Compositions and kits for treating pruritus and methods of using the same

Abstract

A treatment for pruritus is described that is based upon amylase. The amylases (α-, β-, γ-amylase) are noted for the cleavage of the α-glycosidic bonds of polysaccharides, yielding lower molecular weight carbohydrate/sugar fragments. It has now been found that α-amylase is effective in the reduction of pruritus (itching) of affected tissue.

1 . An enzymatic pruritic composition for topically treating pruritus, comprising a non-proteolytic enzyme component and up to 20 wt-% of a proteolytic enzyme component, wherein said non-proteolytic enzyme component comprises at least 80% by weight of amylase, and wherein a weight ratio of non-proteolytic enzymes to proteolytic enzymes in the enzymatic pruritic composition is at least 4:1. 
     
     
         2 . The composition according to  claim 1 , wherein said amylase is selected from the group consisting of amylase isolated from humans, animals, bacteria, plants, fungi, and by genetic recombination of human, animal, bacteria, plant, or fungi amylase. 
     
     
         3 . The composition according to  claim 1 , wherein said non-proteolytic enzyme component comprises at least 10% by weight of α-amylase. 
     
     
         4 . The composition according to  claim 3 , wherein said non-proteolytic enzyme component comprises β-amylase, γ-amylase, or both. 
     
     
         5 . The composition according to  claim 1 , further comprising a pharmaceutically acceptable carrier or excipient. 
     
     
         6 . The composition according to  claim 1 , wherein said non-proteolytic enzyme component comprises up to 20% by weight of other hydrolytic enzymes selected from the group consisting of chondroitinases, hyaluronidases, lipases, glycosidases, heparanases, dermatanases, pullulanases, N-acetylglucosaminidase, lactases, phospholipases, transglycosylases, esterases, thioester hydrolyases, sulfatases, escharases, nucleases, phosphatases, phosphodiesterases, mannanases, mannosidases, isoamylases, lyases, inulinases, tannases, pentosanases, glucanases, arabinosidases, pectinases, cellulases, chitinases, xylanases, cutinases, pectate lyases, hemicellulases, and combinations thereof. 
     
     
         7 . The composition according to  claim 1 , wherein the amylase comprises α-amylase obtained from at least one source selected from the group consisting of human pancreas, animal pancreas, and bacteria. 
     
     
         8 . The composition according to  claim 1 , wherein said non-proteolytic enzyme component comprises up to 20% by weight of enzymes selected from the group consisting of oxidases, peroxidases, glucose oxidases, catalases, oxidoreductases, phenoloxidases, laccases, lipoxygenases, isomerases, and ligninases. 
     
     
         9 . The composition according to  claim 1  further comprising at least one polymeric biguanide in an amount of at least 0.01 weight percent to 1.0 weight percent based on a combined weight of amylase and biguanide. 
     
     
         10 . The composition according to  claim 9 , wherein said polymeric biguanide comprises poly(hexamethylene biguanide) or one of its salts. 
     
     
         11 . The composition according to  claim 1  further comprising a water-soluble polymer at a concentration of from 0.01 weight % to 50 weight % of the composition, wherein the water-soluble polymer is selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, guar gum, hydroxyethylguar, hydroxypropylguar, hydroxypropylmethylguar, carboxymethylguar, carboxymethylchitosan, locust bean gum, carrageenan, xanthan gum, gellan gum, Aloe vera gel, scleroglucan, schizophyllan, gum arabic, tamarind gum, poly(vinyl alcohol), poly(ethylene oxide), poly(ethylene glycol), poly(methyl vinyl ether), Carbomer and its salts, poly(acrylic acid) and its salts, poly(methacrylic acid) and its salts, sodium poly(2-acrylamido-2-methylpropanesulfonate), polyacrylamide, poly(N,N-dimethylacrylamide), poly(N-vinylacetamide), poly(N-vinylformamide), poly(2-hydroxyethyl methacrylate), poly(glyceryl methacrylate), poly(N-vinylpyrrolidone), poly(N-isopropylacrylamide) and poly(N-vinylcaprolactam), and combinations thereof. 
     
     
         12 . The composition according to  claim 1  further comprising a chelating agent at a concentration of from 0.01 weight % to 1 weight % based on a total weight of the composition, wherein said chelating agent is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid, nitrilotripropionic acid, diethylenetriaminepentaacetic acid, 2-hydroxyethylethylenediaminetriacetic acid, 1,6-diaminohexamethylenetetraacetic acid, 1,2-diaminocyclohexanetetraacetic acid, O,O′-bis(2-aminoethyl)ethyleneglycoltetraacetic acid, 1,3-diaminopropanetetraacetic acid, N,N′-bis(2-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid, ethylenediamine-N,N′-diacetic acid, ethylenediamine-N,N′-dipropionic acid, triethylenetetraaminehexaacetic acid, ethylenediamine-N,N′-bis(methylenephosphonic acid), iminodiacetic acid, monosodium-N-lauryl-β-iminodipropionic acid (sodium lauriminodipropionate, Deriphat® 160C), N,N-bis(2-hydroxyethyl)glycine, 1,3-diamino-2-hydroxypropanetetraacetic acid, 1,2-diaminopropanetetraacetic acid, ethylenediaminetetrakis(methylenephosphonic acid), N-(2-hydroxyethyl)iminodiacetic acid, biphosphonates, editronate, salts thereof, and combinations thereof. 
     
