US 2003OO26794A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0026794 A1 Fein (43) Pub. Date: Feb. 6, 2003 (54) SELECTIVE ENZYME TREATMENT OF (52) U.S. Cl. ..................... 424/94.2; 424/946; 424/94.63 SKIN CONDITIONS (76) Inventor: Howard Fein, Cincinnati, OH (US) (57) ABSTRACT Correspondence Address: A method of treating skin conditions by providing compo Beverly A. Lyman Sitions containing enzymes to Selectively remove Specific Wood, Herron & Evans, L.L.P. layers of skin. The depth of skin removed (that is, vertical 2700 Carew Tower Surface treated) is regulated by the type and concentration of 441 Wine Street enzyme or enzymes in the composition. The Surface area of Cincinnati, OH 45202-2917 (US) skin removed (that is, radial Surface treated) is regulated by the area of topical application. Conditions treatable by the (21) Appl. No.: 09/919,102 method include, but are not limited to, age-related condi (22) Filed: Jul. 31, 2001 tions Such as lines and wrinkles, infections, pigmentary disorders, follicular disorderS Such as acne, and hyperkera Publication Classification totic disorders such as warts. The inventive method and composition thus achieves the Specificity and efficacy of (51) Int. Cl." ......................... A61K 38/54; A61K 38/46; more invasive methods Such as Surgery, while providing a A61K 38/48 composition that may be topically applied and is easy to use. Patent Application Publication Feb. 6, 2003. Sheet 1 of 3 US 2003/0026794 A1 FIG FIG. 2 Patent Application Publication Feb. 6, 2003 Sheet 2 of 3 US 2003/0026794 A1 FIG. 4 FIG. 5 Patent Application Publication Feb. 6, 2003 Sheet 3 of 3 US 2003/0026794 A1 FIG. 6 FIG. 7 US 2003/0026794 A1 Feb. 6, 2003 SELECTIVE ENZYME TREATMENT OF SKIN treating various skin disorders, especially those involving CONDITIONS Some type of keratinization disorder. While most of these products are available over-the-counter, Some topical skin FIELD OF THE INVENTION care formulations that contain enzymes are available by 0001. The invention relates to the use of skin treatment prescription only. These include Accuzyme(E) (papain) and compositions containing enzymes that Selectively target one GranuleXOR (trypsin), whose application is limited for debri or more layers of skin. dement of wounds. 0006 There are, however, other skin conditions whose BACKGROUND OF THE INVENTION treatment involves more than just removal of the outer layers of the epidermis. Such conditions may affect, and hence 0002 The skin, the largest organ of the human body, is of require removal of, either deeper epidermal layers, full interest from biological, medical and cosmetic points of thickness epidermis, or even dermal and/or Subcutaneous View. Many products exist which purport to target one or layers. Current treatment methods for these conditions usu more of these aspects of skin care. Confounding Such ally consist of methods that destroy the skin at the treatment treatment is the fact that conditions affecting the skin may be Site. These methods include cryotherapy (freezing with Specific to the Skin, Such as psoriasis and atopic dermatitis, liquid nitrogen), Surgical removal, electroSurgery (tissue or may be manifestations of a general disease, Such as destruction with electricity), laser Surgery (tissue destruction general allergic reactions. with light), burning, and chemical destruction with caustic 0003. There are a variety of over-the-counter and pre agents Such as trichloroacetic acid and phenol. Most of these Scription products that contain enzymes which are used for methods are non-Selective in terms of tissue destruction, and the purpose of skin care. Reported applications for these damage or destroy not only the affected Site, but other products include Softening skin, treating skin conditions healthy layers and Surfaces of Skin as well. These methods Such as dryneSS, wrinkles, and acne, and/or removing devi also incur pain, Scarring, pigmentary alterations, delayed talized or necrotic skin. In general, enzyme-containing prod wound healing, and lesion recurrence. ucts have been directed to conditions in which it is desirable 0007. Therefore, it would be desirable to combine the to remove the upper layers of the skin. In this process, beneficial features of the above known skin treatment com termed exfoliation, the skin that has been removed is even positions and methods, Such as the convenience and ease of tually replaced with newly generated Skin from Surrounding use of a topically applied Skin care product, with the and StructureS. applicability of a more invasive method, to achieve Selective 0004 One class of enzymes used in skin-related products destruction of affected layers of skin. Such a combination is proteolytic enzymes, also called proteases or peptidases, has not, until now, been disclosed. which function to hydrolyze, or break down, proteins. Pro SUMMARY OF THE INVENTION teins known as adhesion molecules are present in the extra cellular matrix of skin where they act to bind and anchor 0008. The invention is directed to a method for treating a keratinocytes (cells that