MXPA00001742A - Method and food product for increasing muscle protein and reducing fat in animals - Google Patents

Abstract

The invention is directed to a method and food product for achieving at least one of the following:increasing muscle protein or reducing fat in an animal. The method comprises administering to the animal an effective amount of a composition comprising a gastrointestinal neuro-modulator antibody in order to neutralize the gatrointestinal neuro-modulator.

Description

METHOD AND FOOD PRODUCT TO INCREASE MUSCLE PROTEIN AND REDUCE FAT IN ANIMALS FIELD OF THE INVENTION This invention relates generally to the neutralization or enhancement of an endogenous hormone or peptide in an animal subject by administration of an antibody or antibody that contains the substance to the animal. More particularly, this invention relates to a method for reducing fat and improving the muscle produced in animals, specifically poultry, by administering to said animals, antibodies to gastrointestinal neuro-modulators, such as cholecystokinin (CCK).

BACKGROUND OF THE INVENTION Producing animals for food that contain more muscle and less fat is a greater purpose for food providers. Animal feed products are a major source of calories in fats in the consumer's diet, supplying REF: 32779 approximately 36% of the calorie consumption. Animal food products account for 57% of the fat consumed in the typical American diet and have been implicated as an important factor contributing to the development of cardiac conditions and other related foods. The American Cancer Society (1984), the American Heart Association (1986) and the National Research Council (1982) have all recommended that only 30% or less of total adult caloric intake is in the form of fats. In particular, it has been concluded that the real solution to reduce fat consumption is found in the production of thinner animals (Designing Fodds: Animal Product Options in the Marketplace, Comittee on Technological Options to Improve the Nutritional Attributes of Animal Poruds, Board in Agriculture, National Research Council, National Academy Press, Washington, DC, 1988).

Successful attempts have been made to increase muscle and reduce fat in animals. Some examples include anabolic steroids and growth hormones. However, both cause some related side effects, such as sterility and in some cases, more serious side effects such as arthritis and gastric ulcers. In addition, there is a serious interest in the consumer, about the possible residual levels of anabolic steroids and growth hormones in the same food product which has led to legislation in many countries proposing a ban on such treatments.

To avoid the problems associated with the administration of exogenous hormones, attempts have been made to regulate animal growth immunologically, by actively immunizing the animal against a specific component or hormone, the lack of which promotes the development of a relatively thin animal (Flint, DJ et al., Hannah Res., pp. 123-127 (1985)).

The gastrointestinal tract (Gl) is equipped with a large endocrine gland, through which the endocrine cells synthesize and secrete a variety of biologically active peptide hormones, which have been designated as gastrointestinal neuro-modulators (Gl). A significant body of evidence suggests that the neurol modulators Gl are released from the stomach, duodenum and small intestine in the lumen of the Gl tract. Some neuro-modulatory peptides Gl include cholecystokinin (CCK), bombesin, gastrin, neuropeptide Y, urocortin, corticotropin releasing factor, and somatostatin, among many others.

The family of cholecystokinin (CKK) peptides has been shown in the prior art to negatively attack food consumption and thus inhibit growth in either mammals (Gibbs et al, 1973) and birds (Savory and Hodgkiss, 1984) . The sulphated tyrosine residue, which is contained within CCK-8, has been shown to be important for biological activity. Antibodies to the CCK peptide that originate naturally, have been successfully produced endogenously in pigs (Pekas and Trout, 1990, Pekas 1991) and rats (McLaughlin et al., 1985). In both species, the adverse effects of CCK on food consumption and weight are again prevented by the endogenous circulation of CCK antibodies.

The antibodies can be administered orally, intravenously to an animal subject. This process is generally preferred in the art as passive transfer. The antibodies to be transferred are generally derived from milk, colostrum, serum, egg yolk and even hybridoma monoclonal antibodies. An example of passive transfer occurs when maternal antibodies are transferred passively to newborns through the placenta and during lactation through colostrum and milk. By this method, young animals obtain protection and natural immunity against harmful antigens in the environment. Similarly, to develop birds, reptiles and other animals that lay eggs, the egg yolk is the maternal source of antibodies.

Recently, therapeutic studies have successfully exploited the oral administration of antibodies for the treatment of some infectious diseases. Through a vaccination process, animals can be immunized against specific microorganisms and other antigens. In addition, increased titers of antibodies can be obtained through a hyperimmunization process. High amounts of specific antibodies can be obtained by immunizing animals with specific antigens and isolating the antibodies from the egg yolk, bed, colostrum or serum.

There are five different classes of antibodies which are also called immunoglobulins (Ig). The most abundant is IgG. The other four are IgM, IgA, IgD, and IgE. These antibodies combine with the antigen and act to neutralize or count the effects of the antigen introduced into the animal. This encompasses this result by binding to the antigen thereby neutralizing it and preventing it from binding to other specific cellular receptors. The main immunoglobulin present in the egg yolk is called IgY, which is similar to IgG but has considerable temperatures and acid resistance.

