EP0252974B1 - Enhancement of enzymatic activity in cleaning contact lenses by the use of hypotonic solutions - Google Patents
Enhancement of enzymatic activity in cleaning contact lenses by the use of hypotonic solutions Download PDFInfo
- Publication number
- EP0252974B1 EP0252974B1 EP87900942A EP87900942A EP0252974B1 EP 0252974 B1 EP0252974 B1 EP 0252974B1 EP 87900942 A EP87900942 A EP 87900942A EP 87900942 A EP87900942 A EP 87900942A EP 0252974 B1 EP0252974 B1 EP 0252974B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- enzyme
- solution
- contact lenses
- cleaning
- lenses
- 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.)
- Expired - Lifetime
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- 238000004140 cleaning Methods 0.000 title claims abstract description 17
- 230000002255 enzymatic effect Effects 0.000 title abstract description 5
- 239000000815 hypotonic solution Substances 0.000 title abstract description 5
- 102000004190 Enzymes Human genes 0.000 claims description 24
- 108090000790 Enzymes Proteins 0.000 claims description 24
- 229940088598 enzyme Drugs 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 9
- 108010019160 Pancreatin Proteins 0.000 claims description 7
- 229940055695 pancreatin Drugs 0.000 claims description 7
- 108090000787 Subtilisin Proteins 0.000 claims description 6
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 230000002797 proteolythic effect Effects 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 102000016943 Muramidase Human genes 0.000 description 8
- 108010014251 Muramidase Proteins 0.000 description 8
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 8
- 108010056079 Subtilisins Proteins 0.000 description 7
- 102000005158 Subtilisins Human genes 0.000 description 7
- 229960000274 lysozyme Drugs 0.000 description 7
- 235000010335 lysozyme Nutrition 0.000 description 7
- 239000004325 lysozyme Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 229940050929 polyethylene glycol 3350 Drugs 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- XPSXBEJFSQZTBS-UHFFFAOYSA-N 2,2-bis(2-methylprop-2-enoyloxymethyl)butyl 2-methylprop-2-enoate 2-hydroxyethyl 2-methylprop-2-enoate N-(2-methyl-4-oxopentan-2-yl)prop-2-enamide Chemical compound CC(=C)C(=O)OCCO.CC(=O)CC(C)(C)NC(=O)C=C.CCC(COC(=O)C(C)=C)(COC(=O)C(C)=C)COC(=O)C(C)=C XPSXBEJFSQZTBS-UHFFFAOYSA-N 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 108091005658 Basic proteases Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 206010015946 Eye irritation Diseases 0.000 description 1
- 206010018258 Giant papillary conjunctivitis Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 231100000013 eye irritation Toxicity 0.000 description 1
- 210000003811 finger Anatomy 0.000 description 1
- 230000005660 hydrophilic surface Effects 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 210000003813 thumb Anatomy 0.000 description 1
- GOCYOWTYSKXMTR-UHFFFAOYSA-N trisodium borate dihydrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]B([O-])[O-] GOCYOWTYSKXMTR-UHFFFAOYSA-N 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/0005—Other compounding ingredients characterised by their effect
- C11D3/0078—Compositions for cleaning contact lenses, spectacles or lenses
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38618—Protease or amylase in liquid compositions only
Definitions
- This invention relates to the potentiation of the enzymatic activity in cleaning contact lenses. More specifically, this invention is a method for potentiating the proteolytic activity of the proteases pancreatin and subtilisin in the cleaning of contact lenses by carrying out the cleaning in a hypotonic solution.
- Contact lenses particularly those with a hydrophilic surface such as the hydrogel lenses and the hard, gas permeable lenses with a treated surface, encounter protein accretions during normal wear. It is beneficial, if not often times necessary, to remove these accretions in order to maintain visual acuity, prevent eye irritation and to prevent the development of giant papillary conjunctivitis.
