CN109223811A - 具有降糖活性的人参皂苷组合物 - Google Patents
具有降糖活性的人参皂苷组合物 Download PDFInfo
- Publication number
- CN109223811A CN109223811A CN201810533787.6A CN201810533787A CN109223811A CN 109223811 A CN109223811 A CN 109223811A CN 201810533787 A CN201810533787 A CN 201810533787A CN 109223811 A CN109223811 A CN 109223811A
- Authority
- CN
- China
- Prior art keywords
- ginsenoside
- group
- cell
- panaxsaponin
- panaxsaponin composition
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 42
- 230000002218 hypoglycaemic effect Effects 0.000 title claims abstract description 20
- 229930182494 ginsenoside Natural products 0.000 claims abstract description 57
- 229940089161 ginsenoside Drugs 0.000 claims abstract description 56
- 125000003827 glycol group Chemical group 0.000 claims abstract description 20
- 150000004072 triols Chemical group 0.000 claims abstract description 17
- RWXIFXNRCLMQCD-JBVRGBGGSA-N (20S)-ginsenoside Rg3 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RWXIFXNRCLMQCD-JBVRGBGGSA-N 0.000 claims abstract description 13
- NJUXRKMKOFXMRX-RNCAKNGISA-N Ginsenoside Rg5 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4C(/C)=C/CC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O NJUXRKMKOFXMRX-RNCAKNGISA-N 0.000 claims abstract description 8
- NJUXRKMKOFXMRX-AXUZFSSLSA-N ginsenoside Rg5 Natural products CC(=CCC=C(C)[C@H]1CC[C@]2(C)[C@@H]1[C@H](O)C[C@@H]3[C@@]4(C)CC[C@@H](O[C@H]5O[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O[C@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O)C(C)(C)[C@@H]4CC[C@@]23C)C NJUXRKMKOFXMRX-AXUZFSSLSA-N 0.000 claims abstract description 8
- NJUXRKMKOFXMRX-UHFFFAOYSA-N ginsenoside Rz1 Natural products CC(C)=CCC=C(C)C1CCC(C2(CCC3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O NJUXRKMKOFXMRX-UHFFFAOYSA-N 0.000 claims abstract description 8
- KWDWBAISZWOAHD-MHOSXIPRSA-N (2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5s,6r)-4,5-dihydroxy-6-(hydroxymethyl)-2-[[(3s,5r,8r,9r,10r,12r,13r,14r,17s)-12-hydroxy-4,4,8,10,14-pentamethyl-17-(6-methylhepta-1,5-dien-2-yl)-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]o Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4C(=C)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O KWDWBAISZWOAHD-MHOSXIPRSA-N 0.000 claims abstract description 6
- KWDWBAISZWOAHD-UHFFFAOYSA-N Ginsenoside Rk1 Natural products CC(C)=CCCC(=C)C1CCC(C2(CCC3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O KWDWBAISZWOAHD-UHFFFAOYSA-N 0.000 claims abstract description 6
