Classifications

• • A61F13/01034—
• • A61F13/01042—
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
• • 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
  • A61L15/44—Medicaments
• • 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
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F13/00—Bandages or dressings; Absorbent pads
  • A61F2013/00089—Wound bandages
  • A61F2013/00246—Wound bandages in a special way pervious to air or vapours
  • A61F2013/00255—Wound bandages in a special way pervious to air or vapours with pores
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F13/00—Bandages or dressings; Absorbent pads
  • A61F2013/00089—Wound bandages
  • A61F2013/0028—Wound bandages applying of mechanical pressure; passive massage
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F13/00—Bandages or dressings; Absorbent pads
  • A61F2013/00361—Plasters
  • A61F2013/00365—Plasters use
  • A61F2013/00463—Plasters use haemostatic
  • A61F2013/00468—Plasters use haemostatic applying local pressure
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F13/00—Bandages or dressings; Absorbent pads
  • A61F2013/00361—Plasters
  • A61F2013/00365—Plasters use
  • A61F2013/00463—Plasters use haemostatic
  • A61F2013/00472—Plasters use haemostatic with chemical means
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F13/00—Bandages or dressings; Absorbent pads
  • A61F2013/00361—Plasters
  • A61F2013/00855—Plasters pervious to air or vapours
  • A61F2013/00863—Plasters pervious to air or vapours with pores
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
  • A61F13/00—Bandages or dressings; Absorbent pads
  • A61F2013/00361—Plasters
  • A61F2013/00902—Plasters containing means
  • A61F2013/0091—Plasters containing means with disinfecting or anaesthetics means, e.g. anti-mycrobic
• • 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
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
  • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
  • A61L2300/254—Enzymes, proenzymes
• • 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
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
• • 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
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
  • A61L2300/406—Antibiotics
• • 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
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
• • 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
  • A61L2400/00—Materials characterised by their function or physical properties
  • A61L2400/04—Materials for stopping bleeding

Definitions

• the invention is generally related to emergency medicine.
• the invention relates to bleeding and bleeding injuries.
• Tourniquets were described more than two millenia (2000 years) ago as an adjuvant to surgical amputation. L. Zimmerman, I. Veith, Great Ideas in the History of Surgery, San Francisco, Calif. : Norman Publishing (1993), 31. Since then, tourniquets have become a primary a primary initial treatment for injuries associated with high pressure bleeding. Unfortunately, tourniquet use is associated with a variety of complications and difficulties including nerve damage, post-tourniquet syndrome, limb ischemia (distal ischemia), compartment syndromes, pulmonary embolus, increased risk of amputation, and limb wastage. A.K. Palmer, "Complications from tourniquet use," Hand Clinics, 2:301-5 (1986); A.S. Estrera, R.P.
• fibrin products such as fibrin glue, fibrin sealant and dry fibrin dressing
• fibrin products do have drawbacks. Fibrin products have had a tendency to be washed from the wound during high pressure bleeding, relative high cost. Some fibrin products put the patient at risk of viral exposure. Virally inactivated fibrin sealant has been developed, and is being used as an adjuvant to multiple types of surgery.
• Fibrin glue has been shown to be effective in speeding hemostasis along vascular graft suture lines.
• Fibrin glue has been tested as an adjuvant to surgery in the treatment of complex hepatic injury.
• Dry fibrin sealant dressing was recently shown to be more effective than standard gauze in decreasing bleeding and maintaining blood pressure in ballistic injury. J Holcomb, M MacPhee, S Hetz, R Harris, A Pusateri, "Efficacy of a dry fibrin sealant dressing for hemorrhage control after ballistic injury," Arch Surg, 133:32-5 (1998).
• Hemostatic means anything with the ability to enhance, speed or support blood clotting. Indeed, a recent patent dealing with hemostat systems still focuses on this process. J J Prior, D G Wallace, D H Sierra, F A DeLustro, "Compositions containing thrombin and microfibrillar nanometer collagen, and methods for preparation and use thereof," U.S. patent no. 6,096,309 (2000).
• Leakage may be stopped or reduced relatively quickly by pressure equalization comprising enclosing a region around the leak and applying direct-pressure in or around the leak.
• bleeding especially high-pressure bleeding from penetrating injuries such as combat wounds
• Such direct-pressure application advantageously may be by a simple medical device (such as a device administrable by a medic).
• An inventive medical device may be placed directly in the wound, where it stops high pressure bleeding.
