CN1122042C - 稀有人参皂甙的制备方法 - Google Patents
稀有人参皂甙的制备方法 Download PDFInfo
- Publication number
- CN1122042C CN1122042C CN 00123074 CN00123074A CN1122042C CN 1122042 C CN1122042 C CN 1122042C CN 00123074 CN00123074 CN 00123074 CN 00123074 A CN00123074 A CN 00123074A CN 1122042 C CN1122042 C CN 1122042C
- Authority
- CN
- China
- Prior art keywords
- ginsenoside
- column chromatography
- protopanoxadiol
- meant
- rare
- 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.)
- Expired - Lifetime
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 229930182494 ginsenoside Natural products 0.000 claims abstract description 30
- 229940089161 ginsenoside Drugs 0.000 claims abstract description 30
- 230000007062 hydrolysis Effects 0.000 claims abstract description 17
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 10
- 239000000178 monomer Substances 0.000 claims abstract description 10
- 238000009835 boiling Methods 0.000 claims abstract description 9
- 238000004440 column chromatography Methods 0.000 claims abstract description 9
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims abstract description 6
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 150000002191 fatty alcohols Chemical class 0.000 claims abstract 4
- RAQNTCRNSXYLAH-RFCGZQMISA-N (20S)-ginsenoside Rh1 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]3[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RAQNTCRNSXYLAH-RFCGZQMISA-N 0.000 claims abstract 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 15
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- -1 polyoxyethylene Polymers 0.000 claims description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical class OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 claims description 5
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 5
- 239000011347 resin Substances 0.000 claims description 5
- 229920005989 resin Polymers 0.000 claims description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- 239000003463 adsorbent Substances 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 238000010521 absorption reaction Methods 0.000 claims description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- 238000000638 solvent extraction Methods 0.000 claims description 2
- CDXSJGDDABYYJV-UHFFFAOYSA-N acetic acid;ethanol Chemical compound CCO.CC(O)=O CDXSJGDDABYYJV-UHFFFAOYSA-N 0.000 claims 1
