OPHTHALMIC AND CONTACT LENS SOLUTIONS USING BICINE

Abstract

The present invention relates to a lens care solution having 0.001 to about 5 weight percent of a low molecular weight amine of the general formula:

##STR00001##

where R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are H or low molecular weight radicals, and R.sub.5 is a low molecular weight radical, or salt thereof; an effective amount of a tonicity agent; and the balance water.

Claims

1. An ophthalmic solution comprising: 0.001 to about 5 weight percent of bicine; an effective amount of biologically compatible buffer to maintain the pH of the solution between 5.5 and 8.5 pH; and the balance water.

2. The ophthalmic solution of claim 1, further comprising an effective amount of a tonicity agent.

3. The ophthalmic solution of claim 1, wherein the ophthalmic solution consists essentially of the bicine, the biologically compatible buffer, an effective amount of a tonicity agent, and the balance water.

4. The ophthalmic solution of claim 1, wherein the ophthalmic solution consists essentially of the bicine, the biologically compatible buffer, an effective amount of a tonicity agent, and a preservative and the balance water.

5. The ophthalmic solution of claim 4, wherein the preservative is poly[dimethylimino-2-butene-1,4-diyl]chloride, alpha[4-tris(2-hydroethyl)ammonium-dichloride.

6. A method for treating a contact lens in order to decrease its affinity to protein deposition which comprises the step of: soaking a contact lens in an aqueous solution comprising 0.001 to about 5 weight percent of bicine; an effective amount of biologically compatible buffer to maintain the pH of the solution between 5.5 and 8.5 pH; and the balance water.

7. The method of claim 6, wherein the aqueous solution further comprises an effective amount of a tonicity agent.

8. The ophthalmic solution of claim 6, wherein the aqueous solution consists essentially of the bicine, the biologically compatible buffer, an effective amount of a tonicity agent, and the balance water.

9. The ophthalmic solution of claim 6, wherein the aqueous solution consists essentially of the bicine, the biologically compatible buffer, an effective amount of a tonicity agent, and a preservative and the balance water.

10. The ophthalmic solution of claim 9, wherein the preservative is poly[dimethylimino-2-butene-1,4-diyl]chloride, alpha[4-tris(2-hydroethyl)ammonium-dichloride.

Description

EXAMPLE 1

Reduced Protein Deposition

[0027] Contact lenses were soaked and heated in test solutions to which a radio -labeled lysozyme was present in a known amount for a period of 12 hours at 37 degrees Celsius. The lenses were rinsed with distilled water in order to remove residual solution. The lenses were then assayed for protein deposition using a Beckman BioGamma 1 counter. Results were reported in ug/lens.

TABLE-US-00002 Lens A Lens B Average ug/lens ug/lens ug/lens Phosphate buffer control 1,043 865 954 Choline Chloride (1%) 14 9 12 in phosphate buffer

[0028] Choline chloride was a 1 percent w/v solution. The matrix control was phosphate buffer and sodium chloride. The low molecular weight amine solution had lower protein binding than the control.

EXAMPLE 2

Reduced Preservative Binding

[0029] Contact lenses were soaked and heated in test solutions to which a radio -labeled C.sup.14-PHMB solution in a known concentration for a period of 12 hours at 37 degrees Celsius. The lenses were rinsed with distilled water in order to remove residual solution. The lenses were then assayed for the radio-labeled protein deposition using a Beckman BioGamma 1 counter. Results were reported in ug/lens.

TABLE-US-00003 Lens A Lens B Average Solution ug/lens ug/lens ug/lens 1% choline chloride 18 11 14.5 in phosphate buffer 1% carnitine in 9 13 11 phosphate buffer 1% betaine HCI in 6 8 7 phosphate buffer Phosphate buffer 73 64 68.5 control

[0030] Each of the additives were at a 1 percent w/v solution in the phosphate buffer. The control was phosphate buffer and sodium chloride. The low molecular weight amines solution had a lower cationic preservative adsorption the control.

EXAMPLE 3A

Example of Protein Deposition Inhibition

[0031] Contact lenses were soaked test solutions overnight. Afterwards, lysozyme was added to the tubes and warmed to 37 degrees Celsius for 12 hours. The lenses were rinsed with distilled water in order to remove residual solution. The lenses were assayed for protein deposition by the BCA method and detected on an HP PDA Spectrophotometer. Results were reported in ug/lens.

TABLE-US-00004 Solution ug lysozyme per lens Marketed Product Control >18.3 (phosphate buffer, Poloxamer) Phosphate buffer control >26.16 Choline chloride (1%) 4.1 Betaine HCI (1%) 2.44

[0032] Choline chloride and Betaine HCl were a 1 percent w/v solution in the phosphate buffer. The control was phosphate buffer and sodium chloride. The low molecular weight amine solution had lower protein binding than the control.