The egg and milk preparations serve as practical sources of antibodies suitable for consumption by animals. Indeed, egg yolks, for example, can contain as much as 100 mg of antibody, and large numbers of eggs laden with antibodies can be produced in a relatively short period of time. Since vaccination of an animal can be used to develop such increased antibody titers in milk and egg, such immunized egg and milk can be foods for animal subjects, thereby the antibodies are transferred passively to animal subjects to confer immunity and protection against microorganisms. The antibodies can be used not only to reject pathogenic antigens or other foreign molecules, but can also be used as described herein, to neutralize the naturally occurring proteins and thereby modulate the normal physiological effect of the protein in the animal system Consequently, antibodies can be used to bind molecules such as CCK and somatostatin, as well as receptors, hormones and other gastrointestinal neuro-modulators in the gastrointestinal tract, nervous system and other body systems in general, to alter their effect.

There is a need for a method to increase muscle and / or reduce fat in an animal that uses a safe nutritional food source. The present invention provides a method for the modulation of gastrointestinal function, using antibodies to improve the performance of the meat and / or reduce the fat in animals.

BRIEF DESCRIPTION OF THE INVENTION The invention relates to a method for achieving at least one of the following: increasing muscle protein or reducing fat in an animal, the method comprising administering to the animal an effective amount of an antibody.

In another embodiment, the invention relates to a method for achieving at least one of the following: increasing muscle protein or reducing fat in an animal, which comprises administering to the animal an effective amount of a composition comprising an antibody gastrointestinal neuro-modulator.

In still another embodiment, the invention relates to a method for achieving at least one of the following: increasing muscle protein or reducing fat in an animal, the method comprising neutralizing or increasing an endogenous gastrointestinal neuro-modulator in said animal.

In still another embodiment, the invention relates to a food product to achieve at least one of the following: increase muscle protein or reduce fat in an animal, the food product comprises an effective amount of a composition comprising an antibody.

In a more particular embodiment, the invention relates to a food product to achieve at least one of the following: increase muscle protein or reduce fat in an animal, the food product comprises an effective concentration of a neuro-modulator receptor antibody gastrointestinal.

In a further embodiment, the invention relates to a method for achieving at least one of the following: increase muscle protein or reduce fat in an animal, the method comprises administering to said animal, a composition obtained from an animal immunized with a gastrointestinal neuro-modulator.

DETAILED DESCRIPTION OF THE INVENTION Definitions: The term "gastrointestinal neuro-modulator (Gl)" means any composition which influences gastrointestinal mobility, including regulatory peptides, neurotransmitters, hormones and immune regulators, among others. Some examples include cholecystokinin (CCK), bombesin, somatostatin, and gastrin among others.

The term "gastrointestinal neuro-modulator receptor (Gl)" means a receptor which is linked to a gastrointestinal neuro-modulator as defined above.

The term "cholecystokinin or CCK" refers to the biologically active peptide and any other form of the peptide including, but not limited to, peptides of different lengths, esterified, hydroxylated, sulphated, fluorinated or non-amide derivatives that bind to the CCK receptor.

The term "CCK-8" refers to the biologically active octapeptide, which forms the amide portion of the larger peptide and generally consists of the following amino acids: Asp-try (S03) -Met-Gly-Trp-Met-Asp-Phe-NH2- The peptide CCK-8 can also be in a non-amide form.

The term "gastrointestinal neuro-modulator antibody" refers to an antibody which binds to a gastrointestinal neuro-modulator receptor.

The term "egg or fraction thereof" means any complete egg (table, hyperimmunized or otherwise) or any product derived therefrom.

The term "egg or fraction thereof" means a whole egg, or any product derived therefrom, obtained from egg-producing animals, which are not maintained in a hyperimmune state.

The term "hyperimmunized egg or fraction thereof" means a whole egg or any product derived therefrom, obtained from an animal that produces egg maintained in a hyperimmune state.

The term "milk or fraction thereof" means milk or products derived therefrom, obtained from an animal that produces milk which is not maintained in a hyperimmune state.

The term "hyperimmunized milk or fraction thereof" means milk or products derived therefrom, obtained from an animal that produces milk which is maintained in a hyperimmune state.

The term "encapsulating composition" means a composition capable of and used to completely round off another composition or compound as if it were wrapped or a capsule, thus no foreign material is allowed to react with another composition or compound until the encapsulated composition has been dissipated. .

The term "neutralization of the gastrointestinal neuro-modulator (Gl)" means any method which uses compositions containing antibodies that bind to or interact with the gastrointestinal neuro-modulators or their receptors to change or modify their action.

The term "animal" means all vertebrates that include fish, birds, amphibians, reptiles and mammals (including humans).

The term "animal subject" refers to the animal to which the antibody produced by the target animal is administered. For example, in the case of peptide neutralization, the animal subject will be administered the antibody until the effect is observed.

The term "target animal" refers to an animal which is used as the animal that produces the antibody. For example, if one wants the production of the antibody inside an egg, then a bird will be the target animal.

The term "gained weight" means an increase in weight.

The term "weight loss" means a decrease in weight.

The term "food efficiency" expresses the efficiency by which an animal converts its food into gained weight. Food efficiency is expressed as the proportion of weight of the food to the weight gained.

The term "increased muscle protein or increased muscle ratio" means an increase in the amount of salable meat (i.e., non-fat muscle) available in an animal. In particular, the protein of the increased or proportioned muscle is expressed as the percentage increase in salable meat per pound or kilogram of the animal.

