U.S. patent application number 10/613633 was filed with the patent office on 2004-05-20 for water-soluble globulin concentrate for improving growth in animals.
This patent application is currently assigned to APC, Inc.. Invention is credited to Thomson, Daniel U., Weaver, Eric M..
Application Number | 20040096440 10/613633 |
Document ID | / |
Family ID | 32303437 |
Filed Date | 2004-05-20 |
United States Patent
Application |
20040096440 |
Kind Code |
A1 |
Weaver, Eric M. ; et
al. |
May 20, 2004 |
Water-soluble globulin concentrate for improving growth in
animals
Abstract
A water soluble globulin concentrate is described. The globulin
concentrate is administered through the animals' water supply and
is effective in increasing growth and weight gain in animals. The
concentrate is especially effective in reducing morbidity in
underweight, stressed pigs, post-weaning.
Inventors: |
Weaver, Eric M.; (Story
City, IA) ; Thomson, Daniel U.; (Ames, IA) |
Correspondence
Address: |
MCKEE, VOORHEES & SEASE, P.L.C.
801 GRAND AVENUE
SUITE 3200
DES MOINES
IA
50309-2721
US
|
Assignee: |
APC, Inc.
1 VisionAire Place, Suite 2
Ames
IA
50010
|
Family ID: |
32303437 |
Appl. No.: |
10/613633 |
Filed: |
July 3, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10613633 |
Jul 3, 2003 |
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09659103 |
Sep 11, 2000 |
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09659103 |
Sep 11, 2000 |
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09258553 |
Feb 26, 1999 |
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09258553 |
Feb 26, 1999 |
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09210490 |
Dec 11, 1998 |
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Current U.S.
Class: |
424/130.1 ;
426/647 |
Current CPC
Class: |
A23K 50/10 20160501;
A61K 2039/505 20130101; C07K 16/06 20130101; A23K 40/00 20160501;
A23K 50/60 20160501; A23K 50/00 20160501; A23K 50/75 20160501; A23K
50/30 20160501; A23K 10/24 20160501; A61P 3/02 20180101 |
Class at
Publication: |
424/130.1 ;
426/647 |
International
Class: |
A61K 039/395; A23L
001/31 |
Claims
What is claimed is:
1. A supplement for animals comprising: a water miscible and stable
globulin concentrate based on animal plasma, said globulin
concentrate containing at lest 15% by weight IgG.
3. A supplement according to claim 1 wherein the concentrate is
contained in a water-based solution.
3. A supplement according to claim 2 wherein the concentrate does
not gel, clot or precipitate in the water.
4. A supplement according to claim 1 which is a dried powder.
5. A supplement according to claim 1 which is substantially
purified.
6. A supplement for animals comprising: water; and the water stable
globulin concentrate of claim 1.
7. A supplement according to claim 6 wherein the globulin
concentrate is present in a concentration of at least 0.1% by
weight.
8. A supplement according to claim 6 which is substantially
purified.
9. A method of improving weight gain and growth, while decreasing
morbidity and mortality in animals comprising: administering a
supplement to an animal post-weaning through the animal's water
source, said supplement comprising the water stable globulin
concentrate of claim 1.
10. A method according to claim 9 wherein the supplement comprises
at least 15% IgG.
11. A method according to claim 9 wherein the supplement is
administered to an animal selected from the group consisting of a
pig, a cow, and a chicken.
12. A method according to claim 11 wherein the supplement is
administered to a pig.
13. A method according to claim 12 wherein the pig is
underweight.
14. A method according to claim 9 wherein the water stable globulin
concentrate is dispersed in the water in a concentration of from
about 0.375 to about 3.0% by weight.
15. A method according to claim 14 wherein the concentration of IgG
in the water is from about 0.1-0.75% by weight.
16. A method according to claim 9 wherein the globulin concentrate
is administered in a dose of 0.5 g immunoglobulin/hd/day or
more.
17. A method according to claim 9 wherein the globulin concentrate
is administered with one or more additives or nutrients selected
from the group consisting of carbohydrates, vitamins, and
minerals.
