JPH0930968A - Eye drop for treating glaucoma and ocular hypertension - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new hydrophilic preparation containing a salt or a monohydrate of 3-(1H-tetrazol-5-yl)oxanilic acid as an active ingredient, having excellent intraocular pressure lowing action and useful for glaucoma and ocular hypertension. SOLUTION: This eye drop contains a compound of the formula (X is an inorganic salt, an organic salt or a monohydrate) as an active ingredient. The monohydrate is preferably used as the active ingredient, because it is industrially advantageously obtained and readily soluble in water. As necessary, an isotonizing agent such as sodium chloride, a buffer such as boric acid, a stabilizer such as sodium edetate, a pH adjuster such as hydrochloric acid can be added to the preparation. The preparation is preferably formulated as an aqueous liquid preparation having about 3% concentration.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an eye drop for treating glaucoma and ocular hypertension. More specifically, the present invention provides 3- (1
The present invention relates to an ophthalmic solution for treating glaucoma and ocular hypertension, which contains H-tetrazol-5-yl) oxanic acid (MTCC) or a salt thereof and a monohydrate thereof as an active ingredient.

[0002]

[Prior Art] Expression

Embedded image

It is known that the compound represented by the formula; a salt thereof or a monohydrate thereof (hereinafter referred to as the present compound) is an excellent antiallergic agent. (JP-A 64-29312
No.) However, it is not known what action the present compound exerts on intraocular pressure.

[0004]

DISCLOSURE OF INVENTION Problems to be Solved by the Invention The present inventors have examined what kind of action the present compounds disclosed in the prior art have on the intraocular pressure, and as a result, they show an excellent intraocular pressure lowering action. It was found that the present compound is extremely effective in the treatment of glaucoma and ocular hypertension, and its efficacy is comparable to that of the currently marketed therapeutic agent for glaucoma [Tymoptol (registered trademark), Banyu Pharmaceutical Co., Ltd.]. Then, the present invention was completed.

[0005]

The compound used in the present invention can be produced based on the description in Japanese Patent Publication No. 5-79063 or in accordance therewith. Examples of the inorganic salt of the present compound include metal salts such as sodium, potassium, calcium and magnesium, and organic amine salts as organic salts. Further, the monohydrate is industrially advantageous in the production of the present compound, and is easily soluble in water, so that it is suitable for the present invention.

All of the compounds of the present invention are readily soluble in water, and it is possible to prepare an aqueous solution having a wide range of concentrations, and thus an aqueous solution having a wide range of application can be created. As the aqueous liquid agent at this time, for example, an aqueous liquid agent which is usually used for producing an ophthalmic drug such as sterile distilled water is used. The eye drops of the present invention include isotonic agents such as sodium chloride, potassium chloride, concentrated glycerin, propylene glycol, sodium phosphate, boric acid, epsilon-aminocaproic acid, buffer agents such as monoethanolamine, sodium edetate, etc. Stabilizers, benzalkonium chloride, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl palmitate, chlorobutanol and other preservatives, polysorbate 80 and other surfactants, sodium hydroxide, hydrochloric acid and other pH adjusters, etc. Are added as needed.

The dose of the present compound in the present invention may be any as long as it can exert a therapeutic effect, and an aqueous solution having a concentration of about 3% is preferable, but it may be appropriately selected depending on the symptoms and age. INDUSTRIAL APPLICABILITY The eye drop of the present invention exhibits an excellent intraocular pressure-lowering effect and is used for treatment of glaucoma, ocular hypertension and the like. next,
Formulation examples of the intraocular pressure lowering eye drop of the present invention are shown.

Formulation Example 1 (Eye drops) MTCC (as monohydrate) 32.3 g Monoethanolamine 15.7 g Epsilon-aminocaproic acid 5.0 g Methyl paraoxybenzoate 0.26 g Propyl paraoxybenzoate 0. 14g Chlorobutanol 2.5g 1N hydrochloric acid until pH 5.5 Purified water up to 1000ml

Methyl paraoxybenzoate, propyl paraoxybenzoate and chlorobutanol are added to 650 ml of purified water preheated to about 60 °, and the resulting mixture is thoroughly stirred to dissolve.
After cooling this solution to room temperature, epsilon-aminocaproic acid is added and dissolved. MTCC monohydrate is dispersed in 200 ml of purified water, and a solution obtained by adding monoethanolamine and dissolving is added and mixed. The pH was adjusted to 5.5 with 1N hydrochloric acid, the volume was adjusted to 1000 ml with purified water, and the bacteria were removed by filtration to give an eye drop having a 3% MTCC concentration. In the same manner, 0.3% and 1% MTCC eye drops were prepared.

[0010]

As described above, the present invention is based on the successful creation of a new hydrophilic eye drop useful for the treatment of glaucoma and ocular hypertension because it has an excellent intraocular pressure lowering action. . Next, it will be described by examples that MTCC monohydrate exhibits an intraocular pressure-lowering effect.

[0011]

The present invention will be described more specifically with reference to the following examples. Example 1 Rabbit tonometry test using 0.3-3.0% MTCC monohydrate ophthalmic solution In the test, a male Japanese white rabbit of 16-18 weeks old (body weight 2.3-3.0 kg) (Japan (Institute of Medical Science Animal Materials) was used after preliminary breeding. On the day of the test, the animals were weighed, and it was confirmed that no abnormalities were found in the conjunctiva and cornea. Benoxir (registered trademark) 0.4% was instilled, and the intraocular pressure of both eyes was measured immediately after the local anesthesia (Alcon pneumat).
ic application tonometer:
It was measured several times at regular intervals (Japan Archon) and the value that became constant was taken as the previous value. A 0.3 to 3.0% aqueous solution of MTCC monohydrate was instilled into each eye with a micropipette, and the intraocular pressure was measured 15, 30, 60, 120, and 180 minutes after the instillation. The measurement was performed three times, and the average value was used as the intraocular pressure at each time point. The results of this test are shown in FIG. 1 and Table 1.

[0012]

[Table 1]

[Brief description of drawings]

1 is a graph showing the effect of MTCC monohydrate and Timoptol® 0.5% on rabbit intraocular pressure. Each measured value is represented by an average value.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Masato Tsuritani 1-5-3 Nihonbashi Muromachi, Chuo-ku, Tokyo Within Wakamoto Pharmaceutical Co., Ltd. (72) Inventor Takeshi Maeda 1-5 Nihonbashi Muromachi, Chuo-ku, Tokyo 3 Wakamoto Pharmaceutical Co., Ltd.

Claims (1)

[Claims] 1. A compound of the general formula (1) X: An eye drop for treating glaucoma and ocular hypertension, which comprises an inorganic salt, an organic salt or a compound represented by a monohydrate as an active ingredient.