JPH0723310B2 - Strong liver - Google Patents
Strong liverInfo
- Publication number
- JPH0723310B2 JPH0723310B2 JP61044171A JP4417186A JPH0723310B2 JP H0723310 B2 JPH0723310 B2 JP H0723310B2 JP 61044171 A JP61044171 A JP 61044171A JP 4417186 A JP4417186 A JP 4417186A JP H0723310 B2 JPH0723310 B2 JP H0723310B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- structural formula
- ganoderic acid
- ganoderic
- activity
- 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
- 210000004185 liver Anatomy 0.000 title claims description 5
- AQUHIKXTCOSRFY-GOEVOFJGSA-N Ganoderic acid S Chemical compound CC1(C)C(=O)CC[C@]2(C)C3=CC[C@]4(C)[C@@H]([C@@H](CC\C=C(\C)C(O)=O)C)CC[C@@]4(C)C3=CC[C@H]21 AQUHIKXTCOSRFY-GOEVOFJGSA-N 0.000 claims description 6
- FRRMMEJOPQSLSE-UHFFFAOYSA-N Ganoderic acid S Natural products CC1(C)C(O)CCC2(C)C3=CCC4(C)C(C(C(CC=C(C)C(O)=O)OC(C)=O)C)CCC4(C)C3=CCC21 FRRMMEJOPQSLSE-UHFFFAOYSA-N 0.000 claims description 6
- AQUHIKXTCOSRFY-UHFFFAOYSA-N tyromycic acid Natural products CC1(C)C(=O)CCC2(C)C3=CCC4(C)C(C(CCC=C(C)C(O)=O)C)CCC4(C)C3=CCC21 AQUHIKXTCOSRFY-UHFFFAOYSA-N 0.000 claims description 6
- RXLRLJSRXDHQCH-WXUPVFRZSA-N Ganoderic acid R Natural products O([C@H]([C@@H](C)[C@@H]1[C@]2(C)[C@](C)(C=3C([C@]4(C)[C@H](C(C)(C)[C@H](OC(=O)C)CC4)CC=3)=CC2)CC1)C/C=C(\C(=O)O)/C)C(=O)C RXLRLJSRXDHQCH-WXUPVFRZSA-N 0.000 claims description 5
- RXLRLJSRXDHQCH-ASNKJFCVSA-N Ganoderic acid R Chemical compound CC1(C)[C@H](OC(C)=O)CC[C@]2(C)C3=CC[C@]4(C)[C@@H]([C@@H]([C@H](C\C=C(/C)C(O)=O)OC(C)=O)C)CC[C@@]4(C)C3=CC[C@H]21 RXLRLJSRXDHQCH-ASNKJFCVSA-N 0.000 claims description 5
- RMKUNHROPPZENV-IXWATKSXSA-N ganodesterone Chemical compound O=C1CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)/C=C/[C@H](C)C(C)C)CC[C@H]33)C)C3=CC(=O)C2=C1 RMKUNHROPPZENV-IXWATKSXSA-N 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 241000583195 Ganodes Species 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000126 substance Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 9
- OCLVBEOPEKEKNM-CAXIOAJTSA-N Ganoderic Acid T Chemical compound CC1(C)[C@H](OC(C)=O)CC[C@]2(C)C3=CC[C@]4(C)[C@@H]([C@@H]([C@H](C\C=C(/C)C(O)=O)OC(C)=O)C)C[C@H](OC(C)=O)[C@@]4(C)C3=CC[C@H]21 OCLVBEOPEKEKNM-CAXIOAJTSA-N 0.000 description 6
- 238000000862 absorption spectrum Methods 0.000 description 6
- OCLVBEOPEKEKNM-UHFFFAOYSA-N ganoderic acid T Natural products CC1(C)C(OC(C)=O)CCC2(C)C3=CCC4(C)C(C(C(CC=C(C)C(O)=O)OC(C)=O)C)CC(OC(C)=O)C4(C)C3=CCC21 OCLVBEOPEKEKNM-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 230000037396 body weight Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 240000008397 Ganoderma lucidum Species 0.000 description 2
- 235000001637 Ganoderma lucidum Nutrition 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000004738 parenchymal cell Anatomy 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- RDMQPKIDHAFXKA-JNORPAGFSA-N Ganoderic Acid Am1 Chemical compound C([C@@]12C)C[C@H](O)C(C)(C)[C@@H]1CC(=O)C1=C2C(=O)C[C@]2(C)[C@@H]([C@@H](CC(=O)CC(C)C(O)=O)C)CC(=O)[C@]21C RDMQPKIDHAFXKA-JNORPAGFSA-N 0.000 description 1
- 229930182735 Ganoderic acid Natural products 0.000 description 1
- 108030000917 Glutamine-pyruvate transaminases Proteins 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WMFYOYKPJLRMJI-UHFFFAOYSA-N Lercanidipine hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 WMFYOYKPJLRMJI-UHFFFAOYSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 101710089165 Protein white Proteins 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 本発明は、ganodesterone,trideacetyl ganoderic acid
T,ganoderic acid S,ganoderic acid Rを有効成分とす
る強肝剤に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to ganodesterone, trideacetyl ganoderic acid.