18. A method according to claim 17 wherein the additives are water
soluble.
19. A method according to claim 9 wherein the globulin concentrate
is administered to young pigs that have not yet begun to consume
feed.
20. A method according to claim 19 wherein the globulin concentrate
is administed to the animal by placing it in the animal's water
system via a stock solution and a liquid dispenser.
21. A method of improving weight gain and growth, while decreasing
morbidity and mortality in pigs comprising: administering a
supplement to a pig post-weaning through the pig's water source,
said supplement comprising the water stable globulin concentrate of
claim 1, and further providing that said supplement comprises at
least 15% IgG.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of co-pending
application Ser. No. 09/210,490, filed Dec. 11, 1998, the
disclosure of which is hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] This invention relates to a composition and method for
treating piglets and other livestock. Specifically, this invention
relates to the treatment of animals with a water-soluble
immunoglobulin product post weaning.
BACKGROUND OF THE INVENTION
[0003] Piglets are born without the ability to fight disease. Pigs
are dependent upon colostrum and later milk from the sow to provide
immunoglobulins which confer passive immunity to disease for the
first 2 to 3 weeks of life and help "tide them over" until their
own immune systems begin functioning. The piglet's endogenous
immune system begins to function and produce antibodies in response
to environmental stimuli at approximately 2 weeks of age. However,
the pig's immune system is not fully competent until about 5 to 6
weeks of age. Until then the pig is susceptible to many biological
challenges.
[0004] Colostrum contains rapidly diminishing levels of
immunologically active, large molecular weight proteins known as
immunoglobulins. These immunoglobulins (Ig) possess antibody
properties and enhance the pig's immunity to infection by organisms
such as bacteria, viruses, and parasites. For various reasons,
however, the piglet does not receive adequate amounts of
immunoglobulins to impart the necessary immunity. These reasons
include problems at lactation, extra large litters, litter
competition, poor nursing sows, low birth weight, and sow death.
This decreased immunity causes the piglets to become more
susceptible to contracting various bacterial, viral, and parasitic
infections, which can cause an increase in mortality from diarrhea
and dehydration.
[0005] In addition to an immature immune system and a deficiency in
immunoglobulins, the animals are often affected by environmental
and health stress, which also weakens the animals and causes
increased susceptibility to disease and various other health
problems, including decreased growth and weight gain.
Traditionally, these occur during the early growth and weaning
period and include stress from the actual weaning process,
shipping, heat, social stresses, and various challenges to the
animals' health. This weakened condition is often caused by
inadequate feed intake and the inability of the animal to
assimilate nutritional elements from the intestine. Undigested
nutrients will end up in the large intestine as a substrate for
undesired intestinal bacteria flora which causes diarrhea in the
animal, further complicating the post-weaning performance of the
pig.
[0006] The mortality from birth to weaning in normal pig production
is generally 12 to 15% but can be as high as 20 to 25% in stressed
pig populations. Many of these piglets that die are the object of
intense care as they are already underweight and under stress after
birth. When the young pig is weaned this is an additional stress
factor, especially so for the lightest pigs of the litter due to
the reasons listed above.
[0007] At birth, pigs have limited enzyme systems efficient only
for digestion of milk. The amount of lactase, the enzyme that
breaks down and digests milk sugar, is high during the first few
weeks of life but then decreases shortly after weaning. Meanwhile,
proteolytic and amylolytic enzymes needed for grain digestion are
not fully developed until 4 to 7 weeks of age. Thus, feed stuffs
other than milk cannot be efficiently digested and absorbed until
the animal is several weeks old. Further, the stress brought about
by abrupt changes in diet and environment are stressful on an
animal's digestive system, further aggravating the delicate balance
of the system.
[0008] Current means for improving growth and reducing post-weaning
morbidity in animals include the inclusion of plasma to the
animals' diet. Such plasma sources have included spray-dried animal
plasma (SDAP). The inclusion of spray-dried animal plasma in the
diet improves feed intake, weight gain, and the efficiency of gain
when compared to other protein sources such as dried skim milk,
whey protein concentrate, soy protein, fishmeal, potato protein,
and dried egg products. The immunoglobulin component of SDAP is
recognized as the factor that improves growth in weaned pigs.