The term "fat reduction" means a reduction in the total amount of fat in an animal. The reduction of fat in general, can go hand in hand with the proportion of the muscle increased. As a proportionate increase in muscle, the fat content is generally reduced in animals of similar weights.

The invention The invention relates to the neutralization or increase of at least one type of endogenous gastrointestinal neuro-modulator (Gl) in an animal, by administering antibodies against said Gl neuro-modulator or its receptor, which increases the efficiency of the muscle and / or reduce fat in these animals. Although the invention is particularly suitable for food animals, such as poultry, bovines, sheep and sheep, the invention is applicable in all animals and humans, and particularly those suffering from malnutrition caused by diseases (such as diarrhea, HIV), gastrointestinal disorders, eating disorders and famine.

In a preferred embodiment, the invention comprises a method for reducing fat and improving meat or muscle provided in an animal, which comprises administering to the animal, of an effective concentration of a specific Gl neuro-modulator, and preferably, a cholecystokinin antibody. (CCK) In particular, the CCK antibody occurs naturally by immunization to a bird or bovine. The recovered antibodies are transferred naturally to the egg or milk of the bird or bovine, and this antibody containing the egg or milk is subsequently administered to the animal subject.

By administering a CCK antibody produced in such a manner, applicants are providing a natural food product to increase muscle protein and reduce fat in an animal subject if the fear of side effects (excluding, of course, general allergies to eggs or milk). The amount of egg, egg yolk or milk that contains antibody to be added to the food, will vary with the species, size and age of the animal. However, since milk and eggs are natural and non-toxic foods, the amount that can be administered is not critical, the more sufficient it will be effective.

The preparation and administration to animals of any neurol modulator Gl, to reduce fat and increase muscle protein, is encompassed by the method of this invention. In particular, it is believed that the antibodies produce some neuro-modular gastrointestinal, its receptor, or its subunits, increase the performance of the muscle by blocking the interaction of the gastrointestinal neuro-modulator with its receptors in the gastrointestinal system and receptors available in the CNS .

Gastrointestinal Neuro-Modulators As briefly referred to in the background of the invention, there are many gastrointestinal neuro-modulators (Gl), which have similar physiological effects on mammalian and avian systems. Some of these Gl neuro-modulators which can be used in the method and food product of the invention include acetylcholine, cholecystokinin (CCK), bombesin, somatostatin, neuropeptide Y, urocortin, corticotropin releasing factor, substance P, 5- hydroxytryptamine, intestinal vasoactive polypeptide, enkephalins, neurotensins, secretin, motilin, gastric inhibitor peptide, gastrin and gastrin release peptide among many others.

The preferred neuro-modulator used in the invention is the CCK peptide. Currently, endogenous CCK consists of a family of peptides, where the predominant molecular form exists in sulfated and desulfated forms in an octapeptide hormone (CCK-8). The CCK, which is released in a normal way from the nerve of the enteric nervous system, after the meat is consumed, increases the transit time in the gastrointestinal tract. The CCK peptide has several receptors which can be subdivided into at least two subtypes, CCKA and CCKB based on pharmacological studies. A subtype of CCKA receptor predominates in the gastrointestinal system, but originates in highly localized areas of the rat CNS, where it modulates the feeding and behavior induced by dopamine. CCKB-like receptors have also been described outside the CNS in gastrointestinal smooth muscle cells, where they can modulate the mobility of the gallbladder and bowel. Both CCK families of peptides and their receptors are widely distributed through the central nervous and gastrointestinal systems, where they regulate secretion, mobility, growth, anxiety and satiety.

Through this action, the CCK peptide controls the relationship to which the food travels through the intestine causing an increase in intestinal contractions. The presence of CCK also alters the taste of food. CKK is responsible for what is known as the satiety effect which is a physiological effect that sharply decreases the animal's appetite. If an antibody is combined with CCK, CCK is neutralized, the anxiety effect is inhibited and the adverse effects of endogenous CCK on gastrointestinal motility are noted. In addition, if the antibodies bind to the receptor for CCK, and in particular to the CCKA receptor / they will also neutralize the effect of CCK. In other words, the CCK receptor binding antibody will reduce intestinal mobility and inhibit the satiety effect. Basically, the animal will eat more and increase the absorption of nutrients.

The endocrine and immune systems can also influence gastrointestinal mobility through actions of the cytokine hormones. The gastrointestinal mucosa is also an endocrine organ and is responsible for the release of such hormones such as gastrin, secretin, cholecystokinin, motilin, gastric inhibitory peptides, neurotensin and gastrin-releasing peptides among others. During feeding, irregular phasic contractions serve to mix the intestinal content and move it more slowly in a direction away from the mouth. The relationship to which phasic contractions occur is determined by the excitability of smooth muscle cells and slow local waves, which are influenced by these compounds.

Neuropeptide Y, bombesin, somatostatin, and gastrin have similar physiological effects in the gastrointestinal tract such as CCK. These hormones of the intestines have effects on nutrient uptake, gastrointestinal mobility and alter eating behavior. In addition, these hormones from the intestines also act as neutrotransmitters in the brain and modify physiological functions, either peripheral or central. It is noted that several of these peptides exist in different molecular forms and in some cases, such CCKs and gastrins, can resemble each other in molecular structure.

