EP0258422A1 - Immunomodulator for improving commercial performance of domestic animals - Google Patents
Immunomodulator for improving commercial performance of domestic animalsInfo
- Publication number
- EP0258422A1 EP0258422A1 EP87901996A EP87901996A EP0258422A1 EP 0258422 A1 EP0258422 A1 EP 0258422A1 EP 87901996 A EP87901996 A EP 87901996A EP 87901996 A EP87901996 A EP 87901996A EP 0258422 A1 EP0258422 A1 EP 0258422A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- kic
- feed
- animals
- cattle
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
- A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
Definitions
- the field of this invention is methods for improving the commercial performance of domestic animals.
- the invention is particularly concerned with the administration of alphaketoisocaproate (KIC) to domestic animals for improving the immune and/or metabolic functions of the animals.
- KIC alphaketoisocaproate
- Keto analogs of essential amino acids have been proposed for use in human nutrition as partial or complete substitutes for the corresponding amino acids, including, for example, leucine, isoleucine, methionine, phenylalanine, and valine.
- leucine leucine
- isoleucine methionine
- phenylalanine and valine.
- the use of such keto analogs was proposed by Dr. MacKenzie Walser as supplementation to protein-reduced diets in uremia. See, for example, Walser, et al., J. Clin. Inv. (1973) 52:678-690.
- Further experiments by Walser and associates demonstrated a nitrogen sparing effect from mixtures of branched-chain keto acids. Saiper and Walser, Metabolism (1977) 26:301-308.
- Patents have issued to Walser on the use of keto analogs of essential amino acids for promotion of protein synthesis and suppression of urea formation in humans.
- U.S. patents 4,100,161 and 4,101,293 A recent review summarized existing knowledge with respect to the administration of branched-chain keto acids to humans. "New Aspects of Clinical Nutrition", pp. 319-324 (Karger, Basel, 1983).
- KIC alpha-ketoisocaproate
- KIC has not been heretofore known as an immunomodulator in humans or animals, nor has it been suggested that KIC can be used to reduce plasma cortisol (hydrocortisone), or that it can be used to favorably alter immune function by enhancing blastogenesis of T lymphocytes.
- T lymphocytes have important functions in immunological defense against microorganisms. See, for example, Williams et al., "Hematology", Chap. 102, pages 927-928 (2nd Ed., 1977, McGraw-Hill). In their immune function, T lymphocytes, which are normally quiescent, undergo mitosis with accelerated DNA production. Williams, et al., above cited, pages 882-884. This process of T lymphocyte activation is known as blastogenesis. The degree of blastogenesis activation of T lymphocytes can be determined in vitro using mitogens. The most commonly employed mitogens for this purpose are phytohemagglutin (PHA), pokeweed mitogen (PWM), and concanavalin A (conA). Williams et al., citedabove, pages 895, and 923.
- PHA phytohemagglutin
- PWM pokeweed mitogen
- conA concanavalin A
- the present invention provides a novel method and novel feed compositions for improving the commercial performance of domestic animals.
- the method utilizes alpha-ketoisocaproate (KIC) as an immunomodulator for improving immune function, and/or as a nutrient additive for improving metabolic function.
- KIC alpha-ketoisocaproate
- the administration of KIC favorably alters immune function, as evidenced by enhanced blastogenesis of the T lymphocytes.
- a further effect on immune function is the marked reduction of plasma cortisol.
- the enhancement of lymphocyte blastogenesis is of value in increasing disease resistance. Reduced plasma cortisol is expected to be ameliorating in counteracting stress associated immunodepression in domestic animals, and should be useful for controlling cattle shipping fever.
- KIC-containing feeds In the case of animals being raised for meat production, such as young cattle and sheep, young chickens, and veal calves, KIC can be used as a "growth promotant immunomodulator"--an unprecedented kind of feed additive.
