Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
  • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
  • C07F15/02—Iron compounds
  • C07F15/025—Iron compounds without a metal-carbon linkage
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/20—Inorganic substances, e.g. oligoelements
  • A23K20/30—Oligoelements
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/28—Compounds containing heavy metals
  • A61K31/295—Iron group metal compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/24—Heavy metals; Compounds thereof
  • A61K33/26—Iron; Compounds thereof
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
  • C07C51/41—Preparation of salts of carboxylic acids
  • C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part

Definitions

• This invention relates to compounds of iron and more particularly to ferrous salts of organic acids.
• this invention is directed to non-hydrated ferrous fumarate and to methods of preparing it.
• the invention also includes new hematinic compositions and animal feed supplements, as well as methods of treating human beings and domestic animals.
• a new compound of iron may be mentioned the provision of a new compound of iron; the provision of a useful hematinic; the provision of a compound of the type indicated which has a high iron content and is substantially nontoxic; the provision of a new and pharmaceutically useful ferrous compounds; the provision of such a compound which is substantially tasteless; the provision of such a compound which is easily prepared relatively free of ferric iron and in substantially anhydrous form; the provision of such a compound which is not readily oxidized upon exposure to air; the provision of such a compound which is relatively stable upon exposure to moist air; the provision of new pharmaceutical compositions containing iron; the provision of methods of preparing anhydrous ferrous fumarate; and the provision of methods for treating both human beings and domestic animals suffering from a deficiency of iron.
• Other objects and features will be in part apparent and in part pointed out hereinafter.
• ferrous salts were generally preferred for this purpose since it is widely accepted that ferrous iron is more readily absorbed from the gastrointestinal tract of man than is ferric iron.
• ferrous iron salts previously known, such as ferrous sulfate, ferrous gluconate, and ferrous lactate, suffer from one or more of the following disadvantages: instability in air with regard to oxidation and/ or changes in color or moisture content; and low iron content; unpleasant taste; and gastrointestinal irritability.
• an anhydrous or non-hydrated salt of ferrous iron and fumaric acid may be readily prepared and that its surprisingly advantageous properties make it particularly useful as a hematinic.
• the novel anhydrous ferrous fumarate compound of the present invention is a free-flowing dark brown to reddish-brown granular powder. The color varies with the method of preparation, the peferred product being reddish-brown. Its empirical composition corresponds to the formula representing about 33% iron. The exact nature of its structure is not known at this time. However, some of its properties, for example, its brown color and its resist- 2,848,366 Patented Aug. 19, 1958 ance to oxidation are not typical of a simple ionic ferrous salt. X-ray diffraction studies by the powder method indicate that its structure is crystalline, as numerous sharp lines are observed in the diffraction pattern.
• ferrous fumarate trihydrate has been previously prepared, it is no more stable than the heretofore wellknown ferrous salts.
• novel anhydrous ferrous fumarate of this invention remains relatively free flowing and shows little tendency to oxidize or hydrate even during several weeks exposure to a hot humid atmosphere.
• anhydrous ferrous fumarate is substantially tasteless it may conveniently be administered in uncoated tablets, while tablets of other iron salts must ordinarily be coated to eliminate the objectionable iron taste. Also, anhydrous ferrous fumarate does not noticeably irritate the gastrointestinal tract.
• the anhydrous ferrous fumarate of this invention is readily prepared by slowly mixing hot solutions of sodium fumarate and ferrous sulfate, whereupon the sparingly soluble anhydrous ferrous fumarate precipitates. While it is preferable that the precipitation be made at a temperature above approximately 94 C. it may be made at any temperature from approximately 70 C. to the boiling point of the solution in which the precipitation is made.
• a suitable product may be prepared by adding the ferrous sulfate solution to the sodium fumarate solution, adding the sodium fumarate solution to the ferrous sulfate solution produces a product containing a smaller proportion of occluded sodium salts. It is substantially free of ferric iron and remains so upon further handling without being specially protected from contact with air.
• a suitable product may also be made using a slurry of sodium fumarate rather than a solution. Such a slurry may occur if the sodium fumarate is made up in a volume of water that is insufficient to dissolve all the salt formed.
• ferrous fumarate may be combined with various other materials to give therapeutically useful compositions in dosage form.
• it may be used in the form of tablets of ferrous fumarate and a carrier (such as fillers, binders, and lubricants), or hard gelatin capsules filled with ferrous fumarate, or other dosage forms particularly useful for oral ingestion.
• a carrier such as fillers, binders, and lubricants
• hard gelatin capsules filled with ferrous fumarate or other dosage forms particularly useful for oral ingestion.
• solid pharmaceutical carriers examples include starch, gelatin, talc, stearic acid, magnesium stearate and the like.
• binders include liquid glucose, starch paste, acacia solution and gelatin solution. Any of the conventional tableting materials used in pharmaceutical practice may be employed as carriers herein where such materials are compatible with ferrous fumarate.