- proteolytic enzymes has been developed to remove such deposits. See, for example, U.S. Patent 3,910,296, and 4,285,738.
- the '296 disclosure makes no comment on the effect of tonicity value on enzyme activity.
- the '738 patent discloses in the specification and stipulates in the claim, that the solution must be hypertonic. Hypertonic is not specifically defined, but the urea concentration is specified as being between 5% through saturation (weight/volume).
- the normal tonicity value is that of a physiological solution as illustrated by the 0.9% by weight/volume concentration of aqueous saline.
- This invention covers a method for enhancing the activity of an enzyme used in the cleaning of contact lenses, said enzyme being pancreatin or subtilisin, which method comprises carrying out the cleaning regimen in a solution having an osmolality value up to about 275 milliosmoles/kilogram.
- Tonicity values may range from 0 up to about 275 mOsm/kg.
- the enzyme itself will be active at tonicity values close to 0, but as a practical matter it is difficult to prepare such solutions because of the solutes normally present in diluents, including purified water. Tests have been carried out where the osmolality was as low as 6 mOsm/kg. A more preferred lower limit is about 50 mOsm/kg. which number allows for the addition of small amounts of salts, stabilizers, enzyme co-factors or other excipients which may be useful and beneficial to solution stability, enzyme activity or the like.
- the upper limit will be between 175 and 200 mOsm/kg.
- tonicity value can be made with any number of excipients and constituents well known in the art. If an enzyme co-factor is critical or essential to the cleaning process, obviously its presence must be given primary consideration in adding materials to the formulation. Salts of any sort including salts which are necessary co-factors for enzymatic activity such as calcium should be accounted for in formulating these hypotonic solutions. The hypotonic value is determined, that is measured, after addition of the enzyme.
- the ability of a given solution and enzyme to remove protein from a contact lens was determined by essentially the same procedure each time. Generically, the procedure was to take a contact lens and coat it with heat denatured lysozyme by placing the lens in a phosphate buffered saline solution to which was then added sufficient lysozyme to make a 0.1% solution by weight. The lysozyme was from egg white. These solutions were then heated for 30 minutes at about 95 C. The lenses were removed, cooled and rinsed with distilled water and viewed to determine what type of lysozyme accretion was on the lens at time zero.
- Protein deposit classification as a means for quantifying the proteolytic activity of enzymes in removing absorbed protein from the lenses, a system was developed whereby the protein on the lenses was visually quantified before and after enzyme treatment.
- the lens After a lens had been heated for 30 minutes in the lysozyme solution, the lens was wetted with distilled water, rubbed between the thumb and finger, then grasped by the edge with plastic tweezers and rinsed with distilled water again. The convex side of the lens was viewed under a microscope at 100X magnification. A film or deposit detected under these conditions was classified according to the percentage of the lens surface covered by the deposit. The protein removal efficacy of an enzyme solution is expressed in terms of the percentage of the lens surface which has been cleaned. This number is derived by subtracting the percentage of the lens surface covered by the protein deposit from 100%.
- a subtilisin enzyme containing solution was prepared as follows: cysteine hydrochloride monohydrate (1.001g), sodium borate dihydrate (1.911 g), sodium carbonate anhydrous (3.106g), polyethylene glycol 3350 (0.403g), tartaric acid (2.002g), S .
- carlsberg (0.041g), obtained from Novo Industries of Denmark, was dissolved in 300 ml of purified water, the pH adjusted to 8.4 with sodium hydroxide or hydrochloric acid, and then water added in a quantity sufficient to make 1000 ml. Three 200 ml portions were removed and the osmolality adjusted with sodium chloride and the pH with NaOH or HCl as needed to obtain the figures given in table I.
- Hydrogel-type lenses (Hydrocurve II®, 55% water, sold by Barnes-Hind, Inc.) were treated with heat-denatured lysozyme as described above.
