MXPA00007005A - Composition and method for treatment and prevention of arthritis and/or autoimmune diseases - Google Patents

Abstract

A natural composition for arthritis prevention and treatment. The composition comprising an effective amount of an egg or fraction thereof. The egg is obtained from an egg-producing animal which as been hyperimmunized with at least one antigen. The egg or fraction thereof is also effective in the prevention and treatment of autoimmune diseases. A method for treating and preventing arthritis and/or autoimmune disease through administration of the egg or a fraction thereof is also disclosed.

Description

COMPOSITION AND METHOD FOR THE TREATMENT AND PREVENTION OF ARTHRITIS AND / OR AUSTOINAL DISEASES FIELD OF THE INVENTION This invention relates to the treatment and prevention of arthritis and autoimmune diseases. More particularly, this invention relates to a natural food product and its use in the prevention, combat, or reduction of arthritis and / or an autoimmune disease.

BACKGROUND OF THE INVENTION Arthritis Arthritis manifests itself in a variety of ways. Some of the most common forms include rheumatoid arthritis, osteoarthritis and generalized rheumatism. Rheumatoid arthritis is an autoimmune disease characterized by pain, swelling and stiffening in the joints. Rheumatoid arthritis is a disease that afflicts REF. 121596 approximately 3% of Americans, and particularly women. Rheumatoid arthritis is an extremely disabling disease and usually attacks adults between the ages of 30 and 40 years, while the occurrence of clinical diseases is greatest among those aged 40-60 years. Although drug therapy is sometimes effective, at most 7% of rheumatoid arthritis patients are incapacitated to some extent as fast as 5 years after the disease starts, and within 10 years, at most 50% are also disabled to work (Medical Sciences Bulletm, December 1994). Osteoarthritis produces symptoms similar to rheumatoid arthritis. In particular, although osteoartptis begins as a degeneration of the articular cartilage while rheumatoid arthritis begins as an inflammation in the smovio, each process approaches the other when the disease progresses. In osteoartptis, when the cartilage deteriorates and the congruence of the joint is altered, a reactive synovitis often develops. Conversely, when rheumatoid arthritis erodes cartilage, secondary osteoarthritis changes bone development and cartilage. In the final stages of both osteoarthritis and rheumatoid arthritis, the involved joints appear the same. Some other forms of arthritis include ankylosing seronegative spondyloarthropathy (ankylosing spondylitis) and reactive arthritis. These conditions are often referred to as the "associated diseases of B-27," and are difficult to differentiate from rheumatoid arthritis. In some cases ankylosing spondylitis, Reiters syndrome or psopathic arthritis are present coincident with RA in the same patient. In many cases, these patients are treated with the same drugs that modify the disease as those suffering from progressive rheumatoid arthritis. The onset of arthritis usually occurs after the age of 30 in those who are susceptible to such disease. However, some forms of arthritis can be initiated by different causes, such as slow virus infections. Because there is a great overlap, many physicians consider these forms as "generalized rheumatism" and address the management of diseases in the same way. Some diseases that fall in This category includes Chronic Fatigue Syndrome, fibromyalgia (fibrositis) and gout. Indeed, for some patients, the statement is the accumulation by superposition of rheumatoid arthritis and fibromyalgia. (Harris, Edward D. and W. B. Saunders, Rheuma toid Arthri ti s, 1997).

Autoimmune diseases As stated above, rheumatoid arthritis is an autoimmune disease, and just as, its etiology is both the same as the etiology of any other autoimmune disease. Generally, the body usually recognizes the difference between its own byproducts and foreign invaders (ie, bacteria, viruses, fungi, and protozoa, to name a few). When an immune cell (T or B lymphocyte) reacts to a "autoprotein" during its development, this cell is considered defective and is usually destroyed or inactivated. However, sometimes, a "self-reactive" immune cell will prevent destruction. At a certain later period, this cell can be activated and unleash an immune response. Activation is thought to occur after the infection with a common virus or bacteria that contains a polypeptide that has an extension of amino acids that binds to an extension on the defective autoprotein. Several bacteria, such as Es trep tococo. My couple, and borrelia, have been implicated in the initiation of the disease, as well as certain viruses, mainly retroviruses. In addition to RA, autoimmunity frequently results in such diseases as juvenile diabetes, multiple sclerosis, Graves' disease, Meneri's disease, myasthenia gravis, lupus ephematosus, and psoriasis. (Medi ca l Scien ces Bul l etm, September, 1994). Several neurological diseases such as Sydenham's Korea, chronic obsessive-compulsive disorders (ODC), attention deficit hyperactivity disorder (ADHD), Tourette's syndrome (by its acronym in Spanish) English, TS) and some cases of schizophrenia may have an autoimmune component and may be associated with antineuronal antibodies (Medical Sciences Bulletm, Sept. 1994). Currently, treatment for rheumatoid arthritis, other arthritis and another autoimmune disease is drug therapy. In general, patients are treated immunically with agents "first line", usually anti-inflammatory drugs, not spheroidal (for its acronym in English, NSAIDs) which mainly relieve symptoms. Patients are subsequently treated with disease modifying or "second line" agents (DMARDs) such as methotrexate, gold compounds, penicillam, sulfasalazine, and antimalarial drugs. However, all the above drugs have serious side effects, especially when administered in high doses. For example, aspirin can cause indigestion and stomach pain; Tenilbutazone can cause stomach ulcers and phenacetin can lead to kidney disease. Methotrexate can cause oral ulceration and gastrointestinal side effects (Gl). Therefore, despite the large number of pharmaceutical drugs that are usually available for the treatment of various forms of arthritis and autoimmune disease, there is still a need for an effective, simple treatment that can alleviate as well as prevent the onset of such diseases. , without the complication of side effects.

