GB2169508A - Ophthalmic solutions containing hydroxyethyl cellulose - Google Patents
Ophthalmic solutions containing hydroxyethyl cellulose Download PDFInfo
- Publication number
- GB2169508A GB2169508A GB08500857A GB8500857A GB2169508A GB 2169508 A GB2169508 A GB 2169508A GB 08500857 A GB08500857 A GB 08500857A GB 8500857 A GB8500857 A GB 8500857A GB 2169508 A GB2169508 A GB 2169508A
- Authority
- GB
- United Kingdom
- Prior art keywords
- solution
- aqueous solution
- sterile aqueous
- hydroxyethyl cellulose
- eye
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
- A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
- A61L12/14—Organic compounds not covered by groups A61L12/10 or A61L12/12
- A61L12/148—Mercury containing compounds, e.g. thimerosal
Abstract
A sterile aqueous solution suitable for topical application to the eye as an artificial tear in the treatment of 'dry- eye' syndrome and as a comfort drop for wearers of contact lenses is described. The solution contains a hydroxyethyl cellulose together with sufficient of an ionic tonicity adjusting agent (e.g. an inorganic salt) to give the solution a tonicity value equivalent to that of a solution containing from 0.3 to 1.1% of sodium chloride. Preferred solutions are hypotonic and additionally contain a buffering agent to buffer the solution to a pH value of about 8.0.
Description
SPECIFICATION
Ophthalmic Compositions and Use
The present invention relates to an ophthalmic composition suitable for topical administration to the eye and to the use of that composition in the treatment of "dry-eye".
Some people suffer from discontinuous lachrymal films and in certain cases the lachrymal film can be almost completely deficient. Such "dry-eye" conditions can lead to discomfort, inflammation, profound damage to the cornea and even to loss of vision in extreme cases. Clearly there is a requirement to provide a remedy for dry-eye and a number of compositions have been described which offer some relief to the sufferer. Generally these known compositions have employed polymers to provide a synthetic lachrymal film as may be observed in the disclosures of United States Patent
Specifications Nos. 3767788,3767789, 3856919, 3907985, 3920810, 3937573,4039662,4120949 and 4131651. A variety of solutions for the remedy of dry eye are commercially available.However, most of these commercially available artificial tear solutions have been either very viscous, making them difficult to use, and their use can result in the build-up of sticky or even powdery residues on the eyelids and eyelashes.thereby causing discomfort, or their viscosity is so low that a tear film is formed only for an unacceptably short time. It has now been found that an aqueous solution of hydroxyethyl cellulose and an ionic tonicity adjusting agent provides an artificial tear composition which provides a satisfactory tear film life time, also known as tear film break up time, without being excessively viscous.
Accordingly the present invention provides a sterile aqueous solution suitable for topical administration to the eye for the treatment of dry-eye which contains an effective amount of a hydroxyethyl cellulose together with sufficient of an ionic tonicity adjusting agent to give the solution a tonicity value equivalent to that of a solution containing from 0.3 to 1.1% of sodium chloride.
The present invention does not include solutions which contain a medicament and in particular they do not contain a medicamentwhich is pharmacologically active in the eye.
The effective amount of hydroxyethyl cellulose required will depend upon its molecular weight and the effect that molecular weight has upon the viscosity of its aqueous solution. Clearly to provide an aqueous solution of suitable viscosity as hereinafter defined more hydroxyethyl cellulose will be required of a material having a low molecular weight than is required of a high molecular weight to give the same viscosity. In general, however, an effective amount of hydroxyethyl cellulose will be between 0.1 and 10%.
Hydroxyethyl celluloses are available commercially for example as Natrosols (Registered trade mark of Hercules Inc.), and Cellosizes (Registered trade mark of Union Carbide Chemical
Co.). Suitable hydroxyethyl celluloses are those for which a 2% aqueous solution has a viscosity of between 4500 and 6500 cps at 25"C using a
Brookfield LVF viscometer with a No. 4 spindle at a spindle speed of 60 rpm. A particularly favoured hydroxyethyl cellulose is available commercially as
Natrosol 250M.
