Note: Descriptions are shown in the official language in which they were submitted.
2126~7
ANIMAL FEED ~DDITIVE ~OI~MUI,~'I'lON
q~e lnventlon rel~t~s ~o a forn~ulatlon for ~n anlme1
feed oddltlvo, end a~o tv en nnimal feod CoMpOsitiOn
lnoluding nuoh a form~letiol).
It le ulro~dy knowl- th~t w~len ~nl~ale oat a dlet in
whlo2l or~ani~ a~ld 19 malntelned or ~dded, f~r6tly ~hoy
demon~trate hlgher wel~ht ~in, end ~eoondly they ~onsum~
tnore feed.
~hu~, a oert~ln amount of work ha~ ehown the
po~ltlvc of~eots on plg-f~tenlng o oitric soid, 0
¦ fuma~io ao~d, and of prop~onio ~cld (Kiroh~e~ner and
Rot~, Fumario aold ~6 a fec~ ~dditivo in pl~ nutrltion,
Pig News nnd ~n~ormatlon 3, 259-~64, 19~27 Gle~tln~ and
E~etor, Re~pot-~e of ~tarter ~l~e to suppleme~tatlon of
15 corn soy4e4n moal diet~ w~tl~ or~nic ac~de, J. Anlm. Scl. ~ :
60, 1288-1294, l9B5).
: Thc ~ia~e of the art i9 el~o lllu~tratod by document
.~ P-~-O 233 ~lg wl-ioh descrll)es a food ad~ltive
form~let~on for ~nim~ls that oomprises ~) u mixture of
ao oo~cl~m sslts and (~ obutyric aoid nod (2) ut least
onc eoid ~e~ected from leova~eri¢ scld, valorlc aold, and
~-~ 2-m~thy~ butyrlo sold, ~b) 5~ to l5S o~ an addltlve
comprl~n~ 60~ to 100~ by weigh~ of oopr~ oli h~vlno An
iodlne indox ~reater tll~n 5~ and 0% ~o 40~ by wel~h~ of
~ as ~allow.
Al~o, v~rio~s cxp~r~mente ln ~nim~l nut~ltlon h~ve
; shown the advantR~e of a food sddltlve based on bu~yrlc
cld or on t~le sAlts ~heree~ for numorou~ ~nl~al ~peole~.
However~ that work 0en~rally le~ds to a ma~or
dlf~icul~y: ~h~t of butyr~ acld boing ropldly
; dl~oole~ed ln ~ho d~gestivo treot lnto o~her
`~ : oon~tltuents hevlng ~hor~or carbon oh~ln~.
; ~ Suoh di~ocle~on causos 2~utyrlo ~cld to oe~Be to
: h~v~ ~ny ~dvantA~O, nnd n~tur~lly 1~ preven~ b~tyrlc
Aald f~om renol-i.n~ the more remo~c portlons of the
dl~ostlve ~reo~, whlch ere of~on ~ho~e ~ t respond best
~` to ~2~e ~ion o~ ~he~butyrlc: eoid.
~ ,
~ ~ . . .. . .. . .. . . .
212fi~ ~
2,
~,The pro41cm ~ohind the inv~n~loll i~ therefore ~o
ipro~o~e en ~nlmal food ~ddltive ~ormul~tlon ln whl~h
butyrlo ~old i~ s~bllizod ~n lt~ C, form, thore~y
onab]in~ the Dvorago wol~ht of onlmal~ tl~t oonsume suo~
¦5 ~ feed additlvo to ~n~re~e ~l~ni~l~antly.
~~0 t~B en~, tho inv~ntion proE)o~:os a formule~ion
~or ~n anima~ feed Dddltlvo in ~iolld form tl~et 16
:,oh~r~oterl~od in ~llat lt aom~rlso~ ~ blnory mlxture of
~~odlun~ butyrate and o ot~yl bu~yratoi, the quontlty of
r`~10 ot~,y~ butyr~o ln th~ mixturo lylng ~n the r~n~4 1~ to
25~ ~y wel~ht rol~ive to ~ot~l ~nixture wcl~ht.
