CN111437302B - 黄杞叶水提后大孔树脂处理后的提取物在制备糖尿病药物中的应用及其分析方法 - Google Patents
黄杞叶水提后大孔树脂处理后的提取物在制备糖尿病药物中的应用及其分析方法 Download PDFInfo
- Publication number
- CN111437302B CN111437302B CN201911170778.6A CN201911170778A CN111437302B CN 111437302 B CN111437302 B CN 111437302B CN 201911170778 A CN201911170778 A CN 201911170778A CN 111437302 B CN111437302 B CN 111437302B
- Authority
- CN
- China
- Prior art keywords
- engelhardtia
- macroporous resin
- water
- extract
- astilbin
- 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.)
- Active
Links
- 239000011347 resin Substances 0.000 title claims abstract description 41
- 229920005989 resin Polymers 0.000 title claims abstract description 41
- 239000000284 extract Substances 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 239000003814 drug Substances 0.000 title claims abstract description 19
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 15
- 229940079593 drug Drugs 0.000 title claims abstract description 11
- 241001002544 Engelhardia Species 0.000 title claims description 39
- 238000003809 water extraction Methods 0.000 title abstract description 13
- 238000004458 analytical method Methods 0.000 title description 5
- ZROGCCBNZBKLEL-FHXNIQKESA-N Astilbin Natural products O([C@H]1[C@@H](c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 ZROGCCBNZBKLEL-FHXNIQKESA-N 0.000 claims abstract description 77
- ZROGCCBNZBKLEL-MPRHSVQHSA-N astilbin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1C(=O)C2=C(O)C=C(O)C=C2O[C@@H]1C1=CC=C(O)C(O)=C1 ZROGCCBNZBKLEL-MPRHSVQHSA-N 0.000 claims abstract description 70
- 241001002545 Engelhardia roxburghiana Species 0.000 claims abstract description 33
- SOSLMHZOJATCCP-AEIZVZFYSA-N afzelin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC1=C(C=2C=CC(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O SOSLMHZOJATCCP-AEIZVZFYSA-N 0.000 claims abstract description 10
- SOSLMHZOJATCCP-PADPQNGGSA-N afzelin Natural products O([C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1)C1=C(c2ccc(O)cc2)Oc2c(c(O)cc(O)c2)C1=O SOSLMHZOJATCCP-PADPQNGGSA-N 0.000 claims abstract description 10
- NCZJHBOLUQWVQK-UHFFFAOYSA-N kaempferol 3-O-rhamnoside Natural products CC1OC(OC2=C(Oc3c(O)cc(O)cc3C2=O)c4ccc(O)cc4)C(O)C(O)C1O NCZJHBOLUQWVQK-UHFFFAOYSA-N 0.000 claims abstract description 9
- ZROGCCBNZBKLEL-AEGLVIMLSA-N Isoastibin Natural products O([C@@H]1[C@H](c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 ZROGCCBNZBKLEL-AEGLVIMLSA-N 0.000 claims abstract description 7
- ZROGCCBNZBKLEL-MFSALPCASA-N neoastilbin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C(=O)C2=C(O)C=C(O)C=C2O[C@H]1C1=CC=C(O)C(O)=C1 ZROGCCBNZBKLEL-MFSALPCASA-N 0.000 claims abstract description 7
- ZROGCCBNZBKLEL-RMPKKLJSSA-N neoastilbin Natural products C[C@@H]1O[C@H](O[C@H]2[C@@H](Oc3cc(O)cc(O)c3C2=O)c2ccc(O)c(O)c2)[C@H](O)[C@H](O)[C@H]1O ZROGCCBNZBKLEL-RMPKKLJSSA-N 0.000 claims abstract description 7
- 235000013305 food Nutrition 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 46
- 239000008280 blood Substances 0.000 claims description 42
- 210000004369 blood Anatomy 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 23
- 235000000346 sugar Nutrition 0.000 claims description 13
- 238000000605 extraction Methods 0.000 claims description 11
- 241001070946 Chrysolepis Species 0.000 claims description 10
- 239000000843 powder Substances 0.000 claims description 10
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000011068 loading method Methods 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 238000007873 sieving Methods 0.000 claims description 6
- 238000010828 elution Methods 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 238000002791 soaking Methods 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 90
- 229930182486 flavonoid glycoside Natural products 0.000 abstract description 60
- 150000007955 flavonoid glycosides Chemical class 0.000 abstract description 60
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 28
- 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 26
- 241000699670 Mus sp. Species 0.000 description 26
- 239000008103 glucose Substances 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 230000002401 inhibitory effect Effects 0.000 description 18
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 12
- 238000001819 mass spectrum Methods 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 229930003944 flavone Natural products 0.000 description 10
- 235000011949 flavones Nutrition 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 9
- 108010028144 alpha-Glucosidases Proteins 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 9
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 229960001052 streptozocin Drugs 0.000 description 8
- 238000001035 drying Methods 0.000 description 7
- -1 flavone compounds Chemical class 0.000 description 7
- 150000002212 flavone derivatives Chemical class 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- CXQWRCVTCMQVQX-LSDHHAIUSA-N (+)-taxifolin Chemical compound C1([C@@H]2[C@H](C(C3=C(O)C=C(O)C=C3O2)=O)O)=CC=C(O)C(O)=C1 CXQWRCVTCMQVQX-LSDHHAIUSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- VQUPQWGKORWZII-UHFFFAOYSA-N Neoisoengelitin Chemical class OC1C(O)C(O)C(C)OC1OC1C(=O)C2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C=C1 VQUPQWGKORWZII-UHFFFAOYSA-N 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 229930182470 glycoside Natural products 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000002798 spectrophotometry method Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 244000269722 Thea sinensis Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- 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 4
- VQUPQWGKORWZII-WDPYGAQVSA-N (2r,3r)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3-dihydrochromen-4-one Chemical class O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1C(=O)C2=C(O)C=C(O)C=C2O[C@@H]1C1=CC=C(O)C=C1 VQUPQWGKORWZII-WDPYGAQVSA-N 0.000 description 4
- IFBHRQDFSNCLOZ-ZIQFBCGOSA-N 4-nitrophenyl alpha-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 IFBHRQDFSNCLOZ-ZIQFBCGOSA-N 0.000 description 4
- VQUPQWGKORWZII-RPJYBVRZSA-N Isoengeletin Chemical compound C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)O[C@H]2[C@H](OC3=CC(=CC(=C3C2=O)O)O)C4=CC=C(C=C4)O)O)O)O VQUPQWGKORWZII-RPJYBVRZSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 229960002632 acarbose Drugs 0.000 description 4
- 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 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 238000002481 ethanol extraction Methods 0.000 description 4
- 229930003935 flavonoid Natural products 0.000 description 4
- 150000002215 flavonoids Chemical class 0.000 description 4
- 235000017173 flavonoids Nutrition 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229960004937 saxagliptin Drugs 0.000 description 4
- 108010033693 saxagliptin Proteins 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000001195 ultra high performance liquid chromatography Methods 0.000 description 4
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 3
- VQUPQWGKORWZII-KTLFEHCLSA-N Dihydrokaempferol-3-O-alpha-L-rhamnopyranoside Chemical class O([C@@H]1[C@H](c2ccc(O)cc2)Oc2c(c(O)cc(O)c2)C1=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 VQUPQWGKORWZII-KTLFEHCLSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- KQNGHARGJDXHKF-UHFFFAOYSA-N dihydrotamarixetin Natural products C1=C(O)C(OC)=CC=C1C1C(O)C(=O)C2=C(O)C=C(O)C=C2O1 KQNGHARGJDXHKF-UHFFFAOYSA-N 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000003304 gavage Methods 0.000 description 3
- 150000002338 glycosides Chemical class 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000003808 methanol extraction Methods 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 238000007410 oral glucose tolerance test Methods 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 2
- 102000016912 Aldehyde Reductase Human genes 0.000 description 2
- 108010053754 Aldehyde reductase Proteins 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 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 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 241000758791 Juglandaceae Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- ZONYXWQDUYMKFB-UHFFFAOYSA-N SJ000286395 Natural products O1C2=CC=CC=C2C(=O)CC1C1=CC=CC=C1 ZONYXWQDUYMKFB-UHFFFAOYSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 235000021053 average weight gain Nutrition 0.000 description 2
