WO1991017469A1 - Kit for contact lenses - Google Patents

Kit for contact lenses Download PDF

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Publication number
WO1991017469A1
WO1991017469A1 PCT/HU1991/000016 HU9100016W WO9117469A1 WO 1991017469 A1 WO1991017469 A1 WO 1991017469A1 HU 9100016 W HU9100016 W HU 9100016W WO 9117469 A1 WO9117469 A1 WO 9117469A1
Authority
WO
WIPO (PCT)
Prior art keywords
weights
lysozyme
wetting
tris
acid
Prior art date
Application number
PCT/HU1991/000016
Other languages
French (fr)
Inventor
Ilona KAHÁN
Original Assignee
Vepex Contractor Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Vepex Contractor Ltd. filed Critical Vepex Contractor Ltd.
Publication of WO1991017469A1 publication Critical patent/WO1991017469A1/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/02Inorganic compounds ; Elemental compounds
    • C11D3/04Water-soluble compounds
    • C11D3/046Salts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L12/00Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
    • A61L12/08Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
    • A61L12/14Organic compounds not covered by groups A61L12/10 or A61L12/12
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/0005Other compounding ingredients characterised by their effect
    • C11D3/0078Compositions for cleaning contact lenses, spectacles or lenses
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/02Inorganic compounds ; Elemental compounds
    • C11D3/04Water-soluble compounds
    • C11D3/042Acids
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16Organic compounds
    • C11D3/20Organic compounds containing oxygen
    • C11D3/2075Carboxylic acids-salts thereof
    • C11D3/2086Hydroxy carboxylic acids-salts thereof
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16Organic compounds
    • C11D3/26Organic compounds containing nitrogen
    • C11D3/30Amines; Substituted amines ; Quaternized amines
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16Organic compounds
    • C11D3/26Organic compounds containing nitrogen
    • C11D3/32Amides; Substituted amides
    • C11D3/323Amides; Substituted amides urea or derivatives thereof
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16Organic compounds
    • C11D3/26Organic compounds containing nitrogen
    • C11D3/33Amino carboxylic acids
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16Organic compounds
    • C11D3/38Products with no well-defined composition, e.g. natural products
    • C11D3/386Preparations containing enzymes, e.g. protease or amylase
    • C11D3/38636Preparations containing enzymes, e.g. protease or amylase containing enzymes other than protease, amylase, lipase, cellulase, oxidase or reductase

