NOVEL FORMULATION

INTRODUCTION

[0001 ] The present invention relates to a novel formulation. More specifically, the present invention relates to a novel polyurethane gel adhesive formulation suitable for contact with the skin. The present invention also relates to processes for the preparation of the formulations defined herein, as well as to processes for the preparation of medical articles comprising the novel formulation, and to the medical articles themselves.

BACKGROUND OF THE INVENTION

[0002] Advanced wound care products are increasingly used in the management of chronic or difficult to heal wounds. Aging populations and the rapid increase in incidence of Type II diabetes are just two of the factors leading to growth in the number of patients worldwide with chronic wounds. There is therefore a growing need for wound care products, together with an associated need for suitable adhesives to adhere these products (and other medical articles, such as, for example, intravenous lines, catheter tubing and transdermal patches) to a patients' body.

[0003] Polyurethane gels are known, for example, from EP0057839, EP0147588 and US4661099. Some of the polyurethane gels described therein are self-adhesive systems containing polyhydroxy compounds (otherwise known as polyols) and aromatic or aliphatic polyisocyanates. Where the gels are intended for use as adhesive layers for skin contact, then those produced from aliphatic isocyanates are preferable to aromatically-based gels. However, due to the comparatively low reactivity of aliphatic NCO groups, the polyurethane formulations described in these documents afford only slow reacting gel mixtures having sub-optimal adhesive properties. The problem is exacerbated where the cytotoxicity of certain reaction catalysts used in these formulations is known to cause skin incompatibility issues, meaning that such catalysts cannot be used in optimum quantities.

[0004] Despite subsequent efforts, such as those evidenced in US6191216, there remains a need for polyurethane gel formulations demonstrating improved cytotoxicity characteristics without unfavorable consequences to their processability into medical products.

[0005] The present invention was devised with the foregoing in mind. SUMMARY OF THE INVENTION

[0006] According to one aspect of the present invention there is provided a polyurethane adhesive formulation comprising:

at least one polyol,

at least one isocyanate,

at least one stabiliser in a total quantity of 0.1 - 1 .5 wt%, and at least one zinc salt catalyst in a total quantity of 0.02 - 1 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index in the range of 0.45 - 0.69.

[0007] According to a further aspect of the present invention, there is provided a method of preparing a polyurethane adhesive formulation as herein defined, the method comprising mixing:

at least one polyol as herein defined,

at least one isocyanate herein defined,

at least one stabiliser herein defined, and

at least one zinc salt catalyst herein defined.

[0008] According to another aspect of the present invention there is provided a medical article comprising a polyurethane adhesive formulation as herein defined.

[0009] According to a further aspect of the present invention, there is provided an adhesive tape comprising a polyurethane adhesive formulation as herein defined.

[0010] According to yet a further aspect of the present invention, there is provided a wound dressing comprising a polyurethane adhesive formulation as herein defined.

[0011 ] According to still a further aspect of the present invention, there is provided a method of preparing a medical article as defined herein, the method comprising the steps of:

coating a formulation as defined herein onto a release paper, curing the formulation to a predetermined extent, and

laminating a backing film onto the free surface of the coated formulation.

[0012] According to still another aspect of the present invention, there is provided a use of a polyurethane adhesive formulation as herein defined for the fixation of a device to the skin. [0013] According to still another aspect of the present invention, there is provided a polyurethane adhesive formulation obtained, obtainable or directly obtained by any of the methods herein defined.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

[0014] Unless otherwise stated, the following terms used in the specification and claims have the meanings set out below.

[0015] The terms "OH value", "OH number" and "OH index" synonymously relate to the quantitative amount of hydroxyl groups available in the polyol for reaction with one or more isocyanates. The OH value is expressed as milligrams of potassium hydroxide equivalent to one gram of the sample (mg KOH/g).

[0016] The term "NCO content" relates to the amount of isocyanate able to combine with one equivalent of n-butyl amine, and is calculated in weight per cent (wt%).

[0017] The term "isocyanate index" is defined by the ratio of free NCO groups to free OH groups, and is represented by the following formula (sometimes multiplied by a factor of 100):

mol NCO

Isocyanate index =

mol OH

Formulations of the Invention

[0018] As herein discussed, the present invention provides a polyurethane adhesive formulation comprising:

at least one polyol,

at least one isocyanate,

at least one stabiliser in a total quantity of 0.1 - 1 .5 wt%, and at least one zinc salt catalyst in a total quantity of 0.02 - 1 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index in the range of 0.45 - 0.69.

[0019] The formulations of the invention offer improved processability and cytotoxicity characteristics for use in medical articles.

[0020] Processability relates to the ability of the formulation to function satisfactorily as a pressure-sensitive adhesive for contact with the skin. Processability is at least partly dependent on properties such as adhesion, tackiness, and moisture vapour transmission rate (MVTR). Such properties are governed, at least in part, by the isocyanate index of the polyurethane formulation, which results from the extent of NCO-OH reactivity. Formulations that exhibit a high isocyanate index demonstrate sub-optimal adhesion and tackiness properties, whereas formulations exhibiting a low isocyanate index are prone to causing localised skin trauma at the site of contact, as well leaving an undesirable residue on the skin's surface. The formulations of the invention advantageous optimise such processing characteristics.