• the acute dressing is both removable for a definitive treatment, and biodegradable if not removed (such as because removal is not warranted).
• the inventive device is simple, easy to apply, much less expensive than other biological products, and does not expose the patient to viral contaminants.
• the invention directly addresses the problem of high pressure by simulating the time honored treatment of direct pressure, particularly, pressure directly within the wound.
• the invention is particularly practical, in that four topics (topics la, lc, If, lg) of the nine research topics proposed in the hemorrhage control section of the Research on Combat Casualty Care program are addressed.
• the inventive medical devices and methods may be used in compressible (topic If) and non-compressible (topic la) bleeding. Medical devices and methods according to the invention are suitable for replacing the tourniquet as the primary field hemostat used by the medic (topic lc). Because medical devices and treatment methods according to the invention are designed to avoid the ischemia associated with tourniquet use, they have no time limit on emergent use (topic lg).
• the invention provides acute dressings and other medical devices that may be removed for definitive treatment while also being biodegradable if not removed.
• the present invention moves away from the conventional treatment paradigm for penetrating high-pressure bleeding injuries of "first save the patient, then spare the limb" to a new paradigm of "save the patient and spare the limb.”
• the invention provides a method of treating a fluid leak (such as a bleeding wound), comprising inserting into the fluid leak a material swellable on contact with the leaking fluid.
• the invention provides a method of treating a bleeding wound, comprising applying direct pressure directly in the bleeding wound.
• direct pressure is particularly preferred.
• direct pressure application continues until bleeding stops.
• the invention provides a medical device comprising a hemostatic substance placeable directly in a bleeding wound, wherein the wound is a compressible wound or a non- compressible wound.
• the invention provides devices that may be removable and/or biodegradable; devices that when placed in a bleeding wound swells at a rate of about 100 to 300% volume increase per minute; devices that produce pressure of greater than about 60 mm Hg in a confined space; devices administrable by a medic, etc.
• inventive methods and devices in an especially preferred embodiment may include applying a back pressure in a confined space around and in the wound.
• the invention may include inserting a direct-pressure-applying substance or article into the wound and enclosing the wound with the direct- pressure-applying substance or article therein.
• the invention may include inserting a hemostatic substance or article into the wound and enclosing the wound (such as by placing a dressing over the wound) with the hemostatic substance or
• the hemostatic substance or article includes polymer fibers of diameter about 1 micron or less.
• a hemostatic substance or article includes polymer fibers of diameter about 1 micron or less.
• the hemostatic substance or article swells upon contact with water molecules (such as water molecules contained in blood leaving the wound).
• water molecules such as water molecules contained in blood leaving the wound.
• the hemostatic substance or article may be lightly crosslinked.
• the hemostatic substance in a particularly preferred embodiment of the invention, the hemostatic substance swells from an initial volume to a 10-fold volume in one minute in a liquid; and/or the hemostatic substance generates at least 60 mm Hg pressure within three minutes of being placed in a bleeding wound.
• a membrane or shell encloses the swellable material, hemostatic substance or article, or the like. Most preferably, the membrane or shell stiffens as the interior hemostatic substance or article or swellable material swells.
• the invention in a particularly preferred embodiment provides for using (such as placing in a wound or disposing in a device) a polymeric substance, such as a polymeric substance that is a microporous, hydrogel- forming polymer with rapid swelling kinetics.
• a polymeric substance such as a polymeric substance that is a microporous, hydrogel- forming polymer with rapid swelling kinetics.
• the polymeric substance may be poly(acrylamide), hydroxypropyl cellulose, or a hydrophilic material.
• the invention in a particularly preferred embodiment provides for placing a clot-inducing substance (such as thrombin, batroxobin, reptilase, a fibrinogen activating enzyme, etc.) in a wound to be treated.
• a clot-inducing substance such as thrombin, batroxobin, reptilase, a fibrinogen activating enzyme, etc.
• Figure 1A is a schematic of an apparatus for electrospraying or electrospinning production.
• Figure IB shows the apparatus of Figure 1A in the process of electrospinning production.
• Figures 2A-2B are microphotographs showing PEVA deposited from a solution in chloroform that is 9wt% solution in chloroform ( Figure 2 A) and 15 wt% solution in chloroform ( Figure 2B).
• Figure 3 is a screening apparatus for substances for pressure development during swelling in a confined space.
