NZ750255B2 - Folic acid rumen by-pass method and composition - Google Patents
Folic acid rumen by-pass method and composition Download PDFInfo
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- NZ750255B2 NZ750255B2 NZ750255A NZ75025517A NZ750255B2 NZ 750255 B2 NZ750255 B2 NZ 750255B2 NZ 750255 A NZ750255 A NZ 750255A NZ 75025517 A NZ75025517 A NZ 75025517A NZ 750255 B2 NZ750255 B2 NZ 750255B2
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- folic acid
- mixture
- added
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- metal salt
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- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 title claims abstract description 227
- 235000019152 folic acid Nutrition 0.000 title claims abstract description 126
- 239000011724 folic acid Substances 0.000 title claims abstract description 126
- 229960000304 Folic Acid Drugs 0.000 title claims abstract description 97
- 239000000203 mixture Substances 0.000 title claims abstract description 90
- 210000004767 Rumen Anatomy 0.000 title claims abstract description 21
- 229910052751 metal Inorganic materials 0.000 claims abstract description 34
- 239000002184 metal Substances 0.000 claims abstract description 34
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000011701 zinc Substances 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 239000011780 sodium chloride Substances 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- HCHKCACWOHOZIP-UHFFFAOYSA-N zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 23
- 210000002966 Serum Anatomy 0.000 claims abstract description 20
- 241000282849 Ruminantia Species 0.000 claims abstract description 18
- PWHULOQIROXLJO-UHFFFAOYSA-N manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000011572 manganese Substances 0.000 claims abstract description 15
- 229910052742 iron Inorganic materials 0.000 claims abstract description 14
- 229910052748 manganese Inorganic materials 0.000 claims abstract description 14
- RYGMFSIKBFXOCR-UHFFFAOYSA-N copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000010949 copper Substances 0.000 claims abstract description 12
- 229910052802 copper Inorganic materials 0.000 claims abstract description 12
- 241000894006 Bacteria Species 0.000 claims abstract description 8
- 235000015872 dietary supplement Nutrition 0.000 claims abstract description 6
- 229940014144 Folate Drugs 0.000 claims description 29
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 24
- 235000005822 corn Nutrition 0.000 claims description 24
- 235000005824 corn Nutrition 0.000 claims description 24
- 239000000969 carrier Substances 0.000 claims description 22
- 241000283898 Ovis Species 0.000 claims description 21
- 239000003637 basic solution Substances 0.000 claims description 20
- 241000209149 Zea Species 0.000 claims description 19
- 240000007582 Corylus avellana Species 0.000 claims description 16
- 235000007466 Corylus avellana Nutrition 0.000 claims description 16
- 241000283690 Bos taurus Species 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 6
- 241000283707 Capra Species 0.000 claims description 5
- 239000005862 Whey Substances 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 5
- 150000001450 anions Chemical class 0.000 claims description 5
- 235000013339 cereals Nutrition 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- 150000002823 nitrates Chemical class 0.000 claims description 5
- 235000021317 phosphate Nutrition 0.000 claims description 5
- 150000001768 cations Chemical class 0.000 claims description 4
- 238000000855 fermentation Methods 0.000 claims description 4
- 230000004151 fermentation Effects 0.000 claims description 4
- 235000013312 flour Nutrition 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 230000003000 nontoxic Effects 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 4
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 210000004080 Milk Anatomy 0.000 abstract description 12
- 235000013336 milk Nutrition 0.000 abstract description 12
- 239000008267 milk Substances 0.000 abstract description 12
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 210000000936 Intestines Anatomy 0.000 abstract description 5
- 230000002708 enhancing Effects 0.000 abstract description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 239000000243 solution Substances 0.000 description 41
- 239000007787 solid Substances 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 239000000725 suspension Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 8
- 240000008042 Zea mays Species 0.000 description 5
- JIAARYAFYJHUJI-UHFFFAOYSA-L Zinc chloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011592 zinc chloride Substances 0.000 description 5
- 235000005074 zinc chloride Nutrition 0.000 description 5
- 244000052616 bacterial pathogens Species 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 229960005069 Calcium Drugs 0.000 description 3
- NMCUIPGRVMDVDB-UHFFFAOYSA-L Iron(II) chloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 3