[0021 ] Cytotoxicity is the quality of being toxic to cells, and is an important consideration in the field of topical formulations. Polyurethane adhesive formulations intended for topical applications often suffer from unacceptable levels of cytotoxicity. This often stems from the inclusion of one or more formulation additives whose presence serves to improve processability. The formulations of the invention provide improved cytotoxicity properties compared to prior art formulations, without compromising processability.

Polyol

[0022] The polyol used in accordance with the present invention may be any polyol suitable for topical use. Suitably, the polyol is a polyether polyol.

[0023] In an embodiment, the polyol has 3 or 4 hydroxy groups. Suitably, the polyol has 4 hydroxy groups.

[0024] In another embodiment, the polyol has an OH value in the range of 20 to 1 12. Suitably the polyol has an OH value in the range of 30 to 56. More suitably, the polyol has an OH value of 32.5 to 37.5. Most suitably, the polyol has an OH value of 35.

[0025] In another embodiment, 1 g of the polyol contains 0.40 - 0.70 mmol OH. Suitably, 1 g of the polyol contains 0.45 - 0.65 mmol OH. More suitably, 1 g of the polyol contains 0.45 - 0.60 mmol OH. Even more suitably, 1 g of the polyol contains 0.50 - 0.60 mmol OH. Most suitably, 1 g of the polyol contains 0.50 - 0.55 mmol OH.

[0026] In another embodiment, 1 g of the polyol contains 0.55 - 0.70 mmol OH. Suitably, 1 g of the polyol contains 0.57 - 0.67 mmol OH. More suitably, 1 g of the polyol contains 0.60 - 0.65 mmol OH. Most suitably, 1 g of the polyol contains 0.62 - 0.63 mmol OH.

[0027] In another embodiment, the polyol is a polyether polyol produced, for example, by polymerising epoxides, such as ethylene oxide, propylene oxide, butylene oxide or tetrahydrofuran, either with themselves or by addition of these epoxides to starter components having at least two hydrogen atoms. Suitably, the polyol is a propylene oxide-ethylene oxide polyether polyol based on a tetrafunctional starter component. More suitably, the polyol contain 70-90% propylene oxide and 10-30% ethylene oxide. Exemplary starter components are water, ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, glycerol, trimethylolpropane, pentaerthyritol, sorbitol or sucrose.

[0028] In another embodiment, the polyol is solvent-free.

[0029] In another embodiment, the polyol has a viscosity of 750 - 1 150 mPa-s at 23 °C. Suitably, the polyol has a viscosity of 850 -1050 mPa-s at 23 °C. More suitably, the polyol has a viscosity of 900 -1000 mPa-s at 23 °C.

[0030] In another embodiment, the polyol has a molecular weight of 50,000 - 80,000 g/mol. Suitably, the polyol has a molecular weight of 60,000 - 70,000 g/mol. More suitably, the polyol has a molecular weight of 60,000 - 65,000 g/mol.

[0031 ] In another embodiment, the polyol contains a stabilising agent. The stabilising agent may be present in the polyol at a quantity of 0.05 - 0.55 wt%. Suitably, the stabilising agent is vitamin E at a quantity of 0.1 - 0.5 wt%.

[0032] In an embodiment, more than one polyol may be used. Alternatively, one only polyol may be present.

[0033] Suitably, the polyol is a diol based on 80 wt% propylene oxide and 20 wt% ethylene oxide. More suitably, the polyol is based on a tertafunctional starter molecule.

[0034] The polyol suitably used herein is available under the trade name Baymedix AR602 (available from Bayer AG, Leverkusen).

[0035] In an embodiment, the quantity of polyol present in the formulation is 70 - 95 wt%. Suitably, the quantity of polyol present in the formulation is 80 - 95 wt%. More suitably, the quantity of polyol present in the formulation is 85 - 95 wt%. Even more suitably, the quantity of polyol present in the formulation is 85 - 92 wt%. Most suitably, the quantity of polyol present in the formulation is 88 to 92 wt%, for example approximately 90 wt%.

Isocyanate

[0036] The isocyanate used in accordance with the present invention may be any isocyanate suitable for topical use. Suitably, the isocyante is an aliphatic diisocyanate.

[0037] In an embodiment, the isocyanate is a monomeric or trimerised hexamethylene diisocyanate. Alternatively, the isocyanate is a hexamethylene diisocyanate modified by biuret, uretidione or allophanate groups. Alternatively, the hexamethylene diisocyanate is modified by prepolymerisation with polyether polyols or mixtures of polyether polyols based on starter components having 2 or more reactive H atoms, and epoxides such as ethylene oxide or propylene oxide, and of an OH value of less than 850. Suitably, the isocyanate is a largely linear aliphatic NCO prepolymer based on hexamethylene diisocyanate.

[0038] In an embodiment, more than one isocyanate may be used. Alternatively, only one isocyanate may be used.

[0039] In another embodiment, the isocyanate has an NCO content of 1 1 - 15 wt%. Suitably, the isocyanate has an NCO content of 12 - 14 wt%. More suitably, the isocyanate has an NCO content of 12.3 - 13.3 wt%.