- a subtilisin-A-containing solution was prepared (0.04 mg/ml of water without excipients, activity: 0.0012 Au/ml) in such a manner as to have pH values between approximately 5.0 and 10.0.
- the osmolality value was then adjusted to 6, 133 and 264 mOsm/kg with NaCl for each of these solutions, each of the tonicity values being tested at pH 9.0.
- Lenses were then soaked in these solutions (five in each) for 2 hours at room temperature, rinsed, and analyzed for percentage residual protein deposit as described above. Results are given in Table II. Table II Effect of pH vs.
- Lenses with lysozyme protein deposits covering at least 98% of the lens surface were cut in half, one half being soaked in one enzyme solution and the other in another enzyme solution in the first comparison (pancreatin data); whole lenses were used in the other studies.
- the enzyme solutions were comprised of enzyme and excipients as indicated in Table III.
- Lenses were bufilcon-A sold by Barnes-Hind, Inc. under the name Hydrocurve II®. Results from each of the several formulations are listed in the following table. The abbreviation DI is used for deionized water.
- a subtilisin enzyme tablet was dissolved in either 10ml of DI water or saline. Each enzyme tablet contained: 30mg N-acetylcysteine, 34mg sodium carbonate, 7mg tartaric acid, 4mg polyethylene glycol 3350, 4mg subtilisin-A (subtilisin carlsberg from NOVO Industries of Denmark), and 50mg of lactose. 5. Allergan HydrocareTM Preserved Saline. It can be seen from the data presented in Table III that for both pancreatin and Subtilisin carlsberg , the solutions with the lowest tonicity produced the highest cleaning efficacy.
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Detergent Compositions (AREA)
- Eyeglasses (AREA)
Abstract
Description
- This invention relates to the potentiation of the enzymatic activity in cleaning contact lenses. More specifically, this invention is a method for potentiating the proteolytic activity of the proteases pancreatin and subtilisin in the cleaning of contact lenses by carrying out the cleaning in a hypotonic solution.
- Contact lenses, particularly those with a hydrophilic surface such as the hydrogel lenses and the hard, gas permeable lenses with a treated surface, encounter protein accretions during normal wear. It is beneficial, if not often times necessary, to remove these accretions in order to maintain visual acuity, prevent eye irritation and to prevent the development of giant papillary conjunctivitis.
- The use of proteolytic enzymes has been developed to remove such deposits. See, for example, U.S. Patent 3,910,296, and 4,285,738. The '296 disclosure makes no comment on the effect of tonicity value on enzyme activity. The '738 patent discloses in the specification and stipulates in the claim, that the solution must be hypertonic. Hypertonic is not specifically defined, but the urea concentration is specified as being between 5% through saturation (weight/volume). The normal tonicity value is that of a physiological solution as illustrated by the 0.9% by weight/volume concentration of aqueous saline.
- It has now been found that where the enzymatic solution is made hypotonic, removal of adhered protein by the enzyme is substantially enhanced throughout the effective pH range of the enzyme. Studies were carried out with subtilisin and pancreatin, each of which clearly domonstrated a substantial increase in activity when the solution was made hypotonic.
- In the documents GB-A- 2 088 581 and GB-A- 2 117 534 papain containing tablets for cleaning contact lenses are described which will in use be dissolved in water to give a solution which is significally less than isotonic, i.e. hypotonic.
- This invention covers a method for enhancing the activity of an enzyme used in the cleaning of contact lenses, said enzyme being pancreatin or subtilisin, which method comprises carrying out the cleaning regimen in a solution having an osmolality value up to about 275 milliosmoles/kilogram.
- Tonicity values may range from 0 up to about 275 mOsm/kg. The enzyme itself will be active at tonicity values close to 0, but as a practical matter it is difficult to prepare such solutions because of the solutes normally present in diluents, including purified water. Tests have been carried out where the osmolality was as low as 6 mOsm/kg. A more preferred lower limit is about 50 mOsm/kg. which number allows for the addition of small amounts of salts, stabilizers, enzyme co-factors or other excipients which may be useful and beneficial to solution stability, enzyme activity or the like.
