Pharmaceutical composition for use in glaucoma treatment

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...

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514601, 514602, 514913, A61K 3118

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active

056632053

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BRIEF SUMMARY
This invention relates to a pharmaceutical composition for use in glaucoma treatment that is virtually free from side effects, stable, and can develop improved intraocular pressure reducing activity at low concentrations.
Glaucoma is a disease characterized by an abnormal increase in intraocular pressure which provokes a variety of symptoms, such as fatigability in the eye, blurred vision, pain in the eye and gradually impaired vision, eventually leading to the risk of loss of vision. The disease causes the eyeball to harden like stone or the depth of the pupil to look green.
Inside the eyeball a watery fluid (the aqueous humor) circulates invariably to maintain a constant pressure within the eye (intraocular pressure=15 to 20 mmHg). The aqueous humor is controlled by the circulation of blood or lymph, resilience of the eyeball wall, action of the dominant nerve etc., and when any of such factors becomes abnormal, intraocular pressure rises and glaucoma develops.
When such abnormality is caused by ophthalmic diseases such as iritis, wounds and hemorrhage in the vitreous body, the resultant disease is called secondary glaucoma. However, the usual type of glaucoma is primary glaucoma in which the abnormality is brought about by unknown causes.
Primary glaucoma is classified into three types: (1) inflammatory glaucoma whose progress is acute, (2) simple glaucoma whose progress is chronic and (3) congenital glaucoma.
In order to treat glaucoma, heretofore, various medicaments have been used with the specific aim of preventing a rise in intraocular pressure or reducing increased intraocular pressure. The intraocular pressure reducing agents known so far include the sympathomimetic drugs such as epinephrine, but epinephrine, with its mydriatic activity prompts angle closure when applied to narrow angle glaucoma, thus possibly causing a rapid increase in intraocular pressure and often producing an increase in blood pressure and pigmentation in the conjunctiva.
The parasympathomimetic drugs such as pilocarpine, with their miotic activity, bring about the sensation of darkness or accommodation abnormality in the visual field.
In recent years, furthermore, .beta.-adrenergic blocking agents such as timolol, by virtue of their suppressory effect against production of aqueous humor, have been extensively used for the treatment of glaucoma (Drug Therapy Practical Series, The Drug Treatment of Glaucoma, pp. 70 to 75, 1990). Nevertheless, such .beta.-adrenergic blocking agents, which have been reported to cause systemic side effects such as bradycardia, cardiac insufficiency and asthma onset, cannot be administered to patients with such symptoms.
It is indicated that .alpha..sub.1 -adrenergic blocking agents promote an aqueous humor outflow, and bunazosin hydrochloride can increase choroidal blood flow, leading to the suggestion that a possibility could be opened up for the development of a novel therapeutic agent against low tension glaucoma (Journal of Japanese Society of Ophthalmology, vol. 42, pp. 710 to 714, 1991). So, this drug substance is considered to find application in the treatment of glaucoma, but conjunctival hyperemia and miosis owing to its vasodilatory activity would be inevitable.
In contrast to the above, .beta.-adrenergic stimulants also are expected to be given to such patients but conventional .beta.-adrenergic stimulants such as salbutamol fail to demonstrate satisfactory activity unless applied at high concentrations, which consequently brings about marked conjunctival hyperemia, thus rendering its continued administration impossible.
As described above, in fact, there has so far not been found satisfactory glaucoma treatment agents that are free from the above-mentioned side effects and remain stable and effective at low concentrations.
In recent years, it was reported that phenylethanolamine derivatives or their salts, inclusive of 5-[1-hydroxy-2-[2-(2-methoxyphenoxy) ethylamino]ethyl]-2-methylbenzenesulfonamide hydrochloride (hereinafter referred to as amosulalol hydrochloride), exhibit both .al

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Drugs Future, vol. 19, No. 7, Jul. 1994, p. 683, "Amosulalol Hydrochloride Lowgan".

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