• Figures 4A-4B are perspective views of a medical device
• Figure 4B showing a wound treatment device expanded after exposure to blood, water or another liquid.
• Figures 5A-5B are representational views of a molecular scale depiction of behavior of a device according to the invention.
• Figures 6A-C are representational drawings of the invention at a molecular-level, in use treating a bleeding wound, including Figure 6A where a fresh inventive device has been placed at a wound to be treated; Figure 6B where the device has been in contact with the bleeding wound for a time; and Figure 6C where the device has been in contact with the bleeding wound for a sufficient time to equalize pressure.
• Figure 7A is a scanning electron microphotograph of an ethylene
• Figures 8A-8B are a graph of swelling properties of swellable materials according to the invention electrospun ethylene-vinyl acetate (EVA) copolymer bags, with time (minutes) plotted against grams water/ grams polymer, for poly(acrylamide)co-acrylic acid copolymer (Figure 8A) and poly(acrylamide)co-acrylic acid copolymer potassium salt ( Figure 8B), respectively.
• EVA ethylene-vinyl acetate
• Figures 9A-9F are representational cross-sections of an initially healthy blood vessel (Figure 9A) that is disrupted ( Figure 9B), with the
• FIGS 10A-10B diagram filling according to the invention.
• Figure 11 is a representative view of an exemplary layered-system device according to the invention.
• Figure 12 is an exemplary system according to the invention for use with external hemorrhage.
• a liquid leak (such as a bleeding wound, etc.) may be stopped or at least reduced by applying direct pressure inside the leak.
• the direct pressure to be applied may be generated by a swellable material, by pneumatic filling of a bladder, singly or in combinations
• the swellable material is selected based on the leaking liquid to which it will be exposed, such as blood in a patient, water in a plumbing system, etc. Most preferably, the swellable material absorbs at least 10 times its weight of the leaking liquid, such as, in the case of bleeding, about 10 times its weight of water.
• the invention provides an
• exemplary method of treating a bleeding wound comprising applying direct pressure directly in the bleeding wound, most preferably applying direct pressure in the range of about 50 to 90 mm Hg directly in a high- pressure bleeding wound (such as a wound bleeding at about 60 to 90 mm Hg pressure).
• the wounds treatable by the invention include high-
• the invention advantageously may be used for treating wounds bleeding in a range of about 60 to 140 mm Hg, or higher, and also may be applied for treating low-pressure bleeding.
• a preferred example of applying direct pressure directly in the bleeding wound is to insert a hemostatic (i.e., hemocompatible direct-pressure-producing) substance or article into the wound and to enclose the wound with the hemostatic substance or article therein.
• a hemostatic i.e., hemocompatible direct-pressure-producing
• swelling of a swellable material enclosed therein may be used to produce a back pressure that advantageously stops or at least slows bleeding.
• high pressure (arterial) bleeding may be stopped or at least slowed, advantageously without compromising collateral blood flow (as occurs with a constrictive treatment such as a tourniquet).
• the application of direct pressure preferably is pressure generated by swelling of at least one swellable material.
• the amount of pressure applied is in an amount for stopping or at least minimizing bleeding from
• the wound preferably such as about 50 to 90 mm Hg pressure (most
• swellable materials for use in the invention may be mentioned polymers, such as polymers that are hydrogel-forming, micro-fibrous and/or water-absorbing, poly(acrylic acid), poly(ethylene oxide), poly(acrylamide), hydroxypropyl cellulose, other polymers or substances used in diapers and/or incontinence pads, etc., and their salts (such as ammonium, sodium, etc.) and derivatives thereof.
• polymers such as polymers that are hydrogel-forming, micro-fibrous and/or water-absorbing, poly(acrylic acid), poly(ethylene oxide), poly(acrylamide), hydroxypropyl cellulose, other polymers or substances used in diapers and/or incontinence pads, etc., and their salts (such as ammonium, sodium, etc.) and derivatives thereof.
• swellable materials are swellable hemostatic substances including the following: ⁇ oly(acrylic acid); polyacrylamide polyacrylamide (crosslinked); poly(acrylic-co-acrylamide) crosslinked (such as N, N-methylene bis-acrylamide crosslinked); crosslinked and modified polyacrylamide; polyhydroxyethyl methacrylate) PHEMA; hydrogels based on poly(vinyl alcohol) (PVA); alginate based hydrogels; HEM-co " -acrylic acid-co-sodium acylate copolymeric hydrogels; isopropylacrylamide-co-acrylic acid-co-sodium acrylate hydrogels; and gelatin gels.
