KR101150964B1 - Antibacterial wound dressing laminate and method of preparing the same - Google Patents

Abstract

The present invention is a silver nanoparticle-containing nanofiber member; Exudate absorbing member stacked on top of the nanofiber member; And a cover member formed of a transflective film and laminated on the exudation absorbing member, wherein the silver nanoparticle-containing nanofiber member electrospins a spinning solution containing a fiber-forming polymer and a silver (Ag) metal salt. The present invention relates to an antimicrobial dressing laminate and a method for producing the same, wherein the fiber diameter is composed of nanofibers manufactured in a web form having a diameter of less than 1 μm.

Nanofibers, Silver Nanoparticles, Electrospinning, Dressing, Wounds, Wet Environment

Description

Antibacterial wound dressing laminate and method of preparing the same

The present invention covers the damaged skin tissue or wounds caused by wounds, burns, bedsores, traumas, etc. to absorb and remove internal wound secretions, to prevent secondary infections caused by bacteria or foreign substances from the outside, and to maintain a wet environment so that wounds It relates to an antimicrobial dressing laminate and a method for producing the same that can be effectively cured.

Dressing is a method used to improve the healing rate by covering the wound surface, which is a skin defect site caused by burns, cuts, bedsores and traumas. In the dressing method, a dry dressing method of drying a wound surface using gauze or the like to form a crust is common, but in 1962, the rate of epithelial formation of a pig wound was dried by a wet environment. Since the announcement that it is twice as fast as the environment, wet dressing has been developed and released one after another, and various ways of treating wounds have been developed.

Wet dressing is to keep the wound surface wet and to keep it wet.When it is closed, it seals not only the wound surface but also the surrounding normal skin, so when excess exudates and moisture of the normal skin gather, Sores). Therefore, the dressing material should be selected in consideration of the condition of the wound and the absorbency and moisture permeability of the dressing material.

The conditions required for the wet dressing material include (1) creation of a wet environment in which epithelial cells can smoothly migrate the wound surface, and (2) prevention of bacterial invasion from the outside due to rapid growth of bacteria in the wet environment. Prevention of infections that can inhibit proliferation, (3) prevention of damage to new epithelial tissue due to adhesion of wound surface and dressing material, (4) improvement of treatment efficiency by high oxygen supply due to warming effect, (5) external physical Protection to prevent damage caused by impact, (6) prevention of drying of wound surface and invasion of surrounding normal skin with proper moisture permeability and absorption, (7) visibility to observe the healing state of wound surface, no irritation, Ease of use and economy have been discussed, but dressing materials that meet the above requirements have not yet appeared. However, various hydrophilic and hydrophobic polymers can be developed and combined in various forms such as film, sheet, nonwoven fabric, foam, rope, pellet, powder, etc. Manufacturing research is being actively conducted and is rapidly developing.

OpSite ™, a wet dressing material on polyurethane films, first manufactured and marketed by Smith & Nephew in 1972, promoted wound healing by keeping the wound in a wet environment, but too much exudates build up the surrounding skin. There were problems such as softness or exudates leaking out, which had to be discharged arbitrarily and had a problem that the thickness was about 30 to 60 μm and was well torn during use.

In addition, Convatec's DuoDERM ™, released in 1982, is a hydro-colloid dressing that reacts with exudates to form gels when attached to create a moist environment to heal wounds. Because it does not pass, there was a drawback of excessive exudation.

According to a recent announcement, the resistance of bacteria due to misuse of various antibiotics is a serious problem. For example, MRSA (Methicillin Resistant Straphylococcus Aureus), Methicillin-resistant Staphylococcus aureus (VSA), or VRA or Vancomycine-resistant enterococcus (VRE) are antibiotic-resistant pathogenic bacteria, most of which appear in the form of skin infections. In people with a weak immune system, development of bloodstream infections, bone infections, pneumonia, and meningitis can have fatal consequences. As is known, more than one-third of the population has bacteria, such as staphylococci, on the skin and nasal mucosa, which are contagious to others, so if they are injured by burns, wounds, or trauma, they are infected. Is likely to be. However, when these bacteria are resistant to antibiotics, dressing may cause significant problems in treatment.

