WO1998056250A1 - Method for reducing side effects - Google Patents
Method for reducing side effects Download PDFInfo
- Publication number
- WO1998056250A1 WO1998056250A1 PCT/US1998/011952 US9811952W WO9856250A1 WO 1998056250 A1 WO1998056250 A1 WO 1998056250A1 US 9811952 W US9811952 W US 9811952W WO 9856250 A1 WO9856250 A1 WO 9856250A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- side effects
- ophthalmic
- compound
- reducing
- reducing side
- 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
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
Definitions
- the present application is directed to the use of a reversible cholinesterase inhibitor to reduce locally expressed side effects caused by topically applied ophthalmic pharmaceuticals.
- 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 reducing locally expressed side effects in topically applied ophthalmic pharmaceuticals.
- 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 reduce locally expressed side effects resulting from the topical administration of ophthalmic pharmaceuticals.
- the Compound reduces the side effects by retarding the hydrolysis of ester containing compounds, such as, prostaglandins, thereby reducing the conjunctival hyperemia associated with the use of prostaglandins.
- the Compound is administered topically to the eye in conjunction with the ophthalmic pharmaceutical at concentrations from 0.001 to 1.0 weight percent (wt.%), preferably .001 to .05 wt.%.
- the Compound can be delivered separately or in the same formulation as the ophthalmic pharmaceutical.
- formulations are suitable for topical delivery to the eye.
- 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.
- 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.
- a formulation containing the Compound is administered to the eye (1-4 times per day according to the discretion of a skilled clinician) of a person in conjunction with an ophthalmic pharmaceutical to reduce the side effects caused by the pharmaceutical.
- the following examples are illustrative, but not limiting.
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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Methods and compositions for reducing locally expressed ophthalmic side effects are disclosed.
Description
IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
METHOD FOR REDUCING SIDE EFFECTS
Docket No. 1601PCT EXPRESS MAIL LABEL No. EL008174930US
The present application is directed to the use of a reversible cholinesterase inhibitor to reduce locally expressed side effects caused by topically applied ophthalmic pharmaceuticals.
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 reducing locally expressed side effects in topically applied ophthalmic pharmaceuticals.
Summary of the Invention
This application is directed to compositions of E2020 and its isomers and methods for its use in reducing locally expressed side effects caused by topically applied ophthalmic pharmaceuticals.
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 reduce locally expressed side effects resulting from the topical administration of ophthalmic pharmaceuticals. The Compound reduces the side effects by retarding the hydrolysis of ester containing compounds, such as, prostaglandins, thereby reducing the conjunctival hyperemia associated with the use of prostaglandins.
The Compound is administered topically to the eye in conjunction with the ophthalmic pharmaceutical at concentrations from 0.001 to 1.0 weight percent (wt.%), preferably .001 to .05 wt.%. The Compound can be delivered separately or in the same formulation as the ophthalmic pharmaceutical.
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.
A formulation containing the Compound is administered to the eye (1-4 times per day according to the discretion of a skilled clinician) of a person in conjunction with an ophthalmic pharmaceutical to reduce the side effects caused by the pharmaceutical.
The following examples are illustrative, but not limiting.
Example 1
Wt.% Based
Ingredient on Free Base
Compound (free base or 0.1 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 0.1 hydrochloride salt) Benzalkonium Chloride 0.01 + 5% XS Tris (Hydroxymethyl) Aminomethane 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. A method for reducing locally expressed side effects caused by topically applied ophthalmic pharmaceuticals which comprises administering a pharmaceutically effective amount of l-benzyl-4-[(5,6-dimethoxy-l-indanon-2yl)methyl]piperidine or an isomer thereof.
2. The method of Claim 1 wherein the ophthalmic pharmaceutical is a prostaglandin.
3. A composition for reducing locally expressed side effects caused by topically applied ophthalmic pharmaceuticals comprising a pharmaceutically effective amount of 1- benzyl-4-[(5,6-dimethoxy-l-indanon-2yl)methyl]piperidine or an isomer thereof.
4. The composition of Claim 4 wherein the ophthalmic pharmaceutical is a prostaglandin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU78311/98A AU7831198A (en) | 1997-06-11 | 1998-06-09 | Method for reducing side effects |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4929097P | 1997-06-11 | 1997-06-11 | |
| US60/049,290 | 1997-06-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1998056250A1 true WO1998056250A1 (en) | 1998-12-17 |
Family
ID=21959057
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1998/011952 WO1998056250A1 (en) | 1997-06-11 | 1998-06-09 | Method for reducing side effects |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU7831198A (en) |
| WO (1) | WO1998056250A1 (en) |
-
1998
- 1998-06-09 AU AU78311/98A patent/AU7831198A/en not_active Abandoned
- 1998-06-09 WO PCT/US1998/011952 patent/WO1998056250A1/en active Application Filing
Non-Patent Citations (1)
| Title |
|---|
| DATABASE STN HCAPLUS 1 January 1900 (1900-01-01), XP002910688, Database accession no. 124:194072 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU7831198A (en) | 1998-12-30 |
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