WO2002062344A1 - Method of administering ophthalmic fluids - Google Patents
Method of administering ophthalmic fluids Download PDFInfo
- Publication number
- WO2002062344A1 WO2002062344A1 PCT/US2002/003130 US0203130W WO02062344A1 WO 2002062344 A1 WO2002062344 A1 WO 2002062344A1 US 0203130 W US0203130 W US 0203130W WO 02062344 A1 WO02062344 A1 WO 02062344A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dose
- eye
- concentration
- fluid
- adrenoceptor blocking
- Prior art date
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
Definitions
- This invention relates to methods for administering ophthalmic agents and, more particularly, to methods of administering ophthalmic fluids.
- ophthalmic fluid medication are in the range of 30-70 micro liters for intra-ocular pressure lowering (IOP) compounds used in treating glaucoma. It has been found that a reduction in dose volume down to 20 microliters leads to an increase in efficacy of the medication. Miller, K., Brown, R.H., Lynch, M.G., Eto, C.Y., Lue, J.C., and Novak, G.D., Does Drop Size Influence The Efficacy Of A Topical Beta Blocker? , Invest. Ophthalmol. Vis. Set, Suppl. 27, 161, 1986. Although the prior art has contemplated the use of doses as small as 10 microliters, the literature has indicated that the concentration of IOP compounds in such small doses should be increased to maintain efficacy. Miller, et al. SUMMARY OF THE INVENTION
- a method of treating an eye is provided with ophthalmologically active compounds, particularly with intra-ocular pressure lowering (IOP) compounds, where a dose of 5-15 microliters is delivered at a standard concentration.
- IOP intra-ocular pressure lowering
- concentration of an ophthalmologically active agent in a fluid medicant does not need to be increased to maintain the efficacy of the drug. Rather, it has been found that because a smaller dose of fluid medication causes less irritation of the eye than with larger doses, reflex tearing and reflex blinking are minimized.
- the concentration of the medication in the tear film is higher than with larger doses, due to the dispersion of the drug in a smaller liquid volume defined by the tear film.
- a greater percentage of the medication is absorbed into the eye and not absorbed systematically after draining.
- the therapeutic effects of the drug are at least as great as with larger doses, even though administered in a smaller amount.
- Typical standard doses that are administered (30-70 microliters) cause reflex blinking and reflex tear generation which, in turn, cause a fairly rapid drainage of the dose, both externally and through the nasolacrimal duct.
- a dose of 5-15 microliters causes minimal reflex blinking and reflex tear generation, resulting in slower drainage than with larger doses.
- the inventive method can be used with IOP agents, and other classes of ophthalmic fluids, such as antibiotics, diagnostic agents, anti-inflammatory agents, and artificial tears and eye whiteners.
- standard concentration shall refer to an ophthalmologically active compound's concentration in a dose of 30-70 microliters of ophthalmic fluid such as the IOP compound concentration in a dose of 30-70 microliters.
- latanoprost sold by Pharmacia Corporation under the trademark "Xalatan” has a standard concentration of 50 micrograms of latanoprost per milliliter (0.005%) for a recommended dose of 30 microliters; thus, one 30 microliter dose (one drop) contains 1.5 micrograms of latanoprost.
- TLMOPTIC is prepared at two different standard concentrations, one standard concentration (referred to as “TDVIOPTIC 0.25%), each milliter of fluid contains 2.5 milligrams of timolol (3.4 milligrams of timolol maleate); while, with a second standard concentration (referred to as “TIMOPTIC 0.5%”), each milliliter of fluid contains 5.0 milligrams of timolol (6.8 milligrams of timolol maleate). Both "TIMOPTIC" fluid medications are administered in one drop doses of approximately 30 microliters. Dorzolamide hydrochlori.de sold under the trademark "TRUSOPT” by Merck & Co., Inc.
- Brimonidine tartrate sold under the trademark "ALPHAGAN” by Allergan, Inc. has a standard concentration of 2 milligrams of brimonidine tartrate (equivalent to 1.32 milligrams as brimonidine free base) per milliliter (0.2%)); whereas, brimonidine tartrate sold under the trademark "ALPHAGAN P", also sold by Allergan, Inc., has a standard concentration of 0.15%.
- a method of treating an eye is provided with ophthalmologically active compounds, particularly with IOP compounds, where a dose of 5- 15 microliters is delivered at a standard concentration.
- the dose is delivered to the eye without punctal occlusion.
- Suitable ophthalmologically active compounds that may be used with the subject invention include
- I. anti-glaucoma/IOP compounds such as: a.) alpha-adrenoceptor blocking agents, e.g., apraclonidine, brimonidine, AGN
- beta-adrenoceptor blocking agents e.g., carteolol, betaxolol, levobunolol, metipranolol, timolol, vaninolol, adaprolol, etc.
