Antimicrobial or wound care materials, devices and uses

文档序号：1431397 发布日期：2020-03-17 浏览：36次中文

阅读说明：本技术 抗微生物或伤口护理材料、装置和用途 (Antimicrobial or wound care materials, devices and uses ) 是由艾米·布鲁斯特罗伯特·克伦普海琳·安妮·勒孔特大卫·斯蒂芬森马修·雷于 2018-07-12 设计创作，主要内容包括：一种作为基体组分的复合材料的抗微生物材料,包括：柔性亲水性聚合物泡沫或纤维基体,所述柔性亲水性聚合物泡沫或纤维基体包括提供释放面和反面或两个释放面的两个基体面,以及在所述两个基体面之间的结构基体框架,所述结构基体框架限定具有泡孔网络表面的泡孔网络以及其中的孔隙或泡孔开口的网络；以及包含抗微生物添加剂或伤口护理添加剂的粉末装料组分,其中所述粉末装料包含在一个所述释放面或两个所述面处和/或在所述泡孔网络内,其中所述复合材料是预形成的基体组分和粉末装料组分的组合物；以及不对称材料,所述不对称材料关于其中的所述粉末装料的分布是不对称的；以及这样的材料,其中所述粉末装料包含流动剂和/或增量剂和/或粘结剂,并且其中所述粘合剂和/或流动剂与所述增量剂和/或所述粘结剂共同定位；包含所述复合材料的装置、用于制造所述装置的包括组装所述基体和所述粉末装料的方法及其用途。(An antimicrobial material for a composite material as a matrix component, comprising: a flexible hydrophilic polymeric foam or fibrous substrate comprising two substrate faces providing a release face and a reverse face or two release faces, and a structural substrate framework between the two substrate faces defining a cell network having a cell network surface and a network of pores or cell openings therein; and a powder charge component comprising an antimicrobial additive or a wound care additive, wherein the powder charge is contained at one or both of the release sides and/or within the cellular network, wherein the composite is a preformed composition of a matrix component and a powder charge component; and an asymmetric material that is asymmetric with respect to the distribution of the powder charge therein; and such materials, wherein the powder charge comprises a flow agent and/or a bulking agent and/or a binding agent, and wherein the binding agent and/or flow agent is co-located with the bulking agent and/or the binding agent; devices comprising said composite material, methods for manufacturing said devices comprising assembling said matrix and said powder charge and uses thereof.)

1. A material for use as a wound care material comprising

A flexible hydrophilic polymeric foam or fibrous substrate comprising a wound-facing side and a reverse side or both wound-facing sides, and a structural substrate framework between the wound-facing side and the reverse side or between the two wound-facing sides, the structural substrate framework defining a cell network having a cell network surface and a network of pores or cell openings therein, and

a powder charge comprising a wound dressing additive or a combination thereof,

wherein the matrix provides a tortuous network of pores, and

wherein the powder charge is included at the wound facing side or the reverse side and within the network of cells proximate the side within the cells, more particularly, the amount of the powder charge gradually decreases with increasing depth within the network.

2. The material of claim 1, wherein the wound dressing additive or combination thereof is selected from any of the antimicrobial substance release additives as defined above or below, and the wound dressing additive is selected from antimicrobial agents, bacterial agents, bacteriostatic agents, fire-retardant agents, odour control agents such as activated carbon or bentonite, protein disruption or denaturing agents, wicking agents, electrically conductive agents, structural propping agents, absorbing agents such as Super Absorbent Polymers (SAP), colouring agents or colour masking agents such as to prevent yellowing of PU foam (optical whiteners, antioxidants).

3. The material of claim 1 or 2, wherein the powder charge is present on one or both of the faces and is absent or present in incidental or negligible amounts within the cell network and within the structural matrix framework.

4. The material of any one of claims 1 to 3, wherein said powder charge is present at one or both of said faces and within said network of cells proximate to said one or more faces, and is absent or present in incidental or negligible amounts within said structural framework.

5. The material of any one of claims 1 to 2 and 4, wherein said powder charge is present at both said faces and within said cellular network proximate one said release face (asymmetric) and absent or present in incidental amounts within the cellular network proximate said opposite face and within said structural framework.

6. The material of any one of claims 1 to 2 and 4 to 5, wherein the powder charge is loaded asymmetrically or in progressively decreasing amounts with increasing depth within the matrix.

7. The material of any one of claims 1 to 2 and 4 to 6, wherein the powder charge extends from the or each release face to between 5% and 50% of the spacing between the face or faces, for example from the face or faces inwardly to cell diameters of 2-6 average sizes.

8. A material according to any one of claims 1 to 7 comprising a powder charge or charges comprising, together or separately, an antimicrobial additive and a superabsorbent polymer (SAP).

9. A material according to any one of claims 1 to 8, comprising a powder charge or charges comprising an antimicrobial additive or SAP and a wound dressing additive as defined in claim 3, wherein a plurality of powder charges are contained at the same face or different faces and/or within a network of cells adjacent to the face.

10. The material of any one of claims 1 to 9, wherein matrix comprises the same or different additives impregnated in background or supplemental content within the structural matrix framework, wherein the background or supplemental content is contained in the preformed matrix.

11. The material of any one of claims 1 to 10 formed as a laminate with one or more fluid permeable webs holding a powder charge.

12. The material of any one of claims 1 to 11, wherein the matrix or a portion thereof comprises a foam matrix selected from natural and synthetic polymer foams such as polystyrene, styrene polymers, polyvinyl chloride, polyvinyl alcohol, polyurethane, phenolic polymers, silicone, polyolefins, rubber and elastomeric thermoplastic polymers and combinations and copolymers thereof.

13. A material according to any one of claims 1 to 12, wherein the matrix or a part thereof comprises a fibrous matrix selected from woven and non-woven fibrous matrices of cellulose, alginate, chitin, chitosan, functionalized derivatives thereof such as rayon and viscose and blends thereof.

14. The material of any one of claims 1 to 13, wherein the atomic antimicrobial substance release additive is selected from elemental silver, silver salts, silver complexes and caged forms thereof and combinations thereof.

15. The material of any one of claims 1 to 14, wherein the antimicrobial atomic species release additive is selected from the group consisting of silver sulfadiazine, silver zeolite, silver sulfate, silver carbonate, silver chloride, silver nitrate, silver oxide, silver phosphate, silver citrate, silver acetate, silver lactate, and combinations thereof.

16. A material as claimed in any one of claims 1 to 15, wherein the diatomic species comprises iodine, for example, caged iodine, such as cadexomer iodine.

17. A material as claimed in any one of claims 1 to 16, in which the superabsorbent polymer is selected from sodium polyacrylate, cross-linked CMC or other absorbent functionalised (by carboxylation or sulphonation) cellulose derivatives, cross-linked polyethylene oxide and PVA copolymers.

18. The material of any one of claims 1 to 17, comprising an additive having a particle size of about 1 micron < D90<30 microns and D50<10 microns.

19. The material of any one of claims 1 to 18, wherein the powder charge comprises a flow agent selected from stearates, clays, silica, charcoal or graphite and combinations thereof having a particle size smaller than the particle size of the additive.

20. A material according to any one of claims 1 to 19 comprising a water-permeable extender and/or binder selected from PEG and PVP and superabsorbent polymers as defined in claim 18, as part of the powder charge or as a solid melt or partial melt, and the powder charge at the one or more substrate faces and/or within the cellular network.

21. Composite material as matrix component

The method comprises the following steps: a flexible hydrophilic polymeric foam or fibrous substrate comprising two substrate faces providing a release face and a reverse face or two release faces, and a structural substrate framework between the two substrate faces defining a cell network having a cell network surface and a network of pores or cell openings therein, and

an additive selected from the group consisting of antimicrobial additives, wound care additives and wound dressing additives or a powder charge component comprising an additive, wherein the material or the powder charge additionally comprises a flow agent and/or a bulking agent and/or a binder

And wherein the additive and the flow agent and/or extender and/or binder are co-located or the powder charge components are co-located at one or both of the release faces and/or within the network of cells, preferably wherein the additive and/or flow agent is partially embedded and retained at the one or more faces and within the cells by the melt-softened co-located extender and/or binder.

22. A method for manufacturing a material according to any one of claims 1 to 21.

23. A method for manufacturing a material, the material comprising

A flexible hydrophilic polymeric foam or fibrous matrix component comprising two matrix sides providing a release side and a reverse side or two release sides, and a structural matrix framework between the two matrix sides defining a cell network having a cell network surface and a network of pores or cell openings therein, and

a powder charge component comprising an antimicrobial substance-releasing additive, wherein the substance is selected from the group consisting of one or more antimicrobial atomic substances and one or more antimicrobial diatomic substances,

the method comprises the following steps: providing the matrix component, and

providing the components of the powder charge in a powder form,

contacting the powder charge component and the matrix component

Wherein said contacting comprises directing said powder charge to one or both of said release surfaces and/or within said cellular network proximate said one or more surfaces.

24. A method for manufacturing a material for use as a wound care material, the wound care material comprising

A flexible hydrophilic polymeric foam or fibrous matrix component comprising a wound-facing side and a reverse side or both wound-facing sides, and a structural matrix framework between the wound-facing side and the reverse side or between the two wound-facing sides, the structural matrix framework defining a cell network having a cell network surface and a network of pores or cell openings therein, and

a powder charge component comprising a wound dressing additive or a combination thereof, wherein the matrix provides a tortuous network of pores, the method comprising

Providing the matrix composition, and

providing the components of the powder charge in a powder form,

contacting the powder charge component and the matrix component

And directing the charge of powder into the wound facing side or the reverse side and the network of cells in cells adjacent the side, the amount of the charge of powder gradually decreasing with increasing depth within the network.

25. A method according to claim 23 or 24, comprising melt-softening a substrate and/or a fluid permeable laminate web laid on the one or more faces and/or providing a binder with a powder charge as defined in any one of claims 1 to 22 in a previous, simultaneous or subsequent step, thereby embedding or bonding the powder charge at the substrate face and/or within the cellular network.

26. The method of any one of claims 23 to 25, comprising providing the matrix component or intermediate surface in a desired orientation, such as a horizontal or inclined orientation with the launch side facing up or down; and

providing the powder charge in one or more hoppers, buckets, cartridges, nozzles or release barrels; and

directing by delivering the powder charge directly to the substrate face or indirectly to the intermediate surface and then contacting the substrate face with any such intermediate surface, wherein delivering is selected from the group consisting of throwing, powder spraying, or depositing.

27. A process as claimed in any one of claims 23 to 26, comprising preparing the powder charge in a preceding step, including selecting additives and any flow agents, extenders and/or binders, and selecting their respective amounts according to additive particle size and their desired availability, in combination with optional blending or mixing, and providing a powder charge for contact and guidance as claimed, the steps further comprising subjecting the additive or the powder charge to a particle size selection process comprising sieving or mass separation or comprising a micronised particle size reduction process.

28. A method according to any one of claims 23 to 27 wherein directing to one of the faces or within the cellular network comprises directly or indirectly placing a powder charge thereon, and simultaneously or subsequently applying a translating force, thereby translating at least a portion thereof within the cellular network.

29. A method as claimed in any one of claims 23 to 28, wherein the translational force comprises a physical force applied directly to the powder charge, such as needle punching, or indirectly to the powder charge through the substrate, for example by crushing or rolling the substrate, thereby displacing the powder charge by translation by gravity or suction or the like.

30. The method of any one of claims 23 to 29, wherein the translational force comprises a field applied on the substrate to which the powder charge is or will be dosed, the field being arranged to fluidize or otherwise cause the powder charge to assume a fluid-like flow, wherein the field is selected from an alternating electrostatic field (AC electric field), a sound field, an ultrasonic field, an aeration field, a pneumatic field, or the like.

31. The method of any one of claims 23 to 30, comprising in a further step distinguishing powder charge portions at the face and powder charge portions within the cell network for respective primary and secondary availabilities by manipulating the respective amounts and distances that secondary availability portions are directed into the cell network and/or into the reverse or secondary release face.

32. A material obtained or obtainable by the method of any one of claims 22 to 31.

33. A device for application to a situs and activation by contact with an aqueous medium provided at said situs, said device comprising

(a) Site-contacting surfaces or layers and/or

(b) Opposed non-site contacting surfaces or layers, and

Wherein (c) comprises a material as claimed in any one of claims 1 to 21 or 32.

