KR20210017726A - Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract - Google Patents
Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract Download PDFInfo
- Publication number
- KR20210017726A KR20210017726A KR1020190097454A KR20190097454A KR20210017726A KR 20210017726 A KR20210017726 A KR 20210017726A KR 1020190097454 A KR1020190097454 A KR 1020190097454A KR 20190097454 A KR20190097454 A KR 20190097454A KR 20210017726 A KR20210017726 A KR 20210017726A
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- group
- present
- gastric
- gastritis
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims abstract description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 208000007882 Gastritis Diseases 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title claims abstract description 11
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 title abstract description 17
- 244000173166 Pyrus ussuriensis Species 0.000 title abstract description 10
- 235000011572 Pyrus ussuriensis Nutrition 0.000 title abstract description 10
- 229960003692 gamma aminobutyric acid Drugs 0.000 title abstract description 9
- 238000004519 manufacturing process Methods 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 23
- 238000000855 fermentation Methods 0.000 claims abstract description 20
- 230000004151 fermentation Effects 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 235000013376 functional food Nutrition 0.000 claims abstract description 14
- 235000014443 Pyrus communis Nutrition 0.000 claims description 23
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 12
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 10
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 8
- 241000894006 Bacteria Species 0.000 claims description 8
- 239000004310 lactic acid Substances 0.000 claims description 8
- 235000014655 lactic acid Nutrition 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 abstract description 8
- 230000002708 enhancing effect Effects 0.000 abstract description 2
- 235000019441 ethanol Nutrition 0.000 description 24
- 240000001987 Pyrus communis Species 0.000 description 21
- 239000013642 negative control Substances 0.000 description 21
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 19
- 238000011282 treatment Methods 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 12
- 210000002784 stomach Anatomy 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 230000002496 gastric effect Effects 0.000 description 11
- 239000013641 positive control Substances 0.000 description 11
- 238000000605 extraction Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 210000001156 gastric mucosa Anatomy 0.000 description 9
- 229960001340 histamine Drugs 0.000 description 9
- 230000002265 prevention Effects 0.000 description 9
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 8
- 208000007107 Stomach Ulcer Diseases 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 240000006024 Lactobacillus plantarum Species 0.000 description 7
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 230000000692 anti-sense effect Effects 0.000 description 6
- 239000000469 ethanolic extract Substances 0.000 description 6
- 201000005917 gastric ulcer Diseases 0.000 description 6
- 210000004969 inflammatory cell Anatomy 0.000 description 6
- 230000003902 lesion Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 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 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 229960002986 dinoprostone Drugs 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 102100025841 Cholecystokinin Human genes 0.000 description 3
- 101800001982 Cholecystokinin Proteins 0.000 description 3
- 206010017856 Gastritis alcoholic Diseases 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 201000005988 alcoholic gastritis Diseases 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
- 210000004556 brain Anatomy 0.000 description 3
- 229940107137 cholecystokinin Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 3
- 230000036732 histological change Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229940072205 lactobacillus plantarum Drugs 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 2
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- 101000782236 Bothrops leucurus Thrombin-like enzyme leucurobin Proteins 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 108020004635 Complementary DNA Proteins 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
- 238000008157 ELISA kit Methods 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
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000009858 acid secretion Effects 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 235000021050 feed intake Nutrition 0.000 description 2
- 235000021107 fermented food Nutrition 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 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
- 210000004877 mucosa Anatomy 0.000 description 2
- 230000003551 muscarinic effect Effects 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000011002 quantification 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
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 238000007447 staining method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000009723 vascular congestion Effects 0.000 description 2
- 238000003809 water extraction Methods 0.000 description 2
- 239000012138 yeast extract Substances 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
- 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
- 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
- 108091006112 ATPases Proteins 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 208000035404 Autolysis Diseases 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 241000132536 Cirsium Species 0.000 description 1
- 206010009944 Colon cancer Diseases 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
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 238000002965 ELISA Methods 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
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 206010017788 Gastric haemorrhage Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation 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
- 241001468192 Leuconostoc citreum Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 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
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010067994 Mucosal atrophy Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 244000025272 Persea americana Species 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 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
- 235000004789 Rosa xanthina Nutrition 0.000 description 1
- 241000220222 Rosaceae Species 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000300264 Spinacia oleracea Species 0.000 description 1
- 235000009337 Spinacia oleracea Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 240000001949 Taraxacum officinale Species 0.000 description 1
- 235000005187 Taraxacum officinale ssp. officinale 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
- 210000001015 abdomen Anatomy 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 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
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000004596 appetite loss Effects 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
- 238000003149 assay kit Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 201000008937 atopic dermatitis Diseases 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
- 235000013361 beverage Nutrition 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 239000002775 capsule Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003850 cellular structure Anatomy 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
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000007799 cork Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 238000000635 electron micrograph Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000001839 endoscopy 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
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 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
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 229940124600 folk medicine Drugs 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000003736 gastrointestinal content Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract 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
- 238000012252 genetic analysis Methods 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 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
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 239000010903 husk Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 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
- 230000007102 metabolic function Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 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
- 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
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 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
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000001711 oxyntic cell Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229940065004 poison ivy extract Drugs 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect 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
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000019204 saccharin Nutrition 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
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 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
- 230000028327 secretion Effects 0.000 description 1
- 230000028043 self proteolysis Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars 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
- 230000008961 swelling Effects 0.000 description 1
- 239000003826 tablet 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
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 150000003626 triacylglycerols Chemical class 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
- 239000012137 tryptone Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
-
- 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
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/065—Microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- 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
- 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
- A23V2250/00—Food ingredients
- A23V2250/02—Acid
- A23V2250/038—Gamma-amino butyric acid
-
- 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
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Botany (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Epidemiology (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
본 발명은 산돌배 추출물에 관한다.The present invention relates to a sandolbae extract.
산돌배나무류는 장미과에 속하는 낙엽활엽수로서 과실, 뿌리, 수피, 줄기, 엽, 과피 등은 식용 뿐만 아니라 해열, 건위, 지갈, 이뇨, 항당뇨 등의 효능이 있어 예로부터 민간약으로 사용되어 왔다. 이와 관련하여 몇 가지 연구와 특허활동이 알려졌다. 대한민국 공개특허공보 제10-2018-0049355호는 배나무속 식물 추출물을 유효성분으로 하는 아토피 피부염의 예방 또는 치료용 약학 조성물을 개시한다. 대한민국 공개특허공보 제10-2010-0087068호는 천연물의 혼합 추출물을 통해 항산화 활성을 갖는 조성물을 제안했는데, 거기서 산돌배나무 줄기 껍질을 이용할 수 있음을 개시했다.As a deciduous broad-leaved tree belonging to the rosaceae family, fruits, roots, bark, stems, leaves, and pericarps are not only edible, but have antipyretic, dry stomach, chigal, diuretic, and antidiabetic effects, and have been used as a folk medicine for a long time. In this regard, several studies and patent activities have been known. Republic of Korea Patent Publication No. 10-2018-0049355 discloses a pharmaceutical composition for the prevention or treatment of atopic dermatitis using a plant extract of the genus pear as an active ingredient. Korean Patent Laid-Open Publication No. 10-2010-0087068 proposes a composition having antioxidant activity through mixed extracts of natural substances, and discloses that the bark of a pear tree can be used therein.
그러나 산돌배나무가 갖는 위 소화개선 및 위 염증 개선에 대한 연구는 알려져 있지 않았다. 특히 알코올에 유도되는 위염증에 관해 산돌배나무의 활용 가능성에 대한 연구는 관심을 얻지 못했다. 위 염증은 국내에서 고질병이라고 불릴 정도로 흔하게 나타난다. 그러나 그만큼 방치되는 경우가 많아 더욱 큰 질환으로 발전될 가능성이 크다. 국민건강보험공단 자료에 따르면 2010년 기준 위염환자는 541만명으로 연평균 4.9%씩 증가 추세였다. 성별로는 여성이 남성에 비해 1.6배 많았으며, 특히 20대에서 여성이 남성보다 2배 이상 높게 나타난다. However, studies on the improvement of gastric digestion and gastric inflammation of the pear tree have not been known. In particular, research on the possibility of using the pear tree for alcohol-induced gastric inflammation has not garnered interest. Gastric inflammation is so common that it is called chronic disease in Korea. However, it is highly likely to develop into a larger disease as it is often neglected. According to data from the National Health Insurance Service, the number of gastritis patients as of 2010 was 5.41 million, increasing by an annual average of 4.9%. By gender, women were 1.6 times more than men, and women in their twenties were more than twice as high as men.