It has been determined that antibodies to any of the aforementioned neuro-modulators and / or their receptors are effective for use in increasing muscle protein and reducing fat in an animal as described by this invention. In addition, antibodies to peptides of various lengths or suitable substitutions, such as, for example, the sulfated tyrosine of CCK-8, are also contemplated as being effective for use in this invention.

Preparation of a vaccine The antibodies can be produced in a variety of ways known to those skilled in the art. Some preferred methods include vaccination, inoculation or imzation of an animal to stimulate an im response. An im response is stimulated in an animal by, for example, administering an antigen or antigens (ie, a vaccine) to said animal. The animal will respond naturally by producing antibodies to those antigens, that is, an im response.

In some cases, an antigen can not be of sufficient size or effectively or optimally stimulate an im response. Indeed, it is generally preferred in the art that a composition having a molecular weight of 10,000 Daltons be used to stimulate an im response. As such, certain modifications to the antigen can be made. For example, the isolated CCK peptide has a molecular peptide of less than 1,500 Daltons. To achieve optimal imgenicity, it is preferred that the CCK peptide be coupled chemically or via a recombinant molecular technique to larger "carrier" molecules. Examples of "carrier" molecules which make a peptide more imgenic, include ovalbumin, bovine gamma globulin (BGG), key limpet hemacyanin (KLH), mouse serum whey and rabbit serum albumin, among others. Due to its small size, it is preferred that the CCK peptide is conjugated with a carrier protein having a molecular weight of about 8,000 Daltons or more, to form a conjugate of a size capable of stimulating an im response.

A preferred method of coupling the CCK peptide to a larger protein carrier to form an imgen is as follows. The CCK peptide is covalently coupled to a purified carrier protein, such as bovine imglobulin G (IgG). The gluteraldehyde-grade electron microscopy [0 = CH- (CH2) 3-HC = 0] is preferably used as a functional coupling reagent, wherein the aldehyde groups form an irreversible bridge between the N-terminal amino group of the peptide and the available amine groups of the carrier molecule of the protein. This procedure can be applied as a single step, wherein the peptide is reacted simultaneously with gluteraldehyde and bovine IgG in the presence of 10 mM sodium acetate at pH 7. The glycine is then added to cool rapidly any of the unreacted aldehyde groups that may still be present. The peptide is then dialyzed and a protein assay is performed to determine the concentration of the peptide. The preparation is then preferably subjected to aliquot and stored in refrigeration.

Once a suitable form of the antigen is available for imzation, it can then be used to formulate a vaccine. For example, in the case of the CCK peptide, the conjugated peptide can be formulated as a vaccine based on adjuvants. This vaccine can then be used to stimulate an antibody production in a target animal. A typical adjuvant which can be used is the complete Freund adjuvant. If the mammal comprises the target animal, then subsequent inoculations should consist of an incomplete adjuvant. Other suitable adjuvants include those as referenced in A compendi um of vaccine adjuvants and excipients, Vogel, F.R. and Powell, M.F. (nineteen ninety five); In Vaccine Design, The Subunit and Adjuvant Approach, Powell, M.F. and Newman M.J. eds. Plenum Press N.Y., as well as others are known to those of ordinary skill in the art. The amounts and concentrations of the adjuvants are readily determined by those of ordinary skill in the art, Antibody Production It is preferred that, for purposes of neutralizing the gastrointestinal neuro-modulator, the target animal is either an egg-producing animal or a milk-producing animal, and more preferably a bird, bovine or sheep. Birds, sheep and cattle are preferred because they produce a form of administration of the antibody easily (ie, the milk or the egg itself). As is well known to those skilled in the art, once an immune response is stimulated, antibodies are produced and transferred to the eggs or milks of the immunized bird or mammal.

Chickens are the most preferable source of eggs, even though any egg-producing animal can be used. Other suitable animals that produce eggs include turkeys, geese, ducks, reptiles, amphibians and the like. As animals that produce milk, daily, cows are preferred, although other animals that produce milk are contemplated by this invention, which include goats, sheep, buffalo or llamas among others. In addition, of the eggs and milks, the antibodies can be obtained from the whole blood, plasma or serum, from any inoculated animal.

In a preferred embodiment, the production of the CCK antibody is encompassed by the use of known immunization technology for the production of antibodies in egg yolks of birds or other egg-producing animals. Specifically, the hens are stimulated by an injection with the CCK peptide which is conjugated to a carrier protein as described above. In response to the conjugated CCK peptide, the eggs that they lay for these hens will contain high levels of CCK antibodies in large amounts in the yolk or supra-normal levels of an antibody that can be generated by hyperimmunization of the target animal. In particular, if, for example, a hen is selected as the target animal, the hen may be brought to a specific state of immunization by means of, for example, periodic boosting administrations of highly sufficient dosages of a gastrointestinal neuro-modulator. The range of preferred dosages should be equal to or greater than the dosage necessary to elicit a primary immune response. Hyper-immunization procedures are well known in the art and have been described in detail (see U.S. Patent No. 4,748,018).

