Note: Descriptions are shown in the official language in which they were submitted.
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110VINE SUPPLEMENTFOfi NEONATAL CALVES
Cross-Reference to Retated.Aalications
This application is a continuation-in-part of U.S.S.N. 16/117,227 filed on
August 30, 2018, which is hereby incorporated by reference in its entirety.
.Field of the Invention.
The present invention relates generally to feed supplement preparations for
administration to ruminant animals and, more particularly, to a formulation
for an oral
bovine supplement for neonatal calves that delivers naturally occurring
caffeine and a
viscosity adjustor in a stable liquid form for absorption through the oral
mucosal of
the neonatal calf.
Backtiround Of the Invention
"Bovine dystocia" refers to a state during the birthing process where it
becomes difficult or impossible for the cow to deliver her calf without human
assistance, it can occur during the first or second stage of labor, and
usually involves
1.5 the calf being misaligned backwards or even sideways in the birth
canal, or otherwise
unsuited for the birth canal's shape and size. The incidence of dystocia in
dairy cattle
has been reported to range from 2-22%, while the proportion of cows requiring
human
assistance during labor ranges from 10-50%.
Contributing factors for bovine dystocia include calf birth weight and the
size
of the pelvic area of the mother cow ("heifer" or "dam"). Thus, dairy and beef
cattle
operations wilt often cull heifers with small pelvic areas from their breeding
programs
and intentionally use hulls that are proven to sire calves with small birth
weights.
Providing proper nutrition to the heifer prior to the labor process can also
ensure her
ability to exert greater propulsive forces for passing the calf through the
birth canal.
However, even with proper herd management and nutrition policies, many
incidents
of bovine dystocia still occur. Given the cost and time expended in
impregnating and
gestating heifers and cows, as well as potential injuries or death for the
mother or calf
due to dystocia, this can pose a substantial economic risk for a dairy or
cattle
operation.
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Indeed, calves requiring human assistance during the labor process experience
a 50% greater risk of mortality. During the calving process, the fetus
experiences
neonatal asphyxia, resulting in low blood oxygen levels and areas of decreased
blood
flow referred to as "hypoxia." Such hypoxia can progress to anoxia (no oxygen
in the
blood). Prolonged anoxia can lead to fetal death within six minutes.
Newborn calves require immediate colostrum supplementation shortly after
birth. But, hypoxic neonatal calves often suffer from a state of drowsiness
and
recumbency that interferes with their physical ability to stand and nurse
colostrum.
Additionally, the ability of the neonatal calf to absorb the immunoglobulins
and other
components of colostrum is compromised if the neonatal calf is in a hypoxic
state.
An unchecked hypoxic state can be prolonged for multiple hours and could
potentially
overlap with naturally occurring gut closer, thereby creating a secondary
scenario to
impair or completely halt the ability of passive transfer of immunoglobulins
from
colostrum. This factor further compounds the need to aid in the rapid
oxygenation
and vigor of the neonatal bovine. Moreover, lethargic calves will typically
receive
supplemental quantities of glucose too in an attempt to stimulate muscle
contraction
and overall vigor. But, such glucose supplementation may produce an insulin
response that decreases appetite in the neonatal calf that results in periods
of
hypoglycemia that further amplifies lethargy. This vicious circle can be
extremely
detrimental to the neonatal calf during the first 12-24 hours of the neonatal
calf s life
when appetite is crucial for colostrum intake.
Caffeine has been documented as effective intervention to alleviate apnea
episodes for human babies. However, caffeine is not considered to be a
required
nutrient for livestock, so synthetic caffeine lacks "generally regarded as
safe"
("GRAS") status by the Association of American Feed Control Officials
("AAFC0")...
Thus, it would be considered illegal to administer human supplements
containing
synthetic caffeine to treat hypoxia in calves. But, tea is given GRAS status
by
AAFC0, and tea leaves contain naturally occurring forms of caffeine.
Various nutritional supplement products containing caffeine are known within
the industry for humans for purposes of improving health. For example, U.S.
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Published Application 2011/0123651 filed by Mower et al, discloses a
nutritional
beverage used to combat the aging process in humans. It contains resveratrol
that can
be sourced from grape skins or in the form of wine produced from grapes and
grape
skins. Also included within the beverage is water, a suspension agent like
sodium
citrate, and optionally quercetin which is an antioxidant and anti-
inflammatory agent.
Mower further discloses that the beverage will also include eatechins that are
polyphenols mostly derived from green tea leaf extract that promote genetic
stimulation for increased proliferation of beneficial cells in humans.