34. An apparatus comprising a wound dressing or a portion thereof for application to a wound site and activation by contact with a fluid, such as wound exudate, at the wound site, the wound dressing comprising

(a) Wound contacting surface or layer and/or

(b) An opposing non-wound contacting surface or layer, and

Wherein (c) comprises the antimicrobial material or wound care material of any one of claims 1 to 24 or 35.

35. The antimicrobial device of any one of claims 33 and 34, wherein layer or surface (a) is a conformable elastomeric apertured film that is tacky or non-tacky.

36. The antimicrobial device of any one of claims 33 to 35, wherein layer or surface (b) is a breathable top film that allows fluid and air conditioning at the site and provides an antimicrobial barrier, preferably a continuous water vapor permeable conformable polymeric film.

37. An antimicrobial device according to any one of claims 33 to 36 comprising an additional layer selected from a masking layer (b') comprised between layer (b) and layer (c) and a super absorbent layer (b ") comprised between layer (b) and layer (c).

38. The antimicrobial material or device of any one of claims 1 to 21 and 32 or 33 to 37 which is sterile, ultimately sterile and/or sealed in a moisture and/or microbe impermeable package.

39. A method for manufacturing a device as claimed in any one of claims 33 to 38.

40. A method for treating a locus to help free or maintain free of microorganisms detrimental to the health of the locus, the method comprising contacting the locus with an antimicrobial material or device as claimed in any one of claims 1 to 22 and 32 or 33 to 38, thereby enabling release of an antimicrobial substance into the material and/or the locus.

41. The method of claim 40, which is a method of treating a wound site, thereby enabling rapid release of an antimicrobial substance into the wound site at a high concentration and a sustained release of the antimicrobial substance for a desired duration.

42. A method for wound care comprising contacting a wound site with a wound care material or device of any one of claims 1 to 22 and 32 or 33 to 38.

43. The material or device of any one of claims 1 to 22 and 32 or 33 to 38, for application to a site selected from: wound management; hygiene and sterilization and point-of-use sterilization of articles including medical and dental articles; hygiene and sterilization of personal care preparations and articles such as sanitary pads, diapers, cosmetics; sanitation and sterilization of food or fluids including air and water or its preparation and production systems such as food preparation or packaging plants, ventilation systems, water management systems; and such uses are particularly beneficial for preventing or combating microbial infections.

44. A method of treating a wound, the method comprising:

placing a wound dressing comprising a loaded wound dressing layer within or over a wound, wherein the loaded wound dressing layer comprises a porous matrix and a powder charge of an antimicrobial release additive loaded within the matrix, wherein the powder charge is concentrated at least on a wound-facing surface of the porous matrix;

wherein the antimicrobial release additive is activated for releasing antimicrobial agent from the wound dressing into the wound upon contact with a moist or aqueous medium.

45. The method of claim 44, further comprising releasing the antimicrobial agent for more than one day.

46. The method of claim 44 or 45, further comprising releasing up to 1.8mg/cm per day²The antimicrobial release agent in an amount.

47. The method of any one of claims 44 to 46, further comprising:

allowing wound exudate to contact the loaded wound dressing layer prior to release of at least a portion of the antimicrobial agent to the wound, wherein the antimicrobial agent is configured to diffuse into the wound exudate upon contact with the wound exudate.

48. The method of any one of claims 44 to 47, further comprising:

applying negative pressure to the wound dressing.

49. The method of any one of claims 44 to 48, wherein the antimicrobial release additive is selected from elemental silver, silver salts, silver complexes, caged forms thereof, caged forms of iodine, and combinations thereof.

50. The method of any one of claims 44-49, wherein the antimicrobial release additive is selected from the group consisting of silver sulfadiazine, silver zeolite, silver sulfate, silver carbonate, silver chloride, silver nitrate, silver oxide, silver phosphate, silver citrate, silver acetate, silver lactate, cadexomer iodine, and combinations thereof.

51. The method of any one of claims 44 to 46, wherein the antimicrobial agent comprises silver ions.

52. The method of any one of claims 44 to 46, wherein the antimicrobial agent comprises iodine.

53. The method of any one of claims 44 to 52, wherein said powder charge of said antimicrobial additive further comprises a superabsorbent polymer.

54. The method of any one of claims 44 to 53, wherein the powder charge of antimicrobial release additive has a particle size of about 1 micron < D90<30 microns and D50<10 microns.

55. The process of any one of claims 44 to 54, wherein said powder charge of said antimicrobial additive further comprises a flow agent selected from the group consisting of stearates, clays, silica, charcoal, graphite, and combinations thereof, and wherein said flow agent has a particle size smaller than said antimicrobial release additive.

56. The method of any one of claims 44 to 55, wherein the wound dressing further comprises an absorbent layer that absorbs wound exudate.

57. The method of any one of claims 44 to 56, wherein the wound dressing further comprises a wound contact layer positioned to contact the wound beneath the loaded wound dressing layer.

58. A wound dressing comprising:

a loaded wound dressing layer, the loaded wound dressing layer comprising:

a porous substrate comprising a wound-facing side and an opposite side; and

a powder charge of an antimicrobial release additive loaded in the matrix, wherein the amount of the powder charge decreases with increasing distance from at least the wound-facing side.

59. The wound dressing of claim 58, wherein the substrate comprises a polymer foam.

60. The wound dressing of claim 58, wherein the matrix comprises a fibrous matrix.

61. The wound dressing of any one of claims 58-60, wherein the substrate comprises a hydrophilic polymer.

62. The wound dressing of any one of claims 58-61, wherein the antimicrobial release additive comprises elemental silver, a silver salt, a silver complex, a caged form thereof, a caged form of iodine, and combinations thereof.

63. The wound dressing of any one of claims 58-61, wherein the antimicrobial release additive is selected from the group consisting of silver sulfadiazine, silver zeolite, silver sulfate, silver carbonate, silver chloride, silver nitrate, silver oxide, silver phosphate, silver citrate, silver acetate, silver lactate, cadexomer iodine, and combinations thereof.

64. The wound dressing of any one of claims 58-63, wherein the amount of the antimicrobial release additive on the wound-facing side is 1.4mg/cm²To 4mg/cm²。

65. The wound dressing of any one of claims 58-64, further comprising a wound contact layer underlying the loaded wound dressing layer.

66. The wound dressing of any one of claims 58-65, further comprising a cover layer over the loaded wound dressing layer.

67. The wound dressing of any one of claims 58-66, further comprising a fluid connector configured to connect the cover layer to a negative pressure source.

68. The wound dressing of any one of claims 58-67, further comprising an absorbent layer over the loaded wound dressing layer.

69. The wound dressing of claim 68, wherein the absorbent layer comprises superabsorbent particles.

70. The wound dressing of any one of claims 58-69, wherein the powder charge further comprises a superabsorbent polymer.

71. The wound dressing of any one of claims 58-70, wherein the powder charge of antimicrobial release additive has a particle size of about 1 micron < D90<30 microns and D50<10 microns.

72. The wound dressing of any one of claims 58-71, wherein the powder charge further comprises a flow agent selected from the group consisting of stearates, clays, silica, charcoal, graphite, and combinations thereof, and wherein the flow agent has a particle size smaller than the antimicrobial release additive.

73. The wound dressing of any one of claims 58-72, wherein the substrate comprises a plurality of cells, and wherein the antimicrobial release additive is at least partially embedded within the cells.

Technical Field

Antimicrobial or wound care materials and devices, methods of manufacture thereof, uses thereof, and methods of treatment therewith are disclosed. The materials and devices include antimicrobial additive powders or wound dressing additive powders loaded thereon or therein (such as asymmetrically loaded thereon or therein) to achieve effective release rates, release profiles, and/or reproducibility of release.

Background

Silver impregnated antimicrobial wound dressings exist in the form of a product comprising a silver salt (in particular silver nitrate, silver sulfadiazine or silver sulfate) as an antimicrobial additive, in combination with a porous absorbent matrix (such as woven and non-woven fibrous articles or polyurethane foam) to treat exudate from the wound. The silver salt is typically incorporated into the porous matrix via a liquid phase solution or suspension. This may occur when the absorbent matrix itself is manufactured, for example during the polymerization of polyurethane foam, wherein silver salts are suspended or dissolved in an aqueous reaction phase, or from the treatment of the absorbent matrix in an impregnation or reaction bath.

There is an increasing need for wound dressings that can remain in place for longer periods of time between dressing changes and that continuously and simultaneously release antimicrobial silver ions in large doses (pre-or rapidly). This results in the use of low solubility silver salts in wound dressings. However, the low solubility of such silver salts limits the amount of salt that can be introduced by conventional solution manufacturing routes. The release of large doses from such limited amounts of low solubility salts may not be sufficient to inhibit or kill bacteria, and as such, sustained release may be difficult to control.

Attempts to address these limitations have met with limited success, such as the incorporation of dissolved and dispersed silver salt combinations into polyurethane foams during polymerization, and the incorporation of silver salts in multilayer, multilayered wound dressings, including hydrophilic foams and films.

Disclosure of Invention

We have now found that these needs can be met by providing an antimicrobial material comprising a low solubility silver salt which is readily available, that is to say has a high effective surface area, can be readily accessed in a matrix and/or is present in high concentrations, and/or provides silver salt in differentiated or manipulatable availability regardless of its solubility, that is to say, to the location within the material where effective and effective availability is required for large doses and sustained release.

We provide herein an antimicrobial material comprising a porous absorbent fibrous or foam matrix containing a powder charge of an antimicrobial release additive in powder form loaded on and/or within a preformed matrix. More specifically we provide herein an antimicrobial wound dressing material comprising a porous absorbent foam matrix, such as a Polyurethane (PU) foam matrix or a porous absorbent fibrous matrix, and a powder charge of an antimicrobial substance-releasing additive, more particularly an iodine-releasing additive or a silver ion-releasing additive. Iodine and silver ions are highly effective antimicrobial agents.

Further we provide herein a wound dressing material comprising a porous absorbent fibrous or foam matrix comprising a powder charge of an additive asymmetrically loaded in powder form in the preformed matrix.

Advantageously, the powder charge is an additive in powder form that is packed into the face and/or cells of the substrate and can be readily subjected to antimicrobial release. The powder charge is dry loaded, that is, it is loaded onto or into the substrate by a dry processing route. The powder charge remains in powder form during and after loading. The materials herein have additive property characteristics of the powder charge dry loaded thereon and/or therein. For example, the antimicrobial materials herein have an antimicrobial release profile, such as a rapid release and/or a high release of the antimicrobial agent, which is characteristic of dry-loaded powder charges of the antimicrobial release additive.

Advantageously, the additives may be selected without regard to density or water solubility, e.g., the additives may be dense or poorly water soluble and still be included in the materials herein in effective amounts, e.g., antimicrobially effective amounts. More specifically, the additives can be loaded onto a foam or fibrous matrix, such as a Polyurethane (PU) foam or a natural or synthetic fibrous matrix, without problems due to limited solubility or maintaining unstable suspension of solids in liquids. Advantageously, the materials herein may be characterized by highly reproducible additive loading, such as symmetric or asymmetric additive loading and/or by reproducible additive dosing, regardless of matrix thickness or absorptive capacity.

In embodiments, provided herein are antimicrobial materials, which are composites of

powder charge component comprising an antimicrobial additive, wherein the additive is an antimicrobial substance release additive

And wherein said powder charge is contained at one or both of said release faces and/or within said cellular network.

Preferably, the antimicrobial substance is selected from the group consisting of one or more atomic substances and one or more diatomic substances and combinations thereof.

Preferably, the composite material comprises a preformed matrix and a preformed powder charge composition, that is to say, each of the matrix and the powder charge is a preformed component assembled in a composite material as defined herein, more particularly, a composite material is a composition of the matrix in the form of a matrix and the antimicrobial additive in the form of a powder.

Preferably, no powder charge, or an incidental or negligible amount of powder charge, is present within the structural matrix frame. Powder charges present in incidental or negligible amounts within the structural matrix framework are suitably present locally at the one or more faces and/or within the cell network.

The pore network herein may be a tortuous pore network having low pore sizes and/or low frequency pores or cell openings, or may be a reticulated pore network, i.e., a reticulated pore network having high pore sizes and/or high frequency pores or cell openings.

