Abstract:
The present invention relates to wound dressings having a wound contacting layer that contains a wound healing composition and which is adapted to maintain a temperature different from ambient, for example achieve and maintain a heat-absorbing effect on the underlying tissues. The specific physico-chemical structure of the devices of the invention allows fluid containment and absorption of wound secretions while avoiding skin macerations.

Description:
FIELD OF THE INVENTION 
     The present invention is in the field of wound covering devices having particular physical surface layer features and which contain compositions designed to promote healing of the wound. 
     BACKGROUND OF THE INVENTION 
     Wound covering devices are known in the art. However, there still exists the need for wound dressings that promote wound healing, allow fluid containment and absorption of wound secretions. The present invention meets this need. 
     SUMMARY OF THE INVENTION 
     The present invention relates to wound dressings having a wound contacting layer that contains a wound healing composition and which is adapted to maintain a temperature different from ambient, for example achieve and maintain a heat-absorbing effect on the underlying tissues. The specific physico-chemical structure of the devices of the invention allows fluid containment and absorption of wound secretions whilst avoiding skin macerations. 
     In one aspect, the present invention thus relates to a cold adapted wound dressing device designed to promote healing of a wound to which it is applied, the dressing device comprising:
         a wound covering having a wound contacting layer with a wound contacting surface;   a wound treatment material contained in the wound contacting layer; and   a heat absorbing layer in heat flow communication with the wound contacting layer,       

     wherein the heat absorbing layer is adaptable to remove heat from the wound contacting layer and to reduce a temperature of the wound contacting surface to below an ambient temperature. 
     In another aspect, the present invention is directed to a method for promoting healing of a wound comprising applying the wound dressing device of the invention to the wound. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic side view of a basic embodiment of the present cold adaptable wound dressing device showing a heat-sink layer adjacent a wound contacting layer. 
         FIG. 2  is a schematic side view of an embodiment of the present cold adaptable wound dressing device showing the heat-sink layer and adjacent wound contacting layer enclosed/sandwiched between a wound contacting bottom surface layer and a dressing cover top layer. 
         FIGS. 3A to 3D  are schematic side views of alternative embodiments of the present cold adaptable wound dressing device. 
         FIG. 4  is a side cross-sectional view of the embodiment of  FIG. 3D  showing the extension of certain support layers to form a “piggy-back” configuration, wherein the SAP matrix can be separately hydrated, while the wound contacting matrix is maintained in a sterile condition by a separate, removable sterile cover. 
         FIG. 5  is a reaction scheme depicting the polymerization of acrylic acid and sodium acrylate. 
         FIG. 6  is a schematic depiction of a cross-linked polymer. 
         FIG. 7  schematically depicts swelling of a super-absorbent polymer upon contact with water. 
         FIG. 8  shows the influence of ions and the pH on the absorption properties of super-absorbent polymers. 
         FIG. 9  shows a picture of SAPs produced by a polymerization (gel) process, in which the monomers are polymerized in solution. SAPs resulting from this process have an irregular (chip-like) morphology. 
         FIG. 10  shows pictures of SAPs produced using an inverse suspension process, in which monomer droplets are suspended in a media stabilized by a surfactant. This process can lead to two different morphologies.  FIG. 10  A shows the agglomerated bead morphology of the thus produced SAPs, whereas  FIG. 10B  shows the broccoli-like morphology. 
     
    
    