- 229940029983 VITAMINS Drugs 0.000 description 3
- 229940021016 Vitamin IV solution additives Drugs 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- MPTQRFCYZCXJFQ-UHFFFAOYSA-L copper(II) chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Cu+2] MPTQRFCYZCXJFQ-UHFFFAOYSA-L 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229930003231 vitamins Natural products 0.000 description 3
- 229940052299 Calcium Chloride Dihydrate Drugs 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000229754 Iva xanthiifolia Species 0.000 description 2
- GLFNIEUTAYBVOC-UHFFFAOYSA-L MANGANESE CHLORIDE Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 2
- 229940050906 Magnesium chloride hexahydrate Drugs 0.000 description 2
- 229940091250 Magnesium supplements Drugs 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- PGEZFWONLSMPGB-YDALLXLXSA-N [Cu].Nc1nc(=O)c2nc(CNc3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)cnc2[nH]1 Chemical compound [Cu].Nc1nc(=O)c2nc(CNc3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)cnc2[nH]1 PGEZFWONLSMPGB-YDALLXLXSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L cacl2 Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 235000013365 dairy product Nutrition 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 229960002089 ferrous chloride Drugs 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 2
- 239000011565 manganese chloride Substances 0.000 description 2
- 235000002867 manganese chloride Nutrition 0.000 description 2
- 229940099607 manganese chloride Drugs 0.000 description 2
- CNFDGXZLMLFIJV-UHFFFAOYSA-L manganese(II) chloride tetrahydrate Chemical compound O.O.O.O.[Cl-].[Cl-].[Mn+2] CNFDGXZLMLFIJV-UHFFFAOYSA-L 0.000 description 2
- 230000000813 microbial Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 210000003165 Abomasum Anatomy 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 230000035633 Metabolized Effects 0.000 description 1
- 230000037165 Serum Concentration Effects 0.000 description 1
- 229940035295 Ting Drugs 0.000 description 1
- 229930003761 Vitamin B9 Natural products 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000001580 bacterial Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000001055 chewing Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 125000003929 folic acid group Chemical group 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000018984 mastication Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 235000019159 vitamin B9 Nutrition 0.000 description 1
- 239000011727 vitamin B9 Substances 0.000 description 1
Abstract
method and composition for dietary supplementation of ruminants with folic acid in a manner that assures the folic acid will not be consumed by rumen bacteria and instead will pass through to the intestine and to the animal's blood serum in order to enhance milk production. The folic acid in water is mixed with a water soluble metal salt of zinc, copper, iron or manganese or mixtures thereof. is mixed with a water soluble metal salt of zinc, copper, iron or manganese or mixtures thereof.
Description
TITLE: FOLIC ACID RUMEN BY-PASS METHOD AND COMPOSITION
FIELD OF THE INVENTION
This invention relates to a method and composition that assures folic acid will by-
pass the rumen so that it will not be consumed by rumen bacteria, and so that it can be
allowed to be used by a ruminant animal to support milk production and health.
OUND OF THE INVENTION
It is well known that for ruminants proper nutrition is essential for efficient and
maximized milk production. If m requirements of proper nutrients including
vitamins such as folic acid are not met, the animal will not produce milk at m yield,
and its health will generally decline.
It has been reported that as much as 97% of the folic acid introduced into the diet of
ruminants is controlled, or rather better put, consumed by the bacteria in the rumen, see L
Daig Sci. 88:2043-2054. In fact, the m is previously known and the real dilemma is
to administer folic acid in a way that it can ively s the rumen, get into the small
intestine and eventually increase the folic acid content in blood serum, which is then
indicative of increased milk tion, see Dietary Supplements of Folic Acid During
ion: Effect on the Performance of Dairy Cows, 1998 J. Daig Sci. 81:1412-1419.
In the past this problem has been recognized, and feed developers have used fats,
carbohydrates and binders to encapsulate folic acid. This technology involves simple
coating of materials in hopes that the coated material is rumen stable. But this has proved
more difficult in application than in theory. A primary problem with any product relying
upon coatings of any kind for rumen stability is that a coating can become abraded during
handling and chewing, resulting in removal of the coating. Moreover, if the coating is too
ive it is not effectively absorbed in the intestine either, and then the benefit to the
animal is lost.
