Skin adhesive composition

Abstract

The present invention relates to a skin adhesive composition comprising at ieast one thermochromic agent and wearable products, such as medical dressings, comprising the skin adhesive composition. The present disclosure also describes a pre-cure composition capable of forming the skin adhesive composition, as well as uses of the skin adhesive composition and a method of manufacturing the skin adhesive composition.

Description

[0001]Skin Adhesive Composition Field of the InventionThe present invention relates to a skin adhesive composition comprising at least onethermochromic agent and wearable products, such as medical dressings, comprising theskin adhesive composition. The present disclosure also describes a pre-cure composition capable of forming the skin adhesive composition, as well as uses of theskin adhesive composition and a method of manufacturing the skin adhesivecomposition. Background of the InventionWound infections and chronic wound inflammation continue to be challenging problemswithin healthcare systems and represent a considerable healthcare burden. Earlydetection, together with prompt and effective intervention, of these infections as well aseffective management of inflammation is becoming increasingly important.Traditionally, clinicians would determine the presence of wound infections andinflammation through the visual assessment of observable markers before then makinga subsequent diagnosis, via a wound culture test, in the case of infection. This type ofapproach is time consuming and requires highly experienced clinicians to perform theassessment and make diagnosis decisions. There is, therefore, a clinical need for newtechnologies that are capable of simplifying and speeding up the clinical assessment anddecision-making process in relation to wound infection and / or chronic inflammation.Commonly used indicators of wound health status include wound temperature, perfusionand bacterial colonization. These indicators, however, are not readily observable withthe naked eye. Whilst technologies capable of measuring skin temperature are readily available (e.g.thermometers) they are not designed to provide real time continuous visualisation andoften require clinician intervention. Such interventions, including removal of wounddressings and / or directly contacting the wound bed with a device like a thermometer,can cause patient discomfort and expose the wound to infection. Even infrared 69797030-1thermometers are currently not suitable since they cannot reliably measure woundtemperature whilst wound dressings are still on the patient. The incorporation of wirelesstemperature sensors into the wound environment is currently being investigated. Suchtemperature sensor technology is however complex, expensive and relies onconnectivity to another device. The present invention seeks to obviate or mitigate one or more of the above-mentioned disadvantages. Summary of the InventionA first aspect of the present invention relates to a skin adhesive composition comprisingat least one thermochromic agent, wherein the at least one thermochromic agent undergoes a thermochromic change at a temperature of from 25°C to 45°C and, during use, is in thermal communication with a subject.The at least one thermochromic agent may be present in an amount of from 0.5 wt% to25 wt% relative to the weight of the skin adhesive composition, optionally, from 2 wt% to 5 wt% relative to the weight of the skin adhesive composition.The skin adhesive composition may have a moisture vapour transmission rate (MVTR)of from 300 g / m2 / 24hrs to 7000 g / m2 / 24hrs, optionally, from 400 g / m2 / 24hrs to 5000 g / m2 / 24hrs.The skin adhesive composition may have a peel strength of from 0.1 N / 2.5 cm to 10N / 2.5 cm, optionally from 0.5 N / 2.5 cm to 8.0 N / 2.5cm, such as from 1.0 N / 2.5 cm to 3.0N / 2.5cm or from 6.0 N / 2.5 cm to 8.0 N / 2.5cm.The skin adhesive composition may be a silicone polymer skin adhesive or an acrylicpolymer skin adhesive.The skin adhesive composition may comprise two or more thermochromic agents.The at least one thermochromic agent may be selected from the group consisting of athermochromic Leuco dye, thermochromic liquid crystal, thermochromic inorganic 69797030-1compound, for example, thermochromic transition metal compound, polymericthermochromic agent or a combination thereof.The skin adhesive composition may be disposed on a substrate, optionally, wherein thesubstrate is a wearable product or a component part of a wearable product.The substrate may be a medical device or a component part of a medical device,optionally, wherein the medical device is a medical dressing.The skin adhesive composition may be provided in the form of a film, optionally, whereina release liner is disposed on the film.A second aspect of the present invention relates to a wearable product comprising a skinadhesive composition according to the first aspect of the present invention, wherein the skin adhesive composition is disposed on the wearable product so as to be capable of adhering the wearable product to the skin of a subject.The wearable product may further comprise a release liner disposed on the skinadhesive composition.A third aspect of the present invention relates to a pre-cure composition capable offorming a skin adhesive composition according to the first aspect of the present invention, the pre-cure composition comprising a skin adhesive composition mixture and the at least one thermochromic agent distributed throughout the mixture. A fourth aspect of the present invention relates to the use of a skin adhesive compositionaccording the first aspect of the present invention for adhering a wearable product toskin, optionally, mammalian skin. A fifth aspect of the present invention relates to the use of a skin adhesive compositionaccording to the first aspect of the present invention for detecting a temperature changeon the skin of a subject, optionally, wherein the temperature change is associated with infection or inflammation of the skin. 69797030-1 A sixth aspect of the present invention relates to the use of a skin adhesive compositionaccording to the first aspect of the present invention for detecting a temperature changein a wound of a subject, optionally, wherein the temperature change is associated with infection or inflammation of the wound.A seventh aspect of the present invention relates to a method of manufacturing a skinadhesive composition according the first aspect of the present invention, the method comprising curing the pre-cure composition the third aspect of the present invention. Description of the Figures The present invention will now be described with reference to the following non-limiting examples and figures, which show:Figure 1 provides photographic images A-E showing a skin adhesive composition of thepresent invention undergoing thermochromic changes as the temperature of the composition is increased from 29.5°C through to 32.5°C.Figure 2 provides photographic images A-E showing another skin adhesive compositionof the present invention undergoing thermochromic changes as the temperature of the composition is increased from 34.0°C through to 36.6°C.Figure 3 provides photographic images A-K showing a further skin adhesive compositionof the present invention, comprising two thermochromic agents, a first thermochromicagent undergoing a thermochromic change (i) as the temperature of the composition isincreased from 29.5°C through to 33.1°C and then a second thermochromic agentundergoing a thermochromic change (ii) as the temperature of the composition isincreased from 33.1°C through to 35.9°C.Figure 4 provides photographic images A-H showing a skin adhesive composition of thepresent invention undergoing thermochromic changes as the temperature of the composition is increased from 27.1°C through to 37.2°C. 69797030-1Figure 5 provides photographic images A-F showing another skin adhesive compositionof the present invention undergoing thermochromic changes as the temperature of the composition is increased from 25.6°C through to 32.9°C.Figure 6 provides microscopic images A-D of a silicone polymer skin adhesive of thepresent invention.Figure 7 provides microscopic images A-D of an acrylic polymer skin adhesive of thepresent invention. Detail description of the invention The skin adhesive composition of the present invention comprises at least one thermochromic agent, wherein the at least one thermochromic agent undergoes a thermochromic change at a temperature of from 25°C to 45°C and, during use, is in thermal communication with a subject. The skin adhesive composition is suitable for adhering to the skin of a subject during use. As described herein, the present disclosure pertains to skin adhesive composition. It willbe appreciated that the term “skin adhesive composition” in this context refers toadhesive compositions that are capable of safely contacting and adhering to the skin ofa subject. Such adhesives are known to be particularly suitable for this purpose as they are typically able to adhere to the skin even in wet environments (e.g. exuding woundenvironments) whilst also being readily removable following use. Exemplary skinadhesive compositions are described in more detail herein.The skin adhesive compositions of the present invention have been found to be surprisingly useful in detecting, and visually indicating, temperature changes to the skin of a subject. The present inventors have successfully incorporated at least onethermochromic agent into skin adhering compositions to provide a simple, cost-effectiveand accurate solution to providing visual monitoring of skin temperature. In particular,the skin adhesive compositions disclosed herein can be utilised as medical skinadhesives (e.g. forming part of medical device or dressing to adhere the medical deviceor dressing to the skin of a subject) to provide a non-invasive way of observing changes in skin temperature on a subject during use. This offers an advantageous alternative to 69797030-1the currently adopted thermometers and temperature sensors, which often requirecontact with mucous membranes, removal of medical dressings and / or insertion intothe body (e.g. insertion into an open wound) in order to function.The thermochromic agents, during use, may be directly in contact with, or in closeproximity to, the surface of the skin of a subject. This allows for thermal communicationbetween the skin of the subject and the thermochromic agents. The thermochromicagents are therefore able to, more rapidly, undergo thermochromic changes in responseto variations in skin temperature during use. This advantageously provides a moresensitive skin temperature