Method Of Treating Inflammation

Abstract

The present invention concerns methods of treating systemic, regional, or local inflammation from a patient suffering or at risk of inflammation comprising administration of a therapeutically effective dose of a sorbent that sorbs an inflammatory mediator in said patient. In some preferred embodiments, the sorbent is a biocompatible organic polymer.

1 . A method of prophylactically treating systemic, regional, or local inflammation from a patient at risk of inflammation comprising administration of a therapeutically effective dose of a sorbent for an inflammatory mediator in said patient; wherein the sorbent is a biocompatible polymer comprises:
 (i) cross-linked, porous styrene or divinylbenzene copolymer; or   (ii) cross-linked, porous styrene or divinylbenzene copolymer, where the cross-linked, porous styrene or divinylbenzene copolymer copolymer is:   (a) macroporous or mesoporous styrene-divinylbenzene-ethyl styrene copolymer submitted to a partial chloromethylation to a 7% molecular chlorine content; or   (b) cross-linked polystyrene produced by crosslinked styrene copolymers through an extensive chloromethylation and a subsequent post-crosslinking through treatment with a Friedel-Crafts catalyst in a swollen state; or   (c) cross-linked polystyrene produced from cross-linked styrene copolymer through an extensive additional post-cross-linking in a swollen state with difunctional cross-linking agents selected from the group which comprises monochlorodimethylether and dicloroparaxylene.   
     
     
         2 . The method of  claim 1 , wherein said inflammatory mediator is one or more of enzymes, cytokines, prostaglandins, eicosanoids, leukotrienes, kinins, complement, coagulation factors, toxins, endotoxins, enterotoxins, lipopolysaccharide, substances that induce apoptosis of cells, cell fragments, caustic substances, bile salts, fatty acids, phospholipids, oxidized byproducts, reactive oxygen species, oxygen radicals, surfactants, ions, irritant substances, interferon and immunomodulatory antibodies, biologics or drugs, including those administered exogenously. 
     
     
         3 . The method of  claim 1 , wherein said inflammatory mediator is present in physiological fluid or a carrier fluid in the patient. 
     
     
         4 . The method of  claim 3 , wherein said physiological fluids is nasopharyngeal, oral, esophageal, gastric, pancreatic, hepatic, pleural, pericardial, peritoneal, intestinal, prostatic, seminal, vaginal secretions, tears, saliva, mucus, bile, blood, lymph, plasma, serum, synovial fluid, cerebrospinal fluid, urine, and interstitial, intracellular, or extracellular fluid. 
     
     
         5 . The method of  claim 1 , wherein said dose of sorbent is administered orally, via a feeding tube, peritoneally, or rectally. 
     
     
         6 . The method of  claim 1 , wherein said inflammatory mediator is associated with systemic inflammatory response syndrome (SIRS) or sepsis, autoimmune disease, surgery, cytotoxic chemotherapy, bone marrow manipulation, major tissue injury or trauma, mesenteric hypoperfusion, gut-mucosal injury, malaria, gastrointestinal inflammatory disease, enteric infection, influenza, acute lung inflammation, pulmonary embolism, pancreatitis, autoimmune and collagen vascular diseases, transfusion-related diseases, burn injury, smoke or inhalation lung injury, graft versus host disease, ischemia or infarction, hemorrhage, anaphylaxis, drug overdose, reperfusion injury, radiation injury or chemical injury. 
     
     
         7 . The method of  claim 1 , wherein said inflammatory mediator results from a disease caused by biowarfare pathogens, toxins or agents. 
     
     
         8 . The method of  claim 1 , wherein said sorbent is a biocompatible polymer. 
     
     
         9 . The method of  claim 8 , wherein said biocompatible polymer is supplied as a slurry, or suspension, or dry powder or other dry particulate capable of being wetted. 
     
     
         10 . The method of  claim 8 , wherein said sorbent is supplied as a slurry or suspension packaged in either single dose or multidose packages for oral administration. 
     
     
         11 . The method of  claim 8 , wherein said sorbent is supplied as a slurry or suspension packaged in either single dose or multidose packages for administration by enema or feeding tube or any combination therein. 
     
     
         12 . The method of  claim 8 , wherein said biocompatible polymer is supplied as a dry powder or other dry particulate capable of being wetted externally or internally in the alimentary canal, including in the gastric or enteric environment, with or without the addition of wetting agents. 
     
     
         13 . The method of  claim 11 , wherein said biocompatible polymer is supplied as tablet, dry powder, other dry particulate, capsule or suppository packaged in bottles or blister packs for administration. 
     
