METHODS OF TREATMENT USING SAME

The present invention relates to medical skin coverings including surgical incision drapes, bacterial barriers for covering wounds and skin closure devices. The invention also relates to use of these devices on patients undergoing surgery, on patients after surgery and/or injury^ and for skin closure applications.

The medical skin coverings mentioned above have in common the feature that they are applied to the skin at a site where a break in the skin surface has occurred, for example cuts, scratches and/or abrasions, or at a site where a break in the skin surface will be made by surgery. In discussing the importance of minimising infections at such sites, it will be convenient to consider them together as skin breakage sites, regardless of whether the skin breakage is new and has occurred as a result of accidental trauma, whether the skin breakage is a minor cut, scratch and/or abrasion or something more major, whether the skin breakage site is an old post- trauma or post-operative skin breakage site, or whether the skin breakage site is newly formed or yet to be formed as a result of surgical incision.

In cases of hospitalisation after surgery, surgical site infections are commonplace and can account for around 40% of hospital-acquired infections among surgical patients. As a result, patients need to stay longer in hospital which increases the cost of hospitalisation and increases anxiety and inconvenience for the patients.

Although the occurrence of surgical site infections can vary from surgeon to surgeon, from hospital to hospital, from patient to patient, and also in accordance with the surgical procedure that is being conducted, it is believed that most surgical site infections are caused by the patient's own normal skin flora which enter the body through the surgical incision. The reason for this is that the patient's skin flora can move from the skin surface to the incision very easily. Also, innocuous bacterial flora on the patient's skin may also be host to pathogenic organisms.

Various surgical site infection countermeasures have been developed over the years to reduce the risk of such infections to patients. Obvious steps such as hygiene management of the operating room personnel and the operating room itself can lower the incidence of exogenous pathogens. Also, the scheduling of elective surgery so that it is conducted when patients have generally good health and hence concomitant healthy immune systems are also thought to be effective. Of course, not all surgery can be timetabled in this way and it is inevitable that many patients will have to undergo surgery when their health is far from perfect.

The application of bactericidal or antimicrobial agents to the patient's skin at the intended site of surgery has, in the past, been effective to kill bacteria. Various pre-operative skin preparation products, washes, surgical scrub tissues, wound cleaners, lotions and ointments have been used for many years for this purpose. However, with the emergence of bacteria that are resistant to antibiotic treatment, the effectiveness of such infection countermeasures is becoming lessened.

Longer lasting antimicrobial effects may be obtained by combining the antimicrobial agent applied pre-operatively with a surgical incision drape, for example in the form of a clear polymeric film with an adhesive backing on one side covered with a release liner. The release liner is removed and the surgical incision drape is placed over the intended site of incision, adhesive side down, and pressed into place on the patient's skin.

Unfortunately, such surgical drapes can be lifted during surgery, which results in entry of bacteria into the surgical site. The lifting of the surgical drape is usually caused by failure of the adhesive to remain in contact with the patient's skin. Increasing the adhesive strength is not necessarily the ideal solution to this problem because more force is then required to remove the drape from the skin, which may result in damage of the skin near the surgical site.

Moreover, such surgical drapes are usually large and difficult to apply to the patient without wrinkling the drape film. Wrinkling of the surgical drape film at the surgical site may impede visibility of the incision site to the surgeon. Also, wrinkling at the site of the incision increases the risk of micro-organisms entering the incision from the patent's skin.

The present invention has been made in view of the aforementioned problems and is based on the discovery that pressure sensitive adhesive polymer compounds, when admixed with non-adhesive curable molecules, can be caused to change from a viscoelastic state to an elastic state upon exposure to visible light or UV light, and can be caused to adhere preferentially to the skin rather than to any carrier layer on which they are supported by controlling the surface properties of the carrier layer or layers. This makes them suitable as surgical incision site coverings, post-operative bacterial barriers or coverings for wounds sustained by injury, and also renders them suitable for skin closure applications.

The invention may use an adhesive composition comprising a mixture, in proportions by weight, of 10% to 95% of a pressure sensitive adhesive component not having pendent curable groups curable by free radical polymerisation, 5% to 85% of curable molecules that are curable by free radical polymerization and 0.1% to 10% of photoinitiator, the balance being incidental constituents. Preferably, the pressure sensitive adhesive component and the curable molecules are mutually soluble when dry, although good results are obtained when the curable molecules are uniformly dispersed in the pressure sensitive adhesive component, said adhesive component and said curable molecules being mutually insoluble or only partly mutually soluble when dry.

Preferably the amount of pressure sensitive adhesive component present in the mixture is in the range 20% to 75% by weight, more preferably 40% to 70% by weight. Preferably the proportion of curable molecules in the mixture ranges from 20% to 75% by weight, more preferably 30% to 60% by weight. Preferably, the photoinitiator is present in the mixture in the proportions 0.1% to 5% by weight, more preferably 0.5% to 2% by weight. Preferably, the photoinitiator is also soluble in the dry mixture of pressure sensitive adhesive component and curable molecules, although it will be capable of exerting its curing initiating effect upon exposure to an activating light source if finely dispersed through the dry mixture but not dissolved in it.

The weight proportion for the pressure sensitive adhesive component polymer is given here in terms of its dry weight and excludes any solvent which might normally be present in a commercially available bulk adhesive polymer.

The composition may also include a polymer cross-linker that is cross- linkable by a mechanism other than free radical polymerization, for cross linking the pressure sensitive adhesive component. The internal cross-linker may be included, for example, for applications in which the cohesive strength of the adhesive composition (before the curable molecules are cured) is important. An example of such an application would be for skin closure, where an adhesive composition with low cohesive strength may be inadequate to hold the skin edges together while the curable molecules undergo their free radical curing upon exposure to visible light or UV light. In these circumstances, a polymer cross-linker in the adhesive component increases the cohesive strength of the composition and enables the composition to hold the skin edges together while the curable molecules undergo curing.

In certain embodiments, the weight proportion of pressure sensitive adhesive component is from one of the following lower endpoints (inclusive), or from one of the following upper endpoints (inclusive). The lower endpoints are 10%, 20%, 30%, 40%, 50%, 60% and 70%; the upper endpoints are 85%, 80% and 75%. In certain embodiments, the weight proportion of curable molecules is from one of the following lower endpoints (inclusive), or from one of the following upper endpoints (inclusive). The lower endpoints are 10%, 20% and 25%; the upper endpoints are 85%, 80%, 70%, 60%, 50%, 40% and 30%. In certain embodiments, the weight proportion of photoinitiator is from one of the following lower endpoints (inclusive), or from one of the following upper endpoints (inclusive). The lower endpoints are 0.1%, 0.2%, 0.5% and 1.0%; the upper endpoints are 10%, 5%, 4% and 3%.

The incidental constituents may be one or more of stabilisers, light scattering particles, fungicides, bactericides, colorants, humectants, etc.

The preparation method for the adhesive compositions used in the invention is very simple. The pressure sensitive adhesive component, the curable molecules (monomers and/or oligomers) and the photoinitiator are stirred together in darkness or under red light conditions for about 30 to 60 minutes, most conveniently at room temperature. The pressure sensitive adhesive component is usually supplied in solution (typically, 40% to 60% solids by weight); the curable molecules are usually solvent free, although some curable molecules of high viscosity may be carried in a solvent; the photoinitiator is usually solid and the most difficult component of the system to dissolve and/or disperse.

Following completion of the stirring together, the resulting solution is coated onto a release liner at a certain thickness - typically about 100 μπι when wet - and then left to dry at room temperature for about 10 minutes. The release liner usually consists of a siliconised material, for example paper, polyethylene, polyethylene terephthalate, polypropylene with a coating of a silicone release agent. The spread adhesive mixture is then further dried at 80-15O°C for 3 to 10 minutes. A slightly higher temperature and a longer drying time can be used if necessary. After drying, the thickness of the spread adhesive mixture will typically be about 60 μπι.

A second release liner is then applied to the other surface of the adhesive mixture. Preferably, one of the release liners has a lower release force compared to the other. A difference in release force helps to enable the adhesive composition to remain in place on one of the release liners whilst the other release liner is removed so that the thus-exposed adhesive can be applied to skin. Differences in release force may be achieved by using a different release material, i.e., a different silicone release agent, or by applying a thicker coating of the silicone release agent.

In order to enable the adhesive composition layer to stick preferentially to skin rather than to the release liners, the material selected for the release liners is one that has a smooth surface. Additionally, as mentioned above, the release liners have a coating of a release agent such as silicone. As a result, the release liners have a low surface energy. By contrast, skin is not smooth (at a microscopic level) and has many surface irregularities, including pores. Hence, skin has an inherently high surface energy compared to the release liners. Typical peel forces for removing the release liners, measured using Finat test method No.10 and TESA 7475 tape of 25 mm width, are given in Table 1 below. Note that, in referring to the force required to remove the release liners from the adhesive composition layer, the terms "peel force" and "release force" are used interchangeably and mean the same thing.