monitoring system that can be incorporated into existingwound dressing designs to provide a non-intrusive but easily observable skintemperature indicator for a user. It will be appreciated that the skin adhesivecompositions of the present invention are suitable for adhering to the bed of a wound,broken or injured skin surrounding a wound and intact skin. During use, thethermochromic agents are therefore able to undergo thermochromic changes in response to variations in both skin temperature but also changes in temperature of awound (e.g. an infected wound).The inclusion of at least one thermochromic agent within the skin adhesive compositions,as described herein, allows for accurate and continuous monitoring of skin temperature.It will be appreciated that this versatile composition can be utilised in a range ofapplications where real time skin temperature monitoring is beneficial. For example, in adevice suitable the detection of pyrexia, in a device suitable for assessing a risk of heatexhaustion, within neonatal devices, in post-operative wound dressings and in deviceswhich assist Raynaud’s patients with body temperature monitoring and regulation.According to the present invention, the at least one thermochromic agent is in thermalcommunication with a subject during use. This will be understood to mean that the at least one thermochromic agent must be incorporated into the skin adhesive compositionto the extent that, during use, the at least one thermochromic agent is capable ofundergoing a thermochromic change in response to a change in the temperatureoccurring on the surface of the subject (e.g. on the subject’s skin or in a subject’s wound).That is, during use, heat from the skin or wound of subject is transferred to thethermochromic agent whilst the skin adhesive composition is adhered to the subject. Insome embodiments, the thermochromic agent is in thermal communication via direct69797030-1 physical contact between the thermochromic agent and a surface of the subject (e.g.skin surface). In other embodiments, the direct physical contact between thethermochromic agent and a surface of the subject is not necessary for thermalcommunication to be achieved. For example, when the skin adhesive composition formspart of a multi-layer product, composition may form a component of that product whichis not in direct contact with the subject. This results in the thermochromic agent beingdistanced away from the subject but still able to undergo a thermochromic change inresponse to a temperature change in the surface of the subject.As referred to herein the term “thermochromic agent” refers to any compound orcomposition that undergoes an observable transformation in response to a change intemperature. In embodiments, the thermochromic agent may undergo a thermochromicchange, which is observable by any suitable means. Typically, the thermochromicchange will be a visually observable transformation in response to a change intemperature. In embodiments, the thermochromic change is a colour change (i.e. atransformation in colour) which is visible or detectable to the naked eye. Typically, thethermochromic change in will occur within the visible light spectrum and is detectable tothe naked eye as a change in colour. In embodiments, the thermochromic change isobservable within the visible light spectrum (typically wavelengths of from 380nanometers to 750 nanometers). That is, the change may result in an observablechange, which is visible to the naked eye (i) from one colour to another colour, (ii) froma colour to colourless or (iii) from colourless to a colour.In embodiments, the thermochromic agent may undergo a reversible thermochromic change or irreversible thermochromic change. Preferably, the thermochromic agent undergoes a reversible thermochromic change. The skin adhesive composition of the present invention comprises at least one thermochromic agent, wherein the at least one thermochromic agent undergoes athermochromic change at a temperature of from 25°C to 45°C. In embodiments, the atleast one thermochromic agent may undergo a thermochromic change at any therapeutically relevant temperature. The thermochromic agent may undergo a thermochromic change at a temperature that is characteristic of normal healthy skin. The thermochromic agent may undergo a 69797030-1 thermochromic change at a temperature that is characteristic of a normal healthy wound. In other embodiments, the thermochromic agent may undergo a thermochromic changeat a temperature that is characteristic of a skin infection or skin inflammation occurring.In some embodiments, when the skin adhesive composition forms part of a wound dressing, the thermochromic agent may undergo a thermochromic change at atemperature that is characteristic of a wound infection or inflammation occurring withinthe wound. This allows a wound to be monitored, real time, for early detection of infectionor inflammation. In embodiments, the at least one thermochromic agent undergoes a thermochromic change at a temperature of from 30°C to 45°C, 35°C to 45°C, 40°C to 45°C, 25°C to40°C, 25°C to 35°C or 25°C to 30°C. In preferred embodiments, the at least onethermochromic agent undergoes a thermochromic change at a temperature of from 29°C to 39°C, 33°C to 39°C, 35°C to 37°C or 29°C to 37°C. The at least one thermochromicagent undergoes a thermochromic change at a temperature of from 29°C to 37°C. Insome embodiments, the at least one thermochromic agent undergoes a thermochromic change at a temperature of from 29°C to 31°C or 31°C to 37°C. The at least thermochromic agent may be any suitable thermochromic agent that can be incorporated into a skin adhesive composition and still maintain its thermochromic properties. It is contemplated that the thermochromic agents suitable for use in the present invention will tend to be distributed throughout the skin adhesive composition. The skin adhesive compositions of the present invention contain at least one thermochromic agent that may be evenly distributed throughout the skin adhesivecompositions. The skin adhesive compositions of the present invention contain at leastone thermochromic agent that is selectively distributed throughout the skin adhesive compositions. In such instances, the selectively distributed thermochromic agent may form indicia or a pattern within the skin adhesive composition to aid the user in identifyinga temperature change and / or performing a diagnosis.The at least one thermochromic agent may be present in an amount of from 0.5 wt% to25 wt% relative to the weight of the skin adhesive composition, optionally, from 2 wt% to5 wt% relative to the weight of the skin adhesive composition. In embodiments, the atleast one thermochromic agent may be present in an amount of from 1 wt% to 25 wt%,from 5 wt% to 25 wt%, from 10 wt% to 25 wt%, from 15 wt% to 25 wt%, from 20 wt% to69797030-125 wt%, from 1 wt% to 20 wt%, from 1 wt% to 15 wt%, from 1 wt% to 10 wt%, from 1wt% to 5 wt%, from 5 wt% to 20 wt% or from 10 wt% to 15 wt% relative to the weight ofthe skin adhesive composition. In embodiments, the at least one thermochromic agentmay be present in an amount of from 1 wt% to 5 wt%, from 3 wt% to 5 wt%, from 4 wt%to 5 wt%, from 1 wt% to 4 wt%, from 1 wt% to 3 wt%, or from 1 wt% to 2 wt% relative tothe weight of the skin adhesive composition.In embodiments, the at least one thermochromic agent may be present in an amount offrom 0.5 wt% to 20 wt%, from 0.5 wt% to 15 wt%, from 0.5 wt% to 10 wt%, from 0.5 wt%to 5 wt% relative to the weight of the skin adhesive composition. In embodiments, the atleast one thermochromic agent may be present in an amount of from 0.5 wt% to 5 wt%,from 3 wt% to 5 wt%, from 4 wt% to 5 wt%, from 0.5 wt% to 4 wt%, from 0.5 wt% to 3wt%, or from 0.5 wt% to 2 wt% relative to the weight of the skin adhesive composition.In embodiments, two or more thermochromic agents may be present in the skin adhesive composition. In such embodiments, each of the two or more thermochromic agents mayindependently be present in an amount of from 0.5 wt% to 25 wt% relative to the weightof the skin adhesive composition, optionally, from 2 wt% to 5 wt% relative to the weightof the skin adhesive composition. In embodiments, each of the two or morethermochromic agents may independently be present in an amount of from 1 wt% to 25wt%, from 5 wt% to 25 wt%, from 10 wt% to 25 wt%, from 15 wt% to 25 wt%, from 20wt% to 25 wt%, from 1 wt% to 20 wt%, from 1 wt% to 15 wt%, from 1 wt% to 10 wt%,from 1 wt% to 5 wt%, from 5 wt% to 20 wt% or from 10 wt% to 15 wt% relative to theweight of the skin adhesive composition. In embodiments, each of the two or morethermochromic agents may independently be present in an amount of from 1 wt% to 5wt%, from 3 wt% to 5 wt%, from 4 wt% to 5 wt%, from 1 wt% to 4 wt%, from 1 wt% to 3wt%, or from 1 wt% to 2 wt% relative to the weight of the skin adhesive composition. Forexample, in embodiments, there may be a first thermochromic agent and a secondthermochromic agent present in the skin adhesive composition. The first thermochromicagent may be present in an amount of from 0.5 wt% to 25 wt% relative to the weight ofthe skin adhesive composition, optionally, from 2 wt% to 5 wt% relative to the weight of the skin adhesive composition. The second thermochromic agent may be present in anamount of from 0.5 wt% to 25 wt% relative to the weight of the skin adhesive composition,optionally, from 2 wt% to 5 wt% relative to the weight of the skin adhesive composition. 