     
         14 . The method of  claim 9 , wherein said biocompatible polymer materials is not metabolizable by human and animal. 
     
     
         15 . The method of  claim 9 , wherein said biocompatible polymer comprises particles having a diameter in the range for 0.1 micron meters to 2 centimeters. 
     
     
         16 . The method of  claim 15 , wherein said biocompatible polymer is in the form of powder, beads or other regular or irregularly shaped particulate. 
     
     
         17 . The method of  claim 8 , wherein said biocompatible polymer has a pore structure that the total pore volume of pore size in the range of 50 Å to 3000 Å is greater than 0.5 cc/g to 3.0 cc/g dry polymer. 
     
     
         18 . The method of  claim 8 , wherein:
 said biocompatible polymer has a pore structure that the total pore volume of pore size in the range of 50 Å to 3000 Å is greater than 0.5 cc/g to 3.0 cc/g dry polymer;   wherein the Ratio of Pore Volume between 50 Å to 3,000 Å in diameter To Pore Volume between 500 Å to 3,000 Å in diameter of the said biocompatible polymer is smaller than 200:1; and   wherein the Ratio of Pore Volume between 50 Å to 3,000 Å in diameter To Pore Volume between 1,000 Å to 3,000 Å in diameter of said biocompatible polymer is greater than 20:1.   
     
     
         19 . The method of  claim 8 , wherein said biocompatible polymer is a coated polymer comprising at least one crosslinking agent and at least one dispersing agent;
 said dispersing agents such as hydroxyethyl cellulose, hydroxypopyl cellulose, poly(hydroxyethyl methacrylate), poly(hydroxyethyl acrylate), poly(hydroxypropyl methacrylate), poly(hydroxypropyl acrylate), poly(dimethylaminoethyl methacrylate), poly(dimethylaminoethyl acrylate), poly(diethylamimoethyl methacrylate), poly(diethylaminoethyl acrylate), poly(vinyl alcohol), poly(N-vinylpyrrolidinone), salts of poly(methacrylic acid), and salts of poly(acrylic acid) and mixtures thereof;   said crosslinking agent selected from a group consisting of divinylbenzene, trivinylbenzene, divinylnaphthalene, trivinylcyclohexane, divinylsulfone, trimethylolpropane trimethacrylate, trimethylolpropane dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane diacrylate, pentaerythrital dimethacrylates, pentaerythrital trimethacrylates, pentaerythrital, tetramethacrylates, pentaerythritol diacrylates, pentaerythritol triiacrylates, pentaerythritol tetraacrylates, dipentaerythritol dimethacrylates, dipentaerythritol trimethacrylates, dipentaerythritol tetramethacrylates, dipentaerythritol diacrylates, dipentaerythritol triacrylates, dipentaerythritol tetraacrylates, divinylformamide and mixtures thereof;   said polymer being developed simultaneously with the formation of the coating, wherein said dispersing agent is chemically bound to said surface of said biocompatible polymer.   
     
     
         20 . The method of  claim 19 , wherein said biocompatible polymer comprises residues from one or more monomers selected from divnylbenzene and ethylvinylbezene, styrene, ethylstyrene, acrylonitrile, butyl methacrylate, octyl methacrylate, butyl acrylate, octyl acrylate, cetyl methacrylate, cetyl acrylate, ethyl methacrylate, ethyl acrylate, vinyltoluene, vinylnaphthalene, vinylbenzyl alcohol, vinylformamide, methyl methacrylate, methyl acrylate, trivinylbenzene, divinylnaphthalene, trivinylcyclohexane, divinylsulfone, trimethylolpropane trimethacrylate, trimethylolpropane dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane diacrylate, pentaerythritol dimethacrylate, pentaerythritol trimethacrylate, pentaerythritol tetramethacrylate, pentaerythritol diacrylate, pentaerythritol triiacrylate, pentaerythritol tetraacrylate, dipentaerythritol dimethacrylate, dipentaerythritol trimethacrylate, dipentaerythritol tetramethacrylate, dipentaerythritol diacrylate, dipentaerythritol triacrylate, dipentaerythritol tetraacrylate, divinylformamide and mixtures thereof. 
     
     
         21 . The method of  claim 8 , wherein said biocompatible polymer is modified with an antibody or ligand and may be porous or solid 
     
     
         22 . The method of  claim 20 , wherein said biocompatible polymer is a porous highly crosslinked styrene or divinylbenzene copolymer.