# US 8,273,327 B2 · Radio-opaque compounds, compositions containing same and methods of their synthesis and use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,273,327 B2 - Document ID: US8273327B2 - Status: Granted - Kind: B2 - Application number: 12/840,376 - Filed: 2010-07-21 - Published: 2010-11-18 - Granted: 2012-09-25 - Earliest claimed: 2003-08-11 - Assignees: Pathak Holdings LLC - Inventors: Chandrashekhar P. Pathak; Sanjay M. Thigle - Web page: https://patentgrep.com/patent/US8273327B2 ## CPC - A61K 49/0442: {Polymeric X-ray contrast-enhancing agent comprising a halogenated group} - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 11/06: Antiasthmatics - A61P 17/04: Antipruritics - A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps - A61P 23/02: Local anaesthetics - A61P 25/16: Anti-Parkinson drugs - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C08G 63/6822: {derived from hydroxy carboxylic acids} - C08G 63/912: {derived from hydroxycarboxylic acids} - C08G 64/0233: {containing halogens} - C08H 1/00: Macromolecular products derived from proteins (food proteins A23; glue, gelatine C09H) - 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 - C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS - C08H: DERIVATIVES OF NATURAL MACROMOLECULAR COMPOUNDS (polysaccharides C08B; natural rubber C08C; natural resins or their derivatives C09F; bituminous materials C10) ## Abstract Radio-opaque biodegradable compositions are formed by modifying terminal groups of synthetic and natural biodegradable polymers such as polylactones with iodinated moieties. The biodegradable property of the compositions renders them suitable for use in medical field such as drug delivery, imaging. Compounds disclosed in this invention exist as neat liquid. Certain compositions disclosed in this invention form hydrophobic iodine rich domains when dissolved in water, such domains provide better contrasting properties as well as ability to dissolve hydrophobic bioactive drugs. Certain iodinated moieties disclosed in the invention are capable of cross linking natural proteins in situ in presence of suitable catalysts and co-catalysts. ## Claims ### Claim 1 A biodegradable radio-opaque composition for implantation in the animal body, the composition comprising: an aqueous solution comprising a thermoreversible polymer and a non-radioactive iodinated organic compound that is not covalently bonded to the polymer, with the solution being a liquid at a temperature below about 15° C. and forming a gel at physiological temperature, wherein the iodinated organic compound in the solution is 3 to 40 percent by weight. ### Claim 2 (depends on 1) The composition of claim 1 wherein the thermoreversible polymer comprises a copolymer of polyethylene oxide and polypropylene oxide. ### Claim 3 (depends on 1) The composition of claim 1 wherein the thermoreversible polymer comprises PLURONIC F127. ### Claim 4 (depends on 1) The composition of claim 1 wherein the thermoreversible polymer comprises polyethylene oxide and poly(lactic acid). ### Claim 5 (depends on 1) The composition of claim 1 wherein the iodinated organic compound is selected from the group consisting of iohexol, metrizamide, iopamidol, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, meglumine diatrizoate, iopentol, iopromide, triiodobenzoic acid, erythrosine, and ioversol. ### Claim 6 (depends on 1) The composition of claim 1, further comprising at least one bioactive compound. ### Claim 7 (depends on 6) The composition of claim 6, wherein the bioactive compound is selected from a group consisting of anti-viral agents, anti-infectives, anti-pruritics, anti-psychotics, cholesterol or lipid reducing agents, cell cycle inhibitors, anti-cancer agents, anti-parkinsonism drugs, HMG-CoA inhibitors, anti-restenosis agents, anti-inflammatory agents, anti-asthmatic agents, antihelmintics, immunosuppressives, muscle relaxants, anti-diuretic agents, vasodilators, beta- blockers, hormones, anti-depressants, decongestants, calcium channel blockers, growth factors, wound healing agents, analgesics and analgesic combinations, local anesthetics agents, antihistamines, sedatives, angiogenesis promoting agents, angiogenesis inhibiting agents, and tranquilizers. ### Claim 8 (depends on 6) A method of delivering a bioactive compound, the method comprising: providing the composition of claim 6 having the bioactive compound; and administering an injectable solution of the composition to a patient comprising a thermosensitive polymer, a non-radioactive iodinated organic compound that is not covalently bonded to the polymer, and the bioactive compound, with the solution being a liquid at a temperature below about 15° C.; and forming a gel at physiological temperature, wherein the iodinated organic compound in the solution is 3 to 40 percent by weight. ### Claim 9 (depends on 8) The method of claim 8 wherein the thermoreversible polymer comprises