are present in the Outermost layer of patient having a condition involving the epidermal, and/or skin). When proteolytic enzymes are applied to the Surface dermal, and/or Subcutaneous layer of skin using a compo of skin, they hydrolyze adhesion molecules, resulting desir Sition containing at least one enzyme that affects one or more ably in exfoliation of the upper skin layers. Generally, most particular layers of skin. In one embodiment, a physiologi of the topically applied enzyme-containing products contain cally acceptable formulation containing an effective amount proteolytic enzymes, and would thus be directed to appli of an enzyme that Selectively affects one or more Skin layers is administered topically to treat the condition. In another cations that involve treating the epidermis (the Outermost embodiment, the enzyme-containing formulation may be layer of skin). administered directly to an underlying skin layer. The 0005 There are several types of proteolytic enzymes. enzyme, naturally occurring or Synthetic, may belong to the Papain, a proteolytic enzyme that is isolated from unripe class of oxidoreductases, transferases, hydrolases, lyases, papaya fruit, is effective in hydrolyzing esters and hydro isomerases, and/or ligases. The enzymes may be produced phobic proteins, and has been used in various types of using recombinant techniques and may contain one or more topical formulations. Papain-containing formulations may modified amino acids while retaining a desired level of also contain other proteolytic enzymes Such as bromelain, activity. Also included in the invention are enzymes that which is isolated from pineapples. The formulations may have the desired therapeutic activity but that are not cur additionally contain protein denaturing chemicals. Such as rently classified in one of the above classifications. urea, and/or other chemicals. Such as alpha hydroxyacid and salicylic acid, both of which lower the pH of the skin and 0009. The method may be used to treat a wide variety of cause exfoliation. AS another example, proteolytic enzymes conditions which include, but are not limited to, neoplasms, obtained from the bacterium MicrococcuS Sedentarius have pigmentary disorders, infectious disorders, follicular disor been shown to degrade calluses in vitro. AS Still another ders, hyperkeratotic disorders, inflammatory disorders, Vas example, U.S. Pat. No. 5,981,256 discloses the use of a cular disorders, aging disorders including photo-aging dis recombinant Stratum corneum chymotryptic enzyme orders, deposition disorders, connective tissue disorders, (SCCE) for pharmaceutical and cosmetic skin care. SCCE, cutaneous cystic disorders, dandruff, Seborrheic dermatitis, a Serine proteolytic enzyme, is responsible for the degrada dry skin, corns, calluses, warts, freckles, acne, wrinkles, tion of desmosomal proteins, which play a role in the cysts, eczema, insect bites, lupus, Varicose veins, tattoos, intercellular cohesion in the epidermis. SCCE activity and/or Scars. results in cell shedding from the surface of the cornified 0010. The inventive composition contains at least one surface layer. Hence, recombinant SCCE could be used for enzyme in a pharmaceutically acceptable formulation and an US 2003/0026794 A1 Feb. 6, 2003 amount effective to remove the affected Skin layer or layers. 0018. In another embodiment, a method for treating a The amount of enzyme can range from about 1x10% to condition affecting skin is disclosed by applying a compo about 80%” of the formulation, more particularly from Sition to the affected skin, where the composition contains at about 1x10%YY to about 10% of the formulation. least one enzyme at a concentration Selective for regulating 0.011 The invention is additionally directed to a compo the depth of skin treatment, and is applied to an area of skin Sition in a pharmaceutically acceptable formulation for Selective for regulating a radial Surface of Skin treatment. Selectively treating skin, and that contains one or more 0019. These and other embodiments will be further hydrolases in an amount ranging from about 1x10% by appreciated from the following detailed description and weight to about 80% by weight of the formulation, more examples. particularly from about 1x10% to about 10% of the formulation. The hydrolase may be one or more of an BRIEF DESCRIPTION OF THE DRAWINGS esterase, a glycosidase, a peptidase Such as collagenase, trypsin, papain, bromelain, elastase, etc., a phosphatase, a 0020 FIG. 1 is a photograph of skin showing a sebor thiolase, a phospholipase, an amidase, a deaminase, and/or rheic keratosis lesion. a ribonuclease. 0021 FIG. 2 is a photograph of the skin lesion of FIG. 0012. Thus, in one embodiment, a method for treating a 1 immediately after treatment with one embodiment of the patient having a condition affecting at least one layer of skin inventive composition. is disclosed. A physiologically acceptable formulation con 0022 FIG. 3 is a photograph of the skin lesion of FIG. taining at least one enzyme Selective for a layer of skin 1 three weeks post treatment.