KR20140017818A - Compositions for preventing or treating for diseases derived from helicobacter pylori comprising extract of black rice and health food thereof - Google Patents
Compositions for preventing or treating for diseases derived from helicobacter pylori comprising extract of black rice and health food thereof Download PDFInfo
- Publication number
- KR20140017818A KR20140017818A KR1020120084430A KR20120084430A KR20140017818A KR 20140017818 A KR20140017818 A KR 20140017818A KR 1020120084430 A KR1020120084430 A KR 1020120084430A KR 20120084430 A KR20120084430 A KR 20120084430A KR 20140017818 A KR20140017818 A KR 20140017818A
- Authority
- KR
- South Korea
- Prior art keywords
- black rice
- extract
- pylori
- helicobacter pylori
- pharmaceutical composition
- Prior art date
Links
- 241000371652 Curvularia clavata Species 0.000 title claims abstract description 156
- 239000000284 extract Substances 0.000 title claims abstract description 121
- 241000590002 Helicobacter pylori Species 0.000 title claims abstract description 41
- 229940037467 helicobacter pylori Drugs 0.000 title claims abstract description 40
- 239000000203 mixture Substances 0.000 title claims description 26
- 235000013402 health food Nutrition 0.000 title claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 8
- 201000010099 disease Diseases 0.000 title description 5
- 239000002904 solvent Substances 0.000 claims abstract description 34
- 239000004480 active ingredient Substances 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
- 108700012359 toxins Proteins 0.000 claims abstract description 23
- RKWHWFONKJEUEF-GQUPQBGVSA-O Cyanidin 3-O-glucoside Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C(O)=C1 RKWHWFONKJEUEF-GQUPQBGVSA-O 0.000 claims abstract description 21
- YTMNONATNXDQJF-UBNZBFALSA-N chrysanthemin Chemical compound [Cl-].O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C(O)=C1 YTMNONATNXDQJF-UBNZBFALSA-N 0.000 claims abstract description 20
- 230000028327 secretion Effects 0.000 claims abstract description 19
- 239000003053 toxin Substances 0.000 claims abstract description 19
- 231100000765 toxin Toxicity 0.000 claims abstract description 19
- 101100476480 Mus musculus S100a8 gene Proteins 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 11
- 108091003202 SecA Proteins Proteins 0.000 claims abstract description 7
- -1 VacA Proteins 0.000 claims abstract description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 208000015181 infectious disease Diseases 0.000 claims description 16
- 230000002265 prevention Effects 0.000 claims description 15
- 208000007882 Gastritis Diseases 0.000 claims description 12
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 12
- 201000005917 gastric ulcer Diseases 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 208000035473 Communicable disease Diseases 0.000 claims description 11
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 10
- 206010017758 gastric cancer Diseases 0.000 claims description 10
- 201000011549 stomach cancer Diseases 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 7
- 239000012046 mixed solvent Substances 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 206010017886 Gastroduodenal ulcer Diseases 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 231100000029 gastro-duodenal ulcer Toxicity 0.000 claims description 4
- 206010019375 Helicobacter infections Diseases 0.000 claims description 3
- 235000013361 beverage Nutrition 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 3
- 238000010298 pulverizing process Methods 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 16
- 241000894006 Bacteria Species 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 230000005764 inhibitory process Effects 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 7
- 108010046334 Urease Proteins 0.000 abstract description 5
- 239000000654 additive Substances 0.000 abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 abstract description 3
- 229940088710 antibiotic agent Drugs 0.000 abstract description 3
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 208000028861 Helicobacter pylori infectious disease Diseases 0.000 abstract 1
- 235000015872 dietary supplement Nutrition 0.000 abstract 1
- 230000009036 growth inhibition Effects 0.000 abstract 1
- 235000013305 food Nutrition 0.000 description 19
- 235000010208 anthocyanin Nutrition 0.000 description 16
- 229930002877 anthocyanin Natural products 0.000 description 16
- 239000004410 anthocyanin Substances 0.000 description 16
- 150000004636 anthocyanins Chemical class 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 14
- 230000006907 apoptotic process Effects 0.000 description 11
- 208000035143 Bacterial infection Diseases 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 208000022362 bacterial infectious disease Diseases 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 230000002496 gastric effect Effects 0.000 description 7
- 230000036541 health Effects 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 241000699684 Meriones unguiculatus Species 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 208000000718 duodenal ulcer Diseases 0.000 description 5
- 230000008029 eradication Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241000589989 Helicobacter Species 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 230000001262 anti-secretory effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000000287 crude extract Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000013376 functional food Nutrition 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 230000001766 physiological effect Effects 0.000 description 3
- 150000008442 polyphenolic compounds Chemical class 0.000 description 3
- 235000013824 polyphenols Nutrition 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 2
- 206010019851 Hepatotoxicity Diseases 0.000 description 2
- 206010029155 Nephropathy toxic Diseases 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 description 2
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 102000000763 Survivin Human genes 0.000 description 2
- 108010002687 Survivin Proteins 0.000 description 2
- 108700031544 X-Linked Inhibitor of Apoptosis Proteins 0.000 description 2
- 102000050257 X-Linked Inhibitor of Apoptosis Human genes 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001875 compounds Chemical group 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000002489 hematologic effect Effects 0.000 description 2
- 230000007686 hepatotoxicity Effects 0.000 description 2
- 231100000304 hepatotoxicity Toxicity 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 229960004592 isopropanol Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000007694 nephrotoxicity Effects 0.000 description 2
- 231100000417 nephrotoxicity Toxicity 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 108020004465 16S ribosomal RNA Proteins 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000004091 Caspase-8 Human genes 0.000 description 1
- 108090000538 Caspase-8 Proteins 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 241000195628 Chlorophyta Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- OIZFQAFWYYKPMR-PEVLUNPASA-N Delphinidin 3-O-glucoside Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)C=1[C-](c2cc(O)c(O)c(O)c2)[O+]c2c(c(O)cc(O)c2)C=1 OIZFQAFWYYKPMR-PEVLUNPASA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000911513 Homo sapiens Uncharacterized protein FAM215A Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241000209510 Liliopsida Species 0.000 description 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 240000000249 Morus alba Species 0.000 description 1
- 235000008708 Morus alba Nutrition 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 244000061458 Solanum melongena Species 0.000 description 1
- 235000002597 Solanum melongena Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 240000002657 Thymus vulgaris Species 0.000 description 1
- 235000007303 Thymus vulgaris Nutrition 0.000 description 1
- 102100021436 UDP-glucose 4-epimerase Human genes 0.000 description 1
- 108010075202 UDP-glucose 4-epimerase Proteins 0.000 description 1
- 102100026728 Uncharacterized protein FAM215A Human genes 0.000 description 1
- 240000001717 Vaccinium macrocarpon Species 0.000 description 1
- 235000012545 Vaccinium macrocarpon Nutrition 0.000 description 1
- 235000002118 Vaccinium oxycoccus Nutrition 0.000 description 1
- 240000004922 Vigna radiata Species 0.000 description 1
- 235000010721 Vigna radiata var radiata Nutrition 0.000 description 1
- 235000011469 Vigna radiata var sublobata Nutrition 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 244000126002 Ziziphus vulgaris Species 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000021329 brown rice Nutrition 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000020230 cinnamon extract Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 235000004634 cranberry Nutrition 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- XENHPQQLDPAYIJ-PEVLUNPASA-O delphinidin 3-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC(O)=C(O)C(O)=C1 XENHPQQLDPAYIJ-PEVLUNPASA-O 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000010437 gem Substances 0.000 description 1
- 229910001751 gemstone Inorganic materials 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- PXUQTDZNOHRWLI-OXUVVOBNSA-O malvidin 3-O-beta-D-glucoside Chemical compound COC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 PXUQTDZNOHRWLI-OXUVVOBNSA-O 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- GXPTVXHTZZVLMQ-GCGJSEPQSA-N myrtillin Natural products O[C@H]1O[C@@H](OCC2=C(OC3=CC(=O)C=C(O)C3=C2)c4cc(O)c(O)c(O)c4)[C@H](O)[C@@H](O)[C@@H]1O GXPTVXHTZZVLMQ-GCGJSEPQSA-N 0.000 description 1
- 239000000974 natural food coloring agent Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- ABVCUBUIXWJYSE-GQUPQBGVSA-O pelargonidin 3-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C=C1 ABVCUBUIXWJYSE-GQUPQBGVSA-O 0.000 description 1
- ZZWPMFROUHHAKY-OUUKCGNVSA-O peonidin 3-O-beta-D-glucoside Chemical compound C1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 ZZWPMFROUHHAKY-OUUKCGNVSA-O 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 235000020095 red wine Nutrition 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000018556 stomach disease Diseases 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000001585 thymus vulgaris Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940111760 white rice extract Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Mycology (AREA)
- Botany (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Nutrition Science (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Molecular Biology (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
본 발명은 흑미 추출물을 유효성분으로 포함하는 헬리코박터 파이로리 (Helicobater pylori)균의 감염 질환인 위염, 위궤양, 위십이지장 질환 치료 또는 예방용 조성물 및 식품 조성물에 관한 것으로, 특히 본 발명에 따른 흑미 추출물은 헬리코박터 파이로리의 병원성 독소인 CagA, VacA, SecA를 선택적으로 저해하는 것을 특징으로 하며 본 발명의 약학 조성물 및 식품 조성물은 안전성이 보장된 천연식물인 흑미 쌀에서 헬리코박터 파이로리 균에 대해 항균활성을 가지는 것을 선택하여 개발한 것으로 내성과 부작용의 위험이 적고 인체 저독성으로 안전한 것을 특징으로 한다.