In this context, recently, dressing products using silver (Ag) have been introduced to provide a wide range of antimicrobial, antifungal and bactericidal action to provide excellent antimicrobial protection against all types of wounds. For example, dressing materials using various types of silver nanoparticle particles, such as PolyMem ^® Silver ™ from Ferris Mfg and Aquacel ^® Ag from SilvaSorb ^® Convatec from AcryMED, have been developed and sold. However, in the case of the dressing material using the silver nanoparticles as described above, it is difficult to uniformly distribute the surface of the silver nanoparticles in the form of a foam dressing, and it is difficult to manage the uniform moisture and keep warm of the wound tissue with a huge pore structure formed of several tens to several hundred μm. There was a drawback of low degree of freedom in form of foam. In particular, when the silver nanoparticles are not uniformly distributed but locally aggregated to have a high concentration, or when the silver nanoparticles detach from the dressing material surface, there is a possibility of damaging or destroying the normal tissue.

Recently, active researches and applications for the electrospinning method for producing a fiber diameter of several tens of nm to several hundred nm using a high voltage electric field in a polymer melt have been conducted. The nanofibers by electrospinning are manufactured in a three-dimensional nonwoven fabric at the same time as the spinning and at the same time nanometer-level fibers are superior to the fibers, and as a new form with a superior surface area, it is likely to be used as a dressing for medical treatment and medical fibers. It's getting very big. Republic of Korea Patent No. 10-0588228 discloses a wound coating using a hydrophilic nanofibers containing a protein component in polyester nanofibers, Patent No. 10-0791039 discloses a method for producing a dressing material using an antioxidant-containing nanofibers It is starting. In case of the above patents, the specific surface area to volume is excellent by using nanofibers, and the wound recovery speed is improved by the functions of proteins, antioxidants, etc., when the wound is healed. It is difficult to expect antimicrobial activity against, and it is difficult to have sufficient mechanical strength by using natural polyester and biocompatible polymer, and there is a problem such as a decrease in strength due to absorption of exudate.

The present invention is to solve the above problems of the prior art, by including a nanofiber member containing silver nanoparticles firmly fixed and uniformly dispersed on the surface of the nanofibers in the wound and contact area, a wide range of antimicrobial On the other hand, it is free from side effects due to desorption of silver nanoparticles, prevents the invasion of pathogens or foreign substances from the outside, and maintains a proper humidity; In addition, an object of the present invention is to provide an antimicrobial dressing laminate and a method for manufacturing the same, which satisfy the optimum humidity conditions for wound healing by a combination of other components constituting the laminate, and completely block invasion of pathogens or foreign substances from the outside. do.

The present invention is a silver nanoparticle-containing nanofiber member; Exudate absorbing member stacked on top of the nanofiber member; And a cover member formed of a transflective film and laminated on the exudation absorbing member.

The antimicrobial dressing laminate, characterized in that the silver nanoparticle-containing nanofiber member is composed of nanofibers produced in the form of a web having a fiber diameter of less than 1 μm by electrospinning a spinning solution containing a fiber-forming polymer and silver (Ag) metal salt. to provide.

In addition, the present invention is a silver nanoparticle-containing nanofiber member; Exudate absorbing member stacked on the nanofiber member; And a cover member formed of a transflective film and stacked on top of the exudation absorbing member, wherein the components are compressed, rolled, thermally bonded, ultrasonically bonded, and a slim sealing tape method. Preparing the laminate by at least one method selected from the group consisting of; And a step of performing a sterilization process by gamma irradiation of 5 kGy to 20 kGy.

In addition, the present invention comprises the steps of placing the exudation absorbing member in advance in the position where the spinning solution containing the fiber-forming polymer and silver (Ag) metal salt is spun; And

The electrospinning of the spinning solution on the exudant absorbing member provides a method of manufacturing the antimicrobial dressing laminate comprising the step of directly depositing the silver nanoparticle-containing nanofiber member on the exudant absorbing member.