[0040] In another embodiment, 1 g of the isocyanate contains 2.5 - 4.5 mmol NCO. Suitably, 1 g of the isocyanate contains 2.7 - 4.3 mmol NCO. More suitably, 1 g of the isocyanate contains 2.9 - 4.1 mmol NCO. Even more suitably, 1 g of the isocyanate contains 3.1 - 3.9 mmol NCO. Most suitably, 1 g of the isocyanate contains 3.4 - 3.8 mmol NCO.

[0041 ] In another embodiment, 1 g of the isocyanate contains 2.90 - 3.20 mmol NCO. Suitably, 1 g of the isocyanate contains 2.93 - 3.17 mmol NCO. More suitably, 1 g of the isocyanate contains 3.00 - 3.10 mmol NCO. Most suitably, 1 g of the isocyanate contains 3.03 - 3.07 mmol NCO.

[0042] In another embodiment, the isocyanate has a viscosity in the range of 3000 - 5000 mPa-s at 23 °C. Suitably, isocyanate has a viscosity in the range of 3300 - 4700 mPa-s at 23 ^< C.

[0043] A suitable isocyanate is available under the trade name Baymedix AP 501 (available from Bayer AG, Leverkusen).

[0044] In an embodiment, the quantity of isocyanate present in the formulation is 4 - 16 wt%. Suitably, the quantity of isocyanate present in the formulation is 6 - 14 wt%. More suitably, the quantity of isocyanate present in the formulation is 7.5 - 12 wt%.

[0045] In another embodiment, the quantity of isocyanate present in the formulation is 9.5 - 10.5 wt%

[0046] In another embodiment, the quantity of isocyanate present in the formulation is 8 - 10 wt%. Suitably, the quantity of isocyanate present in the formulation is 9 - 10 wt%, for example approximately 9 or 9.5 wt%. Stabiliser

[0047] The stabiliser used in accordance with the present invention may be any stabiliser or anti-oxidant suitable for topical use.

[0048] In one embodiment, the stabiliser is a sterically hindered phenol.

[0049] In another embodiment, the stabiliser has a viscosity in the range of 100 - 400 mPa-s at 23°C. Suitably, the stabiliser has a viscosity in the range of 200 - 300 mPa-s at 23 °C. More suitably, the stabiliser has a viscosity of approximately 220 mPa-s at 23 °C.

[0050] In another embodiment, the stabiliser has a molecular weight of 200 - 500 g/mol. Suitably, the stabiliser has a molecular weight of 350 - 450 g/mol. More suitably, the stabiliser has a molecular weight of approximately 390 g/mol.

[0051 ] In another embodiment, the stabiliser is selected from the group consisting of Irganox 1 135 (Benzenepropanoic acid, 3,5-bis (1 ,1 -dimethyl-ethyl)-4-hydroxy-C7-C9 branched alkyl esters), BHT (2,6-di-tert.-butyl-4-methylphenol), Vulkanox BKF (2,2'- methylene-bis-(6-tert.-butyl-4-methylphenol)) (available from Bayer AG, Leverkusen), Irganox 1010 (pentaerythrityltetrakis[3-(3,5-di-tert.-butyl-4-hydroxyphen yl) propionate]), Irganox 1076 (octadecyl-3-(3,5-di-tert.-butyl-4-hydroxyphenyl) propionate), Irganox 1330 (1 ,3,5-trimethyl-2,4,6-tris(3',5'-di-tert. -butyl-4'-hydroxybenzyl)benzene), Irganox 1520 (2- methyl-4,6-bis[(octylthio)methyl]phenol) (available from Ciba-Geigy) and/or tocopherols. Further exemplary stabilisers are stated, for example, in Ullmann (volume A3, pp. 91 - 1 1 1 ; volume A20, pp. 461 -479; volume A23, 381 -391 ).

[0052] In another embodiment, the stabilising characteristics of such phenolic stabilisers may be still further improved by the addition of organically substituted sulfides or disulfides, such as for example Irganox OS800 (3,3'thiodipropionic acid dilauryl ester) or dioctyldidecyl disulfide.

[0053] In another embodiment, more than one stabiliser may be used. Alternatively, only one stabiliser may be used.

[0054] Suitably, the stabiliser is Irganox 1 135 (Benzenepropanoic acid, 3,5-bis (1 ,1 - dimethyl-ethyl)-4-hydroxy-C7-C9 branched alkyl esters). Optionally, the stabiliser is a vitamin E stabiliser. [0055] In an embodiment, the quantity of stabiliser present in the formulation is 0.1 - 1 .0 wt%. Suitably, the quantity of stabiliser present in the formulation is 0.2 - 0.7 wt%. Suitably, the quantity of stabiliser present in the formulation is 0.2 - 0.6 wt%.

[0056] In another embodiment, the quantity of stabiliser present in the formulation is 0.4 - 0.6 wt%. Suitably, the quantity of stabiliser present in the formulation is approximately 0.5 wt%.

Catalyst

[0057] The stabiliser used in accordance with the present invention may be any zinc salt catalyst suitable for topical use.

[0058] In an embodiment, the catalyst is a tin-free catalyst based on zinc carboxylate. Suitably, the catalyst is based on zinc neodecanoate, or zinc octoate.

[0059] In another embodiment, the catalyst is a solvent free or solvent-borne zinc salt catalyst.

[0060] In another embodiment, the zinc salt catalyst contains no organic complexing agents.

