Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
2002-07-17
2004-01-27
Weddington, Kevin E. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
C514S530000
Reexamination Certificate
active
06683071
ABSTRACT:
This invention relates to a process for the inititation of oestrus and ovulation early postpartum, especially but not exclusively, in dairy cows. The invention also relates to methods of increasing milk production.
Reproductive performance is one of the important factors determining the profitability of dairy herds. Ideally, the calving interval should average one year, but this can only be achieved if the pregnancy success and detection rate of oestus are high and the interval between parturition and first service is less than 90 days (Bulman, D. C. and Lamming G. E. J Reprod. Fert (1978) 54: 447-58).
In milked cows, there is a suppression of ovarian follicular development for a variable period after parturition and there is current evidence that a significant number of animals (about 12%) exhibit prolonged anovulatory periods postpartum (PP) (Royal, M. D., et al., (1999)
Animal Science
). In dairy cows there are significant changes in plasma (lutenizing hormone) LH levels after parturition, directly related to the initiation of ovarian cycles, with low basal LH levels immediately postpartum followed by increases in mean levels and the development of clear LH episodes with increasing episode frequency (Peters A. R. et al., (1981) Journal of Reproduction & Fertility 62: 567-573). There is clear evidence that the low levels of progesterone, secreted as a result of the initiation of postpartum ovarian follicular development, contribute to establishing a normal oestrous cycle pattern (Lamming, G. E., et al., (1981)
Journal of Reproduction and Fertility Supplement
30: 155-170). Furthermore, the incidence of the silent ovulation in cycles prior to insemination delays the intervals to first PP insemination and conception (Senger, P. L. (1994)
Journal of Dairy Science
77: 2745-2753).
There is a marked interdependence of activity between the ovaries and the uterus shortly after parturition in mammals such as cows. The early resumption of ovarian activity leading to the availability of circulating oestradiol—17&bgr;, may help to hasten uterine involution through a reduction in size, a marked increase in uterine tone (for a review see Hussein, A. M. (1989) J. Vet Med 36: 641-451) and benefits to the uterine defence mechanisms (Rowson, L. E. A. et al., (1953)
Veterinary Record
65: 335-341). Similarly, the interval to post partum (PP) uterine involution is significantly correlated with the occurrence of the first PP ovulation (Madej, A. et al., (1984)
Theriogenology
21: 279-287; Buch, N. C. et al., (1955)
Journal of Dairy Science
38: 73-79). An early return to ovarian cyclicity PP was found by most workers to be associated with high fertility (Thatcher, W. W. and Wilcox, C. J., (1973)
Journal of Dairy Science
56: 608-610; Stevenson, J. S. and Call, E. P. (1983)
Theriogenology
19: 367-375; Staples, C. R et al., (990)
Journal of Dairy Science
73: 938-947; Senatore, E. M. et al., (1996)
Animal Science
62: 17-23; Darwash, A. O. et al., (1997)
Animal Science
65: 9-16; Kinsel, M. L. and Etherington, W. G. (1998)
Theriogenology
50: 1221-1238; Mann, G. E. et al., (1998)
Nottingham Cattle Fertility Conference
11-12. Based on this premise, a number of workers have used prostaglandin F
2&agr;
. (PGF
2&agr;
) administration in an attempt to induce early postpartum uterine recovery or alternatively progesterone (P
4
) to initiate early return to a pattern of normal oestrous cycles, but with inconsistent results. Where a prostaglandin alone has been supplied, it has been reported that a single dose of PGF
2&agr;
administered prior to day 40 postpartum is beneficial to herd fertility Young, I. M. et al., (1984)
Veterinary Record
115: 429-431; Bernard, M. and Stevenson, J. S. (1986)
Journal of Dairy Science
69: 800-811; Young, I. M. and Anderson, D. B. (1986)
Veterinary Record
115: 429-431; Etherington, W. G. et al., (1988)
Theriogenology
29: 565-575; MeClary, D. G. et al., (1989)
Theriogenology
31: 565-570; White, A. J. and Dobson, H. (1990)
Veterinary Record
24: 588-592; Etherington, W. G. et al., (1994)
Theriogenology
42: 739-752; Pankowski et al., (1995)
Journal of Dairy Science
78: 1477-1488, but others have concluded that Here was no significant improvement (Mortimer et al., (1984)
Theriogenology
21: 869-874; Macmillan et al., (1987)
Proceeding of the New Zealand Society of Animal Production
47: 65-68; Stevenson, J. S. and Call, E. P. (1988)
Journal of Dairy Science
71; 1926-1933; Armstrong et al., (1989)
Veterinary Record
125: 597-600; Morton et al., (1992)
Australian Veterinary Journal
69: 158-160).