- On the upper side, 275 milliosmoles is approximately the top end of the range so far as enjoying substantially enhanced proteolytic activity is concerned. More preferably, the upper limit will be between 175 and 200 mOsm/kg.
- The adjustment of tonicity value can be made with any number of excipients and constituents well known in the art. If an enzyme co-factor is critical or essential to the cleaning process, obviously its presence must be given primary consideration in adding materials to the formulation. Salts of any sort including salts which are necessary co-factors for enzymatic activity such as calcium should be accounted for in formulating these hypotonic solutions. The hypotonic value is determined, that is measured, after addition of the enzyme.
- In the following examples, the ability of a given solution and enzyme to remove protein from a contact lens was determined by essentially the same procedure each time. Generically, the procedure was to take a contact lens and coat it with heat denatured lysozyme by placing the lens in a phosphate buffered saline solution to which was then added sufficient lysozyme to make a 0.1% solution by weight. The lysozyme was from egg white. These solutions were then heated for 30 minutes at about 95 C. The lenses were removed, cooled and rinsed with distilled water and viewed to determine what type of lysozyme accretion was on the lens at time zero.
- Protein deposit classification (typing): as a means for quantifying the proteolytic activity of enzymes in removing absorbed protein from the lenses, a system was developed whereby the protein on the lenses was visually quantified before and after enzyme treatment.
- After a lens had been heated for 30 minutes in the lysozyme solution, the lens was wetted with distilled water, rubbed between the thumb and finger, then grasped by the edge with plastic tweezers and rinsed with distilled water again. The convex side of the lens was viewed under a microscope at 100X magnification. A film or deposit detected under these conditions was classified according to the percentage of the lens surface covered by the deposit. The protein removal efficacy of an enzyme solution is expressed in terms of the percentage of the lens surface which has been cleaned. This number is derived by subtracting the percentage of the lens surface covered by the protein deposit from 100%.
- Twenty-four Hydrocurve® II hydrogel lenses (Barnes-Hind, Inc. Sunnyvale, California) were coated with lysozyme using the standard procedure. Each was viewed after treatment and determined to have at least 98% of its surface covered by a protein film. In most cases, 100% of the lens surface was covered by a protein film. A subtilisin enzyme containing solution was prepared as follows: cysteine hydrochloride monohydrate (1.001g), sodium borate dihydrate (1.911 g), sodium carbonate anhydrous (3.106g), polyethylene glycol 3350 (0.403g), tartaric acid (2.002g), S. carlsberg (0.041g), obtained from Novo Industries of Denmark, was dissolved in 300 ml of purified water, the pH adjusted to 8.4 with sodium hydroxide or hydrochloric acid, and then water added in a quantity sufficient to make 1000 ml. Three 200 ml portions were removed and the osmolality adjusted with sodium chloride and the pH with NaOH or HCl as needed to obtain the figures given in table I.
- Three lenses were soaked in each of the solutions for 3 hours at room temperature, then a determination of percentage residual protein deposit and cleaned lens surface made as per the standard procedure described above.
TABLE I Effect of Osmolality Average % Lens Surface Cleaned pH 9 98.3±2.9 23.3±5.8 11.7±5.8 8.5 100 11.7±2.9 13.3±2.9 7.8 90±17 -------- 3.3±2.9 150 326 420 Osmolality (mOsm/kg)
Table I shows that greater cleaning was observed at 150 mOsm/kg than at either 326 or 420 mOsm/kg. - Hydrogel-type lenses (Hydrocurve II®, 55% water, sold by Barnes-Hind, Inc.) were treated with heat-denatured lysozyme as described above.