Exemplary light transmitting materials for the release liners for supporting the release agent include polyethylene, polypropylene, polyurethane, ethylene/propylene copolymers, ethylene/ethylacrylate copolymers, ethylene/vinyl acetate copolymers, silicone elastomers, especially the medical-grade polydimethylsiloxanes, neoprene rubber, polyisobutylene, polyacrylates, chlorinated poly-ethylene, polyvinyl chloride, vinyl chloride-vinyl acetate copolymer, crosslinked polymethacrylate polymers (hydrogel), polyvinylidene chloride, poly (ethylene terephthalate), butyl rubber, epichlorohydrin rubbers, ethylenevinyl alcohol copolymers, ethylene-vinyloxyethanol copolymers; silicone copolymers, for example, polysiloxane-polycarbonate copolymers, polysiloxanepolyethylene oxide copolymers, polysiloxane- polymethacrylate copolymers, polysiloxane-alkylene copolymers (e.g., polysiloxane- ethylene copolymers), polysiloxane-alkylenesilane copolymers (e.g., polysiloxane- ethylenesilane copolymers), and the like; cellulose polymers, for example methyl or ethyl cellulose, hydroxy propyl methyl cellulose, and cellulose esters; polycarbonates; polytetrafluoroethylene; and the like.

The pressure sensitive adhesive components may be water-soluble, but will most often be soluble in, and hence commercially supplied as solutions in, organic solvents such as ethyl acetate, hexane, toluene, acetone, etc.

In the broadest sense, any conventional known unsaturated compounds could be used as the curable molecules, but preferred examples, used alone or in mixtures, are curable molecules such as acrylic acid esters or methacrylic acid esters of alcohols, glycols, pentaerythritol, trimethylpropane, glycerol, aliphatic epoxides, aromatic epoxides including bisphenol A epoxides, aliphatic urethanes, silicones, polyesters and polyethers, as well as ethoxylated or propoxylated species thereof.

Most effective are curable molecules having more than one unsaturated site, i.e., greater than single functionality. Multiple functionalities of 2 or more, for example 3 or more, or functionalities of 4 or more are especially effective because curable molecules of this type are able to form highly cross-linked three-dimensional polymeric networks which are an important feature of transforming the adhesive composition used in the invention from its viscoelastic state to the elastic state. Also, many curable molecules having multiple lunctionalities are commonly available at reasonable cost.

The photoinitiator may be any species which is capable of producing radical species under mild conditions, e.g., visible light, in order to promote radical polymerization reactions in the curable molecules. As a consequence, when the photoinitiator becomes activated by exposure to visible light, the curable molecules form chemical bonds with other curable molecules and hence create polymeric cross- linking. The effect of such cross-linking is to build a three-dimensional polymeric network entangling the polymer chains of the pressure sensitive adhesive constituent, thereby reducing their mobility and free volume. The polymer chains of the pressure sensitive adhesive constituent do not become cross-linked with each other as a result of the free radical polymerisation of the curable molecules. Rather, they merely become entangled with the three-dimensional polymeric network formed by the curable molecules and the resulting reduction in mobility and free volume causes the switchable adhesive mixture to transform from a viscoelastic state to an elastic state.

Alternatively, the photoinitiator may produce radical species upon exposure to UV light. Preferably, for the medical applications described here, the UV exposure is under the mild conditions of long wave UV.

Curable molecules having multiple functionality are able to form highly cross- linked three-dimensional polymeric networks easily.

The adhesive mixture may also contain stabilisers which are added in order to prevent spontaneous reaction of the curable molecules during storage. Examples of such stabilisers are hydroquinones such as ethoxy phenol (sometimes referred to as hydroquinone monomethyl ether), or l-Piperidinyloxy-4,4'- [1,10-dioxo- 1,10- decanediyl) bis (oxy)] bis [2,2,6,6-tetra methyl] and Pentaerythritol tetrakis(3-(3,5-di- tert-butyl-4-hydroxyphenyl)propionate).

The adhesive mixture may also include photo-sensitisers. Since a sensitising species often absorbs energy in a different part of the spectrum from the initiator, more effective use of the light source may be achievable through the incorporation of sensitisers into the mixture. Many photo-sensitisers are complex organic molecules, absorbing in the visible portion of the spectrum.

The adhesive mixture may also incorporate light scattering particles to increase the effect of irradiation of the adhesive mixture by scattering light through the thickness of the adhesive mixture. Preferably, the light scattering particles are an inorganic compound such as silica powder, alumina powder, silica-alumina powder or mica powder with particle sizes of the order of 10 nm or greater, typically up to 1 μπι. Any conventionally known free radical initiators may be used. Particularly preferred are those initiators which react to visible light radiation, although initiators which react under shorter wavelength light may be used. Thus, suitable free radical initiators include titanocene photoinitiators; dye/co-initiator systems, e.g., thionine/triethanol-amine; dye/borate salt systems; dye/peroxide systems and 1,2- diketone/co-initiator systems, e.g., camphor-quinone/tertiary amine.

Examples of visible light photoiniti tors (which include Irgacure 784 because it absorbs light both in the UV and visible spectrum) are: Benzildimethyl ketal; Phenanthrenequinone; Titanocenes (of which Irgacure 784 is one example); Bis(2,4,6-trimethyl-benzoyl)-phenylphosphineoxide.

Examples of UV photoinitiators are: Benzoin and ethyl, isopropyl or isobutyl ethers of Benzoin; Benzophenone and hydroxy or methyl benzophenones; 2-Methyl- l[4-(methylthio)phenyl]-2-morpholinopro an-l-one; Acetophenone and 4'- Phenoxyacetophenone; Benzoyl-biphenyl; Benzil; Anisoin, as well as the Irgacures such as Irgacure 651 (benzyl dimethyl ketal) or Irgacure 907 (2-methyl-l-[4- (methyίthio)phenyl]-2-mo holino-pro an -1-one); or the Uvatones, such as Uvatone 8302 (2,2-diethoxy-l,2-diphenyl ethanone).

Preferred free radical photoinitiators are the titanocene initiators such as bis.(.eta.5-cyclopentadienyl) -bis (2,6-difluoro-3-[pyrrol-l-yl]-phenyl) titanium, sold in the UK by Ciba Geigy as Irgacure 784 (Trade Mark).

The composition may also include a component containing aliphatic thiol groups for reducing oxygen inhibition of the radical polymerization at the surface and preventing the surface from remaining tacky after cure when the surface is not protected by a film (second release liner). Apart from having oxygen-scavenging properties, the aliphatic thiols can also take part in the radical polymerization of the curable molecules via thiol-ene reactions. For more effective contribution to the curing reaction, a component with two or more thiol groups could be used, such as trimethylolpropanetris(3 -mercaptopropionate) or pentaerythritoltetrakis(2-mercapto acetate). Amine synergists such as triethanol amine or ethyl-4- dimethylaminobenzoate could also be used to reduce oxygen inhibition of the radical polymerization at the adhesive surface when this is not protected by a film. Surgical Incision Drapes

Rather than using an adhesive as the medium to adhere a clear plastic film to the intended incision site, in the case of surgical incision drapes, the present invention uses the adhesive itself as the material of the incision drape.

In a surgical incision drape using the present invention, a switchable adhesive composition in accordance with the present invention is sandwiched between two release liners. The release liners may include a light occlusive layer to prevent premature curing of the curable molecules in the switchable adhesive composition by preventing exposure to incident light. Alternatively, the surgical incision drape may be packaged in a light occlusive covering that is removed before the surgical incision drape is deployed. The first release liner is removed just before the surgical incision drape is applied to the intended site of incision. Then the surgical incision drape is pressed on to the surface of the patient's skin at the intended site of incision, with the second release liner being uppermost and the adhesive composition layer being next to the patient's skin. The adhesive composition of the surgical incision drape is initially viscoelastic and is able to flow into irregularities and pores in the patient's skin surface and good "wetting" occurs. If present, any light occlusive layer on the second release liner is removed. Then the adhesive composition layer of the surgical incision drape is exposed to visible light or UV light through the second release liner to effect curing of the curable molecules in the adhesive composition. The resultant cured adhesive composition layer is elastic, and therefore moves with the patient's skin, but it is no longer visco-elastic and cannot easily be removed from the skin. Removal of the second release liner after curing leaves the elastic adhesive composition in place as a thin layer on the patient's skin. Preferably, the thin adhesive composition layer left in place on the patient's skin is transparent so that it is possible for the surgeon to see any markings that may have been made on the patient's skin before commencement of the surgical procedure. There is no wrinkling of the adhesive composition layer to obscure the surgeon's view of the incision site and the surgeon is able to make the incision through the cured elastic adhesive composition layer. Migration of the patient's normal skin flora, if not removed by pre-operative swabbing, is inhibited by the adhesive overlayer. Towards the end of the surgical procedure, when the incision is to be closed, the cut edges of the skin can be brought together and sutured, stapled or taped in the usual way through the adhesive composition layer that constituted the surgical incision drape. Following closure of the incision, an area around the site of the incision may be cleared of the adhesive composition layer by peeling it away to leave the incision site ready to receive a dressing, although removal of the adhesive composition layer is not necessary.

