|Title of Invention||
A METHOD FOR MANUFACTURING METAL METHIONE HYDROXY ANALOGUE CHELATE
|Abstract||A method of manufacture of metal alpha hydroxy aliphatic carboxylic acid chelate wherein the cation of the salt is divalent or trivalent cation which is an essential trace element comprising a 1: 1 to 1:4 ratio of a complex ion formed between a metal and methionine and any suitable anion, either inorganic or organic. The metal alpha hydroxy aliphatic carboxylic acid chelate have the generic formula: Wherein RI is methyl or ethyl, R2 is hydrogen, methyl or ethyl, R3 is hydrogen or methyl, M is a covalent or trivalent trace mineral cation, OH is an Hydroxide anion and w and n are integers to balance the anionic charge of OH. For Bivalent mineral cation w can be 1 or 2, the n will be 1 or 0 respectively. For Trivalent mineral cation w can be 1, 2 or 3, then n will be 2, 1 or 0 respectively. For Tetravalent mineral cation w can be 1,2,3 or 4, then n will be 3, 2, I or 0 respectively. These compounds are useful nutritional supplements, both for animals and humans, in that they provide a readily available source of precursor of methionine which is essential amino acid, relevant metal and if desired an relevant organic or inorganic acid in a stable and bioavailable form.|
Alpha - hydrojq^ aliphatic carboxylic acids like 2- hydroxy- 4 methylthiobutanoic acid [also referred to as Methyl Hydroxy Analogue (MHA)] find large scale application in animal supplemoitation diets being used as substitute for DL Methionine.
The present invention relates to the field of Biochemistry more particularly to method of manufacturing metal alpha hydroxy aliphatic carboxylic acid chelates. The product is prepared by reacting in an aqueous solution, a calcium oxide and / or hydroxide, an alpha hyckoxy aliphatic carboxylic acid, and a soluble metal salt at a ratio sufficient to allow substantially all of the ions jnesent in solution to react forming a metal alpha hydroxy aliphatic carboxylic acid chelates, calcium salt and water. The metal alpha hydroxy aliphatic carboxylic acid chelates of the present invention have a ligand to metd molar ratio fi-om 1:1 to 4: L The chelated form of MHA thus help both bioabsorption of MHA and Nutritionally relevant minerals.
BACKGROUND OF THE INVENTION
The importance of an adequate supply of methionine to the diet of both animals and humans has long been reported in literature. Methionine is an amino acid needed in the building of body protein. Adequate dietary intdce of metiiionine for swine, cattle and poultry has been known for some time to be of importance. An adequate level of methionine in the diets of swine, poultry and cattle tos been slwwn to be important for healthy growth of the animals. Animal diets are often supplemented with DL-methionine to assure the adequacies of the sulfiir amino acid content.
The DL-alpha-hydroxy aimlog of metiiionii^ (MHA) has been used as a substitute for DL-methionine, particularly in poultry diete. The efficacy of the alpha-hydroxy analog and its calcium salt were comfmred with ^t of DL-methionine in a chick bioassay. These studies indicated that the calcium salt of alpha-hydroxy analog is superior to the free acid and has approxinmtely equivalent efficacy to the DL-methionine.
Accordingly, it is an object of this invention to jKovide novel compounds of DL-alpha hydroxy analogs of methionine wherein the DL-alpha hydroxy analogs of methionine are in a form which can be readily absorbed after ingestion by animals and readily distributed and utilized in orde^ to provick adequate n^thionii^ and mii^ral levels for prof^r health, growth, and dietary balance of the animals.
Another object of this invention is to provide a process for making novel compounds of DL-alpha hydroxy analogs of methionine which is simple to perform and can be economically utilized in large scale plant i^3^ice to pr^>are the novel compounds of this invention in bulk for ready utilization in large quantities to supplement the diets of animals and hinnans. The nwtlMxl of accomplishing these aiKi other objects will become apparent fi'om the following description of the invention.
