WO1990011820A2

WO1990011820A2 - Porous articles

Info

Publication number: WO1990011820A2
Application number: PCT/GB1990/000531
Authority: WO
Inventors: Dennis Keith Gilding; Christopher Louis Ives; Mark Michael Galusza; Simon Ashley Dixon; Ian Philip Middleton
Original assignee: Beam Tech Limited
Priority date: 1989-04-06
Filing date: 1990-04-06
Publication date: 1990-10-18
Also published as: AU5446190A; WO1990011820A3; EP0466794A1; GB8907740D0; CN1047317A; IN173502B

Abstract

A porous article, for example a membrane, which comprises a porous hydrophobic polymer body whereof the surfaces including those within the pores have integrally incorporated therein a hydrophilic polymer which has been co-precipitated with the hydrophobic polymer under conditions such that substantially all of the hydrophilic polymer is at said surface and provides a hydrophilic surface throughout the hydrophobic body. The porous article may be a membrane, in particular for use as a wound dressing. Adhesives for wound dressings are also disclosed.

Description

POROUS ARTICLES

The present invention relates to the production of porous polymeric articles, particularly (but by no means exclusively) membranes which have application in the field of medicine and biotechnology. For convenience, the porous articles of the invention will be referred to herein as membranes.

US-A-4 704 130 describes the production of biocompatible microporous articles in which a solution of a hydrophobic polymer (eg. a segmented polyether urethane) is dissolved in an organic solvent to obtain a viscous solution which may be shaped into a 'precursor' which takes the form of the desired article. The precursor is then immersed in a bath of a liquid which will dissolve the organic solvent but not the polymer/solvent solution. As a result the solvent is preferentially dissolved out of the precursor to leave an elastomeric article which may have a selective variation in pore size across its thickness. After subsequent stages of washing, drying and heat treatment there is obtained the final porous article. The article may take the form of a membrane having a void volume in the range 50 to 80%. The membrane may have porous surface layers with a pore size in the range 0.1 to 100- microns, and an intermediate layer defining relatively larger voids of finger-like configuration with their longitudinal aces being substantially normal to the surface layers. Particular uses for such porous articles are as wound dressings, vascular grafts, and protheses.

However, the articles produced in accordance with US-A-4 704 130 suffer from a number of disadvantages. In particular the porous matrix made from a single polyurethane has an equilibrium water level of approximately 30% by weight. This restricts the quantity of aqueous medium (eg., plasma, blood, tissue culture fluids, etc.), which may be taken up into the article. This is particularly disadvantageous in the case where the article is a wound dressing. This not only allows the equilibrium water, plasma exudate, blood culture fluid level to be increased but also the rate at which this equilibrium is approached. A further advantage of having a hydrophilic surface within a hydrophobic porous matrix is that the matrix does not swell as water/exudate is absorbed, ie., the dimensions of the matrix are controlled by the hydrophobic component and the kinetics of absorption and final level of absorption is controlled by the hydrophilic component.

Furthermore, in the field of wound dressings, adhesives are often used for attaching the dressing to the wound.

One example of such a prior adhesive for a wound dressing is a copolymer of at least 95% by mole of ethyl hexyl acrylate (ERA) and at most 5% by mole of acrylic acid. The ethyl hexyl acrylate provides adhesive properties for the polymer whereas the acrylic acid is used for providing cohesive strength. However such adhesives have the disadvantage that they do not allow ready release of the dressing from the wound, and the removal of the dressing can therefore be painful.

Other adhesives comprising a copolymer of a C₈-acrylate and acrylic acid are also known. Thus, for example, GB-A-868 157 discloses a pressure sensitive adhesives (which may for example be coated on to a metal, fibreglass, paper or plastic backing) comprising a copolymer of 1 to 15% by weight of acrylic acid and 99 to 85% by weight of an alkyl acrylate having 8 to 10 carbon atoms in the alkyl group. Similarly GB-A-1 539 131 discloses in Examples 39 and 40 thereof adhesives comprising a copolymer of 10% by weight of acrylic acid and 90% of iso-octyl acrylate. The adhesives of GB-A-868 157 and GB-A-1 539 131 are prepared by processes in which amounts of the monomer corresponding to the amounts in the final copolymer composition are charged into a reaction vessel with a solvent and free radical catalyst, the vessel is capped and polymerisation is effected.

