US 2002O187986A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2002/0187986 A1 Horn (43) Pub. Date: Dec. 12, 2002 (54) OPHTHALMIC FORMULATION WHICH Related U.S. Application Data MODULATES DILATION (62) Division of application No. 09/710,758, filed on Nov. (76) Inventor: Gerald Horn, Deerfield, IL (US) 8, 2000, now Pat. No. 6,420,407. Publication Classification Correspondence Address: Bell, Boyd & Lloyd LLC (51) Int. Cl." .................. A61K 31/517; A61K 31/4745; P.O. BOX 1135 A61K 31/4168; A61K 31/4164 Chicago, IL 60690 (US) (52) U.S. Cl. ..................... 514/252.17; 514/283; 514/401 (57) ABSTRACT (21) Appl. No.: 10/165,459 An ophthalmic formulation is disclosed which reduces dila (22) Filed: Jun. 7, 2002 tion in dim light and reduces redness. US 2002/0187986 A1 Dec. 12, 2002 OPHTHALMC FORMULATION WHICH 0007 A formulation for optimizing pupil size in extreme MODULATES DILATION lighting conditions is disclosed. The formulation is prefer ably a Solution of the type used in an artificial tear formu FIELD OF THE INVENTION lation having dissolved therein a therapeutically effective 0001. The present invention relates to a composition amount of a compound characterized by its ability to reduce formulated and administered to a human eye to reduce dilation of the eye, particularly in dim light. The compound dilation and redness. generally interferes with a natural biochemical reaction which results in the stimulation of the dilator muscles of the BACKGROUND OF THE INVENTION eye. The formulation is preferably further comprised of a compound which reduces eye redness, e.g. tetrahydrazolene. 0002 While it is known that pupil size varies in its The compound which has the ability to disrupt endogenous diameter in darkness between individuals from 3 mm to 9 compounds which Stimulate dilator muscles of the eye may mm, little attention has been paid to the effect of this be an alpha 1 antagonist which belongs to a class of difference on the night vision and vision in dim light compounds with phentolamine or phenoxybenzamine (Scotopic vision is dark adapted vision). Those with large groupS. pupils Suffer from much more light Scatter, glare, halo, and related aberrant focus of light rays that can make function 0008 Amethod of optimizing pupil diameter is disclosed under certain conditions of lighting very difficult. wherein the pupil diameter in dim light is effected So that it is not more than 200% greater than its size in bright light. 0.003 Laser vision correction in particular has added new The method encompasses administering a therapeutically quality of vision difficulties for many of these individuals. effective amount of an alpha 1 antagonist to an eye of a Exposing the retina to light focusing from as much as nine perSon in need thereof. The optimized pupil diameter in dim times more Surface area essentially magnifies every varia light may be no more than 5 mm, and the pupil diameter in tion in curvature from the ideal. Currently, only direct acting bright light may be constricted no more than 1 mm. Further, miotic agents Such as pilocarpine are used in an effort to the optimized pupil diameter in dim light may be between decrease pupil size. and including 3 mm and 5 mm and will vary with different 0004 Pilocarpine causes brow ache, ciliary muscle con patients. Actual results with human patients are shown in traction and pseudo myopia, excessive dimneSS when first the Examples. applied, and redness. Its effect lasts only a few hours, and it 0009. In accordance with the method of the invention an has known, though remote, risk of retinal detachment prob application device Such an eyedropper is utilized in order to ably related to pull on the retina from stimulated ciliary apply a therapeutically effective amount of an alpha 1 muscle contraction. For these reasons it is rarely tolerated or agonist to the eye of a patient which is preferably the eye of considered a clinically useful alternative for patients with a human patient. Thereafter, the formulation is allowed to large pupils in dim light. effect the pupil of the eye and contract the pupil So that the 0005 Another medication used to affect pupil size is pupil does not expand above a level which is twice the level dapiprazole, an alpha-1 adrenergic receptor blocking agent of dilation when the eye of the patient is present in bright Dapiprazole is 5,6,7,8-tetrahydro-3-2-(4-O,tolyl-1-piperazi light. Accordingly, another aspect of the invention is a nyl)ethyl-8-triazolo 4,3-alpyridine hydrochloride. It is formulation comprised of an aqueous Solution having an available in a 0.5% solution to partially counteract, or alpha 1 agonist present therein wherein the formulation is reverse, the dilation effect of phenylephrine, an adrenergic present in an eyedropper. dilating agent, and the dilating and accommodation loSS 0010. The present invention is also directed to a method