Polymeric delivery system for a nonviscous prostaglandin-based solution without preservatives

Abstract

This invention concerns an ophthalmic solution including:at least one prostaglandin;a solubilizing agent;a gelling agent of the carbomer type;a carbomer polymerization-inhibiting agent;a co-gelling / co-solubilizing agent.

Description

RELATED APPLICATIONS[0001]The present application claims priority under 35 U.S.C. §119(a) to French application no. 1055236, filed Jun. 29, 2010, and claims priority under 35 U.S.C. §119(e) to U.S. provisional application, U.S. Ser. No. 61 / 359,699, filed Jun. 29, 2010, each of which is incorporated herein by reference.FIELD OF THE INVENTION[0002]The invention concerns eye drops or an ophthalmic solution whose active ingredient includes at least one prostaglandin, said solution containing no antimicrobial agents, notably of the quaternary ammonium type (such as benzalkonium chloride [BAK]).[0003]More precisely, and in the context of the invention, a polymeric delivery system has been developed to allow the prostaglandin solution to be as effective as a solution containing BAK, but without the disadvantages from a toxicological and allergenic point of view.BACKGROUND OF THE INVENTION[0004]Prostaglandins are well-known active ingredients administered topically to humans or animals in t...

AI Technical Summary

Benefits of technology

[0035]Another important characteristic of the ophthalmic solution is its viscosity. This is advantageously between 8 and 20 mPa·s (cP), even more advantageously between 10 and 14 mPa·s (cP), when measured with a Brookfield RVDV III rotational viscometer at 25° C. This solution can indeed be distinguished from an aqueous gel, typically characterized by a viscosity between 400 and 800 mPa·s (cP) and which constitutes a long-acting form to obtain sustained release of the active ingredient.

[0045]Indeed, the solution's fluidity, combined with the product's stability when packaged in a LDPE container, makes its production compatible with BFS technology.

[0051]The present application reveals that contrary to the technical solutions disclosed in the prior art, administering a composition according to the present invention leads to a regular and progressive decrease of the intra-ocular pressure (TOP), without an intermediary initial IOP increase. Thanks the present composition, the IOP decrease starts earlier, with an end-effect at least equal possibly better. Without being bound to a theory, this effect on TOP could be due to the presence of the delivery system able to counteract or at least to attenuate the agressivity of the solubilizing agent. Moreover, a composition according to the invention is safe and well-tolerated.

Problems solved by technology

The first disadvantage of prostaglandins is that they are not water-soluble, meaning that they require a solubilization step before including them in the eye drop solution.

It should be pointed out that, despite the presence of BAK, these eye drops are not stable at ambient temperature and must be stored cold, at a temperature of approximately 5° C. Furthermore, the Allergan company sells eye drops under the Lumigan® brand, combining bimatoprost and BAK at 0.005% by weight.

However, many publications discourage the use of antimicrobial preservatives, and particularly BAK, for long-term treatments in ophthalmology, as is notably the case of glaucoma, due to tolerance problems (on this subject, see “The New Class of Ophthalmic Agents: Here's how to choose the right prostaglandin for the each patient” by J. James Thimons, O.D., F.A.A.O.—Optometric Management, May 2002).

It thus has now been established that antimicrobial preservatives are toxic in long-term use, to such an extent that today there is a tendency to limit their use by reducing their concentration as much as possible in eye drops or, even better, to eliminate them completely from the formulas.

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