GB2166951A - Steroidal immunogens for increasing ovulation in sows - Google Patents
Steroidal immunogens for increasing ovulation in sows Download PDFInfo
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- GB2166951A GB2166951A GB08527437A GB8527437A GB2166951A GB 2166951 A GB2166951 A GB 2166951A GB 08527437 A GB08527437 A GB 08527437A GB 8527437 A GB8527437 A GB 8527437A GB 2166951 A GB2166951 A GB 2166951A
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- United Kingdom
- Prior art keywords
- immunogenic
- steroidal
- sows
- derivative
- steroid
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- 230000003637 steroidlike Effects 0.000 title claims abstract description 28
- 230000016087 ovulation Effects 0.000 title claims abstract description 17
- 230000002163 immunogen Effects 0.000 claims abstract description 27
- 239000000262 estrogen Substances 0.000 claims abstract description 19
- 239000003098 androgen Substances 0.000 claims abstract description 17
- 238000002649 immunization Methods 0.000 claims abstract description 13
- 150000003431 steroids Chemical class 0.000 claims abstract description 13
- 229940030486 androgens Drugs 0.000 claims abstract description 10
- 239000002671 adjuvant Substances 0.000 claims abstract description 7
- 102000008100 Human Serum Albumin Human genes 0.000 claims abstract description 5
- 108091006905 Human Serum Albumin Proteins 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 27
- 241001465754 Metazoa Species 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 230000013011 mating Effects 0.000 claims description 11
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 claims description 10
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 claims description 6
- 230000035558 fertility Effects 0.000 claims description 6
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 claims description 5
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 244000144980 herd Species 0.000 claims description 4
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 claims description 3
- 230000001076 estrogenic effect Effects 0.000 claims description 3
- 229960003399 estrone Drugs 0.000 claims description 3
- 150000003515 testosterones Chemical class 0.000 claims description 3
- 229920002491 Diethylaminoethyl-dextran Polymers 0.000 claims description 2
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 claims description 2
- 229960003604 testosterone Drugs 0.000 claims description 2
- -1 7a - (2 - carboxyethylthio) -androst - 4 - ene Chemical compound 0.000 claims 2
- ZZHNYTLKRMBVAI-NLPXPOPTSA-N (8r,9s,10r,13s,14s)-13-(hydroxymethyl)-10-methyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound C([C@]1(CO)C(=O)CC[C@H]1[C@@H]1CC2)C[C@@H]1[C@]1(C)C2=CC(=O)CC1 ZZHNYTLKRMBVAI-NLPXPOPTSA-N 0.000 claims 1
- IATKKATWPOVYCC-VMXHOPILSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-2,3,6,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1CC2=CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 IATKKATWPOVYCC-VMXHOPILSA-N 0.000 claims 1
- BTTWKVFKBPAFDK-UHFFFAOYSA-N (9beta,10alpha)-Androst-4-ene-3,17-dione Natural products OC1CCC2(C)C3CCC(C)(C(CC4)O)C4C3CCC2=C1 BTTWKVFKBPAFDK-UHFFFAOYSA-N 0.000 claims 1
- 150000008065 acid anhydrides Chemical class 0.000 abstract 1
- 230000003053 immunization Effects 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229920002307 Dextran Polymers 0.000 description 4
- 229960005471 androstenedione Drugs 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000012173 estrus Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- DBHJTOHPFSRBBU-XEGGJJFLSA-N (8r,9s,10r,13s,14s)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthrene-3,17-dione Chemical class O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1.O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DBHJTOHPFSRBBU-XEGGJJFLSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- OZLABWUNIWIISO-UQHDCFDMSA-N 3-[[(7r,8r,9s,10r,13s,14s)-10,13-dimethyl-3,17-dioxo-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-7-yl]sulfanyl]propanoic acid Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3[C@H](SCCC(O)=O)CC2=C1 OZLABWUNIWIISO-UQHDCFDMSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000006003 cornification Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000003715 nutritional status Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000002294 pubertal effect Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 239000012465 retentate Substances 0.000 description 1
- 210000001625 seminal vesicle Anatomy 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 201000010653 vesiculitis Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C07J41/0016—Oximes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6081—Albumin; Keyhole limpet haemocyanin [KLH]
Abstract
The ovulation rate in sows, especially immature sows (gilts) is increased by immunization against one or more steroidal androgens or steroidal oestrogens, by administering an immunogenic derivative or conjugate of the steroid such as a conjugate with human serum albumin or an acid anhydride or the steroid combined with an adjuvant.
