medical dressing and method of making a medical dressing

专利摘要:
A medical dressing (1; 20) is disclosed, comprising a substrate (2) comprising a first chemical compound, said substrate having a first surface (4), wherein said medical dressing additionally comprises an adhesive layer (3) having a skin-facing surface (6) for gluing said medical dressing to a dermal surface, wherein at least a part of said skin-facing surface comprises a coating (9) comprising a second chemical compound. Also revealed is a method of making a medical dressing like this.
公开号:BR112017004789B1
申请号:R112017004789-6
申请日:2015-09-09
公开日:2020-12-01
发明作者:Niclas Flach；Kristina Hamberg；Ulf Johannison；Bengt Söderström
申请人:Mölnlycke Health Care Ab；
IPC主号:

专利说明:

[0001] [0001] The present invention relates to a medical dressing. Background of the Invention
[0002] [0002] An injury caused by an injury or illness can be treated by using a bandage or wound dressing to promote healing by preventing infection and leakage of the wound. Many known wound dressings include a self-adhesive patch, also known as pressure sensitive adhesive (PSA), the purpose of which is to adhere to the wound and / or the skin surrounding the wound and thus fix the dressing in a desirable position. Various adhesives are being used to fix medical products to the skin, some of the most common being covered by the terms acrylic adhesives, silicone based adhesives and hot melt adhesives, among others.
[0003] [0003] In order to ensure that a medical device such as a wound dressing remains in the same position after a certain period of use, an adhesive having a strong adhesion, for example, an acrylic adhesive, can be used. However, in the case where a medical device is to be attached directly to the skin, an acrylic adhesive increases the risk of pain and damage to the skin when such a medical device is to be removed from the skin, for example, because of skin tearing.
[0004] [0004] In contrast to acrylic adhesives, silicone based adhesives are known in the art for being very smooth on the skin. This is because a silicone based adhesive is typically relatively soft and for this reason it can follow the contours of the skin well, resulting in a large contact surface area between the adhesive and the skin. Thus, although the actual adhesive strength at each contact point of a silicone-based adhesive is less than that of an acrylic adhesive, the large contact surface area achieved with a silicone-based adhesive provides a high total adhesion to the skin , while at the same time being skin-friendly, that is, when a silicone-based adhesive is removed from the skin, few skin cells are removed because of the low adhesive strength at each contact point, and thus the previously mentioned problem skin peeling can be avoided.
[0005] [0005] For some types of injuries, such as, for example, severe burns and chronic injuries, there is a particular need to use a wound dressing that includes an antimicrobial agent to eliminate or thereby reduce the risk of wound infection. To that end, several types of antimicrobial dressings have been developed. Examples of antimicrobial agents that have been explored for use in wound dressings include conventional antiseptics, antibiotics, antimicrobial peptides, or metal agents with antimicrobial properties. For example, silver-containing compounds, such as silver salts, are commonly used in dressing for antimicrobial wounds.
[0006] [0006] WO2008057155 discloses silicone gel forming compositions for temporarily bonding a medical device to a biological substrate, such as skin. Said disclosure shows silicone gel compositions comprising active agents such as, for example, antibiotics, antiseptics, antifungals, anti-inflammatory agents, hormones, anti-cancer agents, histamine blockers, beta blockers, vitamins, sedatives, analgesics, proteolytic enzymes and peptides, which can be linked in the composition. However, the release of the active agent from the hydrophobic adhesive matrix, that is, the silicone gel-forming composition, is typically limited since the active agents are bound in the composition.
[0007] [0007] WO 2011/129759 discloses an antimicrobial silicone gel adhesive (and wound dressing including a layer of such silicone gel adhesive) comprising at least one silver salt and at least one hydrophilic component, wherein the component hydrophilic facilitates the absorption of moisture in the adhesive layer and thereby provides an improved release of silver from the adhesive matrix.
[0008] [0008] However, there is still a need in the art to provide an improved adherent medical dressing. Summary of the Invention
[0009] [0009] In view of the aforementioned and other disadvantages of the prior art, a general objective of the present invention is to provide an adherent medical dressing, in particular to provide an adherent medical dressing capable of achieving an immediate and sustained release of a chemical compound, such as as an antimicrobial compound, while maintaining the presence of a chemical compound in the dressing.
[0010] [00010] According to a first aspect of the invention, these and other objectives are achieved by means of a medical dressing comprising a substrate comprising a first chemical compound, the substrate having a first surface, wherein the medical dressing additionally comprises a layer of adhesive having a skin-facing surface for gluing the medical dressing on a dermal surface, wherein at least a portion of the skin-facing surface comprises a coating comprising a second chemical compound.
[0011] [00011] The invention is based on the understanding that an improved release of active chemical compound (s) and / or an improved biological activity (eg, antimicrobial and / or wound healing activity) from a adherent medical dressing can be achieved by combining an internal substrate comprising a first chemical compound with an adhesive layer having a skin-facing surface comprising a coating containing a second chemical compound, the coating of which is intended to be in direct contact with the wound and / or surrounding the dermal surface during use. In this way, the coating on the adhesive layer provides a rapid initial release of the second chemical compound while the inner substrate provides a slower release of the first chemical compound to ensure that the release of the chemical is maintained for a desirable period of time and / or that a biological (for example, antimicrobial) activity of this is maintained within the internal substrate.
[0012] [00012] In embodiments of the invention, the first surface of the substrate faces the adhesive layer, and the skin-facing surface of the adhesive layer faces away from the first surface of the substrate.
[0013] [00013] In embodiments of the invention, the adhesive layer may comprise a silicone based adhesive. The inventors have found that a silicone based adhesive is particularly suitable since chemical compounds can be included in a coating on it without substantially affecting the adhesive properties of the adhesive layer while chemical compounds can be readily released from it.
[0014] [00014] The term "coating", in the context of this application, should be understood as at least one continuous layer on a surface, or a plurality of points or layers, or a discontinuous covering on a surface such as, for example, a plurality of particles distributed over an area of a surface.
[0015] [00015] In embodiments of the invention, the coating comprising the second chemical compound on at least a part of the skin-facing surface of the adhesive layer may comprise a plurality of particles of the second chemical compound distributed on at least a part of the surface facing the skin. the skin, where a first part of each particle can penetrate the adhesive layer while a second part of the particle can protrude out of the adhesive layer.
[0016] [00016] In embodiments of the invention, the coating comprising the second chemical compound in the adhesive layer can be, for example, a film coating comprising a composition of the second chemical compound and a forming chemical or film carrier (e.g. polymeric compound).
[0017] [00017] In embodiments of the invention, the substrate may comprise an absorbent material. For example, the absorbent material may be a polymeric foam such as a hydrophilic polyurethane foam, a nonwoven material, fibrous material such as hydrophilic polymeric material, gel-forming fibers, hydrogel, a matrix containing hydrocolloids, braided and knitted fibers or combinations thereof. In this way, the medical dressing is able to absorb and retain exudates from a wound.
[0018] [00018] As used in this document, the term "hydrophilic" refers to the water-permeable property of a material or the property of attracting water to a molecule. In the context of a material with pores (such as, for example, open cell foams) or materials with through holes, a material like this is "hydrophilic" if the material absorbs water. In the context of a material without pores or any through holes, a material like this is considered "hydrophilic" if it cannot resist the flow of water into or through the material. For example, a material's water absorption capacity can be tested using a water column up to 25.4 millimeters (1 inch) high by exerting pressure on the material for at least 60 minutes, at least 90 minutes or at least 24 hours. By "resisting" it means that any flow of water into or through the foam in a test like this is below a detection limit for the test.
[0019] [00019] In embodiments of the invention, the substrate may comprise a layer of hydrophilic polyurethane foam material. For example, the hydrophilic foam may be a porous open cell foam such as a hydrophilic polyurethane foam. The foam, for example, can be a polyurethane foam produced from a composition comprising a prepolymer based on: hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI) or diphenyl methylene diisocyanate (MDI).
