US2848366A - Non-hydrated ferrous fumarate and hematinic composition thereof - Google Patents

Non-hydrated ferrous fumarate and hematinic composition thereof Download PDF

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US2848366A
US2848366A US585633A US58563356A US2848366A US 2848366 A US2848366 A US 2848366A US 585633 A US585633 A US 585633A US 58563356 A US58563356 A US 58563356A US 2848366 A US2848366 A US 2848366A
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ferrous
fumarate
iron
solution
ferrous fumarate
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Hugh C Bertsch
John F Lemp
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Mallinckrodt Chemical Works
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Priority to IT573230D priority Critical patent/IT573230A/it
Priority to NL101664D priority patent/NL101664C/xx
Priority to BE569591D priority patent/BE569591A/xx
Priority to CA572556A priority patent/CA572556A/en
Priority to US585633A priority patent/US2848366A/en
Application filed by Mallinckrodt Chemical Works filed Critical Mallinckrodt Chemical Works
Priority to GB8501/57A priority patent/GB807638A/en
Priority to FR1175193D priority patent/FR1175193A/en
Priority to DEM34212A priority patent/DE1087126B/en
Priority to CH6212658A priority patent/CH371558A/en
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    • 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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Description

United States Patent C NON -HYDRATED FERRQUS FUMARATE AND HEMATINIC COMPOSITION THEREOF Hugh C. Bertsch, St. Louis, Mo., and John F. Lemp, Alton, IlL, assignors to Mallinckrodt Chemical Works, St. Louis, Mo., a corporation of Missouri No Drawing. Application May 18, 1956 Serial No. 585,633
12 Claims. (Cl. 167-68) This invention relates to compounds of iron and more particularly to ferrous salts of organic acids.
Briefly, 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.
Among the objects of this invention 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.
The invention accordingly comprises the products and methods hereinafter described, the scope of the invention being indicated in the following claims.
The use of iron preparations in the treatment of certain anemias is well established. 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.
However, the pharmaceutically useful 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.
In accordance with the present invention it has now been found that 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.
While ferrous fumarate trihydrate has been previously prepared, it is no more stable than the heretofore wellknown ferrous salts. In contrast, the 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.
Because 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. Although 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.
According to the present invention, ferrous fumarate may be combined with various other materials to give therapeutically useful compositions in dosage form. For example, 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.
Examples of solid pharmaceutical carriers include starch, gelatin, talc, stearic acid, magnesium stearate and the like. Examples of 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.
When anhydrous ferrous fumarate is administered orally to human patients suffering from an iron-deficiency anemia the rate of hemoglobin regeneration is as satisfactory as that obtained with ferrous sulfate. Moreover, the reticulocyte response is higher and more prompt than usually occurs with iron therapy, and there is no noticeable gastrointestinal discomfort.
The following examples illustrate the invention.
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. During theaddition the, solution. was d. and, heated. The resulting solution of; sodium fumarate, having a pH of 6.8, was added slowly with rniX- ing to a v solution of. ferrous sulfate (.118 lb. FeSO -7H O gallonsofwater) having a pH of 3 .3., both solutions .hei ng maintained at or near boiling temperature during thef, mixing. The resulting slurry of.reddish-brown anf4 samples were removed and assayed for ferrous and ferric iron-n-"The-results are shown in the following table:
Portion 1- Room Portion II80 C. 5 Temperature and and approximately Atmosphere 100% relative humidity Elapsed Time Ferrous Ferric Ferrous Ferric Iron Iron Iron Iron (as Fe) w (as Fe) I (as Fe) (as Fe) Percent Percent Percent 0.8 31. 0.8 '31. 2 0.8 31. 2 0. 9 0.7 31.0 0. 8 31. 1 1. 1 31.1 0. 6 30. 95 0. 8 31.1 0.7 30.6 1.0 31.1 p 0.7 30.8 0. 9 I 31.2 0.
hydrous ferrous fumarate was filtered and washed in a centrifuge and dried in a tray drier hours at 110 C.). Yield: 63 lbs. 86% of theory. Calculated for .feC H O F e, 32.9%. Found; Fe, 32.6%. ,Only 0.2% of ferric iron (Fe+++) was found.
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
Example 5 Two groups of adult male albino rats, each group; con- -=sisting "of six rats, received ferrous sulfate and anhydrous ferrous furnarate, respectively, by stomach intubation. 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.
.All rats receiving anhydrous ferrous furnarate survived. The average body weights and food consumption -were normaland at autopsy all organs appeared normal. -Of the six control rats which received ferrous sulfate -one died afterthe second dose and a second died after the fifth dose. The four survivors generally appeared normal after the second day. The average body weights and food consumption were within the normal range and at gross autopsy all organs appeared normal.
Example 6 A. portion of anhydrous ferrous furnarate-wasexposed to the atmosphere atproom temperature for; sixmonths. A second portion was oonfined overv water in a desiccator at 80 C. for four. weeks. The desiccatorwas closed ex- -eept,while samples were being drawn for analysis but no attemptwas made to exclude. air. a From time to itime Example 7 .-;A.=portion of anhydrous ferrous fumarate was exposed -..to air-:saturatedwith. water vapor at a temperature of ..:J:6365 Czfor a period of four weeks. At weekly intervals, samplesswere withdrawn and assayed for ferrous .,,iron,-. ferric iron,- total iron and moisture content. The
.-.-results..are shown in the following table:
' Percent Iron -I1g31e.psed-'lirne Percent H2O 4O Ferrous F errre Total 0 0.1 31.1 0.6 32.2 .tweek 0.7 29.2 1.8 31.8 2 weeks 0. 7 28. 7 3. 3 31. 7 3 weeks; 0. 5 28. 7 3. 3 31. 5 gtweeksrufl vnu 0.5 3.4 31.6 d5
While we prefer to use sodium fumarate andferrous zsulfate to prepare anhydrous ferrous .fumarate, 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 reactionconditionsto be used.
.It-, will-be-understood that the term substantially an- .hydrous ferrous fumaratefas used'herein designatesthe non-hydratedgferrous salt of fumaric vacid having the em r c l qrm e e a i- In view of; -the above, it will be seen thatthe several objects of the invention are achieved and other advan- -tageo us resultsattained.
As various changescould be made in the above methods andproducts-without departing from the scope of the .-.invention, it is intended that all'matter containedin; the 65 above deseription shall be interpreted as illustrative and not in a E limiting, sense.
T .We-claim:
1. ..IfIon-hydrated ferr9usfumarate. Z N n-hYdrated ferrous fumarate, having the empirical formu1a-EeQ H O and characterizedbybeing substantially stable upon exposure to moist air.
3. The method of preparing non-hydrated ferrous ;.;furna rate which comprises mixing a water-soluble ferrous 5 salt andt a;..water-solublev-.salt. of furnaric .acid in. an aqueous n edium. at atemperature.v above approximately 70 C. to precipitate substantially anhydrous ferrous fumarate, and thereafter separating the non-hydrated ferrous fumarate from the aqueous medium.
4. 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.
5. 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.
6. 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.
7. 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.
8. A hematinic composition in'dosage form, compris-' ing non-hydrated ferrous fumarate and a pharmaceutical carrier.
9. A hematinic composition in dosage form, comprising a major amount of non-hydrated ferrous fumarate and a minor amount of a pharmaceutical carrier.
10. A hematinic composition in tablet form, comprising a major amount of non-hydrated ferrous fumarate and a minor amount of magnesium stearate.
11. A process for treating an iron-deficiency anemia which comprises orally administering non-hydrated ferrous fumarate to an animal.
12. A process for treating an iron-deficiency anemia which comprises orally administering non-hydrated ferrous fumarate in tablet form to an animal.
References Cited in the file of this patent UNITED STATES PATENTS 2,135,031 Brown Nov. 1, 1938

