# US 2014/0155449 A1 · New use of l-histidine and derivatives thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0155449 A1 - Document ID: US20140155449A1 - Status: Published application - Kind: A1 - Application number: 14/235,128 - Filed: 2012-07-24 - Published: 2014-06-05 - Earliest claimed: 2011-08-02 - Assignees: Bracco Imaging S.P.A. - Inventors: Baranyai Zsolt; Ernö Brücher; Simona Bussi; Alessandro Maiocchi; Fulvio Uggeri - Web page: https://patentgrep.com/patent/US20140155449A1 ## CPC - A61K 31/4172: Imidazole-alkanecarboxylic acids, e.g. histidine - A61K 31/28: Compounds containing heavy metals - A61P 13/12: of the kidneys - A61P 17/00: Drugs for dermatological disorders - A61P 39/02: Antidotes - A61P 39/04: Chelating agents - 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 The present invention discloses the use of L-Histidine to reduce Gadolinium accumulation into target organs, preventing its toxic effects, after administration of gadolinium based contrast agents. The invention thus, also disclose the use of L-Histidine to prevent the NSF syndrome in patients with renal functionality impairment. A kit of part is also disclosed by the use of which toxicity associated to free Gd3+, deriving from GDBCA, is prevented by oral administration of L-histidine before administration of the contrast agent. A method for the prevention of toxic metal accumulation which consists in the administration, preferably by the oral route, of L-Histidine is also disclosed. L-Histidine is preferably administered a s a single oral dose comprised from 0.2-20 g. ## Claims ### Claim 1 A method of preventing Gadolinium (Gd3+) accumulation in a patient's target organ after a GDBCA (Gadolinium Based Contrast Agent) administration comprising: administering L-Histidine or a derivative thereof before or simultaneous with administration of a GDBCA (Gadolinium Based Contrast Agent). ### Claim 2 (depends on 1) The method according to claim 1, wherein said L-Histidine derivative is selected from the group consisting of: L-Histidine di-hydrochloride, L-Histidine monohydrochloride monohydrate. ### Claim 3 (depends on 1) The method according to claim 1, wherein said target organ is selected from the group consisting of: bones, skin, blood, plasma and liver. ### Claim 4 (depends on 1) The method according to claim 1, wherein said GDBCA is an ionic or non-ionic macrocyclic or linear Gd chelating agent selected from the group consisting of: Gadoversetamide, Gadodiamide, Gadopentetate dimeglumine, Gadoxetic acid or Gadoxetate disodium, Gadobutrol, Gadofosfeset, Gadobenate dimeglumine, Gadoteridolo, Gadoteric acid. ### Claim 5 (depends on 4) The method according to claim 4, wherein said GDBCA is selected from the group consisting of: Gadodiamide, Gadoversetamide, Gadopentetate dimeglumine, Gadobenate dimeglumine and Gadoxetic acid or Gadoxetate disodium. ### Claim 6 (depends on 1) The method according to claim 1, wherein said condition is a dermopathy. ### Claim 7 (depends on 1, 5) The method according to any one of claim 1 or 5, wherein said condition is NSF (Nephrogenic systemic fibrosis). ### Claim 8 (depends on 1, 5) The method according to claim 1 or 5 where, in said patient, the renal function is impaired. ### Claim 9 A method for the prevention of a condition associated with accumulation of Gadolinium (Gd3+) in patient's target organs after administration of a GDBCA (Gadolinium Based Contrast Agent) comprising administration of a composition comprising L-Histidine or derivatives thereof prior to or simultaneous with administration of the GDBCA. ### Claim 10 (depends on 9) The method according to claim 9, wherein the composition comprises 0.2-20 g/L-Histidine. ### Claim 11 A kit of parts for administration of a GDBCA, comprising a first container comprising a composition wherein the active ingredient is L-Histidine or a derivative thereof and a second container comprising a GDBCA. ### Claim 12 (depends on 11) The kit of parts according to claim 11, wherein said GDBCA is selected from the group consisting of Gadoversetamide, Gadodiamide, Gadopentetate dimeglumine, Gadoxetic acid or Gadoxetate disodium, Gadobutrol, Gadofosfeset, Gadobenate dimeglumine, Gadoteridolo, Gadoteric acid. ### Claim 13 (depends on 11, 12) The kit of parts according to any one of claims 11-12, wherein the GDBCA is comprised in a prefilled syringe. ### Claim 14 (depends on 13) The kit of parts according to claim 13, wherein said composition is an oral composition comprising multiple or single dosage unit(s) of L-Histidine. ### Claim 15 (depends on 14) The kit of parts according to claim 14, wherein said single unit dose comprises 0.2-20 g L-Histidine or derivatives thereof ### Claim at position 16 16-17. (canceled)