• Some polymer structures are shown in Table 2, below.
• polymer fibers of diameter about 10 microns or less, most preferably 1 micron or less. That small-diameter polymer fibers are particularly preferred may be seen by considering that, for a gel fiber, the contraction rate t is equal to a
• c is approximately 2 x 10 9
• Electrospinning of polymers for biomedical appliations, poly(lactaic-co- glycolic acid) and poly(ethylene-co-vinylacetate), Proc. SAMPE Conf, Boston, Nov. 2000; D H Reneker, I Chun, "Nanometer diameter fibers of polymer produced by electrospinning," Nanotechnology, 7:216-223 (1996). Electrospinning may be used to afford small diameter (i.e., 10 microns or less) hydrogel-forming polymer fibers having rapid swelling
• Starting materials suitable for electrospinning or electrospraying include elastomeric materials such as thermoplastic elastomers, such as segmented polyurethanes, ethylene-vinylene acetate (EVA) copolymer, etc. Biocompatible starting materials (such as EVA copolymer) are
• biocompatible starting materials that serve as a host for the delivery of a wide variety of small and large therapeutic molecules (such as EVA copolymer) are most preferred. J Folkman, R Langer, "Polymers for the Sustained Release of Proteins and Other Macromolecules," Nature, 263:797 (1976). Although theoretically non- biocompatible materials could be used if enclosed in an expandable impermeable membrane (such as a syringe port), such a course is not preferred and to be avoided when the starting materials are to be used to formulate a system for wound treatment or other use on or in a patient.
• an expandable impermeable membrane such as a syringe port
• electrospinning system comprises a syringe pump 100 for pumping a
• melt 100A is preferably confined in any material formed into a nozzle with various tip bore diameters (such as a disposable pipette tip), with a very thin source electrode 97 immersed in it.
• the collector 98 can be a flat plate, wire mesh, rotating metal drum or plate on which the polymer is wound, etc.
• the solution 100A to be spun or sprayed can be doped
• the electrospinning process preferably is continued until a mat accumulates (such as an EVA mat) of approximate dimensions as desired, such as on the order of mm by mm, or cm by cm by length and width, and micrometers to millimeters for thickness.
• a mat accumulates (such as an EVA mat) of approximate dimensions as desired, such as on the order of mm by mm, or cm by cm by length and width, and micrometers to millimeters for thickness.
• swellable materials may be obtained commercially,
• alginate based hydrogels such as alginate based hydrogels; HEMA-co-Acylic acid-co-Sodium acylate copolymeric hydrogels; poly(vinyl alcohol)/poly(acylic acid) hydrogels; isopropyylacrylamide -co-acrylic acid-co-sodium acrylate hydrogels; gelatin gels; etc.
• the polymer When a polymer is used as the swellable material, the polymer may be uncrosslinked or crosslinked, preferably crosslinked. Crosslinking can be accomplished during polymerization with the use of polyfunctional monomers such as bisacrylamide, or by treatment of the polymer with ionizing radiation (e.g., D-radiation). Where electrospinning is carried
• the polymer is treated with ionizing radiation.
• the swellable material may be provided for use with a leaking material in a variety of forms, such as a mat of a swelling material, a swelling material contained within a shell or membrane, a swelling material dispensed from a tube or aerosol, etc.
• the form used may be
• the swellable material preferably is contained within a biocompatible, hemocompatible shell or membrane that permits the leaking liquid to pass through the shell or membrane to reach the swellable material.
• the shell or membrane is selected with regard to the leaking material (such as blood), the swellable material, and any other treating material (such as clotting promoters, antibiotics, analgesics, etc.) disposed within the shell or membrane.
• the shell or membrane is porous, elastic, provides stiffness as the hydrogel inside swells, and/or allows easy ingress of the particular leaking material (such as blood), and most preferably meets all of these characteristics.
• Elastomeric polymers and hydrophilic, expansile polymers are particularly preferred as shells or membranes as they typically increase in stiffness when stretched due to chain orientation. Such stiffening of the shell upon swelling of the interior hemostatic substance or article is desirable for generating back pressure.