69797030-1The amount of thermochromic agent (i.e. wt%) present in the skin adhesive compositionmay be modified according to a given application (e.g. to provide a more visible or lessvisible colour change, as required). It will be appreciated that increasing the amount ofthermochromic agent in the skin adhesive composition will be expected to increase the visible intensity of the thermochromic change that the thermochromic agent undergoes. However, depending on the nature of the thermochromic agent, significant increases in the amount present will increase the viscosity of the pre-cure adhesive mixture used to form the adhesive, therefore making handling of the pre-cure composition more difficult, and making it difficult to obtain a uniform adhesive coating to be cured onto anappropriate substrate. It is therefore desirable to avoid using excessively highconcentrations of thermochromic agent, for practical purposes The skin adhesive composition may have a moisture vapour transmission rate (MVTR) of from 300 g / m2 / 24hrs to 7000 g / m2 / 24hrs, optionally, from 400 g / m2 / 24hrs to 5000g / m2 / 24hrs. In embodiments, the skin adhesive composition may have a moisture vapourtransmission rate (MVTR) of from 500 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 1000 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 1500 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 2000 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 2500 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 3000 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 3500 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 4000 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 4500 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 5000 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 5500 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 6000 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 6500 g / m2 / 24hrs to 7000 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 6500 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 6000 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 5500 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 5000 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 4500 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 4000 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 3500 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 3000 g / m2 / 24hrs, from 300g / m2 / 24hrs to 2500 g / m2 / 24hrs, from 300 g / m2 / 24hrs to 2000 g / m2 / 24hrs, from 300g / m2 / 24hrs to 1500 g / m2 / 24hrs or from 300 g / m2 / 24hrs to 1000 g / m2 / 24hrs. In embodiments, the skin adhesive composition may have a moisture vapour transmission rate (MVTR) of from 300 g / m2 / 24hrs to 700 g / m2 / 24hrs, from 2000 g / m2 / 24hrs to 2500g / m2 / 24hrs or from 4500 g / m2 / 24hrs to 5000 g / m2 / 24hrs. MVTR values are determinedaccording to the test described herein. The skin adhesive composition may have a peel strength of from 0.1 N / 2.5 cm to 10N / 2.5 cm, optionally from 0.5 N / 2.5 cm to 8.0 N / 2.5cm, such as from 1.0 N / 2.5 cm to 3.069797030-1N / 2.5cm or from 6.0 N / 2.5 cm to 8.0 N / 2.5cm. In embodiments, the skin adhesivecomposition may have a peel strength of from 0.1 N / 2.5 cm to 10 N / 2.5 cm, from 0.5N / 2.5 cm to 10 N / 2.5 cm, from 1.0 N / 2.5 cm to 10 N / 2.5 cm, from 2.0 N / 2.5 cm to 10N / 2.5 cm, from 3.0 N / 2.5 cm to 10 N / 2.5 cm, from 4.0 N / 2.5 cm to 10 N / 2.5 cm, from 5.0N / 2.5 cm to 10 N / 2.5 cm, from 6.0 N / 2.5 cm to 10 N / 2.5 cm, from 7.0 N / 2.5 cm to 10N / 2.5 cm, from 8.0 N / 2.5 cm to 10 N / 2.5 cm, from 9.0 N / 2.5 cm to 10 N / 2.5 cm, from 0.1N / 2.5 cm to 9.0 N / 2.5 cm, from 1.0 N / 2.5 cm to 8.0 N / 2.5 cm, from 1.0 N / 2.5 cm to 7.0N / 2.5 cm, from 1.0 N / 2.5 cm to 6.0 N / 2.5 cm, from 1.0 N / 2.5 cm to 5.0 N / 2.5 cm, from1.0 N / 2.5 cm to 4.0 N / 2.5 cm or from 1.0 N / 2.5 cm to 3.0 N / 2.5 cm. In preferredembodiments, the skin adhesive composition may have a peel strength of from 1.0 N / 2.5cm to 4.0 N / 2.5cm or from 5.0 N / 2.5 cm to 8.0 N / 2.5cm. Peel strength values aredetermined according to the test described herein. As described herein, the skin adhesive composition is suitable for adhering to the skin of a subject during use. The skin adhesive composition may be a hydrocolloid skin adhesive composition, silicone polymer skin adhesive, acrylic polymer skin adhesive,polyurethane polymer skin adhesive or any combination thereof. Preferably, the skinadhesive composition is silicone polymer skin adhesive or an acrylic polymer skin adhesive. Where the skin adhesive composition is a silicone polymer skin adhesive composition,the peel strength does not exceed 10 N / 2.5 cm. In embodiments, the peel strength doesnot exceed 7.0 N / 2.5 cm. The peel strength may be in the range of from 3.0 N / 2.5 cm to7.0 N / 2.5 cm. In some embodiments, the peel strength is at least 0.5 N / 2.5 cm, such asat least 0.8 N / 2.5 cm, or at least 1.0 N / 2.5 cm, such as at least 1.5 N / 2.5 cm. Typically,the peel strength does not exceed 5.0 N / 2.5 cm. Suitably, the silicone polymer skinadhesive composition may have a peel strength of from 0.5 N / 2.5 cm to 3.5 N / 2.5cm,such as 1.0 N / 2.5 cm to 3.5 N / 2.5cm.The silicone polymer skin adhesive composition may be a so-called “low-traumaadhesive”. The term “low trauma” in this context is intended to qualify that the skin adhesive has a suitable adhesive strength to adhere directly to the skin, but which doesnot have an adhesive strength, which would cause significant pain and / or trauma to thesubject upon removal. A peel strength of from 0.1 to 2.0 N / 2.5 cm is exemplary of a lowtrauma adhesive in the context of the invention. 69797030-1In embodiments, where the skin adhesive composition is a silicon polymer skin adhesivecomposition, the silicone polymer skin adhesive composition may have a peel strengthof from 0.5 to 3.5 N / 2.5cm, such as 1.0 to 3.5 N / 2.5cm and a moisture vapourtransmission rate (MVTR) of from 100 g / m2 / 24hrs to 1500 g / m2 / 24hrs or from 300 g / m2 / 24hrs to 700 g / m2 / 24hrs. In such embodiments, the at least one or morethermochromic agent is present in an amount of from 1 wt% to 10 wt% relative to theweight of the silicon polymer skin adhesive composition, optionally, from 2 wt% to 5 wt%relative to the weight of the silicon polymer skin adhesive composition.In embodiments, where the skin adhesive composition is a acrylic polymer skin adhesivecomposition, the acrylic polymer skin adhesive composition may have a peel strength offrom 5.0 to 9.0 N / 2.5cm, such as 6.0 to 8.0 N / 2.5cm and a moisture vapour transmissionrate (MVTR) of from 500 g / m2 / 24hrs to 5000 g / m2 / 24hrs or from 3000 g / m2 / 24hrs to 5000g / m2 / 24hrs. In such embodiments, the at least one or more thermochromic agent ispresent in an amount of from 1 wt% to 10 wt% relative to the weight of the acrylic polymerskin adhesive composition, optionally, from 2 wt% to 5 wt% relative to the weight of theacrylic polymer skin adhesive composition.The at least one thermochromic agent may be selected from the group consisting of athermochromic Leuco dye, thermochromic liquid crystal, thermochromic inorganic compound, for example, thermochromic transition metal compound, polymericthermochromic agent or a combination thereof.In embodiments, the at least one thermochromic agent may be a thermochromic Leucodye. In such embodiments, the thermochromic Leuco dye may be a spiropyran Leuco dye, quinone Leuco dye, thiazine Leuco dye, oxazine Leuco dye, phenazine Leuco dye, phthalide Leuco dye, triarylmethane Leuco dye, fluoran Leuco dye, tetrazolium salt Leuco dye or any combination thereof.In embodiments, the at least one thermochromic agent may be a thermochromic liquidcrystal. The at least one thermochromic agent may be a cholesteric liquid crystal, suchas, cholesteryl nonanoate, cholesteryl oleyl carbonate or cholesteryl benzoate.69797030-1In embodiments, the at least one thermochromic agent may be a thermochromicinorganic compounds, for example, thermochromic transition metal compounds. Inembodiments, the at least one thermochromic agent is cobalt (II) chloride or vanadiumoxide. In embodiments, the at least one thermochromic agent may be a polymeric thermochromic agent. For example, the at least one thermochromic agent may bepolydiacetylene or derivative thereof.The at least one thermochromic agent may be in an encapsulated form. That is, the thermochromic agent may be located within a microcapsule. In some instance, the microcapsule may be a shelled microcapsule wherein the least one thermochromic agent is located in the core of the shelled microcapsule. In certain embodiments, where the at least one thermochromic agent is a thermochromic Leuco dye, the thermochromic Leuco dye is encapsulated. In particular, the thermochromic Leuco dye is contained within a microcapsule. It will be appreciated that thermochromic agents, such as thermochromic Leuco dye, are encapsulated to protect the agents from external environments factorsthat might damage, destroy or hinder the functionality of the agents.The at least one thermochromic agent may be distributed throughout the skin adhesivecomposition. The skin adhesive composition may comprise a polymer network that, inembodiments, is formed during a curing process and forms via crosslinking of startingmaterials. The at least one thermochromic agent may be distributed throughout the polymer network. In some instances, where the skin adhesive composition comprises a polymer network, the at least one thermochromic agent may be entrapped within the polymer network which ensures that the thermochromic agent is retained within the bulkof the skin adhesive composition during use.In embodiments, the skin adhesive composition comprises two or more thermochromicagents. The skin adhesive composition may comprise two, three, four or fivethermochromic agents. Where two or more thermochromic agents are present in the skinadhesive composition, each of the two or more thermochromic agents may each independently undergo a thermochromic change each at a different temperature. That is, where two or more thermochromic agents are present, each thermochromic agent may undergo a thermochromic change at a temperature of range independently selected 69797030-1 from 30°C to 45°C, 35°C to 45°C, 40°C to 45°C, 25°C to 40°C, 25°C to 35°C or 25°C to 30°C. In preferred embodiments, from 29°C to 39°C, 33°C to 39°C, 35°C to 37°C or 29°Cto 37°C. In embodiments, where two or more thermochromic agents are present, eachthermochromic agent may undergo a thermochromic change at a temperature of range independently selected from 29°C to 31°C or 31°C to 37°C.In an embodiment, the skin adhesive composition comprises two thermochromic agents.In such an embodiment, a first thermochromic agent undergoes a thermochromic change at 29°C to 31°C and a second thermochromic agent undergoes a thermochromic change at 31°C to 37°C. The first thermochromic agent undergoes a thermochromic change that is visually observable to the naked eye as a first colour change. The second thermochromic agent undergoes a thermochromic change that is visually observable to the naked eye as a second colour change. The fist colour change and the second colour change are visually observed by the naked eye as being different. The skin adhesive composition may be disposed on a substrate, optionally, wherein thesubstrate is a wearable product or a component part of a wearable product. The skinadhesive composition may be provided as continuous layer. The skin adhesivecomposition may be present as a discontinuous layer, e.g. containing perforations.The skin adhesive composition may be provided in any suitable form and dimensionsdepending on the wearable product and the intended practical use.For example, the skin adhesive composition may be formed as a margin portion within an island wound dressing system. In other