This invention relates to a method for the prevention and treatment of eye inflammation due to exposure to an irritant.
It has long been known that eye irritation and inflammation can occur from exposure to a wide variety of chemical irritants, e.g., smog, building fires, tobacco smoke and industrial chemicals. More recently, contact lenses have become a major source of such eye irritation and inflammation. There are several non-prescription products marketed today to treat such eye ailments. However, some patients are sensitive to the chemicals in them, some do not respond thereto and none are reliably effective in preventing the irritation which often is associated with wearing contact lenses. The prescription drugs, such as antibiotics and steroidal anti-inflammatory agents, while generally more effective have their own disadvantages.
There therefore is a long standing need for safe and effective opthalmic anti-inflammatory agent for treating eye irritation, especially that associated with contact lens use. There is also a need for a non-toxic, non-allergenic bacteriostat and fungistat which is also effective in promoting the normal healing of the surface of the eye by suppressing infection and/or the natural inflammatory process. The present invention meets those needs.
The compositions employed in this invention comprise biphenamine (.beta.-diethylaminoethyl 3-phenyl-2-hydroxybenzoate), either as the free base or a pharmaceutically acceptable acid addition salt thereof. Salts of this compound are known to have a variety of activities, including local anesthetic (U.S. Pat. No. 1,976,922); treatment of seborrhea capitis in a shampoo (U.S. Pat. No. 3,123,531); as well as antihistaminic and bactericidal activity and fungicidal properties (U.S. Pat. No. 2,593,350; Report Annual Meeting So. Med. Assoc., Nov. 6, 1961).
Biphenamine hydrochloride has been sold as a 1% ointment, under the trademark "Melsaphine," as a topical anesthetic agent possessing bactericidal, fungicidal and antihistamine properties and as a 1% aqueous shampoo under the trademark "Alvinine," Federal Register, Vol. 34, No. 189, page 153, Oct. 2, 1969. See also U.S. Pat. No. 3,123,531.
Although its use in a shampoo for treating seborrhea and related conditions is claimed in U.S. Pat. No. 3,123,531, nothing was known concerning its ability to prevent or ameliorate inflammation in eyes which are exposed to an irritant.
The topical compositions employed in the method of this invention preferably also comprise a small amount of a skin penetrant, e.g., DMSO (dimethyl sulfoxide) or polypropylene glycol, which has no anti-inflammatory effects in the eye at the concentration employed. U.S. Pat. No. 3,551,554 and 3,711,602 disclose that DMSO is effective as an agent for enhancing tissue penetration of physiologically active agents. U.S. Pat. No. 3,549,770 discloses (Example 36) the topical application of a mixture of acetylsalicylic acid and DMSO is more effective than DMSO alone to relieve the pain and muscle spasm of rheumatoid spondylitis. See also U.S. Pat. Nos. 3,711,602; 3,711,606; and 3,743,727 and references cited therein. These patents disclose that the tissue penetration of physiologically active compounds, inter alia, steroidal agents and certain antimicrobial agents, can be enhanced by DMSO. U.S. Pat. No. 3,740,420 discloses DMSO compositions for topical administration containing thickening agents.
The foregoing patents disclose that concentrations of DMSO of 10% by weight and above can effect penetration of such agents through various mucous membrane barriers and that concentrations of 50% by weight and above are effective to achieve penetration thereof through the skin. DMSO is also known to enhance the antiperspirant activity astringent of aluminum, zinc and zirconium salts (U.S. Pat. No. 3,499,961).
DMSO has been disclosed as useful for treating a variety of pathological conditions. U.S. Pat. No. 3,549,770 discloses topical application as a particularly advantageous route. This patent claims methods of relieving the signs and symptoms of tissue inflammation; of vascular insufficiency in the blood and lymph circulatory system; of respiratory distress; of arthritis and a method of promoting tissue repair, by administering an effective amount of DMSO, preferably topically. Dosages as low as 0.01 g/kg and up to 1.0 g/kg per day and sometimes higher dosages are contemplated with 0.1-0.2 g/kg individual doses being average. Higher concentrations of DMSO, such as at least 25% and more often at least about 50% are preferred for topical application. In one example (Example 27) the pain associated with skin abrasion was relieved with 15% DMSO in isotonic saline. 10% to 90% water solutions of DMSO, preferably 20% to 40%, in water, alcohol or glycerine are useful for topical application to the mucous membranes of the body although " . . . lower concentrations of DMSO say down to 3% by weight may be useful in some instances."
The use of DMSO as an ataratic agent is disclosed in U.S. Pat. No. 3,790,682. Pharmaceutical compositions containing DMSO and thickening agents are disclosed in U.S. Pat. No. 3,740,420, along with their use to treat and repair damaged tissue, as an anti-inflammatory agent, as an analgesic agent, as a muscle relaxant, as an agent for treating vascular insufficiency, and relieve the signs and symptoms of certain specific syndromes, viz., respiratory distress, arthritis and burns. None of the foregoing references disclose or suggest that the prevention and amelioration of eye inflammations can be achieved with low concentration of DMSO at concentrations below 10%, although U.S. Pat. No. 3,549,770 discloses (Col. 10, lines 42-49) that for pharyngitis or hiccups, the subject may gargle with a more dilute aqueous solution, e.g., containing 1% or preferably 10% by weight of DMSO, and (Col. 28, lines 44-56) that concentrations of DMSO down to 3% by weight may be useful in some instances, with 10% to 90% water solutions being particularly suitable. The use of DMSO in ophthalmic solutions at concentrations below 10% by weight is not suggested in the prior art. Moreover, low concentrations of DMSO or propylene glycol alone have little if any beneficial effect in treating eye inflammations.