AU8434791A

AU8434791A - Bilayer wound dressing

Info

Publication number: AU8434791A
Application number: AU84347/91A
Authority: AU
Inventors: James E Guillet; D. Gary Murray
Original assignee: Medipro Sciences Ltd
Current assignee: Medipro Sciences Ltd
Priority date: 1990-09-17
Filing date: 1991-09-12
Publication date: 1992-04-15
Anticipated expiration: 2011-09-12
Also published as: KR930702033A; EP0544778A1; WO1992004923A1; CA2092704A1; AU649475B2; JPH06501857A

Description

BILAYERWOUND DRESSING

This invention relates to wound coverings, of the type commonly applied adhesively to minor cuts, burns, post-operative incision sites and wounds. More particular¬ ly, the invention relates to adhesive bandages or patches which are applied domestically to cover and protect such wounds, by adhesion to the wound itself or to its periph¬ ery. The best known examples of such adhesive patches are those sold under the names BAND-AID (trade-mark of Johnson & Johnson, Inc.), ELASTOPLAST (trade-mark of Smith & Nephew Limited) and HANSAPLAST (trade-mark of Beiersdorf A.G.).

These familiar strip bandages commonly comprise a patch of sterile gauze mounted on a plastic or fabric strip, with an adhesive coating for attachment to the skin. The gauze may be covered with a perforated plastic strip, to prevent adhesion of the gauze to the wound surface. It is known also to incorporate medicaments such as antisep¬ tics in the gauze patches thereof.

Although simple, convenient and generally effec¬ tive in their use on the household or domestic scale, the commonly available strip bandages have certain disadvan¬ tages. For example, frequent and sometimes painful changes of such bandages are necessary in order to check the healing process and apply medications. In many cases moisture cannot adequately escape through them, so that the tissue swells and healing is retarded. When the wound site is washed, the bandage may be removed or loosened. When it is wetted, a retained water layer in the fibrous material favours microbial growth and swelling of the tissue. Application to highly contoured parts of the body is difficult.

An important factor in the wound healing process is the maintenance of an appropriately moist environment around the wound site. Wound coverings which may protect the wound site from contamination, or which promote drying and scab formation, are not totally satisfactory. The healing process is better promoted by contact of the wound with an appropriately moisture controlled atmosphere, as well as protection of the wound from contamination.

U.S. Patent 4.750,482 (Sieverdinσ) discloses a water-insoluble, hydrophilic, pressure-sensitive adhesive useful for attaching electrodes and wound dressings and the like to mammalian tissue. The adhesive composition includes an irradiation crosslinked synthetic organic polymer formed from a solution or dispersion of at least one gel-forming, uncrosslinked synthetic organic polymer, in the solubilizing plasticizer. On irradiation crosslink- ing, a gel is formed which retains a solubilizing plasticizer within the three dimensional network. Poly¬ acrylic acid admixed with polyethylene oxide, in the weight ratio of 14:1, is given as one example of an uncrosslinked synthetic organic polymer suitable for subsequent irradi¬ ation crosslinking. The solubilizing plasticizer includes a non-volatile elasticizer, which is generally a liquid at room temperature.

Canadian Patent 1.180.244 fMuchin) discloses a medical covering for adhesive fixing to a subject, and comprising a stretchable film sheet of polyurethane or other copolymer material carrying an adhesive on one surface, and an unstretchable, rigid film sheet carrier on the opposed surface, removable from the stretchable sheet after adhesive application of the assembly to a patient. The adhesive is of conventional form.

U.S. Patent 3.419.006 CKinσ) discloses a polyethylene oxide polymer complex dressing. The polymer complexes disclosed have a very high water content. An object of the present invention is to provide novel skin and wound coverings employing polymer complexes as skin and wound contacting material.

The present invention provides a novel adhesive covering for application to skin lesions (this term being understood to cover cuts, burns, abrasions, lesions due to skin infection or skin disorder, post-operative incision sites and other skin damaged or skin punctured locations) as well as bruised areas and skin locations overlying damaged or inflamed tissues, bruised bones or muscles which can when appropriate be applied at the domestic or house¬ hold level. The adhesive covering according to this invention has a water vapour permeable self-supporting outer backing layer and a wound contacting layer of biocom¬ patible high water content polymer complex capable of adhering to the wound site, and supported by the backing layer. It has been found according to the present inven¬ tion that biocompatible, wound and skin adhesive polymer complexes as described herein, in combination with an appropriate backing layer, provide a highly satisfactory, controlled-moisture environment for the promotion of healing of skin lesions.

The polymer complexes used as the skin lesion- contacting layer in the products of the present invention are tacky, solid or semi-solid materials. In order for them to be skin adherent, they typically have a water content of from about 20 - 70% by weight. The complexes are swellable in water but essentially water-insoluble. They are prepared by coprecipitation from mixed solutions, preferably aqueous solutions, of at least two hydrophillic polymers, followed by removal of the coprecipitate from the medium, optionally followed by adjustment of the residual water content of the coprecipitate. The polymer complexes lose substantial amounts of water when exposed to a normal room environment, but this is essentially reversible upon immersion in water or exposure to very high humidity. The polymer complexes are inter-reacted products of the indi¬ vidual polymers in the sense that they are not physically separable into their individual polymeric constituents, but are essentially chemically non-crosslinked. Tackiness of them is increased by moistening.

Thus according to one aspect of the present invention, there is provided an adhesive covering suitable for adhesive attachment to mammalian tissue for contacting treatment areas thereof, and comprising:

an outer layer of self-supporting, water vapour permeable film;

an inner, treatment-area contacting layer of high water content, tacky polymer complex supported by the outer layer;

the polymer complex layer composition being substantially wound- and skin-compatible, having a water content sufficient to render it skin-adhesive, and compris¬ ing the tacky, polymer complex product produced by copreci- pitation as a result of mixing solutions of first and second coprecipitatable hydrophilic polymers, and optional¬ ly adjusting the water content thereof.

According to another aspect of the invention, there is provided a process for making an adhesive covering material suitable for adhesive attachment to mammalian tissue for contacting treatment areas thereof, which comprises:

mixing together solutions of coprecipitatable, hydrophilic polymers and forming a solid or semi-solid coprecipitated wound-compatible polymer complex thereof;

forming a laminate of said polymer complex with a self-supporting water vapour-permeable film by applica¬ tion of the polymer complex to a surface of said film;

and, before or after its application to the film surface, if necessary, adjusting the water content of said polymer complex as necessary to render it skin adhesive.

