CA2053908A1 - Method of enhancing egg laying in turkeys using epostane - Google Patents
Method of enhancing egg laying in turkeys using epostaneInfo
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- CA2053908A1 CA2053908A1 CA002053908A CA2053908A CA2053908A1 CA 2053908 A1 CA2053908 A1 CA 2053908A1 CA 002053908 A CA002053908 A CA 002053908A CA 2053908 A CA2053908 A CA 2053908A CA 2053908 A1 CA2053908 A1 CA 2053908A1
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- Prior art keywords
- epostane
- egg laying
- egg
- turkey
- hen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
The method of enhancing egg laying in the turkey which comprises administering to a turkey hen an amount of epostane sufficient to increase significantly the number of eggs laid during the egg laying cycle of said turkey hen is disclosed.
Description
WO9~3/15608 ~ U ~ PCT/U~90/02933 Use of epostane to enhance egg laying .n turkeys.
Fleld of .he I~ven~ion ; The inven~ion relates co a process of ennancing eg~ laYing in turkevs us.ng epostane. I
Infor~a~ion Disclosure S~atemen~
Epos.ane is the Uni~ed Staees Adopted Name (1988 US~ and the USP Dic~ionary of Drug ~ames, 1961-1987 Cumulative List) for (4~
17~)-4.5-epoxy-3,17-dihydroxy-4,17-dLme~hylandros~-2-ene-2-carboni-trLle ha~ing the s~ructural formula C
~ .... C:~
.`;C ~,J Formula I
"~
(represanelng th~ onol eorm) an~ haviA~ ucLli~ a~ an Lncer~eptLve ' (pregnaney disrupein~) agenc.
Chriscians0n U.S. Pat. ~,160,027 lssu~d July 3, 1979 describes epostane as the produe~ Oe part (f) of E~PLE 1, thac is, ~l~, 5~-epoxy-17~-hydroxy-4,17-dime~hyl-3-oxoandrostane-2~-carbonicrile having the struetural formula C~. OH
C~3 ~ --c-~
.~C., /\~ /~/~
o ~J Formula Il .i ~3 i :. : .: .. .. ... : . : , . : . : :: , . . :; : ::
W O 90/l560~ 2 0 ~ 3 9 ~ ~ PCT/US90/02933 -2~
which represen~s ~he keto forrn of epostane, The pacent shows the interceptive utilit~ of epos~ane in the rat and ~he monkev.
Epos ane has been st~cied for e~fects on fertility in numerous ma~malian species and the published resules of ~he studies conseituee a bibliography which in March of 1989 nu~bered 66 references, none of which relates to any avian species, Three of the references for which the bibliography contalns ahstracts relaee to ovulation. De Paolo (J. Endocrinol., vol.
118~1), pp. 53 68, 1~88, arld Snyder et al. (Proc. Soc. i`~'~?. Biol, .~ed., voL 1-7~3), pp. 238 247i, 1984) show lnhiblcion of ovulation in the ra~ with epostane and Webb ~. Reprod. F~.rtJI., vol 79(t), rr.
231-240, 1987) shows increase in ovulacion race in che ewe wieh epostane, The onl~ prior ar~ known co applicane relaeing to use of epostnno in an n~L~In ~pocios ~Iro 3S ~ollows~ (1) nn unpub1ir,hQd repor~ showin~ closo r~l3~d ~loar~s~ o pla~m~ pro~Q~3ron~3 nnd estrncliol concenerntLorls Lrl tho chick~rl eherow:Lth. Til~3 r~Qre L9 1n tho forrn ~ a lote~3~ dlle~t~ US~ 19, 1~85 Eroln ilo~i3L J. ~h~lrp of 'i~l-le A~r l a~ll tlO~rA ~ d i~ 3 ~ ~ AI'~ h ~ ln~ e L'~ R~ 3 n r(~ 3 R ~
Mlcllothian, ScocL~Rcl co i~. LoL30n o~ Sc~rlLng ~ln~hrop Gro~p Lcd. 1n Guildford, Englancl, throu~ whom epostane for the work had boen supp1ied; (ii~ 3 publlc.3eLGn entLtled STERLIhG DRUG I~C. PRESENTATIO~
TO E'INANCIAL COMMUN~T~' dated October 23, 1986 ln a part cntitlcd EPOSTA~E a~ pages 79-80 states at page 80 that "[t¦he endocrine 25 effects ~of eposeane] on egg produceion in poulery are also being pursued" and ehat "[t]his lateer indication is of particular impor-tance in the broiler industry". The first scatemenc merely sets rorth a goai and does no~ identify a species, The second s~atement identifies the chicken as a species "of particular impo~tance" and does not men~ion the turkey, Accordingly the presently described invention is not described or made obvious by the publication, Moreover, as shown below epostane was found not effective in enhanc-ing egg laying in the chicken.
