WO2016020911A1 - Use of biomass from citric acid or gluconic acid production for preventing, ameliorating or treating bowel diseases - Google Patents
Use of biomass from citric acid or gluconic acid production for preventing, ameliorating or treating bowel diseases Download PDFInfo
- Publication number
- WO2016020911A1 WO2016020911A1 PCT/IL2015/050629 IL2015050629W WO2016020911A1 WO 2016020911 A1 WO2016020911 A1 WO 2016020911A1 IL 2015050629 W IL2015050629 W IL 2015050629W WO 2016020911 A1 WO2016020911 A1 WO 2016020911A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- biomass
- bowel disease
- ameliorating
- preventing
- Prior art date
Links
- 239000002028 Biomass Substances 0.000 title claims abstract description 65
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 201000010099 disease Diseases 0.000 title claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 48
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 title claims abstract description 31
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 18
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 239000000174 gluconic acid Substances 0.000 title claims abstract description 16
- 235000012208 gluconic acid Nutrition 0.000 title claims abstract description 16
- 239000000203 mixture Substances 0.000 claims abstract description 52
- 235000015872 dietary supplement Nutrition 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 20
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 19
- 235000016709 nutrition Nutrition 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 102000004169 proteins and genes Human genes 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 12
- 208000011231 Crohn disease Diseases 0.000 claims description 11
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 9
- 235000013305 food Nutrition 0.000 claims description 8
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 241000228245 Aspergillus niger Species 0.000 claims description 6
- 239000008187 granular material Substances 0.000 claims description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 239000002417 nutraceutical Substances 0.000 claims description 6
- 235000021436 nutraceutical agent Nutrition 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 5
- 235000013350 formula milk Nutrition 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 239000004606 Fillers/Extenders Substances 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 239000003655 absorption accelerator Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 239000004067 bulking agent Substances 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 4
- 239000011248 coating agent Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000007884 disintegrant Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 239000000796 flavoring agent Substances 0.000 claims description 4
- 235000013355 food flavoring agent Nutrition 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 230000000968 intestinal effect Effects 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 235000010755 mineral Nutrition 0.000 claims description 4
- 235000000346 sugar Nutrition 0.000 claims description 4
- 150000008163 sugars Chemical class 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 235000013343 vitamin Nutrition 0.000 claims description 4
- 239000011782 vitamin Substances 0.000 claims description 4
- 229940088594 vitamin Drugs 0.000 claims description 4
- 229930003231 vitamin Natural products 0.000 claims description 4
- 239000000080 wetting agent Substances 0.000 claims description 4
- 208000027496 Behcet disease Diseases 0.000 claims description 3
- 208000009137 Behcet syndrome Diseases 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 235000015173 baked goods and baking mixes Nutrition 0.000 claims description 3
- 235000013361 beverage Nutrition 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 235000009508 confectionery Nutrition 0.000 claims description 3
- 235000013365 dairy product Nutrition 0.000 claims description 3
- 235000013325 dietary fiber Nutrition 0.000 claims description 3
- 239000008298 dragée Substances 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 238000000855 fermentation Methods 0.000 claims description 3
- 230000004151 fermentation Effects 0.000 claims description 3
- 235000012041 food component Nutrition 0.000 claims description 3
- 239000005417 food ingredient Substances 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 235000014655 lactic acid Nutrition 0.000 claims description 3
- 239000004310 lactic acid Substances 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 235000011888 snacks Nutrition 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 235000014347 soups Nutrition 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 239000000829 suppository Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 206010049416 Short-bowel syndrome Diseases 0.000 claims description 2
- 208000025865 Ulcer Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 208000003243 intestinal obstruction Diseases 0.000 claims description 2
- 231100000397 ulcer Toxicity 0.000 claims description 2
- 239000003531 protein hydrolysate Substances 0.000 claims 1
- 206010009887 colitis Diseases 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 20
- 229920003045 dextran sodium sulfate Polymers 0.000 description 20
- 230000000694 effects Effects 0.000 description 17
- 102000003896 Myeloperoxidases Human genes 0.000 description 14
- 108090000235 Myeloperoxidases Proteins 0.000 description 14
- 206010061218 Inflammation Diseases 0.000 description 12
- 230000004054 inflammatory process Effects 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 10
- 238000012360 testing method Methods 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 210000001072 colon Anatomy 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102100040247 Tumor necrosis factor Human genes 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 230000002550 fecal effect Effects 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 210000002429 large intestine Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 210000000664 rectum Anatomy 0.000 description 4
- 208000016261 weight loss Diseases 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 210000000467 autonomic pathway Anatomy 0.000 description 3
- 238000011088 calibration curve Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 208000035861 hematochezia Diseases 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 238000001050 pharmacotherapy Methods 0.000 description 3
- 235000000891 standard diet Nutrition 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- UXTIAFYTYOEQHV-UHFFFAOYSA-N 4-(4-amino-3-methoxyphenyl)-2-methoxyaniline;hydron;dichloride Chemical compound [Cl-].[Cl-].C1=C([NH3+])C(OC)=CC(C=2C=C(OC)C([NH3+])=CC=2)=C1 UXTIAFYTYOEQHV-UHFFFAOYSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 241000147041 Guaiacum officinale Species 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028116 Mucosal inflammation Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 210000000436 anus Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 208000027503 bloody stool Diseases 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000009266 disease activity Effects 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 229940091561 guaiac Drugs 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000011903 nutritional therapy Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 235000021067 refined food Nutrition 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 102000014777 Adipokines Human genes 0.000 description 1
- 108010078606 Adipokines Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241000252983 Caecum Species 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000478 adipokine Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 210000004953 colonic tissue Anatomy 0.000 description 1
- 235000020940 control diet Nutrition 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000020805 dietary restrictions Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 235000020882 elemental diet Nutrition 0.000 description 1
- 239000003532 endogenous pyrogen Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 235000020828 fasting Nutrition 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 235000021197 fiber intake Nutrition 0.000 description 1
- 235000014105 formulated food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000019534 high fructose corn syrup Nutrition 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 108010052620 leukocyte endogenous mediator Proteins 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 235000004213 low-fat Nutrition 0.000 description 1
- 235000021073 macronutrients Nutrition 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N para-benzoquinone Natural products O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- 235000016236 parenteral nutrition Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- -1 quinone compound Chemical class 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000021476 total parenteral nutrition Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/062—Ascomycota
-
- 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
-
- 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
- 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
- A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
Definitions
- Gastrointestinal diseases refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestions, the liver, gallbladder and pancreas.
- An inflammatory bowel disease refers to a disease in which a mucosa of the intestine is led to cause inflammation by some causes that may lead to ulcerative colitis, Crohn's disease or intestinal Behcet disease.
- the inflammation is usually considered to begin in the rectum near the anus, and thereafter it spreads toward the colon behind the rectum.
- Colitis and Crohn's disease are inflammatory disorders of the gastrointestinal track caused by genetic, environmental and nutritional causes.