Description
SPECIFICATION
Biological method
This invention relates to a method of increasing fecundity in sows, particularly in immature sows such asgilts.
Because of their considerable economic importance, studies ofthe reproductive biology of domestic livestock have long been directed toward processes by which the fecundity offarm animals can be manipulated.
It has been shown thatthe ovolution rate of sheep can be increased by immunisation of sheep against steroidal androgens orsteroidal oestrogens, e.g.
using conjugates of steroidal androgens or steroidal oestrogens with immunogenic proteins.
In mature sows, the factor limiting fecundity (i.e.
littersize) is often uterine capacity ratherthan the ovolution rate as is the case with ewes. In immature sows such as gilts, i.e. young female pigs having a lowerovolution rate than mature sows,this is not always the case. Thus, for example, in the gilt, ovulation rate increases with increasing sexual age (number of oestrous cycles) up to about the fourth post pubertal heat; a sow at herfirst post farrowing oestrous may have a reduced ovulation rate due to her declining nutritional status in early lactation, an effect which the heavier mature sow does not exhibit. It has been found that in the case of immature sows fecundity can be increased by increasing the ovulation rate, and indeed, increasing the ovulation rate of maturesowscanalso be advantageous.
We have now found that it is possible to more fully utilise uterine capacity by increasing the ovulation rate in sows, especially immature sows, and ultimate lytheirfecundity, by immunisation ofthe sows against one or more steroidal androgens or steroidal oestrogens, e.g. using conjugates of such steroids with immunogenic carriers.
According to one aspect ofthe present invention, we thus provide a method of increasing the ovulation rate in a sow which comprises immunising the said sow against one or more steroidal androgens or steroidal oestrogens.
It will be appreciated that the lower ovulation rate of immature sows is a natural phenomenon and that immunisation according to the invention has the effect of increasing the natural ovulation rate of such animals to a higher level.
The term steroidal androgens as used herein is any steroidal substance that stimulates the expression of secondary sex characteristics of the male. Androgenic activity can be assessed by measuring the regrowth of the involuted comb of a castrated cock following androgen administration or by measuring the growth response ofthe seminal vesicles in castrated male rats following androgen administration. The term steroidal oestrogen as used herein isanysteroidal substance that stimulates the expression of secondary sex characteristics in the female. Oestrogenic activity can be assessed by measurement of uterine growth or cornification of the vaginal epithelium following oestrogen administrationtospayedfemale rats or mice.
An immunogenic conjugate between an im munogenic carrier and a steroidal androgen deriva tive or asteroidal oestrogen derivative for use in a method according to the present invention may be prepared by a technique known in the art (see, for example, British Patent 2071107 (CSIRO)). Suitable steroidal oestrogen derivatives include, for example, derivatives of androst - 4- ene - 3,17 - dione (androstenedione) ortestosterone. Suitable steroidal
oestrogen derivatives include, for example, derivatives of oestrone.
Thus preferred immunogens are prepared by the conjugation of an immunogenic carrier e.g. an im munogenic protein with adrost - 4 - ene - 3,17 - dione derivativesfunctionalised with an acid group at position 1,7, 11 or 15 ofthe steroid ring for example.
For preparation of immunogens againsttestosterone, testosterone derivatives functionalised with an acid group atthe 3 or 17 position may be used.