The present invention, Helicobacter pylori containing black rice extract as an active ingredient ( Helicobater The present invention relates to a composition for the treatment or prevention of gastritis, gastric ulcer, gastroduodenal diseases, and food compositions, wherein the black rice extract according to the present invention selectively inhibits CagA, VacA, and SecA, which are pathogenic toxins of Helicobacter pylori. The pharmaceutical composition and the food composition of the present invention have been developed by selecting an antimicrobial activity against Helicobacter pylori bacteria in black rice, which is a safe natural plant, and has low risk of resistance and side effects, and is safe for humans. It features.
현대사회는 경제발전과 더불어 고령화, 삶의 질 향상, 건강 등에 대한 인식이 확산되고 있으며 이를 추구하는 현상은 우리나라 뿐만 아니라 전 세계적인 추세가 되었으며 이러한 현상은 향후 더욱 가속화 될 것으로 예측된다. 하지만 현대인들은 불규칙한 식생활과 과중한 스트레스를 받음으로서 다양한 질병에 노출되어 있고 특히 자극성이 강한 음식을 좋아하는 한국사람들은 위염, 위암, 위궤양, 위십이지장 질환 등의 위장질환은 국내 발병율이 높은 실정이다. 따라서 매우 빠른 속도로 변화되고 있는 사회현상과 점차 다양화 되어가는 소비자의 기대를 충족시킬수 있는 새로운 바이오메디컬 소재개발, 기능성 식품소재 개발 및 웰빙소재 개발이 필요한 실정이다. In modern society, the awareness of aging, quality of life, and health is spreading along with the economic development, and the phenomenon that pursues this has become a global trend not only in Korea but also in the future. However, modern people are exposed to various diseases by irregular eating habits and excessive stress. In particular, gastric diseases such as gastritis, stomach cancer, stomach ulcer and gastroduodenal disease are highly prevalent in Koreans who like food with strong irritation. Therefore, it is necessary to develop new biomedical materials, functional food materials, and well - being materials to meet the social phenomenon changing at a very fast pace and increasingly diverse consumers' expectations.
헬리코박터 파이로리 (Helicobacter pylori)는 1983년 호주의 마샬 박사와 워렌 박사에 의하여 순수 분리, 배양하는데 성공하여 그 이름이 명명되었고, 많은 논문에서 이 세균이 위염, 위궤양, 십이지장궤양 환자의 위생검사에서 높은 비율로 검출되는 것이 알려지면서, 현재는 위궤양, 위염, 위암 및 십이지장 궤양의 발병인자 중 하나로 인정되고 있다(Gastroenterol. 2009. 136:1863-1873, Lancet. 1995. 345(8964):1525-1528, IARC Monogr Eval Carcinog Risks Hum. 1994. 61:1-241, N Engl J Med. 2002. 347:1175-1186, PLoS ONE. 2009. 4(3):e4754). Helicobacter Pylori ) was named after successful isolation and cultivation by Australian and Dr. Marshall and Warren in 1983. In many papers, the bacterium was found to have a high rate of hygiene in patients with gastritis, gastric ulcer and duodenal ulcer. Known, it is now recognized as one of the pathogens of gastric ulcer, gastritis, gastric cancer and duodenal ulcer (Gastroenterol. 2009. 136: 1863-1873, Lancet. 1995. 345 (8964): 1525-1528, IARC Monogr Eval Carcinog Risks Hum. 1994. 61: 1-241, N Engl J Med. 2002. 347: 1175-1186, PLoS ONE. 2009. 4 (3): e4754).
상기 헬리코박터 파이로리는 위점막 상피세포간 접합부에 서식하는 그람 음성의 간균으로서 최적의 생육 pH는 7.0 ∼ 7.4이며 온도는 30 ∼ 37℃의 미호기적 조건에서 생장한다. 헬리코박터 파이로리의 병독인자들을 보면 위에서 분비되는 위액의 강산조건에 생존하기 위해 분비되는 CagA, VacA를 분비하는 단백질인 SecA, 운동성을 유지하기 위해 있는 편모, 위점막 상피세포에 부착을 용이하게 도와주는 외막단백질 등이 알려져 있다. (Trends Microbiol. 2003. 11(3):134-138) 이중 유레아제는 위점막 조직 내의 요소를 암모니아와 이산화탄소로 분해하여 균체 주의를 알카리화 시킴으로서 위에서 분비되는 강산의 조건을 중화시켜 생존 할 수 있는 조건을 만드는 특성을 갖는다. The Helicobacter pylori is a gram-negative bacterium in the gastric mucosal epithelium junction. The optimal growth pH is 7.0 ~ 7.4 and the temperature is 30 ~ 37 ℃. Helicobacter pylori infection is characterized by CagA secreted to survive the strong acidity of gastric juice secreted from the stomach, SecA secreted by VacA, monocotyledon to maintain mobility, Proteins are known. (Trends Microbiol 2003. 11 (3): 134-138) The double urease agent decomposes elements in gastric mucosal tissues into ammonia and carbon dioxide to alkalize the microbial cells, neutralizing the conditions of the strong acid secreted from the above, It has the characteristic of making condition.
본 개발은 국내외를 아울러 최초로 연구된 유색미추출물 및 흑미 유래의 안토시아닌에 의한 H. pylori 독소 억제 메커니즘을 기반으로 하고 있다. 일부 연구 성과들이 안토시아닌에 의한 H. pylori 제균 가능성을 간접적으로 제시하고 있다. 2010년 최근의 보고에 따르면, 흑미겨 추출물 처리를 통하여 화학물질 유래의 염증반응을 억제할 수 있다는 보고가 있으나, 그 원인물질이 안토시아닌일 가능성이 높다고만 언급하고 있다(최선필 외 J Agric Food Chem 2010;58:10007-10015). 이 외에 유색미추출물을 이용한 위장질환 개선 관련 in vitro 연구보고는 없는 것으로 파악되었다. Mongolian gerbil 감염모델에 일본산 흰쌀 추출물을 경구 투여하였을 때, 14주(2주간 감염시킨 후, 12주간 쌀추출물 치료) 후에 염증치료효과와 동시에 H. pylori 제균 효과를 보였음을 보고하였다(Satoshi Ishizone 외 Int J Med Sci 2007;4(4):203-208). 이 외에 유색미추출물을 이용한 위장질환 개선 관련 전임상 연구보고는 없는 것으로 파악되었다. 천연물유래의 추출물을 이용하여 H. pylori를 억제하기 위한 다양한 시도가 보고되고 있으나, 이들 관련 연구들은 모두 안토시아닌에 의한 억제메커니즘을 구체적으로 증명하지 못하였다. 그 중에서도 안토시아닌의 효능을 메커니즘 분석을 통하여 확인한 연구 보고는 아직까지 없는 것으로 파악되며, 단지 cranberry, optiberry, 등 자색을 띄는 딸기에 안토시아닌이 가장 많이 함유되어 있으며, 해당 추출물 처리시 H. pylori 억제효과가 있었다는 간접적인 영향에 대한 보고들만 존재한다(J. Cote 외 Critical Rev Food Sci Nutri 2010;50:666-679, Shirley Zafra-Stone 외 Mol Nutr Food Res 2007;51:675-683, Liisa J Nohynek 외 Nutr Cancer 2006;54(1):18-32.). 이 외에 역시 안토시아닌을 다량 함유한 가공식품인 red wine을 처리하여 H. pylori의 독소 중 하나인 VacA를 억제할 수 있다는 연구보고가 있으나, 이 역시 구체적인 메커니즘은 밝히지 못하였다(Paolo Ruggiero 외 World J Gastroenterol 2007 21;13(3):349-354).This development is based on the inhibition mechanism of H. pylori toxin by anthocyanin derived from porkworm extract and black rice. Some research results indirectly suggest the possibility of H. pylori eradication by anthocyanin. According to a recent report in 2010, it has been reported that the treatment of black flax bark extract inhibits chemical-induced inflammation, but it is said that the causative agent is likely to be anthocyanin (Choi et al., J Agric Food Chem 2010 ; 58: 10007-10015). In addition, there were no reports of in vitro studies on the improvement of gastrointestinal diseases using pukyongmi extract. When oral administration of Japanese white rice extract to Mongolian gerbil infection model, H. pylori bactericidal effect was shown simultaneously after 14 weeks (2 weeks of infection and 12 weeks of rice extract treatment) (Satoshi Ishizone et al. Int J Med Sci 2007; 4 (4): 203-208). In addition, there were no reports of preclinical studies related to the improvement of gastrointestinal diseases using pukyongmi extract. Various attempts have been made to inhibit H. pylori using extracts derived from natural materials, but all of these related studies have not been able to demonstrate specifically the mechanism of inhibition by anthocyanin. Among them, there have been no studies to confirm the efficacy of anthocyanin through mechanism analysis.Only, cranberry, optiberry, and other purple berries contain anthocyanin, and H. pylori inhibitory effect is obtained when the extract is treated. There are only reports of indirect impacts (J. Cote et al. Critical Rev Food Sci Nutri 2010; 50: 666-679, Shirley Zafra-Stone et al. Mol Nutr Food Res 2007; 51: 675-683, Liisa J Nohynek et al. Nutr. Cancer 2006; 54 (1): 18-32. In addition, research has shown that the treatment of red wine, a processed food containing high amounts of anthocyanins, may inhibit VacA, one of the toxins of H. pylori , but this also has not revealed a specific mechanism (Paolo Ruggiero et al. World J Gastroenterol). 2007 21; 13 (3): 349-354.
