EP1229930A1 - Compositions et methodes pour le traitement des troubles allergiques - Google Patents
Compositions et methodes pour le traitement des troubles allergiquesInfo
- Publication number
- EP1229930A1 EP1229930A1 EP00975685A EP00975685A EP1229930A1 EP 1229930 A1 EP1229930 A1 EP 1229930A1 EP 00975685 A EP00975685 A EP 00975685A EP 00975685 A EP00975685 A EP 00975685A EP 1229930 A1 EP1229930 A1 EP 1229930A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- bacteria
- probiotic bacteria
- administration
- antigen
- administered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 59
- 239000000203 mixture Substances 0.000 title claims abstract description 35
- 208000010668 atopic eczema Diseases 0.000 title claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 4
- 230000000172 allergic effect Effects 0.000 title description 3
- 241000894006 Bacteria Species 0.000 claims abstract description 98
- 239000006041 probiotic Substances 0.000 claims abstract description 64
- 230000000529 probiotic effect Effects 0.000 claims abstract description 64
- 235000018291 probiotics Nutrition 0.000 claims abstract description 64
- 208000026935 allergic disease Diseases 0.000 claims abstract description 25
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 10
- 230000007815 allergy Effects 0.000 claims abstract description 10
- 239000000427 antigen Substances 0.000 claims description 46
- 102000036639 antigens Human genes 0.000 claims description 46
- 108091007433 antigens Proteins 0.000 claims description 46
- 239000013566 allergen Substances 0.000 claims description 43
- 241000894007 species Species 0.000 claims description 32
- 230000001580 bacterial effect Effects 0.000 claims description 31
- 235000013305 food Nutrition 0.000 claims description 15
- 108060003951 Immunoglobulin Proteins 0.000 claims description 10
- 102100037850 Interferon gamma Human genes 0.000 claims description 10
- 108010074328 Interferon-gamma Proteins 0.000 claims description 10
- 240000001046 Lactobacillus acidophilus Species 0.000 claims description 10
- 102000018358 immunoglobulin Human genes 0.000 claims description 10
- 102000004388 Interleukin-4 Human genes 0.000 claims description 9
- 108090000978 Interleukin-4 Proteins 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- 241000186660 Lactobacillus Species 0.000 claims description 8
- 210000002966 serum Anatomy 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 229940039696 lactobacillus Drugs 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 229940039695 lactobacillus acidophilus Drugs 0.000 claims description 5
- 239000004816 latex Substances 0.000 claims description 5
- 229920000126 latex Polymers 0.000 claims description 5
- 206010002198 Anaphylactic reaction Diseases 0.000 claims description 4
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 208000004262 Food Hypersensitivity Diseases 0.000 claims description 4
- 206010016946 Food allergy Diseases 0.000 claims description 4
- 244000199866 Lactobacillus casei Species 0.000 claims description 4
- 235000013958 Lactobacillus casei Nutrition 0.000 claims description 4
- 230000036783 anaphylactic response Effects 0.000 claims description 4
- 208000003455 anaphylaxis Diseases 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 4
- 229940017800 lactobacillus casei Drugs 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims description 3
- 241000238631 Hexapoda Species 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 231100000740 envenomation Toxicity 0.000 claims description 3
- 235000020932 food allergy Nutrition 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000001932 seasonal effect Effects 0.000 claims description 3
- 230000035945 sensitivity Effects 0.000 claims description 3
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- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 238000003018 immunoassay Methods 0.000 claims 1
- 239000007909 solid dosage form Substances 0.000 claims 1
- 108010058846 Ovalbumin Proteins 0.000 description 25
- 229940092253 ovalbumin Drugs 0.000 description 23
- 241000699670 Mus sp. Species 0.000 description 22
- 230000004044 response Effects 0.000 description 20
- 230000001629 suppression Effects 0.000 description 16
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000005875 antibody response Effects 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 235000013618 yogurt Nutrition 0.000 description 4
- 206010051841 Exposure to allergen Diseases 0.000 description 3
- 206010070834 Sensitisation Diseases 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 206010027654 Allergic conditions Diseases 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 229940037003 alum Drugs 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 239000003659 bee venom Substances 0.000 description 2
- 238000000586 desensitisation Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010073310 Occupational exposures Diseases 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000013572 airborne allergen Substances 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000007233 immunological mechanism Effects 0.000 description 1
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- 239000000843 powder Substances 0.000 description 1
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- 206010039083 rhinitis Diseases 0.000 description 1
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- 210000000952 spleen Anatomy 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/07—Bacillus
-
- 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
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- 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
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- 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
- A61K39/35—Allergens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6866—Interferon
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/113—Acidophilus
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/125—Casei
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria
- G01N2333/335—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Lactobacillus (G)
Definitions
- the invention relates to the field of allergic disease prevention and/or treatment, and in particular to probiotic bacteria which have the capacity to prevent and/or treat allergic disease.