The present invention relates to a strong liver drug containing T, ganoderic acid S and ganoderic acid R as active ingredients.
上記４種の化合物は、本発明者らがマンネンタケ（Gano
derma lucidum）の子実体、漢方薬でいうところの霊芝
より得たものであり、鋭意研究の結果これらの化合物
は、肝障害に対して強い抑制作用を示すことを知見し本
発明に至ったものである。The above four kinds of compounds were prepared by the inventors of the present invention.
derma lucidum), a fruiting body of derma lucidum), which was obtained from Ganoderma lucidum, which is a Chinese herbal medicine. Is.
以下本発明物質の理化学的性質、製法、生理学的性質及
び使用態様等につき詳細に分説する。The physicochemical properties, production method, physiological properties and usage of the substance of the present invention will be described in detail below.
理化学的性質 １） ganodesterone （ａ）構造式 （ｂ）融点:156−159℃（分解）。Physicochemical properties 1) ganodesterone (a) Structural formula (B) Melting point: 156-159 ° C (decomposition).
（ｃ）紫外線吸収極大波長： （ｄ）赤外線吸収極大： （ｅ）マススペクトル： 高速マススペクトル；〔Ｍ〕+m/z408.3034 EIマススペクトル;408〔Ｍ〕+,325〔Ｍ−C6H12〕＋（8
0）,283〔Ｍ−side chain〕＋（100）,229〔Ｍ−C
13H23〕＋（33）,125〔side chain〕＋（18） （ｆ）1H−NMRスペクトル300MHz（CDCl3 σ＝ppm）:0.6
9（3H,s）,0.83（3H,d,J＝6.6Hz）,0.85（3H,d,J＝6.6H
z）,0.93（3H,d,J＝6.6Hz）,1.05（3H,d,J＝6.6Hz）,1.
30（3H,s）,5.14（1H,dd,J＝15.0,6.7Hz）,5.98（1H,t,
J＝1.8Hz）,6.47（1H,s） （ｇ）13C NMRスペクトル75.2MHz（CDCl3 σ＝ppm）:1
2.8（３）,17.6（３）,19.5（３）,19.7（３）,20.0
（３）,21.1（３）,21.9（２）,22.6（２）,27.7
（２）,33.1（１）,34.3（２）,35.4（２）,38.5
（２）,39.1（０）,40.2（１）,42.9（１）,44.6
（０）,47.1（１）,56.1（１）,56.3（１）,123.9
（１）,126.0（１）,132.8（１）,134.8（１）,158.2
（０）,167.7（０）,187.0（０）,199.3（０）。(C) UV absorption maximum wavelength: (D) Infrared absorption maximum: (E) Mass spectrum: high-speed mass spectrum; [M] + m / z 408.3034 EI mass spectrum; 408 [M] + , 325 [M-C 6 H 12 ] + (8
0), 283 [M-side chain] + (100), 229 [MC
13 H 23 ] + (33), 125 [side chain] + (18) (f) 1 H-NMR spectrum 300 MHz (CDCl 3 σ = ppm): 0.6
9 (3H, s), 0.83 (3H, d, J = 6.6Hz), 0.85 (3H, d, J = 6.6H
z), 0.93 (3H, d, J = 6.6Hz), 1.05 (3H, d, J = 6.6Hz), 1.
30 (3H, s), 5.14 (1H, dd, J = 15.0,6.7Hz), 5.98 (1H, t,
J = 1.8Hz), 6.47 (1H, s) (g) 13 C NMR spectrum 75.2MHz (CDCl 3 σ = ppm): 1
2.8 (3), 17.6 (3), 19.5 (3), 19.7 (3), 20.0
(3), 21.1 (3), 21.9 (2), 22.6 (2), 27.7
(2), 33.1 (1), 34.3 (2), 35.4 (2), 38.5
(2), 39.1 (0), 40.2 (1), 42.9 (1), 44.6
(0), 47.1 (1), 56.1 (1), 56.3 (1), 123.9
(1), 126.0 (1), 132.8 (1), 134.8 (1), 158.2
(0), 167.7 (0), 187.0 (0), 199.3 (0).
