Methods and means for drug administration

Details Methods and means for drug administration Methods and means for drug administration

1997-06-05

1999-09-14

Fay, Zohreh

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

514573, 514912, A61K 31215, A61K 3119

Patent

active

059523786

DESCRIPTION:

BRIEF SUMMARY
The invention is concerned with a method of enhanced delivery of drugs to the optic nerve head in the eye, for instance for treatment of glaucoma, utilising prostaglandins. The invention also relates to the use of prostaglandin analogues for the preparation of ophthalmic compositions for such enhanced delivery as well as the compositions as such.
Glaucoma is an eye disorder characterized by increased intraocular pressure, excavation of the optic nerve head and gradual loss of the visual field. An abnormally high intraocular pressure is commonly known to be detrimental to the eye and there are clear indications that in glaucoma the intraocular pressure is the most important factor causing degenerative changes in the retina and the optic nerve head. The exact pathophysiological mechanism of open angle glaucoma is, however, still unknown. Unless treated, glaucoma may lead to blindness, the course of the disease typically being slow with progressive loss of vision.
The intraocular pressure (IOP) can be defined according to the formula:
where Pe is the episcleral venous pressure, Ft the formation of aqueous humour, Fu the part of the aqueous humour which exits the eye through the uveoscleral outflow pathway and R is the resistance in the trabecular outflow pathway. The aqueous humour in the anterior and posterior chambers of the eye is formed in the ciliary processes behind the iris. It then flows through the pupil into the anterior chamber and normally exits the eye through the trabecular meshwork and Schlemm's canal into the episcleral veins outside the eye globe. However, part of the aqueous humour may leave the eye through the uveoscleral outflow route. The flow in this route is regarded as only minimally influenced by the intraocular pressure (Bill, 1975).
The intraocular pressure in humans is normally in the range of 12-22 mmHg. At higher values, e.g. above 22 mmHg, there is an increased risk that the eye may be affected. In one particular form of glaucoma, low tension glaucoma, damage may occur at intraocular pressure levels that are within the normal physiological range. The opposite situation is also known, i.e. some individuals may exhibit an abnormally high intraocular pressure without any manifest defects in the visual field or the optic nerve head. Such conditions are usually referred to as ocular hypertension.
Glaucoma treatment can be given by means of drugs, laser or surgery. In drug therapy usually the purpose is to lower either the formation of aqueous humour (Ft) or the resistance to outflow of aqueous humour (R), which according to formula (1) above will result in reduced intraocular pressure; alternatively to increase the outflow of aqueous humour through the uveoscleral route which according to the same formula (1) also reduces the intraocular pressure.
Prostaglandins and typically PGF.sub.2.alpha. and its derivatives, especially the esters, reduce the intraocular pressure mainly by increasing uveoscleral outflow of aqueous humour (Crawford et al, 1987; Nilsson et al, 1989; Stjernschantz and Resul, 1992; Toris et al, 1993). The use of prostaglandins and their derivatives is described in several patents and patent applications, see for instance U.S. Pat. No. 4,599,353 (Bito), U.S. Pat. No. 4,952,581 (Bito), WO89/03384 (Resul and Stjernschantz), EP 170258 (Cooper), EP 253094 (Goh) and EP 308135 (Ueno).
In addition to reducing the intraocular pressure in glaucoma it would be very desirable to treat the optic nerve head and the ganglion cells of the retina directly, e.g. with neuroprotective agents and vasoactive agents to prevent further loss of nerve cells. A problem, however, is the delivery of the drugs to the site of action, the optic nerve head, which is positioned in the rear part of the eye behind the crystalline lens which is an effective barrier against passive diffusion of compounds posteriorly in the eye, and even in pseudophakic eyes in which the crystalline lens has been removed and exchanged for an intraocular plastic lens, diffusion posteriorly is ineffective. Thus, drugs can o

REFERENCES:
Eye, vol. 7, 1993, Williamson et al. Colour Doppler Velocimetry of the Arterial Vasculature of the Optic Nerve Head and Orbit, pp. 74-79.

Affiliated with

Also associated with

Rating

Methods and means for drug administration does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods and means for drug administration, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and means for drug administration will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1510280