Such adhesives (as prepared by the processes of GB-A-868 157 and GB-A-1 539 131) are not suitable for use as adhesives for wound dressings because their aim is to generate high bond strengths under both dry and moist environments over extended periods of time. This is in contrast to the properties required for a wound dressing adhesive which should provide adequate but controlled bond strength, ideally with controlled reduction in addition with time in the environment of the moist wound. It is therefore an object of the present invention to obviate or mitigate these disadvantages.

According to a first aspect of the present invention there is provided a membrane which comprises a porous hydrophobic polymer body whereof the surfaces including those within the pores have integrally incorporated therein a hydrophilic polymer which has been co-precipitated with the hydrophobic polymer under conditions such that substantially all of the hydrophilic polymer is at said surface and provides a hydrophilic surface throughout the hydrophobic body.

According to a second aspect of the present invention there is provided a method of producing a porous article comprising the steps of

(i) preparing a homogeneous solution comprising, a hydrophobic polymer and a hydrophilic polymer,

(ii) forming the resultant solution into a predetermined shape,

(iii) immersing the shape in a precipitation bath which will dissolve said solvent to effect precipitation of the polymers, said hydrophilic polymer being one which co-precipitates more slowly in the bath than the hydrophobic polymer whereby there is obtained a porous matrix of the hydrophobic polymer with the hydrophilic polymer being integrally incorporated in the surfaces of the hydrophobic matrix; and

(iv) washing and drying the membrane.

According to a third aspect of the invention there is provided an adhesive for a wound dressing comprising a copolymer of 65 to 90% by mole of an alkyl acrylate in which the alkyl group has 6 to 10 carbon atoms (preferably 7 or 8 carbon atoms) and 10 to 35% by mole of an unsaturated carboxylic acid, the individual copolymer chains having a composition within plus or minus 2% by mole of the overall composition of the polymer.

The first and second aspect of the invention will firstly be described, followed by the third aspect.

FIRST AND SECOND ASPECTS

The membrane in accordance with the first aspect of the invention comprises a porous hydrophobic body having hydrophilic surfaces as provided by the co-precipitated hydrophilic polymer. The provision of the hydrophilic surfaces ensured that a significantly greater quantity of aqueous fluids (eg., plasma, blood, tissue culture fluids, etc) may be taken up by the article as compared to a similar article comprised only of a hydrophobic polymer. Typically, the membrane will be able to take up at least 200% by weight (based on the weight of the membrane) of aqueous fluids. The hydrophilic polymer may thus be considered to promote a 'wicking' action to ensure the take-up of the aqueous fluids. This not only allows the equilibrium water, plasma exudate, blood culture fluid level to be increased but also the rate at which this equilibrium is approached. A further advantage of having a hydrophilic surface within a hydrophobic porous matrix is that the matrix does not swell as water/exudate is absorbed, ie., the dimensions of the matrix are controlled by the hydrophobic component and the kinetics of absorption and final level of absorption is controlled by the hydrophilic component.

The porous articles of the first aspect of the invention are produced by a process which takes advantage of the different rates of precipitation which can be achieved for a hydrophobic (< 1% equilibrium water content) and hydrophilic (> 10% equilibrium water or water soluble) polymers. The hydrophobic component is selected to produce a porous article with sufficient strength to be practical use and whose pore size and shape can be controlled by factors such as concentration, temperature, molecular weight, solution viscosity and surface tension and ionic strength of the precipitation bath. The pore size will generally be such as to give a microporous membrane (0.1-250 micron pore size) or an ultra filter membrane (< 0.1 micron pore size). A preferred membrane in acordance with the invention comprises opposite surfaces with pores having a size in the range of 0.1 to 1 micorn and a 'body' with columnar pores having a pore size in the range of 100 to 200 microns. The membrane will generally have a void volume of 55 to 85% (usually 75-80%) and will have a Moisture Vapour Transport value in the range of 2000-30,000 (eg., 5000-15,000) gms/m²/day. The hydrophilic polymer is selected to precipitate more slowly than the hydrophobic component in the precipitation bath in such a way that the chains of the hydrophilic component are entangled within the hydrophobic matrix which is thus covered by the hydrophilic component. The invention thus allows the membranes to be assembled on a molecular basis, rather than simply providing a coating of the hydrophilic polymer on the hydrophobic polymer.

It is thus possible to produce a membrane with the mechanical properties of the hydrophobic polymer and with the surface properties of the hydrophilic component. Hence the porous structure develops strong water absorbing properties, ie. the total void space may be filled, without the loss of mechanical properties that would result from the hydration of a purely hydrophilic polymer membrane.