Alternate modes of hyperimmunized target animals may be used in place of gastrointestinal neuro-modulatory vaccines, and include the use of genetic vaccines. In particular, any DNA construct (generally consisting of a promoter region and a sequence encoding an antigen) will trigger the release of the antibody. Genetic vaccines consist of vectors encoding the antigen, unprotected DNA fragments, plasmid DNA, DNA-RNA antigens, DNA protein conjugates, DNA liposome conjugates, DNA expression libraries, and a viral and bacterial DNA released produce an immune response. Methods of DNA release include particle bombardment, direct injection, viral vectors, liposomes and jet injections among others. When these release methods are applied, such smaller amounts are necessary and will generally result in more persistent antigen production. When such genetic procedures are used, the preferred method for introducing DNA into birds is through an intramuscular injection of DNA into the chest muscle.

Any form of neuro-modulator can be administered to the target animal to stimulate an immune response, which includes the purified and synthesized neuro-modulator. Means well known in the art can be used for the purification of the neuro-modulator such as known peptide synthesis techniques including fractionation, chromatography, precipitation or extraction. Peptide synthesis is well known in the art, and suitable synthesis systems are available from several commercial sources (ie, PerSeptive Biosystems, Inc. Framingham, MA 01701).

For administration to the target animals to stimulate an immune response, a particular modality is contemplated in which the CCK peptide is encapsulated prior to administration. Generally, it is preferred that matrix materials in encapsulated form contain the CCK peptide be formed from polymers of biocompatible materials, or more preferably, from biodegradable materials such as polylactic acid, polyglycolic acid, copolymers of lactic acid and glycolic acids , polycaptolactone, copolyoxalates, proteins such as collagen, esters of glycerol fatty acids, and cellulose esters. These polymers are well known in the art and are described for example in U.S. Pat. Nos. 3,773,919; 3,887,669; 4,118,470 and 4,076,798 In one embodiment, the hyperimmunization of an animal is carried out by a single administration of a microencapsulated vaccine. The feeding of a microencapsulated vaccine results in a constant, pulsed release of the vaccine in the animal and eliminates the need for repetitive injections. In addition, a greater immune response, as measured by the production of antibodies, is achieved using a controlled release vaccine. Many different compositions for the slow release of vaccines have been described, which could be applicable to the method of the invention, for example, as described in Sanders, H. J., Chem & Engineering New, April 1, 1985, pp. 30-48.

Other sources of antibody production include cell fusion using hybridoma techniques, genetically altered cell cultures and fermentation, using, among others, recombinant technology.

Administration of the antibody Once the antibodies are produced, they can be administered to an animal subject to neutralize the particular gastrointestinal peptide or its receptor and thereby increase the smooth muscle protein and reduce the fat. While eggs, and more preferably immunized eggs, are the preferred source of massive quantities of antibodies, it is possible, as is stated early, to collect the antibodies from the milk, whole blood, plasma or serum of the target animal.

The antibodies can be isolated and purified from animals that produce egg and milk or their respective eggs or milk, by methods known in the art. A number of methods for the extraction of antibodies from egg yolk have been described. Polson et al 1985 and Jensenius et al., 1981, successfully use polyethylene glycol and sodium dextran sulfate respectively, as precipitating proteins in the isolation of pure immunoglobulin from egg yolk. Yokoyama et al. 1992 obtains the water soluble protein fraction after the lipid components are precipitated with an aqueous dispersion of acrylic resins. (US Pat. No. 5,367,054,1994) discloses a high yield, high purity method for the isolation and purification of immunoglobulins or fragments thereof from egg yolk by extracting the yolk with a composition containing one or more fatty acids. of medium chain, The neuro-modulator antibody Gl of the present invention is administered to an animal subject by any means that increases muscle protein and / or reduces fat in the animal subject. It is preferred that administration occurs by feeding the egg or egg yolk of vaccinated animals that produce egg or of vaccinated animals that produce milk. Eggs, yolk and milk are natural food ingredients and are safe and non-toxic.

Other embodiments include administration of the purified antibody parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, intranasally or orally.

In the case where the neuro-modulator antibody Gl is produced in the egg of an immunized bird, it is preferred that the egg itself, which contains the neurol modulator antibody Gl, whether it works as, or is processed in, a food product. A preferred method for preparing the egg to be processed into a food product involves drying the egg in the egg powder. Although several methods are known for drying eggs, spray drying is a preferred method. A temperature of not more than 140 F (60 ° C) is preferably used. The samples are monitored for their moisture content during the drying process to obtain a final product that has some desired consistency.

The dry powder egg can be mixed with food rations for food animals or can be directly atomized into food pellets preferably in oil and thus directly feed food animals in a simple form. With reference to the CCK antibody, typically 0.1 to 1 of the egg containing the CCK antibody of this invention, is used per 8 pounds of feed. In the case of poultry, the atomized egg yolk powder is typically sprayed or mixed in poultry feed at 50-500 grams per ton, consistent with the maintenance of antibody titers, sufficient to increase muscle protein and reduce fat in the animal subject.

