WO2011070565A1 - Compositions pour le traitement d'une allergie alimentaire - Google Patents

Compositions pour le traitement d'une allergie alimentaire Download PDF

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WO2011070565A1
WO2011070565A1 PCT/IL2010/001004 IL2010001004W WO2011070565A1 WO 2011070565 A1 WO2011070565 A1 WO 2011070565A1 IL 2010001004 W IL2010001004 W IL 2010001004W WO 2011070565 A1 WO2011070565 A1 WO 2011070565A1
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food
pharmaceutical composition
glucan
oxidized cellulose
sensitivity
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PCT/IL2010/001004
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English (en)
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Oded Shoseyov
Nir Shani
Ziv Shani
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Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd.
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Publication of WO2011070565A1 publication Critical patent/WO2011070565A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A23L33/24—Cellulose or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/717—Celluloses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • 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
    • A61P37/08—Antiallergic agents

Definitions

  • This invention relates to methods and compositions for the treatment and/or prevention of food sensitivity and diseases and disorders associated therewith.
  • Food sensitivity resulting in adverse reactions to food, can be roughly categorized into food intolerance and food allergy.
  • Food intolerance or non-allergic food hypersensitivity
  • lactose which is found in milk and other dairy products, is the most common food intolerance.
  • FA food allergy
  • GI gastro-intestinal
  • IgE IgE-mediated mechanism of injury
  • non-IgE mechanisms may also be involved in the pathogenesis of FA.
  • the clinical manifestations of FA, expressed in affected target organs, are possibly the result of immunologic injury mediated by interaction of food antigens with contiguous elements of mucosal associated lymphoid tissue.
  • food allergy may be defined as a complex of clinical syndromes resulting from the sensitization of the patient to one or more foods, in which symptoms manifest locally in the gastrointestinal (GI) tract or in remote organs as a result of an immunologic reaction.
  • GI gastrointestinal
  • celiac disease a disorder induced by gluten (a protein found in wheat, rye and barley), cannot be distinctly characterized as either food intolerance or FA.
  • celiac can be categorized as a food intolerance since gluten is, by itself, toxic to the intestine and since unique peptides that are formed by its ineffective digestion are involved in the disease progression.
  • gluten or gluten peptides that are formed by gluten's partial digestion induces a Thl immune reaction that causes an inflammation of the intestine and thus can be categorized as a food allergy (FA is characterized by an abnormal immunologic reactivity to food proteins).
  • celiac disease is arbitrarily classified as food intolerance in this application.
  • Celiac disease (gluten intolerance) affects between 0.5 and 1 percent of people in the United States and its only known effective treatment is a lifelong gluten-free diet.
  • Food allergies can range from merely irritating to life-threatening. Approximately 30,000 Americans go to the emergency room each year to be treated for severe food allergies, according to the Food Allergy and Anaphylaxis Network (FAAN). It is estimated that 150 to 200 Americans die each year because of allergic reactions to food. Food allergy may coexist with eating disorders, metabolic problems, diabetes and other disease states.
  • FAAN Food Allergy and Anaphylaxis Network
  • the clinical manifestations of food allergy are many and include symptoms in the digestion system, skin, respiratory system and a systematic anaphylactic shock.
  • Symptoms in the digestive system include allergic eosinophilic infiltration of the esophagus, stomach and intestine that can result in vomiting, abdominal pain and diarrhea, blood loss in the stools, iron deficiency anemia and weight loss.
  • the most common skin disorders that are provoked by food allergy are acute urticaria and angioedema; however, there is also a strong link between ingestion of food allergens and exacerbations in the cutaneous manifestations of atopic dermatitis.
  • Anaphylaxis which is an IgE dependent acute systemic allergic reaction, causes systemic vasodilation that can result in a sudden drop in blood pressure, edema of bronchial mucosa resulting in bronchoconstriction and breathing difficulties and in severe cases cardiovascular symptoms, including hypotension, vascular collapse, and cardiac dysrhythmias.
