# US 2004/0072809 A1 · Ophthalmologic irrigation solutions and method > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2004/0072809 A1 - Document ID: US20040072809A1 - Status: Published application - Kind: A1 - Application number: 10/630,626 - Filed: 2003-07-30 - Published: 2004-04-15 - Earliest claimed: 2002-07-30 - Assignees: Omeros Corporation - Inventors: Gregory A. Demopulos; Pamela Pierce Palmer; Jeffrey M. Herz - Web page: https://patentgrep.com/patent/US20040072809A1 ## CPC - A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone - A61K 9/0048: {Eye, e.g. artificial tears} - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} - A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol - A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)} - A61K 31/4164: 1,3-Diazoles - A61K 31/4174: Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole - A61K 31/4409: only substituted in position 4, e.g. isoniazid, iproniazid - A61K 31/445: Non condensed piperidines, e.g. piperocaine - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 23/00: Anaesthetics - A61P 23/02: Local anaesthetics - A61P 25/02: for peripheral neuropathies - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61P 27/02: Ophthalmic agents - A61P 27/04: Artificial tears; Irrigation solutions - A61P 27/08: Mydriatics or cycloplegics - A61P 27/12: for cataracts - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 29/02: without antiinflammatory effect - A61P 39/06: Free radical scavengers or antioxidants - A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - 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 ## Abstract Solutions for perioperative intraocular application by continuous irrigation during ophthalmologic procedures are provided. These solutions include multiple agents that act to inhibit inflammation, inhibit pain, effect mydriasis (dilation of the pupil), and/or decrease intraocular pressure, wherein the multiple agents are selected to target multiple molecular targets to achieve multiple differing physiologic functions, and are included in dilute concentrations in a balanced salt solution carrier. ## Claims ### Claim 1 A method for perioperatively inhibiting inflammation, inhibiting pain, effecting mydriasis, and/or decreasing intraocular pressure during an ophthalmologic procedure, comprising continuously irrigating ocular tissues during an ophthalmologic procedure with a solution including at least first and second agents in a liquid irrigation carrier, the first and second agents being selected to act on a plurality of differing molecular targets, each agent being selected from the physiologic functional classes of anti-inflammatory agents, analgesic agents, mydriatic agents and agents for decreasing intraocular pressure (“IOP reducing agents”), the second agent providing at least one physiologic function different than a function or functions provided by the first agent. ### Claim 2 (depends on 1) The method of claim 1, wherein the solution comprises an anti-inflammatory agent selected from the group consisting of steroids, non-steroidal anti-inflammatory drugs (NSAIDS), anti-histamines, mast cell inhibitors, and inhibitors of inducible nitric oxide synthase (iNOS). ### Claim 3 (depends on 2) The method of claim 2, wherein: the steroid, if selected, is selected from the group consisting of dexamethasone, fluorometholone and prednisolone; the NSAID, if selected, is selected from the group consisting of flurbiprofen, suprofen, diclofenac, ketoprofen and ketorolac; the anti-histamine, if selected, is selected from the group consisting of levocabastine, emedastine, olopatadine, ketotifen, and azelastine; the mast cell inhibitor, if selected, is selected from the group consisting of cromolyn sodium, Iodoxamide, nedocromil, ketotifen and azelastine; and the inhibitor of iNOS, if selected, is selected from the group consisting of NG-monomethyl-L-arginine, 1400 W, diphenyleneiodium, S-methyl isothiourea, S-(aminoethyl) isothiourea, L-N6-(1-iminoethyl)lysine, 1,3-PBITU and 2-ethyl-2-thiopseudourea. ### Claim 4 (depends on 1) The method of claim 1, wherein the solution comprises an analgesic agent selected from the group consisting of local anesthetics and opioids. ### Claim 5 (depends on 4) The method of claim 4, wherein: the local anesthetic, if selected, is selected from the group consisting of lidocaine, tetracaine, bupivacaine, and proparacaine; and the opioid, if selected, is selected from the group consisting of morphine, fentanyl and hydromorphone. ### Claim 6 (depends on 1) The method of claim 1, wherein the solution comprises a mydriatic agent selected from the group consisting