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.
Claims19
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 (TOP) in a mammalian eye.
The method of claim 10, wherein Y is ═O.
The method of claim 10, wherein Y is 2 hydrogen radicals.
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 (I)
- or a pharmaceutically acceptable salt or ester prodrug thereof, wherein the wavy segments represent an α or β bond, dashed lines represent a double bond or a single bond, R is a substituted heteroaryl radical, wherein each R1 is independently selected from the group consisting of hydrogen and a lower alkyl radical having up to six carbon atoms, X is —OR1, —N(R1)2, or —N(R1)SO2R6, wherein R5 represents hydrogen or CH2OR6, R6 represents hydrogen, a lower alkyl radical having up to six carbon atoms, a halogen substituted derivative of said lower alkyl radical, or a fluoro substituted derivative of said lower alkyl radical, and R15 is hydrogen or a lower alkyl radical having up to six carbon atoms;
- and Y is =O or represents 2 hydrogen radicals, wherein the substituent(s) on the substituted heteroaryl radical in Formula I is/are selected from the group consisting of C1 to C6 alkyls, halogens, trifluoromethyl, COR1, COCF3, SO2N(R1)2, NO2, and CN.
A method for obtaining Compound 1:
- in the form of a solid, the method comprising:
- 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 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 of Compound 1 is prepared by the method comprising
- i) dissolving an oil form of 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) 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.