Definitions

  • the invention relates to kits for wetting and cleaning of contact lenses.
  • tears were carried out for several decades by using tear substitutes in the form of arteficial tears. Efforts had been made to sooth the sensation of "dryness" of the eye in the case of insufficiency of tear production and at contact lens wear. Contact lens fitting and wetting solutions are employed all over the world.
  • the tear covers the healthy cornea in form of a tear film consisting of 3 layers.
  • the innermost layer of the 10 nm thick tear film consists mainly of ucin, the middle layer is an aqueous layer containing different organic and inorganic molecules, the outermost layer contiguous with the air is of lipid nature.
  • the mucin layer has been implicated in the formation of the tear film. At the application of tear substitutes efforts had been made for the substitution of mucin.
  • the thickness of the mucin layer had been measured to be 0.02-0.05 nm, but according to recent easurings the thickness of the mucin layer can attain even 10 nm (Nichols et al: Invest. Ophthalmol. Vis. Sci. 26, 464-473, 1985).
  • the tear fluid adheres to the cornea uniformly. By the surface activity of mucin the tear fluid is not drop-shaped, but forms a three-layered film upon the cornea, one of the most important tissues regarding the optic of the eye.
  • the tear film ensures the physical, chemical and microbiological protection of the cornea. Hence one of the most important guarantee of vision if the uniform and constant tear film.
  • the contact lens wear is also a cause of dry eye (Ferris R.: CLAD journal 12, 234-246, 1986).
  • Lenses produced from different synthetic materials can be grouped according to their physical properties fundamentally in three groups: hard lenses, oxygen permeable semi-hard lenses and soft lenses.
  • contact lens wetting solutions are necessary while fitting or simply inserting hard contact lenses and for soaking of soft contact lenses, for proper wetness.
  • Contact lens wetting solutions are also necessary for the prevention of the development of eye dryness (sicca syndrome).
  • the right contact lens wetting solution should have a prophylactic defensive natur in prevention of the eye from the develop- ment of the sicca syndrome.
  • the wetting solution should be supplemented by a cleaning solution which is free of toxic materials.
  • the tear substitutes and contact lens wetting solutions contain synthetic macromolecules for the substitution of mucin and to attain adequate viscosity.
  • These "artificial tears" and contact lens wetting solutions are completed with preservatives to prevent bacterial contami ⁇ nations, since solutions containing macromolecules (e.g. polyvinylalcohol, dextran etc.) become easily culture mediums for bacteria. They also easily obstruct the pores of the soft lenses.
  • solutions containing macromolecules e.g. polyvinylalcohol, dextran etc.
  • these solu ⁇ tions contain some preservatives, e.g. benz- alkonium chloride, chlorbutanol or some mercury compounds, e.g. thiomersal. These compounds easily cause allergic reactions,, moreover they are also toxic.
  • Preservatives being lipophil compounds interact with the superficial lipid layer of the tear film. Mucin of the tear film coats the lipophil preservatives linked to tear lipid and discharges them through the dacro-lachrymal system. Tear deficiency develops in the case of mucin consumption.
  • contact lens cleaning solutions are of great importance, since visual acuity and integrity of the cornea depend on them.
  • contact lens cleaning solutions are of great importance, since visual acuity and integrity of the cornea depend on them.
  • deposits of contaminations might impede visiion, pores of contact lenses might be ob ⁇ structed, by which . oxygen supply of the cornea decreases and cornea metabolism might get impaired.
  • deposits of contamina ⁇ tions might injure the cornea and might cause inflammation of the conjunctiva and the cornea, in many cases even before the appearance of visible contaminations. Life expectancy of the lenses is also dependent on the appropriate cleaning solution.
  • contact lens wear all three types, soft, hard and oxygen permeable
  • Cleaning solutions can be grouped according to their application a) disinfection solutions, b) disinfection and storing solutions, c) solutions for heat disinfection, d) general cleaning solutions, e) intensive cleaning solutions, f) periodically used cleaning solutions, g) cleaning solutions for daily use.
  • One object of the invention is to prepare a kit for the treatment of hard, semi-hard and soft contact lenses which have a composition similar to the composition of tear, by use of which kit the wetting and cleaning of the contact lenses can be effected.
  • Another object of the invention is to decrease the number of manipulations necessary to use contact lenses and to eliminate the impairment (damage) of eye.
  • the kit suitable for treatment of contact lenses comprises a wetting and a cleaning composition and the wetting composition contains 0.1 to 1.0 weight?, of lysozyme (egg white lysozyme EC 3.2.1.17),
  • the wetting composition has a pH value of 6.8 which is adjusted by means of tris(hydroxymethyl)- aminomethane.
  • a preferred wetting composition contains 0.1 weights of . chicken egg white lysozyme, 1.8 weights of tris(hydroxymethyl)aminomethane, 0.5 weights of boric acid, 0.5 weights of ascorbic acid, 0.45 weights of sodium chloride in solution prepared with distilled water.
  • Another preferred wetting composition contains
  • the lysozyme activity of the wetting compositions is 18.500 U/ml (determination of activity according to Shugar, D: Biochim. Biophys. Acta 8_, 302, 1952).
  • the surface activity of the wetting composition iiss 4455--5500 ddyynn ccmm " -1
  • a preferred cleaning composition contains 3 weights of urea, 0.1 weights of egg white lysozyme,
  • Another preferred cleaning composition contains 12 weights of urea, 0.1 weights of egg white lysozyme, 0.45 weights of sodium chloride,
  • the quality of the components equals to the purity required by the pharmaceutical composi ⁇ tions.
  • the lysozyme-HCl (mucopeptide N-acetyl muramoyl hydrolase, EC 3.2.1.17 quality (Worthington product, Free Ltd., New Jersey, USA)).
  • the tris(hydroxy- methyl)aminomethane, the boric acid, the citric acid and the ethylenediaminotetraacetic acid disodium salt are dissolved in freshly distilled ion free water.
  • the pH value of the solution is adjusted to 6.0 to 6.5.
  • the lysozyme HC1 is added to the solution and after the dissolution thereof the pH value of the solution is adjusted to 6.8 by means of tris(hydroxy- methyDaminomethane and finally the solution is completed with distilled water to the end volume.
  • the solution is left standing, the substances precipitated are removed by sterile filtration, then the sterilized solution is filled into the container, the composition is clear, turbidity free and has the required lysozyme activity.
  • Relative viscosity of the tear substitute and contact lens wetting solution is low (1.07 referring to water) compared to the commercially available arteficial tear solutions and contact lens wetting solutions, containing synthetic macromolecules. Inspite of it, it has advantageous absorbtive properties on the corneal epithelium.
  • the tris(hydroxymethyl)aminomethane used for the dissolution of lysozyme and for the regula ⁇ tion of the pH and of the osmosis pressure of the solution gives unexpectedly a significant enzyme activity enhancing effect.
  • compositions of the invention dispose im ⁇ portant microbiological defense mechanism. According to the investigations they display significant bacteriostatic effects against the most dangerous Gram positive and Gram negative bacteria strains to the eye, e.g. Staphylococcus aauurreeuuss aanndd PPsseeuuddoi monas aerugonosa (2.10 cells/ml within 4 hours).
  • the wetting composition may be used in addition for the following purposes:
  • the composition for cleaning of hard, soft and oxygen permeable semihard contact lenses should be harmless to the cornea and should contain mainly lacrophil natural compounds.
  • Contaminations of contact lenses can be prevented when adding urea to the wetting composition.
  • By increasing the amount of urea a definite cleaning effect has been achieved.
  • the main compounds of the contact lens cleaning solution are urea and chicken egg white lysozyme (muramidase, N-acetyl-muramyl/1-4/ glycanohydrolase EC 3.2.1.17).
  • the lysozyme enhances the aggregation of bacteria such as Staphylococcus aureus and thus inhibits the adherence thereof to the contact lens.
  • the contact lens cleaning composition contains beside the above mentioned compounds tris(hydroxy ⁇ methyl)aminomethane (TRIS), which acts as a pH regulator and enzyme activator, citric acid, which exerts favourable effects on protein structure and boric acid and ethylenediaminetetraacetic acid disodium (EDTA Na opinion) which synergetically increase the bacteriostatic effect of the composi ⁇ tion.
  • TriS tris(hydroxy ⁇ methyl)aminomethane
  • citric acid which exerts favourable effects on protein structure
  • Concentrations of all components are similar to that of the contact lens wetting composition.
  • Great advantage of the cleaning composition is that most of the components are also present in the natural tear fluid.
  • the natural tear fluid also contains urea, though in a much smaller concentration (0.03-0.05S) . Lysozyme content of tears
  • the cleaning solution can be employed as a general cleaning solution, as a periodical cleaning solution or as a daily cleaning solution.
  • the two compositions form a "kit" for contact lens wearer.
  • the contact lens wearer inserts the contact lenses (in case of hard lenses with 3-4 drops in case of soft contact lenses immerses his contact lenses for soaking) with the contact lens wetting solution into the eyes. Should the contact lens wearer feel the eyes “dry” during contact lens wear, a few drops of the contact lens wetting composition suffice to comfort the eyes. "Dryness” feeling ceases and by this contact lens wetting solution works also as a lubricating and rewetting solution.
  • the cleaning effect of the contact lens cleaning composition is of such a degree, that immersing contact lenses (soft, hard or oxygen permeable semihard lenses) into the contact lens cleaning composition for 4-5 hours, contaminations can be simply shaken off, without rubbing. So contact lenses are spared to a high degree, and they can be removed from the cleaning composition without a scratch.
  • Example 1 egg white lysozyme 0.10 S sodium chloride 0.45 S tris(hydroxymethyl)aminomethane (TRIS) 1.80 S borid acid 0.50 S ascorbic acid 0.50 S in aqueous solution (sterile distilled water). This composition is suitable as a tear substitute and/or as a contact lens wetting composition.
  • TIS tris(hydroxymethyl)aminomethane
  • Tear substitute and contact lens_ wetting composi ⁇ tion chicken egg white lysozyme.
  • aqueous solution sterile distilled water
  • Lysozyme activity measurings were repeated after storage at 4 C for 14 month: lysozyme activity proved to be 18.500 U/ml.
  • Dry ampoule and dissolving ampoule can be stored separately for years.
  • Contact lens wetting composition chicken egg white lysozyme 0.1 S sodium chloride 0.3 S
  • Contact lens wetting composition chicken egg white lysozyme I .
  • U 7o sodium chloride 0.45 S TRIS 1.8 S ascorbic acid ethylenediamine tetraacetic acid di ⁇ sodium (EDTA Na-,) 0.05
  • Contaminations of contact lenses are cleaned with mild rubbing after 4-5 hours immersing in the solution.
  • the solution can be employed for immersing contact lenses (soft, hard, oxygen permeable semihard contact lenses) for 5-6 hours. Contaminations can be removed by mere shaking off.