of alpha-I adrenergic receptor agonists and anticholinergic agents. ### Claim 7 (depends on 6) The method of claim 6, wherein: the alpha-1 adrenergic receptor agonist, if selected, is selected from the group consisting of phenylephrine, epinephrine, and oxymetazoline; and the anticholinergic agent, if selected, is selected from the group consisting of tropicamide, cyclopentolate, atropine and homatropine. ### Claim 8 (depends on 1) The method of claim 1, wherein the solution comprises an IOP reducing agent selected from the group consisting of beta adrenergic receptor antagonists, carbonic anhydrase inhibitors, alpha-2 adrenergic receptor agonists, and prostaglandin agonists. ### Claim 9 (depends on 8) The method of claim 8, wherein: the beta adrenergic receptor antagonist, if selected, is selected from the group consisting of timolol, metipranolol and levobunolol; the carbonic anhydrase inhibitor, if selected, is selected from the group consisting of brinzolamide and dorzolamide; the alpha-2 adrenergic receptor agonist, if selected, is selected from the group consisting of apraclonidine, brimonidine and oxymetazoline; and the prostaglandin agonist, if selected, is selected from the group consisting of latanoprost, travoprost and bimatoprost. ### Claim 10 (depends on 1) The method of claim 1, wherein each of the first and second agents in the solution is included at a concentration of no more than 100,000 nanomolar. ### Claim 11 (depends on 1) The method of claim 1, wherein each of the first and second agents in the solution is included at a concentration of no more than 10,000 nanomolar. ### Claim 12 (depends on 1) The method of claim 1, wherein the liquid irrigation carrier further comprises an adjuvant selected from electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent, a free-radical scavenger and mixtures thereof. ### Claim 13 (depends on 12) The method of claim 12, wherein: the electrolytes, if selected, comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate; the buffer, if selected, comprises bicarbonate at a concentration of from 10 to 50 millimolar; the cellular energy source if selected, is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and the free-radical scavenger, if selected, comprises glutathione at a concentration of from 0.05 to 5 millimolar. ### Claim 14 (depends on 1) The method of claim 1, wherein the liquid irrigation carrier further comprises electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent and a free-radical scavenger. ### Claim 15 (depends on 14) The method of claim 14, wherein: the electrolytes comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate; the buffer comprises bicarbonate at a concentration of from 10 to 50 millimolar; the cellular energy source is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and the free-radical scavenger comprises glutathione at a concentration of from 0.05 to 5 millimolar. ### Claim 16 (depends on 1) The method of claim 1, wherein the pH of the irrigation solution is between 5.5 and 8.0. ### Claim 17 (depends on 1) The method of claim 1, wherein the first and second agents comprise one or more anti-inflammatory agents in combination with one or more analgesic agents, and optionally may also include one or more IOP reducing agents and/or mydriatic agents. ### Claim 18 (depends on 1) The method of claim 1, wherein the first and second agents comprise one or more anti-inflammatory agents in combination with one or more IOP reducing agents, and optionally one or more analgesic and/or mydriatic agents. ### Claim 19 (depends on 1) The method of claim 1, wherein the first and second agents comprise one or more anti-inflammatory agents in combination with one or more mydriatic agents, and optionally one or more analgesic agents and/or IOP reducing agents. ### Claim 20 (depends on 1) The method of claim 1, wherein the first and second agents comprise one or more analgesic agents in combination with one or more IOP reducing agents, and optionally one or more anti-inflammatory agents and/or mydriatic agents. ### Claim 21 (depends on 1) The method of claim 1, wherein the first and second agents comprise one or more analgesic agents in combination with one or more mydriatic agents, and optionally one or more anti-inflammatory agents and/or IOP reducing agents. ### Claim 22 (depends on 1) The method of claim 1, wherein the first and second agents comprise one or more mydriatic agents in combination with one or more IOP reducing agents, and optionally one or more anti-inflammatory and/or analgesic agents. ### Claim 23 (depends on 1) The solution of claim 1, wherein the solution comprises