- XIRZPICFRDZXPF-UHFFFAOYSA-N Ginsenoside Rg3 Natural products CC(C)=CCCC(C)(O)C1CCC(C2(CC(O)C3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O XIRZPICFRDZXPF-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 13
- 241000208340 Araliaceae Species 0.000 claims description 10
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims description 10
- 235000003140 Panax quinquefolius Nutrition 0.000 claims description 10
- 235000008434 ginseng Nutrition 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- OZTXYFOXQFKYRP-TXRYYSRHSA-N Ginsenoside Rh4 Chemical compound O([C@@H]1[C@H]2C(C)(C)[C@@H](O)CC[C@]2(C)[C@H]2C[C@@H](O)[C@H]3[C@@]([C@@]2(C1)C)(C)CC[C@@H]3C(/C)=C/CC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O OZTXYFOXQFKYRP-TXRYYSRHSA-N 0.000 claims description 7
- OZTXYFOXQFKYRP-RISAHGKBSA-N Ginsenoside Rh4 Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@H]1[C@H]2C(C)(C)[C@@H](O)CC[C@]2(C)[C@@H]2[C@](C)([C@@]3(C)[C@H]([C@H](O)C2)[C@@H](/C(=C\C/C=C(\C)/C)/C)CC3)C1 OZTXYFOXQFKYRP-RISAHGKBSA-N 0.000 claims description 7
- 229930182490 saponin Natural products 0.000 claims description 7
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims description 5
- 150000007949 saponins Chemical class 0.000 claims description 5
- 239000000470 constituent Substances 0.000 claims description 4
- 235000013376 functional food Nutrition 0.000 claims description 2
- 235000013402 health food Nutrition 0.000 claims description 2
- AVXFIVJSCUOFNT-QXPABTKOSA-N (2R,3R,4S,5S,6R)-2-[[(3S,5R,6S,8R,9R,10R,12R,13R,14R,17S)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(6-methylhepta-1,5-dien-2-yl)-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-6-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical group O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@H]1[C@H]2C(C)(C)[C@@H](O)CC[C@]2(C)[C@@H]2[C@](C)([C@@]3(C)[C@H]([C@H](O)C2)[C@@H](C(=C)CC/C=C(\C)/C)CC3)C1 AVXFIVJSCUOFNT-QXPABTKOSA-N 0.000 claims 2
- 229930182470 glycoside Natural products 0.000 claims 2
- 150000002338 glycosides Chemical class 0.000 claims 2
- 239000000344 soap Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 19
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 17
- 239000008103 glucose Substances 0.000 description 37
- 210000004027 cell Anatomy 0.000 description 35
- 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 34
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 22
- 241000699666 Mus <mouse, genus> Species 0.000 description 21