[0061 ] Suitably, the zinc salt catalyst is selected from Borchi Kat 15 and Borchi Kat 22 (available from OMG Borchers GmbH, Berghausener Str. 100 / 40764 Langenfeld; www.borchers.com). More suitably, the catalyst is Borchi Kat 22.

[0062] In another embodiment, more than one zinc salt catalyst may be used. Alternatively, only one zinc salt catalyst may be used.

[0063] In an embodiment, the quantity of catalyst present in the formulation is 0.02 - 0.75 wt%. Suitably, the quantity of catalyst present in the formulation is 0.05 - 0.2 wt%. More suitably, the quantity of catalyst present in the formulation is 0.07 - 0.2 wt%.

[0064] In another embodiment, the quantity of catalyst present in the formulation is 0.07 - 0.15 wt%. Suitably, the quantity of catalyst present in the formulation is 0.08 - 0.12 wt%. Suitably, the quantity of catalyst present in the formulation is approximately 0.1 wt%.

Particular embodiments of the invention

[0065] In an embodiment of the invention, the formulation comprises:

at least one polyol, at least one isocyanate,

at least one stabiliser in a total quantity of 0.2 - 0.8 wt%, and at least one zinc salt catalyst in a total quantity of 0.02 - 0.75 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index in the range of 0.45 - 0.69.

[0066] In an embodiment of the invention, the formulation comprises:

at least one polyol,

at least one isocyanate,

at least one stabiliser in a total quantity of 0.2 - 0.6 wt%, and at least one zinc salt catalyst in a total quantity of 0.07 - 0.2 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index in the range of 0.45 - 0.69.

[0067] In a further embodiment of the invention, the formulation comprises:

at least one polyol,

at least one isocyanate,

at least one stabiliser in a total quantity of 0.3 - 0.7 wt%, and at least one zinc salt catalyst in a total quantity of 0.07 - 0.15 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index in the range of 0.45 - 0.69.

[0068] In an embodiment of the invention, the formulation comprises:

at least one polyol,

at least one isocyanate,

at least one stabiliser in a total quantity of 0.2 - 0.6 wt%, and at least one zinc salt catalyst in a total quantity of 0.07 - 0.2 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index in the range of 0.53 - 0.57.

[0069] In still a further embodiment of the invention, the formulation comprises:

at least one polyol,

at least one isocyanate,

at least one stabiliser in a total quantity of 0.3 - 0.7 wt%, and at least one zinc salt catalyst in a total quantity of 0.07 - 0.15 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index in the range of 0.53 - 0.57.

[0070] In still a further embodiment of the invention, the formulation comprises:

at least one polyol,

at least one isocyanate,

at least one stabiliser in a total quantity of 0.4 - 0.6 wt%, and at least one zinc salt catalyst in a total quantity of 0.08 - 0.12 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index in the range of 0.53 - 0.57.

[0071 ] In still a further embodiment of the invention, the formulation comprises:

at least one polyol,

at least one isocyanate,

at least one stabiliser in a total quantity of approximately 0.5 wt%, and at least one zinc salt catalyst in a total quantity of approximately 0.1 wt%, wherein the total quantities of polyol and isocyanate are such that the polyurethane adhesive formulation has an isocyanate index of approximately 0.55.

[0072] In an embodiment of the invention, the formulation comprises:

at least one polyol in a total quantity of 70 - 95 wt%,

at least one isocyanate in a total quantity of 3 - 15 wt%,

at least one stabiliser in a total quantity of 0.2 - 0.8 wt%, and at least one zinc salt catalyst in a total quantity of 0.02 - 0.75 wt%.

[0073] In another embodiment of the invention, the formulation comprises:

at least one polyol in a total quantity of 80 - 95 wt%,

at least one isocyanate in a total quantity of 6 - 12 wt%,

at least one stabiliser in a total quantity of 0.3 - 0.7 wt%, and at least one zinc salt catalyst in a total quantity of 0.07 - 0.15 wt%.

[0074] In another embodiment of the invention, the formulation comprises:

at least one polyol in a total quantity of 85 - 95 wt%,

at least one isocyanate in a total quantity of 8 - 10 wt%,

at least one stabiliser in a total quantity of 0.2 - 0.6 wt%, and at least one zinc salt catalyst in a total quantity of 0.07 - 0.2 wt%.

[0075] In another embodiment of the invention, the formulation comprises:

at least one polyol in a total quantity of 85 - 95 wt%,

at least one isocyanate in a total quantity of 8 - 10 wt%,

at least one stabiliser in a total quantity of 0.4 - 0.6 wt%, and at least one zinc salt catalyst in a total quantity of 0.08 - 0.12 wt%.

[0076] In another embodiment of the invention, the formulation comprises:

at least one polyol in a total quantity of approximately 90 wt%,

at least one isocyanate in a total quantity of approximately 9 wt%, at least one stabiliser in a total quantity of approximately 0.5 wt%, and at least one zinc salt catalyst in a total quantity of approximately 0.1 wt%.

[0077] In the preceding embodiments, the at least one polyol suitably comprises a polyether polyol. More suitably, the at least one polyol has an OH value in the range of 32.5 - 37.5. More suitably, the at least one polyol comprises 70 - 90% propylene oxide and 10 - 30% ethylene oxide by weight. More suitably, the at least one polyol is a diol based on 80% propylene oxide and 20% ethylene oxide by weight. A suitable polyol is available under the trade name Baymedix AR602 (available from Bayer AG, Leverkusen).