  • anaphylaxis can lead to death due to heart failure and blockage of the airways.
  • particles e.g., micro or nano in size, of glucans may be employed to prevent and/or treat allergic non-food reactions [5].
  • OVA ovalbumin
  • grass allergens that have also been shown to bind OC
  • CBM carbohydrate binding molecule
  • the present invention relates to the use of at least one glucan, such as oxidized cellulose, for preparing medicaments for therapeutic treatment and/or prophylaxis of conditions mediated by or associated with food sensitivity (i.e. food allergy and/or food intolerance), to pharmaceutical compositions comprising said glucan and to related methods of therapeutic treatment and/or prophylaxis.
  • glucan such as oxidized cellulose
  • the present invention also relates to kits or commercial packages containing any one of the compositions of the invention as particular formulations and dosage forms.
  • the present invention provides a use of at least one glucan for the preparation of a pharmaceutical composition (or a medicament) for the treatment and/or prophylaxis of food sensitivity, i.e., a condition associated with or mediated by consumption of a food allergen or a food that causes food intolerance.
  • the invention also provides a use of at least one glucan in a method of treatment and/or prophylaxis of food sensitivity.
  • the invention provides a pharmaceutical composition comprising at least one glucan for the treatment and/or prophylaxis of food sensitivity.
  • the pharmaceutical composition comprising the at least one glucan may also be used in delaying the onset or lessening the severity of a condition associated with food sensitivity and/or in reducing a subject's sensitivity to a food allergen and/or to a food that causes food intolerance.
  • glucan refers to a polysaccharide of sugar monomers linked together by glycosidic bonds.
  • the glucan may be a- or ⁇ -glucan and may be of natural, synthetic or semi-synthetic origin.
  • the at least one glucan may be a combination (e.g., a mixture) of two or more glucans.
  • the term does not encompass cellulose or any unoxidized form thereof (i.e., cellulose ethers, cellulose esters, etc.).
  • the at least one glucan may be one or more of the glucans known in the art.
  • the glucan is selected amongst polysaccharides that bind protein allergens.
  • Non-limiting examples of the at least one glucan are oxidized cellulose, pullulan, starch, glycogen, dextran, lichenin, mannan, galactomannan, arabinoxylan, galacton and any derivative thereof.
  • the at least one glucan is oxidized cellulose.
  • the oxidized cellulose is in the form of a salt.
  • the oxidized cellulose salt is microdispersed oxidized cellulose (in short MDOC, usually prepared as a mixed calcium/sodium salt, with equal molar concentrations of calcium and sodium cations, typically in the form of a finely dispersed powder).
  • the at least one glucan is a derivative of oxidized cellulose.
  • food sensitivity refers, in general, to an undesirable response (short term or long term condition or disorder) that occurs during or after the ingestion of food or a food compound, such as an adverse reaction to food that may range from a slight rash to a severe allergic response.
  • Food sensitivity is broadly divided into two categories: food allergy and food intolerance.
  • the "food allergy” is the undesirable allergic response, against the effect of which the methodologies of the invention have been formulated; it is an abnormal response of the body to a food (most often a food protein), comprising a food allergen, triggered by the body's immune system.
  • the "food allergen” is any agent or chemical in a food product or inherently associated with the consumption thereof, which is capable of inducing, promoting, or stimulating allergy, i.e., the hypersensitive state induced by an exaggerated immune response to the food allergen, in a subject consuming the food product.
  • the food allergen may be associated with any one food ingredient, including but not limiting to proteins, carbohydrates and fats as well as additives, artificial flavors and colors employed in the food industry.
  • the allergen may be one which is an additive to a food product or which is derived from any one food group.
  • food-groups include milk; eggs- the main allergens being the egg white proteins ovomucoid, ovalbumin, and ovotransferrin; peanuts; tree nuts, such as Brazil nuts, hazelnuts, walnut and pecan; soybeans; wheat; rye; barely; oat; fish, such as bass, flounder, cod; crustacean shellfish, such as crab, lobster, and shrimp; mustard; and vegetables such as celery.
