WO2021072254A1 - Foam patent surfactant - Google Patents

Abstract

A urethane foam wound dressing; one or more hydrophilic surfactants incorporated therein, and optionally, one or more antimicrobials also incorporated therein, preferably as a pre-formed mixture with the hydrophilic surfactants.

Description

FOAM PATENT SURFACTANT

[001] The present application claims benefit of U.S. Provisional Application No. 62/913,696, filed October 10, 2019, which is hereby incorporated by reference in its entirety including all tables, figures, and claims and from which priority is claimed.

BACKGROUND OF THE INVENTION

Field of the Invention

[002] The present invention relates generally to wound dressings such as are useful in treatment of exuding wounds both in first aid as well as longer term treatment situations, particularly where the dressing prevents or inhibit the growth of microbes in the wound bed, thus accelerating healing of the wound.

Description of the Prior Art

[003] Flexible cellular polyurethane foams are used from such things as furniture cushioning, carpet underlayment, and cosmetic pads and applicators. Cellular urethane foams have traditionally been prepared using TDI (toluene diisocyanate) polyisocyanate components. In similar fashion, MDI (methylene diisocyanate) has been used to make high density open cell flexible polyurethane foams. These starting materials can be used to manufacture dense foams, i.e., greater than 4.5 lb/ft³. Various references in the prior art teach the use of resiliently compressible foamed plastic and similar synthetic materials for wound dressings. Such materials can permit comfortable application of pressure even on curved or other non-planar body surfaces.

[004] While the material properties of a foamed plastic may not be critical in the case of cushioning, insulating or packing materials, they are highly critical for purposes of an adequate wound treatment-dressing. For example, it is important or desirable with wound dressings to have surface properties which for the wound-facing surfaces permit easy flow of moisture into the dressing while avoiding sticking to the wound, and for the outer surface of the dressing to provide, at least to a certain extent, a water-resistant, breathable barrier. However, a number of problems arise in connection with the provision of satisfactory material properties in the context of foam materials of the type under consideration. [005] British Patent 1417962 discloses the use of a non-reticulated polyurethane foam which is modified at the wound-facing inner surface, by application of heat and pressure, to give a layer of collapsed cells, which layer is soft, pliant, and facilitates flow of moisture from the wound into the body of the foam material.

[006] A further refinement of such polyurethane foams, involving the use of a body of open-celled hydrophilic foam, is disclosed in WO 92/13576. The addition of an alginate composition to the foam is said to raise the absorptive capacity of the foam and facilitates flow of moisture at a relatively high rate suited to use with very moist wounds.

[007] U.S. Pat. No. 3,903,232 discloses hydrophilic cross-linked polyurethane foams, which are said to be useful for the absorption of body fluids and may be used for external body cleaning, for internal body usage, and as absorptive products such as diapers. The foams are prepared by reacting particular isocyanate-capped polyoxyethylene polyols having an isocyanate functionality greater than 2 with large amounts of an aqueous reactant, preferably water.

[008] EP-A-0335669 discloses a hydrophilic foam composition comprising the “in situ” reaction product of an isocyanate-capped polyether prepolymer, a hydrophilic agent capable of absorbing water, an adjuvant comprising an alcohol, a wetting agent and water. One application which is proposed for the foam composition is in the manufacture of wound dressings. The composition is said to carry the adjuvant releasably, so that at least a portion of the adjuvant is released into an external liquid (e.g., wound exudate) with which the foam composition comes into contact.

[009] U.S. Pat. No. 4,728,323 discloses a method of manufacturing a wound dressing which is comprised of a “substrate” coated with an antimicrobially effective film of a silver salt. The film is preferably deposited on the substrate by vapor or sputter deposition techniques. The support sheet with the attached dressing is suspended in a vacuum vessel and all of the air is removed. The material is vaporized by heating to its melting point with an electron beam.

[0010] U.S. Pat. No 4,738,849 discloses a composite wound dressing with separate layers which are subjected to what appears to be a liquid treatment followed by freeze drying.

