The invention relates to bandages which protect wounds from infectious organisms while allowing the natural process of healing to take place.

During the healing process of a wound, the body typically exudes an aqueous solution of salts, proteins, complex carbohydrates and other biological materials. As water in the exuded solution evaporates, the dissolved substances coagulate to form a scab which protects the wound from attack by harmful microorganisms. Scabs allow the healing process to proceed without infection, so long as the scab remains intact. Rapid formation of a strong., coherent, protective scab is very desirable to promote healing.

Bandages are commonly applied to wounds to exclude dirt and other foreign material which may include infectious organisms. Bandages are frequently changed daily to permit cleansing the wound of any foreign materials which may cause infection. Unfortunately, existing bandages tend to stick to the scab-forming materials. Some bandages ^" are even designed to promote skin cell growth to the bandage. Both of these tend to remove part of the scab-forming materials when the bandage is changed.

Repetitive bandage changing can extend the period of time required for a coherent, protective scab to form. The longer a wound goes without a protective scab, the greater the chance for the wound to become infected.

Many approaches have.been tried in an attempt to solve the problem of bandages sticking to the incipient

scab material when the bandages are removed. Three of the more successful types of bandages will be described and some of their limitations noted.

In a petrolatum impregnated gauze, one or more layers of cotton gauze are impregnated with petrolatum (petroleum jelly) . This causes the normally hydrophilic porous cotton fibers to be water repellent. It also, prevents water from imbibing into the fibers, evaporating and leaving scab-forming material attached to the fibers. When the bandage is removed, there is a greatly reduced tendency of the bandage material to stick to the wound and remove incipient scab-forming material. This type of bandage, however, has few if any open passages through which the body fluids can pass in either the liquid or vapor phase. Thus, scab formation is delayed for a .long period of time because there is little chance for the essential evaporative process to take place. The few open areas that do form in this type of bandage to permit fluid evaporation are typically large enough to permit the passage of infectious organisms.

A hydrophilic - hydrophobic bilayer bandage is another approach. The layer near the wound is made from a- hydrophobic impermeable plastic film. To permit the passage of body fluid, the film is perforated with a multiplicity of fine holes, typically about 100 microns or larger. The area occupied by the holes is typically less than 5% of the bandage area. The second layer is typically a pad of cotton, gauze-like, sorbent, hydrophilic material. In operation, the mucous-like aqueous solution of body fluids passes through the fine holes in the hydrophobic film and is absorbed into the hydrophilic gauze where the water rapidly evaporates leaving a viscous semi-solid residue. The residue exists as a continuous thread reaching from the wound itself, through the holes of the plastic film and terminating in

the gauze layer. This type of bandage permits relatively rapid evaporation of body fluids, and has non-stick qualities superior to standard bandages. However, when the bandage is changed, the continuous threads of scab- like material are removed along with the bandage, and part of the newly formed scab is torn apart. The mucous material absorbed in the gauze is also susceptible to bacterial attack despite the presence of any added antibiotic. Bacteria thus have an open conduit from the mucous filled gauze directly to the wound.

A collagen gel bandage is made from a hydrophilic gel containing materials that chemically resemble those found in skin tissue. The gel is predominantly water (perhaps 90% by weight) but its chemical structure gives it mechanical strength and a certain amount of rigidity. This bandage is placed in direct contact with the wound and absorbs water from it. As water evaporates into the air from the top surface of the gel, the concentration of dissolved substances increases relative to the bulk of the gel. This concentration difference causes a difference in osmotic pressure which draws water from the water-rich areas of the gel near the wound to the water- poor area at the gel surface. Thus, there is a net flow of water from the wound to the surrounding air. As long as the wound continues to exude body fluids, the gel will absorb the water and transfer it to the air as a vapor. When the wound heals and stops- exuding fluid the gel eventually dries up and becomes part of the scab.

The collagen gel bandage is very effective, but it has several serious drawbacks. It is mechanically fragile and cannot take much mechanical stress without breaking into pieces. Any breaks expose the wound to airborne microorganisms. Because the bandage is an aqueous gel, it can serve as a natural habitat or culture medium for bacterial growth. Because of its complex

chemistry and method of manufacture and storage, it is extremely expensive, perhaps 20-40 times as expensive as the other state of the art non-stick bandages. An additional and perhaps more serious problem with the gel type bandage is the fact that it is substantially impermeable to oxygen or air. Oxygen, especially in high concentrations, is a well known treatment for open wounds, such as in burn therapy where the wounds are frequently massive.

