MXPA00010967A - Anti-diarrheal and method for using the same - Google Patents

Abstract

A food product and method for treating and preventing diarrhea in a subject animal suffering from or susceptible to diarrhea. The method comprises administering an egg product to the subject animal wherein the egg product is obtained from a hyperimmunized avian.

Description

ANTIDIARREICO AND METHOD FOR THE USE OF THE SAME FIELD OF THE INVENTION The invention relates to a product and method for treating and preventing diarrhea. More particularly, this invention relates to a natural food product which, when administered to a subject animal, treats and prevents diarrhea in this subject animal.

BACKGROUND OF THE INVENTION Diarrhea is a global problem for individuals of all ages. Diarrhea is a common condition, which in the least of cases is a life switch and can be life-threatening. Acute diarrhea can be produced by a variety of. pathological organisms, functional interruptions of the intestinal function and as a collateral effect related to the drug. Some of the conditions in which diarrhea occurs are infant diarrhea (for example, rotavirus-induced diarrhea), diarrhea of the Réf. 124968 childhood, organ-induced diarrhea (ie, food poisoning), increased gastrointestinal disorders, and diseases that indirectly affect the gastrointestinal system. Infants and children suffering from diarrhea have a major problem since they can become severely dehydrated and require fluids and medications. Diarrhea is also common in patients with cancer and can interfere with the treatment of cancer (Ippoliti, 1998). Chemotherapy, radiation therapy, surgery, severe graft disease (GVHD), bone marrow transplantation, or infection can induce diarrhea. Bacterial pathogens can also produce symptoms of diarrhea with a spectrum of effects ranging from severe tissue damage to a lack of noticeable damage. It is a complete toxigenic substance that causes acute and severe diarrhea, thus producing powerful toxins, which act by altering the biological activity in epithelial cells. (Isaacson, 1998). The common treatment of diarrhea consists of an antibiotic treatment of the causative organisms or pharmacological intervention in the pathophysiological function. Antidiarrheal drugs reduce the symptoms of diarrhea (consistency of loose excretion, frequency of defecation and excessive weight of excretions or bowel movements) due to effects on intestinal transit, mucosal transport or luminal contents (Schiller, 1995). Opioids such as loperamide are the most useful antidiarrheal agents and act by a combination of intestinal transit inhibition, pro-absorption and antisecretory effects. Other pharmacologically useful therapies include the use of alpha-adrenergic agonists such as somatostat ina analogs and clonidine. These drugs can modify mucosal transport in addition to slow transit but have limited clinical utility due to the non-specificity of the action. Absorbents (Kaopec t at e), bismuth (Pepto-Bismol) and texture modifiers of the stools are frequently used on the opposite medication, but their efficacy, in addition to Pepto-Bismol, is widely disapproved.

A natural antidiarrheal agent, safe and effective, could be very useful in the therapy of acute or chronic diarrheic conditions.

BRIEF DESCRIPTION OF THE INVENTION The invention is based on the discovery of the inventors that there is anti-diarrheal activity in egg or egg products and particularly in egg products obtained from hyperimmunized birds, which when administered to a subject animal, prevent or reduce diarrhea in this animal subject. In particular, the invention is directed to a method for treating and preventing diarrhea in a subject animal suffering from or susceptible to diarrhea, the method comprising administering to the subject animal an effective amount of an egg product. The invention is also directed to a composition containing beneficial properties that prevent or reduce diarrhea in a subject animal who is suffering from or who is susceptible to diarrhea, the composition comprising a product obtained from an animal that has been hyperimmunized with at least one immunogenic substance.

DESCRIPTION OF THE INVENTION The hyperimmune egg product of the invention, when administered to a subject animal, is used for the treatment and prevention of diarrheal diseases in this subject animal.

Terminology: The term "diarrhea" means abnormal frequency and liquidity of fecal discharges resulting from an imbalance between absorption and secretion in the intestine. The term "hyperimmunization" means exposing one or more immunogens so that an immune response is raised and maintained above the state without natural exposure. The terms "egg" or "egg product" mean any whole egg (table, hyperimmunization or otherwise) or any product or fraction derived therefrom. The terms "table eggs" or "table egg product" mean a whole egg medium, or any product or fraction derived therefrom, obtained from animals that produce eggs which are not maintained in a hyperimmune state. The terms "hyperimmune egg" or "hyperimmune egg product" means whole egg or any product or fraction derived therefrom, obtained from an egg that produces an animal maintained in a hyperimmune state. The term "supranormal levels" means levels in excess of those found in eggs of animals that produce eggs not maintained in a hyperimmune state. The term "immunogen" means a substance that is capable of inducing a humoral and / or immune-mediated antibody response by cells rather than immunological tolerance. The term means the ability to stimulate an immune response as well as react with its products, eg, antibody.