Bacterial Barrier

After surgery, as described above, the present invention may find further use as a bacterial barrier applied over the closed incision site.

As discussed above, if a surgical drape in accordance with a first aspect of the invention has been used during the surgical procedure, an area around the site of the incision may be cleared of the adhesive composition layer that constituted the incision drape, for example by peeling away the adhesive composition layer. The cleared site is then disinfected by wiping it with an antibacterial wipe, in the usual way, so that it is then ready to receive a bacterial barrier in accordance with the second aspect of the invention.

Alternatively, the bacterial barrier may be applied directly over the surgical incision drape without clearing the surgical incision drape from the area around the site of the incision. Preferably, before applying the bacterial barrier, the intended site of its application is disinfected, for example by wiping with an antibacterial wipe.

In other situations, a bacterial barrier may be applied to a wound sustained through injury. The wound site is first cleaned and disinfected before applying the bacterial barrier.

Such a bacterial barrier comprises a layer of a switchable adhesive composition containing curable groups in accordance with the present invention sandwiched between two release liners. The adhesive composition layer is initially viscoelastic prior to switching, but is transformable to an elastic state by curing of the curable molecules by exposure to visible light and UV light. The release liners may include a light occlusive layer to prevent premature curing of the curable molecules through exposure to incident light. Alternatively, the bacterial barrier may be packaged in a light occlusive covering that is removed before the bacterial barrier is deployed. To apply the bacterial barrier to the closed incision site or over the wound, the first release liner is removed and the bacterial barrier is applied over the site of the closed incision, adhesive side down, pressing gently on the remaining release liner. The viscoelastic adhesive composition flows into the surface irregularities and pores of the patient's skin, including the edges of the incision or the edges of the wound. If necessary, any light occlusive layer on the second release liner is removed. The curable molecules in the adhesive composition layer are then caused to cure by exposure to visible light or UV light through the second release liner, causing the adhesive composition layer to change from its viscoelastic state to an elastic state. In the elastic state, the adhesive composition layer is no longer flowable, but is elastic so that it remains conformable with the patient's skin over the closed incision site, as the patient moves about.

The second release liner is removed after the curing step and the patient "wears" the bacterial barrier in the form of a cured elastic adhesive composition layer. If required, a dressing may be placed over the bacterial barrier, for example to relieve direct pressure on the closed site of the incision or wound.

Any bacteria remaining on the patient's skin prior to applying the bacterial barrier become immobilised in the cured adhesive composition layer and cannot migrate into the closed incision site or wound. The cured adhesive composition layer is breathable and allows moisture to escape from the pores of the patient's skin. Good wound healing is promoted by this breathability and by the exclusion of bacteria. The bacterial barrier eventually sloughs away with the shedding of skin cells from the surface of the patient's skin as wound healing progresses.

When the wound has healed sufficiently to permit removal of any sutures or staples, these can be removed without requiring the bacterial barrier to be removed beforehand. Rather, the sutures or staples can be removed through the bacterial barrier that remains if it has not already fallen away with the patient's dead skin cells.

Skin Closure

In a third aspect, the present invention may find use in skin closure applications. In recent times, cyanoacrylate adhesives have found widespread use as an alternative to the traditional methods of suturing and/or stapling and/or the application of surgical tape(s) for closing wounds. Such cyanoacrylate adhesives are fast and relatively simple to use; they are also comfortable for the patient to wear. They form an effective bacterial barrier and, from the physician's point of view, there is no risk of needle sticks. Finally, there is no need for a second visit to the physician for removal of the cyanoacrylate adhesive because it sloughs away with the patient's dead skin cells as wound healing progresses.

However, there are a number of disadvantages to using such cyanoacrylate adhesives in a skin closure application. Firstly, they give rise to toxic vapours when applied and during the cure; they undergo a pronounced exothermic reaction when curing, resulting in a burning sensation on the patient's skin. There is also a risk of scarring from adhesive flowing into the wound and, for wounds close to the eye, a risk of the adhesive entering into the patient's eye and sticking the eyelids together and/or sticking the eyelids to the eyeball. The curing speeds of cyanoacrylate adhesives depend on the formulation, but as curing is triggered by moisture, they can cure very rapidly on the patient's skin as a result of the moisture present at the skin surface. Sometimes, curing is too rapid and occurs before the edges of the wound have been properly brought together. Although simple to use in theory, mishandling of the cyanoacrylate adhesive as a skin closure medium can result in the adhesion of foreign objects to the wound, including the physician's fingertips or gloves.

The skin closure product according to the third aspect of the present invention does not suffer from these drawbacks.

As with the surgical incision drape and bacterial barrier embodiments of the medical skin covering according to the present invention discussed above, the skin closure product is most conveniently supplied as a layer of a switchable viscoelastic adhesive composition containing curable molecules sandwiched between two release liners. The release liners may include a light occlusive layer to prevent premature curing of the curable molecules through exposure to incident light. Alternatively, the skin closure product may be packaged in a light occlusive covering that is removed before the skin closure product is deployed. The curable molecules in the viscoelastic adhesive composition layer are curable to an elastic state by exposure to visible light or UV light.

In applying the skin closure product as described above to a patient, the first release liner is removed and the skin closure product is placed on the patient's skin, adhesive side down, at one end of the wound to be closed. The physician uses the thumb and fingers of one hand to close together the edges of the skin of the wound andvuses his other hand to press down the skin closure product progressively along and over the wound as the wound edges are progressively brought together.

When the skin closure product has been applied along the length of the wound, any light occlusive layer on the second release liner is removed. The curable molecules in the adhesive composition layer are then caused to cure by exposure to visible light or UV light through the second release liner. After curing, the second release liner is removed and a layer of the adhesive composition remains in place on the patient's skin. In its cured state, the adhesive composition layer is elastic and moves with the patient's skin, but has sufficient tensile strength to keep the edges of the wound together.

Curing of the curable molecules in the adhesive composition by radiation through the second release liner means that there is no risk of foreign objects becoming adhered to the wound and no risk of the physician's fingertips or gloves becoming adhered to the wound.

The cured adhesive composition layer is breathable and allows moisture to escape from the pores of the patient's skin. Moreover, the cured adhesive composition layer has good water resistance and does not require special care by the patient when bathing or showering.

The adhesive composition layer is gradually sloughed away with the patient's dead skin cells as wound healing progresses.

In yet another embodiment, a curable skin closure composition comprising curable molecules that are curable by free radical polymerisation and a photoinitiator in admixture may be dispensed from a tube, in similar fashion to the known cyanoacrylate adhesive skin closure products. The skin closure composition thus dispensed is spread on the patient's skin as the edges of the wound are held together by the physician or nurse. Then, the curable molecules in the applied skin closure composition are cured by irradiation using visible light or UV light, for example shone from a lamp aimed at the wound. After curing, the upper surface (i.e., the non- skin contact surface) of the applied skin closure layer may be slightly tacky as a result of exposure to oxygen in the ambient air which inhibits the free radical polymerization of the curable molecules in the composition at the exposed surface.

This can be rectified in a number of ways, for example by applying a bacterial barrier in accordance with the second embodiment described above, or by applying a second layer of the skin closure adhesive composition dispensed from the tube and immediately spreading it on the patient's skin by the act of applying a siliconised transparent release liner over the dispensed adhesive. Then, the curable molecules in the second layer of the skin closure adhesive composition are cured by irradiation through the release liner using visible light or UV light. After curing of the second layer of the skin closure adhesive composition, the release liner is removed as described above, to leave twin layers of the cured elastic skin closure composition in place over the wound site, the upper layer having no residual tackiness.

Alternatively, inhibition of the free radical polymerization of the curable molecules at the exposed surface can be reduced by including in the skin closure composition a component containing aliphatic thiol groups. Besides having oxygen- scavenging properties, the aliphatic thiols can also take part in the radical polymerization of the curable molecules via thiol-ene reactions. For a more effective contribution to the curing reaction, a component with two or more thiol groups could be used, such as trimethylolpropanetris(3-mercaptopropionate) or pentaerythritol tetrakis(2-mercaptoacetate). Amine synergists such as triethanol amine or ethyl-4- dimethylaminobenzoate could also be used to reduce oxygen inhibition of the radical polymerization at the exposed surface when this is not protected by a film.

