JP2008137925A - α−グルコシダーゼ阻害剤 - Google Patents
α−グルコシダーゼ阻害剤 Download PDFInfo
- Publication number
- JP2008137925A JP2008137925A JP2006324346A JP2006324346A JP2008137925A JP 2008137925 A JP2008137925 A JP 2008137925A JP 2006324346 A JP2006324346 A JP 2006324346A JP 2006324346 A JP2006324346 A JP 2006324346A JP 2008137925 A JP2008137925 A JP 2008137925A
- Authority
- JP
- Japan
- Prior art keywords
- fraction
- inhibitory activity
- glucosidase
- reagent
- glucosidase inhibitor
- 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
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 title claims abstract description 15
- 239000003888 alpha glucosidase inhibitor Substances 0.000 title claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 37
- 239000000126 substance Substances 0.000 claims description 12
- 235000000346 sugar Nutrition 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 5
- 238000010521 absorption reaction Methods 0.000 claims description 4
- 239000003472 antidiabetic agent Substances 0.000 claims description 4
- 229940127003 anti-diabetic drug Drugs 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 11
- 241000647991 Salacia reticulata Species 0.000 abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 239000003153 chemical reaction reagent Substances 0.000 description 21
- 102000016679 alpha-Glucosidases Human genes 0.000 description 16
- 108010028144 alpha-Glucosidases Proteins 0.000 description 16
- 238000012360 testing method Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 241000196324 Embryophyta Species 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 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
- 238000002835 absorbance Methods 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000005194 fractionation Methods 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 4
- 244000309464 bull Species 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000002032 methanolic fraction Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 229960001729 voglibose Drugs 0.000 description 4
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 3
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 3
- BGMYHTUCJVZIRP-UHFFFAOYSA-N Nojirimycin Natural products OCC1NC(O)C(O)C(O)C1O BGMYHTUCJVZIRP-UHFFFAOYSA-N 0.000 description 3
- 244000087020 Salacia prinoides Species 0.000 description 3
- 229960002632 acarbose Drugs 0.000 description 3
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 229960001110 miglitol Drugs 0.000 description 3
- BGMYHTUCJVZIRP-GASJEMHNSA-N nojirimycin Chemical compound OC[C@H]1NC(O)[C@H](O)[C@@H](O)[C@@H]1O BGMYHTUCJVZIRP-GASJEMHNSA-N 0.000 description 3
- 239000008057 potassium phosphate buffer Substances 0.000 description 3
- 201000009104 prediabetes syndrome Diseases 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 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
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- LXBIFEVIBLOUGU-UHFFFAOYSA-N Deoxymannojirimycin Natural products OCC1NCC(O)C(O)C1O LXBIFEVIBLOUGU-UHFFFAOYSA-N 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 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
- 241001465754 Metazoa Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- SOWRVDSZMRPKRG-YRPOCYRVSA-N S(=O)(=O)(O[C@@H](CO)[C@@H](C[S@+]1[C@@H]([C@H]([C@@H](C1)O)O)CO)O)[O-] Chemical compound S(=O)(=O)(O[C@@H](CO)[C@@H](C[S@+]1[C@@H]([C@H]([C@@H](C1)O)O)CO)O)[O-] SOWRVDSZMRPKRG-YRPOCYRVSA-N 0.000 description 2