Suitably this hydroxyethyl cellulose will be present in an amount from 0.1 to 1.5%, more suitably from 0.25% to 0.75% and preferably 0.3 to 0.6% for example 0.4% or 0.5%. (When used herein % refers to percentage weighVvoiume).
It is particularly surprising that a solution containing simply 0.1 to 1.5% of hydroxyethyl cellulose together with an ionic tonicity agent will give suitable values for tear film break up time in the absence of film forming agents such as polyvinyl alcohol which are present in prior art formulations.
In order to obtain satisfactory tear film break up time without making the solution excessively viscous it is desirable that the tonicity of the solution is adjusted using an ionic tonicity agent. It has been found surprisingly that if an equivalent amount of a non-ionic tonicity agent is used the resulting tear film break up time is significantly lower than that of a solution containing an ionic tonicity agent.
Suitable ionic tonicity adjusting agents include sodium chloride, potassium chloride, sodium borate with boric acid, mixtures of sodium and potassium salts of phosphoric acid or mixtures of any of these components, for example, a mixture of sodium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate. Particularly apt ionictonicity agents are sodium chloride and sodium chloride mixed with sodium salt of boric acid. Preferred ionictonicity adjusting agent is a mixture of sodium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate.
Suitably the solutions of the present invention will have a tonicity which is equivalent to that of an aqueous solution which contains from 0.3 to 1.1% of sodium chloride More aptly the tonicity will be equivalent to a 0.45 to 0.75% sodium chloride solution. It is preferred that the solutions are hypotonic that is have a tonicity less than that of a 0.9% solution of sodium chloride. This has been found to provide a comfortable solution when applied to the eye and a satisfactory tear film break up time for the artificial tearfilm.
It is desirable that solutions of the present invention should contain buffering agent. Suitably the pH value of the solution will lie in the range from 6.0 to 9.0 and preferably from 7.0 to 8.5 and most preferably will be between 8.0 and 8.5. The pH of the natural tear film is approximately 7.4 and it is believed by some authorities that an artificial tear solution having a pH higher than 7.4 has a soothing effect on the eye in people suffering from dry eye. It is an advantage of solutions of the present invention that at such pHs the viscosity of the solution is not deleteriously raised or lowered thereby adversely affecting tear film break up time.
Suitable buffering agents include those based on mixtures of alkali metal salts of phosphoric acid, mixtures of sodium borate and boric acid and mixtures of potassium chloride, boric acid and sodium hydroxide which give suitable pH values.
From the foregoing the skilled man will appreciate that the use of such buffering agents will contribute to the tonicity of the solution and he will be aware of tables which provide formulations of suitable
isotonic buffered aqueous solutions (see for
example United States National Formulary 1980).
Suitably the aqueous solutions of the present invention will also contain a polyalkylene glycol.
The presence of a polyalkylene glycol is believed to aid retention of the artificial tear film on the eye, thereby contributing to the satisfactory film life found with these solutions. Suitably the
polyalkylene glycol is a polyethylene glycol having a molecular weight of between 200 and 8000. Such polyethylene glycols are known as the Carbowaxes
(Registered trade mark of Carbide and Carbon
Chemicals Company). A preferred polyethylene glycol is one having a molecular weight of 300, as exemplified by Carbowax 300. The amount of polyalkylene glycol present in the composition is suitably from 0.1 to 2.5%, and is more suitably 0.5 to 2.0% and is preferably 0.75 to 1.25%, for example
1%.
Most aptly the aqueous solution of this invention will be preserved with an ophthalmically acceptable preservative such as benzalkonium chloride, thiomersal, chlorbutanol and phenylethanol, phenylmercuric salts such as the nitrate or acetate.
The preservative should be chosen to be compatible with the other components ofthe solution and not to effect unduly the tonicity. Each preservative has a concentration at which it is an effective bacteriostat without causing irritation to the eye. Thus suitably benzalkonium chloride will be present in an amount of 0.001 to 0.05% of the composition, preferably 0.005 to 0.02%. Thiomersal will be present at 0.001 to 0.05% of the composition and more suitably 0.002 to 0.01% and preferably 0.003 to 0.006%.
