U.S. patent application number 15/029230 was filed with the patent office on 2016-09-08 for composition preventing necrotic enteritis in galloanserans.
This patent application is currently assigned to Perstorp AB. The applicant listed for this patent is PERSTORP AB. Invention is credited to Richard DUCATELLE, Conrad Gerard SCHWARZER, Richard SYGALL, Karolien Van DRIESSCHE, Filip Van IMMERSEEL.
Application Number | 20160256426 15/029230 |
Document ID | / |
Family ID | 52828442 |
Filed Date | 2016-09-08 |
United States Patent
Application |
20160256426 |
Kind Code |
A1 |
Van IMMERSEEL; Filip ; et
al. |
September 8, 2016 |
Composition preventing necrotic enteritis in galloanserans
Abstract
The present invention refers to the use of a glycerol ester
composition of at least one short chain fatty acid for preventing
and/or alleviating necrotic enteritis in the gastric tract of
galloanserans. The glycerol ester composition comprises at least
75% by weight of glyceryl tributyrate, below 25% by weight of
glyceryl dibutyrate and below 8% by weight of glyceryl
monobutyrate. The present invention also refers to the use of said
composition for modulating the gut flora of galloanserans.
Inventors: |
Van IMMERSEEL; Filip; (Eke,
BE) ; SYGALL; Richard; (Riethoven, NL) ; Van
DRIESSCHE; Karolien; (Zele, BE) ; DUCATELLE;
Richard; (Wortegem-Petegem, BE) ; SCHWARZER; Conrad
Gerard; (Beringen, BE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
PERSTORP AB |
Perstorp |
|
SE |
|
|
Assignee: |
Perstorp AB
Perstorp
SE
|
Family ID: |
52828442 |
Appl. No.: |
15/029230 |
Filed: |
October 6, 2014 |
PCT Filed: |
October 6, 2014 |
PCT NO: |
PCT/SE2014/000123 |
371 Date: |
April 13, 2016 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/22 20130101;
A23V 2002/00 20130101; A61P 1/04 20180101; A23K 50/70 20160501;
A61K 9/167 20130101; A23V 2002/00 20130101; A61K 9/0056 20130101;
A23K 20/158 20160501; A61K 31/22 20130101; A61K 31/225 20130101;
A23K 50/75 20160501; A61K 9/50 20130101; A23V 2250/1884 20130101;
A23V 2200/32 20130101; A61K 2300/00 20130101 |
International
Class: |
A61K 31/225 20060101
A61K031/225; A23K 50/70 20060101 A23K050/70; A23K 50/75 20060101
A23K050/75; A23K 20/158 20060101 A23K020/158; A61K 9/50 20060101
A61K009/50; A61K 9/00 20060101 A61K009/00 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 14, 2013 |
SE |
1300646-5 |
Claims
1. A glycerol ester composition comprising at least 75% by weight
of glyceryl tributyrate, below 25% by weight of glyceryl dibutyrate
and below 8% by weight of glyceryl monobutyrate, for use in
prevention and/or alleviation of necrotic enteritis in the gastric
tract of galloanserans.
2. A glycerol ester composition according to claim 1, wherein said
necrotic enteritis is caused by Clostridium perfringens.
3. A glycerol ester composition according to claim 1, wherein said
galloanserans are galliformes.
4. A glycerol ester composition according to claim 1, wherein said
galloanserans are anseriforms.
5. A glycerol ester composition according to claim 1, wherein said
glycerol ester composition comprises at least 80% by weight of
glyceryl tributyrate, below 20% by weight of glyceryl dibutyrate
and below 5% by weight of glyceryl monobutyrate.
6. A glycerol ester composition according to claim 1, wherein said
glycerol ester composition comprises at least 85% by weight of
glyceryl tributyrate, below 15% by weight of glyceryl dibutyrate
and below 4% by weight of glyceryl monobutyrate.
7. A glycerol ester composition according to claim 1, wherein said
glycerol ester composition comprises at least 90% by weight of
glyceryl tributyrate, below 10% by weight of glyceryl dibutyrate
and below 2.5% by weight of glyceryl monobutyrate.
