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WO1999036077A1 - Composition et methode de traitement et de prevention de l'arthrite et/ou de maladies auto-immunes - Google Patents

Composition et methode de traitement et de prevention de l'arthrite et/ou de maladies auto-immunes Download PDF

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Publication number
WO1999036077A1
WO1999036077A1 PCT/US1999/000749 US9900749W WO9936077A1 WO 1999036077 A1 WO1999036077 A1 WO 1999036077A1 US 9900749 W US9900749 W US 9900749W WO 9936077 A1 WO9936077 A1 WO 9936077A1
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WIPO (PCT)
Prior art keywords
dna
egg
arthritis
composition
egg product
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PCT/US1999/000749
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English (en)
Inventor
Orn Adalsteinsson
Michael J. Daley
Sandra G. Fitzpatrick-Mcelligott
Hellen Chaya Greenblatt
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Dcv, Inc.
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Priority to JP2000539850A priority Critical patent/JP2002509109A/ja
Priority to CA002317813A priority patent/CA2317813A1/fr
Priority to AU21157/99A priority patent/AU2115799A/en
Publication of WO1999036077A1 publication Critical patent/WO1999036077A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/57—Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/542—Mucosal route oral/gastrointestinal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/11—Immunoglobulins specific features characterized by their source of isolation or production isolated from eggs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/23—Immunoglobulins specific features characterized by taxonomic origin from birds