- 229930182470 glycoside Natural products 0.000 claims 1
- 150000002338 glycosides Chemical group 0.000 claims 1
- 239000012429 reaction media Substances 0.000 claims 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 abstract description 6
- 229930182490 saponin Natural products 0.000 abstract description 6
- 150000007949 saponins Chemical class 0.000 abstract description 6
- CKUVNOCSBYYHIS-UHFFFAOYSA-N (20R)-ginsenoside Rg3 Natural products CC(C)=CCCC(C)(O)C1CCC(C2(CCC3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1O CKUVNOCSBYYHIS-UHFFFAOYSA-N 0.000 abstract description 2
- CKUVNOCSBYYHIS-IRFFNABBSA-N (20S)-ginsenoside Rh2 Chemical compound O([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 CKUVNOCSBYYHIS-IRFFNABBSA-N 0.000 abstract description 2
- CKUVNOCSBYYHIS-LGYUXIIVSA-N 20(R)-Ginsenoside Rh2 Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@H]1C(C)(C)[C@H]2[C@@](C)([C@H]3[C@](C)([C@@]4(C)[C@H]([C@H](O)C3)[C@@H]([C@](O)(CC/C=C(\C)/C)C)CC4)CC2)CC1 CKUVNOCSBYYHIS-LGYUXIIVSA-N 0.000 abstract description 2
- PWAOOJDMFUQOKB-WCZZMFLVSA-N ginsenoside Re Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]3C(C)(C)[C@@H](O)CC[C@]3(C)[C@@H]3[C@@]([C@@]4(CC[C@@H]([C@H]4[C@H](O)C3)[C@](C)(CCC=C(C)C)O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O PWAOOJDMFUQOKB-WCZZMFLVSA-N 0.000 abstract description 2
- AOGZLQUEBLOQCI-UHFFFAOYSA-N ginsenoside-Re Natural products CC1OC(OCC2OC(OC3CC4(C)C(CC(O)C5C(CCC45C)C(C)(CCC=C(C)C)OC6OC(CO)C(O)C(O)C6O)C7(C)CCC(O)C(C)(C)C37)C(O)C(O)C2O)C(O)C(O)C1O AOGZLQUEBLOQCI-UHFFFAOYSA-N 0.000 abstract description 2
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 2
- 238000001953 recrystallisation Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- TXEWRVNOAJOINC-UHFFFAOYSA-N ginsenoside Rb2 Natural products CC(=CCCC(OC1OC(COC2OCC(O)C(O)C2O)C(O)C(O)C1O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CCC45C)C TXEWRVNOAJOINC-UHFFFAOYSA-N 0.000 abstract 4
- 150000001720 carbohydrates Chemical class 0.000 abstract 3
- FBFMBWCLBGQEBU-GYMUUCMZSA-N 20-gluco-ginsenoside-Rf Natural products O([C@](CC/C=C(\C)/C)(C)[C@@H]1[C@H]2[C@H](O)C[C@H]3[C@](C)([C@]2(C)CC1)C[C@H](O[C@@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@H]1C(C)(C)[C@@H](O)CC[C@]31C)[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 FBFMBWCLBGQEBU-GYMUUCMZSA-N 0.000 abstract 2