[0011] U.S. Pat. No. 4,997,425 discloses a wound dressing which, in one embodiment, is said to release an antimicrobial material. The antimicrobial solution is poured into a vessel and then subjected to quenching and freezing under vacuum so that a sheet-molded porous layer is produced. [0012] U.S. Pat. No. 5,455,604 discloses a wound dressing of multiply layers which includes a “net” in which the strands and junctures are formed integrally during manufacture. The use of a hydrophilic polyurethane foam together with a silver salt which incorporation into the proto-foam prior to polymerization is discussed.

[0013] U.S. Patent Publication No. 2002/0168400 discloses a resin foam wound dressing in which the resin layer has a collagen layer dispersed over the foam layer, followed by freeze drying.

[0014] U.S. Patent Publication No. 2005/0124724, discloses a polymer composition which has a bio-active agent “distributed therein.”

SUMMARY OF THE INVENTION

[0015] It is an object of the invention to provide an absorbent matrix which comprises with an anti-microbial composition, and which is processed in a specially designed fashion to produce a wound-treatment dressing.

[0016] Another object of the present invention is to provide a wound dressing having at least a wound contacting layer which comprises an absorbent polyurethane foam, and a composition comprising a combination of active wound treatment-dressing components or agents incorporated therein.

[0017] The wound dressing of the invention provides wound treatment, by providing a wound dressing (for humans and animals) that can have embedded within the dressing itself, anti-microbial/anti- viral/anti-fungal/anti-anthelmintic molecules.

Together, this combination of features exhibits the ability to assist skin and exposed tissue to heal faster and more naturally by preventing and aborting infection, and by actually encouraging tissue growth via increased blood-flow, while noticeably reducing wound pain and discomfort.

[0018] The preferred invention comprises a urethane foam pad dressing; one or more hydrophilic surfactants incorporated therein, and optionally, one or more antimicrobials also incorporated therein, preferably as a pre-formed mixture with the hydrophilic surfactants.

[0019] The preferred wound treatment-dressing includes a dressing body having at least a wound contacting surface layer which is formed from a biocompatible, moisture permeable, urethane open-cell foam. The foam which makes up at least the wound contacting surface of the dressing body exists as a foam matrix comprised of interconnected foam cells with cell walls which has incorporated therein a combination of inorganic antimicrobials as active agents, the active agents being incorporated into the foam matrix both topically on a foam cell surface and integrally within the foam cell wall. [0020] The preferred hydrophilic surfactants can be of several different types such as the alkylene oxide polymers discussed in Herzberger et ah, Chem. Rev. 116: 2170- 2243, 2016. These include, but are not limited to amphiphilic block copolymers based on ethylene oxide and propylene oxide known in the art as Poloxamers and Pluronics. Examples include, but are not limited to, poloxamer-101, -105, -105 benzoate, -108, -122, -123, -124, - 181, -182, -182 dibenzoate, -183, -184, -185, -188, -212, -215, -217, -231, - 234, - 235, -237, -238, -282, -284, -288, -331, -333, -334, -335, -338, -401, -402, -403, and -407 and pluronics L10, L31, L35, L44, L61, L62, L64 L92, and L121.

