# US 10,478,450 B2 · Methods and compositions for administration of iron > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,450 B2 - Document ID: US10478450B2 - Status: Granted - Kind: B2 - Application number: 14/683,415 - Filed: 2015-04-10 - Published: 2015-10-22 - Granted: 2019-11-19 - Earliest claimed: 2006-01-06 - Assignees: Luitpold Pharmaceuticals, Inc. - Applicants: Luitpold Pharmaceuticals, Inc. - Inventors: Mary Jane Helenek; Marc L. Tokars; Richard P. Lawrence - Web page: https://patentgrep.com/patent/US10478450B2 ## CPC - A61K 31/7135: Compounds containing heavy metals - A61K 31/715: Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters - A61K 31/721: Dextrans - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) - A61P 7/06: Antianaemics - A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - A61P 13/12: of the kidneys - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - C07H 23/00: Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00) - 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 - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) ## Abstract The present invention generally relates to treatment of iron-related conditions with iron carbohydrate complexes. One aspect of the invention is a method of treatment of iron-related conditions with a single unit dosage of at least about 0.6 grams of elemental iron via an iron carbohydrate complex. The method generally employs iron carbohydrate complexes with nearly neutral pH, physiological osmolarity, and stable and non-immunogenic carbohydrate components so as to rapidly administer high single unit doses of iron intravenously to patients in need thereof. ## Claims ### Claim 1 A method of treating a disease, disorder, or condition characterized by iron deficiency or dysfunctional iron metabolism resulting in reduced bioavailability of dietary iron, comprising administering to a subject in need thereof an iron carbohydrate complex in a single dosage unit of at least 0.7 grams of elemental iron, wherein: the iron carbohydrate complex is substantially non-immunogenic, and has substantially no cross reactivity with anti-dextran antibodies; and the iron carbohydrate complex is an iron polyisomaltose complex. ### Claim 2 (depends on 1) The method of claim 1, wherein the disease, disorder, or condition comprises anemia. ### Claim 3 (depends on 2) The method of claim 2, wherein the anemia comprises iron deficiency anemia. ### Claim 4 (depends on 2) The method of claim 2, wherein: (i) the anemia comprises an iron deficiency anemia associated with chronic blood loss; acute blood loss; pregnancy; childbirth; childhood development; psychomotor and cognitive development in children; breath holding spells; heavy uterine bleeding; menstruation; chronic recurrent hemoptysis; idiopathic pulmonary siderosis; chronic internal bleeding; gastrointestinal bleeding; parasitic infections; chronic kidney disease; dialysis; surgery or acute trauma; chronic ingestion of alcohol; chronic ingestion of salicylates; chronic ingestion of steroids; chronic ingestion of non-steroidal anti-inflammatory agents; or chronic ingestion of erythropoiesis stimulating agents; or (ii) the anemia is of a chronic disease selected from among rheumatoid arthritis; cancer; Hodgkin's leukemia; non-Hodgkin's leukemia; cancer chemotherapy; inflammatory bowel disease; ulcerative colitis thyroiditis; hepatitis; systemic lupus erythematosus; polymyalgia rheumatica; sclerodema; mixed connective tissue disease; Sjogren's syndrome; congestive heart failure/cardiomyopathy; and idiopathic geriatric anemia; or (iii) the anemia is due to impaired iron absorption or poor nutrition; or (iv) the anemia is associated with Crohn's Disease; gastric surgery; ingestion of drug products that inhibit iron absorption; or chronic use of calcium. ### Claim 5 (depends on 1) The method of claim 1, wherein the disease, disorder, or condition is selected from among restless leg syndrome; blood donation; hair loss; and attention deficit disorder. ### Claim 6 (depends on 1) The method of claim 1, wherein the single dosage unit of elemental iron is at least about 1.0 grams. ### Claim 7 (depends on 1) The method of claim 1, wherein the single dosage unit of elemental iron is at least about 1.5 grams. ### Claim 8 (depends on 