Drug – bio-affecting and body treating compositions – Topical body preparation containing solid synthetic organic... – Ophthalmic preparation
Reexamination Certificate
1997-09-18
2001-08-21
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Topical body preparation containing solid synthetic organic...
Ophthalmic preparation
C514S912000
Reexamination Certificate
active
06277365
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to ophthalmic compositions containing a cationic glycoside in combination with a therapeutic agent. In particular, the cationic glycoside can be used to improve the efficacy of an anionic therapeutic agent or an anionic polymer delivery vehicle in combination with a therapeutic agent. The present composition can be applied to the eye or to a silicone-containing contact lens.
BACKGROUND
In general, the delivery of therapeutic substances to the surface of the eye has inherent difficulties because the washing action of the tear film removes much of the therapeutic substance. Typically, 90% or more of an ophthalmic drug in the form of an eye drop does not penetrate or adhere to the eye and is removed by tears through the lachrymal ducts.
Anionic therapeutic agents may lack affinity for the surface of an eye due to the anionic nature of the surface of the eye. Thus, the therapeutic effect provided by such agents may be short lived due to the rate at which the agent is flushed away from the eye. Attempts to solve this problem have resulted in the development of delivery systems for therapeutic agents. For example, U.S. Pat. No. 5,358,706 to Marlin et al. discloses a delivery system comprising a cationic polysaccharide in order to bind anionic therapeutic agents to the surface of the eye. Exemplary anionic therapeutic agents are glycosaminoglycans such as hyaluronic acid for the treatment of dry eye, as disclosed by Marlin et al. Synthetic anionic polymers have also been shown to be effective for the treatment of dry eye, for example, the carboxy vinyl polymers disclosed in U.S. Pat. No. 5,209,927 to Gressel et al. Combinations of cationic polymers (as delivery vehicles) with anionic therapeutic agents have also been used in the treatment of keratinous tissues such hair, skin and nails. See, for example, U.S. Pat. Nos. 4,913,743 and 4,767,463 to Brode et al.
U.S. Pat. No. 5,192,535 to Davis et al. discloses a topical ophthalmic medicament delivery method and system that employs carboxy vinyl polymers having certain physical properties that provide for the controlled, sustained release of medicaments after administration in drop form. The delivery system is designed to be administrable at a viscosity suitable for reliable drop dosages, but to substantially increase in viscosity after administration.
It is also possible to provide for the delivery of therapeutic agents with the aid of contact lenses as a delivery device, especially if the person being treated wears contact lenses anyway. Although not related to the delivery of a therapeutic agent, a variety of cationic compounds have been used to temporarily modify the surface properties of contact lens. For example, cationic polymers have been used in aqueous compositions for lubricating and cushioning rigid gas permeable (RGP) lenses. Since RGP lenses typically have an anionically charged surface, cationic polymers tend to associate with the lens surface and can remain associated for an extended period of time. Examples of such cationic polymer are the cationic cellulosic polymers described in U.S. Pat. Nos. 4,168,112 and 5,401,327 to Ellis et al. As indicated above, U.S. Pat. No. 5,358,706 discloses similar cationic polymers as delivery vehicles for therapeutic agents.
Other cationic compounds have also been used to modify the surface properties of contact lenses. For example, quaternary nitrogen-containing ethoxylated glycosides are described in U.S. Pat. No. 5,405,878 to Ellis et al for use in contact-lens care solutions. These compounds each comprise a cationic hydrophobic moiety attached to an ammonium ion and a hydrophilic moiety consisting of a polyethoxylated glycoside derivative, preferably an alkylated glycoside. It is believed that the cationic moiety associates with the negatively charged surface of a lens, while the hydrophilic moiety extends from the lens surface to maintain moisture near the lens surface.
In administering therapeutic agents to the eye, a variety of factors, including consistency and accuracy of dosage, type and time of vision interference, ease of administration, and timing of delivery can be important. Prior ophthalmic delivery vehicles have suffered drawbacks in one or more respects and, in any case, improvement in performance is always desirable. New topical ophthalmic delivery systems for controlled, sustained release of therapeutic agents are, therefore, continually being developed. It is especially challenging to find an ophthalmic delivery vehicle that is safe and effective for human use and that does not have undesirable aide effects or cause undesirable interactions between components in a solution, particularly when limited to use in buffered solutions having osmolality values most common for in-eye solutions (typically from 270 to 330 mOsmols/kg).
SUMMARY OF THE INVENTION
The present invention provides a means for prolonging the association of a therapeutic agent with the surface of the eye and/or a contact lens in the eye, thereby increasing the beneficial effect offered by the therapeutic agent. In particular, the present invention utilizes quaternary nitrogen-containing ethoxylated glycosides to tether a therapeutic agent to the surface of the eye or to a contact lens. In one embodiment of the invention, the glycoside is used in combination with an anionic therapeutic agent. In a second embodiment of the invention, the glycoside is used in combination with both an anionic polymer and a therapeutic agent.
DETAILED DESCRIPTION OF THE INVENTION
As indicated above, the present invention is directed to ophthalmic compositions and their use for the treatment of eyes with therapeutic agents. The invention utilizes a cationic glycoside which is believed to act as a cationic tether, holding an anionic therapeutic agent, or an anionic delivery vehicle for a therapeutic agent, in association with the surface of the eye and/or a contact lens that is worn in the eye. The subject glycoside is non-polymeric and soluble in buffered aqueous solutions when combined with the subject anionic compounds, as described below.
The cationic glycosides employed in the present invention are described in detail in U.S. Pat. No. 5,405,878 which is incorporated herein by reference. These glycosides can be described as quaternary nitrogen-containing ethoxylated glycosides represented. A particularly preferred class of compounds is by Formula (I):
wherein R
1
is alkyl, preferably C
1
-C
18
; the average sum of w, x, y, and z per mole of compound is within the range of about 1 to about 200, preferably about 4 to about 20; n is 0 or 1; R
2
, R
3
, R
4
, and R
5
are individually hydrogen or quaternary nitrogen-containing groups; provided that at least one of R
2
, R
3
, R
4
, or R
5
is a quaternary nitrogen-containing group and that at least one of R
2
, R
3
, R
4
, or R
5
is hydrogen. Representative quaternary nitrogen-containing groups for R
2
, R
3
, R
4
, and R
5
are represented by Formula (II):
wherein R
6
is a C
1
-C
4
hydroxyalkylene; R
7
, R
8
, and R
9
are an alkyl from C
1
-C
16
, and X is an anion, preferably a halide. Especially preferred compounds of Formula (I) include compounds wherein R
1
is methyl, each of R
2
, R
3
, and R
4
is hydrogen, and R
5
is a quaternary nitrogen-containing group as represented by Formula (II).
Such quaternary nitrogen-containing ethoxylated glycosides are commercially available or can be prepared by methods known in the art, such as the methods described in U.S. Pat. No. 5,138,043 to Polovsky et al. An especially preferred material is available under the CTFA designation lauryl methyl gluceth-10 hydroxypropyldimonium chloride, including the product commercially available under the tradename Glucquat-100® (from Amerchol Corp., Edison, N.J.).
The cationic glycoside of the present invention may be employed in the subject compositions at about 0.001 to about 10 weight percent, and preferably at about 0.001 to about 0.5 weight percent.
As mentioned above, the subject glycoside-containing compositions may be used in the t
Ellis Edward James
Ellis Jeanne Yang
Bausch & Lomb Incorporated
Fay Zohreh
Furr, Jr. Robert B.
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