The antimicrobial dressing laminate of the present invention includes a nanofiber member containing silver nanoparticles that are firmly fixed and uniformly dispersed on the surface of the nanofibers on the wound surface and in contact with each other, thereby having a wide range of antibacterial properties, while desorption of the silver nanoparticles. It is free from side effects due to, prevents the invasion of pathogens or foreign substances from the outside, and has the effect of maintaining a moderate humidity. In addition, the combination of exudation absorbing member, support layer member, protective layer member, cover member, etc., meets the optimum humidity condition for wound healing and is very effective in wound healing by completely blocking the invasion of pathogens and foreign substances from the outside. .

The present invention is a silver nanoparticle-containing nanofiber member; Exudate absorbing member stacked on top of the nanofiber member; And a cover member formed of a transflective film and laminated on the exudation absorbing member.

In the antimicrobial dressing laminate, the silver nanoparticle-containing nanofiber member is composed of nanofibers manufactured in the form of a web having a fiber diameter of less than 1 μm by electrospinning a spinning solution containing a fiber-forming polymer and silver (Ag) metal salt. It is about.

In the antimicrobial dressing laminate of the present invention, the nanofibers constituting the silver nanoparticle-containing nanofiber member preferably contain silver nanoparticles of 0.5 ppm to 5 ppm relative to the total nanofiber member weight. The antibacterial effect is widely exhibited in the above content range, and side effects on normal tissues due to excessive distribution of silver nanoparticles can be avoided.

In addition, the thickness of the silver nanoparticle-containing nanofiber member is preferably about 10 ~ 300㎛, the handling inconvenience during assembly and molding of the dressing material in the above range is minimized, too thick to affect the conductivity of the collecting plate during spinning. There is no fear of making uniform and smooth nanofibers difficult.

In the antimicrobial dressing laminate of the present invention, the fiber-forming polymer included in the silver nanoparticle-containing nanofiber member includes one or two or more selected from the group consisting of a biocompatible polymer, a biocompatible polymer, and a medical polymer. Can be used in combination. Specific examples include polyacrylnitrile (PAN), cellulose-based polymer (cellulose), polyurethane (polyurethane), polyimide, polybenzimidazole, polymethylmethacrylate (polymethylmethacrylate, PMMA), Polyvinylpyrrolidone (PVP), Polylatic Acid (PLA), Polycarpolactone, Polyvinylachol (PVA), Polyethylene Oxide, Nylon Polymer (nylon), polysulfone-based polymer (poly sulfone), polycarbonate, polystyrene, chitosan (chitosan), collagen (collagen), polyglycolic acid and the like, these may be used alone or two The above can be combined and used.

In the antimicrobial dressing laminate of the present invention, the silver metal salt may be at least one selected from the group consisting of silver nitrate (AgNO ₃ ), silver chloride (AgCl), silver sulfide (Ag ₂ S) and the like.

In the antimicrobial dressing laminate of the present invention, a solvent capable of dissolving a polymer may be used as the electrospinning solvent, and a phenomenon such as solidification or phase separation during dissolution when blending a single component or a multicomponent component may be used. Solvents in which this does not occur are preferred. Representative solvents may be used alone or in combination of two or more selected from the group consisting of DMF, DMAc, THF, acetone, alcohols, chloroform, DMSO, dichloromethane (DCM), acetic acid, fluorine alcohols, water and the like. It is desirable to.

In the present invention, the electrospinning can be carried out by a method known in the art, for example, by connecting the spinning solution to the electrospinning nozzle using a supply device, using a high voltage generator between the nozzle and the current collector This is done by forming a system (10kV ~ 100kV). The magnitude of the electric field is related to the distance between the nozzle and the current collector, and in order to facilitate the electrospinning, a relationship between them is used in combination. In this case, as the electrospinning apparatus to be used, generally used ones may be used, and an electro-blowing method or a centrifugal electrospinning method may be used. Nanofibers prepared by the method as described above is in the form of a nonwoven fabric composed mostly of less than 1㎛.

The silver nanoparticle-containing nanofiber member manufactured by the above method has a feature that the silver particles are firmly fixed and uniformly dispersed.

Since the silver nanoparticle-containing nanofiber member constituting the antimicrobial dressing laminate of the present invention has a fiber diameter of less than 1 μm, since the specific surface area is large, the blockage of viruses, bacteria, and micro-pollution sources is prevented. It is excellent in the wettability that can absorb and maintain the has a feature that can be effectively used in wet dressing.