[0009] Spray-dried animal plasma is also utilized commercially in
milk replacement products (milk replacers) for pigs, calves and
sheep. Milk replacers are typically dry powders containing milk
by-products (whey, dried skim milk, whey protein concentrate),
soluble, further processed grain products (soy protein concentrate
or wheat gluten), fats and oils and appropriate vitamin and mineral
fortification. Research has shown that the use of milk replacers
fortified with SDAP derived from whey (or colostral whey) results
in faster weight gain and reduced morbidity and mortality in calves
and pigs. Thomson, D. U., Weaver, Eric M. (1997), "Using Blood
Proteins in Calf Milk Replacers," Large Animal Practice, Vol. 18,
No. 6, p. 16. Large Animal Practitioner. The administration of SDAP
in milk-replacers has several drawbacks, however.
[0010] First, milk replacers which include SDAP are usually
provided to pigs or calves through a self-contained feeding system
of some type. The feeding systems vary in complexity from a bottle
with a nipple to automatic feeding devices. SDAP contains
fibrinogen, a water soluble protein, which is activated by very low
concentrations of calcium to form fibrin, an insoluble protein
matrix. Most sources of tap water contain enough calcium to
initiate the activation of the conversion of fibrinogen to fibrin.
If the concentration of spray-dried animal plasma in a milk
replacement product is high enough and the material is given enough
time to form a protein matrix, the resulting gel will plug most
feeding devices. While various anticoagulants can be used at high
levels to prevent activation of the clotting process, such a level
of anticoagulants may have undesirable effects on the animal either
by decreasing the availability of beneficial minerals, increasing
the osmotic load, or interfering with the blood clotting process in
the animal.
[0011] Second, milk replacers are expensive and difficult to
administer to young pigs, especially those containing significant
concentrations of spray-dried animal plasma. Such products are
normally prepared between 2-4 times per day in small quantities.
Modern swine production is labor-intensive, and these businesses
find it difficult to find and keep employees. The addition of
labor-intensive production methods, i.e. feeding milk replacement
products to the pigs 2-4 times daily, is often not feasible due to
the lack of available farm staff.
[0012] Further, commercially available milk replacement products
usually contain greater than 10% crude fat. This level of fat
accumulates and plugs the water lines unless it can be completely
removed from the system. Yet another major drawback with milk
replacement feeding systems is that the feeding devices must be
thoroughly cleaned and disinfected daily to prevent bacterial
contamination.
[0013] Moreover, although the addition of SDAP to the starter diet
of piglets has made it much easier to feed and manage young pigs
(less than 21 days of age), it still has not proven to be
completely successful in managing the light-end group of pigs,
which comprise the bottom 10% of the population. This weight
difference at weaning between the heaviest and lightest pigs often
leads to greater differences in body weight between the heaviest
and lightest pigs at the end of the nursery phase and at slaughter.
Such pigs consume very little feed from 0 to 2 days post-weaning.
The presence of SDAP in the feed does little to improve the health
of the gut in these very small or young pigs since they do not
consume adequate concentrations of feed for 2 days post-weaning.
The resulting effect in these pigs is temporary gut atrophy, loss
of absorptive capacity, an increase in intestinal permeability and
bacterial colonization and translocation.
[0014] Elliot et al. describe formulations for milk replacement for
artificial rearing of neonatal pigs. (U.S. Pat. No. 4,623,541). The
formulations include purified immunoglobulins which are
subsequently commingled with condensed skim milk and spray dried.
The Elliot formulations are problematic, however, since the
procedure for separating the immunoglobulins from the blood
involves the use of high levels of ammonium sulfate. While ammonium
sulfate is satisfactory for small batches of blood, it is not
useful for large-scale separation operations due to problems in
disposing of this environmentally hazardous compound. In addition,
the Elliot process is not economical to use due to its low yields
of immunoglobulin powder.