However, this Mower anti-aging supplement product only includes caffeine as
a secondary ingredient on a trace basis (i.e., 0.067% wt). He also provides
his product
in liquid form which is "buccally delivered" to the human customer by which
the
human must retain the beverage in his mouth for one minute before swallowing.
Needless to say, a neonatal calf cannot be expected to delay swallowing a
liquid
supplement product for one minute, while retaining it in its mouth in order to
produce
is delivery of an ingredient like resveratrol or caffeine through the
inside of the mouth.
Towards this end, Mower only includes a very small amount of xanthan gum as a
thickener, since his product is delivered in liquid form free of mucosal
adsorption.
U.S. Published Application 2008/0038409 -file by Nair et al. discloses a
"cocoa water beverage" made from water steeped in a coca product or powder.
The
2 0 resulting product is consumed by a human to stimulate the immune
system, improve
heart health, detoxif', recuperate muscles, enhance cognitive abilities, etc.
However,
Nair's corn syrup is used as a sweetener agent, instead of as a viscosity
adjustor.
Likewise, his vegetable oil ingredient is used to prevent oxidation of the
polyphenol
and flavanol compounds extracted from the coca products. He does not use his
25 vegetable ingredient to facilitate the suspension of the green tea
extract in the neonatal
bovine dietary supplement.
Food products are known within the industry that contain caffeine, including
caffeine that is sourced from green tea extract. For instance, U.S. Patent No.
5,879,733 issued to Ekanayake et al, illustrates green tea extract beverages,
wherein
3 0 the green tea extract is acid extracted, run through a cation exchange
resin to remove
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metal cations that produce turbidity, and then run through nano filtration to
remove
higher molecular weight components that harm the color and clarity of the
beverage.
But, not only is Ekanayake's product in liquid form that is unsuitable for
absorption
through the oral mucosal lining of the neonatal calf, but also its 0.5% wt of
the green
tea concentrate found in the sugar-sweetened beverage is significantly lower
than the
level required to stimulate a neonatal calf suffering from dystocia or
hypoxia. indeed,
the Ekanayake reference discloses a 992 ppm caffeine level in his final
product. At
1000 ppm being equivalent to 0,1% wt, 992 ppm caffeine translates to 0,0992%
wt
caffeine, which is very low.
Meanwhile, U.S. Patent No. 5,624,698 issued to Dake et at, teaches syrup
products used in a "soda fountain" to dispense dilute juice beverages. The
syrup
comprises a flavor component like green tea or black tea together with the
juice
flavor, An oil component like a vegetable oil provides desired opacity and
cloud to
the resulting juice beverage. In order to prevent dispersion of the oil
component that
would cause it to separate out from the syrup, xanthan gum is added to the
syrup as an
emulsifying agent.
Even if one were to feed Dake's syrup product to a neonatal calf, it would
fail
to treat the effects of dystocia. The viscosity of the product at less than
250 cps,
preferably less than 150 cps, is simply too low for mucosa] delivery of the
product to
2 0 the neonatal calf By contrast, Dake means his syrup product to be added
to a
fountain beverage to be drunk by a human. Moreover, Mike only uses his black
or
green tea ingredient 0.5% wt) as a flavorant, instead of as a stimulating
source of
caffeine. Furthermore, Dake makes no mention of a target caffeine content for
the tea
in his final solution.
Even the popular "energy drinks" that are consumed by humans to provide
rapid stimulation are unsuitable for treating neonatal calves suffering from
dystocia.
For example, U.S. Published Application 2017/0231996 filed by Levi et al.
discloses
energy drinks containing supersaturated caffeine levels. They contain 1.7-3.0%
(w/v)
levels of caffeine. They are also disclosed as containing 150-250 mg caffeine
in 9 ml
water. However, this 150 mg in 9 ml water dose only delivers 1.66% wt of
caffeine.
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This is a surprisingly low caffeine level. Moreover, Levi seems to use
synthetic
caffeine in the form of caffeine citrate, instead of the naturally occurring
caffeine
source required by AAFCO regulations for food animals.
Even Clif Bar & Co.'s popular "Clif Shot Turbo Double Espresso Energy Gel"
product and the even more popular "5-Hour Energy" drink only contain 0.24% wt
and
0.41% wt caffeine levels, respectively. Furthermore, the 5-Hour Energy product
has a
viscosity level < 150 cps, which is significantly lower than the viscosity
level required
for mucosal delivery to a neonatal calf. Hence, despite what the "energy gel"
term
suggests, these types of products are not very viscous, and certainly would be
incapable of retaining in the neonatal calf's mouth and delivering caffeine
via the
mucosal lining.