From the above description it can be seen that there is a real and continuing need
for the development of folic acid fortified nutritional ment that remains stable (will
not be consumed by bacteria) in the rumen and yet when in the intestine will be absorbed
into the blood serum in order to enhance blood serum levels of folic acid to enhance milk
production and animal . It is a primary objective of this invention to fulfill this need
, effectively, efficiently and at low cost. The method and means of lishing this
primary ive as well as others, or at least providing the public with a useful choice, will
become apparent from the detailed description of the invention which follows.
SUMMARY OF THE INVENTION
A method and composition for dietary supplementation of ruminants with folic acid in
a manner that assures the folic acid will not be consumed by rumen ia and instead will
pass through to the intestine and to the animal’s blood serum in order to enhance milk
production and animal health. The folic acid is mixed with a water soluble metal salt of zinc,
copper, iron or manganese.
In particular, provided herein is:
(1) A method of inhibiting consumption of folic acid by rumen bacteria in dietary
supplementation of ruminants, comprising:
feeding to a ruminant animal a mixture made by mixing, in water, a water e metal salt
with folic acid, wherein the metal is selected from the group consisting of zinc, copper, iron
and manganese.
(2) The method of (1), wherein the nt is selected from the group ting of
cattle, goats and sheep.
(3) The method of (1) or (2), wherein the water soluble metal salt has an anion selected
from the group consisting of sulfates, chloride, acetate, phosphates and nitrates.
(4) The method of any one of (1) to (3), n the molar ratio of folic acid to water
soluble metal salt in the mixture is from about 1:1 to about 1:25.
(5) The method of any one of (1) to (4), wherein the mixture is placed on a non-toxic
(6) The method (5), wherein the carrier is selected from the group consisting of distillers
fermentation solubles, feed grains, corn cob flour, whey, and other cellulosic materials.
(7) The method of any one of (1) to (6), wherein the feeding of the mixture occurs at a
rate of from 20 mg/head/day to 160 mg/head/day of folic acid equivalents.
(followed by page 2A)
(8) The method of (7), wherein the feeding occurs at a rate of from 40 d/day to 80
mg/head/day.
(9) The method of (5), where the mixture on a carrier is mixed with additional common
feed ingredients.
(10) A composition which is formed to inhibit absorption of folic acid by rumen bacteria
and provide increased ruminant animal blood serum folic acid levels, comprising:
a metal folate x formed by making a basic solution consisting essentially of a water
soluble metal salt of a metal cation and folic acid, wherein the metal cation is selected from
the group consisting of iron, copper, zinc and manganese, wherein the complex so formed is
combined with a carrier selected from the group consisting of distillers formulation solubles,
feed grains, corn cob , whey, and other cellulosic carriers.
(11) The composition of (10), n the metal salt has an anion ed from the group
consisting of sulfates, nitrates, phosphates, chloride, and acetate.
(12) The composition of (10) or (11), n the ruminant is selected from the group
consisting of cattle, goats and sheep.
(13) The composition of any one of (10)-(12), wherein the molar ratio of folic acid to
water soluble metal salt is from about 1:1 to about 1:25 in the process of forming the metal
folate complex.
(14) The composition of any one of (10) to (13), wherein the feeding of the mixture occurs
at a rate of from 20 mg/head/day to 160 mg/head/day of folic acid equivalents.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is the effect of treatment on average serum folic acid concentrations of
sheep, pre and post ent.
Figure 2 is the effect of treatment on median serum folic acid concentrations of sheep,
ing no treatment, folic acid alone, and zinc folate.
(followed by page 2B)
Figure 3 is a bar graph of the change in median serum folic acid concentrations of
sheep, pre and post treatment.
Figure 4 is a bar graph of % change in median serum folic acid for sheep.
Figure 5 is an average change in folic acid for cattle using the formulations of
examples three and sixteen.
Figure 6 is an average change graph for sheep with the product of examples five and
seven.
Figure 7 shows zinc folic acid mixture with silica gel until free g then blended
with ground corn cob.
Figure 8 shows liquid mixture of both zinc and manganese folic acid sprayed directly
on ground corn.