The invention will now be particularly described by way of example only and without limitation by reference to the drawings in which:

Figure 1 is a perspective view showing an incision being made through a surgical incision drape according to a first embodiment of the present invention;

Figure 2 is a cross-sectional view through the surgical incision drape in accordance with the first embodiment of the invention; Figure 3 is a perspective view showing the act of removal of one of the release liners of the surgical incision drape according to the first embodiment of the present invention;

Figure 4 is a perspective view of the surgical incision drape according to the first embodiment of the present invention in the act of being applied to the torso of a patient prior to surgery;

Figure 5 is a perspective view showing the act of removal of a light occlusive layer from the second release liner of the surgical incision drape according to the first embodiment of the present invention;

Figure 6 is a perspective view of the surgical incision drape according to the first embodiment of the present invention in position on the torso of a patient and undergoing irradiation to effect cure of the adhesive;

Figure 7 is a perspective view showing the act of removal of the remaining layer of the second release liner of the surgical incision drape according to the first embodiment of the invention;

Figure 8 is a perspective view of a bacterial barrier in accordance with a second embodiment of the present invention in place on a patient's thigh, overlying a sutured wound;

Figure 9 is a cross-sectional view of the bacterial barrier in accordance with the second embodiment of the present invention;

Figure 10 is a perspective view showing the act of removal of the first release liner from the bacterial barrier according to the second embodiment of the invention;

Figure 11 is a perspective view of the bacterial barrier according to the second embodiment of the present invention being applied to the thigh of a patient to cover a sutured wound;

Figure 12 is a perspective view showing the act of removal of a light occlusive layer from the second release liner of the bacterial barrier of the second embodiment of the invention;

Figure 13 is a perspective view of the bacterial barrier according to the second embodiment of the invention in position on a patient's thigh and in the act of being irradiated to cure the adhesive; Figure 14 is a perspective view showing the act of removal of the siliconised release layer of the bacterial barrier of the second embodiment of the invention, leaving just the cured adhesive layer in place on the patient's thigh;

Figure 15 is a perspective view showing a skin closure device according to a third embodiment of the invention in the act of being applied to a gaping wound on a patient's forearm as the skin edges are progressively brought together by a physician's thumb and fingers;

Figure 16 is a cross-sectional view through the skin closure device in accordance with the third embodiment of the invention;

Figure 17 is a perspective view showing the removal of the first release liner from the skin closure device in accordance with the third embodiment of the invention;

Figure 18 is a perspective view showing the act of removal of a light occlusive layer from the second release liner of the skin closure device in accordance with the third embodiment of the invention;

Figure 19 is a perspective view of the skin closure device in accordance with the third embodiment of the invention in position on a patient's forearm and in the act of being irradiated to effect cure of the adhesive;

Figure 20 is a perspective view showing the act of removal of the siliconised release layer of the skin closure device in accordance with the third embodiment of the invention, leaving just the cured adhesive layer in place on the patient's forearm;

Figure 21 is a perspective view showing a curable skin closure composition being dispensed from a tube in accordance with a fourth embodiment of the invention; and

Figure 22 is a perspective view of a film of the skin closure composition in accordance with the fourth embodiment of the invention in position on a patient's skin and in the act of being irradiated to effect curing of the composition;

Figure 23 is a perspective view showing the cured skin closure film in accordance with the fourth embodiment of the invention in position over a closed wound on a patient's skin;

Figure 24 is a schematic diagram showing peel force direction relative to the plane of application of an adhesive test strip during peel force tests on skin. First Embodiment

A first embodiment of the present invention in the form of a surgical incision drape will now be described with reference to Figures 1 to 7.

Figure 1 is a perspective view showing a scalpel 80 making an incision 70 in the torso of a patient 10 through the adhesive layer 102 of a surgical incision drape in accordance with a first embodiment of the invention. The physician's hand holding the scalpel has been omitted from Figure 1 for clarity.

As shown in cross-sectional view in Figure 2, the surgical incision drape 100 is a multiple layer article comprising a switchable adhesive composition layer 102 sandwiched between a first release liner 101 and a second release liner 103.

The first release liner 101 is a layer of siliconised plastic film, siliconised on the surface that faces the switchable adhesive composition layer 102. In addition, the first release liner 101 is an occlusive material that prevents visible light and/or UV passing through it and reaching the underlying switchable adhesive composition layer 102.

The second release liner 103 comprises an occlusive layer 104 which prevents visible light and UV radiation from reaching the underlying switchable adhesive composition layer 102. The second release liner 103 also has a siliconised release layer 105, siliconised on the surface that faces the switchable adhesive composition layer 102. Siliconised layer 105 is transparent to visible light and/or UV radiation. The layers 104 and 105 of the second release liner 103 are held together by a very low peel strength adhesive (not shown) that enables the occlusive layer 104 to be removed preferentially, leaving the siliconised layer 105 in place whilst the curable molecules in the switchable adhesive composition layer 102 undergo curing by irradiation with visible light or by irradiation with UV light.

The occlusive first release liner 101 and the occlusive layer 104 of the second release liner 103 prevent inadvertent curing of the curable molecules in the switchable adhesive composition layer 102 before the intended time by preventing the switchable adhesive composition layer 102 from being exposed to visible light or UV light.

Figure 3 is a perspective view of the surgical incision drape 100 showing the removal of the first release liner 101 to expose the underlying switchable adhesive composition layer 102. The second release liner 103, comprising its occlusive layer 104 and its underlying siliconised release layer 105, is still in place on the other side of the switchable adhesive composition layer 102. After removal of the first release liner 101, the surgical incision drape 100 is quickly positioned over the site of the intended incision to minimise exposure of the switchable adhesive composition layer

102 to any radiation that might bring about curing of the adhesive, and also to minimise exposure of the uncured adhesive to atmospheric oxygen. Positioning of the surgical drape is discussed in the next paragraph.

Figure 4 is a perspective view showing the remaining layers of the surgical incision drape being applied to the torso of a patient 10 by the hands 20, 21 of a physician or nurse. In this view, the occlusive layer 104 of the second release liner

103 is uppermost and the switchable adhesive composition layer 102 is the layer that is brought into contact with the skin of the patient. The siliconised release layer 105 of the second release liner 103 is between the occlusive layer 104 and the switchable adhesive composition layer 102. Because the curable molecules of the adhesive composition of the switchable adhesive composition layer 102 are uncured at this stage, the switchable adhesive composition layer 102 is still in its viscoelastic state. In this state, the adhesive is able to flow into surface irregularities and pores of the skin to ensure intimate contact between the surgical incision drape and the patient's skin.

Figure 5 is a perspective view showing the physician's hand 21 removing the light occlusive layer 104 from the second release liner of the surgical incision drape after the drape has been positioned on the patient 10 over the intended site for incision. After removal of the occlusive layer 104, only the siliconised release layer

105 remains of the second release liner 103; the switchable adhesive composition layer 102 is beneath the siliconised release liner 105 and in contact with the patient's skin. The siliconised release layer 105 is transparent to visible light and/or UV light, for reasons which will be explained below.

Figure 6 is a perspective view of the surgical incision drape in position on the torso of the patient 10 and undergoing irradiation, in this example from a lamp 60, to effect cure of the curable molecules in the adhesive composition of the adhesive layer 102. The light from the lamp 60 (visible light or UV light, preferably long wavelength UV light) passes through the transparent siliconised release layer 105 to the underlying adhesive layer 102 to initiate curing of the curable molecules in the adhesive composition. Curing transforms the adhesive composition layer from its viscoelastic state to an elastic state. Curing also transforms the adhesive composition layer from a tacky state to a non-tacky or low-tack state. However, by virtue of the siliconised coating on the release layer 105, the cured adhesive composition is able to be left in place on the patient's skin after the siliconised release layer 105 is removed, as discussed below.

The transparent siliconised release layer 105 is retained in place over the adhesive layer 102 during the curing step to prevent oxygen in the ambient air from reacting with the adhesive composition as the curable molecules in the adhesive mixture undergo curing. Exposure to oxygen during curing causes the upper surface (i.e., the non skin contact surface) of the adhesive composition to remain slightly tacky after curing is complete. This slight tackiness is preferably avoided in a surgical incision drape because it may result in foreign objects (fluff, dust, etc.) becoming stuck to the surgical incision drape. Also, the slight tackiness may increase the possibility that parts of the surgical incision drape will be prematurely removed, for example by being abraded by contact with the physician's gloves. By retaining the siliconised release layer 105 in place over the adhesive layer 102 and curing the curable molecules in the adhesive layer 102 by irradiation through the siliconised release layer 105, the occurrence of surface tackiness in the cured adhesive composition layer is avoided.

Figure 7 is a perspective view showing the physician's hand 21 removing the siliconised release layer 105 from the adhesive layer 102 of the surgical incision drape after the curable molecules in the adhesive composition of the adhesive layer 102 have been cured. After removal of the siliconised release layer 105, only the cured adhesive composition layer 102 remains on the patient's skin. Even though the adhesive layer 102 is no longer tacky, it sticks preferentially to skin because the siliconised layer 105 is very slippery. The cured adhesive layer 102 is surprisingly adherent to skin and is difficult to peel off.

