Note: Descriptions are shown in the official language in which they were submitted.
L3~
ion in Ruminants
The present invention relates to improvement of feed utilization in
ruminants, particularly to a composition for improving feed utilization of
ruminants, an animal foodstuff intended to improve feed utilization of
ruminants and to processes of producing the same.
As one of their characteristics, ruminants are able to utilize
cellulose, hemicellulose and nonproteineous nitrogen effectively which single-
stomach animals can hardly utilize. However, ruminants have the disadvantage
that the energy from concentrates once ingested is significantly lost as
heat and gases in the fermentation process within their rumen ~the first
stomach). Ruminants obtain more than a half of their energy requirements
from the volatile fatty acids produced by microorganisms in the rl~nen. Thus,
the carbohydrates ingested orally are decomposed to pyruvic acid in the rumen
and various volatile fatty acids are produced via this pyruvic acid. Princ-
ipally produced fatty acids are acetic acid, propionic acid and butyric acid,
as well as small amount of isovaleric acid and valeric acid. No loss of
energy is involved in the process of conversion from pyruvic acid to propionic
~,,, - 1 - .~
~ i
~9L357
acid but, here, rather a slight increase of energy retention occurs by ut-
ilizing hydrogen ion pool efficiency. However, in the production of acetic
acid or butyric acid, part of the energy is lost in the form of methane,
carbon dioxide or hydrogen. Therefore, in ruminants, the utilization of
carbohydrates as energy sources can be increased by adjusting the condition
of fermenta~ion in the rumen, so as to decrease the relative production of
acetic acid and butyric acid and increase
- la -
3~35
-- 2 --
-the relative produc-tion of propionic acid,
I-t is known that cer-tain antibiotics including
monensin (U.S. Pa-ten-t ~o. 3839557) and salinomycin
(Japanese ~nexamined Published Paten-t ~o. 93578/1977 ;
Belgian Patent 8~61L~2) have the abili-ty to improve -the
u-tilization of feed in r.uminants bu-t in view of the
vast feed requirements of these animals and narrow safety
margin between eEfec-tive and toxic levels of those
compounds, a need has been fe:Lt for the development of
a safer compound having a higher activity to increase
the feed utilization. Since :ruminan-ts are poor converter
of concentrates to mea-t, improvement of feed utilization
by rumen fermentation manupulation would be a great
economic and social contribution.
~he intensive research conducted by the present
inventors for agents that would be conductive to a hig'~er
relative production of propionic acid in the fermentation
. process within the rumen resul-ted in the unexpected
- finding that carriomycin exhibits an especially potent
activity -to increase the production of propionic acid and
tha-t whereas the above-mentioned known agents have only
a narrow effective concentration range beyond which a
sharp decrease of production of volatile fatty acids
due to their to~ic effect was confermed carrio~ycin is
greater in the breadth of effective concen-tration and
fea-tures an increasing ~roductian of propionic acid in
proportlon to dosage, thus ha~ing characteristics which
are of great practical utility.
~he research subse~uent].y carried out further led -to
the finding that when carriomycin or a salt thereof is
added -to a whole ration for ruminants, their feed
conversion ratio is remarkably improved and, their body
weight is also increased, withou-t inducing a decrease of
appetite.
~nother surprlsing finding was that whereas the
:Eeed utilization improving activity o:E the conventional
~f~5~ 24205-~3l
polyether antibiotics such as monensin and salinomycin is such
that while -they increase the body weight oE animals when added
to feeds based on roughage, they do not appreciably display
their activity because of a reduced feed intake when added to
feeds based on concentrates, carriomycin products marked body
weight increases, irrespective of whether i-t is added to rough
age type feeds or to feeds based on concentrates.
Thus, this invention provides for an animal food-
stuff comprising animal feed and carriomycin or a physiologi-
cally acceptable salt thereof in an amount effective to improve
feed utilization in ruminants.
In a further aspect, this invention provides for
a process for the preparation of an animal foodstuff, which
process comprises:
admixing carriomycin or a phsiologically acceptable salt
thereof in an amount sufficient to improve feed utilization
in ruminants with ruminant animal feed.
Carriomycin is a polyether antibiotic which is a]so
known as Antibiotic T-42082, and the properties of the pro-
ducer of -this antibiotic, the method of producing the anti-
biotic and the physicochemical and biological characteris-
tics of the antibiotic are well documented in United S-tates
Patent No. 4069316, Journal of Antibio-tics (Tokyo) _ (1),
7-14 (1978). Moreover, .Streptomyces hygroscopicus T-42082,
one oE the carriomycin-producing strain, has been deposited
at the Institute for Fermentation, Osaka, Japan and American
3 -
5'~
Type Cultllre Collection, United States of America under the
accession numbers of IFO 13609 and ATCC 31080, respectively.
Carriomycin may be used as the free acid form or in
the form of the salt with a physiologically acceptable base
such as an alkali metal (sodium, potassium, etc.), alkaline earth
metal (calcium, etc.) or the like. Par-ticularly preferred are
the sodium and potassium salts.
In the practice of this invention, carriomycin or
its salt need not be a purified product. It may be economi-
cally more advantageous to use the dried fermentation broth,
either as it is or as diluted with ordinary feed or drinking
water according to the carriomycin concentration of the broth~
The animal foodstuff composition according to thisinvention is prepared by mixing carriomycin or a salt thereof
with ruminant animal feed.
Animal feed that may be employed include roughage
such as hay, forage grass, silage, etc., concentrates such as
cereals (corn, barley, wheat, rye, oat, etc.), oil meals
(soybeen meal, safflower
~ 3a -
35~
meal, etc.) and brans (rice bran, wheat bran, etc.), yeast,
fish meal, and so on. It is possible to add o-ther auxiliary
agents such as emulsifiers, dispersing agents, suspending
agents, wetting agents, thickeners, gelling agents, solubili-
zers, etc. in appropriate amounts~ Further, preservatives,
fungicides, growth promoting factors (syntheti.c follicle
stimulati.ng hormone, etc.), antibiotics, enzyme preparations,
lactic acid bacterial preparations, etc. may also be incorpor-
ated.
The easiest and practical method of using carriomycin
or its salt for improving the feed utilization in ruminants
such as cattle, goats and sheep is administration by -the oral
route as incorporated in feed. While this animal foodstuff
can-be effectively fed
~ 5~
to ruminan-ts a-t any stage of growth, i-t is best appliecl
after es-tablishment of their rumen fermentation function
(e.g. about 3 months after par-turition in the case of
cattle).
While -the dosage of carriomycin or physiologically
acceptable salts thereof varies with the species and
age of animal, the daily dosage is normally about
60 ~g to 3 mg and preferably about 200 ~g to 1.5 mg per kg
body weight of ruminants. ~he preferred concentration
of the active agent in feed is about 0 3 to 100 ppm and
preferably about 1 to 50 ppm.
If necessary, the present agen-t may be administered
in combination with small amounts of protein feed,
minerals, molass feed, etc.
Compared with the conventional feed utilization
improving agents of the polyether type, carriomycin
can be more safely administered to ruminants.
In ruminants, while the magni-ture of improvement
in feed utilization brought about by the addition of
20 conventional agents is about 10 percent, carriomycin
according to this invention produces an improvement of
about 15 to 20 percent. Moreover, the latter
characteristically produces a body weight gain of about
10 to 20% over the control value. The present agent is
an excellent feed additive especially because it causes
a body weight gain of about 15% when added to feeds based
on concentrates.
~ he following examples illustrate -the effects of
administra-tion of carriomycin or a sal-t thereof
3o
Example 1
An in vitro rumen fermentation test with cat-tle
rumen ~juice
~he rumen contents of fistulated catt]e raised on rice
straw, hay cube and concentrate containg TDN (-total
cligestive nutrient): 73.6% and DCP (digestive clude protein
~ S7
-- 6 --
10.5%) was filtered through 4 layers of cheesecloth,
and to the fil-tra-te was added an equal volume o~ McDougal].'s
buffer solution -to prepare a buffered solution of
rumen juice.
~ach of carriomycin and monensin (Journal of Animal
Science 43~3), 657-664 (1976) ~ was dissolved in 1 ml of
methanol and added to 29 ml of the above McDougall
buffered soluti~n of rumen juice. The mixture was incubate
with 1 g of corn starch as substrate for 8 hours in
accordance with the method described in Journal of Animal
Science 4~(2), 385-392 (1977) . ~he incubated culture
was centrifuged at 3,000 r.p,m. for 20 minutes and
a predetermined portion of the supernatant fluid was
subaected to gas chromatography (detector ~ID ~flame
15 inoniza-tion detector)) for a quantitative estimation of
volatile fatty acids produced microbiologically from
the substrate,
Table 1 Production of volatile_fatty acids
after 8 hours_o in vitro culture
- __ ~otal amountlAc~e-tic-Propl~ ~utyric
Additive (~g/ml) fatty ac1ds!aCid onic acid
____ ~M/~)a) (molar percent~)
--- - ~' '----'- - 64 ~ 2 18.3 17.5
Jarriomycin 1 40.3 59.2 25.9 14.9
sodium 3 42.4 59.6 25.3 15.1
lo L~ 9 58.1 28 ~ 3 13.6
3o 3o 37.8~,_ 56.3 31,2 12 5
Monensin 1 38,5 60.1 23.8 16.1
sodium 3 37.7 60.1 24.1 15.7
lo 35. 59,6 26.2 14.2
_ 30 32.1 55.1 29. L~ 15 ~ 5
, . . ~ . _ _
7 --
a) I'he sum for acetic acld, propionic acid and
butyric acid
b) lhe mol percent of each fatty acid relative -to
the total amoun~ of vola-tile fatty acids~
It is apparent from ~able l that the addi-tion
of suitable amount;s of carriomycin does not decrease, but
rather increases 9 the total production of volatile fatty
acids and causes an increase of 42 to 93% in the molar
percent of propionic acid with decreases in the amounts
of acetic acid and butyric acid. ~he increase of production
of propionic acid by the addition of carriomycin is
significantly high as compared wi-th the addition of
monensin which is known to have an analogous activity.