- Michael D. Kappelman et al. entitled “The Prevalence and Geographic Distribution of Crohn's Disease and Ulcerative Colitis in the United States", published in Clinical Gastroenterology and Hepatology, Vol 5, Issue 12, December 2007, pages 1424-1429, it is mentioned that the current prevalence of colitis and Crohn's disease in children younger than 20 years is 43 and 28 per 100,000, respectively.
- the prevalence of colitis and Crohn's disease is 201 and 238, respectively. The prevalence of both conditions is lower in the South, compared with the Northeast, Midwest, and West of the United States.
- Colitis is a disease characterized by inflammation of the colon, which is usually described as an inflammation of the large intestine (colon, caecum and rectum). Colitis broadly fits into the category of digestive diseases because it may be acute and self-limited or chronic, i.e. persistent.
- Colitis and Crohn's disease have high frequency of incidence. Nevertheless, these diseases are difficult to be clinically treated and therefore fundamental therapies directed to these diseases have not yet been established.
- Therapies such as nutritional therapy that include, e.g., total parenteral nutrition therapy, enteral nutrition therapy and alimentotherapy have been used along with pharmacotherapy.
- drugs such as sulfasalazine (a sulfa drug), mesalazine (an anti-inflammatory drug), prednisolone (a steroid drug) and azathioprine (immunosuppressant) have been used stepwise for treating Colitis and Crohn's disease depending on the stage of the disease.
- abnormality in the immunity system such as an autoimmune mechanism may be the cause of said diseases.
- the immune system of the human body functions by enabling a mechanism of releasing antigens aimed to bind to the epitopes of invading pathogens.
- This immune function also acts in the intestine.
- said mechanism may regard its own mucosa as the foreign pathogen, consequently attack the mucosa, and thereby cause a continuous inflammation.
- IBS irritable bowel syndrome
- the majority of other inflammatory bowel diseases are basically curable with internal treatment and nutritional therapy such as fasting, dietary restriction, elemental diet, high-calorie parenteral nutrition and pharmacotherapy that may include administration of an antibacterial drug, or the like depending on the symptoms.
- IBS irritable bowel syndrome
- a therapy is carried on for a long period of time, an individual may be subject to lack of nutritional balance, thereby making the symptoms more serious in some cases.
- pharmacotherapy has some disadvantages such as side effects along with the desired therapeutic effect.
- a surgical operation may be necessitated in some cases.
- the human nutritional requirements vary with age, metabolic states and diseases affecting the gastrointestinal and other systems of the human body. Adequate human nutrition is essential to avoid complications associated with nutritional deficiencies. However, the western nutrition of many individuals suffer from poor eating habits and excessive consumption of processed foods rich with sugars (such as high fructose corn syrup), saturated fats and low fiber consumption. Such prolonged unhealthy diet may lead to the development of bowel diseases.
- the present invention provides a composition for preventing, ameliorating or treating a bowel disease, said composition comprises biomass from, e.g., citric acid or gluconic acid production and optionally at least one additive.
- the present invention also provides the direct use of whole bulk biomass of Aspergillus niger for preventing, ameliorating or treating a bowel disease.
- the present invention provides the direct use of said biomass, which is a whole bulk biomass of Aspergillus niger from fermentation processes of citric acid or gluconic acid production for preventing, ameliorating or treating a bowel disease.
- said whole bulk biomass is subjected to washing with water, e.g., to washing with hot water followed by drying to afford dried whole bulk biomass.
- said composition can be a nutritional composition (e.g., infant formula), a nutraceutical composition (e.g., a dietary supplement), a medical food, or a pharmaceutical composition.
- said pharmaceutical composition can be a formulated dosage form.
- the present invention provides pharmaceutical compositions in admixture with pharmaceutically acceptable excipients, and optionally other therapeutic agents.
- adequate routes of administration of said composition for an individual who is in need for such treatment thereof, are oral, buccal, eternal and sublingual administration or administration via a feeding tube.
- the composition can be administered orally.
- the pharmaceutical compositions of the present invention that can be, e.g., formulated dosage forms, can be administered, for example, as tablets, pills, powders, granules, dragees, liquids, suspensions, emulsions, granules, capsules, suppositories, injection preparations (solutions and suspensions), patches and the like.
- compositions comprising the biomass of the present invention can be prepared by mixing said biomass of the present invention with at least one additional active ingredient selected from absorption accelerators, binders, bulking agents, carriers, coating agents, diluents, disintegrants, extenders, fillers, flavoring agents, lubricants, surface-active agents, wetting agents and the like.
- dietary supplements comprising the biomass of the present invention can be prepared by mixing said biomass of the present invention with food ingredients such as sugars and starches, dietary fibers, lipids, amino acids, proteins such as protein isolates or protein hydtrolyzates, lactic acid, vitamins, minerals and other ingredients that are commonly used in food preparations.
- food ingredients such as sugars and starches, dietary fibers, lipids, amino acids, proteins such as protein isolates or protein hydtrolyzates, lactic acid, vitamins, minerals and other ingredients that are commonly used in food preparations.
- the dietary supplement of the present invention may include bakery product, beverage, bar, candy, dairy product, infant formula, snack, soup, spread and the like.
- BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 depicts the experimental in vivo effect of DSS induced colitis in two groups of mice vs. control.
- Figure 2 depicts the mice weight comparison before starting the DSS treatment.
- Figure 3 depicts the colonic length at the end of the experiment.
- Figure 4 depicts the results of DAI score during the five days of DSS administration.
- Figure 5 depicts the calibration curve for MPO activity.
- Figure 6 depicts the results of Hemoccult SENSA test (the arrow points at the stained blue area).
- Figure 7 depicts the results of histopathology examination.
- Figure 8 depicts the calibration curve of MPO activity.
- the inventors of the present invention have surprisingly uncovered that biomass from citric acid or gluconic acid production, which is known to confer preferred physical properties to various industrially manufactured products, such as processed foods, have an effect of preventing, ameliorating or treating a bowel disease, e.g., an inflammatory bowel disease.
- a bowel disease e.g., an inflammatory bowel disease.
- the present invention provides the direct use of whole bulk biomass of Aspergillus niger for preventing, ameliorating or treating a bowel disease.
- the present invention provides the direct use of said biomass, which is a whole bulk biomass of Aspergillus niger from fermentation processes of citric acid or gluconic acid production for preventing, ameliorating or treating a bowel disease.
- said whole bulk biomass is subjected to washing with water, e.g., to washing with hot water followed by drying to afford dried whole bulk biomass.
- the bowel disease is selected from gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), inflammatory bowl diseases, Crohn's disease, ulcerative colitis, intestinal Behcet disease, short bowel syndrome, ulcer, intestinal obstruction and irritable bowel syndrome (IBS).
- GER gastroesophageal reflux
- GERD gastroesophageal reflux disease
- IBS irritable bowel syndrome
- the use of said biomass is highly safe to the human body for preventing, ameliorating or treating a bowel disease and unlike a synthetic drug it is free of side effects.