- AGBCLJAHARWNLA-DQUQINEDSA-N Ginsenoside RG2 Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]3C(C)(C)[C@@H](O)CC[C@]3(C)[C@@H]3[C@@]([C@@]4(CC[C@@H]([C@H]4[C@H](O)C3)[C@@](C)(O)CCC=C(C)C)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O AGBCLJAHARWNLA-DQUQINEDSA-N 0.000 abstract 2
- 239000003814 drug Substances 0.000 abstract 2
- PFSIGTQOILYIIU-UHFFFAOYSA-N ginsenoside Rb3 Natural products CC(=CCCC(C)(O)C1CCC2(C)C3CCC4C(C)(C)C(CCC4(C)C3CC(OC5OC(COC6OCC(O)C(O)C6O)C(O)C(O)C5O)C12C)OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C PFSIGTQOILYIIU-UHFFFAOYSA-N 0.000 abstract 2
- AGBCLJAHARWNLA-UHFFFAOYSA-N (20R)-ginsenoside Rg2 Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C3C(C)(C)C(O)CCC3(C)C3C(C4(CCC(C4C(O)C3)C(C)(O)CCC=C(C)C)C)(C)C2)OC(CO)C(O)C1O AGBCLJAHARWNLA-UHFFFAOYSA-N 0.000 abstract 1
- 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 abstract 1
- FBFMBWCLBGQEBU-RXMALORBSA-N (2s,3r,4s,5s,6r)-2-[(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-[(2s)-6-methyl-2-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhept-5-en-2-yl]-2,3,5,6,7,9,11,12,13,15,16,17-dodecah Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O FBFMBWCLBGQEBU-RXMALORBSA-N 0.000 abstract 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 abstract 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 abstract 1
- UFNDONGOJKNAES-UHFFFAOYSA-N Ginsenoside Rb1 Natural products CC(=CCCC(C)(OC1OC(COC2OC(CO)C(O)C(O)C2O)C(O)C(O)C1O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CC(O)C45C)C UFNDONGOJKNAES-UHFFFAOYSA-N 0.000 abstract 1
- HYPFYJBWSTXDAS-UHFFFAOYSA-N Ginsenoside Rd Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C4CCC5C(C)(C)C(CCC5(C)C4CC(O)C23C)OC6OC(CO)C(O)C(O)C6OC7OC(CO)C(O)C(O)C7O)C HYPFYJBWSTXDAS-UHFFFAOYSA-N 0.000 abstract 1
- UZIOUZHBUYLDHW-MSJHMJQNSA-N Ginsenoside Rf Natural products O([C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@@H]1O[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@@](O)(CC/C=C(\C)/C)C)CC3)C1)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 UZIOUZHBUYLDHW-MSJHMJQNSA-N 0.000 abstract 1
- 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 abstract 1
- RAQNTCRNSXYLAH-UHFFFAOYSA-N Ginsenoside Rh1 Natural products CC(C)=CCCC(C)(O)C1CCC(C2(C3)C)(C)C1C(O)CC2C1(C)CCC(O)C(C)(C)C1C3OC1OC(CO)C(O)C(O)C1O RAQNTCRNSXYLAH-UHFFFAOYSA-N 0.000 abstract 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 abstract 1