Phenylmercuric salts such as the nitrate and acetate will be present at 0.001 to 0.01%, more suitably 0.0015 to 0.006% and preferably 0.002 to 0.004% of the composition. Most suitably the preservative used will be phenylmercuric nitrate.
Generally the viscosity of compositions of this invention will suitably iie between 10 and 100 centipoise and more suitably between 15 and 60 centipoise and preferably 20 to 50 centipoise.
Viscosities are measured on a Brookfield LVF Viscometerusing a UL adaptor at 12 rpm and art a temperature of 22"C.
Generally the tear film break up time of compositions of this invention will be above 250 seconds, more suitably will be above 300 seconds and preferably will be above 500 seconds. The tear film break up times are measured using an in vitro technique similarto that described in "The break-up time of artificial pre-ocularfilms on the rabbit cornea" J. W. Lamble, D. Gilbert, J. J. Ashford in J.
Pharm. Pharmac. 1976 28 450--451.
Favourably the present invention provides a sterile aqueous solution suitable for topical administration to the eye for the treatment of dry eye which contains from 0.1 to 1.5% of hydroxyethyl cellulose, sufficient of an ionic tonicity adjusting agent to give the solution a tonicity value equivalent
to that of a solution containing from ().4to 0.8% of
sodium chloride, 0.001 to 0.05% of an
ophthalmically acceptable preservative, the solution
being buffered at pH 7.0 to 8.5.
Preferably the present invention provides a sterile
aqueous solution suitable for topical administration
to the eye for the treatment of dry eye which
contains from 0.25 to 0.75% of hydroxyethyl
cellulose, 0.3 to 0.5% sodium chloride, 0.002 to
0.004% phenylmercuric nitrate, the solution being
buffered art a pH of 8.0 to 8.5 using a mixture of
sodium borate and boric acid, the solution having a
tonicity equivalent to an aqueous solution
containing 0.45 to 0.75% sodium chloride.
In a second preferred embodiment the present
invention provides sterile aqueous solution
suitable for topical administration to the eye for the treatment of dry eye which contains from 0.25 to
0.75% of hydroxyethyl cellulose, 0.1 to 1.5% of
polyethylene glycol 0.3 to 0.5% sodium chloride,
0.002 to 0.004% phenylmercuric nitrate, the solution
being buffered at a pH of 7.5 to 8.0 using a mixture
of sodium dihydrogen phosphate and disodium
hydrogen phosphate, the solution having a tonicity equivalent to an aqueous solution containing 0.45 to 0.75% sodium chloride.
The aqueous solutions of the present invention are sterile. Sterilisation may be carried out prior to preparation of the solution by steriiising the components separately, for example by sterilising hydroxyethyl cellulose aqueous solution by heat for example by autoclaving and then sterilising the aqueous solution containing the other components by filtration. The two sterile components are then broughttogether in appropriate amounts under aseptic conditions and filled into pre-sterilised eyedropper bottles by conventional means. In a second method the solutions may be prepared by mixing the components in appropriate quantities. The resultant solution may be filled into eye-dropper bottles and the bottles and contents sterilised by heat, for example by autoclaving at 116"C for 30 minutes at 10 psi.In a third manner, the solution may be sterilised in bulk by heat, for example by autoclaving and the sterilised solution filled into pre-sterilised eye-dropper bottles under aseptic conditions.
Further the present invention provides a unit dose of the solution of the present invention having a volume of from 0.01 to 0.08 ml (thatis a drop of 10 to 80 microlitres) and more usually 0.02 to 0.05 ml.
The aqueous solutions of this invention are aptly provided in a multidose container from which drops may be dispensed into the eye. Such containers are well known in the art for dispensing liquid drops into the eye and such conventional containers may be employed. Aptly such containers are adapted to hold 1 to 20 mls, more usually 2 to 12 mls and preferably 3 to 10 mls.
The solutions of the present invention may be prepared by dissolving appropriate amounts of the components in water. Most suitablythe water is distilled water.