현재 헬리코박터 파이로리의 대표적인 치료방법은 메트로니다졸 (Metronidazole), 아목시실린 (amoxicillin)과 같은 항생제에 의존하고 있고, 이러한 약제의 반복사용은 항생제 저항성 증가 및 다양한 부작용을 야기하는 것으로 보고 되고 있으며(Gut. 1998;439(suppl):61S-65S, Gastroenterol. 1999;116:248-253, Aliment Pharmacol Ther. 1999;13:1523-1530, Aliment Pharmacol Ther 1997;11:943-952, Am J Gastroenterol. 1999;94:1751-1759, Aliment Pharmacol Ther. 1999;13:1047-1055), 현재는 다양한 천연물 소재를 이용하여 헬리코박터 파이로리를 억제 할 수 있는 추출물 및 활성성분을 찾기 위한 노력이 지속되고 있다. 포도, 사과 껍질로부터 추출한 다양한 폴리페놀들 (J Appl Microbiol. 2011 Jan;110(1):139-46, J Agric Food Chem. 2010 Jun 23;58(12):7172-9)과 블랙베리 잎에서 분리된 폴리페놀 등이 헬리코박터 파이로리 생장을 억제능을 확인 (Int J Antimicrob Agents. 2009 Jul;34(1):50-9)한바 있고, 이외에도 백리향 (J. Appl. Bacteriol., 1996, 80, 667-672) 이나 다양한 플라보노이드계 화합물들로 부터도 강력한 억제 활성이 보고 되고 있다. (J Gastroenterol. 2008;43(6):441-7; J Nat Prod. 2007 Oct;70(10):1570-7) 또한, 최근까지 발표된 헬리코박터 파이로리 관련 특허 및 보고자료 로는 헬리코박터 파이로리 억제 효능을 가지는 강화순수 추출물의 제조방법 및 이를 유효성분으로 함유하는 제품 (공개번호 10-2012-0053352), 녹조류 추출물을 함유하는 항헬리코박터 조성물 (공개번호 10-2011-0023844), 계피 추출물을 유효성분으로 함유하는 헬리코박터 감염 질환의 예방 또는 치료용 약학적 조성물 및 건강식품 (공개번호 10-2011-0117491), 구절초 추출물 또는 분획물을 유효성분으로 함유하는 위장관 질환의 예방 및 치료용 조성물 (공개번호 10-2010-0044433) 등이 있다. Currently, the most common treatment methods for Helicobacter pylori depend on antibiotics such as metronidazole and amoxicillin. Repeated use of these agents has been reported to cause increased antibiotic resistance and various side effects (Gut. 1998; 439 (suppl): 61S-65S, Gastroenterol. 1999; 116: 248-253, Aliment Pharmacol Ther. 1999; 13: 1523-1530, Aliment Pharmacol Ther 1997; 11: 943-952, Am J Gastroenterol. -1759, Aliment Pharmacol Ther. 1999; 13: 1047-1055), and currently efforts are being made to find extracts and active ingredients that can inhibit Helicobacter pylori using a variety of natural materials. Polyphenols Extracted from Grape and Apple Peel (J Appl Microbiol. 2011 Jan; 110 (1): 139-46, J Agric Food Chem. 2010 Jun 23; 58 (12): 7172-9) and Blackberry Leaves Isolated polyphenols have been shown to inhibit the growth of Helicobacter pylori (Int J Antimicrob Agents. 2009 Jul; 34 (1): 50-9), as well as thyme (J. Appl. Bacteriol., 1996, 80, 667- 672) and various flavonoid compounds have also been reported to have strong inhibitory activity. (J Gastroenterol. 2008; 43 (6): 441-7; J Nat Prod. 2007 Oct; 70 (10): 1570-7) In addition, recently published patents and reports related to Helicobacter pylori have shown the efficacy of Helicobacter pylori inhibition. Method of preparing eggplant-enriched pure water extract and a product containing the same as an active ingredient (Publication No. 10-2012-0053352), an anti-helicobacter composition containing the green algae extract (Publication No. 10-2011-0023844), and a cinnamon extract as an active ingredient Pharmaceutical composition for the prevention or treatment of Helicobacter infection diseases and health foods (Publication No. 10-2011-0117491), Gujeolcho composition or composition for the prevention and treatment of diseases of the gastrointestinal tract containing as an active ingredient (Publication No. 10-2010- 0044433).
최근까지 발표된 흑미 관련 특허 및 보고자료는 면역력 증강을 통한 항아토피 활성을 갖는 슈퍼 C3GHi 흑자미벼(공개번호 2012-0000388), 초크베리 생물활성분획물 C3G 복합체를 유효성분으로 함유하는 동맥경화 및 고혈압 예방 및 치료용 약학적 조성물(공개번호 2011-0133931), 시아니딘-3 배당체 또는 이를 포함하는 흑미 추출물을 함유하는 고지혈증 예방 및 치료용 조성물 (공개번호 10-2003-0061650), 흑미추출물을 이용한 알레르기성 질환 예방 또는 치료용조성물 및 이들의 치료학적 용도 (공개번호 10-2004-0021843), 흑미 추출물을 유효성분으로 함유하는 피부미백 화장료 조성물 (공개번호 10-2004-0003013), 안토시아닌을 함유하는 비스테로이드성 항염증제에 의해 유발된 위염 및 위궤양 치료용 조성물 (공개번호 10-2007-0070841), 흑찰거대배아미 추출물을 함유하는 식음료 조성물 (공개번호 10-2010-0099133), 흑미 추출물의 마우스 피부의 염증반응에 대한 보호 효과 (Journal of Agricultural and Food Chemistry, 2010), 흑미 추출물의 항산화 활성 (Journal of health science v.52 no.5 , pp.495 - 511 , 2006) 등이 있다. 또한 보유색미 미강 발효물의 면역활성 효과 (김동주 et al, 한국식품영양학회지, 24(3), 273-281, 2011) 등이 있다.Until recently, patents and reports related to black rice have shown that super C3GHi black mica (anti-atopic activity through immunity enhancement) (No. 2012-0000388), atherosclerosis and hypertension prevention containing active ingredient C3G complex of Chalkberry bioactive fraction (Publication No. 10-2003-0061650) containing a cyanidin-3 glycoside or a black rice extract containing the same, a composition for treating and alleviating allergy (Publication No. 10-2004-0021843), a skin whitening cosmetic composition containing an extract of black rice as an active ingredient (Publication No. 10-2004-0003013), a non-steroid containing anthocyanin Compositions for treating gastritis and gastric ulcer induced by anti-inflammatory drugs (Publication No. 10-2007-0070841), food compositions containing a macrophage macrophylla extract (Journal of Agricultural and Food Chemistry, 2010), the antioxidant activity of black rice extract (Journal of health science v.52 no.5 , pp.495-511, 2006). (Kim Dong-ju, et al, Journal of the Korean Society of Food Science and Nutrition, 24 (3), 273-281, 2011).
지금까지의 흑미의 생리활성 연구는 주로 조추출물을 이용하여 제품의 제조 등에 사용되었고, 항산화 활성에 기초한 염증억제, 미백효과 등의 생리활성 검정이 대부분이고, 조추출물에서 안토시아닌 및 지질성분을 분리하여 흑미의 품종별 폴리페놀류의 함량을 측정하였다. Studies on the physiological activity of black rice have been mainly used for the production of products using crude extracts. Most of the studies on physiological activity such as inhibition of inflammation and whitening effect based on antioxidant activity, and separation of anthocyanin and lipid components from crude extract The content of polyphenols was determined by the variety of black rice.
그러나, 흑미 추출물을 유효성분으로 하는 헬리코박터 파이로리 (Helicobacter pylori)를 억제활성을 가지는 추출물 및 유효성분에 대한 물질의 분리, 구조동정된 성분별 함량분석, 생리활성 검정 및 유효성분 최대 생산을 위한 추출조건 등에 대한 연구는 부족한 실정이다. However, Helicobacter pylori to the black rice extract as an active ingredient (Helicobacter Pylori ) is insufficient to study the separation of substances for extracts and active ingredients with inhibitory activity, content analysis of structurally identified components, assay of physiological activity and extraction conditions for maximum production of active ingredients.
따라서 본 발명은 그동안 선행연구가 이루어지지 않았던 흑미의 추출물의 유효성분이 헬리코박터 파이로리에 의한 위염, 위궤양, 위십이지장 궤양 및 위암을 일으키는 인자인 분비독소 (CagA, VacA, SecA), 유레이즈 (urease), 등을 억제함으로서 위염, 위궤양, 위십이지장 궤양 및 위암 등에 효과가 있는 건강식품, 약학적 조성물 및 음료 등의 활용에 관한 분야와 흑미의 안토시아닌 등의 헬리코박터 억제활성을 가지는 유효성분을 구명 및 함량을 정량분석 하고, 흑미의 헬리코박터 억제활성을 가지는 유효성분을 분리 하기위한 추출방법, 유효성분을 다량 함유하는 추출물 제조 및 이를 이용한 활용에 관한 분야이다.
Therefore, the present invention is a secretion toxin (CagA, VacA, SecA), U-raise (urease), which is an active ingredient of the extract of black rice, which has not been studied in the past, causes gastritis, gastric ulcer, gastroduodenal ulcer and gastric cancer caused by Helicobacter pylori By inhibiting the back and the like, the fields related to the use of health foods, pharmaceutical compositions and beverages that are effective in gastritis, gastric ulcer, gastric duodenal ulcer and gastric cancer, and active ingredients having helicobacter inhibitory activity such as anthocyanin of black rice Analysis, and extraction method for separating the active ingredient having a Helicobacter inhibitory activity of black rice, an extract containing a large amount of the active ingredient and the field of the use thereof.
이에, 본 발명자들은 흑미 유래 기능성 물질을 탐색하던 중 흑미의 추출물이 강한 헬리코박터 파이로리 억제 효과를 보임을 확인하였고, 이 활성인자에 관여하는 물질을 분리, 정제 및 화학구조를 동정하였으며, 각각의 생리활성을 검정한 결과 안토시아닌 중 시아니딘-3-O-글루코사이드 (Cyanidin-3-O-glucoside)가 흑미의 헬리코박터 억제활성을 가지는 유효활성 물질임을 확인하였다. 흑미 추출물 및 시아니딘-3-O-글루코사이드에 의한 H. pylori CagA, VacA 독소 분비 억제 메커니즘은 현재까지 국내외에서 보고된 바가 없었다. 본 발명을 통하여 최초로 흑미추출물 및 시아니딘-3-O-글루코사이드가 H. pylori의 병원성 인자들의 억제 메커니즘에 관여한다는 사실을 규명하고, 이러한 효능을 가진 물질들을 이용한 위염, 위궤양, 십이지장 궤양 및 위암 등의 식품, 천연물의약품 등의 활용에 관해 본 발명을 완성하였다.
