WO2016130861A1 - Composition et procédé pour l'utilisation d'un pansement activé par énergie - Google Patents

Composition et procédé pour l'utilisation d'un pansement activé par énergie Download PDF

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Publication number
WO2016130861A1
WO2016130861A1 PCT/US2016/017634 US2016017634W WO2016130861A1 WO 2016130861 A1 WO2016130861 A1 WO 2016130861A1 US 2016017634 W US2016017634 W US 2016017634W WO 2016130861 A1 WO2016130861 A1 WO 2016130861A1
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Prior art keywords
composition
wound dressing
wound
gelatin
tissue
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PCT/US2016/017634
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English (en)
Inventor
Tien Nguyen
Ary Chernomorsky
Stanley R Conston
Ronald Yamamoto
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Medterials, Inc
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Publication of WO2016130861A1 publication Critical patent/WO2016130861A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/48—Surfactants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/425—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/60—Liquid-swellable gel-forming materials, e.g. super-absorbents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222—Gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/502—Plasticizers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges

Definitions

  • Wound dressings are applied to areas of trauma or surgery to physically protect the wound, provide a barrier to infection, promote healing and in some cases deliver medication.
  • wound dressings comprise several layers, including an adhesive layer to provide securement.
  • tissue surfaces are not suitable for the use of adhesive wound dressings. These surfaces include mucosal tissues, exudative tissue surfaces and bleeding tissue surfaces.
  • Mucosal tissues are sensitive to chemical irritation, especially from reactive adhesives capable of bonding to moist surfaces. Many adhesives, such as those used on the skin, are not effective when the underlying tissue is moist or producing fluid.
  • applications where the wound dressing is within the body or in a location in which the dressing may be internalized such as the nasopharyngeal cavity, it is desired to have a dressing that is non-toxic and may be readily metabolized or eliminated by the body through natural processes. Due to these constraints, there are no satisfactory wound dressings for use after nasopharyngeal surgery, organ resection, or gastrointestinal surgery.
  • Collagen welding rod material for use in tissue welding
  • the present invention provides a wound dressing that adheres or bonds directly to tissue when activated by energy without the use of an adhesive layer.
  • the invention comprises natural biological materials and provides adhesion through direct interaction and integration with the wound surface.
  • the wound dressing may be applied to wounds due to trauma, arthroscopic surgery, spinal surgery, tracheobronchial surgery, neurosurgery, and surgery used in otolaryngology, urology, gynecology, gastroenterology, reconstructive surgery, and general surgery to protect the wound, promote healing, and reduce pain.
  • the wound dressing may be applied in conjunction with nasopharyngeal surgery such as tonsillectomy, adenoidectomy, uvulopalatoplasty, uvulectomy and base of the tongue reduction.
  • the wound dressing may also be used to stabilize and protect organs after resection such as lung reduction surgery, excision of solid tumors, and surgical repair of the gastrointestinal system.
  • Some embodiments provide a wound dressing composition comprising gelatin and a plasticizer, wherein the composition is in the form of a film and crosslinked by physical or chemical means.
  • the film further comprises through holes.
  • the composition has a transition upon the application of energy to adhere or bond to an underlying wound.
  • the composition has a transition to a material with increased flexibility or elongation properties after the application of energy.
  • a wound dressing composition comprising gelatin, a plasticizer, and a surfactant, wherein the composition is in the form of a film and crosslinked by physical or chemical means.
  • a wound dressing composition comprising gelatin and cysteine, wherein the composition is the form of a film and crosslinked by physical or chemical means.
  • the film further comprises through holes.
  • Some embodiments provide a wound dressing composition comprising gelatin, wherein the composition is in the form of a film and crosslinked by physical or chemical means.
  • the film further comprises a coating on the external facing surface of the film.
  • a wound dressing composition comprising gelatin, wherein the composition is in the form of a film and crosslinked by physical or chemical means and further comprises a coating on the external facing surface of the film.
  • the coating comprises a material which prevents sticking of a probe or instrument applying energy to the wound dressing.
  • the coating material comprises a lipid, oil, fatty acid or emulsion.