Typically the membrane will comprise 0.05 to 10% by weight of the hydrophilic polymer.

Wetability by water and liquid water absorption within the pores is therefore one significant property provided by the membranes of the invention. In the preferred membranes of the invention the hydrophilic polymer is a bioactive polymer so as to provide a bioactive surface for the membrane, eg., a surface which promotes or facilitates in vivo or in vitro cell growth.

Bioactive polymers are generally medical grade polymers (with no leachable components) having a chemical structure providing a strong interaction with cells, proteins and/or micro-organisms. The polymer backbone is usually charged (positive or negative) and the properties of the polymer can be adjusted by the influence of counter ions. An increase in the charge on the polymer will generally increase cell adhesion or cell growth but growth will be reduced above a particular level of negative charge. Cell adhesion may also be reduced at higher levels of charge. Mammalian cells will adhere more strongly to the polymer as the charge density in the surface increases but mammalian cell growth will be inhibited as positive charge is increased.

Acid groups in bioactive polymers allows binding to peptides by the N-terminus, whereas amino groups in the polymer allow binding to peptides by the C-terminus. Thus the use of bioactive polymers provide potential for drug delivery systems.

Such hydrophilic polymers may be co-, ter or tetrapolymers derived from monomers with pendant groups that can provide a suitable charge distribution and density for providing particular properties for cell growth.

Membranes with controlled surfaces for cell growth are special for at least three reasons:

(1) the surface chemistry on the molecular scale may be tailored and optimised either for cell growth in vitro or healing in vivo

(2) the surface geometry is on such a scale that the interaction between the membrane and the living system (whether cells in vitro or whole tissues in vivo) may be optimised; and

(3) flow of nutrients and gases through the membrane matrix is possible, thus allowing continuous growth.

A particular use for the membrane with bioactive surfaces are as wound dressings in which the pores of the membrane can take up protein and cell debris exudate, from the wound and there is production of scab tissue within the pores. Further uses of membranes with bioactive surfaces are as vascular grafts; artificial implants; materials for reconstructive surgery; substrates for cell growth; substrates for immuno diagnostics; bio-sensors; immuno absorbents for purification; enzyme reactors, etc., blotting membranes and separating media for proteins and DNA purification and identification. If the hydrophobic polymer is biodegradable then such membranes are potentially useful in plant cell culture, and in artificial organs, eg artificial arteries, tracheas, ureters and nerve splints, where the biodegradable component may act as a nutrient in the healing process.

For the purposes of wound management it is desirable that no material is leeched into the wound environment from the dressing and that the hydrophilic component of the porous article should therefore be highly swellable but not water soluble. This restriction need not apply when the porous article is applied to other applications, for example in the area of tissue culture substrates.

It is also possible for the hydrophilic polymer to be one which provides ion-exchange properties, and such membranes have useful properties for drug delivery.

Membranes in accordance with the invention may also be used in ultra-filtration applications, for modifying ultra-filtration membranes for pervaporation techniques, or as materials for diagnostic kits and bio-sensors. Additionally membranes with a biodegradable hydrophobic polymer may be used in incontinence applications.

Examples of hydrophobic polymers which may be used for producing the porous matrix are polyurethanes, polyetherurethanes polyurethane ureas, polyetherurethane ureas, polyvinylidene fluorides, polyvinyl fluoride, polysulphones, polyamides, polyether sulphones, polyesters, polycarbonates, and copolymers thereof. The hydrophobic polymer is preferably one capable of producing a 500 to 6000 centipoise solution. The hydrophobic polymer is preferably an elastomeric material thus resulting in the production of a elastomeric membrane.

We prefer to use a polyetherurethane with an Mn value greater then 30,000 as the hydrophobic polymer. The preferred polyetherurethane is produced by reacting

(i) an isocyanate terminated prepolymer of a polyalkylene ether glycol and an aromatic polyisocyanate (preferably a diisocyanate) or a hydrogenated derivative thereof; and (ii) a hydroxy terminated prepolymer of an aliphatic diol and a aromatic polyisocyanate (preferably a diisocyanate) or a hydrogenated derivative thereof.

With regard to prepolymer (i) the preferred polyalkylene ether glycols are those having three or more (preferably 3 to 6 carbon atoms in the alkylene residues.

Most preferably polytetramethylene ether glycol (PTMEG) (preferred Mn = 1000 - 2000) is used. This is preferred to polypropylene glycol because of less chance of discolourations and also improved, mechanical properties. Pure MDI is the preferred polyisocyanate. The preferred prepolymer (i) is an MDI/PTMEG prepolymer containing three MDI and two PTMEG residues.

