Aqueous ophthalmic solutions of phentolamine and medical uses thereof
The invention provides aqueous ophthalmic solutions of phentolamine or pharmaceutically acceptable salts thereof, medical kits, and methods for using such ophthalmic solutions to improve visual performance in a patient. Exemplary aqueous ophthalmic solutions include those containing phentolamine mesylate, mannitol, sodium acetate, and water.
1 . A method of making an aqueous ophthalmic solution, the method comprising combining:
a. phentolamine or a pharmaceutically acceptable salt thereof, wherein the phentolamine or a pharmaceutically acceptable salt thereof has a concentration of from about 0.1% (w/v) to about 4% (w/v) in the aqueous ophthalmic solution;
b. at least one polyol compound selected from the group consisting of mannitol, glycerol, propylene glycol, ethylene glycol, sorbitol, and xylitol;
c. at least one buffer, wherein said buffer has a concentration of from about 0.1 mM to about 10 mM in the aqueous ophthalmic solution;
d. water;
provided the aqueous ophthalmic solution does not contain any additional ingredient that is a chelating agent, and wherein the aqueous ophthalmic solution does not contain any additional ingredient that is a stabilizer.
2 . The method of claim 1 , further comprising adjusting the pH of the solution to a pH of about 4.0 to about 7.5.
3 . The method of claim 2 , wherein the solution comprises about 1% (w/v) of phentolamine mesylate; the buffer comprises sodium acetate; and about 4% (w/v) mannitol is present in the solution.
4 . The method of claim 1 , further comprising storing the aqueous ophthalmic solution at temperature in the range of 2-8° C.
5 . The method of claim 2 , further comprising storing the aqueous ophthalmic solution at temperature in the range of 2-8° C.
6 . The method of claim 3 , further comprising storing the aqueous ophthalmic solution at temperature in the range of 2-8° C.
7 . A method of making an aqueous ophthalmic solution, the method consisting essentially of combining:
a. phentolamine or a pharmaceutically acceptable salt thereof, wherein the phentolamine or a pharmaceutically acceptable salt thereof has a concentration of from about 0.1% (w/v) to about 4% (w/v) in the aqueous ophthalmic solution;
b. at least one polyol compound selected from the group consisting of mannitol, glycerol, propylene glycol, ethylene glycol, sorbitol, and xylitol;
c. at least one buffer, wherein said buffer has a concentration of from about 0.1 mM to about 10 mM in the aqueous ophthalmic solution;
d. water;
provided the aqueous ophthalmic solution does not contain any additional ingredient that is a chelating agent; and wherein the aqueous ophthalmic solution does not contain any additional ingredient that is a stabilizer;
wherein optionally the pH of the solution is adjusted to a pH of about 4.0 to about 7.5, and optionally the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
8 . The method of claim 7 , wherein the pH of the solution is adjusted to a pH of about 4.0 to about 7.5.
9 . The method of claim 8 , wherein the solution contains about 1% (w/v) of phentolamine mesylate; the buffer comprises sodium acetate; and about 4% (w/v) mannitol is present in the solution.
10 . The method of claim 7 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
11 . The method of claim 8 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
12 . The method of claim 9 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
13 . A method of making an aqueous ophthalmic solution, the method consisting of combining:
a. phentolamine or a pharmaceutically acceptable salt thereof, wherein the phentolamine or a pharmaceutically acceptable salt thereof has a concentration of from about 0.1% (w/v) to about 4% (w/v) in the aqueous ophthalmic solution;
b. at least one polyol compound selected from the group consisting of mannitol, glycerol, propylene glycol, ethylene glycol, sorbitol, and xylitol;
c. at least one buffer, wherein said buffer has a concentration of from about 0.1 mM to about 10 mM in the aqueous ophthalmic solution;
d. water; and
e. optionally one or more of a poly(C 2-4 alkylene)glycol polymer, dextran, pharmaceutically acceptable carrier, cellulose agent, carbohydrate, alkali metal halide, alkaline earth metal halide, boric acid, cyclodextrin, dextrose, glycerin, urea, viscosity modifying agent, demulcent polymer, wetting agent, or water-miscible solvent;
wherein optionally the pH of the solution is adjusted to a pH of about 4.0 to about 7.5, and optionally the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
14 . The method of claim 13 , wherein the pH of the solution is adjusted to a pH of about 4.0 to about 7.5.
15 . The method of claim 14 , wherein the solution comprises about 1% (w/v) of phentolamine mesylate; the buffer comprises sodium acetate; and 4% (w/v) mannitol is present in the solution.
16 . The method of claim 13 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
17 . The method of claim 14 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
18 . The method of claim 15 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
19 . A method of making an aqueous ophthalmic solution, the method consisting essentially of combining:
a. phentolamine or a pharmaceutically acceptable salt thereof, wherein the phentolamine or a pharmaceutically acceptable salt thereof has a concentration of from about 0.1% (w/v) to about 4% (w/v) in the aqueous ophthalmic solution;
b. at least one polyol compound selected from the group consisting of mannitol, glycerol, propylene glycol, ethylene glycol, sorbitol, and xylitol;
c. at least one buffer, wherein said buffer has a concentration of from about 0.1 mM to about 10 mM in the aqueous ophthalmic solution;
d. water; and
e. optionally one or more of an alkali metal halide or alkaline earth metal halide;
provided the aqueous ophthalmic solution does not contain any additional ingredient that is a chelating agent; and wherein the aqueous ophthalmic solution does not contain any additional ingredient that is a stabilizer;
wherein optionally the pH of the solution is adjusted to a pH of about 4.0 to about 7.5, and optionally the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
20 . The method of claim 19 , wherein the pH of the solution is adjusted to a pH of about 4.0 to about 7.5.
21 . The method of claim 20 , wherein the solution comprises about 1% (w/v) of phentolamine mesylate; the buffer comprises sodium acetate; and 4% (w/v) mannitol is present in the solution.
22 . The method of claim 19 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
23 . The method of claim 20 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
24 . The method of claim 21 , wherein the aqueous ophthalmic solution is stored at a temperature in the range of 2-8° C.
25 . An aqueous ophthalmic solution made by the method of claim 13 .
26 . An aqueous ophthalmic solution made by the method of claim 14 .
27 . An aqueous ophthalmic solution made by the method of claim 15 .
28 . An aqueous ophthalmic solution made by the method of claim 19 .
29 . An aqueous ophthalmic solution made by the method of claim 20 .
30 . An aqueous ophthalmic solution made by the method of claim 21 .