JP3998282B2 - A new saponin glycoside derived from Ginseng - Google Patents
A new saponin glycoside derived from Ginseng Download PDFInfo
- Publication number
- JP3998282B2 JP3998282B2 JP23904796A JP23904796A JP3998282B2 JP 3998282 B2 JP3998282 B2 JP 3998282B2 JP 23904796 A JP23904796 A JP 23904796A JP 23904796 A JP23904796 A JP 23904796A JP 3998282 B2 JP3998282 B2 JP 3998282B2
- Authority
- JP
- Japan
- Prior art keywords
- ginseng
- methanol
- glu
- saponin glycoside
- liquid
- 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 - Fee Related
Links
- 235000008434 ginseng Nutrition 0.000 title claims description 15
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 title claims description 14
- 235000003140 Panax quinquefolius Nutrition 0.000 title claims description 14
- -1 saponin glycoside Chemical class 0.000 title claims description 11
- 241000208340 Araliaceae Species 0.000 title claims description 3
- 229930182470 glycoside Natural products 0.000 title description 9
- 239000001397 quillaja saponaria molina bark Substances 0.000 title description 9
- 229930182490 saponin Natural products 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 244000131316 Panax pseudoginseng Species 0.000 description 14
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108010062580 Concanavalin A Proteins 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000000401 methanolic extract Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 230000000704 physical effect Effects 0.000 description 4
- 208000034656 Contusions Diseases 0.000 description 3
- 235000002791 Panax Nutrition 0.000 description 3
- 241000208343 Panax Species 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 3
- 230000023597 hemostasis Effects 0.000 description 3
- 238000002000 high resolution fast-atom bombardment mass spectrometry Methods 0.000 description 3
- 238000000622 liquid--liquid extraction Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SMRPGWBDLOQHOS-UHFFFAOYSA-N 5-[4,5-dihydroxy-6-(hydroxymethyl)-3-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxy-3,4-dihydroxy-6-[[9-hydroxy-4-(hydroxymethyl)-4,6a,6b,8a,11,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]oxane-2-carboxylic acid Chemical compound OC1C(O)C(O)C(C)OC1OC1C(OC2C(OC(C(O)C2O)C(O)=O)OC2C(C3C(C4C(C5(CCC6(C)C(O)CC(C)(C)CC6C5=CC4=O)C)(C)CC3)(C)CC2)(C)CO)OC(CO)C(O)C1O SMRPGWBDLOQHOS-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 241000180649 Panax notoginseng Species 0.000 description 2
- 235000003143 Panax notoginseng Nutrition 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 208000034526 bruise Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 231100000753 hepatic injury Toxicity 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- PPRSVUXPYPBULA-UHFFFAOYSA-N saponin A Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(OC6OC(CO)C(O)C(O)C6=O)C(C)(C)C5CCC34C)C2C1)C(=O)O PPRSVUXPYPBULA-UHFFFAOYSA-N 0.000 description 2
