Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Reexamination Certificate
1999-08-11
2001-03-27
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
C424S468000
Reexamination Certificate
active
06207190
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention is in the field of pharmacology, and relates specifically to the pharmacological treatment of the chronic glaucomas of the eye.
2. Description of the Prior Art
Pertinent Anatomy of the Eye
The eye is a closed, fluid-filled environment divided into two segments separated by the crystalline lens. The anterior segment is bordered anteriorly by the arching, clear cornea and posteriorly by the anterior surface of the lens and the iris. The posterior segment is bordered in the front by the back surface of the lens and iris and posteriorly by the concave surface of the retinal lining of the globe. The only significant opening in this otherwise closed globe is through the retina in the distal back; the exit point of approximately 1 million bundled axonal nerves gathered from all points of the retina carrying their electrically digitized images for manipulation and display by the brain—our impression of this electrical activity is called vision. This opening for the bundled coaxial cable of nerves is called the optic nerve head and represents the weakest point in an otherwise very strong, inelastic globe. A locally dense, layered network of blood vessels supplies the optic nerve head and its health is almost totally dependent upon the oxygen delivered to it by this labyrinth of small vessels. These fine vessels are derived, in the main, from the short posterior ciliary arteries that arise from the ophthalmic artery. This particular vascular source for the eye is important when consideration is given to vascular reactions to vasoconstrictors and vasodilators such as endothelin-1 and nitric oxide (vide infra).
At the peripheral circumference of the posterior surface of the iris is a fringe of secretory cells (ciliary processes) which secrete a thin, watery fluid (aqueous fluid) at a relatively constant, though variable rate. This fluid passes through an intervening meshwork (trabecular meshwork) and then exits the eye through tiny openings into a collection channel that circles the interior periphery of the cornea concentric with the outer edge of the anterior iris (Schlemm's canal). The flow of aqueous fluid, therefore, originates in the periphery of the posterior chamber, washes forward around the crystalline lens through the pupil and exits through Schlemm's canal in the periphery of the anterior chamber.
Pertinent Physiology of the Eye
The eye is maintained in a homeostatic shape by a relatively stable intraocular pressure (IOP) which varies within a reasonably narrow range. This is true so long as the production of aqueous fluid by the ciliary processes remains equal to its exit through Schlemm's canal. However, should aqueous production outstrip aqueous outflow, the IOP increases. Because the eye is a closed, fluid-filled, minimally expansile organ, any hydraulic pressure increase in one part of the eye is transmitted equally throughout the eye.
So long as the availability of oxygen from the posterior ciliary arteries and the small optic nerve head arterioles remains adequate, the nerve head itself can tolerate relatively high levels of IOP. However, it is perhaps intuitively obvious that the ability of arterially-delivered oxygen to move efficiently from the red blood cells of terminal arterioles, through the arteriolar wall and into the oxygen-dependent tissues of the optic nerve head, is at least partially dependent upon the difference between the intravascular oxygen pressure and the extravascular pressure countering its diffusion. Thus, if the intraocular pressure of the globe which compresses the outside of the arterioles is higher than the oxygen diffusion pressure driving oxygen through the arteriole into the surrounding tissues, decreasing amounts of oxygen will reach the optic nerve head and nerve disability will result. Over a variable period of time this chronic, local vascular disability results in atrophy, progressive functional death of the nerve, visual field defects and blindness.
Similarly, if the vessels which carry blood to the nerve head are unable to provide sufficient volumes of blood, and thus oxygen, to the optic nerve or have structural barriers to oxygen diffusion, then even in an environment of normal or “low” intraocular or extravascular pressure (<21 mm Hg.), local tissues will be oxygen deprived and optic nerve dysfunction or atrophy will follow. These arteriolar deficiencies may occur because of vasoconstriction secondary to generalized or localized microvascular dysregulation, or in conjunction with arteriolar muscular hypertrophy (perhaps as a result of chronic spasm), atherosclerotic luminal reduction, changes in the viscosity or laminar flow patterns of the arterial blood, or in either essential or iatrogenic systemic hypotension. Interestingly, there is significant evidence that “low” or normotensive glaucoma patients do indeed have reduced optic nerve head blood flow
Clearly if the intraocular pressure is elevated and the vascular ability to provide sufficient volumes of blood is compromised, the danger of optic nerve head failure is greatly increased.
Chronic Glaucoma—The Disease
Glaucoma in various guises affects a large segment of the public. It is estimated that 2% to 2.5% of the population over the age of 40 has chronic open angle glaucoma (COAG), sometimes, synonymously, referred to as Primary Open Angle Glaucoma (POAG). In this disease, there is no major structural obstruction to aqueous access to the outflow trabeculum, but there is increased resistance to aqueous transit through the trabeculum to Schlemm's canal. This is the most common form of glaucoma.
Smaller but additive segments of the population suffer from other types of chronic glaucoma: pigmentary glaucoma, angle recession glaucoma, pseudoexfoliative glaucoma and combined (mixed) mechanism glaucoma.
Although, as noted, there are several forms of the disease, all incorporate a limited number of common features, the most disastrous of which is an ultimate failure of the optic nerve leading to complete blindness. Except for some less common varieties of glaucoma, this failure usually involves asymptomatic, slowly progressive visual field loss over a very long period of years and, as a result, the patient is frequently unaware of the disease. All too often the diagnosis is made after much damage to the optic nerve has occurred and some irreversible loss of vision has taken place.
Normal IOP is given as 18 mm. Hg. Elevated IOP is classically defined as pressure over 21 to 24 mm. Hg.
Because optic nerve damage is known to occur in patients with chronically elevated or, less frequently, acutely elevated IOP, present treatment methods concentrate on reducing this easy-to-measure, objective clinical finding by the application of a variety of modalities: topical eyedrops, oral medications, intravenous medications, surgical procedures, laser phototherapy, etc. While each of these treatment approaches may function differently, they are all focused upon the reduction of pressure inside the eye and rely upon this pressure fall to prevent optic nerve damage. In some cases the therapy attempts to reduce the production of aqueous fluid by the ciliary processes, in other cases therapy attempts to increase the outflow of aqueous fluid through Schlemm's canal.
For some patients this approach is adequate and effective. However, the effectiveness of each of these treatments has a place on a treatment continuum which runs from total ineffectiveness and progressive optic atrophy and eventual blindness, to an arrest of the disease, complete cessation or prevention of further optic nerve failure and preservation of vision.
This treatment solution, however, is complicated by two facts:
a. Some patients develop progressive and seemingly irreversible optic nerve failure and visual loss in the face of normal IOP or lower than normal IOP (sometimes very much lower). These states are referred to as “normotensive glaucoma” or “low tension glaucoma”.
b. Although optic nerve failure does in fact occur in patients w
Pearson Don C.
Richardson Kenneth T.
ChronoRX LLC
Spear James M.
Townsend and Townsend / and Crew LLP
LandOfFree
Dosage forms for the treatment of the chronic glaucomas does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Dosage forms for the treatment of the chronic glaucomas, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Dosage forms for the treatment of the chronic glaucomas will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2520621