Broodiness in the turkey hen i5 a physiological condition characterized by aggressive territorlal n~s~ pro~ection and lncr~ase nesting beh~vior with cessa~lon o~ egg production, whlch eogether with costs of additlonal labor and acilieies needed to maintain W O~30/1560X 2 0 5 3 9 0 g PCT/US90/02933 -3~
broody hens result in significant economic loss in the turkey indus~ry. The presently described and claimed invention fills a need for a solution to the egg production aspect of ~he proble~ in the ~urkey industry.
S SU~ARY OF THE INVE~TION
The Lnvention is the me;hod of enhancing egg laying in the curkey which comprises adminiseering eo a curkey hen an amounc of eposeane sufElclene eo Lncrease sLgnlflcantly ehe number of eggs laid durln~ the ~gg l~yLng c~ycle of s~ld turk~ h~n.
D~TAIL~ ~ESCRIP'rTO~ OF ~IE INV~,~TION
The egg laying cycle in the eurkey hen is aboue six months in duraeion. Near che end of the cycle egg productlon declines. At ehe end o che cyclc eho hen moles. E~8 productlon C0~.9~ flnd rises agaln ~s th~ n~w c~cl~ ensues, A hon rlormally produces 75-~0 c~g3 por cycle, thus one ~g every 2.0-2.4 dnys. A9 9t~t~d nbovo broodl-noss i5 A100 nn import~ e nctor Qf~ceLn~ ~,g produeeloF~ ln eurkoyhons. ~ccordLn~ly ~n ~rryLn~ o~le ~:ho 1nvonelon ~ c~ oE opos~no on nctors whlch r~lneo eo b~oodlnoss ~nd o~s~s prod~celvley n9 w~
egg productLon ies~lf w~re nlso studL~d.
Any amounc Oe epostana suffLclene co eEect a signiricanc incr~ase in thc numbor of eggs laid during the o~g laying cycle can be usod, The preeerr~d dose is in the ranQe of 0,1-10 mg./kg, per day. The epostane can be prepared for administration in any pharma-ceutically acceptable oral or paren~eral dosage form. The oraldosage form can be solid or liquid and thus granùles, capsule, tablet, solution, suspension or emulsion. The parenteral dosage form can be solution, suspension or e~ulsion. An ethanol-cottonseed oil vehicle is preferred. An oral dosage form is preferred. Gelatin : 30 capsules can be used, but the preferred oral dosage form is granules which may be mixed into or top-dressed onto the feed. Sustained release dosage for~s can be used. The daily dose can be given for as few as one day or as many as all the days of the egg laying cycle.
Daily doses for one day and five weeks (weeks 3~7) of the cycle werc used ln th~ tes~s descrlb~d bclow.
In a first t~st of ~h~ inv~lleion th~ cffeces o~ a singl~ 0, 1.25, 2,5, 5 or 10 mg,/kg, oral or parenteral dose of epostane on W 0 90/15608 2 0 ~ 3 9 0 ~ Pcr/us90/02933 -4- ~
blood plasma concencracion of progesterone, estradiol, corticosterone and prolactin and on eg~ production in the curkey h~n were deter-~ined. One hundred hen (110) 52-week old firse cycle turkey hens were divided randomly inco 10 groups of 11 hens each for the test.
The oral doses of epostane were given in gelatin capsules. For parenteral ad~inistracion the eposeane was dissolved in echanol-cot~onseed oil (10:90) at a concencration of 20 mg./ml. and given subcutaneously. 8100d samples were taken one w~ek b~Eore modicaeion and at 6, 12, 24 nncl ~-a hours posem~dlcation. Anal,sLci of the Eour blood plasma variables was done by radloLmmunoassay. Egg produceion was measured for 12 days before medication and 3 days postmedication, whereupon the hens were sacrificed. Daca were analy~ecl by analysis of variance.
Unlike the cffecc of eposcanc on blood plnsma progesterono concentration in ~namrnals tlO significant overall ofE~ct of do50 or route Oe fldrnlnl~r~tion Oe ~po~n~ on thls vnrl~bl~ w~s ob~rvod ln the curk6y h~n. A 91gnLEie~tle ~p ~ 0.0001) docr~Q ~hQrO1n WA9 corr~ L ci~ n~ a ~1 ~ 6 nr~ r ~ llnll le~ n, b~
ehLs wa~ ov~rcoln~3 hy r~bound rl~ 2l~ ~In~ 8 ho-lr~ ~ose~n~dleaeioR ~o thnt no sL~nlELc~nt ov~rall e~ ct o~ sa~npllll~ tilll~ was shown.
Significant r~duc~Lon of estradiol concen~ration based overall on doso Oe Qpostntle (p e 0.0001) and sampling timo (p ~ 0.02) WA9 observed, bue ~he effect of rouee oE adrnlnlscr~tLon w~s rloC signl-ficant. SLgnlican~ reduction of corticoseerone conc~ntraeion based overall on dose (p < 0.0001) and rou~e of administration (p <0.02) of epostane and sampling time (p < 0.03) was observed. No significant overall effect of dose or route of administration of epostane or ; sampling time on prolactin concentration was observed.