In embodiments, the substrate provides a tortuous network of pores, and the material comprises a powder charge that decreases in concentration within the cellular network proximate to the one or more release faces and/or with increasing depth within the cellular network from one or both of the faces. For example, the substrate may resemble a surface-loaded or depth-loaded filter. In an alternative embodiment, the matrix provides a reticulated pore network, and the material comprises a powder charge uniformly loaded throughout the cellular network. For example, the substrate resembles a stent.

In embodiments, the powder charge is retained at and/or within the one or more faces by the action of the binder and/or by mechanical retention by the tortuosity of the pore network and/or by the cell size and/or the pore size between cells. For example, the interconnection of the cells is achieved by "windows" between the cells that are smaller than the size of the cells themselves, thereby limiting the possibility of the loaded powder charge falling out of the cell network and thus out of the matrix. This also creates a high tortuosity within the matrix, which is advantageous for achieving loading asymmetry, as the powder charge needs to traverse a tortuous path to penetrate the matrix. Examples of tortuous cell interconnections are shown in non-limiting manner in fig. 3a and 3c against polyurethane foam, the "closed cell" pattern having small interconnected windows or pores in the cell walls, or the "open cell" pattern being reticulated with struts defining pores.

Further, provided herein are wound care materials comprising

a powder charge comprising a wound dressing additive or a combination thereof,

wherein the matrix provides a tortuous network of pores, and

wherein the powder charge is included on the wound facing side or the reverse side and in the network of cells proximate the side of the cells, more particularly, the amount of the powder charge gradually decreases with increasing depth within the network.

The wound dressing additive herein or a combination thereof is preferably selected from any of the antimicrobial substance release additives as defined above or below, and the wound dressing additive is selected from antimicrobial agents, bactericides, bacteriostats, fireproofing agents, odor control agents such as activated carbon or bentonite, protein disruption or denaturing agents, wicking agents, conductive agents, structural proppants, absorbents such as Super Absorbent Polymers (SAP), colorants or color masking agents such as to prevent yellowing of PU foam (optical whiteners, antioxidants), and the like, as well as combinations with viscosity modifiers, and the like.

First, embodiments herein are directed specifically to antimicrobial substances to release additives and to help control the particle size of additive powders, such as silver salts. This is of particular interest where a particular particle size (e.g., micron particle size) enhances the release of antimicrobial substances such as silver ions. When loading the liquid phase, i.e. when using wet processing, the particle size of the salt or additive of interest can vary greatly depending on temperature, concentration and solubility. In the present invention, by keeping the powder additive dry during loading of the powder additive onto or into the matrix or finished antimicrobial porous material, changes in particle size during processing are avoided. Furthermore, the advantages herein may be important for materials and methods that generally include wound dressing additives that are sensitive to particle size or moisture content or hydration or both.

Second, advantageously, embodiments herein comprise powder charges of an additive, such as an antimicrobial additive (e.g., a silver salt), that are located on the substrate side and/or the cellular network so as to be readily contactable with a fluid at a site, e.g., to absorb the fluid or release an antimicrobial substance. Thus, the dosing of the additive used may potentially be reduced, or may be loaded with a greater or faster effect, compared to other loading techniques with less readily available additives, e.g. introduced at the point of manufacture of the porous matrix. This allows for improved safety characteristics of the material (such as a wound dressing) without compromising performance, or for more effective materials, such as antimicrobial materials that provide a higher log reduction of microorganisms or potentially are capable of killing a wider range of microorganisms.

More advantageously, embodiments herein facilitate excellent dosing control because the basis weight of the porous matrix component does not affect the loading. This is in contrast to, for example, the method of incorporating additives at the point of manufacture of the porous matrix.

Advantageously, embodiments herein enable the use of dense or sparingly water-soluble additives, such as silver sulfate, without the need for liquid phase or wet processing. The materials are simple to manufacture, cost effective, and do not require large amounts of solvents, nor do they present inherent handling and processing problems.

More advantageously, embodiments herein provide high concentrations of additives. For example, dry-loaded powders can be loaded quickly, simply, and efficiently at any desired concentration. This is in contrast to prior art wet processing methods (i.e., solution/dispersion methods). The present invention is not affected by suspensions that are limited or unstable in solubility.

The composite material herein is to be understood in its ordinary sense. For example, a composite material may be defined by its theoretical ability to break down and restore its intact component parts by reversing its assembly. The powder charge contained at the face and/or within the cells of the substrate herein retains its pre-assembly identity and, without regard to any retention (such as by a tortuous network of pores) or embedding in the cell surface, can theoretically be recovered by shedding from the face and from the cells by means of the network of pores. Likewise, the matrix retains its pre-assembly identity and, without any embedment, can theoretically be restored by shedding the powder charge without destroying the matrix fabric, i.e., the structural matrix framework.

The composite antimicrobial material retains the characteristic properties of the preformed or premanufactured matrix component and the powder charge, such as the flexibility or softness properties of the matrix, as well as the properties of the powder charge, such as the release, absorption, solubility or surface area or hydration or water content of the individual particles or powders that make up the powder charge. Wet processing typically reduces the softness and flexibility properties of the matrix as well as the particle surface area properties.

The composite material herein therefore differs from prior art materials comprising a powder which is dissolved or dispersed in a solution, applied to a matrix and dried or mixed in situ into a reactive foam component, followed by formation of the matrix, whereby the identity of the starting powder is lost or changed in each case. In the latter case, theoretically the identity of the starting matrix will also be lost in recovering the additive from the network of structural matrices.

Composite materials herein may conveniently be defined as an intimate association of the matrix with the powder charge, e.g. a solid in dry, solid or gas phase loading, etc.

The cells and cell network herein can be any interconnected cells, voids or free space and networks thereof, contained within a structural matrix framework, such as within a polymer foam or between woven or nonwoven fibers. Pores and pore networks herein include any pore, cell opening, or cell window that interconnects adjacent cells and their networks. The pores and pore networks herein allow for fluid (liquid and gas) transport between cells and provide a fluid path. Preferably, the pore network comprises pores of finite pore size and frequency, the pores providing a misaligned arrangement, thereby impeding air transport in the tortuous fluid path.

An antimicrobial material release additive herein is an additive that can be activated to release a defined antimicrobial material by a release event involving contact with a humid or aqueous medium. Thus, the antimicrobial substance releasing additive or a part thereof is soluble or leachable into water, preferably having a solubility of more than 0.15mg/L at 25 ℃. Ideally, materials and matrices as defined herein are ideally stored away from moisture or aqueous media, for example packaged in a water impermeable package. Thereby avoiding premature release of the antimicrobial substance.

The powder herein may take its ordinary meaning and may be understood to mean fine dry particles, including primary particles and agglomerates and aggregates defined as secondary particles. The primary particles are characterized by a particle size, or particle size distribution in the case of a range of particle sizes.

The surface area of the clusters and aggregates (defined as secondary particles) of the primary particles is the same as or similar to the cumulative surface area of the primary particles. Thus, individual agglomerates, aggregates or secondary particles generally have a larger surface area than a single primary particle of a corresponding size.

Reference herein to a powder charge refers to a powder charge delivered to and contained in a matrix. The powder charge may be a non-metered charge or may be a metered charge. For example, the powder charge delivered to the substrate may be wholly or partially contained in the material.

The powder charge may be an intermittent charge or a discontinuous charge, or may be a continuous charge, such as a total charge on or in a discontinuous substrate (such as a sheet substrate), or a charge per unit volume or area on or in a continuous substrate (such as a roll or web of substrates).

The powder charge of additive may be variously referred to herein as a powder charge, a powder-loaded additive, or a dry-loaded additive. "dry loading" or "powder loading" herein may be conveniently understood to indicate the phase of the powder charge and/or the manner of loading thereof, e.g., "solid phase loading" additives, "solid in gas phase loading" additives, etc., and is not intended to indicate ambient moisture content.

The powder charge herein may be loose and flowing or fixed, e.g., at least partially embedded in the cell network surface. It is important, however, that the embedding has no or only an incidental effect on the primary particle size.

In embodiments, the material is asymmetric with respect to the additive, wherein the powder charge is contained within the network of cells at and/or near one of the substrate sides (e.g., the release side or wound-facing side) or the reverse side, and is absent or present in incidental or negligible amounts within the network of cells at and/or near the other of the substrate sides. The release side may provide for easier antimicrobial release, fluid absorption, etc. than the reverse side, such that the release side may be disposed as a microorganism-facing side or a primary microorganism-facing side, e.g. positioned to face a wound surface. The wound facing side or the opposite side may provide easier fluid absorption, color masking or other additive properties as defined herein.

Alternatively, the material is symmetrical with respect to the distribution of additives, wherein the powder charge is contained within the network of cells at and/or near the two faces. The material can provide easy antimicrobial release, fluid absorption, color masking, etc., at either or both substrate sides. Either side may be configured as a microorganism-facing side or a wound-facing side, e.g., positioned to face a site such as a wound surface. Thus, the material may provide the option of facing microorganisms, facing the site, or facing the wound.

In embodiments, the powder charge is present at the one or more faces and is not present or present in incidental or negligible amounts within the cell network and within the structural matrix framework.

In embodiments, the powder charge is present throughout the matrix at the one or more faces and within the cell network.

Preferably, the material is asymmetric with respect to the additive, wherein said powder charge is present at one or both of said faces and within said cellular network adjacent to one of said faces. The powder charge is absent or present in incidental or negligible amounts in the cell network near the reverse side and within the structural matrix framework.

Alternatively, the powder charge is present at both of the faces and within the network of cells adjacent each of the faces (symmetrical).

In embodiments, the materials herein provide the option of an antimicrobial release face, a wound facing face, etc., i.e., the material is non-treated and is suitable for direct contact with a site or manufacture in a device, either of which is proximal to the site. Alternatively, the materials herein are treated and adapted for direct contact with a site or manufacture in a device wherein the additive-rich face is proximal or distal to the site.

The powder charge herein may be loaded uniformly within the cellular network, asymmetrically or in progressively decreasing amounts with increasing depth in the matrix, for example may be present in progressively decreasing amounts or concentrations with increasing distance from the or each face. The concentration at the face may be continuous or discontinuous, the concentration or amount within the cellular network facilitating independent manipulation of the respective concentration or amount during assembly thereof.

The powder charge may extend from the or each said substrate face to between 5% and 100%, such as 85% or 50% of the spacing between said faces, for example may extend inwardly from said one or more faces to cell diameters of 2-6 average sizes.

In embodiments, the materials herein comprise a powder charge or charges comprising, together or separately, an antimicrobial additive and a superabsorbent polymer (SAP).

In embodiments, the material herein comprises a powder charge or charges comprising an antimicrobial additive or SAP and a wound dressing additive as defined above. Multiple powder charges may be included at and/or adjacent to the same or different faces within the cellular network.

In embodiments, the matrix herein comprises the same or different additives (e.g. the same or different antimicrobial substance release additives) impregnated in the background content or supplemental content within the structural matrix framework of the materials herein contained in the preformed matrix, that is, not introduced into the preformed matrix as a powder charge. During assembly of the matrix and powder charge components into a material as defined herein, the background additive content remains impregnated, preventing its leaching from the structural matrix framework.

In embodiments, the powder charge is disposed or embedded, preferably partially embedded and protruding from, in the one or more substrate faces and/or cell network surfaces. The placement or embedding may prevent or limit powder charge shedding from the one or more substrate faces and/or from the cell network.

Alternatively or additionally, the materials herein may be formed into a laminate with one or more powder charge retaining fluid permeable webs. Furthermore, the powder charge provided within the cell network as defined above may be retained within the cell network as defined above by the tortuosity or cell and/or pore size of the cell network.

In embodiments, the materials herein comprise additives having a solubility of less than 100g/L (25 ℃), more preferably less than 10g/L (25 ℃). Preferably, such additives are present at the face and/or within the cellular network at concentrations in excess of those that might be provided by absorption and drying of the additives from a saturated solution.

In embodiments, the powder charge contained herein at the substrate face and within the cellular network is provided in individually distinct amounts and concentrations appropriate for the desired overall additive property profile (such as its release profile). Advantageously, the composite material herein provides the convenience of independently distinguishing or manipulating the powder charges contained at the substrate face and cell network, respectively, during assembly thereof. For example, for a given material, the proportion of powder charge at the substrate release surface may be greater than, equal to, or less than its proportion within the cell network.