Definitions

  • 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 preventing, countering, or reducing arthritis and/or an autoimmune disease.
  • Rheumatoid arthritis is an autoimmune disease characterized by pain, swelling and stiffness in the joints. Rheumatoid arthritis is a disease which afflicts approximately 3% of Americans, and particularly women. Rheumatoid arthritis is an extremely disabling disease and usually strikes adults between the ages of 30 and 40 years, while the occurrence of clinical illness is greatest among those aged 40 - 60 years. Although drug therapy is somewhat effective, as many as 7% of rheumatoid arthritis sufferers are disabled to some extent as quickly as 5 years after disease onset, and within 10 years, as many as 50% are too disabled to work (Medical Sciences Bulletin, December 1994).
  • Osteoarthritis produces similar symptoms to rheumatoid arthritis.
  • osteoarthritis begins as a degeneration of articular cartilage
  • rheumatoid arthritis begins as inflammation in the synovium
  • each process approaches the other as the disease progresses.
  • cartilage deteriorates and joint congruence is altered
  • a reactive synovitis often develops.
  • rheumatoid arthritis erodes cartilage, secondary osteoarthritis changes in bone and cartilage develop.
  • 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 "B-27 associated diseases," and are difficult to differentiate from rheumatoid arthritis. In some cases ankylosing spondylitis, Reiters syndrome or psoriatic arthritis are present coincidingly with RA in the same patient. In many cases, these patients are treated with the same disease modifying drugs as those suffering from progressive rheumatoid arthritis.
  • Onset of arthritis generally occurs after the age of 30 in those who are susceptable to such disease.
  • some forms of arthritis may be initiated by different causes, such as slow virus infections. Because there is great overlap, many physicians consider these forms as "generalized rheumatism" and approach management of the diseases in the same way.
  • Some diseases which fall into this category include Chronic Fatigue Syndrome, fibromyalgia (fibrositis) and gout.
  • fibromyalgia fibrositis
  • gout fibromyalgia
  • rheumatoid arthritis is an autoimmune disease, and as such, its etiology is much the same as the etiology of any other autoimmune disease.
  • the body normally recognizes the difference between its own by-products and foreign invaders (i.e. bacteria, viruses, fungi and protozoans, to name a few).
  • an immune cell T or B lymphocyte
  • T or B lymphocyte reacts to a "self-protein" during its development, that cell is deemed defective and usually destroyed or inactivated.
  • a self-reactive immune cell will escape destruction. At a certain later time, that cell can be activated and trigger an immune response.
  • Activation is thought to occur after infection with a common bacteria or virus which contains a polypeptide having a stretch of amino acids which match a stretch on the defective self-protein.
  • bacteria such as Streptococcus. Mycoplasma, and borrelia, have been implicated in the initiation of the disease, as well as certain viruses, namely retroviruses.
  • autoimmunity often results in such diseases as juvenile diabetes, multiple sclerosis. Graves' disease, Meneri's disease, myasthenia gravis, lupus erythematosus and psoriasis. (Medical Sciences Bulletin,
  • rheumatoid arthritis other arthritis and other autoimmune diseases
  • patients are initially treated with "first-line” agents, usually non-steroidal anti-inflammatory drugs (NSAIDs) which primarily relieve the symptoms.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • second-line or disease- modifying agents DMARDs
  • methotrexate gold compounds
  • penicillamine sulfasalazine
  • antimalarial drugs antimalarial drugs
  • U.S. Patent No. 4,357,272 discloses the isolation of antibodies from the yolks of eggs derived from hyperimmunized hens. The hyperimmunization was elicited by repetitive injections of antigens derived from plant viruses, human IgG. tetanus antitoxin, snake antivenoms, and Serameba.
  • U.S. Patent No. 4,550,019 discloses the isolation from egg yolks of antibodies raised in the hen by hyperimmunization with immunogens having a molecular or particle weight of at least 30,000. The antigens used to hyperimmunize the chickens were selected from among plant viruses, human immunoglobulins, tetanus toxin, and snake venoms.
  • U.S. Patent No. 4,748,018 discloses a method of passive immunization of a mammal that comprises parenterally administering purified antibody obtained from the eggs of an avian that has been immunized against the corresponding antigen, and wherein the mammal has acquired immunity to the eggs.
  • the invention is based on the inventors' discovery that there is activity in egg and egg products, and particularly in egg products obtained from hyperimmunized avians, which when administered to a subject animal, in particular, mammals, prevents or reduces arthritis and/or autoimmune diseases in the subject animal.
  • 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 an avian which has been hyperimmunized 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 additionally 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-steroidal, anti-inflammatory drugs and disease-modifying, anti- arthritic drugs.