結晶は淡黄色鱗片状晶である。The crystals are pale yellow scaly crystals.
２） Ganoderic acid T （ａ）構造式 （ｂ）融 点 202−204℃ （ｃ）元素分析 C:70.40％,H:8.54％ （ｄ）分子式 C36H52O8 （ｅ）紫外吸収スペクトル （ｆ）赤外吸収スペクトル （ｇ）13C−NMR（75MHz,CDCl3）ppm 12.42（３）,12.83（３）,15.91（３）,18.58（３）,2
1.15（３）,21.40（３）,21.52（３）,22.59（３）,22.
70（３）,22.99（２）,22.28（２）,27.91（３）,30.72
（２）,32.09（２）,36.69（０）,36.81（２）,37.50
（０）,38.10（１）,39.78（１）,44.07（１）,44.12
（０）,45.62（２）,51.58（０）,74.62（１）,77.35
（１）,78.22（１）,115.50（１）,121.55（１）,129.4
4（０）,139.17（１）,140.15（０）,142.17（０）,17
0.73（０）,170.87（０）,171.16（０）,172.43
（０）． （ｈ）比旋光度 ▲〔α〕24゜ D▼＋23.3゜ （Ｃ＝0.13,CHCl3） （ｉ）結 晶 無色針状 ３） Ganoderic acid S （ａ）構造式 （ｂ）融 点 194−196℃ （ｃ）元素分析 C:74.93％,H:9.55％ （ｄ）分子式 C32H48O5 （ｅ）紫外吸収スペクトル （ｆ）赤外吸収スペクトル （ｇ）1H−NMR（300MHz,CDCl3）ppm 0.57（3H,s,18−CH3）,0.87（3H,s,32−CH3）,0.94（3
H,s,19−CH3）,0.98（3H,s,30−CH3）,0.98（3H,d,J＝
6.7Hz,21−CH3）,1.0（3H,s,30−CH3）,1.86（3H,s,27
−CH3）,2.05（3H,s,OCOCH3）,2.22（1H,d,J＝17.4Hz,1
2−Ｈ）,2.36（1H,ddd,J＝16.6,8.4,4.2Hz,23−Ｈ）,2.
56（1H,ddd,J＝16.6,8.4,4.2Hz,23−Ｈ）,3.45（1H,dd,
J＝1.4,1.4,3β−Ｈ）,5.10（1H,ddd,J＝6.8,6.0,1.7H
z,22−Ｈ）,5.33（1H.dd,J＝16.4,3.4Hz,11−Ｈ）,5.47
（1H,dd,J＝4.5,2.1Hz,7−Ｈ）,6.82（1H,ddd,J＝7.5,
7.6,1.6Hz,24−Ｈ）． （ｈ）13C−NMR（75MHz,CDCl3）ppm 12.5（３）,12.58（３）,15.37（３）,20.97（３）,22.
48（３）,27.47（３）,28.67（２）,29.77（２）,31.28
（２）,31.70（２）,37.11（０）,37.26（０）,37.63
（２）,39.27（２）,43.05（２）,43.56（０）,47.24
（２）,50.29（０）,74.56（１）,76.05（１）,115.49
（１）,120.34（１）,128.97（０）,139.48（１）,142.
21（０）,145.89（０）,170.59（０）,172.24（０）． （ｉ）比旋光度 ▲〔α〕28゜ D▼＋19.8゜（Ｃ＝0.085,CHCl3） （ｊ）結 晶 無色針状 ４） Ganoderic acid R （ａ）構造式 （ｂ）融 点 201−202℃ （ｃ）元素分析 C:73.77％,H:9.13％ （ｄ）分子式 C34H56O6 （ｅ）紫外吸収スペクトル （ｆ）赤外吸収スペクトル （ｇ）1H−NMR（300MHz:CDCl3）ppm 0.56（3H,s,18−CH3）,0.88（3H,s,32−CH3）,0.90（3
H,s,19−CH3）,0.98（3H,.d,J＝6.5Hz,21−CH3）,0.99
（3H,s,31−CH3）,1.05（3H,s,30−CH3）,1.87（3H,s,2
7−CH3）,2.05（3H,s,OCOCH3）,2.06（3H,s,OCOCH3）,
2.33（1H,d,J＝17.5Hz,12−Ｈ）,2.37（1H,ddd,J＝15.
3,8.3,3.8Hz,23−Ｈ）,2.57（1H,ddd,J＝15.3,8.3,3.8H
z,23−Ｈ）,4.67（1H,dd,J＝3.3,1.7Hz,3β−Ｈ）,5.11
（1H,ddd,J＝7.1,7.0,1.4Hz,22−Ｈ）,5.32（1H,d,J＝
4.6Hz,11−Ｈ）,5.47（1H,dd,J＝4.6,2.1Hz,7−Ｈ）,6.