The term "combinatorial derivative immunogens" refers to a new process of generation of molecular diversity between immunogens by means of combinatorial synthesis. The term "bioengineering immunogens" refers to immunogens which are obtained through the process of gene cloning technologies and genetic rearrangements that allow the insertion of coding nucleotides that can result in molecules that have immunogenic properties. The term "genetic vaccine" refers to a nucleic acid vaccine which is generally produced by recombinant technologies and which can produce an immune response. The term "treatment" means that the onset of symptoms (including pain) of the disorder and / or pathogenic origin of the disorder can be treated or completely prevented, or, if present, symptoms can be improved or eliminated completely. For example, the hyperimmune egg product treats arthritis and / or an autoimmune disease not only by suppressing the symptoms of the disorder in humans and other mammals, but also by acting as a prophylactic agent to counteract the presence of the disorder in the recipient. The term "prevention" means that the progression of the disease is reduced and / or eliminated, or that the onset of the disease is eliminated. The term "administrator" means any method for providing a subject with a substance, including orally, intranasally, parentically. (intravenously, intramuscularly, or subcutaneously), rectally or topically. The term "animal" means the definition of the animal kingdom. The term "white animal" refers to an animal which functions as the egg or product of the egg produced by the animal. The term "subject animal" refers to the animal to which the egg or egg product produced by the target animal is administered.

The invention The hyperimmune egg product of the invention, when a subject animal is administered, is useful in the treatment and prevention of diarrhea in the subject animal. The product and method of the invention particularly relates to the use of the hyperimmune egg product, which is a natural food product, in the treatment and prevention of diarrhea and related disorders in a subject animal. Being natural, this limenticio product can be used to treat and prevent diarrhea and related disorders without the danger of side effects. Those allergic to eggs or who have an intolerance to eggs may not be able to ingest the hyperimmune egg product in certain admirable forms. In a preferred embodiment, the invention comprises an egg or hyperimmune egg product obtained from an animal that produces eggs, and more preferably, a bird, which has been hyperimmunized with at least one inmonogenic substance. The hyperimmune egg product is one which is preferably administered orally to the subject animal although the egg or hyperimmune egg product can be further separated into more potent fractions which can be administered subsequently to an animal subject in a variety of shapes . The egg or hyperimmune egg product of the invention, when administered to a subject animal, is effective in the treatment and prevention of all forms of diarrhea and related disorders, in this subject animal, but is not limited to, acute diarrheal diseases or chronic diseases such as diarrhea of infants (for example, including those that are induced by viruses or bacteria), diarrhea of childhood, diarrhea induced by adult organism, and diarrhea induced by gastrointestinal disorders, among others.

Product of the Hyperimmune Egg The product of the hyperimmune egg can be produced by any animal that produces eggs. It is preferred that the animal be a member of the Ave class or, in other words, a bird. Within the class of birds, domesticated birds are preferred, but other members of this class, such as turkeys, ducks, and geese, are an adequate source of the hyperimmune egg product. When the egg-producing animals are kept in a specific state of immunization by means of, for example, periodic administration of booster vaccines of immunogenic substances, the animals will produce eggs having beneficial properties which, when consumed by the subject, such properties charities will treat and prevent diarrhea in this subject. This special state of hyperimmunization is preferably achieved by the administration of an initial immunization, followed by periodic booster vaccines with sufficiently high doses of specific immunogenic substances or mixtures of immunogens. The preferred dose of booster vaccines should be equal to or greater than 50% of the dose necessary to produce the primary immunization of the bird. Thus, there is a dosage of threshold booster vaccines below which the properties are not produced in the egg of the bird, although the bird is in what could normally be called an immune state.

