IMPROVEMENTS IN OR RELATING TO A METHOD FOR INCREASING THE FEED INTAKE OF AN ANIMAL

Abstract: This invention provides a method of increasing the feed intake of pigs, chickens, or dairy cattle, which have elevated levels of growth hormone, by administering a thyroid-active substance.

Description: Increasing the feed consumption or intake of an animal is known to increase the weight, or in the case of dairy cow or lactating sow, the milk production of the animal. For example, increasing the growth and weight of the animal brings it to market weight in a shorter period of time, resulting in a substantial savings to the grower. Although animals always have a certain blood level of growth hormone or related substances, when the growth hormone level is increased above normal, the feed intake or consumption of certain animals decreases. Therefore, it is important to increase the feed intake of these animals, such as pigs, because they will suffer from a feed intake depression. We have discovered that the administration of thyroid-active substances (also including thyrotropic principles) will increase the feed intake of pigs having above-normal or elevated blood levels of growth hormone. In particular, the invention provides a method of increasing the feed intake of a pig which has been treated with a growth hormone related substance resulting in an elevated blood level of growth hormone or factor, which comprises administering to said pig a thyroid-active substance. It has now been discovered that pigs (including lactating sows), having elevated levels of growth hormone, resulting in a feed-intake depression for pigs, can have their feed intake increased by the administration of thyroid-active substances. The type of thyroid-active substance administered to the pigs includes iodinated casein, thyroprotein, thyroid hormone, thyroid (thyroglobulin, thyroidine, or proloid), T₄ (tetraiodothyronine, L-thyroxine, or levothyroxine), or T₃ (triiodothyronine, liothyronine, tertroxin, or cytomel). In addition, substances that stimulate the thyroid to produce T₄ or T₃ can be administered also and may include: TSH (thyroid-stimulating hormone, thyrothropin, thyrotropic hormone, thytropar, ambinon, or DERMATHYCIN™), TRH (thyrotropin-releasing hormone), and the like. The administration of iodinated casein is preferred. The method of this invention preferably is practiced by orally administering an effective amount of the thyroid-active substance to the animal. However, other routes of administration can be employed, for instance by implant or by intramuscular or intravenous injection. For oral administration, the thyroid-active substance preferably is admixed with suitable carriers or diluents commonly employed in animal husbandry, such as animal feedstuffs. Typical carriers and diluents commonly employed in feedstuffs include corn meal, soybean meal, alfalfa meal, rice hulls, soybean mill run, cottonseed oil meal, bone meal, ground corn, corncob meal, sodium chloride, urea, cane molasses, and the like. These carriers promote a uniform distribution of the thyroid-active substance in the finished feed ration, thereby, ensuring proper distribution of the thyroid-active substance throughout the feed. While the preferred method for orally administering the thyroid-active substance is through daily feed rations, the thyroid-active substance can be incorporated into salt blocks and mineral licks, as well as being added directly to drinking water for convenient oral consumption. Additionally, the substance can be formulated with polymorphous materials, waxes, and the like, for long-term controlled release, and administered to an animal as a bolus or only as needed to maintain the desired daily payout of the thyroid-active substance. For parenteral administration, the thyroid-active substance can be mixed with conventional carriers, such as corn oil, sesame oil, carbowax, calcium stearate, and the like. These formulations can be administered as an injection or as a slow-release subcutaneous implant. Other types of implants also can be used to administer the thyroid-active substances and can be located subcutaneously. These implants include silastic implants; polymeric implants, such as polyurethanes, hydrogels, and the like; microcapsules; microspheres; liposomes; and the like. The implant can be removed at the end of the desired administration period. In addition, the thyroid-active substance can be administered by mechanical pumping devices, osmotic, and chemical pumps, and the like. An "effective amount of thyroid-active substance" to be administered to an animal is that amount which is effective in causing an increase in the feed consumption or intake. The effective amount to be administered will vary somewhat depending upon the particular animal species being treated and the form of the thyroprotein administered. For example, the amount of iodinated casein that can be used is from 50 to 1000 mg/day (milligrams per day) and the length of time for administration is 1-5 months for pigs (the length of the finishing period). Iodinated casein also can be administered from about 1 to 1000 ppm (parts per million) of the total daily feed intake. This amount will provide a dosage of 0.05 to 50 mg/kg/day (milligrams per kilogram per day). A preferred embodiment employs 1 to 500 ppm, and more preferably from 5 to 250 ppm. A typical amount of active ingredient to be administered to pigs will be from 25 to 150 ppm. For example, when practicing the method, iodinated casein can be added to the daily feed ration of the animal at about 100 ppm of the daily feed ration. The animals, which are to be treated with thyroid-active substance, have an above-normal blood level of growth hormone or somatomedin. The above-normal or elevated blood levels of growth hormone or somatomedin are caused by artificial or exogenous administration of a growth hormone related substance. The administration of a growth hormone related substance can include the administration of growth hormone (somatotropin), growth hormone releasing factor, somatomedin, or any substance that stimulates the production of endogenous growth hormone and subsequently the production of somatomedin. Substances that stimulate endogenous growth hormone include enkephalins or enkephalin-like compounds, prostaglandins, alpha-adrenergics, benzodiazapines, barbiturates, opiate antagonists, gamma-aminobutyric acid (GABA), GABAnergic compounds, and the like. Other substances that can be administered include any analogues of growth hormone or growth hormone releasing factor, such as methionyl bovine growth hormone, 29 amino acid growth hormone releasing factor, and the like. The type of growth hormone related substance to be administered can be derived from natural or recombinant sources or can be prepared by solid-phase synthetic procedures. In addition, the growth hormone or related substance does not have to be species specific. For example, porcine, bovine, or human growth hormone can be used in the administration of growth hormone to pigs. The amount of growth hormone related substance needed to maintain an above-normal blood level of growth hormone in the pig is from 5 mcg/kg/day (micrograms per kilogram per day) to 300 mcg/kg/day. In pigs, the administration of from 10 to 300 mcg/kg of growth hormone will achieve an above-normal blood level. The preferred administration to pigs is from 20 to 100 mcg/kg/day. Because the growth hormone related substance is a protein, it is not desirable to administer orally the hormone. Intramuscular, intravenous, or subcutaneous injections can be used. In addition, the growth hormone related substance may be administered by implant. Typically, the pig can receive growth hormone related substance by the parenteral route and can receive the thyroid-active substance by either an oral or parenteral route. However, the growth hormone related substance and thyroid-active substance can be administered parenterally in single drug delivery devices to achieve the desired effect. These devices include implants, micro-capsules, pumps, and the like. The effect of the administration of thyroid-active substances on the feed intake of pigs is shown in the following experiments. Trial 1 Seventy-two crossbred (Yorkshire X Hampshire) barrows and gilts, weighing approximately 130 pounds, were placed in pens with 4 pigs to a pen. The animals were fed ad libitum with a swine corn/soy ration containing approximately 16% crude protein. Fresh water also was made available at all times. The feed ration was comprised of the following ingredients: The pigs were divided into three groups for treatment, with each group having 3 pens of barrows and 3 pens of gilts. The first group was used as the control and the other two groups were treated with 1.5 or 3.0 mg/day of pGH (porcine growth hormone) for the first 28 days of the trial. The dose was increased to 2.0 or 4.0 mg/day from day 29 to the end of the trial. The hormone was put in solution using sterilized 0.2 M (molar) potassium phosphate buffer (pH 7.8). (The buffer was prepared with pyrogen-free water.) The final concentration of pGH in the buffer was 1.0 mg/ml (milligrams per milliliter). The treated pigs received a daily subcutaneous injection of the pGH solution in their flank areas. The injection volume for each group was as follows: The pigs were individually weighed at the beginning of the trial, every 14th day thereafter, and at the end of the trial. Pigs were removed from the trial when they reached approximately 230 pounds of body weight (in approximately 55 days). The feed consumption for each pig was recorded also. The average daily feed intake and the average daily gain in pounds were calculated and recorded. Table 1 shows the dosage-related reduction in feed intake resulting from administration of the growth hormone alone. Trial 2 Fifteen crossbred barrows, each weighing approximately 90 kg, were maintained in individual stainless steel crates and fed swine corn/soy ration. All pigs were given a constant amount of feed, approximately 2000 g/day (grams per day), which was divided into two feedings of 1000 g/feeding (grams per feeding). Water also was mixed with the feed at the time of feeding. The barrows were divided into 5 groups with each group consisting of 3 barrows. The groups were as follows: 1 - Control (4.5 ml of carrier/day) 2 - pGH (9 mg/day) 3 - pGH (9 mg/day) + IC (250 mg/day) 4 - pGH (9 mg/day) + IC (500 mg/day) 5 - pGH (9 mg/day) + IC (1000 mg/day) IC (iodinated casein) was used in Groups 3-5. One half of the daily dosage for each pig was mixed into the feed at each of the two-daily feedings. The pGH solution was prepared as described in Trial 1, except that the concentration of pGH in the buffer was 2.0 mg/ml. The pGH was administered daily by subcutaneous injection in the flank area. The daily injections of solution were as follows: The feed intake of each pig was recorded daily for a period of 12 days. The feed-intake results are shown in Table 2. The animals were weighed at the beginning of the trial and at the end of 12 days. The 12-day weight gain for each group was calculated and recorded in pounds. The weight gain results are found in Table 3.