8. A glycerol ester composition according to claim 1, wherein the
amount of free butyric acid in said glycerol ester composition is
below 1% by weight.
9. A glycerol ester composition according to claim 1, wherein the
amount of free butyric acid in said glycerol ester composition is
below 0.5% by weight.
10. A glycerol ester composition according to claim 1, wherein the
amount of free butyric acid in said glycerol ester composition is
below 0.2% by weight.
11. A glycerol ester composition according to claim 1, wherein said
glycerol ester composition is adsorbed on a carrier, such as a
silica carrier, thereby allowing said glycerol ester composition to
be distributed as a dry product.
12. A glycerol ester composition according to claim 11, wherein
said carrier comprises porous silica particles with an average
particle size of 20-70 .mu.m.
13. A glycerol ester composition according to claim 11, wherein
said glycerol ester composition is adsorbed on silica particles in
a weight ratio of 50-80% glycerol ester and 20-50% silica
particles.
14. A glycerol ester composition according to claim 1, wherein said
glycerol ester composition is fed to said galloanserans in an
amount of between 0.05 to 1.5% by weight of the galloanserans'
daily feed ration.
15. A glycerol ester composition according to claim 1, wherein said
glycerol ester composition is fed to said galloanserans in an
amount of between 0.1 to 1.0% by weight of the galloanserans' daily
feed ration.
16. A glycerol ester composition according to claim 14, wherein
said amount of said glycerol ester composition is administered over
time intervals of 5-10 days and wherein said amount is decreased
over a 1-5 week period.
17. A glycerol ester composition according to claim 16, wherein the
decrease of said amount is 20-50% of the amount given during the
previous interval.
18. A glycerol ester composition according to claim 15, wherein
said amount of said glycerol ester composition is administered over
time intervals of 5-10 days and wherein said amount is decreased
over a 1-5 week period.
19. A glycerol ester composition according to claim 3, wherein said
galloanserans are galliformes selected from the group consisting of
chicken, turkey, grouse and pheasant.
20. A glycerol ester composition according to claim 4, wherein said
galloanserans are anseriforms selected from the group consisting of
ducks, goose and swan.
Description
FIELD OF THE INVENTION
[0001] The present invention refers to the use of a glycerol ester
composition of at least one short chain fatty acid for preventing
and/or alleviating necrotic enteritis in the gastric tract of
galloanserans. The glycerol ester composition comprises at least
75% by weight of glyceryl tributyrate, below 25% by weight of
glyceryl dibutyrate and below 8% by weight of glyceryl
monobutyrate. The present invention also refers to the use of said
composition for modulating the gut flora of galloanserans.
BACKGROUND OF THE INVENTION
[0002] Necrotic enteritis is an acute infection affecting
galloanserans. Galloanserans are divided into the subgroups
galliformes (landfowls) like chicken, turkey, grouse and pheasant,
and anseriforms (waterfowls) like ducks, goose and swan. Necrotic
enteritis has become an emerging problem especially among poultry
and is characterized by severe necroses of intestinal mucosa. The
clinical illness is usually very short and often the only signs are
a sudden increase in mortality. However, birds with depression,
ruffled feathers, and diarrhea may also be seen. The gross lesions
are primarily found in the small intestine (jejunum), which may be
ballooned, friable, and contain a foul-smelling, brown fluid.
[0003] The causative agent is the gram-positive, obligate,
anaerobic bacteria Clostridium perfringens. There are two primary
C. perfringens types, A and C, associated with necrotic enteritis
in galloanserans. Toxins produced by the bacteria cause damage to
the small intestine, but also liver lesions, and mortality.
[0004] C perfringens is a nearly ubiquitous bacteria readily found
in soil, dust, feces, feed, and used poultry litter. It is also a
normal inhabitant of the intestines of healthy galloanserans.
[0005] Development of necrotic enteritis depends on the presence of
predisposing factors, such as mucosal damage caused by coccidial
pathogens and feed containing high protein levels.