• the to-be-used membrane is formed as a relatively flat bag, with relatively little unoccupied space around the swellable material. Loose-fitting placement of the swellable material within the membrane is preferred, corresponding to the expansion geometry. Namely, as the membrane limits the material expansion, a too-tight between the swellable material
• the membrane preferably is non-leaking with regard to the swellable material, and, where a polymer is used as the swellable material, polymer leakage may be minimized by crosslinking the outermost portions of the polymer matrix to the membrane.
• the membrane When a membrane is used for enclosing the swellable material, preferably the membrane is perforated. Pore sizes are such as to limit the leakage of polymer; the pores can increase with swelling because the size
• the membrane is not required to be completely uniform in its characteristics, and may be customized. For example, where the membrane is perforated, most preferably the perforations are relatively large and numerous on the part of the membrane that is to contact the bleeding (or other leaking material), so that exiting blood and other liquid may enter the membrane and activate the swellable material so that the swellable material swells and exerts a backpressure.
• Customizing the membrane on the non- wound side may include features to retain the swelled material, blood, liquid, etc., such as non-perforation, reinforcement of the membrane, coating, etc. It will be appreciated that on the non-wound side, it is not desired that blood, body fluids, or other materials escape. Where a customized membrane with a wound-side and non-wound differential is used, the person to be applying the membrane-enclosed swellable material will require training and/or specific markings on the membrane are included.
• determining whether to customize a membrane or to provide a unitary membrane there may be considered the training of the person who will administer the membrane-enclosed swellable material, whether the membrane can be marked to direct the person administering the swellable material which side to place into the wound, etc.
• a clot-promoting substance such as thrombin, preferably lyophilized thrombin.
• a concentration of the clot- promoting substance is one that speeds clotting without clogging the swellable material with clot.
• the swellable material must be kept away from materials which may cause it to swell.
• materials which may cause it to swell For example, in the case of a swellable material intended for use with
• the swellable material must be kept dry.
• the invention also provides certain devices (such as medical
• FIG. 5A and 6A are respective molecular-scale versions corresponding to Figure 4A, with
• swellable material molecules 3 are shown for simplicity; it will be appreciated that generally a device comprises a large population of
• a device comprising a swellable material 3 within a membrane 2 is contacted with a leaking material 5 (such as blood) and the leak (such as a wound) is enclosed with an enclosure material 6 (such as a dressing).
• a leaking material 5 such as blood
• an enclosure material 6 such as a dressing
• Membrane 2 on the wound side 2Y permits leaking molecules (such as blood molecules, water, etc.) 5 to pass into the interior of the device, and that as such blood molecules, water and other leaking molecules 5 come in contact with swellable material molecules 3, the blood and other water-containing molecules 5 bond to the molecules 3 and remain inside the membrane, causing the membrane to expand.
• expanded membrane 2A has reached its maximum expansion for the pressure being applied by the leaking molecules 5.
• Leaking molecules 5 inside the membrane 2A cannot readily exit the membrane 2A on the wound side 2Y because more leaking molecules 5 are entering at the wound side 2Y of the membrane 2 A.
• membrane 2A (including the membrane 2A on the wound side 2Y and on
• the dressing side 2Z together and respectively act as a barrier to leaking
• device 1 accepts additional molecules and membrane 2 expands, forming expanded device 1A (see Figure 4B) of which the exterior is expanded membrane 2.
• expanded device 1A see Figure 4B
• a swellable material within the device controUably swells when exposed to aqueous solutions (such as found in a bleeding wound), with the desired result of the expansion being to generate a back pressure.
• a medical device containing a swellable material is introduced into a bleeding wound, and the wound and device enclosed together, bleeding can be stopped or at least reduced by the back pressure generated by the device.
• An exemplary device 1 according to the inventive is a clotting- promoter containing device, such as a thrombin-containing device.
• a clotting-promoter containing device such as a thrombin-containing device.
• FIGs 9A-9E An example of using a clotting-promoter containing device may be appreciated with regard to Figures 9A-9E.
• Figure 9A is shown a
• healthy blood vessel 7 (such as a vessel having a typical pressure of
• a clotting-promoter containing device 9 (such as a thrombin-containing device) towards the bleeding wound 8.
• arrows show the direction in which blood travels.
• the device 9 is inserted directly into the bleeding
• the device 9 After the device 9 has been in the wound 8 held by the dressing 6 for a time (such as about three minutes), the device will have expanded
• Expanded device 9A as a result of its expansion exerts pressure on its environment, namely on the patient's blood. In addition to the pressure exertion effects provided by
• the bleeding wound 8A also experiences clotting promotion from the clotting promoters released from the device 9, 9A.