~;O~hQr oh~ractcrlst~o~ olld advunt~ge~ ~f th~
lnventlon ~ppo~r on rcadln~ th~ following dotalled
desoripti~n and examples.
Tho formulatlon o~ e lnvontion for an ~nim~l feed
addltlve 1~ ln so~d ~orm ~nd oomprl~cs a blnary mixt~re
of ~odlum butyrate ~nd of ethyl butyr~te .
8~oh a ~ormu~tloll ~erv~ ln partiou~sr ~o stablll~e
butyrlc aoid in lt~ C~ fo~n~
: 20 ~odlum bu~yratQ h~ multiple influonoe~ on anlmal
. metHbol l~m, . .
Pr~or to bnit-9 absor~od, 1t govcrn~ the oompo~itlon
: of the eplmural flor~ (dlreot o~ot I) by lnhlblting ~he
: ~ro~fer~ W oll of v~riou~ hactcrla (Esoherloh~ B coll) or
~5 by h~vln~ no ef~oct on thc ~ivi~lon o~ other bacter~
(~noto~c~ h~ 8 me~ns t1-at tho m~keup of the
~:epimural f~or~ i6 fornled 1n mor~ optimum manner ln the
pre~enoe of b~tyrate.
~-~;In ad~lt;ion, the butyr~te e~o has an optlmum effect
~;30 Wlli le lt ~ being ab orhod. ~t ~nor~a~es N~ oxchange
(dlrect ~ffeot ~I).
5~he butyrsto then pcn~tr~tos lnto tl~o cells oov~rlng
th~ dlgegtive trsct w~ero it. may be transformed by
:~.; ~metaboll~m or lt m~y eorv~ ~e an aotlvator for varlou~
en~me~ (d~re~t o~feot Ill ) .
Onoe ab~orbod, lt i~ brou~ht lnto oontact by
clroulotion o~ the 4100d wlt.l~ varlouB ocll8 of tho
. . .
2126 .~7
orgBni~:ln, thUB Bt,illlU~ -ti l~g E~l~CrC~tiOJl o:t oert41n hormones
~n~ulln, glyo~on, dlreo~ of~oot I~).
Tlli B lncre~c In horlllone conoen~ru~ion o~n ~lve rl Be
to ~tlmul~tlon ond ~ro~f~rotlon ls~ ~he oell~ of the
dlgosW ~Q ~rac~ ~lnd~reot effno~ V). ~hl~ lndlreot
notlon of ~utyrate O~U~OB ~n lncrcaso ln ~he ebsorptlon
~r~e of the dlg~tive traot, ~tlmulatln~ trnn~port
m~ohnnl~
Slnce the pre~enoe of butyrate el~o incre~scs
~0 p~oduotlon of butyrat.~ elf (o~eot I), orel
Qdmlni~tra~lon of ~utyr~c, o~e~l ln enlell qu~ntltle~,
~l~y~ ~n lm~or~n~ rol~. q'he butyr~ oonsumod lncre~sos
ln quanti~y in th~. d~e~tlvc tra~t in ~ oh~ln re~otlon.
In ~ddltlon, orel~y admln~tered ~utyra~e ~1BO ha~ ~n
optln~um effect ln r~motc portlolls of the dlge~tlve truct,
; whi~l o~ten ro~pond bost to lt~ ~otlon (c.g. ~he
stom~ch).
¦ q~o ~c~l~eve ~uoh Optilllllm ~ction, ~-e qUDn~ity of
ethyl but~r~te ln ~l~e bln~ry mixturo of ~l-c type of the
: 20 inv~ntion 1108 in ~hc ra~ge 14 to 25~ ~y wel~h~ rel~tlv~
- to th~ ~o~el mlxt;ure wcl~ht.