알코올은 주로 위장과 소장에서 흡수되어 간으로 옮겨져 대사된다. 흡수된 알코올의 사람에 따라 최대 1/3 정도는 위장에서 알코올 가수분해 효소(alcohol dehydrogenase: ADH)에 의해 분해됨으로써 혈액을 통한 알코올 흡수가 최소화된다. Alcohol is mainly absorbed by the stomach and small intestine, transferred to the liver and metabolized. Depending on the person, up to a third of the absorbed alcohol is decomposed by alcohol dehydrogenase (ADH) in the stomach, thereby minimizing the absorption of alcohol through the blood.
알코올성 위염은 알코올로 인한 만성적인 자극에 의해 위 점막이 손상된 상태를 일컫는다. 알코올성 위염에 걸리면 소화가 잘 되지 않고 쓰린 느낌을 호소하는 경우도 있지만 대부분 특별한 증상이 없다가 내시경 검사와 초음파 검사를 통해 심각한 증상이 발견된다. 만성적으로 술을 마시는 경우 위염뿐만 아니라 췌장이나 간 등도 손상시켜 관련질환을 유발하며, 또한 식도암, 위암, 대장암의 위험도 높아진다. 특히, 알코올로 인한 위염 및 위궤양은 가장 주의를 요하는데, 알코올은 위벽의 세포를 자극해 산 분비를 증가 시키며, 과도한 알코올 섭취는 위점막의 부종을 발생시켜 출혈을 일으키고 염증세포들의 생성을 유도한다. 또한, 산화적 스트레스로 인한 괴사 혹은 세포사멸을 유도하여 위점막을 손상시키고, 위출혈이 나타나게 된다. Alcoholic gastritis refers to a condition in which the gastric mucosa is damaged by chronic irritation caused by alcohol. Alcoholic gastritis is difficult to digest and sometimes complains of a sore sensation, but most do not have any special symptoms, and then serious symptoms are found through endoscopy and ultrasound. Chronically drinking alcohol causes related diseases by damaging not only gastritis, but also the pancreas or liver, and also increases the risk of esophageal cancer, stomach cancer, and colon cancer. In particular, gastritis and gastric ulcers caused by alcohol require the most attention. Alcohol stimulates the cells of the stomach wall to increase acid secretion, and excessive alcohol consumption causes swelling of the gastric mucosa, causing bleeding and inducing the production of inflammatory cells. . In addition, by inducing necrosis or apoptosis due to oxidative stress, the gastric mucosa is damaged, and gastric bleeding occurs.
종래의 위염 및 위궤양의 치료제로는 과다 분비된 위산을 중화시키는 제산제(antacid), 산 분비 억제 목적의 히스타민 길항제(histamine antagonist), 프로톤 펌프 저해제(proton pump inhibitor), 콜린 억제제, 위내막의 내성을 증가시키고 회복을 돕는 위점막보호제 등이 있다. 다만, 이와 같은 치료제들은 합성 의약품으로 식욕감퇴, 무력감, 알레르기 등의 부작용이 발생하는 문제점이 있었다.Conventional treatments for gastritis and gastric ulcer include antacids that neutralize excess gastric acid, histamine antagonists for the purpose of inhibiting acid secretion, proton pump inhibitors, choline inhibitors, and resistance to gastric lining. And gastric mucosa to help increase and recover. However, such treatments are synthetic drugs, and have problems such as loss of appetite, weakness, and allergies.
이러한 문제점을 회피하기 위해 다양한 천연 추출물에 대한 관심이 높아지고 있다. 그런 연구에 관련한 선행특허문헌으로는 대한민국 공개특허공보 제10-2009-0046425호(천마 추출물을 함유하는 위염 또는 위궤양의 예방 또는 치료용 조성물), 대한민국 특허공보 제10-1091025호(복분자 추출물을 함유하는 비스테로이드성 항염증제에 의해 유발된 위염 및 위궤양 예방 및 치료용 조성물), 대한민국 공개특허공보 제10-2012-0051904호(옻나무 추출물을 포함하는 위 염 및 위궤양 치료제 조성물), 대한민국 특허공보 제10-1204981호(고로쇠 수액을 함유하는 위염 및 위궤양의 예 방 및 치료용 조성물), 대한민국 공개특허공보 제10-2018-0085079호(엉겅퀴 및 흰민들레의 꽃과 뿌리를 제거한 전초 추출물을 함유하는 알코올성 위염의 예방, 개선 또는 치료용 조성물) 등이 있다.In order to avoid this problem, interest in various natural extracts is increasing. Prior patent documents related to such research include Korean Laid-Open Patent Publication No. 10-2009-0046425 (composition for preventing or treating gastritis or gastric ulcer containing Cheonma extract), Korean Patent Publication No. 10-1091025 (Containing Bokbunja extract) Composition for the prevention and treatment of gastritis and gastric ulcer caused by non-steroidal anti-inflammatory drugs), Korean Patent Publication No. 10-2012-0051904 (Gastritis and gastric ulcer treatment composition containing poison ivy extract), Korean Patent Publication No. 10- No. 1204981 (Composition for the prevention and treatment of gastritis and gastric ulcers containing Gorose sap), Korean Patent Laid-Open Publication No. 10-2018-0085079 (An alcoholic gastritis containing an outpost extract from which flowers and roots of thistle and white dandelion are removed Prevention, improvement or treatment composition), and the like.
본 발명의 발명자들은 산돌배나무를 건강 기능성 식품 또는 약제학적 조성물로 활용할 수 있는 가능성을 확인하기 위해 과학적인 방법론에 따라 오랫동안 실험한 끝에 본 발명을 완성하기에 이르렀다. The inventors of the present invention reached the completion of the present invention after long experiments according to scientific methodology in order to confirm the possibility of utilizing the pear tree as a health functional food or a pharmaceutical composition.
현대의 라이프 스타일을 감안하면 우리 현대 직장인들에게 위염에 걸리기 좋은 습관들이 만연되어 있다. 위염의 원인과 생활 속 치료법에 대해 명확하게 알고 개선하려는 노력이 매우 필요하다. 본 발명의 발명자들은, 현대 사회에서 빈번한 만성질환 중 하나인 위염에 사용 가능한 항위염 예방/치료/개선 용도로 활용 가능한 제품의 개발을 위하여 국내 임산자원 활용 가능성을 연구해 왔다. 그것이 성공한다면 국내 임산자원의 부가가치 창출을 위한 새로운 전기를 마련할 수 있을 것이다. 본 발명의 목적은 이러한 큰 기획 속에서 산돌배나무 추출물이 위 염증의 예방/치료/개선 관련한 제품화에 적합하다는 사실과 가장 바람직한 방법론을 동물실험결과에 의해 뒷받침되는 데이터에 기초하여 제안함에 있다.Considering the modern lifestyle, habits that are good for gastritis are prevalent among our modern office workers. It is very necessary to know clearly about the cause of gastritis and the treatment in life and to try to improve it. The inventors of the present invention have been studying the possibility of utilizing domestic forest resources to develop a product that can be used for gastritis prevention/treatment/improvement that can be used for gastritis, which is one of the frequent chronic diseases in the modern society. If it is successful, it will be able to provide a new momentum for creating added value of domestic forest resources. It is an object of the present invention to propose the fact that the extract of pear tree is suitable for commercialization related to the prevention/treatment/improvement of gastric inflammation in such a large project, and the most preferable methodology based on data supported by the results of animal experiments.
한편, 본 발명의 명시되지 않은 또 다른 목적들은 하기의 상세한 설명 및 그 효과로부터 용이하게 추론할 수 있는 범위 내에서 추가적으로 고려될 것이다.On the other hand, other objects not specified of the present invention will be additionally considered within a range that can be easily deduced from the detailed description and effects thereof below.
같은 과제를 달성하기 위해 본 발명의 제1국면은 산돌배 추출물을 유효성분으로 포함하는 알코올 유도성 위염 개선, 예방 또는 치료용 약제학적 조성물을 특징으로 한다.In order to achieve the same problem, the first aspect of the present invention is characterized by a pharmaceutical composition for improving, preventing or treating alcohol-induced gastritis, comprising an extract of Sandolbae as an active ingredient.
본 발명의 바람직한 어느 실시예에 따른 알코올 유도성 위염 개선, 예방 또는 치료용 약제학적 조성물에 있어서, 상기 산돌배 추출물은 젖산균, 효모, 고초균 중 두 개 이상의 균주를 이용하여 발효한 것이 좋다.In the pharmaceutical composition for improving, preventing or treating alcohol-induced gastritis according to a preferred embodiment of the present invention, the Sandolbae extract is preferably fermented using at least two strains of lactic acid bacteria, yeast, and Bacillus bacillus.