     DESCRIPTION OF THE INVENTION 
     The present invention is a cold adapted wound dressing device, which has cooling and liquid absorption capabilities, and is useful in sterile and non-sterile environments for dressing wounds and other injuries. The present invention is not a bandage in the broad usage, because it is adapted to be sterilizable and to be in direct contact with a dermal/transdermal wound or surgical incision on the body. The cooling ability of the device is intended to temporarily lower the temperature of the body at the site of application, and to provide the attendant benefits of such a local temperature reduction. 
     In a preferred embodiment, a heat-sink made of hydrated absorbent polymers is contained in a portion of the device. Preferably, the hydrated polymers are of a type known as: super-absorbent polymers (SAPs) in the form of a hydrogel. See for examples: U.S. Pat. No. 4,668,564 to Orchard, and U.S. Pat. No. 5,750,585 to Park et al. Super-Absorbent Polymers typically are cross-linked copolymers of acrylic acid and sodium acrylate ( FIG. 5 ). Other materials for super-absorbent polymers comprise, but are not limited to, polyacrylamide copolymer, ethylene maleic anhydride copolymer, cross-linked carboxy-methyl-cellulose, polyvinyl alcohol copolymers, cross-linked polyethylene oxide, and starch grafted copolymer of polyacrylonitrile. They are commercially available in a powder or particulate form. These materials are characterized as super-absorbent in that they are able to rapidly (i.e., in a few seconds under appropriate conditions) adsorb on the order of 500 time their weight in pure water. 
     For this material to obtain “super-absorbent” properties, requires cross-linking the copolymer chains with a cross-linking agent, such as a bifunctional molecule. The bifunctional molecule must be able to react with the free carboxylic groups. After cross-linking, the polymer chains are attached to one another ( FIG. 6 ). 
     Exemplary cross-linking agents comprise, but are not limited to polyhydroxy compounds, diepoxy compounds, isocyanates, ethyleneglycoldimethacrylate (EGDM), and N,N-methylenebisacrylamide (BIS). 
     In the dry state the matrix network of the super-absorbent material is folded/compressed on itself. The matrix is highly hydrophilic and expands upon hydration when it comes into contact with water ( FIG. 7 ). The initial dry (powder or particulate) material turns into a gel, expanding to a volume several hundred times larger than the initial volume. A large percent of synthetic SAPs are powders/particles. Typical average particle size of commercially available product is about 450 μm, with a relatively narrow distribution of particle sizes. 
     The performance of SAPs is characterized by its physical parameters: cross-linking, particle size distribution, morphology, etc., and also by the fluid they are hydrated with and/or subsequently come into contact with. The influence of ions and the pH on the absorption properties is exemplarily shown in  FIG. 8 . Divalent ions in hard water, such as magnesium and calcium, as well as sodium ions may significantly decrease the absorption properties of SAPs. In addition, the pH also may influence absorption with a common absorption maximum being between pH values of 4 and 8. 
     Most SAPs are synthesized by a polymerization (gel) process, in which the monomers are polymerized in solution. This results in the formation of a polymer block, which is sieved to obtain the desired particle size. SAPs resulting from this process have an irregular (chip-like) morphology ( FIG. 9 ). 
     However, it is possible to obtain SAPs having a more uniform morphology. This is accomplished using an inverse suspension process, in which monomer droplets are suspended in a media stabilized by a surfactant. Polymerization takes place in each droplet, and can lead to two different morphologies, agglomerated beads ( FIG. 10A ) or a broccoli-like morphology ( FIG. 10B ). The former hydrate, when contacted with water, to produce a gel in about 100 seconds. The latter can hydrate to produce a gel in about 5 seconds due to their very high specific surface area (in the order of 1 m 2 /gm). 
     Table I shows desirable characteristics of SAPs for practice in the present invention. 
     
       
         
               
               
             
               
               
               
             
               
               
               
               
             
           
               
                 TABLE I 
               
               
                   
               
             
             
               
                 Adsorption in demin water 
                 About 500 g/g 
               
               
                 Appearance 
                 White powder 
               
             
          
           
               
                 Available morphology 
                 (See FIG. 10A) 
                 (See FIG. 10B) 
               
               
                 Gelling time 
                 100 s 
                 5 s 
               
             
          
           
               
                 Particle size distribution 
                 100-800 μm 
                 100-500 μm  
                 0-150 μm 
               
               
                 Bulk density 
                 0.74 
                 0.42 
                 0.60 
               
               
                 Typical products 
                 D60 
                 S35 
                 XFS 
               
               
                   
               
             
          
         
       
     
