Compositions and Methods for Treatment of Glaucoma
The invention provides α-2 adrenergic receptor agonist compositions and methods for treating glaucoma and other intraocular conditions. The preferred α-2 agonist used in the inventive compositions and methods is dexmedetomidine at acidic pH and extremely low concentrations.
1 . A pharmaceutical composition comprising dexmedetomidine at a concentration from between about 0.007% to about 0.07% weight by volume, wherein said pharmaceutical composition has a pH of between about 4.0 and 6.2, and wherein said pharmaceutical composition is effective for the treatment of glaucoma in a patient in need thereof.
2 . The pharmaceutical composition of claim 1 , wherein dexmedetomidine is at a concentration from between about 0.025% to 0.035% weight by volume.
3 . The pharmaceutical composition of claim 2 , wherein said pH is between about 5.0 and 5.7.
4 . The pharmaceutical composition of claim 1 , further comprising a salt selected from the group consisting of citrate, mesylate, hydrobromide/bromide, acetate, fumarate, sulfate/bisulfate, succinate, phosphate, maleate, nitrate, tartrate, benzoate, carbonate, and pamoate.
5 . The pharmaceutical composition of claim 4 wherein said salt is citrate at a concentration of from 0.10% to about 0.50% weight by volume.
6 . A pharmaceutical composition comprising dexmedetomidine at a concentration from between about 0.02% to about 0.04% weight by volume, wherein said pharmaceutical composition has an octanol-water partition coefficient Log D of between about 0.70 and about 2.20, and wherein said pharmaceutical composition is effective for the treatment of glaucoma in a patient in need thereof.
7 . The pharmaceutical composition of claim 6 , wherein said octanol-water partition coefficient is between about 1.25 and 2.00.
8 . The pharmaceutical composition of claim 6 , wherein said pharmaceutical composition further comprises carboxymethyl cellulose, hydroxymethylcellulose, polyvinylpyrridone, or another viscosity enhancer.
9 . The pharmaceutical composition of claim 6 , wherein said pharmaceutical composition has a pH of between about 4.0 and 6.2.
10 . A pharmaceutical composition comprising dexmedetomidine at a concentration from between about 0.02% to about 0.035% weight by volume, further comprising one or more salts selected from the group consisting of citrate, mesylate, hydrobromide/bromide, acetate, fumarate, sulfate/bisulfate, succinate, phosphate, maleate, nitrate, tartrate, benzoate, carbonate, and pamoate, wherein said pharmaceutical composition has a pH of between about 4.0 and 6.2, wherein said pharmaceutical composition has an octanol-water partition coefficient Log D of between about 1.25 and about 2.20, and wherein said pharmaceutical composition is effective for the treatment of glaucoma in a patient in need thereof.
11 . The pharmaceutical composition of claim 10 comprising
a. dexmedetomidine at a concentration from between 0.002% and about 0.02% weight by volume;
b. 0.9% normal saline; and
c. a viscosity enhancer, wherein said viscosity enhancer results in the viscosity of the pharmaceutical composition to be about 3.0 cps.
12 . The pharmaceutical composition of claim 11 where the pH range is between 4.0 and 6.2.
13 . The pharmaceutical composition of claim 10 , comprising a buffer at a concentration between 1 mM and 100 mM, wherein said buffer is selected from acetate, citrate, maleate, sorbate, or phosphate buffer.
14 . A pharmaceutical composition comprising:
a. dexmedetomidine at a concentration from between about 0.01% and about 0.05% weight by volume;
b. 0.9% normal saline; and
c. a mucoadhesive,
wherein the salinity of said pharmaceutical composition is about 280-320 milliosmoles.
15 . The pharmaceutical composition of claim 14 where the concentration of dexmedetomidine is between about 0.030% and about 0.040%.
16 . The pharmaceutical composition of claim 14 where said mucoadhesive is selected from carbapols, poloxamers, xanthum gums, and cellulose derivatives, and wherein said mucoadhesive is at a concentration from between about 0.5% and about 10%.
17 . The pharmaceutical composition of claim 16 where said poloxamer is Poloxamer 407.
18 . A method of treating glaucoma in a patient in need thereof comprising administering to said patient the pharmaceutical composition of claim 1 .