  • the invention is finally directed to a composition for reducing antibodies against autoimmune diseases in a subject animal, the composition comprising an effective amount of an egg product derived from an avian which has been hyperimmunized with an antigenic or genetic vaccine.
  • the invention generally relates to a composition and method for treatment and prevention of arthritis and autoimmune diseases.
  • the composition is preferably a natural food product which comprises hyperimmune egg or egg product.
  • the food product when administered by the method of the invention, not only provides relief from the pain and other symptoms caused by arthritis and autoimmune diseases, but can delay, and even prevent, the onset of such diseases.
  • the preferred antigen mixture injected into the avians to produce the hyperimmune egg product does not contain specific antigens which are known to cause arthritis or autoimmune diseases. Therefore, it is surprising that administration of the egg product obtained from avians immunized against a mixed antigen vaccine is effective in reducing the symptoms of and preventing arthritis and autoimmune diseases when administered to a subject.
  • arthritis means any of a variety of disorders marked by inflammation and degeneration of connective tissue structures, especially the joints and related structures. It may be attended by pain, stiffness, or limitation of motion of these parts.
  • Some forms of arthritis include rheumatoid arthritis, osteoarthritis, ankylosing seronegative spondyloarthropathy, reactive arthritis, chronic fatigue syndrome, fibromyalgia (fibrositis) and gout.
  • autoimmune disease is applied 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, Graves' disease, Meneri's disease, myasthenia gravis, lupus erythematosus, psoriasis, systemic scleroderma, rheumatic fever and Sjogren syndrome.
  • hyperimmunization means exposure to one or more antigens such that an immune response is elevated and maintained above the natural unexposed state.
  • egg or "egg product” each mean any whole egg (table, hyperimmunized or otherwise) or any product or fraction derived therefrom.
  • table egg or “table egg product” each mean a whole egg, or any product or fraction derived therefrom, obtained from egg-producing animals which are not maintained in a hyperimmune state.
  • hyperimmune egg '* or hyperimmune egg product each mean whole egg or any product or fraction derived therefrom, obtained from an egg producing animal maintained in a hyperimmune state.
  • combinatorial derived antigens refers to a novel process of generating molecular diversity among antigens by way of combinatorial synthesis.
  • bioengineered antigens refers to antigens which are obtained through the process of gene cloning technologies and genetic rearrangements which allow the insertion of encoding nucleotides which can give rise to molecules having antigenic properties.
  • genetic vaccine refers to a nucleic acid vaccine which is generally produced by recombinant technologies and which may elicit an immune response.
  • treatment means that the onset of the symptoms (including pain) of the disorder and/or pathogenic origin of the disorder be delayed or completely prevented, or, if present, the symptoms be ameliorated or completely eliminated.
  • 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.
  • prevention means that the progression of the disease is reduced and/or eliminated, or that the onset of the disease is eliminated.
  • adjuvant means any method of providing a subject with a substance, including orally, intranasally, parenterally (intravenously, intramuscularly, or subcutaneously), rectally or topically.
  • animal means the animal kingdom definition.
  • target animal refers to an animal which functions as the egg or egg product producing animal.
  • subject animal refers to the animal which is administered the egg or egg product produced by the target animal.
  • the product and method of the invention relate particularly to the use of hyperimmune 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 fear of side effects, except, of course, for allergic reactions in those intolerant to eggs.
  • the invention comprises a hyperimmune egg or egg product which is effective in treating and preventing arthritis and/or an autoimmune disease in a subject animal.
  • the hyperimmune egg is obtained from an egg-producing animal, and more preferably, an avian, which has been hyperimmunized with at least one antigen.
  • the hyperimmune egg product is one which is preferably administered orally to the subject animal.
  • the hyperimmune egg or egg product can be further separated into more potent fractions which can subsequently be administered to a subject animal in a variety of forms.
  • the hyperimmune egg or egg product of the invention is effective in treating and preventing all forms of arthritis, including, but not limited to, rheumatoid arthritis, osteoarthritis, ankylosing seronegative spondyloarthropathy, reactive arthritis, chronic fatigue syndrome, fibromyalgia (fibrositis) and gout.
  • the egg product of the invention is equally effective in treating autoimmune diseases, such as rheumatoid arthritis, juvenile diabetes, multiple sclerosis, Graves' disease, Meneri ' s disease, myasthenia gravis, lupus erythematosus, psoriasis, systemic scleroderma, rheumatic fever and Sjogren syndrome among others.
