PHARMACEUTICAL COMPOSITIONS FOR TREATING PRESBYOPIA AND METHODS FOR FABRICATING THEREOF
Pharmaceutical compositions for treating presbyopia are described, the compositions comprising choline esterase inhibitor(s) and several other components such as α-1-adrenergic antagonist(s), non-steroid anti-inflammatory drug(s), and/or adrenergic antagonist(s). Methods for fabricating the compositions and using the compositions are also described.
1 . An ophthalmological pharmaceutical composition for treating, alleviating, and/or mitigating presbyopia, the composition comprising:
(a) a therapeutically effective quantity of at least one cholinesterase inhibitor;
(b) a therapeutically effective quantity of at least one α-1-adrenergic antagonist;
(c) optionally, a therapeutically effective quantity of at least one non-steroid anti-inflammatory drug;
(d) optionally, at least one penetration enhancer;
(e) optionally, a quantity of glycerol;
optionally, a quantity of dextran;
(g) optionally, a quantity of chondroitin sulfate; and
(h) a quantity of de-ionized water.
2 . The ophthalmological pharmaceutical composition of claim 1 , wherein the cholinesterase inhibitor is selected from the group consisting of echothiophate iodide, physostigmine, pyridostigmine, neostigmine, aceclidine, ambenonium, demecarium, rivastigmine, galantamine, caffeine, rosmarinic acid, α-pinene, donepezil, tacrine, edrophonium, huperzine A, ladostigil, ungeremine, lactucopicrin, acotiamide, diisopropyl fluorophosphate, cadusafos, chlorpyrifos, cyclosarin, dichlorvos, dimethoate, metrifonate, and any combination thereof.
3 . The ophthalmological pharmaceutical composition of claim 2 , wherein the cholinesterase inhibitor is selected from the group consisting of echothiophate iodide, physostigmine, pyridostigmine, neostigmine, and any combination thereof.
4 . The ophthalmological pharmaceutical composition of claim 2 , wherein the cholinesterase inhibitor is neostigmine.
5 . The ophthalmological pharmaceutical composition of claim 1 , wherein the α-1-adrenergic antagonist is selected from the group consisting of dapiprazole, tamsulosin, alfuzosin, doxazosin, prazosin, terazosin, phentolamine, phentolamine mesylate, phenoxybenzamine, tolazoline, and trazodone, and any combination thereof.
6 . The ophthalmological pharmaceutical composition of claim 5 , wherein the α-1-adrenergic antagonist is dapiprazole.
7 . The ophthalmological pharmaceutical composition of claim 1 , wherein the non-steroid anti-inflammatory drug is selected from the group consisting of bromfenac, ketorolac, diclofenac, nepafenac, and combinations thereof.
8 . The ophthalmological pharmaceutical composition of claim 1 , wherein the penetration enhancer is selected from the group consisting of non-ionic polyoxyethlene-polyoxypropylene block copolymers, cross-linked polyacrylic acid, and combinations thereof.
9 . The ophthalmological pharmaceutical composition of claim 8 , wherein the penetration enhancer is poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol).
10 . The ophthalmological pharmaceutical composition of claim 1 , wherein the concentration of the cholinesterase inhibitor(s) in the composition is between about 0.0001% (w/v) and about 0.25% (w/v), and the concentration of the α-1-adrenergic antagonist(s) is between about 0.1% (w/v) and about 0.5% (w/v).
11 . A method for treating, alleviating, and/or mitigating presbyopia in a human subject in need of such treatment, comprising administering to the subject the ophthalmological pharmaceutical composition of claim 1 , thereby treating, alleviating, and/or mitigating presbyopia.
12 . The method of claim 11 , wherein the ophthalmological pharmaceutical composition is administered by eye drops.
13 . The method of claim 11 , wherein the ophthalmological pharmaceutical composition is administered into one eye of the subject, or to both eyes of the subject.