     
         13 . The composition according to  claim 1  further comprising a monoalkyl glycol selected from the group consisting of 1,2-propanediol (propylene glycol), 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol (caprylyl glycol), 1,2-nonanediol, 1,2-decanediol, 1,2-undecanediol, 1,2-dodecanediol, 1,2-tridecanediol, 1,2-tetradecanediol, 1,2-pentadecanediol, 1,2-hexadecanediol, 1,2-heptadecanediol, 1,2-octadecanediol, 2-methyl-2,4-pentanediol, 1,3-butanediol, diethylene glycol, triethylene glycol, glycol bis(hydroxyethyl)ether, and combinations thereof. 
     
     
         14 . The composition according to  claim 1  further comprising a glycerol alkyl ether selected from the group consisting of 1-O-heptylglycerol, 1-O-octylglycerol, 1-O-nonylglycerol, 1-O-decylglycerol, 1-O-undecylglycerol, 1-O-dodecylglycerol, 1-O-tridecylglycerol, 1-O-tetradecylglycerol, 1-O-pentadecylglycerol, 1-O-hexadecylglycerol (chimyl alcohol), 1-O-heptadecylglycerol, 1-O-octadecylglycerol (batyl alcohol), 1-O-octadec-9-enyl glycerol, selachyl alcohol, glycerol 1-(2-ethylhexyl)ether, octoxyglycerin, 2-ethylhexyl glycerin, 3-(2-ethylhexyloxy)propane-1,2-diol, glycerol 1-heptyl ether, glycerol 1-octyl ether, glycerol 1-decyl ether, glycerol 1-dodecyl ether, glycerol 1-tridecyl ether, glycerol 1-tetradecyl ether, glycerol 1-pentadecyl ether, glycerol 1-hexadecyl ether, glycerol 1-octadecyl ether, and combinations thereof. 
     
     
         15 . The composition according to  claim 1  further comprising:
 at least one polymeric biguanide in an amount of at least 0.05 weight %, 
 a chelating agent at a concentration of 0.01 weight % to 1 weight %, and 
 a vicinal diol component, comprising a vicinal diol selected from the group consisting of a monoalkyl glycol, a monoalkyl glycerol, and a combination thereof, at a concentration of 0.05 weight % to 4 weight %, wherein the percentages of polymeric biguanide, chelating agent, and vicinal diol are based on a total weight of the composition. 
 
     
     
         16 . The composition according to  claim 1  further comprising at least medicament is selected from the group consisting of an analgesic agent, an anesthetic agent, a neuropathic pain agent, and mixtures thereof. 
     
     
         17 . The composition according to  claim 16  wherein the at least one medicament is selected from the group consisting of lidocaine, capsaicin, calamine lotion, benzocaine, tetracaine, prilocaine, bupivacaine, levobupivacaine, procaine, carbocaine, etidocaine, mepivacaine, nortripylene, amitriptyline, pregabalin, diclofenac, fentanyl, gabapentin, ketoconazole, opiods, non-steroidal anti-inflammatory agents, salicylates, and mixtures thereof. 
     
     
         18 . The composition according to  claim 1 , wherein the composition is in a form selected from the group consisting of a powder, an aqueous solution, an organic liquid solution, a silicone fluid, a gel, a hydrogel, a cream, a film, a latex, an aerosol, a slurry, a paste, a balm, an ointment, and a foam. 
     
     
         19 . The composition according to  claim 1 , further comprising a dressing wherein said non-proteolytic enzyme component is adsorbed on or in a natural or synthetic fiber, mesh, gauze, cloth, hydrocolloid, alginate, hydrogel, semipermeable film, permeable film, or a natural or synthetic polymer. 
     
     
         20 . The composition according to  claim 1 , further comprising a buffering agent. 
     
     
         21 . The composition according to  claim 1 , wherein said non-proteolytic enzyme component comprises at least 20% by weight of α-amylase and 20% by weight or less of other non-proteolytic, non-amylase enzymes. 
     
     
         22 . The composition according to  claim 1 , wherein said nono-proteolytic enzyme component is present in an amount of at least 0.001% by weight based on a total weight of the composition. 
     
     
         23 . The composition according to  claim 1 , comprising a reverse microemulsion comprising α-amylase solubilized by a hydrophobic reverse emulsion surfactant in a non-stinging, volatile, hydrophobic solvent, wherein said non-stinging, volatile, hydrophobic solvent is selected from the group consisting of volatile linear and cyclic siloxanes, volatile alkanes, volatile fluorocarbons and chlorofluorocarbons, liquid carbon dioxide under pressure, and combinations thereof. 
     
     
         24 . A method of treatment of pruritic tissue comprising
 topically administering a therapeutically effective amount of an enzymatic pruritic composition to itching tissue, wherein said enzymatic pruritic composition comprises a non-proteolytic enzyme component, said non-proteolytic enzyme component comprising at least 80% by weight of an amylase, wherein said non-proteolytic enzyme component comprises at least 10% by weight of α-amylase, based on a weight of the non-proteolytic enzyme component and wherein a ratio of non-proteolytic enzymes to proteolytic enzymes in the enzymatic pruritic composition is at least 4:1.   
     
     
         25 . (canceled) 
     
     
         26 . The method according to  claim 24  of preparing an anti-pruritic composition comprising α-amylase with a pharmaceutically acceptable carrier or emollient. 
     
     
         27 . A kit, comprising:
 an enzymatic pruritic composition comprising a non-proteolytic enzyme component, wherein said non-proteolytic enzyme component comprises at least 80% by weight of amylase, and wherein a ratio of non-proteolytic enzymes to proteolytic enzymes in the enzymatic pruritic composition is at least 4:1; and   instructions for topically applying said enzymatic pruritic composition to itchy tissue.   
     
     
         28 . The composition according to  claim 1 , wherein said proteolytic enzyme component is present in an amount of less than 0.01% by weight based on a total weight of the composition.