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 21
- 239000000243 solution Substances 0.000 description 19
- 239000000178 monomer Substances 0.000 description 18
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 102000004877 Insulin Human genes 0.000 description 11
- 108090001061 Insulin Proteins 0.000 description 11
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 11
- 239000001963 growth medium Substances 0.000 description 11
- 229940125396 insulin Drugs 0.000 description 11
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 8
- 101000907578 Homo sapiens Forkhead box protein M1 Proteins 0.000 description 8
- 206010022489 Insulin Resistance Diseases 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 230000003833 cell viability Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 5
- 235000017709 saponins Nutrition 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- -1 Ge Lienai Class Chemical class 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 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 4
- 238000004737 colorimetric analysis Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000007850 degeneration Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000000496 pancreas Anatomy 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 239000003472 antidiabetic agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000005229 liver cell Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 235000002722 Dioscorea batatas Nutrition 0.000 description 2
- 235000006536 Dioscorea esculenta Nutrition 0.000 description 2
- 240000001811 Dioscorea oppositifolia Species 0.000 description 2
- 235000003416 Dioscorea oppositifolia Nutrition 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 208000017170 Lipid metabolism disease Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 description 2
- 240000006365 Vitis vinifera Species 0.000 description 2
- 235000014787 Vitis vinifera Nutrition 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000003178 anti-diabetic effect Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 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
- 230000007246 mechanism Effects 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 230000007863 steatosis Effects 0.000 description 2