instances, the skin adhesive composition may be formed as an annular ring component suitable for attaching faecal or ostomy collection pouches to the perianal or peristomal skin of a subject. The skin adhesive composition may be provided in the form of a film, optionally, whereina release liner is disposed on the film. It will be appreciated that such films may be coatedon a suitable substrate, such as a backing layer or absorbent pad. For instance, asdescribed below, the film may be suitably formed by casting the pre-cure compositiononto a substrate (e.g. backing layer or absorbent pad) and then curing the adhesivecomposition directly on the substrate (e.g. backing layer or absorbent pad) to form amulti-layer structure including a substrate and adhesive disposed thereon, e.g. in the 69797030-1 form of a film coating. In embodiments, the multi-layer structure including a substrateand the skin adhesive composition disposed thereon may have a moisture vapourtransmission rate (MVTR) of from 700 g / m² / 24hrs to 6000 g / m² / 24hrs, optionally from900 g / m² / 24hrs to 6000 g / m² / 24hrs or from 950 g / m² / 24hrs to 4000 g / m² / 24hrs. Typically,the skin adhesive composition may have a moisture vapour transmission rate (MVTR) offrom 1000 g / m² / 24hrs to 3000 g / m² / 24hrs such as from 1000 g / m² / 24hrs to 2000 g / m² / 24hrs. The substrate may be a polymer film or a polymer foam or a combination thereof (e.g. a laminate). As referred to in this context the polymer film may be a polyurethane (PU) film. The polymer foam may be a polyurethane foam. The foam may be provided in flood and / or pattern formats. Other substrates are also contemplated, such as polyethylene (PE), polypropylene (PP), ethyl methacrylate, paper, or non-woven articles (such as non- wovens made from fibrous polysaccharides, cellulose, rayon, or melt blown PU, PE, PP). The substrate may also be in the form of a mesh, typically, a woven mesh fabric. In embodiments, the substrate is a PU film. The PU film may have a thickness of from 5μm to 100μm, preferably from 10μm to 50μm. The PU film may have a thickness of from 10μm to 20μm, such as around 15μm, or from 20μm to 40μm, such as around 30μm. Polymer films, such as a PU film, suitable for use as a substrate / backing layer mayhave a moisture vapour transmission rate (MVTR) of from 3000 g / m² / 24hrs to 16000g / m² / 24hrs, for instance, of from 3000 g / m² / 24hrs to 4000 g / m² / 24hrs or from 15000g / m² / 24hrs to 16000 g / m² / 24hrs.The combined thickness of the skin adhesive composition and substrate may be from 25μm to 1000 μm or from 50 μm to 250 μm optionally from 75 μm to 150 μm, such asaround 100 μm.Typically, to prevent unwanted adhesion of the skin adhesive composition in transit(bonding to itself or to packaging), the adhesive may be provided with a release liner disposed thereon. This liner can then be readily removed prior to practical use. Thus, arelease liner may be disposed on the adhesive (e.g. film) and / or the adhesive (e.g. film)may be disposed on a substrate.69797030-1 The substrate may be a medical device or a component part of a medical device, optionally, wherein the medical device is a medical dressing or an ostomy device. A second aspect of the present invention relates to a wearable product comprising a skinadhesive composition according to the first aspect of the present invention andembodiments thereof, wherein the skin adhesive composition is disposed on the wearable product so as to be capable of adhering the wearable product to the skin of a subject. The wearable product may further comprise a release liner disposed on the skin adhesive composition.The wearable product may be a medical product or component part of a medical product.The medical product may be a medical device, optionally a medical dressing (e.g. wounddressing) or an ostomy device.The wearable product may be a wound dressing comprising the skin adhesivecomposition as a wound or skin contact layer (as protection for minor cuts, abrasion oreven areas of fragile skin). The wound dressing may be a post-operative wound dressing comprising the skin adhesive composition as a wound or skin contact layer. It is envisaged that incorporation of the thermochromic agents within the wound or skincontact layer will provide live, real time, monitoring of wound and / or skin temperaturethus providing an indicator of infection, inflammation and / or risk of wound dehiscence. This can help healthcare practitioners in mitigating the risk of complications and allowing for timely intervention. Alternatively, the wearable product may be a wound dressing comprising the skin adhesive composition as layer that is not a skin or wound contact layer. For example, the skin adhesion composition may an intermediate layer within a multilayer device (e.g. wound dressing) or located on a surface of the multilayer devicewhich is facing away from the skin or wound. In such scenarios, of course, thethermochromic agent is still maintained in thermal communication with the skin or wound. The wearable product may be a negative pressure wound therapy (NPWT) devicecomprising the skin adhesive composition as an interface layer (drape).69797030-1The wearable product may be an ostomy barrier or annular ring component comprisingthe skin adhesive composition as part of the interface between ostomy pouch and skin.The wearable product may be an adhesive patch for pyrexia detection comprising theskin adhesive composition as a skin contact layer. The thermochromic changes in theskin adhesive composition provides a visually observable and real time monitoring of asubject’s skin temperature. The wearable product may be a skin patch for neonatal care comprising the skin adhesive composition, in particular the silicone polymer skin adhesive composition, as a skin contact layer. The thermochromic changes in the skin adhesive compositionprovides a skin patch capable of monitoring the skin temperature of premature infants toensure that they remain an acceptable temperature.The wearable product may be a deformable skin patch for assisting patients sufferingfrom Raynaud’s. The patch comprising the skin adhesive composition as a skin contactlayer, which can be easily applied and shaped to the contours of the body. Thermochromic changes can provide visual cues of anatomical areas prone to be affected by Raynaud’s and help patients regulate the temperature of these areas in order to prevent unnecessary exposure to cold environments. The wearable product may be an adhesive patch for heat exhaustion comprising the skin adhesive composition as a skin contact layer. The thermochromic changes in the skin adhesive composition provides a visually observable and real time monitoring of a subject’s skin temperature in high temperature environments, which can be used to prevent early signs of heat exhaustion progressing towards a heat stroke.The skin adhesive composition of the present invention may form part of a wearableproduct as described herein. Such a wearable product may be multi-layer wearableproduct that, for instance, comprises two or more layers. When the wearable product isa multi-layer wearable product, the multi-layer wearable product may comprises the skinadhesive composition as a wound or skin contact layer. That is, the skin adhesive composition, during use, is in direct contact with the wound or skin in order to adhere themulti-layer wearable product to the wound or skin. It will be appreciated that when theskin adhesive composition is used as part of a wearable product, as described herein, it69797030-1 is required that any thermochromic change resulting from the at least one of thethermochromic agent must be visually detectable to the naked eye of the user. Forexample, any thermochromic colour change must be observable to the user without theneed to remove or wearable product. In embodiments, when the multi-layer wearable product comprise the skin adhesive composition as a wound or skin contact layer, at least a portion of the skin adhesive composition is visible and observable to the user during use when adhered to a subject. In such embodiments, the skin adhesive composition may be visible through a viewing window extending through the multi-layer product. For example, when the multi-layer wearable product is a multi-layer wound dressing comprising an absorbent pad layer sandwiched between a backing layer andthe skin adhesive composition as the wound or skin contact layer, the viewing windowmay extend through the backing layer and absorbent pad layer. In other embodiments,when the multi-layer wearable product is a multi-layer island dressing or patch, the skinadhesive composition as the wound or skin contact layer may form a visible border ormargin around the island during use. In some embodiments, the multi-layer wearableproduct may comprise the skin adhesive composition as a wound or skin contact layerand other layers that are transparent to the extent that the skin adhesion composition isvisible those transparent layers during use.In another aspect, the present invention relates to a diagnostic tool comprising a skinadhesive composition according to the first aspect of the present invention andembodiments thereof, wherein the skin adhesive composition is disposed on thediagnostic tool so as to be capable of adhering the diagnostic tool to the skin of a subject.In embodiments, the diagnostic tool is for detecting a temperature change on the skin ofa subject, wherein the temperature change is associated with the diagnosis of aninfection or inflammation of the skin. In other embodiments, the diagnostic tool is fordetecting a temperature change in a wound of a subject, wherein the temperaturechange is associated with the diagnosis of an infection or inflammation of the wound. A third aspect of the present invention relates to a pre-cure composition capable of forming a skin adhesive composition according to the first aspect of the present invention and embodiments thereof, the pre-cure composition comprising a skin adhesivecomposition mixture (i.e. precursor mixture capable of forming a skin adhesive matrix orpolymer network upon curing) and the at least one thermochromic agent distributedthroughout the mixture. 