Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1999-05-25
2002-11-19
Jones, Dwyane C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S015800, C424S405000, C422S028000, C530S327000, C530S328000
Reexamination Certificate
active
06482799
ABSTRACT:
CROSS-REFERENCE TO RELATED APPLICATIONS
[NOT APPLICABLE]
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
[NOT APPLICABLE]
FIELD OF THE INVENTION
This invention relates to novel ophthalmic compositions useful for conditioning and/or cleaning and/or disinfecting contact lenses. In particular, the present invention provides ophthalmic compositions that contain one or more indolicidin antimicrobial polypeptides and typically have a low halide ion concentration.
BACKGROUND OF THE INVENTION
During normal use, contact lenses are “soiled” or “contaminated” with a wide variety of compounds that immediately or ultimately degrade lens performance. For example, while being worn on the eye, a contact lens is liable to be contaminated with biological materials such as protein or lipid that are found in the tear fluid and that adheres to the surfaces of the contact lens. In handling or cleaning the contact lens, sebum (skin oil) or cosmetics or other materials adhering to the hands of the user tend to soil the contact lens. In addition, particularly as contact lenses accumulate organic contaminants they promote the growth on their surface of a wide range of microbes.
If the contact lens is worn on the eye with such contaminants on its surface, the contact lens suffers from deteriorated water wettability or hydrophilicity and lowered oxygen permeability, causing considerable discomfort to the lens wearer. In addition, the lens wearer may suffer from deterioration in his eyesight, pain in the eye, hyperemia or congestion of the eye, due to the continuous wearing of the contaminated contact lens. In addition, a contaminated lens can become immunogenic stimulating an adverse immune response on the eye and associated tissues. In view of this, it is important to remove the soil debris adhering to the contact lens surfaces and to disinfect the lens for safe and comfortable wearing of the contact lens on the user's eye.
In view of these, and other, factors effecting lens performance, a care regimen for contact lenses typically involves various functions, such as regularly cleaning the lens with a contact lens solution. Rinsing of the contact lens is generally required following cleaning to remove loosened debris and to remove potential irritants in the cleaning solution. Additionally, the regimen may include treatment to disinfect the lens, treatment to render the lens surface more wettable prior to insertion in the eye, or treatment to condition (e.g., lubricate or cushion) the lens surface so that the lens is more comfortable in the eye. As a further example, a contact lens wearer may need to rewet the lens during wear by administering directly in the eye a solution commonly referred to as rewetting drops.
Separate solutions may be provided for the individual segments of the care regimen. For convenience purposes, multipurpose contact lens solutions have gained popularity, i.e., solutions which can be used for several segments of the care regimen.
As an example, multipurpose contact lens solutions that can be used for cleaning, storage and conditioning of contact lenses have been suggested (see, e.g., U.S. Pat. No. 5,141,665 (Sherman) discloses a cleaning, conditioning, storing and wetting system for rigid gas permeable contact lenses. The system is described as including: (1) a cleaning, conditioning and storing solution; and (2) a separate wetting solution, where both solutions include a disinfectant or preservative. Lenses treated with the first solution are rinsed and then wet with the separate wetting solution prior to insertion in the eye.
Multipurpose contact lens solutions that effectively clean a contact lens, and can also be used to treat the lens immediately prior to insertion of the lens in the eye, are much more challenging multipurpose solutions to develop. Conventional surface active agents having good cleaning activity for contact lens deposits, as well as various other components such as antimicrobial agents included as a preservative or disinfectant, tend to be irritating to the eye. Accordingly, new ophthalmic compositions, particularly multipurpose formulations, are desirable.
In recent years, researchers have come to recognize that many organisms use peptides as part of their host defense systems. These organism include a full range of species from prokaryotes to humans. The antimicrobial peptides can be subdivided into a number of groups based on their amino acid content, structure and source. Several reviews of several classes of these peptides have been recently published (See, for example, Lehrer & Ganz (1966)
Annal. N.Y. Acad. Sci.,
797:228-239; Maloy & Kari (1995)
Biopolymers,
37:105-122).
Antimicrobial peptides have common structural features, including a net cationic charge due to the presence of multiple charged residues (Arg, Lys), the presence of multiple cysteine residues, and in most cases the ability to form amphipathic structures. These properties are important for the mechanism of action that is currently thought to involve a non-receptor-mediated interaction with the anionic phospholipid bilayer of the target cell, followed by incorporation of the peptide into the membrane, and a resulting disruption of the membrane structure.
The spectrum of activity of host defense peptides is very broad, killing many species of bacteria, protozoa, fungi, and virally infected cells and even cancer cells (Maloy & Kari (1995)
Biopolymers,
37:105-122). Moreover, these peptides have a low toxicity on most healthy mammalian cells and tissues. It is thought that the peptides are preferentially selective for prokaryotic membranes because of the lipid composition of the membrane. In particular, there is a higher concentration of anionic phospholipids in the outer leaflet of bacteria than in normal eukaryotic membranes, and cholesterol is present in mammalian membranes but not in bacterial membranes. Whatever the reason for the preference, the selectivity of antimicrobial peptide for prokaryotes compared to eukaryotes, these peptides are ideal components in products intended for human use.
While attempts have been made to utilize antimicrobial polypeptides in ophthalmic solutions, to date such efforts have been largely unsuccessful. For example, Sousa et al. (1996)
CLAO J.,
22(2):114-117, showed that the use of a synthetic cecropin analog in combination with various ophthalmic solutions failed to be highly effective in disinfecting, particularly when used by itself. Cullor et al. (1990)
Arch. Ophthalmol.,
108: 861-864 examined the in vitro efficacy of rabbit defensins, NP-1 and NP-5, against ocular pathogens isolated from cases of severe ulcerative keratitis in humans and horses. Unfortunately, these antimicrobial peptide-containing compositions were found to have toxicity to human eye tissue. Similarly U.S. Pat. No. 5,549,894 describes ophthalmic compositions containing D-enantiomeric peptides, such as cecropins, magainins and defensins. These polypeptides, however are toxic and eye care products containing these peptides can not be made in commercial quantities, as the peptides must be chemically synthesized and can not be made using biological expression systems.
SUMMARY OF THE INVENTION
This invention provides novel ophthalmic solutions based on the use of indolicidins as antimicrobial agents. In particular, the solutions of this invention are self-preserving and require no additional preservatives or disinfectants. The solutions are well suited for ophthalmic use and are effective in cleaning, disinfecting, and sterilizing the contact lens upon exposure to the composition without the need for physical or thermal treatment of the lens. Moreover, because indolicidins are safe for topical application to the eye, the solutions enable immediate application of the contact lens to the eye without the need for neutralization, deactivation, or washing any of the compositions' components. In addition, the compositions have extremely long shelf life at room temperature.
In particular, it was a discovery o
Chapoy Larry L.
Hokama Leslie A.
Mortelmans Kristien
Quinn Michael H.
Selsted Michael E.
Delacroix-Muirheid C.
Jones Dwyane C.
The Regents of the University of California
Townsend and Townsned and Crew LLP
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