84（1H,ddd,J＝7.5,7.6,1.6Hz,24−Ｈ）． （ｈ）13C−NMR（75MHz:CDCl3）ppm 12.17（３）,12.62（３）,15.39（３）,21.00（３）,2
1.25（３）,22.36（３）,22.45（３）,22.76（２）,23.
04（２）,25.60（３）,27.50（２）,27.68（３）,30.46
（０）,31.33（２）,31.75（２）,36.43（０）.37.14
（０）,37.62（２）,39.33（１）,43.61（０）,44.03
（１）,47.29（１）,50.29（０）,74.58（１）,78.06
（１）,115.50（１）,120.24（１）,128.96（０）,139.
55（１）,142.21（０）,145.84（０）,170.59（０）,17
0.79（０）,172.25（０）． （ｉ）比旋光度 ▲〔α〕28゜ D▼＋8.7゜（Ｃ＝0.092,CHCl3） （ｉ）結 晶 無色針状 尚、測定機器の型式を付言すれば、紫外分光光度計（日
立自記分光光度計340型）、赤外線分光光度計（日本分
光IR A−100）、微量融点測定器（柳本製作所）、NMRス
ペクトロメータ（Varian XL−400,XL−300）、クロマト
グラフ用カラム（和光純薬、Wako−gel C−200,800g φ
＝74mm）、HPLC用カラム（Chemcopak,Nucleosil C18 5
μm,10φ×300mm）等である。2) Ganoderic acid T (a) Structural formula (B) Melting point 202-204 ℃ (c) Elemental analysis C: 70.40%, H: 8.54% (d) Molecular formula C 36 H 52 O 8 (e) UV absorption spectrum (F) Infrared absorption spectrum (G) 13 C-NMR (75 MHz, CDCl 3 ) ppm 12.42 (3), 12.83 (3), 15.91 (3), 18.58 (3), 2
1.15 (3), 21.40 (3), 21.52 (3), 22.59 (3), 22.
70 (3), 22.99 (2), 22.28 (2), 27.91 (3), 30.72
(2), 32.09 (2), 36.69 (0), 36.81 (2), 37.50
(0), 38.10 (1), 39.78 (1), 44.07 (1), 44.12
(0), 45.62 (2), 51.58 (0), 74.62 (1), 77.35
(1), 78.22 (1), 115.50 (1), 121.55 (1), 129.4
4 (0), 139.17 (1), 140.15 (0), 142.17 (0), 17
0.73 (0), 170.87 (0), 171.16 (0), 172.43
(0). (H) Specific rotation ▲ [α] 24 ° D ▼ + 23.3 ° (C = 0.13, CHCl 3 ) (i) Crystalline colorless needles 3) Ganoderic acid S (a) Structural formula (B) Melting point 194-196 ° C (c) Elemental analysis C: 74.93%, H: 9.55% (d) Molecular formula C 32 H 48 O 5 (e) Ultraviolet absorption spectrum (F) Infrared absorption spectrum (G) 1 H-NMR (300 MHz, CDCl 3 ) ppm 0.57 (3H, s, 18-CH 3 ), 0.87 (3H, s, 32-CH 3 ), 0.94 (3
H, s, 19-CH 3 ), 0.98 (3H, s, 30-CH 3), 0.98 (3H, d, J =
6.7Hz, 21−CH 3 ), 1.0 (3H, s, 30−CH 3 ), 1.86 (3H, s, 27
−CH 3 ), 2.05 (3H, s, OCOCH 3 ), 2.22 (1H, d, J = 17.4Hz, 1
2-H), 2.36 (1H, ddd, J = 16.6,8.4,4.2Hz, 23-H), 2.
56 (1H, ddd, J = 16.6,8.4,4.2Hz, 23−H), 3.45 (1H, dd,
J = 1.4,1.4,3β-H), 5.10 (1H, ddd, J = 6.8,6.0,1.7H
z, 22-H), 5.33 (1H.dd, J = 16.4,3.4Hz, 11-H), 5.47
(1H, dd, J = 4.5,2.1Hz, 7−H), 6.82 (1H, ddd, J = 7.5,
7.6, 1.6Hz, 24-H). (H) 13 C-NMR (75 MHz, CDCl 3 ) ppm 12.5 (3), 12.58 (3), 15.37 (3), 20.97 (3), 22.
48 (3), 27.47 (3), 28.67 (2), 29.77 (2), 31.28
(2), 31.70 (2), 37.11 (0), 37.26 (0), 37.63
(2), 39.27 (2), 43.05 (2), 43.56 (0), 47.24
(2), 50.29 (0), 74.56 (1), 76.05 (1), 115.49
(1), 120.34 (1), 128.97 (0), 139.48 (1), 142.