Accordingly, the inventors of the present invention found that the black rice extract showed a strong inhibitory effect on Helicobacter pylori during the search for functional materials derived from black rice, and identified, purified and chemical structures of the substances involved in the activity factors, As a result, it was confirmed that cyanidin-3-O-glucoside (Cyanidin-3-O-glucoside) in anthocyanin was an effective active substance having a helicobacter-suppressing activity in black rice. The mechanism of inhibiting H. pylori CagA and VacA toxin secretion by black rice extract and cyanidin-3-O-glucoside has not been reported at home and abroad. Through the present invention, the first time that black rice extract and cyanidin-3-O-glucoside are involved in the inhibitory mechanism of pathogenic factors of H. pylori , it is confirmed that gastritis, gastric ulcer, duodenal ulcer and gastric cancer, etc. The present invention has been completed regarding the use of food, natural medicines and the like.
이에, 본 발명의 목적은 흑미 추출물 또는 흑미 용매 분획물을 유효성분으로 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 치료용 약학적 조성물을 제공하는데에 있다.Accordingly, an object of the present invention is a Helicobacter pylori ( Helicobater) comprising a black rice extract or a black rice solvent fraction as an active ingredient pylori ) to provide a pharmaceutical composition for the prevention or treatment of infectious diseases.
본 발명의 다른 목적은 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 치료용 약학적 조성물인 흑미 추출물 또는 흑미 용매 분획물을 제조 방법을 제공하는데에 있다.Another object of the present invention is Helicobacter pylori ( Helicobater pylori ) to provide a method for producing black rice extract or black rice solvent fraction, which is a pharmaceutical composition for the prevention or treatment of infectious diseases.
본 발명의 또 다른 목적은 흑미 추출물 또는 흑미 용매 분획물을 유효성분으로 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 경감을 위한 건강식품을 제공하는데에 있다.
Still another object of the present invention is a Helicobacter pylori ( Helicobater) comprising black rice extract or black rice solvent fraction as an active ingredient pylori ) to provide health foods for the prevention or alleviation of infectious diseases.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.
Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
본 발명의 일 양태에 따르면, 본 발명은 흑미 추출물 또는 흑미 용매 분획물을 유효성분으로 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 치료용 약학적 조성물을 제공한다.
According to an aspect of the present invention, the present invention, Helicobacter pylori ( Helicobater) comprising a black rice extract or a black rice solvent fraction as an active ingredient pylori ) provides a pharmaceutical composition for the prevention or treatment of infectious diseases.
본 발명의 다른 양태에 따르면, 본 발명은 According to another aspect of the invention, the invention
i) 흑미를 분쇄하고, 분쇄한 흑미를 물, 탄소수 1-4의 저급알코올, 발효주정 또는 이들의 혼합용매를 이용하여 추출하는 단계; 및i) pulverizing black rice and extracting the pulverized black rice using water, a lower alcohol having 1 to 4 carbon atoms, fermented alcohol or a mixed solvent thereof; And
ii) 상기 추출물을 크로마토그래피를 이용하여 전개액으로 물, 메탄올을 이용하여 로 분리하여 시아니딘 3-O-글루코사이드를 순수 분리 동정하는 단계;ii) separating the extract with water and using methanol as a developing solution using chromatography to identify and isolate pure cyanidin 3-O-glucoside;
를 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 치료용 약학적 조성물의 제조 방법을 제공한다.
Helicobacter pylori (Helicobater containing pylori ) provides a method for producing a pharmaceutical composition for the prevention or treatment of infectious diseases.
본 발명의 또 다른 양태에 따르면, 본 발명은 흑미 추출물 또는 흑미 용매 분획물을 유효성분으로 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 경감을 위한 건강식품을 제공한다.
According to another aspect of the present invention, the present invention, Helicobacter pylori ( Helicobater) comprising a black rice extract or a black rice solvent fraction as an active ingredient pylori ) Provides health foods for the prevention or alleviation of infectious diseases.
본원 발명의 특징 및 이점을 요약하면 다음과 같다.The features and advantages of the present invention are summarized as follows.
(i) 본 발명의 흑미 추출물 또는 흑미유래 시아니딘 3-O-글루코사이드 흑미 분획물의 유효성분은 헬리코박터 파이로리의 생육 억제활성, 헬리코박터 파일로리 유레이즈 억제활성 및 CagA, VacA, SecA의 독소 분비억제 활성을 나타낸다.(i) The active ingredient of the black rice extract or black rice-derived cyanidin 3-O-glucoside black rice fraction of the present invention shows inhibitory activity on the growth of Helicobacter pylori, inhibitory activity on Helicobacter pylori Urease, and activity of inhibiting toxin secretion of CagA, VacA and SecA .
(ii) 본 발명의 흑미 추출물 또는 흑미 용매 분획물은 흑미 유래의 안전한 천연소재 이므로 인체에 안전성, 저독성 및 항생제 남용에 의한 내성균 발생을 억제하는 안전한 헬리코박터 파이로리 예방 또는 치료용 약학적 조성물, 건강식품, 음료 및 첨가물로 유용하게 이용 될 수 있다.
(ii) Since the black rice extract or the black rice solvent fraction of the present invention is a safe natural material derived from black rice, it is possible to provide a safe pharmaceutical composition for preventing or treating Helicobacter pylori which suppresses the safety, low toxicity and the generation of resistant bacteria by abuse of antibiotics in the human body, And additives.
도 1은 흑미 추출물 처리시 헬리코박터 파이로리의 생육억제 사진이다.
도 2는 흑미 추출물(BRE)의 처리농도별 KATO III 세포의 독성을 나타내는 그림이다.
도 3은 흑미 추출물(BRE)의 처리농도별 KATO III 세포의 세포사멸인자에 대한 웨스턴 브랏팅 결과이다.
도 4는 H. pylori에 감염된 KATO III(위암세포)의 세포흑미 추출물 처리시 세포독성 결과이다.
도 5는 H. pylori에 감염된 KATO III(위암세포)에 흑미 추출물을 처리시 세포사멸 회복에 대한 웨스턴 블랏팅 결과이다.
도 6은 흑미 추출물 처리시 H. pylori 분비 독소 (CagA, VacA)의 분비 억제 효과에 대한 웨스턴 블랏팅 결과이다.
도 7은 흑미 추출물 처리시 H. pylori 분비 독소 (CagA, VacA)의 분비역제효과에 대한 RT-PCR 결과이다.
도 8은 흑미 추출물에서 분리한 안토시아닌 및 안토시아닌 종류별 헬리코박터 파이로리에 처리시 분비 독소 (CagA, VacA)의 억제 효과에 대한 RT-PCR 결과이다.
패널(a) 내지 패널(d)는 각각 (a) cagA, (b) vacA, (c) secA and (d) 16s rRNA (internal control)의 mRNA 발현량을 측정한 것이다. 각 RT-PCR 레인에 대하여 래인(lane) M; 100bp DNA 래더(ladder), 래인 1; Cyanidine-3-O-glucoside (100 μM), 래인 2; Peonidin-3-O-glucoside (100 μM), 래인 3; Pelargonidin-3-O-glucoside (100 μM), 래인 4; Delphinidin-3-O-glucoside (100 μM), 래인 5; Malvidin-3-O-glucoside (100 μM), and 래인 6; black rice extract.(400 μg/ml)의 조건으로 실시하였다.
도 9는 H. pylori 감염모델 (전임상) 확인 및 흑미 추출물 처리시 헬리코박터 파이로리 억제활성의 Immunohistochemistry (면역조직화학) 염색 사진이다.
도 10은 H. pylori 감염모델 (전임상) 흑미 추출물 처리시 위장 염증 억제효과 검정 결과이다.
도 11은 H. pylori 감염모델(전임상)에 흑미추출물을 처리후 실시한 혈액학적 분석결과이다.
도 12는 H. pylori 감염모델 (전임상) 흑미 추출물 처리시 다른 장기(신장, 간)의 조직 독성 사진이다. Fig. 1 is a picture showing inhibition of growth of Helicobacter pylori in the treatment of black rice extract.
FIG. 2 is a graph showing toxicity of KATO III cells according to treatment concentration of black rice extract (BRE). FIG.
FIG. 3 is a Western blotting result of KATO III cell apoptosis factor by treatment concentration of black rice extract (BRE).
Figure 4 shows the cytotoxicity of H. pylori -infected KATO III (stomach cancer cells) treated with the cell black rice extract.
Figure 5 is a Western blotting result for apoptosis recovery when treated with black rice extract to KATO III (gastric cancer cells) infected with H. pylori .
Figure 6 is a Western blotting result for the secretion inhibitory effect of H. pylori secretion toxin (CagA, VacA) when black rice extract treatment.
Figure 7 shows the RT-PCR results of the anti-secretory effect of H. pylori secretion toxin (CagA, VacA) upon treatment of black rice extract.
FIG. 8 shows RT-PCR results of the inhibitory effect of secretory toxins (CagA, VacA) upon treatment of anthocyanin and anthocyanin type Helicobacter pylori isolated from black rice extract.
Panels (a) to (d) show the mRNA expression levels of (a) cag A, (b) vac A, (c) sec A and (d) 16s rRNA (internal control). Lane M for each RT-PCR lane; 100 bp DNA ladder,
9 is a photograph of Immunohistochemistry (immunohistochemistry) staining of H. pylori infection model (preclinical) confirmation and Helicobacter pylori inhibitory activity in black rice extract treatment.