  • Non-limiting examples of food allergens are ovomucoid, ovalbumin, ovotransferrin and lysozyme (egg white), Cas s 5 and 8 (chestnut), Ber e 1 and 2 (Brazil nut), Cor a 1, 2, 8, 9 and 11 (hazelnut), Jug n 1 and 2 and Jug r 1 to 4 (walnut), Ara h 1 to 8 (peanut), tropomyosin (shelfish), parvalbumins (fish), Mus xp Hevein (banana) and Pers a Hevein (avocado).
  • the allergen may be any food, or ingredient thereof, which has been identified to cause an allergic reaction in sensitive individuals.
  • food sensitivity is a food allergy
  • the "condition mediated by or associated with food sensitivity" is typically one or more symptoms which occur after the entering of a food allergen into the gastro intestinal (GI) system or when coming in contact with any part of the GI tract.
  • the ensued condition may be one directly induced by the food allergen or a condition which may not be directly mediated by the initial allergen exposure, but which may deteriorate due to continued exposure thereto.
  • Symptoms of a food allergy or of a disease or disorder associated therewith usually develop within about an hour after eating the food containing the allergen.
  • the most common signs and symptoms of a food allergy include hives, itching, or skin rash; swelling of the lips, face, tongue and throat, or other parts of the body; wheezing, nasal congestion, or trouble breathing; abdominal pain, diarrhea, nausea, or vomiting; dizziness, lightheadedness, or fainting.
  • anaphylaxis a subject suffering from more extreme versions of the above reactions may even experience life-threatening signs and symptoms, such as swelling of the throat and air passages that makes it difficult to breathe; shock, with a severe drop in blood pressure; rapid, irregular pulse and loss of consciousness.
  • the symptoms may also manifest as delayed food allergy symptoms whereby the symptomatic process begins with the action of food materials in the digestive tract and continues into the blood stream and then affects the function of a target organ which receives the food.
  • Some non-limiting examples include symptoms that are limited to the digestive tract such as tract-indigestion, abdominal pain, bloating, nausea, vomiting, and diarrhea.
  • the symptoms may be general or systemic: fever, fatigue, sweating and chills.
  • the lungs may be affected, such as in food-induced bronchitis and asthma. In some cases the joints are the affected target organs (such as in food allergic arthritis).
  • Other symptoms include pain, stiffness, and swelling of the muscles and connective tissue; weakness and reduced tolerance (which may or may not be associated with pain); itching, rashes, hives, thickening, redness, swelling, and scaling of the skin such as in eczema and psoriasis. Disorganized, disturbed thinking, feeling, remembering, and behaving may also occur in cases where the brain is the target organ.
  • the term "food intolerance” refers to a negative reaction, often delayed, to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems, but it is not a true food allergy (e.g., does not require the presence of IgE antibodies against the food in contrast to food allergy).
  • the "food that causes food intolerance” is a food or a food compound which ingestion, even at very small quantities (e.g., a few micrograms or even less) results in food intolerance or in a condition associated therewith.
  • the food compound that causes intolerance is gluten or a gluten component.
  • Gluten is a highly complex protein that occurs in four main grains: wheat, rye, barley and oats (Gluten is also present in all baked foods that are made from these grains, e.g. bread, pies, cake, breakfast cereals, porridge, cookies, pizza and pasta).
  • the term 'gluten components' refers generally to gliadin (a prolamin) and glutenin (a glutelin) which are known for their role in the formation of gluten.
  • the food that causes intolerance is gluten and the gluten intolerant people are celiacs, i.e., people having coeliac disease.
  • condition mediated by or associated with food sensitivity refers to any pharmacologic, metabolic, and gastro-intestinal responses to foods or food compounds which cause food intolerance.
  • the condition is coeliac disease.
  • the pharmaceutical composition of the invention is formulated for mucosal application, as an oral formulation, as an intranasal administration or as a formulation suitable for inhalation.