A recent effort to provide an improved bandage is illustrated in U.S. Patent 4,846,164, which issued to Martz on July 11, 1989. Martz describes an adhesive strip for applying gauze over a wound which is constructed of a thin elastomeric film protected by a layer of non-woven fabric. The film itself is made to be permeable to water vapor but impermeable to liquid water, but gauze tends to stick to a scab as it forms.

U.S. Patent 4,344,999, which issued to Gohlke on August 17, 1982, describes a flexible, breathable laminate for use in hospital gowns and tents. The laminate includes an inner layer of hydrophobic material and an outer attached layer of hydrophilic material.

U.S. Patent 4,194,041, which issued to Robert w. Gore et al on March 18, 1980, describes a breathable and waterproof article for use in protective clothing.

The invention involves a bandage for wounds, especially those that ooze body fluids. The portion of the bandage in physical proximity with the wound is made of a hydrophobic material which allows water vapor and oxygen to pass through it substantially unimpeded, but which restricts or prevents passage of liquid water, aqueous solutions, and bacteria or other infectious organisms. The bandage is so constructed that the

hydrophobic material can be applied directly to the wound and removed at a later time without sticking to the sensitive wound area or disrupting the healing process. The hydrophobic material should have an effective pore size which is smaller than the size of substantially all of the microorganisms available to harm the wound in a particular environment.

The bandage material itself may be a naturally hydrophobic, microporous material made of polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, polymethyl methacrylate, polytetrafluoroethylene (Teflon)® or the like. The hydrophobic material contains pores which are very small,. preferably below about 0.2 micron in effective pore size (Test Method S.E.M.), and preferably with less than 1% of the pore area being greater than 1.0 micron. The hydrophobic material has the unique property of not allowing liquid water or aqueous solutions to pass through the minute pores of the material, but allowing water vapor and air to pass through substantially unimpeded by the presence of the material.

Water contained in the body fluids associated with the wound may evaporate through the open pores of the membrane at a rapid rate. Water transpiration rates of about 500 to about 5,000 grams of water per square meter per 24 hours may be considered typical (ASTM method E96- 66B) , although the* rates should be selected to avoid too much dehydration of the wound while promoting the healing process. Since the transpiration rate for skin is about 50, rates between about 50 and about 5,000 may be considered for a particular application. The dissolved salts, proteins, and other biological entities remain beneath the hydrophobic material and form a scab which does not stick to the microporous, hydrophobic material.

The membrane may also allow certain non-aqueous liquid solvents or solutions to pass through it freely. Because of this property, when the bandage is applied directly to an open wound and secured in place by any convenient means, the wound can be sterilized or medicated if desired by applying a non-aqueous solution of the sterilant, antibiotic, growth factor, or other medication directly to the outer surface of the bandage. The membrane will imbibe the solution and carry it to the wound surface. Alternatively, the bandage can be made sterile before application to the wound by contacting the bandage with a non-aqueous solution of a sterilant such as iodine, or by conventional sterilizing techniques.

Because the hydrophobic membrane is not wetted by aqueous solutions of body fluids, when the bandage is removed, it does not remove scab forming material as is common with conventional non-stick bandages. This invention allows wounds to heal faster while excluding bacteria from the wound during the healing process.

FIGS. 1A, IB, 1C and ID are schematic diagrams of capillary pores of hydrophobic and hydrophilic materials in contact with water;

FIG. 2 is a schematic diagram of the cosine function associated with the contact angle in a capillary pore containing a non-wetting liquid (aqueous solution) and a wetting liquid (non-aqueous liquid) ;

FIG. 3 is a schematic, sectional diagram of a bandage of the invention over a wound.

The invention provides a bandage with a flexible, mechanically strong, hydrophobic membrane with very fine pores as the part to be in contact with scab-forming material exuded from a wound. If any other material is

to be -located between the membrane and the scab-forming material, the other material should not adhere to or become intertwined with the scab-forming material. The membrane of the present invention is highly permeable to water vapor and air. It allows the area around the wound to remain saturated with oxygen from air while allowing water from the wound to evaporate through the membrane as vapor. The pores must be smaller than the common microorganisms that may cause infections. Most bacteria will not pass through a 1.0 micron pore and practically all living organisms will be stopped by a pore about 0.1 micron in diameter. Bacteria are microscopic plant cells which normally have an average length within a range of 2 to 5 microns, although some are as small as 0.2 micron or as large as 100 microns. Thus, the pores of the membrane, should be less than about 0.2 micron in effective pore size, preferably less than about 0.1 micron, with fewer than 1% of the pores being larger than about 1.0 micron. Such membranes are available, relatively inexpensive, and commonly used in filtration technology and in all-weather garments. In circumstances where bacteria are known to be larger, the effective pore size can be larger as long as the pore size accomplishes the purposes of this invention.