- the use of said biomass is as it is, without any physical or chemical treatment except for washing and drying, hence obviating the need to carry out complicated physical and chemical manipulations in order to isolate active components from said biomass, such as, t- RNA.
- the present invention also provides a composition for preventing, ameliorating or treating a bowel disease, said composition comprises said biomass from citric acid or gluconic acid production and optionally at least one or more excipients.
- said composition can be a nutritional composition (e.g., infant formula), a nutraceutical composition (e.g., a dietary supplement), a medical food, or a pharmaceutical composition.
- said pharmaceutical composition can be a formulated dosage form.
- DSS Dextran Sodium Sulfate
- the DSS -induced colitis model has some advantages when compared to other animal models of colitis. For example, an acute, chronic, or relapsing model can be produced by changing the concentration of administration of DSS in rats and other strains of mice.
- DAI Disease Activity Index
- myeloperoxidase is a peroxidase enzyme expressed in neurophil granulocytes that are subtype of white blood cells and a sign of inflammation.
- the Hemoccult test that includes using the SENSA card is a test based on oxidation of guiaconic acid by hydrogen peroxide (the developer) to a blue colored quinone compound.
- the heme portion of haemoglobin if present in the fecal specimen, has peroxidase activity that catalyzes the oxidation of a-guaiaconic acid by hydrogen peroxide.
- TNF-a refers to an adipokine involved in systemic inflammation.
- TNF-a which is an endogenous pyrogen, is involved in the regulation of immune cells and it is able, inter alia, to induce inflammation. Dysregulation of TNF-a production has been connected to several human diseases including inflammatory bowel diseases.
- the Tukey-Kramer method is a single-step multiple comparison procedure, which is statistically used to find means that are significantly different from each other.
- the present invention provides pharmaceutical compositions in admixture with pharmaceutically acceptable excipients and optionally other therapeutic agents.
- a composition of the present invention when administered to a model mouse for an inflammatory bowel disease such as colitis, not only prevents, ameliorates or treats an inflammatory bowel disease, but also significantly lowers the activity of myeloperoxidase, which is an inflammation marker.
- a composition of the present invention is capable of preventing, ameliorating or treating an inflammatory bowel disease while administered to an individual, and the evaluation thereof can be carried out by determining the activity of myeloperoxidase, which is an inflammation marker, and/or the activity of TNF-a.
- adequate routes of administration of said composition for an individual who is in need for such treatment thereof, are oral, buccal, eternal and sublingual administration or administration via a feeding tube.
- the composition can be administered orally.
- the pharmaceutical compositions of the present invention that can be, e.g., formulated dosage forms, can be administered, for example, as tablets, pills, powders, granules, dragees, liquids, suspensions, emulsions, granules, capsules, suppositories, injection preparations (solutions and suspensions), patches and the like.
- compositions comprising the biomass of the present invention can be prepared by mixing said biomass of the present invention with at least one or more additional excipents selected from absorption accelerators, binders, bulking agents, carriers, coating agents, diluents, disintegrants, extenders, fillers, flavoring agents, lubricants, surface-active agents, wetting agents and the like.
- additional excipents selected from absorption accelerators, binders, bulking agents, carriers, coating agents, diluents, disintegrants, extenders, fillers, flavoring agents, lubricants, surface-active agents, wetting agents and the like.
- the present invention further provides methods of using the compositions of the present invention in the treatment of diseases or conditions including diseases or conditions for which said compositions provide therapeutic benefit to an individual having the disease or condition, such as, colitis or Crohn's disease, by administering to the individual in need thereof a therapeutically effective amount of at least one of said compositions.
- said dried biomass contains at least 5% of non-soluble nutritional fibers, preferably more than 50% of non-soluble nutritional fibers and more preferably more than 70% of non-soluble nutritional fibers.
- said biomass has low fat content and therefore it has low caloric value and in addition, it includes high content of non- digestible nutritional fibers.
- said dried biomass contains at least 1% of proteins, preferably more than 5% of proteins and more preferably more than 10% of proteins.
- the exact dose and regimen of administration of the composition is dependent upon the therapeutic effect to be achieved (e.g., treatment of a bowel disease) and it may vary with the particular formulation, the route of administration, and the age and condition of the individual to whom the composition is to be administered.
- the content of said biomass is, when it is used alone in a composition for preventing, ameliorating or treating a bowel disease, e.g., an inflammatory bowel disease, is from 0.1 to 100% by weight of the composition or from 1 to 50% by weight of the composition or from 10 to 15% by weight of the composition.
- a bowel disease e.g., an inflammatory bowel disease
- dietary supplements comprising the biomass of the present invention can be prepared by mixing said biomass of the present invention with food ingredients such as sugars and starches, dietary fibers, lipids, amino acids, proteins such as protein isolates or protein hydtrolyzates, lactic acid, vitamins, minerals and other ingredients that are commonly used in food preparations.
- food ingredients such as sugars and starches, dietary fibers, lipids, amino acids, proteins such as protein isolates or protein hydtrolyzates, lactic acid, vitamins, minerals and other ingredients that are commonly used in food preparations.
- the dietary supplement of the present invention may include bakery product, beverage, bar, candy, dairy product, infant formula, snack, soup, spread and the like.
- the dose of administration of the composition for obtaining the desired effects of preventing, ameliorating or treating a bowel disease is from 1 to 75 g/day, or from 5 to 20 g/day.
- a bowel disease e.g., an inflammatory bowel disease
- said dose of the present invention is not limited to the above range. The dose may be properly set specifically for each individual who is in need for such composition thereof.
- the present invention further provides the use of a composition comprising the whole bulk biomass from citric acid or gluconic acid production for the preparation of a nutritional, pharmaceutical or nutraceutical composition or a medical food, for preventing, ameliorating or treating a bowel disease, e.g., an inflammatory bowel disease.
- a bowel disease e.g., an inflammatory bowel disease.
- the use of said composition comprising the whole biomass from citric acid or gluconic acid production comprises dried whole bulk biomass.
- the biomass of the present invention has prevented or retarded the symptoms of DSS-induced colitis in mice.
- the two use doses administered to the mice have suppressed the myeloperoxidase activity in direct relation to the shortening of the large intestine.
- bloody stool was avoided in all the mice treated with the biomass of the present invention. Histological damage was diminished in both use doses of 10% and 15% of the dried biomass that have been used.
- This example demonstrates the preparation of mice with induced colitis.
- the experiment included 50 eight-week-old female C57BL/6 mice that were divided into 5 groups of 10 mice each: 20 mice received standard diet without addition of dried biomass of the present invention.
- mice received standard diet containing 10% of died biomass of the present invention.
- mice received standard diet containing 15% of dried biomass of the present invention.
- mice were exposed to 5 days treatment of 3% Dextran Sodium Sulfate (DSS) for induction of colitis. The experiment lasted for 25 days out of which in the last five days (day 21-day 25) DSS was added.
- the control diet included macronutrients such as proteins, fats and carbohydrates, minerals, trace elements and vitamins.
