JPS6032713A - Antimutagenic agent - Google Patents

Abstract

PURPOSE:To provide the titled agent containing polyoxyethylene sorbitan monolaurate as an active component. CONSTITUTION:An antimutagenic agent is prepared by using the compound of formula (10<=x+y+z<=30) (e.g. a compound wherein x+y+z is 20, ''Tween 20'', etc.) as an active component. The compound of formula is a safe drug having an LD50 of 725,000mg/kg(mouse). It is administered preferably orally in the form of tablet, capsule, granule, syrup, etc. Dose: preferably 0.01-1,000mg/kg dialy in 1-several divided doses. The agent is effective for the prevention and remedy of various diseases caused by mutagenicity, such as cancer.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an antimutagenic agent containing polyoxyethylene sorbitan monolaurate as an active ingredient.

Polyoxyethylene sorbitan monolaurate was previously known only as a nonionic surfactant, and its physiologically active effects were completely unknown.

The present inventors have conducted extensive studies on the physiological activity of this polyoxyethylene sorbitan monolaurate, and have discovered that this compound exhibits an extremely excellent antimutagenic effect, and have completed the present invention.

Therefore, the present invention provides the following formula (1), 0- (CH, -C-0)2H (1) (wherein, X + y + Z has a total of 10 to 30
The present invention provides an antimutagenic agent containing polyoxyethylene sorbitan monolaurate represented by the following (indicating a positive number) as an active ingredient.

The polyoxyethylene sorbitan monolaurate used in the present invention is a compound that can be prepared by adding ethylene oxide to sorbitan monolaurate by a known method, and is widely used as a nonionic implantation active agent.
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As a representative compound, a compound commercially available under the trade name "Tween 20" (in formula (I), X + y + z =
20), and its physical properties are as follows9.

) ILB value: 16.7 Acid value: 0.4-1.1 Saponification value = 45-47 Water #R group value = 105-112 Properties: Pale yellow oily liquid Dissolution a: Water, methanol, ethanol, acetic acid Soluble in ethyl. Insoluble in mineral oil.

Next, the results of testing the antimutagenic effect of Tween 20 will be shown.

(1) Effect on mutations induced by l-ethyl-2-nitro-3-nitronoguanidine (ENNG), Salmonella enterica typhimurium (8 μlmonella
yphimurium) TAl 00 1 culture (cultured with shaking at 37°C for 15 to 16 hours) was centrifuged to remove other components, washed with physiological saline, and further diluted with physiological saline. A sample bacterial solution was prepared by adding 4 d of water. (2-6×10”/me).

100 μt of ENNG solution (equivalent to 5 μ2), 700 μt of phosphate buffer (I) H6,8), and 200 μt of bacterial solution were placed in a test tube, and reacted at 37°C for 20 minutes to obtain a reaction solution.
After appropriately diluting 100 μt of the solution, the number of viable bacteria was measured.

Next, soft agar 2- containing histidine and biotino was added to the reaction solution from which the supernatant was removed by centrifugation, and the mixture was layered on a minimum glucose agar medium.

Thereafter, soft agar containing various concentrations of Tween 20 was further layered, and the number of colonies grown after culturing at 37°C was measured. The same procedure was used to measure the number of viable bacteria, and the influence of Tween 20 was examined. The results are shown in Table 1. The mutation frequency was calculated by dividing the number of colonies generated by mutation by the number of viable bacteria.

Table 1 ($1) Effect on mutations induced by 2-nitrofluorene (2NF) Studies were carried out using the same procedure as (2NF) using 2NFC (5 μv) as the mutagen and Salmonella typhimurium TA98 as the test bacterium. The results (4) are shown in Table 2.

Table 2 As shown above (polyoxyethylene sorbitan monolaurate exhibits an extremely excellent preventive effect against mutagenic substances).

Moreover, the toxicity of polyoxyethylene sorbitan monolaurate is LDso: 725000119/Kf (mouse), making it a safe drug.

Next, the administration method and dosage when administering the anti-mutation principle of the present invention to the human body will be explained.

Administration can be carried out in various ways, but oral administration in the form of tablets, capsules, granules, syrups, etc. is preferred. The appropriate oral dosage for adults is usually 0.01 to 1000 ■/Kr, and it is preferable to take this once a day or in divided doses. , can be manufactured according to conventional manufacturing methods. Namely, excipients such as starch, lactose and mannitol, binders such as sodium carboxymethyl cellulose and hydroxypropyl cellulose, disintegrants such as crystalline cellulose and carboxymethyl cellulose calcicum, and talc.

Tablets, capsules, and granules can be produced by appropriately combining lubricants such as magnesium stearate, flowability improvers such as light anhydrous silica, and the like.

The antimutagenic agent of the present invention obtained as described above is useful for the prevention and treatment of various diseases based on mutations, such as cancer. In the field of biochemistry, when it is necessary to suppress bacterial mutations,
For example, it can be used for culturing bacteria, biochemical analysis, etc.

Next, examples of formulations will be given and explained.

(7) Total amount 10001v Example 1 (tablet) One tablet with the following ingredients and quantities was manufactured according to a conventional method.

Polyoxyethylene sorbitan monolaure) 100
Hf ((I) in formula
With 1v stearin-based magnesium and 2q lactose, make total i 350 cape.

Example 2 (granules) Granules with the following ingredients and amounts were manufactured according to a conventional method.

Polyoxyethylene sorbitan monolaure) 100
11v (in formula (1), x + y + z = 20) Light silicic anhydride 100■ Mannit 65019 Starch 135111F Polyvinylpyrrolidone 15■ (8) Applicant Nisnis Pharmaceutical Co., Ltd.

Claims (1)

[Scope of Claims] t Polyoxyethylene sorbitan represented by the following formula (1) % formula %) (in the formula, X*Y+" represents the sum of these or a positive number from 10 to 30) An antimutagenic agent containing monolaurate as an active ingredient.