  • Some embodiments provide a wound dressing composition of the disclosed compositions in a generally planar configuration, a convex curved configuration or a concave curved configuration to match the shape of the wound that is being treated with the wound dressing. Some embodiments provide a method for application of a wound dressing composition comprising gelatin and a plasticizer wherein the wound dressing is applied to a mucosal surface and energy is applied to create adherence or bond to the underlying mucosal surface. Some embodiments provide a method for application of a wound dressing composition comprising gelatin and a plasticizer wherein the wound dressing is applied to a surface of an organ and energy is applied to create adherence or bond to the underlying organ surface.
  • FIG. 1 depicts an energy source for the activation of the wound dressing.
  • FIG. 2 illustrates energy activation of the wound dressing in the nasopharyngeal cavity.
  • FIG. 3a illustrates the wound dressing being placed onto a post-tonsillectomy wound.
  • FIG. 3b illustrates activation energy emitted by the wand applied to the external facing surface of the wound dressing to activate the wound dressing.
  • FIG. 4a illustrates a perspective view an embodiment of the present invention with a plurality of through holes.
  • FIG. 4b illustrates a perspective view of an embodiment of the present invention with two layers.
  • FIG. 5 illustrates a perspective view of an embodiment of the present invention with a coating of a wand interfacing material as the surface exposed to the environment external to the wound.
  • FIG. 6 illustrates a wound dressing configured for energy activation on the periphery of the dressing.
  • the present invention is a composition for a wound dressing that may be activated by energy to create adherence or a direct bond of the wound dressing to the underlying tissue on which it is placed.
  • the wound dressing may bond to the tissues and integrate with the wound surface.
  • the composition of the present invention comprises gelatin and a plasticizer formed into a thin film that conforms to the surface of the wound. While not wishing to be bound to a particular theory of operation, it is believed that the application of energy to the wound dressing while in intimate contact with the wound allows interaction of the dressing components and the wound to provide adherence or bonding.
  • the energy source may be a source of plasma, radiofrequency (RF) electrical energy, ultrasound, light or heat.
  • the energy source system includes a power supply module 1 providing power to a probe 2.
  • the probe 2 also called a wand, includes a combination connector housing and handle 3 at its proximal end and a probe cable 4 connected to the power supply 1.
  • Power supply 1 has an operator controllable power level adjustment 5 to change the applied power output, which is observable at a power display 6.
  • Power supply 1 may optionally include a foot pedal control 7 attached with a cable 8 to the power supply 1.
  • the ultrasound activation of the wound dressing is enabled by cavitation of the wound and tissue fluids or additional fluid from irrigation.
  • a means for control of the intensity of the applied energy may be used to provide the appropriate amount of energy without significant damage to the underlying tissue.
  • a small amount of energy may be delivered to the tissue through the wound dressing to increase bonding to the wound dressing or to provide hemostasis simultaneous with the activation of the wound dressing.
  • the wound dressing composition is in the physical form of a film, with a first surface for application to a wound or tissue surface and an opposing second surface exposed to the environment external to the wound. Other forms suitable for specific applications of the wound dressing may also be used.
  • the thickness and energy conductive properties of the film are selected to allow penetration of the energy source applied to the second surface to reach the first surface and bond the wound dressing to the underlying tissue.
  • Appropriate film thickness ranges from about 30 to 250 microns, about 40 to 200 microns or about 50 to 150 microns.
  • the film may be in a generally planar configuration or may be curved to match the approximate shape of the wound to be treated.
  • the wound dressing may have a concave curved configuration to fit a tissue excision site such as after tonsillectomy or have a convex curved configuration to match the exterior of a resected organ such as the lung.
  • the film can be fabricated by molding of the gelatin composition including film casting from solution.
  • the gelatin is prepared in a heated solution with a physiologically compatible buffer to provide a pH and tonicity to allow prolonged contact with tissue without irritation.
  • Suitable buffer systems include phosphate buffer, HEPES, bicarbonate buffer and glycine buffer.
  • Tonicity may be adjusted to the physiological range by the addition of sodium chloride and/or potassium chloride.
  • the film is crosslinked after formation to form the wound dressing. Crosslinking may be performed by exposure to chemical agents such as formaldehyde, dialdehydes, including glutaraldehyde, diisocyanates, carbodiimides and difunctional epoxides.
  • Physical methods include vacuum treatment, freeze- thaw, dehydrothermal and ultraviolet (UV) irradiation.
