JPS6157283B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an ulcer therapeutic agent containing as an active ingredient an isoprenoid alcohol represented by the general formula ROH () (wherein R represents a solanesyl group, a decaprenyl group, an isodecaprenyl group, or a saturated decaprenyl group). Conventionally, it has been used as a therapeutic agent for gastric ulcers, duodenal ulcers, etc.
For example, gefalnate [trade name of Sumitomo Chemical Industries, Ltd.;
Geffanil, chemical name; 3,7-dimethyl-2.
6-octadienyl 5,9,13-trimethyl-
Although many compounds having anti-ulcer properties have been reported, such as [4,8,12 tetratecatrienoate], nothing groundbreaking has yet been found. The inventors of the present invention have conducted various studies in order to find a more excellent ulcer treatment agent, and as a result, have discovered a group of extremely effective compounds. Solanesol, decaprenol and isodecaprenol represented by the above general formula () according to the present invention can be produced by known methods, but saturated decaprenol, which is a new compound, can be produced according to the following reaction formula. be able to. That is, saturated decaprenol represented by formula () can be obtained by completely reducing decaprenol represented by formula () with hydrogen in the presence of a catalyst such as Raney nickel in an alcohol solvent. The obtained saturated decaprenol can be purified by column chromatography or the like, if necessary. Next, the physiological activities of the active ingredients according to the present invention are shown below. The assay method for reserpine ulcers is Arch.Int.Pharmacodym.Ther. 147 , 113
(1964), and acetic acid ulcers were generated in rats according to the method described in Jap.J.Pharmac., 19 , 418 (1969), and the test compound was administered. The effect was measured. (i) Resepin ulcer After fasting for 24 hours in male SD rats (6 rats per group, weighing 150-200 g), the test compound was administered at 100 mg/Kg.
is administered orally, and 30 minutes later, reserpine 15 mg/Kg is injected intraperitoneally. 18 hours after administration, the rats are killed with chloroform, the stomach is removed, and the area of the ulcer is measured. The cure rate was determined using reserpine 15 mg/day as a control.
Kg was calculated using the following formula from the ulcer area of the rat group injected intraperitoneally. Curing rate = Control value - Test value / Control value x 100 (%) Next, the test results are shown in Table 1 below.

[Table] Display ± ＋ ＋＋ ＋＋＋
(ii) Acetic acid ulcer The stomachs of six male SD rats weighing 150 to 200 g per group are pulled out under ether anesthesia, and 0.05 ml of a 15% aqueous acetic acid solution is injected subserosa while being careful to avoid blood vessels. After injection, 100 mg/Kg of the test compound is orally administered for 14 days, and on the 14th day, the rats are killed with chloroform, the stomachs are removed, and the ulcer area is measured. The healing rate was determined by measuring a control group to which no test compound was administered, and using the formula used in the reserpine ulcer test. Next, the test results are shown in Table 2 below.

[Table] Display ± ＋ ＋＋ ＋＋＋

【table】

[Table] As is clear from the above test results, it can be seen that the active ingredient according to the present invention has an extremely excellent anti-ulcer effect. Furthermore, the compounds of the present invention have excellent effects not only on reserpine ulcers and acetic acid ulcers, but also on various other types of ulcers. Furthermore, the acute toxicity in mice of intraperitoneal administration of the ester, which is the active ingredient of the present invention, is extremely low as shown in Tables 1 and 2. The active ingredient compound of the present invention is administered by intravenous injection, subcutaneous injection, intramuscular injection, orally, and oral administration and intramuscular injection are particularly preferred. The dosage of the active ingredient compound is 1 day when used for the treatment of adults.
A range of 100 to 1000 mg, particularly 200 to 300 mg, is preferred. When the active ingredient of the present invention is orally administered, it may be administered in the form of tablets, granules, or powders, and in particular, granules and powders can be made into unit dosage forms in the form of capsules, if necessary. These solid preparations for oral administration contain commonly used excipients, such as silicic anhydride, magnesium aluminate metasilicate, synthetic aluminum silicate, lactose, sugar, corn and starch, microcrystalline cellulose, hydroxypropyl-
starch, or glycine, binders such as gum arabic, gelatin, tragacanth, hydroxypropylcellulose or porvinylpyrrolidone,
It may contain lubricants such as magnesium stearate, talc or silica, disintegrants such as potato starch, calcium carboxymethylcellulose or wetting agents such as polyethylene glycol, sorbitan monooleate, polyoxyethylene hydrogenated castor oil, sodium laurile sulfate, and the like. The tablets may be coated according to conventional methods. Oral liquid preparations are aqueous or oily emulsion solutions,
It may be made into a syrup or the like, or it may be a dry product which can be redissolved in a suitable vehicle before use. Such liquid preparations contain commonly used additives such as emulsifying aids such as sorbitol syrup, methylcellulose, gelatin, hydroxyethylcellulose, etc., and emulsifying agents such as lecithin, sorbitan monooleate, polyoxyethylene hydrogenated castor oil, etc. A non-aqueous vehicle such as fractionated coconut oil, almond oil, peanut oil, a preservative such as methyl p-hydroxybenzoate, propyl p-hydroxybenzoate or sorbic acid may be added. Furthermore, these preparations for oral administration may contain preservatives, stabilizers, etc., if necessary. Next, when using this compound as an injection, it may be in the form of an oil solution, emulsion, or aqueous solution.
These solvents may contain commonly used emulsifiers, stabilizers, etc. These compositions can contain the compound at one time depending on the method of administration.
% or more, preferably 5% to 50%. Next, specific production examples and formulation examples of the present invention will be given, but the present invention is not limited to the following examples. Production example 1 Saturated decaprenol Dissolve 26 g of decaprenol in 300 ml of ethanol. To this, Raney nickel catalyst (W-1) 1.5
Add 10 ml of an ethanol suspension of 50 g to the mixture and shake in an autoclave at 90 kg/cm ² of hydrogen at 80° C. for 10 hours.
After separating the catalyst, it is concentrated. 26 g of the residue was purified by silica gel column chromatography to obtain 7.2 g of saturated decaprenol. The physical properties of this material are as follows. IRν _nax cm ^-1 ; 3350 (-OH) NMRδ ^CDCl3 _TMS 3.70 (CH ₂ O) 1.20 (CH ₂ ) 0
.85
(CH ₃ ) Elemental analysis (C ₅₀ H ₁₀₂ O) Calculated value H: 14.29% C: 83.48% Actual value H: 14.23% C: 83.38% Formulation example 1 Hard capsule for oral use 25 g of decaprenol and 7.5 g of polyoxyethylene castor oil g in acetone and then mixed with 25 g of silicic anhydride. After evaporating the acetone, add 5 g of carboxymethyl cellulose calcium.
and 5 g of corn starch, 7.5 g of hydroxypropyl cellulose and 20 g of microcrystalline cellulose.
Mix, add 30ml of water, knead, and granulate.
This was granulated using a No. 24 mesh (BS) granulator equipped with a screen (Eck pelleter, manufactured by Fuji Paudal Co., Ltd.). The granules are dried to a moisture content of 5% or less.
No.16 Metsuyu (BS) sieve. Next, these particles are made into one capsule using a capsule filling machine.
Filled with 190mg. Formulation example 2 Oral soft capsules Solanesol 50g and fractionated coconut oil 130g
g to make a homogeneous solution. Separately gelatin 93
A gelatin solution was prepared with a composition of g, glycerin 19 g, D-sorbitol 10 g, ethyl paraoxybenzoate 0.4 g, propyl paraoxybenzoate 0.2 g and titanium oxide 0.4 g, and this was used as a capsule coating agent by manual plate punching. Contents 180mg
A soft capsule containing the following was produced. Formulation Example 3 Injection 5 g of saturated decaprenol, an appropriate amount of peanut oil and 1 g of benzyl alcohol are mixed, and the total amount is made up to 100 c.c. using peanut oil. Dispense 1 c.c. of this solution into ampoules using aseptic technique and seal.

Claims (1)

[Claims] 1. An ulcer treatment characterized by containing an isoprenoid alcohol represented by the general formula ROH (wherein R represents a solanesyl group, a decaprenyl group, an isodecaprenyl group, or a saturated decaprenyl group) as an active ingredient. agent.