- 241000545263 Salacia <hydroid> Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- OMKXVFDVAGCPBS-GTEYUELZSA-N [(2s,3s,4r,5r,6s)-1-[(2r,3s,4s)-3,4-dihydroxy-2-(hydroxymethyl)thiolan-1-ium-1-yl]-2,4,5,6,7-pentahydroxyheptan-3-yl] sulfate Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](OS([O-])(=O)=O)[C@H](O)C[S+]1C[C@@H](O)[C@H](O)[C@H]1CO OMKXVFDVAGCPBS-GTEYUELZSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- LXBIFEVIBLOUGU-JGWLITMVSA-N duvoglustat Chemical compound OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-JGWLITMVSA-N 0.000 description 2
- 238000010265 fast atom bombardment Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000000752 ionisation method Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 150000002611 lead compounds Chemical class 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
- 239000000203 mixture Substances 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- -1 thio sugars Chemical class 0.000 description 2
- ZHMWOVGZCINIHW-FTYOSCRSSA-N 1-D-1,2-anhydro-myo-inositol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H]2O[C@H]21 ZHMWOVGZCINIHW-FTYOSCRSSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 229920000310 Alpha glucan Polymers 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000208365 Celastraceae Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010022489 Insulin Resistance 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
- 241000134253 Lanka Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000001280 Prediabetic State Diseases 0.000 description 1
- 101710184309 Probable sucrose-6-phosphate hydrolase Proteins 0.000 description 1
- 241000051611 Salacia oblonga Species 0.000 description 1
- 241000187180 Streptomyces sp. Species 0.000 description 1
- 102400000472 Sucrase Human genes 0.000 description 1
- 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 1
- 101710112652 Sucrose-6-phosphate hydrolase Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- XPHOBMULWMGEBA-UHFFFAOYSA-N Valienamine Natural products NC1C=C(CO)C(O)C(O)C1O XPHOBMULWMGEBA-UHFFFAOYSA-N 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical class C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- QPYJXFZUIJOGNX-HSUXUTPPSA-N afegostat Chemical compound OC[C@H]1CNC[C@@H](O)[C@@H]1O QPYJXFZUIJOGNX-HSUXUTPPSA-N 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 102000006995 beta-Glucosidase Human genes 0.000 description 1
- 108010047754 beta-Glucosidase Proteins 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 238000009739 binding Methods 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
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229930182483 coumarin glycoside Natural products 0.000 description 1
- 150000008140 coumarin glycosides Chemical class 0.000 description 1
- 150000003999 cyclitols Chemical group 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000003929 heteronuclear multiple quantum coherence Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000002207 metabolite Substances 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
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 231100000150 mutagenicity / genotoxicity testing Toxicity 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Chemical group 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 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
- 239000007901 soft capsule Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 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
- 239000001648 tannin Substances 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 229920001864 tannin Polymers 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