Abstract

The invention relates to a kit for treating contact lenses comprising a wetting and a cleaning composition. The wetting composition contains egg white lysozyme and enzyme activating tris(hydroxymethyl)aminomethane in addition to lacrophyl components. The pH value and surface tension is similar to the properties of natural tear. The cleaning composition contains urea and egg white lysozyme and lacrophyl components.

Description

KIT FOR CONTACT LENSES
The invention . relates to kits for wetting and cleaning of contact lenses.
Replacement of tears were carried out for several decades by using tear substitutes in the form of arteficial tears. Efforts had been made to sooth the sensation of "dryness" of the eye in the case of insufficiency of tear production and at contact lens wear. Contact lens fitting and wetting solutions are employed all over the world.
An important recognition is that the tear covers the healthy cornea in form of a tear film consisting of 3 layers. The innermost layer of the 10 nm thick tear film consists mainly of ucin, the middle layer is an aqueous layer containing different organic and inorganic molecules, the outermost layer contiguous with the air is of lipid nature. In the last years the greatest attention has been drawn to the innermost layer adhesing to the cornea. A decisive role of the mucin layer has been implicated in the formation of the tear film. At the application of tear substitutes efforts had been made for the substitution of mucin. Originally the thickness of the mucin layer had been measured to be 0.02-0.05 nm, but according to recent easurings the thickness of the mucin layer can attain even 10 nm (Nichols et al: Invest. Ophthalmol. Vis. Sci. 26, 464-473, 1985). The tear fluid adheres to the cornea uniformly. By the surface activity of mucin the tear fluid is not drop-shaped, but forms a three-layered film upon the cornea, one of the most important tissues regarding the optic of the eye.
The tear film ensures the physical, chemical and microbiological protection of the cornea. Hence one of the most important guarantee of vision if the uniform and constant tear film. In the last years it had been realized that besides the grave pathological dry eye condi¬ tions the contact lens wear is also a cause of dry eye (Ferris R.: CLAD journal 12, 234-246, 1986).
Contact lens wear spread all over the world for the correction of errors of refraction. Lenses produced from different synthetic materials can be grouped according to their physical properties fundamentally in three groups: hard lenses, oxygen permeable semi-hard lenses and soft lenses.
The use of contact lens wetting solutions are necessary while fitting or simply inserting hard contact lenses and for soaking of soft contact lenses, for proper wetness. Contact lens wetting solutions are also necessary for the prevention of the development of eye dryness (sicca syndrome). The right contact lens wetting solution should have a prophylactic defensive natur in prevention of the eye from the develop- ment of the sicca syndrome.
The wetting solution should be supplemented by a cleaning solution which is free of toxic materials.
The tear substitutes and contact lens wetting solutions contain synthetic macromolecules for the substitution of mucin and to attain adequate viscosity. These "artificial tears" and contact lens wetting solutions are completed with preservatives to prevent bacterial contami¬ nations, since solutions containing macromolecules (e.g. polyvinylalcohol, dextran etc.) become easily culture mediums for bacteria. They also easily obstruct the pores of the soft lenses. To prevent bacterial contaminations these solu¬ tions contain some preservatives, e.g. benz- alkonium chloride, chlorbutanol or some mercury compounds, e.g. thiomersal. These compounds easily cause allergic reactions,, moreover they are also toxic.
These facts need distinguished attention when contact lens wetting solutions are used. Contact lenses take up preservatives and by the inter¬ action of these toxic compounds with the material of the lenses, they are concentrated by the lenses. The effective concentration, of the preservatives at the surface of the contact lens is much higher than the concentration in the contact lens wetting solution. The toxic effect is the greatest at the corneal epithelium, where the preservatives are released from the lens material.
Preservatives being lipophil compounds interact with the superficial lipid layer of the tear film. Mucin of the tear film coats the lipophil preservatives linked to tear lipid and discharges them through the dacro-lachrymal system. Tear deficiency develops in the case of mucin consumption.
It is the aim all over the world to eliminate preservatives in the tear substitutes.
In addition to the contact lens wetting solutions contact lens cleaning solutions are of great importance, since visual acuity and integrity of the cornea depend on them. In case of the use of insufficient contact lens cleaning solu¬ tions deposits of contaminations might impede visiion, pores of contact lenses might be ob¬ structed, by which . oxygen supply of the cornea decreases and cornea metabolism might get impaired. In all three types of lenses (hard, soft and oxygen permeable lenses) deposits of contamina¬ tions might injure the cornea and might cause inflammation of the conjunctiva and the cornea, in many cases even before the appearance of visible contaminations. Life expectancy of the lenses is also dependent on the appropriate cleaning solution. While life expectancy of the hard lenses is of several years, soft lenses have life expectancy from one half a year to one year. Reason of this is that cleaning of soft lenses is much more difficult than cleaning of hard lenses. Hence the wear of soft contact lenses is of a great expense than the wear of hard contact lenses.
The use of cleaning solutions of good quality enables the contact lens wearer with less danger and also the life expectancy of contact lenses can be elongated. By this means contact lens wear (all three types, soft, hard and oxygen permeable) becomes more economical.
Cleaning solutions can be grouped according to their application a) disinfection solutions, b) disinfection and storing solutions, c) solutions for heat disinfection, d) general cleaning solutions, e) intensive cleaning solutions, f) periodically used cleaning solutions, g) cleaning solutions for daily use.
