ANTIMICROBIAL WOUND DRESSING
20240245556 ยท 2024-07-25
Inventors
Cpc classification
A61L2300/106
HUMAN NECESSITIES
A61F13/00063
HUMAN NECESSITIES
A61L15/46
HUMAN NECESSITIES
A61L2300/404
HUMAN NECESSITIES
International classification
Abstract
The present invention concerns antimicrobial multi-layer wound dressings having an antimicrobial agent located at one or more interfaces between opposing surfaces of the layers of the wound dressing. This improves the migration of antimicrobial agent and allows the dressing to provide a higher overall concentration of antimicrobial agent throughout the dressing. This will assist clinicians when treating wounds by reducing the microbial load at the wound bed thereby reducing the risk of wound infection.
Claims
1. A multi-layer wound dressing comprising at least a first layer and a second layer, wherein the first layer is adjacent to the second layer and bonded thereto; and an antimicrobial agent, wherein the antimicrobial agent is located at an interface between opposing surfaces of the first and the second layer.
2. A multi-layer wound dressing according to claim 1, wherein the multi-layer wound dressing further comprises a third layer, the third layer being adjacent to the second layer.
3. A multi-layer wound dressing according to claim 2, wherein an antimicrobial agent is further located at a second interface between opposing surfaces of the second and the third layer.
4. A multi-layer wound dressing according to claim 2, wherein the multi-layer wound dressing further comprises a fourth layer, the fourth layer being adjacent to the third layer.
5. A multi-layer wound dressing according to claim 4, wherein an antimicrobial agent is located at a third interface between opposing surfaces of the third and the fourth layer.
6. A multi-layer wound dressing according to claim 1, wherein the antimicrobial agent is located at more than one interface.
7. A multi-layer wound dressing according to claim 1, wherein the first and the second layers are bonded by an adhesive at the interface between opposing surfaces of the first and the second layer.
8. A multi-layer wound dressing according to claim 1, wherein the antimicrobial agent is mixed with the adhesive.
9. A multi-layer wound dressing according to claim 1, wherein the antimicrobial agent is dry.
10. A multi-layer wound dressing according to claim 9, wherein the antimicrobial agent is in the form selected from the group consisting of a film, powder, flake, granules, crystals and combinations thereof.
11. A multi-layer wound dressing according to claim 1, wherein the antimicrobial agent is selected from the group consisting of silver, derivatives of silver, lactic acid, citric, acid, benzalkonium chloride, iodine, iodine salts, iodate salts, copper, copper salts, zinc, zinc salts, toluidine blue O, xylitol, chlorhexidine gluconate, polyhexamethylene biguanide (PHMB), miconazole nitrate and combinations thereof.
12. A multilayer wound dressing according to claim 11, wherein the antimicrobial agent is silver and/or a derivative of silver.
13. A multilayer wound dressing according to claim 11, wherein the antimicrobial agent is iodine.
14. A multilayer wound dressing according to claim 13, wherein an iodate salt and iodide salt react to form iodine in situ.
15. A multi-layer wound dressing according to claim 1, wherein the antimicrobial agent is present in an amount of from 0.001 to 10 wt % of the total composition.
16. A multi-layer wound dressing according to claim 1, wherein the antimicrobial agent is further located in a layer of the multi-layer wound dressing.
17. A multi-layer wound dressing according to claim 1, wherein the first layer is a wound contact layer and the second layer is an absorbent layer.
18. A method of manufacturing a multi-layer wound dressing, the method comprising the steps of applying an antimicrobial agent to a surface of the first and/or the second layer, locating the first and second layers adjacent to each other and bonding the first layer to the second layer, such that the antimicrobial agent is located at an interface between opposing surfaces of the first and the second layer.
19. A multi-layer wound dressing as claimed in claim 1 for use as a medicament.
20. A multi-layer wound dressing as claimed in claim 1 for use in killing or inhibiting the growth of microorganisms.
21. A multi-layer wound dressing as claimed in claim 1 for use in absorbing fluid discharged from a physiological target, or for use in stemming a flow of a fluid discharged from a physiological target site.