  • the hyperimmune egg product can be produced by any egg-producing animal. It is preferred that the animal be a member of the class Aves or, in other words, an avian. Within the class Aves, domesticated fowl are preferred, but other members of this class, such as turkeys, ducks, and geese, are a suitable source of hyperimmune egg product.
  • egg-producing animals When such egg-producing animals are brought to a specific state of immunization by means of, for example, periodic booster administrations of antigens, the animals will produce eggs that, when consumed by a subject, will have beneficial properties in the treatment and prevention of arthritis and autoimmune diseases in that subject.
  • any DNA construct (generally consisting of a promoter region and an antigen encoding sequence) will trigger an immune response.
  • Genetic vaccines consist of antigen- coding vectors, fragments of naked DNA, plasmid DNA, DNA-RNA antigens, DNA- protein conjugates, DNA-liposome conjugates, DNA expression libraries, and viral and bacterial DNA delivered to produce an immune response.
  • Methods of DNA delivery include particle bombardment, direct injection, viral vectors, liposomes and jet injection, among others.
  • DNA into avians is through intramuscular injection of the DNA into the breast muscle.
  • Step 1 Any antigen or combination of antigens may be employed as a vaccine.
  • the antigens can be bacterial, viral, protozoan, fungal, cellular, 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 capable of inducing immune and hyperimmune states in the egg-producing animal.
  • one preferred vaccine is a mixture of polyvalent bacterial and viral antigens selected from the following antigen families: the enteric bacilli and bacteroides, pneumococci, pseudomonas, salmonella, streptococci, bacilli, staphylococci, neisseria, clostridia, mycobacteria, actinomycetes chlamydiae, and mycoplasma.
  • Viral antigens are preferably selected from the following antigen families: adenoviruses, picornaviruses and herpes viruses, although other viral antigen families will work.
  • S-100 polyvalent vaccine referred to as Series 100
  • the bacteria included in the S-100 vaccine are listed in table 1 of Example 1. This vaccine has been previously described in US patent Nos. 5.106,618 and
  • the vaccine can be either a killed or live-attenuated vaccine and can be administered by any method that elicits an immune response. It is preferred that immunization be accomplished by administering the antigens through intramuscular injection.
  • the preferred muscle for injection in an avian is the breast muscle. Dosage is preferably 0.05-5 milligrams of the antigenic vaccine.
  • Other methods of administration include intravenous injection, intraperitoneal injection, intradermal, rectal suppository, aerosal or oral administration. When DNA techniques are used for the hyperimmunization process, much smaller quantities are required, generally 1-100 micrograms.
  • the vaccine has elicited an immune response in the egg- producing animal through a number of methods known to those having skill in the art of immunology. Examples of these include enzyme-linked immunosorbent assays (ELIS A), tests for the presence of antibodies to the stimulating antigens, and tests designed to evaluate the ability of immune cells from the host to respond to the antigen.
  • the minimum dosage of antigen necessary to induce an immune response depends on the vaccination procedure used, including the type of adjuvants and formulation of antigen(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 repeated booster administrations of an appropriate dosage at fixed time intervals.
  • the time intervals are preferably 2-8 week intervals over a period of 6-12 months.
  • Such processes are well known in the art.
  • Several combinations of primary and hyperimmunization are known to those skilled in the art.
  • the eggs from these animals are collected and processed to produce a hyperimmune egg product. Subsequently, the hyperimmune egg product can be administered to the subject.
  • the egg and/or egg product of the present invention is administered to a subject animal by any means that treats or prevents arthritis and/or autoimmune disease in the subject animal. It is preferred that administration occur by directly feeding the egg or any derivative of the egg.
  • Egg and egg yolk are natural food ingredients and are non- toxic and safe.
  • the egg is integrated into a nutritional supplement.
  • One preferred method for preparing the egg to be incorporated into a nutritional supplement involves drying the egg into an egg powder.
  • spray drying is a preferred method.
  • the process of spray drying eggs is well known in the art.
  • the dried egg powder can be incorporated into drinks in the form of, for example, protein powders, power building drinks, protein supplements and any other nutritional, athlete-associated products.
  • the egg powder can be used in bake mixes, power bars, candies, cookies, etc.
  • Other examples of egg processing include making an omelet, soft or hard-boiling the egg, baking the egg, or, if desired. the egg can be eaten raw or processed as liquid egg.
  • the yolk and/or white fractions contain the agent or agents responsible for the beneficial properties observed and referred to above.