Claims (2)

1. NON-HYDRATED FERROUS FUMARATE.
8. A HEMATINIC COMPOSITION IN DOSAGE FORM, COMPRISING NON-HYDRATED FERROUS FUMURATE AND A PHARMACEUTICAL CARRIER.
US585633A 1956-05-18 1956-05-18 Non-hydrated ferrous fumarate and hematinic composition thereof Expired - Lifetime US2848366A (en)

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Application Number Priority Date Filing Date Title
BE569591D BE569591A (en) 1956-05-18
CA572556A CA572556A (en) 1956-05-18 Iron compound and methods of preparation
IT573230D IT573230A (en) 1956-05-18
NL101664D NL101664C (en) 1956-05-18
US585633A US2848366A (en) 1956-05-18 1956-05-18 Non-hydrated ferrous fumarate and hematinic composition thereof
GB8501/57A GB807638A (en) 1956-05-18 1957-03-14 Substantially anhydrous ferrous fumarate and a method of preparing same
FR1175193D FR1175193A (en) 1956-05-18 1957-05-15 Fumarate manufacturing process
DEM34212A DE1087126B (en) 1956-05-18 1957-05-17 Process for the production of anhydrous ferrofumarate
CH6212658A CH371558A (en) 1956-05-18 1958-07-23 Process for the production of organic ferrous salts

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US585633A US2848366A (en) 1956-05-18 1956-05-18 Non-hydrated ferrous fumarate and hematinic composition thereof
CH6212658A CH371558A (en) 1956-05-18 1958-07-23 Process for the production of organic ferrous salts