Description
DETAILED DESCRIPTION OF THE INVENTION
[0122] In order that the invention may be more clearly understood, one or more embodiments thereof will now be described, by way of example only, with reference to the accompanying drawings of which:
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[0140]
[0141] Referring to
[0142] The absorbent foam is a polyurethane open celled foam having a thickness between 1.5 mm-3.25 mm. The superabsorbent material is a polyacrylate superabsorbent fibrous nonwoven material.
[0143] The adhesive (104) is a powder adhesive that is applied by scattering over either the wound contact layer (102) or absorbent layer (103) and laminated using heat.
[0144] The antimicrobial agent (105) is a silver salt.
[0145] Referring to
[0146] In addition to the first interface (106), the absorbent layer (103) also comprises an antimicrobial agent (205).
[0147] The antimicrobial agent (105, 205) located at the first interface (106) and in the absorbent layer (203) is a silver salt.
[0148] The wound contact layer (102), absorbent layer (203) and adhesive (104) are the same materials as described in
[0149] Referring to
[0150] In addition, to the first interface (106), the wound contact layer (302) also comprises an antimicrobial agent (305).
[0151] The wound contact layer (302), absorbent layer (103), adhesive (104) and antimicrobial agents (105, 305) are the same materials as described in
[0152] Referring to
[0153] The materials of the wound contact layer (102), adhesive (104), absorbent layer (103) and antimicrobial (105) agent is the same as
[0154] The backing layer (407) is a polyurethane film. The backing layer (407) is permeable to air and moisture vapour but impermeable to microorganisms and water droplets.
[0155] Referring to
[0156] In addition to the first interface (106), the superabsorbent layer (203) comprises an antimicrobial agent (205).
[0157] The materials of the wound contact layer (102), adhesive (104), absorbent layer (203) and antimicrobial agents (105, 205) are the same as
[0158] Referring to
[0159] In addition to the first interface, the absorbent foam wound contact layer (302) comprises an antimicrobial agent (305).
[0160] The materials of the wound contact layer (302), adhesive (104), absorbent layer (103) and antimicrobial agents (105,305) are the same as
[0161] Referring to
[0162] The materials of the wound contact layer (102), adhesive (104,704), absorbent layer (103), backing layer (407) and antimicrobial agents (105, 705) are the same as
[0163] Referring to
[0164] In addition to the first and second interfaces (106, 706), the absorbent layer (203) also comprises an antimicrobial agent (205).
[0165] The materials of the wound contact layer (102), adhesive (104,704), absorbent layer (203), backing layer (407) and antimicrobial agents (105, 205, 705) are the same as
[0166] Referring to
[0167] In addition to the first and second interfaces (106, 107), the wound contact layer (302) comprises an antimicrobial agent (305).
[0168] The materials of the wound contact layer (13), adhesive (12,18), absorbent layer (11), backing layer (17) and antimicrobial agents (14, 16, 19) are the same as
[0169] Referring to
[0170] The absorbent layer (1003) is an alginate fibre.
[0171] The materials of the wound contact layer (102), adhesive (104), backing layer (407) and antimicrobial agent (105) are the same as
[0172] Referring to
[0173] In addition to the first interface (106), the absorbent layer (1103) comprises an antimicrobial agent (1105).
[0174] The materials of the wound contact layer (102), adhesive (104), absorbent layer (1103), backing layer (407) and antimicrobial agents (105, 1105) are the same as
[0175] Referring to
[0176] In addition to the first interface, the wound contact layer (302) comprises an antimicrobial agent (305).
[0177] The materials of the wound contact layer (302), adhesive (104), absorbent layer (1103), backing layer (407) and antimicrobial agents (105, 305) are the same as
[0178] Referring to
[0179] The material of the wound contact layer (102), the adhesive (104, 704) and the antimicrobial agent (105, 705) is the same as
[0180] Referring to
[0181] In addition to the first and second interfaces (106, 706), the second layer (1403) comprises an antimicrobial agent (1405).
[0182] The material of the wound contact layer (102), the adhesive (104, 704) and the antimicrobial agent (105, 705) is the same as
[0183] Referring to
[0184] In addition to the first and second interfaces, the second layer (1403) and the third layer (1503) comprises an antimicrobial agent (1405, 1505).