Thus, it would be highly beneficial to provide a bovine supplement for
neonatal calves that contains non-synthetic caffeine as a stimulant for
prompting the
calves to consume colostrum and stimulate their respiration and reduce edema
to
enable them to survive the effects of bovine dystocia and hypoxia. Such a
bovine
supplement should exhibit a relatively high viscosity level for mucosal
delivery of the
supplement's ingredients to the calves.
Summary of the Invention
A neonatal bovine dietary supplement that is provided to a newborn calf to
enhance nutritional intake during this vulnerable early stage of the calls
life is
provided by the invention. Bovine dystocia can cause systemic depression and
recumbency that weakens the neonatal calf and prevents it from standing up to
consume colostrum. The neonatal bovine dietary supplement comprises non-
synthetic
caffeine obtained from a natural source like green tea extract and viscosity
adjustors
like corn syrup and xanthan gum or guar gum that increase the viscosity of the
liquid
supplement to about 400-800 centipoise at 2PC, so that the supplement is
absorbed
by the neonatal calf through its oral mucosal lining in its mouth and tongue.
The
specific gravity (relative density) of the supplement product is preferably in
a range of
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about 0,9-1.6. The neonatal bovine dietary supplement may optionally include
antioxidants and electrolytes,
in this manner, the supplement reliably provides the caffeine to the neonatal
calf to increase its energy level, stimulate respiration, and reduce edema
that
otherwise may thwart the neonatal calf's crucial nutritional intake of
colostrum and
other animal feed ingredients within the hours following birth. Moreover, the
concentrated caffeine level in the green tea extract allows a 10-40 ail dose
of the
liquid solution supplement product to contain about 100-400 mg of caffeine for
delivery to the neonatal calf without filling its stomach which might
otherwise prompt
it to stop consuming colostrum and other critical animal feed ingredients.
Moreover,
this novel formulation for a bovine supplement for neonatal calves delivers
naturally
occurring caffeine in a stable liquid form at elevated viscosity that may
optionally
include antioxidants, and other electrolytes. The supplement successfully
incorporates natural caffeine in a highly concentrated liquid oral dose
formulation in
which the viscosity of the liquid supplement is such that it facilitates
adherence to the
tongue and oral cavity, thereby facilitating mucosa' absorption, which greatly
enhances the effectiveness of the supplement. Additionally, due to the
concentrated
nature of the product, caffeine can be delivered with minimal volume, thereby
minimizing satiety, resulting is ample capacity to intake sufficient
quantities of
2 0 colostrum,
The formula successfully adds naturally occurring caffeine in the form of
green tea, which may be an extract, which is also rich in antioxidants and
contains a
high concentration of caffeine in a unique mix with xanthan gum or guar gum,
corn
syrup, water and electrolytes. The corn syrup and xanthan gum are added to
adjust
the viscosity so that the solution sticks to the oral cavity and tongue to
allow more
rapid absorption of caffeine.
Detail0 thsCritjti6n olthe Preferred Embod . .......
A unique formulation for a neonatal bovine calf supplement to be
administered following birth that delivers naturally occurring, concentrated
dose of
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caffeine sourced from, e.g., green tea extract, antioxidants, and electrolytes
for
overcoming the adverse effects of dystocia is provided by the invention. The
supplement successfully incorporates a viscosity adjustor like xanthan gum or
guar
gum and corn syrup to produce a product which remains shelf stable in a liquid
form,
while greatly enhancing the effectiveness of the supplement for absorption
through
the oral mucosa of the neonatal calf for rapid treatment, The supplement not
only
provides needed multi-system (i.e., CNS/cardiacirespiratory) stimulation to
the newly
borne calf, but it also stimulates respiration, reduces edema, and stimulates
muscle
contraction. in this manner, the supplement treats the three biggest problems
encountered by hypoxic calves: lethargy, respiratory rate, and high
concentrations of
adenosine.
The neonatal bovine dietary supplement of the present invention comprises a
concentrated dose of non-synthetic caffeine and water in a liquid solution
that is
modified by a viscosity adjustor to produce a viscosity of about 400-800
centipoise
15 ("cps") at 21 C, preferably about 500-650 cps, even more preferably
about 600 cps,
so that when the supplement is introduced into the mouth of the neAily-born
calf who
is suffering from dystocia or hypoxia, the supplement sticks to the neonatal
calls
tonne and internal cheeks in the mouth for rapid absorption of the caffeine
through
the mucosa! lining. Due to the close proximity of blood vessels to the oral
mucosa!