[0078] In the preceding embodiments, the at least one isocyanate suitably comprises an aliphatic diisocyanate. More suitably, the at least one isocyanate has a total NCO content of 12 - 14 wt%. Most suitably, the at least one isocyanate is an NCO-terminated prepolymer based on hexamethylene diisocyanate and ether diol.

[0079] In the preceding embodiments, the at least one stabiliser suitably comprises a sterically hindered phenol. Most suitably, the at least one stabiliser is benzenepropanoic acid, 3,5-bis (1 ,1 -dimethyl-ethyl)-4-hydroxy-C7-C9 branched alkyl esters.

[0080] In the preceding embodiments, the at least one zinc salt catalyst is suitably tin- free. More suitably, the at least one zinc salt catalyst is based on a zinc carboxylate. More suitably, the at least one zinc salt catalyst is based on zinc neodecanoate or zinc octoate. Most suitably, the at least one zinc salt catalyst is selected from Borchi Kat 15 and Borchi Kat 22 (available from OMG Borchers GmbH, Berghausener Str. 100 / 40764 Langenfeld; www.borchers.com).

Methods of the Invention

Preparation of the formulation

[0081 ] As herein discussed, the present invention provides a method of preparing a polyurethane adhesive formulation as herein defined, the method comprising mixing:

at least one polyol as herein defined,

at least one isocyanate herein defined,

at least one stabiliser herein defined, and

at least one zinc salt catalyst herein defined.

[0082] In an embodiment, prior to mixing, the at least one stabiliser and at least one zinc salt catalyst are provided as a pre-mixture containing one or more polyol. This pre- mixture suitably comprises 80-90 wt.% of polyol (e.g. approximately 84 wt.%); 0.5-12 wt.% of catalyst (e.g. approximately 3 wt.%); and 3-14 wt.% of stabiliser (e.g. approximately 13 wt.%).

[0083] In another embodiment, the components of the formulation are mixed using a 3 component in-line mixer. Suitably, the raw materials are protectively stored under a nitrogen atmosphere once drums are opened to exclude moisture and humidity from the system, and are preconditioned by controlling the temperature at 23 °C +1-2 °C for 48hrs prior to use.

[0084] In an embodiment, the components of the formulation are mixed using a high speed mixing head. Suitably, a protective blanket is used during pumping of the components to the mixing head. More suitably, the protective blanket it a nitrogen blanket.

[0085] In a further embodiment, the mixing apparatus is calibrated prior to mixing. Suitably, the mixing apparatus is calibrated for every batch of formulation.

Preparation of a medical article

[0086] As herein discussed, the present invention provides a method of preparing a medical article as herein defined, the method comprising the steps of:

coating the formulation herein defined onto a release paper,

curing the formulation to a predetermined extent, and

laminating a backing film onto the free surface of the coated formulation.

[0087] In an embodiment, the mixed polyurethane adhesive formulation is provided to a coating head where it is coated using a knife-over-roll coater onto a release paper. Suitably, the release paper is a siliconised release paper.

[0088] In another embodiment, the coated release paper is exposed to a heat source to accelerate the curing reaction between the polyol and isocyanate.

[0089] In a further embodiment, once the polyurethane adhesive formulation has cured to the desired extent, a polyurethane film is laminated onto the exposed surface of the polyurethane adhesive formulation layer. Suitably, the polyurethane film has a thickness of 25 μηι. Suitably, the resultant laminate is wound into rolls.

[0090] In another embodiment, the laminate is subject to further processing steps depending on the nature of the dressing. Other materials, such as cushioned pads or waterproof layers, may be incorporated where the dressing is required to exhibit additional characteristics. DESCRIPTION OF THE DRA WINGS

[0091 ] Embodiments of the invention will now be further described, by way of example only, with reference to the accompanying figures, in which:

Figure 1 is schematic representation of the apparatus assembly use to prepare the PU gel formulations of the present invention.

[0092] Referring to figure 1 , separate reservoirs of polyol, isocyanate and catalyst masterbatch pre-mix (described further herein in Examples 1 and 2) are prepared and stored in compartments A, B and C respectively under a nitrogen atmosphere. Each component is drawn from its respective compartment through a filter by a dosing pump. A flow meter is used to accurately control the flow of each component into the mix head chamber to give the desired PU gel formulation composition within the mix head chamber. The PU gel formulation is mixed within the mix head chamber prior to being delivered to a coating head where the PU gel formulation is applied as a film to a release paper and cured.

EXAMPLES

General methods

Liner Release Assessment (180° method)

[0093] The liner release test method is designed to measure the force required to remove the release liner from the PU film.

Nature of test:

[0094] The sample was fixed to a standard plate by means of double sided tape and then fixed vertically in the movable clamp of the tensile testing machine. The stressing clamp of the machine pulls the free end of the liner an angle of 180° to the plate. The release value is measured by the force required to peel the liner continuously from the plate, the line separation being at rights angles to the direction of the applied force.

Equipment and conditions:

Tensile testing machine:

[0095] An electronic type situated in the standard test conditions with the following characteristics:

1 ) The force shall be indicated with a maximum error of 2%.