Egg production W2S measured as percent hen-day egg production, which is defined for a given group of hens and a given number of days as:
percent hen-day eg8 production ~ the number of eg~s laid x 100 the number of hen9 x the number oE
days Egg produccion results o~ ~h~ ~lrs~ cesc ~rc prescn~d in T~bl~ 1.
~va~u~
~0 90/~560X ' ' PCT/US90/02933 Table I
Flrst Test - E~P Production Epos~ane Percent Hen-Dav E~g Produc~ion Dose Premedicatlon Postmedicaeion 5 (mg./k~.~ Qral Parenteral Oral Parenteral 0 47.0 34.5 24.0 51.7 1.25 37~3 35,5a 26,7 6o~oa 2.50 27.1 30.9 12.0 ~6.7 ;.00 '~9.8 ~0~9b 21.0 70~ob 10.~0 57.3 39.1 66.7 56.7 a~D Significantly diferent (p < 0.03) As shown by Table I the 1.25 and 5.00 mg./kig. parenteral dose groups showed slgnLf'icanc increases in egg production. This was consldered l; encourflglng bocause onlv .~ singl~ do5~ W~S gLvon to e~ch han nnd only threc days' egg pro~luction pos~n~ecllcaticln w~s. mo~aurocl, Ll~ CO~ ti o~ lv~nel~n ~ih~ 0, 0,625, 1.25 ~nd 2.50 l~lg,/k~. ornl do~;~9 n~ flpo~ ln~ dnLly ~r ~Lv~
W~ ;3 ~tl hlo~ 6~ ,0R~ eL~ r~s~it~ r~ L, corcLcos~rona, prol~cein, c~lelwn nncl protaln, ~gg production and egg charac~rlscLcs ln the broocly-pronc t~lrke~ hen were decermined.
Two hundred ~200) Elrsc cycle turkev hens prone to broodlnoss were divid~d r~ndomly inco 5 ~roups oE 40 hens each ancl lnduced to molt and ~herebv to be~in the'ir second laying cycles synchronously. The daily oral doses of epostane were given in gelatin capsules beginning with the third week of the egg laying cycle. Blood samples were taken daily from 10 hens in each dose group. Egg production and nesting behavior were determined six times daily. The hens were sacrificed two weeks after termination of medication and at necropsy the o~aries and uterus were examined. Analysis of progesterone, estradiol, corticosterone and prolactin concentrations were done by radiommunoassay. Analysis of calcium and protein concentrations was done colorimetrically. Data were analy~ed by analysis oE variance except egg charac~eris~ics and necropsy data, which were analy~ied by chi square analysis, A~i necropsy ~he ovary o~ ~ch hcn whlch cornplo~ecl ~ho ~esc WA~
examined. A normal ovary was considered indicatLve of egg produc~
.. , .. , . .. ~ ~ .
WC~90~60X 2 0 ~ 3 9 ~ ~ P~T/US90/02933 -6- ~
tivicy during ~he test period. A tumorous, juvenile or regressed ovary or one having a~resic follicles was considered indicative o~
lack of egg productivity during the tese period. The number of hens having normal ovaries (11/37, 10/38, 19/27, 13/40) was significantlv ; Breater (p < 0.27) in the groups medicated with epostane tO.313, O.625, 1.25, 2.50 mg./kg. respectively) than in ~he unmeclicated group (7/40). Each ovary was also examined for los5 of hierarchy oE
follicles ~ncl numbcr of prlmnry folllcles. The numbcr of hens showLrlg los~ o~ hl~rarchy oE Colllcl~3 ~5~35, 9/38, 7~36, 8/40~ was sLgnlfic~ ly gr~ater ~p ~ 0.03~-) ln the groups medicated with epostane (0.313, 0.62S, 1.25 ~g./kg. respectively) ehan in the unmedicated group (none). The number of primary follicles was significantly greater (p < 0.028) in the groups medicaeed with epost~ne than in the u~ncdicntccl gro-lp. Eposean~ thor~forc slgnl icantly revors~d ~he t~ncl~ncy cow~lrd n~re~.ic ov~rLfs ~nd tll~
con~cqucn~ inabiLl~y CO procluc~ og~ ncl slgni~lcnnel~ Incr~n~3Q
rccrulemenc o~ Polllcle3 fcr ov~llnelon ~In~l ehQ eon~l~aq~ne ~Ibllley eo prod-lc~ Inorc~ Ln ellrkoy hal~ prono e~ LoodillQ!~
Ov~arall e~3ge.q o~ a~o~ednQ ro~a~llen~3.0Fl orl bloocl pln9raa ~nrn~nuC-ers are shown in Tabl~
T~bl~ I~
Sec.ond Tes~ e~all alood Pl~s!na ~ara~ee~. E ~ç c es : Parameter Concentration 25 (Concentration Units) Unmedicated Hens EPostane Medicated Hens Progesterone 561a 825a (pg./ml.) Estradiol 57.66b 61.14b (pg./ml.) -Corticosterone 3 93C 5 07c (ng./ml.) Prolactin 1049 1095 (ng./ml.) Calci~m 15.8 16~1 tm~./dl.) Pro~ein /~ . 98 5 . 02 (g./dl. ) W O 90/1560~ 2 0 5 3 9 0 8 PCT/US90/02933 ~ .