If a natural food product effective in the treatment and prevention of such diseases could be obtained, a readily administered, readily available, and safe therapeutic composition could be provided.

Related Technique: US Pat. No. 4,357,272 describes the isolation of antibodies from egg yolks derived from hyperimmunized hens. Hyperimmunization is produced by repeated injections of antigens derived from plant viruses, human IgG, tetanus antitoxin, live antivenom, and Serameba. U.S. Patent No. 4,550,019 discloses the isolation of egg yolks from antibodies presented in the hen by hyperimmunization with immunogens having a molecular or particle weight of at least 30,000 Antigens used for chickens were selected from plant viruses. , human immunoglobulms, tetanus toxin, and living poisons. U.S. Patent No. 4,748,018 describes a method of passive immunization of a mammal comprising purified antibodies of parenteral administration obtained from the eggs of a bird that has been immunized against the corresponding antigen, and wherein the mammal has acquired immunity to the eggs. The eggs of chickens immunized against specific bacterial antigens are described because they provide antiatherosclerotic effects in mammals in US Patent No. 5, 15,746. However, none of these references disclose or suggest that hypePnmunal eggs can be administered to animals to treat arthritis and / or an autoimmune disease. None of these references describe or suggest a method to provide a reasonable expectation that the hyperimmunization of a bird could produce a bird that lays eggs that have a capacity.

BRIEF DESCRIPTION OF THE INVENTION The invention is based on the discovery of the inventors that there is activity in egg and egg products, and particularly in egg products obtained from birds hyperiminumerated, which when administered to a subject animal, in particular mammals, prevent or reduce arthritis and / or autoimmune diseases in the subject animal. In particular, the invention is directed to a composition for the treatment and prevention of arthritis and an autoimmune disease, the composition comprising an egg product obtained from a bird which has been immunized with an antigenic or genetic vaccine. The invention is also directed to a method of treating at least one of the following disorders in a subject animal: arthritis and an autoimmune disease, the method comprising administering to the subject an effective amount of an egg product. The invention is further directed to a method wherein the egg product is administered to the subject animal in combination with a drug selected from the group consisting of non-spheroidal drugs, anti-inflammatory drugs and antiarthritic drugs, modifiers of the disease. The invention is finally directed to a composition for reducing antibodies against autoimmune diseases in a subject animal, the The composition comprises an effective amount of an egg product derived from a bird which has been hyperimmunized with an antigenic or genetic vaccine.

DETAILED DESCRIPTION OF THE INVENTION The invention generally relates to a composition and method for the treatment and prevention of autoimmune diseases and arthritis. The composition is preferably a natural food product which comprises the product of the egg or hyperimmune egg. The food product, when administered by the method of the invention, not only provides relief of pain and other symptoms caused by arthritis and autoimmune diseases, but may delay, and even prevent, the onset of such diseases. The preferred antigen mixture injected into the birds to produce the hyperimaged egg product does not contain specific antigens which are known to cause arthritis or autoimmune diseases. Therefore, it is surprising that the administration of the egg product obtained from birds immunized against a mixed antigen vaccine is effective for reduce the symptoms of and prevention of arthritis and autoimmune diseases when administered to a subject.

Definitions : The following definitions apply throughout The term "arthritis" means any of a variety of disorders marked by inflammation and degeneration of connective tissue structures, especially joints and related structures. It can be understood by pain, stiffness, or limitation of movement of these parts. Some forms of arthritis include rheumatoid arthritis, osteoarthritis, ankylosing seronegative spondyloarthropathy, reactive arthritis, chronic fatigue syndrome, fibromyalgia (fibrositis) and gout.

The term "autoimmune disease" applies to the standard medical definition as found in standard medical dictionaries such as Dorland's and Taber's. The following disorders are considered autoimmune diseases: rheumatoid arthritis, juvenile diabetes, multiple sclerosis, Grave's disease, Menep's disease, myasthema severe, lupus eptematosus, psoriasis, systemic sclerodermis, rheumatic fever and Sjogren's syndrome. The term "hypermunization" means being exposed to one or more antigens so that an immune response rises and maintains above the unexposed natural state. The terms "egg" or "egg product" each means any complete egg (food, hypemuminated or other form) or any product or fraction derived from it. The terms "food egg" or "food egg product" each means a complete egg, or any product or fraction derived therefrom, obtained from animals that produce eggs which are not maintained in a hypermmune state. The terms "hyperimmune egg" or "hyperimmune egg product" each means complete egg or any product or fraction derived therefrom, obtained from an animal that produces eggs 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 "combinatorial derivative antigens" refers to a new process of generation of molecular diversity between antigens by means of combinatorial synthesis. The term "biotechnical antigens" refers to antigens which are obtained through the process of genetic cloning technologies and genetic rearrangements which allow the insertion of coding nucleotides which can result in molecules that have antigenic properties. The term "genetic vaccine" refers to a nucleotide 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 are completely delayed or prevented, or if they arise, the symptoms are 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 or other mammals, but also acting as a prophylactic agent that counteracts the presence of disorder in the receiver. The term "prevention" means that the progress of the disease is reduced and / or eliminated, or that the onset of the disease is eliminated. The term "administer" means any method for providing a subject with a substance, including orally, intranasally, parenterally, (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-producing animal or egg product. The term "subject animal" refers to the animal to which the product of the egg or egg produced by the white animal is administered.