Having knowledge of the requirement to develop and maintain a hyperimmune state, it is within the skill of the art to vary the amount of immunogenic substance administered, depending on the gender of the animal producing the eggs and the strain used, to keep the animal in the hyperimmune state. . The hyperimmune state is preferably produced by any immunogen or combination of immunogens. Hyperimmunization is preferably achieved by multiple exposures to multiple immunogens, multiple exposure to single or single immunogens, or simple exposures to immunogen libraries. In addition to immunizations with immunogenic substances that are naturally present, immunization can also be performed using immunogenic substances which are synthetically derived by combination chemistries. The basic strategy is to join multiple combinations of manufacturing blocks in chemistry to produce a population of molecules with diversity. Several methods have recently been developed by solid-phase combinatorial synthesis and solution of oligomer libraries (Fodor, S. et al., Science 251: 767 (1991); Houghton, R. et al., Nature 354: 82 (1991)). as well as small organic molecules (Bunin, B. &Ellman, J., J. Am. Chem. Soc. 114: 10997 (1992)). Rapid multiple peptide and oligomer synthesis can serve as a source for derived immunogens. In addition, an alternative strategy could allow the addition of organic building blocks or combinatorial form to a skeleton molecule for improved immunogenicity Alternative modes of hyperimmunization of egg producing animals can be used in place of immunogenic vaccines and include the use of genetic vaccines In particular, any DNA construct (usually consisting of a promoter region and an immunogenic substance coding sequence) will activate a DNA response. Immune vaccines: Genetic vaccines consist of immunogenic coding vectors, untitled DNA fragments, plasmid DNA, DNA-RNA immunogens, DNA protein conjugates, DNA liposome conjugates, DNA expression libraries, and viral DNA or bacterial administered to produce an immune response. Methods of DNA release or expression to produce an immune response. Methods of DNA expression include particle bombardment, direct injection, viral vectors, liposomes and jet injection, among others. When these expression methods are applied, many smaller amounts may be necessary and generally result in more persistent immunogenic production. When genetic processes are used, the preferred method for introducing DNA into birds is through intramuscular injection of the DNA into the breast muscle. Methods of DNA expression or release include but are not limited to, particle bombardment, direct injection, liposomes, jet injection (Fynan, E.F. et al., Proc.

Nati Acad. Sci. USA 90: 11478-11482 (1993)). Nucleic acids that encode known or unknown immunogens, promoter regions (notably the CMV cauliflower mosaic virus) and bacterial origin of SV40 can be replicated in bacteria to produce the plasmid DNA for use in DNA injections. Although several routes of parenteral administration of DNA are effective in chickens, the preferred method is intramuscular injection into the breast muscle. Tests for vaccines are carried out on birds hatching eggs, preferably chickens. Repeated immunizations are given at intervals of one to two weeks for up to six months. It is preferred that the amounts of DNA used are generally in the order of 50-300 μg of DNA in. saline solution for direct injection. For the bombardment of particles, 4-100 μg of DNA coprecipitated in beads or gold globules by the addition of 2.5 M CaCl 2 are preferred. Repeated immunizations can be given intradermally by this acceleration method of the particles coated with DNA in the living animal.

Hyperimmunization procedure The following list of steps is an example of a preferred procedure used to bring an egg-producing animal to an enhanced state of immunity from which the resulting egg or hyperimmune egg product can be administered to a subject: 1. Select one or more immunogenic substances. 2. Produce an immune response in the egg-producing animal by primary immunization. 3. Administer booster vaccines of appropriate dosage immunogenic substances to induce and maintain the hyperimmune state.

Step 1 Any immunogenic or combination of immunogens can be used as a vaccine. Immunogens can be bacterial, viral, protozoan, fungal, cellular substances, or any other substances to which the immune system of an animal that produces eggs will respond. The critical point in this step is that the immunogen (s) must be capable of inducing immune and hyperimmune states to the egg producing animal. Although only a single immunogen can function as the vaccine for the method of the invention, a preferred vaccine is a mixture of polyvalent bacteria and fungal immunogens selected from the following immunogenic families: the enteric bacillus or bacteroides, pneumococci, Pseudomonas, Salmonella, Streptococci, Bacillus, S taf ilococos, Neisseria, Clostridia, Mycobacteria, Actinomyce Chlamydia, and Mycoplasma. Viral immunogens are preferably selected from the following immunogenic families: adenovirus, picornavirus and herpes virus, although other viral immunogenic families will work. In an alternative modality, a polyvalent vaccine referred to as Series 100 (S-100) is used. The bacteria included in the S-100 vaccine are listed in Table 1 of Example 1. These vaccines have been previously described in US Patent Nos. 5,106,618 and 5,215,746, both assigned to Stolle Research and Development Corporation.

Step 2 The vaccine can be either an attenuated or short-lived or an extermination vaccine and can be administered by any method that produces an immune response. It is preferred that the immunization be performed by the administration of immunogens through intramuscular injection. The preferred muscle for injection in a bird is the muscle of the breast. The dose is preferably 0.05-5 milligrams of the immunogenic vaccine. Other methods of administration that can be used include intravenous injection, intraperitoneal, intradermal, rectal suppository, aerosol or oral administration. When DNA techniques are used for the hyperimmunization process, many small amounts are required, usually 300 micrograms. It can be determined whether the vaccine has elicited an immune response in the animal that produces eggs through a number of methods known to those skilled in the immunology art. Examples of these immunosorbent assays linked to the enzyme (ELISA), tested for the presence of antibodies for the stimulation of immunogens, and tests designed to evaluate the ability of immune cells from the host to respond to the immunogen. The minimum dose of immunogen necessary to induce an immune response depends on the vaccination method used, including the type of adjuvants and the formulation of immunogen (s) used as well as the type of egg producing animal used as the host.