[0015] Newson et al. (U.S. Pat. No. 4,096,244) describe the
administration of a composition containing active immunoglobulins
to newborn piglets by feeding. An important feature of this
invention is the reduction of the saline content of the blood serum
to increase the palatability of the serum to the pigs. The
invention also emphasizes the administration of immunoglobulins to
newborn piglets by feeding and describes a feed composition similar
to milk replacer. The Newson formulation is not economical to use
since it is difficult to administer on a large-scale basis and does
not provide for the needs of the newly-weaned pig.
[0016] There is therefore a need in the art for a supplement for
young pigs (>2 days of age) which is economical and convenient
to use on a large scale basis, yet also effective for
administration to newly-weaned, underweight pigs.
[0017] The present inventors have now synthesized a purified,
water-stable immunoglobulin product that can be administered
inexpensively through the water supply of animals. The product is
highly effective in increasing growth and weight gain in
animals.
[0018] Accordingly, it is a primary objective of the present
invention to provide a composition and method for treating animals
using a water-stable, immunoglobulin product based on animal
plasma.
[0019] It is a further objective of the present invention to
provide a composition and method for treating animals which is
effective in decreasing the adverse symptoms of stress in young
animals, post-weaning.
[0020] It is a further objective of the present invention to
provide a composition and method for treating animals which
increases growth and weight gain.
[0021] It is still a further objective of the present invention to
provide a composition and method for treating animals which is
convenient and economical to administer.
[0022] It is still a further objective of the present invention to
provide a composition and method for treating animals which is easy
and economical to manufacture.
[0023] The method and means of accomplishing each of the above
objectives as well as others will become apparent from the detailed
description of the invention which follows hereafter.
SUMMARY OF THE INVENTION
[0024] The invention describes a water-stable, immunoglobulin
concentrate (WSIG) which improves the health and growth rate of
animals at times of stress. The invention is especially effective
in improving growth and reducing morbidity in young pigs, post
weaning. The WSIG is derived from animal plasma which may be
treated to separate the globulin and albumin fractions. The
water-stable globulin fraction is then administered to the animals
through their water system.
[0025] Treatment with the globulin significantly improves health
and increases the growth and weight gain in animals, especially in
underweight, stressed pigs, post-weaning. The globulin composition
is inexpensive to manufacture and is easy and economical to
administer.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0026] The present invention relates to a new method and
composition for improving growth and weight gain in animals through
the administration of immunoglobulin in the animals' water supply.
Reference is often made to the use of this invention with respect
to pigs, however it is to be understood that the invention is not
limited to any particular animal. One of skill in the art can
readily appreciate that the invention will be applicable to any
food or companion animal.
[0027] Previous attempts at decreasing morbidity and mortality in
young pigs have focused on the delivery of supplements, including
immunoglobulin fortified supplements, via dry feed or milk prior to
the weaning period. While moderately successful in reducing
morbidity and mortality, these methods have many problems,
including the expense and difficulties involved with the
administration and use of milk replacement products. Further,
light-end pigs do not benefit from the use of supplements
administered through feed since they will consume primarily water
during periods of stress post-weaning.
[0028] The present invention is predicated upon the discovery that
the administration of immunoglobulins through the animals' water
system is effective in increasing weight gain and growth in
animals. This method is especially effective in highly stressed
pigs that are weak with a reduced appetite. Further, unlike
previous methods of supplementation, the present invention is
especially effective in treating young, underweight pigs that are
in a transitory starvation period post-weaning.
[0029] The composition of this invention is a plasma-based,
substantially purified globulin concentrate. The term
"substantially purified" refers to the fact that the globulin
concentrate contains insufficient amounts of other substances that
will cause the concentrate to clot or gel in water.
[0030] Similarly, the term "substantially free" of albumin refers
to the fact that the globulin concentrate contains insufficient
amounts of albumin to clot or gel when mixed in a highly
concentrated form in water (>10% solution).
[0031] Also, the term "water-stable" refers to the fact that the
globulin concentrate of this invention does not gel, precipitate,
or clot. Instead, the water-stable product is a fluid with
free-flowing solution characteristics.