The coverings of the present invention are thus produced by a simple procedure easily adapted to an econ¬ omically large scale, in order to produce materials of the desired structure and composition.

In the accompanying drawings:

FIGURE 1A is a diagrammatic cross-section of a basic structure of a packaged bilayer adhesive wound dressing of the invention;

FIGURE IB and FIGURE 1C are similar views of modifications of the embodiment of FIGURE 1A;

FIGURE 2 is a similar diagrammatic cross-section of an alternative embodiment of the invention;

FIGURE 3A is a similar diagrammatic cross-section of a further embodiment of the invention;

FIGURE 3B is a similar view of a modified form of the FIGURE 3A embodiment;

FIGURE 3C is an underneath plan view of the embodiment of FIGURE 3A and FIGURE 3B with the bottom release sheet removed for application;

FIGURE 4 is a similar diagrammatic cross-section of a further embodiment of the invention;

FIGURE 5 and 6 are similar diagrammatic cross- sections of further and most preferred embodiments of the invention, in packaged form. In the drawings, like reference numerals indicate like parts.

With reference to FIGURE 1 of the accompanying drawings, this basic embodiment includes an outer package 13 with good water vapour barrier properties to enclose an atmosphere 20 of high humidity around the packaged wound covering. The wound covering itself comprises a self- supporting layer 22 of film (optionally perforated) , foam or fabric of high water vapour transmission, a polymer complex layer 24 supported by layer 22 and release sheet 30 protecting the undersurface of the polymer complex layer 24. Release sheet 30 is provided with an end-projecting tab 32 to facilitate its removal prior to application. In the modification shown in FIGURE IB, the tab is replaced by an integral lateral extension 32b. In the modification shown in FIGURE 1C, the release sheet 30 is provided in two parts, each with a projection 32c to facilitate removal. The high humidity atmosphere 20 within the package 13 prevents drying out of the polymer complex layer 24. Release sheet 30 prevents adhesion of the assembly to the package.

With reference to FIGURE 2, the embodiment shown thereon (omitting the package) is essentially similar to that of FIGURE 1 with the difference that an adhesive layer 26 is interposed between the top, self-supporting layer 22 and the polymer complex 24, to improve the adhesion of the polymer complex to the supporting carrier layer. The combination of adhesive layer 26 and self-supporting layer 22 must have adequate water vapour transmission.

With reference to FIGURE 3A, this embodiment (also omitting the package) includes a rim 36 of adhesive material surrounding the polymer complex layer 24. The adhesive rim 36 is provided on the underside of the lat¬ erally extending periphery of the self-supporting layer 22. In FIGURE 3A, this rim 36 constitutes the only portion of adhesive, other than polymer complex 24, in the structure. In FIGURE 3B, this rim 36 is formed by the peripheral extension of the adhesive layer 26, which bonds the self- supporting layer 22 to the polymer complex layer 24, beyond the layer 24. In either case the adhesive rim 36 is dis¬ posed between the top layer and the release sheet 30, to become exposed for skin adhesion when the release sheet 30 is removed. Then the underneath of the assembly has the appearance shown in FIGURE 3C in either embodiment. The adhesive 26 in this embodiment is skin compatible.

With reference to FIGURE 4, this embodiment includes a covering for the top layer 22, in the form of a self-supporting film 34 and a weak adhesive layer 46 to attach film 34 to top layer 22. Tabs 42 and 32 are pro¬ vided to facilitate the removal of the release sheets 34 and 30 respectively. With this embodiment, the top layer 22 is protected until application. The weak adhesive layer 46 should be strong enough to hold the film 34 in position while release sheet 30 is removed. Adhesive 46 remains attached to film 34 after removal of film 34 from the structure.

The embodiments shown in FIGURES 5 and 6, which are the most preferred embodiments, have a release sheet 34 attached over the top layer 22, as in the embodiment shown in FIGURE 4. In the FIGURE 5 embodiment, the upper release sheet 34 has a lateral extension 43 forming a tab to facilitate its removal, and is attached to the top layer 22 by means of an adhesive layer 46. The portion of the adhesive layer 46 underlying the extension 43 is provided with a protective patch 44 of suitable material. The release sheet 30 covering the polymer complex layer 24 has a tab 32 to facilitate its removal. An adhesive layer 26 is provided, as in FIGURE 3B, to protrude peripherally beyond the layer 24 for adhesion to the skin. The whole is packaged in a sealed outer package 13, preferably contain¬ ing an atmosphere of high humidity, to keep the polymer complex 24 in moist condition prior to application. The package 13 is suitably of aluminum foil/thermoplastic laminate or metallized thermoplastic film, so as to be heat sealable. The heat seal should allow convenient package opening by peeling apart of the package edges. Alterna¬ tively, the package may be suitably marginally notched for ease of opening. In the FIGURE 6 embodiment, the release sheet 34 is non-adhesively attached to the top layer 22, e.g. by solution casting of the top layer 22 onto the release sheet surface. Otherwise it is the same as the FIGURE 5 embodiment.

It will be appreciated that the illustrated embodiments are exemplary only, and do not limit the scope of the invention.

In use, the sealed outer package is opened and the assembly removed from its package. The release sheet 30 covering the polymer complex layer 24 is removed and the patch is applied to the wound site with the layer 24 contacting the wound. Adhesion of the patch to the wound is effected by the inherently adhesive nature of the polymer complex layer 24 and, in the embodiments of FIGURES 3, 5 and 6, by the adhesion of the peripheral adhesive layer 36 to the skin surrounding of the wound site. Substantially immediately after the patch has been applied to the wound site, pressure can be applied on or through the top layer 22, to retard bleeding from the wound site. Thereafter, the patch provides an appropriately moist environment to the wound site. The polymer complex compositions used as the wound-contacting layer in the coverings of the present invention are substantially wound compatible and skin compatible. The term "wound compatible" used herein describes materials which can be applied to a flesh wound site of a human or other animal and will not deleteriously interfere with the normal healthy biological processes encountered at the wound site. The term "skin compatible" means not deleterious to normal healthy skin on which it is applied. The adhesive coverings of the present invention provide appropriate water vapour transmission between the wound site and the environment, and act as suitable bar¬ riers for the wound against microorganisms including viruses, and against harmful contaminations and physical contact damage, which would otherwise impede the healing process. After removal of these adhesive coverings, the skin surrounding the wound area is relatively free from swelling and discoloration, largely due to the appropriate water vapour transmission properties of the assembly.