- Improved metabolic function can also be obtained with mature animals, including dairy cattle, wool-producing sheep, and laying chickens.
- the production of milk, wool, and eggs can be improved, while at the same time increasing the disease resistance of the animals.
- nursing domestic mammals such as cattle, sheep, and hogs
- the improvement in the quality and quantity of the milk benefits the offspring.
- a further benefit is that the nursing mother mammals are more disease resistant.
- KIC KIC to cattle prior to shipment
- the administration of KIC to cattle prior to shipment is expected to mitigate the stress-related effects of shipping fever.
- the KIC should be in a nutritionally-utilizable form.
- the KIC should be absorbable in the digestive system, while for parenteral administration a water-soluble form is preferred.
- it may be used in its free acid form, but its sodium, potassium, ammonium, or calcium salts are preferred.
- Ammonium and alkali metal salts are more water-soluble, while alkaline earth metal salts such as calcium salt are less water-soluble.
- KIC Alpha-ketoisocaproate
- Sodium and calcium salts of KIC as supplied commercially are substantially pure compounds and are in the form of dry powders. However, high purity is not necessarily required for the purposes of the present invention.
- KIC powders can be mixed with dry feeds, or for non-ruminant mammals and poultry water-soluble KIC salts can be administered by dissolving in drinking water.
- parenteral administration such as intramuscular injection
- sodium KIC can be dissolved in a sterile water.
- feed use to assure administration at a desired level, it is preferred to mix the dry KIC salt with the dry feed ingredients at a predetermined concentration.
- the KIC salt can be incorporated by dry blending using standard mixing equipment.
- the KIC should be substantially uniformly distributed throughout the feed. After mixing, if desired, the feed material may be further processed, such as by conversion to pellets.
- feed compositions are composed of mixtures of feed ingredients.
- Such mixed feed compositions may comprise complete feeds or feed concentrates. It has been found preferable in promoting metabolic function with KIC to use only limited quantities of proteinaceous feed ingredients which are high in leucine content.
- feed ingredients include blood meals, which may contain 16 to 20% leucine, and corn gluten meal containing 18 to 20% leucine (based on the protein dry weight).
- soybean meal contains only about 8 to 9% leucine, and can therefore be used as a carrier for KIC in the form of a protein supplement.
- the amount of leucine in the diet is not over 12% of the dry weight of the total protein being consumed by the animal.
- the amount of protein can be calculated by determining nitrogen and multi plying by a standard conversion factor of 6.25 (viz. N x (6.25).
- the amount of leucine is limited to less than 10% by weight of total protein. Consequently, in the formulation of complete feeds or feed concentrates which are to provide a major portion of the animal's diet, it is preferred to maintain the leucine content of the feed composition to not over 12% and preferably less than 10% (based on total protein).
- the immune function improvement of KIC can still be obtained at higher leucine levels.
- the method of this invention can comprise orally administering from as low as 0.5 to 2 milligrams (mg) up to as much as 500 to 1000 mg of alpha-ketoisocaproate (KIC) per kilogram of body weight per 24 hours (hrs).
- KIC alpha-ketoisocaproate
- the amount of KIC administered to the animals can range from 1 to 100 mg (Na KIC basis ) per kg body weight per 24 hrs.
- the amounts of KIC should be understood to relate to the sodium salt of KIC as the weight basis, or to a molar equivalent amount of the calcium salt or other salts or derivatives, which are nutritionably absorbable and utilizable.
- the amount of KIC may be specified in relation to the feed composition.
- the admixed feed composition may contain from as low as 0.01 to 0.1 up to 1.5 to 2.0 wt % KIC (Na KIC dry feed weight basis).
- Such feed compositions will usually contain at least 10% protein and may contain up to 24% protein N x 6.25).
- KIC tablets may be coated with animal blood or with corn protein (zein).
- zein corn protein
- Other proteins can be employed as coating materials which are resistant to rumen breakdown.