• the expanding device 9, 9A, 9B reduces and stops blood loss.
• direct pressure application inside the wound is combined with clotting promotion to stop blood loss from a penetrating wound in as little as 3 or 4 minutes, or even less.
• Figures 9C-9F show a device 9, 9A, 9B being used to treat a bleeding wound, with the fresh device 9 slightly smaller than the wound 8 into which it is being placed.
• the expanded device 9B be of a volume at least equal, preferably greater, than the wound.
• Devices 9 of different starting size may be provided.
• expanded devices 9B of different volumes may be provided.
• combinations of two or more devices may be used for treating a bleeding wound, such as treating a relatively large penetrating wound with two or more devices (which may be the same or different). In determining how many devices 9 to use, or what
• expanded device 9B may be desirable for a particular bleeding wound to
• wound (such as insertion into the wound of a first device 9 that expands into expanded device 9B) only reduces bleeding but is insufficient to stop bleeding, further direct pressure in the wound (such as insertion into the
• wound of a follow-up device may be applied.
• expanded device 9B may be permitted to remain in the wound or may be removed. Whether to remove the expanded device 9B or not may be based on factors such as need for access to an internal area for
• the device 9B is left in the patient unless a reason
• formulations are desired that promote clotting at a rate of preferably about less than one minute, with relatively faster clotting being preferred.
• Clotting is desired to proceed apace with the swelling, with clotting to be complete as expansion is complete. Promoting more rapid clotting raises the possible complication of clotting before the device swells sufficiently to develop adequate back pressure.
• approximate clotting rate can be provided by the amount of hemostatic agent and/or amount of clotting promoter used, and/or by the size and amount of pores in the membrane.
• another technique for generating direct pressure comprises filling (such as pneumatic filling,
• a bladder comprising a membrane enclosing a swellable material wherein the swellable material swells on contact with the leaking material (such as blood in a bleeding wound).
• leaking material such as blood in a bleeding wound
• a device 14 (which may be device 9) is provided with a syringe port 13 for receiving a syringe 11 (such as a syringe containing a volume of clotting promoter (such as thrombin) or other biocompatible material; a syringe containing air; a syringe containing water or another liquid, etc.).
• a syringe 11 such as a syringe containing a volume of clotting promoter (such as thrombin) or other biocompatible material
• An initial-setting pressure monitor 12 is provided. Upon depressing the syringe plunger
• the device 14A by virtue of its greater volume provides direct pressure on its surroundings (shown by arrows).
• the device 14A may be
• inflated entirely due to pneumatic filling or may be inflated by pneumatic filling combined with one or more other inflating methods (such as swelling of a swellable material).
• a filler according to the invention may be separable from, or attached to, the device into which it is inserted.
• the device into which the filler is inserted may be a bladder with or without a swellable material
• a bladder comprising a membrane as mentioned herein.
• a bladder may be mentioned an elastic non-permeable bladder, an impermeable bladder, a permeable membrane, singly or in combinations thereof, etc.
• a device according to the invention optionally may comprise a layered system, such as a layered system of membrane(s) (such as a permeable membrane), bladder(s) (such as an impermeable bladder), membrane contents, and/or bladder contents.
• a layered system 15 is shown in Figure 11, comprising an impermeable expandable
• the expandable bladder 16 inside a permeable membrane 17.
• contents 18 comprising one or more of a swellable material (such as an absorbent polymer), a clotting promoter (such as thrombin), antibiotics,
• swelling material preferably included, most preferably a swelling material including an absorbent polymer.
• a layered system 15 preferably may be used by, once the layered system 15 is placed in a bleeding wound, inflating or expanding bladder
• the swellable material is included in contents 18, the swellable material preferably is treated (such as by crosslinking) to minimize passage of the
• a clotting promoter such as thrombin
• antibiotics such as thrombin
• analgesics such as acetylcholine
• anesthetics are included
• inventive methods and devices are particularly usable by a combat medic in treating bleeding wounds such as combat wounds.
• the combat medic is a skilled individual, and may readily use the invention.
• Inventive methods and devices also may be used by less skilled or relatively unskilled individuals in treating bleeding wounds.
• the invention provides the treatment paradigm of saving the patient without compromising limb salvage.
• An acute treatment is provided for both civilian and military medical treatment of penetrating wounds, in human and veterinary medicine.