With regard to prepolymer (ii), the preferred diol has 3 to 6 carbon atoms. The preferred diol is n-butane diol (BD). The preferred polyisocyanate is MDI. A preferred prepolymer (ii) is a BD/MDI prepolymer in which the ratio BD:MDI residues is n:(n-l) where n is 3 to 6.

The MDI/BD/PTMEG polyurethane is particularly preferred because it is very soft (possibly because there is no domain formation in the BD/MDI segments), it is comparatively tough (having similar properties to polyurethane ureas), and is a heat sealable thermoplastic thus making it possible to convert the membranes into various articles, eg. gloves.

The ratio of the amount of prepolymer (i) relative to prepolymer (ii) used in the production of the polyetherurethane is preferably 7:1 to 20:1, eg. about 10:1. the choice of any particular value within the range determines the concentration of the polymer required to produce a solution of a predetermined viscosity.

As mentioned above, it is preferred that the hydrophobic polymer is one capable of producing a solution of viscosity 500-6000 centipoise. It is possible to provide a range of polymers (of different molecular weights) which meet this requirement, and the particular polymer used for producing the hydrophobic matrix will determine the properties thereof.

Hydrophilic polymers which may be used include 1. Polyacrylic (or methacrylic) acids and co-, ter- and tetrapolymers.

2. Polyacrylic (or methacrylic) esters.

3. Polyacrylic (or methacrylic) salts, particularly H⁺, Na⁺, K⁺. Mg²⁺, Ca²⁺, Zn²⁺, Cu²⁺, Ag⁺ and Ce²⁺ and cations that are enzyme cofactors and/or radioisotopes.

4. Polyhydroxethyl (or propyl) acrylate (or methacrylate) or hydroxypropyl or trishydroxypropyl acrylamide and co-, ter- and tetrapolymers.

5. Polydimethyl (or diethyl) a ino ethyl acrylate (or methacrylate or amino propylmethacrylamide) and co-, ter- and tetrapolymers.

6. Polyacrylamide (or N-hydroxymethyl) acrylamide and co-, ter- and tetrapolymers.

7. Polyvinylpyrolidone and co-, ter- and tetrapolymers.

8. Carboxymethyl cellulose.

9. Hydroxethyl (or hydroxypropyl) cellulose.

The hydrophilic polymer is preferably on which swells in water without being water soluble.

The hydrophilic polymers may be synthesised to have controlled molecular weight as well as narrow composition ranges (ie., the individual chains have substantially the same relative amount of the monomer residues as the overall polymer compositions) so that their precipitation behaviour can be predicted and controlled.

Preferred values are Mn = 35,000 to 100,000 and Mw = 60,000 to 180,000 (as measured by GPC in DMF at 80°C using polystyrene standards). In order to produce a co-, ter- or tetra-polymer with as narrow composition range it is necessary to determine the relative reactivities of the monomers concerned. The initial monomer composition which provides the desired polymer composition is placed in the reaction vessel. The reaction is begun and is fed by monomer in the same ratio as those appearing in the polymer (ie., the same composition as that being consumed by the vessel). The feeding rate of the monomer fed reaction is equivalent to the rate at which the polymer is produced. In this way the initiator and monomer concentration are maintained constant throughout the reaction and a narrow composition polymer results.

The preferred hydrophilic polymer is a copolymer of acrylic or methacrylic acid and an alkyl acrylate or methacrylate. If the copolymer comprises acrylic acid then preferably the co-monomer is a methacrylate. For a copolymer comprising methacrylic acid the co- monomer is preferably an acrylate. Preferably the alkyl group has 1- 12 carbon atoms, more preferably 1-4 carbon atoms. Preferably the copolymer comprises 70 to 98% by mole of the acid and 2 to 30% by mole of the acrylate.

The preferred hydrophilic polymer comprises 70-98% by mole acrylic acid and 2-30% by mole of ethyl hexyl methacrylate.

As a first step in the preparation of the membrane, the hydrophobic and hydrophilic polymers are dissolved in a suitable solvent to produce a homogeneous solution. Generally the solvent will be an aprotic organic solvent, for example dimethyl formamide (DMF), dimethyl sulphoxide (DMSO), dimethyl acetamide (DMAC), N-methyl pyrollidone and N-methyl pyrrole.