Step 3: The hyperimmune state is preferably induced and maintained in the target animal by the administration of repeated booster vaccines of an appropriate dose at fixed time intervals. The time intervals are preferably ranges of 2-8 weeks over a period of 6-12 months. However, it is essential that administrations of booster vaccines do not lead to immune tolerance. Such processes are well known in the art. It is possible to use other hyperimmunization maintenance procedures or combination of procedures, such as, for example, intramuscular injection for primary immunization and intravenous injection for booster injections. Additional methods include simultaneously administering microencapsulated or liquid immunogen, or intramuscular injection for primary immunization, and booster dosages by oral administration or parenteral administration by microencapsulation means. Several combinations of primary and hyperimmunization are known to those skilled in the art.

Processing and Administration Once the egg-producing animals have been sufficiently hyperimmunized, it is preferred that the eggs of these animals be collected and processed to produce a product of hyperinvulsive eggs in the administrable form. Consecutively, the hyperimmunity egg product can be administered to the subject. The egg and / or egg product of the present invention is administered to an animal subject by any means that treats or prevents diarrhea in the subject animal. It is preferred that administration occurs by direct feeding of the egg or any other egg derivative. The egg or the yolk of the egg are natural food ingredients and are not toxic and safe. In one embodiment, the product of the egg of the invention is integrated into a dietary supplement. A preferred method for preparing the egg of the invention is incorporated in a dietary supplement that involves drying the egg in an egg powder. Although various methods are known to dry eggs, vaporization drying is a preferred method. The process of drying by vaporization of the eggs is well known in the art. Dry egg powder can be added in a variety of administrable forms, such as beverages in the form of, for example, protein powders, beverages for energy production, protein supplements and any other nutritional products, associated with athletes. . In addition, egg powder can be used in baking mixes, energy bars, candies, cookies, etc. Alternatively, the egg powder can be placed in a capsule form and administered as such. Other examples of egg processing include the production of an omelet, soft or very cooked egg, baking the egg or, if desired, the egg can be eaten raw or processed as a liquid egg. Finally, it is generally known in the art that the yolk and / or clear fractions contain the agent or agents responsible for the beneficial properties observed and referred to above. Those of ordinary skill in the art could clearly recognize that the additional separation should provide more potent fractions or the elimination of undesirable components, and could allow for other modes of administration such as administration of the egg product parenterally, subcutaneously, intravenously, by intramuscular, intraperitoneal, intranasal, oral or topical. Such additional separation will provide the ability to make encapsulated products and pharmaceutical compositions with said egg or fraction thereof. To determine the efficiency of the hyperimmunized egg product in the treatment and prevention of diarrhea, the inventors use an animal model of diarrhea. The resulting data suggest that a high dose of the hyperimmunized egg product can both prevent and treat diarrhea in a well-known animal model referred to the administration of castor oil., and described later (See E xemplo 2). The inhibition of diarrhea induced by castor oil has been used as an animal model for the development of antidiarrheal agents such as diphenoxylate and loperamide and has been shown to be a good predictor of antidiarrheal activity in humans for at least 25 years (Awouters et al, 1974). The present study indicates that acute egg dosing obtained from chickens immunized against a variety of immunogens can inhibit the diarrhea induced by castor oil. The mechanism of the diarrheogenic activity of castor oil is complex. Castor oil should be metabolized first to ricinoleic acid in the lumen of the intestinal tract. Ricinoleic acid then produces a marked increase in the amount of fluid and electrolyte secretion in the intestine resulting in diarrhea. The mechanism of action of beaver oil has recently been studied by Mascolo N et al who found an activation of platelet activating factor (FAP) in duodenal tissue by nitric oxide (NO) released in response to castor oil. The detailed study in Example 2 shows that long periods of pretreatment are not necessary to show activity of the hyperimmune egg product and that the hyperimmune egg product is effective when given orally in a pill dose. Accordingly, it is the conclusion of the inventors that the hyperimmune egg product is an effective and safe therapy for the relief of acute or chronic diarrhea regardless of cause and can be a valuable addition for therapy in diarrheal conditions. The study showed that when the hyperimmune egg product is given per dose of oral pill for two days, it will significantly inhibit the diarrhea induced by beaver oil in a mouse. When the treatment and prevention of diarrheal disorder is reached, the hyperimmune egg product is preferably administered to the subject in an amount that is immunologically effective in the treatment and prevention of the particular disorder. A dose-related effect was observed when doses of 1, 2 and 4 grams / kg were administered in the beaver oil study. The dosage and duration of administration, however, will depend on the particular condition, if present, and, if so, the improvement of the condition in the subject. It is preferred that the hyperimmune egg product be provided in any amount that is necessary and effective in the treatment and / or prevention of the condition and symptoms of the condition. For example, in some cases, daily amounts ranging from less than one to several hyperimmune, complete eggs (or hyperimmune egg products that contain the equivalent of less than one to several hyperimmune, complete eggs) can be administered to the subject depending on the particular circumstance of the condition. More potent fractions can be separated and concentrated by methods well known in the art, from several hundred eggs. It is of significant importance to note that the egg product of this invention has been shown to be safe, non-toxic, ideal for long-term use and has no other side effects unless it is on humans allergic to eggs. The egg product can be administered orally either alone or in combination with drug therapy, for use in prolonged periods for disorders related to diarrhea. The advantageous properties of this invention can be observed by reference to the following examples illustrating the invention.