- 231100000240 steatosis hepatitis Toxicity 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- VJRLOPVXROQXLO-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;urea Chemical compound NC(N)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O VJRLOPVXROQXLO-BTVCFUMJSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- HCEQQASHRRPQFE-UHFFFAOYSA-N 5-chloro-n-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxybenzamide;3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N.COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 HCEQQASHRRPQFE-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 241000208343 Panax Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- XECUMCLPUKPRLJ-UHFFFAOYSA-N [O].C1=CN=CN=C1 Chemical compound [O].C1=CN=CN=C1 XECUMCLPUKPRLJ-UHFFFAOYSA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004490 capsule suspension Substances 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229940112611 glucovance Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000000229 preadipocyte Anatomy 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000000837 restrainer Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011122 softwood Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Botany (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
本发明公布了一种具有降糖活性的人参皂苷组合物,其包含选自人参皂苷Rk1、Rg3、Rg5中的一种或两种或三种的二醇组人参皂苷、以及选自人参皂苷Rk3、Rh4中的一种或两种的三醇组人参皂苷作为有效成分,该组合物用于预防或治疗糖尿病,效果显著。
Description
技术领域
本发明属于生物化工领域,具体而言,本发明涉及一种人参皂苷组合物及其在糖尿病预防及治疗领域中的应用。
背景技术
糖尿病是一种与胰岛素的产生和作用异常相关、以高血糖症为主要特征的代谢紊乱综合征,是一种严重危害健康的慢性疾病,是当前人类所面临的主要健康问题之一。糖尿病可分为胰岛素依赖型糖尿病(I型糖尿病)及非胰岛素依赖型糖尿病(II型糖尿病),其中90%以上为II型糖尿病。随着社会经济的发展和人们生活方式的改变,糖尿病患者的数量迅速增加。据最新统计数据表明全世界约有2.46亿人患有II型糖尿病,预计在20年内II型糖尿病患者数目将增至3.8亿。我国目前糖尿病患者人数已高达8000多万人,占全世界糖尿病患者总数的三分之一,成为全球糖尿病第一大国。目前糖尿病发病率在全球范围内呈上升趋势,尤其在发展中国家上升的趋势更加明显,其死亡率仅次于心脑血管疾病、癌症,被认为是人类第三大杀手。因此,积极预防和治疗糖尿病已迫在眉睫。
现阶段治疗II型糖尿病的药物主要为传统抗糖尿病药物,包括磺酰脲类、格列奈类、双胍类、噻唑烷二酮类、α-葡萄糖苷酶抑制剂及胰岛素等,这些药物均存在不同程度的不良反应,如引发低血糖、胃肠道不适、肥胖等。随着对糖尿病基础理论研究的深入,开发作用于新靶点、避免传统降糖药物的副作用、对胰岛β细胞具有保护作用的糖尿病治疗新药成为国内外研究的热点。
人参为五加科植物人参属的根茎,为多年生草本植物,是驰名中外的名贵药材。现代医学研究表明人参在免疫功能调节,抗糖尿病、增强肝功能、改善心脑血管障碍、抗动脉硬化、血压调节等方面均有明显的功效,因此人参皂苷作为人参的主要有效成分,其在抗糖尿病领域的应用正成为糖尿病新药开发的热点。
发明内容
本发明要解决的技术问题在于提供新的人参皂苷组合物,充分发挥各组分的降糖活性,提高降糖效果。
另外,本发明还提供了该人参皂苷组合物在制备预防和治疗糖尿病产品中的应用。
本发明实现过程如下:
一种人参皂苷组合物,其包含选自人参皂苷Rk1、Rg3、Rg5中的一种或两种或三种的二醇组人参皂苷、以及选自人参皂苷Rk3、Rh4中的一种或两种的三醇组人参皂苷作为有效成分。
优选地,所述二醇组人参皂苷为人参皂苷Rg5。
优选地,所述三醇组人参皂苷为人参皂苷Rh4。
上述二醇组人参皂苷与三醇组人参皂苷的质量比是20:1~1:5,优选为3:1~1:1。更优选为,人参皂苷Rg5与人参皂苷Rh4的质量比是2:1。
上述人参皂苷组合物可用于制备具有降糖活性药物。
上述人参皂苷组合物可用于制备具有降糖活性保健食品。
上述人参皂苷组合物可用于制备具有降糖活性功能食品。
本发明所述人参皂苷组合物,还包括药学上可接受的辅剂。在本发明中,药学上可接受的辅剂包括药学上可接受的载体、赋形剂、稀释剂等,且与活性成分人参皂苷组合物相容。本发明的药品制剂将活性成分人参皂苷组合物和药学上可接受的辅剂组合在一起,配制成各种制剂,优选本发明第三方面的药品制剂是口服药物制剂或注射剂,如颗粒剂、片剂、丸剂和胶囊,最优选为片剂或胶囊剂。