Both the polymer complex layer and the outer layer and, if present, the adhesive layer between them, remain overlying the wound after application, and can if desired be made transparent, so that the wound can be inspected and process in its healing can be monitored visually. Moreover, such an adhesive covering can be made cosmetically appealing, e.g. by coloration, opacity or gloss reduction, and can carry medication to treat the wound site. These layers are all suitably permeable to water vapour, for best healing properties. Preferably, they are also oxygen permeable.

The polymer complexes used in the present inven¬ tion are wound compatible, tacky products produced by coprecipitation from solution of at least two water-sol¬ uble, hydrophilic polymers. Preferably, the polymers are coprecipitated form aqueous solution. The two polymers are chosen, in relationship to one another so that, when solutions of the two polymers are mixed together, a copre¬ cipitate of the two polymers forms, either on mixing, after standing, or on subsequent concentration of, pH adjustment of or addition of a suitable solute to, the resultant solution.

The coprecipitate is usually of a semi-solid "gummy¹* consistency, and may be separated by decantation and dissolved in an appropriate solvent such as aqueous ethanol, aqueous acetone or aqueous isopropanol, at room or slightly elevated temperatures. Then this solution can be applied to the self-supporting, outer layer and allowed to dry. Alternatively, the polymer solution may be cast on a suitable transfer surface, allowed to dry, applied to the self-supporting outer layer as a transfer coating and, if deemed necessary subsequently rehydrated to some extent to increase tack, before the final assembly of the product, with release sheets etc. Preferred polymer complexes used in the present invention are those which can be dried to a non-tacky, self supporting film, and subsequently remoist- ened to a tacky condition. Such materials are convenient to handle in their dry film form, e.g. in manufacturing and cutting machines.

If the gummy coprecipitate is sufficiently mobile at room cr elevated temperatures, dissolution in a solvent may not be necessary, and the coprecipitate may be case directly onto the outer layer or onto a suitable transfer surface. After formation and application to the self- supporting layer, the polymer complexes are preferably maintained in a moist condition until use, e.g. by packag¬ ing in a sealed, water vapour containing envelope as previ¬ ously described. When it is desired to add additional ingredients such as plasticizers, colourants, medicaments, etc. for incorporation in the polymer complex layer, these are suitably mixed with the coprecipitate or the coprecipitate solution.

Thus it is necessary, in accordance with the present invention, to choose polymers which are hydrophi¬ lic, water-soluble, coprecipitatable together from sol¬ utions, preferably aqueous solutions, to form a wound compatible polymer complex coprecipitate. The choice of first polymer may be made from polymers and copolymers of acrylic acid (PAA) , polymers and copolymers of methacrylic acid (PMA) , polymers and copolymers of itaconic acid (PIA) , polymers and copolymers of maleic acid (PMLA) , and combina¬ tions thereof. The second hydrophilic polymer may be selected from polymers or copolymers of vinyl pyrrolidone, polymers or copolymers of ethylene oxide, including copolymer combinations of propylene oxide and ethylene oxide [P(EO/PO)], chitosan, derivatives of chitosan such as N,0-carbomethoxy chitosan, gelatin, and combinations thereof.

At the time of application to the self-supporting layer and when packaged in the envelope, the polymer complex layer has a very substantial water content, i.e. 20 - 70% by weight of the total, the corresponding 80 - 30% by weight being solid polymer. After application to the wound site, the water content of the polymer complex comes to an equilibrium, dependent upon the rate of water vapour loss through the wound dressing as a whole, and the rate of water vapour production by the wound and skin beneath the dressing. The contact of the wound site with the assembly of the polymer complex of 20 - 70% water content and the self supporting layer has a beneficial effect on wound healing, by avoiding dehydration of the wound site. Additional benefits may be obtained, on occasion, by inclusion of appropriate medicaments such as antibiotics, anti-infectives, analgesics, antipruritics, growth factors and the like, in the polymer complex layer. Such materials are particularly easy to incorporate in the polymer com¬ plexes of the present invention, since the polymer com¬ plexes, after formation by coprecipitation, are subsequently redissolved in organic solvents, generally a particularly good medium in which to add the medicaments to the polymer complex.

Accordingly, the adhesive coverings of the present invention can serve as an especially useful trans- dermal drug delivery system, for example, for delivery of medicaments to alleviate the discomfort of muscle pains, bruises and the like. In addition, these adhesive coverings are particularly valuable for delivery of those drugs which penetrate the skin with difficulty and consequently are unsuitable for membrane rate controlling or membrane based transdermal drug delivery devices.

When adherent to a treatment site, the assembly of the polymer complex layer and the self-supporting backing film provides an effective barrier to microorgan¬ isms and other healing-inhibiting foreign substances. The adherent assembly will withstand immersion in sea water or tap water, or normal washing, and will withstand applica¬ tions of common skin creams and lotions.

The tacky polymer complex layer may also include a reinforcing mesh disposed within the thickness of the polymer complex layer, to strengthen it and to increase its cohesiveness. Such a reinforcing mesh may be a non-woven, fibrous sheet, consisting essentially of cellulose fibres and of high porosity, resembling tea-bag tissue. Such materials are known for use in connection with hydrogel wound dressing materials.

Examples of suitable commercially available such material are high strength, lightweight, high porosity tissues comprised of a special blend of hemp and other selected cellulose fibres, marketed by The Nonwoven Divi¬ sion of The Dexter Corporation, Windsor Locks, Connecticut, as Dexter Grades 785D and 198T.

Alternatively, the reinforcing mesh may be a thermoplastically welded fibrous web, of thermoplastic fibres such a polypropylene, high density polyethylene or polyester. An example of a suitable, commercially avail¬ able such web is that sold under the trade name DELNET, by Applied Extrusion Technology, Middleton, Delaware.

Such reinforcing meshes may be incorporated into the polymer layer during or after the application of the polymer in liquid form to the self-supporting outer layer.

Particularly preferred for use as the second hydrophilic polymer is a polymer or copolymer of ethylene oxide, or a polymer or copolymer of vinyl pyrrolidone, especially polyethylene oxide or polyvinyl pyrrolidone.