EXAMPLES EXAMPLE 1 Preparation of the S-100 Vaccine A bacterial culture containing the spectrum of the bacteria shown in Table 1 below, as obtained from the American Type Culture Collection, was reconstituted with 15 mL of the medium and incubated overnight at 37 C. Good growth was obtained , approximately one part of the bacterial suspension was used to inoculate one liter of broth with the inoculated one that is incubated at 37 C. After the good development in the culture was visible, the bacterial cells were collected by centrifugation of the suspension by 20 minutes. minutes to eliminate the medium. The obtained bacterial pellet was resuspended in sterile saline and the bacterial sample was centrifuged three times to wash the medium from the cells. After the third wash with sterile saline, the bacterial pellet was resuspended in a small amount of twice as much distilled water. The free bacterial suspension of the medium was removed by placing the suspension in a glass flask in a water bath at 80 C overnight. Viability if the broth culture was tested with a small amount of the bacteria removed, incubated at 37 C for five days and verified daily for development. < certifies that the bacteria have been eliminated. The dead bacteria were lyophilized to dryness. The dried bacteria were then mixed with sterile saline at a concentration of 2.2 10 'of. bacterial cells / mL of saline solution (optical density reading 1.0 at 660 nm). The bacteria contained in the S-100 vaccine are listed in Table 1 below.

TABLE 1 Bacterial list of the S-100 Escherichia coli Escherichia coli (aerabacter) Klebsiella pneumoniae Pseudomonas aeruginosa Salmonella typhi urium Salmonella dysenteriae Salmonella enteriditis Salmonella epidermis Salmonella simulans Streptococcus pyogenes, type 1 Streptococcus pyogenes, type 3 Streptococcus pyogenes, type 5 Streptococcus pyogenes, type 8 Streptococcus pyogenes, type 12 Streptococcus pyogenes, type 14 Streptococcus pyogenes, type 18 Streptococcus pyogenes, type 22 Pseudomonas vulgaris Streptococcus agalactiae Streptococcus mitis Streptococcus mutans Streptococcus salavarius Streptococcus sanguis Streptococcus pneumoniae Propionibacterium acnes Haemophilis influenzae Immunization Procedure for the Hyperimmunozoid Egg Product A eliminated preparation of the pathogens was prepared as described above. For the first vaccination, the bacteria were mixed with complete Freund's adjuvant, and 5.6 mg of the bacterial material was injected into the breast muscle of a chicken. For the remaining vaccines, the bacterial preparation was mixed with incomplete Freund's adjuvant and the chickens were injected at two-week intervals for six months. The eggs were collected from the hyperimmunized chickens and then dried by evaporation in a powder form. During the evaporative drying process, the inlet temperatures do not exceed 160 ° C (320 Degrees F), the outlet temperatures were maintained according to the dust production in the range of 3.0 to 4.0 percent final moisture, and the pump pressure remained around 2500 to 4000 PSI The lower temperatures ranging from 37.7-71.1 ° C (100-160 F) were used, and the samples were checked for moisture content during the drying process to obtain a final product having some desired consistency.

EXAMPLE 2 Use of the Hyperimmune Egg Product in the Treatment of Diarrhea The purpose of these tests was to identify, characterize, and document the preventive actions of the hyperimmune egg product in an experimental model of diarrhea in mice. In this model that uses mice, diarrhea is induced by oral administration of castor oil. This test is a standard test for the antidiarrheal agent for human use and was used for the discovery of the two most commonly used antidiarrheal agents, loperamide and di phenoxylate.

