JP2019205386A - α−グルコシダーゼ活性阻害剤および血糖値上昇抑制剤 - Google Patents
α−グルコシダーゼ活性阻害剤および血糖値上昇抑制剤 Download PDFInfo
- Publication number
- JP2019205386A JP2019205386A JP2018102765A JP2018102765A JP2019205386A JP 2019205386 A JP2019205386 A JP 2019205386A JP 2018102765 A JP2018102765 A JP 2018102765A JP 2018102765 A JP2018102765 A JP 2018102765A JP 2019205386 A JP2019205386 A JP 2019205386A
- Authority
- JP
- Japan
- Prior art keywords
- glucuronide
- glucosidase activity
- inhibitor
- isocartamidine
- cartamidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000000694 effects Effects 0.000 title claims abstract description 64
- 102100024295 Maltase-glucoamylase Human genes 0.000 title claims abstract description 61
- 108010028144 alpha-Glucosidases Proteins 0.000 title claims abstract description 61
- 239000003112 inhibitor Substances 0.000 title claims abstract description 60
- 239000008280 blood Substances 0.000 title claims abstract description 55
- 210000004369 blood Anatomy 0.000 title claims abstract description 55
- 235000000346 sugar Nutrition 0.000 title claims abstract description 25
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 28
- 235000013305 food Nutrition 0.000 claims abstract description 27
- 239000004480 active ingredient Substances 0.000 claims abstract description 13
- 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 claims description 43
- 239000008103 glucose Substances 0.000 claims description 43
- 235000013361 beverage Nutrition 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 abstract description 4
- NPLTVGMLNDMOQE-NSHDSACASA-N carthamidin Chemical compound C1=CC(O)=CC=C1[C@H]1OC2=CC(O)=C(O)C(O)=C2C(=O)C1 NPLTVGMLNDMOQE-NSHDSACASA-N 0.000 abstract description 3
- NPLTVGMLNDMOQE-UHFFFAOYSA-N carthamidin Natural products C1=CC(O)=CC=C1C1OC2=CC(O)=C(O)C(O)=C2C(=O)C1 NPLTVGMLNDMOQE-UHFFFAOYSA-N 0.000 abstract description 3
- 229930014626 natural product Natural products 0.000 abstract description 3
- NUNODKNZSZKXGY-LBPRGKRZSA-N (2s)-5,7,8-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one Chemical compound C1=CC(O)=CC=C1[C@H]1OC2=C(O)C(O)=CC(O)=C2C(=O)C1 NUNODKNZSZKXGY-LBPRGKRZSA-N 0.000 abstract 2
- NUNODKNZSZKXGY-UHFFFAOYSA-N isocarthamidin Natural products C1=CC(O)=CC=C1C1OC2=C(O)C(O)=CC(O)=C2C(=O)C1 NUNODKNZSZKXGY-UHFFFAOYSA-N 0.000 abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 238000000605 extraction Methods 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000002994 raw material Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 206010012601 diabetes mellitus Diseases 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- -1 aliphatic alcohols Chemical class 0.000 description 5
- 235000009508 confectionery Nutrition 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 235000013376 functional food Nutrition 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000012264 purified product Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000012752 auxiliary agent Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 210000000813 small intestine Anatomy 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
- 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 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical group OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- 206010012655 Diabetic complications Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 102000004366 Glucosidases Human genes 0.000 description 2