Grouping of cleaning solutions according to the chemical reactions involved in the cleaning procedure:
1) heat denaturation,
2) proteases,
3) peroxides and iodine,
4) mercury compounds,
5) benzalkonium chloride and chlorhexidine (Brewitt H. and Mandel S.: Contactologia
10D, 53-58, 1988), 6) silver compounds (Bonkhoff P.: Contactologia 10D, 59-66, 1988),
7) compounds which prevent adhesion of proteins to contact lenses (Cerulli et al: Contactologia 10D, 62-72, 1988).
Inspite of the many kinds of cleaning and disin¬ fection possibilities of contact lenses being available, cleaning and disinfection are still a problem (Donzis P.B. et al : Am. J. Ophthalmol. 104, 325-333, 1987, Herve L. et al: Contactologia 10D, 151-154, 1988, Bisignano G. et al: Contacto¬ logia 10D, 155-158, 1988).
One object of the invention is to prepare a kit for the treatment of hard, semi-hard and soft contact lenses which have a composition similar to the composition of tear, by use of which kit the wetting and cleaning of the contact lenses can be effected. Another object of the invention is to decrease the number of manipulations necessary to use contact lenses and to eliminate the impairment (damage) of eye.
The kit suitable for treatment of contact lenses comprises a wetting and a cleaning composition and the wetting composition contains 0.1 to 1.0 weight?, of lysozyme (egg white lysozyme EC 3.2.1.17),
0.02 to 10.0 weights of ascorbic acid and/or 0.01 to 1.0 weights of citric acid 0.18 to 3.6 weights of tris(hydroxymethyl)amino- methane
0.05 to 1.0 weights of boric acid and/or
0.05 to 0.1 weights of ethylenediaminetetraacet'ic acid disodium salt
0.45 to 0.9 weights of sodium chloride
99.4 to 83.4 weights of distilled water
while the cleaning composition contains
0.1 to 1.0 weights of lysozyme (egg white lysozyme
EC 3.2.1.17)
3.0 to 12.0 weights of urea
0.02 to 10.0 weights of ascorbic acid and/or citric acid
0.18 to 3.6 weights of tris(hydroxymethyl)amino- ethane
0.05 to 1.0 weights of boric acid and/or
0.05 to 0.1 weights ethylenediaminetetraacetic acid disodium salt
0.45 to 0.9 weights of sodium chloride
96.0 to 71.4 weights of distilled water.
The wetting composition has a pH value of 6.8 which is adjusted by means of tris(hydroxymethyl)- aminomethane.
A preferred wetting composition contains 0.1 weights of . chicken egg white lysozyme, 1.8 weights of tris(hydroxymethyl)aminomethane, 0.5 weights of boric acid, 0.5 weights of ascorbic acid, 0.45 weights of sodium chloride in solution prepared with distilled water. Another preferred wetting composition contains
0.1 weights of egg white lysozyme HC1,
2.7 weights of tris(hydroxymethyl)aminomethane,
0.5 weights of boric acid,
1.64 weights of citric acid,
0.1 weights of ethylenediaminetetraacetic acid disodium salt.
The lysozyme activity of the wetting compositions is 18.500 U/ml (determination of activity according to Shugar, D: Biochim. Biophys. Acta 8_, 302, 1952).
The surface activity of the wetting composition iiss 4455--5500 ddyynn ccmm" -1
(measured by means of Du Nouy tensiometer) .
A preferred cleaning composition contains 3 weights of urea, 0.1 weights of egg white lysozyme,
2.7 weights of tris(hydroxymethyl)aminomethane, 0.5 weights of boric acid, 1.64 weights of citric acid, 0.1 weights of ethylenediaminetetra¬ acetic acid sodium salt.
Another preferred cleaning composition contains 12 weights of urea, 0.1 weights of egg white lysozyme, 0.45 weights of sodium chloride,
1.8 weights of tris(hydroxymethyl)aminomethane, 1.6 weights of citric acid, 0.5 weights of boric acid and 0.05 weights of ethylenediamine tetraacetic acid disodium salt.
The quality of the components equals to the purity required by the pharmaceutical composi¬ tions. The lysozyme-HCl (mucopeptide N-acetyl muramoyl hydrolase, EC 3.2.1.17 quality (Worthington product, Free Ltd., New Jersey, USA)).
On preparing the compositions the tris(hydroxy- methyl)aminomethane, the boric acid, the citric acid and the ethylenediaminotetraacetic acid disodium salt are dissolved in freshly distilled ion free water. The pH value of the solution is adjusted to 6.0 to 6.5. Thereafter the lysozyme HC1 is added to the solution and after the dissolution thereof the pH value of the solution is adjusted to 6.8 by means of tris(hydroxy- methyDaminomethane and finally the solution is completed with distilled water to the end volume. The solution is left standing, the substances precipitated are removed by sterile filtration, then the sterilized solution is filled into the container, the composition is clear, turbidity free and has the required lysozyme activity.
It has been found that applying a lysozyme (muramidase, N-acetylmuramyl beta/1-4/ glycano- hydrolase, EC 3.2.1.17) the tear film could advantageously be re-established similar to the effect of mucin. The role and effect of tear lysozyme could be achieved by .applying its isoenzyme. A sufficient effect could be gained by employing an isoenzyme of tear lysozyme e.g. chicken egg white lysozyme. This is capable to form linkages with mucin which broadens the innermost layer of the tear film and regulate surface tension. By this fact tear "break up time" ("BUT") characteristic for tear film stability becomes also appropriate. (Surface
_*1 tension of the composition is 49 dyn. cm , mean of surface tension of tears of healthy subjects is 41 dyn. cm (Holly F. et al.: Exp. Eye Res. 2_4, 479-491, 1977)). It should be emphasized that this very advantageous surface tension is formed without preservatives, which being of lipid nature (but are toxic!) would lower the surface tension, in fact they lower the surface tension of the commercially available wetting compositions (arteficial tears) /Lemp M.A. and Holly F.: Ann. Ophthalmol. 15-20, 1972/. Relative viscosity of the tear substitute and contact lens wetting solution is low (1.07 referring to water) compared to the commercially available arteficial tear solutions and contact lens wetting solutions, containing synthetic macromolecules. Inspite of it, it has advantageous absorbtive properties on the corneal epithelium.
The tris(hydroxymethyl)aminomethane used for the dissolution of lysozyme and for the regula¬ tion of the pH and of the osmosis pressure of the solution, gives unexpectedly a significant enzyme activity enhancing effect.