caused by tropicamide. In addition to producing redneSS for optimizing pupil diameter in dim light by minimizing its upon instillation, dapiprazole has very little effect on pupil dilatation in response to leSS light, comprising administering Size in dim light in clinical application when used topically a therapeutically effective amount of an alpha 1 antagonist for this purpose, and therefore its Sole use is as a treatment to an eye of a perSon in need thereof. In this method, of iatrogenically induced mydriasis produced by adrenergic dilatation of the pupil diameter in dim light may be mini or parasympatholytic agents. mized in response to leSS light compared with bright light, SUMMARY OF THE INVENTION and the method may not induce ciliary muscle contraction. 0011. In the method of the present invention, the patient 0006 An ophthalmic formulation of the invention pref may Suffer from excessively large pupils in dim light, and erably obtains two simultaneous effects (a) reducing the the patient may Suffer from poor quality of vision, and the amount of dilation the eye would normally undergo in a low patient may be undergoing medication that results in dila light environment; and (b) reducing eye redness. Reducing tation of the pupil diameter. Alternatively, the pupil diameter normal dilation can be obtained by administering a com of the patient may be naturally excessively dilated as a result pound which interferes with the normal stimulation of of response to dimming of light. muscles which cause dilation. This can be done, for example, with an alpha 1 antagonist. However, redness may 0012. The method of the invention may be carried out by be reduced using an alpha 1 agonist. The antagonist and directly instilling onto the eye an eye drop formulation of the agonist will, in general, counteract each other. The present invention. Optionally, the alpha 1 antagonist may be admin invention provides a particularly preferred formulation of (a) istered by contacting a contact lens, and the contact lens an alpha 1 antagonist which is phentolamine; and (b) an applied to the eye. In the method of the invention, the used alpha 1 agonist which is tetrahydrozoline and Specifically alpha 1 antagonist preferably may belong to a class of tetrahydrozoline hcl. This combination reduces dilation and compounds belonging to the phentolamine or phenoxyben redness. Zamine groups. US 2002/0187986 A1 Dec. 12, 2002 0013 The present invention is directed to a method for is the formulation of the invention present within an appli reducing pupil diameter in dim light in cases where dilation cation device Such as a conventional or improved eyedrop of the pupil is excessive, Such as 6 mm or greater. Admin per of the type described herein. istering a formulation of the invention does not induce ciliary contraction or undesirable pseudomyopia that may 0019. An advantage of the invention is that it can be result from taking certain medication. Formulations dis utilized to treat patients who have been Subjected to laser closed here reverse mydriasis of parasympatholytic agents. Surgery and have developed a range of different vision Formulations of the invention are effective on agents para problems as a result of excessive dilation of their pupils. lyzing accommodation Such as 1% cylogyl, which can then 0020. A feature of the invention is that the alpha 1 be used for more complete cycloplegia and accurate prelaser antagonist can be formulated in a manner which is readily refractive measurement. administered to the eye to obtain a desired effect. 0.014. There are no generally available eye drops for 0021. These and other aspects, advantages and features of optimizing pupil Size Such as by reducing pupil diameter in the invention will become apparent to those skilled in the art dim light without undesirable side effects. The present upon reading this disclosure. invention recognizes that the alpha-1 antagonists which are currently used for treatment of high blood pressure, treat DETAILED DESCRIPTION OF THE ment of pheochromocytoma, migraines, bladder Spasm, INVENTION prostate enlargement, and Sexual dysfunction can be formu 0022. Before the present formulations and methods are lated used in reducing pupil diameter. described, it is to be understood that this invention is not 0.015 The present invention provides an ophthalmic limited to particular compounds, formulas or Steps composition which achieves the combined requirements of described, as Such may, of course, vary. It is also to be understood that the terminology used herein is for the comfort and pupil diameter optimization. purpose of describing particular embodiments only, and is 0016 Alpha adrenergic receptor antagonists function to not intended to be limiting, Since the Scope of the present block alpha-1 receptor mediated contraction of arterial and invention will be limited only by the appended claims.