  • the composition of the invention may be administered to a subject in need thereof prior to the consumption of a food product known to or suspected of containing an allergen.
  • the composition alternatively, is administered regularly at predetermined time periods so as to avoid or minimize any potential exposure to an allergen even where absolute avoidance of food products known to contain the allergen is practiced.
  • the composition of the invention may be taken after the consumption of a food. Where an allergic reaction after food consumption ensues, the composition may be taken even during that allergic episode in order to minimize or arrest further deterioration of symptoms.
  • composition of the invention may comprise one or more glucans, as defined, one of which optionally being oxidized cellulose, and in addition may compirse at least one pharmaceutically active additive, such as anti-allergy agent, as known in the art.
  • the composition may also comprise a pharmaceutically acceptable carrier, such as a vehicle, an adjuvant, an excipient, or a diluent.
  • a pharmaceutically acceptable carrier such as a vehicle, an adjuvant, an excipient, or a diluent.
  • a pharmaceutically acceptable carrier be one which is chemically inert to the glucan, e.g., oxidized cellulose or any other component of the composition and one which has no detrimental side effects or toxicity under the conditions of use.
  • the choice of carrier will be determined in part by the particular composition, as well as by the particular method used to administer the composition. Accordingly, there is a wide variety of suitable formulations of the pharmaceutical composition of the present invention.
  • the present invention provides a method for the treatment and/or prophylaxis of a condition associated with or mediated by a food allergen, said method comprising administering to a subject in need thereof a pharmaceutical composition comprising at least one glucan, as defined.
  • the invention also provides a method for delaying the onset or lessening the severity of a condition associated with or mediated by a food allergen and/or a food that causes food intolerance, said method comprising administering to a subject in need thereof a pharmaceutical composition comprising at least one glucan.
  • the present invention provides a method for reducing a subject's sensitivity to a food allergen and/or a food that causes food intolerance, said method comprising administering to a subject in need thereof a pharmaceutical composition comprising at least one glucan.
  • the at least one glucan is not cellulose or any unoxidized form thereof. In other embodiments, the at least one glucan is oxidized cellulose. In some embodiments, the at least one glucan is a salt or a derivative of oxidized cellulose. In some embodiments, the at least one glucan is microdispersed oxidized cellulose. In further embodiments, said at least one glucan, e.g., oxidized cellulose, a salt or derivative thereof, is in the form of solid particulates, which may, in some embodiments be in an amorphous form.
  • the solid particulates are microparticles or nanoparticles, e.g., having average diameter of between 0.01 and 100 microns.
  • the food allergen as defined herein, is associated with the consumption of milk, chicken, egg, nuts, wheat, soybeans, vegetables and legumes, fruit and melons, fish and shellfish, grains and seeds and spices.
  • the pharmaceutical composition of the invention is administered to the subject prior to, in conjunction with (simultaneously to) or after a meal wherein said meal comprises or is suspected to comprise a food allergen (or is known or suspected to initiate an allergic response) and/or a food that causes food intolerance.
  • the pharmaceutical composition comprising OC is used in a method for the treatment of coeliac.
  • the condition associated with or mediated by food sensitivity may be one or more of those recited herein.
  • the condition may be one or more of coeliac, inflammation, allergic and non-allergic disease or disorder of the respiratory system or the skin.
  • Some non-limiting examples of the diseases and disorders are allergic asthma, asthma, extrinsic bronchial asthma, chronic obstructive pulmonary disease, hay fever (seasonal rhinitis), allergic rhinitis, allergic conjunctivitis, hives, eczema, urticaria, angioedema, onchocercal dermatitis, atopic dermatitis, dermatitis, swelling, hypersensitivity pneumonitis and bronchopulmonary dysplasia.