The dry egg powder can be used in beverages, protein supplements and any other nutritional product associated with athletes, which are particularly suitable for human consumption. In addition, the egg powder can be used in baking mixes, powder bars, candy, cookies, etc.

To increase or improve the effect, a synergistic effect can be achieved by the administration of the neuro-modulator antibody Gl in combination or coincidentally with other antibiotics and growth promoting substances. Antibiotics and growth promoting substances, such as flavomycin, are well known in the art, and those skilled in the art can readily determine the appropriate dosages to be administered to animal subjects.

Alternatively, whole eggs can be administered to the animal subject or, if desired, the whole egg can be eaten raw. In other words, there is no need to separate the yolk from albumin, except to reach higher concentrations of the antibody.

In chaos of administration of the purified antibody, oral administration is the preferred method and it is preferred to encompass it through solid dosage forms, which include capsules, tablets, pills, powders and granules, among others. In solid dosage forms, the neuro-modulator antibody Gl is preferably mixed with at least one inert diluent such as sucrose, lactose, starch or fats. Such dosage forms may also comprise, as a normal practice, additional substances in place of the diluent. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents, pH sensitive polymers, or any other slow release encapsulated composition which are typically used for the purposes of encapsulation in food and industry. The tablets and pills can be prepared alternatively with an enteric layer.

The liquid dosage forms of the neuro-modulator antibody Gl for oral administration, preferably include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs, containing inert diluents commonly used in the pharmaceutical art. Following the inert diluents, the compositions may also include humectants, emulsifiers, suspending agents and sweetening agents.

Preparations of the neuro-modulator antibody Gl for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions or emulsions. Examples of non-aqueous solvents or carriers are propylene glycol, polyethylene glycol, vegetable oils such as olive oil and injectable organic esters such as ethyl oleate.

The dosages of the active ingredients may vary; however, it is necessary that the amount of the active ingredient be such that a dosage form is released. It will be recognized that the selected dosage form depends on the desired therapeutic effect, the route of administration and the duration of the treatment.

The dosage and frequency of administration will depend on the size, age and general health condition of the subject, taking into consideration the possibility of side effects. Administration will depend on the concurrent treatment with other drugs and the tolerance of the subject to the drug administered.

Effective Amounts The exact amount of the antibody or a composition containing the antibody will be administered in course, depending on the animal, the amount of specific antibody present, the route of administration and the age and size of the animal. In the preferred embodiment, administration to a subject with a hyper-immunized egg CCK or fraction thereof, has been determined, and is detailed in the following examples, in which the referred dose range of hyper-immunized egg or fraction of the same to be given to an animal subject is between 0.1 and 3 eggs per day. In addition, typically, eggs containing 0.1 to 1 CCK are used for 8 pounds of feed to effectively increase muscle protein and reduce fat in poultry. The dry egg yolk powder is typically added to a human food or animal feed at 0.007% up to 10% dry weight. The upper limit of egg which can be administered is not critical because the immunized eggs are not relatively toxic and are normal constituents of the human and animal diet.

When they are fed dry egg yolk, sprayed on the poultry, the powder is typically sprayed or mixed in the feed at 50 - 500 grams per ton.

The effective amounts of antibodies to be administered to an animal subject will generally vary from 1 μg to 50 mg of the antibody per kg of the body weight of the animal subject.

Applications of the Antibody The antibodies or compositions containing the antibody of this invention are used to increase smooth muscle protein and reduce fat in any animal, and more preferably, in an animal which functions as a source of lament. Some sources which are beneficial include poultry, including chickens and turkeys; meat and skin of sheep; beef and veal; pork meat; and rabbits. With respect to all animal groups, and, in particular, humans, antibodies and compositions containing antibodies of the invention increase the performance of smooth muscle and reduce fat in the groups of animals suffering from gastrointestinal disorders, alterations to eat, hormonal alterations, famine, and poor nutrition caused by diseases such as diarrhea and HIV, among others; The antibodies and compositions containing antibodies of the invention are additionally applicable for weight control in domestic animals and pets, such as cats, dogs, horses, rabbits and the like.

Additionally, antibodies and compositions containing antibodies of the invention are effective in improving athletic performance in humans and purebred, among others.

Having now to generally describe this invention, it will be further described by reference to certain specific examples which are provided herein for purposes of illustration only and are not intended to be limiting unless otherwise specified.

EXAMPLES EXAMPLE 1 Stimulation of CCK-8 antibodies in eggs Methods CCK peptide vaccines were prepared by conjugation of synthetic cholecystokinin (CCK-8) (Fragment 26-33 of amide with sulfated tyrosine) to bovine gamma globulin (BGG) using glutaraldehyde. These vaccines were emulsified with complete Freund's adjuvant (1: 1) and injected (100 ug CCK) in the laying hens. A second injection of the CCK-8 conjugate in the incomplete Freund adjuvant was injected 7 days after the first injection. A second group of control chickens did not receive the CCK vaccination. Approximately 2,880 eggs were collected after 5 months of the initial injection and the whole eggs were separated into the yolk and egg white. The egg yolk was spray-dried in 8 batches and the antibody titers of the mixed spray dry powder yolk were measured.