The concentration of the hydrophobic and hydrophilic polymers to be used in the solution will depend on a number of factors, eg the particular polymers and the type of membrane to be produced. Generally however the solution will contain 10 to 25% (preferably 10 to 15%) by weight of hydrophobic polymer and up to 10% by weight (based on the weight of the hydrophobic polymer) of hydrophilic polymer.

Whatever the concentrations of the polymer, it is essential that they are thoroughly dissolved and evenly dispersed in the solvent. The solution can also include any additional components for incorporation in the final membrane. For example, in the production of membrane for wound dressings the solution may include Ag⁺ ions (which provide bactericidal action), Zn²⁺ ions (which reduce scarring and promote healing), Cu²⁺ (anti-microbial) and/or Ce²⁺ (anti immunosuppressant).

The solution will generally have a viscosity in the range 1500 to 3000 centipoise and may be formed into a desired shape by a variety of techniques. For example, the solution may be cast on a plate or extruded using hollow fibre techniques into a tubular structure. Alternatively, for continuous production of elongate lengths of the membrane, the solution may be extruded onto a moving carrier web which then passes through the precipitation both (see below). Typically, the thickness of the solution prior to treatment in the precipitant bath will be 0.05 to 0.8mm, preferably 0.2-0.6mm.

Once the desired shape has been produced, it is immersed in the precipitant baths. This will generally be an aqueous bath at a temperature of 25-55°C (usually 40-45°C). In the precipitation bath, the solvent in the polymer solution is dissolved by the bath liquid resulting in initial precipitation of the hydrophobic polymer into a porous structure followed by later precipitation of the hydrophilic polymer to provide a hydrophilic surface throughout the hydrophobic body. The bath can include additional components eg. alcohols or surface active agents to change the symmetry of the membrane, eg. by providing a differential pore size across the width of the membrane.

Ideally, the solvent (for the polymer solution) and the composition of the precipitant bath are such as to maximise the surface area of the hydrophobic body so as to maximise the surface area of hydrophilic polymer in the membrane.

The residence time in the bath will generally be 15-45 mins, after which the membrane is passed through a series of water baths (eg. at 20-40°C) to remove all residual solvent, the membrane may be subject to pressing on alternative sides (a so-called serpentine action) as it passes through the baths to assist removal of the solvent.

Next, the membrane is squeezed (by using a serpentine action) in air to remove excess water. In the next stage the membrane is passed to a drier (eg. using microwave IR heaters) having a controlled and channelled air flow to remove water vapour, and the surface of the membrane is finally scrubbed with filtered compressed air.

If the membrane is to be used as a wound dressing, the next stage is to apply adhesive thereto. This may be done on a laminating machine. For this purpose, the membrane is rolled-up and interleaved with paper prior to being put on the laminator. The adhesive (which is preferably one in accordance with the third aspect of the invention - see infra) may for example be a 20%-40% solid solution in ethyl acetate and be gravure printed at a thickness of 0.005" (125 microns) to 0.0025" (62.5 microns) to give 20 to 50% coverage on a release paper. The adhesive may then be passed through an IR heater tuned to the maximum energy, absorption of ethyl acetate to produce a final adhesive thickness of 5 to 50 microns (preferably 25 microns).

Next, the membrane is unwound and the adhesive laminated thereto prior to cutting of the membrane to the desired shape/size and packing as required.

THIRD ASPECT

This aspect relates to adhesive (as defined broadly above) which may be used in conjunction with wound dressings. The adhesive comprises a copolymer of 65-90% by mole of an alkyl acrylate in which the alkyl group has 6 to 10 carbon atoms (preferably 7 to 8 carbon atoms) and 10-35% by mole of an unsaturated carboxylic acid, the individual copolymer chains having a composition within plus or minus 2% by mole of the overall composition of the polymer.

Preferably the acrylate (or methacrylate) monomer is a branched chain alkyl acrylate (or methacrylate). The preferred monomers in this category are 2-ethyl hexyl acrylate and 2-methyl pentyl acrylate.

The unsaturated carboxylic acid may for example be methacrylic acid, itaconic acid but is most preferably acrylic acid.

The preferred adhesive copolymer is one comprising 20-30% by mole (preferably about 20%) of acrylic acid and 70-80% by mole of ethyl hexyl acrylate.

The adhesive copolymer will generally have an Mn value of 20,000 to 90,000, more usually 40,000 to 60,000. Additionally the molecular weight distribution Mw/Mn should be as narrow as possible, and will typically be 1.4 to 1.8 (more usually 1.4 to 1.55).