  • the subject to be treated according to methods of the invention for the purposes of treatment and/or prophylaxis, is a subject having predisposition (genetic or environmental) to suffer from a condition associated with or mediated by the consumption of a food allergen, a food that causes food intolerance or any disease or disorder associated therewith or a subject already suffering, at the onset of treatment, from such a condition, disease or disorder.
  • the subject may also be one who desires to avoid a potential reaction to food allergens, independently of one's prior health and predisposition.
  • treatment and/or prophylaxis refers to the administering of a therapeutic amount of a composition of the invention which is effective to ameliorate undesired symptoms associated with a food sensitivity or any condition, disease or disorder associated therewith, to prevent the manifestation of such symptoms before they occur, slow down the deterioration of symptoms, slow down the irreversible damage caused in the progressive chronic stage of the disease, to delay the onset of said progressive stage, to lessen the severity or cure the disease, to improve survival rate or more rapid recovery, or to prevent the condition, disorder or disease form occurring or a combination of two or more of the above.
  • the present invention provides a food additive composition comprising at least one glucan.
  • the present invention also provides a method of reducing the allergenicity and/or the intolerability of a food product, said method comprising adding to said food product an amount of said food additive composition.
  • the at least one food additive composition is added to the food product during its production. In other embodiments, the food additive composition is added to the food product immediately prior to consumption by a subject, e.g., suffering or having a predisposition to suffer from food sensitivity.
  • the invention also provides a food product comprising a food additive composition, as defined herein.
  • said food product is selected from spreads, margarines, dressings, puddings, custards, low fat cheeses, toppings, sauces, mayonnaises, ice creams, yogurts, frozen desserts, icings, sour creams, batters, bakery creams, batter coatings, baked products, creamers, shortenings, baby foods, powdered soups, liquid soups and breadings.
  • a composition of the invention or at least one glucan, e.g., oxidized cellulose
  • food comprising allergens and/or to food that causes food intolerance
  • oxidized cellulose e.g., oxidized cellulose
  • the oxidized cellulose, as well as other glucans as defined herein prevents the cross linking of IgE by allergens in two main ways: 1. due to its large size, an oxidized cellulose-allergen complex has a substantially reduced ability to penetrate the tight epithelial layer and reach mast cell bound IgE that is found beyond this layer, or
  • the invention also provides a kit or a commercial package comprising at least one glucan and instructions of use.
  • Fig. 1 demonstrates the effective binding of ovalbumin (OVA) to oxidized cellulose (OC); B - bound fraction, UB - unbound fraction.
  • OVA ovalbumin
  • OC oxidized cellulose
  • Fig. 2 shows the binding of gluten extract (gliadins) with OC microparticles; B - bound fraction, UB - unbound fraction.
  • Adverse reactions to dietary proteins in food sensitivity may or may not be immune-mediated.
  • the immune-mediated adverse reaction to food is defined as food allergy (FA) which is roughly divided into IgE-mediated or non-IgE-mediated FA (NFA), also known as delayed-type food allergy.
  • FFA food allergy
  • NFA non-IgE-mediated FA
  • a mixed IgE- and non- IgE-mediated FA is also possible.
  • NFA mainly affects the GI mucosa.
  • the gut mucosal barrier is thought to have developed to execute an enormously difficult task—the digestion and absorption of nutrients without provoking immune responses and cohabiting with commensal flora in a mutual beneficial relationship, while maintaining an immune defense against pathogenic microbes.
  • IgE-mediated FA NFA is rarely life-threatening.
  • NFA to dietary proteins can cause significant morbidity in rapidly growing infants and young children.
  • allergic symptoms in IgE-mediated FA occur within two hours of eating. Allergic symptoms in NFA do not appear for at least 2 hours, not infrequently showing up to 24 to 48 hours later (there are reports of delayed symptoms appearing 3 to 7 days after eating). Flu-like symptoms are typical manifestations of the delayed patterns of food allergy. Patients often complain of fatigue, irritability, aching and cognitive dysfunction. Delayed food allergy begins in the gastrointestinal tract mucosa and spreads inward to any body tissue if food antigens enter the circulation and interact with the circulating immune system. Incoming food antigens tend to form immune complexes, and can injure target organs by triggering inflammatory responses in a variety of ways. Consequently, the delayed (non IgE) mechanisms of food allergy tend to produce recurrent or chronic symptoms and the symptom complexes occur both generally and in target organs such as the gastrointestinal tract. These mechanisms are not demonstrable by skin tests.