[0021] The active agents that can be incorporated into the hydrophilic foam of the present invention can be selected from a group consisting of gram-positive antimicrobials, gram negative antimicrobials, iodine, and ionic and colloidal silver. Antibacterial, antifungal, and antiviral properties may be conveyed in any appropriate matter for example the addition of silver salts in the form of zinc oxides, titanium dioxides, silver sulfates, silver citrates, silver acetates, silver carbonates, silver lactates and silver phosphates, for example. Additionally, zeolites containing approximately 15% by weight of silver ion may also be used. Particularly preferred antimicrobials include the combination of gentian- violet, methylene-blue and colloidal or ionic silver. Most preferably, the foam body of the wound treatment dressing has incorporated therein a zirconium phosphate-based ceramic ion-exchange resin containing silver in the form of silver ions which slowly releases silver ions via an ion exchange mechanism. The preferred foam body has a volume absorbency ratio which is greater than about 12:1 and the gentian- violet and methylene blue components are present in the foam matrix as particles which range in diameter from about 10 nanometers to 800 microns. The active agents are at least partially embedded within the foam cells, which thereby immobilizes the active agent. This can be accomplished during the manufacture of the foam, wherein a given weight percentage of the hydrophilic surfactant and optionally, each antimicrobial agent is physically mixed into the polymer foam ingredients prior to foaming. As the foam is being formed, the selected antimicrobial agents are embedded in the foam compartment walls.

[0022] In certain embodiments, the foam is non-leaching with respect to the anti microbial agents. “Non-leaching” as used herein refers to no more than 10%, preferably no more than 5%, and most preferably no more than 1% or 0.1% of one or more anti microbial agents are leached when measured in accordance with BS EN ISO 10993- 12:2012. Most preferably, the anti-microbial agents include methylene blue, gentian violet and silver (as ions or salts), and the silver is non-leachable.

[0023] While a particularly preferred form of the invention utilizes a hydrophilic surfactant incorporated into the polyurethane foam, it will be appreciated that other hydrophilic materials such as hydrogels, or natural or synthetic fibers or sponges may find utility as well.

[0024] Additional objects, features and advantages will be apparent in the written description which follows.

DETAILED DESCRIPTION OF THE INVENTION

[0025] Exemplary polyurethane foams of the invention are composed of diisocyanate molecules either as monomers or as pre -polymers, a hydrophilic surfactant and, optionally, one or more antimicrobial agents. The resulting hydrophilic foam products can be used wherever wound dressings are required and in combination with other wound care products including, but not limited to, cosmetic pads, puffs, applicators, foam gauzes, bandages, wipes, gels, collagen pads, creams, ointments or the like. Various open-cell- structure polymer “foam” membranes are known in the prior art. So-called “liquid immersion” techniques with air drying are taught in the prior art for manufacturing foams of the general type under consideration.

[0026] A preferred wound treatment-dressings comprise a dressing body having at least a wound contacting surface layer which is formed from a medically inert urethane open-cell foam. However, there may be other polymer foams of the same general type, such as open-cell sponge rubber or foamed plastics, which can be impregnated with the active agents to be described, and which may become obvious to others skilled in the art of open-cell foam production. Such open-cell polymer foams are included in the scope of this invention, as well as absorbent fiber materials.

[0027] By way of example, a foam preparation may be prepared as follows:

[0028] An aqueous solution is prepared by mixing 120 gallons distilled H2O) with

4-lbs of Pluronic (e.g., L-62), 77.18 g methylene blue, 77.18 g gentian violet, and 4.67 lb Milliken SelectSilver ZR2K. Prior to mixing, bring the H2O to 120°F to 140°F, then add the powdered ingredients with agitation. Maintain agitation until the powders are dissolved. After solvation of the powdered ingredients, chill the solution to nominal 50°F with agitation.

[0029] Mix 1000 lbs of Hypol 2002 with 1250 to 15001bs of the aqueous solution. Each 1000 lbs of the aqueous solution will produce about 670-lbs of dry foam. Use a low pressure, high shear polyurethane mixing head. Variation of the final temperature of the exiting emulsion will affect pore size. The temperature of the aqueous solution can be in the range of 45° F to 50° F, and the Hypol 2002 may be at 80° F. The mixing head creates an emulsion of Hypol 2002 pre-polymer in water, and the function of the mixing head is to create a uniform emulsion. The mixing head emulsifier unit is the primary determinant of the size and distribution of the polymer-aqueous emulsion and the resulting cell structure of the foam.

