SE451070B - APPLICATION OF A CARBOSTYRIC DERIVATIVE FOR THE PREPARATION OF A MEDICINE FOR THE TREATMENT OF GLAUCOM - Google Patents

Description

The alkyl groups designated R1 and R2 are, for example, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, etc. Suitable acid addition salts of the carbostyril derivatives illustrated by formula (I) are acid addition salts thereof, which are usually pharmaceutically acceptable and which include, for example, salts of hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, ocalic acid, maleic acid. fumaric acid, citric acid, tartaric acid, etc.

Typical examples of active compounds of formula (I), which are suitable for the present compositions for the treatment of glaucoma, are the following: 8-hydroxy-5- (1-hydroxy-2-isorpopylaminobutyl) carbostyril, 8-hydroxy 5- (1-hydroxy-2-t-butylaminopropyl) carbostyril, 8-hydroxy-5- (1-hydroxy-2-ethylaminobutyl> -3,4-dihydrocarbostyril, B-hydroxy-5- (1-hydroxy) 2-isopropylaminobutyl) -3,4-dihydrocarbostyril.

The compounds which are illustrated by the formula (I) and which are suitable as active principles are known compounds which are prepared, for example, according to the process described in Japanese Patent Application Laid-Open and Examined Patent Application No. 10994/1978. The active compounds have bronchodilator activity and are useful for curing bronchial asthma.

For the present use, glaucoma treatment compositions are prepared in the form of suitable dosage unit forms by mixing a derivative of the formula (I) or an acid addition salt thereof with a conventional carrier for ophthalmic preparations.

The use according to the invention usually takes place by administering a daily dose of 0.1-0.5 mg, preferably 0.05-0.1 mg for adults, of the active principle. Preferably, the administration takes place in two or three doses distributed throughout the day. It is generally preferred that the active principle content of the ophthalmic solution or ointment be in the range of about 0.04% to about 2% by weight. The use according to the invention takes place by mixing the active principle with a suitable carrier or a suitable excipient and that the resulting mixture is optionally prepared into the desired dosage unit form. Suitable carriers or diluents are selected for use. Examples of carriers which are suitable for the preparation of ophthalmic ointments are emulsifiable carriers, water-soluble carriers and suspendable carriers. Typical such carriers are white petroleum jelly, purified lanolin, liquid paraffin, etc.

Typical diluents for the preparation of ophthalmic solutions are sterile, distilled water.

Solubilizers, stabilizers, buffers, antioxidants, preservatives, etc. can be further used. Examples of suitable solubilizers are sodium carboxymethylcellulose, polyoxyethylene ethers such as polyoxyethylene lauryl ether and polyoxyethylene oleyl ether; higher fatty acid esters of polyethylene glycol, such as polyethylene glycol monolaurate and polyethylene glycol monooleate, fatty acid esters of polyoxyethylene, such as polyoxyethylene sorbitan monolaurate and polyoxyethylene sorbitan monooleate, etc. Examples of suitable stabilizing vinylcellulose cellulose EDTA, etc. Examples of suitable buffering agents are sodium hydrogen phosphate, potassium hydrogen phosphate, boric acid, sodium borate, citric acid, sodium citrate, tartaric acid, sodium tartrate, etc. Examples of suitable antioxidants are sodium bisulfite, sodium thiosulfite, ascorbic acid suitable, etc. nol, benaalkonium chloride, cetylpyridinium chloride, phenylmercury salt, thimerosal, phenethyl alcohol, methylparaben, propylparaben, etc.

The ophthalmic solutions used according to the invention are preferably made isotonic with the tear fluid. For this purpose, common table salt or the like can be added to the ophthalmic solution. It is desirable to adjust them to pH 5.5-8.5, preferably 5.5-7.5. Ophthalmic solutions are applied dropwise to the eye from a suitable container or sprayed onto the eye from a syringe device. Ophthalmic ointments are also applied to the eye.

The invention is described in more detail below with reference to preparation examples and tests of medical efficacy; the invention is not limited to these examples. 8 15 Hydroxy-5- (1-hydroxy-2-isopropyl-aminobutyl) carboatyryl hydrochloride 0.2 g Benzalkonium chloride 0.01 g Sodium dihydrogen phosphate 0.56 g Potassium dihydrogen phosphate 0.8 g water permissible amount A total of 100 ml of the beet parts are dissolved in distilled water and the solution is sterilized by filtration through a suitable filter paper to prepare a glaucoma treatment composition in the form of an ophthalmic solution prepared by using the invention.

Preparation Example 2. 8-Hydroxy-5- (1-hydroxy-2-isopropylaminobutyl-3,4-dihydrocarbostyril hydrochloride 0.2 g Benzalkonium chloride 0.01 g Sodium dihydrogen phosphate 0.56 g Potassium dihydrogen phosphate 0.8 g Distilled water suitable amount Total 100 ml The ingredients are dissolved in de-distilled water and the solution is sterilized by filtration through a suitable filter paper to prepare a glaucoma treatment solution in the form of an ophthalmic solution prepared according to the invention.

Effect Tea A drop (approximately 25 μl) of the ophthalmic solution obtained according to Preparation Example 1 is given twice daily, in the morning and in the evening, for three days to each of the eyes of three male patients with open-angle glaucoma. The intraocular pressure in the eye is measured between 10 am and 11 am with a Goldmann applanation tonometer. Table 1 shows the results. i »fx 10 15 20 451 070 Ta ell 1 Intraocular pressure (mm Hg) Before 1 day 2 days 3 days C * Left eye ** Right eye Table 1 shows that by using the invention ophthalmic solutions for the treatment of glaucoma greatly reduce intraocular pressure in patients with glaucoma and provides an outstanding therapeutic effect.

The glaucoma treatment composition obtained according to Preparation Example 2 is tested for efficacy in the same manner as indicated. The composition gives essentially the same effect in reducing the intraocular pressure.

Claims (5)

451 070 6 Egtggtkrav Use of a carboethyril derivative or an acid addition salt thereof for the preparation of an ophthalmic solution or ointment for the treatment of glaucoma, the carboethyril derivative having the formula: on 111 I | 2 CH-CHNHR wherein R 1 and R 2 represent straight or branched chain alkyl group having 1 to 4 carbon atoms and the carbon-carbon bond between the 3-position and the 4-position is a single bond or double bond. Use of a carboethyril derivative or an acid addition salt thereof according to claim 1, wherein the concentration of carbostyril derivative in the solution or ointment is 0.04-2% by weight. Use of a carboethyril derivative or an acid addition salt thereof according to claim 1 or 2, wherein the derivative is in the form of a solution. Use of a carboethyril derivative or an acid addition salt thereof according to claim 3, wherein the solutions pH is 5.5-8.5, preferably 6.5-7.5. Use of a carboethyril derivative or an acid addition salt thereof according to any one of claims 1-4, wherein the carbostyril derivative is 8-hydroxy-5- (1-hydroxy-2-isopropylamino-butyl) -carbostyril hydrochloride or 8-hydroxy -5- -2-isopropylaminobutyl) -3,4-dihydrocarbostyril hydrochloride. A 'ß ha