ED DESCRIPTION OF THE PREFERRED EMBODIMENTS
This invention is for ruminant s. Ruminants ingest feed which first passes into
the rumen where it is partially broken down by bacterial fermentation. During fermentation
rumen microbes utilize nitrogen from nitrogen compounds that they have
(followed by page 3)
WO 26676
degraded to form ial protein. Nitrogen sources for rumen microbes include protein
that is degraded in the rumen, rumen degradable peptides, free amino acids such as
crystalline amino acids, and vitamins, including folic acid. Microbial protein and
undegraded feed n pass to the abomasum and small ine where hydrochloric acid
and mammalian enzymes degrade microbial protein and undegraded feed n to free
amino acids and short peptides. The amino acids and short peptides are absorbed in the
intestine, and the ruminant animals utilize the amino acids for synthesis of protein to
sustain life, grow, reproduce, and produce milk. However, if vitamins like, vitamin B9
folic acid have been “used” or metabolized by rumen microbes, its value to the host animal
is lost.
This is especially important for ruminants that are used for milk production since
research has determined that folic acid is essential to increased milk production.
As earlier mentioned there are some patents and literature on encapsulated forms of
folic acid but as far as the applicant knows, nothing like the chemistry currently presented,
which does not rely upon encapsulation.
The structure below is folic acid:
0 OH
o N
N o
HN \
X'/ H
H2N N N
folic acid
What this applicant has discovered is that if folic acid is mixed in water with a
water e metal salt of a metal that is either zinc, copper, iron or manganese, with the
salt being a sulfate, chloride, acetate, phosphate or nitrate, something occurs that ts
the folic acid from being ed by the microbes in the rumen. Moreover, to the
applicant’s surprise other soluble metal salts (other than the four metals specifically
mentioned) do not work to achieve the same result. For example, calcium and magnesium
salts, do not provide the same results, as evidence by some of the comparative examples set
forth below. In order for the invention to work the original mixing of the folic acid and the
water soluble metal salt must be in water. After the mixing occurs the solution can then be
mixed with any suitable non-toxic carrier if one wishes or added to the feed directly.
In making nutritional supplements for the addition of these compositions to the
diets of animals, it is preferred that the mixtures of the present invention be added to a
carrier or filler material for processabilty, ease of ng and sale. They can, however,
also be sold as spray dried powders without any carrier. The use of a carrier or not is a
preference of the processing manufacturer and feed supplier. If rs are used, examples
of suitable carriers include distillers’ tation solubles, feed grains, corn cob flour,
whey, and other cellulosic carrier materials, all well known for carrying trace mineral
preparations.
The amount of supplement added to the feed ration will, of course, depend on
whether one is using the pure spray dried powders, or whether it is being used with a
carrier, such as corn cob flour. Basically, the supplement will simply be mixed in with the
feed ration as sold.
Generally, the e should be mented at a level to provide from about 20
mg/head/day to about 160 mg/head/day of folic equivalents, preferably from about 40
mg/head/day to 80 mg/head/day.
The ratio of folic acid to water soluble metal salt on a molar ratio basis should be
from about 1:1 to 1:25. While the mixtures must be mixed in solution they can be used as
is, dried, dried on a non-toxic carrier afterwards or the carrier can be used as an absorbing
r to absorb the liquid mixture.
Once the mixture is free flowing it can be combined with other common feed
ingredients.
As earlier mentioned while this is suitable for any nts the primary ones for
domesticated milk production are dairy cattle, goats and sheep.
The following examples are d to further illustrate but not limit the invention
and to demonstrate surprisingly that it appears critical that the water soluble metal salt to
be used be a metal salt of zinc, iron, ese or copper. The anion is not al as long
as it is water soluble, but those earlier referenced are most common.
Example 1
Zinc Folate Mixture
Sodium Hydroxide (54.42g, 1.36mols) was added to 3000mL of (11 H20. To this
basic solution was added Folic Acid (300.1g, 0.681mols) which turned a bright orange.
The suspension became a solution over the course of 20 minutes of uous stirring.
Zinc Chloride (91.81g, ols) was added to the bright orange solution. This mixture
was dried at 60°C in the vacuum oven to produce a red-orange non-hydroscopic solid
(415g, 98.3% Theory).
