Compositions and methods for the treatment of presbyopia
The invention provides compositions and methods for the treatment of presbyopia. The compositions preferably comprise aceclidine and a polyol. The compositions optionally contain a cycloplegic agent, a surfactant, a viscosity enhancer, an osmolarity modifier and a preservative.
1. An ophthalmological composition for the treatment of presbyopia comprising:
an active agent selected from the group consisting of about 1.75% w/v aceclidine and a mixture of about 1.75% w/v aceclidine and tropicamide; and
about 2.5% w/v mannitol,
wherein w/v denotes weight by volume of the total composition.
2. The ophthalmological composition of claim 1 , further comprising:
about 1.0% to about 6.0% w/v of a nonionic surfactant; and
about 0.1% to about 2.25% w/v hydroxypropylmethyl cellulose.
3. The ophthalmological composition of claim 2 , further comprising:
about 0.10% to about 0.12% w/v sorbic acid; and
about 0.005% to about 0.02% w/v benzalkonium chloride.
4. The ophthalmological composition of claim 3 , further comprising one or more antioxidants selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), ethylenediaminetetraacetic acid dihydrate, sodium citrate and citrate buffer.
5. The ophthalmological composition of claim 4 , wherein the one or more antioxidants consist of:
ethylenediaminetetraacetic acid dihydrate; and
sodium citrate or citrate buffer.
6. The ophthalmological composition of claim 2 , wherein the nonionic surfactant is selected from a polysorbate, tyloxapol, a poloxamer, a cyclodextrin, vitamin E TPGS and a polyoxyl.
7. The ophthalmological composition of claim 2 , wherein the nonionic surfactant is polysorbate 80.
8. The ophthalmological composition of claim 7 , wherein the concentration of polysorbate 80 is from about 1.0% to about 5.0% w/v and the concentration of hydroxypropylmethyl cellulose is from about 0.75% to about 1.5% w/v.
9. The ophthalmological composition of claim 7 , wherein the concentration of polysorbate 80 is from about 2.0% to about 4.0% w/v and the concentration of hydroxypropylmethyl cellulose is from about 1.0% to about 1.25% w/v.
10. The ophthalmological composition of claim 1 wherein the active agent is a mixture of 1.75% w/v aceclidine and tropicamide and wherein tropicamide is at a concentration from:
about 0.004% to 0.015% w/v.
11. A method of treating presbyopia comprising administering to a subject in need thereof the ophthalmological composition of claim 1 .
12. A method of treating irregular astigmatism, keratoconic ectasia, night vision halos/starbursts, night vision reduced contrast, and low myopia, or hyperopia, with or without astigmatism, comprising administering to a subject in need thereof the ophthalmological composition of claim 1 .
13. An ophthalmological composition for the treatment of presbyopia comprising:
an exclusive active agent selected from the group consisting of about 1.75% w/v aceclidine and a mixture of about 1.75% w/v aceclidine and about 0.01% w/v tropicamide;
about 2.5% w/v mannitol;
about 4.0% w/v polysorbate 80;
about 1.25% w/v hydroxypropylmethyl cellulose;
about 0.12% w/v sorbic acid;
about 0.1% w/v ethylenediaminetetraacetic acid dihydrate;
about 0.02% w/v benzalkonium chloride; and
about 0.1% w/v sodium citrate or citrate buffer,
wherein w/v denotes weight by volume of the total composition.
14. A method of treating presbyopia comprising administering to a subject in need thereof the ophthalmological composition of claim 13 .
15. A method of treating presbyopia comprising administering to a subject in need thereof the ophthalmological composition of claim 13 , wherein near vision acuity of the subject is improved by at about 4 lines of resolution or more for at least 8 hours.
16. A method of treating irregular astigmatism, keratoconic ectasia, night vision halos/starbursts, night vision reduced contrast and low myopia, or hyperopia, with or without astigmatism, comprising administering to a subject in need thereof the ophthalmological composition of claim 13 .
17. A method of stabilizing aceclidine comprising providing a first composition comprising about 1.75% w/v aceclidine and about 2.5% w/v mannitol in a first chamber and a second composition comprising about 0.01% w/v tropicamide, about 4.0% w/v polysorbate 80, about 1.25% w/v hydroxypropylmethyl cellulose, about 0.12% w/v sorbic acid, about 0.1% w/v ethylenediaminetetraacetic acid dihydrate, about 0.02% w/v benzalkonium chloride and about 0.1% w/v sodium citrate or citrate buffer in a second chamber, wherein upon mixing the first composition and the second composition the efficacy of aceclidine is maintained for at least one month, wherein w/v denotes weight by total volume after mixing of the first and second composition.
18. A method of inhibiting microbial and fungal growth comprising the following steps:
(i) providing an ophthalmological composition comprising about 1.75% w/v aceclidine,
(ii) about 2.5% w/v mannitol, about 0.01% w/v tropicamide, about 4.0% w/v polysorbate
(iii) 80 and about 1.25% w/v hydroxypropylmethyl cellulose;
(iv) adding from about 0.10% to 0.12% w/v sorbic acid; and
(v) adding one or more of about 0.1% w/v ethylenediaminetetraacetic acid dihydrate and about 0.1% w/v sodium citrate or citrate buffer,
wherein w/v denotes weight by volume of the total composition.