  • Chemical methods in which ionic groups of the gelatin are utilized often increase hydrophobic properties of a gelatin based material.
  • UV irradiation has been found to provide a hydrophilic surface after crosslinking, which provides good surface contact with a moist wound surface and mucosal tissue.
  • Crosslinking is desired to be sufficient to provide physical integrity to the wound dressing material, but without crosslinking to a degree in which mobility of the material and tissue bonding properties are reduced. Suitable crosslinking has been found to be achieved with 2.5 to 10 minutes of UV exposure at a wavelength of 254 nm and an intensity of 950 milliwatts per cm 2 .
  • Additives may be added to the film composition to increase UV crosslinking, such as photo initiators or reactive sugars.
  • the extent of crosslinking may be determined by the equilibrium water absorption of the wound dressing material. Equilibrium water absorption of about 70.5% to 741 .1 %, about 313.9% to
  • plasticizers include glycerol, water, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol and polyethylene-propylene glycol copolymers.
  • Plasticizers in the amount of approximately 4.7% to 12.8% by weight (wt %) of the dry composition have been found to provide flexibility to the wound dressing composition to provide improved tissue adherence or bonding.
  • a surfactant may be added to the composition to aid film fabrication and, for some surfactants, to provide added plasticization effect.
  • Suitable surfactants are non-toxic and include fatty acids, alkyl carboxylates-fatty acid salts, alkyl sulfates, alkyl ether sulfates, fatty acid esters, sorbitan fatty acids (Span ® ), polyoxyethylene sorbitan fatty acids (Tween ® ).
  • the wound dressing 12 has a first surface 15 intended for application to a tissue surface and a second surface 16 that is exposed to the external environment.
  • the wound dressing 12 has a plurality of through holes 17 traversing the thickness of the wound dressing to connect the first surface 15 with the second surface 16. Through holes from the first surface to the second surface provide a path for fluid and gas flow.
  • the holes may, in some embodiments, provide a pathway for applied energy to the wound and wound dressing interface to promote tissue bonding. Holes in the range of 0.41 mm to 0.71 mm diameter, corresponding to a cross-sectional area range of 0.13 mm 2 to 0.40 mm 2 have been found to provide sufficient transport properties.
  • the holes may have various geometries, such as circular, polygonal, oblong, or slotted, with characteristic cross-sectional dimensions.
  • the holes of various geometries may have a characteristic cross-sectional dimension, such as a diameter or an axial length in the range of 0.41 mm to 0.71 mm or a cross- sectional area in the range of 0.13 mm 2 to 0.40 mm 2 .
  • a plurality of holes may be incorporated into the wound dressing.
  • a density of holes ranging from 8 to 16 holes per square cm has been found to provide transport properties without significant reduction of the barrier benefits of the wound dressing.
  • a property of the wound dressing composition is the transition of the material properties after application of energy.
  • the wound dressing composition has been found to increase in flexibility or elongation properties after exposure to energy. Flexibility is evident from the increased elongation properties during mechanical characterization. The transition allows the material to better conform to the microarchitecture of the wound surface.
  • the wound dressing integrates into the wound surface to provide a resurfacing of the wound. The transition effect is also useful in that a stiff wound dressing is more easily applied to the wound, but results in a conformal and flexible protective barrier on the wound surface after energy activation.
  • the surface of the wound dressing intended for contact with the wound surface is textured.
  • Surface textures may be selected to facilitate integration of the wound dressing into the wound or promote wound healing. Textured surfaces may be fibrous, porous, dimpled, striated or other textures, including combinations thereof.
  • the texture is molded into the film used to fabricate the wound dressing.
  • the film may be etched or imprinted to impart texture.
  • the wound dressing may be composed of more than one layer.
  • a layer adjacent the first surface intended for application to tissue may be comprised of several layers, each having a structure and composition the same as or different from another layer. Each layer may be structured to achieve specific properties.
  • a layer adjacent the second surface exposed to the environment may be a barrier layer comprised of several layers, each having a structure and composition the same as or different from another layer.
  • the wound dressing 12 comprises two layers.
  • Layer 18 comprises a first surface intended for application to a tissue surface with through holes 17.
  • Layer 19 comprises a porous material to function as the second surface exposed to the environment external to the wound.
  • one or more layers of the dressing may be colored to provide ease of use or to identify the different layers.
  • part or all of the dressing may be colored to help a physician or patient confirm that the dressing is still in place, how much of the dressing has dissolved, or the like.
  • the wound dressing composition of the present invention may be used as a portion of a composite wound dressing.
  • the wound dressing composition of the present invention is used to form a perimeter of a composite wound dressing where the center of the dressing has a different composition and function, but the perimeter acts to secure the dressing to the wound.
  • the wound dressing 12 comprises a peripheral area 21 for energy activation and adherence of the dressing to underlying tissue and a central area 22 for treatment of the wound.
  • the central portion of the composite wound dressing may be tailored to absorb exudate, deliver medications or transmit signals that may be magnetic, electrical or optical in nature.
  • the second surface of the wound dressing exposed to the environment is designed for contact with the probe or wand transmitting the energy to activate the wound dressing.
  • the wound dressing 12 comprises a base layer 18 comprising a first surface intended for application and adhesion to a tissue surface with through holes 17.
  • Coating 20 comprises a wand interfacing material to function as the second surface exposed to the environment external to the wound.
  • the probe makes physical contact with the wound dressing and may stick to the wound dressing material, especially during or after energy activation.
  • a layer of material on the second surface may be designed to interface with the probe and prevent adherence to the wound dressing material.
  • Such probe interfacing materials may be a liquid, semi-solid or a solid such as oil, lipid, lipid derivative, fatty acid, fatty acid derivative, surfactant or an emulsion.
  • the oil may comprise naturally derived oil or a synthetic oil such as low molecular weight
  • the probe interfacing material is desired to be non-toxic and eliminated by the body by natural processes.
  • the interfacing material may have a temperature transition from solid to liquid during activation of the wound dressing with energy such as lauric acid, palmitic acid and stearic acid.
  • a coating of the probe interfacing material may also aid application of the wound dressing by acting as an electrical insulator or thermal conductor to promote even distribution of the energy to activate the wound dressing.
  • the interfacing material may be applied as a coating on the second surface by thin film deposition, film casting or spray coating.
  • the probe interfacing material may be applied to the probe surface as a coating or sleeve that may be applied to the probe prior to activation of the wound dressing.
  • the wound dressing may be used in the nasopharyngeal cavity 11 , with the wand 2, hand held by the operator 9 and positioned against the tonsil tissue 10 of the patient.
  • the wound dressing 12 is placed onto a post-tonsillectomy wound 13 and activation energy 14 emitted by the wand 2 applied to the second surface of the wound dressing 12 to activate the wound dressing.
  • the wound dressing is not a risk for obstruction if dislodged, which could cause choking or aspiration of the material.
  • the transition of the material to a material of greater flexibility, integration into the wound and the plurality of through holes provides an adherent wound dressing that is difficult to remove in a single or several large pieces. Attempts to remove the bonded dressing with forceps results in loss of small fragments that are not a risk for obstruction.
  • Additives may be incorporated into the wound dressing composition to enhance performance or provide other functional benefits.
  • addition of the amino acid cysteine, cysteine derivatives including cystine, or other cysteine containing compounds increases the tissue bonding properties of the composition.
  • cysteine incorporated into the dressing may provide for disulfide bonds between the wound dressing and the macromolecules of the underlying tissue.
  • Mucin present on mucosal surfaces has high disulfide bond content and may be receptive to disulfide bonding to the cysteine- containing composition.
  • the energy source when applied to the wound dressing creates oxidative conditions to promote disulfide bonding between the wound dressing composition and the interfacing tissue. It has been found that a cysteine content of 0.044 wt % to 1 1 .8 wt % of the dry film provided increased adherence of the wound dressing to tissue.
  • additives may be incorporated into the wound dressing, such as anti-inflammatory agents, antibiotics, antimicrobial agents, anesthetics, analgesics, agents to prevent post-operative surgical adhesion, and wound healing mediators.
  • flavorings may be incorporated.
  • a steroid is added to the wound dressing composition to provide a local antiinflammatory effect and energy activated to adhere or bond to tissue using a low temperature energy source such as saline plasma or ultrasound. A low temperature energy source may be used to minimize degradation of drug during activation of the wound dressing.