Method These studies were conducted at the Product Safety Laboratories, East Brunswick, New Jersey. Male mice weighing 25-30 grams were obtained from Ace Laboratories, Boyertown, Pennsy1 vania. They were isolated for at least 5 days and then taken at random in groups of 10 and placed in plastic boxes with straw beds. The treatments were all administered by priming the mice for food on two consecutive days between 8:00 and 9:00 A.M. The mice gave 4.0 grams / kg po of either powdered control egg or immune powder in 20 mL / kg of distilled water. Hyperimmune egg powder dried by evaporation was provided by DCV, Inc., Wilmington, DE. This was obtained from eggs of chickens that have been repeatedly vaccinated with large amounts of dead enteric pathogens of human origin. Table eggs dried by evaporation were used as the control. One hour after the treatment on the second day with fattening, a dose of 0.3 mL of the castor oil was administered by means of the priming. The mice were then placed in cages with individual barbed surfaces and a faecal production was observed and recorded at 2, 4, and 6 hours after the administration of castor oil. A positive or negative response was used to measure the presence of diarrhea. The number of normal, soft or loose stools was also recorded. The evacuations were provided either normal or diarrheal in each of these periods of time. The results are expressed as the number of mice with diarrheal stools.

Test A: The mice were dosed with: 1. Control egg - Product DCV A-98-06-Jan ID # 843 lot 951600FB. PSL 80108 3D - 4.0 grams / kg PO 2. Hyperimmune egg - Product DCV B-98-06-Jan ID # 3059 batch 96298VOFP PSL 80108 4D - 4.0 grams / kg PO Test B: The mice were dosed with 1. Distilled water - 20 mL / kg PO 2. Hyperimmune egg - Product DCV B-98-06-Jan ID # 3059 lot 96298 VOFP PSL 80108 4D - 1.0 grams / kg PO 3. Hyperimmune egg - Product DCV B-98-06- Jan ID # 3059 lot 96298 VOFP PSL 80108 4D - 2.0 grams / kg PO 4. Hyperimmune egg - Product DCV B-98-06-Jan ID # 3059 lot 96298 VOFP PSL 80108 4D - 4.0 grams / kg PO Data analysis and statistics The results were analyzed using all or no criteria, with soft stools and staining of the genital anus that are counted as diarrhea. The results are given as the percentage of mice with diarrhea each time and the cumulative number of positives during the 6-hour period. The percent inhibition was calculated by comparison with the appropriate control. The statistical analyzes were completed using the chi-square test.

RESULTS The results of the study are shown in Table 2. The data are presented as the percent of mice with diarrhea and as the percent inhibition compared to the control for studies 1 and 2. The initial study (Test A) comparing the hyperimmune egg with the control egg showed a significant difference in the ability to inhibit the diarrhea induced by beaver oil by the hyperimmune egg. Four grams / kg of hyperimmune egg significantly blocked the diarrhea induced by castor oil in the tested subjects at a 4-hour observation period when compared to the normal egg. No diarrhea was noted in the 2 hour period and the smallest amount of diarrhea was found in all groups in the 6 hour period. A significant inhibition in the cumulative event of diarrhea during the full 6 hours was noted in the groups treated with hyperimmune egg. Three doses of hyperimmune egg were compared with distilled water in the second study (Test B). All groups were dosed on two consecutive days. On the second day, beaver oil was administered and the study was conducted in a manner similar to Test A. This was a minimal event of diarrhea noted in the first observation period. Nevertheless, significant diarrhea was noted in control treated mice at 4 and 6 hours observation period. The hyperimmune egg administered at 1 gram / kg did not show significant antidiarrheal activity in any period of time. The hyperimmune egg, administered at 2 grams / kg, showed significant activity in the 6 hour period but not at 2 o'clock or in the cumulative 0-6 hour period. The hyperimmune egg administered at 4 grams per kg had significant effects in all periods of time in which diarrhea was noted in the control period. The percent inhibition for diarrhea with castor oil during the period of 0-6 hours was dosed related to 38% inhibition with 1 gram / kg, 43% with 2 grams / kg and 62% with 4 grams / kg. An estimated effective dose of 50% could be between 2 and 4 grams / kg.