Similarly, the administration of P
4
during the PP period is designed to initiate an early return to normal function of the hypothalamic-pituitary-ovarian axis considered necessary for the early initiation of oestrus, ovulation and luteal activity. However, the use of a progeterone-releasing intra-vaginal device (PRID) on Days 10 to 15 PP (Kyle, S. D. (1992)
Journal of Dairy Science
75: 1456-1460 or on Days 5 to 15 PP (Stevenson, J. S. and Purseley, R. (1994)
Journal of Dairy Science
77: 726-734) did not include the expected early ovulation compared with untreated animals. The latter workers reported a significant increase in the number of treated animals showing overt oestrus at the first PP ovulation compared with untreated controls (64 vs 20%).
In an attempt to improve fertility through the induction of a cyclic ovarian pattern early PP, a protocol was developed by the inventors utilising a sequence of PGF
2
. and controlled internal drug (progesterone) release (CIDR). Prostaglandin was chosen because of its cleansing effect on the uterine environment (Gustaffson, B. et al., (1976)
Theriogenology
6: 45-50; Etherington, W. G., et al., (1985)
Canadian Journal of Comparative Medicine
49: 261-267) and in the promotion of uterine involution (Lindell, J. O. and Kindhal, H. (1983)
Theriogenology
24: 269-274; Bonnet, B. N., et al., (1990)
Theriogenology
33: 877-890) while a short period (7 days) of progesterone treatment using CIDR was designed to stimulate the short luteal phases frequently observed in PP cows (Lamming, G. E., et al., (1981)
Journal of Reproduction
&
Fertility
(
Supplement
) 30: 155-170; Eger, M., et al., (1988) Animal Reproductive Science 16: 215-224). Furthermore, CIDR insertion for five days was found to increase the oestrous response to subsequent PGF
2&agr;
treatment (Zu, Z. Z., et al., (1997)
Theriogenology
47: 687-701).
Folman et al., (Anim. Reprod. Sci., 4, 117-26, 1981), discloses a method of synchronising oestrus in cows, wherein prostaglandin is given late post partum (after 60 days) followed by progesterone. No indication is given suggesting that by giving prostaglandin early post partum followed by progesterone that ovulation and oestrus can be initiated.
Johari et al., (Malay. Agric. Res. Dev. Inst., Res. J., 18, 117-122, 1990) discloses a method of synchronising oestrus late post partum (60-90 days) comprising giving progesterone followed by prostaglandin.
The object of the present invention is to initiate ovarian hormone cycles in cows during the early post partum period; previously claimed to be conducive to improved reproductive performance (Stevenson, J. S. and Call, E. P. (1983)
Theriogenology
19: 367-375, Darwash, A. O. et al., (1997)
Animal Science
65: 9-16).
However, the concept that an early return to PP ovarian cyclicity is conducive to higher fertility has recently been challenged by Smith, M. C. A. and Wallace, J. M. (1998) Reproductive Fertility Development 10: 207-216 and their findings, albeit on a limited number of animals, merit scrutiny. These authors showed from milk P
4
analysis of a single herd that multiparous cows ovulating before 21 days PP exhibited poorer reproductive performance than similar animals ovulating later, an effect not observed in their primiparous cows. In the multiparous PP cows, there was a high incidence of persistent corpora lutea (PCL), a finding we have confirmed by study of a wider progesterone database involving several herds, which showed a significa
Fulbright & Jaworski LLP
The University of Nottingham
Weddington Kevin E.
LandOfFree
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