  • the additives may be incorporated into the wound dressing composition directly or alternatively in a separate layer attached to the second surface of the wound dressing.
  • the additives may be introduced into the wound dressing that will elute out of the dressing at a desired rate once the dressing is applied to tissue.
  • the wound dressing compositions of the present invention provides strong adherence to tissue, regardless of the moisture conditions during bonding. In tests performed with saline plasma energy activation, the wound dressing composition was thoroughly wet by the saline flow from the probe during energy activation, however the composition demonstrated strong tissue adherence. Wound dressing compositions containing cysteine in particular demonstrated strong tissue adherence under wet and high moisture conditions.
  • Example 1 Gelatin Wound Dressing Composition and Fabrication Wound dressings according to the invention were made from films dried from aqueous solutions of 10% by weight (wt %) gelatin and 10 mM HEPES buffer.
  • the solution was prepared in a 100ml_ Wheaton glass bottle by adding 0.5ml_ of 1 M HEPES (Sigma H0887), 5g gelatin (Gelita Medella Pro 260 Bl NF), and 49.5ml_ deionized water. The solution was heated at 50 to 65°C for several hours until the gelatin dissolved into solution. A drop of water soluble dye colorant (blue or green) was added to the solution to aid the visual detection of film adhesion to tissues.
  • Example 2 Adhesion Testing of Wound Dressings
  • Various films were prepared by casting and drying of aqueous solutions containing 10 wt % gelatin as described in Example 1 .
  • Wound dressings were prepared by crosslinking films to increase their strength by exposure to saturated formaldehyde vapor for 30 min. Through holes 0.71 mm diameter were introduced to each film by using a 25 gauge needle punch, at a density of 8 holes per cm 2 . Resultant wound dressings were tested for tissue adherence by placing the film onto freshly cut beef tongue.
  • the wound dressings were wetted by the saline flow during energy activation. A few minutes after the dressing was treated with the Coblator wand, the film was evaluated by using a pair of forceps to gently peel the film from the tissue, and the results were qualitatively scored for adherence to the tissue using the following scoring format.
  • Gelatin films placed on tissue without energy activation showed no adherence.
  • Gelatin films without additives (100% gelatin) were slightly adherent to tissue after energy activation.
  • the addition of 1 wt % glycerol, and 1 wt % glycerol plus 0.01 wt % Tween ® 20 to the solution used for film fabrication increased the tissue adherence of resultant films.
  • Films formed from 10 wt % gelatin solution with the addition of 1 wt % glycerol had a resultant dry composition of 90.9 wt % gelatin and 9.1 wt % glycerol.
  • Example 3 Adhesion of Gelatin Films with Plasticizer Gelatin films containing Tween ® 20 without plasticizer were stiff and not compliant to the tissue surface. It was found that the addition of both Tween ® 20 and glycerol resulted in soft, compliant gelatin films. Gelatin films were fabricated from gelatin A277 with 10mM HEPES buffer, 0.01 % Tween ® 20, and different concentrations of glycerol using the fabrication method described in Example 1 . Films were dried from a 1 ml_ dispensed volume.
  • Wound dressings were prepared by crosslinking the films by UV irradiation in a UV chamber (Bio-Rad GS Gene Linker) for 5 min on each side and forming 8 holes/cm 2 with a hole diameter of 0.71 mm.
  • the resultant wound dressings had a glycerol and gelatin composition as listed in Table 3.
  • the wound dressings were tested for energy activated tissue adherence as described in Example 2.
  • Films from Gelatin A277 were prepared by drying of an aqueous solution of 10 wt % gelatin, 1 wt % glycerol, 0.01 wt % Tween ® 20 and 10mM HEPES buffer as described in Example 1 . Different volumes, 0.5 to 1 .5 ml_, were dispensed into small weigh boats, and allowed to dry. The dry films had a composition of 88.9 wt % gelatin, 8.9 wt % glycerol, 0.1 wt % Tween ® 20 and 2.1 wt % HEPES. Their thickness were measured at 3 to 5 different locations on the films, and averaged.
  • Wound dressings were prepared by crosslinking the films by exposure to saturated formaldehyde vapor for 30 min. Needle punches were used to introduce holes with different diameters and hole densities to each dressing, before they were tested for tissue adherence, using the Coblator system as described in Example 2.