- BACKGROUND ART Allergy is a clinical syndrome affecting about one third of the population, manifest as rhinitis, asthma, eczema or food hypersensitivity.
- target tissue changes play a role in determining the pattern of disease
- the central abnormality (known as atopy) is the genetically influenced propensity to develop an IgE antibody response following antigen exposure.
- atopy the central abnormality
- the characteristics of the gut bacterial flora may drive IgE-promoting immunological mechanisms possibly by affecting the cytokine balance produced by CD4+ T lymphocytes.
- the present invention provides a method of lowering IgE levels by administration of a therapeutically effective amount of live probiotic bacteria, or a live probiotic bacteria-containing composition, to a subject in need thereof.
- a method of prophylactic or therapeutic treatment of allergy by administration to a subject requiring such treatment a therapeutically effective amount of live probiotic bacteria, or a live probiotic bacteria- containing composition preferably, the probiotic bacteria is, or the probiotic bacteria-containing composition includes. Lactobacillus.. Most preferably, the Lactobacillus is Lactobacill s acidophil s and/or Lactobacillus casei.
- IgE is lowered from elevated levels induced by an allergen or as a consequence of an allergic disorder.
- the probiotic bacteria, or a probiotic bacteria-containing composition is administered at the time of exposure to an allergen or shortly thereafter.
- the term "exposure" with reference to an antigen or allergen includes natural exposure such as for example day-to-day contact with or ingestion of food products and the like, or seasonal exposure or re-exposure to allergens such as pollen or other air-borne allergens or by contact with skin and other body surfaces which may involve contact with synthetic materials or natural substances.
- allergens such as pollen or other air-borne allergens or by contact with skin and other body surfaces which may involve contact with synthetic materials or natural substances.
- the probiotic bacteria or compositions containing such bacteria are preferably administered at the time of exposure to the antigen/allergen or shortly thereafter.
- the treatment is preferably commenced at the beginning of the season or shortly thereafter.
- the term “exposure” includes natural exposure such as for example day-to-day contact with or ingestion of food products and the like, or seasonal exposure or re-exposure to allergens such as pollen or other air-borne allergens or by contact with skin and other body surfaces which may involve contact with synthetic materials or natural substances.
- antigen/allergen when used with reference to antigen/allergen also includes artificial exposure or administration such as for example the injection of antigen/allergen in desensitisation procedures or under-tongue administration of antigen/allergen.
- the antigen/allergen is preferably co-administered (co-presented) with the probiotic bacteria or a composition containing them.
- probiotic bacteria may also be administered shortly after administration of the antigen/allergen.
- the subject in need thereof is selected from the group consisting of high risk infants; those subjected to high risk occupational exposure to allergens; those exposed to high risk allergens; those having recognised allergy to specific allergens; and those prone to anaphylaxis.
- the high risk infants are children of parents who both have allergic disease.
- those subject to high risk occupation exposure to allergens are selected from the group consisting of aluminium smelter workers, woodworkers, chemical factory workers, and those working with latex-containing materials, especially gloves.
- those exposed to high risk allergens are exposed to bee venom.
- exposure to high risk allergens is parenteral exposure.
- the specific allergens are present in the pre-pollen season, foods or latex-containing materials.
- the trigger for the allergic response is insect envenomation, and food and drug sensitivities.
- the probiotic bacteria or probiotic bacteria-containing composition is in tablet or capsule form.
- the probiotic bacteria may be present in a food source such as a yoghurt or other dairy product.
- the amount of probiotic bacteria administered to a human subject is at least 10 10 live bacteria. More preferably the amount administered is from about 10 10 to about 10 n live bacteria.
- the required dosage amount will vary according to the severity of the allergic condition, the nature of the allergic condition, age of the subject and other standard clinical parameters. These parameters as well as the required dosage can be easily assessed by those skilled in the art. In human subjects it is preferred that the probiotic bacteria or a composition containing them be administered daily.
- the present invention provides the use of live probiotic bacteria for the manufacture of a medicament for lowering IgE levels.
- the present invention provides use of live probiotic bacteria for the manufacture of a medicament for treating allergy.