The invention The product and method of the invention is particularly related to the use of hypepmune egg, which is a natural food product, in the treatment and prevention of autoimmune diseases and arthritis. Being natural, this food product can be used to treat and prevent such diseases without the danger of side effects, except, of course, by allergic reactions in those intolerant to eggs. In a preferred embodiment, the invention comprises an egg or hyperimmune egg product which is effective in the treatment and prevention of arthritis and / or an autoimmune disease in an animal subject. The hypepmune egg is obtained from an animal that produces eggs, and more preferably, a bird, which has been hyperinmummed with at least one antigen. The product of the hypermmune egg is one which is preferably administered orally to the subject animal. The egg or hyperimmunized egg product can be further separated into more potent fractions which can subsequently be administered to an animal subject in a variety of ways. The egg or hypepnmune egg product of the invention is effective in the treatment and prevention of all forms of arthritis, including, but not limited to, rheumatoid arthritis, osteoarthritis, spondyloarthropathy seronegative ankylosing, reactive arthritis, chronic fatigue syndrome, fibromyalgia (fibrositis) and gout. The egg product of the invention is equally effective in the treatment of autoimmune diseases, such as rheumatoid arthritis, juvenile diabetes, multiple sclerosis, Grave's disease, Meneri's disease, myasthema grave, lupus erythematosus, psoriasis, systemic sclerodermis, rheumatic fever and Sjogren syndrome among others.

Hypermmune egg product The product of the hyperimmunized egg can be produced by any animal that produces eggs. It is preferred that the animal be an element of the class of Birds or, in other words, a bird. Within the Aves class, domestic birds are preferred, but other elements of this class, such as turkeys, ducks, and geese, are a suitable source of the hypermmune egg product. When such egg-producing animals are brought to a specific state of immunization by means of, for example, administrations of antigens by periodic booster injections, the animals will produce eggs which, when consumed by a subject, they will have beneficial properties in the treatment and prevention of arthritis and autoimmune diseases in this subject. Having knowledge of the requirement for the development and maintenance of a hypermmune state, it is within the skill of the art to vary the amount of the antigen administered, depending on the gender of the animal that produces eggs and generated ancestry, to maintain the animal in the hypermmune state. Alternative modes of animals that produce hyperimmunized eggs can be used in place of antigenic vaccines and include the use of genetic vaccines. In particular, any DNA construct (generally consisting of a promoter region and an antigen coding sequence) will activate an immune response. Genetic vaccines consist of vectors encoding antigens, unprotected DNA fragments, plasmid DNA, DNA-RNA antigens, DNA protein conjugates, DNA liposome conjugates, DNA expression libraries, and viral or bacterial DNA supplied to produce an immune response. DNA distribution methods include particle bombardment, direct injection, vectors viral, liposomes and jet injection, among others. When these methods of administration are applied, many smaller amounts may be necessary and generally result in more persistent antigen production. When such genetic processes are used, the preferred method for introducing DNA into birds is through intramuscular injection of the DNA into the chest muscle.

Hypepnmunization procedure The following list of steps is an example of a preferred procedure used to bring an egg-producing animal to a high state of immunity: 1. Select one or more antigens. 2. Derive an immune response in the egg producing animal by primary immunization. 3. Administer booster antigen vaccines of appropriate dose to induce and maintain the hypermmune state.

Step 1: Any antigen or combination of antigens can be used as a vaccine. Antigens can be bacterial, viral, protozoa, fungal, cellular substances, or any other substances to which the immune system of an egg-producing animal will respond. The critical point in this step is that the antigen (s) must be able to induce immune and hyperpnemonic states in the animal that produces eggs. Although only a single antigen can function as the vaccine for the method of the invention, a preterm vaccine is a mixture of polyvalent bacteria and viral antigens selected from the following families of antigens: the enteric and bacteroid bacilli, pneumococci, pseudomonas, salmonella, streptococcus , bacilli, staphylococci, neissepas, clostridia, mycobacteria, actinomycetes, chlamydia, and mycoplasma. Viral antigens are preferably selected from the following families of antigens: adenovirus, picornavirus and herpes virus, although other families of viral antigens will work. In an alternative modality, a polyvalent vaccine referred to as Series? OO (S-100) is used. The bacteria included in the S-100 vaccine is listed in Table 1 of Example 1. This vaccine has been described previously in U.S. Patents Nos. 5,106,618 and 5,215,746, both assigned to Stolle Research and Development Corporation. Another preferred vaccine for use is the EB-100E vaccine, the details of which are also described in Example 1.

Step 2: The vaccine can be either an attenuated or deleted life vaccine and can be administered by any method that produces an immune response. It is preferred that the immunization be performed by administering the antigens through intramuscular injection. The muscle of choice for injection in a bird is the muscle of the breast. The dosage is preferably 0.05-5 milligrams of the antigenic vaccine. Other methods of administration that can be used include intravenous injection, intraperitoneal, intradermal injection, rectal suppository, aerosol or oral administration. When DNA techniques are used for the hyperimmunization process, many smaller amounts are required, usually 1-100 micrograms. It can be determined if the vaccine has produced an immune response in the egg producing animal through a number of known methods for those who have experience in the immunology technique. Examples of this include enzyme linked immunosorbent assays (ELISA), tests for the presence of antibodies for the stimulation of antigens, and tests designed to evaluate the ability of immune cells from the host to respond to the antigen. The minimum dose of antigen needed to induce an immune response depends on the vaccination procedure used, including the type of adjuvants and antigen formulation (s) used as well as the type of egg-producing animal used as the Guest.