본 발명의 제2국면은 복합 발효 과정을 거쳐 감마-아미노뷰트라산 함량을 증진한 산돌배 추출물을 유효성분으로 포함하는 기능성 식품 조성물을 특징으로 한다.A second aspect of the present invention features a functional food composition comprising, as an active ingredient, an extract of gamma-aminobutraic acid with enhanced gamma-aminobutraic acid as an active ingredient.
본 발명의 바람직한 어느 실시예에 따른 산돌배 추출물을 유효성분으로 포함하는 기능성 식품 조성물에 있어서, 상기 복합 발효 과정은 젖산균, 효모, 고초균 중 두 개 이상의 균주를 각각 이용하여 단계별로 발효하는 것이 좋다.In the functional food composition comprising the extract of Sandolbae according to a preferred embodiment of the present invention as an active ingredient, the complex fermentation process is preferably fermented step by step using two or more strains of lactic acid bacteria, yeast, and Bacillus bacillus, respectively.
본 발명에 따르면 산돌배 추출물의 위염증 개선 효능의 구체적인 실시예 데이터에 의해 확인되었다. 그러므로 위염증의 예방 및 치료를 위한 약제학적 조성물 또는 기능성 식품 조성물을 제조할 수 있다. According to the present invention, it was confirmed by the data of specific examples of the efficacy of improving gastric inflammation of the extract of sandol pear. Therefore, it is possible to prepare a pharmaceutical composition or a functional food composition for the prevention and treatment of gastric inflammation.
또한 본 발명에 따르면 기능성 식품을 제조할 때 혼합 발효를 실시함으로써. 감마-아미노뷰트라산의 생성량과 효율을 향상시킬 수 있다.In addition, according to the present invention, by performing mixed fermentation when manufacturing a functional food. It can improve the production amount and efficiency of gamma-aminobutraic acid.
한편, 여기에서 명시적으로 언급되지 않은 효과라 하더라도, 본 발명의 기술적 특징에 의해 기대되는 이하의 명세서에서 기재된 효과 및 그 잠정적인 효과는 본 발명의 명세서에 기재된 것과 같이 취급됨을 첨언한다.On the other hand, even if it is an effect not explicitly mentioned herein, it is added that the effect described in the following specification and its provisional effect expected by the technical features of the present invention are treated as described in the specification of the present invention.
도 1은 본 발명의 비교예에서 위궤양 정량화를 통해 각 시험군을 궤양 수치를 비교하여 나타낸 도면이다.
도 2는 각 시험군의 위 점막의 형태를 나타내는 전자현미경사진이다. A는 CMC군, B와 C는 NC군, D는 PC군, E는 T1군, F는 T2군의 위 점막의 형태를 보여준다.
도 3은 각 시험군의 위 조직의 염색 조직학적 변화를 나타내는 사진이다.
도 4는 각 시험군의 PGE2, Histamine, cAMP 수준의 검출 결과를 비교하여 나타낸다.
※ 첨부된 도면은 본 발명의 기술사상에 대한 이해를 위하여 참조로서 예시된 것임을 밝히며, 그것에 의해 본 발명의 권리범위가 제한되지는 아니한다.1 is a view showing the comparison of ulcer values for each test group through gastric ulcer quantification in a comparative example of the present invention.
2 is an electron micrograph showing the shape of the gastric mucosa of each test group. A shows the morphology of gastric mucosa of CMC group, B and C group NC, D group PC, E group T1, and F group T2.
3 is a photograph showing the histological change of staining of gastric tissue of each test group.
Figure 4 shows the comparison of detection results of PGE2, Histamine, and cAMP levels of each test group.
※ The accompanying drawings are exemplified as reference for understanding the technical idea of the present invention, and the scope of the present invention is not limited thereto.
이하, 실험데이터와 테이블 및 도면을 참조하여 본 발명의 다양한 실시예가 안내하는 본 발명의 내용을 살펴본다. 본 발명을 설명함에 있어서 관련된 공지기능에 대하여 이 분야의 기술자에게 자명한 사항으로서 본 발명의 요지를 불필요하게 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명을 생략한다.Hereinafter, the contents of the present invention guided by various embodiments of the present invention will be described with reference to experimental data, tables, and drawings. In describing the present invention, when it is determined that the subject matter of the present invention may be unnecessarily obscured as matters obvious to those skilled in the art with respect to known functions related to the present invention, detailed description thereof will be omitted.
<산돌배 추출물(Pyrus Ussuriensis extract)>< Pyrus Ussuriensis extract>
바람직하게는 열수 추출법에 의해 산돌배 추출물을 제조하였다. 우리가 진행했던 방법을 예시적으로 설명하자면, 건조 산돌배(Pyrus ussuriensis Maxim)의 9배에 해당하는 양의 증류수 끓인 후, 건조 산돌배를 넣어 30분간 용출시켰다. 그다음 침지시킨 산돌배를 핸드블랜더를 이용하여 분쇄한 후, 거름망을 이용하여 씨와 껍질 등의 불용성 물질들을 제거함으로써 산돌배 추출물을 얻을 수 있었다.Preferably, a sandol pear extract was prepared by hot water extraction. To illustrate the method we proceeded exemplarily, after boiling in distilled water equivalent to 9 times the amount of dry sandol pear (Pyrus ussuriensis Maxim), the dried sandol pear was added and eluted for 30 minutes. Then, after crushing the soaked sandol pear using a hand blender, insoluble substances such as seeds and skins were removed using a strainer to obtain a sandol pear extract.
그밖에 주정추출, 약탁추출 등의 대용 방법을 사용할 수도 있음을 첨언한다.In addition, it should be noted that alternative methods such as alcohol extraction and medicine turbid extraction may be used.
그런 다음 위와 같은 산돌배 추출물로부터 열수 추출액을 얻었다. 바람직하게는 50% 에탄올 추출물이 최적이었다. 50% 에탄올 추출물의 추출온도와 추출시간을 설정하고자 실험한 결과는 아래의 표 1과 같다.Then, a hot water extract was obtained from the above sandolbae extract. Preferably, 50% ethanol extract was optimal. The results of the experiment to set the extraction temperature and extraction time of the 50% ethanol extract are shown in Table 1 below.
결과적으로 추출물의 추출온도는 80℃, 추출시간은 6시간으로 50% 알코올 산돌배 추출 시료를 얻고 추출시료를 분석하였다. As a result, the extraction temperature of the extract was 80°C and the extraction time was 6 hours to obtain a 50% alcoholic acidol pear extraction sample and analyzed the extraction sample.
상기 산돌배 열수 추출액의 시료를 이화학적으로 분석한 결과 pH 4.49, 산도 0.32%를 보였으며, 총 당 5.6%, 환원성 당 2.7%로 나타났다. 또한 단백질 36.3μg/mL, 총 플라보노이드 함량이 29.5μg/mL로 측정되었으며, 추출액(w/w)의 폴리페놀 함량은 400.4μg/mL으로 상당히 높은 것이 확인되었다. As a result of physicochemical analysis of the sample of the Sandolbae hot water extract, the pH was 4.49 and the acidity was 0.32%, and the total sugar was 5.6% and the reducing sugar was 2.7%. In addition, the protein 36.3 μg/mL and the total flavonoid content were measured to be 29.5 μg/mL, and the polyphenol content of the extract (w/w) was found to be quite high as 400.4 μg/mL.
또한 상기 산돌배 열수 추출액 시료에 대하여 총 7종의 무기질 분석을 수행하였다. 칼륨이 127.6mg/100g으로 가장 높은 함량을 나타내었으며, 인 8.52mg/100g, 소듐 5.11mg/100g, 마그네슘 4.78mg/100g, 칼슘 3.51mg/100g, 철 0.23mg/100g, 망간 0.05mg/100g 순으로 함유하고 있는 것을 확인하였다. 칼륨이 많은 식품으로는 아보카도, 감자, 시금치 등이 있으며 나트륨 흡수 저해와 비만에 영향을 준다는 연구가 많이 보고되고 있다. 따라서 산돌배를 이용하여 위장보호 뿐 아니라 성인병의 원인이 되는 비만과 나트륨 흡수를 저해하여 긍정적인 영향을 주는 제품을 개발 가능할 것으로 판단하였다.In addition, a total of 7 kinds of inorganic analysis were performed on the sample of the hot water extract of the sandol pear. Potassium showed the highest content at 127.6mg/100g, followed by phosphorus 8.52mg/100g, sodium 5.11mg/100g, magnesium 4.78mg/100g, calcium 3.51mg/100g, iron 0.23mg/100g, manganese 0.05mg/100g It confirmed that it contained. Foods high in potassium include avocado, potatoes, and spinach, and many studies have been reported that inhibit sodium absorption and affect obesity. Therefore, it was judged that it would be possible to develop a product that has a positive effect by inhibiting the absorption of sodium and obesity, which is the cause of adult diseases, as well as gastrointestinal protection by using Sandolbae.
