JPS61210030A - Antitumor agent - Google Patents

Abstract

PURPOSE:An antitumor agent comprising a tocotrienol as an active ingredient. CONSTITUTION:An antitumor agent containing a compound [e.g., 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyl-3,7,11-tridecatrie ny)-2H-1-benzopyr anol-6, etc.] shown by the formula (R<1>, R<2>, and R<3> are H, or methyl) as an active ingredient. Capsule, microcapsule, suspension, solution, emulsion, injection etc., may be cited as the dosage form. These various preparations can be manu factured by using excipient, binder, extender, surface active agent, dispersant, buffering agent, preservative, dissolution auxiliary, solvent, etc. The tocotrienol as the active ingredient may be a synthetic tocotrienol, a naturally occurring tocotrienol obtained by separation form a deodorized ditillate or a deodorized and deacidified distillate which is separated from purifying process of plant fats and oils, and by concentration, or a natural tocotrienol obtained from a plant source such as latex of Hevea brasiliensis.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an antitumor agent characterized by containing tocotrienols represented by the general formula (wherein RL, R2, and R3 represent a hydrogen atom or a methyl group) as an active ingredient. It is something.

In this case, the tocotrienols may be either synthetic products or natural products separated and concentrated from deodorized distillates or deodorized deoxidized distillates that are separated in the refining process of vegetable oils and fats.

Tocotrienols are compounds that have already been recognized to exist in four types in nature, but their physiological effects have not been studied much because their vitamin E activity is lower than that of the corresponding tocopherols. Furthermore, even when natural vitamin E is separated and recovered from vegetable oils and fats, it has not been used as tocotrienol itself, such as by hydrogenating it and converting it into the corresponding tocopherol.

The present invention has been carried out through various studies on the effective use of such unused compounds, and the present invention has been completed after discovering that tocotrienols can be used as antitumor agents.

In the present invention, when tocotrienols are used as antitumor agents, they can be applied to tumors in various forms such as capsules, microcapsules, suspensions, solutions, emulsions, and injections. .

These various formulations contain commonly used excipients.

Binders, fillers, surfactants, dispersants, buffers.

It can be manufactured by conventional methods using preservatives, solubilizing agents, solvents, etc.

Next, the antitumor activity of the active ingredient according to the present invention will be explained in detail with reference to Examples.

Example α-Tocotrienol separated and concentrated from the deodorized distillate or the deodorized deoxidized distillate separated in the refining process of vegetable oils and fats was added to physiological saline containing about 10% each of methanol and a surfactant (Tveen 80). The dissolved material was used as a drug.

The main physical properties of α-tocotrienol are as follows.

(2) Molecular weight 424 (3) Main mass fragment m/z of mass spectrometry 424
, 205, 165 The tumor used in this example was IMC rutinoma, CDF, mouse as host, i.
The cells that had been passaged by p transplantation were used.

CDF, 6-week-old male mice were used in each dose group, with 5 mice each. Tumor cells obtained from mouse ascites were prepared with MEN medium and transplanted ip into host mice at I x 10' cells/mouse.

The day when the tumor was transplanted was Day O, and drug administration (IP) was started from the next day, and the administration schedule was Day 5.
', Day7-109. Follow, a treatment, wa7e.

Antitumor activity was determined from the following survival rate ILS during 60 days after the start of treatment.

(T/C-1)xtoo=rLS%T: Mean survival days (MSD) of treatment group C: Mean survival days (MSD) of control group The results of the treatment are shown in Table-1.

Table 1 As can be seen from the above test results, α-tocotrienol has a total dose of 100H/kg x 10
showed a therapeutic effect on IMC rutinoma *T
otal dose 25m eel kg x 10, 85
On day 040, IL5150%, the effect was somewhat low.

Next, specific formulation examples of the present invention will be given, but the present invention is not limited to the following examples.

Formulation example [injection] α-tocotrienol 5g benzyl alcohol 1g vegetable oil
Appropriate amount of vegetable oil may be commonly used such as olive oil or peanut oil, or may be ethyl oleate or isobutyl oleate. Make the total volume of vegetable oil to 100 cc, dispense one bottle of solution into an ampoule using aseptic operation, and fuse and seal. .

Patent applicant: Director of the Agency of Industrial Science and Technology Todoroki Written amendment to the procedure (spontaneous) 60 Kagiken No. 828 1, Indication of case: 1985 Patent Application No. 4'9894
No. 2, Title of the invention Anti-@ Boat agent 3, Patent applicant related to the amended case Address 1-3-1 Kasumigaseki, Chiyoda-ku, Tokyo Name (114) Tatsu Todoroki, Director of the Agency of Industrial Science and Technology (Shipping date Showa) (Year, Month, Day) & Contents of Amendment The following amendments have been made to the specification of this application.

(1) "Separated and concentrated 000." in lines 7 and 8 of page 2 is replaced with "separated and concentrated natural products" and Hevea.
Any natural product obtained from plant resources such as Hevia brasiliensis latex may be used."

(2) Correct "6-week-old male" on page 4, line 11 to "6-week-old female."

Claims (2)

[Claims] (1) The active ingredient is tocotrienols represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1, R^2, R^3 mean hydrogen atoms or methyl groups) An antitumor agent characterized by: (2) The active ingredient is 3,4-dihydro-2,5,7,8
-tetramethyl-2-(4,8,12-trimethyl-3
, 7,11-tridecatrienyl)-2H-1-benzopyranol-6.