Patent Application: US-64340206-A

Abstract:
this disclosure provides a method and a product to treat fungal nail infections and athlete &# 39 ; s foot in a fast and non expensive way . the product contains one or more lytic peptides in water solution .

Description:
over the last 20 years , a great deal of information has been published describing naturally occurring peptides that possess antibiotic activity ( 113 - 17 ). hundreds of these so - called lytic peptides have been characterized , with numerous variations added to the structural repertoire by design ( 18 - 22 ). these molecules are small basic proteins that appear to be major components of the antimicrobial defense systems of a number of animals including insects , amphibians , and mammals ( 23 - 25 ). they have also been found in numerous plant species and have even been found in some types of bacteria ( 26 - 28 ). they exist in a range of sizes and virtually all have the potential to form amphipathic alpha - helices or partial beta - pleated sheets that are locked in this conformation by formation of specific disulfide linkages , all types interacting with most cells at their membrane surfaces . by inspection of the physical properties of those naturally occurring peptides containing no more than two cysteine residues , we suggest that they can be catalogued into one of three distinct alpha - helical classes ( unpublished data ). more than 90 % of these types of natural peptides conveniently fall within this classification system consisting of different arrangements of highly cationic amphipathic and hydrophobic regions ( 29 - 40 ). representative examples of natural peptides in this organizational system are melittin — class 1 ( amphipathic region is c - terminal and the n - terminal region comprises a hydrophobic tail ), cecropins — class 2 ( hydrophobic tail at the c - terminus while the n - terminal region is amphipathic , mirror image of class 1 ), and magainins — class 3 ( more or less amphipathic the full length of the molecule ). defensins and similar peptides ( containing more than two cysteine residue ) exist as beta - sheet peptides and do not fall into these kinds of class distinction . these physical characteristics have guided our efforts in peptide design for the last 15 years . we have generated a great deal of data from extensive in vitro and in vivo experiments during this time and have come to appreciate the range and complexity of the cellular interactions of these molecules ( 33 - 38 ). perhaps , in some respects , the so - called “ lytic ” activity of these peptides is the least important of their capabilities ( unpublished results ). we have designed more than 30 , 000 separate synthetic peptides and tested more than 300 of these designs in order to help determine the structural features relevant to the control and treatment of diseases in plants , animals , and humans . the more important physical criteria of the peptides are : 1 ) degree of amphipathy , 2 ) length of amphipathy , 3 ) heterogeneity of amphipathic section , 4 ) placement of amphipathic section ( n or c terminal ), 5 ) positive charge density ( less or more ), 6 ) hydrophobicity of amphipathic section , 7 ) presence of hydrophobic tail , 8 ) length of hydrophobic tail , 9 ) hydrophobicity of tail , 10 ) placement of hydrophobic tail ( n or c terminal , 11 ) absence or presence ( and position of ) of positive charged center , 12 ) absence or presence ( and position of ) of flanking sequence , 13 ) predominating secondary structure , 14 ) termini modification ( n - acetylation , c - amidation ), 15 ) surface area of hydrophilic and hydrophobic faces and 16 ) steric or volume considerations . antimicrobial peptides are small effector molecules with broad distribution at tissue sites initially exposed to microbial invasion [ 1 , 2 ]. these peptides are produced by several cell types including phagocytes and epithelial cells , including those within the vaginal and endocervical mucosa [ 1 , 2 ]. epithelial expression may be both constitutive and inducible [ 3 ] with efficacy against bacteria , fingi , protozoa , tumor cells , and enveloped viruses ( including hiv ) [ 4 , 5 ]. consistent features of microbial peptides are their small size ( 12 - 100 amino acids in length ), amphipathic secondary structure associated with an alpha helix or beta pleated sheet , and polycationic charge . the mechanism of action of antimicrobial peptides is not fully understood however direct antiviral effects occur at concentrations well below that necessary to cause any observable cellular effect ( unpublished data ). peptide - lipid interactions lead to membrane permeabilization [ 6 ] and there is data to support that this occurs by an electrostatic charge - based mode of action rather than pore formation [ 7 , 8 ]. synthetic analogues to natural microbicidal peptides such as defensins and magainins have been designed based on modulating sequence , secondary structure and other properties of naturally occurring alpha helical and beta pleated sheet peptides . these synthetically derived antimicrobials have been shown to have potent antiviral effects in vitro against fiv and hiv ( detailed in preliminary data ), herpes simplex virus ( hsv ) [ 9 ], chlamydia trachomatis [ 10 ] and neisseria gonorrhea ( unpublished data ). in addition , vaginal application of synthetic antimicrobial peptides prevents infection by trichomonas vaginalis [ 11 ]. however , synthetic antimicrobial peptides proposed for use against vaginal lentivirus transmission have also been shown to spare lactobacilli species thus demonstrating selective antimicrobial