21 (0), 145.89 (0), 170.59 (0), 172.24 (0). (I) Specific optical rotation ▲ [α] 28 ° D ▼ + 19.8 ° (C = 0.085, CHCl 3 ) (j) Crystals, colorless needles 4) Ganoderic acid R (a) Structural formula (B) Melting point 201-202 ° C (c) Elemental analysis C: 73.77%, H: 9.13% (d) Molecular formula C 34 H 56 O 6 (e) Ultraviolet absorption spectrum (F) Infrared absorption spectrum (G) 1 H-NMR (300 MHz: CDCl 3 ) ppm 0.56 (3H, s, 18-CH 3 ), 0.88 (3H, s, 32-CH 3 ), 0.90 (3
H, s, 19−CH 3 ), 0.98 (3H, .d, J = 6.5Hz, 21−CH 3 ), 0.99
(3H, s, 31−CH 3 ), 1.05 (3H, s, 30−CH 3 ), 1.87 (3H, s, 2
7-CH 3 ), 2.05 (3H, s, OCOCH 3 ), 2.06 (3H, s, OCOCH 3 ),
2.33 (1H, d, J = 17.5Hz, 12-H), 2.37 (1H, ddd, J = 15.
3,8.3,3.8Hz, 23-H), 2.57 (1H, ddd, J = 15.3,8.3,3.8H
z, 23-H), 4.67 (1H, dd, J = 3.3,1.7Hz, 3β-H), 5.11
(1H, ddd, J = 7.1,7.0,1.4Hz, 22−H), 5.32 (1H, d, J =
4.6Hz, 11-H), 5.47 (1H, dd, J = 4.6,2.1Hz, 7-H), 6.
84 (1H, ddd, J = 7.5,7.6,1.6Hz, 24-H). (H) 13 C-NMR (75MHz: CDCl 3 ) ppm 12.17 (3), 12.62 (3), 15.39 (3), 21.00 (3), 2
1.25 (3), 22.36 (3), 22.45 (3), 22.76 (2), 23.
04 (2), 25.60 (3), 27.50 (2), 27.68 (3), 30.46
(0), 31.33 (2), 31.75 (2), 36.43 (0) .37.14
(0), 37.62 (2), 39.33 (1), 43.61 (0), 44.03
(1), 47.29 (1), 50.29 (0), 74.58 (1), 78.06
(1), 115.50 (1), 120.24 (1), 128.96 (0), 139.
55 (1), 142.21 (0), 145.84 (0), 170.59 (0), 17
0.79 (0), 172.25 (0). (I) Specific rotation ▲ [α] 28 ° D ▼ + 8.7 ° (C = 0.092, CHCl 3 ) (i) Crystalline colorless needles In addition, if the model of the measuring instrument is added, the ultraviolet spectrophotometer ( Hitachi autograph spectrophotometer 340 type), infrared spectrophotometer (JASCO IR A-100), trace melting point instrument (Yanagimoto Seisakusho), NMR spectrometer (Varian XL-400, XL-300), chromatographic column ( Wako Pure Chemical, Wako-gel C-200,800g φ
= 74 mm), HPLC column (Chemcopak, Nucleosil C 18 5
μm, 10φ × 300 mm) etc.
化合物の製法 １） ganodesterone Roux flask 100本にて６週間培養したマンネンタケの菌
糸体をナイロンメッシュ（20メッシュ）でろ過し、培地
を除いて菌糸体5.32kg（fr.wt.）を得た。MeOH 101を加
えてWaking Blenderで粉砕した後（15,000rpm×5min）
室温にて１週間冷浸した。これを吸引ろ過し、残査とろ
液に分け、残査はMeOH 10lで１週間再抽出した。ろ液を
合わせてMeOHを留去した後、水500mlを加え、CHCl31lに
て２回抽出を行い、無水Na2SO4にて乾燥後、溶媒を留去
してCHCl3Fr.16.78gを得た。Compound Production Method 1) Mycelium of Ganoderma lucidum that had been cultured in 100 ganodesterone Roux flasks for 6 weeks was filtered through a nylon mesh (20 mesh), and the medium was removed to obtain 5.32 kg (fr.wt.) of mycelium. After adding MeOH 101 and grinding with Waking Blender (15,000 rpm x 5 min)
It was soaked at room temperature for 1 week. This was subjected to suction filtration, separated into a residue and a filtrate, and the residue was re-extracted with 10 L of MeOH for 1 week. After distilling off the MeOH the combined filtrates water 500ml was added, it was extracted twice with CHCl 3 1l, dried over anhydrous Na 2 SO 4, CHCl 3 Fr.16.78g the solvent was distilled off Got
CHCl3Fr.を、benzene:AcOEt系の溶出溶媒を用いたsilic
a gel column chromatography（Wako−gel C−200,800g
φ＝74mm）にかけ、fr.I−１〜fr.I−９までの9fractio
nに分けた。CHCl 3 Fr. was added to silicic acid using benzene: AcOEt elution solvent.
a gel column chromatography (Wako−gel C−200,800g
φ = 74mm), 9 fractio from fr.I-1 to fr.I-9
Divided into n.