[0032] Nutritional supplements, including SDAP, have generally been
administered through the animal's feed or as part of milk
replacement therapy. Blood plasma itself gels in water. Now, using
the applicants' globulin separation method, the globulin can be
administered inexpensively through the animals' water. The globulin
concentrate of the present invention is stable in water, and
therefore does not clog the lines of the animal's water system.
Further, in contrast to spray-dried animal plasma and other feed
and milk replacement supplements, Applicants' globulin concentrate
does not need to be placed in the food supply numerous times per
day, thereby decreasing labor costs.
[0033] The globulin concentrate of the present invention can be
administered to animals during all stages of their life cycles to
improve their health and nutrition, but is more effective in
periods of stress, and is especially effective in young, stressed
pigs, post-weaning. These pigs are usually weak from both disease
and lack of appetite. The consumption of immunoglobulin from the
water improves the short-term enteric health of the animal which
promotes feed and water intake. The provision of immunoglobulin in
the water ensures the short-term protection of the pig's enteric
health.
[0034] Swine producers can use the globulin concentrate of the
present invention to improve the health and growth rates of pigs.
The product is efficacious, especially in young stressed, pigs,
cost-effective, and a labor saving tool in the management of pigs.
The commercial applications of this invention are many and range
from the use of the concentrate to more successfully wean large
groups of pigs at very young ages (<10 days of age) to the
administration of the product to weaned pigs in traditional swine
production systems to overcome typical health challenges. Swine
units have progressively grown in size and there is less management
time allotted to the care of individual pigs. Health management is
critical in minimizing disease outbreaks since such outbreaks are
expensive in terms of medication cost and management time. This
invention is successful in promoting the maintenance of enteric
health by supplying an appropriate, adequate source of
gastrointestinal protection to the animals.
[0035] The immunoglobulin concentrate and water delivery method is
also effective in protecting the gastrointestinal health of other
stressed animals, including cattle, horses, and poultry. Stress
such as mild to severe starvation, shipping, surgery,
socialization, corticosteroid treatment, intentional weight
reduction, force molting (poultry), physical disability, and
birthing, all can result in a reduction in feed intake and
breakdowns in gastrointestinal health. The opportunity for disease
is decreased through the administration of the present
water-soluble immunoglobulin concentrate.
[0036] The immunoglobulin concentrate of the present invention is
derived from animal blood. The source of the blood can be from any
animal that has blood which includes plasma and immunoglobulins.
For convenience, blood from beef, pork, and poultry processing
plants is preferred. Anticoagulant is added to whole blood and then
the blood is centrifuged to separate the plasma. Any anticoagulant
may be used for this purpose, including sodium citrate and heparin.
Persons skilled in the art can readily appreciate such
anticoagulants. Calcium is then added to the plasma is to promote
clotting, the conversion of fibrinogen to fibrin. This mixture is
then centrifuged to remove the fibrin portion.
[0037] As described above, it is the fibrin portion which combines
with calcium from the water source to gel and clog water lines.
Once the fibrin is removed from plasma resulting in serum, the
serum can be used as a principal source of Ig. Alternatively, one
could also inactivate this portion of the clotting mechanism using
various anticoagulants.
[0038] In addition, one could simply inject the water-stable plasma
into the water as the immunoglobulin source. Either serum or plasma
may be used as an immunoglobulin souce in the globulin concentrate
product. The further processing to concentrate immunoglobulin
simply ensures fewer problems with line obstruction because less
protein will be injected into the line.
[0039] The defibrinated plasma is next treated with an amount of
salt compound or polymer sufficient to precipitate the albumin or
globulin fraction of the plasma. Examples of phosphate compounds
which may be used for this purpose include all polyphosphates,
including sodium hexametaphosphate and potassium polyphosphate. The
globulin may also be isolated through the addition of polyethylene
glycol or ammonium sulfate. For reasons of convenience and economy,
the polyphosphate compounds are preferably added to the plasma in a
concentration of about 0.5-1% by weight of the plasma.