An important feature of the adhesive is that it has a narrow composition range and molecular weight distribution so that the individual copolymer chains have a composition preferably within plus or minus 2% by mole of the overall copolymer composition.

The narrow composition range may be achieved by reacting the monomers together in amounts determined by their reactivity ratios such that the growing end of the chain has a substantially equal probability of reacting with either monomer. Such a narrow composition range will not be obtained for the adhesives described in GB-A-868 157 and GB-A-1 539 131 since by the very nature of their production they will have broad compositions and molecular weight distributions whereas we require narrow compositions and molecular weight distributions in order to achieve the controlled reduction of adhesion.

There are a number of advantages in the use of amounts of the carboxylic acid (eg. acrylic acid) in the range 10-35% (as compared to a maximum of 5% in the prior art wound dressing adhesives). In particular, the higher acid content provides a hydrophilic negative surface which promotes the growth of cells. Furthermore, the increased amount of acid allows a degree of ion exchange such that over a period of time the protons of the acid are exchanged with sodium ions (for body fluids). These sodium ions are hydrated and this hydration of the adhesive results in controlled reduction of adhesion and release of the dressing from the wound. By ensuring that the adhesive is of narrow composition range, the adhesive will release uniformly over its area of contact with the wound.

The adhesive may also incorporate large concentrations of metal ions eg. as mentioned for the hydrophilic polymer.

The adhesive may be used as a continuous or discontinuous coating on the dressing. A discontinuous pattern is preferred to provide a more flexible attachment to the tissues surrounding the wound and also to produce a dressing whose gas nd moisture vapour transport and exudate uptake properties are not limited by diffusion through the adhesive. It should be appreciated that the adhesive may be used in conjunction with dressings in accordance with the first aspect of the invention or of any other type.

The invention will be further described by way of example only with reference to the accompanying drawings, in which;

Fig. 1 schematically illustrates a wound dressing in accordance with the invention in position on a wound; and

Fig. 2 illustrates release of the dressing from the wound.

The dressing 1 schematically illustrated in Fig. 1 comprises a porous matrix 2 of hydrophobic polymer whereof all surfaces have an integral layer 3 of a hydrophilic polymer. The dressing may for example have a thickness of 0.1-lmm and has a differential pore size across its width. Typically the maximum pore size (which will be at the face of the dressing adjacent the wound) will be approximately 200 microns and the minimum pore size (which will be on the opposite face) will typically be several Angstroms so as to exclude a molecule of 10,000 daltons or more. Between the opposite faces of the dressing, are columnar shaped interconnecting pores 4 extending generally perpendicular to the surfaces of the dressing. The dressing is attached to a wound site 5 by an adhesive 6 which is in accordance with the third aspect of the invention.

In view of the hydrophilic nature of the pores 4, exudate 7 from the wound passes into these pores together with protein and cell debris 7a. Additionally the porosity of the dressing allows transport of oxygen, carbon dioxide and water vapour into and out of the dressing in the direction of the illustrated arrows. Typically the dressing will have a permeability with respect to water vapour of 4000-20,000 gms/m²/day. As the healing of the wound progresses, scab tissue 8 (Fig. 2) is formed within pores 5 and a new cell layer 9 grows over the wound. Additionally, there is ion exchange between the adhesive and the body fluids resulting in hydration of the adhesive and its release from the wound, as illustrated in Fig. 2, leaving cell layer 9 intact.

The following non-limiting examples also illustrate the invention.

Example 1

A wound dressing was produced by the following procedure.

a. A polyetherurethane (hydrophobic polymer) based on polytetramethylene glycol 2000, MDI, and butane diol was prepared in accordance with the procedure discussed above. The polymer had a Shore hardness of less than 85A (< 65A).

The polyetherurethane was dissolved in DMF to give a solution (solution 1) with a concentration of 14% by weight.

b. A copolymer of acrylic acid containing 3% by weight ethyl hexyl methacrylate was dissolved in dimethyl formamide to give solution (solution 2) having a concentration of around 5% by weight..

c. Solutions 1 and 2 were mixed on a roller mill overnight in proportions such that solution 2 comprised less than 10% by weight of the mix.

d. The mixed solution was spread on a flat substrate (glass, PE or silicone coated release paper or polyester film) using a glass rod to a thickness that is controlled by the number of layers of standard vinyl electrical insulation tape on each side of the glass plate - typically 0.5mm.

e. Solution is precipitated in water with 0-10% by weight Isopropanol (IPA) and optionally various ions (depending on the desired composition of the dressing) at 35-50°C to produce a white opaque asymmetric membrane, which is formed with the open side against the glass substrate.

f. The membrane is removed after 10-20 minutes and allowed to leach in a bath of water at 50°C for 10 to 20 minutes.

g. The membrane is dried at 65°C under minimal tension under a combination of microwave infra red and convection filtered air heating and the resulting structure has a thin skin on one side which behaves as an antimicrobial barrier. The bulk consists of interconnected pores of 100-200 microns dimensions. The other surface consists of an ultrathin hydrophilic skin which serves to stop the pores being blocked by adhesive while allowing important transport of exudate.