- Polymer coating may also be used such as those known to protect protein against rumen destruction. (See the rumen-protective coatings described in the U.S. Patents 4,181,708, 4,181,709, and 4,181,710).
- the coating employed should be one which is resistant to the mildly acid environment of the rumen while dissolving in the more acid environment of the abomasum.
- the amount of KIC required can be monitored by increasing the dosage until an appreciable reduction in plasma cortisol is observed.
- a useful range is from 1 to 100 mg KIC per kg body weight per 24 hrs (Na KIC basis).
- the amount administered can be from 2 to 50 mg KIC per kg body weight per 24 hours (NaKIC basis).
- Feed compositions containing such rumen-protected KIC and comprising substantially the entire diet of the ruminants may contain 0.1 to 0.5% KIC (NaKIC and feed dry weight basis). If unprotected KIC is used these amounts should be increased by a factor of 9 to 10.
- KlC-feeding is especially useful in the feeding of female and castrated and intact male cattle and sheep, but it can also be used with male ruminants if raised for meat production.
- Other uses include breeding stock and replacements.
- the method is preferably used with steers and heifers for beef production, and with wethers, rams, and ewes for lamb meat production and/or wool production.
- improvements in meat production in relation to protein intake and/or increased wool production can be obtained.
- With mature sheep which are primarily being raised for wool production the benefit of increased wool production in relation to protein intake is especially valuable.
- an additional advantage can be reducing the cholesterol content of lean meat, and also probably improving carcass quality or grade.
- improvement in T lymphocyte function is obtainable.
- This invention is also usable with calves being raised for veal production.
- veal calves are not ruminants. They are suckling calves which remain monogastric, i.e., they do not develop a rumen, being fed milk or a milk substitute which provides a balanced diet for the veal calves. KIC fed to veal calves is therefore not subject to rumen loss.
- a liquid milk replacer for veal calves may contain from 0.01 to 0.5% (NAKIC basis) KIC based on the dry matter content of the milk replacer, and preferably from 0.01 to 0.5% KIC on the same basis.
- Sodium KIC is preferred because of its water solubility. The limitations on leucine in the diets for the veal calves are preferably observed, as previously described. Lactating Domestic Mammals
- the method and feed compositions of this invention are applicable to dairy cattle being managed for commercial milk production, and the method and feed compositions can also be advantageously used with lactating goats fed for commercial milk production.
- the invention provides a means for improving the milk produced by nursing mammals, including cattle, sheep, goats, horses, and swine. The young mammals being nursed thereby obtain the benefits of greater milk production and increased butterfat content. All of the foregoing instructions about the form and amount of KIC are applicable.
- the feeds employed can be adapted for the particular animal and the purpose for which it is being raised.
- the KIC feeding method of this invention is particulaly suitable for use in raising "broilers", which are hen chickens usually marketed around 10 weeks of age. It is also applicable to the raising of capons.
- the feeding method of this invention may reduce the cholesterol content of the meat in the finished chickens. This cholesterol reducing effect becomes more pronounced as the protein content of the diet is increased, being especially marked with diets containing more protein than normally required for the growth stage of the chickens.
- the chicken feed compositions will usually be composed of mixtures of feed ingredients, including protein-providing ingredients.
- the feed compositions may comprise complete feeds or feed concentrates.
- the feeds preferably should contain at least a normally adequate amount of protein for the age ot the chickens. Diets essentially deficient in protein should be avoided.
- Starter feeds containing at least 22% protein by weight (feed dry basis) are preferred for 0 to 4 weeks of age. Finishing rations used from 5 weeks on may contain a lesser amount of protein, but preferably contain at least 18% protein.
- the amount of leucine in the diet of the chickens is preferred to not over 12% by weight based on the dry weight of the total protein being consumed, and preferably less than 10% by weight.
- the method of this invention as applied to young chickens comprises orally administering at least 0.01 and preferably at least 0.05 weight percent (wt %) of alphaketoisocaproate (KIC), based on the dry weight of the total diet.