DETAILED DESCRIPTION OF THE INVENTION:
It is important to note that compounds with this invention are herein referred to as "Methionii^ Hydroxy Acid (MHA) teace mineral chelates." These salts are to be carefully distinguished from conventional salts such as, for example, zinc sulfate and magnesium sulfete, which contain only an electrostatic attraction between the cation and tlK anion. The complexed salts of this invention differ from conventional salts in that while they have an electrostatic atteaction between tiie cation and the anion, there is also a covalent bond formed between tte metal and the hydro?^ moiety of the hydroxy acid MHA. Methionine hydroxy analogue metal chelates have the general formula:
Wherein Ri is methyl or ethyl, R2 is hydrogen, methyl or ethyl, R3 is hydrogen or methyl, M is a divalent or trivalent trace mineral cation, OH is an anion and w and n are integers to balaiKe the anionic charge of OK For Bivalent mineral cation w can be 1 or 2, the n will be 1 or 0 respectively. For Trivalent mineral cation w can be 1,2 or 3, then n will be 2,1 or 0 respectively. For Tetravalent mineral cation w can be 1,2,3 or 4, then n will be 3,2, 1 or 0 respectively. The cation of these complex salts is represented by the bracketed material in the above formula and represents a 1:1 complex of trace mineral and alpha-hydroxy analog of methionine. Sterically, tte cation moiety can be represented as follows:
In the above-described formula, M represents a bivalent or trivalent trace mineral cation. Preferred trace mineral cations include zinc, coppo*, cobalt, calcium, magnesium, manganic, iron and chromium.
As can be seen from this formula, the five membered ring formation exists wherein the trace mineral anion is complexed by a covalent bond with a hydroxy moiety, and electrostatic attraction with the carbo?tylic acid moiety of the alpha hydroxy zwXog of methionine. In addition, the complex is formed by a 1:1 ratio of the alpha hydroxy aimlog of methionine molecules and trace mineral anions with each trace mineral anion becoming complexed with one MHA molecule. Preferably, the source of the anion, is an Hydroxide (OH). Utiliration of monovalent hydroxide anion is preferred because of the readily available source of this common inorganic aniotL
The following examples are offered to ftuther illustrate the product and process of this invention. They are not intended to limit the scope of the inventi
Preparation of Zinc Methyl Hydroxy Analogue (MHA) Hydroxide Chelate
One molar equivalent (150.2gms) of 2 Hydroxy 4 methylthiobutonic acid was diluted in 5 litres of water. One molar equivalent of Calcium Hydroxide (74 gms) was adcted to the above solution and stirred till dissolution. One molar equivalent (136.4gms) of Zinc Chloride was add^ and stir contimH>usly. The reaction produced a molar equivalent (231,6 gms) of Zim: Methyl Hydroxy Aiudt^^e Hydroxicte ctelale A^ch precipitated out. This product was dried using the conventioiml form of drying.
Manufacture of Manganese Methyl Hydroxy Analogue (MHA) Hydroxide Chelate
One molar equival^it (150,2 gjm) of 2- Ifydroxy- 4 thiomethylbutonic said ws^ diluted in 5 litres of water. One molar equivalent of Calcium Hydroxide (74 gms) was added to the above solution and stirred till dissolution, Ons molar equivalent of Mmig^iese Sulphate (151 gms) was added to the above solution and stir it till dissolution. An one molar equivalent of Manpnese Methyl Hydroxy Analogue Hydroxide chelate and Calcium Sulphate precipitated out and were dried by the arts conventionally known.
1. A method of manufacturing metal 2-Hydroxy-4-(Methylthio)-butanoic acid chelate
as structured below by reacting in aqueous solvent, an alkaline earth metal
oxide/hydroxide, 2-Hydroxy-4-(Methylthio)-butanoic acid also know as Methionine
Hydroxy Analogue and soluble metal salt.
Wherein Ri is methyl or ethyl, R2 is hydrogen, methyl or ethyl, R3 is hydrogen or methyl, M is a covalent or trivalent trace mineral cation, OH is an anion and w and n are integers to balance the anionic charge of OH. For Bivalent mineral cation w can be 1 or 2, the n will be 1 or 0 respectively. For Trivalent mineral cation w can be 1, 2 or 3, then n will be 2,1 or 0 respectively. For Tetravalent mineral cation w can be 1, 2,3 or 4, then n will be 3,2,1 or 0 respectively.
2. A method of manufacturing metal 2-Hydroxy-4-(Methylthio)-butanoic acid as
claimed in Claim 1 wherein the metal is selected from a group of divalent, trivalent
or tetravalent metals consisting of Calcium, Copper, Cobalt, Zinc, Iron, Manganese,
Magnesium, Chromium, Selenium and combinations thereof.
3. A method of manufacturing metal 2-Hydroxy-4-(Methylthio)-butanoic acid chelate as
claimed in Claim 1 wherein soluble metal salts are Chlorides, Nitrates, Sulphates of
the metals claimed in Claim 2.
|Indian Patent Application Number||937/CHE/2003|
|PG Journal Number||26/2007|
|Date of Filing||17-Nov-2003|
|Name of Patentee||SUNDAR CHEMICALS PRIVATE LIMITED|
|Applicant Address||6G,CENTURY PLAZA 560-562,ANNA SALAI TEYNAMPET CHENNAI-600 018|
|PCT International Classification Number||C 0 7C 51/00|
|PCT International Application Number||N/A|
|PCT International Filing date|