- 238000010009 beating Methods 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000035619 diuresis Effects 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 229930003949 flavanone Natural products 0.000 description 2
- 235000011981 flavanones Nutrition 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000007446 glucose tolerance test Methods 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical compound C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 description 2
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000035922 thirst Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- PADQINQHPQKXNL-LSDHHAIUSA-N (+)-dihydrokaempferol Chemical compound C1([C@@H]2[C@H](C(C3=C(O)C=C(O)C=C3O2)=O)O)=CC=C(O)C=C1 PADQINQHPQKXNL-LSDHHAIUSA-N 0.000 description 1
- VQUPQWGKORWZII-ZUSBORFQSA-N (2s,3s)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3-dihydrochromen-4-one Chemical class O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C(=O)C2=C(O)C=C(O)C=C2O[C@H]1C1=CC=C(O)C=C1 VQUPQWGKORWZII-ZUSBORFQSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- CDAISMWEOUEBRE-SHFUYGGZSA-N 1L-chiro-inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@H]1O CDAISMWEOUEBRE-SHFUYGGZSA-N 0.000 description 1
- YEDFEBOUHSBQBT-UHFFFAOYSA-N 2,3-dihydroflavon-3-ol Chemical class O1C2=CC=CC=C2C(=O)C(O)C1C1=CC=CC=C1 YEDFEBOUHSBQBT-UHFFFAOYSA-N 0.000 description 1
- SBMBZNDXQINZKP-UHFFFAOYSA-N 2-ethoxy-5-hydroxynaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(OCC)=CC(=O)C2=C1O SBMBZNDXQINZKP-UHFFFAOYSA-N 0.000 description 1
- RMZNXRYIFGTWPF-UHFFFAOYSA-N 2-nitrosoacetic acid Chemical compound OC(=O)CN=O RMZNXRYIFGTWPF-UHFFFAOYSA-N 0.000 description 1
- HHGPYJLEJGNWJA-UHFFFAOYSA-N 5-hydroxy-3,3',4',7-tetramethoxyflavone Chemical compound C=1C(OC)=CC(O)=C(C(C=2OC)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HHGPYJLEJGNWJA-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 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 1
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000003638 Glucose-6-Phosphatase Human genes 0.000 description 1
- 108010086800 Glucose-6-Phosphatase Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 244000241838 Lycium barbarum Species 0.000 description 1
- 235000015459 Lycium barbarum Nutrition 0.000 description 1
- 235000015468 Lycium chinense Nutrition 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- MNIDWWPXTZZMMY-GZKZZBPGSA-N Quercetin 3-O-alpha-L-rhamnopyranoside Natural products O(C[C@H]1[C@H](O)[C@H](O)[C@@H](O)[C@H](OC2=C(c3cc(O)c(O)cc3)Oc3c(c(O)cc(O)c3)C2=O)O1)[C@H]1[C@H](O)[C@@H](O[C@H]2[C@@H](O)[C@@H](O)[C@@H](O)[C@@H](C)O2)[C@@H](O)[C@H](C)O1 MNIDWWPXTZZMMY-GZKZZBPGSA-N 0.000 description 1
- NSZQOXBBEWYGQH-UHFFFAOYSA-N Quercetin-3-rhamnosid Natural products CC1OC(O)C(O)C(OC2=C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)c(O)c4)C1O NSZQOXBBEWYGQH-UHFFFAOYSA-N 0.000 description 1
- GXAPLLMJHZBIPX-UHFFFAOYSA-N Retusine Natural products O1C(=O)C(C)C(C)C(C)(O)C(=O)OCC2CCN3C2C1CC3 GXAPLLMJHZBIPX-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000005513 chalcones Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- RAYJUFCFJUVJBB-UHFFFAOYSA-N dihydrokaempferol Natural products OC1Oc2c(O)cc(O)cc2C(=O)C1c3ccc(O)cc3 RAYJUFCFJUVJBB-UHFFFAOYSA-N 0.000 description 1
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 150000002207 flavanone derivatives Chemical class 0.000 description 1
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
- 150000002216 flavonol derivatives Chemical class 0.000 description 1
- 235000011957 flavonols Nutrition 0.000 description 1
- 229940124600 folk medicine Drugs 0.000 description 1
- 235000021550 forms of sugar Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 235000008777 kaempferol Nutrition 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 235000020162 malted milk drink Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 210000004279 orbit Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- OXGUCUVFOIWWQJ-HQBVPOQASA-N quercitrin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OXGUCUVFOIWWQJ-HQBVPOQASA-N 0.000 description 1