[0185] Referring to
[0186] Moreover, when the wound contact layer (102) is placed on a wound, wound exudate will pass through the wound contact layer (102) and into the absorbent layer (103). As the wound exudate passes through the dressing and by the antimicrobial agent (105) at the interface (106) between the wound contact layer (102) and the absorbent layer (103), the antimicrobial agent is solubilised in the wound exudate, thereby allowing the antimicrobial agent (105) to be carried with the wound exudate into the absorbent layer (103). This beneficially prevents the growth of microorganisms in an area of the dressing away from the initial application location of the antimicrobial agent (105).
[0187] Further embodiments of the present invention will now be further described with reference to the following non-limiting examples.
EXAMPLE WOUND DRESSINGS
Example 1
[0188] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm containing 0.52% silver chloride salt by weight of the layer and a second layer comprising a superabsorbent fibre were manufactured. Silver lactate salt antimicrobial agent and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 2% by weight. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Example 2
[0189] A first layer being an open celled polyurethane foam with a thickness of 1.5 mm containing 0.78% silver chloride salt by weight of the layer and a second layer comprising a superabsorbent fibre were manufactured. Silver lactate salt antimicrobial agent and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 4% by weight. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Example 3
[0190] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm containing 0.52% silver chloride salt and 2% citric acid by weight of the layer and a second layer comprising a superabsorbent fibre were manufactured. Silver lactate salt and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 2% by weight. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Example 4
[0191] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm containing 0.52% silver chloride salt by weight of the layer and a second layer comprising a superabsorbent fibre were manufactured. Potassium iodide, potassium iodate and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall molecular iodine content of the mixture was 2% by weight. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Example 5
[0192] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm containing 0.52% silver chloride salt by weight of the layer and a second layer comprising a superabsorbent fibre. Chitosan citrate and chitosan lactate granules were then mixed with an adhesive. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Example 6
[0193] A first layer being a perforated silicone wound contact layer and a second layer comprising open celled polyurethane foam with a thickness of 3.25 mm containing 0.52% silver chloride salt by weight of the layer, and a third layer comprising a superabsorbent fibre were manufactured. Silver lactate salt and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 4% by weight. This mixture was then applied to both a surface of the first layer and a surface of the second layer. The first layer was then adjacently bonded to the second layer and the second layer was adjacently bonded to the third layer by the application of heat.
Example 7
[0194] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm and a second layer comprising a superabsorbent fibre was manufactured. Silver lactate salt and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 2% by weight of the layer. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Example 8
[0195] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm containing 0.13% silver lactate salt by weight of the layer, a second layer comprising a superabsorbent fibre and a third layer comprising a PU backing film were manufactured. Silver lactate salt and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 2% by weight of the layer. This mixture was then applied to both a surface of the first layer and a surface of the second layer. The first layer was adjacently bonded to the second layer and the second layer was adjacently bonded to the third layer by the application of heat.
Example 9
[0196] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm, a second layer comprising a 50:50 blend of silver alginate fibre and superabsorbent fibres and a third layer comprising a PU backing film were manufactured. Silver lactate salt and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 2% by weight of the layer. This mixture was then applied to both a surface of the first layer and a surface of the second layer. The first layer was adjacently bonded to the second layer and the second layer was adjacently bonded to the third layer by the application of heat.
Example 10
[0197] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm and a second layer comprising an open celled polyurethane foam with a thickness of 3.25 mm were manufactured. Silver lactate salt and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 2% by weight of the layer. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Example 11
[0198] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm and a second layer comprising a superabsorbent fibre were manufactured. Silver lactate salt and a heat sensitive adhesive powder were then mixed in an amount to ensure that the overall silver ion content of the mixture was 2% by weight of the layer. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Example 12
[0199] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm and a second layer comprising a superabsorbent fibre were manufactured. Silver chloride salt antimicrobial agent and a heat sensitive adhesive powder was then mixed in an amount to ensure that the overall silver ion content of the mixture was 2% by weight. This mixture was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Reference Example 13
[0200] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm containing 0.52% silver chloride salt by weight of the layer and a second layer comprising a superabsorbent fibre were manufactured. A heat sensitive adhesive powder was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Reference Example 14
[0201] A first layer being an open celled polyurethane foam with a thickness of 3.25 mm containing 0.52% silver chloride salt and 2% citric acid by weight of the layer and a second layer comprising a superabsorbent fibre were manufactured. A heat sensitive adhesive powder was then applied to a surface of the first layer and the first layer was adjacently bonded to the second layer by the application of heat.