Acrylic acid polymers or copolymers, especially polyacrylic acid, are particularly preferred choices of first hydrophilic polymer for forming the polymer complex adhesive layer in the adhesive patches of the present invention. A wide range of grades and molecular weights of PAA may be used, choice of which is within the skill of the art. Suitable PAA has a molecular weight of at least 2,500 and preferably 5,000 - 450,000. Especially preferred for use in the present invention are polymer complexes derived from PAA as first polymer and PEO as second polymer. PEO of widely varying molecular weights, from about 2,500 up, can be used, with those of molecular weight 6,000 to 600,000 being especially suitable.

As noted, plasticizers can be incorporated in the polymer complex layers of this invention, to adjust the final consistency of the layer. Suitable such plasticizers include urea, propylene glycol, polyhydroxy compounds of low molecular weight including glycerol, sorbitol, glucono- lactone, triethanolamine and gluconic acid. Alkaline plasticizers such as triethanolamine can be used to reduce the level of complexation in the polymer complex, by neutralization of some of the carboxylic acid groups of the first hydrophilic polymer, to increase the tackiness on rehydration. Conventional alkalies e.g. caustic soda or ammonia may also be advantageous for the same purpose in some instances. Additionally, the wound contacting polymer complex material may include suitable preservatives to control icrobial growth. Many frequently used preserv¬ atives known in the art are suitable for this use, includ¬ ing sodium benzoate and sorbic acid.

In another embodiment of the present invention, the polymer complex layer is subjected, after application to the outer film layer, to a crosslinking process, to effect a limited degree of crosslinking of the polymers for strength improvement and sterilization purposes. This is conveniently effected by subjecting the polymer layer to a controlled dose of suitable radiation, e.g. gamma radiation of 3 - 4 Mrad, after application to the film layer. In practice, it is found that the irradiated products tend to give better bleeding control when applied to wound sites, as compared with non-irradiated products. The outer layer of the assembly according to the invention is self-supporting and has a high water vapour transmission, which may result from high inherent permea¬ bility, from microporosity or from perforations. Preferab¬ ly, it also has high oxygen transmission, good drape properties so as to be conformable to wound sites, and good extensibility and elasticity.

The combination of the outer layer and the polymer complex acts as a barrier to the dehydration of the wound site, but must permit adequate water vapour trans¬ mission away from the wound site such that the wound site and adjacent skin do not become edematous (swollen) , thereby having a deleterious effect on wound healing, or resulting in fluid build-up at the patch-wound interface such that the adhesion is lost. For this purpose the backing layer suitably has a water vapour permeability of at least 100 gm/m²/24 hours. When necessary, the water vapour permeability can be increased by introduction of perforations or microporosity. The degree of perforation is not critical, and is determined by the requirement for the backing layer to protect and hold the polymer complex. Thus the size and nature of any such perforation should not be such as to interfere with the function of the backing sheet to protect the polymer complex. It must of course hold the polymer complex in position, and not allow diffu¬ sion of the polymer through the backing sheet. For a discussion of water vapour permeability of wound dressings and their methods of measurement, reference may be made to an article by Marcel F. Jonkman et al., "New Method to Assess the Water Vapour Permeance of Wound Dressings", Biomaterials, 1988, Volume 9, May, pages 263 - 267.

Perforations provided in the outer layer also serve the additional purpose of enhancing the bonding of the polymer complex layer to the outer layer, and counter¬ acting the tendency towards delamination. In effect, the perforations form a type of physical interlock between the outer layer and the polymer complex. Advantageously, the perforations are in the form of lacerations, i.e. a series of slits. The physical interlock can also be provided by embossing, pin pointing or roughening the surface of the outer film layer which is to receive the polymer complex or adhesive.

The outer layer can be made of substantially any skin compatible material exhibiting suitable properties of permeability. It may be a self-supporting film, foam or fabric. Suitable such materials are known in the prior art, and those useful in prior art adhesive wound covering patches are generally useful in the present invention. Examples include polyester polyurethanes, polyether polyurethanes, silicones, polyethylene, polypropylene, ethylene-vinyl acetate copolymers, polyvinyl chloride, etc. It may be opaque, semi-opaque, coloured or transparent, or printed with designs or character.

Ultra-thin polyurethane films which are semi- permeable to water vapour, as exemplified by the commer¬ cially available wound dressing OP-SITE, which consists of a polyurethane film coated with a medical grade adhesive, are particularly preferred. These often have appropriate permeability without perforation. Elastic silicone mem¬ branes constitute another preferred film outer layer. They need to be perforated to provide appropriate permeability.

Foam sheets, preferably of open cell foam or perforated closed cell foam, non-woven or woven fabric bandages of natural, synthetic of mixed fibres, may also be used as the outer layer for the assembly of the invention. Similarly, non-polymer complex adhesives used for skin contacting layers in the assembly of embodiments of the present invention are suitably those known from the prior art. for use with conventional wound dressing patches. Pressure sensitive, skin-compatible adhesives are commonly used. Porous adhesive coatings are especially preferred. These adhesives may comprise acrylic polymers or silicones (e.g. Dow Corning Medical adhesive) ; these are merely exemplary of suitable, available materials.

With reference again to the accompanying draw¬ ings, and specifically to FIGURES 4 and 5, the adhesion of upper release sheet 34 to the outer self-supporting layer 22 effected by adhesive layer 46, should be strong enough to withstand the removal of lowermost release sheet 30 but significantly weaker than the adhesion of the polymer complex layer 24 to the wound site (augmented, in the embodiment shown in FIGURE 5, by the adhesion of adhesive 26 to the wound surrounds) . This will permit the removal of release sheet 34 after application of the dressing to the wound area. The adhesive 46 should have sufficiently stronger adhesive bonding to the upper release sheet 34 than to the outer, self-supporting layer 22. Thus the choice of material of adhesive 46 will be determined to some extent by the nature of the top surface of layer 22.

For polyurethane films, the adhesive 46 would be much weaker than the adhesive 26. Such weak adhesives are often referred to in the art as "repositionable adhesives". If still weaker adhesion is required, the adhesive may be applied to a part only of the surface of sheet 34, or a backside coating may be applied to the top surface of top layer 22.

Another preferred embodiment of the invention is as illustrated in FIGURE 6. As compared with that shown in FIGURE 5, it omits the adhesive layer 46 so that the top release sheet 34 is in direct adhesive contact with the top surface of backing sheet 22. This can be accomplished by solution casting of a solution of the backing sheet 22 onto the appropriate surface of the top release sheet, and allowing it to dry and if necessary, curing. Alternatively it may be applied to the release sheet by a hot melt process. The end result is adhesion of the backing sheet to the release sheet, by direct contact, without the inter¬ mediary of a layer of adhesive.