Preferably, the cured adhesive composition layer is transparent so that the physician can see the site of the intended incision and any markings that may have been made on the patient's skin prior to commencement of the surgical procedure. As mentioned above, in the cured state, the adhesive composition of the adhesive layer 102 is transformed from its initial viscoelastic state to an elastic state. In this state, the adhesive remains firmly stuck to the patient's skin but, by virtue of its elasticity, the adhesive layer is able to move with the patient's skin as the skin moves. Moreover, the cured adhesive layer is an effective barrier to bacteria. Any bacteria that remained on the surface of the patient's skin after the preliminary antibacterial swabbing step become immobilised in the cured adhesive layer and migration to the incision site is thereby inhibited.

Referring again to Figure 1, the cured adhesive composition layer 102 of the surgical incision drape remains in position on the patient's skin and is incised, along with the patient's skin, when a physician (not depicted in Figure 1) makes an incision 70 with a scalpel 80.

After surgery, the adhesive layer 102 may be left in place and the incision can be closed in the usual way, for example by suturing or by means of surgical staples or surgical tapes. The adhesive composition layer 102 is gradually sloughed away with the shedding of skin cells from the surface of the patient's skin as healing takes place.

Second Embodiment

A second embodiment using the present invention in the form of a bacterial barrier will now be described with reference to Figures 8 to 14.

Figure 8 is a perspective view showing a bacterial barrier 200 using a switchable adhesive composition in accordance with the invention in place on a patient's thigh 12, overlying a sutured wound 13. The bacterial barrier 200 in this view consists of a single layer 202 of cured adhesive composition, as will be explained in more detail below.

As shown in cross-sectional view in Figure 9, the bacterial barrier 200 is a multiple layer article, comprising a switchable adhesive composition layer 202 sandwiched between a first release liner 201 and a second release liner 203.

The first release liner 201 is a layer of siliconised plastic film, siliconised on the surface that faces the switchable adhesive composition layer 202. In addition, the first release liner 201 is an occlusive material that prevents visible light and UV light passing through it and reaching the underlying switchable adhesive composition layer 202.

The second release liner 203 comprises an occlusive layer 204 which prevents visible light and/or UV radiation from reaching the underlying switchable adhesive composition layer 202. The second release liner 203 also has a siliconised release layer 205, siliconised on the surface that faces the switchable adhesive composition layer 202. Siliconised layer 205 is transparent to visible light and UV radiation. The layers 204 and 205 of the second release liner 203 are held together by a very low peel strength adhesive (not shown) that enables the occlusive layer 204 to be removed preferentially, leaving the siliconised layer 205 in place whilst the curable molecules in the switchable adhesive composition layer 202 undergo curing by irradiation with visible light or by irradiation with UV light.

The occlusive first release liner 201 and the occlusive layer 204 of the second release liner 203 prevent inadvertent curing of the curable molecules in the switchable adhesive composition layer 202 before the intended time by preventing the switchable adhesive composition layer 202 from being exposed to visible light or UV light.

Figure 10 is a perspective view of the bacterial barrier 200 showing the removal of the first release liner 201 to expose the underlying switchable adhesive composition layer 202. The second release liner 203, comprising its occlusive layer 204 and its underlying siliconised release layer 205, is still in place on the other side of the switchable adhesive composition layer 202. After removal of the first release liner 201, the bacterial barrier 200 is quickly positioned over the site of the wound to be covered (see Figure 8) so as to minimise exposure of the switchable adhesive composition layer 202 to any radiation that might bring about curing of the curable molecules in the adhesive composition, and also to minimise exposure of the uncured adhesive composition layer to atmospheric oxygen. Positioning of the bacterial barrier is discussed in the next paragraph.

Figure 11 is a perspective view showing the remaining layers of the bacterial barrier being applied to the thigh 12 of a patient by the hands 20, 21 of a nurse or physician. In this view, the occlusive layer 204 of the second release liner is uppermost and the switchable adhesive composition layer 202 is the layer that is brought into contact with the skin of the patient. The siliconised release layer 205 of the second release liner is between the occlusive layer 204 and the switchable adhesive composition layer 202. Because the curable molecules of the adhesive composition of the adhesive layer are uncured at this stage, the switchable adhesive composition layer 202 is still in its viscoelastic state. In this state, the adhesive is able to flow into surface irregularities and pores of the skin to ensure intimate contact between the bacterial barrier in a surface and the patient's skin.

Figure 12 is a perspective view showing the physician's or nurse's hand 21 removing the light occlusive layer 204 from the second release liner of the bacterial barrier after the bacterial barrier has been positioned on the patient's thigh 12 over the wound intended to be covered. After removal of the occlusive layer 204, only the siliconised release layer 205 remains of the second release liner. The switchable adhesive composition layer 202 is beneath the siliconised release liner 205 and in contact with the skin of the patient's thigh 12. The siliconised release layer 205 is transparent to visible light and/or UV light, for reasons which will be explained below.

Figure 13 is a perspective view of the bacterial barrier 200 in position on the thigh 12 of the patient and undergoing irradiation, in this example from a lamp 60, to effect cure of the curable molecules in the adhesive composition of the adhesive layer 202. The light from the lamp 60 (visible light or UV light, preferably long wavelength UV light) passes through the transparent siliconised release layer 205 to the underlying adhesive layer 202 to initiate curing of the curable molecules in the adhesive composition. Curing transforms the adhesive composition layer from its viscoelastic state to an elastic state. Curing also transforms the adhesive composition layer from a tacky state to a non-tacky or low-tack state. However, by virtue of the siliconised coating on the release layer 205, the cured adhesive composition is able to be left in place on the patient's skin after the siliconised release layer 205 is removed, as discussed below.

The transparent siliconised release layer 205 is retained in place over the adhesive layer 202 during the curing step to prevent oxygen in the ambient air from reacting with the adhesive composition as the curable molecules in the adhesive mixture undergo curing. Exposure to oxygen during curing causes the upper surface (i.e., the non skin contact surface) of the adhesive composition layer to remain slightly tacky after curing is complete. This slight tackiness is preferably avoided in a bacterial barrier because it may result in foreign objects (fluff, dust, etc.) becoming stuck to the bacterial barrier. Also, the slight tackiness may cause the bacterial barrier to be unintentionally removed, for example by being abraded by contact with the patient's clothes. By retaining the siliconised release layer 205 in place over the adhesive layer 202 and curing the curable molecules in the adhesive layer 202 by irradiation through the siliconised release layer 205, the occurrence of surface tackiness in the cured adhesive composition layer is avoided.

Figure 14 is a perspective view showing the physician's or nurse's hand 21 removing the siliconised release layer 205 from the adhesive layer 202 of the bacterial barrier after the curable molecules in the adhesive composition of the adhesive layer 202 have been cured. After removal of the siliconised release layer 205, only the cured adhesive composition layer 202 remains on the patient's thigh 12.

As mentioned above, in the cured state, the adhesive composition of the adhesive layer 202 is transformed from its initial viscoelastic state to an elastic state. In this state, the adhesive layer remains firmly stuck to the patient's skin but, by virtue of its elasticity, the adhesive layer is able to move with the patient's skin as the patient moves. The cured adhesive composition layer is an effective barrier to bacteria. Any bacteria that remained on the surface of the patient's skin after preliminary antibacterial swabbing become immobilised in the cured adhesive composition layer and migration to the site of the wound is thereby inhibited. The bacterial barrier is also a mechanical barrier against dirt and other foreign particles and substances.

Referring again to Figure 8, the cured adhesive composition layer 202 of the bacterial barrier remains in position on the patient's skin over the wound 13. In practice, the wound 13 may be a wound that has arisen as a result of trauma to the patient or, as discussed above in relation to the first embodiment, the wound 13 may be the site of a surgeon's incision which has been sutured, stapled or taped closed after completion of the surgery.

The bacterial barrier is breathable and allows moisture to escape from the pores of the patient's skin. Moreover, the cured adhesive composition layer 202 has good water resistance and does not require special care by the patient when bathing or showering. Preferably, the cured adhesive composition layer 202 is transparent to allow inspection of the underlying skin surface without needing to remove the bacterial barrier.

The adhesive composition layer 202 is gradually sloughed away with the shedding of skin cells from the surface of the patient's skin as wound healing progresses.

Third Embodiment

A third embodiment using the present invention in the form of a skin closure film will now be described with reference to Figures 15 to 20.

Figure 15 is a perspective view showing a skin closure film 300 using a switchable adhesive composition in accordance with the invention being applied in place on a patient's forearm 14 for closing a gaping wound 15. The skin edges of the gaping wound 15 are shown being progressively urged together by the physician's or nurse's hand 21 as the skin closure film 300 is applied over the newly closed part of the wound 15. The second hand that the physician or nurse uses to apply the skin closure film 300 progressively to the newly closed part of the wound 15 is omitted from this view for reasons of clarity. The skin closure film 300 applied at this stage is a multiple layer product, as will be explained in more detail below.

