Surgery – Controlled release therapeutic device or system – Osmotic or diffusion pumped device or system
Patent
1985-09-26
1988-04-19
Apley, Richard J.
Surgery
Controlled release therapeutic device or system
Osmotic or diffusion pumped device or system
6048911, A61K 922
Patent
active
047386797
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a method of regulating the reproductive functions of animals, particularly domesticated ruminants, and to veterinary implants for use in such a method.
In our earlier Australian patent application No. 78305/81 there is described a method of artificially mimicking changing photoperiod and thus the seasonal breeding activity of sheep and goats by the judicious feeding of melatonin or other related indoles or indole derivatives.
The role of seasonal environmental factors, in particular the photoperiod, in determining the breeding period of sheep is well established. Under natural conditions the shortening of day length as summer leads to autumn is the main trigger to the reproductive system to commence ovarian cyclicity. Our previous application shows that melatonin treatment can mimick the effects of short day length on ewes, such that the breeding season is advanced and basal prolactin levels are depressed.
In the earlier patent specification this was achieved by feeding the animal with food containing melatonin or related indole or indole derivatives for a period of time sufficient for the animal to commence cyclic ovarian activity. This was achieved by absorbing the melatonin in food pellets, and in this way 2 mg of melatonin per day was fed to each animal.
This however requires the daily feeding of the pellets to the animals for a period of three to six weeks.
It is therefore an object of the present invention to overcome, or at least alleviate, some of the difficulties related to the prior art.
Accordingly, in a first aspect, the present invention provides a veterinary implant including an effective amount of
(a) an active ingredient selected from melatonin, related indoles and derivatives thereof, or mixtures thereof and
(b) a veterinarily acceptable carrier or excipient selected to provide, in use, in combination with the active ingredient (a), a generally continuous release rate of active ingredient sufficient to maintain blood melatonin, or its equivalent, at, or above, natural night time level. For domesticated ruminants such as sheep and goats this level is approximately 100 pg/ml. Preferably the veterinary implant according to the present invention is formed by compression.
In a further aspect the present invention provides a method of modifying the seasonal breeding activity of animals which method includes inserting a veterinary implant of the type described herein into an animal to be treated.
The modification of breeding activity may be such as to accelerate the onset of breeding activity or delay the onset of puberty. In delaying the onset of puberty the onset of the breeding season of the animal may be altered. This effect may continue for an extensive period e.g. 2-4 years.
By the term "melatonin" as used herein, we mean the active ingredient in the veterinary implant selected from melatonin, related indoles and derivatives thereof or mixtures thereof.
In the following description reference will be made to the ethicacy of the veterinary implants in sheep, goats and cattle. It should be understood, however, that such animals are mentioned for illustrative purposes only and the veterinary implant is applicable to animals generally. The veterinary implant may be applied to animals including sheep, goats, horses, cattle, deer, buffalo, pigs, ferrets, mink, fox, sable, ermine, bear, camels, lamas and the like. The veterinary implants may further be applied to the regulation of seasonal breeding activity in birds, reptiles, including alligators, crocodiles, turtles and snakes, and fish including sturgeon, trout, salmon and eels.
As discussed below, initial experiments exploring the effects of continuous melatonin administration were carried out utilizing implants in the form of melatonin filled silastic sachets. Whilst these implants were useful for experimental purposes, such implants are deficient in a number of aspects. Firstly, they are difficult and therefore expensive to manufacture and are therefore impractical for large scale application. Further, their size mak
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patent: 3428729 (1969-02-01), Anderson et al.
patent: 3991750 (1976-11-01), Vickery
patent: 4163011 (1979-07-01), Orts
patent: 4322398 (1972-03-01), Reiner et al.
patent: 4346709 (1982-08-01), Schmitt
patent: 4576604 (1986-03-01), Guittard et al.
Kennaway et al., Endocrinology, 110 (6), 2186-2188 (1982).
Dunstan Eugene
Kennaway David J.
Seamark Robert F.
Apley Richard J.
Cannon Alan W.
Gene Link Australia Limited
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