BIFIDOBACTERIUM BIFIDUM STRAINS FOR APPLICATION IN GASTROINTESTINAL DISEASES

• US 20140056852A1
• Filed: 01/27/2012
• Published: 02/27/2014
• Est. Priority Date: 01/31/2011
• Status: Active Grant

• Current Assignee: Synformulas GmbH
• Original Assignee: Naturwohl Pharma GmbH (Perrigo Company PLC)
• Inventors: Guglielmetti, Simone, Mora, Diego
• Granted Patent: US 9,408,879 B2
• Time in Patent Office: Days
• US Class Current: 424/93.4
• CPC Class Codes: A23L 33/135 Bacteria or derivatives thereof, e.g. probiotics
• CPC Class Codes: A61K 35/745 Bifidobacteria
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention provides a strain of Bifidobacterium bifidum or mutant or variant thereof showing at least an adhesion of about 10 bacterial cells per mm2 of epithelial cell monolayer or having at least an adhesion index of 1.5 and a strain of Bifidobacterium bifidum or mutant or variant thereof being Bifidobacterium bifidum MIMBb75, deposited under deposit No. DSM 24514, or a mutant or variant thereof for use as probiotic, in foodstuff and/or as a medicament. Further provided is a probiotic for mulation, comprising any of the strains, mutants or variants mentioned above, uses of said probiotic formulation, strains, mutants and variants thereof and a method for producing said probiotic formulation.

Claims

1. A strain of Bifidobacterium bifidum or mutant or variant thereof for use as probiotic, in foodstuff and/or as a medicament, the strain being Bifidobacterium bifidum MIMBb75, deposited under deposit No. DSM 24514, or a mutant or variant thereof.

2. The strain, mutant or variant of claim 1 for use as probiotic, in foodstuff and/or as a medicament in the prophylaxis and/or treatment of a disease correlated with a functional disorder of the gastrointestinal tract, with undesirable gastrointestinal inflammatory activity, with an imbalance of the intestinal microbiota, a reduction of Bifidobacteria in the gastrointestinal tract and/or a dysfunctional intestinal barrier of the gastrointestinal tract, or for use in alleviating, preventing and/or treating a subject suffering from abdominal pain, discomfort, distension, bloating, digestive disorder, urgency and/or reduced and/or increased number of bowel movements, feeling of incomplete evacuation and/or combinations thereof or for improving the quality of life of a patient.

3. The strain, mutant or variant of claim 2, wherein the disease is a member selected from the group consisting of irritable bowel movement, inflammatory bowel disease, e.g. Crohn'"'"'s disease or ulcerative colitis, irritable bowel syndrome, pouchitis or post infection colitis, gastrointestinal cancer, a systemic disease such as rheumatoid arthritis, an autoimmune disorders due to undesirable inflammatory activity, diarrhoeal disease due to undesirable inflammatory activity, such as Clostridium difficile associated diarrhoea, antibiotics associated diarrhoea, Rotavirus associated diarrhoea or post infective diarrhoea, and combinations thereof.

4. A probiotic formulation comprising the strain, mutant or variant of claim 1, for use as a probiotic, in foodstuff and/or as a medicament.

5. The probiotic formulation of claim 4 further comprising at least one prebiotic, optionally comprising at least inulin and/or a fructooligosaccharide.

6. The probiotic formulation of claim 4 further comprising at least one pharmaceutically acceptable compound, an ingestible carrier, an adjuvant, a bacterial component, a drug entity, a biological compound and/or a protein and/or peptide, in particular a protein and/or peptide that is rich in glutamine/glutamate, a lipid, a carbohydrate, a vitamin, mineral and/or trace element;

optionally said at least one pharmaceutically acceptable compound is a member selected from the group consisting of one or more vitamins, such as vitamins of the B group, one or more minerals, such as calcium or magnesium, one or more carbohydrates, such as lactose, maltodextrin, inulin, dextrose, mannitol, maltose, dextrin, sorbitol, fructose, and a mixture thereof.