As shown in cross-sectional view in Figure 16, the skin closure laminate 300 is a multiple layer article comprising a switchable adhesive composition layer 302 sandwiched between a first release liner 301 and a second release liner 303.

The first release liner 301 is a layer of siliconised plastic film, siliconised on the surface that faces the switchable adhesive composition layer 302. In addition, the first release liner 301 is an occlusive material that prevents visible light and/or UV passing through it and reaching the underlying switchable adhesive composition layer 302.

The second release liner 303 comprises an occlusive layer 304 which prevents visible light and/or UV radiation from reaching the underlying switchable adhesive composition layer 302. The second release liner 303 also has a siliconised release layer 305, siliconised on the surface that faces the switchable adhesive composition layer 302. Siliconised layer 305 is transparent to visible light and UV radiation. The layers 304 and 305 of the second release liner 303 are held together by a very low peel strength adhesive (not shown) that enables the occlusive layer 304 to be removed preferentially, leaving the siliconised layer 305 in place whilst the switchable adhesive composition layer 302 undergoes curing by irradiation with visible light or by irradiation with UV light.

The occlusive first release liner 301 and the occlusive layer 304 of the second release liner 303 prevent inadvertent curing of the curable molecules in the switchable adhesive composition layer 302 before the intended time by preventing the switchable adhesive composition layer 302 from being exposed to visible light or UV light.

Figure 17 is a perspective view of the skin closure laminate 300 showing the removal of the first release liner 301 to uncover the underlying switchable adhesive composition layer 302. The second release liner 303, comprising its occlusive layer 304 and its underlying siliconised release layer 305, is still in place on the other side of the switchable adhesive composition layer 302. After removal of the first release liner 301, the skin closure laminate 300 is preferably quickly positioned over the site of the wound to be closed (see Figure 15) so as to minimise exposure of the switchable adhesive composition layer 302 to any radiation that might bring about curing of the curable molecules in the adhesive, and also to minimise exposure of the uncured adhesive composition to atmospheric oxygen. Positioning of the skin closure laminate is discussed in the next paragraph.

Returning to Figure 15, this is a perspective view showing the remaining layers of the skin closure laminate being applied to the forearm 14 of a patient by a nurse or physician. In this view, the occlusive layer 304 of the second release liner is uppermost and the switchable adhesive composition layer 302 is the layer that is brought into contact with the skin of the patient. The siliconised release layer 305 of the second release liner is between the occlusive layer 304 and the switchable adhesive composition layer 302. Because the curable molecules in the adhesive composition of the adhesive layer are uncured at this stage, the switchable adhesive composition layer 302 is still in its viscoelastic state. In this state, the adhesive is able to flow into surface irregularities and pores of the skin to ensure intimate contact between the skin closure film and the patient's skin. Figure 18 is a perspective view showing the physician's or nurse's hand 21 removing the light occlusive layer 304 from the second release liner of the skin closure laminate after the skin closure laminate has been positioned on the patient's forearm 14 over the closed wound. After removal of the occlusive layer 304, only the siliconised release layer 305 remains of the second release liner. The switchable adhesive composition layer 302 is beneath the siliconised release liner 305 and in contact with the skin of the patient's forearm 14. The siliconised release layer 305 is transparent to visible light and/or UV light, for reasons which will be explained below.

Figure 19 is a perspective view of the skin closure laminate 300 in position on the forearm 14 of the patient and undergoing irradiation, in this example from a lamp 60, to effect cure of the curable molecules in the adhesive composition of the adhesive layer 302. The light from the lamp 60 (visible light or UV light - long wavelength UV is the preferred form of UV light) passes through the transparent siliconised release layer 305 to the underlying adhesive layer 302 to initiate curing of the curable molecules in the adhesive composition. Curing transforms the adhesive composition layer from its viscoelastic state to an elastic state. Curing also transforms the adhesive composition layer from a tacky state to a non-tacky or low- tack state. However, by virtue of the siliconised coating on the release layer 305, the cured adhesive composition is able to be left in place on the patient's skin after the siliconised release layer 305 is removed, as discussed below.

The transparent siliconised release layer 305 is retained in place over the adhesive layer 302 during the curing step to prevent oxygen in the ambient air from reacting with the adhesive as the curable molecules in the adhesive mixture undergo curing. Exposure to oxygen during curing causes the upper surface (i.e., the non skin contact surface) of the adhesive composition layer 302 to remain slightly tacky after curing is complete. This slight tackiness is preferably avoided in a skin closure product because it may result in foreign objects (fluff, dust, etc.) becoming stuck to the skin closure film. Also, the slight tackiness may cause the skin closure film to be prematurely removed, for example by being abraded by contact with the patient's clothes. By retaining the siliconised release layer 305 in place over the adhesive layer 302 and curing the curable molecules in the adhesive layer 302 by irradiation through the siliconised release layer 305, the occurrence of surface tackiness in the cured adhesive composition layer is avoided.

Figure 20 is a perspective view showing the physician's or nurse's hand 21 removing the siliconised release layer 305 from the adhesive layer 302 of the skin closure film after the curable molecules in the adhesive composition of the adhesive layer 302 have been cured. After removal of the siliconised release layer 305, only the cured adhesive composition layer 302 remains on the patient's forearm 14.

As mentioned above, in the cured state, the adhesive composition of the adhesive layer 302 is transformed from its initial viscoelastic state to an elastic state. In the elastic state, the adhesive composition layer 302 remains firmly stuck to the patient's skin but, by virtue of its elasticity, the adhesive layer is able to move with the patient's skin as the patient moves. The cured adhesive composition layer is an effective barrier to bacteria. Any bacteria that remained on the surface of the patient's skin after preliminary antibacterial swabbing become immobilised in the cured adhesive composition layer and migration to the site of the wound is thereby inhibited. The cured adhesive composition layer 302 is also a mechanical barrier against dirt and other foreign particles and substances.

The cured adhesive composition layer 302 of the skin closure film remains in position on the patient's skin over the wound 15. The skin closure film is breathable and allows moisture, including sweat, to escape from the pores of the patient's skin. Moreover, the cured adhesive composition layer 302 has good water resistance and does not require special care by the patient when bathing or showering. Preferably, the cured adhesive composition layer 302 is transparent to allow inspection of the underlying skin surface without needing to remove the skin closure film.

The adhesive composition layer 302 is gradually sloughed away with the shedding of skin cells from the surface of the patient's skin as wound healing progresses.

Although the first, second and third embodiments have been described above in terms of a particular construction for the laminated product, the present invention is not limited to such a construction.

For example, at least the first release liner may have a tab that is not coated with the adhesive composition, the tab serving to facilitate handling of the laminated product so that the release liner can be separated from the adhesive composition layer without the adhesive composition layer coming into contact with the physician's or nurse's fingers or gloves. A non-adhesive-coated tab may also be provided on the second release liner to assist in its removal from the adhesive composition layer after the curable molecules in the adhesive composition layer have undergone their curing reaction to transform the adhesive composition layer from its viscoelastic state to its elastic state.

The first release liner does not need to be formed of a light occlusive material. If the packaging for the laminated product is light occlusive, the first release liner may be transparent though, of course, the first release liner will need to be removed quickly and the laminated product will need to be applied quickly to the patient's skin if the photoinitiator in the adhesive composition layer is activated by visible light. The need for quick deployment of the laminated product is not as critical for adhesive composition layers that use a photoinitiator responsive to UV light but not responsive to visible light.

Similarly, the second release liner does not need to have a light occlusive layer. If the second release liner consists of two layers as in the first, second and third embodiments described above (light occlusive layers 104, 204, 304 and siliconised release layers 105, 205 305), the layers do not have to be stuck together using a low peel strength adhesive. As an alternative, for example, they may be heat laminated together.

The release liners may be siliconised paper rather than siliconised plastic films.

100% transparency is not essential for the second release liner. It may be semi-transparent provided that it allows sufficient light (visible light and/or UV light) to pass through it to enable photoinitiated radical reaction of the curable molecules in the underlying adhesive composition layer.

Fourth Embodiment

A fourth embodiment of the present invention in the form of an alternative skin closure product will now be described with reference to Figures 21 to 23. Figure 21 is a perspective view showing a skin closure product 400 in accordance with the fourth embodiment of the invention being applied in place on a patient's forearm 14 for closing a gaping wound 15. The skin edges of the gaping wound 15 are shown being urged together by stretching the ends of the wound apart by the thumb and forefinger of the physician's or nurse's hand 21 as the skin closure product 400, in the form of a switchable viscoelastic composition that is curable by free radical polymerisation, is dispensed from a tube 90. After dispensing the composition onto the patient's skin, the physician or nurse may, if necessary, use a spatula or similar tool held in his or her free hand to spread the composition over the wound site to achieve a skin closure film 402 of substantially even thickness.