- UGJAEDFOKNAMQD-DVQDXYAYSA-N (-)-Falcarinol Natural products CCCCCCC\C=C\CC#CC#C[C@@H](O)C=C UGJAEDFOKNAMQD-DVQDXYAYSA-N 0.000 description 1
- UGJAEDFOKNAMQD-MQNTZWLQSA-N (3S,9Z)-1,9-Heptadecadiene-4,6-diyn-3-ol Chemical compound CCCCCCC\C=C/CC#CC#C[C@@H](O)C=C UGJAEDFOKNAMQD-MQNTZWLQSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- UGJAEDFOKNAMQD-UHFFFAOYSA-N Falcarinol Natural products CCCCCCCC=CCC#CC#CC(O)C=C UGJAEDFOKNAMQD-UHFFFAOYSA-N 0.000 description 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 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 240000004371 Panax ginseng Species 0.000 description 1
- 235000002789 Panax ginseng Nutrition 0.000 description 1
- 239000009759 San-Chi Substances 0.000 description 1
- BMWPBKOFJSHJAW-UHFFFAOYSA-N Saponin B Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(OC6OC(CO)C(O)C(OC7OC(CO)C(O)C(O)C7O)C6=O)C(C)(C)C5CCC34C)C2C1)C(=O)O BMWPBKOFJSHJAW-UHFFFAOYSA-N 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229940076810 beta sitosterol Drugs 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- AEUTYOVWOVBAKS-UWVGGRQHSA-N ethambutol Natural products CC[C@@H](CO)NCCN[C@@H](CC)CO AEUTYOVWOVBAKS-UWVGGRQHSA-N 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 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 description 1
- 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 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- KKAHGGJBKUXDNQ-KRWDZBQOSA-N panaxynol Natural products CCCCCCCC=CC=CCC#C[C@@H](O)C=C KKAHGGJBKUXDNQ-KRWDZBQOSA-N 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- LVTJOONKWUXEFR-UEZXSUPNSA-N protodioscin Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O[C@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)O[C@@H]1CC2=CC[C@H]3[C@@H]4C[C@@H]5O[C@]([C@H]([C@@H]5[C@@]4(C)CC[C@@H]3[C@@]2(C)CC1)C)(O)CC[C@@H](C)CO[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O LVTJOONKWUXEFR-UEZXSUPNSA-N 0.000 description 1
- QDQWGYLCDZBAMD-UHFFFAOYSA-N saponin C Natural products CC1C2C3CCC4C5(C)CCC(O)C(C)(COC6OC(CO)C(O)C(O)C6O)C5CCC4(C)C3(C)CCC27C8OC8C1(C)OC7=O QDQWGYLCDZBAMD-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Description
【０００１】
【発明の属する技術分野】
本発明は三七人参由来の新規サポニン配糖体に関する。
【０００２】
【従来の技術】
三七人参は、ウコギ科（Araliaceae）のサンシチニンジン ［Panax notoginseng（Burk.）F.H.Chen （= P. sanchi Hoo, P. pseudo-ginseng Wall. var. notoginseng（Burk.）Hoo et Tseng）］ の根を乾燥したものであり、現在市場では「三七」「人参三七」「参三七」「田三七」「田七」「田七人参」などと称し、また別名を「山漆」「金不換」という。