The substrate or a portion thereof herein suitably comprises a foam substrate selected from natural and synthetic polymeric foams such as polystyrene, styrene polymers, polyvinyl chloride, polyvinyl alcohol, polyurethane, phenolic polymers, silicone, polyolefins, rubber and elastomeric thermoplastic polymers and combinations and copolymers thereof.

The matrix herein or a part thereof suitably comprises a fibrous matrix selected from any woven and non-woven fibrous matrix of natural or synthetic fibres including absorbent and superabsorbent fibres such as cellulose, alginates, chitin, chitosan, functionalised derivatives thereof such as rayon and viscose and blends thereof. The matrix may comprise a foam and/or fibrous bi-or multi-layer.

The atomic or diatomic species herein can be charged or uncharged. The antimicrobial atomic species is preferably an antimicrobial ion, more preferably an antimicrobial cation, and most preferably a silver cation. The antimicrobial diatomic species is preferably uncharged, more preferably a homonuclear diatomic species such as I2. The antimicrobial substance releasing additive as defined above may release additional antimicrobial substances, for example water-decomposed forms of iodine.

Preferably, the antimicrobial atom-releasing or diatomic-releasing additive is selected from the group consisting of elemental silver, silver salts, silver complexes, caged forms of silver and caged iodides and combinations thereof, more preferably from the group consisting of silver salts, silver complexes and caged forms thereof, and from the group consisting of caged iodides.

Thus, preferably, provided herein is an antimicrobial material that is a composite of a flexible hydrophilic polymeric foam or fibrous matrix comprising two matrix sides providing a release side and a reverse side or two release sides, and a structural matrix framework between the two matrix sides defining a cell network having a cell network surface and a network of pores or cell openings therein, and

a powder charge comprising an antimicrobial substance-releasing additive, wherein the substance is selected from the group consisting of an antimicrobial atomic substance and an antimicrobial diatomic substance,

wherein said powder charge is contained at said one or more faces and/or within said cellular network, characterized in that said antimicrobial additive is selected from the group consisting of elemental silver, silver complexes, silver salts, caged forms of silver, caged iodides, and combinations thereof.

Preferred silver complexes and silver salts are selected from one or more of colloidal silver, silver zeolite, silver sulfadiazine, silver sulfate, silver carbonate, silver chloride, silver nitrate, silver oxide, silver phosphate, silver citrate, silver acetate, silver lactate, and combinations thereof. Preferably, the caged iodine is selected from the group consisting of cadiomer iodine (cadiomer iodine).

The SAP herein may be selected from known medical grade superabsorbent polymers such as sodium polyacrylate, cross-linked CMC or other absorbent functionalized (by carboxylation or sulfonation) cellulose derivatives, cross-linked polyethylene oxide and PVA copolymers.

The powder charge herein may also comprise a flow agent. A flow agent is included with the additive particles within the charge, thereby providing improved powder handling. Preferably, the additive is co-located with the flow agent.

The flow agent may reduce or inhibit agglomeration or aggregation of the additive, and may aid in flow or lubrication of the powder charge and may prevent agglomeration. The flow agent may facilitate uniform delivery of the additive to the surface and may also reduce waste, cleaning and maintenance of the treatment equipment. The flow agent may be a high melting point insoluble powder such as stearate, clay, silica, charcoal or graphite, and the like. The flow agent may have the same or different primary particle size as the additives herein.

The material or powder charge herein may comprise a bulking agent contained within the cellular network at the one or more substrate faces and/or at the surface thereof as part of the powder charge or as a solid melt or part of a melt together with the powder charge. Preferably, the additive is co-located with the extender or a solid or partial melt thereof.

The extender is a powder diluent that increases the volume of the powder charge. The bulking agent may facilitate accurate and reproducible dosing of the matrix herein and the powder charge within the matrix herein. Bulking agents may be particularly beneficial where dosing accuracy is required. The bulking agent can help to direct the powder charge into the cellular network, particularly to a given depth within the network. The extender may have a smaller particle size than the additives herein and be contained at a greater depth within the cellular network, or may have a larger particle size than the additives and be contained at a smaller depth within the cellular network.

The bulking agent is water permeable. The water permeability allows fluid transport through the cellular network. The extender may be a low softening or melting point material such as PEG, PVP, and the like. The bulking agent is provided with the powder charge components in powder form. The extender, which is contained in the material in molten form, may bind the powder charge to the matrix.

The SAP contained in the powder charge herein may provide an extender function during manufacture in addition to the absorption function in the material as a finished product.

The materials herein may comprise a binder at the one or more substrate faces and/or within the cellular network and the powder charge. The binder is contained in the form of a solid melt or a partial melt. The binder is provided in powder form with the powder charge components and may be the same as or different from the extender as defined above. An additive is co-located with the solid melt or partial melt binder.

The adhesives herein are non-tacky at ambient temperatures and soften at elevated temperatures of 20 ℃ to 90 ℃, e.g., 30 ℃ to 90 ℃. The binder adheres to the substrate and the powder charge by instantaneous softening. The binder-containing material maintains fluid permeability properties at the matrix side and fluid absorption through the matrix side.

In embodiments herein, there is provided a material of a composite material as a matrix component

And wherein the additive and the flow agent and/or extender and/or binder are co-located, or the powder charge components are co-located on the release face or the two faces and/or within the cellular network.

The co-located additives and flow agents and/or extenders and/or binders can be demonstrated by SEM, for example by means of secondary electrons (morphology) and backscattered electrons, as shown, for example, in fig. 3g) and 3 h).

Additives and/or flow agents are included, and co-located extenders and/or binders are partially embedded and retained at the one or more faces and within the cells by melt softening.

In another aspect, a method for making an antimicrobial material is provided, the method comprising

Providing a flexible hydrophilic polymeric foam or fibrous matrix component comprising two matrix sides providing a release side and a reverse side or two release sides, and a structural matrix framework between the two matrix sides defining a cell network having a cell network surface and a network of pores or cell openings therein, and

providing a powder charge component comprising an antimicrobial additive, wherein the additive is an antimicrobial substance-releasing additive,

contacting the powder charge component and the matrix component

And directing said powder charge to one or both of said release surfaces and/or within said cellular network, preferably adjacent to said one or more surfaces.

In another aspect, there is provided a method for manufacturing a wound care material, the method comprising

Providing a flexible hydrophilic polymeric foam or fibrous matrix component comprising a wound-facing side and a reverse side or both wound-facing sides, and a structural matrix framework between the wound-facing side and the reverse side or between the two wound-facing sides, the structural matrix framework defining a cell network having a cell network surface and a network of pores or cell openings therein, and

providing a powder charge component comprising a wound dressing additive or a combination thereof, wherein the matrix provides a tortuous network of pores, and

contacting the powder charge component and the matrix component

And directing the powder charge into the wound facing side or the reverse side and the network of cells in cells proximate the side, more particularly, the amount of the powder charge gradually decreases with increasing depth within the network.

Preferably, the method is a method for manufacturing an antimicrobial material or a wound care material as defined above and below, more preferably a method for manufacturing a material comprising assembling a composite material of a matrix component and a powder charge component as defined above and below.

The method may comprise melt softening the matrix and/or the fluid permeable laminate web laid on the one or more faces and/or the binder provided with the powder charge as defined above in a previous, simultaneous or subsequent step. Melt softening embeds or binds the powder charge at the substrate face and/or within the cellular network. An additive is co-located with the melt-softened binder.

The degree of softening or degree of web lamination or the amount of adhesive may determine the depth or degree of embedment or bonding.

Providing a powder charge as defined herein includes selecting the additive, and any flow agent, extender and binder as defined above, according to its solubility, and selecting their respective amounts according to the additive particle size and its desired availability, and providing a powder charge for contacting and directing as defined.

The primary availability additive is useful for initial contact with fluid at the site and tends to diffuse antimicrobial substances to the site, absorb fluid from the site or have other wound dressing properties. The secondary usability additive may be used to make secondary contact with a fluid that is gradually absorbed from a site within the cellular network, such as to diffuse an antimicrobial substance through the cellular network to the site.

In embodiments where a matrix component is provided, the methods herein comprise providing a matrix with background content or supplemental content of the same or different additives contained within the structural matrix framework. Such background inclusion additives may be used to make three contacts with fluids gradually absorbed from a site within the cellular network and thus within the structural matrix framework, thereby allowing diffusion of the antimicrobial substance from the framework to the site via the cellular network.

Preferably, the method comprises providing the matrix component or intermediate surface in a desired orientation, such as horizontal or inclined, with the drop side facing up or down, although a vertically facing orientation is also contemplated; and

providing the powder charge in one or more powder charge containers such as hoppers, buckets, cartridges, nozzles, release drums, cartridges, and feed lines from or to such containers; and

directing by delivering the powder charge directly to the substrate face or indirectly to the intermediate surface and then contacting the substrate face with any such intermediate surface; wherein

The dispensing is selected from the group consisting of throwing, powder spraying, powder jetting, entrainment, and deposition on the surface or surface.

Containers are known in various forms, such as those provided on carousels or conveyors. The release buckets include inverted buckets, hinged buckets and hopper buckets on an inverted carousel or conveyor.

The intermediate surface may comprise a release liner for depositing and optionally temporarily adhering the powder charge thereto or an intaglio for releasably containing the powder charge.

Both said substrate surfaces may be directed simultaneously or sequentially by one or more of said direct or indirect delivery methods. The resulting material may be asymmetric or preferably symmetric.

Dosing may be continuous or discontinuous and may be by powder charge volume or weight per substrate face or per surface area of the substrate face or per volume of the substrate. Dispensing involves dispensing onto the face of the partially formed matrix that is still tacky, or casting the matrix onto a dispensed release liner.

In embodiments, the method comprises preparing the powder charge in the preceding steps, including selecting the additive or combination thereof, and any flow agents, extenders and/or binders as defined above, and their respective amounts, which are related to the additive particle size and its desired availability in the materials herein, in combination with optional blending or mixing, and providing the powder charge and optional extenders and/or binders provided therewith for contact and directing as defined.

In embodiments, the step of preparing a powder charge further comprises subjecting the additive or the powder charge to a particle size selection or reduction process. Particle size selection may include sieving, centrifuging or cyclonic separation of commercially available powders by mass, or otherwise separating out a desired particle size or mass fraction. The particle size reduction process may be selected according to the desired primary or secondary particle size or particle size distribution of the additive or powder charge or components thereof. Major particle size reduction techniques include known bottom-up techniques for controlling particle size recrystallization and top-down techniques such as grinding or milling. Secondary particle size reduction techniques include top-down techniques such as milling or grinding for deagglomerating or deagglomerating the additive or powder feed.

In embodiments, the methods herein comprise micronizing the additive or powder charge. Micronization may comprise dry particle collision with self-collision or collision with other solid particles, for example by using a grinding medium selected from gaseous and particulate media, comprising high velocity jets of gas inert to the additive (such as high velocity air jets and high velocity nitrogen jets) and high density grinding beads or balls, such as microbeads, into which the additive is directed, for example a turbulent bed of high density microbeads, or to which the microbeads are directed, for example as jets of the microbeads, as further disclosed in our co-pending uk provisional application No. 1711179.0 filed on 12.7.7.2017, the contents of which are incorporated herein by reference.

Examples of known dry milling apparatus and methods using high velocity gas jet milling media include DEC (Dietrich Engineering mills) Conika dry mills, IKA Pilotina MC dry mills, and MC Jetmill and FPS (food pharmaceutical systems) screw jet mill trains.

Directing to one of said faces or within said cellular network suitably comprises dispensing a powder charge as defined above, and simultaneously or subsequently applying a translating force to translate at least a portion thereof within said cellular network.

The translation may be a distance between the faces. Alternatively, the translation may be throughout the entire substrate including the other face. The resulting material may be asymmetric or symmetric.

The translational force includes a physical force applied directly to the powder charge, such as a needle stick, or indirectly to the powder charge through the substrate, such as by crushing or rolling the substrate, thereby displacing the powder charge by translation by gravity, suction, or the like.

Alternatively, the translational force comprises a field applied on the substrate onto which the powder charge is or is to be dosed, more particularly a fluidization field arranged to fluidize or otherwise cause the powder charge to assume a fluid-like flow. Fields include alternating electrostatic fields (AC fields), sound fields, ultrasonic fields, ventilation fields, pneumatic fields, and the like.