Thesteroidal androgen derivative may thus be testosterone - 3 - carboxy. methyloxime or more preferably 11 a - hydroxy - androst -4 - ene - 3,17 dione -11 cc - hemisuccinate or 70c- (2 - carboxyethylthio)androst -4- ene - 3,17 - dione. The preferred oestrone derivatives are those which after conjugation with protein and administration to an animal produce oestrone-specific antibody.
Non-limiting examples of such oestrone derivatives already known in the art include oestrone-3-hemisuc ci nate, oestrone-3-carboxymethylether, oestrone-6carboxy-methyloxime and 1 5-carboxymethyloestrone. Preferably the steroidal oestrogen derivative is oestrone-3-ca rboxymethylether.
The immunogenic carrier will generally be a protein of high molecularweight which is antigenicto the animal. Certain naturally occurring antigenic proteins are of particular interest, forexample homologous and heterologous serum albumins and thyroglobulins. In general, human serum albumin is preferred.
In general, the immunogenic compositions may additionally contain an adjuvant, in particular, diethylaminoethyl dextran, but any suitabble adjuvant known in the art can be used.
One aspect ofthe invention relates to a method of increasing the ovulation rate in sows, especially immature sows, which comprises administering to the sows an immunogenic composition comprising at least one immunogenic conjugate between an immunogeniccarrierandan androgenicsteroidderivative or an oestrogenic steroid derivative.
A further aspect of the present invention relates to a method of increasing the ovulation rate of a herd of sows which comprises immunising sows in the herd, especially immature sows, against one or more steroidal adndrogensorsteroidal oestrogens.
According to a furtheraspect ofthe present invention,we provide a method for increasing the fecundity of sows, especially immature sows, which comprises immunising the sows against one or more steroidal androgens orsteroidal oestrogens priorto the start ofthe mating period whereby steroid-binding antibodies are present in said animals during the mating period at a high enough titre to produce a significant increase in the ovulation rate, but low enough to ensure that substantially all the animals have displayed oestrus before the end of said period.
Thus,forexample, immunity is desirably increased, especially in immature sows such as gilts, by immunisation againstoneormoresteroidal androgens orsteroidal oestrogens,to produce a mean steroidbinding antibodytitre of 1 in 10 to 1 in 5000, preferably 1 in 30to 1 in 5000, at the start ofthe mating period and to maintain the said titre so that it is in the range of 1 in lotto 1 in 10000, preferably 1 in 30 to 1 in 10000, atthe conclusion ofthe mating period.
The steroid antibody titres in the case of immunisation with a conjugate between an immunogenic carrier and androstenedionefor example, can be measured using a dextran-coated charcoal radioimmunoassay procedure. Serial dilutions of plasma are prepared in buffer and a 300111 sample is incubated overnight with 1 00C1l of (1 ,2,6,73H) androstenedione (15,000 disintegrations per minute : 20-25 picog rams) at 4 C. Afterincubation, the bound and free fractions are separated using a dextran-coated charcoal suspension (500yI) and the radioactivity in the bound fraction which remains in the supernatant is counted in a liquid scintillation counter.The androstenedione antibodytitre ofthe sample is that dilution of plasma which binds 40% of the total radioactivity added The animals being immunised are desirably in moderateto good conditionfor age atthetime of mating.
In general, theinitial dose of hormone conjugate for immunisation per animal will be between 0.3-5mg.
Thus, for example, gilts weighing 100kg can receive initially between 1.2mg and 3.6mg ofthe conjugate, preferably 2.4mg of the conjugate. One or more booster doses at suitable intervals, e.g. between 14 and 35 days, preferably 21 days may be desirable in order to achieve the steroid-binding antibodytitres indicated above. The overall effective dose ofthe hormone conjugate maythus,forexample, be in the range 0.6mgto 8.0mg. Administration ofthe composition is most conveniently effected parentally, for example intradermally, subcutaneously or intramuscularly.