[예비 동물실험][Preliminary animal experiment]
SD(Sprague Dowley) 랫드(rat)의 평균 체중 70-80g의 횐쥐를 예비실험에 사용하였다. 실험동물은 한국의 오리엔트 바이오(경기도, 한국)에서 무균으로 사육한 실험동물을 구입하였다. 사료와 음수는 자유롭게 급식을 실시하였다. 체중과 사료섭취량은 매일 측정을 하였다.Sprague Dowley (SD) rats with an average weight of 70-80 g were used in the preliminary experiment. Experimental animals were purchased aseptically bred at Orient Bio (Gyeonggi-do, Korea) in Korea. Feed and drinking water were fed freely. Body weight and feed intake were measured daily.
산돌배 에탄올 추출물의 위염 예방 확인시험을 위하여 10 마리의 Sprague-Dawley 랫드를 무작위로 4군으로 구분하였다. 시험군은 다음과 같다.In order to confirm the prevention of gastritis with the ethanol extract of Sandolbae, 10 Sprague-Dawley rats were randomly divided into 4 groups. The test groups are as follows.
Group A n=2, (only 0.5% CMC administration), Group A n=2, (only 0.5% CMC administration),
Group B: Normal Control (n=2, receiving 1 ml of 40% ethanol), Group B: Normal Control (n=2, receiving 1 ml of 40% ethanol),
Group C (n=3, 250 mg/Kg low dose of extract) Group C (n=3, 250 mg/Kg low dose of extract)
Group D (n=3, 500 mg/Kg high dose of extract)Group D (n=3, 500 mg/Kg high dose of extract)
이를 정리하면 아래의 표 2와 같다.This is summarized in Table 2 below.
* Pyrus Ussuriensis extract* Pyrus Ussuriensis extract
적응 기간은 1주일이었고 그 이후에 각 그룹의 투여를 실시하였다. 체중, 사료는 1일 간격으로 측정하였다.The adaptation period was one week, after which each group was administered. Body weight and feed were measured at 1 day intervals.
랫드 실험은 14일간 투여하였다. 40% 알코올 및 시료 투여 14 일째에 모든 동물은 희생하기 전에 1 시간 동안 대조군을 제외하고 70% 에탄올 (150mM HCl) 1 ml를 경구투여하였다. 모든 동물은 CO2로 마취시킨 후에 심장에서 혈액을 채취하고 경추탈골로 희생시켰다. 모든 동물은 육안적 소견으로 관찰을 하였으며 이상이 있을 경우 조직학적 소견을 진행하였다. 채취한 위장은 육안적 소견으로 위충혈과 위염의 정도를 확인하였다. 일부는 절단하여 포르말린에 고정하였고 일부는 유전자 분석을 위하여 -70℃에 보관하였다.Rat experiment was administered for 14 days. On the 14th day of 40% alcohol and sample administration, 1 ml of 70% ethanol (150 mM HCl) was orally administered to all animals for 1 hour before sacrifice, except for the control group. All animals were anesthetized with CO 2 , then blood was collected from the heart and sacrificed by cervical dislocation. All animals were observed with gross findings, and histological findings were performed in case of abnormalities. The collected gastrointestinal tract was visually confirmed to confirm the degree of gastritis and gastritis. Some were cut and fixed in formalin, and some were stored at -70°C for genetic analysis.
14일 동안 대조구를 포함한 모든 동물에서 체중의 변화에는 의미 있는 차이를 보이지 않았다. 예비 시험기간 동안 실험 전반에 걸쳐 체중 증가가 정상적으로 유지되고 수분 섭취도 정상이었다. 14일 후에 해부를 한 후에 랫드의 위장의 검사를 실시하였다.There was no significant difference in body weight change in all animals including the control for 14 days. During the preliminary test period, body weight gain was maintained normally throughout the experiment and water intake was normal. After 14 days of dissection, the rat's stomach was examined.
14 일 동안 40%의 에탄올만을 섭취 한 랫드(그룹 B: NC Group)는 혈관 상피 괴사와 심한 위염이 발견되었다.Rats (Group B: NC Group) who consumed only 40% ethanol for 14 days had vascular epithelial necrosis and severe gastritis.
저용량 250 mg/kg 추출물 투여군(그룹 C: group T1)은 작은 괴사 부위가 발견되었다.In the low-dose 250 mg/kg extract group (group C: group T1), small necrotic sites were found.
반면, 고용량 투여군의 랫드(그룹 D: group T2)는 약간의 위염만 보였으며 정상과 큰 차이를 보이지 않았다.On the other hand, rats in the high-dose group (group D: group T2) showed only slight gastritis, and there was no significant difference from normal.
[동물실험][Animal experiment]
시중에서 구입한 건조된 Pyrus ussuriensis 로부터 동일한 추출물을 얻기 위하여 Tang, X., et al 및 Reza, M.A., et al. [11, 12]에 기술된 방법을 따랐다. 요약하면 말린 Pyrus ussuriensis 과실을 분말 형태로 분쇄하고 전 실험에서 확인된 추출 비율인 건조된 산돌배분 1과 50% 에탄올 20을 무게중량비로 혼합하여 90℃에서 10시간 동안 환류 열수 추출을 실시하였다. 추출된 추출액은 여과지 (70 mm, Advantec, Toyo Roshi Kaisha Ltd, Japan)를 이용하여 추출 필터액을 얻었다. 여과된 여과액은 95℃에서 회전진공증발기(Buchi R-114, BUCHI Labortechnik AG, Flawil, Switzerland)로 농축을 농축시키고, 최종적으로는 동결건조(BioTron, Gangneung, Korea)를 실시하여 20℃에서 저장하였다.To obtain the same extract from commercially available dried Pyrus ussuriensis , Tang, X., et al and Reza, MA, et al. The method described in [11, 12] was followed. In summary, dried Pyrus ussuriensis fruit was pulverized into a powder form, and dried
Sprague Dowley (SD) rat 4 주령(체중 80-90g)의 수컷 50마리를 Orient BioInc.(경기도, 한국)에서 구입하여 7일 동안 적응기간을 거쳤다. 실험실의 사육조건은 24±3℃의 온도와 12 시간의 양/암 주기로 상대 습도에서 50±10%로 유지하였다. 사료와 음수는 자유롭게 섭취를 시켰다. 실험동물 시험은 경북대학교 동물윤리위원회의 승인(승인 번호 : KNU 2018-107)을 득한 후 실시하였다. 실험동물의 분류는 표 3과 같다. 본 동물실험은 총 50마리의 SD 랫드를 체중을 기초로 한 무작위로 각 군에 10마리씩 5그룹으로 구성하였다. 시험 약제는 투여 직전에 바로 제조하여 경구투여를 실시하였다.50 Sprague Dowley (SD) rats, 4 weeks old (weight 80-90g), were purchased from Orient BioInc. (Gyeonggi-do, Korea) and were acclimated for 7 days. The breeding conditions in the laboratory were maintained at a temperature of 24±3℃ and a relative humidity of 50±10% with a sheep/dark cycle of 12 hours. Feed and drinking water were freely ingested. Experimental animal tests were conducted after obtaining approval from the Animal Ethics Committee of Kyungpook National University (approval number: KNU 2018-107). The classification of experimental animals is shown in Table 3. In this animal experiment, a total of 50 SD rats were randomly divided into 5 groups of 10 rats in each group based on body weight. Test drugs were prepared immediately before administration and administered orally.
