Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1993-09-24
1995-11-07
Warden, Jill
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 19, 514 9, 514 11, 530330, 530331, 530322, 536 172, 562433, 564161, 564192, 558154, A61K 3800, C07K 500, C07K 700, C07K 1700
Patent
active
054648211
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to small peptidic compounds, pharmaceutical preparations containing such compounds and a method for treating glaucoma.
2. Description of the Prior Art
Glaucoma is a very common eye disease affecting millions of people in the later stages of their life. Glaucoma is characterized by abnormally high intraocular pressure and, if untreated, damage to the optic nerves which may cause narrowing of the visual field, and eventually irreversible blindness.
The intraocular pressure is determined by the rates of inflow and outflow, i.e. the dynamics of the aqueous humour. The aqueous humour enters into the posterior chamber of the eye, and then flows through the pupil to the anterior chamber, from where it eventually leaves the eye through the trabecular meshwork.
The aqueous humour supplies nutrients to the lens and cornea, and its proper supply is thus of the utmost importance for maintaining healthy eyes.
Any disturbance of aqueous humour dynamics by either excess inflow, or reduced outflow, results in an increase in the intraocular pressure above the normal value (for adults) of 17-20 mm Hg, i.e. the eye becomes hypertensive. A prolonged hypertensive state will result in nerve damage and blindness. Detailed descriptions on glaucoma can be found in "An Outline of Ophthalmology", by R. L. Coakes, and P. J. Holmer Sellars, published by Wright, Bristol (1985), cf. pp. 54/57, and in the series: Current Topics in Eye Research", edited by J. A. Zadunaisky and K. Davson, Academic Press.
All known antiglaucoma drugs on the market lower the intraocular pressure, either by decreasing formation of aqueous humour, or by increasing the outflow, i.e. the elimination of aqueous humour from the eye. Glaucoma drugs are thus all hypotensive agents.
The most common class of antiglaucoma agents are adrenergic antagonists; many of them are .beta.-blockers (the most widely used of this type is timolol), adrenergic agonists, dopaminergic agents, cholinergic agents (the most widely used of this type is pilocarpine), or several other classes of compounds. For detailed overviews, see for example Annual Reports in Medicinal Chemistry, Vol. 20, chapter 9: "Antiglaucoma Agents", by M. F. Sugrue and R. L. Smith (1985, Academic Press), and the text: "The Pharmacological Basis of Therapeutics" by A. Goodman and L. Gilmans.
Thus one of the characteristics of glaucoma theory is the fact that an enormous variety of chemical structural types can be used to reduce excessively high intraocular pressure.
None of the currently used drugs is fully satisfactory. There are serious side effects affecting the heart, the kidneys, the lungs and/or the libido. Some of the side effects are, especially in the case of carbonic anhydrase inhibitors, .alpha.-adrenergic antagonists and .beta.-adrenergic antagonists, directly implicated with the different modes of action, while others are not. Furthermore, there are problems of metabolic stability which necessitates several applications of eye drops per day. Great efforts are therefore made to develop new antiglaucoma agents which would be free of the above constraints. Recently, an entirely new chemical structural type of compounds, namely peptides and peptide derivatives, was described as having antiglaucoma activity, i.e. as hypotensive agents. Examples are carboxyalkyl dipeptides (European Patent No. 0088350) and the atrial natriuretic factor, a long peptide of 29 amino acids in length (Fortschritte der Ophthalmologie, Volume 89, pp. 89/91 (1989)).
U.S. Pat. No. 4,634,698 describes ophthalmological pharmaceutical compositions comprising carboxyalkyl dipeptides Joined through a sulfonamido group to a benzothiadiazinyl sulfonylphenyl moiety and to a method for using said composition in the treatment of glaucoma. The compositions contain as active agent cyclic, proline-type amino acids, which differ substantially from the compounds according to the .invention. Besides the peptide moiety being different from the one in the compounds cl
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Gauri Kailash K.
Stig Aasmul-Olsen
Widmer Fred
Carlbiotech, Ltd.
Huff Sheela J.
Warden Jill
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