Example 2
Zinc Folate on Silica Mixture
Sodium ide (3.63g, 0.091mols) was added to 100.1mL of (11 H20. To this
basic solution was added Folic Acid (20.0g, 0.045mols) which turned a bright orange. The
suspension became a solution over the course of 20 minutes of continuous stirring. Zinc
Chloride (6.08g, 0.045mols) was added to the bright orange solution. Silica gel (134.19g)
is then added to the aqueous e until the mixture becomes a free flowing solid. Total
weight: 220.5g of free flowing solid.
Example 3
Copper Folate Mixture
Sodium Hydroxide (3.65g, 0.090mols) was added to 200mL of (11 H20. To this
basic solution was added Folic Acid (20.00g, 0.045mols) which turned a bright orange.
The suspension became a solution with 20 minutes of continuous stirring. Copper Chloride
dihydrate (7.75g, 0.045mols) was added to the bright orange solution. This mixture was
dried at 60°C in the vacuum oven until dry to product a green-yellow non-hydroscopic
solid (25.5g, 91.4% ).
Example 4
Copper Folate e on Silica
Sodium Hydroxide (3.60g, 0.090mols) was added to 300mL of (11 H20. To this
basic solution was added Folic Acid (20.10g, 0.045mols) which turned a bright orange.
The suspension became a on with 20 minutes of continuous ng. Copper Chloride
dihydrate (7.74g, 0.045mols) was added to the bright orange solution. Silica gel (271.56g)
is then added to the aqueous e until the mixture becomes a free flowing solid. Total
weight: 603g of free flowing solid.
Example 5
Manganese Folate Mixture
Sodium Hydroxide (7.32g, 0.182mols) was added to 400mL of (11 H20. To this
basic solution was added Folic Acid (39.93g, 0.09lmols) which turned a bright orange.
The suspension became a solution with 20 minutes of stirring with a magnetic stir bar. To
the solution anhydrous Manganese de (11.48g, 0.09lmols) was added in one portion
which was dried at 60°C in the vacuum oven until dry to e a dark orange/red non-
hydroscopic solid (52.3g, 94.1% Theory).
Example 6
Manganese Folate e on Silica
Sodium Hydroxide (3.65g, 0.090mols) was added to 200mL of (11 H20. To
this basic solution was added Folic Acid (20.01g, 0.045mols) which turned a bright orange.
The suspension became a solution with 20 minutes of continuous stirring. Manganese
Chloride (5.74g, 0.045mols) was added in one n. Silica gel (307.6g) is then added to
the aqueous mixture until the solution becomes a free flowing solid. Total weight: 537g of
free flowing solid.
Example 7
Iron Folate Mixture
Sodium Hydoxide (3.66g, 0.090mols) was added to 200mL of (11 H20. Folic acid
(19.95g, 0.045mols) was added to this basic solution which turned a bright orange. The
suspension became a on with 20 minutes of continuous stirring with a ic stir
bar. Ferrous Chloride tetrahydrate (9.05g, 0.045 mols) was added to the bright orange
solution which was dried at 60°C in the vacuum oven until dry to produce a green-brown
non-hydroscopic solid (26.1g, 95.9% Theory).
Example 8
Iron Folate Mixture on Silica
Sodium ide (3.63g, 0.090mols) was added to 200mL of (11 H20. To this
basic solution was added Folic Acid g, 0.045mols) which turned a bright orange.
The suspension became a solution with 20 minutes of continuous stirring. Ferrous Chloride
tetrahydrate (9.00g, 0.045 mols) was added to the bright orange solution. Silica gel
2017/044580
(225.3g) is then added to the aqueous mixture until the e becomes a free flowing
solid. Total weight: 458g of free flowing solid.
Example 9
Magnesium Folate Mixture
Sodium Hydroxide (5.44g, ols) was added to 200mL of (11 H20. To this
basic solution was added Folic Acid (30.01g, 0.068mols) which turned a bright orange.
The suspension became a solution with 20 minutes of stirring with a magnetic stir bar. To
this solution was added Magnesium Chloride Hexahydrate g, 0.068mols) which was
dried at 60°C in the vacuum oven until dry to produce a light orange non-hydroscopic solid
(37.3g, 94.6% Theory).