69797030-1 Where the skin adhesive composition is a silicone polymer skin adhesive composition,the skin adhesive composition mixture may for instance include a polyorganosiloxanecontaining at least one reactive functional group (e.g. a carbon-carbon double bond), and an organosiloxane containing a functional group capable of reacting with the reactive functional group of the polyorganosiloxane (e.g. containing an Si-H group), and optionally a curing catalyst capable of catalysing reaction between the polyorganosiloxane and organosiloxane polymer upon curing, e.g. platinum. In embodiments, the pre-cure composition may include an alkenyl-substituted polydimethylsiloxane having a silicon-bonded vinyl, allyl or hexenyl group, and anorganosiloxane containing a silicon-bonded hydrogen atom (Si-H group), and a catalyst,such as a platinum metal, for causing cross-linking via the reaction of the Si-H groupswith the Si-alkenyl groups. Suitable reaction conditions for curing of the pre-cure composition are described herein. Where the skin adhesive composition is an acrylic polymer skin adhesive composition,the skin adhesive composition mixture (i.e. pre-cure mixture) may for instance includeacrylic based pre-polymer material that can be cured to form the acrylic polymer skin adhesive composition. A fourth aspect of the present invention relates to the use of a skin adhesive compositionaccording the first aspect of the present invention and embodiments thereof for adheringa wearable product to skin, optionally, mammalian skin. The wearable product may beany wearable product as defined herein, e.g. a medical device. In embodiments, the medical device is a wound dressing or medical skin patch. A fifth aspect of the present invention relates to the use of a skin adhesive compositionaccording to the first aspect of the present invention and embodiments thereof fordetecting a temperature change on the skin of a subject, optionally, wherein the temperature change is associated with infection or inflammation of the skin. Another aspect of the present invention relates to the use of a skin adhesive compositionaccording to the first aspect of the present invention and embodiments thereof fordetecting a temperature change on the skin of a subject and; optionally diagnosing theoccurrence of a skin infection or inflammation of the skin.69797030-1 A sixth aspect of the present invention relates to the use of a skin adhesive compositionaccording to the first aspect of the present invention and embodiments thereof fordetecting a temperature change in a wound of a subject, optionally, wherein the temperature change is associated with infection or inflammation of the wound. A further aspect of the present invention relates to the use of a skin adhesive compositionaccording to the first aspect of the present invention and embodiments thereof fordetecting a temperature change in a wound of a subject and; optionally diagnosing theoccurrence of a wound infection or inflammation of the wound.Yet another aspect of the present invention relates to a method of diagnosing a condition in a subject, wherein the method comprises disposing the skin adhesive compositionaccording to the first aspect of the present invention and embodiments thereof onto theskin of a subject and detecting a temperature change on the skin of a subject. Thecondition may be an infection of the subject’s skin or a wound. The condition may beinflammation of the subject’s skin or a wound. The condition may be hypothermia. Thecondition may be pyrexia. A further aspect relates to a skin adhesive composition according to the first aspect ofthe present invention and embodiments thereof for use in a method of diagnosing acondition in a subject, wherein the method comprises disposing the skin adhesivecomposition according to the first aspect of the present invention and embodimentsthereof onto the skin of a subject and detecting a temperature change on the skin of asubject. The condition may be an infection of the subject’s skin or a wound. The condition may be inflammation of the subject’s skin or a wound. The condition may behypothermia. The condition may be pyrexia.An aspect of the present invention relates to a method of predicting and / or treating an infection in a subject, the method comprising applying the skin adhesive composition according to the first aspect of the present invention and embodiments thereof onto theskin of a subject and detecting a temperature change indicative of an infection. Inembodiments, the method further comprises treating the infection with a suitable anti- infective medication. 69797030-1 Also disclosed is a method of predicting infection comprising the use of the skin adhesive composition according to the first aspect of the present invention and embodiments thereof. An another aspect of the present invention relates to a method of predicting and / or treating inflammation in a subject, the method comprising applying the skin adhesive composition according to the first aspect of the present invention and embodiments thereof onto the skin of a subject and detecting a temperature change indicative of inflammation. In embodiments, the method further comprises treating the inflammation with a suitable anti-inflammatory medication. Also disclosed is a method of predicting inflammation comprising the use of the skin adhesive composition according to the first aspect of the present invention and embodiments thereof. A further aspect of the present invention relates to a method of detecting and / or treatinga pyrexia in a subject, the method comprising applying the skin adhesive compositionaccording to the first aspect of the present invention and embodiments thereof onto the skin of a subject and detecting a temperature change indicative of a pyrexia.Disclosed herein is a method of detecting a pyrexia comprising the use of the skinadhesive composition according to the first aspect of the present invention and embodiments thereof. An aspect of the present invention relates to a method of detecting and / or treating hypothermia in a subject, the method comprising applying the skin adhesive composition according to the first aspect of the present invention and embodiments thereof onto the skin of a subject and detecting a temperature change indicative of hypothermia. Disclosed herein is a method of detecting a hypothermia comprising the use of the skin adhesive composition according to the first aspect of the present invention and embodiments thereof. 69797030-1 Throughout the present application, it will be appreciated that the references to skin andadhesion to skin typically refer to mammalian skin, e.g. primate skin, preferably humanskin. Skin as referred to herein includes breached or broken skin as well as intact skin. A seventh aspect of the present invention relates to a method of manufacturing a skinadhesive composition according the first aspect of the present invention andembodiments thereof, the method comprising curing the pre-cure composition the third aspect of the present invention. The step of curing the pre-cure composition may include casting or disposing the pre- cure composition onto a substrate (e.g. backing layer). The substrate, as describedherein, may be a PU film or polyethene terephthalate (PET) film. The pre-curecomposition may be cast or disposed upon the substrate at a coat weight of from about 5 grams per m2to about 300 grams per m2or from about 10 grams per m2to about 200grams. Preferably, at a coat weight of from about 20 grams per m2 to about 175 gramsper m2 is used, for instance, 40 grams per m2 or 150 grams per m2. The step of castingor disposing may be performed using any suitable coating liner apparatus, such as wherein casting blades may be used to control the coat weight.The step of curing the pre-cure composition according to the method of manufacturing askin adhesive composition as described herein may include curing the pre-curecomposition at a temperature of from 70°C to 200°C, such as 140°C to 180°C or 160°C. This can be achieved by feeding the pre-cure composition through an oven set a suitable temperature. The pre-cure composition may be fed to the oven at a rate (line speed) of from 0.1 meters / minute to 2.0 meters / minute, for instance, from 0.5 meters / minute to 1.5 meters / minute. Preferably the rate (line speed) is 0.6 meters / minute to 1.0 meters / minute, such as, 0.8 meters / minute. The step of curing is typically performed after the step of casting or disposing the pre-cure composition onto a substrate is performed, as described herein. In such embodiments, the pre-cure composition cast upon the substrate is fed into the oven at a rate (line speed) of 0.6 meters / minute to 1.0meters / minute, such as, 0.8 meters / minute In embodiments, where the skin adhesivecomposition is an acrylic polymer skin adhesive composition, the curing may beperformed first at 70°C to 90°C and then at 110°C to 120°C at a line speed of from 1.0meters / minute to 1.5 meters / minute. In embodiments, where the skin adhesivecomposition is a silicone polymer skin adhesive composition, the curing may be69797030-1performed at 120°C to 150°C at a line speed of from 0.5 meters / minute to 1.0meters / minute. In accordance with the invention, the pre-cure composition comprises the at least onethermochromic agent distributed throughout the mixture (as described herein). Inembodiments, the method includes the step of preparing the pre-cure composition by mixing the skin adhesive precursor mixture and the at least one thermochromic agentsuch that the agent is distributed throughout the mixture. This is, in some embodiments,achieved using a suitable mixing apparatus such as a paddle mixer. The pre-cure composition described herein may include the precursor mixture in amount of at least than 75 %wt, for example, at least 90 %wt or 95 %wt relative to the total weightof the pre-cure composition. The pre-cure composition may include the at least onethermochromic agent in amount of at least 0.5 %wt, such as at least 25 %wt, relative tothe total weight of the pre-cure composition. The at least one thermochromic agent maybe present in the pre-cure composition in an amount of from 0.5 %wt to 10 %wt. skin adhesive The silicone polymer skin adhesive composition of the present invention may be suitably prepared according to the exemplary method provided below:Preparation of pre-cure silicone polymer skin adhesive composition (i.e. uncuredprecursor to the silicone skin adhesive composition)1. A suitable silicone gel starting material which is capable of undergoing curing toform a silicone polymer skin adhesive material is used. Typically, in an exemplary composition, the silicone gel starting material is SILPURAN® 2114 A / B which issupplied as two separate gel components (component A and component B). The silicone gel starting material contains polydimethylsiloxane with reactivefunctionality (e.g. unsaturated aliphatic group) in component A, an organosiloxane with reactive functionality (silicone-hydride group) in component 69797030-1 B and a platinum catalyst to allow for cross-linking once gel components A and B are brought together and cured. 