     As further examples, the following SAPs are can be practiced in the present invention: Aquakeep® and Norsocryl® which are SAPs that are able to absorb more than several hundred times their weight of pure water in a few seconds. (Arkema, Colombes Cedex, France: www.arkema.com). After swelling, the SAP liquid becomes a gel. Generally, SAPS are practicable for the absorption and retention of non viscous fluids, and used in such disposable products such as baby diapers, training pants, adult incontinence products and sanitary napkins. These SAPs typically are cross-linked copolymers of acrylic acid and sodium acrylate. 
     When hydrated with NaCl 0.9% or demineralised/sterile water in a proportion not exceeding about 20% of the total absorption capacity of the above SAPs (free absorption g/g—Edana recommended test method), the heat sink can be appropriately cooled or frozen. Chilling of the hydrated super-absorbent hydrogel prior to application of the present dressing to a wound site provides the heat sink (heat absorbing) feature of the dressing. 
     Referring now to the drawings, the details of preferred embodiments of the present invention are graphically and schematically illustrated. Like elements in the drawings are represented by like numbers, and any similar elements are represented by like numbers with a different lower case letter suffix. 
     As illustrated in  FIG. 1 , the present cold adapted wound dressing device  10  designed to promote healing of a wound to which it is applied comprises two main structural components: a wound covering  12 ; and a heat sink or heat absorbing layer  50 . Additionally, the present wound dressing device  10  includes a wound treatment material  40  disposed in the wound covering  12 . In a preferred embodiment exemplified in  FIG. 1 , the wound covering  12  has a wound contacting layer  16  with a wound contacting surface  20 . A wound treatment material  40  is contained in the wound contacting layer  16 . The heat absorbing layer  50  is in heat flow communication with the wound contacting layer  16 . The heat absorbing layer  50  is adapted to remove heat from the wound contacting layer  16 , and thus reduce the temperature of the wound contacting surface  20  to below ambient temperature. Heat from the wound area where the dressing is applied is drawn to the heat sink layer  50 , which reduces the local body temperature in the area of the wound. In this manner, the present cold adapted wound dressing device  10  provides the healing benefits associated with cooling the wound site. Additionally, the wound treatment material  40  in the wound contacting layer  16  can diffuse out of the contacting layer  16  and into the wound site, and function as a bio-acting composition to biochemically promote wound healing. Therefore, the present cold adapted wound dressing device  10  provides the benefit of a duplex wound healing mechanism to actively promote healing, rather than only the passive protective function of a plain dressing. These benefits for promoting healing of the wound are: the physical function of removing heat, absorbing wound exudate and blood and the biochemical function of providing a bio-active composition 
     The wound covering portion  12  of the present cold adapted wound dressing device  10  has a wound contacting layer  16  configured as a porous matrix  30  that allows aqueous fluids to freely diffuse into and through the matrix  30 . The matrix  30  in this embodiment is comprised of a fibrous material  32 . However, materials other than fibrous may be used if they are adapted to maintain the structural integrity appropriate for a wound dressing. The porous matrix  30  has fluid absorbing properties and can absorb body-fluids and/or wound exudate. Fibrous SAPs having appropriate fluid absorption properties are known in the art and are selectable by the ordinary skilled artisan for practice in the present invention. Examples of cross-linked SAP&#39;s supports practicable in the matrix are: cellulose, wood pulp, alginates, etc. The wound-contacting layer and the dressing cover top layer can comprise polypropylene, polyethylene, polyester or any other bio-compatible synthetic layer as are known in the art. 