  • the difficulty in diagnosing FA lies in the identification of the allergens due to their slow, cell-mediated, non-IgE mechanism of action. This makes skin prick tests and serum measurement of food- specific IgE levels less sensitive in detecting the food allergens. Furthermore, the clinical reactivity to a food upon oral challenge may take up to a few days to develop, which adds to the difficulty in its identification. Moreover, most non-IgE-mediated allergic disorders involve more than one food allergen.
  • Another problem with treating and diagnosing IgE-mediated FA and in particular delayed type non-IgE-mediated FA is that skin prick testing for food allergens may be unreliable and "false negatives" may occur where the reaction to food is not immediate. Thus, skin prick testing is typically restricted to IgE mediated FA.
  • carbohydrate binding antigens are often used by pathogens to initiate the attachment and penetration to host epithelia which is covered by glycoproteins.
  • the host immunogenic response induced by allergens that contain some sort of carbohydrate binding capacity may arise from the similarity between pathogens and allergens carbohydrates binding antigens.
  • CBM containing allergens may be found in many types of allergen groups including food allergens.
  • the major latex allergen hev b 6.01 also termed prohevein
  • hevein domain A group of class I chitinases food allergens from various fruits (Kiwi, Banana, avocado, chestnut and others) contain a chitin binding domain, termed the hevein-like domain that shares high sequence similarity with hevein. This similarity results in cross reactivity between latex and food allergens which is responsible for the "latex-fruit syndrome".
  • Example 1 Ovalbumin binding to oxidized cellulose
  • OVA ovalbumin
  • Fig. 1 shows, after incubation of OVA with OC microparticles, most of the OVA protein was found in the bound fraction (B) while only traces of the protein were found in the unbound fraction (UB). In contrast to the efficient binding of OC, the majority of OVA that was incubated with crystalline cellulose (not oxidized cellulose) was found in the UB fraction while only a minute fraction of the total protein was found in the B fraction.
  • OC was added to various allergen containing food products or consumed separately as a food additive on regular bases. It is believed that the binding of OC to food allergens prevents the allergenic potential of food allergens during the production of food products that contain allergens or precursors thereof and also after the consumption of said food products.
  • OC may be consumed separately from the allergy containing food and may encounter the allergen inside the oral cavity or digestion system.
  • OC may be taken by allergic individuals before each meal as a preventive treatment, whether the meal is known to contain allergic food or as a precautionary measure against unknown allergic ingredients in the food;
  • OC may be taken in order to allow allergic patients to consume allergic food that would otherwise cause them harm;
  • OC may be taken after the unintended consumption of allergenic food as an emergency procedure.
  • the OC is consumed orally: 1. as a pill or inside a capsule; 2. as a powder suspension in water (allowing quick delivery to the digestion system in the detoxification example, similar to the consumption of activated charcoal); or 3. as a powder inhalation. It is known that the majority of the powder in any inhalation procedure reaches the oral cavity and the digestion system. Additionally, it is known that allergens are already absorbed from the oral cavity. Thus, OC powder that is efficiently spread in the oral cavity by powder inhalation can prevent allergen absorption from this area more efficiently.
  • Example 2 Clearance of oxidized cellulose from the airways and intestines and its metabolism in the body.
  • OC microparticles were fluorescently labeled with Cye5.5, intranasally administered to mouse and their clearance was followed via in vivo imaging (not shown). Intranasal administration of OC resulted in ⁇ 50%/50% distribution of OC between the airways and the digestion system. OC was detectable in the nose, tracheal area and the left lung at 40 min post-administration. OC was found in large quantities in the intestines within 4h of administration but was completely cleared from the digestion system within 24 hours. As intranasal administration of OC suspensions resulted in OC overdose in the lungs, it allowed to follow OC clearance from the lungs over time.
