US2877253A - Therapeutic iron complex - Google Patents

Description

United States Patent 2,877,253 THERAPEUTIC IRON COMPLEX Claims priority, application Germany August 8, 1955 1 Claim. (Cl. 260-439) The present invention relates to a therapeutic complex in which the ferrous ion is made readily available for absorption.

When iron preparations are employed to replenish the body stores of iron it is necessary that they be administered in forms which are readily absorbable and well tolerated. Oral iron preparations are known to be much better absorbed as ferrous compounds (oxidation number=2, i. e. bivalent) than as ferric compounds (trivalent). In addition, they are better tolerated.

Ferrous compounds have the limitation that they tend to oxidize rather readily, especially in alkaline environment, thus being converted to the less desirable ferric form. It is usual practice to attempt to counteract this tendency by adding reducing agents. However, many of the best reducing agents are toxic and those that are usable for pharmaceutical purposes may deteriorate rather rapidly during production and storage. The result is that by the time a preparation including such an agent reaches the patient a significant proportion of the ferrous compound may have been converted into the corresponding undesirable ferric form. Hence it is a principal purpose of the present invention to provide a preparation which contains the ferrous ion in readily absorbable form but which nevertheless is stable over a wide range of conditions and particularly those found in the gastrointestinal tract. 1,

Another purpose ofthe present invention is to provide simple and efficient procedures for making such a preparation.

These and other objects are achieved in the ferrous complex which results from the reaction in an inert environment of ferrous sulphate and glycine. The resulting complex when administered orally, preferably in the form of a coated pill, has been found to be an excellent source of physiological iron. It is stable over the whole pH range found in the gastrointestinal tract, the same varying from weakly acid to alkaline. The complex is also quite stable in comparison with other ferrous compounds, there being no noticeable conversion to ferric forms. Clinical experience with the complex has demonstrated that iron therefrom is rapidly and etfectively absorbed.

It was not possible to anticipate from the literature which preceded the present development that the combination of ferrous sulfate and glycine would yield iron in such readily absorbable form since such literature taught that iron would combine with amino acids to form insoluble, non-absorbable iron complexes. However, contrary to such teaching, it was found both clinically and in a number of experiments on the isolated intestine with radioactive iron that the present preparation not only is highly absorbable but that the complex provides an unusually stable form of ferrous ion and broadly protects said ion from conversion into non-absorbable compounds such as hydroxides and phytates which one might expect to find in the digestive tract.

A preferred method of preparing the subject ironglycerine complex is as follows.

*2 EXAMPLE 1 10.0 g. of ferrous sulfate 'and 2.7 'g. of "glycine are thoroughly mixed and carefully heated under initr'ogen to 0. Reaction occurs rapidly, "and the "complex compound is obtained as soon as'the 'colortur'nsluniformly light-brown.

After cooling to 20 C., 12.7 g. "of "Ferrous Sulfate- Glycine Complex are obtained, which contains mg. Fe -ions per 0.63 g. For identification of Ferrous Sulfate-Glycine Complex the usual methods can be applied.

Another effective method is as follows.

(EXAMPLE II Ferrous sulfate and glycine (in a molar ratio of 1:1) are left to react in a little oxygen-free Water under nitrogen and gentle warming. The Ferrous Sulfate-Glycine Complex thus obtained is precipitated with ethyl alcohol or any other water-miscible organic solvent. The lightbrown deposit is dried in a vacuum evaporator.

The complex is preferably administered in the form of a coated pill, a sufiicient quantity of the same being incorporated in each pill so that the unit dose is equal to 40 mg. of ferrous ion. Work with the preparation has established that a good daily dosage is six tablets, i. e. a total of 240 mg.

The efiicacy of Ferrous Sulfate-Glycine Complex is strikingly demonstrated when its absorption, as indicated by blood serum iron concentration measurement is contrasted to that obtained with ferrous sulfate alone. Thus, in Table I, there is set forth a series of seven cases in which ferrous sulfate alone was administered in the dosage indicated, with the increased iron concentration shown.

T able I Increase of iron concentration in Administered the serum in meg. dose of Fe" as a percent ferrous salt from t0 120 mg. 99 109 120 mg. 85 108 120 mg. 114 136 120 mg. Fe 68 240 mg. 25 126 240 mg. 42 65 240 mg. 102 126 Note that in spite of the fact that the starting iron concentration in blood serum in the case of most of the subjects described in Table I was extremely subnormal, nevertheless only a small portion of the iron administered was absorbed and incorporated in the serum. Contrast this with a set of observations made upon patients who received Ferrous Sulfate-Glycine Complex.

Table II Increase of iron concentration in Administered the serum in mcg. dose of Fe as a percent glycine complex fromto- It is shown by Table II that despite the fact that the serum iron concentrations were substantially normal, 3.

,like most iron preparations, the same does not have a constipating elfect upon those to whom it is administered.

What is claimed is:

Ferrous Sulfate-Glycine Complex substantially free 10 of iron in therferric form.

References Cited in the file of this patent UNITED STATES PATENTS Ruskin Sept. 17, 1940 Desnoyers Dec. 9, 1941 Weinniayr -s July 6, 1954 Kopelman Aug. 31, 1954 Schmidt Ian. 18, 1955 FOREIGN PATENTS Australia June 12, 1952