  • further separation could provide more potent fractions or elimination of undesirable components, and would allow for other modes of administration such as administering egg product parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, intranasally, orally or topically.
  • Such further separation will provide for the ability to make encapsulated products and pharmaceutical compositions with said egg or fraction thereof.
  • the hyperimmune egg product is preferably administered to the subject in an amount that is immunologically effective in treating and preventing the particular disorder. Duration and intensity of the treatment will depend upon the particular condition, whether it is present, and, if so, the advancement of the condition in the subject.
  • the hyperimmune egg product is provided in any amount that treats and/or prevents the condition and the symptoms of the condition. For example, in some cases, daily amounts ranging from less than one to several whole, hyperimmune eggs (or hyperimmune egg products containing the equivalent of less than one to several whole, hyperimmune 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.
  • the egg product of the invention was found to be effective in treating rheumatoid arthritis in rats using a collagen-induced arthritis animal model (see Example 2).
  • This animal model is well recognized by those in the art as one which parallels the rheumatoid arthritis effect in humans.
  • the egg product when administered to rats prior to induction of arthritis, delayed, and in some cases, prevented the onset of the arthritic symptoms.
  • the egg product of the invention is effective in not only treating the symptoms of the disease, but also delaying and/or preventing the onset or progression of the disease.
  • the egg product was tested in humans and showed positive effects in treating various forms of arthritis in several humans suffering from such symptoms (see Examples 2A-2C).
  • the humans who were treated by the egg product demonstrated 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 was also seen 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, Graves' disease, Meneri's disease, myasthenia gravis, lupus erythematosus, psoriasis, systemic scleroderma, rheumatic fever and Sjogren syndrome among others.
  • autoimmune diseases such as juvenile diabetes, multiple sclerosis, Graves' disease, Meneri's disease, myasthenia gravis, lupus erythematosus, psoriasis, systemic scleroderma, rheumatic fever and Sjogren syndrome among others.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • DMARDs disease modifying anti-arthritic drugs
  • the egg product of this invention has been shown to be safe, non-toxic, ideal for long term use and has no side effects other than on humans allergic to eggs.
  • the egg product can be orally administered either alone or in combination with drug therapy, for long term use for arthritic and autoimmune diseases.
  • the media-free bacterial suspension was killed by placing the suspension in a glass flask in an 80 C water bath overnight. The viability if the broth culture was tested with a small amount of killed bacteria, incubated at 37 C for five days and checked daily for growth to certify that the bacteria had been killed.
  • the killed bacteria were lyophilized until dry.
  • the dry bacteria were then mixed with sterile saline solution to a concentration of 2.2 x 10° bacterial cells/mL saline (1.0 optical density reading at 660 nm).
  • Bacteria contained in S-100 vaccine are listed in Table 1 below.
  • 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
  • Propionibacterium acnes Haemophilis influenzae EB-100E Vaccine The EB-100E vaccine is known by the trade name of Scourmune®-CRT, manufactured by Schering-Plough Animal Health, of Kenilworth, New Jersey, USA.
  • the vaccine consists of Clostridium perfringens, type C, Escherichia coli, porcine rotavirus, and transmissible gastroenteritis.
  • a killed preparation of pathogens was prepared as described above.
  • the bacteria were mixed with complete Freund's adjuvant, and 5.6 mg of bacterial material were injected into the breast muscle of a chicken.
  • the bacterial preparation was mixed with incomplete Freund's adjuvant and injected into the chickens at two week intervals for six months.
  • Collagen-induced arthritis is an experimental animal model of Rheumatoid arthritis and autoimmune diseases, which has been explored by scientific investigators since 1977 (Trentham et al 1977).
  • Rheumatoid arthritis is a classical autoimmune disease in which elevated immune responses to collagen in patients have been reported (Stuart et al 1983). Since its initial discovery, the animal model of collagen-induced arthritis has demonstrated many parallels to human rheumatoid arthritis. For example, Stuart et al., 1982, has demonstrated that several of the histological changes observed in the joints of arthritic rats resemble those in patients with rheumatoid arthritis.
  • the arthritis in mice and rats is generally induced by immunization with heterologous type II collagen, which initiates a combined humoral and cellular immune response targeted to joint tissues. Current therapies are inadequate or have side effects that limit their prolonged use.
  • the present example looks at the effect of the egg product of the invention orally administered to rats prior to and during arthritis induction with collagen II.