本发明人经过研究和实践,发现人参皂苷的不同单体在对抗不同糖尿病模型引起的高血糖时表现出降糖效果具有明显差异,在此基础上进一步研究发现不同皂苷混合形成的组合物与单个皂苷成分相比降糖作用显著提高。同时经过大量的实验,总结归纳获得了一种组合物,其由二醇组人参皂苷及三醇组人参皂苷组成,能够充分发挥各组分的作用,同时降低了单个皂苷的使用浓度,具有高效,低成本,低毒副作用等特点,成药性很强。本发明取得的优异效果包括:
1)通过不同类型人参皂苷单体之间的组合,合理优化单体的比例,充分发挥了各单体降糖机制的互补特性,显著提高降糖效果;
2)在保证降糖效果的同时,人参皂苷的使用量没有明显增加,降低了生产的成本,同时也为产品的生物安全性提供了保障;
3)相比于单个人参皂苷单体的降糖效果,人参皂苷组合物在药效上更能达到新药开发的要求,具有成药性强,易于大规模生产的特点,更易用于成药开发。
附图说明
图1:在人参皂苷单体及组合物对II型糖尿病小鼠模型的治疗过程中II型糖尿病小鼠的体重变化;
图2:在人参皂苷单体及组合物对II型糖尿病小鼠模型的治疗过程中II型糖尿病小鼠的肝脏HE染色切片。
具体实施方式
为了便于理解,以下将通过具体的实施例对本发明进行详细地描述。需要特别指出的是,这些描述仅仅是示例性的描述,并不构成对本发明范围的限制。依据本说明书的论述,本发明的许多变化、改变对所属领域技术人员来说都是显而易见的。以下通过实施例进一步说明本发明的内容。如未特别指明,实施例中所用均为本领域技术人员所熟知的常规手段和市售的常用仪器。
实施例1 人参皂苷单体体外降糖实验
实验药品:二醇组人参皂苷:人参皂苷Rk1、Rg3、Rg5;
三醇组人参皂苷:人参皂苷Rk3、Rh4;
以上药品纯度均>98%。
实验细胞:INS-1大鼠胰岛瘤细胞、HepG2人肝癌细胞和3T3-L1小鼠前脂肪细胞均购自上海博古生物科技有限公司,代数在10代以内。
试验方法及结果:
1. 人参皂苷单体对四氧嘧啶诱导的INS-1损伤模型细胞活力的影响实验
INS-1细胞复苏后用含10%灭活小牛血清的RPMI 1640培养液转入100ml培养瓶中,在37℃、5%CO2条件下培养。当细胞贴壁长满后,倾去培养基,用0.25%胰蛋白酶消化,每3天按1:3比例传代1次,对数生长期的细胞用于实验。
取对数生长期的细胞,用含10% FBS的RPMI1640培养基调整至合适的细胞浓度接种于96孔培养板中,实验分为正常对照组及四氧嘧啶组(30,25,20,15,10,5 mM)。待细胞生长至90%融合时,按照实验分组加药,在37℃、5% CO2培养箱中培养48h后,MTT比色法于570nM波长下测定各组吸光度值,并计算细胞存活率及IC50(半数抑制率)。四氧嘧啶对INS-1细胞的IC50为16 mM,因此,在药效评价中,选择16 mM作为四氧嘧啶诱导INS-1细胞损伤的浓度。
将处于对数生长期的细胞消化后,将细胞稀释至1×105细胞/mL,接种于96孔板中,每孔接种100 μL。将接种细胞后的96孔板置于5%CO2、37℃恒温培养箱中培养,待细胞生长至90%融合时,将细胞随机分为:空白对照组:2%FBS的DMEM培养基;模型对照组:四氧嘧啶浓度为16 mM的并含有2%FBS的DMEM培养基;给药组:四氧嘧啶浓度为16 mM的并含有2%FBS的DMEM培养基培养的同时给予不同样品的药液;二甲双胍组:四氧嘧啶浓度为16 mM的并含有2%FBS的DMEM培养基培养的同时给予1 mM二甲双胍。培养48h后,MTT比色法于570nM波长下测定各组吸光度值。照如下公式计算人参皂苷单体对INS-1损伤模型细胞活力的增加率,结果见表1。
INS-1细胞活力的增加率=(给药组细胞活力-模型组细胞活力)/模型组细胞活力*100%
实验结果:16 mM四氧嘧啶处理INS-1细胞48h能够建立稳定的细胞损伤模型,受试药品的加入能够有效的提高损伤模型的细胞活力,与二醇组人参皂苷相比较,三醇组人参皂苷具有更好的修复损伤模型能力,其中人参皂苷Rh4作用的细胞活力提高可达93.96%,修复效果理想。
2. 人参皂苷单体对高糖高脂诱导的HepG2胰岛素抵抗细胞葡萄糖消耗作用的影响
人肝癌细胞HepG2 10000个/孔接种于96孔板,每孔100 μL培养液。24h后,将培养液换成含不同浓度人参皂苷单体、0.5 mM棕榈酸、0.5% BSA、1nM胰岛素、不含血清的高糖DMEM培养基,实验另设无细胞空白组(无细胞、含0.5%BSA、1 nM胰岛素的无血清低糖DMEM培养基)、对照组(含0.5% BSA、1 nM胰岛素的无血清低糖DMEM培养基)、模型组(0.5 mM棕榈酸、0.5% BSA、1 nM胰岛素、不含血清的高糖DMEM培养基)和阳性药组(1 mM二甲双胍、0.5 mM棕榈酸、0.5% BSA、1 nM胰岛素、不含血清的高糖DMEM培养基)。孵育24h后,每孔取10 μL上清液,用葡萄糖测定试剂盒(葡萄糖氧化酶-过氧化物酶法)测定每孔的葡萄糖消耗量。移去96孔板中的培养液,MTT比色法于570 nM波长下测定各孔吸光度值。
以无细胞空白组的葡萄糖含量减去接种细胞的测试孔中的葡萄糖含量,即得各孔的葡萄糖消耗量。同时,除以各孔细胞的MTT值进行细胞数量的校正。
实验结果:结果如表2所示,0.5 mM棕榈酸在高糖环境下能够建立稳定的HepG2胰岛素抵抗模型,受试药品的加入能够改善模型细胞的葡萄糖消耗,具有缓解胰岛抵抗的作用。二醇组人参皂苷(人参皂苷Rk1、Rg3、Rg5),在解除高糖高脂建立的胰岛抵抗模型效果上明显优于三醇组人参皂苷(人参皂苷Rk3、Rh4),其中二醇组人参皂苷Rg3促进胰岛素抵抗的HepG2细胞的葡萄糖消耗的效果最为显著,其次为人参皂苷Rg5。
3. 人参皂苷单体对3T3-L1胰岛素抵抗细胞葡萄糖消耗作用的影响
