Title:  Drug delivery system for antiglaucomatous medication

United States Patent:  6,410,045

Appl. No.:  507437

A drug delivery system for antiglaucomatous medications utilizing a polymeric hydrogel which can absorb an ophthalmic medication which can then be transferred into the ocular fluid of the eye.

DETAILED DESCRIPTION OF THE INVENTION

It is known to use polymeric hydrogel compositions to as medication delivery systems. The use of polymeric hydrogels as contact lenses to dispense medications in the eye is known as disclosed in U.S. Pat. Nos. 4,617,299; 4,668,506, and 5,723,131, the teachings of which are herein incorporated by reference. It is further known to use polymeric hydrogel contact lenses to deliver antiglaucomatous medications in combination with corticosteroid medications to reduce IOP as disclosed in U.S. Pat. No. 5,212,168. Polymeric hydrogel contact lenses are also known to be used as carriers of antibiotics which are dispensed into the eye as disclosed in U.S. Pat. No. 5,723,131.

However, it is not known to use polymeric hydrogel contact lenses to which timolol maleate or brimonidine tartrate, have been passively transferred, in concentrations lower than their currently known dosages, to treat elevated IOP in humans.

Patients, previously diagnosed with elevated IOP, were used as subjects in clinical tests conducted to determine whether or not hydrogel lenses containing passively transferred dilute concentrations of timolol maleate or brimonidine tartrate could effectively control increased IOP.

A further understanding of the invention may be obtained from the following non-limiting examples.

EXAMPLE 1

A hydrogel contact lens for the right eye was prepared by washing an etafilcon A lens in a saline solution and then drying the lens briefly. This partially desiccated lens was then placed in an aqueous solution of brimonidine tartrate at a concentration 0.02% or 0.2 mg of brimonidine tartrate/ml, at a pH of 7.0-7.4 for 3 hours. This prepared lens was then tested in a patient who had previously been using one drop of a brimonidine tartrate 0.2% solution in his right eye every twelve hours and which had maintained his IOP below 20 mmHg. The IOP in this patient's left eye was normal and did not require treatment. After a 4 day washout period in which all ocular medications were discontinued, the patient's IOP rose above 22 mmHg in the right eye. The patient then wore the lens treated with the brimonidine tartrate in his right eye for 30 minutes once a day. Within 24 hours the IOP in this patient's right eye had dropped to below 20 mmHg. No signs of ocular toxicity were noted upon subsequent slit lamp examination.

EXAMPLE 2

The lenses were tested in a patient who had a history of elevated IOP in both eyes and who had been treated with one drop of 0.25% timolol maleate ophthalmic solution in both eyes every 12 hours which had controlled her IOP for approximately 2 years. Eventually her IOP rose and it was necessary to change her anti-glaucoma medication to one drop every twelve hours of 0.25% timolol maleate ophthalmic gel forming solution. Provision of this medication in a gel carrier increases the time in which the medication remains in the ocular environment which should improve the efficacy of the drug. Following this treatment approach the patient's IOP remained controlled for the next 5 years.

The patient then volunteered to test etafilcon A contact lenses which were prepared for use by washing the contact lenses in a saline solution and then drying the lenses briefly. These partially desiccated lenses were then placed in an aqueous solution of diluted timolol maleate at a concentration of 0.05% or 0.68 mg timolol maleate/ml for 3 hours. After this soaking period in which timolol maleate was passively transferred to the lenses, the lenses were subsequently worn by the patient for 30 minutes once a day. During the time this patient followed this regimen her IOP was maintained at less than 20 mmHg. Slit lamp examination after this treatment revealed no signs of ocular toxicity.

Subsequently the patient's elevated IOP was effectively managed with the administration of daily timolol maleate ophthalmic gel forming solution at one fifth of her previous dosage of this medication.

EXAMPLE 3

The medicated lenses of this invention were tested in a patient who had a history of elevated IOP and had been controlled with a daily dose of 0.5% timolol maleate ophthalmic gel forming solution in each eye for two years. However, after this two year period the patient's IOP was no longer properly controlled by this medication regimen. The patient began a four day washout period during which all anti-glaucoma medication was discontinued. The patient's IOP remained above 20 mmHg during this interval. After this period the patient then tested a set of etafilcon A hydrogel lenses which were prepared by washing them in a saline solution and then drying them briefly. These partially desiccated lenses were then soaked in a dilute, aqueous solution of timolol maleate 0.05% by concentration or 0.68 mg timolol maleate/ml for 3 hours. Timolol maleate at this concentration was passively transferred to the lenses which were then worn by the patient for 30 minutes once a day. The patient's IOP was well controlled at a level of less than 20 mmHg for at least 6 months. No signs of ocular toxicity were noted on subsequent slip lamp examination.

Subsequently the procedure of Example 3 was repeated with 4 different types of polymeric hydrogel lenses, differing particularly in polymer type or water content. Each of the 4 differing types of polymeric hydrogel lenses; polymacon, vifilcon, ocufilcon and omnifocon, were capable of delivering an effective dose of timolol maleate which had been passively transferred to the lens.

This invention is principally directed at the passive transfer of an antiglaucomatous medicament into a polymeric hydrogel and this subsequent delivery of this medicament into the ocular fluid of the eye.

The polymeric material of this invention is a polymeric hydrogel which has been described as a hydrophilic polymer capable of forming a hydrogel when contacted with water as disclosed in U.S. Pat. No. 5,256, 751.

It is known to use various polymeric hydrogel lenses with absorbed medicinal agents as medication delivery systems. To be effective for the purposes of this invention, the lens must be a polymeric hydrogel with a water content of about 38-60% by weight and the medicinal agent must be capable of being absorbed in a dilute form into the lens in an amount sufficient to allow a period of sustained delivery of this medication into the ocular fluid. The polymer can be ionic or nonionic. A preferred composition of the polymer is a tetrapolymer of hydroxymethylmethacrylate, ethylene glycol, dimethylmethacrylate, and methacrylic acid. A preferred monomer forming the hydrophilic polymer is the hydroxyester 2-hydroxyethyl methacrylate (HEMA).

Numerous medications are known to be absorbed into a polymeric hydrogel contact lenses and subsequently transferred into the ocular liquid. A preferred additive in this invention is dilute timolol maleate. In this preferred embodiment the dilute timolol maleate is delivered in an aqueous solution to a polymeric hydrogel contact lens in a concentration of 0.68 mg of timolol maleate/mi or a 0.05% concentration of timolol maleate solution at a pH of about 7.0-7.4 for at least three hours, after this contact lens has been washed in saline solution and then dried for at least 15 minutes.

An additional preferred additive in this invention is dilute brimonidine tartrate which is delivered in an aqueous solution to a polymeric hydrogel contact lens in a concentration of 0.2 mg brimonidine tartrate/ml or a 0.02% concentration of brimonindine tartrate solution at a pH of about 7.0-7.4 for at least three hours, after this contact lens has been washed in saline solution and then dried for at least 15 minutes.

In the foregoing the invention has been described in terms of certain preferred embodiments for the purpose of illustration and not limitation. It is to be understood that any changes or modifications obvious to those skilled in the art based on this disclosure are intended to be within the scope of the invention as claimed.

Claim 1 of 18 Claims

What is claimed is:

1. A drug delivery system comprising a polymeric hydrogel contact lens containing timolol maleate in a concentration of between 0.05% and 0.25% by weight absorbed in said contact lens which is capable of being delivered into the ocular fluid.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.