JPH059123A - Carcinostatic agent - Google Patents
Carcinostatic agentInfo
- Publication number
- JPH059123A JPH059123A JP3160661A JP16066191A JPH059123A JP H059123 A JPH059123 A JP H059123A JP 3160661 A JP3160661 A JP 3160661A JP 16066191 A JP16066191 A JP 16066191A JP H059123 A JPH059123 A JP H059123A
- Authority
- JP
- Japan
- Prior art keywords
- ginsenoside
- carcinostatic agent
- suppressing
- cells
- meyer
- 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
- 230000003327 cancerostatic effect Effects 0.000 title abstract description 9
- 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 19
- 239000004480 active ingredient Substances 0.000 claims abstract description 9
- 239000002246 antineoplastic agent Substances 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 abstract description 8
- 240000004371 Panax ginseng Species 0.000 abstract description 7
- 235000002789 Panax ginseng Nutrition 0.000 abstract description 7
- 235000008434 ginseng Nutrition 0.000 abstract description 7
- 230000008595 infiltration Effects 0.000 abstract description 7
- 238000001764 infiltration Methods 0.000 abstract description 7
- 206010027476 Metastases Diseases 0.000 abstract description 6
- 230000009401 metastasis Effects 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 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 description 4
- 230000037396 body weight Effects 0.000 abstract description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 abstract description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 abstract description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 abstract description 2
- 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 description 2
- 229960002949 fluorouracil Drugs 0.000 abstract description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 229960000485 methotrexate Drugs 0.000 abstract description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 abstract description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 abstract description 2
- 229960004528 vincristine Drugs 0.000 abstract description 2
- 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 3
- 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
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 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 1
- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(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)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 230000035755 proliferation Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 206010028980 Neoplasm Diseases 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 210000005033 mesothelial cell Anatomy 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 210000003126 m-cell Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000009545 invasion Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 229930182494 ginsenoside Natural products 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 210000000713 mesentery Anatomy 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- -1 owl Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 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 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 208000001382 Experimental Melanoma Diseases 0.000 description 1
- 206010022998 Irritability Diseases 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
- 239000004166 Lanolin Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
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- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- RAWGYCTZEBNSTP-UHFFFAOYSA-N aluminum potassium Chemical compound [Al].[K] RAWGYCTZEBNSTP-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
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- 229940092738 beeswax Drugs 0.000 description 1
- JAONZGLTYYUPCT-UHFFFAOYSA-K bismuth subgallate Chemical compound OC(=O)C1=CC(O)=C2O[Bi](O)OC2=C1 JAONZGLTYYUPCT-UHFFFAOYSA-K 0.000 description 1
- 229960000199 bismuth subgallate Drugs 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
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- 239000000284 extract Substances 0.000 description 1
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- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】この発明は、ジンセノシドＲｇ3
を含有する制癌剤に関する。より詳しくは、癌細胞浸
潤、転移の抑制作用を示す新しいタイプの制癌剤に関す
る。This invention relates to ginsenoside Rg 3
The present invention relates to an anticancer agent containing More specifically, the present invention relates to a new type of antitumor agent having an action of suppressing cancer cell infiltration and metastasis.
