Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02202145 1997-04-08
W O 96!11907 PCT/US95113222
ENHANCED SOLUBILIZATION OF ZINC AND MANGANESE
METHIONINE COMPLEX SALTS BY ADDITION OF FERRIC
ION
BACKGROUND OF THE INVENTION
This invention relates to an improvement in the
properties of dry powder complexes of zinc and manganese with
methionine in the 1:1 ratio. In that sense it represents a
significant improvement over the process disclosed in
commonly owned U.S. Patent 4,764,633, and as well, over
commonly owned and now expired U.S. Patent 3,941,818 issued
March 2, 1976 entitled "1:1 ZINC METHIONINE COMPLEXES", and
United States Letters Patent 3,950,372 issued April 13, 1976,
and entitled "1:1 MANGANESE ALPHA AMINO ACID COMPLEXES".
Thus patent 3,941,818 and U.S. Patent 3,950,372 relate to 1:1
complexed salts per se of zinc and manganese with the amino
acid methionine. These salts, as identified in the earlier
patents, have the useful feature of being highly body
absorbable nutritional supplements for animals that provide
readily available sources of zinc and manganese on the one
hand, and the essential amino acid methionine on the other.
The common assignee of both of these patents makes a
variety of transition metal complexes with alpha amino acids
for sale. For example, see U.S. Patent 5,061,815 relating to
metal lysine complexes and methods for producing metal lysine
complexes, as well as U.S. Patent 5,278,329 for L-form 1:1
metal methionine complexes.
Complexes of lysine are very easily soluble in water.
However, complexes of metals such as zinc and manganese and
methionine are less soluble in water than the complexes of
metals and lysine.
In Anderson, U.S. Patent 4,764,633, an improvement in
the complexing process is disclosed wherein the complexing of
either zinc or manganese ions with methionine is conducted in
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the presence of a catalytically effective amount of ferric
ion. The amount of ferric ion described is about 2% to about
10% based on the dry weight basis of the methionine,
preferably from about 4% to about 8% based on the dry weight
basis of the methionine.
For effective feed supplements, the supplement must be
in a powdered, dry form, and it must be readily soluble in
the gut of animals; otherwise, much of the supplement will
not be absorbed into the blood stream. It also is useful to
have water soluble supplements so that the user may
administer them through aqueous systems.
While U.S. Patent 4,764,633 enhances the amount of
complexation, it does not enhance the solubility of the final
dry product.
Accordingly, there has been a real and a continuing need
for the discovery of a process which will enhance the
solubility characteristics of the dry 1:1 complexes of zinc
and manganese with methionine.
This invention has as its primary objective the
fulfillment of this need in order that dry 1:1 manganese
methionine complexes and dry 1:1 zinc methionine complexes
have enhanced solubility in comparison with those prepared as
described in U.S. Patent 3,941,818 and U.S. Patent 3,950,372.
For details of the desirability and the utility of 1:1
manganese methionine complexes, see the previously referred
to U.S. Patent 3,950,372.
For details of the desirability and the utility
of 1:1 zinc methionine complexes, see U.S. Patent No.
3,941,818.
The method of accomplishing each of the above objectives
of this invention will become apparent from the detailed
description of the invention which follows hereinafter.
SUMMARY OF THE INVENTION
Method of enhancing the water solubility of dry zinc
methionine complex salts by reacting in water soluble zinc
salt with methionine in the presence of ferric ion with the
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amount being between 15 mole percent and 30 mole percent of
the amount of zinc present.
DETAILED DESCRIPTION OF THE INVENTION
It is important to note that the respective zinc and
manganese compounds which are prepared in accordance with
this invention are referred to as complexed salts. These
salts are to be carefully distinguished from conventional
salts such as, for example, zinc chloride or manganese
chloride. Such conventional salts such as zinc chloride or
manganese chloride contain only an electrostatic attraction
between the cation and the anion. The 1:1 complexed salts
prepared by this invention differ from conventional salts in
that while they have an electrostatic attraction between the
cation and the anion, there is also a coordination bond
between the cation and the amino moiety of the alpha amino
acid.
With regard to the zinc methionine complexed salts which
are prepared in accordance with the improved process of this
invention, they have the general formula:
O
CH3-S-CH2-CH2-CH-C-O~Zn X
NH2 w
wherein X is an anion and w is an integer equal to the
anionic charge of X. The cation of these complexed salts is
represented by the bracketed material in the above formula
and represents a 1:1 complex of zinc and methionine.
With regard to the manganese alpha amino acid complex
salts of the present invention, they have the formula:
O
CH3-S-CH2-CH2-CH-C-O~I~n X
NH2 w
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X and w are as previously defined.
The process of preparing the desired zinc and methionine
1:1 complex salts of methionine as referred to herein is
straightforward and direct. Commonly it begins with the use
of a water soluble zinc salt and/or a water soluble manganese
salt, respectively. Suitable zinc salts which can be
employed are the halides, the sulfates, and the phosphates.
The desired molar ratio of zinc salt to methionine is 1:1.
Suitable manganese salts which can be employed are likewise
halides, sulfates and phosphates. The desired molar ratio of
manganese to methionine is 1:1. In each instance, the
sulfate salts are preferred from the standpoint of
availability and, at least currently, cost.
In the general process, these salts are at least
partially water dissolved, preferably at elevated
temperatures. Temperatures within the range of from about
180°F to about 205°F have been found desirable, most
preferably temperatures within the range of 190°F to about
205°F. In actual practice, one common technique is to stir
the salt into a water solution while simultaneously injecting
steam to elevate the temperature within the desired range.
In accordance with the process of our prior patent, U.S.
Patent 4,764,633, along with these reactants, a catalytically
effective amount of ferric ion is added to enhance
complexation yield. The amount added is from about 2$ to
about 10~ based upon the dry weight of methionine. The
earlier patent teaches that levels above the 10 molar percent
level based upon the dry weight of methionine should be
avoided. This corresponds to the same molar percentages for
zinc, i.e. 2~ to 10~, and preferably 4~ to 8~. As previously
mentioned in the earlier patent, it was discovered that when
percentages of ferric ion are added to the reactants at the
levels there specified, desirable things occur. In the first
instance, the dissolving of the salt and the amino acid in
the water appears to be significantly enhanced, and in the
second instance there is an increased yield of the desirable
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1:1 complexes formed. That earlier discovery, however, -
involved formation of the reactants and did not involve
solving the problems that zinc and manganese methionine
complexes are inherently difficultly soluble at best after
formation.
It has now been surprisingly discovered that if
substantially increased amounts of ferric ion are added
during the formation reaction for the complexes, not only
does one get a substantially increased yield of the desirable
1:1 complexes, but in addition the dry product produced by
the process is more soluble, and the solution produced is
more stable.
For purposes of this invention, the amount of dry weight
molar basis based upon the mole weight of zinc or manganese
should be from about 15$ to about 30~ on a mole weight basis.
Preferably the amount is within the range of from 15~ to 20~.
As evidenced by the examples, the amount appears to be
critical in order to achieve the desired solubility of the
dry weight product. In other words, the enhanced solubility
phenomena of the present invention is not achieved until the
level of ferric ion salt added is at least 15~. Thus the
levels expressed in U.S. Patent 4,764,633 are too low to
provide the observed enhanced solubility phenomena of the
present invention.
While not wishing to be bound by any theory of
operability, it is believed that the presence of the ferric
ion, along with the manganese or the zinc ion and methionine,
brings about an equilibrium between ferric methionine
complexes and those of zinc and manganese. Since the ferric
ion complexes formed are much more soluble than either the
zinc or the manganese complexes, the equilibrium that occurs
seems to shift the equilibrium in the reaction of the zinc
and the methionine to provide a far more soluble product. In
any event, the important fact is not theoretically how the
reaction works, but that it does simply work to provide a
product of significantly enhanced solubility.
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WO 96/11907 PCT/US95/13222
The ferric ion which is added may be in the form of any
water soluble salt such as ferric chloride, ferric sulfate,
ferric phosphate, ferric acitate, or any other suitable water
soluble ferric salt. The most preferred, however, is ferric
chloride and ferric sulfate.
The following examples are offered to further illustrate
the improved process of the present invention and the
critical levels of ferric ion required to achieve the
enhanced solubility of the dry products prepared.
EXAMPLES OF ZINC METHIONINE ACID SULFATE SOLUBILIZATION BY
FERRIC CHLORIDE
The addition of ferric chloride was found to enhance the
solubility of zinc methionine acid sulfate. However, the
concentration of ferric chloride required to produce a
readily soluble and stable material is critical. The
following experiment was conducted to determine the optimum
concentration of ferric chloride.
Seven samples of zinc methionine acid sulfate containing
variable concentrations of Fecl3 were prepared. Zinc sulfate
heptahydrate (ZnS06.7H20; 14.388; 0.05 mole) was dissolved in
30 mL of distilled water in a 250 mL beaker. DL-Methionine
(7.468, 0.05 mole) was added. The mixture was heated to
boiling, and the heating continued for an additional 10
minutes.
Ferric chloride hexahydrate (Fec13.6H20, 13.528; 0.05
mole) was transferred into a 100 mL volumetric flask. The
solid was dissolved in approximately 50 mL of H20. Water was
added to volume.
Using a 50 mL burret, a specific volume of the ferric
chloride solution was added to each of the boiling solutions
of zinc methionine acid sulfate (Table 1). Each solution was
evaporated to dryness under reduced pressure at 70°C using a
rotary evaporator. A sample (l.Og) of each of the dried
products was transferred into a stoppered test tube. '
Distilled water was added in 0.5 mL increments and thoroughly
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mixed. The volume required for complete solubilization of
the sample is reported in Table 2.
TABLE 1
SampleZinc SulfateDL- Ferric Ferric Fe/Zn mole
~
No. wt. mole Methionine Chloride Chloride
g.
~at.g.mole solution mole
1 14.3%0.05 7.46 0.05 5 0.0025 5
2 14.3%0.05 7.46 0.05 7 0.0035 7
3 14.3%0.05 7.46 0.05 9 0.0045 9
4 14.3%0.05 7.46 0.05 11 0.0055 11
14.3%0.05 7.46 0.05 13 0.0065 13
6 14.3$0.05 7.46 0.05 15 0.0075 15
7 14.3$0.05 7.46 0.05 17 0.0085 17
TABLE 2
Fe/za Feal3/Methionine vol. of waterSolubility
Molar % w/w% to Dissolve g/mL
lg
Sample (mL)
1 5 5.44 12.5 0.08*
2 7 7.62 12.5 0.08*
3 9 9.80 11.0 0.09*
4 11 11.97 10.5 0.10*
5 13 14.15 9.5 0.11*
6 15 16.33 2.5 0.40
7 17 18.51 2.0 0.50
*Solution unstable. A white ppt of Methi onine was formed
was
uponstanding.
From the above Table 1 and Table 2 it can be seen that a
critical limit occurs with the demarcation line between 13
molar percent and 15 molar percent. In practice with other
experiments (not specifically shown here), it seems that only
a little increased value is obtained in going beyond 15~. In
other words, the increased solubility does not significantly
improve, even though the level might go up to as much as 30~.
Thus, at least 15$ appears to be the critical distinction and
30~ is a practical and economic upper limit.
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