JPS6212716A - Carcinostatic agent - Google Patents

Abstract

PURPOSE:To provide a carcinostatic agent containing a specific fatty acid as an active component and exhibiting excellent carcinostatic effect against almost all kinds of cancers without causing side effects. CONSTITUTION:The objective carcinostatic agent can be produced by using a fatty acid of formula RCOOH (RCO is 8-22C fatty acid residue). When the fatty acid is saturated fatty acid (e.g. caprylic acid, capric acid, undecanoic acid, etc.), a 11-21C acid is effective, and when it is an unsaturated fatty acid (e.g. undecenoic acid, linoleic acid, oleic acid, etc.), a 16-18C acid is effective. The fatty acid of the present invention can be administered in arbitrary form such as emulsion, tablet, solution, etc.

Description

[Detailed description of the invention] [Industrial application fields] The present invention relates to an anticancer agent containing fatty acids as an active ingredient.

[Prior art] Recently, anticancer drugs include alkylating agents that inhibit the metabolism of cancer cells (Metabolism 17 1534-15441980) and competitive inhibitors of nucleic acid synthesis (Cancer and Chemotherapy 1 1029).
-1086 1983).

Antibiotics and plant alkaloids (Yamamura Yu-1, written by Takashi Hayashimura,
Various drugs such as [Cancer J 251-270 published by Kyoritsusha Co., Ltd.] have been proposed for use as anticancer agents.

In addition, extracts extracted from plants and animals have been recognized to have anticancer properties and have been made into various formulations.

[Problems to be solved by the invention] As mentioned above, many anti-cancer drugs have been formulated or proposed, but none of the anti-cancer drugs and proposals have anti-cancer properties, but have no side effects. However, those with no observed side effects had weak anticancer performance.

[Means for Solving the Problems] As a result of research conducted by the present inventors in search of an anticancer drug that does not exhibit side effects, the general formula RCOOH is shown, and RCO has 8 carbon atoms.
The present invention was completed based on the knowledge that products containing fatty acids, which are fatty acid residues of ~22, as active ingredients have anticancer properties without exhibiting side effects.

That is, one gist of the present invention is represented by the general formula RCOOH,
It is an anticancer drug whose active ingredient is a fatty acid in which RCO is a fatty acid residue having 8 to 22 carbon atoms.

The fatty acid may be either a saturated fatty acid or an unsaturated fatty acid as long as it has 8 to 22 carbon atoms, but when it is a saturated fatty acid, it is preferable that the carbon number is 11 to 21, and when it is an unsaturated fatty acid, it is preferably a saturated fatty acid or an unsaturated fatty acid. It is effective that the number of carbon atoms is 16 to 18.

The fatty acids used in the present invention are obtained by decomposing natural fats and oils, while fatty acids with an odd number of carbon atoms are obtained by synthesis.

Examples of saturated fatty acids are caprylic acid, capric acid, undecanoic acid, lauric acid, and tridecanoic acid.

These include myristic acid, pentadecanoic acid, palmitic acid, nurgalic acid, stearic acid, nonadecanoic acid, arachidic acid, and behenic acid.

Examples of unsaturated fatty acids include undecenoic acid, palmitooleic acid, palmitoelaidic acid, petroselic acid, oleic acid, elaidic acid, cis-vaccenic acid, transvaccenic acid, erucic acid, brassic acid, linoleic acid,
Examples include linolelaidic acid and linoleic acid.

The above fatty acids may be used alone or in combination of two or more thereof.

The fatty acids used in the present invention can be administered directly in any form such as emulsion, tablet, or solution.

Administration methods include oral and parenteral administration, but direct administration to the affected area is preferred.

The dosage varies depending on the type of target cancer, symptoms, administration method, etc., but is in the range of 1 to 200 mg/kg/day.

[Effects of the Invention] The anticancer agent of the present invention has an excellent anticancer effect on almost all types of cancer, and since it is a normal fatty acid, it does not cause any side effects on living organisms.

[Example] The present invention will be described with reference to examples.

Examples were carried out in the following manner.

(1) Method for measuring anticancer activity (a) Preparation method of fatty acid emulsion for administration Place 200 mg of the fatty acid to be tested in a test tube, and
Add 5mfi of liquid and apply ultrasonic waves for 30 seconds in an 80℃ water bath.
5 mn of solution B is added to the obtained mixed solution to prepare a drug.

Liquid A: Hydrogenated castor oil (manufactured by Nikko Chemical Co., Ltd.; trade name HCO-60) is dissolved in distilled water to a concentration of 0.4% by weight.Liquid B: Hydrogenated castor oil is 0.4% by weight. (b) Selection of mice and method of administration The number of mice used per group was 5 to 10. In addition, the type of mouse used in the experiment is clearly stated in each example.

(c) Method of administering the drug 20 m of the fatty acid prepared by method (a) into the abdominal cavity as usual.
The drug was administered at 0 and 25 mQ/day/mouse once daily for 5 consecutive days.

Example 1 Caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, and lauric acid were prepared according to the above method (a) for preparing a fatty acid emulsion.

tridecanoic acid, myristic acid, pentadecanoic acid.

For palmitic acid, margaric acid, stearic acid, nonadecanoic acid, arachidic acid, heneicoic acid, and behenic acid, each administered fatty acid emulsion was transferred into the ascites of Ehrlich ascites carcinoma into the peritoneal cavity at a density of 2 x 10' cells/mouse. A group of mice administered at a level of 0.25 mfi/day/mouse (fatty acid amount 5 mg/day/mouse) using method (c) and its 174 dose (fatty acid amount 1.25 mg/day/mouse)
The efficacy rate of this drug was determined by directly injecting two doses into the cavity of mice (mice), and the relationship with the carbon number of the fatty acid is shown in Figure 1.

In addition, the effectiveness rate is calculated from the formula (1) below by calculating the total number of effective days.
1tt, (II), $7), 6. *9Jym*
*ct (m) t,,h,IHB l:・.
(Efficacy rate = Effective population rate x Total effective days・
・・・・・・・・・(1).

Total effective number of days = Ox [(Number of days that effective individuals survived) i.

−3°′“0-/l/″%″″゛°“)] °(“)
i. Effective population rate = Effective number of individuals/Number of experimental individuals...(■) (As is clear from Figure 1, saturated fatty acids are anticancer. It was found that saturated fatty acids with an odd number of carbon atoms of 13.15 and 21 have a significant anticancer effect.

Example 2 An unsaturated fatty acid, undecanoic acid, was used instead of the saturated fatty acid used in Example 1 (since the number of carbon atoms in the fatty acid residue is 11 and the document number is No. 1, it is abbreviated as 111 in Figure 2). do.

(hereinafter the same) palmitooleic acid (16”), palmitoic acid (163), petroselinic acid (18’)
, oleic acid (is'), elaidic acid (18'), cis-vaccenic acid (18'), transvaccenic acid (18@)
, linolelaidic acid (18'), linoleic acid (18')
”), linoleic acid (18”), erucic acid (2212
) and brassicic acid (2213) were used under the same conditions as in Example 1 to prepare respective fatty acid emulsions. The anticancer drug effect of each of the administered fatty acids was determined according to Example 1, and the results are shown in FIG.

As is clear from this result, the anticancer agent containing unsaturated fatty acids as an active ingredient had the highest effect when the number of carbon atoms in the fatty acid was around 18.

Example 3 Effect of intraperitoneal administration of fatty acids on various cancers Each of the cancer cells shown in Table 1 was transplanted into the peritoneal cavity of the mice shown in Table 1 according to Example 1. The anticancer activity of the indicated fatty acids was determined.

The results are shown in Table 1. As a result, the fatty acid was S-180 (
Sarcomas such as sarcoma-180) and Ehrlich (Ehrlich's sarcoma) and MM-46 (breast cancer) have been found to have significant anticancer effects.

Also, although it was generally not very effective against leukemia, MLB
- It was found that it has excellent effects on MN (B cell lymphoma).

Example 4 Change in administration method Cancer cells shown in Table-1; The anticancer effects of each were determined and the obtained results are shown in Table 2.The results showed that there is no effect unless directly administered intra-abdominally.

Table 2 Effect of administration method (mouse used MM-46) Example 5 Each of the types of solid tumors shown in Table 3 was administered to each of the mice shown in Table 3 in combinations shown in Table 3. 2×10s of each cancer cell was subcutaneously transplanted. Next, the same fatty acid drug used in Example 4 was administered to each of the mice transplanted with the solid tumor by direct local subcutaneous injection once/day for 5 consecutive days to determine the anticancer effect.
The results obtained are shown in Table 3.

As is clear from Table 3, fatty acids were found to have a significant anticancer effect on solid cancers.

Table 3 Effect of fatty acids on solid tumors Example 6 Effect of treatment start date after cancer cell transplantation The number of days shown in Table 4 after transplantation of breast cancer cells (MM-46) 2xlO' into the abdominal cavity of mice Each mouse was then treated with a subcutaneous injection of fatty acids. Treatment was performed once a day, and Table 4 shows the relationship between the number of days left after cancer cell transplantation and survival rate.

Table 4: Influence of the start date of treatment after cancer cell transplantation This result shows that not only can patients be treated 0, 1, 2.3 days after cancer cell transplantation, but even if they do not receive any treatment for 4 days and then start treatment for the first time 4 days later. The terrifying result of complete recovery was obtained.

[Brief explanation of the drawing]

Figure 1 shows the relationship between the number of carbon atoms in saturated fatty acids and the anticancer rate of these saturated fatty acids, and Figure 2 shows the number of carbon atoms in unsaturated fatty acids and the anticancer rate of these unsaturated fatty acids.

Claims (1)

[Claims] (1) An anticancer agent containing a fatty acid represented by the general formula RCOOH (RCO represents a fatty acid residue having 8 to 22 carbon atoms) as an active ingredient.