     The wound contacting layer  16  of the wound covering  12  has a wound contacting surface  20 , which is intended to contact the wound at the wound site. In the embodiment exemplified in  FIG. 1 , is merely a surface of the wound contacting layer  16  itself. However, as exemplified in  FIG. 2 , the wound contacting surface  20   a  can be a separate porous surface layer  22  made of the same material or a material different from the wound contacting layer  16 , which has an appropriate plurality of pores  24  distributed across the porous surface layer  22  to allow fluids and solutes passage through. For example, if the matrix material  30  of the wound contacting layer  16  is to be prevented from adhering to the wound, the wound contacting surface  20   a  can be accomplished using a non-sticking separate porous surface  22 . This non-sticking separate porous surface may be impregnated with natural Hyaluronic Acid (HA) or crosslinked HA (as fibers, granules, powder, gel) or HA-compositions like creams, gels, aequeous solutions and/or chitosan, diacerhein and/or derivatives thereof. The above mentioned compositions provide anti-inflammatory functions (e.g. Diacerhein, HA) and analogues for the substitution of endogenous HA which is normally required in the wound healing process. 
     In another embodiment, the material of the wound contacting layer can be collagen, poly(L-lactide) (polylactic acid; PLLA), and/or poly(glycolic-co-lactic acid) (PGLA) which are impregnated with the above mentioned compositions. 
     As also illustrated in the figures, the present cold adapted wound dressing device  10  has a wound contacting layer  16  that is a porous matrix  30  comprised of a fibrous material  32 , which fibrous material  32  is impregnated with a wound treatment material  40 . The wound treatment material  40  is a bio-affecting composition having wound healing efficacy, and can be composed of one or more active constituents  46 . In the embodiment illustrated, a natural Hyaluronic Acid composition  46   a  is an active constituent of the wound treatment material  40 . The natural Hyaluronic Acid composition can be contained in the matrix material  30  in the form of a gel, a cream, natural Hyaluronic Acid fibers  46   a  or a combination of any of these. Other active constituents  46   b  can be contained in the matrix material  30  as well, such as those noted above. 
     As illustrated in  FIG. 3A , the present cold adapted wound dressing device  10  wherein the wound covering  12  has a wound contacting surface  22   a  that is a separate porous surface of the wound contacting layer  16 , the separate porous surface  22   a  having physical surface features  60  that mechanically engage the wound contacting layer  16 . The physical surface feature  60  serves to engage the wound contacting layer  16  and prevent it sliding relative to the wound contacting surface  22   a , and to prevent the disengagement of the wound contacting layer  16  from the wound contacting surface  22 . This is useful in view of the hydrated nature of the heat absorbing layer  50  in embodiments where the heat absorbing layer  50  is in fluid communication with the wound contacting layer  16 . For example, in  FIGS. 3A and 3B , the heat absorbing layer  50  is in open fluid flow communication with the wound contacting layer  16 . In  FIG. 3C , a partial fluid barrier  66  separates the heat absorbing layer  50  from the wound contacting layer  16 . In this embodiment, the heat absorbing layer  50  is in partially restricted fluid flow communication with the wound contacting layer  16 , because of the pores  25  through the partial fluid barrier  66 . In  FIG. 3D , a full fluid barrier  68  separates the heat absorbing layer  50  from the wound contacting layer  16 . The full fluid barrier  68  may allow gas exchange through the layers. In this embodiment, the heat absorbing layer  50  precluded from being in fluid flow communication with the wound contacting layer  16 . In the embodiments illustrated in  FIGS. 3A to 3D , the engaging surface features  60  are holes roughly punched through the separate wound contacting surface  22   a . The physical surface features are not necessarily the same as the pore feature  24  of the separate porous layer  22 . Although a physical surface feature  60  may additionally serve the passage function of a pore feature  24 , they also provide a mechanical engagement feature that a simple pore feature  24  may not. 