- KIC alphaketoisocaproate
- the amount of KIC is referenced to sodium KIC and its molar equivalents.
- the amount of KIC administered to the chickens is from 0.05 to 0.1 up to 0.5 wt % KIC (sodium KIC basis) based on the dry weight of the feed consumed by the chickens. Higher levels of KIC, such as in the range from 0.5 to 1%, could be used but have not been found to provide any added benefit.
- the amount of KIC may be specified in relation to the feed composition.
- admixed feed compositions may contain from 0.05 to 1.0 wt % KIC (sodium KIC basis) in relation to the dry weight of the feed composition.
- the feed compositions preferably contain from 0.1 to 0.5 wt % KIC (sodium KIC basis) of the feed dry weight.
- the feed compositions also preferably contain at least an adequate amount of protein.
- Illustrative feed compositions for use in practicing the present invention witn young chickens are set out below.
- the compositions are specially designed for use with chickens being raised for broiler production.
- Ration A is designed for use from 0 to 4 weeks of age, and Ration B from 4 to 6 or 4 to 8 weeks of age.
- NaKIC or CaKIC is added to these rations in amounts on a dry matter basis equal to 0.1 to 0.2 wt. %.
- the method of this invention can have beneficial effects on both the quantity and quality of the eggs laid.
- the number of eggs laid can be increased.
- the cholesterol content of the egg yolks can be reduced. Both of these advantages can be important in connection with commercial egg production.
- KIC powders can be mixed with dry feeds for dry feed compositions or the water-soluble KIC salts can be administered by dissolving in drinking water.
- Sodium KIC is preferred, and it is preferred to mix the dry KIC salt with the dry chicken feed ingredients at predetermined concentrations.
- the KIC salt can be incorporated by using standard mixing and blending equipment. KIC is probably substantially uniformly distributed throughout the feed. After mixing, if desired, the feed material may be further processed, such as by conversion to pellets.
- complete feed compositions or diets for the laying chickens preferably contain not over 12% leucine based on the total protein being consumed, and less than 10% by weight leucine is believed to be optimum.
- the amount of KIC to be administered to the laying chickens is in general from 0.01 to 1.0 weight percent (wt %) of KIC based on the dry weight of the total feed diet. This amount of KIC is referenced to sodium KIC and its molar equivalents.
- the amount of KIC administered to the laying chickens is from 0.05 to 0.5 wt % KIC (sodium KIC basis) on the dry weight of the feed consumed by the chickens, such as 0.1 to 0.2% NaKIC.
- the amount of KIC may be specified in relation to the feed composition.
- admixed feed compositions may contain from 0.01 to 1.0 wt % KIC (sodium KIC basis) in relation to the dry weight of the feed composition.
- the feed compositions preferably contain from 0.05 to 0.5 wt %.
- KIC sodium KIC
- Such feed compositions will usually contain at least 10% protein and may contain up to 18% protein (N x 6.25).
- Cattle which may be beef cattle or dairy cattle, can be fed KIC as an additive to their feed for several days prior to shipment, such as preferably at least 5 to 10 days, if the cattle have not been regularly receiving KIC-containing feeds.
- the amount of KIC administered can be increased over that used for regular feeding.
- rumen-protected KIC sodium KIC basis
- rumen-protection of the KIC is desirable, as previously described. If sodium KIC is used in unprotected form, the amount orally administered may be increased up to 20 to 500 mg KIC (NaKIC basis) per kilogram of body weight per 24 hours.
- the KIC may be parenterally administered, such as by intramuscular injection. Unprotected KIC can be used. It will probably be preferable to administer two or more injections on successive days prior to shipment.
- the injections may be prepared in a sterile aqueous solution of sodium KIC, and may contain from 50 to 4000 milligrams of sodium KIC per dose.