20 surface of the neonatal calf, this allows for much more rapid entry of
the caffeine into
the circulation system compared with the digestive system that could take
multiple
hours for an ingested product to enter the circulatory system. The neonatal
bovine
dietary supplement may contain a number of other optional ingredients,
including
antioxidants, electrolytes, solubility aides, anti-foaming agents, and
preservatives for
s
producing a stable solution that enhances the health of the neonatal calf who
is under
duress.
For purposes of the neonatal bovine dietary supplement, the non-synthetic
caffeine may be sourced from a variety of naturally occurring caffeines that
have not
been chemically synthesized. Such non-synthetic caffeine sources include green
tea,
30 green tea extract, black tea, coffee, and cocoa. Green tea extract
having a caffeine
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level of about 90%, preferably about 99%, is preferred. The non-synthetic
caffeine
ingredient should comprise about 1-15% wt, preferably about 1-5% wt, of the
formulated neonatal bovine dietary supplement product.
The water component of the neonatal bovine dietary supplement product may
constitute tap water or deionized water. The water should be clean and free of
any
contaminants that would impair the health of the neonatal calf The water
ingredient
should comprise about 30-60% wt, preferably 35-50% wt, even more preferably
about
39% wt, of the formulated neonatal bovine dietary supplement product.
One or more thickening agents should be added to the solution containing
water, non-synthetic caffeine, and tri-sodium citrate dihydrate to obtain the
desired
viscosity level of about 400-800 cps at 21 C, preferably about 500-650 cps,
even
more preferably about 600 cps. Corn syrup may be used to enhance the viscosity
of
the resulting neonatal bovine dietary supplement product, although other
suitable
substitute viscosity-enhancing ingredients include molasses, glycerin,
vegetable oil,
glucose syrup, and high fructose syrup. This corn syrup or substitute
viscosity
enhancer should comprise about 40-75% wt, preferably about 50-60% wt, of the
formulated neonatal bovine dietary supplement product.
A second viscosity adjustment component for further thickening the neonatal
bovine dietary supplement product can be xanthan gum, although guar gum, corn
starch, potato starch, or an acid like citric acid, formic acid, ascorbic
acid, acetic acid,
or phosphoric acid may be used, This further thickening agent should only
comprise
about 0.05-5.0% wt, preferably about 0.05-0.20% wt, of the formulated neonatal
bovine dietary supplement product.
The neonatal bovine dietary supplement of the present invention may also
2 5 contain one or more antioxidant agents. Such antioxidant agents will
address the
buildup of free radicals in the neonatal calf caused by a lack of oxygen
during the
labor process. Caffeine functions as an antioxidant for purposes of the
supplement
product of the present invention. As noted above, suitable non-synthetic
sources of
caffeine include green tea, green tea extract, black tea, coffee, and cocoa.
it is
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convenient, .therefore, to have the caffeine source perform double duty within
the
product formulation by additionally providing the antioxidant function. Green
tea
extract is preferred for contributing antioxidants to the neonatal calf.
Sodium citrate can be added to the product formulation to help to solubilize
the caffeine component into solution to make the antioxidants more accessible
to the
neonatal calf. Sodium citrate will also reduce metabolic acidosis in the
neonatal calf
caused by hypoxia, or water imbalance. it buffers the blood in the neonatal
calf to a
proper pH level.
The resulting sodium dissociated from the sodium citrate also serves as an
electrolyte for the neonatal calf Such an electrolyte will help to manage the
hydration status of the newborn calf. Sodium helps with absorption and storage
of
water within the animal. Other suitable electrolytes for purposes of the
neonatal
bovine dietary supplement product formulation include sodium chloride and
potassium chloride.
Tr-sodium citrate dihydrate is the preferred form of sodium citrate for
purposes of the formulation. Such sodium citrate should comprise about 1-10%
wt,
preferably about 1-5% wt, of the flarmulated neonatal bovine dietary
supplement
product.
Trans-400 represents a 100% active, food-grade, detbaming agent designed to
destroy foam in aqueous environments that builds up during the food product
manufacturing process. It may be obtained from Applied Material Solutions,
Inca of
Elkhorn, Wisconsin. As a vegetable oil-based defoamer, it may be added to the
neonatal bovine dietary supplement product in the United States and some
foreign
countries in order to release bubbles that accumulate during the manufacturing
process, so that the bubbles escape to produce a smooth, even end product. If
used,
Trans-400 should comprise about 0.0-1,0% wt, preferably about 0.1-0,5% wt, of
the
formulated neonatal bovine dietary supplement product.