     In the preferred embodiment illustrated, the heat absorbing layer  50  of the cold adapted wound dressing device  10  comprised a hydrated “super absorbent polymer” (SAP)  70 . SAPs  70  are known in the field. Examples include those disclosed in U.S. Pat. No. 5,750,585 to Parl et al. and U.S. Pat. No. 6,800,278 to Perrault et al. Choice of the SAP  70  to be practiced and it relative bio-compatibility will influence whether an embodiment wherein the heat absorbing layer  50  is in flow communication with the wound contacting layer  16  can be practiced. 
     To make the present cold adapted wound dressing device  10  a self contained unit, a bandage covering  74  can be added to the top surface  72  of the heat sink layer  50 . See  FIGS. 3B to 3D . The bandage covering  74  can be accomplished using any of a number of materials and configurations known to and selectable by one of skill in the art. For example, the top covering dressing layer  74  can be occlusive, can have limited gas-permeability or can it have pores  25  to pass fluids. The top covering dressing layer  74  can protected with an adhesive backed covering (not shown). 
     Also, as exemplified in  FIG. 4 , the embodiment of  FIG. 3D  can be adapted to form a “piggy-back” configuration, wherein the SAP matrix  50  can be separately hydrated, while the wound contacting matrix  12  is maintained in a sterile condition by a separate, removable sterile cover  90 . 
     The inventive wound dressings can be used in methods for promoting the healing of a wound in a patient, for example a mammal, such as a human being, said methods comprising applying the wound dressings of the invention to said wound. 
     The invention is further illustrated by the following non limiting examples and the appended figures. As one of ordinary skill in the art will readily appreciate from the disclosure of the present invention, other compositions of matter, means, uses, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding exemplary embodiments described herein may likewise be utilized according to the present invention. 
     EXAMPLES 
     Example 1 
     Loading the Matrix with Hyaluronic Acid 
     Adequate amounts of matrix material, like cellulose fibers, thermoplastic fibers and SAP powder with a total weight of 50-500 g/m 2  were given into a powder mixer along with a defined quantity of dry medical grade sodium hyaluronate granules (for example a quantity to obtain a HA concentration of 0.1% w/w) and mixed for one hour at 120 rpm. Thereafter the resulting mixture was compressed by a calendar press at 55° C. to a dry “cake” with a diameter of 2-4 mm. A matrix obtained by this process, when being eluted with water having a temperature of 36° C., will release 60-80% of the HA as determined by the carbazol method. This shows that a matrix loaded with HA can serve as a reservoir for the uptake and release of HA to wound surfaces. 
     Example 2 
     Loading the Matrix with Deacetylated Chitosan 
     The same process was used for loading the matrix with medical grade chitosan of animal or non-animal origin, which is characterized by a deacetylation ratio of 60-95%. 
     Example 3 
     Impregnating the Encasing Material with Hyaluronic Acid 
     Webs of non-woven thermoplastic fibers of an adequate texture and strength were lead through an aerosol chamber first and, subsequently, through a drying chamber in order to achieve an impregnation of the encasing material with 0.1 to 0.5% of HA (w/w). Spraying and padding the nonwoven material with HA based aqueous solutions before drying are alternative methods of impregnation. 
     Example 4 
     Bonding the Matrix with the Encasing Material 
     Mechanical stabilization of the matrix inside the encasing material is an important measure in order to avoid lumping/agglomeration leading to dislocation of the matrix material inside the pad once this is soaked with water and exposed to vertical forces. This was achieved, for example, by partial ultrasound bonding of the encasing material to the matrix, which—to this extent—contained an adequate amount of thermoplastic fibers or powder. 
     Example 5 
     Positive Cooling and Wound-Healing Effects of the Device 
     A sterilized prototype version of the cold-adapted wound dressing device was used in patients after arthroscopic meniscectomy in order to improve their postsurgical course. The pads were sterilised by ethyleneoxide and unpacked in the sterile op-environment.
 