2) The speed of the movable clamp shall be 300 ± 30 mm/minute.

3) The clamps shall be of a design that prevents slipping or tearing of the foam.

4) 180 Grit finish stainless steel plates 200mm long X 50mm wide and about 2mm thick. 5) Standard test conditions 23 ° ± 2 °C.

Test specimens:

[0096] The test is performed on at least 2 specimens. Each specimen shall be at least 200mm long and 25mm width. A sharp knife is used to obtain clean cut edges.

[0097] Samples are taken in the machine direction. Specimens can be taken from slit rolls. In this case, if the width was less than 25mm then the width needs to be measured and used to calculate the force required to peel the liner per 25mm width.

Test procedure:

[0098] The following procedure was followed:

1 ) Clean the stainless steel plates.

2) Adhere the PU film liner of the sample strips to the metal test plate using double sided tape, ensuring the edge of the tape is parallel to the long edge of the plate, so that one end of the sample is flush with the end of the test plate and the other end hangs free.

3) Peel off sufficient release liner from the free end of the sample to enable a "tail" of Sellotape to be attached.

4) Adhere 25mm cellulose tape to the back of the sample so that the cellulose tape completely aligns with the back side of the sample and extends beyond the end of the sample forming the tail.

5) Fix the plate in the lower clamp of the tensile testing machine.

6) Fold back the tail and fix it in the upper clamp so that the foam surfaces backed with cellulose are almost in contact and exactly aligned.

7) Set the tensile testing machine to speed of 300± 30 mm/min and start separation of clamps.

8) Record the average value.

Results:

1 ) Calculate the average of the 2 samples and take the average as the release

value of the liner under test.

2) Record the results as N/25mm

Peel adhesion test method

[0099] The peel adhesion test method is designed to measure the force required to remove adhesive coated product which has been applied to a specified substrate test plate.

Nature of the test:

[00100] The material to be assessed was applied to a substrate plate which is then fixed vertically to the tensometer with a movable clamp. The upper holding clamp of the machine pulls the free end of the test piece at an angle of 180° to the plate. The adhesive strength is measured by the force required to peel the tape continuously from the plate, the line of separation being right angles to the direction of the applied force. Equipment and conditions:

1 ) Tensile testing machine: An electronic type situated in the standard test conditions with the following characteristics:

2) Force applied shall be indicated with a maximum error of 2%.

3) The speed of the moveable clamp shall be set as required by the method required.

4) Test clamps utilised shall be of a design that prevents slippage or tear of the test piece.

5) Substrate plate of sufficient width and length for material application - see plate type.

6) Rubber Coated Roller with a mass as required by specific method requested - see roller type.

7) Standard test conditions: 23° + 2°C.

Test specimens:

[00101] Specimens for testing should ideally be cut from a sample of full manufactured roll width allowing for testing across the whole sample. Standard sample size is 25mm in width but samples can be tested up to the width of the substrate plate. Standard peel extension is 225mm but samples can be tested down to 40 - 50mm. Samples should be cut using a clean sharp blade. Slit rolls of material can also be used for test samples. Procedure:

1 ) Take a clean plate of the type as stated in the table below and adhere the sample strips to the upper face of the plate ensuring the edge of the tape is parallel to the long edge of the plate.

2) Adhere 25mm cellulose tape at right angles to the sample so that any backing material (if required as indicated in the appended table) or the tag can be attached to the sample.

3) Pass the roller over the backside of the sample to and fro to ensure bonding. The roller weight, type & speed of rolling and number of passes are specified in the table below.

4) Leave the sample for the required dwell time as indicated in the appended table.

5) Stripping the test specimen from the test plate: Peel off about 25mm of the sample from the starting end of the plate, the line of separation being perpendicular to the axis of the test specimen, and place plate in clamp 6) Fold back the free end of the tape end tail and then fix it in the other clamp so that there is a small tension free loop of no more than 5mm, the surfaces are almost in contact and exactly aligned.

7) Check that the speed of the peel is correct for the specified test, "zero the force" on the loadcell and initiate the peel.

8) For all peel adhesion measurements where the failure mode is either True Peel or Cohesive failure set the margins for records at 25 - 75mm, (i.e. disregard the first 25mm of peel), for failure mode Foam delamination set the margins zero - 75mm. Record the peel force average, the maximum load force and failure mode.

Results:

1 . Record the results found in N/25mm.

2. Calculate the average of 3 strip samples and take this as the peel strength of the adhesive coating under test.

Cytotoxicity Test - Agar Overlay

[00102] Acceptance Criteria : The United States Pharmacopeia & National Formulary (USP <87>) states that a test article meets the requirements of the Agar Overlay test if the reactivity grade measured using the protocol below is not greater than grade 2 (or a mild reactivity). The ANSI/AAMI/ISO 10993-5 standard states that the achievement of a numerical grade greater than 2 is considered a cytotoxic effect. The acceptance criteria was based upon the negative control receiving "0" reactivity grade and positive control receiving 3-4 reactivity grades (moderate to severe).

