US 20080 103103A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0103103 A1 Memarzadeh et al. (43) Pub. Date: May 1, 2008 (54) REAGENTS AND METHODS TO TREAT Publication Classification OCULAR DISEASES AND INFECTION (51) Int. Cl. A63L/7048 (2006.01) (76) Inventors: Bahram Memarzadeh, San Carlos, A63L/353 (2006.01) CA (US); Lyle Bowman, A6II 3/12 (2006.01) Pleasanton, CA (US) A63L/05 (2006.01) (52) U.S. Cl. ........... 514/27: 514/456; 514/454: 514/733; Correspondence Address: 514f678 MCDERMOTT, WILL & EMERY (57) ABSTRACT 4370 LA JOLLAVILLAGE DRIVE, SUITE 700 SANDIEGO CA 92122 The invention provides compositions and methods of treating 9 an ocular condition by administering to an eye of a patient having an ocular condition an effective amount of a catechin (21) Appl. No.: 111590,617 or polyphenol. The compositions and methods can be used to treat ocular conditions such as ocular infection, ocular (22) Filed: Oct. 30, 2006 inflammation, ocular cancer or benign eye tumors. OH O OH OH O OH OH Patent Application Publication May 1, 2008 US 2008/O103103 A1 OH OH HO O OH OH FIGURE 1. US 2008/O 103103 A1 May 1, 2008 REAGENTS AND METHODS TO TREAT can be used to treat ocular conditions such as ocular infec OCULAR DISEASES AND INFECTION tion, ocular inflammation, ocular cancer or benign eye tumors. 0001. The present invention relates generally to the field BRIEF DESCRIPTION OF THE DRAWINGS of medicine and more specifically to pharmaceutical com positions and method for topical application for treating or 0007 FIG. 1 shows the structure of epigallocatechin preventing viral infection, inflammation, and cancer in the gallate (EGCG). eye. DETAILED DESCRIPTION OF THE BACKGROUND OF THE INVENTION INVENTION 0002 The conjunctiva is the thin, clear membrane over the white part of the eye, and it also lines the eyelids. As with 0008. The present invention provides compositions and any mucous membrane, infectious agents can adhere to the methods for treating conjunctivitis and other eye conditions. conjunctiva and overwhelm normal defense mechanism. The invention is based on the use of epigallocatechin gallate Inflammation of this membrane is called conjunctivitis. (EGCG) to treat conjunctivitis or other eye conditions such Conjunctivitis, also known as "pink eye.” is one of the most as cancer of the eye or inflammation of the eye and/or common nontraumatic eye complaints. Causes of conjunc Surrounding tissues. Despite the lack of complete knowledge tivitis include allergic, viral, bacterial, chlamydial, parasitic about eye disease, there are several known causes for the and chemical agents. The causes of conjunctivitis can vary inflammation, infection, and cancer of the eye. The infection seasonally, with some causes increasing or decreasing in of the eye is also known as "pink eye' and is manifested as different seasons. epidemics in School children, military personnel or in the 0003 Conjunctivitis can be highly contagious, especially general population. The present invention relates to the use in environments with close human contact. Conjunctivitis of pharmaceutical preparations to ameliorate signs or symp outbreaks in Schools or daycare facilities can result in the toms associated with eye conditions such as conjunctivitis, spread to many students or young children. Additionally, inflammation of the eye or eye cancer, for example, by close confinement Such as found in the military can also be shortening the duration of conjunctivitis or eye inflammation an environment in which conjunctivitis can occur and spread or reducing the severity of eye cancer. rapidly. Other types of environments in which conjunctivitis 0009 Compositions and methods of the invention are can occur and readily spread include Swimming pools, based on the use of epigallocatechin gallate. Epigallocat campgrounds, hotels, hospitals, nursing homes, offices, or echin gallate (EGCG) belongs to the family of catechins and other environments in which close human contact is com is a member of the chemical class known as polyphenols mon. Although conjunctivitis is generally self-limiting, con (see FIG. 1). EGCG is a potent antioxidant found in black junctivitis can progress to increasingly sever and sight tea or Chinese green tea, from which it can be extracted. threatening infections, depending on the immune state of the EGCG is estimated to be 10 to 50% of the total green tea patient and the etiology. catechins, which consists of epicatechin (EC), epicatechin 0004. Due to the ease with which conjunctivitis can gallate (ECG), epigallocatechin (EGC), epigallocatechin spread and the impact it can have on lost work hours in gallate (EGCG), gallocatechin gallate (GCG). While exem business and the military as well as lost student hours, as plified herein with