14 . An ophthalmological pharmaceutical composition for treating, alleviating, and/or mitigating presbyopia, the composition comprising:
(a) a therapeutically effective quantity of a cholinesterase inhibitor selected from the group consisting of echothiophate iodide, physostigmine, pyridostigmine, neostigmine, aceclidine, ambenonium, demecarium, rivastigmine, galantamine, caffeine, rosmarinic acid, α-pinene, donepezil, tacrine, edrophonium, huperzine A, ladostigil, ungeremine, lactucopicrin, acotiamide, diisopropyl fluorophosphate, cadusafos, chlorpyrifos, cyclosarin, dichlorvos, dimethoate, metrifonate, and any combination thereof;
(b) a therapeutically effective quantity of a non-steroid anti-inflammatory drug selected from the group consisting of bromfenac, ketorolac, diclofenac, nepafenac, and any combination thereof;
(c) optionally, a therapeutically effective quantity of an α-1-adrenergic antagonist selected from the group consisting of dapiprazole, phentolamine, phentolamine mesylate, tamsulosin, alfuzosin, doxazosin, prazosin, terazosin, and any combination thereof;
(d) optionally, at least one penetration enhancer selected from the group consisting of non-ionic polyoxyethlene-polyoxypropylene block copolymers, cross-linked polyacrylic acid, and any combination thereof;
(e) optionally, a quantity of glycerol;
optionally, a quantity of dextran;
(g) optionally, a quantity of chondroitin sulfate; and
(h) a quantity of de-ionized water.
15 . The ophthalmological pharmaceutical composition of claim 14 , wherein the cholinesterase inhibitor is selected from the group consisting of echothiophate iodide, physostigmine, pyridostigmine, neostigmine, aceclidine and any combination thereof.
16 . The ophthalmological pharmaceutical composition of claim 14 , wherein the penetration enhancer is poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol).
17 . An ophthalmological pharmaceutical composition for treating, alleviating, and/or mitigating presbyopia, the composition comprising:
(a) a therapeutically effective quantity of a cholinesterase inhibitor selected from the group consisting of echothiophate iodide, physostigmine, pyridostigmine, neostigmine, ambenonium, demecarium, rivastigmine, galantamine, caffeine, rosmarinic acid, α-pinene, donepezil, tacrine, edrophonium, huperzine A, ladostigil, ungeremine, lactucopicrin, acotiamide, diisopropyl fluorophosphate, cadusafos, chlorpyrifos, cyclosarin, dichlorvos, dimethoate, metrifonate, and any combination thereof;
(b) a therapeutically effective quantity of an adrenergic agonist selected from the group consisting of apraclonidine, brimonidine, and any combination thereof;
(c) optionally, a therapeutically effective quantity of a non-steroid anti-inflammatory drug selected from the group consisting of bromfenac, ketorolac, diclofenac, nepafenac, and any combination thereof;
(d) optionally, a therapeutically effective quantity of an α-1-adrenergic antagonist selected from the group consisting of dapiprazole, tamsulosin, alfuzosin, doxazosin, prazosin, terazosin, phentolamine, phentolamine mesylate, phenoxybenzamine, tolazoline, and trazodone, and any combination thereof;
(e) optionally, at least one penetration enhancer selected from the group consisting of non-ionic polyoxyethlene-polyoxypropylene block copolymers, cross-linked polyacrylic acid, and any combination thereof;
(f) optionally, a quantity of glycerol;
(g) optionally, a quantity of dextran;
(h) optionally, a quantity of chondroitin sulfate; and
(i) a quantity of de-ionized water.
18 . The ophthalmological pharmaceutical composition of claim 17 , wherein the cholinesterase inhibitor is selected from the group consisting of echothiophate iodide, physostigmine, pyridostigmine, neostigmine, and any combination thereof.
19 . The ophthalmological pharmaceutical composition of claim 17 , wherein the adrenergic agonist is brimonidine.
20 . The ophthalmological pharmaceutical composition of claim 17 , wherein the penetration enhancer is poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol).