Corneal treatment agents

Abstract: Pharmaceutical compositions comprising aliphatic alcohols are disclosed for use in therapy, for example eye therapy and in particular for the treatment of discomfort and visual artifacts following laser surgical procedures on the cornea of the eye. Such compositions reduce the inflammation associated with photorefractive keratectomy and promote the regrowth of epithelial tissue over the reprofiled corneal surface. The compositions may comprise aliphatic alcohols having a chain length ranging from about C-20 to about C-26, and may include docosanol, tetracosanol or hexacosanol, or mixtures thereof.

Description: The technical field of this invention is corneal surgery and, in particular, the invention relates to pharmaceutical compositions for treating the cornea following laser reprofiling operations. Various surgical techniques are known for altering the surface of the cornea to correct refractive errors in vision. Such techniques include radial keratotomy ("RK") in which a set of radial incisions, i.e., resembling the spokes of a wheel, are made in the eye, down into the stroma of the cornea. As the incisions heal, the curvature of the eye is flattened, thereby remedying myopic conditions. Additionally, operations, such as keratoplasty, have been performed in which the surface of the cornea is sculpted to a new desired shape. Until recently, such surgical operations on the cornea were most commonly carried out using diamond or steel knives or razors. However, corneal surgery, particularly with mechanical instruments, has often been less than satisfactory because the basement membrane upon which the epithelium attaches to the corneal proper is destroyed or damaged to an extent where epithelial cells cannot regrow and form a continuous protective layer over the surface of the eye. Recently, new laser surgical techniques have been developed to ablate or otherwise treat corneal defects without mechanical abrasion. These techniques include photorefractive keratectomy ("PRK") and phototherapeutic keratectomy ("PTK") in which laser radiation is applied to the cornea with minimal heating effects to ablate or smooth refractive aberrations. Such laser techniques will usually create a pseudo basement membrane (or smooth anterior surface) on the outside of the cornea which facilitates epithelial cell attachment and, hence, healing of the eye. Nonetheless, even with laser surgical approaches, there exists a need for methods and agents to facilitate corneal healing. A new technique for corneal reshaping involves the use of a pulsed laser photoablation apparatus to ablate very thin layers of corneal tissue with greater precision than can typically be achieved with mechanical means. Such laser photoablation procedures typically employ a beam shaping or masking apparatus which varies the size of the exposure area on the corneal surface over time or provides a predefined profile of resistance to the laser radiation, such that areas of the cornea receive different cumulative exposures and thereby are ablated to varying depths. These laser corneal reprofiling operations are typically referred to as photorefractive keratectomy ("PRK") and are performed with a high energy excimer laser which emits ultraviolet ("UV") laser radiation which is capable of ablating biological tissues without thermal damage to surrounding tissue. For further details on PRK techniques, see Marshall et al, "Photo-ablative Reprofiling Of The Cornea Using An Excimer Laser: Photorefractive Keratectomy," cit. Vol. I, Lasers in Ophthalmology , pp. 21-48 (1986) and U.S. Patents 4,856,513 and 4,941,093. In clinical trials of PRK procedures, patients typically experience some ocular discomfort immediately following surgery, together with a "cloudiness" in vision, which usually resolves itself in a matter of days or weeks. There exists a need for methods for treating the newly reprofiled surface of the cornea to minimize the discomfort and visual artifacts that often accompany PRK procedures. In particular, compositions which can be topically applied to the eye in order to reduce discomfort and/or visual artifacts would satisfy an important medical need. The invention provides the use, for the manufacture of a medicament, of an aliphatic alcohol having a chain length ranging from C-20 to C-26 as the or a pharmacologically-active agent of said medicament for use in the treatment of the eye, to reduce discomfort and/or visual artefacts. The invention also provides the use for the manufacture of a medicament, of an aliphatic alcohol having a chain length ranging from C-20 to C-26 as the or a pharmacologically-active agent of said medicament, for use in the treatment of the eye to promote regrowth of epithelial tissue. The invention also provides a pharmaceutical composition comprising 0.2 - 30% by weight of an aliphatic alcohol having a chain length ranging from C-20 to C-26 in a physiologically acceptable carrier, said composition further comprising one or more other pharmacologically-active agents selected from analgesics, growth factors, immuno-modulators, anti-allergenics and steroids except hydrocortisone. The description which follows is given by way of example of the invention only and not by way of limitation thereof. Pharmaceutical compositions comprising aliphatic alcohols ire disclosed for the treatment of discomfort and visual artifacts following laser surgical procedures on the cornea of the eye. Such compositions reduce the inflammation associated with photorefractive keratectomy and proate the regrowth of epithelial tissue over the reprofiled corneal surface. The compositions are preferably formulated in a physiologically compatible carrier which is non-irritating to the corneal surface and substantially inactive physiologically. The aliphatic alcohols useful in the present invention have chain lengths ranging from C-20 to C-26. Particular aliphatic alcohols useful in the present invention include docosanol, tetracosanol and hexacosanol. The present invention can be practiced using the aliphatic alcohol compositions alone or together with other physiologically active agents, such as steroids, analgesics, growth factors, anti-oxidants, immunomodulators and/or antiallergics. Pharmaceutical carriers useful in the present invention include water and non-irritating organic compounds. When water is used to form an aqueous carrier, it is preferable to include dispersants or co-solvents to stabilize the formulation. Alternatively, ointments can be prepared, for example, using white petrolatum, water, and fatty acid eaters and/or glycols to form a stable carrier. The active alcohols of the present invention can be added to the carrier in amounts ranging from 0.2 to 30% by weight, typically in the range of from 1% to 5% by weight. Aliphatic alcohols having a chain length ranging from C-20 to C-26 are employed. Shorter chain aliphatic articles tend to be irritants while longer chain aliphatic articles appear to have less efficacy in wound healing. As known by those skilled in the art, the administration, sequence of administration and the concentration of the treatment agent depends upon a number of factors, including, the nature of the surgical procedure, the extent of the corneal reprofiling, the medical history, symptoms prior to, during or after surgery, and the extent of visual artifacts. Selection of a particular concentration or combination of aliphatic alcohols can be made by the skilled clinician guided by the foregoing description. During ophthalmic surgery the compositions of the present invention can be applied before laser exposure, during the procedures, and/or following the reprofiling operation.