- YQKCHRBAJSATCG-UHFFFAOYSA-N UNPD30744 Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC(C)(CCC=C(C)C)C2C3C(C4(CCC5C(C)(C)C(OC6C(C(O)C(O)C(CO)O6)OC6C(C(O)C(O)C(CO)O6)O)CCC5(C)C4CC3O)C)(C)CC2)O1 YQKCHRBAJSATCG-UHFFFAOYSA-N 0.000 abstract 1
- YURJSTAIMNSZAE-UHFFFAOYSA-N UNPD89172 Natural products C1CC(C2(CC(C3C(C)(C)C(O)CCC3(C)C2CC2O)OC3C(C(O)C(O)C(CO)O3)O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O YURJSTAIMNSZAE-UHFFFAOYSA-N 0.000 abstract 1
- CNHRRMQBWQJRPN-UHFFFAOYSA-N chikusetsusaponin LM5 Natural products C1CC(C2(CC(O)C3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OC(CO)C(O)C1O CNHRRMQBWQJRPN-UHFFFAOYSA-N 0.000 abstract 1
- GZYPWOGIYAIIPV-JBDTYSNRSA-N ginsenoside Rb1 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GZYPWOGIYAIIPV-JBDTYSNRSA-N 0.000 abstract 1
- NODILNFGTFIURN-GZPRDHCNSA-N ginsenoside Rb2 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1OC[C@H](O)[C@H](O)[C@H]1O NODILNFGTFIURN-GZPRDHCNSA-N 0.000 abstract 1
- NODILNFGTFIURN-USYOXQFSSA-N ginsenoside Rb3 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O NODILNFGTFIURN-USYOXQFSSA-N 0.000 abstract 1
- JDCPEKQWFDWQLI-LUQKBWBOSA-N ginsenoside Rc Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1O[C@@H](CO)[C@H](O)[C@H]1O JDCPEKQWFDWQLI-LUQKBWBOSA-N 0.000 abstract 1
- UZIOUZHBUYLDHW-XUBRWZAZSA-N ginsenoside Rf Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[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]3[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZIOUZHBUYLDHW-XUBRWZAZSA-N 0.000 abstract 1
- UVBLDLGZDSGCSN-UHFFFAOYSA-N ginsenoside-Rb3 Natural products C1=CC2C3(C)CCC(O)C(C)(C)C3CCC2(C)C2(C)CCC34CCC(C)C(C)C4C21OC3=O UVBLDLGZDSGCSN-UHFFFAOYSA-N 0.000 abstract 1
- SPFXZQZPHXUJSR-UHFFFAOYSA-N ginsenoside-Rc Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1OC2OC(CO)C(O)C2O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CCC45C)C SPFXZQZPHXUJSR-UHFFFAOYSA-N 0.000 abstract 1
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- JURZHOVRCOWZFN-UHFFFAOYSA-N notoginsenoside R1 Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5C(CC34C)OC6OC(COC7OCC(O)C(O)C7O)C(O)C(O)C6O)C JURZHOVRCOWZFN-UHFFFAOYSA-N 0.000 abstract 1
- 229910052710 silicon Inorganic materials 0.000 abstract 1
- 239000010703 silicon Substances 0.000 abstract 1