The membrane should be strongly hydrophobic, that is, water will not spread on, imbibe into, or wet the surface of the material. By definition, hydrophobic materials have a liquid/solid contact angle greater than 90 degrees. Hydrophilic surfaces such as glass, cotton, wool, etc. readily absorb water whereas materials like polyethylene, polypropylene, polytetrafluoroethylene and many other plastic materials repel water and cause it to bead up rather than spread out on their surfaces. Non- aqueous solvents, however, such as alcohols and other organic solvents, can wet the hydrophobic material and spread on its surface.

When a single hydrophilic, capillary pore is placed in contact with water, water will be spontaneously sucked into the capillary. If the capillary material is hydrophobic, it will resist imbibition of water, and extensive pressure will be required to force water into the capillary. Non-aqueous solvents or solutions, however, will be spontaneously sucked up into the hydrophobic* capillary pores. The capillary action is shown schematically in Figures 1A, IB, 1C, and ID.

In the capillary A illustrated in Fig. 1A, which is strongly hydrophobic, the water in the pore tends to be rejected. The meniscus 2 so formed within the capillary • A is substantially below the liquid level outside the capillary A and is a pronounced curve with a relatively short radius of curvature r _A and an advancing contact angle θ _A approaching 160 ^* .

In capillary B of Fig. IB, the hydrophilic material. actually sucks the column of liquid in the capillary B above the liquid level and the water at the pore wall advances more than the water at the center of the pore. The meniscus 4 so formed is substantially above the liquid level outside the capillary B and is a pronounced curve with a relatively short radius of curvature r _B and a contact angle Θ _B approaching 0 ^* .

With weak hydrophilic and hydrophobic materials, as illustrated in capillaries C and D of Figs. 1C and ID, the radii of curvature r _c and r _D are much longer to form flatter menisci 6 and 8 and the advancing contact angles θ _c and Θ _D are relatively closer to either side of 90', such as 70' and 110'.

Hydrophilic materials are those with a contact angle less than 90 ^* . The smaller the contact angle the more

strong-ly hydrophilic is the material. Conversely hydrophobic materials are those with a contact angle against water greater than 90 ^* . The greater the angle the more hydrophobic is the material.

The pressure required to force fluid into or prevent fluid from entering a capillary is given by the equation:

-> ₌ ^{2 δ} _ _W here P = pressure (in dynes/cm ² ) (1) ^R <- δ = surface tension (in dynes/cm)

R _c = radius of curvature (in cm) of liquid surface

Glasstone, S. Textbook of Physical Chemistry, Second Edition 1953, D. Van Nostrand Co., Inc. 250 Fourth Avenue, New York, N.Y. 10003, Page 486 et seq. .

The surface tension ό ^" is a physical constant for a given liquid. The pressure (external or suction) required to force a liquid into a capillary is dependent primarily on the radius of curvature of the liquid interface.

The radius of curvature of the liquid surface is dependent on the radius of the capillary, and the contact angle between the liquid and the solid surface. This relationship is shown in the equation:

(2) = R _n cosθ where R_. is the radius of the capillary (pore) .

The contact angle is defined as the angle formed between the solid surface and the tangent to liquid surface at its point of contact with the solid. The contact angles Θ _A , Θ _B , θ _c and Θ _D are shown in Figure 1. By convention, the contact angle is drawn through the liquid phase, and is referred to as the advancing contact angle.

C mbining the above equations , the result is: ( 3 ) P = 2<Scosθ

where R-, ~~ ^s ^~-~~- ^ra dius of the pore in the capillary and θ is the contact angle between the liquid and the capillary wall.

The cosine function and therefore the entry pressure for aqueous solutions are positive when the contact angle is between 0 and 90', as demonstrated in Equation 3 above. Conversely, the entry pressure is negative when the contact angle is between 90' and 180 ^* . By convention, positive pressures mean aqueous liquid is sucked into the capillary pore. Negative pressures- indicate that an external pressure is required to.force aqueous liquid into the capillary. The cosine function for aqueous liquid is illustrated in Fig. 2.

Even though liquid water or body liquids cannot flow through the fine pores of the membrane, water vapor is able to flow through the pores very freely. Thus, water from the wound will evaporate freely and oxygen from the air will diffuse to the wound site, but germs, microorganisms, and dirt will not be able to enter the pores. As long as the membrane is intact, the wound will remain dry and sterile and a scab will rapidly form beneath the membrane without sticking to it.

Non-aqueous solutions containing medications, on the other hand, can be applied directly to the wound by applying them to the outside of the membrane where the solutions can pass through the hydrophobic micropores to the area of the wound. Even if the outside of the bandage is dirty or contaminated with microorganisms, the medication can still be applied safely because the fine pores of the membrane will filter out anything but the non-aqueous solution itself.

-Thus, there may be no need to change the bandage until the wound is completely healed. If the bandage is removed accidentally or prematurely for inspection of the wound, the bandage will not stick to the wound or scab because body fluids cannot stick to the membrane or lodge in its pores. The hydrophobic, water rejecting property of the membrane will also allow the patient to bathe or wash the wound area without removing the bandage, and without fear of introducing harmful bacteria to the wound site.

Medication may also be applied in an aqueous solution by incorporating a chemical such as a surfactant in the solution which adjusts the contact angle of the solution to below 90' to allow passage of the' solution through the hydrophobic material to treat the .wound.

A bandage designed to prevent water or aqueous solutions from entering its pores should have pores with as small an average or effective radius as reasonably possible, should not have many pores large enough to pass microorganisms, and should be made from a material that has as high a contact angle as reasonably possible. Water vapor, oxygen and air molecules will pass through a pore having a diameter of 0.0003 microns, while most common bacteria need at least about 3 microns to pass through.

Thus, pores having an effective pore size of about 1.0 micron, preferably 0.1 micron or less, will prevent passage of infectious organisms from the atmosphere through a pore to the wound below while allowing transpiration of oxygen and water vapor. Effective pore size is the least dimension, either diameter, width or length, which effectively prevents passage through the pore.

A material with the highest known contact angle with water is polytetrafluoroethylene, more commonly known by its initials P.T.F.E. and most commonly by duPont's trademark TEFLON®. Another material is Celgard® by Hoechst Celanese, a microporous isotactic polypropylene. Another material is Thintech® made by 3M Company. Other materials with high contact angles with water may be selected from paraffin wax, polypropylene, polyethylene, poly ethyl ethacrylate, polyvinyl chloride, polyvinylidene chloride, and many other synthetic polymeric materials.

The membrane may also be made from a normally hydrophilic material which is treated to become hydrophobic, although such materials are currently not believed to be as desirable as the naturally hydrophobic ' plastics. The normally hydrophilic material may be cellulose, or a cellulosic compound, or wool or other natural proteinaceous material. These compounds can be rendered hydrophobic by reaction with amines, quaternary ammonium compounds, organic silanes and other chemicals known to those in the waterproofing art.

In a preferred embodiment, the hydrophobic, microporous membrane or material used for covering wounds comprises a multiplicity of fine pores smaller than about 0.1 microns and is substantially free of pin holes or randomly large pores, e.g., fewer than 1% of the pores are larger than 1 micron. The membrane does not permit the passage of liquid water, but is permeable to water vapor and atmospheric gases especially oxygen. An effective pore size of less than about 0.075 micron (test method S.E.M.) appears to be particularly advantageous.

The membrane should be made from a hydrophobic material with an advancing contact angle to water greater than 90', and preferably between about 110' and about

150'. -Contact angles greater than 150' are also suitable and desirable but are not generally available as membranes.

The pore volume (porosity) of the material should be between 15% and 90% and preferably between about 35% and about 75%. This range gives an excellent combination of mechanical strength and area for transpiration of liquid. Celgard 2500, a product of Hoechst Celanese, has a porosity of about 45% (ASTM D-2873) .

The membrane thickness is preferably between about 0.6 and about 1.0 mil, but may be between about 0.3 and 3.0 mils depending on strength and flexibility requirements.

The water vapor transpiration rate of the hydrophobic material should be at least as great or greater than normal skin tissue, but should not be so high as to dehydrate the wound in a harmful way. A preferred water transpiration rate is between about 500 and about 5,000 grams/m ² /24 hrs (as tested by Method ASTM E96-66B) . Such rates are obtainable with commercial filter membranes such as Gortex, manufactured by W.L. Gore, and Celgard manufactured by Hoechst-Celanese. Celgard 2500 has a water vapor transpiration rate of between about 1,000 and 1,200 grams water vapor per square meter per 24 hours (ASTM method) . Transpiration rates in individual cases may need to be limited to avoid too rapid loss of water from the wounds such as in the case of massive burns. Transpiration rates in individual membranes can be decreased as needed by masking some of the micropores with adhesives or other materials, heat sealing, or lamination of two microfilms together. Transpiration notes of about 5000 grams/m ² /24 hrs. can be reduced to desired levels by blocking some of the pores.

Reported studies have indicated that the evaporative water loss from an open excision decreases from about 5,000 to about 3,250 g/m ² /24 hr. (20 to 13 mg/cm ² /hr) after 1 day; to about 1,800 after 2 days; to about 1,500 after 3 days; to about 1,400 after 4 days; to about 750 after 5 days; and to about 50 after 6 days. Thus, a bandage may need to have different transpiration rates depending on the stage of healing of the wound, or the area of the membrane available for transpiration may need to be altered to adjust the amount of water vapor transpired. A hydrophobic membrane having a transpiration rate of at least about 500 g/m ² /24 hr is believed to be desirable to promote healing.

The schematic, sectional view in Fig. 3 shows how a thin, microporous membrane placed over an open wound may function. The wound 10 is surrounded by normal skin 12. A hydrophobic, microporous membrane 14 is placed over the wound 10. Scab-forming material 16 on the wound 10 may- be in direct contact with membrane 14, but it will not stick to the membrane 14. Water in the scab-forming material will evaporate as vapor to the atmosphere through the micropores 18 in the membrane 14. Because of the size of the micropores 18, bacteria cannot enter the area of the wound 10. Adhesive tape 20, preferably but not necessarily impermeable to bacteria, holds the microporous membrane 14 in place over the wound 10. The adhesive tape may be selected from many commercially available products, such as MICROPORE®, DURAPORE®, Blenderm®, Transpore®, Tegaderm®, Opsite®, or Accuderm®. Alternatively, a medically acceptable adhesive could be applied between the outer edges of the membrane 14 and the skin 12.

As noted earlier, the transmission characteristics of the bandage. aterial preferably allows a non-aqueous solution or sufficiently fine mixture, such as a

colloidal suspension, to be applied to the wound surface by allowing the membrane to imbibe the non-aqueous solution or mixture after application to the outer surface of the membrane, such as from a spray bottle, aerosol, medicine dropper, or the like. The non-aqueous solution or mixture may contain medication to enhance cell growth in the wound or other medication which is beneficial to the healing process. A disinfectant or biocide, such as a solution of iodine in isopropyl alcohol (about 0.01 to about 1.0 percent iodine by volume) may be used to sterilize the wound either by application to the inside of the bandage before application to the wound, or to the outside of the bandage after application.

The hydrophobic material of the bandage is preferably applied directly over the wound with no intermediate materials which tend to stick to the scab. The bandage material of the present invention may be retained in place by any suitable means, but it is preferably retained in place by an adhesive or adhesive strip which does not come into contact with the wound, but which is impermeable to transmission of harmful organisms from the external environment to the wound, even though it may be permeable to organisms in a direction toward intact skin. If an adhesive strip is used over the hydrophobic material in a way which restricts transpiration rates undesirably, the strip should be made sufficiently porous to allow adequate passage of water vapor and oxygen. In fact, controlling the number and size of holes in an impermeable adhesive strip is a desirable way to control the water vapor permeability of the bandage. Alternatively, particularly for massive wounds, the microporous membrane may be held in place mechanically by permeable, flexible, elastic material, such as the material in nylon stockings, which could extend around the wounded body part and hold the

me brane in place. Edges of the membrane could be sealed as desired or as possible.

A particularly advantageous bandage for a wound comprises a macroporous strip and attached to it within the outer boundaries of the macroporous strip a microporous hydrophobic material which does not stick to the scab of the wound and which has a pore size sufficiently small and contact angle sufficiently large to transmit water vapor from the wound and oxygen to the wound while preventing transmission of liquid water and organisms harmful to the wound. The macroporous strip should be made sufficiently permeable to water vapor and air to avoid interference with the intent of the invention, and should have a medically acceptable adhesive on the macroporous strip outside the area of microporous material not over the wound.

Alternatively, although not as desirable to prevent transmission of microorganisms, the hydrophobic material can be attached to a macroporous strip so that the microporous hydrophobic material is over the wound even though its side edges are not sealed. The hydrophobic material will not stick to the wound.

While the invention has been described in detail, particularly in connection with certain examples and preferred embodiments, the foregoing is deemed to be illustrative of the principles of the invention. Since modifications and changes will occur to those skilled in the art, the invention is not to be considered as limited to the exact construction and operation shown and described, and accordingly all suitable modifications and equivalents may be resorted to which fall within the spirit and scope of the invention.