. . ~
a Si~nificanely different (p < 0.006) b Significantly different (p < 0.01) c Significantly differen~ (p < 0.005) Increases in progescerone, estradiol and corticosterone concentra-tions were even more significantly (p < 0.0001) increased in produc-tive hens than in nonproductive hens. Plasma protein concencracions were also significancly (p < 0.0001) increased in productive hens.
Pla~ma prolacc~n concen~ra~lons were slgniflcanclv ~p ~ 0.0001) described in prcducelve hans.
Egg productlon resulcs of tho second test are shown in Table III.
Table III
~ w~ iQo Wock _ Q ~_Q~ Q~ 5 l ~0 ~ 3 2 5 l~
20 2 31 25 ~9 ~8 28 4 19 ~ 11 16 18 6 12 lS 11 32 25 8 4 ; 12 19 11 Egg production declined steadily in the unmedicated group due to increased broodiness during the test period. Epostane appeared to reverse this tendency partially in the medicated groups. During week 5 (the third week of ~edication) egg production was significantly greater (p 5 0.04) in the 1.25 and 2.50 mg./kg.dose groups than in 35 the 0.313 and 0.625 mg./kg. dose groups. During we~ks 6 and 7 ~the fourth and PlPth w~ks of medicfltion) egg productl~n w~Y slgnlEl~
cantly great~r ~p 5 0.04 and 0.01, respectively) in the 1.25 and 2.50 W O 90/1SfiO8 PCT/US90/02933 205~90~ -8- ~ I
Gsg./kg. dose groups ehan in the 0, 0.313 and 0.625 mg./~g. dose groups. During ~eek 8 (~he firs~ week postmedication) e~g production was significan~ly greater (p < 0.008) in the 1.25 mg,/kg, dose group than in the O and O.313 mg./kg. dose groups. This pattern of ' significance is not greatlY affeoted by correcting che results for hens which were unproduc~ive or which died or by normalizing the medicated groups against the un~edicated group, E8g weLgh~s and eggshell weights were sllghely decr~sasod in the ~ucllcat~sd do~s zroups, bue ~hes specL~ic g-avle~y of ch~ ~sggs WAS not a~feceed by ns~sdlcatlon. Th~so efEtscts are no~ consLder~scl important.
COMPARATTVE TEST I~ T~IE CHICKEN
A test was conducted to determine the effects of epostane on blood plasma hormone concentratic)ns and egg laying efficiency in chickens nearing the ~erminaeion of theLr a,ctive egg produc~lon, Two hundred ~200) hens were clivlded lneo 10 groups o~ 20 hens ~ach for the tu~t. ~n dupllcato groups opostancS was glven Ln the Eo~cl ~ally ior four weeks ae 0, 1.25, 2.5, 5,0 and 10 mg.~kg. IlloQtl plas~mrS.
concentra~lon~ o~ prog~raeQrono, oseracl:Lol, coreLcc,~e~,ronso ~nd ~rol~c~ln w~sro d~srlnLllt~sd l~s ~ t~ fl~Q ~ ~
Egg produceion rlnd ogg qualiey wesrQ tloeormln~d ln ~ll groups.
Preliminary evaluaeion Oe ehe data showJ thae eposeflne dLd not have a maJor eect on blood plasma hormone concenerations or egg laying eficlency in eh~ chicken.
: `~
Fleld of .he I~ven~ion ; The inven~ion relates co a process of ennancing eg~ laYing in turkevs us.ng epostane. I
Infor~a~ion Disclosure S~atemen~
Epos.ane is the Uni~ed Staees Adopted Name (1988 US~ and the USP Dic~ionary of Drug ~ames, 1961-1987 Cumulative List) for (4~
17~)-4.5-epoxy-3,17-dihydroxy-4,17-dLme~hylandros~-2-ene-2-carboni-trLle ha~ing the s~ructural formula C
~ .... C:~
.`;C ~,J Formula I
"~
(represanelng th~ onol eorm) an~ haviA~ ucLli~ a~ an Lncer~eptLve ' (pregnaney disrupein~) agenc.
