WO1998056380A1 - Method to reverse mydriasis - Google Patents
Method to reverse mydriasis Download PDFInfo
- Publication number
- WO1998056380A1 WO1998056380A1 PCT/US1998/010780 US9810780W WO9856380A1 WO 1998056380 A1 WO1998056380 A1 WO 1998056380A1 US 9810780 W US9810780 W US 9810780W WO 9856380 A1 WO9856380 A1 WO 9856380A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- mydriasis
- compound
- reverse
- ophthalmic
- eye
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
Definitions
- the present application is directed to the use of a reversible cholinesterase inhibitor to reverse mydriasis.
- U.S. Patent No. 4,895,841 is directed to cyclic amine compounds and their pharmaceutical use, in particular, for the treatment of senile dementia.
- the patent discloses the compound, l-benzyl-4-[(5,6-dimethoxy-l-indanon-2yl)methyl]piperidine, also known as
- This application is directed to compositions of E2020 and its isomers and methods for its use to reverse mydriasis.
- the present invention is directed to using l-benzyl-4-[(5,6-dimethoxy-l-indanon- 2yl)methyl]piperidine (E2020), and its stereo and optical isomers, hereinafter "Compound,” to reverse mydrias, particularly following dilation of the eyes after an eye examination or ophthalmic surgery, by inhibiting aceycholinesterase and not inhibiting pseudocholinesterase which will hydrolize and inactivate mydriatics, such as, tropicamide, atropine, cyclopentolate, etc.
- E2020 l-benzyl-4-[(5,6-dimethoxy-l-indanon- 2yl)methyl]piperidine
- Compound stereo and optical isomers
- the Compound is administered topically to the eye in a pharmaceutically acceptable vehicle at concentrations of .01 to 1.0 weight percent (wt.%), preferably .05 to 0.5 wt.%.
- Ophthalmic solution formulations may be prepared by dissolving the Compound in a physiologically acceptable isotonic aqueous buffer. Further, the ophthalmic solution may include an ophthalmologically acceptable surfactant to assist in dissolving the Compound.
- the ophthalmic solution may contain a thickener such as hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethyl-cellulose, methylcellulose, polyvinylpyrrolidone, or the like, to improve the retention of the formulation in the conjunctival sac.
- a thickener such as hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethyl-cellulose, methylcellulose, polyvinylpyrrolidone, or the like.
- the active ingredient is combined with a preservative in an appropriate vehicle, such as, mineral oil, liquid lanolin, or white petrolatum.
- Sterile ophthalmic gel formulations may be prepared by suspending the active ingredient in a hydrophilic base prepared from the combination of, for example, carbopol-940, or the like, according to the published formulations for analogous ophthalmic preparations; preservatives and tonicity agents can be incorporated.
- N formulation containing the Compound is administered to the eye of a person following dilation, for example, during an eye examination or ophthalmic surgery.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Methods and compositions for reversing mydriasis are disclosed.
Description
METHOD TO REVERSE MYDRIASIS
The present application is directed to the use of a reversible cholinesterase inhibitor to reverse mydriasis.
Background of the Invention
U.S. Patent No. 4,895,841 is directed to cyclic amine compounds and their pharmaceutical use, in particular, for the treatment of senile dementia. The patent discloses the compound, l-benzyl-4-[(5,6-dimethoxy-l-indanon-2yl)methyl]piperidine, also known as
E2020. U.S. Patent No. 5,100,901 and European Patent Application Nos. 0 579 263 Al and 0 296 560 A2 also disclose the compound and are related applications. None of the references disclose the compounds for use in ophthalmic surgery to reverse mydriasis.
Summary of the Invention
This application is directed to compositions of E2020 and its isomers and methods for its use to reverse mydriasis.
Description of Preferred Embodiments
The present invention is directed to using l-benzyl-4-[(5,6-dimethoxy-l-indanon- 2yl)methyl]piperidine (E2020), and its stereo and optical isomers, hereinafter "Compound," to reverse mydrias, particularly following dilation of the eyes after an eye examination or ophthalmic surgery, by inhibiting aceycholinesterase and not inhibiting pseudocholinesterase
which will hydrolize and inactivate mydriatics, such as, tropicamide, atropine, cyclopentolate, etc.