CMC: Carboxymethyl cellulose, PUE: 50% ethanol Extract from Pyrus ussuriensis CMC: Carboxymethyl cellulose, PUE: 50% ethanol Extract from Pyrus ussuriensis
시험물질 투여 후 살처분 마지막인 15일째에 실험에 사용된 모든 동물은 CO2 로 마취를 시킨 후 1 시간 동안 70% 에탄올(150 mM HCl 중) 1 ml를 투여하였고 그 후 쥐의 복부 대동맥으로부터 혈액 3 ml를 채혈하였다. 채혈된 혈액의 일부는 CBC 분석을 실시하였고 일부는 4℃에서 10 분 동안 1600 x g에서 원심분리 후에 혈청을 얻었다. 분리된 혈장은 생화학 분석 전까지 -20℃의 냉장고에 보관 하였다.After administration of the test substance, on the 15th day, the end of killing, all animals used in the experiment were anesthetized with CO 2 and then 1 ml of 70% ethanol (in 150 mM HCl) was administered for 1 hour, and then blood from the abdominal aorta of the rat. 3 ml was collected. Some of the collected blood was subjected to CBC analysis, and some were centrifuged at 1600 xg for 10 minutes at 4° C. to obtain serum. The separated plasma was stored in a refrigerator at -20°C until biochemical analysis.
위와 같이 혈액채취를 실행한 후에, 마취된 상태에서 랫드를 경추 탈구로 희생시키고 복부를 열고 부검을 실시하고 위의 상부와 하부를 봉합사로 결찰을 실시한 후에 제거하였다. 그 후에 중요 부검의 장기인 간, 비장, 신장을 제거한 후에 기관의 무게를 측정하였다. 격리된 위는 개방하여 위 내용물을 채취하고 pH를 측정한다. 생리적 Phosphate buffer(PBS)로 세척 한 후 육안적 소견으로 모든 시험군의 위의 상태를 검사하였다. 위장의 일부 조직은 조직 병리학적 연구를 위해 autolysis 일어나기 전에 빠르게 적출하여 즉시 10% 포르말린으로 고정하였다. 고정을 하는 이유는 사후변화를 정지시키고 특정 조직성분을 응고(coagulation) 또는 침전(precipitation)시켜 불용성 상태(insoluble state)로 전환하여 조직세포학적 검사에 적합한 상태로 만드는 것이다. 즉, 생체를 구성하는 각종 조직 또는 세포가 생체상태와 같이 구조가 잘 보존되도록 하는 것이다. 다른 조직의 일부분은 즉시 -70℃의 냉장고에 분석 전까지 보관하였다.After blood sampling was performed as above, the rat was sacrificed by cervical dislocation under anesthesia, the abdomen was opened, an autopsy was performed, and the upper and lower parts of the stomach were ligated with sutures and then removed. After that, the liver, spleen, and kidney, which were the organs of the major autopsy, were removed and the weight of the organ was measured. The isolated stomach is opened, the stomach contents are collected and the pH is measured. After washing with physiological Phosphate buffer (PBS), the gastric conditions of all test groups were examined with the naked eye. Some tissues of the stomach were rapidly excised before autolysis for histopathological study and immediately fixed with 10% formalin. The reason for immobilization is to stop the post-change and to convert to an insoluble state by coagulation or precipitation of certain tissue components to make it a state suitable for histocytologic examination. In other words, the structure of various tissues or cells constituting a living body is well preserved as in the living state. Parts of other tissues were immediately stored in a refrigerator at -70°C until analysis.
모든 시험군의 궤양 정도는 혈관 혼잡의 중증도, 위 안색의 병변 및 병변을 기준으로 0~5의 등급으로 결정되었다. 궤양 점수에 대해서는 닦은 위를 코르크 판에 펴고 접안 렌즈 해부 현미경을 사용하여 표 4에 따라 점수화를 하였다.The severity of ulcers in all test groups was determined on a scale of 0-5 based on the severity of vascular congestion, lesions and lesions of the upper complexion. For the ulcer score, the wiped stomach was spread on a cork plate and scored according to Table 4 using an eyepiece dissecting microscope.
포르말린에 고정된 위와 간 조직은 한국병리(주)에 전달되어 위와 간에 대해 HE 염색을 실시하였다. H&E staining은 검푸른 색을 내는 헤마톡실린(hematoxylin)과 붉은 색을 내는 에오진(eosin)의 두 염료를 이용하는 방법은 생물 시료의 검사에 가장 유용한 염색법이다. 세포핵은 검푸르게 염색되며 대부분의 세포질 성분은 분홍색 또는 붉은색으로 염색된다. 이 염색법을 이용하여 세포의 핵과 세포질을 관찰할 수 있다.The stomach and liver tissues fixed in formalin were transferred to Korea Pathology Co., Ltd., and HE staining was performed on the stomach and liver. H&E staining is the most useful staining method for testing biological samples, using two dyes: hematoxylin, which gives a dark blue color, and eosin, which gives a red color. Cell nuclei are stained dark blue and most cytoplasmic components are stained pink or red. Using this staining method, the nucleus and cytoplasm of the cell can be observed.
혈청에서 PGE, cAMP 및 gastric mucosal histamine 정량을 분석하였다. 먼저 ELISA에 의한 프로스타글란딘 E2 (PGE2) 수준의 결정은 PGE2 ELISA 키트 (Abnova, 미국 카탈로그 번호 : KA0326)를 사용하여 제조자 지시를 따랐다. cAMP 및 위 점막 히스타민 수준의 결정은 각각 Cell Biolabs, USA의 cAMP ELISA 키트(Colorimetric, Cat. No : STA-500) 및 히스타민 분석 키트(Cat. No : AKR-360)를 사용하여 제조업체 지침에 따라 분석하였다.Serum was analyzed for quantification of PGE, cAMP and gastric mucosal histamine. First, determination of the level of prostaglandin E2 (PGE2) by ELISA followed the manufacturer's instructions using the PGE2 ELISA kit (Abnova, US catalog number: KA0326). Determination of cAMP and gastric mucosal histamine levels were analyzed according to the manufacturer's instructions using the cAMP ELISA kit (Colorimetric, Cat. No: STA-500) and histamine assay kit (Cat. No: AKR-360) from Cell Biolabs, USA, respectively. I did.
다음으로 Real time PCR은 다음과 같이 진행하였다. 시험군의 랫드에서 분리된 위 조직을 TRIzol (Life Technologies, USA)로 균질화하여 제조자의 지시에 따라 Total RNA를 분리하였다. 즉, 다음과 같이 처리하였다. Qiagen RNeasy mini kit을 사용하였다. -70℃에 얼려 있는 조직은 액체질소를 부으면서 막자사발로 갈아서 가루로 만든다. Mercaptanol을 넣은 RLT buffer 600 ul에 넣어서 vortexing하여 lysis하고 Qiagen shredder colum에 넣어서 3분 동안 원심분리하였다. 상보적인 DNA(cDNA)는 AccuPower® RT-premix 시스템 (BioNEER, 한국)을 사용하여 5ug의 정제된 RNA로부터 합성하였다. 히스타민(H2) 수용체, H+/K+ ATPasepump, Cholecystokinin(CCK) 수용체 및 Muscarinic(M3) 수용체에 사용된 프라이머는 표 5의 정보와 함께 실시하였다.Next, real time PCR was carried out as follows. The gastric tissue isolated from the rats of the test group was homogenized with TRIzol (Life Technologies, USA), and total RNA was isolated according to the manufacturer's instructions. That is, it was processed as follows. Qiagen RNeasy mini kit was used. The tissues frozen at -70℃ are ground with a mortar while pouring liquid nitrogen into powder. It was placed in 600 ul of RLT buffer containing Mercaptanol, vortexed, lysed, and then centrifuged for 3 minutes in Qiagen shredder colum. Complementary DNA (cDNA) was synthesized from 5 ug of purified RNA using the AccuPower® RT-premix system (BioNEER, Korea). Primers used for histamine (H2) receptor, H+/K+ ATPasepump, Cholecystokinin (CCK) receptor, and Muscarinic (M3) receptor were performed together with the information in Table 5.
Temp.(℃)Annealing
Temp.(℃)
[실험결과][Experiment result]
모든 시험군에서 체중의 변화의 차이점은 유의미적으로 관찰되지 않았다. 즉, 알코올 섭취를 하지 않은 정상군이 알코올 투여군에서 유의성 있는 사료 섭취량의 차이는 보이지 않았다. The difference in body weight was not significantly observed in all test groups. In other words, there was no significant difference in feed intake between the non-alcohol intake group and the alcohol-administered group.
[위궤양 확인][Check for gastric ulcer]
육안적으로 위염의 상태를 검사한 결과, 음성 대조군의 거의 모든 쥐가 위염을 소견을 보였다. 그러나 대조적으로 양성 대조군(PC), 저용량 (T1) 및 고농도 (T2) 군에서 위 내벽의 육안적 소견은 NC군과 비교시 유의성 있는 작은 궤양 수치를 보였다. 이를 도 1로 나타내었다.As a result of visually examining the state of gastritis, almost all mice in the negative control group showed gastritis. However, in contrast, in the positive control group (PC), the low dose (T1) and the high concentration (T2) group, the gross findings of the gastric lining were significantly smaller than those of the NC group. This is shown in Figure 1.