The invention further provides a method of treating dry eye by administering topically to the eye a sterile aqueous solution containing hydroxyethyl cellulose together with an ionic tonicity adjusting agent. Suitable compositions containing hydroxyethyl cellulose and ionic tonicity agent are described herein.
EXAMPLE 1
Artificial Tear Solution
An aqueous solution suitable for use as an artificial tear was formulated as follows:
Hydroxyethylcellulose 0.44%
Sodium chloride 0.34%
Disodium hydrogen phosphate 0.54%
Phenylmercuric nitrate 0.002%
Sodium hydroxide solution to
adjust pH to 8.5
Distilled water to 100 ml
The aqueous solution was prepared by dissolving the hydroxyethylene cellulose, sodium chloride, disodium hydrogen phosphate and phenyl mercuric nitrate in water (90 ml). The pH value of this solution was adjusted to 8.5 by the addition of 0.1 M sodium hydroxide. Finally the volume of the solution was adjusted to 100 ml by the addition of distilled water.
The solution may be filled into eye-dropper bottles and the bottle and its contents subsequently sterilised by heat for example by autoclaving at 116"C for 30 minutes at 10 psi pressure.
The solution had a viscosity of 30 cps when measured using a Brookfield LVF Viscometer using a UL adaptor at 12 rpm and at a temperature of 22"C.
The solution had a tear film break up time when tested on the rabbit cornea as hereinbefore referred to of 555 seconds. The solution had a tonicity equivalent to a 0.7% solution of sodium chloride.
EXAMPLE 2
Artificial Tear Solution
An aqueous solution suitable for use as an artificial tear was formulated as follows:
Hydroxyethylcellulose 0.44%
Sodium chloride 0.34%
Boric acid 0.50%
Phenylmercuric nitrate 0.002%
Sodium hydroxide solution to
adjust pH to 8.5
Distilled water to 100 ml
The aqueous solution was prepared in a similar manner to that described in Example 1. The solution may be packaged and sterilised as described in
Example 1.
This solution had a viscosity of 30 cps and had a tonicity equivalent to a 0.7% solution of sodium chloride. The solution had a tear film break up time of 500 seconds.
EXAMPLE 3
Artificial Tear Solution
An aqueous solution suitable for use as an artificial tear was formulated as follows:
Hydroxyethyl cellulose 0.44%
Disodium hydrogen phosphate 0.57%
Sodium dihydrogen phosphate 0.12%
Sodium chloride 0.34%
Distilled water to 100 ml
The aqueous solution was prepared in a similar manner to that described in Example 1. The solution may be packaged and sterilised as described in
Example 1.
This solution had a viscosity of 33.5 cps and was substantially isotonic, having a pH of 7.4. This solution had a tear film break up time of 573 seconds.
EXAMPLE 4
Artificial Tear Solution
An aqueous solution suitable for use in an artificial tear was formulated as follows:
Hydroxyethyl cellulose 0.4%
Sodium chloride 0.44%
Disodium hydrogen phosphate 0.57%
Sodium dihydrogen phosphate 0.12%
Polyethylene glycol (molecular
weight 300) 1.0%
Phenylmercuric nitrate 0.002%
Distilled water to 100 ml
This aqueous solution was prepared in a similar manner to that described in Example 1. The solution may be packaged and sterilised as described in
Example 1.
This solution had a viscosity of 30 cps and was isotonic at a pH of 7.4. The solution had a tear film break up time of 780 seconds.
EXAMPLE 5
Artificial Tear Solution
An aqueous solution suitable for use in an artificial tear is formulated as follows:
Hydroxyethyl cellulose 0.5%
Sodium chloride 0.44%
Disodium hydrogen phosphate 0.57%
Sodium dihydrogen phosphate 0.12%
Phenylmercuric nitrate 0.002% Distilledwaterto 100 ml
The hydroxyethyl cellulose is dissolved in water (50 ml). The resultant solution is sterilised by heat, for example autoclaving at 116"C for 30 minutes at 10 psi pressure and is then stored under aseptic conditions. The sodium chloride, phosphate salts and phenylmercuric nitrate are dissolved in water (40 ml) and the resultant solution is sterilised by filtration through a 0.22 micron cellulose ester membrane filter.