The invention is further described in the follow¬ ing illustrative but non-limiting examples.

EXAMPLE 1 — PREPARATION OF POLYMER COMPLEX LAYER— PAA/PEO WITH PLASTICIZERS

A solution of 30 g of polyethylene oxide (Polyox WSR-205 from Union Carbide) in 600 ml of distilled water was stirred rapidly at room temperature as 120 g of Acrysol A-3 (a 25% aqueous solution of polyacrylic acid from Rohm and Haas) were added. After completion of the addition, the mixture was stirred for 25 minutes. It was then covered and allowed to stand at room temperature for 6 weeks. At the end of this time, the mixture consisted of a turbid, non-viscous liquid and a translucent, rubbery solid. The liquid phase was discarded. The rubbery solid weighed 143 g. A total of 91 g of ethanol was worked into the rubbery solid by gentle warming (bath at 35-60"C) and by kneading/stirring with a stiff rod having a ring at the bottom. The following materials, in order, were then worked into the mixture by stirring at room temperature:

a solution of 6 g of urea in a mixture of 7 g of distilled water and 20 g of ethanol; a solution of 5 g of triethanolamine and 2.3 g of tartaric acid B.P. in 24 g of distilled water and 8 g ethanol; and a total of 80 g of distilled water and 267 g of ethanol added in portions individually and as mixtures. The mixture was allowed to stand for 2 days, and finally was diluted with a total of 58 g of distilled water and 145 g of ethanol. The hazy, viscous solution was cast on a sheet of low density polyethylene attached to a levelled glass plate. The cast liquid was left exposed to the laboratory atmosphere (about 40% relative humidity) for 17 days, after which it was a transparent and somewhat elastic film. The top of the film was covered with #1361 release liner (3M Co.). Sections of film about 0.17 mm thick were used as the polymer complex layer of bilayer wound coverings. The required shape was cut while the polyethylene and #1361 release liner were still attached.

EXAMPLE 2 — PREPARATION OF POLYMER COMPLEX LAYER— PAA/PEO WITHOUT PLASTICIZERS

A solution of 60 g of polyethylene oxide (Polyox WSRN-750 from Union Carbide) in 1050 g of distilled water was rapidly stirred at room temperature as 240 g of Acrysol A-l (a 25% aqueous solution of PAA from Rohm & Haas) diluted with 250g of distilled water were added over a period of 5 minutes. The mixture was stirred for a further 5 minutes after completion of the addition, and was then allowed to stand for 22 hours. At the end of this time, it consisted of a translucent gum and a semi-opaque, mobile liquid. The liquid was decanted, and the gum was kneaded to express occluded liquid. The resulting gum weighed 282 g. Of this, 56.2 g were separated and allowed to stand at room temperature in a covered vessel for 4 months. The gum was then dissolved to form a solution suitable for casting by the addition, in portions, of ethanol/water mixtures followed by stirring at room temperature. In total, 154.8 g of ethanol and 82.3 g of distilled water were used. The solution was cast on sheets of 7 mil high density polyethylene secured to levelled glass plates. The cast liquid was exposed to the laboratory atmosphere (relative humidity 30-37%) for 4 days, after which the resulting film was transparent and elastic. It was cooled to 4°C to facilitate removal from the polyethylene. The film was stored with #W-89-SP/P release liners (Mead Release Products) on either side. Sections of film about 0.11 mm thick were used for the polymer complex layer of bilayer wound coverings. The required shape was cut while the release liners were still attached.

EXAMPLE 3 --**^■ ASSEMBLY AND PERFORMANCE OF A BILAYER POLYMER COMPLEX WOUND COVERING

The bilayer wound covering for this example was produced in accordance with the preferred embodiment of the invention, FIGURE 5. The adhesive layer 46, which was supplied as a weak film between two release sheets, was placed on the self-supporting top film 34. One release sheet was removed to leave a sandwich of adhesive between a release sheet and film 34. Then the assembly was cut to an appropriate rectangular shape and size, and the release sheet was removed. The rectangular tab 44 was next applied over adhesive 46. An oval shape of top layer 22 with adhesive 26 thereon, and having a release sheet protecting the adhesive 26, was placed over the adhesive 46 on top film 34 and pressed firmly into place. The release sheet was removed. Cast polymer complex film was cut to the appropriate size and shape, and after removal of one of the release sheets, was applied over top layer 22 with the exposed face of the polymer complex against the top layer. It was pressed firmly in place, and the remaining release sheet was removed. The assembly was maintained under conditions of high humidity to hydrate the polymer complex until it became tacky. The bottom release sheet 30, with removal tab 32, was then applied, to complete the assembly. It was then heat sealed into a laminated aluminum foil package 13.

The above-described procedure was used to assemble a bilayer wound covering from the following specific components, reference numbered to accord with the drawings, especially FIGURE 5: top layer release sheet 34 and adhesive layer 46 — 2 mil polyester backing coated with strips of a re-positionable adhesive 2 mm wide placed 2 mm apart. The adhesive strips were parallel to the long direction of the patch;

tab 44 covering part of adhesive 46 — 5 mil high density polyethylene;

top layer 22 and adhesive coating 26 — 1.5 mil polyester polyurethane coated with a porous pressure sensitive adhesive (PSA) (#KM1393-00 from Semex Medical);

polymer complex layer 24 — film from Example 2;

polymer complex release sheet 30 — 3 mil high density polyethylene with a silicone coating cured with an electron beam (#3-HID-S233L-WHITE from Mead Release Products).

TEST ON HEALTHY SKIN

The complete, assembled wound covering was removed from its hermetically sealed pouch and applied to a forearm test site of a human volunteer. After 11 days, 95% of the area of the wound covering was still adherent to the skin. During the entire test period, there was no discomfort, and no evidence of skin irritation. At 15 days, when the wound covering was removed, there was no noticeable edema. TEST ON FINGER CUT

A male, 47, in good health, suffered a paper cut on the end of the ring finger, perpendicular to the plane of the hand. The cut was 5 mm long and had an estimated depth of 2 mm. Bleeding was substantial. Blood was absorbed with a facial tissue for about 60 seconds, and then a complete, assembled wound covering prepared as described above was removed from its hermetically sealed pouch and applied. The patch was left on the injury for five continuous days. During this time, the hand was involved in all normal activities, except that it was kept from immersion in water.