In par~iou~er th~ quantl~y of ct)~yl bu~yr~te ln the
mlx~ure.ll~ in tho rongo 10~ to 20~, and more
partioul~rly 1~ a~ou~ 20~ by woight rcl~tlve to the totol
mixture woight.
Aooording to allother ol~araotcrl6tlc of the
lnvontion ~e sodlum butyra~e 1~ synthesi~ed by
n~utral~7.1.ng bu~y~io eold wi.th ~odlum ~lt~ of phosphorlc
acld ~lec~ed from tho grouE oomprlsing in p~rticulor
~odlum dilydrogon pl~o~phat~ dlsodlum pho~phate and
~rlsodlum pho~plla~e.
~urln~ thi~ neutralizot.lon of tho ~utyrlc oold ~I~o
~9 ~odlum ~al~ ~f pho~phorlo ~old 18 B~l ooted ~o that the
pKo of tho butyrl~ ocld iB ~ han the mathema~l~al
3S - menn of thc ~econd end third dl~sool~tlon eona~anto o~
pho~pho~lo aold.
~n o preferr¢d v~rlent o~ tl~o inventlon the sodium
.
~ 21 2 6 J~ I
butyratn ~ Rynthosized by n~ut;r~llzll-~ butyria 4cld wlth
trlsodium ~hosp}~a~e.
~he syn~le~l~ o~ ~diu~l butyr~t;e i~ porfo~med on the
'ba~ls of e mix~urn of butyrlo ~oid ~nd of the salt~ of
.,~S pho~phorlc ~old in ~ mo~eJ~ ~tlo o~ 2:1 respoctlvely.
~In i~ preerrod ~ri~nt of ~}le inventlon, the EoAlum
;:~uty~te 1~ synthe~lzod ~rom a n~lxture of butyrlc ~ol~
.~nnd salt~ of phos~l~orio ~cld ln equlmol~r proportlons.
~~s mentlonod ~bovo, or~l adnlini~trution of the feed
¦10 addit;~ve formul~t~on of tl~o lnvcnt,lon ~ proferred,
p~rtlcul~r~ in tllo forlll oi t~let~ und/or gr~nul~tes,
~ ho formulet.~ori of t~o inventlon 1B ~dded to feed in
Bn ~moun~ t~t 11c~ ` ln tho r~n~e 0,1~ to 10~ by wel~l~t of
t;he fecd.
15MorQ p~rtiou~lrly, it i~ addod to t,ho feed ln an
~$l
~mount oorrespolldln~ to ~bout 0,17~ by wel~ht of tho
feed.
~ hu~, if thi~ concen~r~tlon of sodiun~ butyrate 18
compere~ with the food ~onool)t~at~ons ~e~orlb~d ln the
;~.20 llter~ture rel~t;ive ~o tllo ~BO c~f cltriG acid, of fumari~
~i
aoid, an~ of proplonlc aoid, in par~loular for pl~B
(wh~oh oononntra~lon~ lle ln the range 0.6~ to 4~), lt 18 .
observod that ~o~lum ~utyrato c~n exort lte poeltlve
eff~ot in conoentratione thflt nro 3.6 to ~4~2 tlmes
~mnllor th~n tllo~e r~qui rod for tl)e orgonlo acld~ th~,.~
oro ln aommon UBC.
~~he lnvan~ion a~ 80 propoBee an ~nlmal feod
¦~oomp~ lon lno~udln~ tho ~n~m~l addlt-lvo formul~t~on
who~e oh~raoteri~tic~ aro glvon ~40v~.
Suoh a ~oe.d composltlon le eppliod to feed fo~
ca~o and~or pl~8 and/or poultry.
~y way of non-~mltlng ex~mple, montion may b~ modo
of tho fol~owlng experimontal ~eRults releting to tho
, .~ nynth~l6 of ~oflium ~utyrato from ~utyrlo ~old ~nd sodlum
x 35 ~ of pho~pl~oric ac:~d.