Figure 10 shows the results of gastrointestinal inflammation inhibitory effect when treated with H. pylori infection model (preclinical) black rice extract.
FIG. 11 is a hematological analysis result of black rice extract treated with H. pylori infection model (preclinical).
12 is a histotoxicity photograph of another organ (kidney, liver) treated with H. pylori infection model (preclinical) black rice extract.
본 발명의 일 양태에 따르면, 본 발명은 흑미 추출물 또는 흑미 용매 분획물을 유효성분으로 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 치료용 약학적 조성물을 제공한다.According to one aspect of the invention, the present invention provides a pharmaceutical composition for the prevention or treatment of Helicobacter pylori ( Helicobater pylori ) infection disease comprising a black rice extract or a black rice solvent fraction as an active ingredient.
본 발명의 바람직한 구현예에 따르면, 상기 흑미 추출물 또는 흑미 용매 분획물을 유효성분으로 포함하는 예방 또는 치료용 약학적 조성물은 헬리코박터 파이로리 감염 질환은 위염, 위궤양, 위십이지장궤양, 소화성 궤양 또는 위암에 효과적이다.According to a preferred embodiment of the present invention, the pharmaceutical composition for preventing or treating the above-mentioned black rice extract or black rice solvent fraction as an active ingredient is effective for gastritis, gastric ulcer, gastroduodenal ulcer, peptic ulcer or gastric cancer .
본 명세서에서, 용어 “흑미 추출물”은 흑미 종자에서 부터 추출하여 얻은 것을 의미한다. 추출물은 당업계에 공지된 통상적인 추출용매, 바람직하게는, (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올 (예: 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올 및 노말-부탄올 등), (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 1,3-부틸렌글리콜, (h) 헥산, (i) 디에틸에테르, 또는 (j) 부틸아세테이트를 이용하여 얻을 수 있다.As used herein, the term " black rice extract " means obtained from black rice seeds. (B) an anhydrous or hydro-lower alcohol having 1-4 carbons such as methanol, ethanol, propanol, butanol, n-propanol, iso Propanol and n-butanol), (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f) chloroform, (g) 1,3-butylene glycol h) hexane, (i) diethyl ether, or (j) butyl acetate.
본 명세서에서, 용어 “흑미 용매 분획물”은 상기 추출 시 이용하였던 용매와 다른 용매를 이용하여 상기 흑미 추출물로부터 본 발명에서 목적으로 하는 활성을 가지는 분획하여 얻은 활성 분획물(fraction)을 의미한다. 흑미 용매 분획물을 얻기 위하여 사용되는 용매는 당업계에서 통상적으로 이용되는 어떠한 추출용매도 가능하며, 바람직하게는, (a) 탄소수 1-4의 무수 또는 함수 저급 알코올 (예: 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올 및 노말-부탄올 등), (b) 상기 저급 알코올과 물과의 혼합용매, (c) 아세톤, (d) 에틸 아세테이트, (e) 클로로포름, (f) 1,3-부틸렌글리콜, (g) 헥산, (h) 디에틸에테르, 또는 (i) 부틸아세테이트이다.As used herein, the term " black rice solvent fraction " means an active fraction obtained by fractionating the black rice extract from the black rice extract using the same solvent as that used in the extraction. The solvent used to obtain the black rice solvent fraction may be any extraction solvent conventionally used in the art, and preferably (a) an anhydrous or a lower alcohol having 1 to 4 carbon atoms (e.g., methanol, ethanol, propanol, (C) acetone, (d) ethyl acetate, (e) chloroform, (f) 1, 2-propanol, 3-butylene glycol, (g) hexane, (h) diethyl ether, or (i) butyl acetate.
본 명세서에서 사용되는 용어 “추출물”은 상술한 바와 같이 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로는 상술한 용매 분획물도 포함한다.The term "extract" as used herein has the meaning commonly used in the art as crude extract as described above, but broadly also includes the solvent fraction described above.
본 발명의 흑미 추출물 또는 흑미 용매 분획물은 상술한 용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피 (크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 흑미 추출물 또는 분획물에 포함되는 것이다.The black rice extract or the black rice solvent fraction of the present invention includes not only those obtained using the above-mentioned solvents but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the above extract through an ultrafiltration membrane having a constant molecular weight cut-off value, and a separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) The fraction obtained through the purification method is also included in the black rice extract or fraction of the present invention.
본 발명의 흑미 추출물 또는 분획물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.The black rice extract or fraction of the present invention can be prepared in powder form by an additional process such as vacuum distillation and freeze drying or spray drying.
본 발명의 조성물이 약제학적 조성물로 제조되는 경우, 본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체를 포함한다. 본 발명의 약제학적 조성물에 포함되는 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약제학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약제학적으로 허용되는 담체 및 제제는 Remington's Pharmaceutical Sciences (19th ed., 1995)에 상세히 기재되어 있다.When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical compositions of the present invention are those commonly used in the preparation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like It doesn't happen. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).
본 발명의 약제학적 조성물은 경구 또는 비경구 투여할 수 있으며, 바람직하게는 비경구 투여, 보다 바람직하게는 도포에 의한 국부 투여 (topical application) 방식으로 적용된다.The pharmaceutical composition of the present invention can be administered orally or parenterally, and is preferably applied by parenteral administration, more preferably topical application by application.
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. 본 발명의 약제학적 조성물에 포함된 생리활성물질인 흑미추출물 및 분획물의 투여량은 성인 기준으로 0.001-100 ㎎/kg, 바람직하게는 0.1-100 ㎎/kg, 보다 바람직하게는 5-50 mg/kg 범위 내이다. The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . The dose of the black rice extract and fraction, which are physiologically active substances contained in the pharmaceutical composition of the present invention, is 0.001-100 mg / kg, preferably 0.1-100 mg / kg, more preferably 5-50 mg / kg. < / RTI >
본 발명의 약제학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캡슐제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
본 발명의 바람직한 구현예에 따르면, 흑미 추출물로부터 수득하는 상기 흑미 용매 분획물은 흑미 추출물을 물, 탄소수 1-4의 저급 알코올, 발효주정 또는 이들의 혼합용매를 이용하여 추출할 수 있다.According to a preferred embodiment of the present invention, the black rice solvent fraction obtained from the black rice extract can be extracted with water, a lower alcohol having 1-4 carbon atoms, a fermented alcohol or a mixed solvent thereof.
본 발명의 바람직한 구현예에 따르면, 상기 흑미 추출물 또는 상기 흑미 용매 분획물은 헬리코박터 파일로리 유레이즈 억제활성 및 CagA, VacA, SecA의 독소 분비억제 활성을 나타낸다.According to a preferred embodiment of the present invention, the black rice extract or the black rice solvent fraction exhibits an inhibitory activity against Helicobacter pylori Urease and a toxin secretion inhibiting activity of CagA, VacA and SecA.
본 발명의 바람직한 구현예에 따르면, 상기 흑미 용매 분획물은 하기 화학식 1로 나타내는 시아니딘 3-O-글루코사이드를 포함하는 것을 특징으로 한다.According to a preferred embodiment of the present invention, the black rice solvent fraction comprises cyanidin 3-O-glucoside represented by the following general formula (1).
[화학식 1][Formula 1]
본 발명의 바람직한 구현예에 따르면, 상기 유효성분인 흑미 추출물 또는 흑미 용매 분획물의 함량은 조성물 총 중량에 대비 0.1∼50 중량%을 차지한다.
According to a preferred embodiment of the present invention, the content of the black rice extract or the black rice solvent fraction as the active ingredient is from 0.1 to 50% by weight based on the total weight of the composition.
본 발명의 다른 양태에 따르면, 본 발명은 According to another aspect of the invention, the invention
i) 흑미를 분쇄하고, 분쇄한 흑미를 물, 탄소수 1-4의 저급알코올, 발효주정 또는 이들의 혼합용매를 이용하여 추출하는 단계; 및i) pulverizing black rice and extracting the pulverized black rice using water, a lower alcohol having 1 to 4 carbon atoms, fermented alcohol or a mixed solvent thereof; And
ii) 상기 추출물을 크로마토그래피를 이용하여 전개액으로 물, 메탄올을 이용하여 로 분리하여 시아니딘 3-O-글루코사이드를 순수 분리 동정하는 단계;ii) separating the extract with water and using methanol as a developing solution using chromatography to identify and isolate pure cyanidin 3-O-glucoside;
를 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 치료용 약학적 조성물의 제조 방법을 제공한다.
Helicobacter pylori (Helicobater containing pylori ) provides a method for producing a pharmaceutical composition for the prevention or treatment of infectious diseases.
본 발명의 또 다른 양태에 따르면, 본 발명은 흑미 추출물 또는 흑미 용매 분획물을 유효성분으로 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 경감을 위한 건강식품을 제공한다.According to another aspect of the present invention, the present invention, Helicobacter pylori ( Helicobater) comprising a black rice extract or a black rice solvent fraction as an active ingredient pylori ) Provides health foods for the prevention or alleviation of infectious diseases.
본 발명의 조성물은 위염, 위궤양 및 십이지장궤양 등의 위염, 위궤양, 위십이지장궤양, 소화성 궤양 또는 위암의 개선을 목적으로 건강기능식품에 첨가될 수 있다. 본 발명의 흑미 용매 분획물을 식품 첨가물로 사용할 경우, 상기 흑미 용매 분획물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다.The composition of the present invention can be added to health functional foods for the purpose of improving gastritis such as gastritis, gastric ulcer and duodenal ulcer, gastric ulcer, gastroduodenal ulcer, peptic ulcer or gastric cancer. When the black rice solvent fraction of the present invention is used as a food additive, the black rice solvent fraction may be added as it is or may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method.
본 발명의 바람직한 구현예에 따르면, 상기 건강식품은 분말, 과립, 정제, 캡슐 및 음료로 이루어지는 군으로부터 선택되는 형태로 제조 가능하다.