Example 10
Magnesium Folate Mixture on Silica
Sodium Hydroxide (3.60g, 0.090mols) was added to 200mL of (11 H20. To this
basic solution was added Folic Acid (19.97g, 0.045mols) which turned a bright orange.
The suspension became a solution with 20 minutes of continuous stirring. To this solution
was added Magnesium Chloride Hexahydrate (9.25g, 0.045mols). Silica gel g) is
then added to the aqueous e until the mixture becomes a free flowing solid. Total
weight: 462g of free flowing solid.
Example 11
Calcium Folate Mixture
Sodium Hydroxide (6.00g, 0.150mols) was added to 200mL of (11 H20. Folic acid
(33.05g, 0.075 mols) was added to the basic solution which turned into a bright orange
suspension. The suspension gradually formed a solution after 20 minutes of stirring with a
magnetic stir bar. To this solution was added Calcium chloride dihydrate (11.01g, 0.075
mols) which was dried at 60°C in the vacuum oven until dry to produce a light orange non-
hydroscopic solid (42.6g, 95.3% Theory).
e 12
Calcium Folate Mixture on Silica
Sodium ide (3.61 g, 0.090mols) was added to 200mL of (11 H20. To this
basic solution was added Folic Acid (20.07g, 0.045mols) which turned a bright orange.
The suspension became a solution with 20 minutes of continuous stirring. To this solution
was added Calcium Chloride Dihydrate (6.69g, ols). Silica gel (281.6g) is then
added to the aqueous mixture until the mixture s a free flowing solid. Total weight:
512g of free flowing solid.
Example 13
Zinc Folate Mixture on Ground Corn Cob
Sodium Hydroxide (1.81 g, 0.045mols) was added to 100mL of (11 H20. To this
on was added Folic Acid (9.99g, 0.023mols) which turned a bright orange. The
suspension became a solution over the course of 20 minutes of continuous stirring. Zinc
Chloride (3.09g, 0.023mols) was added to the bright orange solution and to the mixture
was added ground corn cob (4.36g) and stirred until homogenous. This mixture is then
dried at 60°C in a vacuum oven. Total Weight: 19.34g of a fine solid.
Example 14
Zinc Folate Mixture on Ground Corn Cob
Sodium Hydroxide (0.91 g, 0.023 mols) was added to 70mL of (11 H20. To this
solution was added Folic Acid , 0.011 mols) which turned a bright orange. The
suspension became a solution over the course of 20 minutes of continuous stirring. Zinc
de (30.87g, 0.23mols) was added to the bright orange solution and to the mixture
was added to ground corn cob (11.7g) and stirred until homogenous. This mixture is then
dried at 60°C in a vacuum oven. Total Weight: 45.6 of a fine solid.
Example 15
Zinc Folate Mixture on Silica
Sodium Hydroxide (1.27g, 0.032 mols) was added to 100mL of (11 H20. To this
basic solution was added Folic Acid (7.00g, 0.016 mols) which turned a bright orange.
The suspension became a solution over the course of 20 minutes of uous stirring.
Zinc chloride (43.2g, 0.3l8mols) was added to the bright orange solution and to the
e was added silica gel (99.98g) until the mixture became a free flowing solid. Total
Weight: g of a free flowing solid.
Example 16
Copper Folate Mixture on Cellulose
Sodium hydroxide (2.72g, 0.068mols) was added to 150mL of (11 H20. To this
basic solution was added Folic Acid (14.98g, 0.034 mols) which turned a bright orange.
The suspension became a solution over the course of 20 minutes of continuous ng.
Copper Chloride dihydrate g, 0.34 mols) was added to the bright orange solution
which was added to cellulose (20.6g) and stirred until homogenous. This mixture was then
dried at 60°C in a vacuum oven. Total Weight: 87.33g of a fine solid.
Example 17
ese Folate Mixture on Ground Corn
Sodium Hydroxide (2.18g, 0.054mols) was added to 100mL of (11 H20. To this
basic solution was added Folic Acid g, 0.027mols) which turned a bright orange.
The suspension became a on over the course of 20 s of continuous stirring.
Manganese Chloride tetrahydrate (5.39g, 0.027mols) was added to the bright orange
solution which was added to ground corn (5.8g) and stirred until homogenous. This
mixture was then dried at 60°C in a vacuum oven. Total Weight: 19.76g of a fine solid.