The patch remained transparent during the five day period. Inflammation at the edges of the cut disappeared over the first few days, leaving a thin reddish brown line as the only evidence of injury. At no time was there any fluid buildup beneath the dressing. On the fifth day, the patch was still adherent to the skin surrounding the injury, although by this time there had been peripheral detachment corresponding to about half of the area of the patch. The patch was pulled off. The injury appeared completely healed, and the adjacent skin which had been covered continuously for five days appeared quite healthy.

TEST ON AN ABRASION INJURY UNDER ADVERSE CONDITIONS

A male, 37, in good health sustained an abrasion injury to the ring finger of the right hand in a routine domestic accident. The injury was located on the top of the finger about 1 cm from the central knuckle toward the end of the finger. The abrasion was about 6 mm in diameter and extended well into the dermis.

Bleeding was stopped by absorption with facial tissue. The wound was left exposed for about four hours, and then a complete, assembled wound covering was removed from its hermetically sealed pouch and applied. There was no sensation on application. After application, the volunteer was involved in vigorous outdoor activities including swimming, water skiing and chopping wood. During these activities, the patch remained adherent to the wound and to immediately adjacent healthy skin for about 36 hours, after which there was some peripheral detachment. The patch was removed at this time. The wound appeared healthy and was left exposed. Subsequent healing was highly satisfactory.

EXAMPLE 4 — ASSEMBLY AND PERFORMANCE OF A BILAYER POLYMER COMPLEX WOUND COVERING

The procedure outlined in Example 3 was used to assemble a bilayer covering from the following components, referring to the drawings as regards the specific components:

top layer release sheet 34 and adhesive 46— as in Example 3; tab 44 covering part of adhesive 46 — as in Example 3; top layer 22 and adhesive coating 26 — 0.7 mil polyether polyurethane coated with a porous pressure sensitive adhesive (#KM1391-02 from Semex Medical); polymer complex layer 24 — film from Example 2; polymer complex layer release sheet 30 — as in Example 3.

The polymer complex layer was moisturized by exposure to an atmosphere of 100% relative humidity for 3.5 hours. The complete, assembled wound covering was kept in a hermetically sealed pouch for 1 day before application to a forearm test site of a human patient. After 5 days, 88% of the area of the covering was still adherent to the skin. During the 5-day period, there was no discomfort and no evidence of skin irritation. When the wound covering was removed, there was no noticeable edema.

EXAMPLE 5 — ASSEMBLY AND TEST OF BILAYER POLYMER COMPLEX WOUND COVERING

The procedure outlined in Example 3 was used to assemble a bilayer covering from the following components, referring to the drawings:

top layer release sheet 34 — laminate of an outer layer of 2.8 mil low density polyethylene bonded to a film of 0.5 mil polyester bonded by a layer of polyacrylate adhesive; adhesive 46 - repositionable adhesive on the 0.5 mil polyester component of the laminate forming top layer release sheet 34 described above; tab 44 covering part of adhesive on 46 — as in Example 3; top layer 22 and adhesive eating 26 — 1.5 mil polyether polyurethane coated with a porous pressure sensitive adhesive (#KM-1393-02 from Semex Medical); polymer complex layer 24 — film from Example l; polymer complex layer release sheet 30 — as in Example 3.

The polymer complex layer was moisturized by exposure to an atmosphere of 100% relative humidity for 16.5 hours. The complete, assembled wound covering was kept in a hermetically sealed pouch one day. The pouch was opened and the covering was applied to a forearm test site of a human patient. After 18 days, 96% of the area of the wound covering was still adherent to the skin. During the 18 day period, the test site was exposed to five warm showers. At the end of the 18 day period, the covering was still transparent. There was never any discomfort or evidence of skin irritation.

EXAMPLE 6 — ASSEMBLY AND TEST OF BILAYER POLYMER COMPLEX WOUND COVERING

A complete, assembled wound covering identical with the one described in Example 5 was kept in a hermetically sealed pouch for a total of 25 days. On the 13th day, while still sealed in the pouch, it was given a dose of 1.92 Mrad of gamma radiation, for sterilization purposes. The pouch was opened at 25 days and the covering was applied to a forearm test site of a human patient. After six days, 94% of the area of the wound covering was still adherent to the skin. During the six-day period, there was no discomfort, and no evidence of skin irritation.

EXAMPLE 7

The procedure outlined in Example 3 was used to assemble a bilayer covering from the following components, referring to the drawings: top layer release sheet 34 and adhesive layer 46 — as in Example 3; tab 44 covering part of adhesive 46 — as in Example 3; top layer 22 and adhesive coating 26 — 3 mil polyvinyl chloride, yellowish tan ("flesh colour"), partially transparent, coated with a pressure sensitive adhesive (No. 1103-5 from Betham Corporation); polymer complex layer 24 — film from Example 2; polymer complex release sheet 30 — as in Example 3.

The polymer complex layer was moisturized by exposure to an atmosphere of 100% relative humidity for 18 hours. The complete, assembled wound covering was kept in a hermetically sealed pouch for 40 days before application to a forearm test site of a human patient. After six days, 93% of the area of the wound covering was still adherent to the skin. Hairs and veins were visible through the dressing. At 11 days, when the wound covering was removed, the skin which had been adherent to the covering was much whiter than the surrounding skin. This whiteness had disappeared after exposure to ambient air for 30 minutes. During the entire test period, there was no discomfort, and no evidence of skin irritation.

EXAMPLE 8

top layer release sheet 34 and adhesive layer 46 — 1 mil polyester backing coated with a repositionable adhesive; tab 44 covering part of adhesive 46 — as in Example 3; top layer 22 and adhesive coating 26-- porous, spunlaced polyester non-woven fabric, fabric weight 1.2 oz/sq.yd., coated with a porous pressure sensitive adhesive (No. PA 1251-01 from Semex Medical); polymer complex layer 24 — film from Example 2; polymer complex release sheet 30 — as in Example 3.

The polymer complex layer was moisturized by exposure to an atmosphere of 100% relative humidity for 22 hours. The complete, assembled wound covering was kept in a hermetically sealed pouch for one day before application to a test site on the back of a finger of a human patient between the first (closest to the fingernail) and second joints. After 3.5 days, 80% of the area of the wound covering was still adherent to the skin. The wound covering was removed at this time; there was no noticeable edema or evidence of skin irritation. All normal activities were carried out during the test period, including approximately 16 washings of the hands with soap and warm water.