- 150000008265 rhamnosides Chemical class 0.000 description 1
- 238000005096 rolling process Methods 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
- 239000007779 soft material Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical compound N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/38—Other non-alcoholic beverages
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/385—Concentrates of non-alcoholic beverages
- A23L2/39—Dry compositions
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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)
- A61K36/52—Juglandaceae (Walnut family)
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/86—Signal analysis
- G01N30/8624—Detection of slopes or peaks; baseline correction
- G01N30/8631—Peaks
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Pathology (AREA)
- Immunology (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Botany (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Alternative & Traditional Medicine (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了一种黄酮苷组合物及其黄杞叶水提后大孔树脂处理后的提取物在制备糖尿病药物中的应用。其中含有新落新妇苷,落新妇苷,异落新妇苷,新异落新妇苷,新黄杞苷,黄杞苷,异黄杞苷,新异黄杞苷,山奈酚‑3‑O‑鼠李糖苷,花旗松素‑3‑O‑(3″‑O‑p‑(E)‑没食子酰基)‑α‑L‑鼠李糖苷及其立体异构体。本发明属于药学、食品、保健食品与药物制剂领域,具体包括黄酮苷的组合物、制备、用途和产品。
Description
技术领域:
本发明属于药物化学、药理学与制剂领域,具体包括黄酮苷的组合物、制备、用途、制剂。
背景技术:
黄杞叶为胡桃科黄杞属植物黄杞(Engelhardtia roxburghiana Wall.)的干燥叶。黄杞属植物主要分布于亚洲热带和亚热带地区,其中我国有8种,产于南方各省,我国广东、广西、海南、湖南、贵州等南方各省均有分布。多为乔木或灌木,资源丰富,可做园林绿化树种。黄杞在广西为民间药,以树皮和叶入药。树皮行气化湿;叶可做茶饮,广西等地已将黄杞叶代茶饮,名为罗汉茶。《广西中药材标准》1996年版收载,罗汉茶具有清热解毒,生津止渴,解暑利湿的作用,可用于脾胃湿滞,胸腹胀闷,感冒发烧等症状。具有清热解毒,生津止渴,解暑利湿的作用,可用于脾胃湿滞,胸腹胀闷,感冒发烧等的治疗。
据文献报道,黄杞叶中主要含有黄酮化合物,甾体类,三萜类等成分。已报道的化学成分有黄酮类化合物,黄酮醇类、二氢黄酮醇类及其苷。主要成分有花旗松素,5,7,4,-三羟基二氢黄酮,山奈酚,二氢山奈酚,槲皮素,异黄杞苷,黄杞苷,落新妇苷,异落新妇苷,山奈酚-3-O-α-L-鼠李糖苷,5,7-二羟基色原酮-3-O-α-L-吡喃鼠李糖苷,5-羟基-3,7,3′,4′-四甲氧基黄酮,槲皮素-3-O-α-L-吡喃鼠李糖苷,2-乙氧基胡桃醌,L-肌醇等。
黄杞叶中主要成分的生物学活性,以黄酮类成分的抗凝血,降脂,降糖,增强免疫力等作用最为引人注目。其主要成分之一,落新妇苷,具有多种显著的生物活性,包括抑制辅酶A还原酶,抑制醛糖还原酶,保护肝脏,镇痛,消肿等。近年来有报道称落新妇苷有显著的选择性免疫抑制作用,且它的选择性作用与以往的免疫抑制剂相比具有明显优势,因此可以作为一种新的免疫抑制剂用于免疫相关疾病的治疗。
然而,落新妇苷难溶于水,25℃时水溶解度仅为250μg/mL,易溶于甲醇、乙醇、乙酸乙酯等有机溶剂,根据中国药典规定属于几乎不溶或不溶范围,因此落新妇苷不易被机体吸收代谢。研究表明,落新妇苷在大鼠体内的绝对生物利用度仅为0.066%,属于口服吸收较差的化合物。目前解决的办法为采取混悬液口服或用环糊精等辅料进行包合以提高水溶性。上述问题极大地限制了落新妇苷的药物应用。
落新妇苷在C-2和C-3位上存在立体异构现象,分别有2(R)∶3(R)(落新妇苷)、2(S)∶3(S)(新落新妇苷)、2(S)∶3(R)(新异落新妇苷)和2(R)∶3(S)(异落新妇苷)四种顺、反异构体。这四种立体异构体可以通过其查耳酮中间体而相互转换,在自然界中同时存在。因此,本发明采用不同的提取分离工艺,将落新妇苷与其立体异构体新落新妇苷、新异落新妇苷、异落新妇苷从黄杞叶中同时提取分离出来,并筛选出水溶性良好的组合物,在此组合物的水溶液中,落新妇苷在水中的溶解度为25℃下大于8mg/mL,这大大改善了落新妇苷的水溶解性,从而提高了其生物利用度。
虽然文献报道过关于黄杞叶对糖尿病的治疗作用,但关于其作用机制并未进行深入的研究。而关于落新妇苷单体对糖尿病的作用机制,仅有涉及体外活性实验的文献进行过报道,例如,Haraguchi等研究发现落新妇苷及其苷元-花旗松素对醛糖还原酶及山梨糖醇的积累有抑制作用;Estrada等研究发现落新妇苷有抑制葡萄糖-6-磷酸酶作用等。但这些靶点并未成为成熟的糖尿病开发途径。
回顾目前已经上市有明确糖尿病治疗作用的口服药物,类别主要有:磺脲类、双胍类、α-糖苷酶抑制剂、格列酮类、列汀类药物。其中α-糖苷酶抑制剂可用于治疗II型糖尿病,其机理是延缓碳水化合物(糖的各种形式)在肠道内吸收,代表药物是阿卡波糖(拜糖平)。虽然曾有文献显示黄杞叶有α-糖苷酶抑制活性,但并未对其中具体的有效成分进行详细研究。
因此,本发明结合从黄杞叶中获得的合落新妇苷及其立体异构体的组合物具备良好水溶性的特点,将不同分离提取工艺获得的组合物以及落新妇苷和黄杞苷及其立体异构体进行了体外α-糖苷酶抑制活性筛选,获得了优选的α-糖苷酶抑制活性的组合物。同时,本发明对优选组合物进行了超高效液相-质谱分析,得到该组合物的具体有效成分及其含量比例。结果显示优选的组合物α-糖苷酶抑制活性明显优于阿卡波糖(拜糖平)。
本发明将筛选出的优选组合物用于STZ(链脲佐菌素)所致的II型糖尿病小鼠模型。结果显示,给药16周后对于II型糖尿病小鼠的空腹糖耐量具有显著改善的能力,其效果优于阳性药物阿卡波糖(拜糖平)。
一系列的实验证明,优选的黄酮苷组合物具备开发为有潜力治疗II型糖尿病药物的条件。
发明内容:
本发明的目的在于提供一种黄酮苷组合物,其特征在于,含有新落新妇苷,落新妇苷,异落新妇苷,新异落新妇苷,新黄杞苷,黄杞苷,异黄杞苷,新异黄杞苷和山奈酚-3-O-鼠李糖苷,花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷及其立体异构体。
上述的黄酮苷组合物,其特征在于,合有新落新妇苷(20.3%),落新妇苷(23.4%),异落新妇苷(14.5%),新异落新妇苷(6.1%),新黄杞苷(7.6%),黄杞苷(12.1%),异黄杞苷(6.2%),新异黄杞苷(4.8%),山奈酚-3-O-鼠李糖苷(2.3%),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷及其立体异构体(2.7%)。本含量采用基于高效液相色谱分析的面积归一化法计算得到,检测器为紫外检测器,280nm。
上述黄酮苷组合物,其特征在于,将黄杞叶用水提取,并采用大孔树脂纯化。
本发明的另一目的在于提供上述黄酮苷组合物在制备糖尿病药物中的应用。
黄杞叶药材中的成分含量的测定
采集广西产胡桃科黄杞属植物黄杞(Engelhardtia roxburghiana Wall.)的叶子,自然晾干,按照下列方法测定黄杞叶中总黄酮含量和落新妇苷的含量。
.1、黄杞叶总黄酮的含量测定方法(紫外分光光度计法)
对照品溶液的制备:精密称取落新妇苷标准品适量,精密称定,加甲醇制成每1mL约含0.1mg的溶液,作为对照品溶液。
供试品溶液的制备:取100g干燥黄杞叶,用粉碎机磨成细粉,取黄杞叶细粉约50mg,精密称定,置50mL索氏提取器中,用50ml甲醇水浴50度加热回流,回流提取2小时,将提取液转移至50ml容量瓶中,用甲醇定容,摇匀,作为供试品溶液。