- A subtilisin-A-containing solution was prepared (0.04 mg/ml of water without excipients, activity: 0.0012 Au/ml) in such a manner as to have pH values between approximately 5.0 and 10.0. The osmolality value was then adjusted to 6, 133 and 264 mOsm/kg with NaCl for each of these solutions, each of the tonicity values being tested at pH 9.0. Lenses were then soaked in these solutions (five in each) for 2 hours at room temperature, rinsed, and analyzed for percentage residual protein deposit as described above. Results are given in Table II.
Table II Effect of pH vs. Osmolality % Lens Surface Cleaned pH 10.0 93.0±4.5 9.0 69.0±8.2 34.0±5.5 18.0±2.7 8.0 62.0±4.5 7.0 58.0±4.5 6.0 23.8±4.8* 5.0 11.0±2.2 6 133 264 Osmolality (mOsm/kg) * Only four lenses.
It can be seen from the data presented in Table II that both solution pH and osmolality are important parameters asserting the cleaning efficacy of an enzyme solution. Since subtilisin-A is an alkaline protease, having its greatest activity between pH 8 and 10, the greatest cleaning efficacy is observed in this pH range also. - Lenses with lysozyme protein deposits covering at least 98% of the lens surface were cut in half, one half being soaked in one enzyme solution and the other in another enzyme solution in the first comparison (pancreatin data); whole lenses were used in the other studies. The enzyme solutions were comprised of enzyme and excipients as indicated in Table III. Lenses were bufilcon-A sold by Barnes-Hind, Inc. under the name Hydrocurve II®. Results from each of the several formulations are listed in the following table. The abbreviation DI is used for deionized water.
Table III Effect of Varying Osmolality on Enzyme Cleaning Efficacy Enzyme Used Diluent pH Osmolality Soak Time Average % Cleaning Pancreatin¹ DI water 8.58 175 4 hrs 32.0±25.4 Pancreatin saline² 7.97 382 4 hrs 1.3±2.3 Subtilisin carlsberg DI water 8.43 157 3 hrs 98.3±2.9 0.04 mg/ml³ water & NaCl 8.43 335 3 hrs 25.6±13.9 Subtilisin carlsberg DI water 8.86 124 1 hr 79.6±11.3 0.04mg/ml⁴ saline⁵ 8.21 418 2 hrs 16.4±.4.6 1. Alcon Optizyme™ tablet. 2. Normal saline. 3. Same formulation excipients as in Example 1, Table I. 4. A subtilisin enzyme tablet was dissolved in either 10ml of DI water or saline. Each enzyme tablet contained: 30mg N-acetylcysteine, 34mg sodium carbonate, 7mg tartaric acid, 4mg polyethylene glycol 3350, 4mg subtilisin-A (subtilisin carlsberg from NOVO Industries of Denmark), and 50mg of lactose. 5. Allergan Hydrocare™ Preserved Saline.
It can be seen from the data presented in Table III that for both pancreatin and Subtilisin carlsberg, the solutions with the lowest tonicity produced the highest cleaning efficacy.
Claims (2)
- A method for enhancing the activity of an enzyme used in the cleaning of contact lenses, said enzyme being selected from pancreatin and subtilisin, which method comprises carrying out the cleaning regimen in a solution having an osmolality value up to 275 mOsm/kg.