a copolymer of polyethylene oxide and polypropylene oxide. ### Claim 10 (depends on 8) The method of claim 8 wherein the iodinated organic compound is selected from the group consisting of iohexol, metrizamide, iopamidol, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, meglumine diatrizoate, iopentol, iopromide, triiodobenzoic acid, erythrosine, and ioversol. ### Claim 11 A biodegradable radio-opaque composition for implantation in the animal body, the composition comprising: a solution comprising a thermoreversible polymer and a non-radioactive iodinated organic compound that is not covalently bonded to the polymer, with the solution being a liquid at a temperature between about 45 and about 55° C. and forming a gel at physiological temperature, wherein the iodinated organic compound in the solution is 3 to 40 percent by weight. ### Claim 12 (depends on 11) The composition of claim 11 wherein the thermoreversible polymer comprises a copolymer of polyethylene oxide and a polyhydroxyacid. ### Claim 13 (depends on 11) The composition of claim 11 wherein the copolymer comprises two blocks of polyethylene oxide and a block of polyhydroxyacid. ### Claim 14 (depends on 11) The composition of claim 11 wherein the thermoreversible polymer comprises gelatin. ### Claim 15 (depends on 11) The composition of claim 11 wherein the iodinated organic compound is selected from the group consisting of iohexol, metrizamide, iopamidol, 3,5-bis(acetylamino)-2,4,6- triiodobenzoic acid, meglumine diatrizoate, iopentol, iopromide, triiodobenzoic acid, erythrosine, and ioversol. ### Claim 16 (depends on 11) The composition of claim 11, further comprising at least one bioactive compound. ### Claim 17 (depends on 16) A method of delivering a bioactive compound, the method comprising: providing the composition of claim 16 having the bioactive compound; and administering an injectable solution of the composition to a patient comprising a thermosensitive polymer, a non-radioactive iodinated organic compound that is not covalently bonded to the polymer, and the bioactive compound, with the solution being a liquid at a temperature between about 45° and about 55° C.; and forming a gel at physiological temperature, wherein the iodinated organic compound in the solution is 3 to 40 percent by weight. ### Claim 18 (depends on 17) The method of claim 17 wherein the thermoreversible polymer comprises a copolymer of polyethylene oxide and a polyhydroxyacid. ### Claim 19 (depends on 17) The method of claim 17 wherein the iodinated organic compound is selected from the group consisting of iohexol, metrizamide, iopamidol, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, meglumine diatrizoate, iopentol, iopromide, triiodobenzoic acid, erythrosine, and ioversol. ### Claim 20 A biodegradable radio-opaque composition for injection implantation in the animal body, the composition comprising an injectable liquid stage and a biodegradable gel stage: the liquid stage being an aqueous solution at a temperature below about 15° C. or between about 45 and about 55° C. and comprising a thermoreversible polymer mixed with a water-soluble non-radioactive iodinated organic compound that is not covalently bonded to the polymer, wherein the iodinated organic compound in the solution is 3 to 40 percent by weight; and the biodegradable gel stage being a non-fluid hydrogel at physiological temperature and having the thermoreversible polymer mixed with the non-radioactive iodinated organic compound that is not covalently bonded to the polymer, wherein the iodinated organic compound in the biodegradable gel is 3 to 40 percent by weight. ### Claim 21 (depends on 20) The composition of claim 20 comprising one or more of the following: the thermoreversible polymer including a copolymer of polyethylene oxide and polypropylene oxide, PLURONIC F127, copolymer of polyethylene oxide and poly(lactic acid), copolymer of polyethylene oxide and a polyhydroxyacid; gelatin; the iodinated organic compound is selected from the group consisting of iohexol, metrizamide, iopamidol, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, meglumine diatrizoate, iopentol, iopromide, triiodobenzoic acid, erythrosine, and ioversol; or at least one bioactive compound selected from a group consisting of anti-viral agents, anti-infectives, anti-pruritics, anti-psychotics, cholesterol or lipid reducing agents, cell cycle inhibitors, anti-cancer agents, anti-parkinsonism drugs, HMG-CoA inhibitors, anti-restenosis agents, anti-inflammatory agents, anti-asthmatic agents, antihelmintics, immunosuppressives, muscle relaxants, anti-diuretic agents, vasodilators, beta- blockers, hormones, anti-depressants, decongestants, calcium channel blockers, growth factors, wound healing agents, analgesics and analgesic combinations, local anesthetics agents, antihistamines, sedatives, angiogenesis promoting agents, angiogenesis inhibiting agents, and tranquilizers.