The two sterile solutions thus prepared are combined under aseptic conditions and the volume is made up to 100 ml with sterile distilled water. The solution is then filled into pre-sterilised eye-dropper bottles.
Claims (13)
1. A sterile aqueous solution suitable for topical administration to the eye which contains an effective amount of a hydroxyethyl cellulose together with sufficient of an ionic tonicity adjusting agent to give the solution a tonicity value equivalent to that of a solution containing from 0.3 to 1.1% of sodium chloride.
2. A sterile aqueous solution as claimed in claim 1 which contains from 0.1 to 10% of hydroxyethyl cellulose.
3. A sterile aqueous solution as claimed in either of claims 1 or 2 which contains from 0.25 to 0.75% of hydroxyethyl cellulose.
4. A sterile aqueous solution as claimed in any one of claims 1 to 3 in which the tonicity value of the solution is equivalent to that of a solution containing from 0.45 to 0.75% of sodium chloride,
5. A sterile aqueous solution as claimed in any one of claims 1 to 4 in which the pH value of the solution lies in the range 7.0 to 8.5.
6. A sterile aqueous solution as claimed in any one of claims 1 to 5 which additionally contains a buffering agent.
7. A sterile aqueous solution as claimed in claim 6 in which the buffering agent is a mixture of disodium hydrogen phosphate and sodiumdehydrogen phosphate.
8. A sterile aqueous solution as claimed in claim 6 in which the buffering agent is a mixture of sodium borate and boric acid.
9. A sterile aqueous solution as claimed in any one of claims 1 to 8 which additionally contains from 0.1 to 2.5% of polyalkylene glycol.
10. A sterile aqueous solution as claimed in claim 9 in which the polyalkylene glycol is a polyethylene glycol having a molecular weight of between 200 and 8000.
11. A sterile aqueous solution as claimed in any one of claims 1 to 10 which additionally contains an ophthalmically acceptable preservative.
12. A sterile aqueous solution as claimed in claim 11 in which the preservative comprises from 0.001 to 0.01% of a phenylmercuric salt
13. A sterile aqueous solution as claimed in any one of claims 1 to 12 in which the viscosity of the solution lies between 10 and 100 centipoise when measured on a Brookfield LVF Viscometer using a UL adapt~r at 12 rpm and at a temperature of 22"C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08500857A GB2169508B (en) | 1985-01-11 | 1985-01-11 | Ophthalmic compositions and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08500857A GB2169508B (en) | 1985-01-11 | 1985-01-11 | Ophthalmic compositions and use |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8500857D0 GB8500857D0 (en) | 1985-02-20 |
| GB2169508A true GB2169508A (en) | 1986-07-16 |
| GB2169508B GB2169508B (en) | 1989-02-01 |
Family
ID=10572810
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08500857A Expired GB2169508B (en) | 1985-01-11 | 1985-01-11 | Ophthalmic compositions and use |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2169508B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4819617A (en) * | 1986-09-04 | 1989-04-11 | University Of Florida | Viscoelastic material for ophthalmic surgery |
| US4923693A (en) * | 1988-01-21 | 1990-05-08 | Sundrops Enterprises, Inc. | Ultraviolet radiation screening method for eyes |
| EP0437179A2 (en) | 1989-12-15 | 1991-07-17 | Ciba-Geigy Ag | PH-controlled protein removing cleaner |
| DE4225489A1 (en) * | 1992-07-30 | 1994-02-03 | Michael Prof Dr Rer Na Dittgen | Aq. eye-drops contg. adhesive bio-polymer, e.g. polyvinyl alcohol and acid - adhere well to the cornea, provide better and longer lasting delivery of active ingredient e.g. pilocarpine |