an NSAID, timolol and phenylephrine. ### Claim 24 (depends on 1) The solution of claim 1, wherein the solution comprises an NSAID, timolol and tropicamide. ### Claim 25 (depends on 1) The solution of claim 1, wherein the solution comprises oxymetazoline and an NSAID. ### Claim 26 (depends on 1) The solution of claim 1, wherein the solution comprises a steroid, an NSAID, timolol and phenylephrine. ### Claim 27 (depends on 1) The solution of claim 1, wherein the solution comprises timolol, an NSAID, tropicamide and a local anesthetic. ### Claim 28 A method for perioperatively inhibiting inflammation, inhibiting pain, effecting mydriasis, and/or decreasing intraocular pressure during an ophthalmologic procedure; comprising irrigating ocular tissues during an ophthalmologic procedure with a solution including at least first and second agents in a liquid irrigation carrier, the first and second agents being selected to act on a plurality of differing molecular targets, each agent being selected from the physiologic functional classes of anti-inflammatory agents, analgesic agents, mydriatic agents and agents for decreasing intraocular pressure (“IOP reducing agents”), the second agent providing at least one physiologic function different than a function or functions provided by the first agent, each agent being included at a concentration of no more than 100,000 nanomolar. ### Claim 29 A perioperative irrigation solution for use during ophthalmologic procedures to inhibit inflammation, inhibit pain, effect mydriasis, and/or decrease intraocular pressure during the procedure, including at least first and second agents in a liquid irrigation carrier, the first and second agents being selected to act on a plurality of differing molecular targets, each agent being selected from the physiologic functional classes of anti-inflammatory agents, analgesic agents, mydriatic agents and agents for decreasing intraocular pressure (“IOP reducing agents”), the second agent providing at least one physiologic function different than a function or functions provided by the first agent, each agent being included at a concentration of no more than 100,000 nanomolar. ### Claim 30 (depends on 29) The solution of claim 29, wherein the solution comprises an anti-inflammatory agent selected from the group consisting of steroids, non-steroidal anti-inflammatory drugs (NSAIDS), anti-histamines, mast cell inhibitors, and inhibitors of inducible nitric oxide synthase (iNOS). ### Claim 31 (depends on 30) The solution of claim 30, wherein: the steroid, if selected, is selected from the group consisting of dexamethasone, fluorometholone and prednisolone; the NSAID, if selected, is selected from the group consisting of flurbiprofen, suprofen, diclofenac, ketoprofen and ketorolac; the anti-histamine, if selected, is selected from the group consisting of levocabastine, emedastine, olopatadine, ketotifen, and azelastine; the mast cell inhibitor, if selected, is selected from the group consisting of cromolyn sodium, Iodoxamide, nedocromil, ketotifen and azelastine; and the inhibitor of iNOS, if selected, is selected from the group consisting of NG-monomethyl-L-arginine, 1400 W, diphenyleneiodium, S-methyl isothiourea, S-(aminoethyl) isothiourea, L-N6-(1-iminoethyl)lysine, 1,3-PBITU and 2-ethyl-2-thiopseudourea. ### Claim 32 (depends on 29) The solution of claim 29, wherein the solution comprises an analgesic agent selected from the group consisting of local anesthetics and opioids. ### Claim 33 (depends on 32) The solution of claim 32, wherein: the local anesthetic, if selected, is selected from the group consisting of lidocaine, tetracaine, bupivacaine, and proparacaine; and the opioid, if selected, is selected from the group consisting of morphine, fentanyl and hydromorphone. ### Claim 34 (depends on 29) The solution of claim 29, wherein the solution comprises a mydriatic agent selected from the group consisting of alpha-1 adrenergic receptor agonists and anticholinergic agents. ### Claim 35 (depends on 34) The solution of claim 34, wherein: the alpha-1 adrenergic receptor agonist, if selected, is selected from the group consisting of phenylephrine, epinephrine, and oxymetazoline; and the anticholinergic agent, if selected, is selected from the group consisting of tropicamide, cyclopentolate, atropine and homatropine. ### Claim 36 (depends on 29) The solution of claim 29, wherein the solution comprises an IOP reducing agent selected from the group consisting of beta adrenergic receptor antagonists, carbonic anhydrase inhibitors, alpha-2 adrenergic receptor agonists, and prostaglandin agonists. ### Claim 37 (depends