# US 10,946,040 B2 · Method of treating inflammation

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- Number: US 10,946,040 B2
- Document ID: US10946040B2
- Status: Granted
- Kind: B2
- Application number: 16/424,747
- Filed: 2019-05-29
- Published: 2019-09-19
- Granted: 2021-03-16
- 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/US10946040B2

## 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 administering a therapeutically effective dose of a sorbent for an inflammatory mediator to a patient where the inflammatory mediator is one or more of enzymes, cytokines, prostaglandins, eicosanoids, leukotrienes, kinins, complement, coagulation factors, endotoxins, enterotoxins, lipopolysaccharide, cell fragments, bile salts, fatty acids, phospholipids, interferon and immunomodulatory antibodies, biologics or drugs.

## Claims

### Claim 1

A method of treating inflammation in a patient comprising administering a therapeutically effective dose of a sorbent for an inflammatory mediator to said patient; wherein the sorbent is a biocompatible polymer;
the biocompatible polymer comprising residues from one or more monomers selected from divinylbenzene, ethylvinylbezene, styrene, ethylstyrene, and mixtures thereof,
the biocompatible polymer having a pore structure such that the total pore volume of pore size in the range of 50 {acute over (Å)} to 3000 {acute over (Å)} is greater than 0.5 cc/g to 3.0 cc/g dry polymer; the sorbent being administered orally, via a feeding tube, peritoneally, or rectally;
wherein said inflammatory mediator is a cytokine resulting from inflammatory bowel disease in said patient, burns to said patient, sepsis in said patient, or exposure of said patient to neurotoxins.

### Claim 2 (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 3 (depends on 2)

The method of claim 2, 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 4 (depends on 1)

The method of claim 1, wherein said biocompatible polymer is supplied as a slurry, or suspension, or dry powder or other dry particulate capable of being wetted.

### Claim 5 (depends on 1)

The method of claim 1, wherein said sorbent is supplied as a slurry or suspension packaged in either single dose or multidose packages for oral administration.

### Claim 6 (depends on 1)

The method of claim 1, 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 7 (depends on 1)

The method of claim 1, 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, with or without the addition of wetting agents.

### Claim 8 (depends on 6)

The method of claim 6, 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 9 (depends on 1)

The method of claim 1, wherein said biocompatible polymer materials is not metabolizable by human and animal.

### Claim 10 (depends on 1)

The method of claim 1, wherein said biocompatible polymer comprises particles having a diameter in the range for 0.1 micron meters to 2 centimeters.

### Claim 11 (depends on 10)

The method of claim 10, wherein said biocompatible polymer is in the form of powder, beads or other regular or irregularly shaped particulate.

### Claim 12 (depends on 1)

The method of claim 1, wherein said biocompatible polymer is a coated polymer comprising at least one crosslinking agent and at least one dispersing agent;
said dispersing agents selected from the group consisting of 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 the group consisting of divinylbenzene, triviny1benzene, 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 13 (depends on 1)

The method of claim 1, wherein said biocompatible polymer is modified with an antibody or ligand.

### Claim 14 (depends on 1)

The method of claim 1, wherein said biocompatible polymer is a porous highly crosslinked styrene or divinylbenzene copolymer.

### Claim 15

A pharmaceutical kit comprising a therapeutically effective dose of a sorbent for an inflammatory mediator to a patient; wherein the sorbent is a biocompatible polymer;
the biocompatible polymer comprising residues from one or more monomers selected from divinylbenzene, ethylvinylbezene, styrene, ethylstyrene, and mixtures thereof,
the biocompatible polymer having a pore structure such that the total pore volume of pore size in the range of 50 {acute over (Å)} to 3000 {acute over (Å)} is greater than 0.5 cc/g to 3.0 cc/g dry polymer; the sorbent being administered orally, via a feeding tube, peritoneally, or rectally;
wherein said inflammatory mediator is a cytokine resulting from inflammatory bowel disease in said patient, burns to said patient, sepsis in said patient, or exposure of said patient to neurotoxins.

### Claim 16 (depends on 15)

The pharmaceutical kit of claim 15, 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, with or without the addition of wetting agents.

### Claim 17 (depends on 15)

The pharmaceutical kit of claim 15, 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 18 (depends on 15)

The pharmaceutical kit of claim 15, wherein said sorbent is supplied as a slurry or suspension packaged in either single dose or multidose packages for oral administration.