紫外分光光度测定法:分别取对照品溶液和供试品溶液,以甲醇为空白,用紫外分光光度计,在280nm波长处测定吸收度,计算得到黄杞叶总黄酮百分含量(%)。
2、黄杞叶落新妇苷成分的含量测定方法(超高效液相色谱测定法)
对照品溶液制备:同紫外分光光度法。
供试品溶液的制备:同紫外分光光度法。
色谱柱:C18色谱柱(100mm×2.1mm i.d.;1.7μm)。
色谱条件:流动相A,(0.1%甲酸);流动相B,乙腈。梯度洗脱条件:0-3min,17-20%B,3-6min,30%B。流速,0.3mL/min;进样体积,5μL。检测波长,280nm;柱温箱,40℃。
含量测定:稀释落新妇苷标准品溶液为不同浓度,分别进样测定,并绘制标准曲线,按照峰面积计算得到黄杞叶中落新妇苷百分含量(%)。
测定结果:本品按干燥品计,含总黄酮以落新妇苷(C21H22O11)计算。本批黄杞叶含总黄酮为34.0%,其中落新妇苷含量为3.5%。
3、不同分离纯化方法制备的黄杞叶黄酮苷组合物的筛选以及活性比较
纯化方案一、50%乙醇提取大孔树脂纯化法
黄杞叶药材粉碎后12倍量50%乙醇回流提取2次,每次2小时,合并两次的提取液,减压浓缩,浓缩到无醇,密度为1.0-1.10(60℃)上清液上HPD100大孔树脂柱层析吸附,上样流速为0.3倍柱体积/小时,树脂充分吸附后,先用水洗脱至无α-萘酚阳性反应,然后用5倍柱体积的30-50%乙醇的洗脱溶液,洗脱流速为0.8倍柱体积/小时,合并收集的洗脱溶液,减压浓缩至无醇,干燥,粉碎过筛60目真空干燥,得到黄杞叶50%乙醇提大孔树脂提取物。
分别用紫外分光光度法和超高效液相法测定该提取物,总黄酮含量为84.1%,其中落新妇苷(2,56.9%),异落新妇苷(3,4.7%),新异落新妇苷(4,3.9%),黄杞苷(6,23.8%),新异黄杞苷(8,2.2%),山奈酚-3-O-鼠李糖苷(9,3.5%),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷(10,0.9%),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷异构体(11,4.2%),见图1。
纯化方案二、甲醇提取大孔树脂纯化法
黄杞叶药材切碎或粉碎后至20-60目,12倍量甲醇回流提取2次,每次2小时,合并两次的提取液,减压浓缩,浓缩到密度为1.0-1.2,静置2-3h,离心,上清液上HPD100大孔树脂柱层析吸附,上样流速为0.3倍柱体积/小时,树脂充分吸附后,先用水洗脱至无α-萘酚阳性反应,然后用5倍柱体积的30-50%乙醇的洗脱溶液,洗脱流速为0.8倍柱体积/小时,合并收集的洗脱溶液,减压浓缩至无醇,干燥,粉碎过筛60目真空干燥,得到黄杞叶甲醇提大孔树脂纯化物。
分别用紫外分光光度法和超高效液相法测定该提取物,总黄酮含量达93.6%,其中落新妇苷(2,59.8%),异落新妇苷(3,3.1%),新异落新妇苷(4,3.0%),黄杞苷(6,23.6%),新异黄杞苷(8,1.6%),山奈酚-3-O-鼠李糖苷(9,3.6%),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷(10,0.7%),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷异构体(11,4.7%),见图2。
纯化方案三、水提取大孔树脂柱纯化法
将黄杞叶粉碎至20-60目,加12倍水,浸泡1-5h,100-150℃加热回流提取2-4h,提取3次,所得提取液用四层纱布过滤,合并滤液。旋转蒸发仪将滤液蒸干至原体积的1/10,冷冻干燥,得到棕褐色粉末状样品。
将水提物冻干粉用水配成1mg/mL溶液,按照1.0g粉末/mL树脂的上样量用弱极性或极性大孔树脂(如:D-101、HPD-100、AB-8等)吸附,上样流速为0.3倍柱体积/小时,树脂充分吸附后,先用水洗脱至无α-萘酚阳性反应,然后用5倍柱体积的20%乙醇进行洗脱,最后用5倍柱体积的50%乙醇进行洗脱,洗脱流速为0.8倍柱体积/小时,收集50%乙醇的洗脱液,浓缩至无醇,冷冻干燥,粉碎过筛60目,即得。
分别用紫外分光光度法和超高效液相法测定该提取物,测得总黄酮含量达87%,其中新落新妇苷(1,20.3%),落新妇苷(2,23.4%),异落新妇苷(3,14.5%),新异落新妇苷(4,6.1%),新黄杞苷(5,7.6%),黄杞苷(6,12.1%),异黄杞苷(7,6.2%),新异黄杞苷(8,4.8%),山奈酚-3-O-鼠李糖苷(9,2.3%),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷(10,1.2%),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷异构体(11,1.5%),见图3。
25℃下不同提取分离方法获得的有效部位的水溶性比较
按照《中国药典》2010版关于溶解度的测定方法,分别将上述各提取物分别研成细粉,各精密称取1g若干份。25℃下,分别置于1ml、10ml、30ml、100ml、1000ml的容量瓶中,水加至刻度,各每隔5min强力振摇30s,观察30min内的溶解情况,如无目视可见的的溶质颗粒或液滴时,即视为完全溶解。极易溶解系指溶质1g(ml)能在溶剂不到1ml中溶解;易溶系指溶质1g(ml)能在溶剂1~不到10ml中溶解;溶解系指溶质1g(ml)能在溶剂10~不到30ml中溶解;略溶系指溶质1g(ml)能在溶剂30~不到10Oml中溶解;微溶系指溶质lg(ml)能在溶剂100~不到1000ml中溶解;极微溶解系指溶质1g(ml)能在溶剂1000~不到10000ml中溶解;几乎不溶或不溶系指溶质1g(ml)在溶剂10000ml中不能完全溶解。结果如下表1:
表1不同提取分离方法获得组合物溶解性比较
结果显示,三种提取物的水溶解性依次为:水提大孔树脂提取物>50%乙醇提大孔树脂提取物>甲醇提大孔树脂提取物。
不同提取分离方法获得的组合物α-糖苷酶体外抑制活性比较
为进一步筛选良好生物活性和较好水溶性的组合物,我们对不同提取纯化方法获得的黄杞叶黄酮苷组合物进行α-糖苷酶抑制活性比较,以确定优选分离纯化方案。
α-糖苷酶抑制活性试验方法:使用底物对硝基苯基α-D-吡喃葡糖苷(pNPG),由α-糖苷酶水解释放产生对硝基苯酚,在405nm下测定吸光度。分别取80μL的50%乙醇提大孔树脂提取物、甲醇提大孔树脂提取物、水提大孔树脂提取物(10μg/ml)溶液,用0.1M磷酸盐缓冲剂(pH 6.8)与200μL的α-糖苷酶溶液(37U/ml)混合。阿卡波糖(1mg/ml)作为阳性对照。pH6.8下酶反应条件最优。取空白试剂,0.1磷酸盐缓冲剂(pH 6.8),作空白对照。混合物在96孔板中,37℃,10分钟持续的振动发生酶催化反应。反应后,取100μL的1mM pNPG溶液加到磷酸盐缓冲剂(pH 6.8)中,在37℃下继续反应。用酶标仪在405nm下连续检测120分钟,检测每分钟由pNPG中释放的对硝基苯酚。结果,获得0-120分钟,不同提取物以及阳性对照和空白对照溶液中α-糖苷酶活性的测量曲线,以及曲线下面积(0-120分钟),计算得到α-糖苷酶抑制的百分比。结果如下表2:
表2三种提取物α-糖苷酶抑制率比较
由测定结果可见,三种提取物抑制α-糖苷酶的强弱如下:水提大孔树脂提取物>50%乙醇提大孔树脂提取物>甲醇提大孔树脂提取物,其中水提大孔树脂提取物的α-糖苷酶抑制活性最强。对比不同提取物的超高效液相色谱图(图1-3),它们的化学成分主要差别在于落新妇苷或黄杞苷的其他异构体组成比例有明显的不同。上述结果提示落新妇苷或黄杞苷及其异构体对α-糖苷酶的抑制活性有所不同,而落新妇苷或黄杞苷及其异构体组合后对α-糖苷酶抑制活性更高。
结合水溶解性试验,故优选水提大孔树脂提取纯化法作为黄杞叶黄酮苷组合物的优化提取方法,将该方法制备的组合物作为黄杞叶优选黄酮苷组合物。
黄杞叶优选黄酮苷组合物成分的分析(超高效液相色谱-质谱法、核磁共振氢谱)
在以往的文献报道中,研究者并未对黄杞叶中抑制α-糖苷酶的活性成分进行深入的研究,对具体的活性成分也并未阐明。本发明深入研究了具有良好α-糖苷酶抑制活性的黄杞叶优选黄酮苷组合物,并进行了成分分析。
超高效液相色谱-质谱法 采用Waters公司的UPLC/Q-TOF-MS液质联用仪进行分析,包括Waters UPLC液相系统和Waters XevoG2 Q-TOF质谱。色谱柱:Waters AcquityUPLC BEHC18色谱柱(100mm×2.1mmi.d.;1.7μm)。色谱条件:流动相A,(0.1%甲酸);流动相B,乙腈。梯度洗脱条件:0-3min,17-20%B;3-6min,30%B。流速,0.3mL/min;进样体积,5μL。检测波长,280nm;柱温箱,40℃。质谱数据采集采用电喷雾离子源(ESI),负离子模式,利用MSE方法在一针进样同时采集母离子及子离子碎片信息。质谱条件如下:毛细管电压3.0kV;锥孔电压40V;离子源温度120℃;去溶剂温度450℃;锥孔气体流速50L/h;去溶剂化气体流速600.0L/h;MS1和MS2扫描范围m/z 100-1500,7min;碰撞能量25-35V。使用WatersMassLynx v4.1软件采集并分析数据。