- the present invention provides a method of identifying a bacterial species capable of lowering IgE levels in a mammal including: a) administration of the bacterial species to a mammal; b) administration of an allergen (antigen) to the mammal; and c) determination of the IgE antibody level in the mammal after treatment with the bacterial species and comparison with a control mammalian which a bacterial species
- steps (a) and (b) were not administered, wherein steps (a) and (b) can be performed consecutively in any order or simultaneously.
- the bacterial species is a Lactobacillus species and most preferably it is Lactobacillus acidophilus or Lactobacillus casei.
- the animal model for identifying useful probiotic bacteria preferably makes use of the mouse.
- other animal models may be developed on the same principle as disclosed herein.
- the bacterial species is preferably administered orally however it may also be administered intraperitoneally and other means. Most preferably, the
- 15 bacterial species is administered in an amount of 10 8 to 10" bacteria, and more preferably, in an amount of 0.6 to 1.0 x 10'° bacteria.
- 1 to 20 oral doses are administered prior to administration of the antigen and most preferably 4 to 8 oral doses are administered prior to administration of the antigen.
- administration of the oral doses is at 1 to 5 day intervals and, most preferably, at 2 day intervals.
- 0 administration is over a 1 to 3 week period and, most preferably, over a 1 to 2 week period.
- the antigen is administered at 5 a dose of 4 to 10 ⁇ g, and most preferably, at a dose of 8 ⁇ g.
- the antigen is administered intraperitoneally.
- the bacterial species is administered at the same time or 1 day after administration of the antigen/allergen.
- the antigen/allergen can be administered after the bacterial species and in such circumstances the antigen/allergen is administered preferably 1 day after the 0 administration of 4 to 8 oral doses of bacteria.
- administration of the bacteria species is continued after administration of the antigen. Most preferably, approximately 8 oral doses of bacteria are administered.
- the bacteria are administered at 2 day intervals.
- the IgE antibody is obtained from serum.
- the serum is collected approximately 14 days after administration of the antigen.
- the IgE antibody level is determined using an ELISA assay.
- the skilled addressee will recognise that other IgE antibody assays may also be used.
- the allergic disease is selected from the group consisting of asthma, eczema, hayfever and food allergy.
- the present invention provides a bacterial species identified by the method of the fourth aspect.
- the present invention provides a composition including a bacterial species according to the fourth aspect.
- composition is in the form of a capsule or tablet or similar formulation however it may also be in the form of a food product.
- a pharmaceutical composition including an effective amount of live bacterial species according to the fourth aspect, together with a pharmaceutically acceptable carrier, adjuvant, solvent or excipient.
- the bacterial species is L. acidophilus.
- a method of assessing efficacy of treatment with live probiotic bacteria or with a composition having live probiotic bacteria including the steps of: a measuring the level of salivary immunoglobulin subclass in a sample obtained before commencement of treatment, b measuring the level of salivary immunoglobulin subclass in a sample obtained after commencement of treatment c comparing the levels of salivary immunoglobulin subclass in a) and b), wherein the change in immunoglobulin subclass level is indicative of effective treatment.
- the immunoglobulin subclass is IgGl or IgG2 and it will be understood that equivalent subclasses in various species can also be advantageously used.
- a method of assessing efficacy of treatment with live probiotic bacteria or with a composition having live probiotic bacteria including the steps of: a measuring the level of LL-4 or IFN- ⁇ in a sample obtained before commencement of treatment, b measuring the level of IL-4 or IFN- ⁇ in a sample obtained after commencement of treatment c comparing the levels of IL-4 or IFN- ⁇ in a) and b), wherein the change in IL-4 or
- IFN- ⁇ level is indicative of effective treatment. It will be clear however that any know cytokine marker for the Thl or the Th2 response will be suitable in place of IFN- ⁇ or IL-4.
- Figure 1 Suppression of IgE antibody response in mice fed probiotic bacteria.
- Figure 5 Suppression of IgE response to OVA, and cytokine and IgG antibody subclass response, by L acidophilus
- a mouse animal model was developed which enabled identification of probiotic bacteria capable of downregulating the IgE response to an antigen/allergen.
- the animal used is a mouse (for example C57BL/6).
- the animals are fed the candidate bacterial species (alive, dose 10 8 -10" , frequency every 1 -5 days, for 1 -3 weeks).
- the animals are fed the bacteria at the same time as the antigen was being introduced or shortly thereafter, for example the following day.