~ho followln~ ~olution~ wore ~sed:
~, N~HP04 ~M ~nd hu~yric ec~id lM
~'
'~
2126.j~
.
Il. NAzHPO~ lM nnd ~utyric aold lM
~II. Na3~0~ lM and but~rlo aoid lM
1~, Na~P04 lM end ~utyrlo ~ld 2M
~he o~Jeot of tho expo~mell~s wes to oxamlne t~e
¦5 neutra]~7.~tl0n of ~utyrlo aoid (for fornllng ths ~odium
~utyrate~ u~n~ Na2HP0~ or Na3P0~, 4nd ~o study th~ -
quantltat;i~e aond~t~ons of th~ ro~otlon.
~o this end, tl~e oporetion~l oondltlons were
~ollow~:
qu~ntity of sodiu~n salis o~ phosphorlo acld uBed:
: 5,000 ~;
determlne~ion of the pll of tho ~mple: 3G0 m~ of the
rosultln~ ~ir-dri.od sam~o~ wero dissolved ln dl~tllled
water, the p~ of tho resultl.~ olution ws~ me~gur~d, Hnd
tl~rated Witll 0.1 ml of ~N 1l~1 (pll 2); and
determ~netlon of th~ ~utyrlc sold concentrntlon:
500 mg o~ ~amplo~ wer~ di~sc11vod ~n ~00 ml of dl~tllled
water (2.5 mg/om3). 1 ml of 0.~ M oxallo ~old ana 5 ml
of ~nmplo were ~dded to ~.0~ of the BO~ utlon obtulne~ in
thl6 way. ~fter contrlf~lglng, tl~e aonoentratlon of
~:~ . butyrlc acld l~er~od w~s do~erminod by ~ns
chrolnatograpll~.
Known qu~nt~ tleB of butyrlc ~cid ~nd of sodlu~ selt~
of pho~phorlo eo~d woro mlxcd without coollng and were
:25 maint~ine.d at amblent ~omper~ture of ~ days- An~lys~s
were perfornlod on t:he flr~t, the thl~d, and t-he ~lxth
da~.
~: EXA~L~ I -
~30 5Q00 m~ of Na~HP0~.2H~0 t2~.i mM)
1293 ~1 of butyri~ uold (14.1 m~)
. mol~r rAtlo Na~Hro~.2H~o~bu~yrla ~oid ~ 2/1
. plt of a O.S~ ~queou~ solution on tho l~t day: 8.92
. butyrlo hold oon~ent on t:)~e lst- d~y: 0.01 mM/l
Re~ults no roa~ion.
.~.
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:
2126 ~7
G
EXAM~E I~
5000 nlg o~ N~21l~0~.2~l~0 (28.1 m~)
+ 2~8~ of buty~io nold (28.1 mM)
. molar r~tio: N~2H~0~.~11zO/hu~y~lc aold ~ 1/1
. p~3 of e 0.5% ~ue~us eolution on the l~t duy: 7.11
pH of a 0.5~ aquoous ~olutlon on ~l1e 3rd d~y; B.~2
. butyrio ~ald oontent on tho lBt day: 7.69 mM/l
. 4utyrlc AC~ d conton~ O~ ~h~ 3rd day: 0.47 mM/l
. butyric aold content on the 6tll day: 0.23 mM/l
Re~ul~: no roaotion.
EX~MP~
5000 mg of Na3HP~4~125~20 (~. 2 n~M )
121~ f ~lutyrlo ~cld (13.2 m~)
~5 . moler rat,io: Na~HPO,.l2~120/bu~yric ~cld ~
. pll of a 0.5% eq~eous Bolutl on en ~he 3rd duy: 10. sa
. butyrlc ucid con~ont on t~e 3rd day: 10.76 nlM/l
. but~ric ~old ~ontent on t~lo 16t day: 9.1~ mM/l
Re~ult: 100~ of th~ ~utyrlo ~cid wa~ ~r~n~forme~ lnto
sodlum bu~yroto.