Figure 22 is a perspective view of the skin closure film 402 in position on the skin of the patient and undergoing irradiation, in this example from a lamp 60, to effect cure of the curable molecules in the adhesive composition whilst the skin edges of the gaping wound 15 are still being urged together by the thumb and forefinger of the physician's or nurse's hand 21 stretching the ends of the wound apart. The light from the lamp 60 (visible light or UV light, preferably long wavelength UV light) initiates curing of the curable molecules ir. the adhesive composition. Curing of the curable molecules transforms the skin closure composition from its viscoelastic state to an elastic state.

Although Figures 21 and 22 show the skin edges of the wound 15 being urged together by the action of stretching the patient's skin at the ends of the wound in the longitudinal direction of the wound, it will be understood that squeezing the skin edges together may be a more suitable technique. Also, more than one hand may be needed to urge the skin edges of the wound together over the entire length of the wound. In these circumstances, a second physician or nurse may assist by dispensing the skin closure composition onto the site of the wound.

Preferably, the skin closure composition in the tube 90 contains only a minor amount of an adhesive polymer constituent, since a substantial proportion of adhesive polymer constituent would make the skin closure composition very viscous and therefore difficult to dispense from a tube. Hence, the purpose of adding an adhesive polymer constituent is for adjustment of the viscosity of the skin closure composition. The viscosity of the skin closure composition is preferably in the range 1 to 100,000 mPa.s, more preferably 100 to 20,000 mPa.s. For example, the skin closure composition may contain up to 10% by weight of an adhesive polymer constituent. More preferably, the skin closure composition contains up to 5% by weight of the adhesive polymer constituent. The adhesive may be a hot melt acrylic material such as Nanostrength M65 or Nanostrength M75. More preferably, the skin closure composition has no adhesive polymer constituent and is comprised mainly of curable molecules curable by free radical polymerization, with photoinitiator and minor incidental ingredients.

After curing, the skin closure film 402 in its elastic state is able to hold the skin edges of the wound 15 together without requiring the assistance of the physician's or nurse's hand 21. Figure 23 is a perspective view of the cured skin closure film 402 in place on the patient's skin, overlying the closed wound.

As mentioned above, in the cured state, the composition of the skin closure film 402 is transformed from its initial viscoelastic state to an elastic state. In the elastic state, the skin closure film remains firmly stuck to the patient's skin. Moreover, the cured skin closure composition layer is an effective barrier to bacteria. Any bacteria that remained on the surface of the patient's skin after preliminary antibacterial swabbing become immobilised in the cured skin closure composition layer and migration to the site of the wound is thereby inhibited. The skin closure film 402 is also a mechanical barrier against dirt and other foreign particles and substances.

The skin closure film 402 thus remains in position on the patient's skin over the wound 15. The skin closure film is breathable and allows moisture to escape from the pores of the patient's skin. Moreover, the skin closure film 400 has good water resistance and does not require special care by the patient when bathing or showering. Preferably, the cured skin closure film 402 is transparent to allow inspection of the underlying skin surface without needing to remove the skin closure film. The skin closure film 402 is gradually sloughed away with the shedding of skin cells from the surface of the patient's skin as wound healing progresses.

Exposure to oxygen during curing causes the uppermost surface of the skin closure film 402 (i.e., the surface not in contact with the patient's skin) to remain slightly tacky after curing is complete. However, this slight tackiness can be counteracted by dusting the skin closure film 402 with talc.

Alternatively, the cured skin closure film 402 can be overlaid with a bacterial barrier 200 of the type described above in the discussion of the second embodiment, the curable molecules in the adhesive composition layer 202 of the bacterial barrier being cured by irradiation using visible light or UV light passing through the siliconised release layer 205 that lies over the adhesive layer 202. Curing the curable molecules in the adhesive composition layer 202 in this way avoids surface tackiness whilst the surface tackiness of the underlying skin closure film 402 helps to keep the bacterial barrier in place. As previously described, the siliconised release layer 205 is removed from the adhesive layer 202 of the bacterial barrier after the curable molecules in the adhesive composition of the adhesive layer 202 have been cured.

The combined skin closure film 402 and adhesive layer 202 gradually slough away with the shedding of skin cells from the surface of the patient's skin as wound healing progresses.

In yet another alternative to combat surface tackiness, the skin closure composition may include a component containing aliphatic thiol groups. Besides having oxygen-scavenging properties, the aliphatic thiols can also take part in the radical polymerization of the curable molecules via thiol-ene reactions. For a more effective contribution to the curing reaction, a component with two or more thiol groups could be used, such as trimethylolpropanetris(3-mercaptopropionate) or pentaerythritoltetrakis(2-mercaptoacetate). Amine synergists such as triethanol amine or ethyl-4-dimethylaminobenzoate could also be used to reduce oxygen inhibition of the radical polymerization at the exposed surface.

Examples

The invention will now be further illustrated with reference to Examples. Example 1

An adhesive composition was prepared by mixing the following components:

Component Amount (g)

GMS 3253 40

CN925 5

Desmolu XP2510 2

Irgacure 784 0.25

Irganox 1010 0.03

Example 2

An adhesive composition was prepared by mixing the following components:

Component Amount (g)

Aroset 1450 Z 40 40

Genomer 4297 6

Irgacure 819 0.5

Irganox 1010 0.10

Example 3

An adhesive composition was prepared by mixing the following components:

Component Amount (g)

Medfiex 5117 40

Genomer 4297 15

Irgacure 819 0.5

Irganox 1010 0.10 Example 4

An adhesive composition was prepared by mixing the following components:

Component Amount (g)

GMS 788 40

Genomer 4297 12

Melamine x-linker 0.35

Irgacure 369 0.24

Irganox 1010 0.03

Example 5

An adhesive composition was prepared by mixing the following components:

Component Amount (g)

Polytex SP8002 40

CN925 4.5

Irgacure 784 0.11

Irganox 1010 0.03

Example 6

An adhesive composition was prepared by mixing the following components:

Component Amount (g)

Polytex SP8002 40

CN925 4.5

Genocure EPD 0.3

Irgacure 784 0.11

Irganox 1010 0.03

Preparative details

All components in Examples 1 to 6 were loaded into a sealable glass jar and mixed to a homogenous solution over a period of approximately 60 minutes using a magnetic stirrer. The adhesive mixture was then spread onto an easy release liner using a spreader to a dry coating thickness of about 60 micrometer and left to dry at room temperature for ten minutes. The adhesive coating spread on the easy release liner was then further dried in a ventilated fan assisted oven at 100°C for an additional 5 minutes. Finally, a very easy release liner was applied to the other side of the adhesive coating in preparation for skin tests.

All procedures for Examples 1 , 5 and 6 (using Irgacure 784) were carried out under red light conditions.

The curable adhesives exemplified above in Examples 1 to 6 were applied to skin in the following way:

Prior to application, the very easy release liner (i.e., the release liner with easier release level) was removed and the curable adhesive with the remaining release liner was applied to a skin surface with the adhesive side facing the skin. The curable adhesive was exposed to UV light and/or visible light to effect cure and the remaining release liner was removed. A thin, flexible, cured adhesive film with high tensile strength remained on the skin protecting the underlying skin surface and adhering the skin surfaces together.

Example 7 - Comparison of peel forces for adhesive on skin and adhesive on release liner

Adhesion to skin

Because the tensile strength of the cured adhesive film is not sufficient to sustain the force when peeled from skin, a medical polyurethane film EU31 (supplied by Smith & Nephew Extruded Films Ltd) was laminated to the uncured adhesive instead of the first (very easy) release liner.

Accordingly, test samples were prepared by spreading the switchable adhesive composition in accordance with Example 5 above onto an easy (second) release liner using a spreader to a dry coating thickness of about 60 μιη and leaving it to dry at room temperature for 10 minutes. The adhesive coating spread on the easy release liner was then further dried in a ventilated assisted fan oven at 100°C for an additional 5 minutes. As indicated above, a medical polyurethane film EU 31 was then applied to the other side of the adhesive coating for skin tests. One forearm of the volunteers was washed gently with water and ordinary soap and dried a few minutes before application of the strips onto the volar aspect of the forearm. The release liner was removed and the strips, measuring 25x100mm, were applied to the volunteers in a room with light filters (UV Safety Sleeve / Type G10 - gold; cut off point at 520 nm supplied by Encapsulite International Ltd) covering the light sources, thus ensuring that the samples of the switchable adhesive composition did not switch during the application step. All strips were attached by rolling a standard Finat test roller three times forwards and backwards over each tape at a speed of 1cm per second, thus firming them to the skin in a controlled manner.

The strips were then illuminated for 30 seconds with a 500w halogen lamp at a light intensity of 20000 Lux before the peel tests were conducted.

The strips were then peeled from the skin, maintaining as far as possible a 45° angle between the skin surface and the direction of the applied peel force using an Instron 5943 tensile tester machine with a speed of 300mm/minute. The peeling procedure is illustrated in Figure 24, in which arrow T indicates the plane of the strips before peeling and arrow F indicates the direction of the applied peel force.