Remarkable results can be achieved by using lysozyme solutions with ascorbic acid and/or citric acid additives. Antiphlogistic and collagenase inhibiting effect of lysozyme is advantageously completed by them. Ascorbic HU91/00016
- 1 1 -
acid and citric acid are also known for their antiphlogistic nature, hence by using the compo¬ sitions containing lysozyme with ascorbic acid and/or citric acid the synergetic action resulted in a significant antiphlogistic effect. The good therapeutic effect is supplemented by hemostatic, analgetic and antihistamin properties.
By the most important effect of lysozyme, the bacteriostatic effect - not merely the eye is protected against infection - but the solution itself is also protected against microbiological contaminations. The use of preservatives is either totally superfluous, or it is needed only to a very little extent. For this purpose boric acid proved useful. Also the use in some cases of ethylenediaminetetraacetic acid proved to be satisfactory.
The compositions of the invention dispose im¬ portant microbiological defense mechanism. According to the investigations they display significant bacteriostatic effects against the most dangerous Gram positive and Gram negative bacteria strains to the eye, e.g. Staphylococcus aauurreeuuss aanndd PPsseeuuddoi monas aerugonosa (2.10 cells/ml within 4 hours).
The wetting composition may be used in addition for the following purposes:
In the "dry-eye" syndrome (developed during ageing, or in connection or consequence of some disease, or appearing as a side-effect of 16
- 1 2 -
medical treatment) as eye-drop solution; after cataract surgery and artificial lens implan¬ tation, for the treatment of bacterial and allergic conjunctivitis, herpes virus, adenovirus or other infective diseases, collagen diseases of the cornea, inflammatory or malign processes of the eye-lid as eye-drop solution or lotion.
Similar to the composition of the contact lens wetting solution, the composition for cleaning of hard, soft and oxygen permeable semihard contact lenses should be harmless to the cornea and should contain mainly lacrophil natural compounds.
Contaminations of contact lenses can be prevented when adding urea to the wetting composition. By increasing the amount of urea a definite cleaning effect has been achieved. By increasing the amount of urea from 0.05 M to 0.5 M - 2.0 M" the cleaning effect can be increased also.
Accordingly the main compounds of the contact lens cleaning solution are urea and chicken egg white lysozyme (muramidase, N-acetyl-muramyl/1-4/ glycanohydrolase EC 3.2.1.17).
The lysozyme enhances the aggregation of bacteria such as Staphylococcus aureus and thus inhibits the adherence thereof to the contact lens.
The contact lens cleaning composition contains beside the above mentioned compounds tris(hydroxy¬ methyl)aminomethane (TRIS), which acts as a pH regulator and enzyme activator, citric acid, which exerts favourable effects on protein structure and boric acid and ethylenediaminetetraacetic acid disodium (EDTA Na„) which synergetically increase the bacteriostatic effect of the composi¬ tion. Concentrations of all components are similar to that of the contact lens wetting composition. Great advantage of the cleaning composition is that most of the components are also present in the natural tear fluid. The natural tear fluid also contains urea, though in a much smaller concentration (0.03-0.05S) . Lysozyme content of tears is about the same as that of the contact lens wetting solution. A subsequent use of the cleaning and wetting solution is possible, because rinsing the contact lens with the wetting solution thoroughly, it can be directly inserted into the eye.
By applying urea to the cleaning solution a decrease of manipulations,, on the use of contact lenses can be achieved and also the errors of manipulations could be decreased, thereby the protection of the cornea can be attained with great security.
The cleaning solution can be employed as a general cleaning solution, as a periodical cleaning solution or as a daily cleaning solution.
As it is to be seen from the above description, two compositions are necessary for the wear - 1 4 -
of contact lenses from which no one contains preservatives. The two compositions form a "kit" for contact lens wearer. The contact lens wearer inserts the contact lenses (in case of hard lenses with 3-4 drops in case of soft contact lenses immerses his contact lenses for soaking) with the contact lens wetting solution into the eyes. Should the contact lens wearer feel the eyes "dry" during contact lens wear, a few drops of the contact lens wetting composition suffice to comfort the eyes. "Dryness" feeling ceases and by this contact lens wetting solution works also as a lubricating and rewetting solution.
The cleaning effect of the contact lens cleaning composition is of such a degree, that immersing contact lenses (soft, hard or oxygen permeable semihard lenses) into the contact lens cleaning composition for 4-5 hours, contaminations can be simply shaken off, without rubbing. So contact lenses are spared to a high degree, and they can be removed from the cleaning composition without a scratch.
The Examples illustrate the details of the inven¬ tion without restricting its scope:
Example 1 egg white lysozyme 0.10 S sodium chloride 0.45 S tris(hydroxymethyl)aminomethane (TRIS) 1.80 S borid acid 0.50 S ascorbic acid 0.50 S in aqueous solution (sterile distilled water). This composition is suitable as a tear substitute and/or as a contact lens wetting composition.
Example 2
Tear substitute and contact lens_ wetting composi¬ tion: chicken egg white lysozyme. HC1 TRIS 2.7 boric acid 0.5 0/ <0 citric acid 1.64S ethylenediaminetetraacetic acid disodium salt (EDTA-Na.,) 0.1 S
in aqueous solution (sterile distilled water).
Preparation of 40 1 contact lens wetting composi¬ tion:
1080 g of TRIS, 200 g of boric acid, 656 g of citric acid and 40 g of EDTA-Na? are dissolved in 32 1 of distilled water. The dissolution can be completed by stirring, ..but every single component should be added in the given sequence. Thereafter pH should be adjusted to pH 6.0- 6.5 with 3 M TRIS. 40 g lysozyme.HC1 should be put on the top of the solution. Lysozyme dissolves without stirring. After complete disso¬ lution the pH should be adjusted to pH = 6.8 with TRIS. Sterilization should be performed by filtration through a bacterium filter in a sterile system.