• the invention advantageously stops bleeding without producing pressure injury or ischemic damage. By retaining the patient's blood, the amount of transfused blood is reduced, and the risks associated with transfusion are correspondingly reduced.
• a wound care dressing comprising a swellable material
• a wound dressing according to the invention promotes hemostasis, prevents infection, and/or relieves pain, delivering one or more features in a relatively quick time frame.
• the external wound dressings may be self-administrable.
• a exemplary system according to the invention for treating an external wound is shown in Figure 12, with the system comprising a swellable material 19 (such as an absorbent
• a porous membrane 20 such as a telfa pad
• a porous membrane 20 such as a telfa pad
• An impermeable material 21 (such as an impermeable plastic) is provided for avoiding contact of the swellable material 19 and/or the
• a fastener system is provided attached to
• a fastener 22 and a Velcro material 23 being preferred.
• a fastener system (such as a Velcro-free adhesive fastener system, etc.) may be provided depending on the size and/or location of the wound-to-be treated.
• the invention may be extended to other forms of bleeding (such as intra- abdominal and intra-pleural), including bleeding that otherwise would be difficult to treat (especially in the acute setting).
• the device is placed in the wound, expanded, and held in place (at least initially) by mechanical
• the invention further provides a drug delivery system (such as a time released drug delivery system), usable in the presence of a wound (such as by insertion into the wound) or absence of a wound (such as by ingestion, surgical implantation, etc.).
• a drug delivery system comprises a swelling material and at least one drug (such as a hemostatic agent, antibiotic, analgesic, etc.).
• a swellable material (such as a polymer system) may be used as a drug delivery system, such as to simultaneously enhance hemo stasis, prevent infection and/or provide pain relief to acute non-penetrating injuries.
• such a drug delivery may be provided as a self-administered dressing (such as an acute dressing).
• a self-administered dressing may prolong the "golden period" between injury and treatment.
• the invention provides leakage control systems extending beyond the medical and bleeding areas, such as to pressure equalization techniques for a quick temporary plug for any type of liquid high pressure leak (such as a plumbing leak, a boating leak, a container or tanker leak, etc.). Any system where even temporary drops in pressure due to leakage is a significant problem may benefit from the inventive pressure equalization methods.
• Leaks may be treated by inserting a swellable material into the leak, preferably while maintaining the swellable material in the leak. Where the leak does not involve treating a patient, less biocompatibility may be acceptable than for treatment of wounds, wound dressings, etc.
• the swellable material is selected based on the leaking liquid to which the swellable material will be exposed. Where the leaking liquid is water or water-based, the water absorbent swellable materials mentioned above for wound treatment may be used.
• the invention also provides a screening apparatus for evaluating the efficacy of a particularly formulation of a swellable material (such as a polymer) when in contact with a particular leaking material (such as a watery liquid), with an exemplary screening apparatus that may be used
• Substances such as polymers of varying diameters
• the ability of a substance to produce pressure in a confined space may be evaluated using a screening apparatus, such as the exemplary apparatus shown in Figure 3.
• a receptable 200 (such as a petri dish) is provided
• a to-be-tested substance 202 for receiving a to-be-tested substance 202, such as a to-be-tested
• the to-be-tested substance is placed in the receptable 200
• a wrap 203 (such as by a cling gauze wrap), optionally including other materials such as a gauze pad 205.
• a pressure probe 206 is placed between the membrane 201 and the wall of the receptable 200. As liquid is poured on the upper surface of the to-be-tested substance, the pressure within the confined space 207 is monitored by the pressure
• charged droplets are generated at the tip of a metal needle (or pipette with a wire immersed in the liquid) with a several kV dc field, and are subsequently delivered to a grounded target.
• the droplets are derived by charging a liquid typically to 5-20kV, which leads to charge injection into the liquid from the electrode. The sign of the injected charge depends upon the polarity of the electrode; a negative electrode produces a negatively charged liquid.
• the charged liquid is attracted to an electrode of opposite polarity some distance away, forming a so-called Taylor cone at the needle tip. Droplets are formed when electrostatic repulsions within the liquid exceed its surface tension.
• Electrospinning is believed to be mechanistically similar to
• EXAMPLE 2B A sample was prepared and tested as in Example 2A, except that instead of using ⁇ oly(acrylamide-co-acrylic acid copolymer, there was used poly(acrylamide-co-acrylic acid copolymer potassium salt). The results are shown in Figure 8B.

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