EXAMPLE 9

top layer release sheet 34 and adhesive layer 46 — as in Example 3; tab 44 covering part of adhesive 46 — as in Example 3; top layer 22 -- 1 mil microporous polypropylene (45% porosity, oblong pores about 0.04 x 0.2 micrometers), Celgard 2500 from Celanese Corporation; adhesive 26 — approximately 0.6 mil coating of polydimethylsiloxane applied to one side of the top layer as follows: the spray from an aerosol can of Hollister Medical Adhesive (No. 7730 from Hollister Incorporated) was directed onto a small jar until about 15 ml had been collected. A portion of this liquid was spread on one side of the top layer material, which had been secured to a levelled surface by taping the edges. The solvent in the coating was allowed to evaporate by exposure to the laboratory atmosphere. The tacky residue was then protected by application of a release sheet of 3 mil polyester; polymer complex layer 24 — film from Example 2; polymer complex release sheet 30 — as in Example 3.

The polymer complex layer was moisturized by exposure to an atmosphere of 100% relative humidity for 68 hours. The complete, assembled wound covering was kept in a hermetically sealed pouch for one day before application to a forearm test site of a human patient. After four days, 85% of the area of the wound covering was still adherent to the skin. About 8% of this adherent area had become transparent, possibly because of migration of low molecular weight silicone polymers into the top layer. One day later, after five days, 65% of the area of the wound covering was still adherent to the skin, and 85% of this adherent area was transparent. When the wound covering was removed at six days, there was no edema and no evidence of skin irritation.

EXAMPLE 10

This example shows that, under favourable conditions, a polymer complex layer 24 which displays little or no adhesion to skin because it has not been moisturized, can become adherent after application of a bilayer wound covering if the wound covering has a peripherally protruding adhesive layer 26 as shown in FIGURES 3-6.

The procedure outlined in Example 3 was used to assemble a bilayer covering, except that the polymer complex layer was never moisturized, the assembly was never completed by the addition of a polymer complex release sheet and was never placed in a hermetically sealed package.

The components used were as follows, with reference to FIGURE 5:

top layer release sheet 34 — laminate of an outer layer of 2.8 mil low density polyethylene bonded to a film of 1 mil polyester with an adhesive layer; adhesive 46 — repositionable adhesive on the 0.5 mil polyester component of the laminate forming top layer release sheet 34 described above; tab 44 covering part of adhesive 46 — as in Example 3; top layer 22 and adhesive coating 26 — as in Example 3; polymer complex layer 24 — film from Example 2. The assembly, complete except for the addition of polymer complex release sheet 30, was kept at ambient temperature and relative humidity (23%) for no more than 30 minutes and was then applied to a test site on the back of a finger of a human patient between the first and second joints. During the next 33 hours, the hand was never in contact with water, but otherwise all normal hand activities were carried out. At the end of the 33-hour period, the entire area covered by the peripherally protruding part of the bilayer wound covering was still adherent. The polymer complex layer had very good adhesion to the skin of the test site.

EXAMPLE 11

top layer release sheet 34 — as in Example 9; tab 44 covering part of adhesive 46 — as in Example 3; top layer 22 and adhesive coating 26-- polyethylene foam, l/16th inch thick (4 lbs.), coated with an acrylic pressure sensitive adhesive (No. 1117-W from Betham Corporation); polymer complex layer 24 — film from Example 2; polymer complex release sheet 30 -- as in Example 3.

The polymer complex layer was moisturized by exposure to an atmosphere of 100% relative humidity for 21 hours. The complete, assembled wound covering was kept in a hermetically sealed pouch for one day before application to a test site on the back of a finger of a human patient between the first and second joints. After one day, only 50% of the bilayer wound covering was still adherent to the skin. This exceptionally rapid loss of adhesion can be attributed to a combination of the stiffness of the foam and the high curvature of the finger. The covering was removed at this time. The area under that part of the wound covering which had maintained adhesion was whitish.

EXAMPLE 12

The bilayer wound covering for this example was produced in accordance with the embodiment shown in FIGURE 4, except for the presence of layer 26 between the top layer 22 and the polymer complex layer 24 as shown in FIGURE 2. Tab 42 in FIGURE 4 was present as an extension of top layer release sheet 34 and adhesive layer 46. The protruding adhesive portion of layer 46 was covered with a tab of 5 mil high density polyethylene. Tab 32 on polymer complex release sheet 30 was present as a folded back extension of sheet 30.

The general method of assembly is as described for Example 3, using the following specific components:

top layer release sheet 34 and adhesive layer 46 — 2 mil polyester backing coated with strips of a repositionable adhesive 2 mm wide placed 1.5 mm apart; top layer 22 and adhesive coating 26 — as in Example 3; polymer complex layer 24 — film from Example 2; polymer complex release sheet 30 -- as in Example 3. The polymer complex layer, which was an oval with maximum dimensions 27 x 16 mm, was moisturized by exposure to an atmosphere of 100% relative humidity for four hours, application of approximately 25 mg of distilled water to the surface in the form of 2 drops from a syringe followed by spreading over the surface, and continued exposure to an atmosphere of 100% relative humidity for 2.5 hours. The complete, assembled wound covering was kept in a hermetically sealed pouch for two days before application to a test site on the back of a finger of a human patient between the first and second joints. After three hours, the test area with the attached wound covering was immersed in a 5% solution of soap at 39°C for one minute and then towelled dry. Thereafter, contact with water was avoided, but all normal hand activities were undertaken. During days two and three, prolonged operation of a power tool with a two-handed overlapping grip caused a significant creep of the wound covering. After four days, 75% of the area of the wound covering was still adherent to the skin, and the adhesion was found to be very good. There was no evidence of skin irritation.

The performance of an identical bilayer wound covering, which had been placed on a similar test site on an adjacent finger and which had been immersed for one minute in distilled water at 39^βC instead of a soap solution, was indistinguishable.