Chriscians0n U.S. Pat. ~,160,027 lssu~d July 3, 1979 describes epostane as the produe~ Oe part (f) of E~PLE 1, thac is, ~l~, 5~-epoxy-17~-hydroxy-4,17-dime~hyl-3-oxoandrostane-2~-carbonicrile having the struetural formula C~. OH
C~3 ~ --c-~
.~C., /\~ /~/~
o ~J Formula Il .i ~3 i :. : .: .. .. ... : . : , . : . : :: , . . :; : ::
W O 90/l560~ 2 0 ~ 3 9 ~ ~ PCT/US90/02933 -2~
which represen~s ~he keto forrn of epostane, The pacent shows the interceptive utilit~ of epos~ane in the rat and ~he monkev.
Epos ane has been st~cied for e~fects on fertility in numerous ma~malian species and the published resules of ~he studies conseituee a bibliography which in March of 1989 nu~bered 66 references, none of which relates to any avian species, Three of the references for which the bibliography contalns ahstracts relaee to ovulation. De Paolo (J. Endocrinol., vol.
118~1), pp. 53 68, 1~88, arld Snyder et al. (Proc. Soc. i`~'~?. Biol, .~ed., voL 1-7~3), pp. 238 247i, 1984) show lnhiblcion of ovulation in the ra~ with epostane and Webb ~. Reprod. F~.rtJI., vol 79(t), rr.
231-240, 1987) shows increase in ovulacion race in che ewe wieh epostane, The onl~ prior ar~ known co applicane relaeing to use of epostnno in an n~L~In ~pocios ~Iro 3S ~ollows~ (1) nn unpub1ir,hQd repor~ showin~ closo r~l3~d ~loar~s~ o pla~m~ pro~Q~3ron~3 nnd estrncliol concenerntLorls Lrl tho chick~rl eherow:Lth. Til~3 r~Qre L9 1n tho forrn ~ a lote~3~ dlle~t~ US~ 19, 1~85 Eroln ilo~i3L J. ~h~lrp of 'i~l-le A~r l a~ll tlO~rA ~ d i~ 3 ~ ~ AI'~ h ~ ln~ e L'~ R~ 3 n r(~ 3 R ~
Mlcllothian, ScocL~Rcl co i~. LoL30n o~ Sc~rlLng ~ln~hrop Gro~p Lcd. 1n Guildford, Englancl, throu~ whom epostane for the work had boen supp1ied; (ii~ 3 publlc.3eLGn entLtled STERLIhG DRUG I~C. PRESENTATIO~
TO E'INANCIAL COMMUN~T~' dated October 23, 1986 ln a part cntitlcd EPOSTA~E a~ pages 79-80 states at page 80 that "[t¦he endocrine 25 effects ~of eposeane] on egg produceion in poulery are also being pursued" and ehat "[t]his lateer indication is of particular impor-tance in the broiler industry". The first scatemenc merely sets rorth a goai and does no~ identify a species, The second s~atement identifies the chicken as a species "of particular impo~tance" and does not men~ion the turkey, Accordingly the presently described invention is not described or made obvious by the publication, Moreover, as shown below epostane was found not effective in enhanc-ing egg laying in the chicken.
Broodiness in the turkey hen i5 a physiological condition characterized by aggressive territorlal n~s~ pro~ection and lncr~ase nesting beh~vior with cessa~lon o~ egg production, whlch eogether with costs of additlonal labor and acilieies needed to maintain W O~30/1560X 2 0 5 3 9 0 g PCT/US90/02933 -3~
broody hens result in significant economic loss in the turkey indus~ry. The presently described and claimed invention fills a need for a solution to the egg production aspect of ~he proble~ in the ~urkey industry.
S SU~ARY OF THE INVE~TION
The Lnvention is the me;hod of enhancing egg laying in the curkey which comprises adminiseering eo a curkey hen an amounc of eposeane sufElclene eo Lncrease sLgnlflcantly ehe number of eggs laid durln~ the ~gg l~yLng c~ycle of s~ld turk~ h~n.
D~TAIL~ ~ESCRIP'rTO~ OF ~IE INV~,~TION
The egg laying cycle in the eurkey hen is aboue six months in duraeion. Near che end of the cycle egg productlon declines. At ehe end o che cyclc eho hen moles. E~8 productlon C0~.9~ flnd rises agaln ~s th~ n~w c~cl~ ensues, A hon rlormally produces 75-~0 c~g3 por cycle, thus one ~g every 2.0-2.4 dnys. A9 9t~t~d nbovo broodl-noss i5 A100 nn import~ e nctor Qf~ceLn~ ~,g produeeloF~ ln eurkoyhons. ~ccordLn~ly ~n ~rryLn~ o~le ~:ho 1nvonelon ~ c~ oE opos~no on nctors whlch r~lneo eo b~oodlnoss ~nd o~s~s prod~celvley n9 w~
egg productLon ies~lf w~re nlso studL~d.