Cassia oil is a flavor enhancer that also acts as a preservative and
antimicrobial agent. Cinnamaldehyde is its essential component. It may be
added to
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the neonatal bovine dietary supplement product at an about 0.1% wt level. Any
phenol propionoid such as oregano oil may be used as a substitute in the
product
formulation.
Polysorbate 80 liquid is an emulsifier that helps oil components within the
neonatal bovine dietary supplement product to integrate into water. Thus, it
represents a solubility aid. It is derived from polyethoxylated sorbitan and
oleic acid,
and it is widely available from a number of manufacturing sources. it should
comprise about 0.0-3.0% wt, preferably about 0.07-0.70% wt, of the formulated
neonatal bovine dietary supplement product.
ic Citric
acid may be added to the neonatal bovine dietary supplement product as
a preservation agent. It should comprise about 0.5-3.0% wt, preferably about
1.2-
1.6% wt, of the formulated neonatal bovine dietary supplement product.
A coloring agent may likewise be added to the neonatal bovine dietary
supplement product. The formulated product is naturally milky white in color.
15 FD&C Blue Dye or beta-carotene are suitable coloring agents.
One successful formula for the neonatal bovine dietary supplement of the
present invention had the following preferred range of ingredients.
INGREDIENT MIN (% MAX (%
Wt) wt)
Water 35,00% 50.00%
Green Tea Extract 1.00% . 5.00%
Trisodium Citrate Dihydrate 1.00% 5.00%
Polysorbate 80 Liquid 0.0% 0.7%
, 'frans 400 - Vegetable oil defoaming agent 0,00% 0,005%
Cassia Oil 0.0% 1.0%
Corn Syrup Blend 50.00% 60.00%
Citric Acid 1.2% 1.6%
Xanthan Gum or Guar Gum 0.05% 0.20%
FD&C Blue Dye ¨ .005% 005
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The supplement is a homogeneous solution when heated and packaged that
becomes a suspension at room temperature. The solution is preferably bottled
when
warm. The supplement is shelf-stable for a time period greater than two hours,
and
does not require a factory vacuum seal and it does not grow mold, yeast or
bacteria.
The process for preparing the neonatal bovine dietary supplement product of
the present invention is as follows:
1, Add the water to a jacketed tank mixer vessel having an impeller
blade. Heat the water with a lid to about > 50 'C, preferably about50-75 'C.,
even
more preferably about52-57 'C.
2. Add half of the xanthan gum or guar gum thickening agent to the
vessel, mixing the composition at about 250-500 rpm, depending upon the volume
of
the batch, for about 15 minutes,
3. Add the other half of the xanthan gum or guar gum thickening agent to
the vessel and repeat the mixing process. It takes time for the xanthan gum or
guar
gum to fully hydrate in the water, If all of the xanthan gum or guar ULM
ingredient
were added to the mixture in the vessel at the same time, the composition
would
thicken too quickly.
At the same time, incorporation of air from the environment should be avoided
during the mixing process.
4. Add the non-synthetic caffeine ingredient to the mixer vessel,
5. Add the tri-sodium citrate dihydrate ingredient to the vessel.
6. Turn off the heat to the mixer vessel,
7. Add the cassia oil to the vessel.
2 5 8. Add the Polysorbate 80 to the vessel,.
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9. Add the corn syrup at about 70 F to the vesselõ
10. Add the citric acid to the vessel.
The final mixture for the neonatal bovine dietary supplement product will
generally exhibit a viscosity level of about 75-150 cps at the prevailing 50 C
temperature immediately after mixing. It takes several hours for the guar gum
or
xanthan gum to fully hydrate. Once the caffeine is fully solubilized, caffeine
crystals
will start to form within 12-24 hours during cooling to room temperature with
a
subsequent increase in viscosity. Thus, approximately 24 hours after the
mixing
process is completed, the neonatal bovine dietary supplement product will
achieve its
desirable viscosity level of about 550-600 cps at 21 'C.
The finished product is preferably packaged in 15-20 ml squeeze tubes or
syringe plunger. Such squeeze tubes or syringe plunger will conveniently
introduce
the product into the newborn calf s mouth.
A typical product dose for the neonatal bovine dietary supplement is about 10-
L5. 40 ml liquid solution containing a concentrated caffeine dose of about
100-400 mg.
The above specification provides a complete description of the components
and preparation process for the neonatal bovine dietary supplement product of
the
present invention. Since many embodiments of the invention can be made without
departing from the spirit and scope of the invention, the invention resides in
the
claims herein appended.
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