Alkyl trypsin compositions and methods of use in contact...

Cleaning compositions for solid surfaces – auxiliary compositions – Cleaning compositions or processes of preparing – For cleaning a specific substrate or removing a specific...

Reexamination Certificate

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C510S114000, C510S370000, C510S374000, C510S382000, C510S383000, C510S392000, C510S393000, C510S405000, C510S420000, C510S421000, C510S465000, C510S530000, C134S042000

Reexamination Certificate

active

06358897

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention relates to the field of contact lens cleaning and disinfecting. In particular, this invention relates to concentrated or multi-purpose compositions containing alkyl trypsin and methods of use in cleaning human-worn contact lenses. The invention also relates to methods of simultaneously cleaning and disinfecting contact lenses by combining the concentrated alkyl trypsin compositions of the present invention with an aqueous composition comprising a disinfecting agent.
Various compositions and methods for cleaning contact lenses have been described in the patent and scientific literature. Some of these methods have employed compositions containing surfactants or enzymes to facilitate the cleaning of lenses. The first discussion of the use of proteolytic enzymes to clean contact lenses was in an article by Lo, et al. in the
Journal of The American Optometric Association
, volume 40, pages 1106-1109 (1969). Methods of removing protein deposits from contact lenses by means of proteolytic enzymes have been described in many publications since the initial article by Lo, et al., including U.S. Pat. No. 3,910,296 (Karageozian, et al.).
Numerous compositions and methods for disinfecting contact lenses have also been described. Those methods may be generally characterized as involving the use of heat and/or chemical agents. Representative chemical agents for this purpose include organic antimicrobials such as benzalkonium chloride and chlorhexidine, and inorganic antimicrobials such as hydrogen peroxide and peroxide-generating compounds. U.S. Pat. Nos. 4,407,791 and 4,525,346 (Stark) describe the use of polymeric quaternary ammonium compounds to disinfect contact lenses and to preserve contact lens care products. U.S. Pat. Nos. 4,758,595 and 4,836,986 (Ogunbiyi) describe the use of polymeric biguanides for the same purpose.
Various methods for cleaning and disinfecting contact lenses at the same time have been proposed. Methods involving the combined use of proteolytic enzymes and peroxides to clean and disinfect contact lenses simultaneously, are described in U.S. Pat. No. Re 32,672 (Huth, et al.). A representative method of simultaneously cleaning and disinfecting contact lenses involving the use of proteolytic enzymes and quaternary ammonium compounds is described in Japanese Patent Publication 57-24526 (Boghosian, et al.). The combined use of a biguanide (i.e., chlorhexidine) and liquid enzyme compositions to simultaneously clean and disinfect contact lenses is described in Canadian Patent No. 1,150,907 (Ludwig, et al.). Methods involving the combined use of dissolved proteolytic enzymes to clean and heat to disinfect are described in U.S. Pat. No. 4,614,549 (Ogunbiyi). The combined use of proteolytic enzymes and polymeric biguanides or polymeric quaternary ammonium compounds is described in copending, commonly assigned U.S. patent application Ser. No. 08/156,043 and in corresponding European Patent Application Publication No. 0 456 467 A2 (Rosenthal, et al.), as well as in U.S. Pat. No. 5,096,607 (Mowrey-McKee, et al.).
The commercial viability of most prior enzyme cleaning products has depended on the use of stable enzyme tablets. More specifically, the use of solid enzymatic cleaning compositions has been necessary to ensure stability of the enzymes prior to use. In order to use such compositions, a separate packet containing a tablet must be opened, the tablet must be placed in a separate vial containing a solution, and the tablet must be dissolved in order to release the enzyme into the solution. This practice is usually performed only once a week due to the cumbersome and tedious procedure and potential for irritation and toxicity. Moreover, the enzymatic cleaning tablets contain a large amount of excipients, such as effervescent agents (e.g., bicarbonate) and bulking agents (e.g., sodium chloride).
There have been prior attempts to use liquid enzyme compositions to clean contact lenses. However, those attempts have been hampered by the fact that aqueous liquid enzyme compositions are inherently unstable. When a proteolytic enzyme is placed in an aqueous solution for an extended period (i.e., several months or more), the enzyme may lose all or a substantial portion of its proteolytic activity. Steps can be taken to stabilize the compositions, but the use of stabilizing agents may have an adverse effect on the activity of the enzyme. For example, stabilizing agents can protect enzymes from chemical instability problems during storage in an aqueous liquid, by placing the enzymes in a dormant physical conformation. However, such agents may also inhibit the ability of the enzymes to become active again at the time of use. Finally, in addition to the general problems referred to above, a commercially viable liquid enzyme preparation for treating contact lenses must be relatively nontoxic, and must be compatible with other chemical agents used in treating contact lenses, particularly antimicrobial agents utilized to disinfect the lenses.
The following patents may be referred to for further background concerning prior attempts to stabilize liquid enzyme formulations: U.S. Pat. No. 5,281,277 (Nakagawa) and U.S. Pat. No. 5,314,823 (Nakagawa) and Japanese Kokai Patent Applications Nos. 92-370197; 92-143718; 92-243215; and 89-180515 describe liquid enzyme compositions for treating contact lenses. The compositions of the present invention are believed to provide significant improvements relative to the compositions described in those publications.
Recently, U.S. Pat. Nos. 5,576,278, 5,604,190, 5,605,661, 5,672,213 5,718,895 and 5,723,421 were issued to Alcon Laboratories, Inc. These patents disclose advanced liquid enzyme compositions particularly suited for contact lens care. The present invention improves on such compositions by providing compositions containing alkyl trypsin enzymes. The alkyl trypsins were discovered to possess superior stability in contact lens care compositions, over native or modified enzymes used in the art.
SUMMARY OF THE INVENTION
The present invention is directed to alkyl trypsin compositions and methods of use in cleaning and disinfecting contact lenses. Alkyl trypsins were discovered by the inventors to possess superior proteolytic stability in a solubilized state suitable for contact lens care use. The inventors have also found that, unlike other highly stable proteases, alkyl trypsins are physiologically well tolerated.
The compositions of the present invention are either formulated as alkyl trypsin concentrates or as alkyl trypsin multi-purpose solutions. The concentrates are employed as single dose cleaning compositions in conjunction with an aqueous solvent, e.g., a disinfecting solution. Prior to each cleaning or cleaning and disinfecting session, the user adds a small amount of the alkyl trypsin concentrate to the aqueous diluting solution. The soiled contact lenses may then be soaked in the resultant diluted enzyme solution for a time sufficient to clean or clean and disinfect the lens. Due to the inherent instability of solubilized enzymes, however, prior liquid enzyme concentrates have only been able to provide a limited storage shelf-life. Thus, one object of the present invention is to provide liquid enzyme concentrates with extended shelf-lives.
Multi-purpose solutions provide a complete solution containing a disinfectant and a cleaning enzyme for the simultaneous cleaning and disinfecting of contact lenses. Multi-purpose solutions are prepared by the addition of a large bolus of protease to a requisite amount of disinfecting diluent. The mixed, ready-to-use multi-purpose solution may now be used over a period of time for the periodic cleaning and disinfecting of contact lenses. Due to the inherent instability of an enzyme in an aqueous environment, however, prior multi-purpose solutions have not yet provided a useful product life for the consumer. Thus, another object of the present invention is to provide multi-purpose compositions with prolonged shelf-lives, both for the pre-mixed components, a

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