EXAMPLE 3B

Improved Antimicrobial Activity

[0033] Formulations containing low molecular weight amines were prepared in a 0.1% phosphate buffer. The solutions were made isotonic with sodium chloride and preserved with polyhexamethylene biquanide at 0.0001% and hydrogen peroxide at 0.0060%. Dequest 2060S was added as a stabilizer. The pH was adjusted to 7.0 with either 1 N sodium hydroxide. The in vitro microbicidal activity of the solutions was determined by exposing C. albicans to 10 ml of each solution at room temperature for 4 hours. Subsequently, an aliquot of each solution was serial diluted onto agar plates and incubated for 48 hours at elevated temperatures. At the conclusion of the incubation period the plates are examined for the development of colonies. The log reduction was determined based on a comparison to the inoculum control. The following table provides the results of the in vitro studies.

TABLE-US-00005 C albicans log reduction Improvement bicine (1%) 0.75 0.34 creatinine (1%) 1.42 1.01 buffer control 0.41

[0034] Each of the low molecular weight amines showed an improvement in the activity against C. albicans as compared to the buffer control.

EXAMPLE 4

Improved Antimicrobial Activity

[0035] Formulations containing exemplary low molecular weight amines were prepared in a 0.2% phosphate buffer. The solutions were made isotonic with sodium chloride and preserved with polyhexamethylene biquanide at 0.0001%. The pH was adjusted to 7.2 with either 1N sodium hydroxide or 1 N hydrochloric acid. The in vitro microbicidal activity of the solutions was determined by exposing C. albicans to 10 ml of each solution at room temperature for 4 hours. Subsequently, an aliquot of each solution was serial diluted onto agar plates and incubated for 48 hours at elevated temperatures. At the conclusion of the incubation period the plates are examined for the development of colonies. The log reduction was determined based on a comparison to the inoculum control. The following table provides the results of the in vitro studies.

TABLE-US-00006 C albicans log reduction Improvement betaine HCI (0.5%) 1.37 0.38 bis-tris (0.5%) 1.21 0.22 carnitine (0.5%) 1.28 0.29 choline (0.5%) 2.24 1.25 creatine (0.5%) 1.72 0.73 tricine (0.5%) 1.33 0.34 triethylamine (0.5%) 1.64 0.65 triethanolamine (0.5%) 1.82 0.83 buffer control 0.99

[0036] Each of the low molecular weight amines showed an improvement in the activity against C. albicans as compared to the buffer control.

EXAMPLE 5

[0037] An example of a preferred disinfecting formulation of the subject invention is provided below in Table 1. This solution is prepared by weighing out the necessary amount of the tricine, creatine, choline chloride, sodium chloride and edetate disodium into a vessel containing approximately 90% of the water volume. After each of the ingredients has dissolved, the pH is adjusted to 7.3 with either 1 N sodium hydroxide or 1 N hydrochloric acid. Following this, the polyhexamethylene biguanide is added and the solution is brought to final volume with purified water. The final product has the composition shown in the Table below.

TABLE-US-00007 TABLE 4 Constituent Weight/Volume Polyhexamethylenebiguanide 20% w/w solution 0.0001% HCI available under the mark Cosmocil CQ from Avecia Tricine 1.0% Creatine 0.25% Choline Chloride 0.5% Edetate Disodium 0.055% Polyoxyl 40 Hydrogenated Cremophor RH 40 0.1% Castor Oil from BASF Co. Sodium Chloride As required for tonicity adjustment 300 mOsm Hydrochloride Acid, 1N as required for pH adjustment to 7.3 Sodium Hydroxide, 1N as required for pH adjustment to 7.3 Purified Water Balance to 100%

[0038] This solution may be used to rinse, clean, and store contact lenses on a daily basis.

EXAMPLE 6

[0039] An example of a preferred formulation for a contact lens vial storage of the subject invention is provided below in Table 1. This solution is prepared by weighing out the necessary amount of the tricine, creatine, choline chloride, and sodium chloride into a vessel containing approximately 90% of the water volume. After each of the ingredients has dissolved, the pH is adjusted to 7.3 with either 1 N sodium hydroxide or 1 N hydrochloric acid. Following this, the polyhexamethylene biguanide is added and the solution is brought to final volume with purified water. The final product had the composition shown in Table 1 below.

TABLE-US-00008 TABLE 4 Constituent Weight/Volume Tricine 1.0% Creatine 0.25% Choline Chloride 0.5% Polyoxyl 40 Hydrogenated Cremophor RH 0.1% Castor Oil 40 from BASF Co. Sodium Chloride As required for tonicity adjustment 300 mOsm Hydrochloride Acid, 1N as required for pH adjustment to 7.3 Sodium Hydroxide, 1N as required for pH adjustment to 7.3 Purified Water Balance to 100%

[0040] An example from another patent: specific representative embodiments of biguanides for use in the contact lens disinfectant methods include free bases and water soluble salts wherein:

EXAMPLE 7

Cleaning and Disinfecting Formulation

[0041] An example of a preferred cleaning and disinfecting formulation of the subject invention is provided. This solution is prepared by weighing out the necessary amount of the tricine, creatine, choline chloride, sodium chloride and edetate disodium into a vessel containing approximately 90% of the water volume. After each of the ingredients has dissolved, the pH is adjusted to 7.3 with either 1 N podium hydroxide or 1 N hydrochloric acid. Following this, the polyhexamethylene biguanide is added and the solution is brought to final volume with purified water. The final product has the composition shown in the following table.