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- XPHOBMULWMGEBA-VZFHVOOUSA-N valienamine Chemical compound N[C@H]1C=C(CO)[C@@H](O)[C@H](O)[C@H]1O XPHOBMULWMGEBA-VZFHVOOUSA-N 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
-
- 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
Abstract
Description
コタラヒムブツ(Salacia reticulata)の乾燥した幹 約1.1kgに10倍量の水を加えて、一晩(14〜15時間)熱水抽出を行った。得られた抽出液中の不溶物は、遠心分離(8,000rpm/30min)及びろ過処理により除去した。これらの操作により、コタラヒムブツ熱水エキス末100gを得た。これに水を添加し、500mlの水溶液を調整した。その後、攪拌しながら当量のエタノールを添加し、生じた沈殿物は遠心分離(8,000rpm/30min)により除去を行った。得られた上清は、減圧濃縮によりエタノール除去を行った(収量69.0g)。これを用いて再度500mlの水溶液を調整した後、HP−20カラム処理(使用担体:三菱化学社製合成吸着剤HP−20を1kg充填、カラム:8×35cm)を行った。溶出は、水(5L)、20容量%、40容量%、60容量%、80容量%のメタノール水溶液(各2.5L)を用いて、ステップワイズ溶出を行い、水溶出画分(「HP−20W」画分;収量34.1g)、20容量%メタノール画分(「HP−20−20」画分;収量5.89g)、40容量%メタノール画分(「HP−20−40」画分;収量9.48g)、60容量%メタノール画分(「HP−20−60」画分;収量4.85g)、80容量%メタノール画分(「HP−20−60」画分;収量0.67g)を得た(全回収率 86.0%)。得られた各分画物について、α−グルコシダーゼ阻害活性試験を実施した。阻害活性試験は、以下の操作方法に従い実施した。その結果を表1に示す。
(粗酵素溶液の調製)
試薬として、試薬1:ラット小腸アセトンパウダー(SIGMA社製)、試薬2:100mMリン酸カリウム緩衝液(5mMEDTA、pH7.0)、試薬3:100mMリン酸カリウム緩衝液(0.1%Triton、pH7.0)、試薬4:10mMリン酸カリウム緩衝液(pH7.0)を用いる。
試験用試薬として、試薬1:粗酵素溶液、試薬2:DMSO、試薬3:100mMスクロース水溶液(25mMマルトース水溶液)、試薬4:2MTris-HCl緩衝液(pH7.0)、試薬5:グルコースCIIテストワコー発色液(和光純薬製)を準備した。試験サンプル溶液は、被験物質(10mg)をDMSO(10mL)にて溶解させたものを(サンプルの阻害活性の強さに応じて適宜希釈する)用いた。また、1検体あたりn=3で測定を行い、検体毎にそれぞれブランクをおいた。次いで、以下の操作により阻害活性を測定した。
阻害率(%)={(Glc0−Glcx)/Glc0}×100・・・・式1
ただし、Glc0:コントロール(サンプルと同量のDMSO)吸光度の平均値(n=3)より相当するブランクの吸光度の平均値(n=3)を差し引いたもの
Glcx:サンプルの吸光度の平均値(n=3)より相当するブランクの吸光度の平均値(n=3)を差し引いたもの
分画物を200mLの水溶液とした後、当量のエタノールを添加攪拌し不溶部分を遠心除去した(7,500rpm/30min)。得られた上清は、減圧濃縮によりエタノールを除去した。これを40mLの水溶液とし、アミノカラム(使用担体 :富士シリシア化学社製NH-DM1020SGを950g充填したカラム:8×49cm)にアプライした。
ODSFr2画分についてさらに数回同様の分取操作を繰り返してほぼ単一の物質を得た。この物質の構造を明らかとするために各種NMR分析(1H、13C、1H−1HCOSY、HMQC及びHMBC)並びにFAB−MS分析を実施し、得られた各種スペクトルデータを用いて構造解析を行った。NMR分析(1D−及び2D−)は、分析装置:JNM AL−400(日本電子製、400MHz)、溶媒:D2O(内部標準試薬としてアセトンを使用)、分析温度:25℃にて行った。FAB−MS分析は、分析装置:7000QQ型(日本電子製)、イオン化法:高速原子衝撃法(FAB)、加速電圧:6kV、マトリックス:グリセリン、測定質量範囲:〜m/z1000にて実施した。図2に1H−NMRスペクトル(inD2O/400MHz)を、図3に13C−NMRスペクトル(inD2O/400MHz)を、図4にFAB−MSスペクトルを示した。
上記構造決定されたα−グルコシダーゼ阻害剤について、コタラヒムブツから得られた既報成分(非特許文献26から引用)及び医薬品として販売が認められているボグリボースとその活性を比較した。その結果を表6に示す。この表から分かるように、上市されているボグリボースとほぼ同程度の活性強度を示し、同じ植物から得られた既報成分と比較して、マルターゼ阻害で約71〜103倍、スクラーゼ阻害では約19〜34倍もの阻害活性強度を示した。このように、本発明によるα−グルコシダーゼ阻害剤は、既報成分をはるかに凌ぐ阻害活性を示す成分であることが明らかとなり、コタラヒムブツ抽出物における主たる活性成分であると考えられる。
〔製造例1:錠剤〕
本発明のα−グルコシダーゼ阻害剤 0.07g
マルトシルサイクロデキストリン 600g
ショ糖脂肪酸エステル 50g
炭酸カルシウム 15g
還元麦芽糖水あめ 75g
無水乳酸 110g
結晶セルロース 100g
ミルクカルシウム 50g
上記処方に従って、常法により錠剤5000錠を製造した。
Claims (4)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006324346A JP4125768B2 (ja) | 2006-11-30 | 2006-11-30 | α−グルコシダーゼ阻害剤 |
PCT/JP2007/067919 WO2008065796A1 (fr) | 2006-11-30 | 2007-09-14 | Inhibiteur de l'α -glucosidase |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006324346A JP4125768B2 (ja) | 2006-11-30 | 2006-11-30 | α−グルコシダーゼ阻害剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008137925A true JP2008137925A (ja) | 2008-06-19 |
JP4125768B2 JP4125768B2 (ja) | 2008-07-30 |
Family
ID=39467594
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006324346A Expired - Fee Related JP4125768B2 (ja) | 2006-11-30 | 2006-11-30 | α−グルコシダーゼ阻害剤 |
Country Status (2)
Country | Link |
---|---|
JP (1) | JP4125768B2 (ja) |
WO (1) | WO2008065796A1 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010134595A1 (ja) | 2009-05-21 | 2010-11-25 | サントリーホールディングス株式会社 | ベンゾトロポロン環含有化合物を含む抗肥満剤 |
WO2012024270A1 (en) * | 2010-08-17 | 2012-02-23 | Abbott Laboratories | Nutritional composition comprising cereal beta-glucan and salacia extract |