3T3-L1前脂肪细胞30000个/孔接种于48孔板,每孔0.5 mL培养液。待细胞汇合之后,继续培养两天,将培养液换成含1 μM地塞米松、0.5 mM 3-异丁基-1-甲基黄嘌呤(IBMX)、10 μg/mL胰岛素、10% FBS的高糖DMEM培养液培养2天;随后将培养液换成含10 μg/mL胰岛素、10% FBS的高糖DMEM培养液培养2天;最后将培养液换成含10% FBS的高糖DMEM培养液,每2天换一次培养液。诱导分化10-12天后,约80%的3T3-L1细胞分化为成熟脂肪细胞。用1 μM地塞米松处理细胞24h,使细胞产生胰岛素抵抗。随后将培养液换成含不同浓度人参皂苷单体的高糖DMEM培养基,同时设置无细胞空白组、对照组、模型组和阳性药组(1 mM二甲双胍),继续培养48h。
用葡萄糖测定试剂盒测定每孔的葡萄糖消耗量。随后将96孔板中的培养液吸尽,MTT比色法于570 nM波长下测定各孔吸光度值,以无细胞空白组的葡萄糖含量减去接种细胞的测试孔中的葡萄糖含量,即得各孔的葡萄糖消耗量。同时,除以各孔细胞的MTT值进行细胞数量的校正。
实验结果:如表3所示,人参皂苷Rk1、Rk3、Rg3、Rg5、Rh4对胰岛素抵抗3T3-L1细胞的葡萄糖消耗均有一定程度的促进作用,其中人参皂苷Rg3促进胰岛素抵抗的3T3-L1细胞的葡萄糖消耗的效果最为显著,其次为人参皂苷Rg5。在解除3T3-L1胰岛抵抗模型效果上,二醇组人参皂苷明显优于三醇组人参皂苷,这与HepG2细胞胰岛素抵抗模型的结果一致。
上述人参皂苷体外模型结果显示,人参皂苷单体对建立的糖尿病体外模型均有缓解效果,但是二醇组皂苷与三醇组皂苷在不同的建模机制下建立的体外模型所表现的缓解效果存在明显的差异。
实施例2 人参皂苷单体及药物组合对Ⅱ型糖尿病小鼠模型的治疗作用
造模:健康雄性、清洁级5~6周龄的C57BL/6小鼠(体重18±2 g)110只,购买于西安交通大学医学院动物中心。小鼠适应性饲养7天,随机分为两组,一组10只,给予基础饲料;一组100只,给予高脂高糖饲料。6周后,高脂高糖饮食组禁食不禁水12h后,腹腔注射STZ(柠檬酸缓冲液配制)30 mg/kg,每天一次,连续注射5天,建立糖尿病模型。将小鼠禁食(不禁水)12h,每只小鼠眼底静脉丛取血0.2 mL,分离血清。取10 μL血清于样品管中按照试剂盒说明的操作方法测定小鼠的空腹血糖值。空腹血糖值≥11.1 mmol/L的小鼠视为糖尿病模型小鼠,可用于后续实验。
动物分组:高血糖小鼠随机分成8组,每组10只动物,分别为模型组、二醇组Rg3(60mg/kg)组、三醇组Rh4(60 mg/kg)组、二醇组Rg5(60 mg/kg)组、二醇组Rg3(40 mg/kg)+三醇组Rh4(20 mg/kg)组、二醇组Rg3(40 mg/kg)+二醇组Rg5(20 mg/kg)组、三醇组Rh4(20 mg/kg)+二醇组Rg5(40mg/kg)组、阳性药二甲双胍组(100 mg/kg)。药物溶于0.5%羧甲基纤维素钠溶液,所有小鼠每天灌胃相应剂量的药物一次,对照组和模型组小鼠给予同等体积溶剂0.5%羧甲基纤维素钠溶液。连续给药三周。
指标检测:给药前和给药后每周测定一次小鼠的空腹血糖,具体操作如下:动物禁食(不禁水)12h,尾静脉采血检测葡萄糖水平即为空腹血糖。从造模开始,到给药结束,每周一次称量小鼠体重。给药结束,处死小鼠,取小鼠肝脏,进行HE染色,制作病理切片。
实验结果:
1)血糖检测
人参皂苷单体和药物组合都能够显著降低糖尿病小鼠的空腹血糖水平,改善血糖代谢,人参皂苷药物组合Rg3+Rh4、Rg3+Rg5、Rh4+Rg5降糖效果优于人参皂苷Rg3、Rh4和Rg5单体。与已有降糖药二甲双胍相比,人参皂苷药物组合其改善葡萄糖代谢能力不弱于二甲双胍,具体结果见表4。
2)安全性评价
体重监测:各组小鼠给药前初始体重无明显差异,灌胃3周后,正常组小鼠体重稳定增加,模型组小鼠体重较正常组显著降低。人参皂苷组和二甲双胍组小鼠体重与模型组基本相当,药物本身不会造成小鼠体重明显下降,结果见图1。
HE染色:对照组光镜下肝小叶结构正常,细胞边界清晰,细胞核呈圆形且位于细胞中央,肝细胞以中央静脉为中心成索状排列;模型组肝索紊乱,肝细胞轮廓模糊,细胞核皱缩或裂解,肝细胞空泡变性,肝组织出现明显病变;二甲双胍组肝小叶结构完整,肝细胞轮廓较模型组清晰,肝细胞空泡变性减少;人参皂苷Rh4组肝小叶结构基本完整,可见轻度的脂肪变性与空泡变性;人参皂苷Rg3、Rg5、Rg3+Rh4、Rg3+Rg5、Rh4+Rg5组肝小叶结构完整,肝细胞索轻度紊乱,核质较清晰,脂肪变性与空泡变性高度缓解。病理切片见图2。
人参皂苷组合物治疗Ⅱ型糖尿病小鼠体内实验结果显示,人参皂苷组合物改善血糖代谢的效果明显高于各人参皂苷单体,与临床一线药二甲双胍相当。给药3周受试动物未见与药物毒性相关的毒性反应,表明该组合物安全性良好。
实施例3 人参皂苷片剂的制备
取人参皂苷组合物(人参皂苷Rg5 60 g和人参皂苷Rh4 30 g)90 g,羧甲基纤维素钠70g,微晶纤维素200 g,羧甲淀粉钠70 g、硬脂酸镁2 g为原料。
将上述主药和辅料分别过80目筛,充分混匀,采用80%乙醇为粘合剂,用16目筛网制粒,55~60℃干燥,14目筛网整粒,压片,每片0.4 g。
实施例4 人参皂苷胶囊剂的制备
取人参皂苷组合物(人参皂苷Rg5 80 g和人参皂苷Rh4 40 g)120 g、枸杞子350 g、知母350 g、山药300 g为原料。
取枸杞子、知母、山药,加水煎煮2次,每次加12倍量水,各煎煮2h,煎液过滤,合并滤液,减压浓缩干燥,粉碎,过80目筛后,与人参皂苷组合物混合,采用80%乙醇制软材,16目筛制粒,55~60℃干燥,分装于0号胶囊中,每粒0.4 g。
实施例5 人参皂苷组合物产品对Ⅱ型糖尿病大鼠模型的治疗作用