- the environmental conditions of the mice facility were set to 22°C and 12 hours of light-to-darkness cycles.
- Table 1 demonstrates the mice treatment including control:
- This example demonstrates the induction of colitis using DSS.
- Colitis was induced in mice by adding 3% DSS to the drinking water during the last 5 days of the 25 days of the feeding period.
- the mice were fed, before and after the addition of DSS to the drinking water, with a food supplement containing 10% and 15% of dried biomass from citric acid production.
- a food supplement containing 10% and 15% of dried biomass from citric acid production.
- the inflammation degree was evaluated by measuring increased histopathology, deceased stool consistency, colon length and determining the myeloperoxidase activity (MPO).
- This example demonstrates the tissue preparation for histology.
- mice After five days of colitis induction by addition of DSS (day 25 of the experiment), the mice were weighed and sacrificed. The entire colon was resected from the colo-cecal junction to the anus and rinsed with sterile saline (0.9%) to remove faecal matter. The colon was weighed and its length was measured. The colon was divided into two parts; the first was used for the MPO determination and the second was saved in 1 mL of buffered formaldehyde for histological tests. The mucosal inflammation in the colon was evaluated in haematoxylin and eosin (H&E) stained sections.
- H&E haematoxylin and eosin
- MPO myeloperoxidase activity
- distal colonic tissue 100 mg was taken and rinsed with ice-cold saline, bottled dry, weighed and homogenized in 0.6 g hexadecyltrimethylammonium bromide in 120 mL phosphate buffer (pH 6.5) on ice using a Polytron homogenizer for 30 seconds. The homogenate was frozen and thawed three times 15 minutes each and then centrifuged for 45 minutes at 4°C. The resulting supernatant was frozen at -70°C until the enzyme activity was determined.
- Spectrophotometric myeloperoxidase activity was assayed as follows: 0.1 mL of the sample was mixed with 2.9 mL of 56 mM phosphate buffer (pH 6.5) containing 0.167 mg/mL o-dianisidine dihydrochloride and 0.0005% (v/v) hydrogen peroxide. The difference in absorbance at 460 nm was measured with UV- based spectrophotometer. The standard curve included myeloperoxidase enzyme diluted in o-dianisidine dihydrochloride and hydrogen peroxide and the absorbance was measured at 460 nm. The calibration curve (see Figure 8) was calculated by measuring the absorbance in triplicate at two different times.
- This example demonstrates the disease activity index (DAI) clinical scoring of colitis.
- the clinical scoring of a DAI for DSS-induced colitis was based on weight loss, stool consistency and bleeding.
- the DAI was scored 1-3 for each parameter and then averaged for each mouse and each group.
- the following Table 2 demonstrates the DAI score parameters.
- This example demonstrates the Hemoccult test (evaluation of blood in faeces).
- Hemoccult test (fecal occult blood test) has been carried out in duplicate by collecting fresh fecal samples in the morning of days 22, 23, 24 and 25 of the test for all the DSS administered groups. Small fecal specimen was smeared onto windows of the Hemoccult SENSA slides (Beckman Coulter Inc., USA), which contained guaiac paper using an applicator stick and then the cover flap was closed. After 5 minutes, the slide was opened and two drops of the developer were applied to the guaiac paper directly over each smear. The results were observed within 60 seconds after applying the developer.
Abstract
The present invention provides compositions comprising whole bulk biomass form citric acid or gluconic acid production for preventing, ameliorating or treating bowel diseases. Also provided by the present invention are food supplements or medicaments that comprise said compositions and use thereof for preventing, ameliorating or treating bowel diseases.
Description
USE OF BIOMASS FROM CITRIC ACID OR GLUCONIC ACID PRODUCTION FOR PREVENTING, AMELIORATING OR TREATING BOWEL DISEASES
BACKGROUND OF THE INVENTION
The number of individuals having bowel diseases such as an inflammatory bowel disease or an irritable bowel syndrome has drastically increased in the last decades as a result of changes in nutritional habits and living environment.
Gastrointestinal diseases refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestions, the liver, gallbladder and pancreas.
An inflammatory bowel disease refers to a disease in which a mucosa of the intestine is led to cause inflammation by some causes that may lead to ulcerative colitis, Crohn's disease or intestinal Behcet disease.
The inflammation is usually considered to begin in the rectum near the anus, and thereafter it spreads toward the colon behind the rectum.
Due to the inflammation, which takes place in the intestine, symptoms such as diarrhea, mucous bloody stool, fever and weight loss may be produced. As the conditions of the disease (amelioration and deterioration) are repeated, the patient may learn to live with the disease for a long time in some cases.
Colitis and Crohn's disease are inflammatory disorders of the gastrointestinal track caused by genetic, environmental and nutritional causes. In an article by Michael D. Kappelman et al. entitled "The Prevalence and Geographic Distribution of Crohn's Disease and Ulcerative Colitis in the United States", published in Clinical Gastroenterology and Hepatology, Vol 5, Issue 12, December 2007, pages 1424-1429, it is mentioned that the current prevalence of colitis and Crohn's disease in children younger than 20 years is 43 and 28 per 100,000, respectively. In adults, the prevalence of colitis and Crohn's disease is 201 and 238, respectively. The prevalence of both
conditions is lower in the South, compared with the Northeast, Midwest, and West of the United States.
Colitis is a disease characterized by inflammation of the colon, which is usually described as an inflammation of the large intestine (colon, caecum and rectum). Colitis broadly fits into the category of digestive diseases because it may be acute and self-limited or chronic, i.e. persistent.
Although several medical research groups have carried out intensive studies on inflammatory bowel diseases, the causes of why said diseases arise are yet to be clearly elucidated because the mechanism for the onset of inflammatory bowel diseases, i.e., how abnormality in immune function is caused, is not explicitly elucidated.
Colitis and Crohn's disease have high frequency of incidence. Nevertheless, these diseases are difficult to be clinically treated and therefore fundamental therapies directed to these diseases have not yet been established. Therapies such as nutritional therapy that include, e.g., total parenteral nutrition therapy, enteral nutrition therapy and alimentotherapy have been used along with pharmacotherapy. For example, drugs such as sulfasalazine (a sulfa drug), mesalazine (an anti-inflammatory drug), prednisolone (a steroid drug) and azathioprine (immunosuppressant) have been used stepwise for treating Colitis and Crohn's disease depending on the stage of the disease.
Without wishing to be bound by any particular theory, it is assumed that abnormality in the immunity system such as an autoimmune mechanism may be the cause of said diseases. The immune system of the human body functions by enabling a mechanism of releasing antigens aimed to bind to the epitopes of invading pathogens. This immune function also acts in the intestine. When this immune function becomes abnormal, said mechanism may regard its own mucosa as the foreign pathogen, consequently attack the mucosa, and thereby cause a continuous inflammation.
According to health statistics in some western countries, about 20 to 30% of the individuals who seek medical attention due to abnormality in bowel movement suffer from irritable bowel syndrome (IBS).