[0006] Because C. perfringens is nearly ubiquitous, it is important
to prevent coccidiosis, as well as changes in the intestinal
microflora that would promote its growth. This has earlier been
accomplished by routinely adding antibiotics to the feed. However,
since the ban of growth promoting antibiotics in the European Union
in 2006, necrotic enteritis has become an emerging disease among,
for instance, poultry. There is a great need for alternative
methods to counteract this disease or malfunction.
[0007] An alternative to counteracting harmful bacteria like C.
perfringens through antibiotics is to try to balance or normalize
the gut flora. The gut flora consists of a complex of microorganism
species that live in the digestive tract. In this context gut is
synonymous with intestinal and flora with microbiota and
microflora. The microorganisms perform a host of useful functions,
such as fermenting unused energy substrates, training the immune
system, preventing growth of harmful, pathogenic bacteria,
regulating the development of the gut, producing vitamins for the
host and producing hormones to direct the host to store fats.
However, in certain conditions, some species are thought to be
capable of causing diseases or malfunction by producing infection
or increasing cancer risk for the host.
[0008] The present invention discloses the use of a glycerol ester
composition for preventing and/or alleviating necrotic enteritis in
the gastric tract of galloanserans, like chicken and turkey. The
use of said composition for modulating the gut flora of
galloanserans is also disclosed. Use of the composition according
to the invention balances or normalizes the gut flora of
galloanserans in such a way that the growth of pathogenic species
is inhibited and diseases like necrotic enteritis are prevented.
One mechanism behind this effect is presently believed to be that
the growth of helpful bacteria is favored and that this prevents
the growth of pathogenic species by competing for nutrition and
attachment sites to the epithelium of the colon.
[0009] The positive effects of butyric acid on gut health in
poultry and other animals have been known for a long time.
Different distribution forms of butyric acid have also been
explored, among them distributing butyric acid in the form of
glycerol esters. In recent years, a lot of interest has been
directed to the use of glyceryl monobutyrate as a feed-additive to
promote animal gut health.
[0010] Use of a glycerol ester composition, comprising mainly
glyceryl tributyrate, has now surprisingly been found to be a more
efficient way of preventing necrotic enteritis in galloanserans,
such as broiler chicken, compared to giving the animal butyric acid
in the form of glyceryl monobutyrate.
DETAILED DESCRIPTION OF THE INVENTION
[0011] The present invention refers to the use of a glycerol ester
composition comprising a short chain fatty acid, which has proven
to be an efficient way of preventing necrotic enteritis in
galloanserans, such as broiler chicken. The glycerol ester
composition comprises at least 75% by weight of glyceryl
tributyrate, below 25% by weight of glyceryl dibutyrate and below
8% by weight of glyceryl monobutyrate. Butyric acid is known to
have a positive effect on gut health in galloanserans. The present
invention shows that distributing the butyric acid mainly as
glyceryl tributyrate is an efficient way of preventing necrotic
enteritis in galloanserans, such as broiler chicken, and it has
proven to be more efficient than distributing butyric acid mainly
in the form of glyceryl monobutyrate.
[0012] According to one embodiment of the present invention the
glycerol ester composition comprises at least 80% by weight of
glyceryl tributyrate, below 20% by weight of glyceryl dibutyrate
and below 5% by weight of glyceryl monobutyrate.
[0013] According to a preferred embodiment of the present invention
the glycerol ester composition comprises at least 85% by weight of
glyceryl tributyrate, below 15% by weight of glyceryl dibutyrate
and below 4% by weight of glyceryl monobutyrate.
[0014] According to a more preferred embodiment of the present
invention the glycerol ester composition comprises at least 90% by
weight of glyceryl tributyrate, below 10% by weight of glyceryl
dibutyrate and below 2.5% by weight of glyceryl monobutyrate.
[0015] Free butyric acid has a very unpleasant smell, which causes
handling problems. These problems can be avoided by distributing
the butyric acid in the form of glycerol esters. According to one
embodiment of the present invention, the amount of free butyric
acid in the glycerol ester composition is below 1%, preferably
below 0.5% and most preferably below 0.2% by weight. Keeping down
the amount of free butyric acid also ensures that the pH in the
glycerol ester composition is kept at a level where the glycerol
ester will not undergo hydrolyzation into glycerol and free acid,
hence, the product is kept stable.