In general the volume ofthe composition given at each administration will be in the range of 1-6mI, preferably 4ml. The concentration of hormone conjugate in the composition will generally be in the range of 0.2-5mg per ml.
Allthepriorartimmunisationtechniques may be used to achieve the desired antisteroid antibody titres.
The following non-limiting example illustrates the invention.
(a) Preparation ofsteroid-protein immunogen composition.
A solution 7a - (2- carboxyethylthio)androst- 4- ene -3,17 - dione (79 mg) in dioxan (SmI) was cooled to 1 00C, stirred and treated with tri-n-butylamine (38 mg) and then with a solution of isobutyl chloroformate (28 mg) in dioxan (2.5 ml). This solution was kept at about 10for40 minutes with occasional shaking. Itwas then added over 2-3 minutes to a stirred solution of human serum albumin (HSA) (275 mg) in 0.1 M pH 7.8 phosphate buffar (10 ml).
After 24 hours the slightly hazysolution was dialysed against distilled water (300 ml, changed 11 times) for 192 hours at 5"C. The retentate was freeze dried to give the steroid-portein conjugate as a white froth (194 mg). Its ultraviolet absorption at 246 nm corresponded to a steroid incorporation of 26 moles per mole.
(b) Preparation ofsteroid-protein immunogen-adjuvantcomposition
The above steroid-protein conjugate (12 mg) was pasted in 0.9% sterile saline (0.2 ml). The paste was slowly diluted with more 0.9% sterile saline, with gentle agitation, to a total volume of 10 ml. Meanwhile a stock solution of DEAE-dextran was prepared by dissolving 15 gin distilled water (100 ml), adjusting the pH to 7.5-7.7 by slow addition of tris - (hydroxymethyl) - methylamine, and then diluting to 150 ml with distilled water. The immunogen-adjuvant composition was made by adding 10 mi ofthe DEAEdextran stock solution to the 10 ml ofconjugate solution in saline.
(c) Immunisation andMating Studies
Gilts were allocated to treatment at 150 to 170 days of age and injected at 14 day intervals with 2mI of the steroid-protein immunogen-adjuvant composition (equivalentto 1.2mg androstenedione-human serum albumin in 2ml DEAE-dextran as adjuvantr. Blood samples were removed atintervalsto determine if any antibodies to androstenedione had been formed by the pigs. The results indicated that successful antibodyformation was achieved in 100% of the animals treated and the range of titres produced were 1 in 10 to 1 in 5500. Control animals were left untreated.
The mean + (SEM) age atthetime of first detected oestrus was 243 7daysfortheinjected gilts compared to 233 + 5 daysforthe controls.
Each treated gilt therefore received between 5 to 7 injections priorto natural mating.
The arithmetic mean + (SEM) antibody titres to androstenedione during the course ofthe mating period ranged from 1 in 626 + 194 at day 230 to day 239 to 1 in 544 + 413 at day 250 to day 259.
(d) Litter Size
The litter size data indicated that immunised gilts produced significantly (P < 0.05) larger litters (10.7 + 0.7, mean + SEM, n = 11 litters) than the controls (9.1 +0.5,n=81itters).
Claims (20)
1. A method of increasing the ovulation rate in a sowwhich comprises immunising the said sow againstone or more steroidal androgensorsteroidal oestrogens.
2. A method of increasing the ovulation rate of a herd of sows which comprises immunising sows in the herd against one or more steroidal androgens or steroidal oestrogens.
3. A method of increasing the fecundity of sows which comprises immunising the sows against one or more steroidal androgens or steroidal oestrogens priorto the start ofthe mating period whereby steroid-binding antibodies are present in said animals during the mating period ata high enoughtitreto produce a significant increase in the ovulation rate, but low enough to ensure that substantially all the animals have displayed oestrous before the end of said period.