The majority of other inflammatory bowel diseases are basically curable with internal treatment and nutritional therapy such as fasting, dietary restriction, elemental diet, high-calorie parenteral nutrition and pharmacotherapy that may include administration of an antibacterial drug, or the like depending on the symptoms.
Among various diseases of the digestive system, irritable bowel syndrome (IBS) is one of the diseases that most frequently occur, which is characterized by abnormality in bowel movement. The main symptoms of IBS include vomiting, diarrhea, abdominal pain and abdominal discomfort.
Stress is regarded as one of the causes of IBS, because organs and nerves are associated to each other. Autonomic nerves govern the actions of organs, and the autonomic nerves act according to signals from the hypothalamus of the brain. When information serving as stress enter into the brain from the external, the hypothalamus reacts to the information, thereby making it difficult to deliver a proper signal to the autonomic nerves, which in turn cause disturbance of the action of the organs.
Since there is no therapy at the present time that can completely cure said inflammatory bowel diseases in some cases, prevention or treatment of an inflammatory bowel disease is a difficult task to achieve.
If a therapy is carried on for a long period of time, an individual may be subject to lack of nutritional balance, thereby making the symptoms more serious in some cases. In addition, pharmacotherapy has some disadvantages such as side effects along with the desired therapeutic effect. When the inflammatory bowel disease is serious, a surgical operation may be necessitated in some cases.
The human nutritional requirements vary with age, metabolic states and diseases affecting the gastrointestinal and other systems of the human body. Adequate human
nutrition is essential to avoid complications associated with nutritional deficiencies. However, the western nutrition of many individuals suffer from poor eating habits and excessive consumption of processed foods rich with sugars (such as high fructose corn syrup), saturated fats and low fiber consumption. Such prolonged unhealthy diet may lead to the development of bowel diseases.
Since at least several treatments used for said bowel diseases are not effective, there is a constant need for novel effective methods for the prevention, amelioration and treatment of bowel diseases such as colitis.
SUMMARY OF THE INVENTION
The present invention provides a composition for preventing, ameliorating or treating a bowel disease, said composition comprises biomass from, e.g., citric acid or gluconic acid production and optionally at least one additive.
The present invention also provides the direct use of whole bulk biomass of Aspergillus niger for preventing, ameliorating or treating a bowel disease. Particularly, the present invention provides the direct use of said biomass, which is a whole bulk biomass of Aspergillus niger from fermentation processes of citric acid or gluconic acid production for preventing, ameliorating or treating a bowel disease.
According to a special aspect of the present invention, said whole bulk biomass is subjected to washing with water, e.g., to washing with hot water followed by drying to afford dried whole bulk biomass.
In some embodiments of the present invention, said composition can be a nutritional composition (e.g., infant formula), a nutraceutical composition (e.g., a dietary supplement), a medical food, or a pharmaceutical composition.
In an embodiment of the present invention, said pharmaceutical composition can be a formulated dosage form.
The present invention provides pharmaceutical compositions in admixture with pharmaceutically acceptable excipients, and optionally other therapeutic agents.
In some embodiments of the present invention, adequate routes of administration of said composition, for an individual who is in need for such treatment thereof, are oral, buccal, eternal and sublingual administration or administration via a feeding tube. In a specific embodiment, the composition can be administered orally.
According to some embodiments, the pharmaceutical compositions of the present invention that can be, e.g., formulated dosage forms, can be administered, for example, as tablets, pills, powders, granules, dragees, liquids, suspensions, emulsions, granules, capsules, suppositories, injection preparations (solutions and suspensions), patches and the like.
In some embodiments, pharmaceutical compositions comprising the biomass of the present invention can be prepared by mixing said biomass of the present invention with at least one additional active ingredient selected from absorption accelerators, binders, bulking agents, carriers, coating agents, diluents, disintegrants, extenders, fillers, flavoring agents, lubricants, surface-active agents, wetting agents and the like.
According to some embodiments of the present invention, dietary supplements comprising the biomass of the present invention can be prepared by mixing said biomass of the present invention with food ingredients such as sugars and starches, dietary fibers, lipids, amino acids, proteins such as protein isolates or protein hydtrolyzates, lactic acid, vitamins, minerals and other ingredients that are commonly used in food preparations.
According to some embodiments of the present invention, the dietary supplement of the present invention may include bakery product, beverage, bar, candy, dairy product, infant formula, snack, soup, spread and the like.
BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 depicts the experimental in vivo effect of DSS induced colitis in two groups of mice vs. control.
Figure 2 depicts the mice weight comparison before starting the DSS treatment.
Figure 3 depicts the colonic length at the end of the experiment.
Figure 4 depicts the results of DAI score during the five days of DSS administration. Figure 5 depicts the calibration curve for MPO activity.
Figure 6 depicts the results of Hemoccult SENSA test (the arrow points at the stained blue area).
Figure 7 depicts the results of histopathology examination.
Figure 8 depicts the calibration curve of MPO activity.
DETAILED DESCRIPTION OF THE INVENTION
The inventors of the present invention have surprisingly uncovered that biomass from citric acid or gluconic acid production, which is known to confer preferred physical properties to various industrially manufactured products, such as processed foods, have an effect of preventing, ameliorating or treating a bowel disease, e.g., an inflammatory bowel disease.
The present invention provides the direct use of whole bulk biomass of Aspergillus niger for preventing, ameliorating or treating a bowel disease. Particularly, the present invention provides the direct use of said biomass, which is a whole bulk biomass of Aspergillus niger from fermentation processes of citric acid or gluconic acid production for preventing, ameliorating or treating a bowel disease.
According to a special aspect of the present invention, said whole bulk biomass is subjected to washing with water, e.g., to washing with hot water followed by drying to afford dried whole bulk biomass.
According to the present invention, the bowel disease is selected from gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), inflammatory bowl diseases, Crohn's disease, ulcerative colitis, intestinal Behcet
disease, short bowel syndrome, ulcer, intestinal obstruction and irritable bowel syndrome (IBS).
According to a preferred embodiment of the present invention, the use of said biomass is highly safe to the human body for preventing, ameliorating or treating a bowel disease and unlike a synthetic drug it is free of side effects.
According to another preferred embodiment of the present invention, the use of said biomass is as it is, without any physical or chemical treatment except for washing and drying, hence obviating the need to carry out complicated physical and chemical manipulations in order to isolate active components from said biomass, such as, t- RNA.
The present invention also provides a composition for preventing, ameliorating or treating a bowel disease, said composition comprises said biomass from citric acid or gluconic acid production and optionally at least one or more excipients.
In some embodiments of the present invention, said composition can be a nutritional composition (e.g., infant formula), a nutraceutical composition (e.g., a dietary supplement), a medical food, or a pharmaceutical composition.
In an embodiment of the present invention, said pharmaceutical composition can be a formulated dosage form.
As used herein, the term Dextran Sodium Sulfate (DSS) refers to an animal induced colitis model of mucosal inflammation that is used in the study of pathogenesis and preclinical studies of bowl diseases such as colitis. The DSS -induced colitis model has some advantages when compared to other animal models of colitis. For example, an acute, chronic, or relapsing model can be produced by changing the concentration of administration of DSS in rats and other strains of mice.