[0016] According to one embodiment of the present invention the
glycerol ester composition is adsorbed on an inert carrier, such as
a silica carrier. This allows the composition to be distributed as
a dry product. Such a silica carrier preferably comprises porous
silica particles with an average particle size of 20-70 .mu.m.
According to one embodiment of the present invention, the glycerol
ester composition is adsorbed on silica particles in a weight ratio
of 50-80% glycerol ester and 20-50% silica particles.
[0017] The glycerol ester composition according to the present
invention can be added to any commercially available feedstuffs for
galloanserans. The glycerol ester composition may be incorporated
directly into commercially available feeds or fed supplementary to
commercially available feeds.
[0018] According to one embodiment of the present invention the
amount of glycerol ester composition fed to the galloanserans is
from 0.05 to 1.5% by weight, preferably from 0.1 to 1.0% by weight
of the galloanserans' daily feed ration.
[0019] According to another embodiment of the present invention the
amount of said glycerol ester composition is administered over time
intervals of 5-10 days and is decreased over a 1-5 week period.
[0020] According to yet another embodiment of the present invention
the decrease of said amount is 20-50% of the amount given during
the previous interval.
EMBODIMENT EXAMPLE
[0021] In vivo trial on the efficacy of glyceryl butyrates to
control Clostridium perfringens-induced necrotic enteritis in
broiler chicken.
Bacterial Strains and Vaccines
[0022] The challenge strain used in the in vivo trials, C.
perfringens strain 56, was isolated from the gut of a broiler
chicken with necrotic lesions from a flock with weight gain
problems and has been shown to be highly virulent in earlier in
vivo trials. The strain was classified as a type A strain (netB
positive, beta-2 and enterotoxin negative) and produces moderate
amounts of alpha toxin in vitro (Gholamiandehkordi et al.,
2006).
[0023] For inoculation, the strain was grown for 24 h in Brain
Heart Infusion broth (BHI, Oxoid, Basingstoke, England).
[0024] A ten-fold dose of the anticoccidial vaccine Paracox.RTM.-8
(Schering-Plough Animal Health, Brussels, Belgium), containing
live, attenuated oocysts of Eimeria (E.) acervulina (two lines), E.
brunetti, E. maxima, E. necatrix, E. praecox, E. mitis and E.
tenella was used in this study. Nobilis Gumboro D 78 vaccine
(Schering-Plough Animal Health, Brussels, Belgium) was given in the
drinking water.
Animals and Housing
[0025] In this experiment, 114 broilers of mixed sex were used.
They were obtained at 1 day old from a commercial hatchery. Before
the trial, all rooms were decontaminated with Metatectyl.RTM.
(Clim'oMedic) and with a commercial anticoccidial disinfectant
(Bi-OO-cyst.RTM.; Biolink Ltd, York, UK). The birds were divided in
4 cages of 1.5 m.sup.2, on wood shavings. They were given drinking
water and feed ad libitum. A 23 h/1 h light darkness program was
applied.
Experimental Study Design
[0026] The first 7 days, the chickens were fed a starter diet and
from day 8 until 15, a grower diet. Both the starter and the grower
diet were a wheat/rye (43%/7.5%) based diet, with soybean meal as
protein source. From day 17 onwards, the same diet was used with
the exception that fishmeal (30%) was used as a protein source. The
feed was provided by the Institute for Agricultural and Fisheries
Research (ILVO). The tested products were mixed in the feed. The
Gumboro vaccine was given in the drinking water at day 16 in all
groups. All groups were challenged orally one time a day with
approximately 4.10.sup.8 cfu C. perfringens strain 56 at days 17,
18, 19 and 20. At day 18 all birds were orally inoculated with a
ten-fold dose of Paracox-8.TM.. At days 21, 22 and 23, 9 animals of
each group were euthanized by intravenous sodium pentobarbital
injection.
Model
TABLE-US-00001 [0027] TABLE 1 Time schedule for the in vivo study.
d 16 d 17 d 18 d 19 d 20 d 21 d 22 d 23 Gumboro x Feed + x x x x x
x x fishmeal Inoculation x x x x C. perfringens Paracox .RTM.