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2985559A (en) * 1958-01-27 1961-05-23 Glaxo Lab Ltd Stabilized therapeutic ferrous fumarate aqueous suspensions
US3259500A (en) * 1961-10-11 1966-07-05 Kentucky Res Foundation Method for inhibiting anemia in young pigs by feeding the sow an iron agent
US3317386A (en) * 1964-05-04 1967-05-02 Burroughs Wellcome Co Method of treating aplastic anaemia using a preparation containing the mitogenic component of phytohaemagglutinin
US3332778A (en) * 1964-07-28 1967-07-25 Nebraska Cons Mills Company Supplying at least about 4% iron and a sweetening agent for the prevention of iron-deficiency anemia in baby pigs
US3478073A (en) * 1966-05-06 1969-11-11 Astra Ab Preparation of anhydrous ferrous fumarate
EP0004691A2 (en) * 1978-04-05 1979-10-17 Ruhr-Stickstoff Aktiengesellschaft Mineral feed supplements for animal nutrition
US5132120A (en) * 1990-05-23 1992-07-21 Norsk Hydro A.S. Fish feed
US20080033196A1 (en) * 2006-08-04 2008-02-07 Swee-Keng Goh Metal carboxylate salts
CN102370055A (en) * 2010-08-24 2012-03-14 北京英惠尔生物技术有限公司 Preparation method of feeding ferrous fumarate
CN105753686A (en) * 2016-01-26 2016-07-13 苏州优合科技有限公司 Process for preparing ferrous fumarate
CN111138271A (en) * 2020-01-20 2020-05-12 太原理工大学 Preparation method of organic metal salt additive
CN113264822A (en) * 2021-05-15 2021-08-17 吉源(淮北)食品科技有限公司 Preparation method of disodium fumarate

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US3125491A (en) * 1962-04-06 1964-03-17 Chew able hematinic vitamin tablet
CA885974A (en) * 1968-04-02 1971-11-16 R. Telfer William Ferrous fumarate capsule and preparation
BE755463A (en) * 1969-08-28 1971-03-01 Laso Martinez Victorino ANHYDROUS FERROUS FUMARATE PREPARATION PROCESS

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US2135031A (en) * 1934-10-09 1938-11-01 Brown Herman Elisha Process for the manufacture of a therapeutic organic compound

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DE682875C (en) * 1935-02-07 1939-10-24 Chem Fab Promonta G M B H Process for the production of stable organic ferrous compounds
US2822317A (en) * 1955-12-12 1958-02-04 Smith Kline French Lab Aqueous iron-ascorbic acid preparation

Patent Citations (1)

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Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2985559A (en) * 1958-01-27 1961-05-23 Glaxo Lab Ltd Stabilized therapeutic ferrous fumarate aqueous suspensions
US3259500A (en) * 1961-10-11 1966-07-05 Kentucky Res Foundation Method for inhibiting anemia in young pigs by feeding the sow an iron agent
US3317386A (en) * 1964-05-04 1967-05-02 Burroughs Wellcome Co Method of treating aplastic anaemia using a preparation containing the mitogenic component of phytohaemagglutinin
US3332778A (en) * 1964-07-28 1967-07-25 Nebraska Cons Mills Company Supplying at least about 4% iron and a sweetening agent for the prevention of iron-deficiency anemia in baby pigs
US3478073A (en) * 1966-05-06 1969-11-11 Astra Ab Preparation of anhydrous ferrous fumarate
EP0004691A2 (en) * 1978-04-05 1979-10-17 Ruhr-Stickstoff Aktiengesellschaft Mineral feed supplements for animal nutrition
EP0004691A3 (en) * 1978-04-05 1979-11-14 Ruhr-Stickstoff Aktiengesellschaft Mineral feed supplements for animal nutrition
US5132120A (en) * 1990-05-23 1992-07-21 Norsk Hydro A.S. Fish feed
US20080033196A1 (en) * 2006-08-04 2008-02-07 Swee-Keng Goh Metal carboxylate salts
US7495117B2 (en) 2006-08-04 2009-02-24 Kemin Industries, Inc. Metal carboxylate salts
CN102370055A (en) * 2010-08-24 2012-03-14 北京英惠尔生物技术有限公司 Preparation method of feeding ferrous fumarate
CN105753686A (en) * 2016-01-26 2016-07-13 苏州优合科技有限公司 Process for preparing ferrous fumarate
CN111138271A (en) * 2020-01-20 2020-05-12 太原理工大学 Preparation method of organic metal salt additive
CN113264822A (en) * 2021-05-15 2021-08-17 吉源(淮北)食品科技有限公司 Preparation method of disodium fumarate
CN113264822B (en) * 2021-05-15 2024-04-05 吉源(淮北)食品科技有限公司 Preparation method of disodium fumarate

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GB807638A (en) 1959-01-21
FR1175193A (en) 1959-03-20
CH371558A (en) 1963-08-31
DE1087126B (en) 1960-08-18
BE569591A (en)
IT573230A (en)

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