A two component composition for preparing polyurethane foam dressing infused with copper and chitosan as antimicrobial

Abstract

The present invention relates to two-component composition for preparing polyurethane,PU foam wound dressing, said composition comprising a first polyol-based mixture component comprising a polyether polyol comprising high-reactivity-capped polyether triol, water, a tertiary amine catalyst in a solution of dipropylene glycol, an emulsifier and pH buffer, a curing agent with a bi-functional organic compound, a foaming agent, a delayed-action blowing catalyst, and a silicone co-surfactant, and copper and chitosan and a second prepolymer based component comprising diphenyl methane diisocyanate,MDI-based prepolymers, characterized in that, said PU foam wound dressing is infused with copper and chitosan as antimicrobial agents.

Description

[0001] A TWO COMPONENT COMPOSITION FOR PREPARING POLYURETHANE FOAM DRESSING INFUSED WITH COPPER AND CHITOSAN AS ANTIMICROBIAL

[0002] FIELD OF THE INVENTION

[0003] The present invention generally relates to polyurethane foam dressings for wound management. In particularly, the polyol-based component and a second prepolymer for preparing polyurethane agents (PU) foam wound dressing infused with copper and chitosan.

[0004] BACKGROUND OF THE INVENTION

[0005] In recent years, the need for developing wound dressings has extended into the utility and development of polyurethane, PU foam-based materials. The increasing attention has been attributed towards PU-based materials portability and curability which has been found to be suitably applied in the enhancement of wound treatments.

[0006] Prior art document GB 2394418 has explored into utilizing fluid wound dressings which are based on low molecular polyols such as castor oil and other esters of ricinoleic acid and its derivatives but has a drawback in not having a property to absorb enough fluids from wound exudates and does not account to wound swelling, hence exerting and undesirable pain or uncomfortable-causing pressure to the wound. Furthermore, said prior art document has a relatively very long curing time of about 2 to 30 minutes. Temperature during curing process not mentioned.

[0007] RU 2471506 C1 discloses a composition for preparing a polyurethane dressing comprising combinations of low molecular weight polyether polyols, water, blowing agents, urethane catalysts such as dimethylcyclohexylamine, co-catalysts such as dibutyltin dilaurate, form regulator, bactericidal additives, and aromatic diisocyanate. These components were mixed and prepared for a two-component polyurethane dressing which could be applied by mixing the two components carried out in a bag or container by intensively rubbing the components and the resulting mixture may be applied to a wound surface. The composition of said RU ‘506 produces a homogeneous mixture which requires about 5-10 minutes after application to the contact surface to be able to completely adhere and cure which is reasonably time consuming. Said prior art document which uses high molecular weight polyols produce rigid polyurethane products. Current polyurethane foam dressings administered with bactericidal additives or silver medication additives have drawbacks of only being suitable for specific wounds and not applicable in other or all types of acute or chronic wounds.

[0008] Commercially available ready-made PU Foam dressings are produced based on certain measurement in its thickness and sizes and almost all with a flat base. Problems arise in having to cut ready made PU foams to cover the exact surface area of the chronic wound shape. Very often, the chronic wounds surface area shape are larger than the ready made PU foams. Having a limitation of a flat base, said foam dressings are unable to conform fully to the chronic wound bed profile and this may cause wound flooding in certain areas that are non-conforming with wound exudates resulting in wound maceration, which will prevent wound healing and poses a risk of contamination and infection.

[0009] Therefore, there is a need to provide an improved two-component antimicrobial polyurethane foam infused with copper and chitosan. This enhanced dressing would provide better antimicrobial activity for use in acute and chronic wound management which provides a quicker hardening / curing time, a more flexible final cured product, usable with helpful exudate indicators when needs replacement upon inspection, easily used and applied to a contact surface, particularly to a contact wound, and provides further antibacterial agents for prevention of wound infection or site co n tarn i natio n / i nfecti o n . SUMMARY OF THE INVENTION

[0010] As will be realized in the following description, the invention is capable of other and different embodiments and its several details are capable of modifications in various respects, all without departing from the scope of the present invention.

[0011] In one embodiment, the present invention provides two-component composition for preparing polyurethane, PU foam wound dressing infused with copper and chitosan, a first polyol-based mixture component comprising a polyether polyol comprising high- reactivity-capped polyether triol, water, a tertiary amine catalyst in a solution of dipropylene glycol, an emulsifier and pH buffer, a curing agent with a bi-functional organic compound, a foaming agent, a delayed-action blowing catalyst, and a silicone cosurfactant, and a second prepolymer based component comprising diphenyl methane diisocyanate, MDI-based prepolymers, characterized in that, said PU foam wound dressing is infused with copper and chitosan.

[0012] In one embodiment, the invention provides preparing two-component polyurethane, PU foam wound dressing comprising the steps of mixing a polyol-based mixture component with a prepolymer based component until a homogenous mixture of temperature equal or no greater than 45°C is attained measured at the base suface areas of the homogeneous mixture which is in contact with the wound surface, wherein said polyol-based component comprises a polyether polyol comprising high -reactivity -capped polyether triol having a molecular weight exceeding 4799 in an amount of 100 parts by weight, water in a total amount of 3.0 to 4.0 parts by weight, a tertiary amine catalyst in a solution of dipropylene glycol in an amount of 0.5 to 1.0 parts by weight, an emulsifier / pH buffer in an amount of 0.3 to 1.0 parts by weight, a curing agent with a bi-functional organic compound in an amount of 0.2 to 1.0 parts by weight, a foaming agent in an amount of 0.5 to 1.5 parts by weight, a delayed-action blowing catalyst in an amount of 1 .5 to 2.5 parts by weight, a silicone co-surfactant in an amount of 0.5 to 2.0 parts by weight, an amount of 0.2 to 0.5 parts by weight of ionized copper and 0.5-1.0 parts by weight of Vegan chitosan. In another embodiment, the invention further provides a two-component polyurethane, PU foam wound dressing obtainable by the method of claim 11 comprising, a first polyol- based component comprising a polyether polyol comprising high-reactivity-capped polyether triol having a molecular weight exceeding 4799 in an amount of 100 parts by weight, water in a total amount of 3.0 to 4.0 parts by weight, a tertiary amine catalyst in a solution of dipropylene glycol in an amount of 0.5 to 1.0 parts by weight, an emulsifier and pH buffer in an amount of 0.3 to 1 .0 parts by weight, a curing agent with a bi-functional organic compound in an amount of 0.2 to 1.0 parts by weight, a foaming agent in an amount of 0.5 to 1 .5 parts by weight, a delayed-action blowing catalyst in an amount of 1 .5 to 2.5 parts by weight, and a silicone co-surfactant in an amount of 0.5 to 2.0 parts by weight, an amount of 0.2 to 0.5 parts by weight ionized copper and 0.5-1.0 parts by weight of Vegan chitosan; and a second prepolymer based component comprising 30 to 43 parts by weight diphenyl methane dissocyanate.M DI -based prepolymers..