2. Appropriate amounts of gel component A and gel component B are weighed andplaced in a vessel. 3. At least one suitable thermochromic agent was then added to the vessel, in anappropriate amount, with gel component A and gel component B before themixture was homogenised using a paddle mixer to form a pre-cure silicone skinadhesive composition. It will be appreciated that further additive / auxiliary components may be added to the mixture as this stage, as required.Casting and curing of pre-cure silicone polymer skin adhesive composition to form thesilicone polymer skin adhesive composition 4. A coating line system was set up with a polyurethane film backing layer substrate(other substrates may be used as described herein) on which to cast the pre-cure silicone skin adhesive composition upon.5. The pre-cure silicone polymer skin adhesive composition is disposed upon thesubstrate at a coat weight of 150 grams per m2(gsm) using casting blades. The polyurethane film backing layer substrate used in this example was a 30μm clear polyurethane film (Inspire® 2301). The coat weight of the layer of pre-curesilicone skin adhesive composition was controlled by varying the height of castingblades relative to the polyurethane film backing layer substrate. 6. The resulting multi-layer product (comprising the pre-cure silicone polymer skinadhesive composition) was then fed through an oven, which was set to atemperature of approximately 140°C. Other suitable temperatures are described herein. This accelerates the curing process within the pre-cure silicone polymer skin adhesive composition and results in the formation of the cured siliconepolymer skin adhesive composition containing the thermochromic agentdistributed throughout. The line speed of the coating line system is set to 0.8 meters / minute. 69797030-17. Once the cured material exits the oven, a suitable non-adherent release liner(e.g. low-density polyethylene film) is placed on top of the composition to provide a multi-layered product containing a backing layer substrate, adhesive layer and release liner. The silicone polymer skin adhesive composition may then be woundinto a roll-stock format and used for downstream applications (e.g. integrationinto a medical dressing). 8. It will be appreciated that the backing layer may take the form of a transfer layer(i.e. useful in transferring the cast silicone polymer skin adhesive composition onto other items / products). The acrylic polymer skin adhesive composition of the present invention may be suitably prepared according to the exemplary method provided below: Preparation of pre-cure acrylic polymer skin adhesive composition (i.e. uncuredprecursor to the acrylic skin adhesive composition)1. Appropriate amounts of acrylic adhesive (ArosetTM PS5333 supplied by BOSTIK)is weighed and placed in a vessel. 2. At least one suitable thermochromic agent was then added to the vessel, in anappropriate amount, with acrylic adhesive before the mixture was homogenised using a paddle mixer to form a pre-cure acrylic polymer skin adhesivecomposition. It will be appreciated that further additive / auxiliary components may be added to the mixture as this stage, as required.Casting and curing of pre-cure acrylic polymer skin adhesive composition to form theacrylic polymer skin adhesive composition 3. A coating line system was set up with a PET release liner substrate (othersubstrates may be used as described herein) on which to cast the pre-cure acrylic polymer skin adhesive composition upon.69797030-14. The pre-cure acrylic skin adhesive composition is disposed upon the substrate ata coat weight of nominally 40 grams per m2(gsm) using casting blades. The PET release liner substrate used in this example was a 75μm clear PET release liner (Silphan S75 M2R). The coat weight of the layer of pre-cure acrylic skin adhesive composition was controlled by varying the height of casting blades relative to the PET release liner substrate. 5. The resulting multi-layer product (comprising the pre-cure acrylic polymer skinadhesive composition) was then fed through a first oven, which was set to atemperature of approximately 75°C. The product was then fed through a second oven at a temperature of approximately 115°C to drive off any remaining solvent. Other suitable temperatures are described herein. This accelerates the curing process within the pre-cure acrylic polymer skin adhesive composition and resultsin the formation of the cured acrylic polymer skin adhesive composition containing the thermochromic agent distributed throughout. The line speed of the coating line system is set to 1.2 meters / minute.6. Once the cured material exits the oven, the desired carrier (e.g. polyurethanefilm) is laminated to the composition to provide a multi-layered product containing a polyurethane substrate, adhesive layer and release liner. The acrylic skin adhesive composition may then be wound into a roll-stock format and used for downstream applications (e.g. integration into a medical dressing). 7. It will be appreciated that the backing layer may take the form of a transfer layer(i.e. useful in transferring the cast acrylic polymer skin adhesive composition onto other items / products). Skin Adhesive Composition Examples Skin adhesive compositions 1-8 according to the present invention were prepared usingthe methods described above. Material information and amounts are detailed in Table 1below. The materials referred to in Table 1 are as follows:“Silicone A” refers to Silicone Gel Component A (supplied by SILPURAN® 2114). “Silicone B” refers to Silicone Gel Component B (supplied by SILPURAN® 2114). “Acrylic” refers to Acrylic adhesive (supplied by ArosetTMPS5333). 69797030-1 “Red-Yellow @ 31°C” refers to Thermochromic Paint (supplied by Atlanta Chemical Engineering) having a red to yellow colour change interval of 29°C to 33°C. “Black-Purple @ 35°C” refers to Thermochromic Paint (supplied by Atlanta Chemical Engineering) having a black to purple colour change interval of 32°C to 37°C.Thermochromic liquid products supplied by Atlanta Chemical Engineering are water-based thermochromic liquids containing proprietary thermochromic agents having colourchange intervals as specified herein. It will be appreciated that the wt % of thethermochromic agents mentioned in Table 1 refers to the weight percentage amount ofthe thermochromic agent itself, not the weight percentage amount of thermochromicliquid used, relative to the weight of the overall skin adhesive composition. It will also beunderstood that, where the wt % values in Table 1 do not total to 100 wt % for a givencomposition, the remainder of the composition can be accounted for as residual water.Silicone A Silicone B Acrylic Thermochromic agentComposition 1 47.5 wt % 47.5 wt % - 2.5 wt % (Red-Yellow @ 31°C)Composition 2 47.5 wt % 47.5 wt % - 2.5 wt % (Black-Purple @35°C) Composition 3 - - 98 wt % 1.0 wt % (Red-Yellow @ 31°C)Composition 4 - - 95 wt % 2.5 wt % (Black-Purple @35°C) Composition 5 45 wt % 45 wt % - Combination of 2.5 wt % (Red-Yellow @ 31°C) AND 2.5 wt %(Black-Purple @ 35°C) Composition 6 - - 90 wt % Combination of 2.5 wt % (Red-Yellow @ 31°C) AND 2.5 wt %(Black-Purple @ 35°C) Composition 7 - - 95 wt % 2.5 wt % (Red-Yellow @ 31°C)Composition 8 49 wt % 49 wt % - 1.0 wt % (Red-Yellow @ 31°C)Table 1 Peel adhesion tests 69797030-1The peel adhesion data presented in Table 2 was obtained using a method aligned withASTM F2256-05, as described below.Skin adhesive compositions 1-2 and 4-7 prepared using the methods and materials asdescribed above were subjected to peel adhesion tests. For the avoidance of doubt, thesamples used to calculate peel adhesion data are the skin adhesive products formed ofa PET or polyurethane film backing layer substrate, skin adhesive composition layer andrelease liner, prepared in line with the methods disclosed above. Samples were cut to25mm x 100mm using a cutting press (M A Series 3 Cutting Press). Approximately 10mm of release liner is removed at one end of the sample to expose a portion of the skin adhesive composition layer. The exposed portion of the skin adhesive composition layer is tape wrapped to form a tab portion of the sample for use with the tensometer (WI230 Zwick Roell Z0.5 tensometer). A piece of Bristol paper of suitable dimensions is prepared. The remainder of the release liner of the skin adhesive composition product sample is removed and the sample is applied to the Bristol paper by bringing the newly exposed skin adhesive composition layer into contact with the surface of the Bristol paper. The tab portion does not adhere to the Bristol paper. The sample and Bristol paper are placed on a calibrated 'roll down' machine at a speed of 12inch / min. The Bristol paper is gripped inside to the upper jaw of the tensometer and the tab portion of the sample is gripped inside the lower jaw. The grip to grip separation is set to 100mm,the test speed is 150mm / min and the test path is 150mm. The peel angle is 180°. Themaximum force and the average force are measured using the software Zwick TestXpertIII. Peel adhesion data is presented in Table 2 below.Average Peel Force Composition 1 (n=5) 3.192 N / 25mmComposition 2 (n=5) 1.172 N / 25mmComposition 4 (n=5) 6.944 N / 25mmComposition 5 (n=5) 3.090 N / 25mm69797030-1Composition 6 (n=5) 6.588 N / 25mmComposition 7 (n=5) 7.016 N / 25mmTable 2 Hotplate testsThe ability of the skin adhesive compositions 1-2 and 5-7, described in Table 1, toundergo thermochromic changes was assessed using hotplate tests. For the avoidance of doubt, the samples used to perform these hotplate tests are the skin adhesive products formed of a PET or polyurethane film backing layer substrate, skin adhesive composition layer and release liner prepared in line with the methods disclosed above. These hotplate tests were performed according to the following steps: 1. The release liners on the skin adhesive composition sample were removed toexpose a surface of the skin adhesive composition. The exposed surface of the skin adhesive composition was placed onto, and in contact with, a top side of asheet-like foam substrate. 2. The foam substrate (AMS MCF03 PU foam - 5mm thick) was then placed on ahotplate. The top side of the foam substrate, on which the skin adhesivecomposition is located, was positioned facing away from the hotplate. The bottomside of the foam substrate, which is absent of skin adhesive composition, waspositioned facing and in contact with the hotplate. 3. Backing liners were then removed from skin adhesive composition. Atemperature probe was then placed on the skin adhesive composition located onthe top side of the foam substrate. 