- KIC KIC
- administration of KIC may be continued by oral feeding. It is believed that this will also be of value in reducing the adverse effects of shipping stress.
- the amount of rumen-protected KIC to be used in the feeds for post-shipment administration can range from .50 to 50 milligrams KIC (sodium KIC basis) per kilogram of body weight.
- the method, feed composition, and results obtainable by the present invention are further illustrated by the following experimental examples.
- the lambs used in Trial 1 consisted of medium-frame crossbred wethers and ewes weighing 26 to 31 kg.
- the lambs used in Trial 2 consisted of medium-framced crossbred rams weighing 18 to 25 kg. Each animal was raised as a single. The lambs were housed in a temperature controlled room in individual pens with nipple waterers. When received, the lambs were vaccinated for enterotoxemia. They were allowed to adjust to the pens and the environment for 10 days. One day before the trial began, the lambs were sheared and placed on their respective dietary treatments. The lambs were allotted blocking by weight and sex into two dietary treatment groups. Growth and feed consumption were measured bi-weekly.
- the SMB (soybean meal-containing) and the CGM (corngluten-containing) diets were fed twice per day in quantities ensuring that feed was before the lambs at all times.
- the diets were calculated to be equivalent to each other with respect to metabolizable protein, ether extract, fiber, and minerals with the exception of calcium and phosphorus.
- the CGM diet contained less calcium (0.68 v. 0.74%) and phosphorus (0.30 v. 0.47%), and had a higher calcium to phosphorus ratio (2.29 v. 1.57) than the SMB diet.
- the CGM diet was calculated to contain slightly more energy (TDN 81.7 vs. 79.0, NEm 1.88 v. 1.86, Neg.
- the CGM diet contained slightly more crude protein on a dry matter basis than did the SBM diet (20.5 v. 19.8%).
- the soybean meal ingredient contained about 3.5 wt % leucine, while the corn gluten meal ingredient contained about 15 wt % leucine.
- the CGM diet was therefore higher in leucine than the SBM diet, containing an estimated 16 wt % leucine as compared with an estimated 8 wt % leucine based on total crude protein in the diet.
- Cows were fed ad libitum a total mixed ration twice daily (7:30 a.m. and 5:30 p.m.) with feed refusals collected before the morning feeding.
- the diet consisted of 31% chopped alfalfa hay, 18% corn silage, and 41% grain mix (as a % of the dry matter).
- the grain mix was calculated to contain 1.55 Meal NE/kg dry matter and 16% crude protein.
- a major portion of the grain protein was from expeller processed soybean meal with higher than usual bypass characteristics.
- the cows were consuming protein in excess of their normal requirements.
- the grain ration contained an estimated 10% leucine (total protein basis), and the complete diet contained an estimated 9% leucine (total protein basis).
- KIC was fed in a mixture which consisted of Na-KIC, corn gluten meal, hvdrogenated soy oil and paraffin in a ratio of 2:1.0:0.1:0.1. The mixture was extruded and formed into crumbles. At least part of the KIC may have escaped rumen degradation with this treatment. Additionally, 100 units of tocopherol were added per gram of Na-KIC to prevent oxidation of KIC. Control animals were fed an equivalent amount of the same mixture but without KIC added.
- control period designated weeks -2 and -1
- all cows received the same diet.
- the trial period extended over the next three weeks (weeks 1, 2, 3) during which cows received either the KIC or control mix top-dressed on their diets twice per day (half the dose in the morning, half in the evening).
- daily milk yield, milk composition, and feed consumption was measured for each cow.
- urinary catheters were inserted and total urine and fecal collections were made for 48 hrs. Results of production and nitrogen balance studies were analyzed statistically using each cow as her own control. The trial effect was measured by subtracting the average control period value from the value during the treatment period. ANOVA was used to detect differences between the KIC-fed and control groups.