[0013] BRIEF DESCRIPTION OF THE DRAWINGS

[0014] This invention will be described by way of non-limiting embodiments of the present invention, with reference to the accompanying drawings, in which:

[0015] Figure 1 shows different views of an example or prototype final cured polyurethane, PU foam moulded: (a) sideview-1 , (b) sideview (c) bottom view, and not-moulded, (d) top view.

[0016] Figure 2 shows an example of a suitable two-compartment packaging container or packaging sachet for the two-component PU foam wound dressing of the invention.

[0017] Figure 3 shows a step-by-step use of the packaging container or packaging sachet comprising the separating two components of the two-component PU foam wound dressing of the present invention when the components are being mixed. Figure 4 shows a step-by-step application or mixing of the two components of the two- component PU foam wound dressing of the present invention when used and mixed in a cup.

[0018] Figure 5 shows the observed emitting temperature of the samples of the two-component PU foam wound dressing of the present invention when the polyol-based mixture component and the prepolymer-based component are mixed and homogenized through the cup method.

[0019] Figure 6 shows the observed pH of the samples of the two-component PU foam wound dressing of the present invention when the polyol-based mixture component and the prepolymer-based component are mixed and homogenized through the cup method.

[0020] Figure 7 shows the observed diameter and height of the samples of the cured two- component PU foam wound dressing of the present invention when the cup method is performed.

[0021] Figure 8 shows the observed weight of the samples of the cured two-component PU foam wound dressing of the present invention when the cup method is performed.

[0022] Figure 9 shows the observed water resistance and absorption of the cured two- component PU foam wound dressing of the present invention when the cup method is performed.

[0023] Figure 10 shows the observed mixing and drying time of the two-component PU foam wound dressing of the present invention when the cup method is performed.

[0024] Figure 11 shows the observed emitting temperature of the samples of the two-component PU foam wound dressing of the present invention when the polyol-based mixture component and the prepolymer-based component are mixed and homogenized through in-sachet mixing of the components. Figure 12 shows the observed pH of the samples of the two-component PU foam wound dressing of the present invention when the polyol-based mixture component and the prepolymer-based component are mixed and homogenized through in-sachet mixing of components.

[0025] Figure 13 shows the observed diameter and height of the samples of the cured two- component PU foam wound dressing of the present invention when in-sachet mixing is performed.

[0026] Figure 14 shows the observed weight of the samples of the cured two-component PU foam wound dressing of the present invention when in-sachet mixing is performed.

[0027] Figure 15 shows the observed water resistance and absorption of the cured two- component PU foam wound dressing of the present invention when in-sachet mixing is performed.

[0028] Figure 16 shows the observed mixing and drying time of the two-component PU foam wound dressing of the present invention when in-sachet mixing is performed.

[0029] Figure 17 shows the structure of the cross section of the polymerized PU foam of the present invention infused with copper and chitosan.

[0030] DETAILED DESCRIPTION OF THE INVENTION

[0031] In the following description, reference is made to the accompanying drawings where, by way of illustration, specific embodiments of the invention are shown. It will also be apparent to the skilled artisan that the embodiments described below are specific examples of a single broader invention which may have greater scope than any of the singular descriptions taught. It is to be understood that other embodiments may be used, and other changes may be made without departing from the scope of the present invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive.

[0032] The present invention discloses two-component composition for preparing polyurethane, PU foam wound dressing infused with copper and chitosan. The two components of said PU foam comprises a first polyol-based mixture component and a second prepolymer based component.

[0033] In a preferred embodiment, an ionized copper is infused with the two component composition PU foam of the present invention. In another preferred embodiment, a food grade or a medical grade Vegan chitosan is infused with the two component composition PU foam of the present invention. Both ionized copper and Vegan chitosan are configured to largely settle at the bottom or base layer of the PU foam after wound application, allowing the ionized copper and Vegan chitosan to touch the wound directly thereby providing immediate antimicrobial protection to the wound. This antimicrobial protection is provided not only during wound application but also as protection against any reinfection during the period by substantially reducing the bioburden within the wound surface areas and thereby resulting in a prolonged protection by the PU foam dressing.

[0034] I n an embodiment of the two-component composition for preparing polyurethane, PU foam wound dressing infused with ionized copper and vegan chitosan of the present invention, said first polyol-based mixture component comprises high-reactivity-capped polyether triol having a molecular weight exceeding 4799 in an amount of 100 parts by weight, water in a total amount of 3.0 to 4.0 parts by weight, a tertiary amine catalyst in a solution of dipropylene glycol in an amount of 0.5 to 1.0 parts by weight, an emulsifier / pH buffer in an amount of 0.3 to 1.0 parts by weight, a curing agent with a bi-functional organic compound in an amount of 0.2 to 1.0 parts by weight, a foaming agent in an amount of 0.5 to 1 .5 parts by weight, a delayed-action blowing catalyst in an amount of 1 .5 to 2.5 parts by weight, and a silicone co-surfactant in an amount of 0.5 to 2.0 parts by weight. The amounts of the components measured in parts by weight are measured relative to the sum of the whole or resulting final amount of all components in a final product.