次に、fr.I−３（0.31g）を第２表に示す分離条件でHPL
Cにかけ分離精製、メタノールにより再結晶を繰り返し
てganodesterone（27.7mg）を淡黄色鱗片状晶として得
た。 Next, fr.I-3 (0.31g) was added under HPL under the separation conditions shown in Table 2.
By repeating C separation, purification and recrystallization with methanol, ganodesterone (27.7 mg) was obtained as pale yellow scaly crystals.
２） ganoderic adid T,S,R １）と同様にして分離したFr.I−４（1.498g）とFr.I−
５（7.834g）を95％メタノールを用いて逆相HPLCにより
分離精製を繰り返し、いずれも無色針状のganoderic ac
id T,S,Rをそれぞれ2.8g,0.86g,0.49g得た。trideacety
l ganoderic acid Tは、ganederic acid Tをアルカリ処
理して得た。 2) Fr.I-4 (1.498g) and Fr.I- separated in the same manner as ganoderic adid T, S, R 1)
5 (7.834 g) was repeatedly separated and purified by reverse phase HPLC using 95% methanol, and both were colorless needle-shaped ganoderic ac.
2.8 g, 0.86 g, and 0.49 g of id T, S, and R were obtained, respectively. trideacety
l ganoderic acid T was obtained by treating ganederic acid T with an alkali.
生理学的性質 後記実験例に示す通り、本発明物質ganodesterone,trid
eacetyl ganoderic acid T,ganoderic acid S及びＲ
は、Ｄ−ガラクトサミン誘導肝障害に対して強い抑制活
性を示した。Physiological properties As shown in the experimental examples below, the substance of the present invention
eacetyl ganoderic acid T, ganoderic acid S and R
Showed a strong inhibitory activity against D-galactosamine-induced liver injury.
急性毒性 本発明に関する４種の化合物のLD50値は第３表に示す通
りである。LD 50 values of the four compounds on acute toxicity the present invention are shown in Table 3.
使用形態 gandesterone,trideacetyl ganoderic acid T,ganoderi
c acid S及びＲは経口投与、皮下注射または静脈注射等
の手段で通用され得、その用量は通常約100mg/kg体重
（１回）、より好ましくは経口投与で約200〜500mg/kg
体重（１回）程度であり、その剤型としては、生理食塩
水等への溶解液剤、注射液剤、乳化製剤、凍結乾燥等に
よる粉末剤あるいは座剤、腸溶剤、舌下剤、顆粒剤、錠
剤、カプセル剤等々通常の剤型を適当なキャリア、増量
剤、希釈剤等と共に適宜選択し得る。 Usage gandesterone, trideacetyl ganoderic acid T, ganoderi
C acid S and R can be used by oral administration, subcutaneous injection or intravenous injection, and the dosage is usually about 100 mg / kg body weight (once), more preferably about 200-500 mg / kg by oral administration.
The dosage is about one body weight, and the dosage form is a solution in physiological saline or the like, an injection solution, an emulsified preparation, a powder or suppository by freeze-drying, an enteric solution, a sublingual agent, a granule, a tablet. Ordinary dosage forms such as capsules and the like can be appropriately selected together with a suitable carrier, filler, diluent and the like.
実験例 Ｉ 生理活性 実験動物としてSprague−Dawley Rat（日本クレア）オ
ス200〜250gを用いた。Experimental Example I Bioactivity Sprague-Dawley Rat (CLEA Japan, Inc.) male 200 to 250 g was used as an experimental animal.
肝臓からの肝実質細胞の分離は、試薬類についてカラゲ
ナーゼ（和光純薬製）に変更した以外は、通常のコラゲ
ナーゼ灌流法で行なった。（中村ら別冊蛋白白核酸酵素
No.24,1981）以上の方法で分離された肝実質細胞は、コ
ラーゲンTypelをコートしたFalcon culture dish（24
穴、1we11 2cm2）に3.8×104cells/125μ1/cm2の濃度で
まいた。尚、培養液はRafael Enat.et.al.Proc.Natl.Ac
ad.Sci.USA 1984 P.1411〜1455に記載の成分からなる無
血清培地を使用した。次に５％炭酸ガスインキュベータ
ー内に静着し、肝実質細胞を生着させた。Separation of hepatic parenchymal cells from the liver was performed by the usual collagenase perfusion method except that the reagents were changed to carrageenase (manufactured by Wako Pure Chemical Industries, Ltd.). (Nakamura et al. Separate Volume Protein White Nucleic Acid Enzyme
No. 24, 1981) The liver parenchymal cells isolated by the above method were used in Falcon culture dish (24
A well, 1we11 2 cm 2 ) was seeded at a concentration of 3.8 × 10 4 cells / 125 μ1 / cm 2 . The culture medium was Rafael Enat.et.al.Proc.Natl.Ac.
A serum-free medium comprising the components described in ad.Sci.USA 1984 P.1411-1455 was used. Next, the cells were allowed to settle in a 5% carbon dioxide gas incubator to engraft hepatocytes.
培養開始24時間後、培地をぬきとり、それぞれ各サンプ
ル125μｇをDMSO（ジメチルスルフォキサイド）2.5μｌ
に溶かしたものと、Ｄ−ガラクトサミン12.5μｇを含む
培地を250μl/well加え、５時間後各々の培地を肝機能
測定サンプルとした。24 hours after the start of culture, the medium was removed, and 125 μg of each sample was added to 2.5 μl of DMSO (dimethyl sulfoxide).
And 250 μl / well of a medium containing 12.5 μg of D-galactosamine was added to each medium and used as a liver function measurement sample after 5 hours.
肝機能はGOT活性（グルタミンオキザロ酢酸トランスア
ミナーゼ活性）、GPT活性（グルタミンピルビン酸トラ
ンスアミナーゼ活性）とLDH活性（乳酸脱水素酵素活
性）を測定し、トリパンブルー染色による形態学的鏡検
を行なった。結果は第４表に示す通りである。GOT,GPT
活性はカルメン法で、LDH活性はWorblewski−Ladue法で
行なった。コントロールはＤ−ガラクトサミン12.5μg,
DMSO2.5μｌを250μｌの培地に溶かしたものとする。For liver function, GOT activity (glutamine oxaloacetate transaminase activity), GPT activity (glutamine pyruvate transaminase activity) and LDH activity (lactate dehydrogenase activity) were measured, and morphological microscopic examination by trypan blue staining was performed. The results are shown in Table 4. GOT, GPT
The activity was determined by the Carmen method, and the LDH activity was determined by the Worblewski-Ladue method. The control is D-galactosamine 12.5 μg,
2.5 μl of DMSO should be dissolved in 250 μl of medium.
実験例 II 1.ICR系マウス（雄、６週令、平均体重30.0±0.3g,各群
10匹）を使用し、生理食塩水0.5mに溶解した6mg,10.5m
g,15mg,19.5mg,24mgの５段階の本発明物質ganodesteron
e,trideacetyl ganoderic acid T,ganoderic acid S,ga
noderic acid Rを皮下投与し、７日間その生死を観察
し、Behrens−karberに従って算出したLD50値は順に1.
5,1.1,1.3,2.7g/kg体重マウスであった。 Experimental Example II 1. ICR mouse (male, 6 weeks old, average weight 30.0 ± 0.3 g, each group)
10 mg), dissolved in physiological saline 0.5 m, 6 mg, 10.5 m
g, 15 mg, 19.5 mg, 24 mg of the present invention substance ganodesteron in 5 stages
e, trideacetyl ganoderic acid T, ganoderic acid S, ga
Noderic acid R was subcutaneously administered, and its life and death was observed for 7 days, and the LD 50 value calculated according to Behrens-karber was 1.
The mice were 5,1.1,1.3,2.7 g / kg body weight.
2.ICR系統マウス（雄、６週令、平均体重30.0±0.3g,各
群10匹）を使用し、生理食塩水0.5mlに溶解した30mg,45
mg,60mg,75mg,90mgの５段階の本発明物質ganodesteron
e,trideacetyl ganoderic acid T,ganoderic acid S及
びＲを経口投与し、７日間その生死を観察しBehrens−k
arber法に従って算出したLD50値は順に4.5,2.7,3.0,5.6
g/kg体重マウスであった。2. ICR strain mice (male, 6 weeks old, average body weight 30.0 ± 0.3 g, 10 mice in each group) were used, and dissolved in 0.5 ml of physiological saline 30 mg, 45
mg, 60 mg, 75 mg, 90 mg of the present invention ganodesteron in 5 stages
Orally administer e, trideacetyl ganoderic acid T, ganoderic acid S and R, and observe their life and death for 7 days.