EX~MPLE IV
5000 ~g of Na3HP0~.12H20 t13.2 mM)
2429 l~l of ~utyrio ~cld ( 26. 4 n~M)
: 25 . mo~ar ra~lo: Na~1P0,.1211-~0/bu~yrlo acid ~ 1/2
~,~ . pTI o~ a O.S~ aqueou~ solution on thc 3rd d~y: 7.g7
. butyria aold oonten~ or~ th~ 3rd day; ll.95 mM/l
. butyrio acld contont on ~le l~t day: 10.15 m~/l
~esU~ t: 50~ ~f the b~tyric eoid wa~ transformea lnto
sodium butyr~te.
~-:
~he fol~owing aonoluslons n~ay bc drswn from the
above example~: :
inco butyric eo~d 1~ we~kor th~n pl~o~phorlo
~cld, Na~PO~ o~m~o~ be fully ~ibereted from lt~ ~nlt by
butyrio ~old.
On the b~sls of the ro~ults o~ ~xan~pl~g I ~o lV
2126~7
:~ ~ r/
gl~en ~bovo, ~t oan ~o ~oon tha~ tl~o ~eaotion Na3PO~ -~
~ Na2HPOJ t~ke~ P1BOO ( ~ QnlU10~ and IV); whercas ~he
i re~otlon N~2ll~0~ ~ Nall2~ dDo~ no~ ta~e plooc tEx~mple~
~nd II).
~hi~ ro~ult aan ~ explainod ~8 follows~ lf lt 1
d~.~irod to llbnr~te N~9rO, fronl it~ ~alt, then ths
di~ooiatlon oon~nt of ~u~yrlo eo~d (pKa ~ 4.8~) ~ugt
;~ be em~ er ~han th~t of pho~pl~orio ~old or. of lte
qu~valent polnt~.
~noe phosphor~ acld lle~ threo di~sool~tlon
aon~ten~ (p~C~ ~ 7..~2; plCe2 ~ 7.21, pXa3 ~ 11.75), lt~
oquiv~len~ ~re ~lvon by th~ arlt.l~ etlo moan~ thsreof
' (flr~t equivalont point: er~h~ct~o nlean of pKu~ ~nd pKa~
¦ - 4.67: ~econd oqui~alent point; ~rlthmetl~ mean of pK~z
~nd pKa~ ~ ~.4R), whloh ~e~ermine the ohellllc~l re~o~lonR
t~t take pl~co.
llowever, ~t c~n ~o ~a~~ t the p~ of butyrlc Mold
1~ greeter tl~n the flr~t. ~qulv~en~ polnt ~ pho~phorlo
aoldt ln other word~:
ao pK~ (~utyrlc Ao~d) ~ Kal ~ P~2)
. ~n ~ont;rast, tho ~8 o~ butyrlc ~old l~ les~ thun
~he ~e~,ond eq~lvA~ ont point of pl~osp~orlo acid; ln other
word~:
pK~ (~utyrlc a~id) c ~(pKez ~ pK~3)
~; 25 That 1~ why only tt)o first, ~bovo-n~cntlonod reootlon
-.j
~: o~n t~ke plaoe.
2) Al~hou~ll ono mo~o of N~3~0~ 18 cap~b~ e of
n~ut~al~ ?.i ng on~ mole o~ ~utyrlo acld, the quantl~le~ of
com~ounfl~ dn~oribod in Exan~p]o III ere tl~e ~o~t
' 30 eppro~r~ete for neutr~ .ln3 ~utyrlo ~cld and, B~ a
result, for ~mplcm~r)tll-g t~le forlllulatlon of tho
in~entlon.
~, 3) lf butyrl~ aoid ~oe~ not forn~ 80dlun~ ~utyrot~, lt
l~ not Bte~le Anfl i B VO~ e-tllo et am~ient to~peratu~e-
.
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