[0035] The utility of high molecular weight polyether polyol, as compared to low molecular weight polyol used in prior art documents, allows to form a more flexible polyurethane foam wound dressing. As low molecular weight polyols form rigid polyurethane foam products, such rigid PU foam products could easily disengage when moved or their adhesion are compromised when a treated patient moves as skin continuously moves or stretches when a patient needs movement. Using high molecular weight polyols in producing flexible PU foam wound dressings addresses these problems which allows a more secured wound dressing which flexibility further allows unaccounted body movement of the patient being treated, hence a highly resilient, and a flexible PU foam product is produced. Flexibility giving properties of high molecular weight polyols also add into consideration that the wound may expand, bulge or increase in size due to swelling, which may happen during or after wound dressing application, to which the final cured dressing may adapt onto said probable unaccounted swelling. In a preferred embodiment, only one type of high molecular weight polyether polyol was used, preferably a high reactivity- capped triol.

[0036] In an embodiment of the two-component composition for preparing polyurethane, PU foam wound dressing infused with ionized copper and vegan chitosan of the present invention, second prepolymer-based component comprises diphenyl methane diisocyanate, MDI- based prepolymers. In a preferred embodiment, said polyol-based component and said prepolymer-based component are liquid in form.

[0037] In an embodiment, a two-component composition for preparing polyurethane, PU foam wound dressing infused with ionized copper and vegan chitosan is provided. Said PU foam wound dressing may be provided for use as a primary or secondary dressing, or for use in managing or enhancing the treatment of acute and chronic wounds. In a more specific embodiments, said PU foam wound dressing may be provided for use in managing or enhancing the treatment of acute and chronic skin wounds.

[0038] In an embodiment of the present invention, the components of said two-component composition for preparing polyurethane, PU foam wound dressing infused with ionized copper and vegan chitosan of the invention may be used in multiple embodiments such as a room temperature-curable two-component antimicrobial polyurethane, PU foam or a foam wound dressing, a kit comprising room temperature-curable two-component antimicrobial polyurethane, PU foam or a PU foam wound dressing, a method for preparing a room temperature -cured two-component antimicrobial polyurethane, PU foam, or a method for manufacturing or producing a room temperature-curable two- component antimicrobial polyurethane, PU foam or polyurethane, PU foam wound dressing.

[0039] In a specific embodiment, said high reactivity capped polyether triol has a hydroxyl value of between 30 to 40, has a polymer functionality of 3 to 5, and a molecular weight of 4799 to 5800. In a more specific embodiment, said high reactivity -capped polyether triol comprises oxyethylene units, oxyalkylene units that comprise oxyethylene end groups, glycerol, propylene oxide, ethylene oxide, or a combination thereof. In another specific embodiment, said high reactivity-capped polyether triol is selected from the group consisting of glycerine based reactive polyoxyalkilenetriol, polyoxypropylene triol, .modified polyoxypropylene triol, tri-funcional glycerine initiated polyol, propylene oxide polyol, ethylene oxide polyol, propylene oxide / ethylene oxide co-polymer polyol, and trifunctional glycerine-initiated triol. In a preferred embodiment, said modified polyoxypropylene triol is modified with ethylene oxide. In another preferred embodiment, said tri-functional glycerine- initiated polyol contains both propylene oxide along with ethylene oxide based polyether polyol triol with 15% ethylene oxide cap. .Suitable polyether polyols or polyether triols may be referred to BASF’s Pluracol range of products, or from PCC Rokita’s Rokopol M5000 range of products, or from Dow Dupont’s Voranol series of products, or from Covestro’s Arcol series of products or from Huntsman’s Jeffol G series of products, respectively.

[0040] The component tertiary amine catalyst in dipropylene glycol solution promotes gelling and secondary blowing catalyst reactions. Said amine catalyst accelerates the blowing reactions between the M DI -prepolymer, water, and the organic hydroxyl ingredients in the production of flexible and semi rigid polyurethane foam. Said amine catalyst accelerates also suppress the odor emission of the urethane polymer and solves the problem of discoloration of the peripheral polyurethane foam.

[0041] In a specific embodiment, said tertiary amine catalyst is selected from the group consisting of 1 ,4-Diazabicyclo(2.2.2]octane, which can be sourced from Evonik’s Amicure TEDA series, or from Vesta Chemicals’s Amincat TEDA series or from Pon Pure Chemical’s under tertiary amine series, or from Tosohasia’s TEDA series.

[0042] The emulsifier cum pH buffer is a viscous organic compound that is both a tertiary amine and a triol that can act as an emulsifier / pH buffers and enables the formulation to fully neutralizes oils and other ingredients that are not soluble in water as well as able to adjust the pH of the foam.

[0043] In a specific embodiment, said emulsifier is a tertiary amine, preferably triethanolamine, such as Trolamine based ingredient which can be sourced from Parchem or Dow or VMP Chemiekontor GmbH.

[0044] The curing agent is a bi-functional organic compound consisting of a tertiary amine and a primary alcohol functional group. It acts as an effective and versatile curing agent and as a viscosity reducing agent to harden the polyurethane foam surface by facilitating the bonding of the molecular components of this formulation through the cross-linking of the polymer chain.

[0045] In a specific embodiment, said curing agent is selected from the group consisting of 2- (Dimethylamino)ethan-l-ol, or DMAE bitartrate or Deanol bitartrate which can be sourced from Eastman under the brand of Amietol -M21 , or Parchem.

[0046] The foaming agent is herein exemplified as an ethanolamine having a N -hydroxyethyl substituent used to produce foam and bubbles for the creation of the porosity of the PU foam. The optimum amount of this ingredient is used to obtain a uniform cavity size distribution in the PU foam by controlling the catalysts and the cross-linking agents. This foaming agent affects pore morphology by preventing phase separation in PU foam matrix and the number of open pores reduces reliant on the optimum quantity of this ingredient.