[0030] Once the emulsion is mixed, foaming reaction begins. Typically, the mixture might be mixed for 15-seconds, dropped onto the continuous roll-table and get evenly spread. The emulsion will begin to creme (rise and foam), and then cure for at least 10- minutes. The mix should be spread quickly and evenly across the width of a release paper roll, and individualized distribution boxes or knife doctor blades, are needed to get a uniform layer prior to the gel and creme time. Once gellation initiates, the formation of the gel provides sufficient strength to sustain the pressure from the CO2 formation which stretches the gel and forms a pore or cell. Dry nitrogen gas is typically introduced at the mix head to instill very fine tiny bubbles into the emulsion to act as nucleation sites for the CO2 off-gassing. It is the precursor to the open cell structure formed by the CO2 gas and constrained by urethane gelation and cross-linking. The foam may then be dried in a radio-frequency (RF) dryer, or, a hot-air suction dryer.

[0031] Table 1. Characteristics of wound dressing foam made with different surfactants.

Pluronic L62 Pluronic L64 Pluronic L101

Surfactant Properties

Molecular Weight 2500 2900 3800

Water Solubility Soluble Soluble Insoluble

Wound Dressing Foam Properties

Porosity

70 40 60

(ppi)

Absorbency¹

9.9 9.6 8.4

(g/g)

Stapylococcus aureus recovered from biofilm incubated with ^l 60 100 foam

(CFU/mL)

'EN 13726-1

[0032] Leachates in deionized water from a foam wound dressing lot prepared according to the invention was were analyzed in triplicate for methylene blue, gentian violet and silver concentrations in accordance with BS EN ISO 10993-12:2012. The methylene blue and gentian violet contents of the extract were analyzed by reverse-phase HPLC. Detection of components was by UV absorbance at 590 nm and 660 nm for methylene blue and gentian violet, respectively. Methylene blue eluted at approximately 6.7 min; gentian violet eluted at approximately 15.3 min. Methylene blue and gentian violet quantification was accomplished by correlation of peak areas to respective standard curves. Measurements were performed in triplicate. Concentrations were reported as averages with standard deviations Silver concentration of the leached liquid was analyzed by ICP-MS. All samples were measured in triplicate according to EPA 6020 \

[0033] The leached methylene blue concentration was 0.1112 + 0.0005 mg/g dressing, the leached gentian violet concentration was 0.0249 + 0.0005 mg/g dressing, and the leached silver concentrations was 1.02 + 0.04 pg/g dressing. Percent leaching from the foam is as follows:

Claims

We claim:

1. A polyurethane foam wound dressing material comprising: a hydrophobic water absorbent polyurethane foam matrix; and a mixture comprising one or more antimicrobials and one or more hydrophilic surfactants dispersed within the polymeric urethane matrix.

2. A urethane -based foam wound dressing according to claim 1, wherein the polyurethane foam matrix is an emulsion foam polymerized as an emulsion with the mixture comprising one or more antimicrobials and one or more hydrophilic surfactants.

3. A urethane-based foam wound dressing according to claim 1 or 2, wherein one or more antimicrobials are non-leachable from the polyurethane foam matrix.

4. A urethane-based foam wound dressing according to one of claims 1-3, wherein the one or more hydrophilic surfactants are block copolymers based on ethylene oxide and propylene oxide.

5. A urethane-based foam wound dressing according to one of claims 1-4, wherein the one or more antimicrobials comprise one or both of gentian- violet and methylene blue.

6. A urethane-based foam wound dressing according to one of claims 1-5, wherein the one or more antimicrobials comprise metallic or ionic silver.

7. A method of preparing a urethane -based foam wound dressing according to one of claims 1-6, comprising: mixing a liquid phase comprising one or more antimicrobials and one or more hydrophilic surfactants with a urethane prepolymer phase to form an emulsion; allowing the emulsion to form a gel; and drying the gel to form the urethane-based foam wound dressing.

8. A method according to claim 7, wherein the mixing step comprises introduction of nitrogen into the mixture during formation of the emulsion.