The translation force may be adjusted in a manner to manipulate the translation depth within the cellular network, etc., for a given powder charge particle size, matrix porosity, etc.

In embodiments, the methods herein comprise in a further step distinguishing a portion of the powder charge comprised at the face and a portion of the powder charge comprised within the network of cells for respective primary and secondary availabilities by manipulating the respective amounts and depths at which the secondary availability portion is directed into the network of cells and/or into the reverse or secondary release face.

The application and translation of force may be sequential or simultaneous, such as by air injection of a powder charge onto the substrate surface, and simultaneous or subsequent translation of the amount thereof within the cellular network.

In another aspect, provided herein is an antimicrobial material or wound care material obtained or obtainable by the methods herein.

In another aspect, provided herein is an antimicrobial device for application to a situs and activation by contact with an aqueous medium provided at the situs, the device comprising

(a) Site-contacting surfaces or layers and/or

(b) Opposed non-site contacting surfaces or layers, and

Wherein (c) comprises an antimicrobial material as defined herein.

In another aspect, there is provided an apparatus comprising a wound dressing or a portion thereof for application to a wound site and activation by contact with a fluid, such as wound exudate, at the wound site, the wound dressing comprising

(a) Wound contacting surface or layer and/or

(b) An opposing non-wound contacting surface or layer, and

Wherein (c) comprises an antimicrobial material or wound care material as defined herein.

Layer or surface (a) may be tacky or non-tacky, such as a conformable elastomeric apertured film.

Layer or surface (b) is conveniently a breathable top film which allows fluid and air conditioning at the site and provides an antimicrobial barrier, preferably a continuous moisture vapour permeable conformable polymeric film. Layer (b) may comprise a border around the perimeter of material (c).

The device may comprise additional layers selected from a masking layer (b') comprised between layer (b) and layer (c) and a super-absorbent layer (b ") comprised between layer (b) and layer (c), etc.

The layers may be laminated and/or sealed in a pouch formed by the outer layers in a continuous and coextensive relationship.

The materials or devices herein may be sterile, ultimately sterile and/or sealed in moisture and/or microorganism impermeable packaging such as a silver foil pouch.

In another aspect, provided herein is a method of making a device herein.

In embodiments, the previously formed individual layers may be formed into a laminate by bonding the layers together in one or more lamination processes. Suitable bonding methods include heat sealing or adhesive bonding, provided that the adhesive layer is water vapor permeable.

In alternative embodiments, the foam layer is formed in contact with one or both of the other layers or additional layers. This process may be advantageous because it reduces or eliminates the number of special bonding operations.

In another preferred process, an outer conformable film layer is formed on the foam layer, for example by spraying a polymer solution.

In a continuous process, the wound dressing may be made in the form of a continuous strip and then cut into suitable sized dressings.

Typically, combining the layers together is a lamination process.

In the preferred process of forming the dressing, the foam layer is created in contact with an outer layer, and it is important that the other outer layer should be laminated to the expanding foam while the foam is still tacky so that a good bond is obtained. After casting the foam, it is suitable to bring the foam into contact with the further outer layer, typically from 2.5 minutes to 5 minutes, for example from 3 minutes to 3.5 minutes.

In another aspect, there is provided a method for treating a site to help free or maintain free the site from microorganisms detrimental to the health of the site, the method comprising contacting the site with an antimicrobial material or device as defined herein, thereby enabling release of an antimicrobial substance into the material and/or the site. Preferably, such a method is a method of treating a wound site, thereby enabling the release of antimicrobial substances into the wound site. Advantageously, the antimicrobial materials and devices herein rapidly release antimicrobial substances, particularly silver ions, at high concentrations for a desired duration of time, e.g., up to 7,8, or 10 days or more.

In a further embodiment, there is provided a method for wound care comprising contacting a wound site with a wound care material or device as defined herein.

In another aspect, a method of treating a wound is provided. The method comprises placing a wound dressing comprising a loaded wound dressing layer in or over the wound, wherein the loaded wound dressing layer comprises a porous matrix and a powder charge of an antimicrobial release additive loaded in the matrix, wherein the powder charge is concentrated on at least the wound-facing surface of the porous matrix; wherein the antimicrobial release additive is activated for releasing the antimicrobial agent from the wound dressing into the wound upon contact with a moist or aqueous medium.

In some embodiments, the method further comprises releasing the antimicrobial agent for more than one day. In some embodiments, the method further comprises releasing up to daily1.8mg/cm²An antimicrobial release agent in an amount. In some embodiments, the method further comprises allowing the wound exudate to contact the loaded wound dressing layer prior to release of at least a portion of the antimicrobial agent to the wound, wherein the antimicrobial agent is configured to diffuse into the wound exudate upon contact with the wound exudate. In some embodiments, the method further comprises applying negative pressure to the wound dressing. The antimicrobial release additive may be selected from elemental silver, silver salts, silver complexes, caged forms thereof, caged forms of iodine, and combinations thereof. The antimicrobial release additive may be selected from the group consisting of silver sulfadiazine, silver zeolite, silver sulfate, silver carbonate, silver chloride, silver nitrate, silver oxide, silver phosphate, silver citrate, silver acetate, silver lactate, cadexomer iodine, copper salts and complexes, zinc salts and complexes, gold salts and complexes, chlorhexidine gluconate, polyhexamethylene biguanide hydrochloride, and combinations thereof. In one embodiment, the antimicrobial release additive may be selected from the group consisting of silver sulfadiazine, silver zeolite, silver sulfate, silver carbonate, silver chloride, silver nitrate, silver oxide, silver phosphate, silver citrate, silver acetate, silver lactate, cadexomer iodine, and combinations thereof. The antimicrobial agent may comprise silver ions and/or iodine. In some embodiments, the powder charge of antimicrobial additive further comprises a superabsorbent polymer. The powder charge of antimicrobial release additive may have a particle size of about 1 micron < D90< 30 microns and D50< 10 microns. The powder charge of antimicrobial additive may further comprise a flow agent selected from the group consisting of stearates, clays, silica, charcoal, graphite, and combinations thereof, and wherein the flow agent has a particle size smaller than the antimicrobial release additive. In some embodiments, the wound dressing further comprises an absorbent layer that absorbs wound exudate, and/or a wound contact layer positioned in contact with the wound underlying the loaded wound dressing layer.

In some embodiments, the wound dressing may further comprise one or more active ingredients in place of or in addition to the antimicrobial release additive. The active ingredients may for example include powdered growth factors and small active organic molecules (for debridement, e.g. collagenase, or for promoting a healing response, e.g. MMP inhibitors), local oxygen delivery compounds (e.g. variants of haemoglobin) and any other organic or inorganic bacteriostatic, antibacterial, antiseptic or antimicrobial agent.

If the disclosed technology is in the form of a slurry, the active substance, e.g., the active ingredient in the slurry, may not include growth factors, MMP inhibitors, collagenase, hemoglobin variants.

In another aspect, a wound dressing is provided. The wound dressing comprises:

a loaded wound dressing layer comprising:

a porous substrate comprising a wound-facing side and an opposite side; and

a powder charge of an antimicrobial release additive loaded in the matrix, wherein the amount of the powder charge decreases with increasing distance from at least the wound-facing side.

In some embodiments, the matrix comprises a polymer foam, a fibrous matrix, and/or a hydrophilic polymer. The antimicrobial release additive can comprise elemental silver, silver salts, silver complexes, caged forms thereof, caged forms of iodine, and combinations thereof. The antimicrobial release additive may be selected from the group consisting of silver sulfadiazine, silver zeolite, silver sulfate, silver carbonate, silver chloride, silver nitrate, silver oxide, silver phosphate, silver citrate, silver acetate, silver lactate, cadexomer iodine, and combinations thereof. The amount of antimicrobial release additive on the wound facing side may be 1.4mg/cm²To 4mg/cm². In some embodiments, the wound dressing may further include a wound contact layer below the loaded wound dressing layer, a cover layer above the loaded wound dressing layer, a fluid connector configured to connect the cover layer to a negative pressure source, and/or an absorbent layer above the loaded wound dressing layer. The absorbent layer may comprise superabsorbent particles. In some embodiments, the powder charge further comprises a superabsorbent polymer. In some embodiments, the powder charge of antimicrobial release additive may have a particle size of about 1 micron < D90< 30 microns and D50< 10 microns. In some embodiments, the powder charge may further comprise a material selected from stearates, clays, silica, charcoal, graphite, and combinations thereofA combined flow agent, and wherein the flow agent has a particle size smaller than the antimicrobial release additive. In some embodiments, the matrix comprises a plurality of cells, and wherein the antimicrobial release additive is at least partially embedded within the cells.

Variations and modifications to these embodiments will occur to those skilled in the art upon review of this disclosure. The foregoing features and aspects may be implemented in any combination and subcombination, including multiple dependent combinations and subcombinations, with one or more other features described herein. The various features described or illustrated above, including any components thereof, may be combined or integrated in other systems. Furthermore, certain features may be omitted or not implemented.

Further areas of applicability of the disclosed apparatus and method will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating specific embodiments, are intended for purposes of illustration only and are not intended to limit the scope of any one of the disclosure or claims that may be pursued.

Drawings

The foregoing and other objects and advantages will be more fully understood from the following detailed description considered in conjunction with the accompanying drawings, in which like reference characters refer to like parts throughout. The described embodiments are to be considered in all respects only as illustrative and not restrictive:

FIGS. 1a-k illustrate variations of the symmetric materials herein;

FIG. 2 shows a prior art polyurethane foam loaded with manufacturing points by cross-sectional SEM;

FIGS. 3(a) - (h) illustrate graphically and cross-sectionally SEM, a tortuous pore network type, asymmetrically loaded polymeric foam herein;

4a-o illustrate variations of the asymmetric materials herein;

FIGS. 5a-d illustrate a wound dressing form comprising the materials herein;

fig. 6 and 7 show silver ion release from a prior art multilayer dressing and the multilayer dressings herein;

fig. 8 shows the release of silver ions from the reverse side herein;

FIG. 9 shows the release of silver ions before and after sterilization;

fig. 10 shows silver ion release from various multilayered dressing forms herein;

fig. 11 is a schematic diagram of an example of a negative pressure wound therapy system;

fig. 12A illustrates an embodiment of a negative pressure wound therapy system employing a flexible fluid connector and a wound dressing capable of absorbing and storing wound exudate;

fig. 12B illustrates an embodiment of a negative pressure wound therapy system employing a flexible fluid connector and a wound dressing capable of absorbing and storing wound exudate;

fig. 12C illustrates an embodiment of a negative pressure wound therapy system employing a flexible fluid connector and a wound dressing capable of absorbing and storing wound exudate;

fig. 12D shows a cross-section of an embodiment of a fluidic connector connected to a wound dressing;

figures 13A-13D illustrate an embodiment of a wound treatment system that employs a wound dressing capable of absorbing and storing wound exudate to be used without the need for negative pressure;

fig. 13E shows a cross-section of an embodiment of a wound treatment system employing a wound dressing capable of absorbing and storing wound exudate to be used without negative pressure;

fig. 14A-14B illustrate an embodiment of a wound dressing incorporating a negative pressure source and/or other electronic components within the wound dressing;

fig. 14C shows an embodiment of the layers of a wound dressing in which the pump and electronic components are offset from the absorbent region of the dressing;

fig. 15A illustrates an embodiment of a negative pressure wound therapy system employing a flexible fluid connector and a wound dressing having a wrap-around spacer layer, the wound dressing capable of absorbing and storing wound exudate;

fig. 15B shows a cross-sectional view of an embodiment of a negative pressure wound therapy system employing a flexible fluid connector and a wound dressing with a wrap-around spacer layer, the wound dressing capable of absorbing and storing wound exudate;

fig. 15C illustrates an embodiment of a negative pressure wound therapy system employing a wound dressing capable of absorbing and storing wound exudate;

fig. 16A shows another embodiment of a wound dressing in cross-section;

fig. 16B shows a perspective view of an embodiment of a wound dressing including a obscuring layer and a viewing window;

FIG. 17 is a schematic view of a portion of an example of a wound dressing;

fig. 18 is a schematic view of an example of a support layer;

FIG. 19A is a schematic view of a portion of another example of a wound dressing;

FIG. 19B is a perspective view of the wound dressing of FIG. 19A;

FIG. 20 is a schematic view of yet another example of a wound dressing; and is

Fig. 21 is a schematic view of yet another example of a wound dressing.