Claims: Use, for the manufacture of a medicament, of an aliphatic alcohol having a chain length ranging from C-20 to C-26 as the or a pharmacologically-active agent of said medicament for use in the treatment of the eye, to reduce discomfort and/or visual artefacts. Use, for the manufacture of a medicament, of an aliphatic alcohol having a chain length ranging from C-20 to C-26 as the or a pharmacologically-active agent of said medicament, for use in the treatment of the eye to promote regrowth of epithelial tissue. Use according to claim 1 or claim 2, wherein the treatment comprises applying the aliphatic alcohol topically to the affected eye. Use according to claim 1, 2 or 3, wherein the aliphatic alcohol is docosanol, tetracosanol or hexacosanol, or mixtures thereof. Use according to any one of the preceding claims, wherein the aliphatic alcohol is applied in a concentration ranging from 0.2 to 30% (e.g. 1 to 5%) by weight in a physiologically acceptable carrier to the cornea. A pharmaceutical composition comprising 0.2 - 30% by weight of an aliphatic alcohol having a chain length ranging from C-20 to C-26 in a physiologically acceptable carrier, said composition further comprising one or more other pharmacologically-active agents selected from analgesics, growth factors, immuno-modulators, anti-allergenics and steroids except hydrocortisone. Pharmaceutical composition according to claim 6, wherein the aliphatic alcohol comprises docosanol, tetracosanol or hexacosanol, or mixtures thereof. A composition according to claim 7, for use to reduce ocular discomfort and/or visual artefacts. A composition according to claim 7, for use to promote regrowth of epithelial tissue in the eye.

Inventors: MULLER DAVID F, MULLER, DAVID F.
Applicants: SUMMIT TECHNOLOGY INC, SUMMIT TECHNOLOGY, INC.
Application year: 1992
Main classification: A61K31
IPC codes: A61K9, A61P27, A61K31