[0040] Following the addition of the phosphate compound, the pH of
the plasma solution is lowered to a range of between 3.5-4.5 to
stabilize the albumin precipitate. The pH should not be lowered
below 3.5, as this will cause the proteins in the plasma to become
damaged. The preferred pH range is 3.5-4.0, with 3.95 being most
preferred. Any type of acid can be used for this purpose, so long
as it is compatible with the plasma solution. Persons skilled in
the art can readily ascertain such acids. Examples of suitable
acids are HCl, acetic acid, H.sub.2SO.sub.4, citric acid, and
H.sub.2PC.sub.4. HCl is preferred, and 2N HCl is most preferred.
The acid is added in an amount sufficient to lower the pH of the
plasma to the designated range. Generally, this amount will range
from a ratio of about 1:4 to 1:2 acid to plasma. The plasma is then
centrifuged to separate the globulin fraction from the albumin
fraction.
[0041] The next step in the process is to raise the pH of the
globulin fraction with a base until it is no longer corrosive to
separation equipment. Acceptable bases for this purpose include
NaOH, KOH, and other alkaline bases. Such bases are readily
ascertainable by those skilled in the art. NaOH is the preferred
base, and a 10% solution of NaOH is most preferred. The pH of the
globulin fraction is raised until it is within a non-corrosive
range which will generally be between 5.0 and 9.0. The preferred pH
range is 7.0-8.0, with 7.5 being most preferred. The immunoglobulin
fraction is then preferably microfiltered to remove any bacteria
that may be present.
[0042] The final immunoglobulin concentrate can optionally be
spray-dried into a powder. The powder allows for easier packaging
and the product remains stable for a longer period of time than the
raw globulin concentrate in liquid or frozen form. The
immunoglobulin concentrate powder has been found to contain
approximately 35-50% IgG. The immunoglobulin concentrate is then
mixed with serum concentrate and other compounds to improve
wettability.
[0043] The globulin concentrate is administered to the animal by
placing it in the animal's water system via a stock solution and a
liquid dispenser. The globulin composition readily dissolves in
water and remains stable in a highly-concentrated solution that
does not obstruct the water line. While animals receive benefit
from any amount of globulin composition placed in their water
source, the concentration of globulin composition in the water
should be at least 0.1% by weight. The response to the product is
titratable, meaning a greater response is observed with a higher
concentration so much higher levels of globulin concentrate can be
added. The concentration of globulin can be increased until the
water becomes saturated with globulin, i.e. the globulin can no
longer be dispersed within the water. Various concentrations of
stock solutions and/or injection rates may be used to alter the
concentration of immunoglobulin in the water.
[0044] For economy and efficiency and to achieve best results in
stressed pigs, the globulin composition should be dispersed in the
water in a concentration of from about 0.375 to about 3.0% by
weight. The concentration of IgG in the water in this concentration
ranges from approximately 0.1-0.75% by weight.
[0045] A preferred water dispenser for use with this invention is
manufactured by Dosatron.RTM. and is sold as the Proportional Non
Electric Liquid Dispenser. The dispenser is installed directly on
the water supply line. The dispenser is activated by water
pressure. As the water passes through the dispenser it takes up the
designated percentage of concentrate to deliver to the animals.
[0046] The globulin concentrate can be administered to the animal
at any stage of the animal's life. However, as a practical matter
it will be most frequently used in young pigs prior to the stage
when they begin consuming feed since this is the group of animals
that have shown the greatest response to the treatment. The
concentrate is most advantageously used during times when the
animals are most stressed. As already described, the globulin
concentrate is especially effective in animals post weaning during
the transient starvation period when they are not yet consuming
feed. The animal drinks the globulin-fortified water and, with
improved health, begins to eat and to drink larger quantities of
the water. As the animal continues to drink, the globulins from the
water help protect the animal from disease by providing additional
protective support to the mucosal barrier. The additional
protection helps the animal overcome the negative effects of
stress, including leaky gut syndrome and diarrhea. Noticeable
improvements in growth will occur with oral administration of 75 mg
immunoglobulin/kg body weight or 0.5 g immunoglobulin/hd/day.
However, concentrations that will provide 375 mg immunoglobulin/kg
body weight or >2.5 g/hd/day are most effective.
