Patent US5585401A successfully refreshed from Google Patents.
US5585401A
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Method for enhancing outflow of aqueous humor in treatment of glaucoma
Assignee: University of California
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Filing: 1994-12-09
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Granted: 1996-12-17
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Expires: 2014-12-09
Abstract
Abstract Elevated intraocular pressure is reduced by administration directly to the eye of compounds that inhibit function of a Na + --K + --2Cl -2 cotransporter mechanism discovered in trabecular meshwork cells of mammalian eyes. These compounds are useful in treatment of diseases of the eye associated with elevated intraocular pressure, such as ocular hypertension and glaucoma. A screening method is provided to discover additional compounds with utility for lowering intraocular pressure by substantially inhibiting the Na + --K + --Cl -2 cotransporter mechanism in trabecular meshwork cells.
Inventors
- 👤 James D. Brandt
- 👤 Martha E. O'Donnell
- 👤 Fitz-Roy E. Curry
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 14:53
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/185; A61K31/19; A61K31/195; A61K31/196; A61K31/33; A61K31/335; A61K31/34; A61K31/341; A61K31/395; A61K31/40; A61K31/402; A61K31/435; A61K31/44
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
69 words
A method for increasing aqueous humor outflow in the eye of a mammalian patient to reduce the intraocular pressure therein, said method comprising administering to said eye a composition comprising an effective amount of a compound that inhibits the Na + --K + --2Cl - co-transport in the trabecular meshwork of the eye, or a pharamaceutically acceptable salt thereof, in a pharamacutically acceptable carrier; wherein the compound is bumetanide.
Claim 2
Independent Claim
69 words
A method for increasing aqueous humor outflow in the eye of a mammalian patient to reduce the intraocular pressure therein, said method comprising administering to said eye a composition comprising an effective amount of a compound that inhibits the Na + --K + --2Cl - co-transport in the trabecular meshwork of the eye, or a pharamaceutically acceptable salt thereof, in a pharamacutically acceptable carrier; wherein the compound is bumetanide.
Claim 3
Dependent Claim
12 words
The method of claim 1 wherein the composition is administered by microinjection.
Claim 4
Dependent Claim
11 words
The method of claim 1 wherein the composition is administered topically.
Claim 5
Dependent Claim
16 words
The method of claim 3 wherein the composition further comprises a compound that enhances corneal penetration.
Claim 6
Dependent Claim
13 words
The method of claim 3 wherein the composition further comprises 0.025% benzalkonium chloride.
Claim 7
Dependent Claim
16 words
The method of claim 3 wherein the compound has an octanol:water coefficient of at least 0.005.
Claim 8
Dependent Claim
16 words
The method of claim 3 wherein the compound has an octanol:water coefficient of at least 0.01.
Claim 9
Dependent Claim
17 words
The method of claim 1 wherein the patient is human and administration is in treatment of glaucoma.
Claim 10
Dependent Claim
23 words
The method of claim 8 wherein dosage of the compound is 50-100 microliters of a 5-10 mM solution of the compound per day.
Claim 11
Dependent Claim
23 words
The method of claim 6 wherein dosage of the compound is 50-100 microliters of a 5-10 mM solution of the compound per day.
Claim 12
Independent Claim
71 words
A method for screening compositions for utility in lowering intraocular pressure comprising: a. determining the IC50 concentration of a composition containing bumetanide in the cortical thick ascending limb of the loop of Henle; b. determining the inhibition of cotransport in mammalian trabecular meshwork cells; and c. selecting the compositions with an IC50 at or below 0.30 and an inhibition of Na + --K + --2Cl - cotransport of at least 50%.
Claim 13
Independent Claim
71 words
A method for screening compositions for utility in lowering intraocular pressure comprising: a. determining the IC50 concentration of a composition containing bumetanide in the cortical thick ascending limb of the loop of Henle; b. determining the inhibition of cotransport in mammalian trabecular meshwork cells; and c. selecting the compositions with an IC50 at or below 0.30 and an inhibition of Na + --K + --2Cl - cotransport of at least 50%.
Claim 14
Dependent Claim
23 words
The method of claim 11 wherein the cortical thick ascending limb is in rabbit and the trabecular meshwork cells are bovine or human.
Claim 15
Independent Claim
44 words
A method for screening compositions containing bumetanide for utility in lowering intraocular pressure comprising screening the compositions in a Na + --K + --2Cl - cotransporter mechanism screen, and selecting a composition that substantially inhibits a Na + --K + --2Cl - cotransporter mechanism.
Claim 16
Independent Claim
44 words
A method for screening compositions containing bumetanide for utility in lowering intraocular pressure comprising screening the compositions in a Na + --K + --2Cl - cotransporter mechanism screen, and selecting a composition that substantially inhibits a Na + --K + --2Cl - cotransporter mechanism.
Claim 17
Dependent Claim
33 words
The method of claim 13 wherein the Na + --K + --2Cl - cotransporter mechanism is in mammalian trabecular meshwork cells and the composition selected has an IC50 of about 0.30 or less.
Claim 18
Dependent Claim
12 words
The method of claim 14 wherein the trebecular meshwork cells are human.
Claim 19
Dependent Claim
12 words
The method of claim 14 wherein the trebecular meshwork cell are bovine.
Claim 20
Dependent Claim
21 words
The method of claim 14 wherein the composition selected further has a coefficient of lipophilicity (log P') of at least 0.005.
Claim 21
Dependent Claim
21 words
The method of claim 14 wherein the composition selected further has a coefficient of lipophilicity (log P') of at least 0.01.
References Cited (Backward Citations)
US4757089A
Cited
US4861786A
Cited
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1999-12-17 | 2000-06-17 | 2000-12-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-12-17 | 2004-06-17 | 2004-12-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-12-17 | 2008-06-17 | 2008-12-17 | $7700.00 | Window Closed / Lapsed |