Thirty patients were included in this pilot, comparative study and divided into 2 groups, a prototype wound pad treatment group (n=20 patients) and a control group (n=10 patients)
 
The prototype wound pad treatment group underwent the following procedures:
 
After completion of arthroscopic meniscectomy, steri-strips were used for skin closure in all the 20 patients. For each patient a prototype cold-adapted wound dressing device (size 12×22 cm) was removed from the sterile packaging and about 100 mL 0.9% NaCl (approx. 0.5-0.8 mL NaCl/cm 2 ) cooled to 4° C. were poured into the upper part of the device. The prototype cold-adapted wound dressing device retained this cold water in the SAP part of the device. 10 ml of Viscoseal (TRB Chemedica), a sterile viscoelastic solution containing 0.5% fermentative hyaluronic acid in a buffer solution, was applied to the lower part of the prototype cold-adapted wound dressing device which would be placed in contact with the wound surface. The prototype cold-adapted wound dressing device was then applied onto the closed incisions wounds (3 per joint) and was covered with an occlusive dressing and an elastic bandage. Patients were prescribed analgesics or classical NSAIDs and the number taken by each patient was recorded.
 
The control group underwent the following procedures:
 
After completion of arthroscopic meniscectomy, Steri-strips were used for skin closure in the 10 patients in this group. Standard, commercially available wound dressings were placed on the wound. No cooling packs were used in this group of patients. Patients were prescribed classical NSAIDs and the number taken by each patient was recorded. Analgesics were prescribed in case patients still had pain despite the intake of NSAIDs and the type and amount of analgesics taken by each patient was recorded
 
Pain in the treated joint was assessed by the patient at about 1 hour post-surgery (by which time the anaesthetic had worn out), and then every 2 hours over a 24 hour post-operative period (when the patient was awake), using a 100 mm visual analogue scale (VAS). This scale has a zero (0) anchor point indicating “no pain” and one hundred anchor point (100) indicating “intense pain”.
 
Skin temperature was measured by a nurse every 10 minutes for the 1 st  hour after surgery using a standard thermometer, the tip of which was placed adjacent to the skin in the operated region).
 
Determined or monitored were:
         the duration of skin temperature reduction;   analgesic consumption in addition to regular NSAIDS intake;   joint effusion;   skin maceration; and   tolerance to cryotherapy or allergic reactions to HA/adverse events
 
Results showed that, in the prototype cold-adapted wound dressing device group, the mean value for pain was 3 cm on the VAS (range: 2-6 cm) in the first 24 hours and 2 patients required a single dose of an analgesic in addition to their NSAIDs at the time of discharge from the hospital about 24 hours post-surgery.
 
In the control group, the mean value for pain was 4.5 cm (range 2-9 cm) in the first 24 hours and 5 patients required analgesics in addition to their NSAIDs at the time of discharge from the hospital about 24 hours post-surgery.
 
It can be concluded that, in comparison to standard dressing, the prototype cold-adapted wound dressing device rapidly decreased post-operative pain and surprisingly had an NSAID-sparing effect. The most significant pain reduction was in the first 4 hours post-surgery in comparison to the control group and patients required fewer escape medication post surgery.
 
The skin temperature near the operation site was taken immediately after the completion of arthroscopy and application of Steri-strips (baseline values) and every 10 minutes thereafter for the first 60 minutes after surgery in both groups. The mean temperature of the skin near the operation site in both groups of patients was 33° C.
 
In the prototype cold-adapted wound dressing device group, the mean skin temperature decreased to 14° C. at 5 minutes after application of prototype device and remained at a low level for a mean period of 22 minutes. Thereafter there was a progressive increase in skin temperature over the next 33 minutes to reach 30° C.
 
Skin temperature in the control group remained at a mean value of 32° C. for the first 60 minutes.
 
In conclusion, the prototype cold-adapted wound dressing device caused a significant decrease in skin temperature compared to the control group.
 
Surprisingly, the use of the cooling pad did not result in condensation of humidity on the skin and no skin maceration was observed in the prototype wound pad-treated group during the observation period of 24 hours.
 
The prototype wound pad was stained with wound exudate but remained dry after absorbing the exudate. The wound contacting surface of the prototype stayed dry due to the residual humidity absorbing capacity of the SAP layer.
 
Patients in the prototype wound pad-treated group had more rapid primary wound healing in all 60 incisions (3 per knee) with no infections observed. At the 6 month visit, no cheloid formation or delayed wound healing was observed.
 
In the control group, primary wound healing in all 30 incisions (3 per knee) was slower with more exudate formation but no infections were observed. At 6 months, 2 patients showed cheloids.
 
In conclusion, the above results showed that the prototype wound pad was safe and effective in post-operative wound care. By its skin cooling effect it reduced the amount of wound exudates and hematoma compared to the control group. The more rapid wound repair in the prototype wound pad-treated group was probably due to the presence of hyaluronic acid. The wound surface was slightly moist and no skin maceration or other adverse event was observe
       

     While the above description contains many specifics, these should not be construed as limitations on the scope of the invention, but rather as exemplifications of one or another preferred embodiment thereof. Many other variations are possible, which would be obvious to one skilled in the art. Accordingly, the scope of the invention should be determined by the scope of the appended claims and their equivalents, and not just by the embodiments. 
     All documents cited herein are incorporated by reference in their entirety.