Example 18
ese Folate Mixture on Ground Corn Cob
Sodium Hydroxide (1.45g, 0.036mols) was added to 120mL of (11 H20. To this
basic solution was added Folic Acid (8.00g, 0.018mols) which turned a bright orange. The
suspension became a solution over the course of 20 minutes of continuous stirring.
Manganese chloride tetrahydrate (17.95g, 0.09lmols) was added to the bright orange
solution which was added to ground corn cob (8.65g) and stirred until homogenous. The
carrier mixture was then dried at 60°C in a vacuum oven. Total Weight: 32.80g of a fine
solid.
Example 19
Iron Folate Mixture on Ground Corn Cob
Sodium ide (2.00g, 0.05mols) was added to 250mL of (11 H20. To this
basic on was added Folic Acid (11.05g, 0.025mols) which turned a bright orange.
The suspension became a solution over the course of 20 minutes of continuous stirring.
Iron (11) chloride tetrahydrate (49.59g, 0.294mols) was added to the bright orange solution
which was added to ground corn cob (20.2g) and stirred until homogenous. The carrier
mixture was then dried at 60°C in a vacuum oven. Total Weight: 58.70g of a fine solid.
Example 20
Sheep Serum Concentrations
Sheep were tested with three different s, sample CSK15083 with no folic
acid present, CSK15084 which is folic acid itself and CSK15085, which represents an
example of the invention zinc folate mixture as prepared in Example 1, (see Figures 1-4).
The animals were separated into groups and housed in a barn with access to a
pasture. The dosing regime was as follows. The daily folic acid dose was mixed with
ground corn to create a test article fed at the rate of 0.5 pounds per sheep per day. The
sheep were fed the test feeds for fourteen (14) days. The folic acid equivalent fed to each
head per day was thirty (30) milligrams.
The results of the study are shown in Figures 1-4. They all indicate that whether
one looks at the mean or the median, serum folic acid concentrations sed the greatest
when the sheep were dosed with CSK15085, the product of the ion es 1-4).
Serum folic acid tration of sheep feed either CSK15084 or CSK15085 increased
while serum folic acid concentrations of sheep feed CSK15083 did not change after being
fed the test articles. Serum blood level enhancement of folic acid is an indication that milk
production will be substantially increased, as indicated in the earlier referenced articles.
Moreover, the zinc folate mixture performed better than folic acid alone.
Sheep fed the calcium and ium salts of Examples 9-12 showed no increase
in blood serum levels of folic acid when ed to controls of folic acid alone.
Example 21 (Calf Study)
Example 21 is a cattle study. In the drawing Figure 5, CSK 16083 represents folic
acid alone, CSK16084 is a copper-folic acid mixture 1:1 (Example 3) and CSK 16085 is a
copper-folic acid mixture 1:10 on cellulose (Example 16).
The cattle calves were fed 120 mg of the folic acid source per day for 14 days along
with feed at the rate of 21bs/head. Comparison with no folic acid control group is shown in
Figure 5. It can be seen that blood serum folic acid changed icantly for the positive
with the formulation of Example 3 and Example 16.
Example 22 (Sheep)
Example 22 is a sheep study using the protocol of Example 20 but with the Mn and
iron mixtures of Example 5 and 7, respectively. In Figure 6, CSK16086 is folic acid alone,
CSK16087 is the 1:1 mixture of iron and folic acid (Example 7) and CSK16088 is the
WO 26676
mixture of manganese and folic acid, [Example 5]. As can be seen in Figure 7 the blood
serum folic acid concentration for the mixtures of example 5 and 7 change significantly for
the positive. In this test the ewes were fed the concentrate metal folate e dried
without any carrier but mixed on ground corn for feeding.
Example 23
In this example the zinc folic acid mixture was mixed with silica gel until free
flowing and then d with ground corn cob for the trial.
Zinc Folic Acid mixture 20:1 dried on the silica, as prepared in Example 15. The
data is shown in Figure 7.
Example 24
Zinc Folate Mixture
Sodium Hydroxide (0.96g, 0.024 mols) was added to 1100mL of (11 H20. To this
basic solution was added Folic Acid (5.40g, 0.012 mols) which turned a bright orange.