| US5352445A (en) * | 1992-05-07 | 1994-10-04 | Lavaux Joseph E | Lavaux tear test lacrimal equilibration time (LET) |
| WO1995013050A1 (en) * | 1993-11-12 | 1995-05-18 | Ciba-Geigy Ag | Ophthalmic formulation useful in the treatment of dry eye syndrom |
| FR2871059A1 (en) * | 2004-06-03 | 2005-12-09 | Oreal | New artificial composition of lacrymal fluid type useful: for preparing a cosmetic or therapeutic composition (for washing eyes); and as a substituent of tears |
| US8791154B2 (en) | 2011-05-19 | 2014-07-29 | Alcon Research, Ltd. | High concentration olopatadine ophthalmic composition |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1090492A (en) * | 1965-07-20 | 1967-11-08 | Merck & Co Inc | Ophthalmic preparations comprising hydroxyethylcellulose |
| GB1337105A (en) * | 1971-07-26 | 1973-11-14 | ||
| GB2001529A (en) * | 1977-08-01 | 1979-02-07 | American Home Prod | Opthalmic compositions |
-
1985
- 1985-01-11 GB GB08500857A patent/GB2169508B/en not_active Expired
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1090492A (en) * | 1965-07-20 | 1967-11-08 | Merck & Co Inc | Ophthalmic preparations comprising hydroxyethylcellulose |
| GB1337105A (en) * | 1971-07-26 | 1973-11-14 | ||
| GB2001529A (en) * | 1977-08-01 | 1979-02-07 | American Home Prod | Opthalmic compositions |
Non-Patent Citations (1)
| Title |
|---|
| WO A1 86/03966 * |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4819617A (en) * | 1986-09-04 | 1989-04-11 | University Of Florida | Viscoelastic material for ophthalmic surgery |
| US4923693A (en) * | 1988-01-21 | 1990-05-08 | Sundrops Enterprises, Inc. | Ultraviolet radiation screening method for eyes |
| WO1991005542A1 (en) * | 1988-01-21 | 1991-05-02 | Sundrops Enterprises, Inc. | Ultraviolet radiation screening drops for the eyes |
| US6096696A (en) * | 1989-12-15 | 2000-08-01 | Ciba Vision Corporation | Alkaline composition for removing protein deposits |
| EP0437179A3 (en) * | 1989-12-15 | 1992-01-08 | Ciba-Geigy Ag | Ph-controlled protein removing cleaner |
| EP0437179A2 (en) | 1989-12-15 | 1991-07-17 | Ciba-Geigy Ag | PH-controlled protein removing cleaner |
| US5352445A (en) * | 1992-05-07 | 1994-10-04 | Lavaux Joseph E | Lavaux tear test lacrimal equilibration time (LET) |
| DE4225489A1 (en) * | 1992-07-30 | 1994-02-03 | Michael Prof Dr Rer Na Dittgen | Aq. eye-drops contg. adhesive bio-polymer, e.g. polyvinyl alcohol and acid - adhere well to the cornea, provide better and longer lasting delivery of active ingredient e.g. pilocarpine |
| WO1995013050A1 (en) * | 1993-11-12 | 1995-05-18 | Ciba-Geigy Ag | Ophthalmic formulation useful in the treatment of dry eye syndrom |
| US5597559A (en) * | 1993-11-12 | 1997-01-28 | Ciba Geigy Corporation | Ophthalmic formulation |
| FR2871059A1 (en) * | 2004-06-03 | 2005-12-09 | Oreal | New artificial composition of lacrymal fluid type useful: for preparing a cosmetic or therapeutic composition (for washing eyes); and as a substituent of tears |
| US8791154B2 (en) | 2011-05-19 | 2014-07-29 | Alcon Research, Ltd. | High concentration olopatadine ophthalmic composition |
| US9533053B2 (en) | 2011-05-19 | 2017-01-03 | Alcon Research, Ltd. | High concentration olopatadine ophthalmic composition |
Also Published As
| Publication number | Publication date |
|---|---|
| GB8500857D0 (en) | 1985-02-20 |
| GB2169508B (en) | 1989-02-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PE20 | Patent expired after termination of 20 years |
Effective date: 20050110 |