4. The temperature of the hotplate was then gradually increased. Temperaturereadings of the skin adhesive composition were recorded using the temperature probe and thermochromic changes to the skin adhesive compositions were assessed visually via observable colour changes in the compositions.69797030-1 The results of the hotplate tests can be observed in Figures 1-5. The results demonstratethat all of tested skin adhesive compositions undergo thermochromic changes attherapeutically relevant temperatures.Photographic images A-E in Figure 1 illustrates that silicone polymer skin adhesivecomposition 1 undergoes thermochromic changes, which are visually observable as agradual colour change of from red to yellow, when the temperature of the skin adhesivecomposition was progressively increased from 29.5°C through to 32.5°C. Table 3 belowdetails the specifics temperature readings taken for images A-E in Figure 1, as recordedusing the temperature probe. Image A B C D ETemp (°C) 29.5 30.5 31.2 31.5 32.5 Photographic images A-E in Figure 2 illustrates that silicone polymer skin adhesivecomposition 2 undergoes thermochromic changes, which are visually observable as agradual colour change of from grey-black to purple, when the temperature of the skinadhesive composition was progressively increased from 34.0°C through to 36.6°C. Table 4 below details the specifics temperature readings taken for images A-E in Figure 2, asrecorded using the temperature probe.Image A B C D ETemp (°C) 34.0 34.6 35.0 35.4 36.6Table 4Photographic images A-G in Figure 3 illustrates that silicone polymer skin adhesivecomposition 5 undergoes a first thermochromic change, which is visually observable asa gradual colour change of from red to grey-black, when the temperature of the skinadhesive composition was progressively increased from 29.5°C through to 33.1°C.Photographic images G-K in Figure 3 illustrates that skin adhesive composition 5 undergoes a second thermochromic change, which is visually observable as a gradualcolour change of from grey-black to off-white, when the temperature of the skin adhesive69797030-1composition was progressively increased from 33.1°C through to 35.9°C. Table 5 belowdetails the specifics temperature readings taken for images A-K in Figure 3, as recordedusing the temperature probe. Image A B C D E F G H I J KTemp29.5 30.4 31.4 31.8 32.1 32.4 33.1 33.3 34.5 35.4 35.9(°C) Photographic images A-H in Figure 4 illustrates that acrylic polymer skin adhesivecomposition 6 undergoes thermochromic changes, which are visually observable as a gradual colour change of from red to off-white, when the temperature of the skin adhesivecomposition was progressively increased from 27.1°C through to 37.2°C. Table 6 below details the specifics temperature readings taken for images A-H in Figure 4, as recorded using the temperature probe. Image A B C D E F G HTemp27.1 30.0 31.3 31.8 32.8 34.0 35.7 37.2(°C) Table 6 Photographic images A-F in Figure 5 illustrates that acrylic polymer skin adhesivecomposition 7 undergoes thermochromic changes, which are visually observable as a gradual colour change of from red to yellow, when the temperature of the skin adhesivecomposition was progressively increased from 25.6°C through to 32.9°C. Table 7 belowdetails the specifics temperature readings taken for images A-F in Figure 5, as recordedusing the temperature probe. Image A B C D E FTemp25.6 26.6 29.8 30.7 31.4 32.9(°C) 69797030-1 Table 7Figure 6 provides microscopic images A-D of silicone polymer skin adhesive composition5 detailed in Table 1. Microscopic images A and B in Figure 6 were taken, whilst the skinadhesive composition was at a temperature of approximately 20°C, at a magnification of20x and 40x, respectively. Microscopic images C and D in Figure 6, were taken whilstthe skin adhesive composition was at a temperature of approximately 40°C, at amagnification of 20x and 40x, respectively.Figure 7 provides microscopic images A-D of acrylic polymer skin adhesive composition5 detailed in Table 1. Microscopic images A and B in Figure 7 were taken, whilst the skinadhesive composition was at a temperature of approximately 20°C, at a magnification of20x and 40x, respectively. Microscopic images C and D in Figure 7, were taken whilst the skin adhesive composition was at a temperature of approximately 40°C, at a magnification of 20x and 40x, respectively. Both Figures 6 and 7 illustrates that when two or more thermochromic agents are used in skin adhesive compositions according to the present invention, the thermochromicagents are well distributed throughout the polymer networks formed with the adhesivecompositions and successfully undergo thermochromic changes, which are visuallyobservable as a gradual colour change, at therapeutically relevant temperatures. Total fluid tests on skin adhesive The Total Fluid Handling (TFH), Moisture Vapour Transmission Rate (MVTR) and FluidAbsorbance data presented in Table 8 was obtained using a method which is alignedwith ISO 13726-1:2002 Test Methods for Primary Wound Dressings - Part 1: Aspects ofAbsorbent section 3.3 Fluid Handling Capacity. Skin adhesive composition samples were prepared using the method as described underthe section titled “Preparation of silicone polymer skin adhesive composition” and“Preparation of acrylic polymer skin adhesive composition” provided above. The sampleswere subjected to fluid handling tests. For the avoidance of doubt, the samples used tocalculate TFH and MVTR are skin adhesive composition products formed of a69797030-1 polyurethane film backing layer substrate, skin adhesive composition layer according to the method described above, and further comprising a release liner disposed on theadhesive to permit ease of handling. The method requires a circular sample of the skinadhesive composition having a 55cm diameter to be cut. Release liners are removedand the circular sample skin adhesive composition is then attached to the flange of apaddington cup and secured in place with a retaining ring. The paddington cup is madeof corrosion-resistant material and has an internal diameter of 35.7mm ± 0.1mm with a cross sectional area of 10 cm2cross-section.The weight of the sample skin adhesive composition and the paddington cup ismeasured (W1) and recorded using a calibrated balance. Then 30ml of Solution A isadded to the paddington cup and the screw top applied. Solution A is a standard testsolution used in wound care containing 142 millimoles of sodium ions and 2.5 millimolesof calcium ions dissolved in distilled water (made as per ISO 13726-1:2002). Thepaddington cup is positioned such that the sample skin adhesive composition is incontact with Solution A. The paddington cup is then weighed again and the weight isrecorded (W2). The paddington cup is placed into a 37°C environmental chamber for 24hours in an upright position. Upon removal from the environmental chamber, thepaddington cup is left to stand for 30 minutes and the weight recorded (W3). The solutionis drained and the paddington cup is inverted for 15 minutes before having the weight ofthe cup measured and recorded for the final time (W4).The Moisture Vapour Transmission Rate (MVTR) and Fluid Absorbance for the skinadhesive composition sample was calculated according to the following wherein the unitweight of W1, W2, W3 and W4 is grams. MVTR = W2 - W3 x 1000 (Units: g / m2 / 24hrs)Fluid Absorbance = W4 - W1 (Units: g / 10cm2 / 24hrs)The total fluid handling is the sum of MVTR and Fluid absorbance values. The MVTR indicates the breathability and moisture wicking ability of the skin adhesive composition,which is an important factor for the skin adhesive composition as it will typically besecured to and in contact with the skin of a user when incorporated as part of a wearable 69797030-1device (e.g. secured to and in contact with the skin of a user when used to secure anmedical dressing to the user’s skin).Total Fluid Handling (TFH), Moisture Vapour Transmission Rate (MVTR) and FluidAbsorbance tests were performed via the method mentioned above.Average MVTR Average Fluid Average TFH (g / m² / 24hrs) Absorbance (g / 10cm² / 24hrs) (g / 10cm2 / 24hrs) Upright cup method Composition 1 (n=4) 536.5 0.889 1.426Composition 2 (n=5) 460.0 0.314 0.774Composition 4 (n=4) 2486.5 0.333 2.819Composition 5 (n=4) 604.0 0.273 0.877Composition 6 (n=5) 4851.0 0.367 5.218Composition 7 (n=4) 526.5 0.318 0.844Table 8It can be seen from Table 8 that the skin adhesive compositions of the present inventiondemonstrate excellent MVTR and TFH characteristics when loaded with thermochromic agents. The data shows that the incorporation of the thermochromic agents within the skin adhesive compositions do not have a detrimental effect on the fluid handling properties of the compositions. As can be seen from the moisture management data in Table 8, the skin adhesive compositions are not prone to excessive swelling and have beneficial wicking properties. This shows that the skin adhesive compositions of the present invention would be expected to have excellent skin and / or wound environmentcompatibility when integrated into a wearable product and in contact to the skin of a userduring use. It will be appreciated that numerous modifications to the embodiments herein may be made without departing from the spirit and scope of the invention, for instance, the scope of the invention as defined in the appended claims. Moreover, any one or more of the above-described aspects and embodiments could be combined with one or more 69797030-1 features of the other aspects and embodiments and all such combinations are intended within the present disclosure. Optional and / or preferred features may be used in other combinations beyond thoseexplicitly described herein and optional and / or preferred features described in relation toone aspect of the invention may also be present in another aspect of the invention, whereappropriate. The described and illustrated embodiments are to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiments have been shown and described and that all changes and modifications that come within thescope of the inventions as defined in the claims are desired to be protected. It should beunderstood that while the use of words such as “preferable”, “preferably”, “preferred” or“more preferred” in the description suggest that a feature so described may be desirable,it may nevertheless not be necessary and embodiments lacking such a feature may becontemplated as within the scope of the invention as defined in the appended claims. Inrelation to the claims, it is intended that when words such as “a,” “an,” or “at least one,”are used to preface a feature there is no intention to limit the claim to only one suchfeature unless specifically stated to the contrary in the claim. 69797030-1

