Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
1998-12-22
2001-08-14
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S568000, C424S078040
Reexamination Certificate
active
06274626
ABSTRACT:
This invention relates to compositions comprising pheniramine. In particular, it has been found that pheniramine and derivatives thereof, when employed in combination with an effective amount of povidone, provides improved comfort and reduces stinging. Compositions according to the present invention have also been found to alleviate the symptoms of dryness in addition to allergic symptoms.
BACKGROUND OF THE INVENTION
Allergic responses include what is referred to as allergic conjunctiva, which is basically a hypersensitivity reaction, which may occur as a component of hayfever or an independent ocular allergy. For example, allergic responses to ragweed, pollen and animal hair may result in minor eye symptoms of itching and redness. The eye, particularly the conjunctiva, has a relatively large number of mast cells. When allergens are present, they can bind to the immunoglobulin on the surface of these mast cells and trigger the breakdown, or what is known as the degranulation, of the cell. On degranulation, mast cell components, including histamines, are released into the environment outside the mast cell. Through a variety of mechanisms, these components can be responsible for symptoms associated with allergic responses such as itching, redness, lid swelling, vasodilatation and chemosis (edema of the conjunctiva). The patient commonly complains of a burning of the eyes.
Antihistamines are compounds which are administered to prevent histamines, released from mast cells in response to the presence of allergens, from binding to, for example, nerves and smooth muscle cells of the conjunctival blood vessels causing redness, itching and swelling. Thus, topical antihistamines do not block the release of histamine, but rather inhibit the allergic reaction by competing with histamine for the histamine receptors on effector cells. Historically, the term antihistamine has been used to describe drugs that act as H
1
-receptor antagonists.
Topical antihistamines are commonly formulated in combination with a vasoconstrictor to create a product that also helps to relieve ocular injection. Clinically available antihistamines that competitively antagonize histamine to some extent include ethanolamines, ethylenediamines, alkylamines, phenothiazines or piperidines. Antihistamine preparations commercially available for topical ophthalmic use include 0.3% pheniramine maleate (an alkylamine), 0.5% antazoline phosphate (an ethylenediamine), and 0.1% pyrilamine maleate (also an ethylenediamine). Conventional vasoconstrictors include, for example, ephedrine, naphazoline, phenylephrine, and tetrahydrozoline.
One commercially available product for treating allergic conjunctivitis, OPCON-A® eyedrops, is a sterile aqueous ophthalmic solution containing 0.025% naphazoline hydrochloride and 0.3% pheniramine maleate, further in combination with the inactives hydroxypropyl methylcellulose, sodium chloride, sodium borate, and edetate disodium, preserved with 0.01% benzalkonium chloride. Such products combine the effects of the antihistamine, pheniramine maleate, with the decongestant or vasoconstrictor naphazoline.
In addition to antihistamines used to treat allergic symptoms, a variety of demulcents are known for topical administration to the eye to protect and lubricate mucous membrane surfaces and relieve dryness and irritation. Conventional demulcents include carboxymethyl cellulose, hydroxyethyl cellulose and other cellulose derivatives, dextran, gelatin, and polyols such as glycerin, polyethylene glycol, polysorbate, propylene glycol, polyvinyl alcohol, and povidone. For example, U.S. Pat. No. 4,120,949 discloses the use of polyvinylpryrrolidone (also referred to as povidone or PVP) as a demulcent. Rankin, in U.S. Pat. No. 3,920,810, discloses the use of polyvinylpyrrolidone (PVP) as a demulcent and lubricant in solutions used to treat dry eye. PVP is known to act as a demulcent lubricant by means of a combination of adhesive and lubricating properties that aid in the spreading of its viscous solution.
A problem with products on the market for treating allergic conjunctivitis is that, despite the use of such products, patients continue to complain about burning and itching. Thus, a more effective product or a product treating a greater range of symptoms is desirable. Furthermore, it would be desirable to provide a single composition that would effectively respond to a fuller range of symptoms, including dryness, itching, and burning. It has been found that, contrary to intuition (because allergic responses may include watering of the eyes), dryness is often associated with allergic conditions, and that compositions that alleviate the symptoms of dryness more fully respond to the range of symptoms associated with the allergic responses. It would, therefore, be desirable to be able to effectively and simultaneously treat both dryness and allergic reactions by the administration of a single composition. Finally, it would be desirable if such compositions could be administered to patients irrespective of whether they were wearing contact lenses.
It is, therefore, an object of the present invention to provide improved ophthalmic compositions comprising an antihistamine for treating allergic responses, including redness and itching, that is comfortable and that elicits minimal stinging. It is a further object to provide an ophthalmic composition designed to alleviate dryness. Finally, it is an object to provide methods for treating ophthalmic allergic conditions through administration of the disclosed compositions.
SUMMARY OF THE INVENTION
This invention is directed towards compositions for preventing and treating ophthalmic allergic responses comprising the antihistamine pheniramine or derivatives thereof, in combination with povidone, in the absence or presence of a vasoconstrictor. In accordance with the invention, povidone is employed in the composition not only to improve comfort, but also alleviate dryness. The present compositions have been found to provide effective relief of itchy, red and swollen eyes without producing significant side effects. The compositions can be formulated as solutions or suspensions for topical administration to the eye. In addition, this invention is directed to methods for preventing and treating ophthalmic allergic responses using the compositions of the present invention. The objects, features, and advantages of the various embodiments of the present invention will become more readily apparent from the following detailed description.
DETAILED DESCRIPTION OF THE INVENTION
Pheniramine is a well-established anti-histaminic compound. Pheniramine, the free base and its ophthalmically acceptable salts, is a compound of the alkylamine type that is commonly used as an antihistamine for local and generalized allergic reactions.
In the preferred form of the maleate salt, it is soluble in water and may be represented by the following formula:
Its chemical name is N, N-dimethyl-gamma-phenyl-2-pyridine-propanamine, butenedoic acid or 1-phenyl-1-(2-pyridyl)-3-dimethylaminopropane maleate. Pheniramine may be prepared in the manner described by Sperber et al. in U.S. Pat. No. 2,567,245 and 2,676,964. Alternately, pheniramine is also commercially available from Loftus Bryan Chemicals Ltd., Rathdrum Co. (Wicklow, Ireland) or Kongo Chemical Co. (Toyama, Japan). Derivatives of pheniramine include, for example, the halogenated derivatives chloropheniramine and bromopheniramine.
According to the present invention, pheniramine (or derivatives thereof), in the amount of 0.10 to 0.50 weight percent, preferably about 0.40 to 0.45 weight percent, in combination with an effective amount of povidone effectively treats the symptoms of both allergy and dryness. The present invention may remove redness, for example, over a period of 5 to 10 minutes. Such compositions have been found to alleviate dryness in combination with the so-called stinging and burning associated with the allergic response.
In addition to pheniramine maleate, other substantially non-toxic or non-irritating pheniramine salts that m
Jonasse Matthew S.
Smerbeck Richard V.
Bausch & Lomb Incorporated
Fay Zohreh
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