4. A method as claimed in claim 3 wherein the
mean steroid-binding antibody titre is between 1 in 10 and 1 in 5000 atthe start of the mating period and between 1 in 10and1 in 10,000 atthe conclusion of the mating period.
5. A method of increasing the ovulation rate in sows which comprises administering tothe sows an immunogenic composition comprising at least one immunogenic conjugate between an immunogenic carrier and an androgenic steroid derivative oran oestrogenic steroid derivative.
6. A method as claimed in any one of claims 1 to 5 wherein immunisation of an immature sow orsows is effected.
7. A method as claimed in any one of claims 1 to6 wherein immunisation is effected against androst - 4 ene -3,17 -dione and/ortestosterone or oestrone.
8. A method as claimed in any one of claims 1 to 7 wherein immunisation is effected by administering an immunogenic conjugate between an immunogenic carrierand an androst-4- ene -3,17 - dionederivative functionalised with an acid group at position 1,7, 11 or 15 ofthe steroid ring.
9. A method as claimed in claim 8wherein the androst-4 - ene -3,17 - dione derivative is 11 a hydroxy - androst - 4 - ene - 3,17 - dione or 7a - (2 - carboxyethylthio) -androst - 4 - ene, - 3,17 - dione.
10. Amethod as claimed in any one of claims 1 to 7 wherein immunisation is effected by administering an immunogenic conjugate between an immunogenic carrier and a testosterone derivative functionalised with an acid group atthe 3 or 17 position.
11. A method as claimed in claim 10 wherein the testosterone derivative is testosterone - 3 rboxymethyloxime.
12. A method as claimed in any one of claims 1 to 7 wherein immunisation is effected by administering an immunogenic conjugate between an immunogenic carrier and an oestrone derivative functionalised at the 3-position.
13. A method as claimed in claim 12 wherein the osetrone derivative is oestrone - 3 -carboxymethylether.
14. A method as claimed in any one of claims 8to 13 wherein human serum albumin is the immunogenic carrier.
15. A method as claimed in any one ofthe preceding claims wherein an immunogenic composition is employed containing an adjuvant.
16. A method as claimed in claim 15 wherein the adjuvant is diethylaminoethyl dextran.
17. An immunogenic composition for use in a method as claimed in claim 1,2,3 oF5 comprising an immunogenic conjugate between an immunogenic carrier and a steroidal androgen our a steroidal oestrogen derivative.
18. The use of an immunogenic conjugate between an immunogeniccarrierand a steroidal androgen derivative our a steroidal oestrogen derivativeforthe preparation of an immunogenic composi tionfor use in a method as claimed in claim 1,2,3 or 5.
19. A method as claimed in any one of claims, 1,2, 3 or 5 substantially as herein before described with referencetothe Example.
20. A composition as claimed in claim 17 substantially as hereinbefore described with reference to the
Example.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848428201A GB8428201D0 (en) | 1984-11-08 | 1984-11-08 | Biological preparations |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8527437D0 GB8527437D0 (en) | 1985-12-11 |
| GB2166951A true GB2166951A (en) | 1986-05-21 |
| GB2166951B GB2166951B (en) | 1989-07-12 |
Family
ID=10569424
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB848428201A Pending GB8428201D0 (en) | 1984-11-08 | 1984-11-08 | Biological preparations |
| GB8527437A Expired GB2166951B (en) | 1984-11-08 | 1985-11-07 | Biological method |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB848428201A Pending GB8428201D0 (en) | 1984-11-08 | 1984-11-08 | Biological preparations |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS61115429A (en) |