EGCG, it us understood that other well as the possibility that conjunctivitis can lead to more catechins or polyphenols can be used in compositions and severe, sight threatening infections, it is important that methods of the invention, including but not limited to, EC, effective methods are used to treat conjunctivitis. Antibiotics ECG, EGC, GCG, and the like. Other exemplary catechins are often used to treat conjunctivitis but are ineffective or or polyphenols include apigenin, anthocyanins, aurones, poorly effective for treating viral conjunctivitis. For viral chalcones, isoflavones, proanthocyanidins, astringin, cou conjunctivitis, treatment is usually limited to symptomatic marins, stilbenes, Xanthones, and the like. Although exem therapy, much as one would treat the common cold. Vaso plified herein with EGCG, it is understood that any of the constrictor and antihistamine combinations in eye-drop form catechins or polyphenols, alone or in combination, can be may be very helpful in relieving symptoms. In cases in used in compositions and methods of the invention. Cat which subepithelial infiltrates develop and affect vision, echins or polyphenols can be extracted from natural sources steroids may sometimes be recommended to control Symp Such as green or black tea. Catechins and other polyphenols toms and speed recovery. However, it is quite possible that are also available commercially (see, for example, Sigma Aldrich, St. Louis Mo., and LKT Laboratories, St. Paul once the steroids are discontinued, the disease may continue Minn.). Alternatively, catechins or polyphenols can be Syn to run its course. Furthermore, long-term steroid use may be thesized using well known methods of chemical synthesis. associated with development of cataracts or glaucoma. Thus, the invention provides a composition comprising a 0005 Thus, there exists a need for effective treatments of catechin or polyphenol, as disclosed herein. In a particular conjunctivitis or other eye conditions. The present invention embodiment, the invention provides a pharmaceutical com satisfies this need and provides related advantages as well. position containing a catechin or polyphenol and a pharma SUMMARY OF INVENTION ceutically acceptable carrier. I0010. The chemical formula for EGCG is CHsO, and 0006. The invention provides compositions and methods is also referred to as (2R,3R)-2-(3,4,5-Trihydroxyphenyl)- of treating an ocular condition by administering to an eye of 3,4-dihydro-1 (2H)-benzopyran-3,5,7-triol 3-(3,4,5-trihy a patient having an ocular condition an effective amount of droxybenzoate). It has a molecular weight of 458.37 and is a catechin or polyphenol. The compositions and methods commercially available as highly purified raw material. US 2008/O 103103 A1 May 1, 2008 0011. The invention provides methods of treating an giant papillae are predominantly on the upper palpebral ocular condition. In one embodiment, the invention provides conjunctiva and can be seen only on lid eversion. a method of treating an ocular infection by administering to 0017. Further exemplary signs and symptoms associated an eye of a patient having an ocular infection an effective with viral conjunctivitis include, for example, discharge, amount of (-)-epigallocatechin gallate (EGCG). In another irritation, red eye, increased tearing, eye pain and facial embodiment, the invention provides a method of ameliorat pain, itching of the eye (pruritis), gritty feeling in the eyes, ing a sign or symptom associated with an ocular infection by blurred vision, sensitivity to light, and crusts that form on the administering to an eye of a patient having an ocular eyelid overnight. Infection generally begins in one eye, but infection an effective amount of (-)-epigallocatechin gal can spread to the other eye. There is generally less discharge late (EGCG). in viral conjunctivitis than in bacterial conjunctivitis. 0012 Conjunctivitis, also known as pink eye, is caused 0018 Adenovirus is one of the most common causes of by a variety of agents, including allergic, viral, bacterial, viral conjunctivitis. Adenoviruses are nonenveloped, chlamydial, parasitic and chemical agents. Conjunctivitis double-stranded DNA viruses. There are 49 immunologi caused by infectious agents is highly contagious. In a cally distinct types, with 6 subgenera, A to F, that can cause particular embodiment of the invention, a method is pro human infections. Adenoviruses are unusually stable to vided to treat a viral ocular infection, for example, an chemical or physical agents and adverse pH conditions, adenoviral ocular infection. A method is also provided for allowing for prolonged survival outside the body. Epidemic prophylactic treatment to prevent an infection, for example, keratoconjunctivitis