[00103] Procedure : Six well cell culture plates were seeded with a verified quantity of industry standard L-929 cells (ATCC CCL-1 ) and incubated at 37 + 1 ^< C with 5 + 1 % C0 ₂ until approximately 80% confluent. The agar overlay consisted of an equal mixture of 1 NAGAR (1 .0%) and 2X MEM + 10% bovine calf serum. Solid test articles were placed directly on the solidified agar overlay testing > 100 mm ² per test well. Positive and negative reference controls were included with each assay.

[00104] All tests were performed using three test wells per test PU film article. After the addition of the test articles, the cell culture plates were incubated as described above for 24-26 hours. Following incubation, cells were evaluated microscopically using the evaluation criteria outline below:

[00105] The results from the three wells were averaged to give an average cytotoxicity score.

Example 1 - preparation of PU gel adhesive formulations with varying levels of a Zinc salt catalyst (Borchi Kat 22)

[00106] The purpose of this study was to evaluate a PU Gel adhesive made using various levels of the Zinc based catalyst system Borchi Kat 22 (within the range of 0.075 wt.% up to 0.20 wt.%).

Raw Materials

Zinc Based Catalyst System - Borchi Kat 22

Stabiliser - Irganox 1 135

Polyol - BayMedix AR 602

Diisocyanate - BayMedix AP 501

Formulation preparation

[00107] The followin formulations were used in this study.

Mixing of Catalyst Masterbatch

[00108] The required addition levels of catalyst and stabiliser used in the PU adhesive gel systems are very low, and therefore to aid accurate addition it is recommended that a catalyst masterbatch pre-mix is prepared.

[00109] The catalyst masterbatch pre-mix was made by dispersing known quantities of the catalyst and the stabilisers in a known quantity of the polyol used in the PU Gel formulation.

[00110] The catalyst masterbatch pre-mix formulations used in the preparation of the above formulations were as follows:

[00111] The polyol was accurately weighed into a mixing vessel and the required amount of stabiliser was then accurately added. The mixture was then stirred for 5 minutes using a paddle stirrer.

[00112] The required amount of catalyst was then weighed an accurately added to the mixture of the polyol and the stabiliser and stirred using a paddle stirrer for a further 10 minutes.

[00113] The catalyst masterbatch pre-mix is then loaded into the C component reservoir of the apparatus shown schematically in Figure 1 . The C compartment wads then sealed and flooded with nitrogen to ensure that no moisture from the atmosphere is present.

Preparation of PU Gel Formulations

Calculation of Formulation Quantities

[00114] To calculate the required quantities by weight of each component to form the formulations at the required isocyanate index you need to know the hydroxyl (OH) content of the PU polyol and the isocyanate (NCO) content of the di isocyanate batches being used.

[00115] In this example, the Polyol has a hydroxyl number of 35 and the diisocyanate has a NCO content of 13.0 %. [00116] As previously indicated, the isocyanate index is calculated by dividing the moles of isocyanate groups present by the moles of hydroxyl groups present

mol NCO

Isocyanate index =

mol OH

[00117] For an isocyanate index of 0.55 (or 55 when multiplied by a factor of 100), the moles of NCO and moles of OH can be calculated as follows:

1 ) Converting the OH number of the polyol to OHwt.%, which is done by dividing the OH number by 33;

2) Converting the OH% to moles OH, which is done by multiplying the OH% by 100 and then dividing by 17;

3) Calculating the moles of NCO needed by multiplying the moles OH by the desired isocyanate index (0.55);

4) Calculating the number of parts by weight NCO needed by multiplying the moles NCO by 42 and then dividing by the NCO content.

Mixing of the Polyol, Diisocyanate and Catalyst Masterbatch Pre-mix

[00118] Mixing of the three components (Polyol, Diisocyanate, and Masterbatch) was done using a high speed dynamic mixer assembly, as shown schematically in Figure 1 . Each component was accurately metered into a mixing head chamber under the control of dedicated gear pumps. The three components were pumped into the mixing head chamber where the mixing head homogenised the mixture at a mix head speed of 3- 4,000 rpm for approximately 2-4 seconds.

Coating and Curing the PU Gel Adhesive

[00119] The PU gel formulation formed in the mixing head was coated on the release side of a suitable release paper using a knife over roll technique. The coating knife can be adjusted to vary the coating weight of the PU gel formulation. Typically the coating blade is configured such that the cured PU gel is at the target weight required - typically 100 g/m2 or 150 g/m2, though lower and higher coating weights can easily be achieved if desired.

[00120] The coated PU gel was then cured in ovens having two temperature zones set at the desired temperature and desired dwell time. Different catalysts and formulations will require different oven temperatures and exposure times to affect a good cure of the PU gel adhesive which will be tough dry and tacky. Varying the Isocyanate index from low to high will vary the cured PU properties from a very tacky adhesive through to a flexible film with no adhesive properties.

[00121] The temperatures and dwell times used in the preparation of the formulations are shown below:

Laminating a PU Gel Adhesive layer onto a PU film

[00122] A layer of the PU gel adhesive formulations was laminated onto the exposed side of the PU film using a roller laminating nip to ensure the laminated film was free of creases and wrinkles. The resultant coated film had the PU Gel adhesive layer protected by the release paper. The PU gel adhesive was then tested to assess its properties, namely peel adhesion, liner release (breaking strength), and cytotoxity using the methodology described herein.