As used herein, the term Disease Activity Index (DAI) is a research tool used to quantify the symptoms of individuals or test animals with diseases such as colitis or
Crohn's disease that is directed, inter alia, to define response or remission of the disease as a reaction to the treatment used.
As used herein, myeloperoxidase (MPO) is a peroxidase enzyme expressed in neurophil granulocytes that are subtype of white blood cells and a sign of inflammation.
As used herein, the Hemoccult test that includes using the SENSA card is a test based on oxidation of guiaconic acid by hydrogen peroxide (the developer) to a blue colored quinone compound. The heme portion of haemoglobin, if present in the fecal specimen, has peroxidase activity that catalyzes the oxidation of a-guaiaconic acid by hydrogen peroxide.
As used herein, the term TNF-a refers to an adipokine involved in systemic inflammation. TNF-a, which is an endogenous pyrogen, is involved in the regulation of immune cells and it is able, inter alia, to induce inflammation. Dysregulation of TNF-a production has been connected to several human diseases including inflammatory bowel diseases.
As used herein, the Tukey-Kramer method is a single-step multiple comparison procedure, which is statistically used to find means that are significantly different from each other.
The present invention provides pharmaceutical compositions in admixture with pharmaceutically acceptable excipients and optionally other therapeutic agents.
A composition of the present invention, when administered to a model mouse for an inflammatory bowel disease such as colitis, not only prevents, ameliorates or treats an inflammatory bowel disease, but also significantly lowers the activity of myeloperoxidase, which is an inflammation marker.
A composition of the present invention is capable of preventing, ameliorating or treating an inflammatory bowel disease while administered to an individual, and the
evaluation thereof can be carried out by determining the activity of myeloperoxidase, which is an inflammation marker, and/or the activity of TNF-a.
In some embodiments of the present invention, adequate routes of administration of said composition, for an individual who is in need for such treatment thereof, are oral, buccal, eternal and sublingual administration or administration via a feeding tube. In a specific embodiment, the composition can be administered orally.
According to some embodiments, the pharmaceutical compositions of the present invention that can be, e.g., formulated dosage forms, can be administered, for example, as tablets, pills, powders, granules, dragees, liquids, suspensions, emulsions, granules, capsules, suppositories, injection preparations (solutions and suspensions), patches and the like.
In some embodiments, pharmaceutical compositions comprising the biomass of the present invention can be prepared by mixing said biomass of the present invention with at least one or more additional excipents selected from absorption accelerators, binders, bulking agents, carriers, coating agents, diluents, disintegrants, extenders, fillers, flavoring agents, lubricants, surface-active agents, wetting agents and the like.
The present invention further provides methods of using the compositions of the present invention in the treatment of diseases or conditions including diseases or conditions for which said compositions provide therapeutic benefit to an individual having the disease or condition, such as, colitis or Crohn's disease, by administering to the individual in need thereof a therapeutically effective amount of at least one of said compositions.
According to an aspect of the present invention, said dried biomass contains at least 5% of non-soluble nutritional fibers, preferably more than 50% of non-soluble nutritional fibers and more preferably more than 70% of non-soluble nutritional fibers.
According to another aspect of the present invention, said biomass has low fat content and therefore it has low caloric value and in addition, it includes high content of non- digestible nutritional fibers.
According to another aspect of the present invention, said dried biomass contains at least 1% of proteins, preferably more than 5% of proteins and more preferably more than 10% of proteins.
According to an embodiment of the present invention, the exact dose and regimen of administration of the composition is dependent upon the therapeutic effect to be achieved (e.g., treatment of a bowel disease) and it may vary with the particular formulation, the route of administration, and the age and condition of the individual to whom the composition is to be administered.
According to some embodiments of the present invention, the content of said biomass is, when it is used alone in a composition for preventing, ameliorating or treating a bowel disease, e.g., an inflammatory bowel disease, is from 0.1 to 100% by weight of the composition or from 1 to 50% by weight of the composition or from 10 to 15% by weight of the composition.
According to some embodiments of the present invention, dietary supplements comprising the biomass of the present invention can be prepared by mixing said biomass of the present invention with food ingredients such as sugars and starches, dietary fibers, lipids, amino acids, proteins such as protein isolates or protein hydtrolyzates, lactic acid, vitamins, minerals and other ingredients that are commonly used in food preparations.
According to some embodiments of the present invention, the dietary supplement of the present invention may include bakery product, beverage, bar, candy, dairy product, infant formula, snack, soup, spread and the like.
According to some embodiments of the present invention, the dose of administration of the composition for obtaining the desired effects of preventing, ameliorating or
treating a bowel disease, e.g., an inflammatory bowel disease, is from 1 to 75 g/day, or from 5 to 20 g/day. However, said dose of the present invention is not limited to the above range. The dose may be properly set specifically for each individual who is in need for such composition thereof.
The present invention further provides the use of a composition comprising the whole bulk biomass from citric acid or gluconic acid production for the preparation of a nutritional, pharmaceutical or nutraceutical composition or a medical food, for preventing, ameliorating or treating a bowel disease, e.g., an inflammatory bowel disease.
According to the present invention, the use of said composition comprising the whole biomass from citric acid or gluconic acid production comprises dried whole bulk biomass.
As demonstrated by the following examples, the biomass of the present invention has prevented or retarded the symptoms of DSS-induced colitis in mice. The two use doses administered to the mice have suppressed the myeloperoxidase activity in direct relation to the shortening of the large intestine. In addition, bloody stool was avoided in all the mice treated with the biomass of the present invention. Histological damage was diminished in both use doses of 10% and 15% of the dried biomass that have been used.
The present invention is further described by the following examples that should not be construed in any way as limiting its scope.
EXAMPLES EXAMPLE 1
This example demonstrates the preparation of mice with induced colitis.
The experiment included 50 eight-week-old female C57BL/6 mice that were divided into 5 groups of 10 mice each:
20 mice received standard diet without addition of dried biomass of the present invention.
10 mice received standard diet containing 10% of died biomass of the present invention.
20 mice received standard diet containing 15% of dried biomass of the present invention.
The mice were exposed to 5 days treatment of 3% Dextran Sodium Sulfate (DSS) for induction of colitis. The experiment lasted for 25 days out of which in the last five days (day 21-day 25) DSS was added. The control diet included macronutrients such as proteins, fats and carbohydrates, minerals, trace elements and vitamins. Control mice (n= 10) were fed also with 15% dried biomass of the present invention in order to determine the effect of the highest concentration of said biomass on the intestinal tissue. The mice had access to their feed 24 hours a day. The environmental conditions of the mice facility were set to 22°C and 12 hours of light-to-darkness cycles. The following Table 1 demonstrates the mice treatment including control:
Table 1
As depicted in Figure 2, according to the Tukey-Kramer model, there is no statistical difference in the average weight of the mice in each test group at to, before starting the DSS treatment.