[HE 염색 조직학적 변화][Histological change of HE staining]
도 2에서 A는 CMC군, B와 C는 NC군, D는 PC군, E는 T1군, F는 T2군의 위 점막의 형태를 보여준다. In FIG. 2, A shows the shape of the gastric mucosa of the CMC group, B and C group NC, D group PC, E group T1, and group F T2.
CMC군(A)에서 위 점막의 형태는 뚜렷한 세포 구조와 명확한 위 구역을 가진 정상상태였다. 정수리 세포는 정상적인 형태의 색을 띄며 세포 침투가 없다. 음성 위염대조군(NC)에서는 에탄올로 인한 위 점막에서 염증세포 침윤과 함께 고도의 퇴행성 세포가 관찰되었다. 또한 이 그룹의 일부 구조에서 세포질 점액, 점막 위축 및 염증세포의 감소가 관찰되었다. Pyrus ussuriensis 에탄올 추출물을 처리 한 그룹의 양성대조군 (PC), 저용량 (T1) 및 고농도 (T2)는 경증 내지 중등도의 세포 변성 및 염증을 보였다.In the CMC group (A), the morphology of the gastric mucosa was in a normal state with a clear cellular structure and a clear gastric region. Parietal cells have a normal color and no cell penetration. In the negative gastritis control group (NC), highly degenerative cells with inflammatory cell infiltration were observed in the gastric mucosa caused by ethanol. In addition, a decrease in cytoplasmic mucus, mucosal atrophy and inflammatory cells were observed in some structures of this group. The positive control (PC), low dose (T1) and high concentration (T2) of the group treated with the ethanol extract of Pyrus ussuriensis showed mild to moderate cellular degeneration and inflammation.
도 3은 위 조직의 염색 조직학적 변화를 보여준다. LCA(CD45) 염색은 염증세포에 cytoplasm에서 갈색으로 발생된다. 는 CMC군, B는 NC군, C는 PC군, D는 T1군, E는 T2군에 해당한다. Submucosa 층에 염증세포를 가늠하여 처리군과 대조군을 비교한 결과 NC군(B)에서 갈색으로 염색된 세포가 많이 관찰되었다. 그러나 이에 비하여 PC군, T1, T2군에서는 갈색 세포가 작게 관찰되었다. CMC 군에서도 약간의 염증세포가 관찰되었다.Figure 3 shows the histological changes staining of the stomach tissue. LCA (CD45) staining occurs in the cytoplasm of inflammatory cells as brown. Is the CMC group, B is the NC group, C is the PC group, D is the T1 group, and E is the T2 group. As a result of comparing inflammatory cells in the submucosa layer and comparing the treatment group and the control group, many brown-stained cells were observed in the NC group (B). However, compared to this, small brown cells were observed in the PC group, T1, and T2 groups. Some inflammatory cells were also observed in the CMC group.
[혈청 프로스타글란딘 E2(PGE2), cAMP 및 위 점막 히스타민 수준의 검출][Detection of serum prostaglandin E2 (PGE2), cAMP and gastric mucosal histamine levels]
도 4는 PGE2, Histamine, cAMP 수준의 검출결과를 나타낸다.4 shows the detection results of PGE2, Histamine, and cAMP levels.
정상 대조군(CMC과 비교하여 혈장 PGE2 수준이 음성 대조군(NC)에서 적게 나타났다. 그러나 T1과 T2 두 치료군의 경우 음성 대조군보다 높았다.The plasma PGE2 level was lower in the negative control group (NC) compared to the normal control group (CMC), but the T1 and T2 treatment groups were higher than the negative control group.
한편, 음성 대조군(NC)의 cAMP 수준의 경우, 정상 대조군(CMC) 및 치료군(T1, T2)과 비교시, 음성 대조군(NC)에서 적게 나타났다. On the other hand, in the case of the cAMP level of the negative control group (NC), when compared with the normal control group (CMC) and the treatment group (T1, T2), the negative control group (NC) showed less.
위산 분비를 억제하는 PGE2의 경우, CMC군과 NC군은 유사하게 나타났다. 그러나 위산 분비를 촉진하는 cAMP와 Histamine의 양은 NC에서 증가를 하여 에탄올은 cAMP와 Histamine의 분비를 촉진하여 위염을 유발하는 것으로 추론되었다. 그러나 이러한 증가는 PC, T1 그리고 T2에서는 감소를 보여주었다.In the case of PGE2, which inhibits gastric acid secretion, the CMC group and the NC group were similar. However, the amounts of cAMP and Histamine that promote gastric acid secretion increased in NC, and it was inferred that ethanol promotes the secretion of cAMP and Histamine to induce gastritis. However, this increase showed a decrease in PC, T1 and T2.
결과적으로 산돌배 50% 에탄올 추출물은 250~500mg/kg에서 위염증 개선 효과가 있음을 위와 같은 동물실험에 의해 뒷받침된다는 결론에 이르게 되었다. As a result, it was concluded that the 50% ethanol extract of Sandolbae is supported by the above animal experiments that it has the effect of improving gastric inflammation at 250~500mg/kg.
한편, 전혈구계산치(complete blood count, CBC)는 혈액검사 중 하나로 실험동물의 건강 상태를 나타내 준다. 주로 백혈구, 적혈구, 혈소판 등을 평가한다. 그 실험결과, 백혈구, 림프구, 적혈구, 혈소판 등의 혈액학적 수치는 각 군 간의 차이는 있었지만 모든 군에서 정상 범위에 속하였고 이상을 보이는 수치는 발견되지 않았다. 경구 투여에 의한 독성검사를 실시했으나 특이한 임상증상도 발견되지 않았다.On the other hand, the complete blood count (CBC) is one of the blood tests and indicates the health status of the experimental animal. Mainly, white blood cells, red blood cells, and platelets are evaluated. As a result of the experiment, hematologic levels such as leukocytes, lymphocytes, red blood cells, and platelets were different between each group, but were within the normal range in all groups, and no abnormalities were found. A toxicity test was performed by oral administration, but no specific clinical symptoms were found.
그렇다면 산돌배추출물을 유효성분으로 포함하는 알코올 유도성 위염 개선, 예방 또는 치료용 약제학적 조성물로 제조될 수 있을 것이다. If so, it may be prepared as a pharmaceutical composition for improving, preventing, or treating alcohol-induced gastritis, which includes the Sandol bae extract as an active ingredient.
그와 같은 본 발명의 바람직한 구현예에 따르면, 본 발명의 조성물은 상술한 본 발명의 산돌배 추출물의 약제학적 유 효량 및 약제학적으로 허용되는 담체를 포함하는 약제학적 조성물을 제조할 수 있다. 약제학적 유효량이란 산돌배 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 의미한다. According to such a preferred embodiment of the present invention, the composition of the present invention can prepare a pharmaceutical composition comprising a pharmaceutically effective amount and a pharmaceutically acceptable carrier of the above-described sandol pear extract of the present invention. A pharmaceutically effective amount refers to an amount sufficient to achieve the efficacy or activity of the sandol pear extract.
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, 메틸셀룰로스, 메틸 히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함할 수 있으나, 이에 한정되는 것은 아니다.When the composition of the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are commonly used at the time of formulation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc. It is not limited thereto.
또한, 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. In addition, the pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like 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, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여, 점막 투여 및 점안 투여 등으로 투여할 수 있다. The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, mucosal administration, and eye drop administration.
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. The appropriate dosage of the pharmaceutical composition of the present invention is prescribed in various ways depending on factors such as the formulation method, the mode of administration, the patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and response sensitivity. Can be.
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, 현 탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily carried out by a person having ordinary knowledge in the art. Or it can be made by incorporating it into a multi-dose container. In this case, the formulation may be in the form of a solution, suspension, syrup, or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally include a dispersant or a stabilizer.
한편, 본 발명의 바람직한 다른 실시예에서는 기능성 식품으로 제조될 수 있다.Meanwhile, in another preferred embodiment of the present invention, it may be manufactured as a functional food.
더욱 바람직하게는, 본 발명의 산돌배 추출물은 발효식품으로 제조될 수 있다. 이하에서는 발효식품으로 제조되는 실시예를 설명한다.More preferably, the sandolbae extract of the present invention may be prepared as a fermented food. Hereinafter, an embodiment prepared as a fermented food will be described.
