# US 2021/0330697 A1 · Method Of Treating Inflammation

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- Number: US 2021/0330697 A1
- Document ID: US20210330697A1
- Status: Published application
- Kind: A1
- Application number: 17/229,265
- Filed: 2021-04-13
- Published: 2021-10-28
- Earliest claimed: 2010-04-01
- Assignees: CytoSorbents Corporation
- Applicants: CytoSorbents Corporation
- Inventors: Phillip P. Chan; Wei-Tai Young; Vincent J. Capponi; Thomas D. Golobish; Humayra Begum Ali
- Web page: https://patentgrep.com/patent/US20210330697A1

## CPC

- A61K 31/745: Polymers of hydrocarbons
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)}
- A61K 9/50: Microcapsules {having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals (A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167)}
- A61K 31/74: Synthetic polymeric materials
- A61K 31/75: of ethene
- A61K 47/58: obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/16: for influenza or rhinoviruses
- A61P 33/06: Antimalarials
- A61P 37/02: Immunomodulators
- A61P 39/02: Antidotes
- B01J 20/261: {obtained by reactions only involving carbon to carbon unsaturated bonds (macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F)}
- B01J 20/28004: {Sorbent size or size distribution, e.g. particle size}
- B01J 20/28073: {being in the range 0.5-1.0 ml/g}
- B01J 20/28076: {being more than 1.0 ml/g}
- B01J 20/3064: {Addition of pore forming agents, e.g. pore inducing or porogenic agents}
- C08F 212/36: Divinylbenzene
- C08J 9/26: by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
- C08J 2201/0444: Salts
- C08J 2207/10: Medical applications, e.g. biocompatible scaffolds
- C08J 2325/02: Homopolymers or copolymers of hydrocarbons
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

The method of claim 1, wherein said inflammatory mediator is present in physiological fluid or a carrier fluid in the patient.

### Claim 4 (depends on 3)

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.

### Claim 5 (depends on 1)

The method of claim 1, wherein said dose of sorbent is administered orally, via a feeding tube, peritoneally, or rectally.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

The method of claim 1, wherein said inflammatory mediator results from a disease caused by biowarfare pathogens, toxins or agents.

### Claim 8 (depends on 1)

The method of claim 1, wherein said sorbent is a biocompatible polymer.

### Claim 9 (depends on 8)

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.

### Claim 10 (depends on 8)

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.

### Claim 11 (depends on 8)

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.

### Claim 12 (depends on 8)

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.

### Claim 13 (depends on 11)

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.

### Claim 14 (depends on 9)

The method of claim 9, wherein said biocompatible polymer materials is not metabolizable by human and animal.

### Claim 15 (depends on 9)

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.

### Claim 16 (depends on 15)

The method of claim 15, wherein said biocompatible polymer is in the form of powder, beads or other regular or irregularly shaped particulate.

### Claim 17 (depends on 8)

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.

### Claim 18 (depends on 8)

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.

### Claim 19 (depends on 8)

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.

### Claim 20 (depends on 19)

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.

### Claim 21 (depends on 8)

The method of claim 8, wherein said biocompatible polymer is modified with an antibody or ligand and may be porous or solid

### Claim 22 (depends on 20)

The method of claim 20, wherein said biocompatible polymer is a porous highly crosslinked styrene or divinylbenzene copolymer.