【０００２】[0002]
【従来の技術と解決しようとする課題】新しい制癌剤の
開発の必要性は高く、天然物、合成化合物について広範
な研究がなされている。オタネニンジンから抽出された
サポニンの中で、例えばジンセノシドＲｈ2 （３−Ｏ−
β−Ｄ−グルコピラノシル−20(S) −プロトパナキサジ
オール）が肝癌細胞などの増殖を抑制する作用があるこ
とが知られている（特公平1-28759号公報参照）。一
方、ジンセノシド Ｒｇ3 〔３−Ｏ−β−Ｄ−グルコピ
ラノシル−（１→２）−β−Ｄ−グルコピラノシル−20
(R) −プロトパナキサジオール〕が、オタネニンジンか
ら分離されその構造が確立されている〔K. Kaku & Y. K
awashima; Arzneim. Forsch. Drug Res., 30,936(198
0)〕が、その薬理作用としてはコラーゲンおよびＡＤＰ
によって誘起される血小板凝集の阻害作用を有すること
が報告されている程度である〔松田ら；生薬学雜誌，3
9,123(1985)〕。この発明の発明者らは、ジンセノシド
Ｒｇ3 の生理活性を検討した結果、新たな活性を見出
し、この発明を完成するに至った。There is a great need for the development of new anticancer agents, and extensive research has been conducted on natural products and synthetic compounds. Among the saponins extracted from Panax ginseng, for example, ginsenoside Rh 2 (3-O-
It is known that β-D-glucopyranosyl-20 (S) -protopanaxadiol) has an action of suppressing the growth of liver cancer cells and the like (see Japanese Patent Publication No. 1-28759). On the other hand, ginsenoside Rg 3 [3-O-β-D-glucopyranosyl- (1 → 2) -β-D-glucopyranosyl-20
(R) -protopanaxadiol] has been separated from Panax ginseng and its structure has been established [K. Kaku & Y. K.
awashima; Arzneim. Forsch. Drug Res., 30 , 936 (198
0)], but its pharmacological actions include collagen and ADP
Is the degree to which has been reported to have an inhibitory action of platelet aggregation induced by [Matsuda et al; Pharmacognosy science, 3
9 , 123 (1985)]. The inventors of the present invention have studied the physiological activity of ginsenoside Rg 3 and , as a result, found a new activity and completed the present invention.
【０００３】[0003]
【課題を解決するための手段】かくして、この発明によ
れば、ジンセノシドＲｇ3 を有効成分として含有するこ
とからなる制癌剤が提供される。この発明の有効成分で
あるジンセノシドＲｇ3 は、オタネニンジンより直接抽
出分離することもできるが、オタネニンジンから抽出分
離されたジンセノシドＲｂ1 、ジンセノシドＲｂ2 また
はジンセノシドＲｃから導くことができる。本化合物
は、 α D −14.7°(c＝1.56、ピリジン）を示し、融
点301 〜302℃を有する無色結晶（メタノールから結晶
化）で、臭いは無い。また本化合物は水、メタノール、
エタノールに可溶である。Thus, according to the present invention, there is provided a carcinostatic agent comprising ginsenoside Rg 3 as an active ingredient. Ginsenoside Rg 3, which is an active ingredient of the present invention, can be directly extracted and separated from Panax ginseng, but can be derived from ginsenoside Rb 1 , ginsenoside Rb 2 or ginsenoside Rc extracted and separated from Panax ginseng. This compound is a colorless crystal (crystallized from methanol) having α D -14.7 ° (c = 1.56, pyridine) and a melting point of 301 to 302 ° C., and has no odor. In addition, this compound is water, methanol,
It is soluble in ethanol.
【０００４】この発明の有効成分であるジンセノシドＲ
ｇ3 は、各種の癌細胞の浸潤を選択的に抑制し、癌細胞
の転移が抑制されるので、結果としてユニークな制癌効
果を奏するものである。ジンセノシドＲｇ3 の経口投与
量は、１〜50mg／１日／60kg体重、好ましくは３〜15mg
／１日／60kg体重である。副作用は殆ど認められない。Ginsenoside R which is the active ingredient of the present invention
Since g 3 selectively suppresses invasion of various cancer cells and suppresses metastasis of cancer cells, g 3 has a unique antitumor effect. The oral dose of ginsenoside Rg 3 is 1 to 50 mg / day / 60 kg body weight, preferably 3 to 15 mg.
/ 1 day / 60 kg body weight. There are few side effects.
【０００５】この発明による制癌剤は、この発明の有効
成分単体、または有効成分と固体もしくは液体の賦形剤
とからなるものである。そして投与法ならびに投与の剤
型としては、通常、散剤、錠剤、乳剤、カプセル剤、茶
剤、顆粒剤、液剤（酒精剤、チンキ剤、流エキス剤、シ
ロップ剤などを含む）などの内服の形がある。また注射
剤、点滴剤の形で体内注入するか、あるいは軟膏剤、液
剤、外用散剤、シップ剤、坐薬、噴霧剤、滋養浣腸剤、
乳剤などの形で外用であってもよい。ここに使用される
固体または液体の賦形剤としては、当該分野で公知のも
のが使用される。ただ前述したような１回の投与量に必
要なこの発明の有効成分を含むように製剤化するのが望
ましい。The anticancer agent according to the present invention comprises the active ingredient alone of the present invention, or the active ingredient and a solid or liquid excipient. The administration method and dosage form are usually as follows: oral administration of powders, tablets, emulsions, capsules, teas, granules, liquids (including alcoholic drugs, tinctures, flow extracts, syrups, etc.) There is a shape. Also, it may be injected into the body in the form of injection or drip, or may be an ointment, liquid, external powder, ship, suppository, spray, nourishing enema,
It may be externally applied in the form of an emulsion or the like. As the solid or liquid excipient used here, those known in the art are used. However, it is preferable to formulate the active ingredient of the present invention in a single dose as described above.
【０００６】いくつかの具体例を挙げると散剤、その他
の内服用粉末剤における賦形剤としては、乳糖、澱粉、
デキストリン、リン酸カルシウム、炭酸カルシウム、合
成および天然ケイ酸アルミニウム、酸化マグネシウム、
乾燥水酸化アルミニウム、ステアリン酸マグネシウム、
重炭酸ナトリウム、乾燥酵母などが挙げられ、外用散剤
の場合は酸化亜鉛、タルク、澱粉、カオリン、ホウ酸
末、ステアリン酸亜鉛、ステアリン酸マグネシウム、炭
酸マグネシウム、沈降炭酸カルシウム、次没食子酸ビス
マス、硫酸アルミニウムカリウム末などが挙げられる。
液剤における賦形剤としては水、グリセリン、プロピレ
ングリコール、単シロップ、エタノール、脂肪油、エチ
レングリコール、ポリエチレングリコール、ソルビトー
ルなどが挙げられる。さらに軟膏剤の場合には脂肪、脂
肪油、ラノリン、ワセリン、グリセリン、ミツロウ、モ
クロウ、パラフィン、流動パラフィン、樹脂、高級アル
コール、プラスチックス、グリコール類、水、界面活性
剤などを組み合わせて作った疎水性基剤あるいは親水性
基剤（乳剤性基剤、水溶性基剤および懸濁剤性基剤を含
む）が賦形剤として使用される。[0006] To give some specific examples, the excipients for powders and other powders for internal use include lactose, starch,
Dextrin, calcium phosphate, calcium carbonate, synthetic and natural aluminum silicate, magnesium oxide,
Dry aluminum hydroxide, magnesium stearate,
Sodium bicarbonate, dry yeast, etc. are mentioned, and in the case of powder for external use, zinc oxide, talc, starch, kaolin, boric acid powder, zinc stearate, magnesium stearate, magnesium carbonate, precipitated calcium carbonate, bismuth subgallate, sulfuric acid. Examples include aluminum potassium powder.
Examples of the excipient in the liquid agent include water, glycerin, propylene glycol, simple syrup, ethanol, fatty oil, ethylene glycol, polyethylene glycol, sorbitol and the like. Furthermore, in the case of ointment, hydrophobicity made by combining fat, fatty oil, lanolin, petrolatum, glycerin, beeswax, owl, paraffin, liquid paraffin, resin, higher alcohol, plastics, glycols, water, surfactant, etc. A hydrophilic base or a hydrophilic base (including an emulsion base, a water-soluble base and a suspension base) is used as an excipient.
【０００７】この発明の制癌剤は、癌細胞の増殖を抑制
または阻害する薬剤（例えば５−フルオロウラシル、ビ
ンクリスチン、エンドキサン、メソトレキセートなど）
と併用すると、一層効果的である。次に、ジンセノシド
Ｒｇ3 の生理作用を示す。 方法： １）癌細胞浸潤の定量（in vitro浸潤系） 培養液 ：イーグル氏培養液（アミノ酸及びビタミ
ンは２倍量）に終濃度10％になるようにウシ胎児血清を
加える。 がん細胞 ：ラット腹水肝癌細胞（ＡＨ細胞） 中皮細胞 ：ラット腸間膜を0.25％トリプシン液にて
消化し、得られた中皮細胞（Ｍ−細胞） 検 体 ：ジンセノシドＲｇ3 をジメチルスルホキ
シド（ＤＭＳＯ）に溶解し５mMとする。本標品を保存液
とし、実験直前にＤＭＳＯで所定の濃度に希釈する。 浸潤実験系 ：単層培養した中皮細胞（Ｍ−細胞）層上
にＡＨ細胞を重層し、中皮細胞層下に侵入したＡＨ細胞
の数を位相差顕微鏡下で測定する。即ち、１×105 個の
Ｍ−細胞を35mm径の培養シャーレで５日間培養し、Ｍ−
細胞がシャーレ面を略完全に覆ったとき、１×105 個の
ＡＨ細胞を重層する。20時間後培養液を除去し、細胞を
10％ホルマリンで固定する。次いで位相差顕微鏡下で60
視野（１視野：1.13mm2 ）を観察する。各視野毎に中皮
細胞層下に侵入したＡＨ細胞の数を計測し60視野分を加
算、最終的に１cm2 当たりの侵入ガン細胞数として表現
した。ジンセノシドＲｇ3 の効果を観察するためには種
々の濃度のジンセノシドＲｇ3 20μl を培養液２mlに懸
濁した２×105 個のＡＨ細胞に加え、直ちに中皮細胞層
上に重層する。対照にはジンセノシドＲｇ3 を含まない
ＤＭＳＯ20μl を加える。 ２）転移実験系 培養液 ：ダルベッコー培養液に終濃度10％になる
ようにウシ胎児血清を加える。 がん細胞 ：Ｂ16メラノーマ細胞（B16FE7） 動物 ：６−８週令のＣ57ＢＬ／６マウス 検体 ：ジンセノシドＲｇ3 をＤＭＳＯに溶解
し、５mMとする。本標品を保存液として実験直前にＤＭ
ＳＯにて所定の濃度に希釈する。次いでそれぞれ培養液
にて50倍に希釈する。 肺転移定量系：培養したB16FE7細胞（1.6 ×105 個）を
300 μl の培養液に懸濁し、Ｃ57ＢＬ／６マウスの尾静
脈より注入し、２週間後、両肺表面に生じたこのがん細
胞の転移腫瘤の数を計測し、この数を肺転移能とする。
ジンセノシドＲｇ3 の効果を観察するためには、上記の
ように作成した種々の濃度ジンセノシドＲｇ3 を培養液
にて50倍に希釈した溶液２mlに、１mlの細胞懸濁液（1.
6 ×106 ／ml）を加え、その300 μl を尾静脈より注入
する。対照には同濃度のＤＭＳＯを細胞懸濁液に加え
る。 結果The anticancer drug of the present invention is a drug that suppresses or inhibits the growth of cancer cells (eg 5-fluorouracil, vincristine, endoxane, methotrexate, etc.).
It is more effective when used together with. Next, the physiological action of ginsenoside Rg 3 will be shown. Method: 1) Quantification of cancer cell infiltration (in vitro infiltration system) Culture medium: Fetal bovine serum is added to Eagle's culture medium (double amount of amino acids and vitamins) to a final concentration of 10%. Cancer cells: Rat ascites hepatoma cells (AH cells) Mesothelial cells: Rat mesentery cells (M-cells) obtained by digesting rat mesentery with 0.25% trypsin solution. Detected: Ginsenoside Rg 3 is dimethyl sulfoxide. Dissolve in (DMSO) to make 5 mM. This preparation is used as a stock solution and diluted with DMSO to a predetermined concentration immediately before the experiment. Invasion experimental system: AH cells are overlaid on a mesothelial cell (M-cell) layer cultured in a monolayer, and the number of AH cells invading under the mesothelial cell layer is measured under a phase contrast microscope. That is, 1 × 10 5 M-cells were cultured in a 35 mm diameter culture dish for 5 days to give M-cells.
When the cells cover the petri dish surface almost completely, 1 × 10 5 AH cells are overlaid. After 20 hours, remove the medium and remove the cells.
Fix with 10% formalin. Then under a phase contrast microscope 60
Observe the visual field (1 visual field: 1.13 mm 2 ). The number of AH cells invading under the mesothelial cell layer was measured for each visual field, 60 visual fields were added, and finally expressed as the number of invading cancer cells per cm 2 . To observe the effect of ginsenoside Rg 3 is added to 2 × 10 5 pieces of AH cells suspended ginsenoside Rg 3 20 [mu] l of various concentrations to the culture 2 ml, overlaid on mesothelial cell layer immediately. As a control, 20 μl of DMSO containing no ginsenoside Rg 3 is added. 2) Metastasis experiment system Culture medium: Add fetal bovine serum to Dulbecco's culture medium to a final concentration of 10%. Cancer cell: B16 melanoma cell (B16FE7) Animal: 6-8 week old C57BL / 6 mouse Specimen: Ginsenoside Rg 3 is dissolved in DMSO to make 5 mM. Use this preparation as a stock solution and DM immediately before the experiment.
Dilute to the specified concentration with SO. Then, each is diluted 50 times with the culture medium. Lung metastasis quantification system: Cultured B16FE7 cells (1.6 × 10 5 cells)
The cells were suspended in 300 μl of the culture medium and injected from the tail vein of C57BL / 6 mice, and 2 weeks later, the number of metastatic tumors of these cancer cells on both lung surfaces was measured, and this number was determined as the lung metastatic potential. To do.
Ginsenosides in order to observe the effect of Rg 3 is a variety of concentrations ginsenoside Rg 3 which was prepared as described above in a solution 2ml diluted 50-fold with the culture solution, 1 ml of cell suspension (1.
6 × 10 6 / ml) and inject 300 μl from the tail vein. As a control, DMSO of the same concentration is added to the cell suspension. result
【０００８】１）ジンセノシドＲｇ3 （２−50μM ）は
ＡＨ細胞の培養系での浸潤（in vitro浸潤）を抑制し
た。1) Ginsenoside Rg 3 (2-50 μM) suppressed the infiltration (in vitro infiltration) of AH cells in the culture system.
【表１】 以上の結果から分かるように、この発明のジンセノシド
Ｒｇ3 は、癌細胞の浸潤を抑制し、また癌細胞の転移を
抑制することが明らかであり、従って制癌剤として使用
できる。[Table 1] As can be seen from the above results, it is clear that the ginsenoside Rg 3 of the present invention suppresses invasion of cancer cells and metastasis of cancer cells, and therefore can be used as an anticancer agent.
Claims (1)
有することからなる制癌剤。Claim: What is claimed is: 1. An anticancer agent comprising ginsenoside Rg 3 as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16066191A JP3160313B2 (en) | 1991-07-01 | 1991-07-01 | Anticancer drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16066191A JP3160313B2 (en) | 1991-07-01 | 1991-07-01 | Anticancer drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH059123A true JPH059123A (en) | 1993-01-19 |
| JP3160313B2 JP3160313B2 (en) | 2001-04-25 |
Family
ID=15719762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16066191A Expired - Lifetime JP3160313B2 (en) | 1991-07-01 | 1991-07-01 | Anticancer drug |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3160313B2 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996040181A1 (en) * | 1995-06-07 | 1996-12-19 | Cheil Je Dang Co. | Processed ginseng having enhanced pharmacological effect |
| WO1997018824A1 (en) * | 1995-11-22 | 1997-05-29 | Cheil Je Dang Co. | Vasodilating composition |
| WO2004056372A1 (en) * | 2002-12-19 | 2004-07-08 | Panagin Pharmaceuticals Inc. | Use of aglycon protopanaxadiol in cancer therapy |
| WO2004056379A1 (en) * | 2002-12-23 | 2004-07-08 | Panagin Pharmaceuticals Inc. | Saponins and sapogenins for use in combination therapy for cancer |
| WO2004056371A1 (en) * | 2002-12-19 | 2004-07-08 | Panagin Pharmaceuticals Inc. | Use of aglycon protopanaxatriol in cancer therapy |
| US7585525B2 (en) * | 2002-01-05 | 2009-09-08 | Lotte Confectionery Co., Ltd. | Method for processing ginseng and the uses of extract of processed ginseng |
| JP2013529899A (en) * | 2010-05-14 | 2013-07-25 | 株式会社ジーシーエイチアンドピー | Process for producing novel processed carrots or processed carrot extracts with increased ginsenoside ingredients |
| US10709749B2 (en) | 2013-08-30 | 2020-07-14 | Green Cross Wellbeing Corporation | Composition for preventing and treating cancer-related fatigue, containing processed ginseng powder or processed ginseng extract having increased ginsenoside constituent |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030092638A1 (en) * | 2001-09-21 | 2003-05-15 | Dong Huang | Protopanaxadiol and protopanaxatriol and their use as anti-cancer agents |
-
1991
- 1991-07-01 JP JP16066191A patent/JP3160313B2/en not_active Expired - Lifetime
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996040181A1 (en) * | 1995-06-07 | 1996-12-19 | Cheil Je Dang Co. | Processed ginseng having enhanced pharmacological effect |
| WO1997018824A1 (en) * | 1995-11-22 | 1997-05-29 | Cheil Je Dang Co. | Vasodilating composition |
| US7585525B2 (en) * | 2002-01-05 | 2009-09-08 | Lotte Confectionery Co., Ltd. | Method for processing ginseng and the uses of extract of processed ginseng |
| WO2004056372A1 (en) * | 2002-12-19 | 2004-07-08 | Panagin Pharmaceuticals Inc. | Use of aglycon protopanaxadiol in cancer therapy |
| WO2004056371A1 (en) * | 2002-12-19 | 2004-07-08 | Panagin Pharmaceuticals Inc. | Use of aglycon protopanaxatriol in cancer therapy |
| WO2004056379A1 (en) * | 2002-12-23 | 2004-07-08 | Panagin Pharmaceuticals Inc. | Saponins and sapogenins for use in combination therapy for cancer |
| JP2013529899A (en) * | 2010-05-14 | 2013-07-25 | 株式会社ジーシーエイチアンドピー | Process for producing novel processed carrots or processed carrot extracts with increased ginsenoside ingredients |
| US10709749B2 (en) | 2013-08-30 | 2020-07-14 | Green Cross Wellbeing Corporation | Composition for preventing and treating cancer-related fatigue, containing processed ginseng powder or processed ginseng extract having increased ginsenoside constituent |
| US11464821B2 (en) | 2013-08-30 | 2022-10-11 | Green Cross Wellbeing Corporation | Composition for reducing cancer cachexia or weight loss caused by anticancer drug therapy or radiation therapy comprising ginseng extract having increased ginsenoside Rg3 and Rh2 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3160313B2 (en) | 2001-04-25 |
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