- miotics e.g., pilocarpine, carbachol, physostigmine, etc.
- sympathomimetics e.g., adrenaline, dipivefrine, etc.
- carbonic anhydrase inhibitors e.g., acetazolamide, dorzolamide, etc.
- prostaglandins e.g., PGF-2 alpha or its prodrug latanoprost
- diagnostic fluids such as anesthetics and medications to dilate the eye
- anti-inflammatory agents both steroid and non-steroid
- the inventive method is particularly well-suited to work with beta-adrenoceptor blocking agents (e.g., timolol maleate); prostaglandins (e.g., latanoprost); alpha-adrenoceptor blocking agents (e.g., brinonidine tartrate); and, carbonic anhydrase inhibitors (e.g., dorzolamide hydrochloride).
- beta-adrenoceptor blocking agents e.g., timolol maleate
- prostaglandins e.g., latanoprost
- alpha-adrenoceptor blocking agents e.g., brinonidine tartrate
- carbonic anhydrase inhibitors e.g., dorzolamide hydrochloride
- the concentration of the ophthalmologically active compound in the fluid medication need not be any greater than its standard concentration.
- the concentration of the dose need not be any greater than .005%>; with respect to beta- adrenoceptor blocking agents (e.g., timolol), no greater than 0.5%>, and more preferably, no greater than 0.25%; with respect to carbonic anhydrase inhibitors (e.g., dorzolamide), no greater than .2%o, and with respect to alpha-adrenoceptor blocking agents (e.g., brimonidine), no greater than 0.2%, and more preferably, no greater than 0.15%.
- beta- adrenoceptor blocking agents e.g., timolol
- carbonic anhydrase inhibitors e.g., dorzolamide
- alpha-adrenoceptor blocking agents e.g., brimonidine
- Tests were conducted to determine the efficacy of smaller doses having standard concentrations of ophthalmologically active compounds.
- 15 microliter doses of TIMOPTIC 0.5%) were administered to 20 subjects who did not have any history of suffering from glaucoma or elevated intra-ocular pressure. Standard concentration of the fluid was utilized.
- a 15 microliter drop was delivered into both eyes of each subject.
- a tonometer was used to measure ocular pressure before administration of the drug; two hours after administration of the drug; and six hours after administration of the drug.
- Table 1 sets forth the average ocular pressure drops at the. two- and six-hour marks. Table 1
- TIMOPTIC 0.5%> 10 microliter doses of TIMOPTIC 0.5%> were administered to 24 subjects who did not have any history of suffering from glaucoma or elevated intra-ocular pressure. Standard concentration of the fluid was utilized. A 10 microliter drop was delivered into both eyes of each subject. A tonometer was used to measure ocular pressure before administration of the drug; two hours after administration of the drug; and six hours after administration of the drug. Table 2 sets forth the average ocular pressure drops at the two- and six-hour marks.
- Dispensers for delivering such doses are known in the prior art, such as U.S. Patent No. 5,152,435, which issued October 6, 1992; U.S. Patent No. 5,881,956, which issued March 16, 1999; and WIPO Published Patent Application No. WO 01/14245. The disclosures of these references are incorporated by reference herein in their respective entireties.
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/467,140 US20040116524A1 (en) | 2002-02-04 | 2002-02-04 | Method of administering opthalmic fluids |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US26627601P | 2001-02-02 | 2001-02-02 | |
US60/266,276 | 2001-02-02 | ||
US27872301P | 2001-03-26 | 2001-03-26 | |
US60/278,723 | 2001-03-26 |
Publications (1)
Publication Number | Publication Date |
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WO2002062344A1 true WO2002062344A1 (en) | 2002-08-15 |
Family
ID=26951734
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2002/003130 WO2002062344A1 (en) | 2001-02-02 | 2002-02-04 | Method of administering ophthalmic fluids |
Country Status (1)
Country | Link |
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WO (1) | WO2002062344A1 (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5886030A (en) * | 1994-05-06 | 1999-03-23 | Alcon Laboratories, Inc. | Use of vitamin E tocopheryl derivatives in ophthalmic compositions |
-
2002
- 2002-02-04 WO PCT/US2002/003130 patent/WO2002062344A1/en not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5886030A (en) * | 1994-05-06 | 1999-03-23 | Alcon Laboratories, Inc. | Use of vitamin E tocopheryl derivatives in ophthalmic compositions |
Non-Patent Citations (1)
Title |
---|
DATABASE USPT [online] ALCON LABORATORIES; accession no. WEST * |
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