Polymer Formulations for nasolacrimal stimulation

#Described herein are polymer formulations that provide electrical contact between an electrode and a nasal or sinus tissue. Specifically, hydrogel formulations that are cross-linked using UV radiation are described. Methods of manufacturing the hydrogels and methods of treating dry eye with nasal stimulator devices including the hydrogels are also described.

#Dry eye disease is a major eye condition throughout the world for which no permanent cure is currently available. For example, it has been estimated that the current average annual cost of treating dry eye disease amounts to $850 per person (Yu, J., Andre, C. V., and Fairchild, C. J. “The economic burden of dry eye disease in the United States: a decision tree analysis.” Cornea 30 4 (2011): 379-387). Epidemiological estimates of frequency of incidence of dry eye disease vary widely, depending on the symptoms being monitored. For example, Friedman reports that the incidence of dry eye disease ranges from 5% to 35% globally (Friedman, N. “Impact of dry eye disease and impact on quality of life.” Current Opinion in Ophthalmology 21 (2010): 310-316).

#Current treatments include the use of lubricants (e.g., hydroxymethyl and sodium carboxypropyl cellulose, generally known as artificial tears), anti-inflammatory therapies (e.g., corticosteroids and immunomodulators such as cyclosporin), tear retention therapies (e.g., punctal plugs), and treatment of underlying causes such as meibomian gland dysfunction, lid abnormalities, etc. These treatments have been shown to have a mild to moderate improvement in the quality of life of the patient. For example, the Lacrisert® ophthalmic insert (Aton Phama, Lawrenceville, N.J.), a hydroxypropyl cellulose ophthalmic insert placed in the inferior eyelid cul-de-sac, was shown to have a 21% improvement in ocular surface disease index scores by McDonald, et al. (McDonald, M. B., D'Aversa, Perry H. D., et al. “Hydroxypropyl cellulose ophthalmic inserts (Lacrisert) reduce the signs and symptoms of dry eye syndrome.” Trans Am Ophthalmol Soc 107 (2009): 214-222). However, these treatments often require multiple administrations per day, and typically do not prevent long term damage to the ocular surface, often caused by the chemical being administered. For example, it is known that preservatives (e.g., benzalkonium chloride) can cause damage to the ocular surface and cause irritation.

#FIG. 1 depicts an exemplary nasal stimulator device having an adjustable pair of stimulator electrodes.

#FIG. 2 depicts a top view of the disposable component of another exemplary nasal stimulator device including a pair of spring-like electrodes substantially enclosed by an opaque sleeve.

#FIGS. 3A-3C depict exemplary configurations of the electrically conductive polymer provided in the disposable component of a nasal stimulator device. FIG. 3A shows a perspective view of the stimulator electrode surrounded by an opaque polymeric sleeve. FIG. 3B is a cross-sectional view of the stimulator electrode in FIG. 3A showing an electrically conductive polymer disposed within the tip portion. FIG. 3B depicts a stylized view of the stimulator electrode in FIG. 3A where the conductive polymer forms a shell around the distal end of the polymeric sleeve.

#The polymer formulations described herein are generally hydrogels that may be used to facilitate an electrical connection between an electrode of a nasal stimulator device and nasal or sinus tissue, as mentioned above. Accordingly, the hydrogels are biocompatible and formed to be non-irritating and non-abrasive to nasal and sinus tissue. The hydrogels are generally also formed so that they do not break or shatter during insertion or use, and have moderate adhesion to nasal or sinus tissue in order to minimize contact resistance, heating, and heat damage to the tissue it contacts. The hydrogels may be prepared by cross-linking of various monomers using UV or visible light. The nasal stimulator device may include a disposable component and a reusable component. The disposable component may generally include a pair of stimulator electrodes and the electrically conductive hydrogel, and the reusable component a source of electrical energy for the stimulator electrodes. However, in some instances the nasal stimulator device can be made to be completely disposable.

#Electrically Conductive Hydrogel Formulations

#The electrically conductive hydrogels (“conductive hydrogels”) may comprise any monomer that is capable of providing a formulation suitable for use with nasal or sinus tissue, and suitable to facilitate an electrical connection between a nasal stimulator device, e.g., a hand-held nasal stimulator device, and nasal or sinus tissue. The formulation is typically prepared by UV cross-linking of the monomers, as further described below. In some variations, the formulations provide electrically conductive acrylate/methacrylate/vinyl hydrogels. In other variations, the formulations provide electrically conductive silicone-acrylate hydrogels.