[0020] [00020] In embodiments of the invention, the adhesive layer may be a coating on at least part of the first surface of the substrate, thereby facilitating the application of the dressing to a dermal surface such as, for example, a wound site, and holding the medical dressing substrate in the desired position, for example, in such a way that the substrate sticks to a wound and covers it. By providing a coating comprising a second chemical compound, such as, for example, an antimicrobial compound or wound healing compound, on the skin-facing surface of the adhesive layer, the release of the second chemical compound can be controlled and restricted to an area desired application.
[0021] [00021] In embodiments of the invention, the medical dressing may additionally comprise a layer of perforated film embedded such as sandwich between the first surface of the substrate and the layer of adhesive, wherein the layer of adhesive is a coating on an unperforated part of the perforated film layer. For example, an upper surface of a layer of perforated film can be attached to the first surface of the substrate, where the adhesive layer can be applied as a coating on a lower surface of an unperforated part of the perforated film, and where the surface upper part of the perforated film layer is opposite or facing away from the lower surface.
[0022] [00022] Therefore, the first surface of the substrate can be exposed through the openings of the perforated film layer, thereby facilitating the absorption of exudates and wound fluids from the wound, and / or facilitating the release of the first chemical compound from the substrate to the wound, through the openings.
[0023] [00023] The term "fixed" as used in this document should be understood as a physical element being in contact with another physical element, for example, a first layer being in contact with an adjacent second layer. For example, in embodiments of the invention, the term "fixed" can mean that one layer is glued or laminated to another layer by means of an adhesive between the fixed layers, alternatively two layers can be "fixed" without direct adhesive between them such as, for example, a layer can be placed on top of another layer in which the layers are held together by means of additional surrounding layers enclosing the "fixed" layers.
[0024] [00024] In embodiments of the invention, the first chemical compound can be distributed or incorporated within the substrate.
[0025] [00025] In embodiments of the invention, the first chemical compound can be a solid dispersion in the substrate. The first chemical compound can be a substantially homogeneous solid dispersion in the substrate. For example, the first chemical compound can be a molecular dispersion or partial molecular dispersion on the substrate. By "molecular dispersion" is meant molecules isolated from the chemical compound, and by "partial molecular dispersion" is meant a plurality of isolated molecules as well as a plurality of isolated groupings of molecules, for example, crystals or particles.
[0026] [00026] In embodiments of the invention, the substrate can be impregnated with the first chemical compound. For example, the substrate can be a foam having an open cell structure, where the first chemical compound can be present as a coating on the foam cell walls. For example, the substrate can be soaked with a solution or dispersion containing the first chemical compound.
[0027] [00027] In embodiments of the invention, the first surface of the substrate may comprise a coating comprising the first chemical compound. In the event that the coating is present on a porous material (e.g. foam), the coating can, at least to some extent, penetrate below the general surface face of the material; for example, the coating can cover at least part of the walls in openings or pores in a foam structure. For example, in embodiments of the invention, the first chemical compound can be present only as a coating on the first surface of the substrate, or the first chemical compound can be present either as a coating on the first surface of the substrate or being distributed within the substrate , and thus a concentration gradient of the first chemical compound can be achieved, in which the first chemical compound can be present in a higher concentration on the first surface of the substrate thus promoting additional release of it, while a lower concentration in the volume of the substrate provides a battery of the first chemical compound that can be released slowly to the wound and / or exercise its activity; for example, antimicrobial activity, within the substrate.
[0028] [00028] In embodiments of the invention, the substrate can include a plurality of layers of the same or different materials. For example, the substrate can comprise a layer that confronts the wound of absorbent foam material, an intermediate fibrous gel-forming layer and an upper non-woven layer, in which the intermediate layer can be sandwiched between the confronting layer the wound and the upper layer. In this way the liquid-absorbing properties of the medical dressing can be adapted as desired. In addition, the first chemical compound can be incorporated into all or only a selected layer of the substrate to achieve a desirable release of the substrate and / or activity within it.
[0029] [00029] In embodiments of the invention, the first chemical compound and / or the second chemical compound can be an antimicrobial compound.
[0030] [00030] In embodiments of the invention, the medical dressing is an antimicrobial dressing.
[0031] [00031] In embodiments of the invention, the first chemical compound and the second chemical compound can be selected independently from the group consisting of a silver compound such as silver salt and metallic silver, biguanide salts such as polyhexamethylene biguanide (PHMB) or any salts thereof, or polyhexamethyl guanide (PHMG) or any salts thereof, or chlorhexidine or any salts thereof, iodine, salicylic acid or any salt thereof, acetylsalicylic acid or any salt thereof, quaternary ammonium salts such as benzethonium chloride, povidone-iodine (betadine), lactoferrin, xylitol, antimicrobial peptides such as human cationic antimicrobial protein 18 (known as hCAP18 or LL37), borneol, bismuth subgalate, antifungal pharmaceuticals and antibiotics such as gentamicin, streptocin .
[0032] [00032] In embodiments of the invention, the first chemical compound and the second chemical compound can be selected independently from the group consisting of a silver compound including, for example, a silver and metallic silver salt; biguanide salts such as PHMB or any salts thereof, or PHMG or any salts thereof; chlorhexidine or any salts thereof; and iodine.
[0033] [00033] For example, the first chemical compound and / or the second chemical compound can be a silver salt such as silver sulfate (Ag2SO4), silver sulfite (Ag2SO3), silver nitrate (AgNO3), silver carbonate ( AgCO3), silver phosphate (Ag3PO4), silver chloride (AgCl), silver phosphate, sodium, hydrogen and zirconium (AlphaSan® from Milliken Chemical, Spartanburg, USA), or PHMB, for example, PHMB hydrochloride or any other salts thereof, or chlorhexidine or any salts thereof.
[0034] [00034] For example, the first chemical compound and / or the second chemical compound can be a silver compound, for example, a silver salt or metallic silver.
[0035] [00035] In embodiments of the invention, the first chemical compound can be present in a first concentration per area of the medical dressing and the second chemical compound can be present in a second concentration per area of the medical dressing, where the first and second concentrations can be different. For example, the concentration of the first chemical compound can be about 5 to 3,000 µg / cm2, and the concentration of the second chemical compound can be about 1 to 2,500 µg / cm2. By varying the concentrations of the first and second chemical compounds, the dressing release profile can be adapted for different applications; that is, different types of injuries.
[0036] [00036] In embodiments of the invention, the first chemical compound can be present in a first concentration per area of the medical dressing and the second chemical compound can be present in a second concentration per area of the medical dressing, wherein said first concentration can be greater than said second concentration.
[0037] [00037] As used in this document, the terms "about" or "approximately" refer, for example, to a number or percentage, generally including numbers that are included in a range of 5%, 10% or 20% in either direction (more or less) of the number unless otherwise reported or otherwise evident from the context (except where a number like this would be physically impossible such as, for example, exceeding 100 % of a possible value or fall below 0% of a possible value).
[0038] [00038] In embodiments of the invention, the adhesive layer may comprise a third chemical compound incorporated within the adhesive layer, wherein the third chemical compound may be the same as the first and / or second chemical compound. For example, the third chemical compound can be a solid dispersion in the adhesive layer.
[0039] [00039] In embodiments of the invention, the medical dressing may include a vapor permeable transmission layer attached to the substrate on a second surface of the substrate, the second surface being opposite the first surface of the substrate. The transmission layer can typically be impermeable to water.
[0040] [00040] According to a second aspect of the invention, these and other objectives are achieved by means of a method of making a medical dressing comprising the steps of: providing a substrate comprising a first chemical compound; provide a layer of adhesive; and providing a coating comprising a second chemical compound in the adhesive layer. In embodiments of the invention, the adhesive layer may comprise a silicone based adhesive.