[0047] In a specific embodiment, said foaming agent is 2,2’-iminodiethanol or diethanolamine or Cocamidopropyl betaine.

[0048] The blowing catalyst with properties of delayed-action, having low to moderate stabilizing effect that can combined with specifically pronounced structure and regulating properties that can regulate the critical zone of the foam structure close to the surface and prevent an undesirable wide cell size and uneven distribution. This blowing catalyst has been proven to produce high resilience and cold cured polyurethane foams.

[0049] In a specific embodiment, said delayed-action blowing catalyst is selected from the group consisting of low potency MDI surfactant preparation of organo modified polysiloxanes or polydimethylsiloxane which can be sourced from Graham Chemical or Evonik.

[0050] The silicone surfactant acting as co-surfactant is used to enhance compatibility of the ingredients or the components in this formulation specially to decrease the surface tension of the flexible foam, improve emulsification and nucleation, prevent coalescence and simultaneously stabilize all the cells membrane, thus, resulting in finer cells structures and presenting pneumaticity for the flexible foam application.

[0051] In a specific embodiment, said silicone co-surfactant is selected from the group consisting of polyethylene oxide-co-propylene oxide pendant groups which can be sourced from Dow Vorasurf DC 5000 series or from Huntsman Jeffamine D series.

[0052] A pre-polymerized diphenyl methane diisocyanate containing some higher functionality isocyanate or a Modified MDI which is ideal for cross-linking of two component PU foam systems. In addition, it has characteristics of good wetting, enhanced adhesion and excellent flow properties, thus suitable for this flexible foam cold cure synthesizing.

[0053] In a specific embodiment, said diphenyl methane diisocyanate-based prepolymer or MDI- based prepolymer is selected from the group consisting of 4,4-diphenylmethane diisocyanate or the Modified MDI, and polycarbodiimide-modified diphenylmethane diisocynate. In a preferred embodiment, said polycarbodiimide-modified diphenylmethane diisocynate is further characterized wherein the carbodiimide linkage assist in the stabilization of the polymer against hydrolytic degradation which can be sourced from Covestro AG, BASF, Huntsman, Dow, and Tosoh Corporations.

[0054] In a preferred embodiment of the two-component composition for preparing polyurethane, PU foam wound dressing infused with ionized copper and vegan chitosan of the present invention, any other bactericidal additives or any other medication is excluded from being incorporated. With the exclusion of any other medication in this formulation, we have a antimicrobial polyurethane foam dressing that can be used in all types of acute or chronic wounds, either as a primary dressing or as a secondary wound dressing and be compatible with most types of medication prescribed by the doctors or medical officer for the treatment of the wound concerned.

[0055] The present invention further discloses a method or process for preparing two-component composition for preparing polyurethane, PU foam wound dressing infused with ionized copper and vegan chitosan, or use of a room temperature-cured two-component antimicrobial polyurethane, PU wound dressing for managing or enhancing the treatment of acute or chronic wounds comprising the steps of, a) mixing a polyol-based component with a prepolymer based component until a warm homogenous mixture is attained; b) applying said warm homogenous mixture to a contact surface; and c) allowing said warm homogenous mixture to harden within 120 to 210 seconds.

[0056] In one embodiment, mixing the polyol-based component with the prepolymer-based component produces initially a warm homogenous mixture that emits a reaction temperature that is equal or not greater than 45 °C, and which temperature further gradually drops upon said homogenous mixture’s contact with a contact surface, preferably a contact wound or skin. In preferred embodiment, the emitting temperature or emitting heat is below 43 °C, about 0 to 45 °C, about 0 to 43 °C, about 30 to 45 °C, or about 35 to 45 °C. In a most preferred embodiment, the emitting heat or emitting temperature is about 40 to 43 °C As curing components when mixed naturally gives of heat due to the chemical reaction of the curing agent and / or components, said novel formulation of the invention’s antimicrobial PU foam wound dressing limits the emitting heat or emitting temperature of the reaction of the curing components to be equal or below 45 °C thereby ensuring that the curing or cured PU foam wound dressing avoids burning the applied contact surface, or avoids burning wound or skin of the patient being applied with said antimicrobial PU foam wound dressing of the present invention. In a preferred embodiment, said warm homogenous mixture is in liquid form after said mixing of polyol- based mixture component and prepolymer-based component. In a specific embodiment, the warm homogenous mixture attained is a liquid mixture that has a sticky property when not yet fully cured, hardened, set, or polymerized.

[0057] In one embodiment, applying homogenous mixture to a contact surface comprises applying a liquid homogenous mixture wherein said contact surface may be any suitable surface to which the invention’s antimicrobial PU foam may be applied, preferably said contact surface is a pressure wound, an acute wound or a chronic wound located on the skin of a patient being treated and being dressed with said antimicrobial PU foam or PU foam wound dressing.

[0058] In one embodiment, allowing said warm homogenous PU mixture applied to a contact surface to harden comprises a curing time, hardening time, or setting time of around 120 to 180 seconds in normal conditions, or around 120 to 210 seconds for humidity interference during humid conditions. In a preferred embodiment, said curing time, hardening time, or setting time of around 120 to 180 is measured or time upon time of application to a contact surface or a contact wound surface. During said curing time, the stickiness or sticky property of the liquid warm homogenous mixture gradually decreases until a solid product is formed. Upon hardening, the cured or hardened antimicrobial PU foam wound dressing applied on a contact wound surface forms a bandage or a wound dressing. The curing time, hardening time, or setting time of around 120 to 210 seconds provide a quick setting or curing time for the user or the person administering said dressing which provides a reduced waiting time requirement as compared to other PU existing foam wound dressing which has a longer waiting or setting time requirement. Such provision of a quick curing, hardening, or setting time allows the user to quickly seal up wounds thereby preventing infection, providing an immediate remedy to a wound, and allowing the user to further perform relevant tasks which may be needed in managing or treating a wound or assisting a patient in need. Furthermore, the use of high molecular weight polyols contribute to the lowering of overall costs of the manufacture of formulation innovative antimicrobial PU foam wound dressings.