EXAMPLE 13 — PREPARATION AND EVALUATION OF POLYMER COMPLEX LAYER - PAA/PVP WITH PLASTICIZERS

100 grams of polyvinylpyrrolidone (PVP) (Plasdone K-29/32 from GAF Corporation) were dissolved in 100 grams of distilled water. 400 grams of Acrysol A-l (a 25% aqueous solution of PAA from Rohm and Haas) were stirred as the PVP solution was added to it. A gum separated during the addition. The liquid phase was decanted and discarded. The gum was kneaded to express occluded liquid, which was discarded. The gum was dissolved in 32 grams of ethanol by heating and stirring, and the solution was diluted with 8 grams of ethanol. The resulting solution was labelled 81-B. To 50.2 grams of 81-B, while kept warm in a hot water bath, were added, in order, with stirring, 12.0 grams of propylene glycol USP (Daminco Inc.) 9.0 grams of urea (BDH Chemicals), 8 grams of ethanol, and finally a mixture of 8.4 grams of distilled water and 7 grams of ethanol. The warm solution, labelled 97-C, was cast on a polyethylene surface kept at 53° C. After one day, the dry film was transparent and flexible.

To 0.70 grams of the dry film in a small pouch of 3 ml polyethylene were added 0.4 grams of distilled water, and the pouch was sealed. After 2.5 days at room temperature, the pouch was cut open and the tack of the film was assessed by pressing clean, dry skin on the end of a finger against it for three seconds. Its tack level was judged "very good".

EXAMPLE 14 — PREPARATION AND EVALUATION OF POLYMER COMPLEX - PAA/PVP WITH PLASTICIZERS

50.9 grams of 81-B from EXAMPLE 13 were warmed in a hot water bath, and the following additions were made in order with stirring: 5.5 grams of propylene glycol; a solution of 4.0 grams of triethanolamine (Fisher Scientific) in 7 grams of ethanol; 16 grams of ethanol.

The resulting solution, while still warm, was cast on a level glass surface kept at room temperature. To 0.70 grams of the dry film in a small pouch of 3 ml polyethylene were added 0.14 grams of distilled water, and the pouch was sealed. After 2.5 days at room temperature, the pouch was cut open and the tack of the film was assessed by pressing clean, dry skin on the end of a finger against it for three seconds. The tack was judged "good".

Claims

What we claim is:

1. An adhesive covering for adhesive attachment to mammalian tissue for contacting treatment areas thereof, and comprising:

an outer layer of self-supporting, water vapour- permeable film; an inner, treatment area contacting layer of tacky polymer complex supported by the outer layer; the polymer complex layer composition being substantially wound- and skin-compatible, having a water content sufficient to render it skin adhesive, and being formed from the tacky, polymer complex product produced by coprecipitation as a result of mixing solutions of first and second coprecipitatable hydrophilic polymers, and optionally adjusting the water content thereof.

2. The adhesive covering of claim 1 wherein the polymer complex product is produced by coprecipitation form mixed aqueous solution.

3. The adhesive covering of claim 2 further includ¬ ing an intermediate layer of skin compatible adhesive disposed between the outer self-supporting layer and the polymer complex layer.

4. The adhesive covering of claim 3 wherein said intermediate layer and said outer layer extend peripherally beyond the edge of said polymer complex layer to provide additional bonding of the covering to the wound location.

5. The adhesive covering according to any preceding claim further including a removable release sheet applied to the potential wound-contacting surface of the polymer complex layer, said release sheet being removable by peeling prior to application of the covering to the wound site.

6. The adhesive covering of claim 1 further includ¬ ing an adhesive release sheet applied to the outer surface of the outer supporting film, the adhesive release sheet being removable by peeling after application of the covering to the wound site.

7. The adhesive covering according to any preceding claim wherein the polymer complex has one or more thera¬ peutic agents incorporated therein.

8. The adhesive covering of any preceding claim wherein the polymer complex layer consists essentially of a complex of a polymer or copolymer of acrylic acid and a polymer or copolymer of ethylene oxide.

9. The adhesive covering of claim 8 wherein the polymer complex layer consists essentially of polyacrylic acid and polyethylene oxide.

10. The adhesive covering of any of claims 1 - 7 wherein the polymer complex layer consists essentially of a complex of a polymer or copolymer of acrylic acid and a polymer or copolymer of vinyl pyrrolidone.

11. The adhesive covering of claim 10 wherein the polymer complex layer consists essentially of a complex of polyacrylic acid and polyvinyl pyrrolidone.

12. A sealed package containing an adhesive wound covering suitable for application to wounds, said package comprising a sealed film envelope confining an atmosphere of high water vapour content in which the adhesive wound covering is stored; the adhesive wound covering comprising an outer layer of self-supporting, water vapour-permeable film, an inner wound contacting layer of tacky polymer complex having a water content sufficient to render it skin adhes¬ ive supported by said outer layer, the polymer complex layer being essentially wound and skin compatible.

13. The sealed package of claim 12 including a removable release sheet applied to the potential wound- contacting surface of the polymer complex layer.

14. The sealed package of claim 12 or claim 13 including an adhesive release sheet applied to the outer surface of the outer supporting film.

15. The sealed packed of claim 12, claim 13 or claim 14 wherein said sealed film envelope is a heat-sealable laminated aluminium foil.

16. A process for making an adhesive covering material suitable for adhesive attachment to mammalian tissue for contacting treatment areas thereof, which com¬ prises:

mixing together solutions of coprecipitatable, hydrophilic polymers and forming a solid or semi-solid wound compatible polymer complex thereof; forming a laminate of said polymer complex with a self-supporting, water vapour permeable film by applica¬ tion of the polymer complex to a surface of said film; and, before or after its application to the film surface, adjusting the water content of said polymer complex ε_s necessary to render it skin adhesive.

17. The process of claim 16 wherein the coprecipi- tated polymer complex is separated from the precipitation medium, dissolved in water-compatible organic solvent, applied to the self supporting film as a liquid solution and dried thereon.

18. The process of claim 16 wherein the coprecipi- tated polymer complex is separated from the precipitation medium, dissolved in water compatible organic solvent, the solution so formed is cast onto a transfer surface and dried thereon to form a film, and applied to the self- supporting film surface as a film.

19. The process of claim 16, claim 17 or claim 18, wherein the solutions of coprecipitatable, hydrophilic polymers are both aqueous solutions.

20. The process of any of claims 16 - 19 wherein the polymer complex film is subsequently rehydrated.

21. The process of any of claims 15 - 19 wherein the polymers are a polymer or copolymer of acrylic acid, and a polymer or copolymer of ethylene oxide.

22. The process of claim 20 wherein the polymers are polyacrylic acid and polyethylene oxide.

23. The process of any of claims 15 - 19 wherein the polymers are a polymer or copolymer of acrylic acid and a polymer or copolymer of vinyl pyrrolidone.

24. The process of claim 22 wherein the polymers are polyacrylic acid and polyvinyl pyrrolidone.