In the antimicrobial dressing laminate of the present invention, the exudate absorbing member absorbs and stores the exudate and discharges it to the outside (for example, in the form of water) and serves to maintain a continuous absorbing ability. The exudant absorbing member may be composed of hydrophilic nanofibers, soft urethane foam, microfiber woven fabric, microfiber nonwoven fabric, and the like, and may be variously selected according to the type or shape of the wound. For example, when the exudate is excessive, it is preferable to use a flexible urethane foam. When the exudate is small, a woven or nonwoven fabric composed of nanofiber members or microfibers may be used instead of the urethane foam.

When the exudate absorbing member is composed of hydrophilic nanofibers, a support layer member consisting of a microfiber woven or nonwoven fabric may be further included between the exudate absorbing member and the cover member.

The antimicrobial dressing laminate of the present invention may further include a protective layer member between the exudate absorbing member and the cover member to prevent pathogens or foreign substances from invading from the outside and to release the exudate of the exudate absorbing member to the outside in the form of water. have. As the protective layer member, nanofibers by electrospinning are preferable, but a semipermeable membrane film made of a microfiber, a nonwoven fabric, or a polyurethane may be used according to the shape or type of the wound.

The protective layer member should have an appropriate moisture permeability, it is preferable to have a moisture permeability of about 10 ~ 100g / ㎡ / hr. If the moisture permeability is too low, the exudates may not be released in the form of water, and the exudates may accumulate in the wound, causing sores to the surrounding normal tissues. If the moisture permeability is too high, the wound surface becomes dry and necrotic tissue is formed. The back may develop and delay wound healing.

In the antimicrobial dressing laminate of the present invention, when the nanofibers by electrospinning are included as the protective layer member, it is preferable to use a soft urethane foam, a microfiber woven fabric or a microfiber nonwoven fabric as the exudant absorbing member. . In the case of having the configuration as described above, the silver nano-containing nanofiber member and the protective layer member have a double defense effect against invading pathogens or foreign substances from the outside.

In the antimicrobial dressing laminate of the present invention, the cover member formed of the transflective film and laminated on the exudation absorbing member serves to fix the dressing material around the wound. Therefore, it is required to have elasticity and excellent high moisture permeability as the adhesive tape. The transflective film may be a highly moisture-permeable polyurethane film, a polyethylene net film, or nanofibers by electrospinning.

In the antimicrobial dressing laminate of the present invention, the sterilization process of the antimicrobial dressing laminate is steam sterilization, ethylene oxide (EtO) sterilization, gamma-ray irradiation method generated from cobalt 60 ( ⁶⁰ Co), which is a radioisotope. It is carried out through a variety of methods, preferably by performing gamma irradiation of 5 kGy ~ 20kGy to finally prepare an antimicrobial dressing laminate. When the antimicrobial dressing laminate is manufactured by gamma irradiation in the sterilization process, the dissolution resistance to blood of the antimicrobial dressing laminate may be improved, and the tensile strength and adhesive properties may be improved.

The antimicrobial dressing laminate of the present invention may include a therapeutic drug in the silver nanoparticle-containing nanofiber member and / or exudate absorbent member.

The method for including the therapeutic drug in the silver nanoparticle-containing nanofiber member or the exudate absorbing member is a method of preparing by including the therapeutic drug in the raw material such as spinning solution in the process of manufacturing the silver nanoparticle-containing nanofiber member or the exudate absorbing member , Method of manufacturing by impregnating the prepared silver nanoparticle-containing nanofiber member or exudate absorbing member into a solution containing a therapeutic drug, spraying the therapeutic drug or coating the surface of the prepared silver nanoparticle-containing nanofiber member or exudate absorbing member Various methods, such as the manufacturing method can be used.

The antimicrobial dressing laminate of the present invention can be usefully used for all types of medical patches and the like that require antibacterial function.

In addition, the present invention is a silver nanoparticle-containing nanofiber member; Exudate absorbing member stacked on top of the nanofiber member; And a cover member formed of a transflective film and stacked on top of the exudation absorbing member, wherein the components are compressed, rolled, thermally bonded, ultrasonically bonded, and a slim sealing tape method. Preparing the laminate by at least one method selected from the group consisting of; And a step of performing a sterilization process by gamma-ray irradiation of 5 kGy to 20 kGy.