- 108010056771 Glucosidases Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 240000008415 Lactuca sativa Species 0.000 description 2
- 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 2
- 208000008589 Obesity Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000207929 Scutellaria Species 0.000 description 2
- 240000004534 Scutellaria baicalensis Species 0.000 description 2
- 235000017089 Scutellaria baicalensis Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000005238 degreasing Methods 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000469 ethanolic extract Substances 0.000 description 2
- 150000002207 flavanone derivatives Chemical class 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229940097043 glucuronic acid Drugs 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 235000012149 noodles Nutrition 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 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
- 239000008213 purified water Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 235000012045 salad Nutrition 0.000 description 2
- 235000015067 sauces Nutrition 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 240000008620 Fagopyrum esculentum Species 0.000 description 1
- 235000009419 Fagopyrum esculentum Nutrition 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010020571 Hyperaldosteronism Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 241000207923 Lamiaceae Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 108010001441 Phosphopeptides Proteins 0.000 description 1
- 241000209504 Poaceae Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 235000015140 cultured milk Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000011850 desserts Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000010459 dolomite Substances 0.000 description 1
- 229910000514 dolomite Inorganic materials 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 235000008446 instant noodles Nutrition 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 235000015094 jam Nutrition 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000003264 margarine Substances 0.000 description 1
- 235000013310 margarine Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000008268 mayonnaise Substances 0.000 description 1
- 235000010746 mayonnaise Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000010330 ougon Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 235000021110 pickles Nutrition 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 235000013547 stew Nutrition 0.000 description 1
- 238000003883 substance clean up Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 208000037911 visceral disease Diseases 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 239000002349 well water Substances 0.000 description 1
- 235000020681 well water Nutrition 0.000 description 1
- 239000008256 whipped cream Substances 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
α−グルコシダーゼ活性を阻害する天然物由来成分として、ピーナッツ渋皮抽出物(特許文献1)が知られている。
本実施形態のα−グルコシダーゼ活性阻害剤および血糖値上昇抑制剤は、カルタミジン7−O−β−D−グルクロニドおよび/またはイソカルタミジン7−O−β−D−グルクロニドを有効成分とするものである。また、本実施形態のα−グルコシダーゼ活性阻害用または血糖値上昇抑制用飲食品は、カルタミジン7−O−β−D−グルクロニドおよび/またはイソカルタミジン7−O−β−D−グルクロニドが配合されるものである。
以上のようにして得られるカルタミジン7−O−β−D−グルクロニドおよびイソカルタミジン7−O−β−D−グルクロニドは、優れたα−グルコシダーゼ活性阻害作用および血糖値上昇抑制作用を有しているため、α−グルコシダーゼ活性阻害剤および血糖値上昇抑制剤の有効成分として用いることができる。本実施形態のα−グルコシダーゼ活性阻害剤および血糖値上昇抑制剤は、医薬品、医薬部外品等の幅広い用途に使用することができる。