Physico-chemical properties of the contact lens wetting composition: pH 6.8 osmolarity 300 mOzmol surface tension 49 dyn.cm -1 relative viscosity (in relation to water) 1.07 lysozyme activity 18.500 U/ml
(Analytical method according to
Shugar, D.: Biochim. Biophys.
Acta 8, 302, 1952)
Lysozyme activity measurings were repeated after storage at 4 C for 14 month: lysozyme activity proved to be 18.500 U/ml.
Clinical tests:
In a double blind study 25 dry patients were treated with the wetting composition (Example 2) for two weeks. After two weeks interval the same patients were treated with a tear substitute containing synthetic macromolecules. 17 patients recommended the lysozyme containing composition for better, 7 patients qualified the two tear substitutes for equally good. No itching, stingig or allergic reactions had been registered. Schirmer and BUT values improved in all 25 patients. By using the wetting composition (Example 2) in only 4 of the 25 patients Rose Bengal staining of the cornea remained slightly positive.
Example 3
Contact lens wetting composition. Dry ampolue: chicken egg white lysozyme 0.01 g ascorbic acid 0.02 g
(in a separate dissolving capsule)
Dissolving ampoule or eye-drop bottle: 10 ml aqueous solution of sodium chloride 0.45 S TRIS 1.8 S boric acid 0.5 S
Content of the dry ampoule is to be dissolved in the content of the dissolving ampoule (eye- drop bottle). pH of the solution is 7.3. Dry ampoule and dissolving ampoule (eye-drop bottle) can be stored separately for years.
Example 4
Contact lens wetting composition: chicken egg white lysozyme 0.1 S sodium chloride 0.3 S
TRIS 2.4 S boric acid 0.05 S citric acid 0.88 S
In aqueous solution (sterile bidistilled water) physico chemical properties: pH 7.1 osmolarity 305 mOzmol surface tension 46.8 dyn.cm relative viscosity 1.07 - 1 8 -
Examp le 5
Contact lens wetting composition: chicken egg white lysozyme I . U 7o sodium chloride 0.45 S TRIS 1.8 S ascorbic acid ethylenediamine tetraacetic acid di¬ sodium (EDTA Na-,) 0.05
in aqueous solution (sterile bidistilled water) pH of the solution: pH = 6.7
Figure imgf000020_0001
in aqueous solution, pH of the solution is ad¬ justed to pH = 6.8 with TRIS.
Contaminations of contact lenses (hard, soft and oxygen permeable semi-hard lenses) are cleaned with mild rubbing after 4-5 hours immersing in the solution.
A several years' trial of an ophthalmologist prescribing and fitting hard, semihard and gas- permeable contact lenses since 50 years proved comfort feeling and decrease of yearly irritation symptoms, when using lysozyme containing contact lens wetting and storage solutions (Example 2) and contact lens cleaning solution (Example 6). The cleaning solution especially worked well by decreasing the inconvenient "greasiness" phenomenon.
Example 7
Contact lens cleaning composition urea egg white lysozyme
TRIS citric acid boric acid
Figure imgf000021_0001
Figure imgf000021_0002
in aqueous solution. pH of the solution is adjusted to pH = 6.8. The solution can be employed for immersing contact lenses (soft, hard, oxygen permeable semihard contact lenses) for 5-6 hours. Contaminations can be removed by mere shaking off.
Preparation of 40 1 contact lens cleaning solution: The process is similar to the preparation of the acontact lens wetting and storage solution (see Example 2), but 3600 g (9 S) urea is dis¬ solved just before lysozyme is added. Physicochemical properties of the contact lens cleaning solution: pH 6.8 lysozyme activity 15.500 U/ml density 1.0642 g/ml 25°C According to microbiological investigations the contact lens cleaning solution has a proper bacteriostatic activity against the most important bacteria (Staphylococcus aureus, Escherichia coli and Pseudomoπas aeruginosa) within the 72 hours examination, even if it is twice diluted.
To prove the advantage of the wetting and storage solution and to assess the cleaning capacity of the cleaning solution complex studies both in vitro and in vivo have been performed. After determining the length of time necessary for cleaning (which proved to be about 3 - 3 1/2 hours) and not to jeopardize the eye and for the sake of soundness of the contact lens well the time for removing urea absorbed by the contact lens had to be determined. From studies in vitro in became clear that the span of time for cleaning and the subsequent soaking in physiological saline or in the wetting solution for the removal of urea proved to be equally about 3 - 3 1/2 hours
In vivo studies for three months has been performed with soft contact lens wearing patients using the lysozyme containing contact lens wetting and storage solution (20 eyes). A comparison of the lysozyme containing cleaning solution with a protein remover (Bausch and Lomb) has been performed.
Group A of soft lenses wearing patients used once a week the lysozyme containing contact lens cleaning lens cleaning solution for 6 hours. After thorough rinsing with physiological saline, inserted their lenses in physiological saline for another 6 hours. The lenses were stored in the Lacrozy wetting and storage solution. Group B of soft lenses wearing patients used the lysozyme containing wetting and storage solution similar to patients of group A, but used for cleaning of contact lenses a protein remover (Bausch and Lomb). Thereafter the lenses were stored in the lysozyme containing wetting and storage solution.
Patients in both groups feeled the solutions for comfortable and easy to handle. Moreover they felt especially useful to apply the wetting solution as eye-drops during the day while wearing the contact lenses. This proved to lengthen wearing time, hence it worked as an in-eye- lens lubricant very advantageously. Lysozyme containing cleaning solution and Bausch and Lomb protein remover proved to be equally effective even in long term use. So even the periodical use of a protein remover -recommended by most of the commercially available contact lens cleaner can be eliminated. By this the risk to have traces of protease residues left on the lenses ceases.
Ex aple 8
Contact lens cleaning composition: urea 12.0 5 egg white lysozyme 0.1 5 sodium chloride 0.45 S TRIS 1.8 S citric acid 1.64 S boric acid 0.5 S
EDTA-Na-, 0.05 S
in aqueous solution. pH of the solution is adjusted to pH = 6.8.