In addition, the present invention comprises the steps of placing the exudation absorbing member in advance in the position where the spinning solution containing the fiber-forming polymer and silver (Ag) metal salt is spun; And

It relates to a method for producing the antimicrobial dressing laminate comprising the step of directly laminating the silver nanoparticle-containing nanofiber member on the exudant absorbing member by performing the electrospinning of the spinning solution on the exudant absorbing member. It is also possible to produce a laminate of the silver nanoparticle-containing nanofiber member and the exudant absorbing member by spinning the exudate absorbing member on the silver nanoparticle-containing nanofiber member.

According to this method, the step of joining the silver nanoparticle-containing nanofiber member and the exudate absorbing member can be omitted, which is very economical.

Hereinafter, the present invention will be described in more detail by way of examples. However, the following examples are provided to illustrate the present invention, and the present invention is not limited to the following examples and may be variously modified and changed.

Example  One.

PLA was dissolved in DMF and chloroform solvent (30/70 wt.%) To 15% by weight (based on solids), and AgNO ₃ was added at 0.0001 parts by weight based on 100 parts by weight of PLA solids to form a spinning solution. Prepared.

The spinning solution prepared in this way was connected to the spinneret, and the electrospinning was carried out while discharging at an applied voltage of 50 kV or less, a distance of 25 cm between the spinneret and the current collector, and 0.1 to 1 cc / g per hole, thereby producing PLA nanofibers containing silver nanoparticles. Got it. At this time, the average diameter of the PLA nanofibers was about 700 ~ 900nm, as shown in Figure 3 (a), the scanning electron micrograph of the cross section is shown in Figure 3 (b).

Figure 4 is to evaluate the antimicrobial activity of silver nanoparticles containing PLA nanofibers, by using the method of KS 0593: 2008 using (a) Staphylococcus aureus and (b) CNS, the causative agent of pneumococcus, which is typically a high antibiotic resistance rate The bacteriostatic reduction rate (%) was evaluated by the number of sugar bacteria. The evaluation results showed that the silver nanoparticle-containing PLA nanofibers exhibited 99.99% antimicrobial activity against (a) Staphylococcus aureus and (b) CNS.

Example  2.

Polyurethane (Polyurethane) was mixed with DMF and THF mixed solvent (40/60% by weight) to 15% by weight (based on solids) to prepare a spinning solution. The prepared spinning solution was electrospun on the silver nanoparticle-containing PLA nanofiber nonwoven fabric prepared in Example 1 in the same manner as in Example 1 to prepare a composite nonwoven fabric.

5 shows a scanning electron micrograph of the polyurethane nanofibers electrospun above. The diameter distribution of the polyurethane nanofibers was about 300-500 nm. In addition, the water vapor transmission rate of the composite nonwoven fabric of the PLA nanofibers containing the polyurethane nanofibers and the silver nanoparticles was expressed as P value using calcium chloride (CaCl ₂ ) [P = CaCl ₂ increase / transmission area X time (mg / cm ² h). )], The measurement conditions were the temperature 40 (± 2) ℃ and humidity 90 (± 5)%, and the average of the five measurements. As a result, there was variation according to thickness, but P value was about 5,000 ~ 8,000.

Example  3.

As a nanofiber support, a fabric composed of poly (isobutyl-co-maleic acid) -salt, which is an absorbent fiber, and PLA nanofibers containing silver nanoparticles prepared in Example 1 were used. Bonding was carried out using a slim sealing tape method. Fig. 6 (a) shows the cross-sectional scanning electron micrograph of the absorbent fiber, and Fig. 6 (b) shows the cross-sectional shape of the composite bonded above with the scanning electron microscope.

1 is a cross-sectional view (a) and a perspective view (B) of an antimicrobial dressing laminate prepared as an embodiment of the present invention.

Figure 2 is a view showing the assembly structure of each component of the antimicrobial dressing laminate produced as an embodiment of the present invention.

3 is a scanning electron micrograph of the silver nanoparticle-containing PLA nanofibers prepared in Example 1 of the present invention ((a) surface, (b) cross section).