  • tissue adherence was observed in the thickness range of 46 to 140 microns, with the optimal range of approximately 100 microns.
  • Example 5 Crosslinking of Gelatin Film Wound Dressings Chemical cross-linking was performed on the films of Example 3 by exposure to saturated formaldehyde vapor for 15 min to 60 min. Physical crosslinking was performed by irradiating films with UV light at 254 nm wavelength and intensity of 950 milliwatts/cm 2 for 2.5 min to 15 min on each side. Films of A277 gelatin were prepared as described in Example 3 with 1 ml_ dispensed volume. Dried films were UV crosslinked at various times to form wound dressings. Each crosslinked wound dressing contained 8 holes/cm 2 with a hole diameter of 0.71 mm. The films were tested for adhesion after activation by the Coblator system as described in Example 2.
  • tissue adherence was observed for UV crosslink time for 2.5 to 10 min at an intensity of 950 milliwatts/cm 2 for each side of approximately 100 micron thick film.
  • Example 6 Textured Film Textures were introduced to films by overlaying nylon or polypropylene mesh on top of the dispensed gelatin solution before the drying process, as described in Example 1 . Circular mesh with 400 to 2000 micron opening sizes were used. The mesh was removed from the film after drying, resulting in a film with a textured surface. Wound dressings were formed by crosslinking the films for 10 minutes of UV exposure on each side as described in Example 5.
  • Example 7 Effect of Cysteine Additive to Composition
  • Gelatin solutions at a concentration of 10 wt % with 1 wt % glycerol, 0.01 wt % Tween 20, and 10 mM HEPES was prepared with various concentrations of cysteine.
  • Films were prepared from a 1 mL dispensed volume and formed as described in Example 1 .
  • Wound dressing were prepared from the films by UV crosslinking for 5 min on each side, and the formation of 8 holes/cm 2 with a hole diameter of 0.71 mm. The wound dressings were tested for tissue adherence after activation by the Coblator system as described in Example 2.
  • cysteine increased tissue adherence in the concentration range of 0.044 wt % to 0.44 wt % of the dry wound dressing composition.
  • the adherence was improved for both type A and type B gelatin compositions.
  • the adherence of the type B gelatin compositions was greater than the type A gel both with and without cysteine.
  • Example 8 Gelatin Films with Dextrose Solutions of 10 wt % A277 gelatin, containing various concentrations of dextrose, 0.01 wt % Tween ® 20 and 10mM HEPES buffer were used to prepare films as described in Example 1 . Films were prepared from 1 ml_ dispensed volume. Wound dressing were fabricated from the films by UV crosslinking for 5 min on each side as described in Example 5, and the introduction of through holes (8/cm 2 , 0.71 mm diameter). The wound dressings were tested for tissue adherence after activation by Coblator system as described in Example 2.
  • Example 9 Wound Dressing Activation with Different Energy Sources
  • Wound dressings were prepared from gelatin films prepared from A294 gelatin in 1 wt % glycerol, 0.01 wt % Tween ® 20 and 10 mM HEPES as described in Example 1 . Films were dried from a 1 ml dispensed volume. Wound dressings were prepared from the films by UV cross-linking for 2.5 min on each side and punching to form 8 holes/cm 2 with a diameter of 0.71 mm. The Coblator system was used to activate the wound dressings as described in Example 2 and the tissue adherence was determined. An ultrasound energy source was also used to activate the wound dressings.
  • Low frequency ultrasound (LFUS) energy between 23 kHz and 28 kHz was generated from an ultrasound generator using piezoelectric transducers to which signals were applied.
  • a titanium waveguide with a flat distal surface at the tip was attached to the ultrasound generator.
  • the wound dressing was placed on the test tissue and the flat surface of the distal end of the waveguide was pressed to the surface of the wound dressing and moved over the desired area for wound dressing activation.
  • Table 1 1 Wound Dressing Activation with Saline Plasma and Ultrasound
  • Gelatin films were fabricated according to Example 1 using two gelatin types, A294 (Gelita
  • the films were dried from an aqueous solution of 10 wt % gelatin solution in 1 wt % glycerol, 0.01 wt % Tween ® 20, 10mM HEPES, and 0.05 wt % Cysteine (4mM), with a one ml dispensed volume.