| DE (1) | DE3539557A1 (en) |
| DK (1) | DK513185A (en) |
| FR (1) | FR2572653B1 (en) |
| GB (2) | GB8428201D0 (en) |
| IT (1) | IT1219682B (en) |
| NL (1) | NL8503055A (en) |
| NZ (1) | NZ214107A (en) |
| PH (1) | PH25536A (en) |
| ZA (1) | ZA858580B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988001177A1 (en) * | 1986-08-15 | 1988-02-25 | Commonwealth Scientific And Industrial Research Or | 2-component immunoadjuvant |
| EP0316320A1 (en) * | 1986-07-11 | 1989-05-24 | Commw Scient Ind Res Org | Reduction of reproductive losses. |
| WO1993007833A1 (en) * | 1991-10-21 | 1993-04-29 | Peptide Technology Limited | Biocompatible implant for the timing of ovulation in mares |
| WO1999042110A1 (en) * | 1998-02-19 | 1999-08-26 | Thorn Bioscience, Llc | Regulation of estrus and ovulation in gilts |
| US7205281B2 (en) | 2003-10-03 | 2007-04-17 | Thorn Bioscience, Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| US8905913B2 (en) | 2009-04-23 | 2014-12-09 | Jbs United Animal Health Ii Llc | Method and composition for synchronizing time of insemination |
| US9724380B2 (en) | 2012-11-28 | 2017-08-08 | Jbs United Animal Health Ii Llc | Method and compositions for synchronizing time of insemination in gilts |
| CN107771742A (en) * | 2017-11-17 | 2018-03-09 | 凤台县瑞普农业发展有限公司 | A kind of method for breeding of the standby boar of promotion heat |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1433783A (en) * | 1972-05-11 | 1976-04-28 | Akzo Nv | Process for the detection and determination of haptens |
| GB1586506A (en) * | 1976-09-29 | 1981-03-18 | Mochida Pharm Co Ltd | Immunochemical process and reagents for the determination of haptens |
| GB2068973A (en) * | 1980-02-07 | 1981-08-19 | Commw Scient Ind Res Org | Steroid/protein conjugates |
| GB2071107A (en) * | 1980-02-06 | 1981-09-16 | Industrial Res Org | Increasing fecundity of ovines with steroids |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3485681D1 (en) * | 1983-10-14 | 1992-06-04 | Unilever Nv | PRODUCTION OF LIVESTOCK OR DERIVED PRODUCTS. |
-
1984
- 1984-11-08 GB GB848428201A patent/GB8428201D0/en active Pending
-
1985
- 1985-11-07 FR FR858516509A patent/FR2572653B1/en not_active Expired - Fee Related
- 1985-11-07 ZA ZA858580A patent/ZA858580B/en unknown
- 1985-11-07 DK DK513185A patent/DK513185A/en not_active Application Discontinuation
- 1985-11-07 IT IT48753/85A patent/IT1219682B/en active
- 1985-11-07 DE DE19853539557 patent/DE3539557A1/en not_active Withdrawn
- 1985-11-07 JP JP60248149A patent/JPS61115429A/en active Pending
- 1985-11-07 NL NL8503055A patent/NL8503055A/en not_active Application Discontinuation
- 1985-11-07 NZ NZ214107A patent/NZ214107A/en unknown
- 1985-11-07 GB GB8527437A patent/GB2166951B/en not_active Expired
- 1985-11-07 PH PH33021A patent/PH25536A/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1433783A (en) * | 1972-05-11 | 1976-04-28 | Akzo Nv | Process for the detection and determination of haptens |
| GB1586506A (en) * | 1976-09-29 | 1981-03-18 | Mochida Pharm Co Ltd | Immunochemical process and reagents for the determination of haptens |
| GB2071107A (en) * | 1980-02-06 | 1981-09-16 | Industrial Res Org | Increasing fecundity of ovines with steroids |
| GB2068973A (en) * | 1980-02-07 | 1981-08-19 | Commw Scient Ind Res Org | Steroid/protein conjugates |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0316320A1 (en) * | 1986-07-11 | 1989-05-24 | Commw Scient Ind Res Org | Reduction of reproductive losses. |