- Mice were immunised intraperitoneally with antigen (for example ovalbumin) at an appropriate dose (eg 4-1 O ⁇ g, preferably 8 ⁇ g), with specific and total IgE measured in serum (eg. at 14 days after immunisation).
- antigen for example ovalbumin
- specific and total IgE measured in serum eg. at 14 days after immunisation.
- feeding with test bacteria continues throughout the experiment (see examples).
- comparisons are made with killed organisms and dose-response is estimated.
- timing of administration of probiotic bacteria in relation to antigen/allergen challenge is examined. The examples demonstrate: (i) that frequent dosage with live probiotic bacteria at an appropriate does can reduce the IgE response to antigen/allergen.
- oral administration of the bacterial species affects the systemic IgE antibody response (following injected antigen) and thus may be of value in subjects who have anaphylaxis (eg insect envenomation, and food and drug sensitivities).
- probiotic bacteria can downregulate IgE production following antigen administration or exposure to antigen - thus continuous oral ingestion of appropriate doses of live bacteria selected by this method may be of value in the ongoing management of allergic disease.
- administration of live probiotic bacteria is particularly effective
- co-administration of probiotic bacteria with the antigen/allergen, or administration of probiotic bacteria shortly after the antigen/allergen challenge is particularly effective
- the probiotic bacteria can be formulated into various compositions and preferably the compositions are pharmaceutical compositions in the form of capsules, tablets, powders and the like.
- Such formulations can be prepared by known means, using pharmaceutically acceptable carriers, excipients, solvents or adjuvants. Such procedures and ingredients are well know and amply described in standard texts and manuals, for example "Remington: The Science and Practice of Pharmacy", 1995, Mack Publishing Co. Easton, PA 18042, USA, which is incorporated herein by reference.
- the probiotic bacteria may also be formulated into food products by the usual well known means.
- Bacteria ⁇ Lactobacillus acidophilus or Lactobacillus casei) were grown in MRS agar petri dishes (3.8% w/v, Oxoid, Basingstoke, UK). Plates were incubated in 5% CO 2 and air in a humid atmosphere at 37°C for 48 hours.
- PBS phosphate buffered saline
- mice Thirty female C57/B16 SPF mice (Animal Resource Centre, Perth, WA, Australia) were fed with 4 or 8 oral doses of 0.6-1.0 x 10 10 L acidophilus or L casei in 0.2 mL PBS or PBS alone given two days apart.
- mice were injected intraperitoneally with 7 ⁇ g of egg albumin (ovalbumin. OVA, Sigma-Aldrich, St Loius, Missouri, USA) and 4 mg aluminium hydroxide (Amphojel, Whitehall Laboratories, Sydney, Australia) in 0.2 mL PBS or with PBS alone.
- egg albumin ovalbumin. OVA, Sigma-Aldrich, St Loius, Missouri, USA
- aluminium hydroxide aluminium hydroxide
- mice Immunised and control mice were then placed on a feeding regime consisting of 8 oral doses of 0.6-1.0 x 10'° bacteria in PBS or PBS alone given two days apart. Mice were bled by the saphenous vein 2 days after the last dose and the serum collected for IgE antibody determination using an ELISA assay.
- Example 2 Suppression of IgE response to OVA by L acidophilus after allergen sensitisation
- mice were fed 10 10 L acidophilus before or 24 hrs after sensitisation with 8 ⁇ g ovalbumin (OVA) in alum per mouse.
- Control mice were sham fed with normal saline.
- a total of 10 feeds was administered before they were assessed for levels of OVA-specific IgE antibody and total IgE in serum.
- L acidophilus was more effective if administered (or co-administered) at the time of exposure to OVA than when administered prior to allergen exposure, as shown by the suppression of OVA-specific IgE antibody and total IgE responses (Figure 2 ).
- Data are mean + SEM from 5-10 mice. *, p ⁇ 0.05 compared with control values from saline-fed sensitised mice.
- Example 3 Suppression of IgE response to OVA by L. acidophilus is dose- dependent Mice were fed orally with 10 8 . 10 9 or 10 10 L acidophilus before they were sensitised 24 hrs later with OVA in alum. Control mice were sham fed PBS. Each dose was administered 10 times every 2 days for 21 days. One week following the final dose, serum IgE and OVA-specific IgE antibody were measured. A dose-dependent suppression of IgE and OVA-specific IgE antibody was noted with a statistically significant effect with 10 l ⁇ bacteria ( Figure 3). Data are mean + SEM from 10 mice. *, p ⁇ 0.05 compared with control values from saline-fed sensitised mice.