  • OC was almost completely cleared from the lungs within 13 days and was completely cleared within a month, demonstrating effective clearance even at overdose OC quantities.
  • the liver, kidney and spleen were removed from mice at different time points following intranasal OC administration for fluorescence evaluation. OC was already detected in high quantities in the liver and kidney but not in the spleen, 7 hours after its administration. OC was consistently found in the liver and kidney over the 13 days following administration and mirrored the gradual decrease in pulmonic OC levels, indicating continuous OC clearance from the lungs but no accumulation in these organs. Fluorescence levels in the liver and kidneys returned to close to basal levels by day 13.
  • OC was efficiently cleared from the airways and digestion system. A portion of OC that reached the blood circulation was metabolized by the liver and kidneys and did not accumulate in these organs. OC was further cleared from the kidneys into the urine as was evident by the detection of degradation products of fluorescent OC by FPLC in the urine of mice that received OC-Cy5.5 (data not shown).
  • coeliac (celiac) disease is a non allergic autoimmune disorder of the digestive system with prevalence estimates of 0.5-1% in the general population.
  • gliadin a gluten protein found in wheat, rye and barley, induces an inflammatory response in the small intestine which can result in diarrhea, weight loss (or stunted growth in children) and fatigue.
  • coeliac disease is caused by a reaction to gliadin.
  • the enzyme tissue transglutaminase modifies the protein, and the immune system cross-reacts with the small-bowel tissue, causing an inflammatory reaction.
  • Gliadin induced inflammation leads to a truncating of the villi lining the small intestine which interferes with the absorption of nutrients, because the intestinal villi are responsible for absorption.
  • the only efficient treatment for this disease is the avoidance of gluten containing foods.
  • Gluten (or a gluten component, such as gliadin or glutenin) binding by OC can prevent the symptoms associated with coeliac disease, employing the same methodologies disclosed herein in connection with the treatment and/or prevention of food allergies.
  • gliadin proteins marked by a bracket, the predominant molecular weight range of reduced ⁇ , ⁇ and ⁇ gliadin polypeptides is 33-37 Kd in SDS PAGE
  • B bound fraction
  • UB unbound fraction
  • the majority of gliadins that were incubated with crystalline cellulose (not oxidized) were found in the unbound fraction while nearly none of the total protein was found in the bound fraction.

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques comprenant du glucane et des utilisations de glucanes pour le traitement et/ou la prophylaxie de conditions associées à ou médiées par une sensibilité alimentaire.
PCT/IL2010/001004 2009-12-07 2010-12-01 Compositions pour le traitement d'une allergie alimentaire WO2011070565A1 (fr)

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US26722409P 2009-12-07 2009-12-07
US61/267,224 2009-12-07
US28612009P 2009-12-14 2009-12-14
US61/286,120 2009-12-14

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WO2005020997A1 (fr) * 2003-08-28 2005-03-10 Australian Biomedical Company Pty Ltd Compositions a usage veterinaire et medical
US20050271613A1 (en) * 2004-03-29 2005-12-08 Toshio Suzuki Beta-1, 3-1, 6-D-glucan and its use
WO2007113835A1 (fr) 2006-04-05 2007-10-11 Yissum Research Development Company Of The Hebrew University Of Jerusalem Compositions anti-allergiques

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US20050271613A1 (en) * 2004-03-29 2005-12-08 Toshio Suzuki Beta-1, 3-1, 6-D-glucan and its use
WO2007113835A1 (fr) 2006-04-05 2007-10-11 Yissum Research Development Company Of The Hebrew University Of Jerusalem Compositions anti-allergiques

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CN109068704A (zh) * 2016-05-16 2018-12-21 兴人生命科学株式会社 具有盐味增强效果的组合物

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