United States Patent 1 Ashmead [54] PURE AMINO ACID CHELATES (75) Inventor: Harvey H, Ashmead, Kaysville, Utah [73] Assignee: Albion Laboratories, Clearfield, Utah [21] Appl. Now 738,068 [22] Filed: May 24, 1985, (51) Int, cL c2sB 1/02 [52] US. "204/72; 204/129; 260/113; 260/115, (58) Field of Seareh 206/129, 128, 72; 260/115, 113 (5) References Cited U.S. PATENT DOCUMENTS 3010018 6/1962 Wingers 200/115 495,176 1/1985 Brule et i. 260/113 Primary Examiner—R. L. Andrews ‘Attorney, Agent, or Firm-—Thorpe, North and Western 4,599,152 Tul. 8, 1986 (11) Patent Number: [4s] Date of Patent: wo ABSTRACT Pure amino acid chelates and a method of their produc~ tion are disclosed. The amino acid chelates are free of ‘contaminating inorganic anions. The chelate consists of| ‘a metal ion comprising iron, zinc, manganese, magne- sium, copper, calcium and mixtures thereof. The metal jon is chelated to one or more ligands comprising alpha ‘amino acids, protein hydrolysates, polypeptides, dipep- tides, and combinations thereof. A novel process is disclosed wherein the amino acid ligand is brought into reactive contact with a divalent metal ion in an environ- ‘ment which is completely anion free but otherwise ‘conducive to the interaction between the amino acid ligand and the metal ion, with the formation of an amino acid chelate in pure form or, at least, which can readily be recovered from the reactive environment in pure form. 8 Claims, No Drawings4,599,152 1 PURE AMINO ACID CHELATES BACKGROUND OF THE INVENTION ‘This invention relates to pure amino acid chelates and toa method of their preparation. More specifically, this invention relates to pure amino acid chelates which are free of contaminating anions and to a method of chelate preparation. ‘Amino acid chelates are becoming well accepted as @ means of increasing the metal content in biological tissues of man, animals and plants. By amino acid che- lates is meant the product resulting from the reaction of a polypeptide, dipeptide or naturally occuring alpha amino acid with a metal jon having a valence of two or more to form a ring structure wherein the positive elec trical charges of the metal ion are neutralized by the electrons available through the carboxylate or free amino groups of the alpha amino acid. For convenience sake metal ions having a valence of two or more will simply be referred to as divalent metal ions or divalent cations, For the same reasons naturally occurring alpha amino acids will be referred to as amino acids. Although the term amino acid as used throughout this specifica tion refers only (o products obtainable through the hydrolysis of proteins, that does not mean that syathet cally produced amino acids are to be excluded provided ‘they are the same as can be obtained through the hydro- lysis of proteins. Therefore, protein hydrolysates such as polypeptides, dipeptides and naturally occuring alpha amino acids are collectively referred to as amino ‘acids. Now included within in this terminology are synthetically produced amino acids such as ethylenedi aminetetraacetic acid (EDTA), monohydroxyethyle- thylenediaminetriacetic acid, diethylenetriaminepenta- acetic acid, monohydroxyethyldiglycine and dihydrox- yethylglycine, all of which are utilized as chelating agents for industrial purposes. These synthetic amino acids are outside the scope of this invention. ‘There are numerous reasons for limiting the scope of 40 the invention to the amino acids defined. These amino acids are important building blocks for proteins and function as such when ingested into biological tissues. In addition, the chemistry is different between substi- tated and naturally occuring amino acids. EDTA type of ligands are strong chelating agents forming chelates having high stability constants of the order of 101628 EDTA type chelates may pass intact through most biological systems and not contribute to such systems by making @ mineral more bioavailable or by adding protein building blocks. EDTA. types of chelating Agents are most often administered as metal scavengers to remove unwanted cations from biological systems. Amino acid chelates, on the other hand, are sufficiently stable that they are absorbed intact into biological sys- tems where the chelate bonding is broken and the metal jon and amino acids are utilized by the system at the appropriate sites. In an animal, for example, most metal absorption occurs in the small intestine. The amino acid chelates have been found to have stability constants ‘which are sufficent to hold the chelate intact while absorbed into biological tissues. Once absorbed, it is broken down by the system and the metal ion and amino acid ligand portion are then utilized as needed. Chelate formation through neutralization of the post- tive charges of the divalent metal ions can be through the formation of ionic, covalent or coordinate covalent ‘bonding, In the past, amino acid chelates have generally 5 50 © 6s 2 been made by first dissolving a water soluble divalent ‘metal salt in water. An amino acid ligand is then reacted ‘with the metal ion ata ratio of ligand to metal of at least 2:1, In order for the reaction to proceed to completion, the amino acid has had to be at a pH which is preferably above or more basic than the isoelectric point of the ‘amino acid. For that reason a certain amount of an alkali metal hydroxide, carbonate or bicarbonate has usuallly been added to the reaction mixture. “Most water soluble salts used in making amino acid chelates have been either sulfates or chlorides. Using the sulfate ion as exemplary, the reaction has generally proceeded as follows: MSO, + 2RCHNH;COOH + 2N:01—> Oo Le al oN OA. ry 4 NapSO4 + 2830 \ cor wt h Wa R where M isa bivalent metal cation and R is a radical of ‘naturally occurring amino acid. cis apparent from the above formula that the sulfate anion is present in the reaction mixture in the form of sodium sulfate. U.S. Pat. No. 2,877,253 teaches a prod- uct formed by the reaction of one mole of glycine with fone mole of ferrous sulfate. That patent indicates that the sulfate anion becomes tied up in the reaction which allegedly forms a ferrous sulfate-glycine complex. ‘Hence, whether or not the sulfate actually partici pates in the reaction or is present as the salt of an alkali Imetal it nevertheless is present in the reaction mixture. Such products are dificult if not impossible, to purify. While sodium sulfate per seis water soluble the reaction between a metal sulfate and an amino acid is never ‘carried to 100% completion and the sulfate ion is al- ways present. The same holds true for the presence of chloride ion when utilizing a metal chloride salt for amino chelate preparation. Tt would often be desirable to be able to utilize a pure form of amino acid chelates when administering them to biological systems to increase the bioavailability of the metal. For example, the presence of the chloride or sulfate anions may present situations where the adminis- tration of the chelate is actually detrimental for the systems requiring divalent metal ions. In non-biological systems it may also be desirable to have a metal present which is not in ionic form and wherein no metal salt anions are present. Such systems include catalysis, and activation of en- ‘zymes. Another area of use not heretofor available is the supplementation of metal ions to plant and soils, soils in particular, where an anion is not also added as part of the supplement. Many soils are deficient in met- als such as calcium, magnesium, iron, manganese, cop- per and zine but, at the same time, have an excess of chloride and sulfate anions. This is particularly true in areas of salinity where chlorides are present in excess and in areas where acid rain returns excess quantities of sulfate ions to the soil in the form of sulfuric acid. Hlow- ever, the accepted treatment of metal deficient soils is to ‘add materials such as gypsum or kieserite (calcium sul- fate) epsom salts (magnesium sulfate), iron sulfate and the like to these soils. This only magnifies the problems