on 36) The solution of claim 36, wherein: the beta adrenergic receptor antagonist, if selected, is selected from the group consisting of timolol, metipranolol and levobunolol; the carbonic anhydrase inhibitor, if selected, is selected from the group consisting of brinzolamide and dorzolamide; the alpha-2 adrenergic receptor agonist, if selected, is selected from the group consisting of apraclonidine, brimonidine and oxymetazoline; and the prostaglandin agonist, if selected, is selected from the group consisting of latanoprost, travoprost and bimatoprost. ### Claim 38 (depends on 29) The solution of claim 29, wherein each of the first and second agents in the solution is included at a concentration of no more than 10,000 nanomolar. ### Claim 39 (depends on 29) The solution of claim 29, wherein the liquid irrigation carrier further comprises an adjuvant selected from electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent, a free-radical scavenger and mixtures thereof. ### Claim 40 (depends on 39) The solution of claim 39, wherein: the electrolytes, if selected, comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate; the buffer, if selected, comprises bicarbonate at a concentration of from 10 to 50 millimolar; the cellular energy source, if selected, is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and the free-radical scavenger, if selected, comprises glutathione at a concentration of from 0.05 to 5 millimolar. ### Claim 41 (depends on 29) The solution of claim 29, wherein the liquid irrigation carrier further comprises electrolytes sufficient to provide a physiological balanced salt solution, a cellular energy source, a buffering agent and a free-radical scavenger. ### Claim 42 (depends on 41) The solution of claim 41, wherein: the electrolytes comprise from 50 to 500 millimolar sodium ions, from 0.1 to 50 millimolar potassium ions, from 0.1 to 5 millimolar calcium ions, from 0.1 to 5 millimolar magnesium ions, from 50 to 500 millimolar chloride ions, and from 0.1 to 10 millimolar phosphate; the buffer comprises bicarbonate at a concentration of from 10 to 50 millimolar; the cellular energy source is selected from dextrose and glucose and is present at a concentration of from 1 to 25 millimolar; and the free-radical scavenger comprises glutathione at a concentration of from 0.05 to 5 millimolar. ### Claim 43 (depends on 29) The solution of claim 29, wherein the pH of the irrigation solution is between 5.5 and 8.0. ### Claim 44 (depends on 29) The solution of claim 29, wherein the first and second agents comprise one or more anti-inflammatory agents in combination with one or more analgesic agents, and optionally may also include one or more IOP reducing agents and/or mydriatic agents. ### Claim 45 (depends on 29) The solution of claim 29, wherein the first and second agents comprise one or more anti-inflammatory agents in combination with one or more IOP reducing agents, and optionally one or more analgesic and/or mydriatic agents. ### Claim 46 (depends on 29) The solution of claim 29, wherein the first and second agents comprise one or more anti-inflammatory agents in combination with one or more mydriatic agents, and optionally one or more analgesic agents and/or IOP reducing agents. ### Claim 47 (depends on 29) The solution of claim 29, wherein the first and second agents comprise one or more analgesic agents in combination with one or more IOP reducing agents, and optionally one or more anti-inflammatory agents and/or mydriatic agents. ### Claim 48 (depends on 29) The solution of claim 29, wherein the first and second agents comprise one or more analgesic agents in combination with one or more mydriatic agents, and optionally one or more anti-inflammatory agents and/or IOP reducing agents. ### Claim 49 (depends on 29) The solution of claim 29, wherein the first and second agents comprise one or more mydriatic agents in combination with one or more IOP reducing agents, and optionally one or more anti-inflammatory and/or analgesic agents. ### Claim 50 (depends on 29) The solution of claim 29, wherein the solution comprises an NSAID, timolol and phenylephrine. ### Claim 51 (depends on 29) The solution of claim 29, wherein the solution comprises an NSAID, timolol and tropicamide. ### Claim 52 (depends on 29) The solution of claim 29, wherein the solution comprises oxymetazoline and an NSAID. ### Claim 53 (depends on 29) The solution of claim 29, wherein the solution comprises a steroid, an NSAID, timolol and phenylephrine. ### Claim 54 (depends on 29) The solution of claim 29, wherein the solution comprises timolol, an NSAID, tropicamide and a local anesthetic.