• Example 1 A solution of sodium fumarate was prepared by slowly adding fumaric acid (41 lb. 2 oz.) to a solution of sodium carbonate (44 lb. Na CO -H O) in water (44 gal.). The pH was approximately 7. During a period of ten minutes a moderately hot (50 C.) clear solution (22.9 gal.) of ferrous sulfate lb. FeSO -7H O) having a pH of 2.4 was added with mixing to the solution of sodium Example 2 i s odiumcarbonate (53.5 lb. of Na CO H O) wasuiissolyed in water; v.(4t045 ;ga1.) and fumaric'. acid 50 lb.) 7 was added slowly.
• fumaric acid 41 lb. 2 oz.
• sodium carbonate 44 lb. Na CO -H O
• the pH was approximately 7.
• Example 3 A- tablet granulation was prepared by m oistening anhydrousferrous fumarate (7.5 kg.) lwitha mixture of equal parts of liquid glucose and water.(64 fl oz. of the mixture). Magnesium stearate (1%) was mixed with the dried granulation and the mixturewas tableted intqtablets each containing approximately 209 mg. of anhydrous, ferrous fumarate.
• Example 4 Tablets Werealso preparedcontaining starch (5%),in addition-to. thepomponents shown in Example 3. These, Whi rsteie s eon-s m c an c strength. h t e v ftage ofgdisintegtfating more rapidly in artificial -gastric :lzlu
• The-ironsalts were administered-daily, five days a Week, for two weeks, atotal of ten doses.
• Each compound was administered as a 5 (w./v.) aqueous suspension.
• the initial dose of each compound contained 36.8 mg. of iron, -but-subsequent.doses were reduced to 18.4 mg. of iron each because of toxic reactions in the controlrats which received ferroussulfate.
• Food consumption and body weights were measured at weekly intervals.
• the rats were observed daily for gross signs of systemic toxicity during thedosage period and for one week afterward. Gross autopsies were performed on rats that died. At the end of the observation period the survivors were sacrificed and gross autopsies were performed.
• other water-soluble ferrous, salts such as ferrous chloride and ferrousacetate, and other water-solublesalts of fumaric acid,- such as; ammonium furnarate and potassium fuma- .rate,;rnay be used as long as the cation of the furnaric acid salt; chosen and the anion ofthe ferrous salt chosen do nob-react to form a sparingly soluble compound under
• the method of preparing non-hydrated ferrous fumarate which comprises mixing a solution of a watersoluble ferrous salt and a solution of a water-soluble salt of fumaric acid at a temperature above approximately 70 C. to precipitate substantially anhydrous ferrous fumarate, and thereafter separating the non-hydrated ferrous fumarate from the solution.
• the method of preparing non-hydrated ferrous fumarate which comprises mixing a solution of a watersoluble ferrous salt and a solution of a water-soluble salt of fumaric acid at a temperature above approximately 94 C. to precipitate substantially anhydrous ferrous fumarate, and thereafter separating the non-hydrated ferrous fumarate from the solution.
• the method of preparing non-hydrated ferrous fumarate which comprises mixing a solution of ferrous sulfate and a solution of sodium fumarate at a temperature between approximately 94 C. and the boiling point of the mixture of said solutions to precipitate substantially anhydrous ferrous fumarate, and thereafter separating the non-hydrated ferrous fumarate from the solution.
• the method of preparing non-hydrated ferrous fumarate which comprises adding a solution of the sodi- 6 um salt of fumaric acid to a solution of ferrous sulfate at a temperature between approximately 94 C. and the boiling point of the mixture of said solutions to precipitate substantially anhydrous ferrous fumarate, and thereafter separating the non-hydrated ferrous fumarate from the solution.
• a hematinic composition in'dosage form compris-' ing non-hydrated ferrous fumarate and a pharmaceutical carrier.
• a hematinic composition in dosage form comprising a major amount of non-hydrated ferrous fumarate and a minor amount of a pharmaceutical carrier.
• a hematinic composition in tablet form comprising a major amount of non-hydrated ferrous fumarate and a minor amount of magnesium stearate.
• a process for treating an iron-deficiency anemia which comprises orally administering non-hydrated ferrous fumarate to an animal.
• a process for treating an iron-deficiency anemia which comprises orally administering non-hydrated ferrous fumarate in tablet form to an animal.

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• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Organic Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Polymers & Plastics (AREA)
• Epidemiology (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Inorganic Chemistry (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Pharmacology & Pharmacy (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Zoology (AREA)
• Animal Husbandry (AREA)
• Food Science & Technology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Priority Applications (9)

Applications Claiming Priority (2)

Publications (1)

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ID=25737741

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Country Status (9)

Cited By (12)

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Citations (1)

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• 0
  • IT IT573230D patent/IT573230A/it unknown
  • NL NL101664D patent/NL101664C/xx active
  • CA CA572556A patent/CA572556A/en not_active Expired
  • BE BE569591D patent/BE569591A/xx unknown
• 1956
  • 1956-05-18 US US585633A patent/US2848366A/en not_active Expired - Lifetime
• 1957
  • 1957-03-14 GB GB8501/57A patent/GB807638A/en not_active Expired
  • 1957-05-15 FR FR1175193D patent/FR1175193A/fr not_active Expired
  • 1957-05-17 DE DEM34212A patent/DE1087126B/de active Pending
• 1958
  • 1958-07-23 CH CH6212658A patent/CH371558A/de unknown

Patent Citations (1)

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