Step 3: The hyperimmune state is preferably induced and maintained in the target animal by repeated booster administrations of an appropriate dosage 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 booster administrations do not lead to immune tolerance. Such processes are well known in the art. It is possible to use other maintenance procedures for hypermmunication or combination of procedures, such as, for example, intramuscular injection for primary immunization and intravenous injections for booster injections. Additional methods include the simultaneous administration of liquid and microencapsulated antigen, or intramuscular injection for primary immunization, and booster doses 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 hyperpneamed, it is preferred that the eggs from these animals be harvested and processed to produce a hyperimmune egg product. Consequently, the hypermmune 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 arthritis and / or autoimmune disease in the subject animal. It is preferred that administration occurs by the direct feeding of the egg or any derivative of the egg. Egg and egg yolk are natural food ingredients and are non-toxic and safe. In an alternative modality, the egg is integrated into a food supplement. A preferred method for preparing the egg to be incorporated in a nutritional supplement involves drying the egg in an egg powder. Although several methods are known for drying eggs, spray drying is a preferred method. The process of spray drying or spraying eggs is well known in the art. The dried egg powder can be incorporated into beverages in the form of, for example, protein powders, energy developing beverages, protein supplements and any other products associated with athletes, nutritious. In addition, egg powder can be used in baked mixes, energy bars, candies, cookies, etc. Other examples of egg processing include making an omelet, boiling the egg until it is soft or hard, baking the egg, or, if desired, the egg can be eaten raw or processed as a liquid egg.

Finally, it is known in the art, in general, that the yolk and / or the clear fractions contain the agent or agents responsible for the beneficial properties observed and referred to above. Those of ordinary skill in the art will be able to clearly recognize that the additional separation could provide more potent fractions or the elimination of undesirable components, and could allow other modes of administration such as administration of the egg product parenterally, subcutaneously, intravenously, intramuscular, intraperitoneal, intranasal, oral or topical Such additional separation will provide the ability to make encapsulated products and pharmaceutical compositions with the egg or fraction thereof. When the same becomes for the treatment and prevention of the disorder, if it is a form of arthritis or an autoimmune disease, the hypermmune egg product is preferably administered to the subject in an amount that is immunologically effective in the treatment and prevention of the particular disorder. . The duration and intensity of the treatment will depend on the particular condition, if it occurs, and, if so, the progress of the condition in the subject. The hyperimmune egg product is provided in any amount that treats and / or prevents 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 hyperenmune egg products containing the equivalent of less than one or more complete, hyperimmune eggs) can be administered to the subject depending on the particular circumstance of the condition. The most potent fractions can be separated and concentrated by methods well known in the art, from several hundred eggs. In one embodiment, the egg product of the invention is found to be effective in the treatment of rheumatoid arthritis in rats using an animal model with collagen-induced arthritis (see Example 2). This animal model is well recognized by those in the art as one which equals the effect of rheumatoid arthritis in humans. In addition to the treatment of arthritis, it was determined that the egg product, when administered to rats prior to the induction of arthritis, retardation, and in some cases, the onset of arthritic symptoms is prevented. Thus, the product of _j ^^^^ The egg of the invention is effective in not only treating the symptoms of the disease, but also retards and / or prevents the onset or progression of the disease. In an alternative embodiment, the egg product was tested in humans and showed positive effects in the treatment of various forms of arthritis in several humans suffering from such symptoms (see Examples 2A-2C). Humans who were treated by the egg product demonstrate a clinical reduction in such symptoms as pain in addition to a general reduction in swelling and stiffness. Indicative of an effect on autoimmune disease is the surprising reduction of Type II collagen antibodies by the egg product of the invention in this disease model, which can also be observed in rats (see Example 3). It is contemplated that the egg product of the invention is effective in reducing antibodies involved with other autoimmune diseases such as juvenile diabetes, multiple sclerosis, Grave's disease, Meneri's disease, myasthenia gravis, lupus erythematosus, psoriasis, systemic sclerodermis, rheumatic fever and Sjogren's syndrome among others. As described in the background of the invention, patients who have arthritis are currently treated with non-spheroidal, anti-inflammatory (NSAIDs) and / or disease-modifying antiartitic drugs (DMARDs). ) to replace the symptoms of the arthritic condition. As shown in the examples (see Example 4) the patients were administered by the egg product of the invention usually with the present drug therapy. The egg product worked synergistically with the drug therapy to reduce the symptoms of the particular disorder The egg product can be administered, therefore, usually with alternative treatment for arthritis and autoimmune diseases to produce a synergistically better effect Moreover, as is well known in the art, NSAIDs and DMARDs can cause severe gastrointestinal damage. U.S. Patent Application Serial No. 08 / 688,576, assigned to DCV, Inc., discloses that the egg product Hypepnmune is effective in the treatment of gastrointestinal damage induced N? AID. Therefore, an alternative modality is contemplated for cases in which the subject is taken or prepared to recover NSAIDs for the treatment of an arthritic condition. In such a case, the subject may also be administered the product of the egg of the invention to not only treat the arthritic condition, but also to protect the gastrointestinal system from damage induced by NSAID. In such treatments, a lower dose of hypermoney eggs may be sufficient. Also, the subject animal suffering from the disorder can be administered with the egg product prior to starting its NSAIDs and DMARDs regimen, to better prepare the gastrointestinal system. It is of significant importance to note that the egg product of this invention has been shown to It is safe, non-toxic, ideal for long-term use and had no side effects except in humans allergic to eggs. The egg product can be administered orally either alone or in combination with drug therapy, for long-term use for arthritis and autoimmune diseases 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 bacteria known in Table 1 below, which is obtained from the American Type Culture Collection, was reconstituted with 15 ml of the medium and incubated overnight at 37 C. Once the good growth or culture was obtained, approximately half of the bacterial suspension was used to inoculate a liter of broth with the inoculated one that is incubated at 37 C. After the good growth or culture was visible in the culture, the Bacterial cells were collected by centrifugation of the suspension for 20 minutes to remove the medium. The bacterial pellet obtained was resuspended in the sterile saline solution 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 distilled water. The free bacterial suspension of the medium is excreted by placing the suspension in a glass bottle in a water bath at 80 C overnight. Viability if the broth culture was tested with a small amount of dead bacteria, incubated at 37 C for five days and observed daily for growth to certify that the bacteria have been exterminated. The dead bacteria were lyophilized to dryness. The dried bacteria were then mixed with sterile saline at a concentration of 2.2 x 10 bacteria cells / mL saline solution (1.0 optical density reading at 660 nm) The bacteria contained in the S-100 vaccine are listed in Table 1 later.