| EP0316320A4 (en) * | 1986-07-11 | 1989-12-04 | Commw Scient Ind Res Org | Reduction of reproductive losses. |
| WO1988001177A1 (en) * | 1986-08-15 | 1988-02-25 | Commonwealth Scientific And Industrial Research Or | 2-component immunoadjuvant |
| US5109026A (en) * | 1986-08-15 | 1992-04-28 | Commonwealth Scientific And Industrial Research Organization | 2-component immunoadjuvant |
| WO1993007833A1 (en) * | 1991-10-21 | 1993-04-29 | Peptide Technology Limited | Biocompatible implant for the timing of ovulation in mares |
| US5545408A (en) * | 1991-10-21 | 1996-08-13 | Peptide Technology Limited | Biocompatible implant for the timing of ovulation in mares |
| WO1999042110A1 (en) * | 1998-02-19 | 1999-08-26 | Thorn Bioscience, Llc | Regulation of estrus and ovulation in gilts |
| US6028057A (en) * | 1998-02-19 | 2000-02-22 | Thorn Bioscience, Llc | Regulation of estrus and ovulation in gilts |
| US7205281B2 (en) | 2003-10-03 | 2007-04-17 | Thorn Bioscience, Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| US8530419B2 (en) | 2003-10-03 | 2013-09-10 | Thorn Bioscience Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| US10028996B2 (en) | 2003-10-03 | 2018-07-24 | Thorn Bioscience Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| US8927496B2 (en) | 2003-10-03 | 2015-01-06 | Thorn Bioscience Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| US8937044B2 (en) | 2003-10-03 | 2015-01-20 | Thorn Bioscience Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| US9018165B2 (en) | 2003-10-03 | 2015-04-28 | Thorn Bioscience Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| US9351818B2 (en) | 2003-10-03 | 2016-05-31 | Thorn Bioscience Llc | Process for the synchronization of ovulation for timed breeding without heat detection |
| US10898539B2 (en) | 2003-10-03 | 2021-01-26 | Thorn BioSciences LLC | Process for the synchronization of ovulation for timed breeding without heat detection |
| US8905913B2 (en) | 2009-04-23 | 2014-12-09 | Jbs United Animal Health Ii Llc | Method and composition for synchronizing time of insemination |
| US9757425B2 (en) | 2009-04-23 | 2017-09-12 | Jbs United Animal Health Ii Llc | Method and composition for synchronizing time of insemination |
| US10668127B2 (en) | 2009-04-23 | 2020-06-02 | United-Ah Ii, Llc | Method and composition for synchronizing time of insemination |
| US9352011B2 (en) | 2009-04-23 | 2016-05-31 | Jbs United Animal Health Ii Llc | Method and composition for synchronizing time of insemination |
| US9724380B2 (en) | 2012-11-28 | 2017-08-08 | Jbs United Animal Health Ii Llc | Method and compositions for synchronizing time of insemination in gilts |
| US10376558B2 (en) | 2012-11-28 | 2019-08-13 | United-Ah Ii, Llc | Method and compositions for synchronizing time of insemination in gilts |
| CN107771742A (en) * | 2017-11-17 | 2018-03-09 | 凤台县瑞普农业发展有限公司 | A kind of method for breeding of the standby boar of promotion heat |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61115429A (en) | 1986-06-03 |
| IT1219682B (en) | 1990-05-24 |
| NL8503055A (en) | 1986-06-02 |
| GB2166951B (en) | 1989-07-12 |
| PH25536A (en) | 1991-07-24 |
| DK513185A (en) | 1986-05-09 |
| FR2572653A1 (en) | 1986-05-09 |
| ZA858580B (en) | 1987-07-29 |
| FR2572653B1 (en) | 1990-09-07 |
| NZ214107A (en) | 1989-06-28 |
| IT8548753A0 (en) | 1985-11-07 |
| DE3539557A1 (en) | 1986-06-05 |
| GB8527437D0 (en) | 1985-12-11 |
| DK513185D0 (en) | 1985-11-07 |
| GB8428201D0 (en) | 1984-12-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19921107 |