먼저 젖산균 스타터와 효모 스타터는 다음과 같이 사용하였다.First, the lactic acid bacteria starter and yeast starter were used as follows.
Lactobacillus plantarum 스타터Lactobacillus plantarum starter
Lactobacillus plantarum (L. plantarum) 은 계명대학교 식품가공학과 식품소재개발연구실에서 미강(Rice mill, Uljin, Korea)으로부터 분리한 균주를 한국미생물보존센터에 기탁한 후 분양받아 사용하였다(KCCM 11545P). 이 균주를 MRS agar plate에 30℃, 24시간 배양한 다음 멸균한 MRS broth 액체배지에 순수 배양된 L. plantarum를 한 백금이를 접종하여 30℃에서 24시간 동안 정치배양하여 스타터로 사용하였다.Lactobacillus plantarum (L. plantarum) was used after depositing a strain isolated from Rice mill (Uljin, Korea) at the Department of Food Science and Technology, Keimyung University Food Materials Development Lab, to the Korea Microbial Conservation Center (KCCM 11545P). This strain was cultured on an MRS agar plate at 30° C. for 24 hours, and then purely cultured L. plantarum was inoculated in sterilized MRS broth liquid medium, and then stationary cultured at 30° C. for 24 hours was used as a starter.
Lactobacillus plantarum 스타터Lactobacillus plantarum starter
Leuconostoc citreum (Leuc. citreum) 균주를 sucrose를 포함함 A agar plate (sucrose 2%, yeast extract 0.5%, tryptone 0.25%, K2HPO4 0.25%)에 25℃, 24시간 배양한 다음 멸균한 MRS broth 액체배지에 순수 배양된 Leuc. citreum을 한 백금이를 접종하여 30℃에서 24시간 동안 정치배양하여 스타터로 사용하였다.Leuconostoc citreum (Leuc. citreum) strain was incubated in A agar plate (
Saccharomyces cerevisiae 스타터Saccharomyces cerevisiae starter
전통 막걸리로부터 분리된 Saccharomyces cerevisiae (Sacch. cerevisiae) 균주를 MRS agar plate에 30℃, 24시간 배양한 다음 멸균한 MRS broth 액체배지에 순수 배양된 Sacch. cerevisiae를 한 백금이를 접종하여 30℃에서 24시간 동안 정치배양하여 스타터로 사용하였다.Saccharomyces cerevisiae (Sacch. cerevisiae) strain isolated from traditional makgeolli was cultured on MRS agar plate at 30°C for 24 hours, and then purely cultured in sterilized MRS broth liquid medium. cerevisiae was inoculated with platinum and cultured at 30°C for 24 hours and used as a starter.
열수 추출한 10%(w/v) 산돌배 추출물을 121℃에서 15분간 멸균처리한 후 젖산발효를 수행하였다. GABA의 전구물질인 MSG 3%(w/v)를 첨가하였다. 또한 질소원 공급을 위해 yeast extract 1%(w/v)를 추가적으로 첨가하였다. 그런 다음 Saccharomyces cerevisiae 1%를 접종하여 1차 발효를 시행한다. 30℃에서 2일간 효모발효를 진행하였다.The 10% (w/v) sandol pear extract extracted with hot water was sterilized at 121° C. for 15 minutes, and then lactic acid fermentation was performed. MSG, a precursor of GABA, 3% (w/v) was added. In addition, 1% (w/v) yeast extract was additionally added to supply nitrogen. Then, 1% of Saccharomyces cerevisiae is inoculated to perform the first fermentation. Yeast fermentation was performed at 30° C. for 2 days.
다음으로 MSG 3%를 첨가하고 L. plantarum을 1%(v/v)를 접종 후 2차 발효를 진행한다. 30℃에서 7일간 효모발효를 진행하였다.Next, 3% of MSG is added and 1% (v/v) of L. plantarum is inoculated, followed by secondary fermentation. Yeast fermentation was performed at 30° C. for 7 days.
이렇게 2차 혼합 발효 시에 MSG는 모두 GABA(감마-아미노뷰티르산)로 전환되었다. During the second mixed fermentation, all MSG was converted to GABA (gamma-aminobutyric acid).
감마-아미노뷰티르산은 자연계에 분포하는 비단백질성 아미노산의 일종으로 뇌나 척수와 같은 중추신경계의 주된 억제성 신경전달물질(inhibitory neurotransmitter)로 알려져 있다. 뇌의 혈류를 활발하게 하고 뇌에 산소 공급량을 증가시켜 뇌세포의 대사기능을 촉진시키며, 혈액 내의 중성지방을 줄이고 간기능을 개선시키는 등의 여러 약리 활성으로 인해, 뇌동맥 휴유증에 의한 두통, 귀 울림, 의욕저하 등의 치료제에 응용되어 왔다. 또한, 고혈압과 같은 성인병 등의 예방 및 개선에 효과적인 것으로 밝혀져, 기능성 식품소재로서의 관심이 고조되고 있고 최근에는 감마-아미노뷰티르산을 다량 함유하는 음료가 출시되기도 했다.Gamma-aminobutyric acid is a kind of non-proteinaceous amino acid distributed in nature, and is known as a major inhibitory neurotransmitter in the central nervous system such as the brain and spinal cord. Due to various pharmacological activities such as activating blood flow to the brain and increasing oxygen supply to the brain to promote metabolic functions of brain cells, reducing triglycerides in the blood and improving liver function, headaches and ringing in the ears caused by cerebral artery dystrophy , It has been applied to treatments such as decreased motivation. In addition, it has been found to be effective in the prevention and improvement of adult diseases such as high blood pressure, and interest as a functional food material is increasing. Recently, beverages containing a large amount of gamma-aminobutyric acid have been released.
위와 같이 산돌배 추출물에 2종의 균주로 혼합발효를 시행함으로써 감마-아니모뷰티르산을 더 효과적으로 증진하는 기능성식품을 제조할 수 있음을 확인하였다.As described above, it was confirmed that a functional food that more effectively promotes gamma-animobutyric acid can be prepared by performing mixed fermentation with two strains of the Sandolbae extract.
본 발명의 바람직한 다른 실시예에 따르면 고초균(Bacillus subtilis) 발효를 접목할 수 있다.According to another preferred embodiment of the present invention, Bacillus subtilis fermentation may be grafted.
건산돌배와 끓인 물의 비율 1:9로 혼합하여 30분 동안 추출한다. 씨앗과 껍질을 제거한다.Mix dry stone pear and boiled water at a ratio of 1:9 and extract for 30 minutes. Remove seeds and husks.
다음으로 산돌배 추출액, 증류수와 MSG 0%, 2.5%, 5%를 농도별로 첨가한 후 85℃에서 20분 동안 멸균한다.Next, add Sandolbae extract, distilled water and 0%, 2.5%, and 5% of MSG by concentration, and sterilize at 85°C for 20 minutes.
멸균된 glucose 40%용액을 사용하여 2%수준으로 첨가한 다음, B. subtilis 5% 접종한다. 고초균 발효는 42℃, 160 rpm에서 2일 동안 진탕배양한다.Add 40% of sterilized glucose at a level of 2%, and then inoculate 5% of B. subtilis . Bacillus fermentation is cultured with shaking at 42° C. and 160 rpm for 2 days.
이와 같이 1차 발효인 고초균 발효 후 2차 젖산균 발효를 실시한다. 이때 균의 생육과 GABA 생산 증대를 위하여 glucose 2%, skim milk 5%를 추가로 고초균 배양액에 첨가한다. In this way, after the first fermentation, Bacillus fermentation, the second lactic acid bacteria fermentation is performed. At this time, 2% glucose and 5% skim milk are additionally added to the Bacillus Bacillus culture medium to increase the growth of bacteria and increase GABA production.
다음으로 L. plantarum 1% 접종 후, 30℃의 온도로 5일 동안 정치 배양한다. Next, after inoculation of L. plantarum 1%, it is incubated for 5 days at a temperature of 30°C.
산돌배 열수추출물 10%(w/v), MSG 5%(w/v)일 때 1차 고초균 발효에서 소진되고 남은 MSG는 2차 젖산균 발효 3일만에 모두 GABA로 전환됨을 확인하였다.When the hot water extract of Sandolbae 10% (w/v) and
위와 같은 실시예들을 통해서 본 발명은 산돌배 추출물을 유효성분으로 포함하는 기능성 식품 조성물을 제공한다. 위 염증의 예방, 개선, 치료뿐만 아니라, 감마-아미노뷰트라산 함유를 증진하는 기능성 효과를 거둔다.Through the above examples, the present invention provides a functional food composition comprising a sandol pear extract as an active ingredient. It not only prevents, ameliorates, and treats gastric inflammation, but also has a functional effect of enhancing the gamma-aminobutraic acid content.