  • the suppression of the incidence of arthritis was examined in a dose dependent manner when compared to a control group.
  • 125 gm were randomized to 3 groups (10 animals/group). The experiment was repeated three times so that the final groups included 30 rats/treatment regimen with total of 90 rats for this study.
  • Spray dried hyperimmune egg product (as described in Example 1 ) was diluted for oral gavage. 10% and 0.2% solutions of egg product for oral gavage were made every other day. The second day solution was stored at 4°C until use.
  • Egg Product (3.5ml of the respective solutions) was orally gavaged into rats for 7 days prior to initiation of the type II collagen induced arthritis in rats and for 14 days after induction.
  • the group arthritis index (Al) is a summation of paw scores based on the degree of incidence of arthritis and severity of arthritis as derived from the mean Al.
  • All rats were sacrificed and bled. Serum were evaluated for antibody titer to type II collagen.
  • Enzyme Linked Immunoassays (ELISA's) were used to measure specific antibody titer to Collagen Type II (Trentham, et al. 1983). The animals were then sacrificed with metafane overdose.
  • Figure 1 shows the prevention of arthritis by the high dose of egg product.
  • Rats from Example 2 were bled on Day 21 and serum samples were collected. A standard ELISA assay was used to measure titers against Collagen II autoimmune antibodies. These results show that the animals fed either high or low doses of egg product had significantly lowered antibody titers to collagen II when compared to controls (Table 3).
  • EXAMPLE 4 Effect of Egg Product on Arthritic Human Patients
  • a nutritional drink supplement was obtained which comprised a high protein, high carbohydrate powder containing 30% of recommended daily allowance of vitamins, and approximately 4.5 grams of hyperimmune powdered egg (approximately equal to 0.4 eggs).
  • the drink supplement was provided by DCV, Inc., Wilmington, DE.
  • Three patients were administered the nutritional drink supplement for a period of two months.
  • Clinical evaluations regarding tolerance to the product an clinical response, as evaluated by each patient's estimation of clinical status and a detailed clinical examination was performed prior to the study at one month, two months and three months (one month after ceasing the product).
  • Clinical chemistry, hematology and urinalysis profiles were performed. Described below are the results of the treatments of each of these patients:
  • Patient #1 was a 29-year-old female, 5'3" 170 lbs with a previous history of rheumatoid arthritis (juvenile). On first examination the patient presented with joint pains, swelling, and tenderness of fingers, wrists, toes, feet, and knees. She complained of functional limitations such as inability to do knee bends or run, and had difficulty with kneeling. Her hematology tests had normal etythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) readings. Patient's cholesterol was at 199mg/dl. She was being treated with Minocin 300mg/week, Loestrin Fe 1.5/30 and used multi vitamins.
  • ESR etythrocyte sedimentation rate
  • CRP C-reactive protein
  • Scoring of the arthritic symptoms was determined from the patient's own assessment of the symptoms. In particular, the patient was asked to indicate the amount of swelling, pain and/or tenderness of the joints. Based upon this patient assessment, numbers were generated showing the degree of the symptoms. The numbers range from a high of 36 (greatest amount of swelling, pain and tenderness) to a low of 0 (no swelling, pain or tenderness).
  • Patient #2 was an 88-year-old female 5'3" 104 lbs. with a previous history of rheumatoid arthritis and chronic sinusitis. She presented with pain in the lower extremities and shoulders. Physical examinations revealed swelling, pain, and tenderness of her fingers and ankles. Functionally she was only able to walk in a limited manner and had difficulty in bending her arms. Her hematology tests indicated elevated ESR (36 mm/hr), CRP (1.64mg/dl) and a total cholesterol at 220 mg/dl.
  • Scoring of the arthritic symptoms was determined from the patient's own assessment of the symptoms. In particular, the patient was asked to indicate the amount of swelling, pain and/or tenderness of the joints. Based upon this patient assessment, numbers were generated showing the degree of the symptoms. The numbers range from a high of 36 (greatest amount of swelling, pain and tenderness) to a low of 0 (no swelling, pain or tenderness).
  • Patient #3 was a 79-year-old male 5' 10" 152 lbs with a history of osteoarthritis and atherosclerotic cardiovascular disease. Symptoms were pain in the lower back, shoulders, knees and feet. Medications included: Nitroderm patch, Digoxin 0.125, aspirin 80mg and Feldene 20mg. Function limitations were: difficulty in moving arms and exhaustion. Hematology results were normal ESR and CRP and cholesterol readings at 217 mg/dl.
  • Scoring of the arthritic symptoms was determined from the patient's own assessment of the symptoms. In particular, the patient was asked to indicate the amount of swelling, pain and/or tenderness of the joints. Based upon this patient assessment, numbers were generated showing the degree of the symptoms. The numbers range from a high of 36 (greatest amount of swelling, pain and tenderness) to a low of 0 (no swelling, pain or tenderness).

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Abstract

L'invention concerne une composition naturelle pour la prévention et le traitement de l'arthrite, laquelle composition comprend une quantité efficace d'un oeuf ou d'une partie d'un oeuf. Ledit oeuf provient d'un ovipare qui a été hyperimmunisé avec au moins un antigène. L'oeuf ou la partie d'oeuf est également efficace pour la prévention et le traitement de maladies auto-immunes. L'invention concerne également une méthode de prévention et de traitement de l'arthrite et/ou de maladies auto-immunes par administration de l'oeuf ou d'une partie de l'oeuf.
PCT/US1999/000749 1998-01-19 1999-01-14 Composition et methode de traitement et de prevention de l'arthrite et/ou de maladies auto-immunes WO1999036077A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2000539850A JP2002509109A (ja) 1998-01-19 1999-01-14 関節炎および／または自己免疫疾患を治療および予防するための組成物および方法
CA002317813A CA2317813A1 (fr) 1998-01-19 1999-01-14 Composition et methode de traitement et de prevention de l'arthrite et/ou de maladies auto-immunes
AU21157/99A AU2115799A (en) 1998-01-19 1999-01-14 Composition and method for treatment and prevention of arthritis and/or autoimmune diseases

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US872898A 1998-01-19 1998-01-19
US09/008,728 1998-01-19

Publications (1)

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WO1999036077A1 true WO1999036077A1 (fr) 1999-07-22

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JP (1) JP2002509109A (fr)
CN (1) CN1304312A (fr)
AU (1) AU2115799A (fr)
CA (1) CA2317813A1 (fr)
WO (1) WO1999036077A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000043020A1 (fr) * 1999-01-19 2000-07-27 Dcv, Inc. Composition anti-inflammatoire a base d'oeuf et methode de traitement et de prevention de l'inflammation
WO2001019374A3 (fr) * 1999-09-14 2001-08-09 Dcv Inc Utilisation de glucosamine et d'oeuf pour reduire l'inflammation
JP2003525868A (ja) * 1999-09-14 2003-09-02 ディーシーヴィー インコーポレイテッド 炎症を低減させるグルコサミンおよび卵
US6706267B1 (en) 1999-09-14 2004-03-16 Arkion Life Sciences Llc Glucosamine and egg for reducing inflammation
WO2008025099A1 (fr) * 2006-08-31 2008-03-06 A.C.N. 135 493 391 Pty Ltd As Trustee For Conca Unit Trust Traitement et/ou prévention des affections médicales non infectieuses en utilisant des compositions contenant des anticorps
CN103599535A (zh) * 2013-11-15 2014-02-26 何建 利用i26免疫蛋粉与中药汤剂制备的外用药膏
WO2017065626A1 (fr) * 2015-10-16 2017-04-20 Romvac Company Sa Fabrication et utilisation d'œuf hyper-immun personnalisé dans le traitement du psoriasis
EP3490602A4 (fr) * 2016-08-01 2020-03-25 Scaled Microbiomics, LLC Systèmes et procédés de modification du microbiome pour réduire le risque de maladie et les manifestations de la maladie
WO2020147950A1 (fr) * 2019-01-16 2020-07-23 Ignova Gmbh Méthodes de traitement de la fibromyalgie