According to a preferred embodiment of the present invention, the health food can be manufactured in a form selected from the group consisting of powder, granule, tablet, capsule and beverage.
본 발명의 조성물이 식품 조성물로 제조되는 경우, 유효성분으로서 흑미 추출물 또는 분획물뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다.When the composition of the present invention is prepared as a food composition, it contains not only the black rice extract or the fraction as an active ingredient but also a component ordinarily added at the time of food production, for example, a protein, a carbohydrate, a fat, a nutrient, And flavoring agents. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings.
예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 욱리인 추출물 또는 분획물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다. For example, when the food composition of the present invention is prepared as a drink, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, jujube extract, licorice extract, Can be included.
유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에는 본 발명의 흑미 용매 분획물은 원료에 대하여 15 중량% 이하, 바람직하게는 10 중량% 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). Generally, the black rice solvent fraction of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range .
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health functional foods in a conventional sense.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01~0.20 중량부의 범위에서 선택되는 것이 일반적이다.
In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.20 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시 예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention, and it is to be understood by those skilled in the art that the present invention is not limited thereto It will be obvious.
1. One. 실시예Example 1: One: 흑미Black rice 추출물의 제조 Preparation of extract
농촌진흥청 국립식량과학원 기능성작물부에서 수확한 흑미를 도정하여 현미를 분쇄한 5kg을 추출용매인 발효주정 20L을 가하여 실온에서 24시간 교반하여 추출한 후, 어드반텍 번호 2 종이여지로 여과 후 여액을 감압농축기를 이용하여 농축하여 진한 적갈색의 점액상의 흑미 추출물을 제조하여 하기 실험예의 시료로 사용하였다. 또한 상기 추출물을 이용하여 역상 실리카겔 컬럼크로마토그래피 (400g, 70~230 메쉬, Merk)를 수행하였으며, 이동상 용매로는 물, 메탄올 (100:1 ~ 1:1 혼합비) 혼합용매을 순차적으로 사용하여 적색의 추출물을 얻고 이를 정제하여 시아니딘 3-O-글루코사이드를 각각 3.5 g 을 얻었다. 순수분리한 흑미 유래 시아니딘 3-O-글루코사이드는의 역상 TLC 페턴은 도 1에 나타내었다.
Rural Development Administration 5kg of brown rice harvested from the Department of Nutritional Science, National Institute of Food Science and Technology was crushed and added with 20L of fermented alcohol as an extraction solvent. The mixture was stirred at room temperature for 24 hours for extraction. After filtration with 2 layers of Advantek filter paper, The concentrate was concentrated using a concentrator to produce dark reddish brown mushroom black rice extract, which was used as a sample in the following experimental example. Reverse phase silica gel column chromatography (400 g, 70-230 mesh, Merk) was carried out using the above extract. As a mobile phase solvent, a mixed solvent of water and methanol (100: 1 to 1: 1 mixture ratio) The extract was purified and purified to obtain 3.5 g of cyanidin 3-O-glucoside, respectively. The reversed-phase TLC pattern of cyanidin-3-O-glucoside derived from pure black rice was shown in Fig.
2. 2. 실험예Experimental Example 1: One: 흑미Black rice 추출물의 Extract 시아니딘Cyanidin 3-O- 3-O- 글루코사이드Glucoside 화합물 구조 분석 Compound structure analysis
상기 실시예 1에서 얻은 물질을 GC-MS/Ms 분석기 (Gas chromatography mass-mass chromatography)를 사용하여 표준물질과 비교하여 검출시간, 분자량 및 분자의 딸이온 등을 통해 분자구조를 결정하였으며 또한, 핵자기공명분광기(Nuclear Magnetic Resonance)를 이용하여 탄소와 수소의 상관관계를 분석환 결과 시아니딘-3-O-글루코사이드 화합물로 동정하였다. 분리한 시아니딘 3-O-글루코사이드의 화학구조는 표 1에 나타내었다.[일반미(남평벼) 및 흑미(조생흑찰외 3종)의 발효주정 추출물의 헬리코박터 파이로리의 억제활성 (처리농도 0.1, 1, 10 mg/disk)]The molecular structure of the material obtained in Example 1 was determined by GC-MS / Ms (mass spectrometry) mass spectrometry using detection time, molecular weight and daughter ion of the molecule. The correlation between carbon and hydrogen was analyzed using a magnetic resonance spectrometer (Nuclear Magnetic Resonance), and the result was identified as a cyanidin-3-O-glucoside compound. The chemical structure of the separated cyanidin 3-O-glucoside is shown in Table 1. [Inhibitory activity of Helicobacter pylori on fermented extract of fermented mung bean (Nambu rice) and
[화학식 1][Formula 1]
화합물 명: 시아니딘 3-O-글루코사이드Compound name: Cyanidin 3-O-glucoside
1) 물성 : 적색파우더 1) Properties: Red powder
2) 분자량 : 449 2) Molecular weight: 449
3) 분자식 : C21H21O11+
3) Molecular formula: C 21 H 21 O 11 +
3. 3. 실험예Experimental Example 2: 2: 흑미의Black 시아니딘Cyanidin 3-O- 3-O- 글루코사이드Glucoside 최적추출법 확인 Optimal Extraction Method
80%(w/v) 발효주정과, 0.1%(w/v) 시트르산을 첨가하여 안토시아닌 색소가 함유된 흑미 추출물을 안정화하고, PH 3이하에서 -5℃ ~ 5℃ 하에서 암소에 저장하며 감압농축한 후 천연식용색소 시아니딘 3-O-글루코사이드가 포함된 흑미 추출물을 제조하였다
A black rice extract containing anthocyanin pigment was stabilized by adding 80% (w / v) fermented alcohol and 0.1% (w / v) citric acid and stored in a dark place at -5 ° C to 5 ° C under
4. 4. 실험예Experimental Example 3: 3: H. H. pyloripylori 배양 culture
면양혈액배지 또는 Brucella 배지를 사용하여 H. pylori (ATCC 49503) 균주를 배양하였으며, 항균활성 실험을 위해서는 Mueller-hinton broth 또는 Mueller-Hinton agar 배지를 사용하였음. 세균은 100% 습도를 유지하는 10% CO2 배양기에서 3일 동안 배양하였다.
H. pylori (ATCC 49503) strains were cultured using sheep blood medium or Brucella medium. Mueller-hinton broth or Mueller-Hinton agar medium was used for antimicrobial activity. Bacteria were cultured for 3 days in a 10% CO 2 incubator maintained at 100% humidity.
5. 5. 실험예Experimental Example 4: 헬리코박터 4: Helicobacter 파이로리Pyory 억제활성 검정에 대한 것( For inhibitory activity assays ( paperpaper diskdisk 법)method)
준비된 여러 가지 흑미를 다양한 농도로 paper disk에 적용하여 도 1에 기재된 바와 같이 H. pylori 억제활성을 검사하였다. 도 1에서 보여지듯이 흑미 추출물들은 헬리코박터 파이로리에 대하여 특이적인 억제활성을 보였다.
Various preparations of black rice were applied to paper disks at various concentrations to examine H. pylori inhibitory activity as shown in FIG. As shown in FIG. 1, the black rice extracts showed specific inhibitory activity against Helicobacter pylori.
6. 6. 실험예Experimental Example 5: 5: 흑미추출물의Black Rice Extract 세포독성 검정 Cytotoxicity assay
위장관 세포주인 KATO Ⅲ에 흑미추출물을 처리하여 48시간에 걸쳐 세포 독성 검사를 실시하였음. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay를 기반으로 하여 흑미추출물 처리에 의한 세포사멸(necrosis, apoptosis를 모두 포함한 세포사멸) 유도 여부를 검사하였다.KATO Ⅲ, a gastrointestinal cell line, was treated with black rice extract and tested for cytotoxicity over 48 hours. Based on the assay of 3- [4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide (MTT), it was examined whether cell death (necrosis, apoptosis including all cell death) .
① 위장관 세포주인 KATO Ⅲ에 흑미추출물을 처리하여 48시간에 걸쳐 세포 독성 검사를 실시한 결과, 흑미추출물은 세포사멸(necrosis, apoptosis를 모두 포함한 세포사멸)을 유도하지 않는다는 결과를 얻었다. 흑미추출물은 세포독성을 유발하지 않는 것으로 확인할 수 있었다(도 2).(1) KATO Ⅲ, a gastrointestinal cell line, was treated with black rice extract for 48 hours. The results showed that black rice extract did not induce apoptosis (necrosis, including apoptosis). It was confirmed that the black rice extract does not induce cytotoxicity (FIG. 2).
② 위장관 세포주인 KATO Ⅲ에 흑미추출물을 처리하여 세포 독성 검사를 실시한 결과, 흑미추출물은 세포사멸(apoptosis)과 관련된 단백의 활성이나 발현에 관여하지 않는다는 결과를 얻었다. 흑미추출물은 세포독성을 유발하지 않는 것으로 판단된다(도 3).
(2) KATO Ⅲ, a gastrointestinal cell line, was treated with black rice extract and cytotoxicity tests revealed that black rice extract was not involved in the activity or expression of apoptosis related protein. It is considered that the black rice extract does not induce cytotoxicity (Fig. 3).
7. 7. 실험예Experimental Example 6: 6: 흑미추출물에In black rice extract 의한 by H. H. pyloripylori 감염 세포의 세포사멸의 억제활성 검정 Inhibition activity of cell death of infected cells
H. pylori에 감염시킨 KATO Ⅲ 세포주(세포 1개 당 세균 200개 비율로 감염)에 흑미추출물을 처리한 뒤에 세균 감염에 의하여 유발된 세포사멸(apoptosis)의 억제 여부를 검사하였으며(caspase-8,-3,-7. PARP에 대한 western blotting 실시), 세포 사멸 억제 단백질들의 발현 변화를 검사하였다.(survivin, XIAP에 대한 western blotting 실시)
The black rice extract was treated with H. pylori -infected KATO III cell line (200 bacteria per cell) and tested for inhibition of apoptosis induced by bacterial infection (caspase-8, Western blotting for PARP) and expression changes of apoptosis inhibitory proteins were examined (survivin, western blotting for XIAP).