TABLE 1 List of S-100 Bacteria Escherichia coli Escherichia coli CAerobacter) Klebsiella pneumoniae Pseudomonas aeruginosa Salmonella typhimurium? Almonella dysenteriae Salmonella enteriditis Salmonella epidermis Salmonella simulans Streptococcus pyogenes, type 1 Streptococcus pyogenes, Streptococcus pyogenes, type 3 type 5 Streptococcus pyogenes, Streptococcus pyogenes, type 8 type 12 Streptococcus pyogenes, Streptococcus pyogenes, type 14 type 18 Streptococcus pyogenes, Pseudomonas vulgaris type 22 Streptococcus agalactiae Streptococcus mitis Streptococcus mutans Streptococcus salavarius Streptococcus eanguie Streptococcus pneumoniae Propionibacterium acnes Haemophilis influenzae Vaccine EB-100E The EB-100E vaccine is known by the trademark of Scourmune®-CR, produced by Schering-Plow Animal Health, of Kenilworth, New Jersey, USA. The vaccine consists of Cl tridium perfrmgens, type C, Escheri chia coli, porcine rotavirus, and transmissible gastroenteritis.

Immunization Procedure for the Hypermmune Egg Product A neutralized pathogen preparation was prepared as described above. For the first vaccination, the bacteria were mixed with complete Freund's adjuvant, and 5.6 mg of 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 injected into the chicks at two-week intervals for six months. The eggs were collected from the hypermuminated chickens and then dried by spraying or spraying into a powder form. During the spray drying process, the inlet temperatures did not exceed 159.9 Degrees C (320 Degrees F), the exit temperatures were they maintained in accordance with the production of the dust in the range of 3.0 to 4.0 percent of final moisture, and the pumping pressure remained around 2500 to 4000 P.S.I. Lower temperatures ranging from 37.7-71.1 C (100-160 F) were used, and samples were observed for moisture content during the drying process to obtain a final product having desired consistency.

EXAMPLE 2 Anti-Arthritis Properties of the Egg Product Hyperimmune in a Model of Arthritis Induced by Collagen in Rats.

Collagen-induced arthritis is an experimental animal model of rheumatoid arthritis and autoimmune diseases, whhas been explored by scientific researchers since 1977 (Trentham et al 1977). Rheumatoid arthritis is a classic autoimmune disease in whelevated immune responses to collagen have been reported in patients (Stuart et al 1983). Since its initial discovery, the animal model of collagen-induced arthritis has shown many parallel to human rheumatoid arthritis. For example, Stuart et al., 1982, has shown that several of the histological changes observed in the joints of arthritic rats resemble those in patients with rheumatoid arthritis. Arthritis in mice and rats is generally induced by immunization with heterologous type II collagen, whinitiates a combined cellular and humoral immune response from target to bind tissues. Common therapies are inadequate or have side effects that limit their prolonged use. The present example considers the effect of the egg product of the invention orally administered to rats prior to and during the induction of arthritis with collagen II. The suppression of the incidence of arthritis was examined in a dose-dependent manner when compared to a control group. Thirty female Sprague-Dawley-VAF + rats (Charles Rivers, Wilmington, MA), weighing 100-125 mg, were randomly selected into 3 groups (10 animals per group). The experiment was repeated three times so the final groups included 30 rats / treatment regimen with a total of 90 rats for this study. The product of the hyperimmune egg Spray dried (as described in Example 1) was diluted for oral priming. 10% and 0.2% of the egg product solutions for oral fattening were made every other day. The solution on the second day was stored at 4 ° C until use. The egg product (3.5 ml of the respective solutions) was primed orally for 7 days prior to the initiation of type II collagen that induces arthritis in rats and for 14 days after induction. The method of induction and evaluation of Arthritis in rats was according to the Trentham, et al. 1977. Briefly, Sprague-Dawley rats are immunized in the lower back by intralulation of collagen from native type II chick collagen treated with Pepsin 400 (CII) (Genzyme, Boston, MA), solubilized at 1 mg / ml in acid. 0.1 M acetic acid and emulsified 1: 1 with IFA (23). Three groups: priming with water (Control), product of the hyperimmune egg 50X (High Dose) (3.5 ml of a 10% solution of the product of hyperopic eggs) and the product of hypepmune eggs IX (lower dose) (3.5 ml) were used. of a 0.2% solution of the hypermmune egg product) with 10 rats per group. The start on day 10 that followed by intradermal collagen II immunization and daily thereafter until Day 21, the rats were clinically evaluated (blind) for periarticular erythema of the legs of the rats (0-4 +) and leg lining (0). -4+) for each member. The group arthritis index (AI) is a sum of paw marks based on the degree of arthritis incidence and severity of arthritis when derived from the average AI. On Day 21, all rats were sacrificed and bled. The serum was evaluated by antibody titrant for type II collagen. Enzyme Linker Immunoassays (ELISAs) were used to measure the specific antibody titrant for Type II Collagen (Trentham, et al., 1983). The animals were then sacrificed with overdosa metafano.