- UOJAEODBOCLNBU-UHFFFAOYSA-N vinaginsenoside R4 Natural products C1CC(C2(CC(O)C3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O UOJAEODBOCLNBU-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 150000008131 glucosides Chemical group 0.000 description 7
- 238000010790 dilution Methods 0.000 description 6
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- 229910052799 carbon Inorganic materials 0.000 description 5
- SHCBCKBYTHZQGZ-DLHMIPLTSA-N protopanaxatriol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2[C@@H](O)C[C@@]3(C)[C@]4(C)CC[C@H]([C@](C)(O)CCC=C(C)C)[C@H]4[C@H](O)C[C@@H]3[C@]21C SHCBCKBYTHZQGZ-DLHMIPLTSA-N 0.000 description 5
- BBEUDPAEKGPXDG-UHFFFAOYSA-N protopanaxatriol Natural products CC(CCC=C(C)C)C1CCC2(C)C1C(O)CC3C4(C)CCC(O)C(C)(C)C4C(O)CC23C BBEUDPAEKGPXDG-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
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Abstract
本发明公开一种稀有人参皂甙的制备方法，将人参皂甙Rb1、Rb2、Rb3、Rc、Rd、Re、Rf等皂甙的单体，或它们的混合物溶于碱金属氢氧化物与高沸点脂肪醇类有机物组成的溶液中，在常压下加热进行水解，水解掉20位上的糖或者进一步把3位或6位上的部分或全部糖水解掉从而获得Rg3、Rh2、Rh1、Rg2等稀有人参皂甙，包括它们的甙元原人参二醇及原人参三醇的单体或混合物，经过硅胶柱层析、ODS柱层析、重结晶或HPLC等方法可获得它们中的任何一种纯度大于90%单体，用于医药目的。在常压下进行碱水解，操作简单安全，能够直接得到20(S)型人参皂甙。产出量大，适合工业化生产，满足医学临床应用。
Description
本发明涉及利用人参皂甙单体或其混合物制备稀有人参皂甙的制备工艺，确切的说是提供了一种稀有人参皂甙的制备方法。
本发明所述的稀有人参皂甙是指20(S)人参皂甙Rg3、Rh2、Rh3、Rh1、Rg2以及它们的甙元原人参二醇和人参三醇，它们具有重要的生理活性，是抗癌作用很强的的天然物质，其制备方法有很多：1、酶解法(CN1229086A)。2、高温高压碱水解法(CN1225366A)。3、从原人参二醇合成人参皂甙Rh2(KR NO.95-7250、JP8-208688)。4、利用人参二醇组皂甙经酸水解获得Rg3的方法(CN1243128A)。上述方法虽可获得人参皂甙Rg3、Rh2等稀有人参皂甙，但得率很低，实现产业化很困难，操作复杂，成本高；影响了稀有人参皂甙的使用和生产。
本发明目的在于提供一种稀有人参皂甙的制备方法，直接从人参皂甙经过常压下的碱水解获得20(S)型的人参皂甙Rg3、Rh2、Rh1、Rh3、Rg2等稀有人参皂甙以及它们的甙元原人参二醇和原人参三醇。
本发明的目的是这样实现的：首先将从人参或西洋参及其茎叶中获得的人参皂甙Rb1、Rb2、Rb3、Rc、Rd、Re、Rf、Rg1、Rg2等皂甙的单体，或它们的混合物溶于碱金属氢氧化物与高沸点脂肪醇类化合物组成的溶液中，在常压下加热进行水解，水解掉碳20位上的糖或者进一步把碳3位或碳6位上的部分或全部糖水解掉，从而获得Rg3、Rh2、Rh1、Rh3、Rg2等稀有人参皂甙，包括它们的甙元原人参二醇及原人参三醇的单体或混合物，经过硅胶和ODS柱层析从而获得Rg3、Rh2、Rh1、Rh3、Rg2、原人参二醇、人参三醇等单体。
具体工艺如下：将碱金属氢氧化物溶于高沸点脂肪醇类化合物中，其浓度一般为0.5％～50％，优选浓度是3～15％，把人参皂甙单体或它们的混合物溶于此碱溶液中，使人参皂甙的混合浓度为0.5％～50％，优选浓度是2～20％，搅拌下继续加热升温进行碱水解，水解温度为170℃～270℃，反应完毕后冷却至室温后加入水稀释，通过有机溶剂萃取或大孔径吸附树脂吸附回收得本发明产物。
前述的高沸点脂肪醇类化合物使指沸点高于180℃的，优选沸点在200～250℃的脂肪醇类有机物，包括乙二醇、丙二醇、1.3-丁二醇、1.4丁二醇、丙三醇、二甘醇及分子量小于700的聚乙二醇。碱金属氢氧化物包括NaOH、KOH。反应温度可根据碱的浓度不同而选择不同的温度，一般在180℃～270℃之间，优选为190～220℃，反应时间则取决于目标产物及反应温度与碱的浓度，一般为几分钟至几小时，优选1分钟至120分钟，根据目标产物的不同可适当增减反应时间。萃取剂包括氯仿、乙酸乙酯、正丁醇等，大孔吸附树脂采用D4020、AB8等。
用上述方法获得的产物，含有20(S)型原人参二醇皂甙Rg3、Rh2、Rh3、原人参三皂甙Rh1、Rg2及甙元原人参二醇、原人参三醇中的一种或几种，经过硅胶柱层析、ODS柱层析、重结晶或HPLC等方法可获得它们中的任何一种纯度大于90％单体，用于医药目的。