[0047] The globulin concentrate may also be administered with
certain additives or nutrients, such as carbohydrates, vitamins and
minerals, that are added to the water directly or mixed in with the
concentrate prior to adding to the water. The only requirement is
that the additives also be water soluble and compatible with the
immunoglobulin concentrate. Such additives can be readily
ascertained by those skilled in the art. An example of such a
composition is included (Table 2). This composition is then
agglomerated to improve wettability.
[0048] In tests involving the globulin concentrate, the
administration of the product to pigs through water reduced the
frequency of medication administration and the severity of disease
outbreaks.
[0049] The following examples are offered to illustrate but not
limit the invention. Thus, they are presented with the
understanding that various formulation modifications as well as
method of delivery modifications may be made and still be within
the spirit of the invention.
EXAMPLE 1
Effect of Immunoglobulin Concentrate on Young Weaned Pigs
[0050] Porcine immunoglobulin was substantially purified from
porcine plasma using the previously described procedures. The
porcine immunoglobulin concentrate was spray-dried and analyzed for
porcine IgG content. In powder form, the product contained by
analysis 45% IgG. This powder was then reconstitued with tap water
and the pH reduced to approximately 4.5 with citric acid to produce
a 30% w/w stock solution. This stock solution was then injected
into the water line in a ratio of 1 part per 100 parts water which
was used as the sole water source for 6 pens of 24 pigs/pen in the
trial. The product was injected into the water line for a period of
one week. The control group (six pens of 24 pigs/pen) were provided
with water injected with an acidified stock solution (as above).
Pig weights were measured initially and at the end of the 7 day
trial period. The number of pigs medicated during the week was
recorded for both the control and treated (+Ig) groups:
1 TABLE 1 Control +Ig Body Weight (kg) Initial Weight 6.02 5.92
Final, d 7* 7.64 7.61 ADG, g/d 231 241 Medication, % of 12.5% 4.0%
pigs *Final body weights represent an average body weight for the
pen of pigs. Pigs were removed from the pen for intensive care when
necessary.
[0051] Table 2 sets forth the composition of the water-stable
globulin concentrate used in the study:
2 TABLE 2 Ingredient As-is, % Serum concentrate 52.21
Immunoglobulin concentrate 24.28 Lactose 15.00
Fructo-oligosaccharide 5.00 Potassium chloride 1.66 Lecithin 1.00
DL-methionine 0.86 Total 100.0
EXAMPLE 2
Effect of Immunoglobulin Concentrate on Young Weaned Calves
[0052] 120 calves 8.9 days of age were fed calf milk replacer (CMR)
for 42 days and commercial calf starter (CS) and water ad lib for
56 days. In the first 15 days of the study and prior to each
feeding, either bovine-derived immunoglobulin concentrate or
placebo was added to the mixing tank (to 1.9 l CMR) at the
following rates:
[0053] 60 g for 5 days (0.51% IgG);
[0054] 45 g for 5 days (0.38% IgG); and
[0055] 30 g for 5 days (0.25% IgG).
[0056] The body weight, feed intake, efficiency, and health of the
calves were then measured using fecal scores and scours, use of
electrolytes and Ab, mortality, blood IgG, and Hct (day 0). The
results are set forth in Tables 3-6 below:
3TABLE 3 Body Weight Body weight (kg) No Gammulin Gammulin Day of
Study 47.3 46.3 0 54.7 53.7 28 71.2 72.3 56
[0057]
4TABLE 4 Body Weight Body Weight Increase (g/d) No Gammulin
Gammulin Days of Study Percent Gain 264 262 0-28 -- 589 665 29-56
+12.9% (P < 0.07) 426 463 0-56 +8.7% (P < 0.10)
[0058]
5TABLE 5 Efficiency CMR (g/d) CS (g/d) G:F g/kg Gammulin 390 486
422 No Gammulin 390 525 459
[0059]
6TABLE 6 Health Fecal Scours (%) Electrolytes (%) Ab (%) Scores* P
< 0.07 (-23%) P < 0.10 (-39%) (-50%) Gammulin 1.6 12.4 4.4
2.2 No Gammulin 1.6 9.6 2.7 1.1 *1 = normal to 4 = severe
scours
Conclusions
[0060] Overall, the delivery of immunoglobulins to the calves had
no significant effect on mortality (1 calf--0.8% mortality), intake
of calf milk replacer or starter, or intake of fat or protein.