カルタミジン7−O−β−D−グルクロニドおよびイソカルタミジン7−O−β−D−グルクロニドは、優れたα−グルコシダーゼ活性阻害作用または血糖値上昇抑制作用を有しているため、α−グルコシダーゼ活性阻害用または血糖値上昇抑制用の飲食品に配合するのに好適である。この場合、カルタミジン7−O−β−D−グルクロニドまたはイソカルタミジン7−O−β−D−グルクロニドをそのまま配合してもよいし、カルタミジン7−O−β−D−グルクロニドまたはイソカルタミジン7−O−β−D−グルクロニドから製剤化したα−グルコシダーゼ活性阻害剤または血糖値上昇抑制剤を配合してもよい。
コガネバナ地上部(353g)を50℃で24時間乾燥し、コガネバナ地上部の乾燥物(99.8g)を得た。得られたコガネバナ地上部の乾燥物99.8gに50容量%エタノール1Lを加え、2時間還流抽出し、抽出液を得た。得られた抽出液を溶媒留去し、さらに凍結乾燥を行うことにより、コガネバナ地上部50%エタノール抽出物(30.6g,原料からの収率:30.7%)を得た。
カラム:Develosil RPAQUEOUS-AR-5(20mm×250mm)(野村化学社製)
移動相:25%MeCN(0.5%TFA)
流速:15mL/min
検出:RI UV(280nm)
サンプル濃度:25mg/mL
注入量:2mL
<マススペクトル>
m/z:465(M+H)+
m/z:463(M−H)−
<1H−NMR(400MHz, DMSO-d6)δ>
2.68(1H, brd, J=16.5 Hz, cis 3-H), 3.38(m, trans, 3-H), 5.41(1H, brd, J=10.5Hz, 2-H), 3.3-4.1(m, sugar, moiety), 5.16(1H, brs, anomeric H of glucuronic acid unit), 6.79(2H, d, J=8.0Hz, 3’, 5’-H), 7.31(2H, d, J=8.0Hz, 2’, 6’-H), 6.30(1H, s, 8-H)
<13C−NMR(100MHz, DMSO-d6)δC>
78.9(C-2), 42.6(C-3), 198.2(C-4), 153.0(C-5), 127.9(C-6), 149.5(C-7), 93.9(C-8), 154.8(C-9), 103.4(C-10), 129.0(C-1’), 128.5(C-2’, C-6’), 115.2(C-3’, C-5’), 157.8(C-4’), 99.6(C-1”), 72.8(C-2”), 75.1(C-3”), 71.3(C-4”), 75.4(C-5”), 170.1(C-6”)
<マススペクトル>
m/z:465(M+H)+
m/z:463(M−H)−
<1H−NMR(400MHz, DMSO-d6)δ>
2.74(1H, brd, J=16.7 Hz, cis 3-H), 3.38(m, trans, 3-H), 5.45(1H, brd, J=10.5Hz, 2-H), 3.3-4.1(m, sugar, moiety), 5.10(1H, brs, anomeric H of glucuronic acid unit), 6.79(2H, d, J=8.0Hz, 3’, 5’-H), 7.33(2H, d, J=8.0Hz, 2’, 6’-H), 6.26(1H, s, 6-H)
<13C−NMR(100MHz, DMSO-d6)δC>
78.8(C-2), 42.5(C-3), 197.8(C-4), 153.6(C-5), 94.9(C-6), 154.8(C-7), 127.2(C-8), 148.9(C-9), 103.4(C-10), 129.0(C-1’), 128.6(C-2’, C-6’), 115.2(C-3’, C-5’), 157.8(C-4’), 100.0(C-1”), 72.8(C-2”), 75.1(C-3”), 71.3(C-4”), 75.4(C-5”), 170.1(C-6”)
上記製造例で得られたカルタミジン7−O−β−D−グルクロニド(試料1)およびイソカルタミジン7−O−β−D−グルクロニド(試料2)について、以下のようにしてα−グルコシダーゼ活性阻害作用を試験した。
96ウェルプレートに、PB10μL、粗酵素液15μL、および上記PBで10倍濃度に調製した被験試料(試料1および2,終濃度は下記表1を参照)25μLを加えた。これに、基質として10mmol/Lマルトースの上記PB溶液200μLを加え37℃で30分反応を行った。その後、沸騰水中に2分間浸し反応を停止させ、さらに氷冷した。反応により生成したグルコース量を、グルコースCII−テストワコー(和光純薬工業社製)を用いて測定した。ブランクとしてマルトース溶液の代わりにPBを用い、コントロールとして被験試料の代わりにPBを用いた。得られた結果から、下記式によりα−グルコシダーゼ活性阻害率(%)を算出した。
式中の各項はそれぞれ以下を表す。
A:被験試料添加・酵素添加でのグルコース濃度
B:被験試料添加・酵素無添加でのグルコース濃度
C:試料無添加・酵素添加でのグルコース濃度
D:試料無添加・酵素無添加でのグルコース濃度
結果を表1に示す。
常法により、以下の組成を有する錠剤を製造した。
カルタミジン7−O−β−D−グルクロニド 5.0mg
ドロマイト(カルシウム20%、マグネシウム10%含有) 83.4mg
カゼインホスホペプチド 16.7mg
ビタミンC 33.4mg
マルチトール 136.8mg
コラーゲン 12.7mg
ショ糖脂肪酸エステル 12.0mg
常法により、以下の組成を有する経口液状製剤を製造した。
<1アンプル(1本100mL)中の組成>
イソカルタミジン7−O−β−D−グルクロニド 0.3質量%
ソルビット 12.0質量%
安息香酸ナトリウム 0.1質量%
香料 1.0質量%
硫酸カルシウム 0.5質量%
精製水 残部(100質量%)
Claims (3)
- カルタミジン7−O−β−D−グルクロニドおよび/またはイソカルタミジン7−O−β−D−グルクロニドを有効成分とすることを特徴とするα−グルコシダーゼ活性阻害剤。
- カルタミジン7−O−β−D−グルクロニドおよび/またはイソカルタミジン7−O−β−D−グルクロニドを有効成分とすることを特徴とする血糖値上昇抑制剤。
- カルタミジン7−O−β−D−グルクロニドおよび/またはイソカルタミジン7−O−β−D−グルクロニドを配合したことを特徴とする、α−グルコシダーゼ活性阻害用または血糖値上昇抑制用飲食品。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2018102765A JP7239135B2 (ja) | 2018-05-29 | 2018-05-29 | α-グルコシダーゼ活性阻害剤および血糖値上昇抑制剤 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2018102765A JP7239135B2 (ja) | 2018-05-29 | 2018-05-29 | α-グルコシダーゼ活性阻害剤および血糖値上昇抑制剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019205386A true JP2019205386A (ja) | 2019-12-05 |
JP7239135B2 JP7239135B2 (ja) | 2023-03-14 |
Family
ID=68766858