本植物は中国雲南省東南部から広西省西南部の極限された地域に分布するもので、既に清代頃から同地域で栽培化されており、１６世紀末頃から中国南部地方で民間的に金瘡、打撲、挫傷などの血症に対し、止血、消炎、鎮痛などの薬として用いられている。
【０００３】
現代においてもこれら止血、消炎（消腫）、鎮痛作用を主体に、内服、外用を問わず、臨床的に優秀な効果が認められている。漢方でいう止血の概念は非常に広範なものであり、補血作用やお血（ふる血）を化して水にすることにより痛みを止めるなどの作用も包含している。
すなわち、打身、ねんざ、腫痛出血、吐血、鼻血、婦人の崩漏、産後のお阻腹痛など諸出血症状に応用する。その他、近年では強心作用が見出され、冠状動脈疾患、狭心症、心筋梗塞、高血圧、コレステロール過多症等にも応用されるようになってきている。また現代中国では、慢性肝炎、急性肝炎等の肝疾患にも用いられており、今後、抗炎症剤としての使用も期待される。
【０００４】
【発明が解決しようとする課題】
三七人参の成分としては、サポニン配糖体であるジンセノサイド（ginsenoside）Rb1, Rg1, Rg2, Ra, Rb2, Rd, Re, Roの他、パナキシノール（panaxynol）、β−シロステロール（β−sitosterol）が知られているが、これらの成分はすべて人参（オタネニンジン＝Panax ginseng C.A.Meyer）と共通するものであって、三七人参特有の成分については精査されておらず、三七人参の薬理作用を説明するには不十分であるといえる。
そこで本発明者らは、三七人参の活性本体であると推測される三七人参特有の成分について精査し、新規化合物３種を単離し、構造決定するに至った。
【０００５】
【課題を解決するための手段】
本発明は次の式で表される三七人参由来のサポニン配糖体を提供するものである。
【化３】
【化４】
【０００６】
【発明の実施の形態】
本発明の新規なサポニン配糖体は、三七人参より下記の抽出操作によって抽出、単離される。
三七人参をメタノールで熱時抽出し、そのメタノール抽出エキスを酢酸エチルと水で液−液分配し、水相移行部にｎ−ブタノールを加えて再度液−液分配し、そのブタノール相について順相シリカゲルカラムクロマトグラフィ［クロロホルム：メタノール：水（５０：１０：１→７：３：０.５→５：５：１）で順次溶出］に付し、薄層クロマトグラフィで確認しながら、順に５つの画分に分け、その第４画分を逆相シリカゲルカラムクロマトグラフィ（６０％、７０％、１００％メタノールにて順次溶出）に付し、その６０％メタノール溶出部をさらに逆相高速液体クロマトグラフィ（ＨＰＬＣ）［溶出液：メタノール−水（６５：３５、ｖ／ｖ）、流速：１０.０ｍｌ／分］で分離精製することにより目的とするサポニン配糖体３種（それぞれサンシチサポニンＡ、サンシチサポニンＢ、およびサンシチサポニンＣと命名した）を得る。
【０００７】
上記で得られるサポニン配糖体は表１に示す化学構造を有する。
【表１】
本発明のサポニン配糖体は、これまで三七人参が用いられていた種々の疾患の治療に有用であると考えられ、とくに肝疾患の治療に有用である。
【０００９】
【実施例】
つぎに実施例および試験例を挙げて本発明のサポニン配糖体の製法および薬理作用の一例を示す。
実施例１〜３
（１）雲南省生三七（１２ｋｇ）を粉末にし、メタノール（１８リットル）で４回熱時抽出した。メタノール抽出液を合わせて減圧下溶媒を留去し、メタノール抽出エキス（１０５０ｇ、生薬からの収率８.８％）を得た。このメタノール抽出エキス（５１０ｇ）を酢酸エチル−水（１：１）で分配し、酢酸エチル移行部（４３.７ｇ、０.７５％）と水移行部を得、この水移行部にｎ−ブタノールを加えてさらに液−液分配抽出してｎ−ブタノール移行部エキス（４３０ｇ、７.４％）および水移行部エキス（３７.９ｇ、０.６５％）を得た。
ｎ−ブタノール移行部エキス（１００ｇ）を順相カラムクロマトグラフィ［３ｋｇ、クロロホルム：メタノール：水（５０：１０：１→７：３：０.５→５：５：１）で順次溶出］に付しＴＬＣで確認しながら順に、画分１（１４.８ｇ、０.９１％）、画分２（２.３ｇ、０.１４％）、画分３（４.０ｇ、０.２５％）、画分４（２７.８ｇ、１.７２％）、画分５（９.４ｇ、０.５８％）を得た。
【００１０】
上記画分４を逆相シリカゲルカラムクロマトグラフィ（１ｋｇ、６０％、７０％、１００％メタノールで順次溶出）に付し、その６０％メタノール溶出部（１.１ｇ）をさらに逆相ＨＰＬＣ［カラム：ＹＭＣ−Pack R & D ODS-5(250 × 20 mm i. d）、溶出液；メタノール−水（６５：３５、ｖ／ｖ）、流速；１０.０ｍｌ／分］で分離精製することによりサンシチサポニンＡ（８５.３ｍｇ、０.００６％）、サンシチサポニンＢ（５５.８ｍｇ、０.００４％）、およびサンシチサポニンＣ（７３.３ｍｇ、０.００５％）を得た。これらの物質は下記の物性を示す。
【００１１】
サンシチサポニンＡの物性
分子式：C54H92O24
融点：１９７〜２００℃
比旋光度(C=0.003, MeOH)：[α]24 D=+18.9°
マススペクトル(FAB-MS)m/z：1169(M+2Na-H)+, 1147(M+Na)+, 1129(M+Na-H2O)+(100%)
マススペクトル(HR-FAB-MS)m/z：C54H92O24Na, 計算値：1147.5876；実測値：1147.5895
赤外線吸収スペクトル(IR, ν max cm-1, KBr)：3432, 1632, 1072
13C NMR (125 Mz、ピリジン-d5、δ ppm）：142.3(d), 122.7(d), 106.0(d), 105.1(d), 104.8(d), 98.1(d), 89.0(d), 83.3(s), 83.3(d), 78.7(d), 78.3(d)x4, 78.1(d), 77.9(d),77.1(d)x2, 75.2(d), 75.0(d), 71.7(d), 71.6(d)x3, 70.5(d), 70.0(s), 70.0(t), 62.8(t)x3, 56.4(d), 52.1(d), 51.4(s), 50.1(d), 49.6(d), 40.1(d), 39.7(t), 39.7(s), 39.2(t), 36.9(s), 35.1(t), 30.8(t), 30.7(q), 30.6(s), 30.6(t), 28.1(q), 26.8(t)x2, 23.3(q), 18.4(t), 17.2(q), 16.6(q), 16.3(q), 16.0(q)
1H NMR (500 Mz, ピリジン-d5, δ ppm)：0.85(3H, s), 0.89(3H, s), 1.03(3H, s), 1.11(3H, s), 1.29(3H, s), 1.55(6H, s), 1.61(3H, s), 4.92(1H, d, J=7.6), 5.10(1H, d,J=7.6), 5.18(1H, d, J=7.6), 5.37(1H, d, J=7.3), 6.08(1H, d, J=15.6), 6.19(1H, m)
【００１２】
サンシチサポニンＢの物性
分子式：C54H90O24
融点：２０１〜２０４℃
比旋光度(C=0.003, MeOH)：[α]23 D=+17.8°
マススペクトル(FAB-MS)m/z：1145(M+Na)+(100%)
マススペクトル(HR-FAB-MS)m/z:C54H90O24Na, 計算値：1145.5720；実測値：1145.5717
赤外線吸収スペクトル(IR, ν max cm-1, KBr)：3410, 1638, 1078
13C NMR (125 Mz, ピリジン-d5, δ ppm)：202.2(s), 144.4(s), 125.6(t), 106.0(d), 105.6(d), 105.1(d), 98.0(d), 89.0(d), 83.5(d), 83.2(s), 79.4(d), 78.5(d)x2, 78.4(d), 78.3(d), 78.1(d), 78.0(d), 77.1(d), 76.7(d), 75.2(d), 74.8(d), 71.8(d), 71.7(d)x2, 71.3(d), 70.3(t), 70.2(d), 62.9(t), 62.8(t), 62.7(t), 56.4(d), 52.1(d), 51.5(s), 50.2(d), 49.5(d), 40.0(s), 39.7(s), 39.2(t), 36.9(s), 35.1(t), 32.8(t), 30.8(t), 30.7(t), 29.8(t), 28.1(q), 26.8(t), 26.7(t), 21.9(q), 18.4(t), 17.8(q), 17.4(q), 16.6(q), 16.3(q), 16.0(q)
1H NMR (500 Mz, ピリジン-d5, δ ppm)：0.82(3H, s), 0.92(3H, s), 0.97(3H, s), 1.11(3H, s), 1.28(3H, s), 1.59(3H, s), 1.83(3H, s), 4.93(1H, d, J=7.6), 5.03(1H, d,J=7.2), 5.11(1H, d, J=7.3), 5.38(1H, d, J=7.6)
【００１３】
サンシチサポニンＣの物性
分子式：C54H92O25
融点：１９９〜２０２℃
比旋光度(C=0.003, MeOH)：[α]22 D=+14.4°
マススペクトル(FAB-MS)m/z：1185(M+2Na-H)+, 1163(M+Na)+, 1145(M+Na-H2O)+(100%)
マススペクトル(HR-FAB-MS)m/z:C54H92O25Na, 計算値：1163.5826；実測値：1163.5873
赤外線吸収スペクトル(IR, ν max cm-1, KBr)：3410, 1638, 1078
13C NMR (125 Mz, ピリジン-d5, δ ppm)：146.0(d), 113.5(d), 106.0(d), 105.2(d), 105.1(d), 98.1(d), 90.0(d), 89.0(s), 83.4(s), 83.3(d), 79.1(d), 78.4(d), 78.3(d)x3, 78.2(d), 78.1(d), 77.1(d), 77.0(d), 75.2(d), 74.8(d), 71.8(d), 71.7(d), 71.6(d), 71.5(d), 70.2(d), 70.0(t), 62.9(t), 62.8(t), 62.7(t), 56.4(d), 51.7(d), 51.4(s), 50.2(d), 49.4(d), 40.0(s), 39.7(s), 39.2(t), 36.9(s), 35.1(t), 32.6(t), 30.9(t), 30.8(t), 28.1(q), 26.8(t), 26.7(t), 26.3(t), 22.6(q), 18.5(t), 17.6(q), 17.4(q), 16.6(q), 16.3(q), 16.0(q)
1H NMR (500 Mz, ピリジン-d5, δ ppm)：0.83(3H, s), 0.94(3H, s), 0.99(3H, s), 1.10(3H, s), 1.28(3H, s), 1.64(3H, s), 1.95(3H, s), 4.79(dd-like), 4.91(1H, d, J=7.3), 5.09(1H, d,-like), 5.10(1H, d-like), 5.36(1H, d, J=7.6)
【００１４】
薬理試験
コンカナバリンＡ誘発肝障害モデル試験
（１）試験方法：
雌性BALB/cマウス（８週令、１群５または６匹）にコンカナバリンＡを１０ｍｇ／ｋｇの用量で尾静脈より投与した。２０時間後に採血し、血清トランスアミラーゼ（ＧＯＴおよびＧＰＴ）を市販キットを用いて測定した。被験薬物はコンカナバリンＡ投与の２時間前に腹腔内投与（i.p.）した。対照群には何らの薬物も投与しなかった。
（２）被験薬物：
前記実施例において得られた、三七人参のメタノール抽出エキスを酢酸エチルと水で液−液分配し、更に水移行部をｎ−ブタノールで液−液分配し、ｎ−ブタノール移行部について、ｎ−ブタノールを留去したエキス部分（サンシチサポニンＡ、ＢおよびＣを含有）を被験薬物とした。
【００１５】
（３）実験結果：
上記実験結果を表２に示す。
【表２】
BACKGROUND OF THE INVENTION
The present invention relates to a novel saponin glycoside derived from Ginseng.
[0002]
[Prior art]
37 Ginseng is the root of Araliaceae, Panax notoginseng (Burk.) FHChen (= P. sanchi Hoo, P. pseudo-ginseng Wall. Var. Notoginseng (Burk.) Hoo et Tseng) In the current market, it is called “37”, “carrot 37,” “sansanchi,” “tasanchi,” “tachichi,” “tabanachi ginseng,” and so on. It's called money exchange.
This plant is distributed in a limited area from southeastern Yunnan to southwestern Guangxi, and has already been cultivated in the same area since the Qing Dynasty. It is used as a medicine for hemostasis, anti-inflammation, analgesia, etc. against blood pressure such as bruise and contusion.
[0003]
Even in modern times, these hemostasis, anti-inflammatory (anti-tumor), and analgesic actions are mainly used, and clinically excellent effects are recognized regardless of internal use or external use. The concept of hemostasis in Kampo is very broad, and includes the effects of supplementing blood and stopping pain by turning the blood into blood.
That is, it is applied to various bleeding symptoms such as bruise, sprains, painful bleeding, vomiting, nosebleed, collapse of a woman, and postpartum sural pain. In addition, a cardiotonic effect has been found in recent years, and it has been applied to coronary artery disease, angina pectoris, myocardial infarction, hypertension, hypercholesterolosis, and the like. In modern China, it is also used for liver diseases such as chronic hepatitis and acute hepatitis, and is expected to be used as an anti-inflammatory agent in the future.
[0004]
[Problems to be solved by the invention]
In addition to ginsenoside Rb1, Rg1, Rg2, Ra, Rb2, Rd, Re, Ro, panaxynol, β-sisterosterol (β-sitosterol) However, all these ingredients are common to ginseng (Panax ginseng CAMeyer), and the ingredients specific to ginseng have not been scrutinized, explaining the pharmacological action of ginseng It's not enough to do that.
Therefore, the present inventors have scrutinized components unique to 37 ginseng, which is presumed to be the active body of 37 ginseng, and have isolated three new compounds to determine the structure.
[0005]
[Means for Solving the Problems]
The present invention provides a saponin glycoside derived from Ginseng represented by the following formula.
[Chemical 3]
[Formula 4]
[0006]
DETAILED DESCRIPTION OF THE INVENTION
The novel saponin glycoside of the present invention is extracted and isolated from the ginseng by the following extraction operation.
37 ginseng was extracted hot with methanol, the methanol extract was liquid-liquid partitioned with ethyl acetate and water, n-butanol was added again to the aqueous phase transition part, and liquid-liquid partition was repeated. Phase silica gel column chromatography [sequential elution with chloroform: methanol: water (50: 10: 1 → 7: 3: 0.5 → 5: 5: 1)] The fourth fraction was subjected to reverse phase silica gel column chromatography (elution with 60%, 70%, and 100% methanol sequentially), and the 60% methanol elution portion was further subjected to reverse phase high performance liquid chromatography (HPLC ) [Eluent: Methanol-water (65:35, v / v), flow rate: 10.0 ml / min] to separate and purify the three saponin glycosides Obtaining Re Panax saponin A, Panax saponin B, and Panax was named saponin C).
[0007]
The saponin glycoside obtained above has the chemical structure shown in Table 1.
[Table 1]
The saponin glycoside of the present invention is considered to be useful for the treatment of various diseases that have been used so far, and is particularly useful for the treatment of liver diseases.
[0009]
【Example】
Next, examples and test examples will be given to show an example of the production method and pharmacological action of the saponin glycoside of the present invention.
Examples 1-3
(1) Yunnan Seizo (12 kg) was powdered and extracted with methanol (18 liters) four times with heat. The methanol extracts were combined, and the solvent was distilled off under reduced pressure to obtain a methanol extract (1050 g, yield 8.8% from crude drug). This methanol extract (510 g) was partitioned with ethyl acetate-water (1: 1) to obtain an ethyl acetate transfer part (43.7 g, 0.75%) and a water transfer part. In this water transfer part, n-butanol was obtained. Was further extracted by liquid-liquid partition extraction to obtain an n-butanol transfer part extract (430 g, 7.4%) and a water transfer part extract (37.9 g, 0.65%).
The n-butanol transfer part extract (100 g) was subjected to normal phase column chromatography [3 kg, eluted sequentially with chloroform: methanol: water (50: 10: 1 → 7: 3: 0.5 → 5: 5: 1)]. While confirming by TLC, fraction 1 (14.8 g, 0.91%), fraction 2 (2.3 g, 0.14%), fraction 3 (4.0 g, 0.25%), fraction Fraction 4 (27.8 g, 1.72%), fraction 5 (9.4 g, 0.58%) were obtained.
[0010]
Fraction 4 was subjected to reverse phase silica gel column chromatography (eluted sequentially with 1 kg, 60%, 70%, and 100% methanol), and the 60% methanol eluate (1.1 g) was further subjected to reverse phase HPLC [column: YMC -Pack R & D ODS-5 (250 × 20 mm id), eluent: methanol-water (65:35, v / v), flow rate: 10.0 ml / min] Saponin A (85.3 mg, 0.006%), Sansitisaponin B (55.8 mg, 0.004%), and Sansitissaponin C (73.3 mg, 0.005%) were obtained. These substances exhibit the following physical properties.
[0011]
Physical properties of Sansitissaponin A: C 54 H 92 O 24
Melting point: 197-200 ° C
Specific rotation (C = 0.003, MeOH): [α] 24 D = + 18.9 °
Mass spectrum (FAB-MS) m / z: 1169 (M + 2Na-H) + , 1147 (M + Na) + , 1129 (M + Na-H 2 O) + (100%)
Mass spectrum (HR-FAB-MS) m / z: C 54 H 92 O 24 Na, calculated value: 1147.5876; measured value: 1147.5895
Infrared absorption spectrum (IR, ν max cm -1 , KBr): 3432, 1632, 1072
13 C NMR (125 Mz, pyridine-d 5 , δ ppm): 142.3 (d), 122.7 (d), 106.0 (d), 105.1 (d), 104.8 (d), 98.1 (d), 89.0 (d) , 83.3 (s), 83.3 (d), 78.7 (d), 78.3 (d) x4, 78.1 (d), 77.9 (d), 77.1 (d) x2, 75.2 (d), 75.0 (d), 71.7 ( d), 71.6 (d) x3, 70.5 (d), 70.0 (s), 70.0 (t), 62.8 (t) x3, 56.4 (d), 52.1 (d), 51.4 (s), 50.1 (d), 49.6 (d), 40.1 (d), 39.7 (t), 39.7 (s), 39.2 (t), 36.9 (s), 35.1 (t), 30.8 (t), 30.7 (q), 30.6 (s), 30.6 (t), 28.1 (q), 26.8 (t) x2, 23.3 (q), 18.4 (t), 17.2 (q), 16.6 (q), 16.3 (q), 16.0 (q)
1 H NMR (500 Mz, pyridine-d 5 , δ ppm): 0.85 (3H, s), 0.89 (3H, s), 1.03 (3H, s), 1.11 (3H, s), 1.29 (3H, s) , 1.55 (6H, s), 1.61 (3H, s), 4.92 (1H, d, J = 7.6), 5.10 (1H, d, J = 7.6), 5.18 (1H, d, J = 7.6), 5.37 ( 1H, d, J = 7.3), 6.08 (1H, d, J = 15.6), 6.19 (1H, m)
[0012]
Physical properties of Sansitissaponin B: C 54 H 90 O 24
Melting point: 201-204 ° C
