Compositions and methods for reducing edema

Abstract

The invention provides compositions and methods for the treatment and/or reversal of an edema, e.g., including a central nervous system (CNS) edema, e.g., a brain or a spinal edema, edema in a burned or an injured tissue such as skin, or any tissue edema. In alternative embodiments, the invention provides compositions and methods for a direct treatment and reversal of an edema, e.g., CNS, brain or spinal edema, including a membrane transport device, in vitro and in vivo characterization of edema, and the sensitive early optical detection of the edema, e.g., tissue, CNS or cerebral edema.

What is claimed is: 
     
         1 . A product of manufacture or a device for reducing an edema, the product of manufacture or device comprising:
 a protein, carbohydrate, polysaccharide or polymer solution, or a non-rigid hydrogel or gel, or a concentrated protein, carbohydrate, polysaccharide or polymer solution, or a concentrated osmolyte solution or rejected solute, or any combination thereof,   wherein optionally these solutions, non-rigid hydrogels or gels are contained within a lumen or a hollow fiber of the device   wherein optionally the lumen solution or lumen contents further comprise nutrients, or drugs, and optionally the drugs and/or nutrients are for the treatment or amelioration of the edema, of a burn or injury, or an underlying disease or condition causing the edema, and optionally the drugs comprise or are small molecules or proteins, and optionally the drugs act as antibiotics, anti-inflammatories, vasoconstrictors, vascular or tissue growth stimulating agents;   a semi-permeable hollow fiber membrane having a lumen, or a bundle or a module having a lumen; and,   a hollow fiber device,   wherein the concentrated protein, carbohydrate, polysaccharide or polymer solution, or osmolyte solution or rejected solute, or non-rigid hydrogel or gel, passes through the lumen of a semi-permeable hollow fiber membrane, and the concentrated protein, carbohydrate, polysaccharide or polymer solution, or osmolyte solution or rejected solute, or non-rigid hydrogel or gel, flowing through the semi-permeable fiber membrane, which is in contact with the tissue, induces osmotic pressure that drives water into a hollow fiber device where it is removed and carried away from the edematous, e.g., the injured, tissue or area of injury,   wherein optionally an aqueous proteinaceous, carbohydrate, polysaccharide, polymer solution, or osmolyte solution or rejected solute, or non-rigid hydrogel or gel, is flowed (e.g., by osmotic force) or is pumped or passively flows (such as head pressure) through the semi-permeable hollow fiber membrane lumen,   wherein optionally the membrane completely or substantially rejects a solute but allows (e.g., relatively allows) easy passage of ions, electrolytes and water, and also nutrients (such as oxygen or glucose) and small molecules, proteins and other drugs,   wherein optionally the hydrogel or an equivalent gel (e.g., a hydrophilic gel) can or is used to maintain a membrane-tissue contact,   and optionally the edema is a central nervous system (CNS) edema, or a spinal or a brain edema, a tissue edema, an edema secondary to an injury or a burn,   and optionally the temperature of the lumen solution is below about 37° C., 36° C., 35° C., 34° C. or 33° C., or below about 25° C. to 30° C.,   and optionally the hydrogel has a sufficient permeability to allow (relatively) easy passage of nutrients, drugs, ions, and water,   and optionally the hydrogel is used to membrane-tissue contact, and optionally the hydrogel is rigid enough to maintain membrane-tissue contact and support the semi-permeable hollow fiber membrane.   
     
     
         2 . The product of manufacture or device of  claim 1 , wherein the concentrated protein, carbohydrate, polysaccharide or polymer solution, or the osmolyte solution or rejected solute solution, or the non-rigid hydrogel or gel, comprises:
 a solute, a polymer, a carbohydrate, an osmolyte or a rejected solute or a combination thereof, wherein optionally the solute, polymer, carbohydrate, osmolyte or rejected solute is partially or completely rejected by the semi-permeable hollow fiber membrane,   wherein optionally the solute, polymer, carbohydrate, osmolyte or rejected solute is present in a concentration of between about 1% to 50% in solution, or between about 0.1% to 60% in solution,   and optionally the lumen solution comprises a serum albumin, or a human or bovine serum albumin (BSA) or equivalent, or the lumen solution comprises an artificial cerebrospinal fluid, or the lumen solution comprises a serum albumin at about 350 g/L or between about 300 to 400 g/L, optionally in an artificial cerebrospinal fluid, optionally at between about pH 7.0 to pH 7.6, or at about pH 7.4.   
     
     
         3 . The product of manufacture or device of  claim 1 , wherein the solute, protein, carbohydrate or polymer is dissolved in an aqueous solution comprising:
 a saline, carbohydrate, or saline and carbohydrate solution,   wherein optionally the saline solution is hypotonic, hypertonic, or isotonic compared to healthy or non-injured tissue surrounding the edematous or injured area;   and optionally the lumen solution or lumen contents further comprise proteins, inorganic molecules, organic molecules, nutrients, or drugs, and optionally the drugs and/or nutrients are for the treatment or amelioration of the edema, of a burn or injury, or an underlying disease or condition causing the edema, and optionally the drugs comprise or are small molecules or proteins, and optionally the drugs act as antibiotics, anti-inflammatories, vasoconstrictors, vascular or tissue growth stimulating agents;   and optionally the solution comprises a cerebrospinal fluid or an artificial cerebrospinal fluid, optionally at between about pH 7.0 to pH 7.6, or at about pH 7.4.   
     