Results Administration of the egg product results in anti-arthritic properties in a dose-dependent manner. The high dose of Egg product produces the most effective reduction in the incidence and severity of arthritis symptoms (Table I). The records in Table I indicate a reduction in the number of swollen joints and a decrease in the severity of the disease with the high dose of the egg product. In addition, both the lower and higher doses of the egg product cause a delay in the onset of the arthritic condition after the injection of collagen II (Table 2).

Tabl a 1 Egg Product in Arthritis Model of the Animal Induced with Collagen Group * Incidence of arthritis "This level of control is historically as good as steroids, NSAIDS, methotrexate / minocycline Average Day for the Maximum Incidence of Arthritis Table 2 * Delay in the onset of maximum arthritis after immunization with Collagen II.

On day 21 the arthritic index which reflects the degree and severity of arthritis was significantly reduced in animals which receive the high dose of the hyperimmune egg product when compared to the control group (2.46 ± .0.55 vs 4.167 + 0.51; > 0.003, Student's t test). The effect of the lower dose of the egg product does not differ significantly from the control. In addition, the incidence of arthritis was significantly suppressed in the high-dose group compared to control (54% vs. 83%; p < 0.03). This decrease in the percent incidence of arthritis observed with the high dose of the egg product Hyperimmune (Table I) is as good as reported for steroids, NSAIDs (nonsteroidal anti-inflammatory drugs), methotrexate, and minocycline. This example 2 also shows that the high dose of egg product, provided prior to the induction of arthritis, prevents the development of arthritis in more animals than those to which the egg is not provided. These results are shown in Figure 1 below.

Figure 1 shows the prevention of arthritis by the high dose of the egg product. A lower percentage of animals, orally primed with the egg product, develop arthritis symptoms when compared to control animals, which do not receive eggs. Animals were primed orally for 21 days, seven days prior to immunization (induction of arthritis) and fourteen days after immunization.

Conclusion The data clearly show a definitive antiarthritic effect in rats for the egg product in a dose-dependent manner in the rat arthritis model induced by type II collagen. Statistically significant decreases in incidence, delay at onset, and a decrease in the severity of arthritis were observed in animals receiving a high dose of the hypepnmune egg product. These data show the preventive effects of the high dose of the egg product on the incidence of arthritis. More importantly, both in the high and low doses the product of the hyperimmune egg is non-toxic.

EXAMPLE 3 Reduction of Collagen II Antibodies The rats of Example 2 were bled on Day 21 and serum samples were collected. A standard ELISA assay was used to measure titers against autoimmune antibodies of Collagen II. These results show that animals bled either at high or low doses of the egg product have antibody titers significantly decreased for collagen II when compared for controls (Table 3).

The decrease in titers of autoimmune antibody to Collagen II in the serum of animals primed with the egg product when they were compared to control animals (no egg product) is highly significant. Because all groups of animals received the same level of collagen II to induce antibodies to collagen II and the resulting arthritic symptoms, it was unexpected that the groups that received the egg product might have low titers of collagen II antibodies on the day 21. This decrease in antibody titers for collagen II indicates a positive influence on both the cellular and humoral response to the hypermmune egg product.

EXAMPLE 4 Effect of the Egg Product on Arthritic Human Patients A nutritional drink supplement was obtained which comprises a high protein, high carbohydrate powder containing 30% of the daily recommended tolerance of vitamins, and approximately 4.5 grams of hyperimmune egg powder (approximately equal to 0.4 eggs). He beverage supplement was provided by DCV, Inc., Wilmington, DE. Three patients were given the nutritional drink supplement for a period of two months. Clinical evaluations with respect to product tolerance, a clinical response, as assessed for each patient estimate of the clinical states and a detailed clinical examination were performed prior to the study in one month, two months and three months (one month then the product ceased). Profiles of clinical chemistry, hematology and urinalysis were made. The results of the treatments of each one of these patients are described later: EXAMPLE 4A Patient # 1 Patient # 1 was a 29-year-old woman, 160.02 cm 77.18 kg (5'3"170 lbs) with a previous history of rheumatoid arthritis (juvenile) .In a first examination the patient presented with joint pains, swelling , and sensitivity in fingers, wrists, toes, feet, and knees. She complained about functional limitations such as the ability to bend her knees or run, and has difficulty kneeling. His hematology tests had a normal etiomythrocyte sedimentation rate (E? R) and C-reactive protein (CRP) readings. The patient's cholesterol was 199mg / dl She was being treated with Mmocín 300 mg / week, Loestrin Fe 1.5 / 30 and use multivitamins. The diagnosis was rheumatoid arthritis with uveitis. After one month of consuming the Nutritional Drink Supplement on a daily basis, the redness and swelling of the patient's hand diminished, and the pain and swelling in her foot disappeared. The patient reported that she felt "less pain" and "felt 75% better". She reported that she had an increase in energy. His ESR and CRP readings remained normal but his cholesterol dropped to 186 mg / dl. The patient continued her medications in conjunction with the egg-based drink. During the second month, the patient felt that her hands were worse and she presented with hmchamiento in the fingers and wrists and reported numbness in the hands during the night. Their legs felt "better". The overall assessment of the doctor was that the patient was delicately worse. She still experiences pain when she carries grocery bags or even to open drawers. Your ESR and CRP readings remain normal and your cholesterol stays at 189mg / dl. She continued the medications and with her plans, for the protocol, she interrupted the use of the product. After a month without the product, the hmchamiento and sensitivity returned to the hands and feet. Her limitations of functions remained as she presented herself first. The patient still felt 75% "better". His ESR and CRP readings remained normal when his cholesterol dropped to 180mg / dl. The result of the arthritic symptoms was determined from the assessment of the patient's symptoms. In particular, the patient was needed to indicate the importance of joint swelling, pain and / or tenderness. Based on the assessment of this patient, the numbers were generated showing the degree of the symptoms. The range of numbers from a higher of 36 (greater importance of swelling, pain and sensitivity) to a lower of 0 (no lynching, pain or sensitivity).

