Title:  Ophthalmic anti-allergy compositions suitable for use with contact lenses

United States Patent:  6,375,973

Assignee:  Alcon Universal Ltd. (Hunenberg, CH)

Filed:  January 24, 2001

Topically administrable anti-allergy compositions comprising olopatadine and a polymeric quaternary ammonium preservative are suitable for use by patients wearing contact lenses.

DETAILED DESCRIPTION OF THE INVENTION

Olopatadine is (Z)-11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]-oxepin-2-aceti c acid. Olopatadine can be made using the methods disclosed in U.S. Pat. No. 5, 116,863, the entire contents of which are hereby incorporated by reference. The concentration of olopatadine in the compositions of the present invention will range from about 0.0001 to 5% (w/v), preferably from about 0.001 to 0.25% (w/v), and most preferably from about 0.1 to 0.25% (w/v), based on the sterilized purified water. The olopatadine ingredient may be present in the form of a pharmaceutically acceptable salt. Unless indicated otherwise, "olopatadine" as used herein refers to both olopatadine and its pharmaceutically acceptable salts. The most preferred form of olopatadine is olopatadine hydrochloride. The most preferred concentration of olopatadine hydrochloride is from about 0.111 to 0.222% (w/v), which is equivalent to 0.1 to 0.2% (w/v) olopatadine.

Emedastine's chemical name is 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiper-azinyl)-benzimidazole. The ophthalmic use of emedastine is disclosed in U.S. Pat. No. 5,441,958. Emedastine can be made using the methods disclosed in U.S. Pat. No. 4,430,343, the entire contents of which are hereby incorporated by reference. The concentration of emedastine in the compositions of the present invention will range from about 0.0001 to 1% (w/v), preferably from about 0.005 to 0.1% (w/v), and most preferably about 0.05% (w/v). The emedastine ingredient may be present in the form of a pharmaceutically acceptable salt. Unless indicated otherwise, "emedastine" as used herein refers to both emedastine and its pharmaceutically acceptable salts. The most preferred form of emedastine is emedastine difumarate. The most preferred concentration of emedastine difumarate is about 0.0884% (w/v), which is equivalent to 0.05% (w/v) emedastine.

In addition to olopatadine or emedastine, or a pharmaceutically acceptable salt thereof, the compositions of the present invention contain a polymeric quaternary ammonium compound as a preservative. The polymeric quaternary ammonium compounds useful in the compositions of the present invention are those which have an antimicrobial effect and which are ophthalmically acceptable. Preferred compounds of this type are described in U.S. Pat. Nos. 3,931,319; 4,027,020; 4,407,791; 4,525,346; 4,836,986; 5,037,647 and 5,300,287; and PCT application WO 91/09523 (Dziabo et al.). The most preferred polymeric ammonium compound is polyquaternium-1, otherwise known as Polyquad.RTM. or Onamer M.RTM., with a number average molecular weight between 2,000 to 30,000. Preferably, the number average molecular weight is between 3,000 to 14,000.

The polymeric quaternary ammonium compounds are generally used in the compositions of the present invention in an amount from about 0.00001 to about 3% (w/v), preferably from about 0.001 to about 0.1% (w/v). Most preferably, the compositions of the present invention contain from about 0.001 to about 0.05% (w/v) of polymeric quaternary ammonium compounds.

It may be necessary or desirable to add boric acid to the compositions to achieve desired levels of preservative efficacy. See U.S. Pat. No. 5,603,929, the entire contents of which are hereby incorporated by reference. The boric acid suitable for use in the compositions of the present invention includes not only boric acid, but also its ophthalmically acceptable acid addition salts, as well as borate-polyol complexes of the type described in U.S. Pat. No. 5,342,620 (Chowhan). If present, the amount of boric acid will generally range from about 0.3 to about 5.0% (w/v).

The compositions of the present invention should have an ophthalmically acceptable tonicity, such as 260-320 mOsm/kg, and an ophthalmically acceptable pH, such as pH 5-8, and preferably pH 6.8-7.6. The topically administrable, multi-dose compositions of the present invention optionally comprise other excipients, such as tonicity adjusting agents, buffering agents, chelating agents, and pH adjusting agents. For example, sodium chloride, mannitol, or the like may be used as the isotonic agent; sodium hydrogenphosphate, sodium dihydrogenphosphate, p-hydroxybenzoic acid ester, boric acid or the like as the buffering agent; sodium edetate or the like as the chelating agent or stabilizer; and sodium hydroxide, hydrochloric acid or the like as the pH adjusting agent.

The compositions of the present invention may also include viscosity modifying agents such as: cellulosic ethers, such as, hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), ethyl hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, and carboxymethyl cellulose; carbomers (e.g. Carbopol.RTM.; polyvinyl alcohol; polyvinyl pyrrolidone; alginates; carrageenans; and guar, karaya, agarose, locust bean, and xanthan gums.

Claim 1 of 19 Claims

What is claimed is:

1. A topically administrable, multi-dose anti-allergy composition suitable for use by patients wearing contact lenses, wherein the composition comprises an anti-allergy effective amount of a drug selected from the group consisting of olopatadine and emedastine; and an ophthalmically acceptable polymeric quaternary ammonium compound as a preservative, provided that the composition does not contain benzalkonium chloride.

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