① 위장세포주인 KATO Ⅲ에 H. pylori를 감염시킨 후, 흑미추출물을 처리하여 세포사멸(necrosis, apoptosis를 모두 포함한 세포사)에 미치는 영향을 살펴본 결과, 흑미추출물 처리 후 48시간이 경과하면 약 58%의 세포사멸 억제효과가 있는 것으로 판단된다(도 4).① After infection of gastrointestinal cell line KATO Ⅲ with H. pylori , the treatment of black rice extract and its effects on cell death (necrosis, apoptosis including cell death) was observed. Approximately 48% after black rice extract treatment It is judged that there is an apoptosis inhibitory effect (FIG. 4).
② H. pylori에 감염시킨 KATO Ⅲ 세포주(세포 1개 당 세균 200개 비율로 감염)에 흑미추출물을 처리한 결과, 세균감염에 의하여 유발된 세포사멸(apoptosis)이 억제되는 경향을 나타내었으며(caspase-8,-3,-7. PARP), 세포사멸억제 단백질들(survivin, XIAP)의 발현이 증가하는 경향이 관찰되었다. 이를 통하여 흑미추출물은 H. pylori 감염에 의하여 유도되는 세포사멸을 억제시키는 효과를 가지는 것으로 판단된다(도 5).
② As a result of treatment of black rice extract on KATO Ⅲ cell line (200 bacteria per cell) infected with H. pylori , apoptosis induced by bacterial infection was suppressed (caspase). A trend of increasing expression of PARP) and apoptosis proteins (survivin, XIAP) was observed. Through this, black rice extract is judged to have an effect of inhibiting apoptosis induced by H. pylori infection (FIG. 5).
8. 실험예 7: 흑미추출물을 이용한 H. pylori 감염동물 치료와 관련된 전임상 실험 
흑미추출물 투여 2주 전에 Mongolian gerbil에게 1 x 109 씩의 H. pylori를 경구를 통하여 감염시킨 후, 고농도(50 mg/kg)와 저농도(10 mg/kg)로 제균을 시도하였다. 주 3회 씩 총 8주간 경구를 통하여 H. pylori에 감염된 동물에게 흑미추출물을 투여하였다. Two weeks before the administration of black rice extract, Mongolian gerbil was orally infected with 1 x 10 9 H. pylori , and then sterilized at high concentration (50 mg / kg) and low concentration (10 mg / kg). Black rice extract was administered to H. pylori -infected animals by oral 3 times a week for a total of 8 weeks.
1) Anti-H. pylori 항체를 이용하여 흑미추출물 처리에 의한 H. pylori 제균 여부를 조직면역화학염색을 통하여 검사하였고, 2) H&E 염색을 실시하여 세균 감염 후 동반되는 염증 개선 효과를 검사하였으며, 3) 세균 감염시 동물의 혈액내에서 증가하였던 면역세포의 수치 변화를 측정하였고, 4) 마지막으로 정상 실험동물에게 흑미추출물을 8주간 반복 투여한 뒤에 H&E 염색을 실시하여 간독성 및 신독성을 유발하는지 검사하였다.
1) H. pylori eradication by anti- H. Pylori antibody treatment using black rice extract was examined by histological immunochemical staining. 2) H & E staining was performed to examine the effects of inflammation improvement after bacterial infection. 3) Changes in the level of immune cells in the blood of the animals during bacterial infection were measured. Inspected.
9. 9. 실험예Experimental Example 8: 8: 흑미Black rice 추출물 처리시 When treating extracts H. H. pyloripylori 분비 독소 ( Secretion toxins ( CagCag A, A, VacVac A)의 A) 분비역제효과Antisecretory effect
흑미 추출물 처리시 H. pylori 분비 독소 (Cag A, Vac A)의 분비역제효과에 대한 웨스턴 블랏팅 결과 및 RT-PCR 결과를 확인하였다(도 6, 도 7 및 도 8).Western blotting results and RT-PCR results for secretion inhibitory effects of H. pylori secretion toxins (Cag A, Vac A) were observed when the black rice extract was treated (FIGS. 6, 7 and 8).
① 웨스턴 블랏팅 실험 결과 H. pylori 배양액에 다양한 농도(0 ~ 1600 μg/ml)의 흑미추출물을 처리하였다(컨트롤, 100, 200, 400, 800, 1600 μg/ml). 도 6에서 보여지듯이, 도 6의 패널 (A)에서는 CagA, VacA 독소의 분비가 억제되는 경향을 보였으며, 패널 (B)에서는 CagA, VacA 독소가 분비되지 못하여 세균 내에 축적되는 경향을 보여준다. 패널 (C)의 경우 분비된 다른 단백질에서는 정량적 변화가 관찰되지 않았다. 패널 (D)는 세균 내 다른 단백질에서는 정량적 변화가 관찰되지 않았다. ① Western blotting experiment results The black rice extract of various concentrations (0 ~ 1600 μg / ml) was treated in H. pylori culture (control, 100, 200, 400, 800, 1600 μg / ml). As shown in FIG. 6, the secretion of CagA and VacA toxins was suppressed in the panel (A) of FIG. 6 and the CagA and VacA toxins were not secreted in the panel (B). In panel (C), no quantitative changes were observed in other secreted proteins. Panel (D) showed no quantitative change in other proteins in bacteria.
② RT-PCR 실험 결과 도 7에서 보여지듯이, H. pylori 배양액에 흑미 추출물을 첨가하였을 때, cagA, vacA, 등의 독소 단백 유전자의 전사(transcription)가 억제되는 경향을 관찰할 수 있었다(패널 A). 이러한 영향으로 인하여 독소 단백의 발현이 억제되는 것으로 판단할 수 있다. 또한, CagA와 VacA 독소의 분비에 관여하는 분비체계(type Ⅳ, Ⅴa secretion system)를 조절하는 효소 유전자인 secA의 전사 역시 억제되는 경향을 보였다(패널 B, 패널 C). 대조군으로 설정한 UDP-galactose 4-epimerase를 비롯한 다른 유전자들의 전사에는 영향이 없었다(패널 D).As a result of the RT-PCR experiment, as shown in FIG. 7, when the black rice extract was added to the H. pylori culture, it was observed that the transcription of toxin protein genes such as cag A, vac A, and the like was suppressed ( Panel A). These results suggest that the expression of toxin protein is inhibited. Transcription of sec A, an enzyme gene regulating the secretion systems involved in the secretion of CagA and VacA toxins (type Ⅳ, Ⅴ a secretion system) also tended to be suppressed (Panel B, Panel C). There was no effect on the transcription of other genes including the UDP-galactose 4-epimerase set as control (panel D).
이로써, 흑미추출물은 H. pylori 독소 단백의 발현은 물론, 독소 단백의 분비 까지도 억제시킬 수 있는 물질인 것으로 판단된다.
Thus, the black rice extract is believed to be a substance capable of inhibiting the expression of H. pylori toxin protein as well as the secretion of toxin protein.
10. 10. 실험예Experimental Example 9: 9: 흑미Black rice 분획물Fraction 처리시 When processing H. H. pyloripylori 분비 독소 ( Secretion toxins ( CagCag A, A, VacVac A)의 A) 분비역제효과Antisecretory effect
도 8에서 보여지듯이, 흑미 추출물에서 분리한 안토시아닌 및 안토시아닌 종류별 H. pylori에 처리시 분비 독소 (CagA, VacA)의 억제 효과에 대한 RT-PCR 결과를 판단하였다.As shown in Figure 8, RT-PCR results were determined for the inhibitory effect of secretion toxins (CagA, VacA) upon treatment of H. pylori by anthocyanin and anthocyanin type isolated from black rice extract.
레인 6은 흑미 추출물을 처리한 결과로 Cag A 및 Vac A의 발현을 억제하는 효과가 있음을 확인할 수 있었으며, 흑미 추출물 중 분획물에 포함되는 시아니딘-3-O-글루코사이드를 처리하였을 때에는 Vac A 및 Sec A mRNA의 발현량이 감소되었다.
11. 11. 실험예Experimental Example 10: 10: H. H. pyloripylori 감염모델 ( Infection Model 전임상Preclinical ) 확인 및 ) OK and 흑미Black rice 추출물 처리시 헬리코박터 Helicobacter during extract treatment 파이로리Pyory 억제활성의 면역조직화학 ( Immunohistochemistry of Inhibitory Activity ( ImmunohistochemistryImmunohistochemistry ) 실험) Experiment
흑미추출물 투여 2주 전에 Mongolian gerbil에게 1 x 109 씩의 H. pylori를 경구를 통하여 감염시킨 후, 고농도(50 mg/kg)와 저농도(10 mg/kg)로 제균을 시도하였다. 주 3회 씩 총 8주간 경구를 통하여 H. pylori에 감염된 동물에게 흑미추출물을 투여하였으며, 위 그림과 같은 치료효과를 확인하였다. (붉은색 화살표는 anti-H. pylori 항체에 대한 양성반응을 나타냄) 흑미추출물은 H. pylori 제균에 있어서 탁월한 효과를 가지는 것으로 판단된다. 고농도에서는 물론, 저농도 치료군에서도 H. pylori 제균이 가능하였다.
Two weeks before the administration of black rice extract, Mongolian gerbil was orally infected with 1 x 10 9 H. pylori , and then sterilized at high concentration (50 mg / kg) and low concentration (10 mg / kg). Black rice extract was administered to H. pylori -infected animals orally three times a week for a total of eight weeks. (Red arrow indicates positive response to anti- H. Pylori antibody) Black rice extract is considered to have an excellent effect on H. pylori eradication. H. pylori eradication was possible in high and low concentration treatment groups.