The results generated by the arthritic condition of Patient # 1 were as follows: In the presentation = 14 One month in the egg-based drink = 2 Two months in the egg-based drink = 6 One month after the interruption of the drink = 8 EXAMPLE 4B Patient # 2 Patient # 2 was an 88-year-old woman 160.02 cm 47.21 Kg (5'3"104 lbs) with a previous history of rheumatoid arthritis and chronic sinusitis, she presented with pain in the lower extremities and shoulders. She revealed that she was only able to walk in a limited way and had difficulty in folding her arms, and her hematology tests indicated elevated ESR (36m? t? / hr). , CRP (1.64mg / dl) and total cholesterol at 220mg / dl. She was being treated with: Methotrexate 5mg / week, Orudis KT 2 / day, Ca 1500 mg, Fosomax lOmg, Prednisone 5mg q2d (every two days), and took multivitamins. Again, the patient continued taking these medications in addition to the egg-based drink. A month after starting the egg-based drink, she still complained of swelling of the hands, knee pain, and inability to sleep. The patient reported that she was "50% better", "feeling generally better" and "walking better". She was still in pain, although her attacks of pain were less frequent. The results of hematology were ESR (30mm / hr) and CRP (1.64mg / dl), and an increase in cholesterol was observed at 232mg / dl.

After two months of product consumption, the patient reported that "she felt 98% better". Its functional limitations, however, remained the same. The results of the hematology indicated a decrease in his ESR (21mm / hr) and a return to normal in the CRP reading (< 0.5mg / dl). His total cholesterol remained at 234mg / dl. The patient continued her medications but, as planned, she interrupted the egg-based drink. One month after the discontinuation of the product the patient complained of severe pain of the joints in his fingers and legs and exhibited swelling of the wrists. She felt that she was "50% worse". His E? R (27mm / hr) and cholesterol (257 mg / dl) levels started to rise, but his CRP levels (< 0.5mg / dl) remained normal. The result of the arthritic symptoms was determined from the evaluation of the patient's symptoms. In particular, the patient was needed to indicate the importance of joint swelling, pain and / or tenderness. Based on the assessment of this patient, the numbers were generated showing the degree of the symptoms. The range of numbers from a higher of 36 (greater importance of swelling, pain and sensitivity) to a lower of 0 (no swelling, pain or sensitivity). The results generated by the arthritic condition of Patient # 2 were as follows: In the presentation = 10 One month in the egg-based drink = 7 Two months in the egg-based drink = 2 One month after the interruption of the drink = 10 EXAMPLE 4C Patient # 3 Patient # 3 was a 79-year-old man 177.8 cm 69 kg (5'10"152 lbs) with a previous history of osteoarthritis and atherosclerotic cardiovascular disease.The symptoms were pain in the lower back, shoulders, knees and foot. Medications included: Nitroderm patch, Digoxin 0.125, aspirin 80 mg and Feldeno 20 mg.The limitations of the function were: difficulty in movement of the arms and exhaustion.Hermatology results were normal ESR and CRP and cholesterol readings. At 217mg / dl, one month after drinking the egg product, along with the medication mentioned above, the patient felt "slightly better (10-20%)." He still reported pain in the shoulder on the right and left side, and reported that he was unstable standing and experiencing lateral flexion of his right knee.The limitations of function remained as previously reported.Their ESR and CRP readings were normal and his cholesterol level was 180 mg / dL.

After two months of product consumption, the patient continued to feel "slightly better". Symptoms include pain in the right knee and difficulty walking. Cholesterol readings were not obtained but ESR and CRP remain at normal levels. After one month without the product, the patient felt slightly better overall but slightly worse than the previous month. Symptoms include lateral flexion of the right leg, pain in the shoulder and pain in the lower back. The evaluation of the joints indicated pain in the shoulders, and lower back. The functional limitations were the difficulty in the movement of the arms and he felt "exhausted". The ESR and CRO readings were normal and the cholesterol remained at 180mg / dl. The result of the arthritic symptoms was determined from the assessment of the patient's symptoms. In particular, the patient was needed to indicate the importance of swelling, pain and / or sensitivity of the joints. Based on the assessment of this patient, the numbers were generated showing the degree of the symptoms. The range of numbers from a superior of 36 (greater importance of lynching, pain and sensitivity) to a lower of 0 (no lynching, pain or sensitivity). The results generated by the arthritic condition of Patient # 3 were as follows: In the presentation = 11.5 One month in the egg-based drink = 2 Two months in the egg-based drink = 3 One month after the interruption of the drink = 8.5 Other case histories showed similar prayers and demonstrated the efficacy of the present invention in the elimination of pain and inflammation in arthritic joints without lateral effects. The invention has been described with particular reference to certain preferred embodiments thereof, but it will be understood that variations and modifications may be made within the spirit and scope of the invention as described above and as defined in the appended claims.

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, the content of the following is claimed as property.

Claims (28)

1. A composition for the treatment and prevention of arthritis in a subject animal, the composition is characterized in that it comprises an egg, a fraction thereof, obtained from a bird which has been hyperimmunized with an antigenic or genetic vaccine.

