Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
1999-06-14
2004-03-30
Spear, James M. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
Reexamination Certificate
active
06713080
ABSTRACT:
FIELD OF THE INVENTION
The invention concerns a lens made from a hydrophilic polymer intended for implantation in the eye of a subject, in substitution for a defective crystalline lens, during a surgical operation.
Such lenses, known as intraocular lenses (IOL) or intraocular implants and artificial lenses are widely used, in particular to replace an opaque crystalline lens, a condition known as of cataract.
Given the nature of the surgery and the products used, the success such operations depends on the concomitant administration of various medications to limit and attenuate the risks of inflammation.
The corresponding treatment comprises the instillation or delivery of appropriate medications, including anti-inflammatory agents, into the eye, two to four times a day, sometimes more, for a long time period, up to a month.
Given that the external membranes of the eye, namely the cornea and the sclera, represent barriers to the passage of medication, the medications must be administered in much higher doses, the excess being either wasted or, which is more serious, drained by the lachrymal liquid and thereafter passing into the systemic circulation, increasing side effects and toxic effects.
The object of the invention is to optimize the therapy by reducing the doses of medication and the risks of side effects by releasing the active principles directly at the site where their action is required, exploiting the fact that, during implantation, an incision is made in the sclera and/or cornea through which the lens is passed.
PRIOR ART
It has been proposed [Journal of Cataract & Refractive Surgery, vol. 21, No. 5, 1995 (Nishi et al): Effect of indomethacin coated posterior chamber intraocular lenses on postoperative inflammation and posterior capsule opacification”, EP-A-0,563,984 (Unitika Ltd)] to form a surface deposit of a polymer containing anti-inflammatory or like agents on IOLs so that the medication acts at the precise location where its action is required. However, the quantity of medication is small (the thickness of the coating is necessarily small), it is released into the aqueous humor practically extemporaneously, and its action is hardly prolonged beyond that of medication injected directly into the aqueous humor during the operation. The authors aim to alleviate the immediate reactions of the eye to implantation. These surface treatments do not remove the need for conventional postoperative treatment, which has the drawbacks mentioned above.
EP-A-0 594 948 describes an implant capable of releasing an appropriate medication into the orbit or the eyeball. This implant, which is in the form of an elongate open ring, consists of a biodegradable polymer into the mass of which a medication has been incorporated. The release of the medication is the result of biodegradation. This mode of operation is manifestly incompatible with its incorporation into an intraocular lens, which is implanted permanently and therefore must not be subject to any degradation.
EP-A-0 594 948 claims that the implant it describes could be used as a component part of an intraocular lens. It seems that a component of this kind could not constitute a functional component of the lens (optic and haptic parts) because of its biodegradable, and therefore essentially temporary, nature.
EP-A-0335785 describes polymers for making contact lenses that include the conventional constituents of a hydrogel and a monomer carrying active product that can be copolymerized with the constituents, the monomer including an aryl radical which has a phenol function esterified by a substance with an acid function of the indomethacin type constituting said active product. The monomer can in particular be 4-methacrylamidophenol indomethacin.
SUMMARY OF THE INVENTION
According to an aspect of the invention, a lens is provided for implantation in the eye of a subject, and notably to be substituted for a defective crystalline lens, after extraction, during a surgical operation, which lens is made from a polymer having a predetermined water content, the polymer containing, dispersed in its mass, an effective quantity of a medicated product with appropriate effects, in particular at least partial inhibition of postoperative reactions of the eye, the association of the polymer and the dispersed medicated product being adapted to release the product progressively into the aqueous humor and intraocular tissues.
Because the polymers from which the lenses are made are hydrophilic, the medicated product is released progressively into the aqueous humor and is therefore in immediate range of the sites where its action is required.
In the present context a hydrophilic polymer is a polymer that is able to contain water to enable release of the active products into the aqueous humor. The water content (hydrophilic rate) must be at least 0.20% by weight and preferably at least 0.25% by weight.
Other prior art
The article “Drug Uptake and Release by an Hydrogel Intraocular Lens and Human Crystalline Lens” (Heyrman T. P. et al.), published in Journal of Cataract & Refractive Surgery, vol. 15, No. 2, 1989, discusses the behavior of polymethyl methacrylate or PMMA IOLs compared to the eyes of living beings (rabbits and humans), vis-à-vis medications, in particular anti-inflammatory medications, used for operative and postoperative treatment in cataract surgery. Experiments in vitro and in vivo (on rabbits only) show that the hydrogel absorbs the medications in quantities and at a rate very similar to those for the crystalline lens and that release into the aqueous (and vitreous) humor occurs under similar conditions. The authors conclude that the IOLs studied cannot function as significant reserves of medications in the eye.
The article “Drug Interaction with Intraocular Lenses of Different Materials” (J. M. Chapman et al.) published in Journal of Cataract & Refractive Surgery, vol. 18, No. 5 (1992), complements earlier studies on the interaction of medications with PMMA and polyhydroxyethyl methacrylate (or polyHEMA) IOLs (including the studies reported in the article mentioned previously), by considering other materials and other medications. The article concludes that IOLs cannot deliver sufficient quantities of medications into the eye to modify significantly the kinetics of medications applied topically, sub-conjunctively or intravenously and replace conventional treatments.
The communication “Use of Methyl Polymethacrylate (PMMA) as a Drug Support” EI Meski, Beyssac and Aiache; Proc. 1st World Meeting APGI/APV, Budapest 9/11 May 1995, pages 323-324, teaches a method of incorporating a medication into PMMA including drying of the polymer, absorption of a solution of medication in a water/ethanol support comprising 57% by weight of ethanol and final drying (5 days at 110° C.) to evacuate the support.
The step from the teaching of the above communication to the method as defined hereinabove has necessitated, on the one hand, the original concept of using the material of a hard intraocular lens as a reservoir of a medicated product that can be released into the aqueous humor and the surrounding ocular tissues and, on the other hand, the unexpected discovery that the polymer treated in accordance with the teachings of the aforementioned communication could provide a lens optically and surgically suited to long-term substitution for the crystalline lens.
The above communication notes that diffusion of the support into the polymer causes profound changes to the structure of the implant, namely a change from the hard vitreous state to an elastic state analogous to rubber during impregnation, followed by a return to the vitreous state on evaporating the support.
Furthermore, the step from the treatment of a material for hard lenses to that of a material for soft lenses, implanted in a swollen state, involved major unknowns because of the different behaviors of the polymers relative to the solvents likely to constitute the supports and the different rates of diffusion and release specific to these types of polymers.
Our work has shown t
Aiache Jean-Marc
El Meski Said
Serpin Gilbert
Tourrette Philippe
Fubara Blessing
Ioltechnologie-Production
Spear James M.
Young & Thompson
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