Figure 4 is a photograph showing the antimicrobial activity evaluation results of the silver nanoparticle-containing PLA nanofibers prepared in Example 1 of the present invention ((a) Staphylococcus aureus, (b) CNS).

5 is a scanning electron micrograph of the moisture-permeable PU nanofibers prepared in Example 2 of the present invention ((a) x1K, (b) x 30K].

6 is a scanning electron micrograph of a fabric composed of a poly (isobutyl-co-maleic acid) salt, which is an absorbent fiber prepared in Example 3 of the present invention, and a PLA nanofiber composite containing silver nanoparticles ((a) Absorbency) Cross section of the fiber, (b) cross section of the composite].

* Description of Drawing Symbols *

100: antimicrobial dressing laminate 10: silver nanoparticle-containing nanofiber member

20: exudate absorbing member 30: protective layer member

40: cover member formed of a transflective film

Claims (13)

Silver nanoparticle-containing nanofiber members; Exudate absorbing member stacked on top of the nanofiber member; And A laminate comprising a cover member formed of a transflective film and stacked on top of the exudant absorbing member. The silver nanoparticle-containing nanofiber member is a nanofiber made in the form of a web having a fiber diameter of less than 1 μm by electrospinning a spinning solution containing a fiber-forming polymer and silver (Ag) metal salt, A protective layer member made of nanofibers having a moisture permeability of 10 to 100 g / m 2 / hr capable of protecting against invading pathogens or foreign substances from outside and releasing the exudates of the exudate absorbing member to the outside between the exudate absorbing member and the cover member The antimicrobial dressing laminate further comprises. The antimicrobial dressing laminate according to claim 1, wherein the exudant absorbing member is composed of hydrophilic nanofibers, soft urethane foam, microfiber woven fabric or microfiber nonwoven fabric. The antimicrobial dressing laminate according to claim 2, wherein the exudant absorbing member is composed of hydrophilic nanofibers, and a support layer member made of a microfiber woven fabric or a microfiber nonwoven fabric is further included between the exudant absorbing member and the cover member. delete delete The antimicrobial dressing laminate according to claim 1, wherein the exudant absorbing member is composed of a flexible urethane foam, a microfiber woven fabric, or a microfiber nonwoven fabric. The antimicrobial dressing laminate according to claim 1, wherein the semipermeable film is a highly moisture-permeable polyurethane film, a polyethylene net film, or nanofibers by electrospinning. The antimicrobial dressing laminate according to claim 1, wherein the nanofibers constituting the silver nanoparticle-containing nanofiber member contain silver nanoparticles in an amount of 0.5 ppm to 5 ppm with respect to the total nanofiber weight. The antimicrobial dressing according to claim 1, wherein the fiber-forming polymer included in the silver nanoparticle-containing nanofiber member is one or a combination of two or more selected from the group consisting of a biocompatible polymer and a biocompatible polymer. Laminate. The silver metal salt contained in the silver nanoparticle-containing nanofiber member is at least one member selected from the group consisting of silver nitrate (AgNO ₃ ), silver chloride (AgCl) and silver sulfide (Ag ₂ S). Antibacterial dressing laminate. The antimicrobial dressing laminate according to any one of claims 1 to 3 and 6 to 10, wherein the therapeutic agent is further included in the silver nanoparticle-containing nanofiber member. Silver nanoparticle-containing nanofiber members; Exudate absorbing member stacked on top of the nanofiber member; A protective layer member composed of nanofibers stacked on top of the exudant absorbing member; And a cover member formed of a transflective film and stacked on the protective layer member. Manufacturing the components into a laminate by one or more methods selected from the group consisting of pressing, rolling, thermal bonding, ultrasonic bonding, and slim sealing tape; And performing a sterilization process by gamma irradiation of 5 kGy to 20 kGy. Placing an exudant absorbing member in advance at a position where a spinning solution comprising a fiber-forming polymer and a silver (Ag) metal salt is spun; And The method of manufacturing the antimicrobial dressing laminate according to claim 1, comprising directly depositing the silver nanoparticle-containing nanofiber member on the exudant absorbing member by performing electrospinning of the spinning solution on the exudant absorbing member.

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