activity [ 12 ]. the treatment according to this invention is called fungall . fungall is very effective against fungal nail infections ( onychomycosis ) and athlete &# 39 ; s foot ( tinea pedis ). the active ingredient of the product according to this invention is a synthetically designed peptide molecule of the class known as “ lytic peptides ” or antimicrobial peptides ”. according to a preferred embodiment the peptide is selected from the sequences listed in table 1 . the peptides according to the sequences in table 1 have been designed for optimal antifungal activity . however , other natural or synthetic peptides with similar structure can also be used . the use of fungall provides almost immediate relief to patients suffering from fungal nail infections or athlete &# 39 ; s foot as compared to currently commonly used products involving cream or pill therapies . the product is applied topically by the podiatrist . application of the product only requires two or three treatments within a single week to effectuate a cure and complete destruction of the fungus — both as it relates to its use against nail fungus or athlete &# 39 ; s foot . in the case of athlete &# 39 ; s foot the product provides almost immediate relief from the itching caused by the pathogen . no known side - effects have been noted or demonstrated as a result of its use topically . in addition to its ability to kill the fungus , the product also is likely to simultaneously contribute two additional benefits : 1 ) protection for the treated area against attack by other opportunistic pathogens ; and 2 ) accelerated healing of the area that may have been damaged by the pathogen . unlike all the other products currently being marketed for use against fungal nail infections and athlete &# 39 ; s foot , the product according to this disclosure can bring almost immediate relief ( requiring only two or three applications within a week , and healthy nail recovery within less than a month ) with no adverse side - effects , and at a much lower cost . in addition , the product of this disclosure will save the patient considerable time and prolonged discomfort . the product according to this disclosure also demonstrates a strong antibacterial and anti - inflammatory activity , and is very likely to prove very effective on a rather broad range of other pathogenic microorganisms . in the case of infected nails , the nail is preferably roughed with an emery board or nail file to help facilitate the absorption of the product . using the eye dropper , enough products sufficient only to cover the infected area is used . the procedure is repeated by the podiatrist at least three times within a single week . the infected nail itself may take a couple of weeks to completely rejuvenate to normal healthiness that can be determined by examination by the podiatrist . the peptide is diluted with distilled water so that the end concentration of the peptide is between 1 and 100 μm and preferably approximately 75 . a few drops of the peptide solution is placed on the infected area and slightly beyond with a wet cotton ball and allowed to air dry . the patient will realize almost immediate relief from the normal itching sensation that normal accompanies athlete &# 39 ; s feet . two or three treatments within a period of one week result in the destruction of the fungus altogether , and healthy skin growth is evident within a day or two following the final application of the product . according to a preferred embodiment the product of this invention is provided in a small brown bottle whose lid is a screw - topped eye - dropper , which is used to actually apply the product . according to this embodiment the bottle contains a preparation of one or more lytic peptides selected from table 1 . the product is to be held or stored under normal refrigeration ( 40 degree f .) until ready for use . it also is not to be subjected to prolonged daylight . when ready for use , the eye - dropper lid is removed and distilled or bottled water is added to the specific level indicated on the bottle , so as to provide preferred concentration of about 75 μm of the peptide . tap water should never to be used due to the normal impurities found in it . once the distilled or bottled water has been added to the product , it should again be stored under normal refrigeration , and used within about a ten ( 10 ) day period . about 200 patients diagnosed with onychomycosis used the composition according to this disclosure under instructions of a certified podiatrist . approximately 80 % of the patients were found to have significant improvement in the appearance of the nail . some patients reported that the nails did not heart as much after the treatment . some patients have experienced a complete cure and others are in process of treatment . generally the nail looks lighter than and not as thick as before treatment . the treatment was more effective on nails where the infection is in its beginning . on nails where the fungus is completely involved the treatment is not quite as effective , however even when applied on such nails the nail becomes softer and more easily to debride . while the invention has been particularly shown and described with the reference to the preferred embodiment thereof , it will be understood by those skilled in the art that various changes in form and details may be made without departing from the spirit and scope of the invention . 1 . quayle a j , porter e m , nussbaum a a , et al . gene expression , immunolocalization , and secretion of human defensin - 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