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030206898A1 (en) * 2002-04-26 2003-11-06 Steven Fischkoff Use of anti-TNFalpha antibodies and another drug
WO2006135915A2 (fr) * 2005-06-13 2006-12-21 Rigel Pharmaceuticals, Inc. Methodes et compositions de traitement de maladies osseuses degeneratives
WO2011082106A1 (fr) * 2009-12-29 2011-07-07 Hill's Pet Nutrition, Inc. Compositions comportant du gingembre pour l'amélioration ou la prévention de conditions inflammatoires

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997035595A1 (fr) * 1996-03-26 1997-10-02 Dcv Biologics L.P. Composition anti-inflammatoire a base d'oeufs, technique d'isolation et usage
WO1998004273A1 (fr) * 1996-07-30 1998-02-05 Dcv Biologics L.P. Procede servant a traiter les lesions gastro-intestinales

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997035595A1 (fr) * 1996-03-26 1997-10-02 Dcv Biologics L.P. Composition anti-inflammatoire a base d'oeufs, technique d'isolation et usage
WO1998004273A1 (fr) * 1996-07-30 1998-02-05 Dcv Biologics L.P. Procede servant a traiter les lesions gastro-intestinales

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000043020A1 (fr) * 1999-01-19 2000-07-27 Dcv, Inc. Composition anti-inflammatoire a base d'oeuf et methode de traitement et de prevention de l'inflammation
WO2001019374A3 (fr) * 1999-09-14 2001-08-09 Dcv Inc Utilisation de glucosamine et d'oeuf pour reduire l'inflammation
JP2003525868A (ja) * 1999-09-14 2003-09-02 ディーシーヴィー インコーポレイテッド 炎症を低減させるグルコサミンおよび卵
US6706267B1 (en) 1999-09-14 2004-03-16 Arkion Life Sciences Llc Glucosamine and egg for reducing inflammation
WO2008025099A1 (fr) * 2006-08-31 2008-03-06 A.C.N. 135 493 391 Pty Ltd As Trustee For Conca Unit Trust Traitement et/ou prévention des affections médicales non infectieuses en utilisant des compositions contenant des anticorps
US20100297140A1 (en) * 2006-08-31 2010-11-25 A.C.N 135 493 391 Pty Ltd As Trustee For Conca Unit Trust Uses of antibodies
AU2007291891B2 (en) * 2006-08-31 2013-10-31 A.C.N. 135 493 391 Pty Ltd Treatment and/or prevention of non-infectious medical conditions using antibody-containing compositions
US8834872B2 (en) 2006-08-31 2014-09-16 A.C.N 135 493 391 Pty Ltd. Uses of antibodies
CN103599535A (zh) * 2013-11-15 2014-02-26 何建 利用i26免疫蛋粉与中药汤剂制备的外用药膏
WO2017065626A1 (fr) * 2015-10-16 2017-04-20 Romvac Company Sa Fabrication et utilisation d'œuf hyper-immun personnalisé dans le traitement du psoriasis
EP3490602A4 (fr) * 2016-08-01 2020-03-25 Scaled Microbiomics, LLC Systèmes et procédés de modification du microbiome pour réduire le risque de maladie et les manifestations de la maladie
WO2020147950A1 (fr) * 2019-01-16 2020-07-23 Ignova Gmbh Méthodes de traitement de la fibromyalgie

Also Published As

Publication number Publication date
JP2002509109A (ja) 2002-03-26
CN1304312A (zh) 2001-07-18
AU2115799A (en) 1999-08-02
CA2317813A1 (fr) 1999-07-22

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