[0041] [00041] According to a third aspect of the invention, those mentioned above and other objectives are achieved by means of a medical dressing manufactured according to the method described above.
[0042] [00042] In accordance with a fourth aspect of the invention, those mentioned above and other objectives are achieved by using the medical dressing according to the invention to treat and / or prevent injuries. For example, the medical dressing according to the invention can be used in the treatment of burns, scars, bacterial infections, viral infections, fungal infection and / or for wound healing.
[0043] [00043] According to a fifth aspect of the invention, those mentioned above and other objectives are achieved by means of a method of treating a wound comprising the step of providing the medical dressing according to the invention on a wound and / or dermal surface. surrounding. Brief Description of Drawings
[0044] [00044] These and other aspects of the invention will now be shown in more detail, with reference to the accompanying drawings showing an exemplary embodiment of the invention, in which: figure 1a is a schematic perspective view of an embodiment of a medical dressing according to the invention; figure 1b is a cross-sectional view along line AA in figure 1a; figure 1c is an enlarged cross-sectional view of the detail Y in figure 1b; figure 2a is a schematic perspective view of an embodiment of a medical dressing according to the invention; figure 2b is a cross-sectional view along the line A'-A 'in figure 2a; figure 2c is an enlarged cross-sectional view of the detail Y 'in figure 2b; and Figures 3a-3b show the results of an antimicrobial activity test with medical dressing modalities according to the invention. Description of Example Modes of the Invention
[0045] [00045] In the description below, exemplary embodiments of the present invention are described with reference to the accompanying schematic drawings.
[0046] [00046] Figures 1a-1c illustrate an exemplary embodiment of a medical dressing 1 according to the invention. Medical dressing 1 comprises a substrate 2 comprising a first chemical compound, wherein medical dressing 1 additionally comprises an adhesive layer 3 having a skin-facing surface 6 for gluing medical dressing 1 on a dermal surface (when the dressing is applied) physician is in use), and wherein at least a portion of the skin-facing surface 6 comprises a coating 9 comprising a second chemical compound. In the embodiment shown in figures 1a-1c, the adhesive layer 3 is a coating on a first surface 4 of the substrate 2, where the skin-facing surface 6 of the adhesive layer 3 is facing away from the first surface 4 of the substrate 2. The medical dressing of figures 1a-1c further comprises a vapor-permeable transmission layer 10, wherein the vapor-permeable transmission layer 10 overlaps a second surface 7 of substrate 2, the second surface of which is opposite the first surface 4 of the substrate 2. The vapor permeable transmission layer 10 can be fixed, for example, to the second surface 7 by means of a continuous or discontinuous glue layer (for example, acrylic adhesive), or by means of hot lamination.
[0047] [00047] Figures 2a-2c illustrate an exemplary embodiment of a medical dressing 20 according to the invention. The medical dressing 20 comprises a substrate 2 comprising a first chemical compound, wherein the medical dressing 20 further comprises a layer of perforated film 11 fitted as interspersed between the first surface 4 of the substrate 2 and the adhesive layer 3, and in whereas the adhesive layer 3 is a coating on an unperforated part 12 of the perforated film layer 11. As shown in figure 2b, an upper surface 17 of the perforated film layer 11 can be attached to the first surface 4 of the substrate 2, wherein the adhesive layer 3 is a coating on a lower surface 18 of a non-perforated part 12 of the perforated film layer 11, and where the upper 17 and lower surfaces 18 are opposite from each other. Therefore, the first surface 4 of the substrate 2 can be exposed through the openings 14 of the perforated film layer 11, thereby facilitating the absorption of exudates and wound fluids from the wound, and / or facilitating the release of the first chemical compound from the substrate. 2 for the wound, through the openings 14.
[0048] [00048] Additionally, at least a part of a skin-facing layer 6 of the adhesive layer 3 comprises a coating 9 comprising a second chemical compound, the coating 9 of which is intended to be in direct contact with the wound and / or surrounding surface when the medical dressing is in use. In this way, a quick release of the second chemical compound to a dermal surface (when dressing is being used) is facilitated, while at the same time maintaining the adhesive properties of the adhesive layer 3.
[0049] [00049] The medical dressing 20, as exemplified in figures 2a-2c, may additionally include a vapor permeable transmission layer 10 that overlaps a second surface 7 of the substrate 2. The permeable transmission layer 10 may be a plastic film, for example, comprising or consisting of polyurethane, polyethylene or polypropylene. The vapor permeable transmission layer 10 can be a polyurethane film having a thickness in the range of 10-100 µm, for example, 10-80 pm such as 10-50 pm.
[0050] [00050] In the embodiment shown in figures 2a-2b, both the perforated layer 11 and the vapor-permeable transmission layer 10 extend outside the periphery of the substrate 2, and the respective parts of the perforated layer 11 and the permeable transmission layer to the steam 10 extending out of the substrate they are attached to each other, thereby forming an edge portion 15 surrounding the substrate 2. The perforated layer 11 can be attached to the first surface 4 of the substrate 2 and / or to the permeable transmission layer steam 10 by means of a layer of continuous or batch glue (not shown in figures 2a-2b).
[0051] [00051] For example, in an embodiment of the invention, the perforated layer 11 outside the periphery of the substrate 2 is attached to the vapor permeable transmission layer 10 (using, for example, an acrylic based adhesive) while the perforated layer 11 confronting the first surface 4 of the substrate 2 is not laminated (by means of, for example, glue or heat) to the first surface 4, and so the substrate 2 can be mobile in relation to the perforated layer 11, which, for example, can desirable if the substrate expands in use. Similarly, in embodiments of the invention, the second surface 7 of the substrate 2 can be mobilely attached to the vapor permeable transmission layer 10, that is, the layers are not laminated by means of glue or heat, for example, but preferably held together by the surrounding laminated edge portion 15.
[0052] [00052] In addition, the perforated layer 11 can comprise a plurality of openings 14 (or through holes) of any desirable size and shape. The shape and size can be adapted to achieve a desirable absorption and / or release of the first chemical compound from substrate 2. For example, the openings 14 can be circular, straight slits, rectangular or quadrangular in shape, among others. In embodiments of the invention, the size and / or shape of the openings 14 in the perforated layer 11 are different. For example, in embodiments of the invention, the part of the perforated layer 11 extending outside the periphery of the substrate 2, at the edge part 15 of the dressing 20, may comprise a smaller number of openings or smaller openings (not shown), or may be a continuous film without openings (not shown), thereby increasing the surface area of the unperforated part 12 of the perforated layer 11 on the edge part 15, and thereby increasing the adherence capacity of the medical dressing 20 since the total area of the dressing adhesive layer 3 on the non-perforated part 12 increases accordingly.
[0053] [00053] In embodiments of the invention, the perforated layer may comprise an opening substantially corresponding to the area of the first surface of the substrate, wherein the perforated layer is positioned in such a way that the first surface of the substrate coincides with the opening in the perforated layer, and thus substantially the entire first surface of the substrate can be in contact with the wound when the medical dressing is in use (modality not shown in the figures).
[0054] [00054] In embodiments of the invention, the perforated layer 11 can be a plastic film having a thickness in the range of 10-150 µm. For example, the perforated film 11 can be made of polyurethane, polypropylene or polyethylene.
[0055] [00055] In embodiments of the invention, the perforated layer 11 can be a polyurethane film having a thickness in the range of 10150 µm, for example, 10-100 µm or 10-80 µm such as 10-50 µm, for example, 25 µm.
[0056] [00056] In embodiments of the invention, the adhesive layer can be arranged adjacent to a peripheral part of the substrate, whereby the adhesive layer extends away from the peripheral part of the substrate. For example, the medical dressing can be an island-shaped dressing in which the adhesive layer surrounds the peripheral part of the substrate.
