This invention relates to amino acid chelated compositions which are formulated for delivery to one or more specific tissue sites within a living organism. More specifically, this invention relates to compositions consisting of selected mineral cations chelated with selected amino acid or peptide ligands. These chelates are absorbed intact into biological tissues and, because of either the selected ligands or the ligands chelated to certain metals, migrate to specific tissue target sites within a living organism where the chelate is utilized as is or is dissociated into mineral cations and amino acids or peptides for utilization at that site.
Amino acid chelates are becoming well accepted as a means of increasing the metal content in biological tissues of man, animals and plants. By amino acid chelates is meant the product resulting from the reaction of a polypeptide, dipeptide or naturally occuring alpha amino acid with a metal ion having a valence of two or more to form a ring structure wherein the positive electrical charges of the metal ion are neutralized by the electrons available through the carboxylate or free amino groups of the alpha amino acid. Chelate formation through neutralization of the positive 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 been made by first dissolving a water soluble divalent metal salt in water. An amino acid ligand is then reacted with the metal ion at a 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. This procedure generally results in a a chelate containing a certain amount of inorganic anion radicals such as sulfates, chlorides and the like. In Ashmead, U.S. Pat. No. 4,599,152, issued July 8, 1986 pure amino acid chelates free of inorganic anion radicals and a method for their preparation is taught. The present invention encompasses the use of both pure amino acid chelates and those containing inorganic anion radicals. However, the use of pure amino acid chelates is preferred.
For convenience sake, metal ions having a valence of two or more will simply be referred to as divalent metal ions or divalent cations. Hence, the ferric ion Fe.sup.3 is considered to be a divylent ion for purposes of this specific cation. 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 specification refers only to products obtainable through the hydrolysis of proteins, that does not mean that synthetically produced amino acids are to be excluded provided they are the same as can be obtained through the hydrolysis of proteins. Therefore, protein hydrolysates such as quadrapeptides, tripeptides, dipeptides and naturally occuring alpha amino acids may collectively be referred to as amino acids. These amino acids are important building blocks for proteins and function as such when ingested into biological tissues.
Amino acid chelates are sufficiently stable, when properly formulated, that they are absorbed intact into biological systems where the chelate is transported to the site of utilization. At that site, the chelate may be utilized intact or the chelate bonding may be broken and the metal ion and amino acids utilized by the system. In mammals, for example, small intestine. Properly formulated amino acid chelates have been found to have stability constants which are sufficient to hold the chelate intact while it is absorbed into, the blood. Once absorbed, it is transported intact via a dipeptide transport mechanism to a specific site within the system where the metal ion and amino acid ligand portions are then utilized as needed.
Exemplary of the prior art teaching the use of amino acid chelates for uptake into biological systems are Ashmead, U.S. Pat. No. 4,076,803, issued Feb. 28, 1978 for "Synergistic Combination of Metal Proteinates With Beta-Chlorovinyl Dialkyl Phosphates"; Ashmead, U.S. Pat. No. 4,103,003 issued July 25, 1978 for "Composition for Improving Biologic Development"; Ashmead, U.S. Pat. No. 4,19,716 issued Oct. 2, 1979 for "Synergistic Metal Proteinate Plant Hormone Compositions"; Ashmead, U.S. Pat. No. 4,169,717 issued Oct. 2, 1979 for "Synergistic Plant Regulatory Compositions"; Ashmead, U.S. Pat. No. 4,172,072 issued Oct. 23, 1979 for "Buffered Enzymatically Produced Metal Proteinates"; Ashmead, U.S. Pat. No. 4,201,793 issued May 6, 1980 for "Oil Cooked Foods Containing Metal Proteinates"; Ashmead, U.S. Pat. No. 4,216,143 issued Aug. 5, 1980 for "Soluble Non-Ferrous Metal Proteinates"; Ashmead, U.S. Pat. No. 4,216,144 issued Aug. 5, 1980 for "Soluble Iron Proteinates"; Ashmead et al, U.S. Pat. No. 3,873,296 issued Mar. 25, 1975 for "Increasing Metal in Biological Tissue"; Ashmead et al, U.S. Pat. No. 4,020,158 issued April 26, 1977 for "Increasing Metal in Biological Tissue"; Jensen, 3,969,540 issued July 13, 1976 for "Enzymatically prepared Metal Proteinates; and Jensen, 4,167,564 issued Sept. 11, 1979 for "Biological Assimilation of Metals".
While the above cited art teaches that amino acid chelates (also sometimes referred to as metal proteinates) are effective in increasing metal content in biological tissue such use is nondiscriminatory in that the increase in metal content is generally "across the board" in all tissues. While such useage is generally beneficial to an organism which is deficient in certain metals, there are also occasions where it is desirable to have a metal ion migrate or be targeted to a certain tissue site within a biological organism. For example, calcium is essential in the growth and repair of bones and teeth. It is also necessary to normal heart functioning, nerve irritability and clotting of blood. Magnesium is also essential to the bones as well as in the liver and certain muscles. Magnesium also aids in the transfer of intercullar water by osmosis, is a catalyzer for some enyzme reaction and in energy production. Copper is needed in combination with iron to build hemoglobin, is necessary for the production of RNA and aids in the development of bones, brains, connective tissue and pigment formation. Zinc is found in liver, bones, epidermal tissues, blood, pancreas, kidneys, and pituitary glands. Also, zinc has been linked to synthesis of protein, as a constituent of insulin, as a constituent in carbohydrate metabolism and aids in healing of wounds. Manganese is a component in activating numerous enzymes such as peptidases, phosphatases, arginase, cozymase, carboxylase and cholinesterase, which aid in digestion, metabolism of carbohydrates, protein and fat. Manganese is stored primarily in the kidney and liver. Other metals capable of being chelated, which also have important biological functions, are chromium, cobalt, molybdenum and selenium.
Certain of nutritional supplements have been marketed consisting of glandular materials allegedly chelated with metal cations. It has been stated that when a metal ion is chelated with a glandular material and ingested into an animal or human being, the glandular material chelate enhances the function of that particular organ, the glandular material was obtained from. While this thesis may sound logical, it is based on the premise that glandular materials are absorbed intact rather than being digested prior to being absorbed. It is well known that most proteins are not absorbed intact. Rather, they are broken down into single amino acids or at best small peptide chains before intestinal absorption can take place. Insulin, for example, cannot be given orally. As compared to insulin, oral hypoglycemic agents are low molecular weight sulfonamides such as tolbutamide, tolazamide or chlorpropamide which are not digested prior to being absorbed through the gut. It, therefore, follows that one ingesting raw processed pancreas will not reap the benefit of any insulin contained therein. The same reasoning may be applied to other bioactive proteins contained in other glandular materials.