Any amounc Oe epostana suffLclene co eEect a signiricanc incr~ase in thc numbor of eggs laid during the o~g laying cycle can be usod, The preeerr~d dose is in the ranQe of 0,1-10 mg./kg, per day. The epostane can be prepared for administration in any pharma-ceutically acceptable oral or paren~eral dosage form. The oraldosage form can be solid or liquid and thus granùles, capsule, tablet, solution, suspension or emulsion. The parenteral dosage form can be solution, suspension or e~ulsion. An ethanol-cottonseed oil vehicle is preferred. An oral dosage form is preferred. Gelatin : 30 capsules can be used, but the preferred oral dosage form is granules which may be mixed into or top-dressed onto the feed. Sustained release dosage for~s can be used. The daily dose can be given for as few as one day or as many as all the days of the egg laying cycle.
Daily doses for one day and five weeks (weeks 3~7) of the cycle werc used ln th~ tes~s descrlb~d bclow.
In a first t~st of ~h~ inv~lleion th~ cffeces o~ a singl~ 0, 1.25, 2,5, 5 or 10 mg,/kg, oral or parenteral dose of epostane on W 0 90/15608 2 0 ~ 3 9 0 ~ Pcr/us90/02933 -4- ~
blood plasma concencracion of progesterone, estradiol, corticosterone and prolactin and on eg~ production in the curkey h~n were deter-~ined. One hundred hen (110) 52-week old firse cycle turkey hens were divided randomly inco 10 groups of 11 hens each for the test.
The oral doses of epostane were given in gelatin capsules. For parenteral ad~inistracion the eposeane was dissolved in echanol-cot~onseed oil (10:90) at a concencration of 20 mg./ml. and given subcutaneously. 8100d samples were taken one w~ek b~Eore modicaeion and at 6, 12, 24 nncl ~-a hours posem~dlcation. Anal,sLci of the Eour blood plasma variables was done by radloLmmunoassay. Egg produceion was measured for 12 days before medication and 3 days postmedication, whereupon the hens were sacrificed. Daca were analy~ecl by analysis of variance.
Unlike the cffecc of eposcanc on blood plnsma progesterono concentration in ~namrnals tlO significant overall ofE~ct of do50 or route Oe fldrnlnl~r~tion Oe ~po~n~ on thls vnrl~bl~ w~s ob~rvod ln the curk6y h~n. A 91gnLEie~tle ~p ~ 0.0001) docr~Q ~hQrO1n WA9 corr~ L ci~ n~ a ~1 ~ 6 nr~ r ~ llnll le~ n, b~
ehLs wa~ ov~rcoln~3 hy r~bound rl~ 2l~ ~In~ 8 ho-lr~ ~ose~n~dleaeioR ~o thnt no sL~nlELc~nt ov~rall e~ ct o~ sa~npllll~ tilll~ was shown.
Significant r~duc~Lon of estradiol concen~ration based overall on doso Oe Qpostntle (p e 0.0001) and sampling timo (p ~ 0.02) WA9 observed, bue ~he effect of rouee oE adrnlnlscr~tLon w~s rloC signl-ficant. SLgnlican~ reduction of corticoseerone conc~ntraeion based overall on dose (p < 0.0001) and rou~e of administration (p <0.02) of epostane and sampling time (p < 0.03) was observed. No significant overall effect of dose or route of administration of epostane or ; sampling time on prolactin concentration was observed.
Egg production W2S measured as percent hen-day egg production, which is defined for a given group of hens and a given number of days as:
percent hen-day eg8 production ~ the number of eg~s laid x 100 the number of hen9 x the number oE
days Egg produccion results o~ ~h~ ~lrs~ cesc ~rc prescn~d in T~bl~ 1.
~va~u~
~0 90/~560X ' ' PCT/US90/02933 Table I
Flrst Test - E~P Production Epos~ane Percent Hen-Dav E~g Produc~ion Dose Premedicatlon Postmedicaeion 5 (mg./k~.~ Qral Parenteral Oral Parenteral 0 47.0 34.5 24.0 51.7 1.25 37~3 35,5a 26,7 6o~oa 2.50 27.1 30.9 12.0 ~6.7 ;.00 '~9.8 ~0~9b 21.0 70~ob 10.~0 57.3 39.1 66.7 56.7 a~D Significantly diferent (p < 0.03) As shown by Table I the 1.25 and 5.00 mg./kig. parenteral dose groups showed slgnLf'icanc increases in egg production. This was consldered l; encourflglng bocause onlv .~ singl~ do5~ W~S gLvon to e~ch han nnd only threc days' egg pro~luction pos~n~ecllcaticln w~s. mo~aurocl, Ll~ CO~ ti o~ lv~nel~n ~ih~ 0, 0,625, 1.25 ~nd 2.50 l~lg,/k~. ornl do~;~9 n~ flpo~ ln~ dnLly ~r ~Lv~
W~ ;3 ~tl hlo~ 6~ ,0R~ eL~ r~s~it~ r~ L, corcLcos~rona, prol~cein, c~lelwn nncl protaln, ~gg production and egg charac~rlscLcs ln the broocly-pronc t~lrke~ hen were decermined.