取Wistar大鼠(200±20 g)60只,适应生长7天后,分为空白组(10只)和模型组(50只),模型组给予高糖高脂饲料,空白组给予正常饲料。喂养一个月后,取血测定其空腹总胆固醇、甘油三脂、胰岛素及血糖的含量,将胰岛素抵抗的大鼠再按30 mg/kg的剂量腹腔注射链脲佐菌素(STZ),7天后测定空腹血糖,血糖值大于11.1 mmol/L的大鼠共40只,随机分成4组(模型组,人参皂苷组合物片剂混悬液组,人参皂苷组合物胶囊剂混悬液组,二甲双胍组,所述人参皂苷组合物片剂和人参皂苷组合物胶囊剂按实施例3制备),每组10只。分组后给糖尿病大鼠再喂以高糖高脂饮食,并于每天灌胃给药。空白组和模型组均给予0.5%的CMC-Na溶液;人参皂苷片剂混悬液组是将人参皂苷片剂混悬于0.5% CMC-Na溶液中,人参皂苷胶囊剂混悬液组是将人参皂苷胶囊剂混悬于0.5% CMC-Na溶液中,按50 mg/kg人参皂苷剂量给大鼠灌胃;二甲双胍组灌胃给予50 mg/kg二甲双胍。连续给药4周后,禁食不禁水12h后眼眶取血,处死大鼠,收集血清。
治疗糖尿病指标测定:测定大鼠给药后体重变化,血清葡萄糖,总胆固醇,甘油三脂。以上指标均用试剂盒测定,试剂盒购自南京建成生物工程研究所。
实验结果:如表5所示,以人参皂苷组合物为主要成分的产品能增加Ⅱ型糖尿病大鼠的体重,显著降低其血糖,降低总胆固醇,甘油三脂含量,改善糖脂代谢紊乱的症状,其改善糖脂代谢紊乱的效果与阳性药二甲双胍相当。
Claims (9)
1.一种人参皂苷组合物,其特征在于:组合物活性成分为二醇组人参皂苷和三醇组人参皂苷,其中二醇组人参皂苷选自人参皂苷Rk1、Rg3、Rg5,三醇组人参皂苷选自人参皂苷Rk3、Rh4。
2.根据权利要求1所述的人参皂苷组合物,其特征在于:所述二醇组人参皂苷为人参皂苷Rg5。
3.根据权利要求1所述的人参皂苷组合物,其特征在于:所述三醇组人参皂苷为人参皂苷Rh4。
4.根据权利要求1至3任意之一所述的人参皂苷组合物,其特征在于:二醇组人参皂苷与三醇组人参皂苷的质量比是20:1~1:5。
5.根据权利要求4所述的人参皂苷组合物,其特征在于:二醇组人参皂苷与三醇组人参皂苷的质量比是3:1~1:1。
6.根据权利要求5所述的人参皂苷组合物,其特征在于:人参皂苷Rg5与人参皂苷Rh4的质量比是2:1。
7.权利要求1所述人参皂苷组合物在制备具有降糖活性药物中的应用。
8.权利要求1所述人参皂苷组合物在制备具有降糖活性保健食品中的应用。
9.权利要求1所述人参皂苷组合物在制备具有降糖活性功能食品中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810533787.6A CN109223811B (zh) | 2018-05-30 | 2018-05-30 | 具有降糖活性的人参皂苷组合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810533787.6A CN109223811B (zh) | 2018-05-30 | 2018-05-30 | 具有降糖活性的人参皂苷组合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109223811A true CN109223811A (zh) | 2019-01-18 |
CN109223811B CN109223811B (zh) | 2022-08-16 |
Family
ID=65084117
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810533787.6A Active CN109223811B (zh) | 2018-05-30 | 2018-05-30 | 具有降糖活性的人参皂苷组合物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109223811B (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108685931A (zh) * | 2018-07-02 | 2018-10-23 | 南京类人生物材料有限公司 | 具有降糖活性的人参皂苷组合物及其应用 |
CN111253459A (zh) * | 2020-01-19 | 2020-06-09 | 云南大学 | 一种三七皂苷炮制品及其制备方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102600189A (zh) * | 2011-01-24 | 2012-07-25 | 吉林农业大学 | 人参次级皂苷及其脂肪酸酯衍生物在糖尿病中的应用 |
KR20150090463A (ko) * | 2014-01-29 | 2015-08-06 | 호서대학교 산학협력단 | 피부 노화 및 염증 질환의 예방 또는 치료용 조성물, 및 건강기능식품 |
CN106109483A (zh) * | 2016-07-29 | 2016-11-16 | 陕西巨子生物技术有限公司 | 具有抗肿瘤活性的二醇组/三醇组稀有人参皂苷组合物 |
CN106377535A (zh) * | 2016-06-24 | 2017-02-08 | 无限极(中国)有限公司 | 一种人参皂苷组合物及其制备方法、应用 |
-
2018
- 2018-05-30 CN CN201810533787.6A patent/CN109223811B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102600189A (zh) * | 2011-01-24 | 2012-07-25 | 吉林农业大学 | 人参次级皂苷及其脂肪酸酯衍生物在糖尿病中的应用 |
KR20150090463A (ko) * | 2014-01-29 | 2015-08-06 | 호서대학교 산학협력단 | 피부 노화 및 염증 질환의 예방 또는 치료용 조성물, 및 건강기능식품 |