Discussion The hyperimmune egg product showed activity related to the significant dose against diarrhea induced by castor oil. Four grams / kg orally as a pill dose was effective in both studies and appears to be a reasonable therapeutic dose. The mechanism of hyperimmune egg activity against beaver oil is not known but may be related to potential intestinal antisecretory activity. The hyperimmune egg was not effective in previous studies in which it was administered in the diet. This may have been due to a lack of an effective hyperimmune egg concentration at the activity sites. The hyperimmune egg can find use as an acute therapy as an antidiarrheal in both animals and humans. This study showed that prolonged periods of pretreatment are not necessary to show activity and that it is effective when given orally in a pill dose.

TABLE 2: Castor Oil that Induces Diarrhea - Chronic Dosing with Nutrut icals Test A Rates # mice cm cti maa / # of ratcns tested Tfcaffrm ei ± o g kg PO 2 hr% 4 hr% 6 br% 0-6 br%% inh Cxx? Trol hole 0/10 0 9/10 90 3/10 30 12/30 40 E80108-3D Egg eraser 0A0 2/10 * 20 2/10 20 4/30 * 13 E8CH.08-4D Test B Dosage # mice with diarrhea / i from pircfcadbs mice Treatment g / Jfg PO 2 hr% 4 hr% 6 br% 0- € hr%% 2Dh Wstóculo 0 1/10 10 10/10 100 10/10 100 21/30 70 Ecotein of New 1 1/10 10 6/10 60 6/10 60 13 30 43 38 ES010808-4D 2 1/10 10 7/10 70 4/10 * 40 12/30 40 43 4 0/10 0 4/10 * 40 2? 0 * 20 8/30 * 27 62 EXAMPLE 3 Substantial Materials and Methods Male subjects with HIV positive (as documented by ELISA and Western Blot analysis) who vary in age from 18-50 years and who suffer from gastrointestinal problems were recruited from Jamshedji Jeejiboy (JJ) Hospital , Mumbai, India. These people have been previously diagnosed with one or more of the secondary conditions that define AIDS (refs.). None have participated in any of the medical research tests within at least 60 days or have been exposed to an innomodulator or vaccine for 90 days. Subjects who have frequent changes in dosage or types of medication to control clinical symptoms, alcohol or substance abusers, history of allergy to eggs or any other ingredient in the tested article were excluded from the study.

Purpose of the Study The open classification study test of a hyperimmune egg fortified diet supplement in the form of evaporative drying (DCV, Inc. Wilmington DE U.S.A.) was conducted for a total of 12 weeks. The diet supplement drink was recently prepared and consumed as a liquid once a day for 8 'weeks. At the end of this two-month period, the test article was not consumed any longer for the remaining 1 month of the study. The same doctor checked the subjects at four-week intervals for the entire duration of the study and the blood samples taken. All subjects maintained their normal diets and medications and were checked during the 60-day and 30-day trial period for some adverse signs or symptoms. The severity, date of initiation, duration, frequency, link of the study product, action taken and result of each of the adverse experiences were recorded. All subjects were required to visit the doctor prior to the beginning of the study (base visit) and after that at four-week intervals for a total of four visits. During each visit, the subject received a physical examination and detailed general assessment of their comfort with a list of issues that include a) estimation of the frequency of bowel movements and b) consistency of bowel movements, among others.

Two reported cases are present in the study: CASE 1 Subject # 1 was admitted with a weight of 46 kg. He has complaints of abdominal pain, nausea, vomiting, diarrhea and is being treated with antipasmodic / antiarrhythmic drugs and the administration of IV fluids. During the trial period in week 8, the subject reported a reduction in his attack of nausea and diarrhea. The general comfort of the subject seems to improve and he experiences a gained weight of 46 kg to 47.5 kg (Table 1).

CASE 2 Subject # 2 was admitted with a weight of 53 kg. He complains of respiratory distress and abdominal pain and was treated for Koch's infection. The subject has tested HIV positive for at least 6 years and has taken sporadic doses of Ayurvedic medicines for congestion and chest cough. The subject was also provided with antibiotics and cough syrups. After eight weeks of the completion of the test article, he showed improvement in general health and comfort throughout with a gained weight of 3 kg. His attacks of abdominal pain and respiratory distress were drastically reduced after four weeks with the product.

Responses of the Subjects Of the 17 subjects registered in the study, 15 (88.2%) showed an increase in weight, varying in what was gained from 0.5 to 6 kg. In some cases, the weights gained added a 10% increase over their initial weights. The quality of the life indexes as assessed by the doctor showed a marked improvement in both the physical and emotional state of the subjects. More recently, some subjects also experienced a greater reduction, or complete abolition, of the number of diarrheal incidents.