2. The composition according to claim 1, characterized in that the bird has been hyperimmunized with an antigenic vaccine comprising at least one antigen selected from the group consisting of bacteria, viruses, protozoa, fungi, and cellular antigens and mixtures thereof.

3. The composition according to claim 1, characterized in that the bird has been hyperimmunized with a genetic vaccine comprising at least one antigen encoding the DNA construct selected from the group consisting of fragments of unprotected DNA, plasmid DNA, viral DNA, bacterial DNA, DNA expression libraries, DNA-RNA antigens, DNA protein conjugates and DNA liposome conjugates, and mixtures thereof.

4. A method for the treatment and prevention of arthritis in an animal subject suffering from or susceptible to arthritis, the method is characterized in that it comprises administering to the animal subject an effective amount of an egg product.

5. The method according to claim 4, characterized in that the egg product is obtained from a bird which has been immunized with an antigenic or genetic vaccine.

6. The method according to claim 5, characterized in that the antigenic vaccine comprises at least one antigen selected from the group consisting of bacteria, viruses, protozoa, fungus, and cellular antigens and mixtures thereof.

7. The method according to claim 5, characterized in that the genetic vaccine comprises at least one antigen that encodes the DNA construct selected from the group consisting of unprotected DNA fragments, plasmid DNA, viral DNA, bacterial DNA, expression libraries of DNA, DNA-RNA antigens, conjugates of the DNA protein and conjugates of the DNA liposome, and mixtures thereof.

8. The method according to claim 4, characterized in that the egg product comprises an egg or fraction thereof.

9. The method according to claim 8, characterized in that the daily effective amount of the egg product administered to the animal is equivalent to 0.25 to 100 eggs.

10. The method according to claim 4, characterized in that the antibody is administered parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, intranasally, orally or topically.

11. The method according to claim 4, characterized in that the egg product is administered to the animal subject in combination with a drug selected from the group consisting of non-spheroidal, anti-inflammatory and antiartitic drugs, disease modifiers.

The method according to claim 11, characterized in that the subject animal has been administered at a drug regimen for a predetermined time prior to the administration of the egg product.

13. A composition for the treatment and prevention of an autoimmune disease in a subject animal, the composition is characterized in that it comprises an egg, or fraction thereof, obtained from a bird which has been hyperimmunized with an antigenic or genetic vaccine.

14. The composition according to claim 13, characterized in that the bird has been hyperimmunized with an antigenic vaccine comprising at least one antigen selected from the group consisting of bacteria, viruses, protozoa, fungi, and cellular antigens and mixtures thereof.

15. The composition according to claim 13, characterized in that the bird has been hyperimmunized with a genetic vaccine comprising at least one antigen encoding the DNA construct selected from the group consisting of unprotected DNA fragments, plasmid DNA, viral DNA , Bacterial DNA, DNA expression libraries, DNA-RNA antigens, DNA protein conjugates and DNA liposome conjugates, and mixtures thereof.

16. A method of treating an autoimmune disease in an animal subject suffering from or susceptible to autoimmune disease, the method is characterized in that it comprises administering to the animal subject an effective amount of an egg product.

17. The method according to claim 16, characterized in that the egg product is obtained from a bird which has been hyperimmunized with an antigenic or genetic vaccine.

18. The method according to claim 17, characterized in that the antigenic vaccine comprises at least one antigen selected from the group consisting of bacteria, viruses, protozoa, fungi, and cellular antigens and mixtures thereof.

19. The method according to claim 17, characterized in that the genetic vaccine comprises at least one antigen that encodes the DNA construct selected from the group that consists of unprotected DNA fragments, plasmid DNA, viral DNA, bacterial DNA, DNA expression libraries, DNA-RNA antigens, DNA protein conjugates and DNA liposome conjugates, and mixtures thereof.

20. The method according to claim 16, characterized in that the egg product comprises an egg or fraction thereof.

21. The method according to claim 20, characterized in that the daily effective amount of the egg product administered to the animal is equivalent to 0.25 to 100 eggs.

22. The method according to claim 16, characterized in that the antibody is administered parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, intranasally, orally or topically.

23. The method according to claim 16, characterized in that the egg product is administered to the animal subject in combination with a drug selected from the group consisting of non-steroidal, anti-inflammatory drugs and anti-arthritic drugs, disease modifiers.

24. The method according to claim 22, characterized in that the subject animal has been administered a drug regimen for a predetermined time prior to the administration of the egg product.

25. A composition for reducing antibodies against autoimmune diseases in an animal subject, the composition is characterized in that it comprises an effective amount of an egg, or fraction thereof, derived from a bird which has been hyperimmunized with an antigenic or genetic vaccine.

26. The composition according to claim 25, characterized in that the bird has been hyperimmunized with an antigenic vaccine comprising at least one antigen selected from the group consisting of bacteria, viruses, protozoa, fungi, and cellular antigens and combinations thereof.

27. The composition according to claim 25, characterized in that the bird has been hyperimmunized with a genetic vaccine comprising at least one antigen encoding the DNA construct selected from the group consisting of unprotected DNA fragments, plasmid DNA, viral DNA , Bacterial DNA, DNA expression libraries, DNA-RNA antigens, DNA protein conjugates and DNA liposome conjugates, and mixtures thereof.

28. The composition according to claim 25, characterized in that the autoimmune disease is selected from the group consisting of rheumatic arthritis, juvenile diabetes, sclerosis multiple, Graves' disease, Meneri's disease, myasthenia gravis, lupus erythematosus, psoriasis, systemic sclerodermis, rheumatic fever and Sjogren's syndrome.