The Compound is administered topically to the eye in a pharmaceutically acceptable vehicle at concentrations of .01 to 1.0 weight percent (wt.%), preferably .05 to 0.5 wt.%.
Various types of formulations are suitable for topical delivery to the eye. The Compound may be combined with ophthalmologically acceptable preservatives, surfactants, viscosity enhancers, penetration enhancers, buffers, sodium chloride, and water to form an aqueous, sterile ophthalmic suspension or solution. Ophthalmic solution formulations may be prepared by dissolving the Compound in a physiologically acceptable isotonic aqueous buffer. Further, the ophthalmic solution may include an ophthalmologically acceptable surfactant to assist in dissolving the Compound. Furthermore, the ophthalmic solution may contain a thickener such as hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethyl-cellulose, methylcellulose, polyvinylpyrrolidone, or the like, to improve the retention of the formulation in the conjunctival sac. In order to prepare sterile ophthalmic ointment formulations, the active ingredient is combined with a preservative in an appropriate vehicle, such as, mineral oil, liquid lanolin, or white petrolatum. Sterile ophthalmic gel formulations may be prepared by suspending the active ingredient in a hydrophilic base prepared from the combination of, for example, carbopol-940, or the like, according to the published formulations for analogous ophthalmic preparations; preservatives and tonicity agents can be incorporated.
N formulation containing the Compound is administered to the eye of a person following dilation, for example, during an eye examination or ophthalmic surgery.
The following examples are illustrative, but not limiting.
Example 1
Wt.% Based
Ingredient on Free Base
Compound (free base or 0.25 hydrochloride salt)
Dibasic Sodium Phosphate (Anhydrous) 0.50
Sodium Chloride 0.60
Benzalkonium Chloride Solution (10%) 0.01 + 3% XS
Hydrochloric Acid or Sodium Hydroxide Adj. pH 6.8-7.2
Purified Water Q.S.
Example 2
Wt.% Based
Ingredient on Free Base
Compound (free base or 0.25 hydrochloride salt)
Benzalkonium Chloride 0.01 + 5% XS
Tris (Hydroxymethyl) Aminomethane, NN 0.5
Sodium Chloride 0.68
Hydroxypropyl Methylcellulose 0.25
Sodium Hydroxide or Hydrochloric Acid Adj. pH 7.4
Purified Water Q.S.
Claims
1. N method for reversing mydriasis in an eye which comprises administering a pharmaceutically effective amount of l-benzyl-4-[(5,6-dimethoxy-l-indanon- 2yl)methyl]piperidine or an isomer thereof.
2. A topical composition for reversing mydriasis comprising a pharmaceutically effective amount of l-benzyl-4-[(5,6-dimethoxy-l-indanon-2yl)methyl]piperidine or an isomer thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU77999/98A AU7799998A (en) | 1997-06-11 | 1998-06-09 | Method to reverse mydriasis |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4934597P | 1997-06-11 | 1997-06-11 | |
| US60/049,345 | 1997-06-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1998056380A1 true WO1998056380A1 (en) | 1998-12-17 |
Family
ID=21959313
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1998/010780 WO1998056380A1 (en) | 1997-06-11 | 1998-06-09 | Method to reverse mydriasis |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU7799998A (en) |
| WO (1) | WO1998056380A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002002526A1 (en) * | 2000-07-03 | 2002-01-10 | Eisai Co., Ltd. | Pharmaceutical compositions for controlling intraocular pressure |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5100901A (en) * | 1987-06-22 | 1992-03-31 | Eisai Co., Ltd. | Cyclic amine compounds and pharmaceutical use |
-
1998
- 1998-06-09 AU AU77999/98A patent/AU7799998A/en not_active Abandoned
- 1998-06-09 WO PCT/US1998/010780 patent/WO1998056380A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5100901A (en) * | 1987-06-22 | 1992-03-31 | Eisai Co., Ltd. | Cyclic amine compounds and pharmaceutical use |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002002526A1 (en) * | 2000-07-03 | 2002-01-10 | Eisai Co., Ltd. | Pharmaceutical compositions for controlling intraocular pressure |
Also Published As
| Publication number | Publication date |
|---|---|
| AU7799998A (en) | 1998-12-30 |
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