本发明与现有技术相比具有以下积极效果：在常压下进行碱水解，操作简单安全，产出量大，适合工业化生产，尤其是能够直接得到20(S)型人参皂甙，以满足临床应用。
下面结合实施例进一步说明本发明：
实施例1
将10gNaOH溶于100ml的乙二醇溶液中，再加入10g西洋参茎叶总皂甙，搅拌下加热进行水解1小时，温度控制在190℃，冷却至室温后加入50倍的水稀释，再用乙酸乙酯萃取，回收乙酸乙酯，得产物7g，经TLC证明其中含有人参皂甙Rg3、Rh2、Rh1、Rg2及原人参二醇和原人参三醇。
实施例2
在100ml二甘醇溶液中溶入30gNaOH，再加入4g西洋参茎叶总皂甙中获得的二醇组人参皂甙，180℃加热水解2小时，冷却至室温后用50倍水稀释，用氯仿萃取，回收氯仿，得产物1g，TLC检测含有Rg3、Rh2、Rg3及甙元原人参二醇。
实施例3
将5gKOH溶入100ml 1.4丁二醇溶液中，加入2.5g二醇组人参皂甙，205℃加热搅拌水解，反应5分钟，冷却至室温后用30倍水稀释，用正丁醇萃取，回收正丁醇，得含有Rg3、Rh3、Rh1、Rh2及甙元原人参二醇产物3.3g。
实施例4
取2gKOH溶于100ml丙三醇中，加入2g人参茎叶总皂甙，230℃加热搅拌水解1分钟，冷却至室温，用50倍水稀释，用大孔吸附树脂AB8吸附后用95％的乙醇洗脱，回收乙醇，得含有Rg3、Rh2、Rh1、Rh3等稀有人参皂甙，以及原人参二醇及原人参三醇的混合物0.5g。
实施例5
取8gNaOH溶于100ml分子量为600的聚乙二醇中，加入5g二醇组人参皂甙，210℃加热搅拌水解20分钟，冷却至室温，加15倍水稀释，用正丁醇萃取，回收正丁醇得产物1.8g，TCL证明含有Rg3、Rh3、Rh2及甙元原人参二醇。
实验例6
取按实施例3获得的反应产物2g，硅胶柱层析(洗拖液CHCI3∶CH3OH∶乙酸乙酯∶水＝2∶2∶7∶1)得150mgRg3，90mgRh2及30mg原人参二醇。
实施例7
将10gNaOH溶于100ml 1.4丁二醇中，加入2g人参皂甙Rg3，206℃加热搅拌水解5分钟，冷却至室温，加10倍水稀释，用乙酸乙酯萃取，回收乙酸乙酯，产物ODS柱层析分离，得Rh2 200mg。
实施例8
将10gNaOH溶于100ml 1.4丁二醇中，加入2g人参皂甙Re，203℃加热搅拌水解3分钟，冷却至室温，加10倍水稀释，用正丁醇萃取，回收正丁醇，产物经ODS柱层析分离，得Rh1 180mg。
Claims (8)
1、一种利用碱水解的方法，从人参皂甙制备稀有人参皂甙的方法，其特征在于人参皂甙发生碱水解所需的较高反应温度是通过使用高沸点脂肪醇作反应介质，在常压下加热实现的。
2、权利要求1所述的制备方法，其具体步骤如下：将碱金属氢氧化物和人参皂甙溶于高沸点脂肪醇中，加热升温进行碱水解，通过有机溶剂萃取或大孔吸附树脂吸附获得稀有人参皂甙混合物，通过柱层析分离获得稀有人参皂甙单体。
3、权利要求1所述的人参皂甙，是指人参、西洋参中含量较高的人参皂甙Ra1、Ra2、Rb1、Rb2、Rb3、Rc、Rd、Re、Rg1及其它们的次级甙的单位或它们的混合物。
4、权利要求1所述的稀有人参皂甙是指人参皂甙Rh1、Rh2、Rh3、Rg2、Rg3和20(S)一原人参二醇、20(S)——原人参三醇。
5、权利要求1所述的高沸点脂肪醇是指乙二醇、丙二醇、1.3丁二醇、1.4-丁二醇、丙三醇、二甘醇及分子量小于700的聚乙二醇。
6、权利要求2所述的具体步骤，其反应条件为碱的浓度是0.5％-50％，人参皂甙的浓度是1％-50％，反应温度为180-270℃。
7、权利要求2所述的碱金属氢氧化物是指氢氧化钠、氢氧化钾。
8、权利要求2所述的萃取用有机溶剂是氯仿、乙酸乙醇、正丁醇；大孔吸附树脂指D101、D4020；AB-8；柱层析是指硅胶柱层析，ODS柱层析。
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| CN1269835C (zh) * | 2002-12-13 | 2006-08-16 | 中国科学院大连化学物理研究所 | 一种催化热解制备低极性人参皂苷及其苷元的方法 |
| CN100390192C (zh) * | 2003-09-28 | 2008-05-28 | 中国科学院大连化学物理研究所 | 一种碱解天然人参皂苷制备单体低极性人参皂苷及其苷元的方法 |
| CN101671384B (zh) * | 2009-10-12 | 2012-05-02 | 玉溪市维和生物技术有限责任公司 | 人参皂苷Rh1的制备方法 |
| CN102311474B (zh) * | 2010-07-07 | 2016-02-24 | 北京师范大学 | 应用无溶剂法制备原人参二醇和原人参三醇 |
| CN102973623A (zh) * | 2012-12-20 | 2013-03-20 | 刘淑莹 | 一种人参须根中人参稀有皂苷组的分离方法 |
| CN104116746A (zh) * | 2013-04-28 | 2014-10-29 | 祁展楷 | 人参皂甙组合物及其制备方法和应用 |
| CN111467358B (zh) * | 2020-03-31 | 2021-05-14 | 陕西巨子生物技术有限公司 | 包含人参皂苷Rh3、PPD和Rh2的药物组合物 |
| CN115260269B (zh) * | 2022-06-28 | 2024-04-05 | 成都大学 | 一种含人参次苷及其苷元的组合物、制备方法和应用 |
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