- mice were fed live or formalin-killed 10 10 L acidophilus and then sensitised with OVA as per standard protocol described in Example 3.
- Figure 4 shows that live bacteria were more effective in suppressing IgE response than killed bacteria. Data are mean + SEM from 5 mice. *, p ⁇ 0.05 compared with values from saline-fed sensitised mice.
- Example 5 Suppression of IgE response to OVA by L acidophilus correlates with cytokine and IgG antibody subclass response
- mice fed 10'° L acidophilus produced higher amounts of IFN- ⁇ and lower amounts of IL-4 in the spleen, a finding consistent with the suppression of IgE response.
- the contrasting cytokine patterns correlated with the production of salivary IgG subclass antibodies which showed an upregulation of IgG2a antibody and a downregulation of IgGl , respectively ( Figure 5 ).
- Data are mean + SEM from 10 mice. *, p ⁇ 0.05; **, p ⁇ 0.01 compared with values from saline-fed sensitised mice.
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Abstract
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AUPQ415899 | 1999-11-19 | ||
AUPQ4158A AUPQ415899A0 (en) | 1999-11-19 | 1999-11-19 | Compositions for and methods of treatment of allergic diseases |
PCT/AU2000/001414 WO2001037865A1 (fr) | 1999-11-19 | 2000-11-20 | Compositions et methodes pour le traitement des troubles allergiques |
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EP (1) | EP1229930A4 (fr) |
JP (1) | JP2003514869A (fr) |
KR (1) | KR20020084066A (fr) |
CN (1) | CN1391480A (fr) |
AU (1) | AUPQ415899A0 (fr) |
BR (1) | BR0015698A (fr) |
CA (1) | CA2391499A1 (fr) |
HK (1) | HK1049115A1 (fr) |
WO (1) | WO2001037865A1 (fr) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
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ID29150A (id) | 1999-01-15 | 2001-08-02 | Entpr Ireland Cs | Penggunaan lactobacillus salivarius |
FI110668B (fi) | 2000-06-20 | 2003-03-14 | Aboatech Ab Oy | Probioottien käyttö atooppisten sairauksien primaariseen ehkäisyyn |
PE20030283A1 (es) * | 2001-07-26 | 2003-05-01 | Alimentary Health Ltd | Cepas de lactobacillus casei |
GB0124580D0 (en) | 2001-10-12 | 2001-12-05 | Univ Reading | New composition |
JP4212838B2 (ja) | 2002-06-26 | 2009-01-21 | カルピス株式会社 | 抗アレルギー剤 |
CA2518947A1 (fr) * | 2003-03-13 | 2004-11-11 | Kirin Beer Kabushiki Kaisha | Composition antiallergique |
JP4712289B2 (ja) * | 2003-08-26 | 2011-06-29 | 株式会社エイ・エル・エイ | 免疫促進用組成物 |
JP4591810B2 (ja) * | 2003-09-19 | 2010-12-01 | 日之出産業株式会社 | 花粉症アレルギー性鼻炎抑制用点鼻組成物 |
CN100421676C (zh) * | 2003-12-17 | 2008-10-01 | 纽迪西亚公司 | 乳酸产生细菌和肺功能 |
US7955834B2 (en) | 2004-06-03 | 2011-06-07 | Biogaia Ab | Method for improved breast milk feeding to reduce the risk of allergy |
TWI356680B (en) * | 2007-01-05 | 2012-01-21 | Promd Biotech Co Ltd | Anti-allergy lactic acid bacteria |
CN101328468B (zh) * | 2007-06-21 | 2012-05-23 | 东宇生物科技股份有限公司 | 抗过敏的乳酸菌 |
CN102657260B (zh) * | 2007-06-21 | 2013-08-21 | 东宇生物科技股份有限公司 | 抗过敏的乳酸菌 |
EP2065048A1 (fr) * | 2007-11-30 | 2009-06-03 | Institut Pasteur | Utilisation d'une souche de L. casei pour la préparation d'une composition pour l'inhibition de l'activation de mastocytes |
PL2244734T3 (pl) | 2008-02-01 | 2017-01-31 | Murdoch Childrens Research Institute | Sposób indukcji tolerancji na alergen |