[0059] In a preferred embodiment, said hardened or cured PU foam wound dressing comprises a hydrophobic skin outer layer, an internal foam with hydrophilic open cell porous foam structures, and a bottom layer with adhesive properties adhering to an applied dry contact surface, dry contact skin, or dry contact surrounding the wound. Said hydrophobic skin outer layer is in the top surface of the polymerized foam which prevents absorption of water and moisture but allows the ion and oxygen permeability to enhance wound healing. Said internal foam allows the absorption and retention of liquids or exudates that may be coming from the wound or fluids that may be present on the wound or on the contact skin surface. Said bottom layer in contact with the dry skin surrounding the wound transforms into an adhesive which adheres and secures the whole PU foam wound dressing into place, while said bottom layer in contact with surface areas on the wet surface, moist surface or wound, or open wound transforms into foam cell structures which enables capillary action or absorption actions.

[0060] In a preferred embodiment, the hardened or room temperature -cured PU foam wound dressing forms a white-colored dressing which allows accurate inspection or assessment of the PU foam wound dressing applied on a wound as exudates fills up the internal structure of the PU foam wound dressing. A pure white color, as compared to yellow- colored or colored PU foams, allows the user or the person administering or assessing said PU foam wound dressing to have a better indication of the level of exudates inside the foam dressing on whether the PU foam wound dressing is appropriately administered, or whether said PU foam wound dressing already requires replacement.

[0061] In one embodiment, a cured two-component antimicrobial PU foam wound dressing obtainable by the method or process for preparing a room temperature-cured two- component antimicrobial polyurethane, PU wound dressing is provided. Said a cured two- component antimicrobial PU foam wound dressing obtainable by the method is characterized to be comprising a first polyol-based mixture component and a second prepolymer based component.

[0062] In a preferred embodiment, the two-component antimicrobial PU foam wound dressing of the present invention whether cured or uncured, or obtainable by a method is suitable to be used in the manufacture or preparation of a primary or secondary dressing such as a wound dressing or a wound bandage for the enhancement of treatment or for use to complement in the treatment or remedy of acute or chronic wounds.

[0063] In Figure 1 different views of an example or prototype final cured polyurethane foam non moulded was shown: (a) sideview-1 , (b) side view, (c) bottom view, and non moulded (d) top view. Figure 1d presents the hydrophobic skin outer layer on the top surface of the polymerized foam which prevents absorption of water and moisture but allows the ion and oxygen permeability to enhance wound healing. Figure 1a shows an internal foam of the cured wound dressing with hydrophilic open cell porous foam structures, and Figure 1c presents a bottom layer with adhesive properties when in liquid form (not fully cured or hardened) suitable for adhering to an applied dry contact surface or dry contact skin surrounding the contact wound.

[0064] In one embodiment, the two-component antimicrobial PU foam wound dressing of the present invention may be used or comprised in a kit for providing a two-component antimicrobial PU foam wound dressing, wherein said kit may further comprise of a suitable packaging container, packaging sachet, twin-pack sachet, dual compartment sachet, or a dual compartment sachet comprising an innovative temporary seal at a part along the middle seal, or at a part along the separating segment or separating means for the two components.

[0065] Figure 2 shows an example of a suitable two-compartment packaging container or packaging sachet for the two-component PU foam wound dressing of the invention. Said packaging sachet or stores segregate the two components on two sealed compartments (1 ] wherein the polyol-based mixture component namely Part A component stores on one sealed compartment (1] and the prepolymer-based component namely Part B component stores on the other remaining sealed compartment (1], The two components are separated by a center packaging seal (2] which comprises a temporary seal (3] located at the bottom of the packaging in a length of about 18mm. The packaging further comprises a top packaging seal (4], side packaging seals (5] and (6], and tear notches (7] and (8] located along the side packaging seals proximal to the top end of the top packaging seal by about 25 mm which allows for easy opening of the components when being applied for a cup method as in Figure 4 or when used in applying the mixed homogenous liquid PU foam directly onto a contact surface or a contact wound. In one embodiment, a method or process for producing or manufacturing a room temperature-curable two-component antimicrobial polyurethane, PU foam wound dressing is provided.

[0066] Figure 3 shows an example of a step-by-step use of the packaging container or packaging sachet comprising the separating two components of the two-component PU foam wound dressing of the present invention when the components are being mixed such as insachet mixing. In Figure 3a, the packaging sachet or the twin-pack sachet is folded twice to gather and compress both components on each compartment towards the side of the temporary seal (3], Figure 3b further shows that after the step in 3a, sufficient pressure was applied to the compressed components to open-up the temporary seal (3] in between components A namely Part A component and B namely Part B component. Afterwards, it is show in Fig 3c that all of the components are moved into only one side or one compartment of the twin-pack sachet, wherein in an example of Fig. 3c, Part B component was moved on to the compartment location of Part A component. Afterwards, the two components were mixed in one compartment by pressing with a thumb or a pressing means for mixing for about 25 to 30 seconds as shown in Fig. 3d. When the sachet or the mixed components bulge up and starts to warm up, a corner of the sachet compartment comprising said mixed component is cut or torn at the tear notch then applied onto a contact surface or a contact wound, wherein said application onto a contact wound is from the center of the wound to the edges capturing about 2-3 cm width of skin from the wound edges and around the wound to seal and cover an entire wound and allowed to set or harden.

[0067] Figure 4 shows a step-by-step application or mixing of the two components of the two- component PU foam wound dressing of the present invention when used and mixed in a cup. Fig. 4a shows that the packaging container, packaging sachet, or twin-pack sachet comprising the components A and B is cut at one end, folded along the center packaging seal (2], then all components are poured out onto a cup and stirred vigorously for 18-20 seconds with at least 30 times clockwise or anti -clockwise rotations or movements until the mixture turns into a milky white homogenous liquid substance is achieved (4c). Said homogeneous liquid substance or also known as the homogenous liquid PU foam wound dressing is poured or applied onto a contact surface or a contact wound, wherein said application onto a contact wound is from the center of the wound to the edges capturing about 2-3 cm width of skin from the wound edges and around the wound to seal and cover an entire wound and allowed to set or harden.