经超高效液相-质谱分析(图4),与文献报道结果对比后,色谱峰1-11分别鉴定为:新落新妇苷(1,C21H22O11),落新妇苷(2,C21H22O11),异落新妇苷(3,C21H22O11),新异落新妇苷(4,C21H22O11),新黄杞苷(5,C21H22O10),黄杞苷(6,C21H22O10),异黄杞苷(7,C21H22O10),新异黄杞苷(8,C21H22O10),山奈酚-3-O-鼠李糖苷(9,C21H20O10),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷(10,C28H26O15),花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷异构体(11,C28H26O15)。
通过超高效液相色谱分析,本发明涉及黄杞叶黄酮苷组合物,其含有如下百分比的组分(百分含量%):1.新落新妇苷(20.3%),2.落新妇苷(23.4%),3.异落新妇苷(14.5%),4.新异落新妇苷(6.1%),5.新黄杞苷(7.6%),6.黄杞苷(12.1%),7.异黄杞苷(6.2%),8.新异黄杞苷(4.8%),9.山奈酚-3-O-鼠李糖苷(2.3%),10.花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷(1.2%),11.花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷异构体(1.5%)。
核磁共振氢谱法 用Varian公司Mercury Plus 500MHz核磁共振仪,在25℃下、以氘代DMSO为溶剂,采集样品的氢谱。通过对组合物的核磁共振氢谱分析,本发明涉及黄杞叶黄酮苷组合物,其有如下核磁共振氢谱特征,见图5。
本提取物中主要的化学成分为二氢黄酮苷类化合物,另有少量的黄酮苷类成分,以及微量的未知成分。其中δ 8.88-12.66的区域,主要是黄酮苷类成分的酚羟基上活泼氢的信号;δ 5.86-7.75的区域,主要是黄酮苷元部分的芳香氢信号;δ3.01-5.47的区域,主要是二氢黄酮苷元部分的2位和3位氢信号以及糖上的氢信号;δ0.74-1.14的区域,主要是鼠李糖上6位甲基的氢信号。核磁共振氢谱结果进一步说明,该优选组合物的化学成分组成的主要特点:落新妇苷、黄杞苷为其中主要成分、另含山奈酚-3-O-鼠李糖苷、花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷等二氢黄酮鼠李糖苷以及其立体异构体等成分。
黄杞叶水提大孔树脂提取物中立体异构体的制备及其α-糖苷酶抑制体外活性比较
为进一步明确组合物中不同异构体生物活性的差异,我们对水提大孔树脂纯化获得的黄杞叶黄酮苷组合物中立体异构体进行了分离和制备,并对其α-糖苷酶抑制体外活性进行了比较,以进一步解释不同方法提取物活性差异的原因。
黄杞叶黄酮苷组合物中立体异构体的制备:采用Agilent公司的1260Infinity液相色谱仪进行制备。色谱柱:Agilent Eclipse XDB-C18色谱柱(9.4mm×250mm,5μm)。色谱条件:流动相A,(0.1%甲酸);流动相B,乙腈。梯度洗脱条件:0-34min,17%B,34-35min,17→35%B,35-40min,35%B。流速,4.0mL/min;进样体积,80μL。检测波长,280nm;柱温,40℃。制备单体经超高效液相色谱检测纯度均大于95%。
α-糖苷酶抑制活性试验方法:采用上述方法测定组合物中不同异构体的α-糖苷酶抑制活性。结果如下表3:
表3组合物中不同异构体的α-糖苷酶抑制活性(IC50值)
由测定结果得,落新妇苷的α-糖苷酶抑制活性较黄杞苷强。对比落新妇苷的四个异构体中,新落新妇苷活性最强;黄杞苷的四个异构体中,新黄杞苷活性最强。而新落新妇苷和新黄杞苷在水提大孔树脂提取物中的含量显著高于其在50%乙醇提大孔树脂提取物和甲醇提大孔树脂提取物中的含量。上述结果显示黄杞叶经水提取后落新妇苷和黄杞苷异构体的含量发生明显变化,α-糖苷酶抑制活性最强的新落新妇苷和新黄杞苷含量明显增加,因此,这种组合物对α-糖苷酶的抑制活性更高。结合上述实验结果,优选水提取大孔树脂纯化法作为黄杞叶黄酮苷组合物的优化提取方法,将该方法制备的组合物作为黄杞叶优选黄酮苷组合物。
黄酮苷组合物对II型糖尿病模型小鼠血糖的影响
为进一步验证黄杞叶优选黄酮苷组合物对II型糖尿病血糖的影响,我们对黄杞叶优选黄酮苷组合物进行了相关药理学研究。本发明采用高脂饲料和链脲佐菌素(STZ)联合诱导的II型糖尿病(C57/BL6J)近交系小鼠模型来进行药理学研究。该动物模型与人体II型糖尿病的生理体征非常相似,较之传统的四氧嘧啶模型、单纯STZ更为稳定,且采用近交系小鼠,试验数据重现性更好,近年来成为研究II型糖尿病的动物模型的主流。本发明是国内第一次采用此动物模型研究黄杞叶中的有效成分。
1实验材料
1.1实验动物
雄性C57/BL6J小鼠,体重18~22g,由广州中医药大学动物实验中心提供。
1.2药品与试剂
试液配制
阳性药:DPP4抑制剂沙格列汀、α糖苷酶抑制剂拜糖平,均以生理盐水配制成目标剂量。
优选黄酮苷组合物的制备:参见纯化方案三、水提取大孔树脂柱纯化法,
优选黄酮苷组合物高剂量(1g/kg)的配制:将上述方法得到的提取物,420mg+14ml用生理盐水溶解,浓度30mg/ml,备用。每天每只0.2ml/10g体重进行灌胃给药。
优选黄酮苷组合物中剂量(0.5g/kg)的配制:将上述方法得到的高剂量中取6ml,用用生理盐水定容到12ml即可,浓度15mg/ml,备用。每天每只0.2ml/10g体重进行灌胃给药。
优选黄酮苷组合物低剂量(0.25g/kg)的配制:将上述方法得到的中剂量中取4ml,用用生理盐水定容到8ml即可,浓度7.5mg/ml,备用。每天每只0.2ml/10g体重进行灌胃给药。
柠檬酸缓冲液∶柠檬酸缓冲液配制(pH4.4)∶柠檬酸2.1g,柠檬酸钠2.94g,分别用生理盐水溶解定量至100ml,使其浓度均为0.1mM。取上述柠檬酸溶液65.1mL,柠檬酸钠溶液54.9mL,充分混匀,用棕色瓶存储于4℃冰箱备用。
STZ溶液:配制用的器具要灭酶,手术器械需要高温处理,缓冲液等高压湿热灭菌。
1%STZ溶液配制:在避光、低温(冰盒里面配制)、干燥环境中把0.2g链脲佐菌素溶于20mL柠檬酸缓冲液中,置于冰水浴中,30min内给动物注射完毕。参考文献STZ腹腔注射剂量为120mg/Kg,120mg/Kg÷10mL/Kg=12mg/mL。小鼠腹腔注射量为10mL/Kg。
1.3高脂饲料配方:
高脂饲料配方组成:猪油10%、蛋黄粉10%、胆盐0.2%、胆固醇1%,其余成分为基础饲料。
1.4饲养管理:
动物饲养在实验动物中心SPF级动物房,动物饲养条件:5~6只/盒,群养,饲养温度与湿度:20~25℃,40~70%,采用12h∶12h昼夜间断照明;自由进食饮水;基础饲料、高脂饲料均由广州中医药大学实验动物中心提供。
每天灌胃时注意观察动物粪便,打架情况,如有打架情况及时分离出打架的小鼠。
1.5主要仪器:
血糖仪瑞迪恩HL588E型
瑞迪恩血糖试纸瑞迪恩生物科技股份有限公司
全自动血生化分析仪日立7020型
2实验方法
表4试验分组表
各组动物按上面方案灌胃给药(容量为20ml/kg),每日1次,给予SPF级别饲料喂养,共12周,实验动物于分组前给予禁食不禁水12小时血糖监测,依据体重、血糖水平分组,给药后第12周进行OGTT实验。
1试验流程
动物适应性饲养4周后,禁食16h,尾尖针刺取血直接于血糖仪上测定血糖值。当天测定完毕后,分正常组和模型组,正常组动物饲以普通维持期鼠料,模型组饲以前述高脂饲料,同时给予模型组注射STZ,120mg/Kg。每周记录小鼠体重一次。
第5周,禁食12小时,尾尖针刺取血直接于血糖仪上测定血糖值。
第6周,禁食12小时,尾尖针刺取血直接于血糖仪上测定血糖值,确定模型成立。然后将模型组平均分成6组,正常组和模型组给予注射用水,其余给予药物。
第8周,禁食12小时,尾尖针刺取血直接于血糖仪上测定血糖值。
第10周,禁食12小时,尾尖针刺取血直接于血糖仪上测定血糖值。
第12周,禁食12小时,尾尖针刺取血直接于血糖仪上测定血糖值。
第14周,禁食12小时,尾尖针刺取血直接于血糖仪上测定血糖值。
第16周,禁食12小时,尾尖针刺取血做OGTT(其余时间点测GLU,最末一时间点眼眶采血,测定全套血生化指标),做出曲线及曲线下面积。
2检测指标
观察:从实验开始至实验结束,每天观察并记录小鼠的日常情况。
体重:从开始给药到实验结束,每周称量小鼠体重1次。
3实验结果
3.1给药后小鼠体重变化
给药后小鼠体重变化见表5。从表5可以看出,开始给药之后,各组动物的体重与模型组相比较其差异没有统计学意义。但拜糖平组与黄杞低剂量组的体重增长的平均值要高于模型组,可认为具有改善II型糖尿病小鼠生存质量的趋势。
各组均与模型组相比较,p<0.1*,p<0.05;**,p<0.01
3.2给药后小鼠空腹血糖变化
给药后小鼠的空腹血糖变化结果见表6。从表6可以看出,从第5周也就是造模开始之后,各组小鼠空腹血糖的均值均大于正常空腹血糖值的上限7.0,可认为模型已经成立。各组动物给药前的基础空腹血糖值经过按照血糖水平随机分组之后,基本一致。当给药至第9周时,沙格列汀组和黄酮苷组合物低剂量组的空腹血糖值均显著低于模型组(p<0.05);第10周时,中剂量组的空腹血糖值显著低于模型组(p<0.05);第12周时,高剂量组的空腹血糖值显著低于模型组(p<0.05);第14周时,沙格列汀组和低剂量组的空腹血糖值均再次显著低于模型组(p<0.05);第16周时,低剂量组的空腹血糖值再次显著低于模型组(p<0.05)。可认为黄酮苷组合物在低剂量水平下具有改善II型糖尿病小鼠空腹血糖水平的能力。该结果提示:黄酮苷组合物中、低剂量水平改善II型糖尿病小鼠空腹血糖水平的能力可能与拜糖平相当,略低于沙格列汀。