Test Data
Migration of Silver Chloride Throughout the Dressing:
[0202] Reference Example 13 was exposed to a solution of simulated wound fluid (foetal bovine serum and peptone water) or saline, designed to replicate wound exudate, for three days, in an inverted Paddington cup arrangement in a temperature and humidity-controlled oven. After three days, the layers of the dressing were separated and subject to elemental analysis. It was found that 7.62% of the silver ions had passed into the second layer.
[0203] Similarly, Example 12 was exposed to a solution of simulated wound fluid (foetal bovine serum and peptone water) or saline, designed to replicate the uptake of wound exudate into the dressing, for three days, in an inverted Paddington cup arrangement in a temperature and humidity-controlled oven. After three days, when the layers of the dressing were separated and subject to elemental analysis. Surprisingly, it was found that 52.2% of the silver ions had passed into the second layer.
[0204] The results of these tests are shown in
[0205] Consequently, it is clear that the location of an antimicrobial agent at the interface between opposing surfaces of two adjacent layers allows the antimicrobial agent to better migrate throughout the dressing, thereby increasing the antimicrobial efficacy of the dressing.
AATCC 100 Adapted Test Method:
[0206] To demonstrate the efficacy of the present invention, example dressings were challenged with the adapted AATCC Test Method 100 against a range of microorganisms.
Test Procedure:
[0207] a) The examples were aseptically prepared and cut to a size of 4.2?4.2 cm. [0208] b) Simulated wound fluid (SWF) is then prepared aseptically as 50% Foetal Calf Serum (heat activated) and 50% peptone diluent. [0209] c) The examples are then partially to fully saturated with SWF and placed in a humidified environment at 37? C. for 3 days (preconditioning phase). [0210] d) After preconditioning, the examples are removed from the SWF and placed in a clean sterile petri dish. [0211] e) Bacterial suspensions are prepared at approximately 1?106 CFUml-1 in an appropriate growth media. [0212] f) The inoculums are enumerated by performing 10-fold dilutions plating out the resulting suspensions onto an appropriate media. [0213] g) One millilitre of bacterial suspension is used to inoculate the examples that have been pre-conditioned for 3 days and the examples are left to incubate for 24 hours. [0214] h) Following the 24 hr incubation period, the examples are placed into an appropriate neutralizer and viable organisms are recovered by sonication. [0215] i) Microorganisms are enumerated by performing 10-fold dilutions of the neutralizer in growth media and plating the resulting suspensions on to appropriate media. [0216] j) The bacterial recovery after 24 h treatment time for each example was compared to a negative control at 0 hours and the resulting log-reduction calculated.
[0217] Example wound dressings 1 and 3 described above were tested on a range of gram-positive and gram-negative bacteria. The Log Recovery for Example 1 is presented in
[0218] Example wound dressing 4 was tested against a gram-positive bacterium, a gram-negative bacterium and a mould. The results are described in Table 2.
TABLE-US-00001 TABLE 1 Log-reduction after 24 h treatment time in the AATCC 100 adapted test method. Log-Reduction after 24 h S. aureus S. epidermidis P. aeruginosa E. coli P. mirabilis Example 1 4.20 5.26 4.04 4.70 6.05 Example 3 3.38 4.93 5.25 5.90 Not tested
TABLE-US-00002 TABLE 2 Log-reduction after 24 h treatment time in the AATCC 100 adapted test method. Log-Reduction after 24 h S. epidermidis B. subtilis P. mirabilis A. brasiliensis Example 4 6.16 4.50 6.05 5.86
[0219] It is clear from Tables 1 and 2 that the dressing of the present invention results in significant log-reduction of a range of microorganisms after 24 h treatment time in the AATTCC 100 adapted test method.
[0220] Moreover, to demonstrate the impact of including an additional antimicrobial between composite layers, Example 3 was compared to Reference Example 14, which is of the same construction but without the additional silver lactate antimicrobial agent mixed with the adhesive between the first and second layers. The dressings were compared in the AATCC-100 adapted test method against P. aeruginosa and E. coli. The results are presented in
[0221] It is clear from
[0222] It is of course to be understood that the present invention is not intended to be restricted to the foregoing examples which are described by way of example only.