Two hundred ~200) Elrsc cycle turkev hens prone to broodlnoss were divid~d r~ndomly inco 5 ~roups oE 40 hens each ancl lnduced to molt and ~herebv to be~in the'ir second laying cycles synchronously. The daily oral doses of epostane were given in gelatin capsules beginning with the third week of the egg laying cycle. Blood samples were taken daily from 10 hens in each dose group. Egg production and nesting behavior were determined six times daily. The hens were sacrificed two weeks after termination of medication and at necropsy the o~aries and uterus were examined. Analysis of progesterone, estradiol, corticosterone and prolactin concentrations were done by radiommunoassay. Analysis of calcium and protein concentrations was done colorimetrically. Data were analy~ed by analysis oE variance except egg charac~eris~ics and necropsy data, which were analy~ied by chi square analysis, A~i necropsy ~he ovary o~ ~ch hcn whlch cornplo~ecl ~ho ~esc WA~
examined. A normal ovary was considered indicatLve of egg produc~
.. , .. , . .. ~ ~ .
WC~90~60X 2 0 ~ 3 9 ~ ~ P~T/US90/02933 -6- ~
tivicy during ~he test period. A tumorous, juvenile or regressed ovary or one having a~resic follicles was considered indicative o~
lack of egg productivity during the tese period. The number of hens having normal ovaries (11/37, 10/38, 19/27, 13/40) was significantlv ; Breater (p < 0.27) in the groups medicated with epostane tO.313, O.625, 1.25, 2.50 mg./kg. respectively) than in ~he unmeclicated group (7/40). Each ovary was also examined for los5 of hierarchy oE
follicles ~ncl numbcr of prlmnry folllcles. The numbcr of hens showLrlg los~ o~ hl~rarchy oE Colllcl~3 ~5~35, 9/38, 7~36, 8/40~ was sLgnlfic~ ly gr~ater ~p ~ 0.03~-) ln the groups medicated with epostane (0.313, 0.62S, 1.25 ~g./kg. respectively) ehan in the unmedicated group (none). The number of primary follicles was significantly greater (p < 0.028) in the groups medicaeed with epost~ne than in the u~ncdicntccl gro-lp. Eposean~ thor~forc slgnl icantly revors~d ~he t~ncl~ncy cow~lrd n~re~.ic ov~rLfs ~nd tll~
con~cqucn~ inabiLl~y CO procluc~ og~ ncl slgni~lcnnel~ Incr~n~3Q
rccrulemenc o~ Polllcle3 fcr ov~llnelon ~In~l ehQ eon~l~aq~ne ~Ibllley eo prod-lc~ Inorc~ Ln ellrkoy hal~ prono e~ LoodillQ!~
Ov~arall e~3ge.q o~ a~o~ednQ ro~a~llen~3.0Fl orl bloocl pln9raa ~nrn~nuC-ers are shown in Tabl~
T~bl~ I~
Sec.ond Tes~ e~all alood Pl~s!na ~ara~ee~. E ~ç c es : Parameter Concentration 25 (Concentration Units) Unmedicated Hens EPostane Medicated Hens Progesterone 561a 825a (pg./ml.) Estradiol 57.66b 61.14b (pg./ml.) -Corticosterone 3 93C 5 07c (ng./ml.) Prolactin 1049 1095 (ng./ml.) Calci~m 15.8 16~1 tm~./dl.) Pro~ein /~ . 98 5 . 02 (g./dl. ) W O 90/1560~ 2 0 5 3 9 0 8 PCT/US90/02933 ~ .
. . ~
a Si~nificanely different (p < 0.006) b Significantly different (p < 0.01) c Significantly differen~ (p < 0.005) Increases in progescerone, estradiol and corticosterone concentra-tions were even more significantly (p < 0.0001) increased in produc-tive hens than in nonproductive hens. Plasma protein concencracions were also significancly (p < 0.0001) increased in productive hens.
Pla~ma prolacc~n concen~ra~lons were slgniflcanclv ~p ~ 0.0001) described in prcducelve hans.
Egg productlon resulcs of tho second test are shown in Table III.