본 발명의 산돌배 추출물을 유효성분으로 포함하는 위 염증의 예방, 개선, 치료 및 감마-아미노뷰트라산 함유를 증진하는 기능성 식품 조성물로 제조되는 경우, 유효성분으로서 산돌배 추출물 뿐 만 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 폴리사카 라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르 히진 등)] 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링 크제로 제조되는 경우에는 본 발명의 산돌배 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과 즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다. When prepared as a functional food composition that prevents, ameliorates, treats, and enhances gastric inflammation containing gamma-aminobutraic acid containing the Sandol pear extract of the present invention as an active ingredient, not only the Sandol pear extract as an active ingredient, but also during food production It includes ingredients that are commonly added, and includes, for example, proteins, carbohydrates, fats, nutrients, flavoring and flavoring agents. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)] and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. 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, fruit juice, cephalopathy extract, jujube extract, licorice extract, etc. I can make it.
본 발명의 보호범위가 이상에서 명시적으로 설명한 실시예의 기재와 표현에 제한되는 것은 아니다. 또한, 본 발명이 속하는 기술분야에서 자명한 변경이나 치환으로 말미암아 본 발명이 보호범위가 제한될 수도 없음을 다시 한 번 첨언한다.The scope of protection of the present invention is not limited to the description and expression of the embodiments explicitly described above. In addition, it is added once again that the scope of protection of the present invention may not be limited due to obvious changes or substitutions in the technical field to which the present invention pertains.
Claims (4)
A pharmaceutical composition for improving, preventing or treating alcohol-induced gastritis, comprising an extract of sandol pear as an active ingredient.
상기 산돌배 추출물은 젖산균, 효모, 고초균 중 두 개 이상의 균주를 이용하여 발효한 것인 알코올 유도성 위염 개선, 예방 또는 치료용 약제학적 조성물.
The method of claim 1,
The sandolbae extract is a pharmaceutical composition for improving, preventing or treating alcohol-induced gastritis that is fermented using two or more strains of lactic acid bacteria, yeast, and Bacillus bacillus.
A functional food composition comprising, as an active ingredient, a sandolbae extract with improved gamma-aminobutraic acid content through a complex fermentation process.
상기 복합 발효 과정은 젖산균, 효모, 고초균 중 두 개 이상의 균주를 각각 이용하여 단계별로 발효하는 것인, 산돌배 추출물을 유효성분으로 포함하는 기능성 식품 조성물.The method of claim 1,
The complex fermentation process is a step-by-step fermentation using two or more strains of lactic acid bacteria, yeast, and Bacillus bacillus, respectively, a functional food composition comprising a sandol pear extract as an active ingredient.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020190097454A KR20210017726A (en) | 2019-08-09 | 2019-08-09 | Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract |
KR1020210080190A KR20210082404A (en) | 2019-08-09 | 2021-06-21 | Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020190097454A KR20210017726A (en) | 2019-08-09 | 2019-08-09 | Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020210080190A Division KR20210082404A (en) | 2019-08-09 | 2021-06-21 | Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract |
Publications (1)
Publication Number | Publication Date |
---|---|
KR20210017726A true KR20210017726A (en) | 2021-02-17 |
Family
ID=74731885
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020190097454A KR20210017726A (en) | 2019-08-09 | 2019-08-09 | Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract |
KR1020210080190A KR20210082404A (en) | 2019-08-09 | 2021-06-21 | Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020210080190A KR20210082404A (en) | 2019-08-09 | 2021-06-21 | Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract |
Country Status (1)
Country | Link |
---|---|
KR (2) | KR20210017726A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102370235B1 (en) * | 2021-11-30 | 2022-03-04 | 청정이슬내린오스카 주식회사 농업회사법인 | Method for producing pure natural tea for eliminating hangover |
KR102390048B1 (en) * | 2021-04-08 | 2022-04-25 | 경상북도(경상북도산림환경연구원) | Composition for preventing or treating alcoholic fatty liver disease comprising fermented pyrus ussuriensis extract as an active ingredient |
-
2019
- 2019-08-09 KR KR1020190097454A patent/KR20210017726A/en not_active IP Right Cessation
-
2021
- 2021-06-21 KR KR1020210080190A patent/KR20210082404A/en not_active Application Discontinuation
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102390048B1 (en) * | 2021-04-08 | 2022-04-25 | 경상북도(경상북도산림환경연구원) | Composition for preventing or treating alcoholic fatty liver disease comprising fermented pyrus ussuriensis extract as an active ingredient |
KR102370235B1 (en) * | 2021-11-30 | 2022-03-04 | 청정이슬내린오스카 주식회사 농업회사법인 | Method for producing pure natural tea for eliminating hangover |
Also Published As
Publication number | Publication date |
---|---|
KR20210082404A (en) | 2021-07-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR101200344B1 (en) | Manufacturing method of functional Momordica charantia tea for lowering blood glucose | |
JP4669920B2 (en) | Functional material that suppresses blood glucose rise and blood pressure rise | |
KR20110048236A (en) | Compositions for prevention and improvement of cancer containing the extracts of native plants as an active ingredient | |
KR20210082404A (en) | Methods for improving alcohol-based gastric inflammation and manufacturing of GABA-containing compounds using Pyrus Ussuriensis extract | |
KR101312491B1 (en) | Manufacturing method of functional Momordica charantia beverage for lowering blood glucose | |
KR101717698B1 (en) | Composition comprising extract of Quercus acuta for prevention and treatment of hyperuricemia and metabolic disorders associated with hyperuricemia | |
KR101819026B1 (en) | Composition for use of inhibition of stomach damage to alcohol or inhibition of alcohol uptake or relief of hangover comprising fermented extract of native plants from Jeju island | |
JP3628999B2 (en) | Anonymous tea and its manufacturing method | |
KR20170132390A (en) | Composition for eliminating hangover | |
KR101706552B1 (en) | A stomach cancer treatment composition comprising extract of job's tears and preparation methods thereof | |
KR20200076040A (en) | Composition for preventing or treating gastritis and gastric ulcer comprising cabbage, broccoli sprout, broccoli leaf, kale as an active ingredient | |
KR101399398B1 (en) | Method for manufacturing submerged-state fermented Allium victorialis and Composition for preventing or treating anti-diabetes or anti-diabetic complication containing fermented Allium victorialis | |
KR20180098882A (en) | Composition for the effect of suppressing the elevation of blood sugar level having extract of peanut sprouts as active component | |
KR101606773B1 (en) | Composition comprising oriental herbal extract for preventing or treating gastrointestinal disorder | |
KR102490206B1 (en) | Composition for preventing, ameliorating or treating benign prostatic hyperplasia comprising Viscum album extract as an active ingredient | |
KR101370679B1 (en) | Method for manufacturing solid-state fermented Allium victorialis and Composition for preventing or treating anti-diabetes or anti-diabetic complication containing fermented Allium victorialis | |
KR101222779B1 (en) | A composition comprising the extract of Barnyardgrass as an active ingredient for preventing and treating inflammatory disease | |
KR101278801B1 (en) | Composition for preventing and treating cardiovascular disease comprising extract of chrysanthemu zawadskii | |
KR102302047B1 (en) | Composition for hepatoprotective and ameliorating hangover | |
KR102639561B1 (en) | Composition for preventing, treating or improving metabolic disease including obesity, diabetes or fatty liver using Lactobacillus plantarum NCHBL-004 strain or culture medium thereof | |
KR101104269B1 (en) | Pharmaceutical composition comprising the extract from Iris nertschinskia for preventing and treating cancer | |
KR101818320B1 (en) | composition for improving, treating or preventing alcoholic steatohepatitis comprising extract from Neolentinus lepideus | |
KR100616914B1 (en) | Composition for treating or preventing gastritis and peptic ulcer comprising Rhizopus sp. | |
TW202200179A (en) | Composition for inhibiting phosphodiesterase 5 activity or improving erectile function by using a plant of the genus Phyllanthus | |
KR20160073566A (en) | The pharmaceutical composition comprising the complex extract for preventing or treating obesity, hyperlipidemia and fatty liver |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AMND | Amendment | ||
E601 | Decision to refuse application | ||
X091 | Application refused [patent] | ||
AMND | Amendment | ||
X601 | Decision of rejection after re-examination |