The resultant membrane is eminently suitable as a wound dressing. The membrane has semi-ocdusive properties able to allow gas and water vapour transport and reduce pain significantly or eliminate it completely, produce faster healing and less scarring than cotto gauze or Opsite.

Additional wound healing properties may be obtained by introducing zinc as a counter ion in the acrylic acid copolymer.

Antimicrobial properties can be achieved by introducing silver or copper as a counter ion into the copolymer.

Antiimmunosuppresive properties can be achieved using eerie counter ion.

Example 2

Substrates for cell growth may be prepared by the following procedure

a. 15-20% Solef 2012 polyvinylidene fluoride PVF2 (Solvay Co) in dimethyl formamide.

b. Add 0.1 - 1% (based on the weight of PVF2) of any one of the copolymers of: Methylmethacrylate 90mm% : Acrylic Acid 10m% " 85mm% : " " 15m%

80mm% : " " 20m%

" 50mm% : Hydroxyethylmethacrylate 25m%

Dimethylaminomethacrylate 25m%

c. Precipitate in water or water containing 10% by weight IPA as above.

Example 3

A biodegradable scaffold for regrowth of internal structures in the body may be prepared by the folliwng procedure.

a. 10 to 20% of Poly-L-lactic acid is dissolved in tetraldrofuran.

b. Add 1 to 5 by weight, based on the weight of (a), copolymer of 80-60m% og butyl acrylate 20 to 40 m% with acrylic acid.

c. Precipitate in water or water/IPA mixtures containing ZnNO₃ or ZnCl₂, or other water soluble salts of zinc, calcium or other divalent ions

This scaffold will cause rigid healing and dissolve as the structures are formed - use for artificial artery, ureter, f allopian tube connection and nerve splints.

d. Splints using hollow fibre techniques into a tubular structure.

Claims

1. A porous article, for example a membrane, which comprises a porous hydrophobic polymer body whereof the surfaces including those within the pores have integrally incorporated therein a hydrophilic polymer which has been co-precipitated with the hydrophobic polymer under conditions such that substantially all of the hydrophilic polymer is at said surface and provides a hydrophilic surface throughout the hydrophobic body.

2. An article as claimed in Claim 1 wherein the hydrophobic polymer is selected from polyurethanes, polyetherurethanes, polyurethane ureas, polyetherurethane ureas, polyvinylidene fluorides, polyvinyL fluoride, polysulphones, polyamides, polyether sulphones, polyesters, polycarbonates, and copolymers thereof.

3. An article as claimed in claim 2 wherin the hydrophobic polymer is a thermoplatic polyetherurethane or poletherurethan urea.

4. A membrane as claimed in Claim 2 wherein the hydrophobic polymer is one capable of producing a 1000 to 3000 centipoise solution.

5. A membrane as claimed in Claim 2 or 3 wherein the hydrophobic polymer is a polyetherurethane with an M_n value greater than 30,000.

6. A membrane as claimed in Claim 4 wherein the polyetherurethane has been produced by reacting

(i) an isocyanate terminated prepolymer of a polyalkylene ether glycol and an aromatic polyisocyanate (preferably a diisocyanate) or a hydrogenated derivative thereof; and

(ii) a hydroxy terminated prepolymer of an aliphatic diol and an aromatic polyisocyanate (preferably a diisocyanate) or a hydrogenated derivative thereof.

7. A membrane as claimed in Claim 6 wherein the polyalkylene ether glycol used in the preparation of prepolymer (i) has at least three carbon atoms (preferably 3 to 6 carbon atoms) in the alkylene residue.

8. A membrane as claimed in Claim 7 wherein the polyalkylene ether glycol is a polytetramethylene ether glycol, preferably having an M_n value of 1000 to 2000.

9. A membrane as claimed in Claim 8 wherein the prepolymer (i) has been prepared from pure MDI and the polytetramethylene ether glycol, preferably in amounts such that the prepolymer (i) contains 3 MDI and 2 PTMEG residues.

10. A membrane as claimed in any one of Claims 6 to 12 wherein the aliphatic diol for prepolymer (ii) has 3 to 6 carbon atoms, and is preferably n-butane diol.

11. A membrane as claimed in Claim 10 wherein the isocyanate for prepolymer (ii) has been provided by MDI.

12. A membrane as claimed in Claim 11 wherein prepolymer (ii) is a n-butane diol (BD)/MDI prepolymer in which the ratio of BD:MDI residues is n:(n-l) where n is 3 to 6.

13. A membrane as claimed in any one of Claims 6 to 12 wherein the ratio of the amount of prepolymer (i) to prepolymer (ii) used in the production of the polyetherurethane is 7:1 to 20:1.

14. A membrane as claimed in any one of Claims 1 to 13 wherein the hydrophilic polymer has a M_n value of 35,000 to 100,000 and an M_w value of 60,000 to 180,000.

15. A membrane as claimed in any one of Claims 1 to 14 wherein the hydrophilic polymer comprises 70-98 per cent by mole acrylic acid and 2-25 per cent by mole of ethyl hexyl methacrylate.

16. A membrane as claimed in any one of Claims 1 to 15 having a pore size of 0.1 - 250 microns.

17. A membrane as claimed in any one of Claims 1 to 15 having a pore size of < 0.1 microns.

18. A membrane as claimed in any of Claims 1 to 17 which incorporates Ag⁺, Zn²⁺, Cu²⁺, Ce²⁺ ions or other divalent ions that are enzyme cof actors.

19. A method of producing a porous article comprising the steps of (i) preparing a homogenous solution comprising a hydrophobic polymer and a hydrophilic polymer,

(ii) forming the resultant solution into a predetermined shape,

(iii) immersing the shape in a precipitation bath which will extract said solvent to effect precipitation of the polymers, said hydrophilic polymer being one which co-precipitates more slowly in the bath than the hydrophobic polymer whereby there is obtained a porous matrix of the hydrophobic polymer with the hydrophilic polymer being integrally incorporated in the surfaces of the hydrophobic matrix; and

(iv) washing and drying the article.

20. A method as claimed in Claim 19 wherein the solvent for the hydrophilic and hydrophobic polymers is an aprotic organic solvent, preferably selected from dimethyl formamide, dimethyl sulphoxide, dimethyl acetamide, N-methyl pyrollidone and N-methyl pyrrole.

21. A method as claimed in any one of Claims 19 or 20 wherein the homogenous solution comprises 10 to 25 per cent by weight of the hydrophobic polymer and up to 10 per cent by weight (based on the weight of the hydrophobic polymer) of the hydrophilic polymer.

22. A method as claimed in any one of Claims 19 to 21 wherein the homogenous solution has a viscosity in the range 500 to 6000 centipoise.

23. A method as claimed in any one of Claims 19 to 22 wherein the precipitant bath is an aqueous bath at a temperature of 25-55°C.

24. A method as claimed in any one of Claims 19 to 23 wherein the residence time in the bath is 15 to 45 minutes.

25. An adhesive for a wound dressing comprising a copolymer of 65-90% by mole of an alkyl acrylate in which the alkyl group has 6 to 10 carbon atoms (preferably 7 to 8 carbon atoms) and 10-35% by mole of an unsaturated carboxylic acid, the individual copolymer chains having a composition within plus or minus 2% by mole of the overall composition of the polymer.

26. An adhesive as claimed in Claim 25 wherein the acrylate monomer is a branched chain alkyl acrylate, preferably selected from 2-ethyl hexyl acrylate or 2-methyl pentyl acrylate.

27. An adhesive as claimed in any one of Claims 25 or 26 wherein the unsaturated carboxylic acid is selected from acrylic acid, methacrylic acid, and itaconic acid.

28. An adhesive as claimed in Claim 25 comprising 10-35% by mole of acrylic acid and 65-90% by mole of ethyl hexyl acrylate.

29. An adhesive as claimed in Claim 28 wherein the copolymer comprises about 20% by mole of acrylic acid and about 80% by mole of ethyl hexyl acrylate.

30. An adhesive as claimed in claim 28 wherein the copolymer comprises about 20% by mole of acrylic acid and about 80% by mole of ethyl hexyl acrylate.

31. An adhesive as claimed in any one of claims 25 to 30 having an M_n value of 40,000 to 60,000 and a molecular weight distributuion of 1.4 to 1.55.