Table III
~ w~ iQo Wock _ Q ~_Q~ Q~ 5 l ~0 ~ 3 2 5 l~
20 2 31 25 ~9 ~8 28 4 19 ~ 11 16 18 6 12 lS 11 32 25 8 4 ; 12 19 11 Egg production declined steadily in the unmedicated group due to increased broodiness during the test period. Epostane appeared to reverse this tendency partially in the medicated groups. During week 5 (the third week of ~edication) egg production was significantly greater (p 5 0.04) in the 1.25 and 2.50 mg./kg.dose groups than in 35 the 0.313 and 0.625 mg./kg. dose groups. During we~ks 6 and 7 ~the fourth and PlPth w~ks of medicfltion) egg productl~n w~Y slgnlEl~
cantly great~r ~p 5 0.04 and 0.01, respectively) in the 1.25 and 2.50 W O 90/1SfiO8 PCT/US90/02933 205~90~ -8- ~ I
Gsg./kg. dose groups ehan in the 0, 0.313 and 0.625 mg./~g. dose groups. During ~eek 8 (~he firs~ week postmedication) e~g production was significan~ly greater (p < 0.008) in the 1.25 mg,/kg, dose group than in the O and O.313 mg./kg. dose groups. This pattern of ' significance is not greatlY affeoted by correcting che results for hens which were unproduc~ive or which died or by normalizing the medicated groups against the un~edicated group, E8g weLgh~s and eggshell weights were sllghely decr~sasod in the ~ucllcat~sd do~s zroups, bue ~hes specL~ic g-avle~y of ch~ ~sggs WAS not a~feceed by ns~sdlcatlon. Th~so efEtscts are no~ consLder~scl important.
COMPARATTVE TEST I~ T~IE CHICKEN
A test was conducted to determine the effects of epostane on blood plasma hormone concentratic)ns and egg laying efficiency in chickens nearing the ~erminaeion of theLr a,ctive egg produc~lon, Two hundred ~200) hens were clivlded lneo 10 groups o~ 20 hens ~ach for the tu~t. ~n dupllcato groups opostancS was glven Ln the Eo~cl ~ally ior four weeks ae 0, 1.25, 2.5, 5,0 and 10 mg.~kg. IlloQtl plas~mrS.
concentra~lon~ o~ prog~raeQrono, oseracl:Lol, coreLcc,~e~,ronso ~nd ~rol~c~ln w~sro d~srlnLllt~sd l~s ~ t~ fl~Q ~ ~
Egg produceion rlnd ogg qualiey wesrQ tloeormln~d ln ~ll groups.
Preliminary evaluaeion Oe ehe data showJ thae eposeflne dLd not have a maJor eect on blood plasma hormone concenerations or egg laying eficlency in eh~ chicken.
: `~
Claims (7)
1. The method of enhancing egg laying in the turkey which comprises administering to a turkey hen an amount of epostane sufficient to increase significantly the number of eggs laid during the egg laying cycle of said turkey hen.
2. The method according to claim 1 wherein the amount of epostane is in the range of 0.01 ? 10 mg./kg. per day.
3. The method according to claim 2 wherein the dally dose daily given for as few as one day or as many as all the days of the egg laying cycle.
4. The method according to claim 3 wherein the epostane is adminis-tered orally.
5. The method according to claim 3 wherein the epostane is adminis-tered parenterally.
6. The use of epostane for the manufacture of a formulation for the enhancement of egg laying in a turkey hen.
7. A formulation for the enhancement of egg laying in a turkey hen comprising epostane and a pharmaceutically acceptable carrier.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36742089A | 1989-06-16 | 1989-06-16 | |
| US367,420 | 1989-06-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2053908A1 true CA2053908A1 (en) | 1990-12-17 |
Family
ID=23447098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002053908A Abandoned CA2053908A1 (en) | 1989-06-16 | 1990-05-31 | Method of enhancing egg laying in turkeys using epostane |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0477218A1 (en) |
| JP (1) | JPH04506070A (en) |
| AU (1) | AU627885B2 (en) |
| CA (1) | CA2053908A1 (en) |
| WO (1) | WO1990015608A1 (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4870068A (en) * | 1986-05-22 | 1989-09-26 | Sterling Drug Inc. | Method of regulating fertility in swine using epostane |
| US4833133A (en) * | 1986-05-22 | 1989-05-23 | Sterling Drug Inc. | Method of regulating fertility in cattle using epostane |
| IL91392A0 (en) * | 1988-09-26 | 1990-04-29 | Sterling Drug Inc | Method of increasing the ovulation rate in swine |
-
1990
- 1990-05-31 AU AU56729/90A patent/AU627885B2/en not_active Ceased
- 1990-05-31 WO PCT/US1990/002933 patent/WO1990015608A1/en not_active Application Discontinuation
- 1990-05-31 EP EP90908765A patent/EP0477218A1/en not_active Withdrawn
- 1990-05-31 CA CA002053908A patent/CA2053908A1/en not_active Abandoned
- 1990-05-31 JP JP2508291A patent/JPH04506070A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU5672990A (en) | 1991-01-08 |
| AU627885B2 (en) | 1992-09-03 |
| WO1990015608A1 (en) | 1990-12-27 |
| EP0477218A1 (en) | 1992-04-01 |
| JPH04506070A (en) | 1992-10-22 |
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