1) The method of claim 1, wherein the single dosage unit of elemental iron is at least about 2.0 grams. ### Claim 9 (depends on 1) The method of claim 1, wherein the single dosage unit of elemental iron is administered in about 15 minutes or less. ### Claim 10 (depends on 1) The method of claim 1, wherein the single dosage unit of elemental iron is administered in about 5 minutes or less. ### Claim 11 (depends on 1) The method of claim 1, wherein: mean iron core size is at least about 1 nm but no greater than about 9 nm; or mean size of a particle of the iron carbohydrate complex is no greater than about 35 nm. ### Claim 12 (depends on 1) The method of claim 1, wherein the iron carbohydrate complex is administered parenterally. ### Claim 13 (depends on 12) The method of claim 12, wherein: (i) parenteral administration comprises intravenous infusion and the single unit dose of iron carbohydrate complex is administered at a concentration of about 1000 mg elemental iron in about 200 ml to about 300 ml of diluent; or (ii) parenteral administration comprises bolus injection and the single unit dose of iron carbohydrate complex is administered at a concentration of about 1000 mg elemental iron in about 200 ml to about 300 ml of diluent; or (iii) parenteral administration comprises intramuscular injection and the single unit dose of iron carbohydrate complex is administered at a concentration of about 500 mg elemental iron in less than about 10 ml diluent. ### Claim 14 (depends on 1) The method of claim 1, further comprising a second administration of said iron carbohydrate complex upon recurrence of at least one symptom of the disease, disorder, or condition. ### Claim 15 (depends on 1) The method of claim 1, wherein the subject does not experience a significant adverse reaction. ### Claim 16 (depends on 1) The method of claim 1, wherein the iron carbohydrate complex has a pH between about 5.0 to about 7.0; physiological osmolarity; an iron core size no greater than about 9 nm; a mean diameter particle size no greater than about 35 nm; and a blood half-life of between about 10 hours to about 20 hours. ### Claim 17 (depends on 1) The method of claim 1, wherein the iron carbohydrate complex contains about 24% to about 32% w/w elemental iron; contains about 25% to about 50% w/w carbohydrate; and has a molecular weight of about 90,000 daltons to about 800,000 daltons. ### Claim 18 (depends on 1) The method of claim 1, wherein the single dosage unit of elemental iron is administered in about 2 minutes or less. ### Claim 19 (depends on 1) The method of claim 1, wherein the single dosage unit of elemental iron is at least about 0.8 grams. ### Claim 20 (depends on 1) The method of claim 1, wherein the single dosage unit of elemental iron is at least about 0.9 grams. ### Claim 21 (depends on 1) The method of claim 1, wherein: (i) the iron deficiency comprises iron deficiency with chronic blood loss; acute blood loss; pregnancy; childbirth; childhood development; psychomotor and cognitive development in children; breath holding spells; heavy uterine bleeding; menstruation; chronic recurrent hemoptysis; idiopathic pulmonary siderosis; chronic internal bleeding; gastrointestinal bleeding; parasitic infections; chronic kidney disease; dialysis; surgery or acute trauma; chronic ingestion of alcohol; chronic ingestion of salicylates; chronic ingestion of steroids; chronic ingestion of non-steroidal anti-inflammatory agents; or chronic ingestion of erythropoiesis stimulating agents; or (ii) the iron deficiency is of a chronic disease selected from among rheumatoid arthritis; cancer; Hodgkin's leukemia; non-Hodgkin's leukemia; cancer chemotherapy; inflammatory bowel disease; ulcerative colitis thyroiditis; hepatitis; systemic lupus erythematosus; polymyalgia rheumatica; scleroderma; mixed connective tissue disease; Sjorgen's syndrome; congestive heart failure/cardiomyopathy; and idiopathic geriatric anemia; or (iii) the iron deficiency is due to impaired iron absorption or poor nutrition; or (iv) the iron deficiency is associated with Crohn's Disease; gastric surgery; ingestion of drug products that inhibit iron absorption; or chronic use of calcium. ### Claim 22 (depends on 1) The method of claim 1, wherein the polyisomaltose is reduced polyisomaltose.