12. 12. 실험예Experimental Example 11: 11: H. H. pyloripylori 감염모델 ( Infection Model 전임상Preclinical ) ) 흑미Black rice 추출물 처리시 위장 염증 억제효과 검정 Gastrointestinal inflammation inhibitory effect on extract treatment
H. pylori 감염 후, 치료를 시행하지 않은 그룹에서는 세균감염에 따른 재반증상인 조직탈락, 출혈, 등의 조직병리학적 염증 소견이 관찰되었으나, 흑미추출물을 투여하여 치료를 시도한 그룹에서는 조직탈락 및 출혈이 현저하게 감소한 결과를 살펴볼 수 있었다(도 10). 이로써, 흑미추출물은 세균 감염에 의하여 유도되는 염증에도 개선 효과를 가지는 것으로 판단된다.
After H. pylori infection, histopathological inflammatory findings such as tissue loss, bleeding, and other recurrent symptoms of bacterial infection were observed in the untreated group. This markedly reduced result could be seen (FIG. 10). Thus, it is considered that the black rice extract has an improving effect on the inflammation induced by the bacterial infection.
13. 13. 실시예Example 12 : 12: H. H. pyloripylori 감염모델( Infection Model 전임상Preclinical )에 )on 흑미추출물을Black rice extract 처리후After processing 실시한 혈액학적 분석결과 Hematological analysis results
도 11에서 보여지듯이 일반적으로 생체 내에서 세균 감염증 발생할 경우, 혈액 내에서 호중구(neutrophil)를 비롯한 면역세포들의 수치가 급증하는 경향을 보이는데, H. pylori에 감염된 Mongolian gerbil에서도 동일한 증상을 살펴볼 수 있었다. 그러나 흑미추출물을 8주간 투여한 결과, 호중구(neutrophil)를 비롯한 면역세포들의 수치가 정상범위로 회복되는 경향을 확인할 수 있었음. 흑미추출물은 H. pylori 제균 효과를 가지는 것으로 판단된다.
As shown in FIG. 11, in general, when bacterial infection occurs in vivo, the level of immune cells including neutrophils tends to increase rapidly in blood, and the same symptom was observed in Mongolian gerbil infected with H. pylori . However, as a result of administration of black rice extract for 8 weeks, the level of neutrophil and other immune cells tended to recover to normal range. Black rice extract is thought to have H. pylori eradication effect.
14. 14. 실시예Example 13: 13: H. H. pyloripylori 감염모델( Infection Model 전임상Preclinical )에 )on 흑미추출물을Black rice extract 처리시 When processing 간독성Hepatotoxicity 및 And 신독성Nephrotoxicity 분석 결과 Analysis
도 12에서 보여지듯이, 정상 Mongolian gerbil에게 두 가지 농도(50 mg/kg, 10 mg/kg)의 흑미추출물을 주 3회 씩 8주간 반복 투여를 실시한 결과, Mongolian gerbil에서 간독성 및 신독성이 나타나지 않았다. 본 실시예의 판단 결과 흑미추출물은 인체에 적용하여도 안전한 물질인 것으로 판단된다.
As shown in Figure 12, the normal Mongolian gerbil two times (50 mg / kg, 10 mg / kg) black rice extract three times a week for 8 weeks repeated administration, Mongolian gerbil did not show hepatotoxicity and nephrotoxicity . As a result of the determination of the present embodiment, it is determined that the black rice extract is a safe substance to be applied to the human body.
Claims (9)
Helicobacter pylori ( Helicobater) comprising black rice extract or black rice solvent fraction as an active ingredient pylori ) A pharmaceutical composition for preventing or treating an infectious disease.
The pharmaceutical composition of claim 1, wherein the Helicobacter pylori infection disease is gastritis, gastric ulcer, gastroduodenal ulcer, peptic ulcer or gastric cancer.
The pharmaceutical composition according to claim 1, wherein the black rice solvent fraction is extracted from black rice extract using water, a lower alcohol having 1 to 4 carbon atoms, fermented alcohol or a mixed solvent thereof.
The pharmaceutical composition according to claim 1, wherein the black rice extract or the black rice solvent fraction exhibits a Helicobacter pylori eurease inhibitory activity and a toxin secretion inhibitory activity of CagA, VacA, SecA.
[화학식 1]
The pharmaceutical composition of claim 1, wherein the black rice solvent fraction comprises cyanidin 3-O-glucoside represented by the following Chemical Formula 1.
[Chemical Formula 1]
The pharmaceutical composition according to claim 1, wherein the content of the black rice extract or the black rice solvent fraction as the active ingredient is 0.1 to 50% by weight based on the total weight of the composition.
ii) 상기 추출물을 크로마토그래피를 이용하여 전개액으로 물, 메탄올을 이용하여 로 분리하여 시아니딘 3-O-글루코사이드를 순수 분리 동정하는 단계;
를 포함하는 헬리코박터 파이로리(Helicobater pylori) 감염 질환의 예방 또는 치료용 약학적 조성물의 제조 방법.
i) pulverizing black rice and extracting the pulverized black rice using water, a lower alcohol having 1 to 4 carbon atoms, fermented alcohol or a mixed solvent thereof; And
ii) separating the extract with water and using methanol as a developing solution using chromatography to identify and isolate pure cyanidin 3-O-glucoside;
Helicobacter pylori (Helicobater containing pylori ) A method for preparing a pharmaceutical composition for preventing or treating an infectious disease.
Helicobacter pylori ( Helicobater) comprising the black rice extract or black rice solvent fraction of any one of claims 1 to 6 as an active ingredient pylori ) Health food for the prevention or alleviation of infectious diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020120084430A KR20140017818A (en) | 2012-08-01 | 2012-08-01 | Compositions for preventing or treating for diseases derived from helicobacter pylori comprising extract of black rice and health food thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020120084430A KR20140017818A (en) | 2012-08-01 | 2012-08-01 | Compositions for preventing or treating for diseases derived from helicobacter pylori comprising extract of black rice and health food thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020140108940A Division KR101644607B1 (en) | 2014-08-21 | 2014-08-21 | Compositions for Preventing or Treating for Diseases Derived from Helicobacter pylori comprising Extract of Black Rice and Health Food thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20140017818A true KR20140017818A (en) | 2014-02-12 |
Family
ID=50266188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020120084430A KR20140017818A (en) | 2012-08-01 | 2012-08-01 | Compositions for preventing or treating for diseases derived from helicobacter pylori comprising extract of black rice and health food thereof |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR20140017818A (en) |
-
2012
- 2012-08-01 KR KR1020120084430A patent/KR20140017818A/en active Application Filing
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110946196B (en) | Lithocarpus litseifolius electuary and preparation method thereof | |
| KR101125224B1 (en) | A composition for skin anti-aging comprising extracts or fractions of Eremochloa ophiuroides as an active ingredient | |
| KR101909999B1 (en) | NOVEL STRAIN OF Leuconostoc mesenteroides AND COMPOSITION FOR PREVENTING OR TREATING OF CANCER USING THE SAME | |
| KR101644607B1 (en) | Compositions for Preventing or Treating for Diseases Derived from Helicobacter pylori comprising Extract of Black Rice and Health Food thereof | |
| KR102315959B1 (en) | A composition for reinforcing immune function comprising the extract of oat sprout | |
| KR101747246B1 (en) | A antibiotic composition for Helicobacter pylori containing the purified honey | |
| KR20110064910A (en) | An antibacterial composition comprising the essential oil extract of kjellemaiella crassifolia and the compounds isolated therefrom | |
| TW202038747A (en) | Kimchi for prevention or treatment of disease related to helicobacter pylori | |
| KR102275055B1 (en) | Composition comprising scutellaria alpina extract | |
| KR101494664B1 (en) | fermented corni fructus composition with antioxidant activity and method of making the same | |
| KR101685829B1 (en) | Method for prepareing fermented extract of mistletoe having enhanced antioxidative effect | |
| KR101077202B1 (en) | Extract Antibiotic to Helicobacter pylori Extracted from Persimmon Leaves | |
| KR102133473B1 (en) | A composition as a prebiotic for improving intestinal microflora containing sweet potato vines | |
| KR102042151B1 (en) | A composition as a prebiotic for improving intestinal microflora containing extract from pepper leaves | |
| KR102064516B1 (en) | An antibacterial composition comprising an leaf and root extract of cudrania tricuspidata, and extract of licorice | |
| KR20110092482A (en) | Improvemnet of anti-inflammatory activity of hibiscus cannabbinus extract by far infrared ray drying process | |
| KR101750854B1 (en) | A antibiotic composition for Helicobacter pylori containing the propolis extraction fractions thereof or subfractional extrats isolated therefrom | |
| KR20140017818A (en) | Compositions for preventing or treating for diseases derived from helicobacter pylori comprising extract of black rice and health food thereof | |
| KR20150106187A (en) | Composition for antioxidation comprising the seed extract of cornus officinalis | |
| KR102341772B1 (en) | Food composition comprising fermented pear and Oenanthe javanica for immunity enhancement and method for preparing the same | |
| KR101624293B1 (en) | Composition for enhancing immune response comprising extract of Benincasa hispida Cogniaux or fermented extract of the same | |
| KR101074348B1 (en) | Anti-helicobacter composition containing green algae extract | |
| KR102036860B1 (en) | A composition as a prebiotic for improving intestinal microflora containing corchorous olitorius | |
| KR101852032B1 (en) | Beverages for preventing hyperlipidemia containing Platycodon grandiflorum and its preparing method | |
| KR20220159594A (en) | Prebiotics composition containing oligosaccharide isolated from soybean fermented food as active ingredient and method for manufacturing same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E601 | Decision to refuse application | ||
| A107 | Divisional application of patent |