Further, the palatability of all the diets was excellent. The study
demonstrates that immunoglobulins delivered through the water can
significantly enhance the growth, feed efficiency, and health of
weaning calves.
EXAMPLE 3
Effect of Immunoglobulin Concentrate on Chicks
[0061] Porcine immunoglobulin concentrate was substantially
purified from porcine plasma using polyphosphate precipitation. The
porcine immunoglobulin concentrate contained by analysis 36% IgG by
weight. A 1% solution of the porcine immunoglobulin concentrate was
prepared fresh each morning and acidified to pH 4.6 using 25%
phosphoric acid to control bacterial growth. This solution was the
only source of water to the birds in the immunoglobulin treatment.
To determine the effectiveness of acidification in controlling
bacterial growth in the immunoglobulin solution, samples of the
solution immediately after mixing and after 24 hours were taken.
Control birds received water that was not acidified.
Diets
[0062] Both the Control and Immunoglobulin groups received
Purina.RTM. Gamebird Chow ad lib during the experiment. This diet
meets all the nutritional requirements of chickens and is
non-medicated.
Animals
[0063] Eighty-four, mixed sex white leghorn chickens were used in
this experiment. The chicks were one day old at the beginning of
the experiment. The chicks were randomly assigned to 4 cages (21
chicks per cage) in a battery brooder. The birds were weighed at
the start of the experiment and on days 4, 7, 14 and 21. Feed
consumption was measured during the third week of the
experiment.
Results
Viable Bacteria in Immunoglobulin Solution
[0064] The immunoglobulin solution used in this experiment was
adjusted to pH 4.6 to control bacterial growth. The number of
viable bacteria in the solution initially and after 24 h in the
trough are shown in Table 7. There was a large increase in the
number of bacteria in the immunoglobulin solution during the 24 h
period. The applicants tried adjusting the pH of the water to 4.2
during one day of the experiment, but this decreased the number of
bacteria by less than 1 log. The dominant organisms were
gram-negative bacilli and cocci. It is suspected that most of these
organisms may be fecal coliforms such as E. coli, Enterobacter
cloacae and Enterobacter aerogenes since the water troughs were
usually contaminated with chicken feces by the end of the feeding
period. It is also possible that some of these bacteria may belong
to spoilage organisms such as Pseudomonas spp.
7 TABLE 7 Total Viable Bacteria (CFU/mL) Starting pH 0 h 24 h 4.6
4.3 .times. 10.sup.3 2.1 .times. 10.sup.8 4.2 9.2 .times. 10.sup.2
7.3 .times. 10.sup.7
Chick Growth and Feed Consumption
[0065] During the first week of the experiment, there were no
significant differences in average daily gains between the Control
and the Immunoglobulin treatment groups (P>0.05) (Table 7).
However, during the second and third weeks of the experiment the
Immunoglobulin treatment chickens gained significantly faster than
did the controls (P<0.05). There were no significant differences
in feed consumption or feed to gain ratios between the two groups
during the third week of the experiment (P>0.05)(Table 7).
Conclusions
[0066] Immunoglobulins delivered through the water can
significantly enhance the growth of laying-type chickens.
EXAMPLE 4
Preferred Manufacturing Method for Globulin Concentrate
[0067] The following illustrates a preferred method of
manufacturing the globulin concentrate of the present invention:
12
[0068] Having described the invention with reference to particular
compositions, theories of effectiveness, and the like, it will be
apparent to those of skill in the art that it is not intended that
the invention be limited by such illustrative embodiments or
mechanisms, and that modifications can be made without departing
from the scope or spirit of the invention, as defined by the
appended claims. It is intended that all such obvious modifications
and variations be included within the scope of the present
invention as defined in the appended claims. The claims are meant
to cover the claimed components and steps in any sequence which is
effective to meet the objectives there intended, unless the context
specifically indicates to the contrary.
* * * * *