Results ELISA determinations of the CCK antibody in the spray dried egg yolk showed higher endpoint titers compared to the negative control egg yolk (TABLE 1). The yolks of hens vaccinated with the peptide CCK-8 showed an average of 1064 ug / gram in contrast to the negative control egg yolk containing 3.4 ug / gram of the specific antibody against the CCK-8 peptide.

EXAMPLE 2 Muscle protein increased by feeding egg yolks containing anti-CCK-8 antibody Methods: Dried egg yolks containing the anti-CCK-8 antibody with CCK antibody top titers were mixed in the poultry feed and fed to the hens to determine the efficiency of yield as a result of the administration of the CCK antibodies. The objective of this test was to determine both yields of individual parts and yields of birds or carcasses before and after cooling. A test field was run in a Chicken of type Tender chicken Gallus Domesticus 592 (Ross x Hubbard, Peterson X Arbor Acre, Avian x Avian). The chickens were of mixed sex, and were started in food formulations at the age of one day after hatching. A single batch of basal ration for each of the formulated diets (starter, breeder, and terminator) were mixed uniformly. The experimental treatments were mixed as follows: A. Control without egg yolk CCK-8 B. 35.25 grams of egg yolk CCK-8 per ton of feed C. 70.5 grams of egg yolk CCK-8 per ton of feed D. 105.75 grams of egg yolk CCK-8 per tonne of food Dried egg yolk powder sprinkled with CCK-8 was mixed in soybean oil and sprayed on the food pellets. Water is provided at will.

A total of 160 birds were selected from each of the treatments and each strain of birds was represented in the trial. This selection contains an equal number of males (80) and females (80). All birds were selected at an average body weight for the treatment +/- 100 grams.

After 47 days of feeding, the birds were humanely sacrificed by feather number and sex groups. Each group was carried through the procedure at the same time. The bleeding time was approximately 5 minutes. All birds were weighed and identified by number. The birds were heated to 280 ° F and drilled for a predetermined time of 9 minutes. The neck and leg were cut and weighed. The following procedures were used to collect the remaining data points: 1. Individual live birds were weighed; 2. The dead were processed without giblets (viscera) (WOG) pre-chilled weight after bowel, neck and anus removal (pre-chilled weight); 3. The liver, neck and gizzard were weighed; 4. Birds were chilled as a group for 30 minutes and then weighed again (post-chill weight); 5. The abdominal fat pad was removed from around the gizzard and abdominal area; and 6. Each bird was cut individually by parts; breast, breast (1 apechet was removed from the rib cage); drum; thigh, total leg; wings and tail. All the parts were calculated based on pre and prost-cooling.

Results The results show that birds that were fed daily with 70 grams / ton and 105 grams / ton of egg containing CCK antibody or fraction thereof daily for the length of their life time, showed either an increase in the yields of muscle proteins as well as a reduction in fat production. In particular, the pre-cooled carcasses showed an average increase in muscle protein yield of approximately 2% and an average fat reduction content of approximately 0.3% both significant under industrial standards.

It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, property is claimed as contained in the following

Claims (35)

1. A method for achieving at least one of the following: increase in muscle protein or reduce fat in an animal, characterized in that the method comprises administering to the animal a composition comprising an effective amount of an antibody, wherein the antibody comprises a gastrointestinal neuro-modulator antibody.

2. The method of claim 1, characterized in that the gastrointestinal neuro-modulator antibody is selected from the group consisting of antibodies to acetylcholine, bombesin, cholecystokinin, gastrin, substance P, 5-hydroxytryptamine, vasoactive intestinal polypeptide, enkephalin, neurotensin, neuropeptide And, secretin, urcortin, corticotropin release factor, motilin, gastric inhibitor peptide and gastrin-releasing peptide.

3. The method of claim 1, characterized in that the gastrointestinal neuromodulatory antibody is the cholecystokinin antibody.

4. The method of claim 1, characterized in that the composition is obtained from an animal that produces egg or an animal that produces milk.

5. The method of claim 4, characterized in that the animal that produces eggs or the animal that produces milk is hyperimmunized with an antigen or genetic vaccine.

6. The method of claim 5, characterized in that the antigenic vaccine comprises at least one gastrointestinal neuro-modulator.

7. The method of claim 6, characterized in that the gastrointestinal neuro-modulator is selected from the group consisting of acetylcholine, bombesin, cholecystokinin, gastrin, substance P, hydroxytryptamine, vasoactive intestinal polypeptide, enkephalin, neurotensin, neuropeptide Y, secretin, urcortin , corticotropin release factor, motilin, gastric inhidior peptide and gastrin-releasing peptide.

8. The method of claim 4 characterized in that the composition comprises an egg or a fraction thereof obtained from an egg-producing animal.

9. The method of claim 8 characterized in that the effective amount of the composition administered to an animal comprises approximately 0.1 to 3 eggs per day.

10. The method of claim 4, characterized in that the composition comprises milk colostrum, or a fraction thereof.

11. The method of claim 3, characterized in that the effective amount of the cholecystokinin antibody ranges from 1 μg to 500 mg per animal ..}.

12. The method of claim 1, characterized in that the antibody is administered parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, intranasally or orally.

13. A composition for achieving at least one of the following: increase in muscle protein or reduce fat in an animal, characterized in that the composition comprises an effective amount of an antibody, wherein the antibody comprises a gastrointestinal neuro-modulator antibody.