Results

Conclusions

[00123] From the results presented above, it can be seen that:

• The zinc-based catalyst Borchi Kat 22 can be used to produce PU gel adhesives at a nominal Isocyanate Index 55 and at loading levels of between 0.075 wt.% and 0.2 wt.% with no significant change in the properties and performance of the PU gel adhesive performance.

• The peel adhesion values are not greatly affected by changes in the zinc-based catalyst levels and all formulations had peel adhesion values within the target range of 1 - 3 N/25 mm.

• The liner release values are not greatly affected by changes in the zinc-based catalyst levels

• The formulations with the zinc-based catalyst at 0.1 wt.% and 0.2 wt.% met the requirements of the Cytotoxicity Agar Overlay test with both formulations scoring Grade 0 (the target being Grade 2 or less).

Example 2 - Evaluation of PU Gel adhesives made using either a tin-based or a zinc-based catalyst system

[00124] This study was to evaluate a PU Gel adhesive made using a tin-based catalyst system (comparator) and a PU Gel adhesive made using a zinc-based catalyst system.

Raw Materials

Tin Based Catalyst System - Catalyst 162 (DBTL)

Zinc Based Catalyst System - Borchi Kat 22

Stabiliser - Irganox 1 135

Polyol - BayMedix AR 602

Diisocyanate - BayMedix AP 501

Formulation Preparation

[00125] The following formulations were prepared in this study.

Formulation component

Tin Based Zinc Based

BayMedix

Polyol AR602 90.59 90.77 % Weight

BayMedix

Diisocyanate AP501 8.72 8.77 % Weight

Stabiliser Irganox 1 135 0.50 0.38 % Weight

Catalyst Tin based Catalyst 162 0.19 0.00 % Weight

Catalyst Zinc Based Borchi Kat 22 0.00 0.08 % Weight

Total 100.00 100.00

Isocyanate Index 49 49 Index

Coat Weight 90 - 1 1 0 90 - 1 1 0 g/m2 Mixing of Catalyst Masterbatch

[00126] As described in Example 1 above, a catalyst masterbatch pre-mix was prepared and loaded into reservoir C of mixing apparatus shown schematically in Figure 1 .

[00127] The catalyst masterbatch pre-mix was prepared by dispersing known quantities of the catalyst and the stabilisers in a known quantity of the polyol used in the PU Gel formulation.

[00128] The catalyst masterbatch pre-mix formulations prepared are shown in the table below:

Preparation of PU Gel Formulation

Calculation of Formulation Quantities

[00129] The quantities of polyol to diisocyanate were calculated as described above in Example 1 .

Mixing of the Polyol, Diisocyanate and Catalyst Masterbatch Pre-mix

[00130] The formulations were mixed in the same manner as described above in

Example 1 .

Coating and Curing the PU Gel Adhesive

[00131] The formulations coated onto PU films and cured in the same manner as described above in Example 1 .

[00132] The temperatures and dwell times used in the preparation of the formulations are shown below:

Laminating a PU film to the PU Gel Adhesive

[00133] PU films were laminated onto the PU gel adhesive in the same manner as described above in Example 1 .

Results

Conclusions

1 ) The Tin based catalysed PU Gel adhesive formulation failed the Cytotoxicity Agar Overlay test with a Grade 3 and is therefore may be unsuitable for healthcare applications.

2) The Zinc based catalysed PU Gel adhesive formulation meets the requirements of the Cytotoxicity Agar Overlay test with a Grade 0 and therefore is suitable for healthcare applications.

3) Both catalysts produced a cured PU Gel adhesive with peel adhesion values within the target range of 1 - 3 N/25 mm.

Example 3 - preparation of PU gel adhesive formulations with varying isocyanate index

[00134] The purpose of this study was to evaluate the effect of varying isocyanate index of PU Gel adhesives on the peel adhesion properties.

Raw Materials

Zinc Based Catalyst System - Borchi Kat 22

Stabiliser - Irganox 1 135

Polyol - BayMedix AR 602

Diisocyanate - BayMedix AP 501 Formulation preparation

The following formulations were used in this study.

[00135] Peel adhesion test results are shown in the following table:

[00136] From the above results, it is clear that by decreasing the isocyanate index (i.e. a reduction in cross-linking density), the peel adhesion increases. An increased peel adhesion value indicates that a greater force is required to remove the adhesive coated product from the substrate. In certain applications, slightly higher adhesion levels are required to ensure a device stays in position, so the ability to fine tune the adhesion is seen as a processing advantage. Example 4 - effect of adhesive coat weight on peel adhesion properties

[00137] The purpose of this study was to evaluate the effect of adhesive coat weight on the peel adhesion properties of products containing PU Gel adhesives formulations of the invention.

Raw Materials

Zinc Based Catalyst System - Borchi Kat 22

Stabiliser - Irganox 1 135

Polyol - BayMedix AR 602

Diisocyanate - BayMedix AP 501

[00138] Peel adhesion properties of two samples prepared using PU gel adhesive formulations having an isocyanate index of 55 are shows in the following table:

[00139] The results shown above indicate that as the adhesive coat weight increases from 100 gsm to 200 gsm, a small increase in adhesion properties is observed.

[00140] While specific embodiments of the invention have been described herein for the purpose of reference and illustration, various modifications will be apparent to a person skilled in the art without departing from the scope of the invention as defined by the appended claims.