Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2001-12-13
2003-09-16
Wilson, James O. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S054000, C514S058000, C514S059000, C514S839000, C514S912000, C514S915000, C536S102000, C536S103000, C536S123100
Reexamination Certificate
active
06620797
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to the field of artificial tear formulations. More specifically, the invention is directed to an improved artificial tear formulation that provides an increased lubricating effect, an enhanced ability to wet the surface of the cornea, and a greater ability to promote the retention of moisture by the cornea.
The sensation of ocular discomfort commonly referred to as “dry eye” can be caused by various factors. The principal causative factors are: (i) inadequate tear production attributable to aging, medical procedures performed on the cornea (e.g., LASIK), or other conditions; (ii) ocular irritants (e.g., dust, smoke, wind, sun or low humidity); and (iii) eyestrain attributable to extended viewing of computer monitors or other circumstances. Various products for alleviating the symptoms of dry eye have been proposed and several such products have been marketed.
One of the earliest and most successful artificial tear solutions is described in U.S. Pat. No. 4,039,662 (Hecht, et al.). This solution has been marketed for many years as TEARS NATURALE® Lubricant Eye Drops (Alcon Laboratories, Inc., Fort Worth, Tex.). The solution described and claimed in the Hecht, et al. '662 patent and the corresponding commercial product are based on the use of a unique combination of hydroxypropyl metbylcellulose, Dextran 70 and benzalkonium chloride. In a later version of this product, which is marketed under the name TEARS NATURALE® II (Alcon Laboratories, Inc.), the benzalkonium chloride was replaced by polyquaternium-1, which is a polymeric antimicrobial agent/preservative.
Both of the above-cited products offer relief from the symptoms collectively referred to herein as “dry eye” and both have been commercially successful. However, a need exists for improved artificial tear products that are uniquely adapted to address the symptoms of dry eye that exist today. In particular, there is a need for an improved formulation that promotes greater moisture retention by the cornea and provides an enhanced lubricating effect. There is also a need for a solution that is particularly well-suited to meet the needs of patients who are experiencing one or more dry eye symptoms as a result of computer eye strain or surgical procedures involving the cornea, particularly LASIK surgery. (The term “LASIK” is an acronym for a refractive surgical procedure known as “laser in situ keratomileusis”.) Finally, there is a need for improved artificial tear formulations that contain very low concentrations of antimicrobial preservatives, so as to reduce the potential for ocular irritation caused by the preservatives. The present invention is directed to filling these needs.
SUMMARY OF THE INVENTION
The present invention is directed to the provision of unique artificial tear compositions having improved properties, relative to the prior artificial tear formulations mentioned above, as well as other formulations. The invention is also directed to methods of alleviating the symptoms of dry eye by applying the compositions of the present invention topically to the affected eyes.
The artificial tear compositions of the present invention contain a unique combination of three demulcents and an ophthalmically acceptable vehicle for the demulcents. The compositions preferably also contain electrolytes to simulate the salt content of the natural tear fluid. The compositions may also contain a nonionic surfactant to lower the surface tension of the compositions and enhance the spreading of the compositions over the surface of the cornea.
The compositions preferably also contain a unique combination of formulation components that enhance the antimicrobial activity of the compositions. This enhancement of antimicrobial activity makes it possible to reduce the amount of antimicrobial preservative (e.g., polyquaternium-1) required to satisfy preservative efficacy requirements for multi-dose ophthalmic pharmaceutical products. The formulation components utilized to enhance antimicrobial activity will include one or more of the following: (i) a borate/polyol complex, and (ii) a low molecular weight amino acid.
The compositions of the present invention are effective in providing relief from burning and irritation caused by dryness of the eyes and discomfort caused by irritation of the eyes. The compositions may also be utilized as ocular moisture drops or ocular lubricants.
DETAILED DESCRIPTION OF THE INVENTION
The artificial tear compositions of the present invention are preferably formulated as sterile, isotonic solutions. The solutions contain a combination of three demulcents: (1) hydroxypropyl methylcellulose (“HPMC”); (2) glycerin; and (3) one or more dextrans, preferably Dextran 70. The total concentration of this demulcent system in the solutions is from about 0.5 to about 5 weight/volume percent (“w/v %”).
In the preferred embodiment of the present invention, the concentration of HPMC is in the range of 0.2 to 2.5 w/v %, the concentration of glycerin is in the range of 0.2 to 1 w/v %, and the concentration of dextran, in the form of Dextran 70, is 0.1 w/v %.
The artificial tear solutions of the present invention will preferably also contain one or more electrolytes to simulate the composition of natural tear fluid. As will be appreciated by those skilled in the art, the natural tear fluid contains several different ions, including potassium, calcium, magnesium and zinc. The presence of these ions in the natural tear fluid and the respective concentrations of these ions is further described in U.S. Pat. No. 5,403,598 (Beck, et al.), the entire contents of which are hereby incorporated in the present specification by reference. The role that these ions play in maintaining the function of corneal tissues is also discussed in the Beck, et al. '598 patent.
The electrolytes utilized in the compositions of the present invention will comprise one or more of the following: potassium at a concentration of between about 11 and about 25 millimoles per liter (“mmol/l”); calcium at a concentration of between about 0.2 and about 0.5 mmol/l; magnesium at a concentration of between about 0.15 and about 0.45 mmol/l; and bicarbonate at a concentration of between about 1 and about 36 mmol/l, preferably between about 6 and about 24 mmol/l. The compositions may additionally contain zinc at a concentration between about 0.005 and about 0.015 mmol/l.
The artificial tear solutions of the present invention may also contain one or more nonionic surfactants to lower the surface tension of the solutions and thereby enhance spreading of the solutions over the surface of the cornea. The preferred nonionic surfactants have an HLB value of 15 or greater. Examples of suitable nonionic surfactants include the polysorbates, such as polysorbate 80, which is also known as “Tween 80”, and tetrafunctional block copolymers derived from the addition of ethylene oxide and propylene oxide to ethylenediamine. Such block polymers are commercially available from BASF Corporation under the trade name “TETRONIC™”, and are also commonly identified as “poloxamines”. The most preferred nonionic surfactant of this type is poloxamine 1107, which has an HLB value of 24 and an average molecular weight of 15,000. Additional examples of suitable nonionic surfactants include Tween 20, Brij 78 and Brij 700.
The artificial tear solutions of the present invention will contain one or more of the above-described nonionic surfactants in an amount sufficient to reduce the surface tension of the solutions and enhance the ability of the solutions to spread over the surface of the cornea. Such an amount is referred to herein as “an effective amount”. The amount of surfactant utilized will be an amount sufficient to provide the solutions with a surface tension of from about 38 to about 45 dynes per centimeter (“dynes/cm”), which corresponds to the surface tension of human tears. The amount of surfactant required for this purpose will vary somewhat depending on the particular surfactant selected, but the surfactant concentration wi
Chen Huagang
Chowhan Masood A.
Alcon Inc.
Brown Gregg C.
Lewis Patrick
Wilson James O.
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