The LD 50 values calculated according to the arber method are 4.5, 2.7, 3.0, 5.6 in order.
g / kg body weight mouse.
製剤例 1.本発明物質2mgを滅菌した生理食塩水1mlに溶解し、注
射剤を調製した。Formulation Example 1. 2 mg of the substance of the present invention was dissolved in 1 ml of sterilized physiological saline to prepare an injection.
2.本発明物質50mgを乳糖950mgと充分に混合し、結合剤
として５％デンプン糊液を用いて湿式法により顆粒をつ
くり、打錠して錠剤とした。2. 50 mg of the substance of the present invention was thoroughly mixed with 950 mg of lactose, and granules were prepared by a wet method using a 5% starch paste solution as a binder and compressed into tablets.
このように本発明物質は、前記標準用量等に基づいて薬
学的に許容され得る担体への溶解、混合により、所定の
活性を有する所望の剤型とすることができる。As described above, the substance of the present invention can be made into a desired dosage form having a predetermined activity by dissolving and mixing it in a pharmaceutically acceptable carrier based on the standard dose and the like.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 米国特許3381021（ＵＳ，Ａ) Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔｓ 54：24869ｉ Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔｓ 89：212270ａ Ｊ．Ａｗｅｒ．Ｃｈｅｍ．Ｓｏｃ．ｖｏ ｌ，90 Ｎｏ．23（1968）Ｐ．6565−6566 Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔｓ 105：94209 ─────────────────────────────────────────────────── --Continued Front Page (56) References US Pat. No. 3,382,011 (US, A) Chemical Abstracts 54: 24869i Chemical Abstracts 89: 212270a J. Awer. Chem. Soc. vol. 90 No. 23 (1968) P. 6565-6566 Chemical Abstracts 105: 94209
Claims (1)
ric acid T,ganoderic acid S,ganoderic acid Rを有効
成分とする強肝剤。1. Structural formula [1], [2], [3], [4] Structural formula [1] Structural formula [2] Structural formula [3] Structural formula [4] Compound represented by ganodesterone, trideacetyl ganode
A strong liver drug containing ric acid T, ganoderic acid S, ganoderic acid R as active ingredients.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61044171A JPH0723310B2 (en) | 1986-03-03 | 1986-03-03 | Strong liver |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61044171A JPH0723310B2 (en) | 1986-03-03 | 1986-03-03 | Strong liver |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62270595A JPS62270595A (en) | 1987-11-24 |
| JPH0723310B2 true JPH0723310B2 (en) | 1995-03-15 |
Family
ID=12684139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61044171A Expired - Lifetime JPH0723310B2 (en) | 1986-03-03 | 1986-03-03 | Strong liver |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0723310B2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3873097B2 (en) * | 1997-11-06 | 2007-01-24 | 独立行政法人理化学研究所 | Anti-obesity agent and lipid metabolism improving agent |
| WO2005079164A2 (en) * | 2004-02-10 | 2005-09-01 | Kyushu Tlo Co Ltd | 5α-REDUCTASE INHIBITORS |
| JP4845393B2 (en) * | 2005-03-04 | 2011-12-28 | ゲオール化学株式会社 | Anti-inflammatory agent containing triterpene compound |
| CN105044237A (en) * | 2015-07-10 | 2015-11-11 | 广西仙草堂制药有限责任公司 | Determination method for ganoderma triterpene |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3381021A (en) | 1967-06-02 | 1968-04-30 | Dow Chemical Co | Method for the preparation of alpha, delta-diketones from alpha, beta-ethylenically unsaturated monoketones |
-
1986
- 1986-03-03 JP JP61044171A patent/JPH0723310B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3381021A (en) | 1967-06-02 | 1968-04-30 | Dow Chemical Co | Method for the preparation of alpha, delta-diketones from alpha, beta-ethylenically unsaturated monoketones |
Non-Patent Citations (4)
| Title |
|---|
| ＣｈｅｍｉｃａｌＡｂｓｔｒａｃｔｓ１０５：９４２０９ |
| ＣｈｅｍｉｃａｌＡｂｓｔｒａｃｔｓ５４：２４８６９ｉ |
| ＣｈｅｍｉｃａｌＡｂｓｔｒａｃｔｓ８９：２１２２７０ａ |
| Ｊ．Ａｗｅｒ．Ｃｈｅｍ．Ｓｏｃ．ｖｏｌ，９０Ｎｏ．２３（１９６８）Ｐ．６５６５−６５６６ |
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| Publication number | Publication date |
|---|---|
| JPS62270595A (en) | 1987-11-24 |
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