The suspension became a on over the course of 20 minutes of continuous stirring.
Zinc Chloride (16.68g, 0.12 mols) was added to the bright orange solution which was
easily stirred. The fine suspension was easily sprayed onto dry animal feed (ground corn).
Example 25
Manganese Folate Mixture
Sodium Hydroxide (0.98g, 0.024mols) was added to 1120mL of (11 H20. To this
basic solution was added Folic Acid (5.30g, 0.012mols) which turned a bright orange. The
suspension became a solution over the course of 20 minutes of continuous stirring.
Manganese chloride ydrate (23.11g, ls) was added to the bright orange
solution which was easily stirred. The fine suspension was easily sprayed onto dry animal
feed (ground corn).
Example 26
Zn Folic Acid mixture 10:1 was ed as described in Example 24, and Mn
Folic Acid mixture (15: 1) as described in Example 25. The liquid mixtures were then
sprayed directly on ground corn. The serum results (sheep) are shown in Figure 8, and
demonstrate effectiveness can be achieved without a carrier, if one wishes.
Claims (16)
1. A method of inhibiting ption of folic acid by rumen bacteria in dietary supplementation of ruminants, comprising: feeding to a ruminant animal a mixture made by mixing, in water, a water soluble metal salt with folic acid, wherein the metal is ed from the group consisting of zinc, copper, iron and manganese.
2. The method of claim 1, wherein the ruminant is selected from the group consisting of cattle, goats and sheep.
3. The method of claim 1 or 2, n the water soluble metal salt has an anion selected from the group consisting of sulfates, chloride, acetate, phosphates and nitrates.
4. The method of any one of claims 1 to 3, wherein the molar ratio of folic acid to water e metal salt in the mixture is from about 1:1 to about 1:25.
5. The method of any one of claims 1 to 4, n the mixture is placed on a nontoxic carrier.
6. The method of claim 5, wherein the carrier is ed from the group consisting of distillers fermentation solubles, feed grains, corn cob flour, whey, and other cellulosic materials.
7. The method of any one of claims 1 to 6, wherein the feeding of the mixture occurs at a rate of from 20 mg/head/day to 160 mg/head/day of folic acid equivalents.
8. The method of claim 7, wherein the feeding occurs at a rate of from 40 mg/head/day to 80 mg/head/day.
9. The method of claim 5, where the mixture on a carrier is mixed with additional common feed ingredients.
10. A composition which is formed to t absorption of folic acid by rumen bacteria and provide increased ruminant animal blood serum folic acid levels, comprising: a metal folate complex formed by making a basic solution consisting ially of a water soluble metal salt of a metal cation and folic acid, wherein the metal cation is selected from the group consisting of iron, copper, zinc and manganese, wherein the complex so formed is ed with a carrier selected from the group consisting of distillers formulation solubles, feed grains, corn cob , whey, and other cellulosic carriers.
11. The composition of claim 10, wherein the metal salt has an anion selected from the group consisting of sulfates, nitrates, phosphates, chloride, and acetate.
12. The composition of claim 10 or 11, wherein the ruminant is selected from the group consisting of cattle, goats and sheep.
13. The ition of any one of claims 10-12, wherein the molar ratio of folic acid to water soluble metal salt is from about 1:1 to about 1:25 in the process of forming the metal folate complex.
14. The composition of any one of claims 10 to 13, wherein the feeding of the mixture occurs at a rate of from 20 mg/head/day to 160 mg/head/day of folic acid equivalents.
15. A method according to claim 1, ntially as herein described or exemplified.
16. A composition according to claim 10, substantially as herein described or exemplified. Ghangfi En Averaga Serum Faik: Aaifi Cancen‘tmfien ....8 aAvg Pm uAvg 93st :39? So... CSKISQBS
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/226,297 | 2016-08-02 | ||
US15/226,297 US10206415B2 (en) | 2016-08-02 | 2016-08-02 | Folic acid rumen by-pass method and composition |
PCT/US2017/044580 WO2018026676A1 (en) | 2016-08-02 | 2017-07-31 | Folic acid rumen by-pass method and composition |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ750255A NZ750255A (en) | 2020-12-18 |
NZ750255B2 true NZ750255B2 (en) | 2021-03-19 |
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