[0068] Figures 5-16 shows the observed emitting temperature-uncured, observed pH-uncured, observed diameter and height -cured, weight -cured, observed water resistance and absorption -cured, and observed mixing and drying time of the samples of the two- component PU foam wound dressing of the present invention when the polyol -based mixture component and the prepolymer-based component are mixed and homogenized through the cup method shown in Fig. 5-10 and through in-sachet mixing shown in Fig. 11-16. The PU foam wound dressing of the invention was replicated or reproduced in about 43 different sample preparations which properties were observed and tested for consistencies and quality of product.

[0069] Figure 16 shows the structure of a polymerized PU foam of the present invention having a top surface skin, an internal porous foam, and wherein the copper and chitosan is settled at the bottom of the PU foam upon setting thereby interacting with the wound surface further providing antibacterial protection and prevention of any reinfection resulting to a toxic reaction within the wound.

[0070] Formulation and Manufacturing Process

[0071] In an example provided, producing or manufacturing the two-component antimicrobial polyurethane foam wound dressing of the inventions consists of the following formulation amounts in parts by weight, pbw:

[0072] PART A Component the Uncured Polyol-based component:

[0073] Sub group Part A-1 ,

[0074] 1 . Polyether polyol with high reactivity capped triol and molecular weight exceeding 4799 - 100 pbw.

[0075] Sub group Part A-2:

[0076] 1. Water 1.5-2.0 pbw

[0077] 2. Tertiary Amine Catalyst in solution of dipropylene glycol 0.5-1.0 pbw

[0078] 3 Emulsifier / pH buffer - 0.3-1 .0 pbw

[0079] 4. Curing Agent with bi functional organic compound 0.2-1 .0 pbw

[0080] Sub Group Part A-3:

[0081] 1. Water. 1.5-2.0 pbw

[0082] 2. Foaming Agent 0.5-1 .5 pbw

[0083] 3. A blowing catalyst with delayed-action 1 .5-2.5 pbw

[0084] 4. A Silicone co-surfactant 0.5-2.0 pbw

[0085] 5. An ionized Copper 0.2-0.5 pbw

[0086] 6. A Vegan Chitosan 0.5-1 .0 pbw

[0087] PART B component the prepolymer-based component: diphenylmethane dissocyanate,MDI based prepolymers. 30.0- 43.0 pbw

[0088] As each raw material, composition, or components under PART A namely Uncured Polyol-based component, and PART B namely prepolymer-based component are measured in parts-by -weight, pbw, it is established that Subgroup Part A-1 is approximated to be about 88% of the total volume of the whole PART A formulation, Part A-2 and Part A-3 has approximately12% of the total volume of Part A Formulation, respectively.

[0089] Manufacturing Process

[0090] In an example provided, the first manufacturing process starts off with the mixing of Part A-2 components in a controlled room environment with a room temperature of equal or below 25 °C, a relative humidity, RH environment of less than 66%. Using an agitator fitted with stainless steel mixing impeller, and as per the formulation listed above in Part A-2 components, water is added first in a high-density polyethylene, HDPE container, followed by the addition tertiary amine catalyst and mixed for 10 minutes at rotation of 200 rpm. Next, the emulsifier is added followed by mixing for 10 minutes at 200 rpm. Finally, the curing agent is added follow by a 20 minutes agitation at 200 rpm. Part A-2 is completed and packed or set aside for next final manufacturing process with Part A-1.

[0091] In another example provided, the second manufacturing process is mixing of ingredients for Part A-3 components, water is first added in a HDPE container, followed by the addition of a foaming agent and mixed for 10 minutes at rotation of 200 rpm. Next, a delayed-action blowing catalyst is added follow by the mixing for 10 minutes at 200 rpm. Next, a silicone co-surfactant is added follow by a 20-minute agitation at 200 rpm followed by the addition of ionized Copper and finally a Vegan Chitosan is added followed by a 25 minute agitation at 200 rpm. Part A-3 is completed and packed for next final manufacturing process with Part A-1.

[0092] The final full-scale production of Part A Component namely uncured polyol-based mixture component is done in another controlled room environment with a room temperature of equal or below 25 degrees Celsius, a relative humidity, RH environment of less than 66%. First, subgroup Part A-1 , Polyether polyol with high reactivity capped triol and molecular weight exceeding 4799 is added into a food grade HDPE tank, part by weight of 100. Next, subgroup Part A-2, prepared as per above formulation, is added into the food grade HDPE tank and mix for 15minutes at 120 rpm using an agitator fitted with stainless steel mixing impeller. Next, followed by adding subgroup Part A-3, prepared as per above formulation, and mixed for 90 minutes at 170 rpm. Thereafter, two samples are collected, one from top of tank and another from the bottom outlet, for quality control. After PART B component (MDI-based prepolymer with 30.0- 43.0 parts by weight) was mixed with Part A Component to synthesized a homogenous uncured liquid finished product of a antimicrobial polyurethane foam dressing, quality testing of the product was performed as described in Table 1 below.

[0093] After product quality testing was performed, the entire final mixed Part A component / s was stabilized for at least 24 hours.

[0094] In embodiment, the method or process for producing or manufacturing a room temperature-curable two-component antimicrobial polyurethane, PU foam wound dressing of the invention further comprises a packaging process, or a packaging step for the polyol-based component namely Part A Component and the prepolymer-based component namely Part B Component.

