1. Field of the Invention
This invention belongs to the fields of animal husbandry and pharmaceutical formulation, and provides a device useful for the sustained delivery of a drug to a ruminant animal over a long period of time.
The problem to which the invention is directed is the delivery of drugs to the digestive tract of ruminants over an extended period of time. Of course, there is no problem in delivering such drugs to ruminants which are housed in a barn or feed lot; the drug is simply mixed with the animals' feed in the proper concentration. However, ruminant animals are frequently kept on pasture without supplemental feed for extended periods of time. Clearly, it is quite difficult to administer such drugs to non-supplemented pastured animals in effective doses. In the past, such drugs have been administered by mixing them with salt blocks, for the animals to lick, or by supplying a daily ration of concentrated feed in which the drug is mixed. Neither procedure is certain to give each animal its daily share of drug, and the latter procedure obviously requires effort on the part of the husbandman, and may be very difficult if the animals are widely dispersed in large pastures.
Thus, it would be desirable to have a better method of administering an orally-active drug over a very long period of time. For example, five months is about the longest period of time that most pasture land is capable of supporting animals in a growing condition, and that period of time is accordingly an approximate maximum period for the use of a rumen delivery device.
The drugs which are particularly desirable for delivery by such a device are the ruminant feed efficiency improvers, of which monensin is the most important. It was disclosed by Raun, U.S. Pat. No. 3,839,557, that monensin can be orally administered to ruminant animals to provide markedly improved weight gain per amount of feed consumed.
Other particularly important orally-administered compounds include anthelmintics, most especially the benzimidazole anthelmintics.
2. State of the Art
Ruminant animals are unique because their digestive tract includes a large vessel, the rumen and reticulum (referred to here collectively as the rumen), in which feedstuffs are held and fermented for a long period and which is continuously full of digesting feedstuffs. Thus, the possibility of retaining a delivery device in the rumen for a long period of time has been recognized and many expedients have been tried.
The primary problems are the design of a device which will mechanically be retained in the rumen, and the formulation of the drug in a form which will reliably release the desired dosage day by day over a long period of time.
The retention of the device has been approached from the aspects of density, and of geometric design. The latest and apparently best previous high-density device was that of Simpson, British Patent No. 2,059,767. That design comprises a core of polymeric drug matrix inside a steel cylinder. Both ends of the cylinder are open to the rumen, and the density of the device as a whole is so great, because of the weight of the steel cylinder, that the device remains at the bottom of the rumen and is not disturbed by movement of feedstuff in and out of the rumen.
Devices which are retained in the rumen because of their shape are typified by Laby's U.S. Pat. No. 4,251,506, showing a cylindrical device, open at one end, having extensible wings which are held closed while the animal is caused to swallow the device, and which open upon entering the rumen.
Both the devices of Simpson and of Laby are intended to produce uniform dissolution of a drug-laden matrix because a constant area--the end of a cylinder--is exposed to rumen fluid. It is obviously necessary to dissolve or suspend the drug in a substance which will dissolve or break down at a uniform rate in rumen fluid, if that approach is to be used. An excellent polymer for the purpose was disclosed by Nevin, U.S. Pat. No. 4,273,920. His polymer is composed of lactic acid and glycolic acid and is prepared by condensation of a mixture of those acids in the presence of a strong acid ion-exchange resin.
The problem with cylindrical delivery devices is that it is quite necessary for the container of the device to prevent any contact of rumen fluid with the walls of the cylinder of drug matrix. Consistent administration of the drug is possible only if the fluid contacts only the faces (or one face) of the cylinder and thus acts on a constant area throughout the life of the device. The problem, the art has found, is the difficulty of preventing leakage of rumen fluid between the drug matrix and the enclosing tube.