Claims

- 23 -
C l a i m s
1. A kit suitable for treatment of contact lenses comprising a wetting and a cleaning composition wherein the wetting composition contains
0.1 to 1.0 weights of lysozyme (egg white lysozyme
EC 3.2.1.17),
0.02 to 10.0 weights of ascorbic acid and/or
0.01 to 1.0 weights of citric acid,
0.18 to 3.6 weights of tris(hydroxymethyl)amino- ethane,
0.05 to 1.0 weights boric acid and/or
0.05 to 1.0 weights of ethylenediaminetetraacetic acid disodium salt
0.45 to 0.9 weights of sodium chloride,
99.4 to 83.4 weights of distilled water,
while the cleaning composition contains
0.1 to 1.0 weights of lysozyme (egg white lysozyme EC 3.2.1.17),
3.0 to 12.0 weights of urea,
0.02 to 10.0 weights of ascorbic acid and/or citric acid,
0.18 to 3.6 weights of tris(hydroxymethyl)amino¬ methane,
0.05 to 1.0 weights of boric acid and/or 0.05 to 1.0 weights ethylenediaminetetraacetic acid disodium salt
0.45 to 0.9 weights of sodium chloride, 96.0 to 71.4 weights of distilled water.
2. A composition according to claim 1 wherein the wetting composition has a pH value of 6.8 adjusted by means of tris(hydroxymethyl )amino¬ methane.
3. A composition according to claim 1 wherein the wetting composition contains
0.1 weights of egg white lysozyme,
1.8 weights of tris(hydroxymethyl)aminomethane,
0.5 weights of boric acid,
0.5 weights of ascorbic acid,
0.45 weights of sodium chloride.
4. A composition according to claim 1 wherein the wetting composition contains
0.1 weights of egg white lysozyme.HC1 ,
2.7 weights of tris(hydroxymethyl )aminomethane,
0.5 weights of boric acid,
1.64 weights of citric acid,
0.1 weights of ethylenediaminetetraacetic acid disodium salt.
5. A composition according to claim 1 wherein the lysozyme activity of the wetting compositions is 18.500 U/ml.
6. A composition according to claim 1 wherein the cleaning composition contains
3 weights of urea,
0.1 weights of egg white lysozyme,
2.7 weights of tris(hydroxymethyl)aminomethane,
0.5 weights of boric acid,
1.64 weights of citric acid,
0.1 weights of ethylenediaminetetraacetic acid disodium salt. 7. A composition according toclaim 1 wherein the cleaning composition contains
12 weights urea,
0.1 S of egg white - lysozyme,
0.45 weights of sodium chloride,
1.8 weights of tris(hydroxymethyl)aminomethane,
1.6 weights of citric acid,
0.5 weights of boric acid and
0.05 weights of ethylenediamine tetraacetic acid disodium salt.
PCT/HU1991/000016 1990-05-09 1991-05-08 Kit for contact lenses WO1991017469A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU902969A HU209538B (en) 1990-05-09 1990-05-09 Set and cleaning composition for treating contactlenses
HU2969/90 1990-05-09