The peel force was recorded and the average value was calculated. The results are presented in the table below, which shows the peel force value for six healthy volunteers, as well as the average value of the peel tests.

Table 2 - Peel force for adhesive applied to skin

Peel force N/25mm

Volunteer no.

Example 5 adhesive

1 1.0

2 1.3

3 1.7

4 1.0

5 1.7

6 2.7

Average 1.6 Adhesion to release liner

In order to perform this part of the test under conditions as similar as possible to the tests for adhesion to skin, the same laminate was used except that it was cut into 25x300mm strips. That is to say, test samples were prepared by spreading the Example 5 switchable adhesive composition onto an easy (second) release liner using a spreader to a dry coating thickness of about 60 μηι and leaving it to dry at room temperature for 10 minutes. The adhesive coating spread on the easy release liner was then further dried in a ventilated assisted fan oven at 100°C for an additional 5 minutes. A medical polyurethane film EU 31 was then applied to the other of the adhesive coating.

The switchable adhesive composition was then illuminated using a 500w halogen lamp at a light intensity of 20000 Lux for 30 seconds through the transparent polyurethane film.

Then the release liner was partially separated from the polyurethane film (with the switched adhesive composition layer adhered to it) and the separated parts were fixed to the lower and upper clamp of the tensile testing machine, respectively. The unseparated end of the laminate was allowed to hang freely and therefore the angle of peel was approximately 180°. The peel force test was performed at a jaw separation speed of 300mm/min and the average peel force was calculated for each of the six test strips.

The peel force was recorded and the average value was calculated. The results are presented in Table 3 below, which shows the peel force value for six samples, as well as the average value of the peel tests.

As can be seen from a comparison of the measured peel force values from Table 2 above and Table 3 below, the average peel force required to remove the switched adhesive from skin is about eight times higher than the average peel force required to remove the switched adhesive from a second (easy) release liner. The different angles of applied peel force in the skin peel force tests and the release liner peel force tests do not affect the values of peel force obtained, but were chosen for reasons of practicality. Note that an even lower average peel force would be required to remove the switched adhesive from a very easy release liner (first release liner). Hence, by selection of suitable release liners, the medical skin covering of the present invention can be made to stick preferentially to skin.

Example 8

An adhesive composition was prepared by mixing the following components:

Component Amount (g)

Genomer 4297 40

Irgacure 784 0.08

Irganox 1010 0.04

Example 9

An adhesive composition was prepared by mixing the following components:

Component Amount (g)

Genomer 4297 40

TriThiol 4

Irgacure784 0.08 Preparative details

All components in Examples 8 and 9 were loaded into a sealable glass jar and mixed to a homogenous solution over a period of approximately 60 minutes using a magnetic stirrer. The glass jar was covered with aluminium foil for light protection.

The curable compositions exemplified above in Examples 8 and 9 were applied to skin in the following way:

The curable composition was spread onto a skin surface with a spatula or other spreading tool. The curable composition was exposed to UV light and/or visible light to effect cure. A thin, flexible, cured film with high tensile strength remained on the skin, protecting the underlying skin surface and being suitable for adhering wound edges together.

Table 4 - Table of Suppliers

Component Description Supplier

Thermosetting acrylic solution

Aroset 1450 Z 40 Ashland Inc

Polymer content 40%

CN925 Aliphatic urethane tetraacrylate Sartomer Co. Inc

Desmolux Dual cure acrylate aliphatic Bayer MaterialScience XP2510 isocyanate oligomer AG

Bis.(.eta.5-cyclo-pentadienyl)-bis

Irgacure 784 (2,6-difluoro-3 - [pyrrol-l-yl] -phenyl) BASF AG

titanium

Bis(2,4,6-trimethylbenzoyl)-

Irgacure 819 BASF AG

phenylphosphineoxide

2-Benzyl-2-dimethylamino- 1 -(4-

Irgacure 369 BASF AG

morpholinophenyl)-butanone- 1

Pentaerythritol Tetrakis(3-(3,5-di-

Irganox 1010 tert-butyl-4-hydroxyphenyl) BASF AG

propionate Table 4 - Table of Suppliers

Component Description Supplier

Non-functional, non-crosslinkable

GMS 3253 Cytec

high glass temperature material

Crosslinkable acrylic solution

GMS 788 Cytec

Polymer content 40%

Medflex 5117 Acrylic/vinyl copolymer ATR Chemicals

Genomer 4297 Aliphatic Urethane methacrylate Rahn AG

Poly(melamine-co-formaldehyde)

Melamine x-linker Sigma Aldrich

methylated 84 wt% in 1-butanol

Block styrene-Block butylacrylate

Nanostrength M75 Arkema

Block styrene copolymer

Acrylic solution

Polytex SP8002 Avery Dennison

Polymer content 44%

Genocure EPD Ethyl-4-dimethylaminobenzoate Rahn AG

Trimethylolpropanetris(3 -

TriThiol Sigma Aldrich

mercaptopropionate)

Although the invention has been particularly described above by reference to particular applications (surgical incision drape, bacterial barrier, skin closure products) and with reference to specific examples of compositions, the invention may find use in other applications.

For example, the invention may be adapted for use in wound dressings where the wound dressing is a laminated product comprising a wound pad surrounded by a layer of the switchable adhesive composition, the wound pad and the curable adhesive composition layer being sandwiched between a first release liner and a second release liner. The first release liner may be a layer of siliconised plastic film, siliconised on the surface that faces the adhesive layer, and may be formed of an occlusive material that prevents visible light and UV light passing through it and reaching the underlying adhesive layer. The second release liner may include a light occlusive layer that prevents visible light and/or UV radiation from reaching the underlying adhesive layer. The second release liner may also have a siliconised release layer siliconised on the surface that faces the adhesive layer. The siliconised release layer of the second release liner is transparent to visible light and UV radiation. The two layers of the second release liner may be held together by a very low peel strength adhesive that enables the occlusive layer to be removed preferentially, leaving the siliconised release layer in place whilst the curable molecules in the adhesive layer undergo curing by irradiation with visible light or by irradiation with UV light.

The wound dressing is applied by removing the first release liner to expose the underlying adhesive layer and wound pad; the wound pad is then positioned over the wound and the surrounding adhesive layer is pressed on to the patient's skin by pressing the wound dressing from the second release liner side.

Then the light occlusive layer of the second release liner is removed and the adhesive layer is exposed to visible light and/or UV light to effect curing of the curable molecules in the adhesive layer.

After curing, the siliconised release layer of the second release liner is removed leaving the wound pad and cured adhesive layer in place on the patient's skin.

This arrangement has the advantages over known wound pads of increased breathability and increased flexibility (conformability with the patient's skin) because of the absence of a carrier film, the second release liner being discarded after curing.

The present invention can also be used to attach electrodes to skin. For example, electrodes that are attached to skin for measuring stress levels of an individual (e.g. during physical exertion) are susceptible to detachment due to sweating. The adhesive composition of the present invention is able to secure electrodes in place on an individual's skin even under conditions of excessive sweating because of the superior breathability that ensues from using an adhesive layer only and no carrier film. The individual's sweat is able to pass through the adhesive layer and evaporate whilst electrodes remain adhered to the skin. Moreover, the absence of a carrier film results in increased flexibility, so the electrodes secured to the individual's skin by the adhesive composition of the present invention remain firmly fixed in position even during physical exertion that fiexes the skin.

Similarly, the present invention may be used to attach other items to skin, such as electrical leads and tubes for delivery and removal of fluids.

Preferably, the laminated products of the present invention are packaged in packaging materials that minimise exposure of the products to visible light and/or UV light. For example, the packaging may consist of a part plastic film and a part paper packet, the paper part being porous to allow passage of ethylene oxide into the packet interior for purposes of sterilisation.

Advantages over prior art

Compared to existing systems, the present invention has the following benefits.

• Faster to use for skin closure than conventional sutures, staples or adhesive tapes

• Simple to handle - no extensive training is necessary

• No risk of needle sticks

• No need for removal, the adhesive will slough off naturally

• Gives a microbial barrier

• Protects wound against dirt and rubbing

• Comfortable to wear

• No poisonous vapour upon curing

• No heavy exothermic reaction

• No risk of burning sensation

• Using the pre-laminated product facilitates handling of the adhesive layer - without a supporting release liner, positioning of the adhesive layer is difficult because the uncured adhesive is flimsy and not self-supporting

• Using the pre-laminated product, there is no risk of runoff of adhesive flowing into the wound causing tattooing

• Using the pre-laminated product, there is no risk of spillage into eyes

• No risk of adhering foreign objects into wound

• No risk of fingertip or glove adhering to adhesive

• Shower-proof straight away after application • Low manufacturing cost

• As good as or better scar cosmetics

• Non-invasive - less tissue trauma, reducing inflammatory reaction.

• Preventing translocation of local skin flora.

• Clear wound site visualisation - no need to remove any dressings and potentially disrupt wound healing.