     
         3 . The product of manufacture or device of  claim 1 , wherein the hollow fiber device is a flexible hollow fiber device, or wherein the hollow fiber device comprises:
 fibers having an outer diameter of between about 150 to 250 μm, or about 200 μm,   a flexible semi-permeable hollow fiber membrane, or several semi-permeable hollow fiber membranes in a bundle or a module,   wherein optionally the hollow fibers have an outer diameter of between about 100 μm to about 1 cm,   and optionally the hollow fibers have an inner diameter of between about 50 to about 750 μm; or   and optionally the hollow fibers comprise cellulose fibers, or regenerated cellulose fibers, or a biocompatible material, or a bioinert material; or   and optionally the hollow fibers have a molecular weight cut-off of less than about 100 daltons for a rejected carbohydrate or a rejected salt;   and optionally the hollow fibers have a molecular weight cut-off of between about 100 to about 1000 Daltons for a carbohydrate or a polymer solution;   and optionally the hollow fibers have a molecular weight cut-off of between about 1 to about 60 kDa or greater than about 60 kDa,   and optionally the hollow fibers are reverse osmosis membranes.   
     
     
         4 . The product of manufacture or device of  claim 1 , wherein the hollow fiber device comprises cellulose fibers, or regenerated cellulose fibers, or a biocompatible material, or a bioinert material,
 wherein optionally the cellulose fibers, regenerated cellulose fibers, biocompatible material or bioinert material have a molecular weight cut-off of between about 5 to 20 kilodalton (kDa), between about 1 to 30 kDa, or about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 or more kDa.   
     
     
         5 . A method for: removing a fluid or a water from a tissue, an edematous tissue, an injured or burned tissue, a central nervous system (CNS) tissue, or a spinal or a brain tissue, in a controlled fashion, or removing a fluid or a water from a central nervous system (CNS) tissue, a spinal or a brain tissue, in a controlled fashion to treat an edema, a central nervous system (CNS) edema, or a spinal or a cerebral edema; or treat an edema, a CNS, spinal or a brain inflammation or a CNS, spinal or a brain injury, or a burn edema, comprising:
 using the product of manufacture or device of  claim 1 , for applying or placing a concentrated protein, carbohydrate, polysaccharide or polymer solution, or osmolyte solution or rejected solute, or a non-rigid hydrogel, soft hydrogel or gel, directly on and/or approximate to an edematous, burned or injured tissue, or an exposed edematous, burned or injured tissue, wherein the soft hydrogel substantially conforms to an edematous, burned or injured area to maximize contact area with the edematous, burned or injured tissue,   wherein optionally an aqueous proteinaceous, carbohydrate, polysaccharide or hydrogel solution is pumped across the edematous, e.g., a burned or an edematous, burned or injured, surface area through the semi-permeable hollow fiber membrane lumen,   wherein optionally a lumen solution induces an osmotic pressure driving force for water removal,   wherein optionally the rate of flowing or pumping is controlled to allow fluid from the tissue to flow up to the membrane device due to osmotic pressure,   wherein optionally a hydrogel or an equivalent gel (e.g., a hydrophilic gel) with significantly large permeability is used to maintain membrane-tissue contact.   
     
     
         6 . A method for: removing water from a tissue, a central nervous system (CNS) tissue, or a spinal or a brain tissue, in a controlled fashion; or removing water from an edematous tissue, an edematous or injured CNS, spinal or a brain tissue, in a controlled fashion to treat or ameliorate an edema, or a CNS or a spinal or a cerebral edema; or to treat or ameliorate a tissue, CNS, or a spinal or a brain inflammation, or a CNS or a spinal or a brain injury, comprising:
 using the product of manufacture or device of  claim 1 , for applying or placing the hollow fiber membrane with a lumen solution of a concentrated protein, carbohydrate, polymer, or other rejected solute or osmolyte solution, or a soft hydrogel, directly on and/or approximate to the tissue, or the edematous or the injured tissue, or an exposed injured tissue, or on healthy tissue approximate to or away from the tissue from which the water will be removed, or the edematous or the injured tissue,   wherein optionally the soft hydrogel substantially conforms to an injured area to maximize contact area with the tissue, the edematous or the injured tissue and/or the healthy tissue from which the water will be removed,   and optionally the hollow fibers are in direct contact with the tissue,   and optionally the hollow fibers conform to the surface of the injured or healthy tissue,   and optionally a protein, carbohydrate, polymer, or other rejected solute or osmolyte solution is pumped or flowed across the tissue, the edematous tissue, or the healthy or injured tissue surface area through the semi-permeable hollow fiber membrane lumen,   and optionally the lumen solution induces an osmotic pressure driving force for water removal,   and optionally the rate of pumping or flow is controlled to allow fluid from the tissue to flow up into the membrane device due to osmotic pressure to alter the rate of water removal,   and optionally the amount or composition of a protein, carbohydrate, polymer or other rejected solute or osmolyte solution in the lumen solution is changed or modified to alter the rate of water removal,   and optionally the concentration of the protein, carbohydrate, polymer, or other rejected solute or osmolyte in the lumen solution is altered to between about 0.1 to about 50% to alter the rate of water removal,   and optionally the temperature of the lumen solution is changed in the range of about 20° C. to about 37° C. to alter the rate of water removal,   and optionally a hydrogel with significantly large permeability is used to maintain membrane-tissue contact while providing (relatively) easy passage of nutrients, ions, drug and/or protein treatments, and water,   and optionally the hydrogel conforms, or substantially conform, to the surface of the tissue contact area, or the treatment area,   and optionally the hollow fibers are flexible and conform, or substantially conform, to the treatment area.   
     
     
         7 . A portable or a small kit comprising a product of manufacture or device of  claim 1 , optionally comprising a tubing, a hollow fiber device and an associated gel, wherein optionally the gel is a hydrogel. 
     
     
         8 . The portable or a small kit of  claim 7 , further comprising instructions for practicing a method of  claim 5 . 
     
     
         9 . The portable or a small kit of  claim 7 , further comprising instructions for practicing a method of  claim 6 .