Detailed Description

Embodiments disclosed herein relate to devices and methods for treating wounds with or without reduced pressure, including optionally a negative pressure source and wound dressing components and devices. The devices and components (if any) comprising the wound covering material and filler material are sometimes collectively referred to herein as dressings.

Preferred embodiments disclosed herein relate to wound therapy for the human or animal body. Thus, any reference herein to a wound may refer to a wound on a human or animal body, and any reference herein to a body may refer to a human or animal body. In addition to having its broad ordinary meaning, the term "wound" as used herein also includes any body part of a patient that can be treated using negative pressure. It should be understood that the term "wound" should be interpreted broadly and encompasses both open and closed wounds in which the skin is torn, cut or punctured or in which trauma causes contusion, or any other surface wound or other condition or defect on the skin of a patient or a wound that otherwise benefits from reduced pressure treatment. Thus, a wound is broadly defined as any damaged tissue area that may or may not produce fluid. Examples of such wounds include, but are not limited to, abdominal wounds or other large or incised wounds that result from either surgery, trauma, sternotomy, fasciotomy, or other conditions, dehiscent wounds, acute wounds, chronic wounds, subacute and dehiscent wounds, traumatic wounds, flap and skin grafts, lacerations, abrasions, contusions, burns, diabetic ulcers, pressure ulcers, stoma, surgical wounds, traumatic ulcers, venous ulcers, and the like.

As used herein, a chronic wound is a wound that cannot heal in an ordered set of phases and within a predictable amount of time in a manner that would heal most wounds; wounds that heal within three months are generally considered chronic. For example, a chronic wound may include an ulcer, such as a diabetic ulcer, a pressure ulcer (or pressure injury), or a venous ulcer.

Treatment of such wounds may be performed using negative pressure wound therapy, wherein reduced or negative pressure may be applied to the wound to aid and promote wound healing. It will also be appreciated that the wound dressings and methods as described herein may be applied to other parts of the body and are not necessarily limited to wound treatment. Other embodiments do not utilize negative pressure to treat the wound or other part of the body.

The material or matrix component as defined herein is a fluid absorbent, more particularly an absorbent for aqueous fluids such as body fluids, e.g. wound fluids, and components thereof. The material or matrix component is permeable to liquids, gases and vapors, for example, to the aqueous fluid, moisture and air. When applied to a location, the material helps regulate moisture and air circulation at the location. The material suitably provides a moist environment, such as a moist wound environment. Preferably, the material or matrix component is hydrophilic porous (i.e., characterized by the ability to create a wet environment and absorb large quantities of fluid. Hydrophilic porous wound dressing materials are characterized by the ability to create a moist wound healing environment and absorb large amounts of exudate.

The materials or matrix components herein are regularly or irregularly shaped or cast continuous or discontinuous objects such as blocks, layers, sheets, mats, sheets, strips, webs or rolls thereof and the like. The materials and matrices herein are non-particulate.

The flexible material or matrix herein is both conformable and elastically extensible. The flexible materials or substrates herein can conform to a surface, such as a shaped surface, e.g., irregular or regular, static, or moving. For example, the material or substrate may conform to the surface of a body part or wound surface, etc., and dynamically conform to changes due to motion, skin drag, stretching, bending, etc. Such materials or matrices may acquire and maintain shape or contour with or without the aid of adhesives or other restraints.

The materials herein are suitable for use in inhibiting or killing microorganisms selected from bacteria, yeasts and fungi, and thus from antifungal, antibacterial, anti-yeast, and in particular fungicidal, bactericidal and fungicidal, fungistatic, bacteriostatic and/or fungistatic and combinations thereof. For the avoidance of doubt, the antimicrobial substance releasing additive herein is not an antibiotic type of antimicrobial agent.

It is contemplated that the antimicrobial material is contacted at the site with an aqueous medium such as an aqueous fluid such as waste fluid, contaminated fluid, bodily fluid such as wound fluid, and the like. Particularly suitable sites are wet.

The antimicrobial material may be a medical material such as a wound care material, a dental material, a personal care material, a hygiene or cleaning material such as a clothing material or upholstery material, a food industry material, a packaging material, or the like. The material may be used directly or included in the device.

Thus, for example, silver salts and/or wound care additives that are advantageous for wound dressings are combined in dry powder form with a porous matrix useful for wound dressings. The resulting material composite may then be used to manufacture wound care devices, such as wound dressings for application to wet wound sites that may or may not exude.

In embodiments, the material applied to the wound site absorbs exudates and particulate matter from the surface of the granulation wound and when the material becomes moist, antimicrobial substances, such as ionic silver or diatomic and ionic iodine substances, are released. Thus, the material has the dual effect of cleansing the wound and exerting an antimicrobial effect.

Advantageously, the asymmetric antimicrobial material herein is adapted to bring a site at risk of microbial infection into contact with the substrate release surface (i.e., the antimicrobial-rich side of the material adjacent to the site, e.g., a wound), such that a maximum amount of antimicrobial additive is close to and most readily available where it is needed.

Advantageously, the asymmetric wound care material herein is adapted to bring a wound into contact with a wound facing side, which may be the additive rich or additive poor side of the material adjacent to the wound, e.g. such that the additive is positioned where it is needed.

Advantageously, the symmetric antimicrobial material or wound care material exhibits a choice of site or wound contact surface, i.e., the material is left intact and suitable for direct contact with a site or fabricated in a device where the release surface or additive rich side of the material is adjacent to the site or wound.

Fig. 1a-h and j show symmetrical material variants herein containing powder charges at both substrate faces and within the substrate cell network. It should be noted that the one or more faces may be free of additives, which may disrupt adhesion in a layered arrangement with additional layers or at a site such as a wound. For example, the substrate may be treated to prevent loading of the powder charge on one or more faces, for example by removing a thin surface layer from the substrate or alternatively slicing the substrate omitting the substrate face. Variations herein with or without the top loading additives may include: a) a uniform low concentration within the network of cells near the face (e.g., within a few cells from each face); b) a uniform high concentration within the network of cells near the face (e.g., within a few cells from each face); c) and d) a decrease from a high concentration to a higher concentration within the cell network proximate the face (e.g., within a few cells from each face) to just less than the depth of the intermediate cell network (in terms of c) and to an intermediate depth (in terms of d)); e) a uniform high concentration within the network of cells near the faces to a depth from each face just short of the intermediate substrate; f) a uniform low concentration within the network of cells adjacent the faces to a depth from each face just short of the intermediate substrate; g) low concentration throughout the cellular network; h) high concentration throughout the cellular network. Fig. 3i) shows a symmetrical variant containing powder charges on both faces only. Fig. 3j) and 3k) show variations of fig. 3b) and 3i) in which the matrix composition prior to assembly includes a background content of an additive, such as the same or a different antimicrobial additive, included within the matrix structural framework.

Figure 2 visually illustrates a cross-sectional SEM of a substrate providing a tortuous pore network herein, a) providing a reticulated cell network or pore network herein, and c) providing a tortuous pore network herein. Matrix types a) and c) may provide asymmetric materials herein, with powder charges of the matrix type loaded asymmetrically or in progressively decreasing concentrations within the cellular network herein. Matrix type b) can provide a symmetrical material herein, with powder charges of the matrix type symmetrically loaded within the cell network herein. Both substrate types may provide symmetric or asymmetric material loading on the one or more faces.

Fig. 3a is a cross-sectional SEM of a prior art manufacturing polyurethane foam containing silver sulfate (bright spots) provided in the aqueous phase of the polymerization reaction and within the overall structural polyurethane framework.

Fig. 3b and 3c show the antimicrobial polyurethane foam matrix herein providing a tortuous pore network comprising silver sulfate powder charges (bright spots) at the foam face and within the cell network. It can be seen that the powder charge has concentrated near the face of the substrate to which the charge is being delivered. In 2mm thick foams and (3c) foam/fiber laminates, there is penetration of silver sulfate concentrated in the cell network up to 1mm depth. There are some silver salt particles deeper in the structure, but these particles are incidental to the concentration near the dosing and release sides.

Fig. 4a-o show asymmetric material variations herein. Figures 4a-h, j and l show asymmetric variants containing powder charges at one substrate face and within the cell network, and it should be noted that the face or faces may be free of additives, which may disrupt adhesion in a layered device with additional layers or at a site such as a wound, as described above in the context of figure 1. Variations herein with or without the top loading additives may include: a) a uniform low concentration within the network of cells near the release face to a depth of a few cells from the face; b) a uniform high concentration within the network of cells near the face to a depth of a few cells from the face; c) decreasing from a high concentration to a low concentration within the network of cells proximate the face to a depth of a few cells from the face; and d) a uniform low concentration within the cell network near the release face to a depth from the face intermediate the matrix; e) a uniform high concentration within the network of cells proximate the face to a depth from the face intermediate substrate; f) decreasing from a high concentration to a low concentration within the network of cells proximate the face to a depth from the face intermediate the substrate; g) a high concentration within the cell network near the face, and a low concentration throughout the remainder of the cell network to the opposite face; h) a high concentration within the cellular network to the depth of the intermediate substrate, and a low concentration throughout the remainder of the cellular network to the opposite side. Fig. 4) and 4k) show an asymmetric variant containing the powder charge only at the faces. Fig. 4j) and 4k) show variants of fig. 2b) and 2i), wherein the matrix composition prior to assembly comprises a background content of an additive, such as the same or a different additive, which is comprised within the matrix structural framework. Figure 4l shows variant 4a) comprising a powder charge both at the two faces and within the network of cells close to one of the faces.

The materials herein may comprise a powder charge within the cell network proximate the face to any desired depth from the face, for example from two average cell diameters to an intermediate substrate depth or full substrate depth from the face, for example from 5% to 50% or 85% or 100%, such as from 10% or 20% to 50% or 85% or 100% of the cell network depth or substrate depth; or a depth of from 0.2mm or 0.3mm or 0.4mm or 0.5mm to 1mm or 2mm or 3mm or 4mm in the material or matrix of 1mm or 2mm or 3mm to 6mm or 7mm or 1cm, that is to say a spacing of 1mm or 2mm or 3mm to 6mm or 7mm or 1cm of each face; or from 0.5mm or 1cm to 2cm in a material or matrix of 1cm to 4cm depth, that is to say a spacing of 1cm to 4cm of each face.

The materials herein may be processed after assembly, e.g., dried, equilibrated, stored or packaged, sterilized, etc., with no or incidental effect on the powder charge or additive properties, such as its release profile. Advantageously, the antimicrobial material herein can thus be treated, e.g., sterilized, with a release profile corresponding to an untreated (e.g., non-sterilized) pre-assembled powder charge. This effect, if any, may therefore be taken into account when determining the amount, dosing and/or guidance of the powder charge.

The materials herein may be sterile or non-sterile, preferably terminally sterile or non-terminally sterile, for example sterilizable by steam, gamma ray, X-ray or electron beam or ethylene oxide. As shown in fig. 9, ionic silver release was comparable to a matching sample of a composite of materials assembled from the same powder charge and the same matrix, one of which was not sterilized and the other was sterilized with ethylene oxide.

The materials herein suitably have a moisture content of less than 10% by weight, preferably less than 8% by weight, preferably less than 5% by weight. The additive or powder charge herein typically has a loss of less than or equal to 0.5 wt% (such as less than or equal to 0.4 wt% or 0.3 wt%) after drying in a vacuum oven for 4 hours at 50 ℃ before or after loading in the matrix herein.

The matrix component herein may have a thickness of from 0.5mm to 20mm, more suitably from 0.8mm to 15mm, preferably from 1mm to 12mm (e.g. 2mm, 3mm, 4mm, 5mm or 6mm), but may have a smaller or greater thickness if desired.

The matrix component may have a cell size of 30 microns to 1000 microns, such as 30 microns to 700 microns or 300 microns to 1000 microns. The porous foam matrix component herein preferably has a cell size with an average diameter of 50 microns to 500 microns (e.g., 200 microns to 250 microns).