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Cited By (8)

* Cited by examiner, † Cited by third party
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WO1992011876A1 (en) * 1990-12-27 1992-07-23 Schering Corporation Method and composition for disinfecting contact lenses
EP0575290A1 (en) * 1992-06-17 1993-12-22 Ciba-Geigy Ag Product for care of hard or soft contact lenses
WO1995006099A1 (en) * 1993-08-27 1995-03-02 Alcon Laboratories, Inc. Process for cleaning and disinfecting contact lenses
AU733386B2 (en) * 1993-08-27 2001-05-10 Alcon Laboratories, Inc. Process for cleaning and disinfecting contact lenses
WO2001082893A1 (en) * 2000-05-04 2001-11-08 Molnarne Kahan Ilona Use of a lacrophyl preparation in eye-drops containing therapeutically active compounds
US6338847B1 (en) 1993-01-26 2002-01-15 Allergan Compositions and methods to disinfect contact lenses
WO2007032997A1 (en) * 2005-09-13 2007-03-22 Bausch & Lomb Incorporated Ophthalmic formulation containing loteprednol etabonate for treatment of dry eye
US8563011B2 (en) 1996-12-13 2013-10-22 Alcon Research, Ltd. Use of low molecular weight amino alcohols in ophthalmic compositions

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GB2019600A (en) * 1978-04-24 1979-10-31 Senju Pharma Co Contact lens cleaning composition
US4355022A (en) * 1981-07-01 1982-10-19 Interon, Inc. Method of dental treatment
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Cited By (19)

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Publication number Priority date Publication date Assignee Title
US5756045A (en) * 1990-12-27 1998-05-26 Allergan Method and composition for disinfecting contact lenses
EP0766970A3 (en) * 1990-12-27 2000-02-23 Allergan, Inc Method and composition for disinfecting contact lenses
WO1992011876A1 (en) * 1990-12-27 1992-07-23 Schering Corporation Method and composition for disinfecting contact lenses
US5817277A (en) * 1990-12-27 1998-10-06 Allergan Method and composition for disinfecting contact lenses
US5422073A (en) * 1990-12-27 1995-06-06 Allergan, Inc. Method and composition for disinfecting contact lenses
US5500186A (en) * 1990-12-27 1996-03-19 Allergan, Inc. Method and composition for disinfecting contact lenses
US5593637A (en) * 1990-12-27 1997-01-14 Allergan Method and composition for disinfecting contact lenses
EP0766970A2 (en) * 1990-12-27 1997-04-09 Allergan, Inc Method and composition for disinfecting contact lenses
TR25734A (en) * 1990-12-27 1993-09-01 Schering Corp A METHOD AND COMPUTER FOR DISINFECTING CONTACT LENSES
EP0575290A1 (en) * 1992-06-17 1993-12-22 Ciba-Geigy Ag Product for care of hard or soft contact lenses
US6338847B1 (en) 1993-01-26 2002-01-15 Allergan Compositions and methods to disinfect contact lenses
AU733386B2 (en) * 1993-08-27 2001-05-10 Alcon Laboratories, Inc. Process for cleaning and disinfecting contact lenses
EP0909808A2 (en) * 1993-08-27 1999-04-21 Alcon Laboratories, Inc. Process for cleaning and disinfecting contact lenses
EP0909808A3 (en) * 1993-08-27 1999-07-28 Alcon Laboratories, Inc. Process for cleaning and disinfecting contact lenses
WO1995006099A1 (en) * 1993-08-27 1995-03-02 Alcon Laboratories, Inc. Process for cleaning and disinfecting contact lenses
US8563011B2 (en) 1996-12-13 2013-10-22 Alcon Research, Ltd. Use of low molecular weight amino alcohols in ophthalmic compositions
WO2001082893A1 (en) * 2000-05-04 2001-11-08 Molnarne Kahan Ilona Use of a lacrophyl preparation in eye-drops containing therapeutically active compounds
US6949241B2 (en) * 2000-05-04 2005-09-27 Ilona Molnarne-Kahan Use of lacrophyl preparation in eye drops containing therapeutically active compounds
WO2007032997A1 (en) * 2005-09-13 2007-03-22 Bausch & Lomb Incorporated Ophthalmic formulation containing loteprednol etabonate for treatment of dry eye

Also Published As

Publication number Publication date
HU209538B (en) 1994-07-28
HU902969D0 (en) 1990-09-28
HUT58531A (en) 1992-03-30

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