Claims: A method of increasing the feed intake of a pig which has been treated with a growth hormone related substance resulting in an elevated blood level of growth hormone or factor, which comprises administering to said pig a thyroid-active substance. A method as claimed in Claim 1 in which the thyroid-active substance is iodinated casein. A method as claimed in Claim 2 in which the iodinated casein is administered at a rate of from 1 to 1000 ppm of daily feed intake. A method as claimed in Claim 3 in which the iodinated casein is administered at a rate of from 5 to 250 ppm of daily feed intake. A method as claimed in any one of Claims 1 to 4 in which the growth hormone related substance is growth hormone. A method as claimed in Claim 5 in which the growth hormone is recombinant growth hormone. A method as claimed in Claim 6 in which the growth hormone is porcine growth hormone. An animal feed ration or animal feed pre-mix for increasing the feed intake of a pig having an elevated blood level of growth hormone or factor which comprises, as an active ingredient, a thyroid-active substance. An animal feed ration or feed pre-mix as claimed in Claim 8 in which the thyroid-active substance is iodinated casein.

Inventors: ANDERSON, DAVID BENNETT, WAGNER, JOHN FREDERICK
Applicants: ELI LILLY AND COMPANY
Application year: 1986
Main classification: A23K1
IPC codes: A23K1, A61P3, A61K38, A61P15