CN106377535A (zh) * | 2016-06-24 | 2017-02-08 | 无限极(中国)有限公司 | 一种人参皂苷组合物及其制备方法、应用 |
CN106109483A (zh) * | 2016-07-29 | 2016-11-16 | 陕西巨子生物技术有限公司 | 具有抗肿瘤活性的二醇组/三醇组稀有人参皂苷组合物 |
Non-Patent Citations (4)
Title |
---|
DENG J ET AL: "Protopanaxadiol and Protopanaxatriol-Type Saponins Ameliorate Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus in High-Fat Diet/Streptozocin-Induced Mice", 《FRONTIERS IN PHARMACOLOGY》 * |
SEO YS ET AL: "Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
刘文君 等: "药对研究——三七、白及药对配伍前后对三七皂苷成分含量的影响", 《中国中药杂志》 * |
杨秀伟 等: "人参中三萜类化学成分的生物学活性和药理学作用", 《中国现代中药》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108685931A (zh) * | 2018-07-02 | 2018-10-23 | 南京类人生物材料有限公司 | 具有降糖活性的人参皂苷组合物及其应用 |
CN111253459A (zh) * | 2020-01-19 | 2020-06-09 | 云南大学 | 一种三七皂苷炮制品及其制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
CN109223811B (zh) | 2022-08-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109549971A (zh) | 一种调节高血糖的功能性食品及其制备方法 | |
CN106176918A (zh) | 一种包含青钱柳叶和葛根的降血糖保健组合物 | |
CN101411760A (zh) | 苹果属花楸苹果组植物的新用途 | |
CN105250789A (zh) | 降糖植物发酵制剂及其制备方法 | |
US10894070B2 (en) | Drug compound for the control of blood glucose, blood lipids and weight | |
CN115364170B (zh) | 一种糖代谢调节剂及其制备方法和应用 | |
CN102526478A (zh) | 一种增强免疫力、降血糖功能的保健药物配方 | |
CN102526479A (zh) | 一种增强免疫力、降血糖功能的保健药物配方 | |
CN102389454B (zh) | 一种复方白背三七降血糖制剂及其制备方法 | |
CN105341893A (zh) | 一种辅助降血糖的组合物及应用 | |
CN109223811A (zh) | 具有降糖活性的人参皂苷组合物 | |
CN104107324A (zh) | 一种治疗2型糖尿病的中药复方制剂及其制备方法 | |
CN103494997B (zh) | 一种治疗高血糖和糖尿病的槐花中药物 | |
CN1618446A (zh) | 一种治疗糖尿病的药物及其制备方法 | |
CN108685931A (zh) | 具有降糖活性的人参皂苷组合物及其应用 | |
CN102940800A (zh) | 治疗糖尿病的中药 | |
CN102858359B (zh) | 一种含有醇溶性且非水溶性甘草提取物的药物组合物,及其药物制剂、制药用途、治疗方法和制备方法 | |
CN101406642B (zh) | 一种降糖的复方制剂 | |
CN100496561C (zh) | 一种改善糖耐量和治疗糖尿病及肥胖症的药物及其制备方法 | |
CN104127816B (zh) | 一种治疗糖尿病的药物组合物及其制备方法和用途 | |
CN103285113B (zh) | 一种预防和/或治疗糖尿病的药物组合物 | |
CN106109951A (zh) | 防治高血糖、高血脂、高血压的药物及其制备方法 | |
CN101406576B (zh) | 一种治疗糖尿病的中药及制备方法 | |
CN108743796A (zh) | 一种治疗肺癌的中药组合物及其应用 | |
CN107669860A (zh) | 一种具有降糖作用的中药组合物及其应用 |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CB03 | Change of inventor or designer information | ||
CB03 | Change of inventor or designer information |
Inventor after: Fan Daidi Inventor after: Yin Shiyu Inventor after: Duan Zhiguang Inventor after: Fu Rongzhan Inventor after: Ma Xiaoxuan Inventor before: Fan Daidi Inventor before: Yin Shiyu Inventor before: Duan Zhiguang Inventor before: Fu Rongzhan Inventor before: Ma Xiaoxuan |