Prostamide-containing intraocular implant
AssigneeAllergan, Inc.
InventorsPatrick M. Hughes, Jie Shen, Michael R. Robinson, David F. Woodward, Robert M. Burk, Hui Liu, Jinping Wan, Chandrasekar Durairaj, Gyorgy F. Ambrus, Ke Wu, Danny T. Dinh
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Abstract
Prostamide-containing biodegradable intraocular implants, prostamide compounds, prostamide-containing pharmaceutical compositions, and methods for making and using such implants and compositions for the immediate and sustained reduction of intraocular pressure and treatment of glaucoma in an eye of a patient are described.
Claims15
A biodegradable intraocular implant comprising a biodegradable polymer material and a therapeutic agent associated with the biodegradable polymer material, wherein the therapeutic agent comprises a compound having the formula (III)
- or a pharmaceutically acceptable salt or ester prodrug thereof, wherein X is —OH or —N(R1)2, and wherein R1 is independently selected from the group consisting of hydrogen and C1-C6 alkyl, and wherein the implant is effective for reducing intraocular pressure (IOP) in a mammalian eye.
A biodegradable intraocular implant comprising a biodegradable polymer material, hexadecan-1-ol, and 8% by weight of a compound having the formula
- wherein the compound and the hexadecan-1-ol are associated with the biodegradable polymer material, and wherein the biodegradable polymer material comprises i) a poly(D,L-lactide) having an ester end group and an inherent viscosity of 0.25-0.35 dl/g, ii) a poly(D,L-lactide) having an acid end group and an inherent viscosity of 0.16-0.24 dl/g, and iii) a poly(D,L-lactide-co-glycolide) having an ester end group, an inherent viscosity of 0.16-0.24 dl/g, and a D,L-lactide:glycolide molar ratio of about 75:25, wherein the inherent viscosity of each poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymer as given above is measured for a 0.1% solution of the polymer in chloroform at 25° C.
A method for reducing intraocular pressure in a patient, comprising administering a therapeutically effective amount of a therapeutic agent directly into the anterior chamber of an eye in the patient, thereby reducing intraocular pressure in the eye, wherein the therapeutic agent has the formula
A method for making a biodegradable intraocular implant effective for reducing intraocular pressure in a patient, the implant comprising or consisting of a biodegradable polymer material and a therapeutic agent associated with the biodegradable polymer material, wherein the therapeutic agent has the formula (Compound 1)
- and wherein the method comprises in order
- (I) obtaining Compound 1 in the form of a solid;
- (II) blending said solid form of Compound 1 with a biodegradable polymer or two or more biodegradable polymers to form a mixture;
- (III) extruding the mixture to form a filament;
- and
- (IV) cutting the filament to lengths suitable for placement in an ocular region of an eye, thereby forming the intraocular implant;
- wherein obtaining Compound 1 in the form of a solid comprises
- a) adding an oil form of Compound 1 to ethyl acetate (EtOAc) at approximately 50° C. to form a mixture;
- b) agitating the mixture of step a) at 50° C. to form a clear solution;
- c) cooling the clear solution of step b) to approximately 30° C. for 1-3 hours;
- d) adding a seed crystal of Compound 1 to the cooled solution of step c);
- e) maintaining the seeded solution of step d) at about 30° C. for 1-3 hours;
- f) cooling the seeded solution from step e) to a temperature of from about 0-5° C. over the course of about 1-5 hours;
- g) agitating the solution from step f) at a temperature of from about 0-5° C. for 1-3 hours to form a suspension;
- h) filtering the suspension from step g) at a temperature of between about 20° C. and 25° C. to thereby produce a solid form of Compound 1;
- and
- wherein the seed crystal Compound 1 is prepared by the method comprising
- i) dissolving an oil form Compound 1 in EtOAc at a temperature of from about 35-40° C. to form a mixture;
- ii) agitating the mixture of step i) at a temperature of from about 35-40° C. to form a clear solution;
- iii) cooling the clear solution of step ii) to a temperature of from about 0-5° C. over the course of about 1-5 hours;
- iv) agitating the cooled solution from step iii) at a temperature of from about 0-5° C. for 1-3 hours to form a white suspension;
- v) filtering the white suspension from step iv) at a temperature of between about 20° C. and 25° C. to thereby produce seed crystal of Compound 1.
Dependencies are inferred from the claim text.