各组均与模型组相比较;*,p<0.05;**,p<0.01
3.3给药16周后小鼠空腹糖耐量(OGTT)的变化
给药16周后,各组小鼠的空腹糖耐量实验结果见表7。从表7可以看出各组动物空腹糖耐量实验的血糖曲线下面积(AUC)与模型组相比较,除空白对照组之外,其他的差异均没有显著性意义。但优选黄酮苷组合物的三个剂量呈现一定的量效关系,提示其可能对II型糖尿病小鼠的胰岛素抵抗具有一定缓解的趋势。拜糖平与沙格列汀则没有体现出这种趋势。
3.4给药16周后小鼠血生化水平的变化
给药16周后小鼠的血生化水平见表8。表4结果提示,本实验所建立的II型糖尿病模型对小鼠的肝、肾功能、血脂水平均存在一定的不利影响,优选黄酮苷组合物和两个阳性对照组对此均没有体现出明显的改善效果。
各组均与模型组相比较;*,p<0.05;**,p<0.01
各组均与模型组相比较;*,p<0.05;**,p<0.01
4药理实验结论
优选黄酮苷组合物对于II型糖尿病小鼠的空腹血糖表现出一定的降低活性;给药16周后对于II型糖尿病小鼠的空腹糖耐量具有显著改善的活性,其效果优于阳性受试物。以上结果提示,本发明的优选黄酮苷组合物可以作为一个有潜力的改善II型糖尿病的药物。
经过上述研究,结果表明黄杞叶黄酮苷组合物可以作为一个有潜力的改善II型糖尿病的药物。结合黄酮苷组合物的良好的水溶性,本发明将其制备成口服制剂,方便患者长期使用。经过研究,结果表明黄杞叶黄酮苷组合物可以作为一个有潜力的改善糖尿病的药品、食品、保健食品或膳食补充剂。
附图说明
图1、黄杞叶50%乙醇提大孔树脂提取物的超高效液相色谱图
图2、黄杞叶甲醇提大孔树脂提取物的超高效液相色谱图
图3、黄杞叶水提大孔树脂提取物的超高效液相色谱图
图4、黄杞叶黄酮苷组合物中化合物1的高分辨质谱图
图5、黄杞叶黄酮苷组合物中化合物2的高分辨质谱图
图6、黄杞叶黄酮苷组合物中化合物3的高分辨质谱图
图7、黄杞叶黄酮苷组合物中化合物4的高分辨质谱图
图8、黄杞叶黄酮苷组合物中化合物5的高分辨质谱图
图9、黄杞叶黄酮苷组合物中化合物6的高分辨质谱图
图10、黄杞叶黄酮苷组合物中化合物7的高分辨质谱图
图11、黄杞叶黄酮苷组合物中化合物8的高分辨质谱图
图12、黄杞叶黄酮苷组合物中化合物9的高分辨质谱图
图13、黄杞叶黄酮苷组合物中化合物10的高分辨质谱图
图14、黄杞叶黄酮苷组合物中化合物11的高分辨质谱图
图15、黄杞叶黄酮苷组合物的1H-NMR图谱
具体实施方式
经过上述研究,结果表明结合黄酮苷组合物的良好的水溶性,本发明将其制备成口服制剂,方便患者长期使用,黄杞叶黄酮苷组合物可以作为一个有潜力的改善II型糖尿病的药物或者食品以及保健食品。。以下实施例用于阐述本发明而不是限制本发明。
实施例1
黄酮苷组合物15g;微晶纤维素75g;95%乙醇50ml;羟丙基纤维素15g;25%淀粉浆120ml;硬酸镁5g,制粒,50℃真空干燥,30-100目筛整粒,压成片剂;
实施例2
黄酮苷组合物15g;微晶纤维素75g;95%乙醇50ml;羟丙基纤维素15g;20%淀粉浆120ml;硬酸镁5g,制粒,50℃真空干燥,60-100目筛整粒,灌胶囊;
实施例3
黄酮苷组合物15g;糊精20g;乳糖10g,25%淀粉浆120ml;糖粉20g;100目筛制粒,50℃干燥,14目筛整粒,分装成袋;
实施例4
将黄酮苷组合物先制备成磷脂复合物,研细后过80目筛,并加入1%微晶纤维素和10%乳糖后过60目筛充分混匀,加入一定量的润湿剂制成软材,经挤出-滚圆造粒机制得湿微丸,在50℃条件下烘12h即可得干燥微丸。
实施例5
黄酮苷组合物15.0g;加入2.0g谷氨酸,加入10.0g甘露醇,加入纯净水,加热溶解,稀释至500ml,过滤、滤液超滤,分装,得到口服液。
实施例6
黄酮苷组合物15g;50%乙醇50ml;糊精20g;乳糖10g,25%淀粉浆120ml;100目筛制速溶固体饮料颗粒,50℃干燥,14目筛整粒,分装成袋。
实施例7
黄酮苷组合物15.0g;加入0.5g柠檬酸,加入1.0g麦乳精,加入10.0g甘露醇,加入纯净水,加热溶解,稀释至500ml,过滤、滤液超滤,分装,得到可口的保健饮料。
Claims (2)
1.黄杞叶水提后大孔树脂处理后的提取物在制备糖尿病药物中的应用和/或在制备辅助降血糖保健食品中的应用,所述提取物的提取方法为:将黄杞叶用水提取,并采用大孔树脂纯化,具体为:
将黄杞叶粉碎至20-60目,加12倍水,浸泡1-5h,100-150℃加热回流提取2-4h,提取3次,所得提取液用四层纱布过滤,合并滤液;旋转蒸发仪将滤液蒸干至原体积的1/10,冷冻干燥,得到棕褐色粉末状样品;
将水提物冻干粉用水配成1mg/mL溶液,按照1.0g粉末/mL树脂的上样量用弱极性或极性大孔树脂吸附,上样流速为0.3倍柱体积/小时,树脂充分吸附后,先用水洗脱至无α-萘酚阳性反应,然后用5倍柱体积的20%乙醇进行洗脱,最后用5倍柱体积的50%乙醇进行洗脱,洗脱流速为0.8倍柱体积/小时,收集50%乙醇的洗脱液,浓缩至无醇,冷冻干燥,粉碎过筛60目,即得;
所述提取物含有20.3%新落新妇苷,23.4%落新妇苷,14.5%异落新妇苷,6.1%新异落新妇苷,7.6%新黄杞苷,12.1%黄杞苷,6.2%异黄杞苷,4.8%新异黄杞苷,2.3%山奈酚-3-O-鼠李糖苷,2.7%花旗松素-3-O-(3″-O-p-(E)-没食子酰基)-α-L-鼠李糖苷及其立体异构体。
2.根据权利要求1所述应用,其特征在于,所述大孔树脂选自AB-8,HPD-400,HPD-100,D-101树脂中任一种。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911170778.6A CN111437302B (zh) | 2015-05-25 | 2016-04-28 | 黄杞叶水提后大孔树脂处理后的提取物在制备糖尿病药物中的应用及其分析方法 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510268187 | 2015-05-25 | ||
CN201610051792 | 2016-01-27 | ||
CN201610269109.4A CN106389453B (zh) | 2015-05-25 | 2016-04-28 | 黄酮糖苷组合物 |
CN201911170778.6A CN111437302B (zh) | 2015-05-25 | 2016-04-28 | 黄杞叶水提后大孔树脂处理后的提取物在制备糖尿病药物中的应用及其分析方法 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610269109.4A Division CN106389453B (zh) | 2015-05-25 | 2016-04-28 | 黄酮糖苷组合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111437302A CN111437302A (zh) | 2020-07-24 |
CN111437302B true CN111437302B (zh) | 2022-03-01 |
Family
ID=58006263
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911170778.6A Active CN111437302B (zh) | 2015-05-25 | 2016-04-28 | 黄杞叶水提后大孔树脂处理后的提取物在制备糖尿病药物中的应用及其分析方法 |
CN201610269109.4A Active CN106389453B (zh) | 2015-05-25 | 2016-04-28 | 黄酮糖苷组合物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610269109.4A Active CN106389453B (zh) | 2015-05-25 | 2016-04-28 | 黄酮糖苷组合物 |
Country Status (1)
Country | Link |
---|---|
CN (2) | CN111437302B (zh) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112326842A (zh) * | 2020-11-27 | 2021-02-05 | 合肥科颖医药科技有限公司 | 一种沙格列汀定量检测分析方法 |
CN112730674B (zh) * | 2020-12-23 | 2022-10-04 | 广西壮族自治区食品药品检验所 | 一种罗汉茶的质量检测方法 |
CN113440536B (zh) * | 2021-08-18 | 2022-02-01 | 黑龙江中医药大学 | 一种用于防治糖尿病的药物及其用途 |
CN113813277A (zh) * | 2021-10-19 | 2021-12-21 | 广州白云山敬修堂药业股份有限公司 | 一种包含落新妇苷和/或其异构体的组合物在制备治疗银屑病的药物中的用途 |
CN113855689B (zh) * | 2021-10-19 | 2022-06-10 | 黑龙江中医药大学 | 黄杞苷或其异构体在制备治疗子宫内膜异位症的药物中的用途 |
CN114796308B (zh) * | 2021-12-14 | 2024-03-19 | 成都大学 | 黄杞叶提取物作为α-葡萄糖苷酶抑制剂的应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1724552A (zh) * | 2005-07-08 | 2006-01-25 | 南京大学 | 一种落新妇苷的制备方法 |