  • Each film was cross-linked by UV at 254 nm, 950 milliwatts/cm 2 , for 5 min on each side.
  • the films averaged 100 microns in thickness.
  • the films were cut into test strip samples measuring 5 mm wide by 30 mm long. A total of 6 test strips of each gelatin type were prepared.
  • the films were divided into three groups for mechanical (tensile) testing under various conditions.
  • the films were tested dry, hydrated and treated with a saline plasma system.
  • the film tensile properties were measured using a Mark-10 Corporation (Copiague, NY) mechanical test system consisting of an ESM301 Test Frame with an M5-50 Force Gauge.
  • the force gauge output was recorded by the Mark-10 Mesur-Lite software program on a laptop computer and the data was transferred to Microsoft Excel for analysis.
  • Two Mark-10 Miniature Component Grips were used to hold the film samples.
  • the test system was set up with a gauge length of 15 mm and a cross-head speed of 10 mm/min.
  • the first test group was tensile tested in the dry state.
  • the second test group was hydrated in deionized, filtered water for 30 minutes.
  • the third test group was treated using the Coblator system as described in Example 2.
  • the test strips were held in place on a sheet of polytetrafluoroethylene (Teflon) with a pair of forceps.
  • the plasma wand was triggered away from the test strips and then swept over the films, without touching them, to treat.
  • the hydrated samples were tested at 30 minutes of hydration and the plasma treated samples were tested immediately after treatment. After mechanical testing, the data was processed to determine the peak tensile strength in grams-force and the percent elongation at break. The results were averaged and the results are presented in the following table.
  • the energy activation of the wound dressing composition demonstrated increased flexibility in handling and increased elongation at break or failure in tension as compared to the composition in dry and hydrated conditions prior to energy activation.
  • Gelatin films prepared as described in Example 1 were chemically crosslinked by exposure to formaldehyde. Film samples were placed in containers saturated with formaldehyde vapor for 5, 10 and 15 minutes. The films were removed and allowed to equilibrate at ambient temperature and humidity. Small portions of the films were weighed and placed in deionized water for 30 minutes. The films were removed and excess water removed by blotting against a dry surface. The hydrated weight of the sample was measured and the water absorption of the samples determined. Three samples were measured for each crosslinking condition and then averaged.
  • CV- coefficient of variation Testing of formaldehyde crosslinked wound dressing films as described in Example 5 demonstrated energy activated tissue adherence after 15, 60 and 90 minutes of formaldehyde exposure, corresponding to a water absorption of 70.5 % to 146.7%.
  • Gelatin films prepared as described in Example 1 were physically crosslinked by exposure to 254 nm wavelength UV light at an intensity of 950 milliwatts/cm 2 for a variable amount of time.
  • the equilibrium water absorption of the samples was determined as previously described for chemical crosslinking with formaldehyde vapor.
  • Example 5 Testing of UV crosslinked wound dressing films as described in Example 5 demonstrated energy activated tissue adherence after 2.5, 5, 10 minutes of UV exposure on each side of the film, corresponding to a water absorption of 741 .1 % to 315.0%.
  • Example 12 Probe Interface Oil Coatings Gelatin films were fabricated according to Example 1 using gelatin B250 (Rousselot Peabody Inc.). The films were dried from an aqueous solution of 10 wt % gelatin solution in 1 wt % glycerol, 0.01 wt % Tween ® 20, 10mM HEPES, and 0.05 wt % Cysteine (4mM), with 1 .0, 1 .2, 1 .5 and 2.0 ml dispensed volume to produce a films of approximately 56, 87, 102 and 145 micron thickness. Each film was cross-linked by UV at 254 nm, 950 milliwatts/cm 2 , for 5 - 10 min on each side.
  • Films were punched to form 8 through holes/cm 2 with a diameter of 0.71 mm. Selected films were coated with low molecular weight silicone fluid, cannola oil, sunflower oil or flaxseed oil with sufficient fluid to coat the surface.
  • the resultant wound dressings were tested for tissue adherence by placing the film onto freshly cut beef tongue.
  • a Valley lab Force EZ electrosurgical system by Covidien/Medtronic was used to apply energy in coagulation mode to the dressing while pressing down lightly on the dressing with the electrosurgical probe.
  • a few minutes after the dressing was treated the film was evaluated by using a pair of forceps to peel the film from the tissue, and the results were qualitatively scored for adherence to the tissue using the scoring format described in Example 2.
  • the oil coating effectively prevented adhesion of the probe surface to the film during and after treatment.
  • Additional films were coated with a fatty acid.
  • a solution of palmitic acid was prepared in hexane at a concentration of 0.2 molar. The palmitic acid solution was warmed to 37 degrees C and pipetted onto films with surface area of 8 cm 2 . Approximately 12.5 mg of palmitic acid was deposited onto the films, resulting in a surface concentration of approximately 1 .6 mg per cm 2 . On some films, the coating process was repeated two or three times, resulting in surface coatings of approximately 3.1 mg per cm 2 and 4.7 mg per cm 2 respectively.
  • the resultant wound dressings were tested for tissue adherence by placing the film onto freshly cut beef tongue and activated using a Valleylab Force EZ electrosurgical system as described in Example 12. The fatty acid coating effectively prevented adhesion of the probe surface to the film during and after treatment. The fatty acid coating was observed to transition from solid particles to a liquid during energy activation.
  • Palmitic acid coating (1 .6 mg/cm ), 145 micron
  • An area of freshly cut beef tongue was excised with either the Cut mode of the Valley lab Force EZ electrosurgical system or the Coblate mode of the Coblator system.
  • the film contained 8 through holes per cm 2 with a holed diameter of 0.71 mm.
  • the coag mode of each system was used to activate the wound dressing.

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  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
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  • Materials For Medical Uses (AREA)

Abstract

La présente invention concerne un pansement qui adhère au tissu ou se lie directement au tissu lorsqu'il est activé par de l'énergie sans l'utilisation d'une couche adhésive. Le pansement peut être appliqué sur une surface muqueuse ou sur des plaies dues à un traumatisme ou à une intervention chirurgicale pour protéger la plaie, favoriser la cicatrisation et réduire la douleur. Le pansement comprend de la gélatine réticulée associée à des additifs, tels qu'un plastifiant, un agent tensio-actif et/ou de la cystéine. Des agents pharmaceutiques pour traiter la plaie peuvent être également ajoutés. L'application d'énergie, telle que le plasma, les ultrasons, la radiofréquence, l'énergie lumineuse ou thermique, permet au pansement d'adhérer ou de se lier à une plaie sous-jacente ou à un tissu sous-jacent et peut également augmenter la souplesse ou l'allongement du pansement. Le pansement peut être en général de forme plane, convexe ou concave pour correspondre à la forme de la plaie à traiter et peut avoir des orifices et/ou un revêtement sur une surface externe du film.
PCT/US2016/017634 2015-02-13 2016-02-11 Composition et procédé pour l'utilisation d'un pansement activé par énergie WO2016130861A1 (fr)

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Cited By (1)

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CN110947021A (zh) * 2019-12-17 2020-04-03 山东朱氏药业集团有限公司 一种可降解伤口敷料制备方法及该敷料的配料设备

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US5071417A (en) 1990-06-15 1991-12-10 Rare Earth Medical Lasers, Inc. Laser fusion of biological materials
US5209776A (en) 1990-07-27 1993-05-11 The Trustees Of Columbia University In The City Of New York Tissue bonding and sealing composition and method of using the same
US5156613A (en) 1991-02-13 1992-10-20 Interface Biomedical Laboratories Corp. Collagen welding rod material for use in tissue welding
US5669934A (en) * 1991-02-13 1997-09-23 Fusion Medical Technologies, Inc. Methods for joining tissue by applying radiofrequency energy to performed collagen films and sheets
WO2008016983A2 (fr) * 2006-08-02 2008-02-07 Baxter International Inc. Moyen de scellement sec agissant rapidement et procédés d'utilisation et de préparation
WO2009153750A2 (fr) * 2008-06-18 2009-12-23 Lifebond Ltd Compositions réticulées améliorées

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110947021A (zh) * 2019-12-17 2020-04-03 山东朱氏药业集团有限公司 一种可降解伤口敷料制备方法及该敷料的配料设备
CN110947021B (zh) * 2019-12-17 2022-03-08 山东朱氏药业集团有限公司 一种可降解伤口敷料制备方法及该敷料的配料设备

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