- The method of claim 1 wherein the osmolality is between 100 and 200 mOsm/kg.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT87900942T ATE83179T1 (en) | 1986-01-06 | 1987-01-05 | INCREASING ENZYMATIC ACTIVITY IN CLEANING CONTACT LENSES BY USING HYPOTONIC SOLUTIONS. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US81651886A | 1986-01-06 | 1986-01-06 | |
US816518 | 1986-01-06 |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0252974A1 EP0252974A1 (en) | 1988-01-20 |
EP0252974A4 EP0252974A4 (en) | 1988-05-03 |
EP0252974B1 true EP0252974B1 (en) | 1992-12-09 |
Family
ID=25220860
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP87900942A Expired - Lifetime EP0252974B1 (en) | 1986-01-06 | 1987-01-05 | Enhancement of enzymatic activity in cleaning contact lenses by the use of hypotonic solutions |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0252974B1 (en) |
AT (1) | ATE83179T1 (en) |
AU (1) | AU6898887A (en) |
DE (1) | DE3782981T2 (en) |
HK (1) | HK113995A (en) |
WO (1) | WO1987004091A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5037647A (en) * | 1988-09-15 | 1991-08-06 | Alcon Laboratories, Inc. | Aqueous antimicrobial opthalmic solutions comprised of quaternary ammonium compound, citric acid, citrate and sodium chloride |
CA2009118C (en) * | 1989-02-21 | 1996-02-27 | Mary F. Mowrey-Mckee | Method and composition for cleaning and disinfecting contact lenses |
US5783532A (en) * | 1993-06-17 | 1998-07-21 | Allergan | Enzyme compositions and methods for contact lens cleaning |
IL109705A (en) * | 1993-06-17 | 1998-07-15 | Allergan Inc | Enzyme compositions and methods for contact lens cleaning |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3240709A (en) * | 1962-05-16 | 1966-03-15 | Burton Parsons Chemicals Inc | Method of cleansing contact lenses |
US3910296A (en) * | 1973-04-20 | 1975-10-07 | Allergan Pharma | Method of removing proteinaceous deposits from contact lenses |
US4048122A (en) * | 1976-01-23 | 1977-09-13 | Barnes-Hind Pharmaceuticals, Inc. | Cleaning agents for contact lenses |
JPS54140553A (en) * | 1978-04-24 | 1979-10-31 | Senju Pharma Co | Contact lens washing liquid |
US4263054A (en) * | 1979-02-23 | 1981-04-21 | George D. Weaver | Contact lens cleaning and rinsing method |
GB2088581A (en) * | 1980-10-02 | 1982-06-09 | Smith & Nephew Associated Cie | Papain and lactose containing tablet for cleaning contact lenses |
US4521254A (en) * | 1981-02-09 | 1985-06-04 | Anderson Ronald L | Cleaning contact lenses with solution of bromelain and carboxypeptidase |
GB2117534B (en) * | 1982-03-31 | 1986-02-19 | Smith & Nephew Ass | Papain containing tablet for cleaning contact lenses |
US4626292A (en) * | 1982-06-01 | 1986-12-02 | Sherman Laboratories, Inc. | Soft contact lens wetting and preservation method |
US4613380A (en) * | 1985-04-01 | 1986-09-23 | Dow Corning Corporation | Method for removing lipid deposits from contact lenses |
US4670178A (en) * | 1985-09-09 | 1987-06-02 | Allergan Pharmaceuticals, Inc. | Method for the simultaneous cleaning and disinfecting of contact lenses |
-
1987
- 1987-01-05 AU AU68988/87A patent/AU6898887A/en not_active Abandoned
- 1987-01-05 DE DE8787900942T patent/DE3782981T2/en not_active Expired - Fee Related
- 1987-01-05 AT AT87900942T patent/ATE83179T1/en active
- 1987-01-05 EP EP87900942A patent/EP0252974B1/en not_active Expired - Lifetime
- 1987-01-05 WO PCT/US1987/000045 patent/WO1987004091A1/en active IP Right Grant
-
1995
- 1995-07-13 HK HK113995A patent/HK113995A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
DE3782981D1 (en) | 1993-01-21 |
WO1987004091A1 (en) | 1987-07-16 |
EP0252974A4 (en) | 1988-05-03 |
AU6898887A (en) | 1987-07-28 |
HK113995A (en) | 1995-07-21 |
DE3782981T2 (en) | 1993-04-08 |
ATE83179T1 (en) | 1992-12-15 |
EP0252974A1 (en) | 1988-01-20 |
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