TABLE-US-00009 Constituent % Weight/Volume Amount Purified water 40 mL Tricine 1.0% 0.500 g Creatine 0.25% 0.125 g Choline Chloride 0.5% 0.250 g Edetate Disodium 0.055% 0.0275 g Polyoxyl 40 Hydrogenated 0.1% 0.5 mL of 10% Castor Oil (Cremophor RH 40 from BASF Co.) Polyhexamethylenebiguanide 0.0001% 50 uL of 0.1% HCI (20% w/w solution available under the mark Cosmocil CQ from Avecia) Sodium Chloride As required for As required for tonicity tonicity adjustment adjustment 300 mOsm 300 mOsm Hydrochloride Acid, 1N as required for pH as required for pH adjustment to 7.3 adjustment to 7.3 Sodium Hydroxide, 1N as required for pH as required for pH adjustment to 7.3 adjustment to 7.3 Purified Water Balance to 100% Dilute to 50 mL

[0042] This solution may be used to rinse, clean, and store contact lenses on a daily basis.

EXAMPLE 8

Lens Vial Storage

[0043] An example of a preferred formulation for a contact lens vial storage of the subject invention is provided. This solution is prepared by weighing out the necessary amount of the tricine, creatine, choline chloride, and sodium chloride into a vessel containing approximately 90% of the water volume. After each of the ingredients has dissolved, the pH is adjusted to 7.3 with either 1 N sodium hydroxide or 1 N hydrochloric acid. Following this, the polyhexamethylene biguanide is added and the solution is brought to final volume with purified water. The final product had the composition shown in Table 1 below.

TABLE-US-00010 Constituent % Weight/Volume Amount Purified water 40 mL Tricine 1.0% 0.500 g Bis-Tris 0.25% 0.125 g Polyoxyl 40 Hydrogenated 0.1% 0.5 mL of 10% Castor Oil (Cremophor RH 40 from BASF Co.) Sodium Chloride As required for As required for tonicity tonicity adjustment adjustment 300 mOsm 300 mOsm Hydrochloride Acid, 1N as required for pH as required for pH adjustment to 7.3 adjustment to 7.3 Sodium Hydroxide, 1N as required for pH as required for pH adjustment to 7.3 adjustment to 7.3 Purified Water Balance to 100% Dilute to 50 mL

EXAMPLE 9

Disinfecting Solution

[0044] Formulation was prepared by dissolving Tricine, Carnitine, Betaine HCl, Choline Chloride, Inositol, Disodium edetate, and Cremophor RH40 in 80% of the water volume. The pH of the solution was adjust to 7.3 with 1 N sodium hydroxide. The tonicity of the solution was adjusted with sodium chloride and polyhexamethylene biguanide. The solution was diluted to volume with water.

TABLE-US-00011 % Weight/ onstituent Supplier Volume Amount Purified water to 80% 40 mL Tricine Spectrum 1.0% 0.500 g Carnitine Spectrum 0.25% 0.125 g Betaine HCl Spectrum 0.1% 0.050 g Choline Chloride Amresco 0.5% 0.250 g Inosito Spectrum 0.1% 0.050 g Edetate Disodium Spectrum 0.055% 0.0275 g Polyoxyl 40 Cremophor 0.1% 0.5 mL of 10% Hydrogenated Castor RH 40 from Oil BASF Co. Sodium Hydroxide, as required for as required for 1N pH adjustment pH adjustment to 7.3 to 7.3 Purified Water to 98% Dilute to 49 mL Sodium Chloride Fisher As required for As required for tonicity tonicity adjustment 300 adjustment 300 mOsm mOsm Polyhexamethylene- 20% w/w solution 0.0001% 50 uL of 0.1% biguanide HCI available under the mark Cosmocil CQ from Avecia Purified Water Balance Dilute to 50 mL to 100%

EXAMPLE 10

Lens Storage Solution (BCL1O6-037-3)

[0045] Formulation was prepared by dissolving Tricine, Camitine, and Inositol in 80% of the water volume. The pH of the solution was adjust to 7.3 with 1 N sodium hydroxide and Cremophor RH40 was added. The tonicity of the solution was adjusted with sodium chloride. The solution was diluted to volume with water.

TABLE-US-00012 Constituent Supplier % Weight/Volume Amount Purified water to 80% 40 mL Tricine Spectrum 1.0% 0.500 g Carnitine Spectrum 0.25% 0.125 g Inositol Spectrum 0.1% 0.050 g Hydrochloride Acid, as required for as required for pH 1N pH adjustment adjustment to 7.3 to 7.3 Sodium Hydroxide, as required for as required for pH 1N pH adjustment adjustment to 7.3 to 7.3 Polyoxyl 40 Cremophor 0.1% 0.5 mL of 10% Hydrogenated Castor RH 40 from Oil BASF Co. Purified Water to 98% Dilute to 49 mL Sodium Chloride Fisher As required for As required for tonicity tonicity adjustment 300 adjustment 300 mOsm mOsm Purified Water to 100% Dilute to 50 mL