It is noted that in relation to this date the best method known to 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, the content of the following is claimed as property

Claims (17)

1. A method for the treatment and prevention of diarrheal symptoms in an animal subject, irrespective of the cause of said diarrheal symptoms, the method is characterized in that it comprises administration to the subject animal of an effective amount of an egg product.

2. The method according to claim 1, characterized in that the animal subject is suffering from or susceptible to diarrheal symptoms.

3. The method according to claim 1, characterized in that the egg product is obtained from an animal that produces eggs which has been hyperimmunized with a genetic or immunogenic vaccine.

4. The method according to claim 3, characterized in that the immunogenic vaccine comprises at least one immunogen selected from the group consisting of bacterial, viral, ovarian, fungal and cellular immunogens and mixtures thereof.

5. The method according to claim 4, characterized in that the immunogenic vaccine consists of a mixture of bacterial immunogens, said mixture comprising at least one immunogen of each of the following bacterial strains: Escherichia coli, Escherichia coli (aerobacter); Klebsiella pneumonia; Pseudomonas aeruginosa; Salmonella typhimurium; Salmonella dysenteriae; Salmonella enteriditis; Salmon epidermis; Salmonella simulans; Streptococcus pyogenes, type 1 Streptococcus pyogenes, type 3 Streptococcus pyogenes, type 5 Streptococcus pyogenes, type 8; Streptococcus pyogenes, type 12; Streptococcus pyogenes, type 14; Streptococcus pyogenes, type 18; Streptococcus pyogenes, type 22; Pseudomonas vulgaris; Streptococcus agalactiae; Streptococcus mitis Streptococcus mutans; Streptococcus sala varius; Streptococcus sanguis; Streptococcus pneumoniae; Propionibacterium acne s; and Haemophilis influenzae

6. The method according to claim 3, characterized in that the genetic vaccine comprises at least one DNA construct encoding the immunogen selected from the group consisting of untitled DNA fragments, plasmid DNA, viral DNA, bacterial DNA, libraries of DNA expression, DNA-RNA immunogens, protein conjugates of DNA and conjugates of DNA liposomes, and mixtures of the same.

7. The method according to claim 1, characterized in that the effective amount of the egg product administered to the animal subject varies from 0.5 - 6 grams of the egg product per kilogram of the weight of the subject animal per day.

8. The method according to claim 7, characterized in that the effective amount of the egg product administered to the subject animal is 4 grams of egg product per kilogram of the weight of the subject animal.

9. The method according to claim 1, characterized in that the egg product is administered parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, intranasally, orally or topically.

10. A composition containing beneficial properties preventing or reducing diarrhea symptoms in an animal subject, indifferent cause such symptoms of diarrhea, the composition is characterized by comprising a product obtained from an animal that has been hiperinmuni Zado with at least one immunogen.

11. The composition according to claim 10, characterized in that the subject animal is suffering from or is susceptible to diarrheal symptoms.

12. The composition according to claim 10, characterized in that the animal also comprises an animal that produces eggs.

13. The composition according to claim 12, characterized in that the product also comprises an egg product.

14. The composition according to claim 10, characterized in that the animal is hyperimmunized with an immunogenic or genetic vaccine.

15. The composition according to claim 14, wherein the immunogenic vaccine comprises at least one selected from the group consisting of bacterial immunogen immunogens, viral, ozoar prot ios, and fungal cell and combinations thereof.

16. The composition according to claim 15, characterized in that the immunogenic vaccine consists of a mixture of bacterial immunogens, said mixture comprising at least one immunogen of each of the following bacterial strains: Escherichia coli, Escherichia coli (aerobacter); Klebsiella pneumonia; Pseudomonas aeruginosa; Salmonella typhimurium; Salmonella dysenteriae; Salmonella enteriditis; Salmon epidermis; Salmonella simulans; Streptococcus pyogenes, type 1; Streptococcus pyogenes, type 3; Streptococcus pyogenes, type 5; Streptococcus pyogenes, type 8; Streptococcus pyogenes, type 12; Streptococcus pyogenes, type 14; Streptococcus pyogenes, type 18; Streptococcus pyogenes, type 22; Pseudomonas vulgaris; Streptococcus agalactiae; S reptococcus mitis; Streptococcus mutans; Streptococcus salavarius; Streptococcus sanguis; Streptococcus pneumoni ae; Propionibacterium acnes; and Haemophilis influenzae

17. The composition according to claim 14, characterized in that the genetic vaccine comprises at least one DNA construct encoding the immunogen selected from the group consisting of untitled DNA fragments, plasmid DNA, virico DNA, "bacterial DNA, DNA expression libraries, DNA-RNA immunogens, DNA protein conjugates and DNA liposome conjugates, and mixtures thereof.