JPH059123A - Carcinostatic agent - Google Patents

Abstract

PURPOSE:To obtain a carcinostatic agent of the type exhibiting suppressing action on cancerous cell infiltration and metastasis containing by ginsenoside Rg3 obtained from Panax ginseng C.A. Meyer as an active ingredient. CONSTITUTION:A carcinostatic agent containing ginsenoside Rg3, directly extracted, and separated from Panax ginseng C.A. Meyer or derivable from ginsenoside Rb1, ginsenoside Rb2 or ginsenoside Rc, extracted and separated from the Panax ginseng C.A. Meyer as an active ingredient. The aforementioned carcinostatic agent is capable of selectively suppressing infiltration of the various cancerous cells and suppressing metastatis of cancerous cells. As a result, the inhibitor is a carcinostatic agent capable of producing unique carcinostatic effects. The oral dose of the ginsenoside Rg3 is preferably about 3-15 mg/day/60 kg body weight. If a medicine, e.g. 5-fluorouracil, vincristine, endoxan or methotrexate capable of suppressing or inhibiting proliferation of the cancerous cells is used in combination, the carcinostatic agent is more effectively used. Any side effects are hardly recognized in the above-mentioned carcinostatic agent.

Description

Detailed Description of the Invention

[0001]

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]

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]

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.

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.

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] 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.

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

1) Ginsenoside Rg ₃ (2-50 μM) suppressed the infiltration (in vitro infiltration) of AH cells in the culture system.

[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)

Claim: What is claimed is: 1. An anticancer agent comprising ginsenoside Rg ₃ as an active ingredient.