[0057] [00057] For example, in embodiments of the invention, the medical dressing may comprise a vapor-permeable transmission layer that overlaps a second surface of the substrate and furthermore extends outside a peripheral part of the substrate to define a edge part of the vapor permeable transmission layer. In these embodiments of the invention, the adhesive layer may be a coating on a skin-facing portion of the vapor-permeable transmission layer (embodiment not shown in the figures).
[0058] [00058] In embodiments of the invention, substrate 2 can typically comprise an absorbent material. For example, such an absorbent material can be selected from the group consisting of a polymeric foam such as a hydrophilic polyurethane foam, a nonwoven material, fibrous material such as hydrophilic polymeric fibrous material, gel-forming fibers, hydrogel, a matrix containing hydrocolloids , braided and knitted fibers.
[0059] [00059] In embodiments of the invention, substrate 2 may comprise a layer of a hydrophilic polyurethane foam, for example, a polyurethane foam produced from a composition comprising a prepolymer based on: hexamethylene diisocyanate (HDI), sodium diisocyanate toluene (TDI) or diphenyl methylene diisocyanate (MDI).
[0060] [00060] For example, in embodiments of the invention, substrate 2 can be a hydrophilic polyurethane foam.
[0061] [00061] In embodiments of the invention, the first chemical compound can be distributed within substrate 2. For example, the first chemical compound can be distributed substantially homogeneously within substrate 2, that is, having a uniform material composition throughout substrate 2. For example, the first chemical compound can be a substantially homogeneous solid dispersion, such as a molecular dispersion or partial molecular dispersion, on substrate 2.
[0062] [00062] In embodiments of the invention, the first chemical compound can be chemically bonded to the internal structure or surface (e.g., pores) of substrate 2. For example, if the first chemical compound is an ionic salt, the first chemical compound it can be attached to a loaded internal surface of the substrate 2. For example, the substrate can comprise cellulose fibers having a charged side group, such as, for example, carboxymethylcellulose (CMC), where the first chemical compound can be attached to the fibers of cellulose through ionic bonds.
[0063] [00063] In embodiments of the invention, the first chemical compound can be incorporated into the substrate by including the first chemical compound in the manufacture of the substrate. For example, the substrate can be a foam, in which the first chemical compound is added to the prepolymer before the foaming step (for example, according to the method disclosed in EP 1 964 580), and thus the first chemical compound can be incorporated within the substrate structure, for example, chemically bound within the cell walls of a foam substrate.
[0064] [00064] In embodiments of the invention, the first chemical compound can be impregnated on substrate 2, for example, the first chemical compound can be a coating on the inner surface of substrate 2. For example, in case the substrate is a substrate of foam, the first chemical compound can be a coating on the inner pore surfaces of the foam.
[0065] [00065] In embodiments of the invention, the first surface 4 of the substrate 2 may comprise a coating comprising the first chemical compound.
[0066] [00066] In embodiments of the invention, the first surface 4 of the substrate 2 may comprise a coating comprising the first chemical compound, wherein said coating may also comprise a carrier or film-forming chemical compound. For example, the chemical carrier or film-forming compound can be a polymeric material such as polyvinylpyrrolidone (PVP), carboxymethylcellulose (CMC), hydroxyethylcellulose (HEC), polyvinyl alcohol (PVA) and / or hydroxypropylcellulose (HPC). The chemical carrier or film-forming compound can be used to also adapt and control the release of the first chemical compound.
[0067] [00067] In embodiments of the invention, the first chemical compound can be a substantially homogeneous solid dispersion within the core of substrate 2, and wherein the first surface 4 of substrate 2 can comprise a coating comprising the first chemical compound. Thus, different concentrations of the first chemical compound within the substrate can be achieved, and in this way the release and / or activity of the first chemical compound can be adapted as desired. For example, by adding a coating of the first chemical compound to the first surface 4 of substrate 2, on whose substrate the first chemical compound is already distributed, a first concentration of the first chemical compound can be achieved on the first surface 4 and a second concentration of the first chemical compound can be achieved within the core of substrate 2, so the release of the first compound from substrate 2 can be controlled by adapting the first concentration and the activity (eg, antimicrobial activity) of the first chemical compound within the substrate can be ensured adapting the second concentration.
[0068] [00068] In embodiments of the invention, the coating comprising the second chemical compound can be in the form of particles (for example, crystals or precipitate) in which at least a part of each particle 9 penetrates the adhesive layer 3, while a second part of the particle protrudes from the adhesive layer 3 above the skin-facing surface 6 thereof. Thus, as the coating comprising the second chemical compound is over and / or extending above the adhesive layer 3, the release of the second chemical compound from the skin-facing surface 6 of the adhesive layer 3 is facilitated.
[0069] [00069] In embodiments of the invention, as illustrated in figure 1c, the adhesive layer 3 may comprise a skin part 22 including the adhesive material of the adhesive layer 3 proximal to the skin-facing surface 6, and a non-adhesive part. skin 23 including the adhesive material proximal to the non-skin surface 5 of the adhesive layer 3 being opposite the skin-facing surface 4, where the substrate part 23 is substantially free of the second chemical compound.
[0070] [00070] In embodiments of the invention, the coating 9 comprising the second chemical compound on the skin-facing surface 6 of the adhesive layer 3 can be a film coating additionally comprising a chemical forming compound or film carrier such as, for example , PVP, CMC, HEC, PVA and / or HPC. For example, in such a film coating the second chemical compound can be enclosed in a matrix of the forming chemical compound or film carrier. In this way, the release of the second chemical compound can also be controlled by selecting a chemical forming compound or film carrier having desirable properties, that is, by selecting, for example, a chemical forming compound or film carrier that has more or less solubility in an aqueous solution (e.g., wound fluid) the release of the second chemical compound can be adapted as desired.
[0071] [00071] In embodiments of the invention, the adhesive layer 3 can comprise a silicone based adhesive, acrylic adhesive or a pressure sensitive adhesive (PSA) hot glue.
[0072] [00072] In embodiments of the invention, the adhesive layer 3 can be a coating having a coating weight of 20 to 300 g / m2, for example, 50 to 200 g / m2 such as 80 to 150 g / m2.
[0073] [00073] In embodiments of the invention, the adhesive layer 3 can be a silicone based adhesive. For example, the silicone-based adhesive may be a soft silicone gel adhesive, the adhesive of which is known for its advantageous skin-friendly properties such as, among other things, no or little skin is peeled off when a layer of adhesive adhesive of soft silicone gel is removed from a dermal surface. The term "silicone gel" refers to a silicone gel that comprises a cross-linked network including lower molecular weight silicone. For example, suitable soft silicone gel adhesives can be composed of an RTV (Room Temperature Vulcanization) cured silicone system that, after mixing, creates cross-links and forms a self-adhesive elastomer. An example of a commercially available RTV addition cured silicone system is the Wacker SilGel 612 which is a two component system, in which the softness and degree of adhesion of the formed elastomer can be varied by varying the proportions of the two components A: B from 1.0: 0.7 to 1.0: 1.3. Other examples of silicone-based adhesives include, among other things, NuSil MED-6340, NuSil MED3-6300 and NuSil MED 126300 from NuSil Technology, Carpinteria, GA, USA, and Dow Corning 79800 from Dow Corning Corporation, Midland, USA . In embodiments of the invention, the first chemical compound and the second chemical compound can be selected independently from the group consisting of a silver compound including, for example, a silver salt and metallic silver, biguanide salts such as polyhexamethylene biguanide (PHMB) or any salts thereof, or polyhexamethyl guanide (PHMG) or any salts thereof, or chlorhexidine or any salts thereof, iodine, salicylic acid or any salt thereof, acetylsalicylic acid or any salt thereof, quaternary ammonium salts such as chloride benzethonium, povidone-iodine (betadine), lactoferrin, xylitol, antimicrobial peptides such as LL37 peptides, borneol, bismuth subgalate, antifungal pharmaceuticals and antibiotics such as gentamicin, streptomycin.
[0074] [00074] In embodiments of the invention, the first chemical compound and the second chemical compound can be selected independently from the group consisting of a silver compound including, for example, a silver and metallic silver salt; PHMB or any salts thereof; PHMG or any salts thereof; chlorhexidine or any salts thereof; and iodine.
[0075] [00075] For example, the first chemical compound and / or the second chemical compound can be a silver salt such as silver sulfate (Ag2SO4), silver sulfite (Ag2SO3), silver nitrate (AgNO3), silver carbonate ( AgCO3), silver phosphate (Ag3PO4), silver chloride (AgCl), silver phosphate, sodium, hydrogen and zirconium (AlphaSan® from Milliken Chemical, Spartanburg, USA), or PHMB, for example, PHMB hydrochloride or any other salts of the same, or chlorhexidine or any salts thereof.
[0076] [00076] For example, in embodiments of the invention, the first chemical compound can be a silver compound, for example, silver salt or metallic silver, wherein the second chemical compound can be PHMB or any salts thereof. Alternatively, the first chemical compound can be PHMB or any salt thereof and the second compound can be a silver compound or both the first and the second can be PHMB or any salt thereof, or both the first and the second can be a silver compound. Alternatively, chlorhexidine or any salts thereof can be combined with a silver compound.
[0077] [00077] In embodiments of the invention, the first chemical compound can be present in a first concentration per area of the medical dressing and the second chemical compound can be present in a second concentration per area of the medical dressing, where the first and second concentrations can be different. For example, said first concentration can typically be greater than said second concentration.
[0078] [00078] In embodiments of the invention, the concentration of the first chemical compound can be about 5 to 3,000 µg / cm2, and the concentration of the second chemical compound can be about 1 to 2,500 µg / cm2. For example, the concentration of the first chemical compound can be about 50 to 2,000 µg / cm2, and the concentration of the second chemical compound can be about 1 to 150 µg / cm2. For example, the concentration of the first chemical compound can be about 1,000 to 2,500 µg / cm2, and where the concentration of the second chemical compound can be about 1 to 300 µg / cm2. For example, the concentration of the first chemical compound can be about 1,500 to 2,000 µg / cm2, and the concentration of the second chemical compound can be about 1 to 100 µg / cm2. For example, the concentration of the first chemical compound can be about 50 to 200 µg / cm2 such as 95 µg / cm2, and the concentration of the second chemical compound can be about 5 to 49 µg / cm2 such as 20 µg / cm2.
[0079] [00079] In many wound treatment applications it is desirable to incorporate a larger amount of the first chemical compound to the substrate, and a smaller amount of the second chemical compound to the surface coating.
[0080] [00080] For example, the ratio between the second and the first concentration can be in the range of 1: 5 to 1: 100, for example, 1:10 to 1:50.
[0081] [00081] This allows for both a strong initial effect and a sustained effect of the first and second chemical compounds. The release of the first and second chemical compounds can be maintained for a desirable period of time and the biological activity of the chemical compounds can be maintained for a desirable period of time.
[0082] [00082] Different types of wounds pose different demands on a dressing. For application to deep wounds, resulting, for example, from surgery, it may be advantageous to provide a more prominent initial release of the second chemical compound to facilitate healing earlier and prevent swelling at the wound site. For the purposes of preventing infection or repairing scars, a slower release may be desired.
[0083] [00083] By varying the concentrations of the first and second chemical compounds, the dressing release profile can be adapted for different applications. This allows for a more controlled release of the first and second chemical compounds.
[0084] [00084] A dressing according to the invention allows a synergistic effect by providing a rapid initial release of the second chemical compound, while a slower release of the first chemical compound from within the substrate. This allows for a more controlled release profile, and thus a strong initial effect as well as a sustained effect.
[0085] [00085] In embodiments of the invention, the first chemical compound and / or the second chemical compound can be a wound healing compound, wherein the first chemical compound and / or the second chemical compound can be selected independently from the group consisting of Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-a); complete protein or peptides from: amelogenin, fibronectin, vitronectin, fibrinogen; arginylglycylpartic acid (RGD) peptides; beta-glucan (BG) (for example, soluble BG or oat BG), growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor (FGF); cytokines such as transforming growth factor (TGF) beta 1, TGF beta 3, interleukin (IL) -10; decellularized animal tissue; and amniotic tissue.
[0086] [00086] In embodiments of the invention, the first chemical compound may be an antimicrobial compound selected from the group consisting of silver compound including, for example, a silver and metallic silver salt; PHMB or any salts thereof; PHMG or any salts thereof, chlorhexidine or any salts thereof; and iodine, wherein the second chemical compound may be a wound healing compound selected from the group consisting of Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-a); complete protein or peptides from: amelogenin, fibronectin, vitronectin, fibrinogen; arginylglycylpartic acid (RGD) peptides; beta-glucan (BG) (for example, soluble BG or oat BG), growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor (FGF); cytokines such as transforming growth factor (TGF) beta 1, TGF beta 3, interleukin (IL) -10; decellularized animal tissue; and amniotic tissue.
[0087] [00087] In embodiments of the invention, the adhesive layer 3, as, for example, discussed above with reference to figures 1a-1c and figures 2a-2c, can comprise a third chemical compound distributed within the adhesive layer 3 , where the third chemical compound can be the same as the first and / or the second chemical compound. In embodiments of the invention, the third chemical compound can be a solid dispersion in the adhesive layer 3.
[0088] [00088] Therefore, chemical compounds can also be distributed within or over the layers or materials of dressing 1, 20, and thus the properties, for example, release properties and / or biological activity (for example, antimicrobial or wound healing) injury), can be further adapted as desired.
[0089] - fornecer um substrato 2 compreendendo um primeiro composto químico; - fornecer uma camada de adesivo 3; e - fornecer um revestimento 9 compreendendo um segundo composto químico na camada de adesivo 3. [00089] The invention also concerns a method of manufacturing a medical dressing comprising the steps of: - providing a substrate 2 comprising a first chemical compound; - provide an adhesive layer 3; and - providing a coating 9 comprising a second chemical compound in the adhesive layer 3.
[0090] [00090] In embodiments of the invention, the step of providing a substrate 2 comprising a first chemical compound may include impregnating substrate 2 with a solution or dispersion of the first chemical compound in a solvent and subsequently drying the impregnated substrate 2. Alternatively, or in addition, the step of providing a substrate 2 comprising a first chemical compound may include adding the first chemical compound to a substrate manufacturing step.
[0091] [00091] In embodiments of the invention, the step of providing an adhesive layer 3 can include the step of coating the first surface 4 of the substrate with an adhesive composition or an unperforated portion 12 of a perforated film layer 11 (e.g. polyurethane film). For example, in case the adhesive layer is a silicone based adhesive, the coating step is typically followed by a step of curing the silicone composition to obtain a cured silicone based adhesive layer. For example, the step of providing an adhesive layer may include first adding and then curing a silicone composition on a second surface 18 of an unperforated portion of a perforated polyurethane film, and subsequently fixing the perforated polyurethane film to the substrate in such a way that a first surface 17 of the perforated polyurethane film faces the first surface 4 of the substrate, and where the first surface 17 of the perforated polyurethane film is opposite the second surface 18 thereof.
[0092] [00092] In embodiments of the invention, the step of providing adhesive layer 3 with a coating 9 comprising a second chemical compound may include adding the second chemical compound to the skin-facing surface 6 of adhesive layer 3 in the form of a solid. , for example, a powder, alternatively, the second chemical compound can be dissolved or dispersed in a suitable solvent, for example, water or organic solvents such as alcohol, so a solution or suspension of the second chemical compound can be applied to the adhesive layer 3, in which case the method typically comprises an additional drying step, for example, evaporating the liquid. In embodiments of the invention, a liquid mixture (e.g., solution or suspension) of the second chemical compound may additionally comprise a film forming or carrier chemical compound (as discussed above), and thereby a film coating comprising the second compound chemical and the film-forming chemical compound can be obtained. A liquid mixture (for example, solution or suspension) of the second chemical compound can be applied using, for example, a sponge applicator, a brush, or a stick, or a roller, or by spreading with a spatula, or by release by means of a release blade, or the liquid mixture can be in the form of a spray, mousse, aerosol or foam that can be applied directly to the surface. For example, a liquid mixture (e.g., solution or suspension) of the second chemical compound can typically be applied to the adhesive layer 3 by spraying the liquid mixture onto the skin-facing surface 6 of the adhesive layer 3. In embodiments of the invention , in the event that the second chemical compound is dissolved or dispersed in a solvent, the viscosity of the solvent can be configured to thereby control the level of penetration of the second chemical compound into the skin-facing surface 6 of the adhesive layer 3. For example , the viscosity of a liquid mixture (e.g., solution or suspension) of the second chemical compound can typically have a relatively low viscosity, such as, for example, within the range of 0.65 to 500 mPas.
[0093] [00093] Where resources, modalities or aspects of the present invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also described in this way in terms of any individual member or subgroup of members of the Markush group. Those skilled in the art will further recognize that the invention is also described in this way in terms of any combination of individual members or subgroups of members of Markush groups.
[0094] [00094] Additionally, it should be noted that modalities and features described in the context of one of the aspects and / or modalities of the present invention also apply mutatis mutandis for all other aspects and / or modalities of the invention.
[0095] [00095] In addition, variations for the revealed modalities can be understood and made by those skilled in the art when applying the claimed invention, from a study of the drawings, the disclosure and the attached claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "one" or "one" does not exclude a plurality. The mere fact that certain measures are reported in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.
[0096] [00096] The advantages of the invention have been demonstrated in experiments. Examples Preparation of Example Modes of the Invention Materials Used:
[0097] [00097] Lyofoam ™ Max (lot 603092), which is a hydrophilic polyurethane foam product, commercially available from Molnlycke Health Care AB. Lyofoam ™ Max includes a polyurethane reinforcement film present on one side of the foam layer; Mepore® Film (20 x 30 cm) commercially available from Molnlycke Health Care AB. Mepore Film consists of a transparent polyurethane (PU) film (25 µm) coated with a polyacrylic adhesive (with a release layer of clay with a paper coating on it) on one side of the PU film and a paper paper frame coated with silicone on the opposite side of the PU film; Wacker SilGel® 612 (lot SR 020539) silicone based adhesive (room temperature vulcanization silicone; two-component system) commercially available from Wacker; silver sulfate (Ag2SO4) commercially available from Alfa Aesar; polyethylene (PE) film (100 pm); polyethylene (PE) coated paper commercially available from Âkerlund & Rausing Group.
[0098] [00098] The method of coating a foam sample with silicone adhesive is based on the method disclosed in WO 97/42985 (see, for example, page 9). The method of perforating the polyurethane film is based on the method disclosed in EP 1 960 164. All of the preparation steps disclosed below are performed at room temperature (25 degrees C) unless otherwise noted. Example 1
[0099] [00099] An aqueous solution of silver sulfate (4.1 g / L) was prepared. The solution was subsequently sprayed substantially uniformly (using any suitable coating apparatus or, for example, a spray can) on the foam surface of Lyofoam ™ Max (20 x 15 cm). The total amount sprayed was 28.3 µL / cm2. Subsequently, a polyethylene (PE) film (20 x 15 cm) was applied to the silver-coated surface of the foam in such a way that the total foam surface was covered with the PE film, and a steel roller was applied over the film. PE to compress the underlying foam and thereby impregnate the foam body with the aqueous solution of silver sulfate. The PE film was then removed, and the Lyofoam ™ Max product was dried at room temperature for at least 24 hours to provide a sample of Lyofoam ™ Max impregnated with silver comprising about 116 µg / cm2 of silver sulfate.
[0100] [000100] A layer (thickness of 0.125 mm) of uncured silicone mixture (Wacker Silgel 612, ratio A: B = 1.2: 1) was applied to a PE coated paper (25 x 25 cm). Subsequently, the sample (20 x 15 cm) of Lyofoam ™ Max impregnated with silver (about 116 µg / cm2) was applied to the uncured silicone mixture layer, such that the foam side of Lyofoam ™ Max became contact with the uncured silicone mixture, and the layers (ie, PE coated paper, silicone, foam layer) were then transported through an oven (90 degrees C). The silicone mixture was cured in its passage through the oven (total curing time of approximately 2 minutes) to give a layer of cured silicone gel on the underside of the foam material. The PE coated paper was removed and a PE film (20 x 15 cm) was added to cover the cured silicone adhesive layer. Example 2
[0101] [000101] A Lyofoam ™ Max product (20 x 15 cm, not impregnated with silver) was coated with a layer of cured silica gel adhesive as described in Example 1. An aqueous solution of silver sulfate (7.70 g / L) was prepared and subsequently sprayed in a substantially uniform manner (using any suitable coating apparatus or, for example, a spray can) on the cured silicone layer, and the sample was dried at room temperature for at least 24 h. The total amount sprayed was 15.0 µL / cm2 giving a total amount of silver sulfate on the silicone layer of about 116 µg / cm2. Example 3
[0102] [000102] A foam sample including the cured silicone gel layer was prepared as described in Example 1, with the exception that an aqueous solution of silver sulfate with a concentration of 3.50 g / L was sprayed (total amount 27.3 µL / cm2) on the foam surface to thereby provide a sample of Lyofoam ™ Max impregnated with silver in which the total amount of silver sulfate contained in the foam body was about 96 µg / cm2.
[0103] [000103] The subsequently cured silicone gel layer was coated with silver sulfate as described in Example 2 with the exception that an aqueous solution of silver sulfate with a concentration of 3.0 g / L was used and the total amount sprayed was 7.5 µL / cm2, giving a total amount of silver sulfate on the silicone layer of about 22 µg / cm2, and thus a total amount of silver sulfate in the final product of about 118 µg / cm2 . Example 4
[0104] [000104] A sample of Lyofoam ™ Max (20 x 15 cm) was impregnated as described in Example 1, to obtain a sample of Lyofoam ™ Max impregnated with silver comprising about 116 µg / cm2 of silver sulfate.
[0105] [000105] The paper frame over Mepore® Film product (20 x 30 cm) was removed and a layer (thickness of 0.200 mm) of uncured silicone mixture (Wacker Silgel 612, ratio A: B = 112: 100) it was applied to the upper (non-adhesive) surface of the Mepore® Film polyurethane (PU) film (20 x 30 cm), and subsequently cured in a specific device (approximately 2 minutes, 90 degrees C). A PE film (20 x 30 cm) was added to cover the cured silicone adhesive layer.
[0106] [000106] The PU film now having acrylic adhesive (with release layer) on one side and silicone adhesive (with PE film release layer) on the opposite side was then perforated using an ultrasonic device as described in EP 1 960 164 (see [0008]), where the PU film laminate and release layers have been displaced by narrowing an ultrasonic device, which comprises an ultrasonic component and an opposite roller provided with a protrusion pattern (see figure 1 on EP 1 960 164). The laminate was inserted through the ultrasonic device in such a way that the PE film confronted the opposite roller. The energy emitted by the ultrasonic device was adjusted in such a way that a local melt of the PU film occurred in the area of each protuberance, thereby drilling through the polyurethane film of the laminate in such a way that a plurality of through holes of approximately 1.5 mm diameter was created. The release layer (over the acrylic adhesive layer) was subsequently removed and the perforated film laminate (cut to 20 x 15 cm) was fixed to the foam surface of the prepared Lyofoam ™ Max (comprising about 116 µg / cm2 of sulfate silver). The total amount of silver sulfate in the final product was thus about 116 µg / cm2. Example 5
[0107] [000107] The paper frame over Mepore® Film product (20 x 30 cm) was removed and a layer (thickness of 0.200 mm) of uncured silicone mixture (Wacker Silgel 612, ratio A: B = 112: 100) it was applied to the upper (non-adhesive) surface of the Mepore® Film polyurethane (PU) film (20 x 30 cm), and subsequently cured in a specific device (approximately 2 minutes, 90 degrees C). An aqueous solution of silver sulfate (7.70 g / L) was prepared and subsequently sprayed in a substantially uniform manner (using any suitable coating apparatus or, for example, a spray can) on the cured silicone layer, and the sample was dried (at 90 degrees C, approximately 2 minutes). The total amount sprayed was 15.0 µL / cm2 giving a total amount of silver sulfate on the silicone layer of about 116 µg / cm2. A PE film (20 x 30 cm) was added to cover the cured silicone adhesive layer, and the laminated film was perforated as described in Example 4 above. Subsequently, the release layer (over the acrylic adhesive layer) was removed and the perforated film laminate (cut to 20 x 15 cm) was fixed to the foam surface of a Lyofoam ™ Max product (20 x 15 cm, not impregnated with silver). The total amount of silver sulfate in the final product was thus about 116 µg / cm2. Example 6
[0108] [000108] A sample of Lyofoam ™ Max (20 x 15 cm) was impregnated as described in Example 1, with the exception that an aqueous solution of silver sulfate with a concentration of 3.50 g / L was sprayed (total amount 27.3 µL / cm2) on the foam surface to thereby obtain a sample of Lyofoam ™ Max impregnated with silver in which the total amount of silver sulfate contained in the foam body was about 96 µg / cm2. A perforated film laminate was prepared as described in Example 5, with the exception that an aqueous solution of silver sulfate with a concentration of 3.0 g / L was used and the total amount sprayed was 7.5 µL / cm2 , giving a total amount of silver sulfate on the silicone layer of about 22 µg / cm2, and thus a total amount of silver sulfate in the final product of about 118 µg / cm2. Example 7
[0109] [000109] The product was prepared according to Example 4, with the exception that a Lyofoam ™ Max not impregnated with silver (20 x 15 cm) was used. The total amount of silver sulfate in the product of Example 7 was thus 0 µg / cm2. Antimicrobial Activity Tests
[0110] [000110] The antimicrobial effect was determined using a modified direct contact method ISO 20743: 2007 (E) Textiles - Determination of antibacterial activity of antibacterial finished products. The ISO method is modified with respect to the test medium and test organisms in order to simulate conditions such as injury. In principle, an inoculated test medium is added to a piece of material or product, which absorbs the test medium. The inoculated part is incubated for a specific time before the number of viable test organisms is determined by washing to remove remaining test organisms using neutralization buffer. Viable counts are determined in the neutralization buffer by means of serial dilution and coating on agar plates. Method Description
[0111] [000111] Antimicrobial effect was determined in Examples 1-3 and Examples 4-6 against Pseudomonas aeruginosa ATCC 15442 (P. aeruginosa) and Staphylococcus aureus ATCC 6538 (S. aureus). Lyofoam ™ Max (Molnlycke Health Care, lot 603092) and Example 7 were included as negative control samples. Any release layers present on the adhesive layer in the examples were removed prior to testing.
[0112] [000112] Overnight cultures of test organisms (approximately 109 CFU / ml) in Trypticase Soy Broth (TSB; Acumedia) were diluted to approximately 107 CFU / ml using Peptone Water (PW; 0.85% NaCl with 0 , 1% Neutralized Bacteriological Peptone (Oxoid)), and then further diluted to approximately 5 x 106 CFU / ml using Simulated Injury Fluid (SWF; Fetal Calf Serum (Hyclone) and PW mixed in 1: 1 proportions) to create inoculum for test samples.
[0113] [000113] Test samples including Examples 1-3 and 4-6, and negative control samples (Lyofoam ™ Max and Example 7), were tested in triplicate for each organism. Circular pieces (Ø 31 mm) from examples 1-3 and 4-6 and negative control samples were punctured under aseptic conditions and placed in separate Petri dishes with the adhesive silicone layer (or foam side of LyofoamTM Max) facing up. 0.5 ml aliquots of the inoculum were added at various points on the adhesive silicone layer (or foam surface) in each test sample. Petri dishes containing test samples were incubated at 35 ° C ± 2 ° C for 24 hours.
[0114] [000114] To determine the initial inoculum levels, additional triplicates of negative control samples, that is, from Lyofoam ™ Max and Example 7, were inoculated and transferred directly to separate 250 mL plug-containing containers containing 100 mL of Room temperature D / E. The number of viable counts was determined on the D / E by means of a ten-fold serial dilution in PW and coated on Petrifilm ™ Aerobic Counting Plates (3M) and incubated for 48 hours before counting colonies. Results were expressed as the average of viable counts (log cfu / sample) per negative control sample.
[0115] [000115] After incubation (at 35 ° C ± 2 ° C for 24 hours), the test samples were transferred to separate 250 mL plug-in containers containing 100 mL of ambient temperature Dey-Engley neutralization buffer (D / E, Becton Dickinson). The containers were shaken rigorously for at least 60 seconds to ensure that surviving test organisms were removed. The number of viable counts was determined on the D / E by means of a ten-fold serial dilution in PW and coated on Petrifilm ™ Aerobic Counting Plates (3M) and incubated for 48 hours before counting colonies. Results were expressed as the average of viable counts (log cfu / sample) per negative control sample. Result and Discussion
[0116] [000116] The silver content in the Examples that were prepared and tested for antimicrobial effectiveness is shown in Table 1 below. Examples 1 to 3 (as described above) comprise a silicone adhesive applied as a coating directly on a first surface of a hydrophilic foam (LyofoamTM Max), while Examples 5 to 8 (as described above) comprise a silicone adhesive. silicone applied as a coating on a perforated plastic film, the plastic film of which is attached to a first surface of the hydrophilic foam.
[0117] [000117] Figure 3a and figure 3b show the result of the antimicrobial activity test against P. aeruginosa and S. aureus, respectively. As can be seen in both figures below, the example modalities according to the invention, that is, Example 3 and Example 6, both comprising silver salt (Ag2SO4) coating the silicone gel adhesive as well as comprising silver salt on the foam substrate, show a significant reduction in viable counts after 24 h, approximately 3 Log CFU / sample, whereas for examples 1, 2, 4 and 5, each having silver salt only on the substrate of foam or as a coating on the silicone gel adhesive, show no reduction or even an increase in viable counts after 24 h when compared to the start inoculum levels measured at 0 h. In fact, these test samples from Examples 1, 2, 4 and 5 show results similar to the control samples Lyofoam ™ Max and Example 7 (not comprising silver salt). It should be noted that the total silver salt concentration in all examples 1, 2, 3, 4, 5 and 6 is maintained at approximately the same total level (i.e., 116-118 µg / cm2). Thus, these results are indeed very surprising, and clearly illustrate the technical effect achieved by the invention. Without being bound by theory, it is believed that the significant difference in antimicrobial activity between the inventive Examples 3 and 6 and Examples 1, 2, 4, 5 is because of the fact that the test organisms are in contact with sufficient quantities of silver salt during the test; regardless of whether the test organisms end in the adhesive silicone gel or foam substrate. This is representative for the clinical situation where microorganisms on the dressing surface, as well as in the immediate vicinity of the dressing, will be affected by the silver salt in the adhesive silicone gel, while microorganisms in wound exudates absorbed by the foam substrate will be reduced by the silver salt present in it. It should also be noted that the detection limit of the method is approximately 2.0 Log CFU / test sample. The initial inoculum levels (measured at 0 h for negative control samples only, according to ISO 20743) were 5.9 Log CFU / test sample in the antimicrobial test against S. aureus (figure 3a) and 6, 2 Log CFU / test sample in the antimicrobial test against P. aeruginosa (figure 3b). Adhesion Experiments
[0118] [000118] The purpose of the adhesion experiments was to determine whether the adhesive properties of the adhesive silicone layer were affected by a salt coating. For this purpose, two tests were used: Adhesive Test A (on a steel surface) and Adhesive Test B (on an artificial skin surface). Both tests are based on ASTM D3330 / D3330M-04, method F, with the following deviations: (i) rest time after calendering is 30 ± 5 min, while in the standard indicated above a maximum of 1 minute is used, (ii) average load measured between 20 and 120 mm, when compared to 25 and 75 mm in the pattern indicated above; and (iii) for test B, roller weight of 445 g, while in the standard indicated above, the roller weight is 2,040 g.