EP2603208B1 (fr) | 2010-08-10 | 2014-06-04 | R.P. Scherer Technologies, LLC | Procédé de fabrication d'une capsule molle stable contenant des bactéries probiotiques micro-encapsulées |
KR101311989B1 (ko) * | 2010-11-17 | 2013-09-26 | 주식회사한국야쿠르트 | 면역 조절 및 강화 효능을 갖는 락토바실러스 카제이 에이치와이7211를 유효성분으로 함유하는 제품 |
PE20210108A1 (es) * | 2018-01-12 | 2021-01-19 | Gi Innovation Inc | Composicion que comprende probioticos y polipeptido que tiene afinidad de union para ige y uso de la misma |
CN111296842B (zh) * | 2020-02-14 | 2021-01-05 | 赵一鸣 | 一种具有抗敏作用的益生菌组合物 |
CN112375722B (zh) * | 2021-01-18 | 2021-04-13 | 山东中科嘉亿生物工程有限公司 | 一种改善过敏的干酪乳杆菌lc-12及其产品、应用 |
WO2024081219A1 (fr) | 2022-10-14 | 2024-04-18 | Csp Technologies, Inc. | Récipient et procédé de stockage et de stabilisation de produits sensibles à l'humidité |
CN117085046A (zh) * | 2023-10-20 | 2023-11-21 | 潍坊君薇生物科技有限责任公司 | 嗜酸乳杆菌ls001后生元及其应用 |
CN117887643B (zh) * | 2024-03-14 | 2024-06-14 | 微康益生菌(苏州)股份有限公司 | 一种抗过敏的益生菌剂及其应用 |
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JPS5522641A (en) | 1978-08-07 | 1980-02-18 | Kyokuto Shibousan Kk | Antiallergic agent |
JPS55122723A (en) | 1979-03-14 | 1980-09-20 | Kyokuto Shibousan Kk | Drug for asthma |
JPH07265064A (ja) | 1993-11-23 | 1995-10-17 | Taketoshi Yamada | 腸内細菌叢改善組成物 |
JPH092959A (ja) | 1995-06-16 | 1997-01-07 | Yakult Honsha Co Ltd | IgE抗体産生抑制剤および抗アレルギー剤 |
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EP0904784A1 (fr) * | 1997-09-22 | 1999-03-31 | N.V. Nutricia | Préparation nutritionnelle probiotique |
JPH11199495A (ja) * | 1998-01-10 | 1999-07-27 | Nichinichi Seiyaku Kk | 腸溶性カプセルを用いた抗アレルギー剤 |
IT1298918B1 (it) * | 1998-02-20 | 2000-02-07 | Mendes Srl | Uso di batteri dotati di arginina deiminasi per indurre apoptosi e/o ridurre una reazione infiammatoria e composizioni farmaceutiche |
JP4074006B2 (ja) * | 1998-06-24 | 2008-04-09 | アサマ化成株式会社 | IgE抗体産生抑制物質の製造方法並びにそれを用いた食品 |
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- 2000-11-20 JP JP2001539479A patent/JP2003514869A/ja not_active Withdrawn
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- 2000-11-20 EP EP00975685A patent/EP1229930A4/fr not_active Withdrawn
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JPS5522641A (en) | 1978-08-07 | 1980-02-18 | Kyokuto Shibousan Kk | Antiallergic agent |
JPS55122723A (en) | 1979-03-14 | 1980-09-20 | Kyokuto Shibousan Kk | Drug for asthma |
JPH07265064A (ja) | 1993-11-23 | 1995-10-17 | Taketoshi Yamada | 腸内細菌叢改善組成物 |
JPH092959A (ja) | 1995-06-16 | 1997-01-07 | Yakult Honsha Co Ltd | IgE抗体産生抑制剤および抗アレルギー剤 |
Non-Patent Citations (2)
Title |
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See also references of WO0137865A1 |
SHIDA K. ET AL.: "LACTOBACILLUS CASEI INHIBITS ANTIGEN-INDUCED IGE SECRETION THROUGH REGULATION OF CYTOKINE PRODUCTION IN MURINE SPLENOCYTE CULTURES", INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, vol. 115, 1998, pages 278 - 287, XP008007352 |
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AUPQ415899A0 (en) | 1999-12-16 |
EP1229930A4 (fr) | 2004-09-22 |
JP2003514869A (ja) | 2003-04-22 |
HK1049115A1 (zh) | 2003-05-02 |
CA2391499A1 (fr) | 2001-05-31 |
BR0015698A (pt) | 2002-07-23 |
CN1391480A (zh) | 2003-01-15 |
KR20020084066A (ko) | 2002-11-04 |
WO2001037865A1 (fr) | 2001-05-31 |
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