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018102765A Active JP7239135B2 (ja) | 2018-05-29 | 2018-05-29 | α-グルコシダーゼ活性阻害剤および血糖値上昇抑制剤 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP7239135B2 (ja) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008133192A (ja) * | 2005-09-29 | 2008-06-12 | Kureha Corp | 抗糖尿病剤 |
CN102492008A (zh) * | 2011-12-12 | 2012-06-13 | 中国医学科学院药用植物研究所 | 一种含异红花素7-O-β-D-葡萄糖醛酸苷的活性提取物及其用途 |
CN103142842A (zh) * | 2013-04-07 | 2013-06-12 | 龚定军 | 一种治疗糖尿病的中药 |
-
2018
- 2018-05-29 JP JP2018102765A patent/JP7239135B2/ja active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008133192A (ja) * | 2005-09-29 | 2008-06-12 | Kureha Corp | 抗糖尿病剤 |
CN102492008A (zh) * | 2011-12-12 | 2012-06-13 | 中国医学科学院药用植物研究所 | 一种含异红花素7-O-β-D-葡萄糖醛酸苷的活性提取物及其用途 |
CN103142842A (zh) * | 2013-04-07 | 2013-06-12 | 龚定军 | 一种治疗糖尿病的中药 |
Non-Patent Citations (3)
Title |
---|
LI, K. ET AL.: ""Structure-activity relationship of eight high content flavonoids analyzed with a preliminary assign", ARABIAN JOURNAL OF CHEMISTRY, vol. 11, JPN6022013767, 2018, pages 159 - 170, ISSN: 0004844849 * |
MIYAICHI, Y. ET AL.: ""Studies on the Constituents of Scutellaria Species (X) : On the Flavonoid Constituents of the Leave", SHOYAKUGAKU ZASSHI, vol. 42, JPN6022013768, 1988, pages 216 - 219, ISSN: 0004844848 * |
TETSUO NISHIOKA ET AL., JOURNAL OF NATURAL PRODUCTS, vol. 61, no. 11, JPN6011050482, 1998, pages 1413 - 1415, ISSN: 0004844847 * |
Also Published As
Publication number | Publication date |
---|---|
JP7239135B2 (ja) | 2023-03-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6222626B2 (ja) | フルクトース吸収阻害剤 | |
EP2799083B1 (en) | Muscle atrophy inhibitor | |
JP6802256B2 (ja) | Glp−1分泌促進用組成物及びその製造方法 | |
JP5403942B2 (ja) | グルタチオン産生促進剤およびグルタチオンの欠乏に起因する疾患の予防・治療剤 | |
JPWO2006033351A1 (ja) | チオレドキシン発現誘導用組成物 | |
KR20060119706A (ko) | 생활 습관병 예방ㆍ개선용의 유지 가공 조성물 | |
JP2003252784A (ja) | α−グルコシダーゼ阻害剤 | |
JP2006225312A (ja) | レプチン分泌抑制組成物 | |
JP7229513B2 (ja) | 脳の機能改善剤および脳の機能改善用飲食品 | |
JP2008137976A (ja) | 脂肪蓄積抑制剤 | |
JP2007230973A (ja) | 抗ガン活性作用を有する組成物。 | |
JP7239135B2 (ja) | α-グルコシダーゼ活性阻害剤および血糖値上昇抑制剤 | |
JP6131275B2 (ja) | Igf−1産生促進剤 | |
KR101794924B1 (ko) | 퉁퉁마디 유래 비알코올성 지방간 질환 예방 또는 치료용 이소람네틴의 분리방법 | |
JP6903367B1 (ja) | 抗肥満用組成物及び経口用組成物 | |
JP2007099635A (ja) | α−グルコシダーゼ阻害剤 | |
KR20180088606A (ko) | 비알코올성 지방간 질환 예방 또는 치료능이 있는 이소람네틴(isorhamnetin)을 함유하는 퉁퉁마디(Salicornia SPP.) 물 추출물의 에틸아세테이트 분획물 | |
WO2021255979A1 (ja) | 抗肥満用組成物及び経口用組成物 | |
KR20170076587A (ko) | 모노테르페닐 마그놀올을 유효성분으로 하는 지방간, 고지혈증 또는 비만의 예방 또는 치료용 조성물 및 후박 분획물의 제조방법 | |
JP2012176916A (ja) | 新規レスベラトロール誘導体 | |
JP7128464B2 (ja) | グネチンc高含有メリンジョエキス及びその製造方法 | |
JP2003095941A (ja) | 糖質消化酵素阻害剤、血糖値上昇抑制剤、肥満治療予防剤、糖尿病治療予防剤、健康飲食物 | |
JP2011132173A (ja) | キサンチンオキシダーゼ阻害剤及び尿酸生成阻害剤 | |
JP2022129479A (ja) | 肝機能向上剤および肝機能向上用経口組成物 | |
JP6637753B2 (ja) | カテキン類吸収促進剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210428 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220412 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220610 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220809 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20221011 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20230214 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230222 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7239135 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |