Biocompatible implant for the timing of ovulation in mares

Details Biocompatible implant for the timing of ovulation in mares Biocompatible implant for the timing of ovulation in mares

1994-06-15

1996-08-13

Krass, Frederick

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Implant or insert

424423, 424425, 424426, 514 8, 514 12, 514 13, 514 14, 514 15, 514 21, 119174, A61D 1900, A61D 700

Patent

active

055454089

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to a method for controlling the timing of the ovulation of mares and to a biocompatible implant for use in such a method.


BACKGROUND ART

The equine industry worldwide is continually improving breeding management. This improvement is driven by many factors; of significance are (i) the need to conserve "stallion power" and (ii) the veterinarians requirement to improve their efficiency by having mares ovulate with more predictability.
In order to achieve the above, the ability to predict, within predetermined time constraints when a mare will ovulate, is critical. The use of injection of human chorionic gonodotrophin (HCG) to stimulate ovulation in mares between 36-48 hours after application is widespread. However, despite success with this hormone, it has a number of serious drawbacks.
They include: Europe). Veterinarians using hCG in countries where it is unregistered are liable for any claims against failure of the product. is a possibility. menopausal women. Collection, isolation and purification are unpleasant, and the possibility of transmission of disease, particularly those of viral origin, is a risk.
As an alternative to hCG, Leutinising Hormone Releasing Hormone (LHRH) has been injected into mares to stimulate ovulation. LHRH is also known as Gonodotrophin releasing hormone (GnRH). The LHRH stimulates the mare to produce its own gonodotrophin which, in turn, stimulates ovulation. An agonist of LHRH (Buserelin) has also been injected into mares and it has been reported that ovulation may be induced by such injections. Injected hormones must be typically administered a number of times to be successful and they are required in relatively large doses.


DISCLOSURE OF THE INVENTION

The present invention is directed to an alternative method and composition for controlling the timing of ovulation in mares.
In a first aspect the present invention consists in a method for the controlled induction of ovulation in mares comprising implanting into a mare which already has an ovarian follicle approaching maturation a solid biocompatible implant comprising a solid carrier and an effective amount of an agonist of LHRH so as to increase the level of LHRH agonist in the mare above that prevailing immediately before that implantation.
In a second aspect the present invention consists in a solid biocompatible implant for controlling the induction of ovulation in mares which already have an ovarian follicle approaching maturation, the implant comprises a biologically absorbable solid and from 1.0 to 5.0 mg of an agonist of LHRH.
Deslorelin is a peptide and a super agonist for LHRH. It is the most preferred LHRH agonist for use in the present invention. The formula for Deslorelin is: ##STR1##
As used herein the term "an ovarian follicle approaching maturation" is taken to mean an ovarian follicle which has developed to a size of at least about 30 mm in diameter.
Deslorelin has the particular advantage that its efficacy in the induction of ovulation in mares is sufficiently high that the biocompatible implant may be made small enough to be very acceptable in practice. There are however a number of other LHRH agonists which could be used in carrying out the present invention. These include the following compounds as discussed in Dutton, A. S., "Luteinizing Hormone--Releasing Hormone (LHRH) Agonists", Drugs of the Future, Vol 13, No. 1, 1988:


__________________________________________________________________________ Agonist Structure Name (Company) __________________________________________________________________________ [D-Ser(But.sup.6.des-Gly--NH.sub.2.sup.10 ]--LHRK(1-9)NHEt Buserelin (Hoechst) [D-Trp.sup.6 ]--LHRH Tryptorelin (Debiopharm) (Decapeptyn) [des-Gly--NH.sub.2.sup.10 ]--LHRH(1-9)NHEt Fertirelin (Takeda) [D-His(Bz).sup.6, des-Gly--NH.sub.2.sup.10 ]--LHRH(1-9)NHEt Histrelin (Ortho) [D-Leu.sup.6, des-Gly--NH.sub.2.sup.10 ]--LHRH(1-9)NHEt Leuprolide (Abbott) [D-Trp.sup.6, MeLeu.sup.7, des-Gly--NH.sub.2.sup.10 ]--LHRH(1-9)NHEt L

REFERENCES:
patent: 4010125 (1977-03-01), Schally et al.
patent: 4589402 (1986-05-01), Hodgen et al.
Chemical Abstracts 112:152152, "Use of Gonadotropin-Releasing Hormone for Hastening Ovulation in Transitional Mares", Harrison et al.
Derwent Abstracts Accession No. 87-329107/47, Class P32, EP, A, 246910 (Gene Link Aust. Ltd.) 25 Nov. 1987 (25.11.87). p. 6 lines 2-11.
Derwent Soviet Inventions Illustrated, Section 1, Chemical, vol. X, No. 14, Issued 12 May 1976, Pharmaceuticals, p. 1, SU 475136 (Livestock Farm Res) 19 Sep. 1975 (19.9.75).
Derwent Soviet Inventions Illustrated, Section 1, Chemical, vol. U, No. 37, Issued 18 Oct. 1973, Pharmaceuticals, p. 4, SU 367866 (Livestock Breeding Res. Inst.) 30 Mar. 1973 (30.3.73).

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