EXAMPLE 2
This example demonstrates the induction of colitis using DSS.
Colitis was induced in mice by adding 3% DSS to the drinking water during the last 5 days of the 25 days of the feeding period. The mice were fed, before and after the
addition of DSS to the drinking water, with a food supplement containing 10% and 15% of dried biomass from citric acid production. After completion of the experiment, the histological and biochemical damage to the large intestine was evaluated. The inflammation degree was evaluated by measuring increased histopathology, deceased stool consistency, colon length and determining the myeloperoxidase activity (MPO).
EXAMPLE 3
This example demonstrates the tissue preparation for histology.
After five days of colitis induction by addition of DSS (day 25 of the experiment), the mice were weighed and sacrificed. The entire colon was resected from the colo-cecal junction to the anus and rinsed with sterile saline (0.9%) to remove faecal matter. The colon was weighed and its length was measured. The colon was divided into two parts; the first was used for the MPO determination and the second was saved in 1 mL of buffered formaldehyde for histological tests. The mucosal inflammation in the colon was evaluated in haematoxylin and eosin (H&E) stained sections.
EXAMPLE 4
This example demonstrates the determination of myeloperoxidase activity (MPO).
100 mg of distal colonic tissue was taken and rinsed with ice-cold saline, bottled dry, weighed and homogenized in 0.6 g hexadecyltrimethylammonium bromide in 120 mL phosphate buffer (pH 6.5) on ice using a Polytron homogenizer for 30 seconds. The homogenate was frozen and thawed three times 15 minutes each and then centrifuged for 45 minutes at 4°C. The resulting supernatant was frozen at -70°C until the enzyme activity was determined. Spectrophotometric myeloperoxidase activity was assayed as follows: 0.1 mL of the sample was mixed with 2.9 mL of 56 mM phosphate buffer (pH 6.5) containing 0.167 mg/mL o-dianisidine dihydrochloride and 0.0005% (v/v) hydrogen peroxide. The difference in absorbance at 460 nm was measured with UV- based spectrophotometer. The standard curve included myeloperoxidase enzyme diluted in o-dianisidine dihydrochloride and hydrogen peroxide and the absorbance
was measured at 460 nm. The calibration curve (see Figure 8) was calculated by measuring the absorbance in triplicate at two different times.
EXAMPLE 5
This example demonstrates the disease activity index (DAI) clinical scoring of colitis.
The clinical scoring of a DAI for DSS-induced colitis was based on weight loss, stool consistency and bleeding. The DAI was scored 1-3 for each parameter and then averaged for each mouse and each group. Weight loss scores were determined 0 = no weight loss, 1 = 1-5%, 2 = 5-10%, 3 = 10-20%. Faeces scores were determined as 0 = normal, 1 = normal/soft, 2 = soft, 3 = very soft. Blood in stool scores were determined as 0 = no bleeding, 1= Hemoccult +/-, 2 = Hemoccult +, 3 = Hemoccult ++. The following Table 2 demonstrates the DAI score parameters.
Table 2
It can be seen in Fig. 4 that in all the 5 days of the experiment, the DAI score is significantly high (according to the Tukey Kramer model) for the group to which no biomass was added to the diet (Line A) in comparison to the groups that the biomass was added to the diet. Line B: DSS treatment followed by addition of 10% biomass to the diet. Line C: DSS treatment followed by addition of 20% biomass to the diet.
EXAMPLE 6
This example demonstrates the Hemoccult test (evaluation of blood in faeces).
Hemoccult test (fecal occult blood test) has been carried out in duplicate by collecting fresh fecal samples in the morning of days 22, 23, 24 and 25 of the test for all the DSS
administered groups. Small fecal specimen was smeared onto windows of the Hemoccult SENSA slides (Beckman Coulter Inc., USA), which contained guaiac paper using an applicator stick and then the cover flap was closed. After 5 minutes, the slide was opened and two drops of the developer were applied to the guaiac paper directly over each smear. The results were observed within 60 seconds after applying the developer.
All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.
The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms "comprising," "having," "including," and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to,") unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.
Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such
variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above- described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein.
Claims
1. A method of preventing, ameliorating or treating a bowel disease by administering to an individual suffering from said inflammatory bowel disease, a sufficient amount of composition comprising whole bulk biomass of Aspergillus niger.
2. A method of preventing, ameliorating or treating a bowel disease by administering to an individual suffering from said inflammatory bowel disease, a sufficient amount of composition comprising whole bulk biomass of Aspergillus niger from fermentation processes of citric acid or gluconic acid production.
3. The method of claim 2, wherein the bowel disease is selected from gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), inflammatory bowel disease, Crohn's disease, ulcerative colitis, intestinal Behcet disease, short bowel syndrome, ulcer, intestinal obstruction and irritable bowel syndrome (IBS).
4. The method of claim 2, wherein said composition comprises biomass from citric acid or gluconic acid production and optionally at least one or more excipients.
5. The method of claim 4, wherein said whole bulk biomass is subjected to washing with water followed by drying to afford dried whole bulk biomass.
6. The method of claim 2, wherein said composition is a nutritional composition, a nutraceutical composition, a medical food, or a pharmaceutical composition.
7. The method of claim 6, wherein said pharmaceutical composition is a formulated dosage form.
8. The method of claim 6, wherein said pharmaceutical composition is in admixture with pharmaceutically acceptable excipients, and optionally other therapeutic agents.
9. The method of claim 2, wherein adequate routes of administration of said composition, for an individual who is in need for such treatment thereof, are: oral, buccal, eternal and sublingual administration or administration via a feeding tube.
10. The method of claim 9, wherein the composition is administered orally.
11. The method of claim 6, wherein said pharmaceutical composition is administered as tablets, pills, powders, granules, dragees, liquids, suspensions, emulsions, granules, capsules, suppositories, injection preparations, which are solutions and suspensions and patches.
12. The method of claim 6, wherein said pharmaceutical composition comprising said biomass is prepared by mixing said biomass with at least one or more additional excipients selected from absorption accelerators, binders, bulking agents, carriers, coating agents, diluents, disintegrants, extenders, fillers, flavoring agents, lubricants, surface-active agents and wetting agents.
13. The method of claim 6, wherein the content of said biomass in said pharmaceutical composition is from 0.1 to 100% by weight of the composition or from 1 to 50% by weight of the composition or from 10 to 15% by weight of the composition for preventing, ameliorating or treating a bowel disease.
14. The method of claim 6, wherein the dietary supplement comprising said biomass is prepared by mixing said biomass with at least one or more food ingredients selected from sugars and starches, dietary fibers, lipids, amino acids, proteins such as protein isolates or protein hydrolyzates, lactic acid, vitamins and minerals.
15. The method of claim 6, wherein said dietary supplement is selected form bakery product, beverage, bar, candy, dairy product, infant formula, snack, soup and spread.