- Laying hens (69 weeks of age) were randomly assigned to either a control diet or a diet containing 0.2 wt % KIC (Na). For the next 28 days feed consumption was recorded and eggs collected. Eggs were weighed and analyzed for egg yolk cholesterol. The feed composition is shown in Table C and the results in Table D. The total protein was about 18% on a dry matter basis, and the amount of leucine was about 9% of the protein. The control diet was the same except for the omission of the KIC.
- Soyabean meal (48% protein) 214.0
- Meat & bone meal (50% protein) 20.0
- experiment 3 72 castrated male cattle were allotted to 12 pens of 6 animals each. Three pens were assigned to each treatment: 0.0% KIC, 0.02% KIC, 0.07% KIC, and 0.20% KIC. Animals were fed ad libitum the respective diets for 6 weeks. At the end of the 6-week periods, 100-ml blood samples were collected from each animal, and lymphocyte and neutrophil function were evaluated.
- Sheep in experiments 1 and 2 were fed diets based on a mixture of 48% corn, 5% molasses, 20% alfalfa meal, 0.8% limestone, 0.6% salt-mineral-vitamin mix and ⁇ 25% of a protein supplement (either soybean meal, corn gluten meal, or corn gluten feed).
- the diets were isonitrogenous and analyzed to be -20% crude protein and 89% dry matter.
- the KIC diet consisted of the basal diet to which was added 1% calcium-KIC, whereas the control diet was the basal diet plus 0.25% calcium carbonate.
- the basal cattle diet (experiment 3) consisted of 49% corn, 24% corn-cobs, 18% soybean meal, 7% molasses, 1.3% limestone, 0.25% dicalcium phosphate, 0.23% salt, 0.02% tracemineral premix, and 0.11% vitamin premix.
- the basal diet was supplemented with w/w 0.05% control pellets, 0.04% KIC pellets or 0.4% KIC pellets. All animals consumed ⁇ 10 kg of feed per day, resulting in ⁇ 0, 2, 7, or 20 g of Ca-KIC consumed per animal per day or 0, .02, .07, and .2% KIC of the total diet.
- KIC pellets were made by mixing zein, ethanol, KIC, limestone, bentonite, and water in a ratio of 8.3:7.4:5.2:3: 2.1. This mixture was extruded through a die of 15 mm directly into a vat of liquid nitrogen. The shattered pellets were spread out and allowed to air-dry for 2 days. The pellets were coated with zein (2% w/w) bv spraying with a 30% zein solution made in 80% ethanol. The pellets again were air-dryed. Control pellets were made similarly to the KIC pellets except that the mixture was zein, limestone, ethanol, bentonite, and water in a ratio of 12:12:7.5:2.7:1. When KIC pellets were placed in the rumen (nylon bag technique), 33% of the KIC added was present in the bags after 24 hr of rumen fermentation. It was estimated that uncoated KIC was 95% degraded in the rumen.
- lymphocyte blastogenesis Blood was collected by jugular venapuncture into acid-citrate-dextrose anticoagulant. Lymphocytes and neutrophils were isolated, and lymphocyte blastogenesis and neutrophil function evaluated. KIC was obtained from SOBAC, Paris, France. Zein was purchased from Freeman Industries, Tuckahoe, NY. Each experiment was statistically analyzed by analysis of variance. In sheep experiments, individual animals were the experimental units, whereas pen means were analyzed in the cattle experiment. The changes in lymphocyte blastogenesis are summarized in Table F. In all three experiments, average background blastogenesis was increased in KIC-treated groups.
- KIC phytohemagglutinin
- ConA Concanavalin A
- PWM pokeweek mitogen
- KIC did not alter neutrophil random migration, Staphylococcus aureus ingestion, cytochrome C reduction, iodination, or antibody-dependent cell-mediated cytotoxicity in any experiment, indicating that KIC does not alter neutrophil function. Feed intake in control and KIC-treated animals was not different in any experiment.