The matrix herein may have a total cell surface area of 20% to 70% as openings. The matrix may have a very large free internal volume, for example about 70% to 90%. The substrate may have any desired cell network and pore network architecture. The microstructure of Polyurethane (PU) foams ranges from foams with small circular cells in the center of the pore surfaces that impede air flow through the foam (as shown, for example, in fig. 2 a) to reticulated low density "open-cell" foams where no pore surfaces remain allowing free air flow through the foam (as shown, for example, in fig. 2 b). The corresponding fibrous matrix ranges from a matrix having misaligned voids between fibers (cells herein) and misaligned pores interconnected with the voids (the matrix impeding the flow of air through the matrix) to a matrix having aligned voids between fibers and aligned pores interconnected with the voids (the matrix allowing the free flow of air through the matrix). The substrate herein may be characterized by an air resistance between its surfaces that varies with the cell network and/or pore network tortuosity, including factors such as the size of the pores in the cell surfaces, their orientation and spacing, the cell size and the fraction of the cell surfaces containing pores. The air flow resistance of PU foam is considered to be a function of the area of the largest pores in the cells and the connecting path between the large pores.

In embodiments, the material comprising the additive at the face of the substrate and within its cellular network comprises a substrate having a high air flow resistance and/or low air transport between faces and/or a high tortuosity pore network, wherein the material is asymmetric as defined above. Preferably, the high-tortuosity polymeric foam or fibrous matrix herein is selected from hydrophilic porous polymeric foams and fibrous matrices intended for wound care applications, more preferably polyurethane foams and combinations thereof, superabsorbent fibre piles and cellulose fibre piles and the like.

Such matrix components are commercially available or can be prepared by techniques known in the art, and include TENCEL fibers (Durafiber), polyurethane foam matrices (Alleyn and Alleyn AgTM), cellulose matrices (post-op TM), cotton gauze fabric (Bactigrastm), and absorbent rayon/polyester matrices (Acticoat TM), all of which are available from Smith & Nephew, Inc., as well as fibrous matrices contained in Mepilex R and Mepilex R Ag, which are available from Moellycke Health Care. Fibrous substrates such as cellulose superabsorbent air-laid (Glatfelter) are commercially available.

The matrix component may comprise a combination of fibers and foam, for example a commercially available combination of fibers as above, such as superabsorbent fibers and a foam matrix, or a commercially available combination, such as MepilexR Border (and Ag), comprising a laminated bi-layer of polyurethane foam and superabsorbent fibers.

The polyurethane foam matrix component may be manufactured as disclosed in, for example, EP0059049 and EP1964580, both of which disclose the option of incorporating the antimicrobial agent into the prototype foam prior to polymerization. The polyurethane foam component may be made by reacting a hydrophilic isocyanate-terminated polyether prepolymer with water, an aqueous liquid or an aqueous surfactant, then cast into or onto a mold or liner, such as a shaped liner, and optionally dried. The matrix component may be a finished product or may be a partially finished product, pre-mixed in the manner herein and cast in situ into a mould or liner containing a powder charge as defined above. The highly tortuous pore network polyurethane foams herein may be made, for example, by mixing 100 parts by weight of an isocyanate such as, for example, Hypol FHP2000, 2001, 3000, 3001, 2002 or 2000HD with 0.3 to 7 parts by weight of a surfactant or a mixture of a surfactant and 30 to 300 parts by weight of water and casting the foaming mixture onto a surface. A typical foaming mixture has an emulsion time of about 20 seconds, a rise time of about 250 seconds, and a set time of about 400 seconds.

Suitably, the silver ion releasing additive is comprised in a material herein or assembled with a matrix component herein in an amount of from 0.05mg to 3.5mg or from 0.05mg to 4mg silver ion/cm 2 of a material as defined herein, such as from 0.1mg to 3.5mg or 4mg silver ion/cm 2 of a material as defined herein or from 0.2mg to 3.5mg or 4mg silver ion/cm²A material as defined herein. The material may contain an additive such as silver sulfate in an amount exceeding 1.4mg/cm²Up to 4mg/cm²Such as at 1.75mg/cm²To 3.5mg/cm²Within the range of (1).

Suitable characteristics of the antimicrobial additive are a substance release profile, i.e. the amount of substance released over time as defined above, such as is known in the art per unit time, e.g. in mg/cm²The material gives the amount released into 50mL of aqueous medium. In embodiments, the release profile begins rapidly, i.e. a large dose release, within 24 hours, after which a sustained steady-state secondary release is maintained for a duration of up to 10 days, e.g. up to 7 or 8 days.

The antimicrobial additive may provide a desired Minimum Bactericidal Concentration (MBC) or Minimum Inhibitory Concentration (MIC) of the antimicrobial agent during the useful life of the material or for a specified time interval after activation. MBC is given as a measure of the concentration of a given antimicrobial substance in a given liquid in mg substance/mL liquid.

For example, the MBC may be 0.4mg to 50mg silver ions per 50mL wound fluid or a simulated wound fluid or aqueous medium or 0.7mg to 2mg iodine per mL, depending on the microorganism in question, the medium selected, the test device and ease of killing.

For a given material having a given absorbency, e.g., thickness, etc., the release may be provided by including a silver salt such as a sulfate salt and providing the salt in mg salt/cm²Equivalent amount of material calculated for antimicrobial material. Preferably, MBC is achieved and exceeded as quickly as possible.

The method for determining ion release is modified as known in the art, for example according to ASTM E2149 (microbiological test). ASTM E2149 allows the ability to evaluate many different types of materials and devices, as well as a wide range of microorganisms. Materials and devices may be subjected to a wide variety of physical/chemical stresses or manipulations, and the test allows testing for versatility in the effects of contamination from such things as hard water, proteins, blood, serum, various chemicals and other contaminants.

The powder charge herein contains the additives herein, which are commercially available and may be included in the form of a powder charge or may be processed, for example, by drying, by reducing the particle size (such as selecting a desired particle size grade), or by methods known in the art.

In embodiments herein, the loss on drying (l.o.d) of the powder charge or additive is less than 2%.

L.o.d. suitable in the powder charge or additive samples herein is determined to have a weight loss of less than 2%, such as less than 1% or less than 0.5%, such as less than 0.4% or less than 0.3% or less than 0.2% or 0.1% within 4 hours in a vacuum oven at 50 ℃ or in a non-vacuum oven at 105 ℃.

The defined l.o.d. allows for precise dosing of additives or powder charges thereof without the need to add or change the moisture content by the dosed amount.

L.o.d can be identified as a powder charge or an additive. Alternatively, the l.o.d. may be determined as a material containing the additive and including the moisture loss of the matrix and the additive. The material humidity varies with atmospheric conditions and can be determined and decoupled in a suitable manner.

Preferably, the powder charge contains an additive having a particle size and distribution that is compatible with the matrix component and manufacturing requirements, such as matrix component cell size and pore size and dosing requirements. The particle size of the high solubility salt (such as silver nitrate) may be selected to be compatible with the substrate cell and pore size, and manufacturing requirements such as launch may be about 50-1000 microns, for example 50-200 microns, such as 100 microns, to be compatible with a 200 micron cell size substrate. The particle size distribution of the additive for loading into the matrix herein may be about 8 microns < D90< 115 microns or 4 microns < D50< 60 microns or 1 micron < D90< 30 microns. Particularly advantageously, the particle size distribution of the additive is D50< 10 μm.

The additives may be provided in any suitable particle size and particle size distribution, such as commercially available, as supplied additives or suitably micronized by reducing the particle size, by methods known in the art, or by the novel method disclosed in uk provisional application No. 1711179.0 filed 2017, 12.7, co-pending, unpublished, the contents of which are incorporated herein by reference.

Preferably, the additive is micronised according to a novel process of our co-pending unpublished british provisional application No. 1711179.0 filed on 12/7/2017, the contents of which are incorporated herein by reference, for example comprising providing an additive or powder charge and dry micronising by particle impact selected from gas phase self-impact and impact with fluidised solid particles, such as contact with a gaseous or particulate milling force such as high velocity air jets or high density milling beads or microbeads.

The powder charge may comprise a flow agent selected from fumed silica, stearates, activated carbon, clays (such as bentonite, montmorillonite, mica) as defined above. The flowable agent may be medically compatible.

The flow agent is provided in the form of a powder charge as defined above as a small particle size powder in the range as defined above for the additive. In the case of low solubility additives as defined above, the flow agent may have a particle size of about D50< 10 microns, for example, contained in the powder charge, and an additive having a low micron particle size, for example, a particle size distribution of D50< 10 microns.

The flow agent may be present in an amount of up to 20 wt%, such as from 0.5 wt% to 8 wt% or from 0.5 wt% to 4 wt%, for example 2 wt%. The amount depends on the nature of the agent chosen and is chosen such as not to reduce the porosity of the matrix, not to affect the flexibility/pliability upon softening.

The flow agent may provide additional functionality. For example, in the case of silver salts that are sensitive to light or absorb colored aqueous media such as wound fluid, blood, charcoal also has the additional function of acting as an odor control agent or as a colorant that masks the discoloration of the substrate. The powder charge may comprise an extender selected from inert organic polymers such as PEG. The extender may be present in an amount of up to 80 wt%, such as from 10 wt% to 80 wt% or from 20 wt% to 80 wt%, for example 25 wt% or 50 wt% or 75 wt%. The extender helps to ensure low deviations in the processing accuracy during dosing.

The particle size of the extender may be less than, equal to, or greater than the particle size of the additive and within the ranges as defined above for the additive. In the case of the low solubility additive as defined above, particularly useful particle sizes are in the range of 50 to 100 microns, for example 80 microns.

One or more further additives may be provided in the matrix component as defined herein or included in the powder charge, for example selected from wound dressing additives as defined above.

The fluid permeable laminate web may inhibit the release of additives from the materials herein. Suitable laminate webs may be porous polymeric sheets or webs typically used to connect and adhere adjacent layers in a wound dressing. Extruded polymeric webs, nonwovens or melt blown polymer variants, such as polyamides, polyesters or polyethylenes, for example DelnetTM,

And(Delstar)。

the fluid permeable laminate web may be heat laminated at elevated temperatures, such as 150-.

Methods of directing the additives to the faces known in the art as defined above include, for example:

i) depositing a charge of powder onto the face of the substrate; or

ii) the charge of powder is delivered to a lining, such as a silicone surface or a silicone-coated surface or to a molten polymer film, and brought into contact with the casting matrix, suitably by casting a foam matrix mixture or a fiber matrix mixture to the lining, applying the casting foam or fiber matrix to the lining at the face thereof or applying the lining to the face of the casting foam or fiber matrix.

For example, a liner providing a "reservoir" of powder charge and a substrate-side "receptacle" are combined together in a batch or continuous process whereby the powder charge translates from the liner to the substrate surface upon contact. The liner may be a tape having a thin layer of powder charge thereon, or may be a tacky or non-tacky or molten polymer film or laminated web that may be heat laminated to the substrate face. The substrate may be a tape or layer of the substrate.

The liner may be a continuous liner in the form of a closed loop conveyor belt positioned in a vertical plane below a hopper, bucket or reservoir of powder charge and having bagging bags that are alternately erected and inverted to receive the powder charge from the hopper, bucket or reservoir and deposit it onto a substrate positioned therebelow.

The method is suitable for using a belt system or a stamp printing system, for example using gravure, as known in the manufacturing art, to bring two surfaces together or to translate the coated surfaces. Such methods are known, for example, in the application of organic powders, for example dry powder coating processes for the production of durable coatings such as organic dyes or inorganic sintered materials.

The matrix may be freshly cast and thus tacky, or the powder charge may contain a medically acceptable adhesive powder or a soft tacky gel. Thereby, the powder charge can be held firmly on the face.

The substrate may be heated at the same time as or after the powder charge is dosed to melt soften the substrate face or a binder optionally included in the powder charge or a commercially available molten polymer liner or laminate web (as described above) placed on the face.

For example, the method may comprise dispensing as defined above, followed by application of heat and/or pressure, such as by contact or lamination, to secure the molten polymeric liner or laminate web to the substrate face.

The powder charge is applied to the face i) of the substrate or to the lining ii) by, for example, air spraying, sprinkling or throwing the dry powder onto the face of the lining or substrate. Air sprays, sprinkles, or slings the hopper, bucket, or reservoir, possibly from a powder charge. The powder charge is fluidized or caused to flow by being entrained in an air jet or flowing or pouring from a hopper or similar reservoir.

