion method;
Step 2:The copper-loaded microsphere polymer solution for preparing different ratio is successively prepared by extraction or spray coating method with copper-loaded The polymer coating of microballoon.
10. according to the preparation method of medical dressing described in claim 9, which is characterized in that use microemulsion legal system in step 1 Standby copper-loaded microballoon includes the following steps:
(1) copper salt solution that mass-volume concentration is 2-120mg/mL is prepared;
(2) the microsphere matrices solution that mass-volume concentration is 2-800mg/mL is prepared, solvent is volume ratio chloroform:Acetone= 1:4—4:1;
(3) the PVA aqueous solutions that mass-volume concentration is 1-200mg/mL are prepared;
(4) copper salt solution is added in microsphere matrices solution, mixed liquor is added in PVA aqueous solutions after stirring evenly;
(5) method of mechanical agitation or ultrasonic vibration is used to prepare varigrained microballoon, wherein agitation revolution is in 500- In the range of 5000rpm, mixing time 2-12h;Ultrasonic power is in the range of 50-100W, ultrasonic time 5-25min;
(6) reaction microballoon obtained is collected using the method for centrifugation or rotary evaporation, wherein:
The revolution that centrifugal process is taken is 500-2000rpm, removes supernatant after centrifugation, microballoon is deposited in distilled water and is suspended Cleaning, it is dry;
The rotating speed that rotary evaporation is taken is 10-50rpm, will settle the solution of certain time, removes supernatant, lower layer is reacted Liquid is added in Rotary Evaporators, and it is 30-45 DEG C that temperature, which occurs, time 30min-2h.
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