Example_2
Effect of a carriom~cin-containin~ feed to fattening cattle
Fifteen Japanese Brown bread steers were used in
groups of 5 animals (average body weight: 237 kg).
- ~he test animals were fed on rations supplemented with
0, lO and 30 ppm of carriomycin sodium for 308 days to
investigate the effect of carriomycin supplementation,
~he feed comprised 9 parts by weight of a concentrate
containing 7~.6% of TDN and 1005% of DCP (la~le 2)
with l part of 5 cm lengths of rice straw, and was
made available ad libitum. ~eparately, mineral salt was
provided for ingestion ad libi-t;um. Wate~ was also provided
for free access from a waterer. Durtng
the experiment, feed intakes and body weights were
recorded at 2-week intervals and -the feed conversion
ratio were computed from -the records.
~able 2 Composi-t,ion of concentrated feed
~t~ L~ Percentage
__ _ _ _ .
Barley 3o
Corn 40
Whea-t bran 16
-
35~f
MaterialsPercentage
. . . _ ~
Rlce bran, defatte 1 6
~oybean meal 6
Sodium chloride 1.
Calci~m carbonate
. `~ 100 ,
~able 3 ~ffect of a carriomycin containing feed
to fattening cattle (average 65 cattles)
. ~r~nc^ _ Daily body ~ Daily feed ~l~3~-a~Z~G
of carriomycin weight gaina' intakeb) ratioC)
sodium in ration
(ppm) (kg) (k~)
0 0~91 8066 9.52
: 15 10 1.10 8.59 7.81
. . . ~ 1.05 8 L l 7.63
a: Body weight gain during the period
~ number of fa-ttening days
b: ~eed intake during the period ~ number of fattening days
c: ~leed intake ~ body weight gain
~ he results are presented in ~able 30 ~he additlon
of carriomycin to feed causes an increase of 15 to 21% in
body weight gain, without any significant change in feed
25 intake, thus resulting in an improvemen-t of 18 to 25% in
feed conversion ratio.
Example ~
Effe_t of a carriom~cin-containing feed to sheeP
~hirty sheep of the Japanese Corriedale breed with
an a~erage body weight of 24 kg were used in groups of
lO:animals, ~he animals were maintained on a ration
supplemented with 0, 3 and 10 ppm of carriomycin sodium
for 70 da~s l;o investigate the effect of carriomycin
35 supplementation, ~he feed contained 40% of a chopped
mixed hay ba~3ed on orchard grass and thimosy, 38% of
wheat bran alld 20% of corn~ ~ortified with 1% each of
- 9 -
calcium carbonate and sodium chloride. ~he ration was
made available ad libitum. Separately, minera] salt was
provlded for free access~ Drinking water was also provided
from a w~terer for lngestion ad libitum.
During -the experimental period, feed in-takes and body
weights were recorded at l-week intervals. The feed
convertion ratio was computed from -the records.
~able 4 ~ffect of a carriamycin-containing feed to
sheep
Concentration Dally body Daily feed ~eed conversion
sodium in ration weight gaina) intakeb) ratioC)
(PP~) (g) (kg) _
0 159 l.L~8 9.31
1~5 1.52 ~. 23
181 1,46 8.05
.... _ ~ _ _ . . . . _ . .. ~
! ``- a: Body weight gain during the period
~ number of feeding days
b: ~eed intake during the period . number of feeding days
c: ~eed intake -~ body weight gain
~ he results are summarized in Table 4. The addition
of carriomycin to feed causes an increase of 14 to 16% in
body weight gain without inducing any significant change in
feed intake, thus resulting in an improvement of 12 to
14% in feed conversion ra-tio.
ExamE~
~or the purpose of improving the feed utiliza-tion
in ruminants, carrlomycin or/and a salt thereof can be
used for example in the following dosage forms.
1) Carriomycin sodium 20%
n meal 80%
Total 100%
~he two ma-terlals are crushed and evenly blended -to
prepare a 20% powder of carriomycin sodium. ~hls 20%
11~4~
powder is added to feed at the level of 1.5 to 500 ppm and -the
resultant fortified feed is given to animals.
2) Carriomycin sodium 5%
Wheat bran 95.%
. . _ . .
Total 100%
The two materials are crushed and evenly blended to
prepare a 5% powder of carriomycin sodium. This 5~ powder is
added to feed at the level of 6 to 2,000 ppm and the resultant
fortified feed is given to animals.
-- 10 --