Claims

CLAIMS:

1. A skin adhesive composition comprising at least one thermochromic agent,wherein the at least one thermochromic agent undergoes a thermochromic change at atemperature of from 25°C to 45°C and, during use, is in thermal communication with asubject.

2. The skin adhesive composition according claim 1, wherein the at least onethermochromic agent is present in an amount of from 0.5 wt% to 25 wt% relative to theweight of the skin adhesive composition, optionally, from 2 wt% to 5 wt% relative to theweight of the skin adhesive composition.

3. The skin adhesive composition according to any one of claims 1 or 2, whereinthe skin adhesive composition has a moisture vapour transmission rate (MVTR) of from300 g / m2 / 24hrs to 7000 g / m2 / 24hrs, optionally, from 400 g / m2 / 24hrs to 5000 g / m2 / 24hrs.

4. The skin adhesive composition according to any one of claims 1 to 3, whereinthe skin adhesive composition has a peel strength of from 0.1 N / 2.5 cm to 10 N / 2.5 cm,optionally from 0.5 N / 2.5 cm to 8.0 N / 2.5cm, such as from 1.0 N / 2.5 cm to 3.0 N / 2.5cmor from 6.0 N / 2.5 cm to 8.0 N / 2.5cm.

5. The skin adhesive composition according to any one of claims 1 to 4, whereinthe skin adhesive composition is a silicone polymer skin adhesive or an acrylic polymer skin adhesive.

6. The skin adhesive composition according to any one of claims 1 to 5, whereinthe skin adhesive composition comprises two or more thermochromic agents.

7. The skin adhesive composition according to any one of claims 1 to 6, whereinthe at least one thermochromic agent is selected from the group consisting of a thermochromic Leuco dye, thermochromic liquid crystal, thermochromic inorganic compound, for example, thermochromic transition metal compound, polymericthermochromic agent or a combination thereof.69797030-18. The skin adhesive composition according to any one of claims 1 to 7, whereinthe skin adhesive composition is disposed on a substrate, optionally, wherein thesubstrate is a wearable product or a component part of a wearable product.

9. The skin adhesive composition according to claim 8, wherein the substrate is a medical device or a component part of a medical device, optionally, wherein the medical device is a medical dressing.

10. The skin adhesive composition according to any one of claims 1 to 9, wherein the skin adhesive composition is provided in the form of a film, optionally, wherein a release liner is disposed on the film.

11. A wearable product comprising a skin adhesive composition according to any one ofclaims 1 to 10, wherein the skin adhesive composition is disposed on the wearable product so as to be capable of adhering the wearable product to the skin of a subject.

12. The wearable product according to claim 11, further comprising a release liner disposed on the skin adhesive composition.

13. A pre-cure composition capable of forming a skin adhesive composition according to any one of claims 1 to 10, the pre-cure composition comprising a skin adhesive composition mixture and the at least one thermochromic agent distributed throughout the mixture.

14. Use of a skin adhesive composition according to any one of claims 1 to 10 foradhering a wearable product to skin, optionally, mammalian skin.

15. Use of a skin adhesive composition according to any one of claims 1 to 10 fordetecting a temperature change on the skin of a subject, optionally, wherein thetemperature change is associated with infection or inflammation of the skin.

16. Use of a skin adhesive composition according to any one of claims 1 to 10 for detecting a temperature change in a wound of a subject, optionally, wherein the temperature change is associated with infection or inflammation of the wound. 69797030-117. A method of manufacturing a skin adhesive composition according to any one of claims 1 to 10, the method comprising curing the pre-cure composition according to claim 13. 69797030-1

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