16. Use of a composition comprising whole bulk biomass from citric acid or gluconic acid production for the preparation of a nutritional, pharmaceutical or nutraceutical
composition or a medical food, for preventing, ameliorating or treating a bowel disease.
17. The use of claim 16, wherein said bulk whole biomass is dried whole bulk biomass.
18. A composition comprising whole bulk biomass from citric acid or gluconic acid production for preventing, ameliorating or treating a bowel disease.
19. The use of claim 18, wherein said whole bulk biomass is dried whole bulk biomass.
20. The composition of claim 18, which comprises a nutritional, pharmaceutical or nutraceutical composition or a medical food.
21. The composition of claim 18, which comprises said biomass from citric acid or gluconic acid production and optionally at least one or more excipients.
22. The composition of claim 21, wherein said at least one or more excipients are selected from absorption accelerators, binders, bulking agents, carriers, coating agents, diluents, disintegrants, extenders, fillers, flavoring agents, lubricants, surface- active agents and wetting agents.
23. The composition of claim 18, which comprises said biomass from citric acid or gluconic acid production and at least one additional active ingredient or additional therapeutic agent.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462033657P | 2014-08-06 | 2014-08-06 | |
IL62/033,657 | 2014-08-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2016020911A1 true WO2016020911A1 (en) | 2016-02-11 |
Family
ID=53783795
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IL2015/050629 WO2016020911A1 (en) | 2014-08-06 | 2015-06-22 | Use of biomass from citric acid or gluconic acid production for preventing, ameliorating or treating bowel diseases |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2016020911A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110731955A (en) * | 2019-10-28 | 2020-01-31 | 中山大学肿瘤防治中心(中山大学附属肿瘤医院、中山大学肿瘤研究所) | Application of dimethyl itaconate in preventing and treating ulcerative colitis and canceration thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4317488A1 (en) * | 1992-06-01 | 1994-02-10 | Forschungszentrum Juelich Gmbh | Fermentative prodn. of gluconic acid from aq. sugar contg. liq. - using new strains of Aureobasidium pullulans, used as preservative and cement additive |
EP1935253A1 (en) * | 2005-09-20 | 2008-06-25 | Idemitsu Kosan Co., Ltd. | Additive for animal feed |
WO2014188005A1 (en) * | 2013-05-24 | 2014-11-27 | Neste Oil Corporation | Microorganism biomass for prevention and reduction of the adverse effects of pathogens in digestive tract |
-
2015
- 2015-06-22 WO PCT/IL2015/050629 patent/WO2016020911A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4317488A1 (en) * | 1992-06-01 | 1994-02-10 | Forschungszentrum Juelich Gmbh | Fermentative prodn. of gluconic acid from aq. sugar contg. liq. - using new strains of Aureobasidium pullulans, used as preservative and cement additive |
EP1935253A1 (en) * | 2005-09-20 | 2008-06-25 | Idemitsu Kosan Co., Ltd. | Additive for animal feed |
WO2014188005A1 (en) * | 2013-05-24 | 2014-11-27 | Neste Oil Corporation | Microorganism biomass for prevention and reduction of the adverse effects of pathogens in digestive tract |
Non-Patent Citations (2)
Title |
---|
AHMED A TAYEL ET AL: "Antimicrobial textile treated with chitosan frommycelial waste", INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, ELSEVIER BV, NL, vol. 49, no. 2, 30 April 2011 (2011-04-30), pages 241 - 245, XP028227812, ISSN: 0141-8130, [retrieved on 20110507], DOI: 10.1016/J.IJBIOMAC.2011.04.023 * |
MICHAEL D. KAPPELMAN ET AL.: "The Prevalence and Geographic Distribution of Crohn's Disease and Ulcerative Colitis in the United States", CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, vol. 5, no. 12, December 2007 (2007-12-01), pages 1424 - 1429 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110731955A (en) * | 2019-10-28 | 2020-01-31 | 中山大学肿瘤防治中心(中山大学附属肿瘤医院、中山大学肿瘤研究所) | Application of dimethyl itaconate in preventing and treating ulcerative colitis and canceration thereof |
CN110731955B (en) * | 2019-10-28 | 2023-05-02 | 中山大学 | Application of dimethyl itaconate in preventing and treating ulcerative colitis and canceration thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Wędrychowicz et al. | Advances in nutritional therapy in inflammatory bowel diseases | |
Rathe et al. | Clinical applications of bovine colostrum therapy: a systematic review | |
Mc Clain et al. | Zinc deficiency: a complication of Crohn's disease | |
EP1332759B1 (en) | Pharmaceutical and nutritional compositions containing a di- or oligosaccharide as insulin secretion promoter | |
JP4793533B2 (en) | Stimulation of the immune system with polydextrose | |
EP3484311B1 (en) | Compositions for use in methods for managing digestive disorders | |
JP2022179617A (en) | Use of short chain fatty acids for the treatment and prevention of diseases and disorders | |
Zhang et al. | Pyrroloquinoline quinone inhibits the production of inflammatory cytokines via the SIRT1/NF-κB signal pathway in weaned piglet jejunum | |
WO2011077800A1 (en) | Hyperlipemia-ameliorating agent, anemia-ameliorating composition, uric-acid-level-reducing composition, and foods and beverages | |
CN103874427A (en) | Probiotic for administration to healthy young mammals during the weaning period for improving tolerance to newly introduced food stuffs | |
Siigur et al. | Faecal short‐chain fatty acids in breast‐fed and bottle‐fed infants | |
Le Bourgot et al. | Short-chain fructooligosaccharide supplementation during gestation and lactation or after weaning differentially impacts pig growth and IgA response to influenza vaccination | |
Barbieri et al. | Nasally administered Lactobacillus rhamnosus accelerate the recovery of humoral immunity in B lymphocyte-deficient malnourished mice | |
ES2856053T3 (en) | Synthetic composition and procedure to promote mucosal healing | |
AU2024200698A1 (en) | Methods and compositions for increasing energy expenditure using cinnamaldehyde | |
JP6669665B2 (en) | Methods and compositions for using cinnamaldehyde and zinc for weight management | |
WO2016020911A1 (en) | Use of biomass from citric acid or gluconic acid production for preventing, ameliorating or treating bowel diseases | |
US20210128567A1 (en) | Compositions and Methods for Cognitive, Immune and Digestive Support in Patients with Autism Spectrum Disorder | |
CA3036494C (en) | Beta-caseins and gut microbiota | |
Pérez-Conesa et al. | Effect of probiotic, prebiotic and synbiotic follow-up infant formulas on iron bioavailability in rats | |
Corsello et al. | Nutraceuticals and biotics in pediatric gastrointestinal disorders | |
JP7184805B2 (en) | Betaine for prevention of obesity | |
JP6993340B2 (en) | Composition for preventing or reducing transepidermal water loss | |
JP6513103B2 (en) | Composition comprising cinnamaldehyde and zinc to improve swallowing | |
CN117441900B (en) | Functional nutritional composition and use thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 15747567 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 15747567 Country of ref document: EP Kind code of ref document: A1 |