7. The probiotic formulation of claim 6, wherein the ingestible carrier is a capsule, tablet, powder or a food product;

optionally the food product is a dairy product, acidified milk, yoghurt, frozen yoghurt;

milk powder, milk concentrate, cheese spread, dressing or beverage.

8. The probiotic formulation of claim 4, wherein the strain, mutant or variant is present at more than 10¹ cfu per capsule or tablet or per unit of powder or food product, optionally not less than 10², 10³, 10⁴, 10⁵ or 10⁶ cfu per capsule or tablet or per unit of powder or food product.

9. The probiotic formulation of claim 4, wherein the daily amount of the strain, mutant or variant administered to a patient is not less than 10¹ cfu per capsule or tablet or per unit of powder or food product, optionally not less than 10², 10³, 10⁴, 10⁵ or 10⁶ cfu.

10. The probiotic formulation of claim 4 for use as probiotic, in foodstuff and/or as a medicament in the prophylaxis and/or treatment of a disease correlated with a functional disorder of the gastrointestinal tract, with undesirable gastrointestinal inflammatory activity, with an imbalance of the intestinal microbiota, a reduction of Bifidobacteria in the gastrointestinal tract and/or a dysfunctional intestinal barrier of the gastrointestinal tract, and/or for alleviating, preventing and/or treating a subject suffering from abdominal pain, discomfort, distension, bloating, digestive disorder, urgency and/or reduced and/or increased number of bowel movements, feeling of incomplete evacuation and/or combinations thereof.

11. The probiotic formulation of claim 10, wherein the disease is a member selected from the group consisting of irritable bowel movement, inflammatory bowel disease, e.g. Crohn'"'"'s disease or ulcerative colitis, irritable bowel syndrome, pouchitis or post infection colitis, gastrointestinal cancer, a systemic disease such as rheumatoid arthritis, an autoimmune disorders due to undesirable inflammatory activity, diarrhoeal disease due to undesirable inflammatory activity, such as Clostridium difficile associated diarrhoea, antibiotics associated diarrhoea, Rotavirus associated diarrhoea or post infective diarrhoea, and combinations thereof.

12. Use of the strain, mutant or variant of claim 1 or of a probiotic formulation thereof as probiotic, in foodstuff and/or as a medicament in the prophylaxis and/or treatment of a disease correlated with a functional disorder of the gastrointestinal tract, with undesirable gastrointestinal inflammatory activity, with an imbalance of the intestinal microbiota, a reduction of Bifidobacteria in the gastrointestinal tract and/or a dysfunctional intestinal barrier of the gastrointestinal tract, and/or for alleviating, preventing and/or treating a subject suffering from abdominal pain, discomfort, distension, bloating, digestive disorder, urgency and/or reduced and/or increased number of bowel movements, feeling of incomplete evacuation and/or combinations thereof.

13. The use of claim 12, wherein the disease is a member selected from the group consisting of irritable bowel movement, inflammatory bowel disease, e.g. Crohn'"'"'s disease or ulcerative colitis, irritable bowel syndrome, pouchitis or post infection colitis, gastrointestinal cancer, a systemic disease such as rheumatoid arthritis, an autoimmune disorders due to undesirable inflammatory activity, diarrhoeal disease due to undesirable inflammatory activity, such as Clostridium difficile associated diarrhoea, antibiotics associated diarrhoea, Rotavirus associated diarrhoea or post infective diarrhoea, and combinations thereof.

14. A method for producing a probiotic formulation of claim 4, comprising at least the following steps:

a) fermenting and/or growing the strain of any of claims 1 to 4 in a protein-rich liquid growth medium,

b) harvesting the cells by centrifugation, stabilising, freeze-drying, milling and sieving of the cells,

c) optionally mixing/blending the cells with one or more members of the group consisting of a prebiotic, a pharmaceutically acceptable compound, an adjuvant, a bacterial component, a drug entity, a biological compound, a protein and/or peptide, and

d) introducing the cells of step b) or the mixture of step c) in an ingestible carrier.