.times.10 x Scoring x x x
Products Tested
[0028] Pen 1: positive control [0029] Pen 2: glyceryl monobutyrate
(adsorbed on a silica carrier), added to the feed at a lower
concentration [0030] Pen 3: glyceryl monobutyrate (adsorbed on a
silica carrier), added to the feed at a higher concentration [0031]
Pen 4: glyceryl tributyrate (adsorbed on a silica carrier)
[0032] The products were added to the feed at the concentrations
shown in Table 2 below:
TABLE-US-00002 TABLE 2 Concentrations of products added to the feed
(kg/ton) Glyceryl Glyceryl monobutyrate, monobutyrate, Glyceryl on
silica carrier on silica carrier tributyrate, low conc high conc on
silica carrier Week 1 5 7.5 5 Week 2 2.5 6 2.5 Week 3 2 5.5 2
[0033] Intestinal lesions in the small intestine (duodenum to
ileum) were scored blinded as follows: [0034] 0: no gross lesions
[0035] 1: congested intestinal mucosa [0036] 2: small focal
necrosis or ulceration (1-5 foci) [0037] 3: focal necrosis or
ulceration (5-16 foci) [0038] 4: focal necrosis or ulceration (16
or more foci) [0039] 5: patches of necrosis 2-3 cm long [0040] 6:
diffuse necrosis typical of field cases
[0041] Lesion scores of 2 or more were classified as necrotic
enteritis positive
Statistical Analysis
[0042] The GraphPad Prism Software, Inc was used to determine
whether there were significant differences between groups.
Statistical significance was determined at a P value of
<0.05.
Clinical Observations
[0043] No abnormal clinical observations were observed.
[0044] 3 chickens died during the trial.
[0045] -1 chicken died in pen 1
[0046] -2 chickens died in pen 3
[0047] Table 3 shows the number of birds with necrotic enteritis
lesions for each group, at day 21, day 22 and day 23. Also, the
total number of birds with lesions per group is shown.
TABLE-US-00003 TABLE 3 Number of birds with macroscopic necrotic
enteritis lesions on the three sampling days. glyceryl glyceryl
monobutyrate, monobutyrate, glyceryl pos control low high
tributyrate day 21 9/9 5/9 4/9 3/9 day 22 4/9 3/9 5/9 2/9 day 23
4/10 2/10 3/8 2/11 total 17/28 10/28 12/26 7/29 Total (%) 61 36 46
24
[0048] The percentage of positive chickens (with macroscopic lesion
score =2) is shown in FIG. 1.
[0049] The results in FIG. 1 states that adding glyceryl
tributyrate to the feed gives a significantly better result, with
respect to preventing Clostridium perfringens-induced necrotic
enteritis in broiler chicken, than adding glyceryl monobutyrate at
either one of the two concentrations tested.
[0050] If the addition of glyceryl monobutyrate at the higher
concentration is compared to the addition of glyceryl tributyrate,
it is about the same weight of butyric acid that is added (making
the assumption that glycerol and butyric acid have about the same
molar weights). Despite this fact, glyceryl tributyrate gives a
much better result (24% positive chicken in total for glyceryl
tributyrate compared to 46% positive chicken in total for glyceryl
monobutyrate at the higher concentration).
[0051] It is also remarkable that adding a lower concentration of
glyceryl monobutyrate gives a better result than adding a higher
concentration (36% positive chicken in total for glyceryl
monobutyrate at the lower concentration compared to 46% positive
chicken in total for glyceryl monobutyrate at the higher
concentration).
[0052] The results show that using a glycerol ester composition
according to the present invention is an effective way of
preventing Clostridium perfringens-induced necrotic enteritis in
galloanserans.
[0053] The embodiment example is to be construed as illustrative
and not limiting in any way. The glycerol ester composition may for
example comprise a blend of glycerol esters of different short
chain fatty acids, such as butyric acid, propionic acid and valeric
acid. The dosage levels will then have to be calculated with
respect to the total amount of glycerol esters.
[0054] It may further prove to be useful to feed the glycerol ester
composition to the animal for a shorter or longer period of time
and to extrapolate the dosage levels accordingly.
* * * * *