Specific rotation (C = 0.003, MeOH): [α] 23 D = + 17.8 °
Mass spectrum (FAB-MS) m / z: 1145 (M + Na) + (100%)
Mass spectrum (HR-FAB-MS) m / z: C 54 H 90 O 24 Na, calculated value: 1145.5720; actual value: 1145.5717
Infrared absorption spectrum (IR, ν max cm -1 , KBr): 3410, 1638, 1078
13 C NMR (125 Mz, pyridine-d 5 , δ ppm): 202.2 (s), 144.4 (s), 125.6 (t), 106.0 (d), 105.6 (d), 105.1 (d), 98.0 (d) , 89.0 (d), 83.5 (d), 83.2 (s), 79.4 (d), 78.5 (d) x2, 78.4 (d), 78.3 (d), 78.1 (d), 78.0 (d), 77.1 (d ), 76.7 (d), 75.2 (d), 74.8 (d), 71.8 (d), 71.7 (d) x2, 71.3 (d), 70.3 (t), 70.2 (d), 62.9 (t), 62.8 ( t), 62.7 (t), 56.4 (d), 52.1 (d), 51.5 (s), 50.2 (d), 49.5 (d), 40.0 (s), 39.7 (s), 39.2 (t), 36.9 ( s), 35.1 (t), 32.8 (t), 30.8 (t), 30.7 (t), 29.8 (t), 28.1 (q), 26.8 (t), 26.7 (t), 21.9 (q), 18.4 ( t), 17.8 (q), 17.4 (q), 16.6 (q), 16.3 (q), 16.0 (q)
1 H NMR (500 Mz, pyridine-d 5 , δ ppm): 0.82 (3H, s), 0.92 (3H, s), 0.97 (3H, s), 1.11 (3H, s), 1.28 (3H, s) , 1.59 (3H, s), 1.83 (3H, s), 4.93 (1H, d, J = 7.6), 5.03 (1H, d, J = 7.2), 5.11 (1H, d, J = 7.3), 5.38 ( (1H, d, J = 7.6)
[0013]
Physical properties of Sansitissaponin C: C 54 H 92 O 25
Melting point: 199-202 ° C
Specific rotation (C = 0.003, MeOH): [α] 22 D = + 14.4 °
Mass spectrum (FAB-MS) m / z: 1185 (M + 2Na-H) + , 1163 (M + Na) + , 1145 (M + Na-H 2 O) + (100%)
Mass spectrum (HR-FAB-MS) m / z: C 54 H 92 O 25 Na, calculated value: 1163.5826; actual value: 1163.5873
Infrared absorption spectrum (IR, ν max cm -1 , KBr): 3410, 1638, 1078
13 C NMR (125 Mz, pyridine-d 5 , δ ppm): 146.0 (d), 113.5 (d), 106.0 (d), 105.2 (d), 105.1 (d), 98.1 (d), 90.0 (d) , 89.0 (s), 83.4 (s), 83.3 (d), 79.1 (d), 78.4 (d), 78.3 (d) x3, 78.2 (d), 78.1 (d), 77.1 (d), 77.0 (d ), 75.2 (d), 74.8 (d), 71.8 (d), 71.7 (d), 71.6 (d), 71.5 (d), 70.2 (d), 70.0 (t), 62.9 (t), 62.8 (t ), 62.7 (t), 56.4 (d), 51.7 (d), 51.4 (s), 50.2 (d), 49.4 (d), 40.0 (s), 39.7 (s), 39.2 (t), 36.9 (s ), 35.1 (t), 32.6 (t), 30.9 (t), 30.8 (t), 28.1 (q), 26.8 (t), 26.7 (t), 26.3 (t), 22.6 (q), 18.5 (t ), 17.6 (q), 17.4 (q), 16.6 (q), 16.3 (q), 16.0 (q)
1 H NMR (500 Mz, pyridine-d 5 , δ ppm): 0.83 (3H, s), 0.94 (3H, s), 0.99 (3H, s), 1.10 (3H, s), 1.28 (3H, s) , 1.64 (3H, s), 1.95 (3H, s), 4.79 (dd-like), 4.91 (1H, d, J = 7.3), 5.09 (1H, d, -like), 5.10 (1H, d-like ), 5.36 (1H, d, J = 7.6)
[0014]
Pharmacological test Concanavalin A-induced liver injury model test (1) Test method:
Concanavalin A was administered to female BALB / c mice (8 weeks old, 5 or 6 mice per group) from the tail vein at a dose of 10 mg / kg. Blood was collected 20 hours later, and serum transamylase (GOT and GPT) was measured using a commercially available kit. The test drug was administered intraperitoneally (ip) 2 hours before the administration of concanavalin A. The control group did not receive any drug.