[0119] [000119] Test A - General test procedure: the steel plate (according to ASTM A 666-94A; PSTC Supplement B 2.6; suitable for blade) was cleaned using an absorbent material free of cotton and acetone, and dried in room temperature for 10 min. Cleaning was repeated three times. The adhesive test product (25 x 220 mm) was applied to the clean steel plate without pressing it onto the plate. The test piece was calendered (mechanical calender; roller weight 2.040 ± 45 g), once forwards and backwards. The sample was left to rest for 30 ± 5 minutes before the test. A cord was attached from the blade to the crosshead. The cord makes the blade move horizontally at the same speed as the crosshead moves vertically. This ensures that the angle at which the test piece is detached from the substrate is maintained at 90 °. The steel plate was placed on the slide, and one end of the test product was carefully delaminated from the steel plate and then attached to the top clamp together with paper to prevent slipping. The stress tester was started, and the average force required to pull the test piece out of the substrate was measured.
[0120] [000120] Test B - General test procedure: double-coated adhesive tape was applied to the steel plate (according to ASTM A 666-94A; PSTC Supplement B 2.6) in such a way that air bubbles were not trapped under the ribbon. The skin substrate (Millipore's 5 μm Mitex Membrane) was applied over the tape carefully to avoid air bubbles between the skin substrate and the tape (cotton gloves should be used). The skin substrate was covered to prevent dirt when pressed on the tape. The adhesive test product (25 x 220 mm; with a strip of paper at the end to prevent dirt from sticking) was applied to the substrate, and the sample was calendered mechanically (roller weight 445 g; or using a manual calender) with rubber surface weight of 185 g), once forwards and backwards. The sample was left to stand for 30 ± 5 minutes, and subsequently the steel plates were placed on the slide and the test product was fixed to the upper support. A cord was attached from the blade to the crosshead. The tension tester was started and the average force required to pull the silicone strip from the substrate was measured. Results and discussion
[0121] [000121] Several products have been prepared by spraying the silicone adhesive layer of commercially available Avance® Film and Mepilex® (from Molnlycke Health Care) with various amounts of sodium chloride (NaCl). The step of spraying a silicone adhesive surface as previously disclosed for Example 2 or 5 was employed. Also, Examples 5 and 7 were included in the adhesive test. The results of the adhesion tests (shown in Table 2 below) show that a large amount (for example, 2,500 µg / cm2) can be added without completely losing the adhesive property of the adhesive layer, and for a smaller amount of salt (for example, example, up to 1,000 µg / cm2) the adhesive properties can be maintained substantially. Thus, the medical dressing according to the invention can actually be adherent.

权利要求:
Claims (15)
[0001]
Medical dressing (1, 20) comprising a substrate (2) comprising a first antimicrobial chemical compound, said substrate having a first surface (4), wherein said medical dressing additionally comprises an adhesive layer (3) having a facing surface for the skin (6) to glue said medical dressing to a dermal surface, wherein at least a part of said surface facing the skin comprises a coating (9) comprising a second antimicrobial chemical compound, characterized by the fact that at least one of said first antimicrobial chemical compound and said second antimicrobial chemical compound is a silver salt.
[0002]
Medical dressing, according to claim 1, characterized by the fact that said first surface of said substrate is facing said layer of adhesive, and wherein said surface facing the skin of said layer of adhesive is facing away said first surface of said substrate.
[0003]
Medical dressing according to claim 2, characterized in that said adhesive layer is a coating on at least a part of said first surface of said substrate.
[0004]
Medical dressing according to claim 2, characterized in that said medical dressing additionally comprises a layer of perforated film (11) disposed between said first surface of said substrate and said layer of adhesive, wherein said layer adhesive is a coating on an unperforated part of said layer of perforated film.
[0005]
Medical dressing according to any one of claims 1 to 4, characterized by the fact that said first chemical compound is distributed within said substrate.
[0006]
Medical dressing according to any one of claims 1 to 2, or 4 to 5, characterized in that said first surface of said substrate comprises a coating of said first chemical compound, and said adhesive layer is a coating on at least a part of said coating of said first chemical compound.
[0007]
Medical dressing according to any one of claims 1 to 6, characterized in that said medical dressing additionally comprises a vapor-permeable transmission layer (10), wherein said vapor-permeable transmission layer overlaps a second surface of said substrate, said second surface being opposite to said first surface of said substrate.
[0008]
Medical dressing according to any one of claims 1 to 7, characterized in that said adhesive layer comprises a silicone based adhesive.
[0009]
Medical dressing according to any one of claims 1 to 9, characterized in that one of said first chemical compound and said second chemical compound are selected from the group consisting of a silver compound such as silver salt and metallic silver , biguanide salts such as polyhexamethylene biguanide (PHMB) or any salts thereof, or polyhexamethyl guanide (PHMG) or any salts thereof, or chlorhexidine or any salts thereof, iodine, salicylic acid or any salt thereof , acetylsalicylic acid or any salt thereof, quaternary ammonium salts such as benzethonium chloride, povidone-iodine (betadine), lactoferrin, xylitol, antimicrobial peptides such as human cationic antimicrobial protein 18 (hCAP18 or LL37) peptides, borneol, subgalate bismuth, antifungal pharmaceutical products and antibiotics such as gentamicin, streptomycin.
[0010]
Medical dressing according to any one of claims 1 to 9, characterized in that said first chemical compound is present in a first concentration per area of said medical dressing and said second chemical compound is present in a second concentration per area of said medical dressing, in which said first and second concentrations are different.
[0011]
Medical dressing according to any one of claims 1 to 10, characterized by the fact that the concentration of said first chemical compound is about 5 to 3,000 µg / cm2, and in which the concentration of said second chemical compound is about from 1 to 2,500 µg / cm2.
[0012]
Medical dressing according to any one of claims 1 to 11, characterized in that said substrate comprises an absorbent material.
[0013]
Medical dressing according to claim 12, characterized in that said absorbent material is selected from the group consisting of polymeric foam such as a hydrophilic polyurethane foam, a nonwoven material, fibrous material such as fibrous hydrophilic polymeric material, fibers of gel formation, hydrogel, a matrix containing hydrocolloids, braided and knitted fibers.
[0014]
Medical dressing according to any one of claims 1 to 13, characterized in that said adhesive layer comprises a third chemical compound distributed within said adhesive layer, wherein said third chemical compound is equal to at least one between said first and said second chemical compound.
[0015]
Method of making a medical dressing (1, 20) as defined in any of claims 1 to 14, characterized by the fact that it comprises the steps of: providing a substrate (2) comprising a first antimicrobial chemical compound; providing a layer of adhesive (3); and providing a coating (9) comprising a second antimicrobial chemical compound in said adhesive layer, wherein at least one of said first chemical compound and said second chemical compound is a silver salt.

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KR20170072187A|2017-06-26|

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法律状态:
2019-08-27| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2020-09-01| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2020-12-01| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 09/09/2015, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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EP14184431.6A|EP2995324A1|2014-09-11|2014-09-11|Medical dressing|

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EP14184431.6|2014-09-11|

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PCT/EP2015/070648|WO2016038109A1|2014-09-11|2015-09-09|Medical dressing|

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