- experiment 1 sixteen female pigs weighing 20-30 kg were used. Seven days before study, catheters were surgically placed in the right atria for blood sampling. Animals were housed in individual cages during the recovery period and had free access to water. Preceding the experiment, animals were fed twice daily a basal diet (2% of body weight per feeding). The basal diet consisted of a corn-soybean mix, adequate in all minerals and vitamins and containing approximately 14% crude protein. Test meals were formulated by additions to a basal diet.
- Cortisol was measured by coated tube kits (Gammacoat, Travenol-Genetech Diagnostics, Cambridge, MA). Leucine and KIC were measured by high pressure liquid chromatography. Crystalline leucine was obtained from Sigma Chemical (St. Louis, MO) and KlC-sodium was obtained from . OBAC (Paris, France). Statistical analysis of the individual pig responses was conducted on mean plasma concentrations before the meal (-20 to 0 min) and after the meal (120 to 240 min). When the overall treatment F-value was significant, differences between individual treatments were determined using the pooled SEM and a T-test.
- Table G presents the changes in plasma leucine, KIC and cortisol concentration in pigs before and after ingestion of control, leucine and KIC meals.
- Ingestion of the control meal resulted in a small significant increase in leucine concentration while plasma KIC concentration remained constant.
- Ingestion of the leucine meal caused plasma leucine concentration to increase 4 fold whereas KIC ingestion caused a doubling of leucine concentration.
- Plasma KIC concentration increased from a basal concentration of ⁇ 40 ⁇ M to 90 ⁇ M and over 100 ⁇ M in pigs fed KIC- and leucine-supplemented meals, respectively.
- Plasma cortisol concentration did not change after the control meal (Table G).
- the addition of leucine to the diet resulted in a small decrease in plasma cortisol (-14%, nonsignificant).
- Addition of KIC to the diet, however, resulted in a 40% decrease in cortisol concentration by 240-300 minutes after the meal (p ⁇ .01).
- the treatments consisted of four levels of Ca-KIC in a pelleted supplement: 0%, 0.02%, 0.07%, and 0.20% of the basal diet (0.05% control pellets, 0.04% KIC pellets, 0.14% KIC pellets, and 0.40% KIC pellets).
- the pellets were preweighted and top-dressed on the basal diet twice daily.
- the cattle on the 0.20% KIC were removed from the experiment.
- the cattle were not implanted with a growth promotant nor were ionophores included in the diet.
- the cattle were placed in the feedlot and fed a growing ration for 5 weeks prior to the start of the experiment.
- the cattle were weighed on 2 consecutive days at the beginning and end of the experiment, and every 14 days during the trial.
- the cattle were sold through a commercial beef processing plant when they were appraised by visual examination to grade Choice. Loin eye area and fat thickness over the loin were measured on each carcass. Quality and yield grades, and percent kidney, heart, and lepvic (KHP) fat were estimated by the federal graders.
- KIC pellets resistant to rumen degradation, were made by mixing zein, ethanol, KIC, limestone, bentonite and water in a ratio of 8.3:7.4:5.2: 3:2:1. This mixture was extruded through a die of 15 mm directly into a vat of liquid nitrogen. The shattered pellets were spread out and allowed to air-dry for two days. The dried pellets were coated with zein (2% w/w) by spraying with a 30% zein solution made in 80% ethanol. The pellets again were air-dried.
- Control pellets were made similar to the KIC pellets except that the mixture was zein, limestone, ethanol, bentonite and water in a ratio of 12:12:7.5:2.7:1.
- KIC pellets were placed in the rumen (nylon bag technique), 45% of the KIC added was present in the bags after 36 hr of rumen digestion.
- KIC was obtained from SOBAC, Paris, France. Zein was purchased from Freeman Industries, Tuckahoe, N.Y. Each experiment was statistically analyzed by analysis of variance with three pens per treatment.
- KIC may have significant potential as a feed additive for growing feedlot cattle.
Abstract
Le rendement commercial d'animaux domestiques peut être amélioré par administration de céto-isocaproate sous une forme nutritionnellement utilisable par l'animal. Le céto-isocaproate améliore la blastogénèse des lymphocytes T de l'animal et réduit les niveaux de cortisole plasmatique. Il en résulte un effet favorable sur la fonction immunitaire de l'animal, effet qui peut être utilisé pour combattre la suppression des réactions immunitaires due à un état de stress. Ledit procédé peut s'appliquer à l'élevage bovin, à l'élevage laitier, à l'élevage ovin, à l'élevage porcin et à l'élevage de volailles, servant respectivement à produire de la viande, du lait, de la laine et des oeufs. Les avantages pratiques peuvent également comprendre une amélioration de la production et une diminution du taux de cholestérol de la viande et des oeufs et une augmentation de rendement dans la production de lait, de laine et d'oeufs.The commercial yield of domestic animals can be improved by administration of keto-isocaproate in a form nutritionally usable by the animal. Keto-isocaproate improves the blastogenesis of animal T cells and reduces plasma cortisole levels. This results in a favorable effect on the immune function of the animal, an effect which can be used to combat the suppression of immune reactions due to a state of stress. Said method can be applied to cattle farming, dairy farming, sheep farming, pig farming and poultry farming, used respectively to produce meat, milk, wool and eggs. Practical benefits may also include improved production and lower cholesterol levels in meat and eggs and increased yield in the production of milk, wool and eggs.
Description
Claims
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/838,356 US4758593A (en) | 1986-03-11 | 1986-03-11 | Method of feeding ketoisocaproate to lactating domestic mammals |
US06/838,357 US4760090A (en) | 1986-03-11 | 1986-03-11 | Method of feeding ketoisocaproate to cattle and sheep |
US06/838,355 US4764531A (en) | 1986-03-11 | 1986-03-11 | Method of feeding ketoisocaproate to laying chickens |
US838356 | 1986-03-11 | ||
US838355 | 1986-03-11 | ||
US838357 | 1986-03-11 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0258422A4 EP0258422A4 (en) | 1988-02-01 |
EP0258422A1 true EP0258422A1 (en) | 1988-03-09 |
Family
ID=27420276
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP87901996A Ceased EP0258422A1 (en) | 1986-03-11 | 1987-03-09 | Immunomodulator for improving commercial performance of domestic animals |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0258422A1 (en) |
JP (1) | JPS63502835A (en) |
AU (1) | AU7162987A (en) |
WO (1) | WO1987005506A1 (en) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2623824A (en) * | 1951-07-05 | 1952-12-30 | Ayerst Mckenna & Harrison | Growth promoting agent |
US2879162A (en) * | 1956-10-04 | 1959-03-24 | Du Pont | Augmenting poultry feed |
-
1987
- 1987-03-09 EP EP87901996A patent/EP0258422A1/en not_active Ceased
- 1987-03-09 AU AU71629/87A patent/AU7162987A/en not_active Abandoned
- 1987-03-09 WO PCT/US1987/000487 patent/WO1987005506A1/en not_active Application Discontinuation
- 1987-03-09 JP JP62501930A patent/JPS63502835A/en active Pending
Non-Patent Citations (2)
Title |
---|
Journal of Dairy Science, Vol. 69, Suppl. 1, 1986, page 111, Champaign, Ill, US; M.J. VANDEHAAR: "Effect of feeding alpha-ketoisocaproate to dairy cows on milk production", page 111, Abstract P60G. * |
See also references of WO8705506A1 * |
Also Published As
Publication number | Publication date |
---|---|
EP0258422A4 (en) | 1988-02-01 |
JPS63502835A (en) | 1988-10-20 |
WO1987005506A1 (en) | 1987-09-24 |
AU7162987A (en) | 1987-10-09 |
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