(2) Test drug:
The extract of 37 ginseng methanol obtained in the above example was subjected to liquid-liquid partitioning with ethyl acetate and water, and the water transfer part was subjected to liquid-liquid partition with n-butanol. -The extract part from which butanol was distilled off (containing sansitaponins A, B and C) was used as a test drug.
[0015]
(3) Experimental results:
The experimental results are shown in Table 2.
[Table 2]
Claims (1)
で示される化合物。The following structural formula, which is isolated from Ginseng:
A compound represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23904796A JP3998282B2 (en) | 1996-09-10 | 1996-09-10 | A new saponin glycoside derived from Ginseng |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23904796A JP3998282B2 (en) | 1996-09-10 | 1996-09-10 | A new saponin glycoside derived from Ginseng |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH1087691A JPH1087691A (en) | 1998-04-07 |
| JP3998282B2 true JP3998282B2 (en) | 2007-10-24 |
Family
ID=17039090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP23904796A Expired - Fee Related JP3998282B2 (en) | 1996-09-10 | 1996-09-10 | A new saponin glycoside derived from Ginseng |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3998282B2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100605114B1 (en) * | 2003-09-06 | 2006-07-28 | 주식회사 오스코텍 | Arthritis prevention and treatment composition containing Samchil root extract as an active ingredient |
| CN102766184B (en) * | 2012-08-01 | 2014-08-13 | 南通大学 | Protopanoxadiol peroxide derivatives as well as preparation method and application thereof |
| KR101621356B1 (en) * | 2014-09-05 | 2016-05-17 | 한국과학기술원 | Use of ginsenoside F2 for prophylaxis and treatment of liver disease |
| CN115453035B (en) * | 2022-10-18 | 2024-08-23 | 湖南祥民制药有限公司 | A method for extracting high-content notoginseng saponin R1 from Panax notoginseng |
-
1996
- 1996-09-10 JP JP23904796A patent/JP3998282B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH1087691A (en) | 1998-04-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2515891T3 (en) | Method of Preparation of a Pharmaceutical Composition Containing Ginseng Secondary Glycosides | |
| WO2004054595A1 (en) | A method for preparing low polar ginsenoside and aglucon thereof by catalytic pyrolysis | |
| CN106967147B (en) | C27 spirosterane type steroidal saponin compound, its pharmaceutical composition and its application | |
| WO2015027929A1 (en) | Traditional chinese medicine composition | |
| Al-Taweel et al. | New flavane gallates isolated from the leaves of Plicosepalus curviflorus and their hypoglycemic activity | |
| Sun et al. | Immunological‐adjuvant saponins from the roots of Panax notoginseng | |
| CN104910240A (en) | Bougainvillea glabra triterpenoid saponin, hpyerglycemic drugs with triterpenoid saponin as active component and preparation method and application thereof | |
| JPS6352013B2 (en) | ||
| JP3998282B2 (en) | A new saponin glycoside derived from Ginseng | |
| JP4020992B2 (en) | A new saponin glycoside derived from Ginseng | |
| CN101119740B (en) | Application of traditional Chinese medicine Burnet and its extract in preparation of drugs for increasing red blood cell and hemoglobin | |
| WO2005095438A1 (en) | Saponins, the preparation and the use of the same | |
| CN111454317B (en) | Panaxadiol type triterpenoid saponin, folium Notoginseng extract, pharmaceutical composition and cosmetic composition with antiinflammatory activity | |
| Lee et al. | Identification of dammarane-type triterpenoid saponins from the root of Panax ginseng | |
| Lacaille-Dubois | Biologically and pharmacologically active saponins from plants: recent advances | |
| CN105147710B (en) | A kind of hypoglycemic drug and its preparation method and application | |
| CN110680819A (en) | Application of a kind of triterpenoid saponins | |
| CN107629106A (en) | A kind of method that notoginsenoside is extracted from pseudo-ginseng | |
| CN1857388A (en) | Preparation and application of notoginseng stem and leaf total saponin composition | |
| CN102351874B (en) | New erigeroster compound with medicinal activity | |
| JPS625126B2 (en) | ||
| KR0179415B1 (en) | New saponin components and its isolation method | |
| US10874705B2 (en) | Extracts and isolated compounds from cakile arabica for treatment of ulcer | |
| CN106243163A (en) | Method for preparing high-purity chemical reference substance Mickeynia saponin I | |
| CN100491393C (en) | Steroid saponins and preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20070412 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070417 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20070710 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20070807 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100817 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100817 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130817 Year of fee payment: 6 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |