JPH0329766B2 - - Google Patents

Description

[Detailed description of the invention]

The present application relates to an antitumor agent, and specifically to an antitumor agent containing a substance represented by the general formula (). The present inventors, in basic research in the development of antitumor agents, discovered that a substance represented by the general formula () has an antitumor effect on tumors, and completed the present application. The substances used in this application have the general formula (): (However, in the formula, It is a salicylic acid derivative (hereinafter referred to as the present substance) represented by O-N(CH ₃ -) ₃ -(CH ₂ ) ₂ -OH R ₂ =COCH ₃ , H). This substance is a medical drug listed in the Japanese Pharmaceutical Formulary No. 7.
Also included are substances having known anti-inflammatory effects, such as those described in Yakugyo Jihosha, 1983, p. 14, pp. 306-307. Its safety has also been fully confirmed. This substance is effective against animal or human tumors. The effectiveness of this substance was determined by confirming its effectiveness in reducing the number of tumor cells, suppressing tumor growth, etc. When this substance is used as an antitumor agent, it can be used in a form convenient for obtaining medicinal effects depending on the symptoms. It may be used alone or in combination with pharmaceutically acceptable diluents and other agents. The materials can be presented in dosage unit form containing an effective dosage of the active ingredient. The forms for oral use include powders, fine granules, granules, tablets, buffered tablets, sugar-coated tablets, capsules, syrups, pills, suspensions, solutions, and emulsions. For parenteral use, it can be in the form of ampoules or bottles as injection solutions. Suppositories and ointments are also available. The diluent may be solid, liquid, or semi-solid, and examples include the following. i.e. excipients, fillers, binders, wetting agents, disintegrants, surfactants, lubricants,
These include dispersants, buffers, fragrances, preservatives, solubilizing agents, and solvents. In the compositions used in the present invention, the active ingredient is generally from 0.01 to 100 wt.%, preferably from 0.05 to 100% by weight.
Contains 80wt.%. The substance is administered orally or parenterally to humans and animals. Oral administration includes sublingual administration. Parenteral administration includes injection administration (eg, subcutaneous, intramuscular, intravenous injection, infusion), rectal administration, and the like. Alternatively, it may be applied by coating. This substance is affected by whether the subject is an animal or a human, as well as by age, individual differences, medical conditions, etc. Therefore, in some cases, doses outside the range shown below may be administered; however, in general, when administering to humans, The dosage of this substance is 0.1-1000mg/Kg per day, preferably 0.5-1000mg/Kg
It is 500mg/Kg. It may be administered in 2 to 4 divided doses. Example 1 Antitumor effect on Sarcoma-180 1 x 10 ⁶ Sarcoma-180 cells were subcutaneously transplanted into the lower armpit of ICR-JCL mice, and 24 hours after transplantation,
The substance dissolved or suspended in 0.5% CMC solution 10 times every other day.

[Formula] R ₂ = COCH ₃ or R ₁ = O-N (CH ₃ ) ₃ - (CH ₂ ) ₂ -OH, R ₂ = H)
were orally administered at 1000mg/Kg and 800mg/Kg, respectively.
Tumor nodules were excised on the 25th day after transplantation, and the growth inhibition rate (IR%) was calculated using the following formula. (1-T/C)×100=IR (%) T: Average tumor weight of administration group C: Average tumor weight of control group The average value was also calculated using 10 mice per group.
The growth inhibition rates were 42.5% and 38.8%, respectively.
In addition, the LD ₅₀ of this substance is 5.0g/orally administered to mice.
Kg, the latter being 2.69g/Kg. Example 2 Antitumor effect against Ehrlich cancer 2 × 10 ⁶ Ehrlich cancer cells were intraperitoneally transplanted into 5-week-old ICR-JCL mice, and 24 hours after transplantation, they were inoculated 14 times daily in 0.5% CMC solution. This substance dissolved or suspended in

[Formula] R ₂ = COCH ₃ or R ₁ = O-N (CH ₃ ) ₃ - (CH ₂ ) ₂ -OH, R ₂ =
H) was orally administered at 1000 mg/Kg and 800 mg/Kg, respectively. The animals were sacrificed on the 14th day after transplantation, and ascites fluid was collected after the sacrifice to measure the number of cancer cells in the ascites fluid. The average value was calculated for each group of 10 animals. The control group
The number of Ehrlich cancer cells in the ascites fluid was 18.3×10 ⁷ cells/ml, but the number of Ehrlich cancer cells in the ascites administration group was 12.3×10 ⁷ cells/ml, respectively.
ml, 12.0×10 ⁷ pieces/ml. Formulation example This substance (R ₁ = O-N(CH ₃ ) ₃ -(CH ₂ ) ₂ -OH,
Dissolve 2 g of R ₂ = H) in physiological saline to make 10 ml,
It was administered as an oral drug.

Claims (1)

[Claims] 1 General formula (): (However, in the formula, An antitumor agent characterized by containing a salicylic acid derivative represented by O-N( _CH3- ) _3- ( _CH2 ) ₂ - _OHR2 = _COCH3 ,H. The antitumor agent according to claim 1, which is the formula: 3. The antitumor agent according to claim 1, wherein _R1 =O-N( _CH3- ) _3- ( _CH2 ) ₂ -OH, _R2 =H.