The powder charge may be dosed according to ii) and loosely retained or supported on the substrate release surface for subsequent or simultaneous translation within the cellular network, as defined above and below.

Translation methods known in the art or as described herein include, for example, by I) physical force or II) -V) excitation field/field force as defined above, projecting and translating within the cellular network, such as by:

I) by laminating or needling, such as by known techniques for interlocking or meshing the nonwoven fibers to form the matrix. Rolling suitably comprises applying a roll or other force on the release surface to translate, optionally with a liner between the release surface or the reverse surface. Needling suitably comprises inserting one or more fine protrusions within the matrix to cause penetration to translate the powder charge within its cellular network;

II) a field of aeration, such as spraying a powder charge onto the substrate face while simultaneously translating a quantity of powder charge in the cell network. Applying an air jet to the face in the direction of the cell network. The air jets may come from a hopper, bucket or reservoir of powder charge. The powder charge is fluidized by entrainment in an air jet. For example, an air gun with a line feed of a hopper, bucket or reservoir entrains the powder charge with air and preferably sprays on the substrate surface from one or more spray heads having an adjustable orifice size. The hopper, bucket or line feed means may include metering means for metering a predetermined dose of powder charge. The spray gun may be automated or robotically operated to facilitate spraying at a desired rate over the entire substrate surface. Alternatively, air spraying may be carried out by dry powder techniques, such as are known from US2017098818, the content of which is incorporated herein by reference. Air spraying equipment is available, for example, from nordson.com;

III) high intensity air jets, for example using air jet technology as defined above, operating at an air jet velocity and/or jet contact area sufficient to direct the fluidized powder charge within the cellular network. Preferably, the method comprises fluidizing the dosed powder charge by means of a plurality of co-aligned air jets or an air jet diffuser head directed to the substrate face. The air jet diffuser head may include a diffuser exit surface area corresponding to the base face surface area or a portion thereof, and the diffuser head may be aligned vertically facing the base face or aligned therewith at suitable intervals, such as 1mm to 5mm intervals or greater. The diffuser head may be recessed in a shroud positioned around the face of the substrate or diffuser head or may be sealed with the substrate in a powder charge containment device such as a vacuum bag to contain the powder charge at the substrate face. In the case of symmetrical loading of the mesh matrix herein, or in the case of face loading in terms of collapse of the tortuous pore network upon application of a vacuum, the vacuum may extract the powder charge within the matrix. Advantageously, fluidization by an air jet diffuser allows for minimal turbulence and minimal powder charge loss.

The high intensity air injector may comprise a hopper, bucket or reservoir for the powder charge, so that dosing and guidance can be performed simultaneously within the matrix;

IV) an alternating electrostatic field, such as an alternating electric field force applied to the substrate perpendicular to the face, optionally with commercially available dipping services provided by fibrilene SA. The method operates a system consisting of 2 facing electrodes connected to an alternative high voltage generator, said electrodes being protected by a dielectric material and spaced apart by a distance suitable to allow the passage of the substrate therebetween. The substrate may pass between the electrodes at a rate of from 10m/min to over 300m/min, either as a continuous substrate such as a roll being transported between the electrodes on a suitable transport device or as discrete portions or lengths of substrate. The fibrine D-Preg, S-Preg or T-Preg process may be selected depending on the scale and size of the material desired and the number and concentration of powder charges provided thereon. The T-Preg process can be selected to produce materials containing low powder loading concentrations or with low powder loadings. This process is disclosed in US2016/0228909, the content of which is incorporated herein by reference.

US2016/0228909 discloses the optimisation of deep impregnation of a powder charge onto a substrate and demonstrates uniform impregnation of the powder dosed at one face throughout the thickness of the substrate. Referring to fig. 3b and 3c, a charge of powder containing silver sulfate is placed on the release surfaces, shown in the respective figures as lowest and highest, and directed into the network of cells closest to the release surface. The salt penetrates but mainly in the first 1mm of the 2mm thick foam. There are some silver sulfate particles deeper in the matrix, but this is an incidental concentration compared to the concentration within the cellular network near the launch face. This is advantageous in the materials herein comprising the antimicrobial substance-releasing additive;

v) an alternative excitation field may be a vibrational excitation field as described in US2016/0228909, produced by a series of freely rotating rods instead of electrodes, the diameter of the rods of polygonal cross-section being selected according to the thickness of the substrate and the speed at which the substrate enters and passes through the field. The rod exerts a variable pressure on the substrate, generates vibrations in the substrate, and fluidizes the powder charge deposited on its surface, thereby directing the fluidized charge into the matrix cell network.

In embodiments, fluidization may be performed by powder excitation in a field selected from the group consisting of an alternating electrostatic field (AC electric field), a sound field, an ultrasonic field, an aeration field, a pneumatic field, and the like, as defined above. Preferably, the method comprises placing a powder charge on a substrate face as defined above, and exciting the powder charge by applying an excitation field to said face. Preferably, the excitation field is applied perpendicular to the face. The field may be applied continuously or discontinuously. The continuous field may be applied as a continuous sheet or roll or as discrete blocks to a substrate that continuously passes through the field.

The above excitation field/field forces such as II) -V) are suitably applied for a duration sufficient to fluidize and translate the powder charge within the cellular network herein. Fluidization and translation are very fast. Suitable durations are less than one minute, for example 3 to 30 seconds, such as 5, 10, 15, 20 or 30 seconds. The excitation field is preferably non-turbulent.

In a preferred embodiment, there is provided herein a method for manufacturing an asymmetric material as defined above, the asymmetric material comprising: a flexible hydrophilic polymeric foam or fibrous matrix component comprising two matrix faces between which is provided a structural matrix framework defining a cell network and a pore network having a cell network surface, and

powder charge components as defined above

The method includes dispensing the powder charge onto the release surface and applying an excitation field to fluidize and direct the powder charge into the cellular network

Wherein said powder charge is included within said cell network proximate said release surface, the concentration of said powder charge decreasing with increasing depth within said cell network, and wherein said powder charge is present in said reverse surface and in the cell network proximate said reverse surface in incidental amounts

Characterized in that the matrix provides a tortuous network of pores.

Preferably, the matrix component includes a foam matrix having a superabsorbent fibrous matrix laminated to an opposite side of the foam matrix, and/or the powder charge includes a superabsorbent polymer and the antimicrobial additive.

Preferably, the method comprises laminating a molten polymeric laminate web to the release surface.

The use of the material herein may be selected from: wound management; hygiene and sterilization and point-of-use sterilization of articles including medical and dental articles; hygiene and sterilization of personal care preparations and articles such as sanitary pads, diapers, cosmetics; sanitation and sterilization of food or fluids including air and water or its preparation and production systems such as food preparation or packaging plants, ventilation systems, water management systems; and such uses are particularly beneficial for preventing or combating microbial infections.

The material may be used for application to wounds that are at risk of contamination or infection by microorganisms that compromise the health of the wound or subject, particularly microorganisms selected from bacteria, yeasts and fungi and combinations thereof.

Wound management includes management of superficial granulation wounds, chronic and acute exuding wounds, full and partial thickness wounds, exuding wounds, infectious wounds, malignant wounds, surgical dehiscence wounds, first and second degree burns, donor sites, fungal wounds, and the like. Wounds for which the above-defined materials have particular utility include, for example, ulcers and pressure sores, such as pressure ulcers, leg ulcers and diabetic foot ulcers; a surgical wound; a wound; partial thickness burn; flap and skin graft donor site wounds; tunnel and fistula wounds; leaving the wound to be secondarily healed; and wounds prone to bleeding, such as wounds that have been surgically or mechanically debrided, cavity wounds, sinuses, and open wounds.

The asymmetric materials herein may be used to provide a wound facing or release face, such as an additive-rich or additive-poor face, e.g., silver-rich, or a silver-rich face selected for site or wound facing positioning, such that a maximum amount of antimicrobial substance may be readily released near where it is needed, or a maximum amount of wound dressing additive near or away from the wound.

The material herein may be suitable for use against gram-positive and/or gram-negative bacteria, for example gram-positive bacteria and/or gram-negative bacteria selected from Staphylococcus (Staphylococcus), such as Staphylococcus aureus (Staphylococcus aureus), Staphylococcus epidermidis (Staphylococcus epidermidis) and MRSA, Streptococcus (Streptococcus), Enterococcus (Enterococcus), Corynebacterium (Corynebacterium) and Clostridium (Clostridium), such as Clostridium difficile (c), also Peptostreptococcus (Peptostreptococcus), Lactobacillus (Lactobacillus), Propionibacterium (Propionibacterium), Bifidobacterium (Bifidobacterium) and Actinomyces (Actinomyces) and/or gram-positive bacteria and/or gram-proteobacteria (proteobacteria), such as Enterobacteriaceae (Enterobacteriaceae), for example Escherichia coli (Escherichia coli), Salmonella (Shigella), Shigella (Pseudomonas aeruginosa), Pseudomonas aeruginosa (Pseudomonas aeruginosa), Pseudomonas aeruginosa (Pseudomonas aeruginosa), there are also gram-negative bacteria of the genera Legionella (Legionella), haemophilus (Hemophilus), Neisseria (Neisseria), Acinetobacter (such as Acinetobacter baumannii), Bacteroides (Bacteroides), Prevotella (Prevotella), clostridium (Fusobacterium), Porphyromonas (Porphyromonas) and cyanobacteria (cyanobacter) and spirochaetes.

The materials herein are particularly suitable for use against one or more microorganisms encountered in a wound environment, for example gram-negative aerobic bacteria such as pseudomonas aeruginosa, gram-positive bacteria such as staphylococcus aureus (more particularly MRSA (methicillin-resistant staphylococcus aureus), also known as ORSA (oxalate-resistant staphylococcus aureus)), anaerobic bacteria such as Bacteroides fragilis, yeasts such as Candida albicans (Candida albicans), and fungi such as aspergillus brazilian (aspergillus brazilianus).

The device as defined above may be a medical or dental sponge or wipe, or a wound dressing together with other functional materials.

In preferred devices herein, layers (a) and/or (a) are independently selected from silica gel, polyurethane, and the like.

The devices herein may comprise the same or different antimicrobial or wound care materials as defined above provided in multiple layers, for example 2 or 3 layers of asymmetric materials may provide an additive layer within the device.

In this embodiment, the device may comprise the materials herein manufactured in the form of commercially available wound dressings, for example in the form of ALLEVYNTM dressing ranges, OPSITETM and OPSITETM POST-Op Visable, PICOTM, Algisite, DurafiberTM, Mepilex dressing ranges, and the like.

Fig. 5 illustrates a form of wound dressing comprising the antimicrobial material herein. A dressing comprising the above layers (a), (b) and (c) is shown in fig. 5a and 5 b. In fig. 5b, the layers are held together by heat laminating outer layers (a) and (c) at the boundary. Fig. 5c shows a variant 5b comprising the above further layers (b') and (b "). Figure 5d shows a variation of figure 5a comprising a double layer of foam and fibre matrix. The bilayer may constitute a bilayer antimicrobial material as defined herein comprising a bilayer matrix component having a powder charge component as defined herein. Alternatively, the bilayer may constitute a separate layer of antimicrobial material, either or both comprising a matrix component and a powder charge component as defined above.

The packaging device herein is suitably packaged in a waterproof bag, such as an aluminium foil bag.

In another aspect, provided herein is a method of making a device herein.

In another preferred process, an outer conformable film layer is formed on the foam layer, for example by spraying a polymer solution.

In a continuous process, the wound dressing may be made in the form of a continuous strip and then cut into suitable sized dressings.

Typically, combining the layers together is a lamination process.

The method of treatment as defined above is for treating a site, such as a wound. Suitable sites for treatment are moist or contain aqueous fluids. Upon contact with moisture or aqueous fluids, the antimicrobial substance release is activated into the site or wound. Suitable wounds are exuding.

Preferably, the treatment methods herein comprise additionally securing the materials or devices herein in a position in contact with the site or wound. Suitably, the means of securing is sufficiently robust to hold the material or device in place for a desired duration, for example 7,8 or 10 days or more. Fixation may be performed by adhering a site-contacting surface, such as a wound-contacting surface, or a cover layer or additional adhesive layer or strip or bandage applied over the material or device to the site, such as the skin surrounding the wound.

With reference to non-limiting examples, embodiments herein are shown below.

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