CN101675944A (zh) * | 2008-09-16 | 2010-03-24 | 杭州华东医药集团生物工程研究所有限公司 | 含有黄杞叶提取物的组合物及制备方法 |
CN103181952A (zh) * | 2011-12-31 | 2013-07-03 | 天津药物研究院 | 一种防治自身免疫疾病的黄杞提取物及其制备方法 |
CN105435007A (zh) * | 2014-09-25 | 2016-03-30 | 中国人民解放军第三〇二医院 | 一种中药组方的煎煮方法 |
-
2016
- 2016-04-28 CN CN201911170778.6A patent/CN111437302B/zh active Active
- 2016-04-28 CN CN201610269109.4A patent/CN106389453B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1724552A (zh) * | 2005-07-08 | 2006-01-25 | 南京大学 | 一种落新妇苷的制备方法 |
CN101675944A (zh) * | 2008-09-16 | 2010-03-24 | 杭州华东医药集团生物工程研究所有限公司 | 含有黄杞叶提取物的组合物及制备方法 |
CN103181952A (zh) * | 2011-12-31 | 2013-07-03 | 天津药物研究院 | 一种防治自身免疫疾病的黄杞提取物及其制备方法 |
CN105435007A (zh) * | 2014-09-25 | 2016-03-30 | 中国人民解放军第三〇二医院 | 一种中药组方的煎煮方法 |
Non-Patent Citations (5)
Title |
---|
HPLC法测定黄杞叶中落新妇苷和黄杞苷;曲佳等;《中草药》;20090212;第40卷(第02期);第306页第2.1-2.4节;第307页第2.9节 * |
大孔树脂分离黄杞叶总黄酮的研究;王芬等;《中国医药指南》;20141210;第12卷(第34期);第22页摘要第2-4行、第1段第1-3行、第1节第1段、第2.1节第1-3行 * |
特色壮药材罗汉茶质量标准研究;覃兰芳,等;《中医药导报》;20121130;第18卷(第11期);第76-77页 * |
高效液相色谱法测定罗汉茶中落新妇苷的含量;姚毅等;《中国现代应用药学》;20061208;第23卷(第9期);第920-921页 * |
黄杞叶提取物降血糖作用的研究;李晨岚等;《中草药》;20081112;第39卷(第11期);第1696页摘要第4-7行;第1698页第4节第1段、第3段第6-10行;第1696页第1段第6-7行 * |
Also Published As
Publication number | Publication date |
---|---|
CN106389453B (zh) | 2019-12-27 |
CN111437302A (zh) | 2020-07-24 |
CN106389453A (zh) | 2017-02-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111437302B (zh) | 黄杞叶水提后大孔树脂处理后的提取物在制备糖尿病药物中的应用及其分析方法 | |
TWI454269B (zh) | 由文冠果(xanthoceras sorbifolia)單離之化合物、其製備方法以及其用途 | |
CN101229181A (zh) | 具有糖尿病及其并发症治疗作用的药物组合物 | |
AU2003236377B2 (en) | Water soluble extract from plant of Solanum genus and the preparation process thereof, and pharmaceutical composition containing the water soluble extract | |
AU2008323968B2 (en) | Extract of fraxinus excelsior seeds and therapeutic applications therefor | |
US20130018009A1 (en) | Anti-obesity product and its method of preparation | |
Peng et al. | Changes in levels of phenylethanoid glycosides, antioxidant activity, and other quality traits in Cistanche deserticola slices by steam processing | |
JP2010528063A (ja) | シャジクソウ属植物、大豆属植物、イチョウ属植物からセコイトール含有抽出物を取得する方法及び用途 | |
CN108440292A (zh) | 异序乌桕素a-h及其药物组合物和其应用 | |
Kerbab et al. | Halimium halimifolium: From the chemical and functional characterization to a nutraceutical ingredient design | |
CN103860638A (zh) | 苦豆子黄酮组合物的制备方法及医药新用途 | |
Chigurupati et al. | Antioxidant and antidiabetic properties of Tamarindus indica leaf ethanolic extract from Malaysia | |
CN102365089B (zh) | 一种预防和治疗阿尔茨海默氏症的药物及其制备方法 | |
CN102875615B (zh) | 大麻药苷a和大麻药总皂苷的提取方法及其应用 | |
CN101239058B (zh) | 原花青素类化合物用于制备防治幽门螺杆菌相关性胃炎的药物和保健食品 | |
CN113185618B (zh) | 一种抗酒精性肝损伤的白术多糖及其制备方法与应用 | |
KR101455177B1 (ko) | 파낙스속 식물 추출물의 마이얄형 갈색화 반응 생성물을 포함하는 신장질환의 예방, 개선 또는 치료용 조성물 | |
CN107115372B (zh) | 一种含有罗布麻叶总黄酮的抗肿瘤药物组合物 | |
KR20150050090A (ko) | 마이크로웨이브 조사에 의해 유효 성분 함량이 증가된 파낙스속 식물 추출물을 포함하는 신장 독성을 억제하기 위한 조성물, 건강기능식품용 조성물, 및 개체의 신장 독성을 억제하는 방법 | |
CN114886945B (zh) | 一种调节嘌呤代谢的超分子药物及其应用 | |
CN111690023B (zh) | 马钱苷乙酰化衍生物类环烯醚萜化合物及其提取方法和应用 | |
El-Azab et al. | In vitro anti-diabetic effect and molecular docking study of Phlomis aurea components as diabetic enzymes inhibitor | |
Abdulrazak et al. | In-vitro α-glucosidase inhibitory potential of extracts from Musa paradisiaca | |
CN100488553C (zh) | 肖菝葜属植物提取物及其制备方法和应用 | |
EP1508334A1 (en) | Water soluble extract from plant of solanum genus and the preparation process thereof, and pharmaceutical composition containing the water soluble extract |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20210709 Address after: 215228 Room 301, business incubation base, science and Technology Innovation Park, South Third Ring Road (Xinan Village), Shengze Town, Wujiang District, Suzhou City, Jiangsu Province Applicant after: Suzhou yunuokang Pharmaceutical Technology Co., Ltd Address before: 101311 Room 301, unit 2, building 3, Jixiang garden, Shunyi District, Beijing Applicant before: Cai Shizhen |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant |