JPS5962523A - Antitumor agent - Google Patents

Abstract

PURPOSE:To provide an antitumor agent having higher activity than higher fatty acids such as palmitic acid, oleic acid, etc., by using palmitoleic acid or its non- toxic salt as an active component. CONSTITUTION:An antitumor agent is obtained by using palmitoleic acid or its non-toxic salt (e.g. alkali metal salt, ammonium salt, etc.) as an active component. Palmitoleic acid has higher antitumor activity than saturated higher fatty acids (e.g. palmitic acid, stearic acid, etc.) and unsaturated higher fatty acids (oleic acid, linoleic acid, etc.). The agent can be administered in the form of tablet, liquid, injection, etc. Dose: preferably 10-100mg of palmitoleic acid per kg daily.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to antitumor agents. More specifically, the present invention is an antitumor agent containing palmitoleic acid or its non-sterile group as an active ingredient.

It has been known that saturated primary higher fatty acids such as palmitic acid and stearic acid, and unsaturated higher fatty acids such as oleic acid, lyluic acid, and linoleic acid possess antitumor activity.

The present inventors continued their research into antitumor substances and completed the present invention after learning that palmitooleic acid has much stronger antitumor activity than the above-mentioned higher fatty acids.

The antitumor agent provided by the present invention is characterized in that it contains palmitoleic acid or a nontoxic salt thereof as an active ingredient.

The above non-toxic salts include alkali metal salts such as sodium salts and potassium salts, carunium salts, magnesium salts,
Alkalies such as aluminum salts; l:'-.

Metal salts, ammonium salts, salts with known non-toxic organic amines, salts with basic amino acids such as orthin, lysine, arginine, etc. are laudable.

The antitumor agent of the present invention is usually used in the form of a general pharmaceutical preparation. The preparations are prepared using commonly used diluents or excipients such as fillers, binders, wetting agents, disintegrants, surfactants, lubricants, etc., and are available in various forms depending on the therapeutic purpose. You can choose.

Examples include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, and injections (solutions, suspensions, etc.). When forming tablets, a wide variety of conventionally known substances can be used as carriers, such as excipients such as lactose, sucrose, glucose, starch, calcium carbonate, kaolin, and crystalline cellulose, water, ethanol, simple syrup, glucose solution, Starch liquid, gelatin solution, carpoquin methylcellulose, shellac, methylcellulose, calcium phosphate, binder such as polyvinylpyrrolidone, dry starch, sodium alginate, agar powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid ester, lauryl Disintegrants such as sodium sulfate, stearic acid monoglyceride, starch, and lactose; disintegration inhibitors such as white sugar, cocoa butter, and hydrogenated oil; absorption enhancers such as fourth-stage ammonium salts, and sodium lauryl sulfate; moisturizers such as glycerin and starch; agent, starch, lactose, kaolin,
Examples include adsorbents such as bentonite and colloidal silicic acid, and lubricants such as talc, magnesium stearate, and polyethylene/glycol. These tablets can be, if necessary, provided with a conventional coating, such as sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, double tablets, or multilayer tablets. When prepared as injections, solutions and suspensions are preferably sterile and isotonic with blood. When preparing these solutions, emulsions, and suspensions, commonly used diluents can be used, such as water, ethanol, propene gelicol,
Glycerin, ethoxylated instearyl alcohol, polyoxylated instearyl alcohol, polyoxyethylene sorbitan fatty acid ester, etc. may be mentioned. It may be included in the preparation, or conventional solubilizing agents, buffering agents, soothing agents, etc. may be added.

The method of administering the antitumor agent of the present invention is not particularly limited, and it is administered in a manner depending on various formulation forms, patient's age, sex, degree of disease, etc. For example, tablets, emulsions, solutions, suspensions,
Emulsions, granules and capsules are administered orally. In the case of an injection, it is administered intravenously alone or mixed with a normal replacement fluid, and if necessary, it is administered alone intramuscularly, subcutaneously, or intraperitoneally. Suppositories are administered rectally.

The dosage of the antitumor agent of the present invention is appropriately selected depending on the usage, patient's age, sex, body weight, degree of disease, etc., but the amount of palmitoleic acid, which is an active ingredient, is usually 1 g per body weight per day. The amount is preferably about 10 to 100 mg per serving. It is also preferred that the dosage unit form contains 50 to 500 mp of the active ingredient.

Next, the acute toxicity and antitumor activity of palmitoleic acid, which is the active ingredient of the present invention, will be described.

[1] Acute toxicity LD 50 => 300 my/Icg' (-rus, intraperitoneal administration) [2] Antitumor activity (1) Test drug Invention group; palmitoleic acid at 750 m9/m for each
1! , 375 mg/me and 187.5 my/
m/! A solution containing 0.2% Twin 80 and 0.15M salt dissolved in water.

Comparison group: 750 m9/ml and 375 m of oleic acid, respectively.
0 to the concentration of 9/me and 187.5 m97 me
．． A solution containing 2% Twin 80 in 0.15M saline.

Control group: 0.15M saline containing 0.2% Twin 80 without addition of palmitooleic acid or oleic acid (2) Test method ■ 2 x 106 mice per group of 10 female CR mice Ehrlich ascites carcinoma cells were inoculated into the peritoneal cavity, and 24 hours later,
Test drug Q, 2ml! was administered intraperitoneally for 10 days, and 60
Observed for days.

(3) Test results are as shown in Table 1. All cases in the non-administered control group died within 16 to 19 days, and oleic acid in the comparison group was found to have antitumor activity, but palmitic acid of the present invention Oleic acid has been found to have much stronger antitumor activity than oleic acid, 75
In the my/ky/day administration group, all cases died after 60 days when oleic acid was administered, but 5 out of 10 cases survived when palmitoleic acid was administered, indicating that the antitumor agent of the present invention is excellent. A life-prolonging effect was observed.

Table 1 150 31.33±&99 184.2 2/
10 shots 75 42.29±4.78 24
8.6 5/10 light 37.5 2
9.47±8.14 178.3 0/10 group control group (0) 17.01±0.78 100
0/10 ratio 15° 26・25±&1314
4.2 2/10 comparison 75 28.63±8
・46 129.8 6710 group 37.5
20.52±1.11 1.12・7
°/10 control group (0) 18.21±0.9
2 100 0/10T Average survival days of drug administration group f't C Average survival days of control subjects Next, the present invention will be specifically explained with reference to Examples.

Example 1 Capsule Palmitooleic acid sodium salt 12.59 Silosaccharide fatty acid ester (manufactured by Daiichi Kogyo Seiyaku Co., Ltd., DK Ester F-1
60) 1.25f Magnesium Stearate 250 m9 Lactose
111 The above ingredients were thoroughly mixed and filled into No. 1 capsules of 250 m9 each to obtain 100 capsules.

Example 2 Soft capsule Palmitoleic acid 251 Silosaccharide fatty acid ester 2.52 Linole salad oil
22.59 Thoroughly mix the above ingredients,
0rn9 each was filled into soft capsules (manufactured by Tokai Capsule Co., Ltd.) to obtain 100 soft capsules.

Example 3 Tablet Sodium Palmitoleate 12.5F Norosaccharide Fatty Acid Ester L25t Magnesium Stearate 250Wui Lactose
11f Mix the above ingredients thoroughly,
m9 rotary tablet press (manufactured by Kikusui Seisakusho Co., Ltd., R'I'
-F-9-2) to obtain 100 tablets.

Example 4 Suppositories Finely divided palmitooleic acid 252 and D-mannitol 152 were heated to 40°C and Lytepsol H-1 was prepared.
5 and thoroughly mixed to obtain 1001, which was further uniformly and well dispersed, and molded into a suppository container to obtain a 1f suppository.

Example 5 injection

Claims (1)

[Claims] 1) An antitumor agent containing palmitoleic acid or a nontoxic salt thereof as an active ingredient.