14. The composition of claim 13, characterized in that the gastrointestinal neuro-modulator antibody is selected from the group consisting of antibodies to acetylcholine, bombesin, cholecystokinin, gastrin, substance P, hydroxytryptamine, vasoactive intestinal polypeptide, enkephalin, neurotensin, neuropeptide Y, secretin, urcortin, corticotropin release factor, motilin, gastric inhidior peptide and gastrin-releasing peptide.

15. The composition of claim 13, characterized in that the gastrointestinal neuro-modulator antibody is the cholecystokinin antibody.

16. The composition of claim 13, characterized in that the composition is obtained from an animal that produces egg or an animal that produces milk.

17. The composition of claim 16, characterized in that the animal that produces eggs or the animal that produces milk is hyper-immunized with an antigen or genetic vaccine.

18. The composition of claim 17, characterized in that the antigenic vaccine comprises at least one gastrointestinal neuro-modulator.

19. The composition of claim 18, characterized in that the gastrointestinal neuro-modulator is selected from the group consisting of acetylcholine, bombesin, cholecystokinin, gastrin, substance P, hydroxytryptamine, vasoactive intestinal polypeptide, enkephalin, neurotensin, neuropeptide Y, secretin, urcortin , corticotropin release factor, motilin, gastric inhidior peptide and gastrin-releasing peptide.

20. The composition of claim 16, characterized in that the composition comprises an egg or a fraction thereof obtained from an egg-producing animal.

21. The composition of claim 21, characterized in that the effective amount of the composition administered to an animal comprises approximately 0.1 to 3 eggs per day.

22. The composition of claim 21, characterized in that the composition comprises milk colostrum, or a fraction thereof.

23. The composition of claim 15, characterized in that the effective amount of the cholecystokinin antibody ranges from 1 μg to 500 mg per animal.

24. A method for achieving at least one of the following: increase in muscle protein or reduce fat in an animal, characterized in that the method comprises neutralizing or increasing an endogenous gastrointestinal neuro-modulator in said animal.

25. The method of claim 24, characterized in that the gastrointestinal neuro-modulator antibody is selected from the group consisting of antibodies to acetylcholine, bombesin, cholecystokinin, gastrin, substance P, hydroxytryptamine, vasoactive intestinal polypeptide, enkephalin, neurotensin, neuropeptide Y, secretin, urcortin, corticotropin release factor, motilin, gastric inhidior peptide and gastrin-releasing peptide.

26. The method of claim 24, characterized in that the gastrointestinal neuro-modulator antibody is cholecystokinin.

27. The method of claim 24, characterized in that it comprises administering to said animal an effective amount of a composition comprising a gastrointestinal neuro-modulator antibody.

28. The method of claiming the gastrointestinal neuro-modulator antibody is selected from the group consisting of antibodies to acetylcholine, bombesin, cholecystokinin, gastrin, substance P, hydroxytryptamine, vasoactive intestinal polypeptide, enkephalin, neurotensin, neuropeptide Y, secretin, urcortin, corticotropin release factor, motilin, gastric inhibitory peptide and gastrin-releasing peptide.

29. The method of claim 27, characterized in that the gastrointestinal neuro-modulator antibody is the cholecystokinin antibody.

30. The method of claim 24, characterized in that it comprises administering to said animal an effective concentration of a gastrointestinal neuro-modulator antibody.

31. The method of claim 30, characterized in that the gastrointestinal neuro-modulator antibody is selected from the group consisting of antibodies to acetylcholine, bombesin, cholecystokinin, gastrin, substance P, hydroxytryptamine, vasoactive intestinal polypeptide, enkephalin, neurotensin, neuropeptide Y, secretin, urokartin, corticotropin release factor, motilin, gastric inhibitor peptide and gastrin-releasing peptide.

32. The method of claim 30, characterized in that the gastrointestinal neuromodulatory antibody is the cholecystokinin antibody.

33. A method for achieving at least one of the following: increase in muscle protein or reduce fat in an animal, characterized in that the method comprises administering to said animal a composition obtained from an animal immunized with a gastrointestinal neuromodulator.

34. The method of claim 33, characterized in that said gastrointestinal neuromodulator is selected from the group consisting of antibodies to acetylcholine, bombesin, cholecystokinin, gastrin, substance P, hydroxytryptamine, vasoactive intestinal polypeptide, enkephalin, neurotensin, neuropeptide Y, secretin, urcortin , corticotropin release factor, motilin, gastric inhibitor peptide and gastrin-releasing peptide.

35. The method of claim 33, characterized in that the composition is selected from the group consisting of milk, colostrum, egg, whole blood, plasma and combinations and fractions thereof. ^ "* METHOD AND FOOD PRODUCT TO INCREASE MUSCLE PROTEIN AND REDUCE FAT IN ANIMALS SUMMARY OF THE INVENTION The invention is directed to a method and food product for increasing muscle protein or reducing fat in an animal. The method comprises administering to said animal a composition comprising a gastrointestinal neuro-modulator antibody to neutralize the gastrointestinal neuro-modulator. 10 fifteen twenty 25