JPS5951928B2 - Glaucoma treatment - Google Patents

Description

[Detailed description of the invention] The present invention relates to a therapeutic agent for glaucoma.

Glaucoma is a group of diseases that are based on persistent or repeated increases in intraocular pressure and cause functional and organic damage to the eye.The treatment is to bring the intraocular pressure back to normal levels in order to preserve visual function. (Masayoshi Mikuni, Kazuo Iwata, Glaucoma, Zenken Publishing Co., Ltd., 1968
Year).

The present inventors have repeatedly conducted various studies on the medicinal efficacy of carbostyril derivatives, which are known as therapeutic agents for arrhythmia and angina pectoris, and have discovered that these derivatives exhibit an intraocular pressure-lowering effect that cannot be expected from known medicinal efficacy. The inventors have discovered that a compound exists that is effective as a therapeutic agent for glaucoma, and have now completed the present invention.

That is, the present invention is based on the general formula [In the formula, R represents a lower alkyl group.

] The present invention relates to a therapeutic agent for glaucoma containing a carbostyril derivative or an acid addition salt thereof as an active ingredient. The lower alkyl group represented by R in the above general formula [I] includes a linear or branched alkyl group having 1 to 4 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group, and a butyl group. , tert-butyl group, and the like. Further, the acid addition salts of the carbostyril derivative represented by the above general formula [I] include conventional pharmaceutically acceptable acid addition salts of the derivatives, such as hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, oxalic acid,
Included are salts of maleic acid, fumaric acid, citric acid, tartaric acid, and the like. Representative examples of the active ingredient compound of the glaucoma therapeutic agent of the present invention represented by the above general formula [I] include the following.

o5-(2-hydroxy-3-ter-brerimino)propoxycarbostyryl o5-(2-hydroxy-3-isopropylamino)propoxycarbostyryl °5-(2-hydroxy-3-ethylamino)propoxycarbo Styril The glaucoma therapeutic agent of the present invention has the general formula [1? The represented derivatives or acid addition salts thereof are prepared in suitable dosage unit form by mixing with conventional ophthalmic pharmaceutical carriers.

As the dosage unit form, any of the usual various forms can be adopted. For example, for topical administration, eye ointments, eye drops, etc.
Examples of systemic administration include tablets, granules, and injections. In particular, the therapeutic agent of the present invention is preferably in the form of eye drops. The dosage of the therapeutic agent of the present invention is not particularly limited, but the amount of active ingredient in the therapeutic agent is usually 0.01 to 0.5 per adult per day.
The dosage is preferably 0.05 to 0.2 mg, and administration is preferably carried out in 1 to 3 divided doses a day. The amount of active ingredient in the therapeutic agent is preferably in the range of about 0.1 to 2% by weight. The therapeutic agent of the present invention can be manufactured by conventional methods.

Specifically, it is produced by using a carbostyryl derivative represented by the general formula [1] or an acid addition salt thereof as an active ingredient, mixing this with an appropriate base, and then shaping as necessary. When the therapeutic agent is an eye ointment, eye drops, injection, etc., it is manufactured by further sterilization. In the above, the base may be appropriately determined depending on the form of the therapeutic agent. For example, when manufacturing an eye ointment, a conventional emulsion base, water-soluble base, suspendable base, etc. Can be used. Representative examples of such bases include white petrolatum, purified lanolin, liquid paraffin, and the like. Furthermore, in producing eye drops, for example, sterile distilled water can typically be used as a base. The therapeutic agent of the present invention further includes, for example, a solubilizing agent,
Stabilizers, buffers, antioxidants, preservatives, etc. can be added.

Specific examples of solubilizing agents include sodium carboxymethyl cellulose, polyoxyethylene glycol ethers such as polyoxyethylene lauryl ether and polyoxyethylene oleyl ether, and polyethylene glycols such as polyethylene glycol monolaurate and polyethylene glycol monooleate. Examples include higher fatty acid esters, polyoxyethylene fatty acid esters such as polyoxyethylene sorbitan monolaurate, and polyoxyethylene sorbitan monooleate. Specifically, the stabilizers include hydroxypropylmethylcellulose, polypinyl alcohol, carboxymethylcellulose, hydroxyethylcellulose, glycerin, and EDT.
Examples include A. Buffers include sodium dihydrogen phosphate, sodium monohydrogen phosphate, potassium hydrogen phosphate,
Examples include boric acid, sodium borate, citric acid, sodium citrate, tartaric acid, and sodium tartrate. Antioxidants include sodium bisulfite, sodium thiosulfite,
Examples include ascorbic acid. Examples of preservatives include chlorobutanol, benzathonium chloride, cetylpyridium chloride, thimerosal, phenethyl alcohol, methylparaben, propylparaben, and the like. Furthermore, when the therapeutic agent of the present invention is in the form of eye drops, the eye drops are preferably made isotonic with lachrymal fluid, and therefore, an isotonic agent such as common salt can be added if necessary.

Furthermore, the eye drops have a pH of 5.5 to 8.5, preferably 6.5 to 8.5.
It is desirable to adjust it to 7.5. The therapeutic agent for glaucoma of the present invention thus obtained is administered by various administration methods depending on its dosage unit form.

For example, in the case of eye drops, they are dropped into the eye from a suitable drop container or sprayed into the eye from a spray device. In the case of eye ointment, it is applied to the eye. In the case of tablets, granules, etc., they are administered orally, and in the case of injections, they are administered subcutaneously, intramuscularly, or intravenously, and in either case, the desired therapeutic effect can be achieved. Formulation examples and drug efficacy tests are listed below to explain the present invention in more detail, but the present invention is not limited thereto.

The above ingredients are dissolved in distilled water and sterilized and filtered using a suitable filter paper to produce the glaucoma therapeutic agent of the present invention in the form of eye drops.

Efficacy test For three glaucoma patients, two drops of the eye drops obtained in the above formulation example were instilled into the eyes, and the intraocular pressure was measured 1, 4, and 24 hours later.

This measurement was performed using a cold pine applanation tonometry device.
It will be held between 11:00 and 11:00. The results are shown in Table 1 below. Acute toxicity test 5-(2-hydroxy-3-Tert-butylamino)
When propoxycarbostiline hydrochloride was administered intravenously to mice and the LD,O value was determined, it was 44.6~/Kg.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R represents a lower alkyl group. ] A therapeutic agent for glaucoma containing a carbostyril derivative or an acid addition salt thereof as an active ingredient.