[0095] Formulation of PPU of Patent No. RU2471506CI for Comparative Analysis

[0096] PART A in parts by weight, pbw:

[0097] 1. Low molecular weight polyether polyol No.1 80.0-90.0 pbw

[0098] 2. Low molecular weight polyether polyol No.2 10.0-20.0 pbw

[0099] 3. Water 1.0-2.0 pbw

[0100] 4. Blowing agent 1.0-3.0 pbw

[0101] 5. Urethane catalyst 0.05-0.30 pbw

[0102] 6. Co-catalyst 0.05-0.3 pbw

[0103] 7. Foam Regulator 2.0-7.5 pbw

[0104] 8. Bactericidal Additives 0.8-1.2 pbw

[0105] PART B component: aromatic di isocyanate 35.0-65.0 pbw In an example provided, PART A component was prepared by first mixing 80 parts by weight of low molecular weight polyether polyol No. 1 which is Propol 1055, then addition of 20 pbw of polyether polyol No. 2 which is Propol 490, then addition of 5 pbw Tegastab 8734 LF2 foam regulator, then addition of 0.3 pbw Tegoamin DMCHA catalyst, then addition of 0.3 pbw co-catalyst DBDLO, and addition of 1.0 pbw water. These aforementioned ingredients were stirred using a high speed mixer with speed of 1000- 1500 rpm for 20-30 seconds. After high-speed mixing, 3 pbw of blowing agent which contains mixture of pentafluorobutane and heptafluorobutane at a ratio of 93:7 was added then mixed at a 1000 rpm run for 10-14 seconds. Bactericidal additives Ag-Bion-2 at 0.8 pbw was then added and mixed for 10-20 seconds to obtain the final PART A component which was then thermostated at room temperature for one,1 hour. Afterwards, PART A of100 pbw was then mixed with PART B of 59.2 pbw. Mixing of PART A with PART B was carried out in a bag or container, intensively rubbing manually the components between each other for 10-20 seconds. The mixed composition is immediately applied to the simulated wound surface.

[0106] It was noted that during the first 3 minutes, the sponge is characterized by sufficient stickiness. After 5-10 minutes later after application, the stickiness disappear.

[0107] The process test parameters for the PPU of Patent No. RU2471506CI were as follows: Start time -40 seconds gelation time; -145 seconds later foam growth time -175 seconds later tack-off time; -5 minutes later temperature at foam formation at 37 degree C; After the formation of the structure, the PPU dressing has a porosity of 68 %; An apparent density of 95kg / m3; a water absorption capacity of 8.05g / g; A vapour permeability of 5.2 mg / cm2; water absorption in 24 hours of 68%.

[0108] While the abovementioned PPU uses bactericidal additives and wound healing features, a number of disadvantages were observed. Ag- Bion-2, in the prior art resulted in a medicated foam dressing that cannot be used for a continuous period of more than 2 weeks as recommended to avoid Argyria or manifestation of chronic silver exposure toxicity. Colloidal Silver may also interact with certain medication such as certain antibiotics and levothyroxine. Furthermore, said PPU’s non-stickiness effect can only be achieved from 5-10 minutes. This means that both the patient with the chronic wound and the nurse or care giver needs to be in the same position during that duration of time before moving into other position. This has presented problems for both the patient and the nurse or caregiver by remaining stationary for that relatively “long” period of time. A quicker setting of the polyurethane foam was highly desirable. The PPU of the prior art also does not have a feature addressing the exothermic reaction upon mixing. It is highly crucial to have an exothermic reaction of the mixture to be as low as possible to be in line with the patient’s body temperature because the mixture of Part A and Part B will have to be applied immediately onto the Patient’s wound during the gelation time period. Having no measure to reduce the exothermic reaction temperature further set backs the need for a quick application to a wound treatment.

[0109] ADVANTAGES OF THE INVENTION

[0110] The Liquid PU Foam mixture of the present invention automatically forms an adhesive on the dry part of the polymerized foam and attached onto the perimeter of the thereby wound sealing the entire wound. In addition, the top surface of the polymerized Liquid PU foam safeguarded the wound from secondary infections of bacteria, fungus and virus as the surface skin of the Liquid PU Foam is resistant to bacteria, virus, fungus and water. However, this Liquid PU foam also enables oxygen to aerate the wound on to the surface top of the wound sticking to the PU foam, which is necessary for wound granulation and recovery.

[0111] The Liquid PU foam will is also able to self-sterilize upon the mixing of Part A and Part B and upon application onto the wound surface. Hence, the risk of contamination of the Liquid PU Foam upon application onto the wound surface is almost none.

[0112] The Liquid PU Foam fully conforms to all chronic wound with tunnel or cavity or underlining wound with pocket as the application of the Liquid PU Foam is done in the mixture aqueous form before it polymerized into solid foam structure as wound bandage or dressing.

[0113] The Liquid PU Foam of the present invention’s infusion of inonized copper in minimal quantity yet effective for antimicrobial activity together with Chitosan, afood / medical grade into our liquid foam dressing to avoid prolong usage toxicity or Arygria and interaction with medication.

[0114] To lessen the foam polymerization waiting time, we have created a formula that enable the mixture of Part A and Part B of our product to set completely before 3 minutes, ±30 seconds depending on the humidity of the environment, and enables the patient to resume movement faster.

[0115] It will be apparent to one with skill in the art that the two-component composition for preparing antimicrobial polyurethane, PU foam wound dressing of the present invention may use some or all of the mentioned features and components without departing the spirit and the scope of the present invention. It will also be apparent to the skilled artisan that the embodiments described above are specific examples of a single broader invention which may have greater scope than any of the singular descriptions taught. There may be many alterations made in the descriptions without departing from the spirit and scope of the present invention.

Claims

CLAIMS1. A two-component composition for preparing polyurethane, PU foam wound dressing, said composition comprising, a first polyol-based component comprising: a polyether polyol comprising high-reactivity-capped polyether triol having a molecular weight exceeding 4799 in an amount of 100 parts by weight; water in a total amount of 3.0 to 4.0 parts by weight; a tertiary amine catalyst in a solution of dipropylene glycol in an amount of 0.5 to 1.0 parts by weight; an emulsifier and pH buffer in an amount of 0.3 to 1 .0 parts by weight; a curing agent with a bi-functional organic compound in an amount of 0.2 to 1.0 parts by weight; a foaming agent in an amount of 0.5 to 1 .5 parts by weight; a delayed-action blowing catalyst in an amount of 1 .5 to 2.5 parts by weight; a silicone co-surfactant in an amount of 0.5 to 2.0 parts by weight;0.2 to 0.5 parts by weight ionized copper; and 0.5 to 1.0 parts by weight Vegan chitosan; and a second prepolymer based component comprising 30 to 43 parts by weight diphenyl methane dissocyanate, MDI-based prepolymers.

2. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said copper is ionized copper.

3. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said chitosan is food grade vegan chitosan or medical grade vegan chitosan.

4. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said Ionized copper and vegan chitosan are both comprised in said first polyol-based mixture component.

5. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said first polyol-based mixture component, and said second prepolymer-based component are liquid in form.

6. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said high-reactivity-capped polyether triol is selected from the group consisting glycerine based reactive polyoxyalkilenetriol, polyoxypropylene triol, modified polyoxypropylene triol, tri-functional glycerine initiated polyol, propylene oxide polyol, ethylene oxide polyol, propylene oxide / ethylene oxide co-polymer polyol, and tri-functional glycerine-initiated triol.

7. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said tertiary amine catalyst is 1 ,4- Diazabicyclo[2.2.2]octane.

8. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1, wherein said emulsifier / pH buffer is triethanolamine.

9. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said curing agent is 2-(Dimethylamino)ethan-1 -ol, or DMAE bitartrate or Deanol bitartrate.

10. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said foaming agent is 2,2’-iminodiethanol, diethanolamine or Cocamidopropyl betaine.

11. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said delayed-action blowing catalyst is selected from the group consisting of low potency MDI surfactant preparation of organo-modified polysiloxanes or polydimethylsiloxanes.

12. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said silicone co-surfactant is from a polyethylene oxide-co-propylene oxide pendant group.

13. The two-component composition for preparing polyurethane, PU foam wound dressing of claim 1 , wherein said MDI-based prepolymers or modified MDI prepolymers is selected from the group consisting of 4,4- diphenylmethane diisocyanate or the modified MDI, and polycarbodiimide-modified diphenylmethane diisocynate.

14. A method of preparing a two-component polyurethane, PU foam wound dressing comprising steps of, preparing components A of a mixture by mixing a polyol-based mixture component with a prepolymer based component until a homogenous mixture of temperature equal or no greater than 45°C is attained by measuring at a base suface area of the homogeneous mixture which is in contact with a wound surface; wherein said polyol-based component comprises a polyether polyol comprising high-reactivity-capped polyether triol having a molecular weight exceeding 4799 in an amount of 100 parts by weight, water in a total amount of 3.0 to 4.0 parts by weight, a tertiary amine catalyst in a solution of dipropylene glycol in an amount of 0.5 to 1 .0 parts by weight, an emulsifier / pH buffer in an amount of 0.3 to 1 .0 parts by weight, a curing agent with a bi-functional organic compound in an amount of 0.2 to 1.0 parts by weight, a foaming agent in an amount of 0.5 to 1 .5 parts by weight, a delayed-action blowing catalyst in an amount of 1.5 to 2.5 parts by weight, a silicone co-surfactant in an amount of 0.5 to 2.0 parts by weight, 0.2 to 0.5 parts by weight ionized copper and 0.5-1.0 parts by weight of Vegan chitosan;.. preparing components B of the mixture wherein said prepolymer based component comprises 30 to 43 parts by weight diphenyl methane dissocyanate,M DI -based prepolymers; and mixing components A and components B in a packaging sachet or in a cup.

15. The method of preparing a two-component polyurethane, PU foam wound dressing of claim 14, wherein mixing components A and components B in the packaging sachet comprising steps of; gathering and compressing both components on each compartment towards the side of a temporary seal (3); applying sufficient pressure to the compressed components to open-up the temporary seal (3) in between components A namely Part A component and B namely Part B component; mixing the two compartment in one compartment by pressing with a thumb or a pressing means for mixing for about 25 to 30 seconds; and mixed components or the sachet bulge up and starts to warm up, a corner of the sachet compartment comprising said mixed component is cut or torn at the tear notch then applied onto a contact surface or a contact wound.

16. The method of preparing a two-component polyurethane, PU foam wound dressing of claim 14, wherein mixing components A and components B in a cup comprising; cutting the components A and B at one end, folded along a center packaging seal (2); pouring the components onto a cup and stirred vigorously for 18-20 seconds with at least 30 times clockwise or anti-clockwise rotations or movements until the mixture turns into a milky white homogenous liquid substance is achieved (4c); andpouring the said homogeneous liquid substance or also known as the homogenous liquid PU foam wound dressing onto a contact surface or a contact wound.

17. The method of preparing two-component polyurethane, PU foam wound dressing of claim 14, wherein mixing said polyol-based mixture component and prepolymer based component is performed until a fila PU foam is polymerized in 3 minutes, +- 30seconds.

18. The method of preparing two-component polyurethane, PU foam wound dressing of claim 1 , wherein said copper is ionized copper incorporated as a main antimicrobial agent.

19. The method of preparing two-component polyurethane, PU foam wound dressing of claim 14, wherein said chitosan is food grade Vegan chitosan or medical Vegan grade chitosan incorporated as a complementary antimicrobial agent to claim 16.

20. A packaging of a two-component polyurethane, PU for preparing a two- component polyurethane, PU foam wound dressing comprising: at least two sealed compartments (1] wherein the polyol-based mixture component namely Part A component stores on one sealed compartment (1] and the prepolymer-based component namely Part B component stores on the another remaining sealed compartment (1); a center packaging seal (2) which comprises a temporary seal (3) located at the bottom of the packaging in a length of about 18mm; a top packaging seal (4); and side packaging seals (5) and (6), and tear notches (7), (8) located along the side packaging seals proximal to the top end of the top packaging seal by about 25 mm which allows for easy opening of the components.

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