US8367718B2 (en) | 2008-08-29 | 2013-02-05 | Suntory Holdings Limited | Epigallocatechin gallate trimer and α-glucosidase inhibitor containing epigallocatechin gallate polymer |
JP2020184909A (ja) * | 2019-05-13 | 2020-11-19 | 学校法人帝京大学 | 血糖降下剤、及び、該血糖降下剤を含有する飲食品 |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
US8933024B2 (en) | 2010-06-18 | 2015-01-13 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4516282B2 (ja) * | 2003-04-24 | 2010-08-04 | 森下仁丹株式会社 | 新規なα−グルコシダーゼ阻害活性を有する物質およびこれを含有する食品 |
-
2006
- 2006-11-30 JP JP2006324346A patent/JP4125768B2/ja not_active Expired - Fee Related
-
2007
- 2007-09-14 WO PCT/JP2007/067919 patent/WO2008065796A1/ja active Application Filing
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8367718B2 (en) | 2008-08-29 | 2013-02-05 | Suntory Holdings Limited | Epigallocatechin gallate trimer and α-glucosidase inhibitor containing epigallocatechin gallate polymer |
WO2010134595A1 (ja) | 2009-05-21 | 2010-11-25 | サントリーホールディングス株式会社 | ベンゾトロポロン環含有化合物を含む抗肥満剤 |
WO2012024270A1 (en) * | 2010-08-17 | 2012-02-23 | Abbott Laboratories | Nutritional composition comprising cereal beta-glucan and salacia extract |
JP2020184909A (ja) * | 2019-05-13 | 2020-11-19 | 学校法人帝京大学 | 血糖降下剤、及び、該血糖降下剤を含有する飲食品 |
Also Published As
Publication number | Publication date |
---|---|
JP4125768B2 (ja) | 2008-07-30 |
WO2008065796A1 (fr) | 2008-06-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4125768B2 (ja) | α−グルコシダーゼ阻害剤 | |
KR101624006B1 (ko) | 벤조트로폴론 고리 함유 화합물을 함유하는 항비만제 | |
US20230270805A1 (en) | A composition comprising an extract of alder tree or the isolated compounds therefrom for treating and preventing skeleton muscle-related disorder and the use thereof | |
JP4516282B2 (ja) | 新規なα−グルコシダーゼ阻害活性を有する物質およびこれを含有する食品 | |
KR100926798B1 (ko) | 페리너스 속 버섯 또는 이노노투스 속 버섯의 균사체배양물로부터 분리된 히스피딘 유사체를 포함하는 항산화조성물 | |
CA2738834C (en) | Alpha-amylase inhibitors: the montbretins and uses thereof | |
KR101590842B1 (ko) | 고요산혈증 또는 통풍에 유효한 섬쑥부쟁이 추출물, 이의 분획물 및 이로부터 분리된 활성화합물 | |
KR101121590B1 (ko) | 비타민나무 잎으로부터 분리한 이소람네틴-3-글루코시드-7-람노시드를 유효성분으로 함유하는 항산화용 조성물 | |
CN114835724B (zh) | (+/-)-spiroganoapplanin A及其药物组合物与应用 | |
WO2012144711A2 (ko) | 층꽃풀 추출물 또는 이로부터 분리된 화합물을 함유하는 간독성 질환 예방 및 치료용 조성물 | |
KR100836941B1 (ko) | 차가버섯으로부터 분리된 항산화 화합물 및 이를 포함하는 조성물 | |
KR102078818B1 (ko) | 지충이 유래 화합물을 유효성분으로 함유하는 간염의 예방 또는 치료용 약학 조성물 | |
KR101839313B1 (ko) | 방사선 처리된 루틴 유도체를 유효성분으로 함유하는 항당뇨용 조성물 | |
KR100490799B1 (ko) | 대나무 추출물 또는 이로부터 분리된 트리신을 포함하는 식품 | |
CN106715452A (zh) | 分离自pseudolysimachion rotundum var. subintegrum的新化合物(ks513),用于预防或治疗变应性疾病、炎性疾病、哮喘或慢性阻塞性肺病的包含该化合物作为活性成分的组合物及它们的用途 | |
JP5655416B2 (ja) | 新規フラバン化合物 | |
KR101834550B1 (ko) | 3-카페오일-4-디히드로카페오일 퀴닉산을 유효성분으로 함유하는 혈관질환의 예방, 개선 또는 치료용 조성물 | |
KR100801550B1 (ko) | 누에 수번데기로부터 아데노신 유도체 화합물을 정제하는방법 및 아데노신 유도체 화합물을 포함하는 발기부전치료용 조성물 | |
JP4840845B2 (ja) | 新規エラグ酸誘導体及びキサンチンオキシダーゼ阻害剤 | |
KR101006702B1 (ko) | 치매치료 효과를 갖는 신규 사포닌계 화합물 | |
US20120004193A1 (en) | Process for production of orally ingestible composition containing arabinofuranosyl vitexin, and use of the composition | |
KR101998087B1 (ko) | 토종다래 유래 신규 화합물 및 이의 용도 | |
KR102069125B1 (ko) | 강황 추출물을 포함하는 간손상 예방 및 치료용 약학 조성물 | |
KR102092729B1 (ko) | 강황 추출물을 포함하는 간손상 예방 및 치료용 약학 조성물 | |
KR101892659B1 (ko) | 말락시닉산을 이용한 인슐린감도개선용 약학조성물 및 건강기능성식품 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
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: 20080507 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20080508 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110516 Year of fee payment: 3 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120516 Year of fee payment: 4 |
|
LAPS | Cancellation because of no payment of annual fees |