Prevention of rosacea inflammation

Abstract

The disclosure demonstrates the role of mast cell stabilizers in treating rosacea. The disclosure also shows the role of mast cells, cathelicidin, serine protease and/or vitamin D3 in rosacea pathology and the use of antagonists and inhibitors thereof to treat rosacea.

1 - 20 . (canceled) 
     
     
         21 . A topical composition comprising one or more topically acceptable excipients and a serine protease inhibitor, a cathelicidin inhibitor, a kallikrein inhibitor, a matrix metalloproteinase I inhibitor or any combination thereof, wherein said serine protease inhibitor, cathelicidin inhibitor, kallikrein inhibitor, matrix metalloproteinase I inhibitor or any combination thereof comprises a peptide, a peptide incorporating a non-natural amino acid, an antibody, a peptidomimetic, a polymer, an amino acid, or an amino acid analog. 
     
     
         22 . The topical composition of  claim 21 , wherein said serine protease inhibitor, cathelicidin inhibitor, kallikrein inhibitor, matrix metalloproteinase I inhibitor or any combination thereof comprises one or more of: Cystatin, aprotinin, 4-(2-aminoethyl)-benzenesulfonylfluoride, aminocaproic acid, MMP-Specific Inhibitor I, BPTI (bovine pancreatic trypsin inhibitor, aprotinin) and variants thereof, kunitz-type protease inhibitor, amyloid beta protein precursor, TFPI (Tissue Factor Pathway Inhibitor), collagen alpha 3, collagen alpha 3 (VI) chain precursor, HKIB9 (Human Kunitz-type Inhibitor type 9), ITI-KD1 (Inter-Trypsin Inhibitor, Kunitz Domain 1), ITI-KD2 (Inter-Trypsin Inhibitor, Kunitz Domain 2), chelonianin, Beta-1-Bungarotoxin B chain, snake venom protease inhibitors, gamma amino butyric acid (GABA), hydroxyproline (Hyp), aminoadipic acid (Aad), o-aminobutyric acid (Aab or Abu), selenocysteine (SeCys2), tert-butylglycine (Bug or tert-BuGly), N-carbamyl amino acids, amino acid methyl esters, amino-propionic acid (or β-alanine; 13-Ala), adamentylglycine (Adg), N-ethylasparagine (Et-Asn), allo-hydroxylysine (aHyl), allo-isoleucine (alle), phenylglycine (Phg), pyridylalanine (Pal), thienylalanine (Thi), α-Δ-aminobutyric acid (Kbu), α-β-diaminopropionic acid (Kpr), 1- or 2-naptithylalanine (1Nal or 2Nal), orthofluorophenylalanine (Phe(o-F)), N-methylglycine (MeGly), N-methyl-isoleucine (Melle), N-methyl-valine (MeVal), 2-amino-heptanoic acid (Ahe), 2- or 3-amino-isobutyric acid (Aib), 2-amino-pimellic acid (Dbu), 2-2′-diaminopimellic acid (Dpm), 2,3-diaminopropionic acid (Dpr), N-ethylglycine (EtGly), phenylglycine (Ph-Gly), cyclohexylalanine (Cha), cyclohexylglycine (Chg), or 4-amino phenylalanine (Phe(4-NH 2 ) or Aph) or any combination thereof. 
     
     
         23 . The topical composition of  claim 21 , further comprising a sugar, polysaccharide, sugar alcohol or an oil. 
     
     
         24 . The topical composition of  claim 23 , wherein said sugar, polysaccharide, sugar alcohol, or oil comprises one or more of lactose, 1,2-propylene glycol, a polygycol, a fatty alcohol, dextrose, glucose, glycogen, a glycolipid, glycerin, tocopheryl glucoside, inositol, lactitol, maltitol, maltose, mannitol, mannose, methoxy polyethylene glycol, polyglyceryl sorbitol, sorbitol, sucrose, vegetable oil, ethyl oleate, jojoba oil, avocado oil, sunflower seed oil, lanosterol, linoleic acid, linolenic acid, a phytosterol, a placental lipid,  vitis vinifera  seed oil, a sphingolipid, stearamidopropylbetaine, stearyl palmitate, tocopherol, tocopheryl acetate, tocopheryl linoleate, mineral oil, petrolatum, acetylated lanolin, apricot kernel oil, butoxyethyl stearate, ethylhexyl myristate, glyceryl isostearates, glyceryl oleate, hexyldecyl stearate, hexyl isostearate, hydrogenated palm glycerides, hydrogenated soy glycerides, hydrogenated tallow glycerides, isostearyl neopentanoate, isostearyl palmitate, isotridecyl isononanoate, laureth-2 acetate, lauryl polyglyceryl-6 cetearyl glycol ether, methyl gluceth-20 benzoate, mineral oil, myreth-3 palmitate, octyldecanol, octyldodecanol,  odontella aurita  oil, 2-oleamido-1,3 octadecanediol, polyethylene glycol castor oil, palm oil, coconut oil, beeswax, corn oil, sodium caproyl lactylate, sodium caprylate, sodium cocoate, sodium isostearate, sodium tocopheryl phosphate, steareths, ceramides, ceteareth-7, cetyl alcohol, glyceryl isostearate, propylene glycol, silicon oil, or trideceths or any combination thereof. 
     
     
         25 . A method of reducing skin inflammation of a subject comprising:
 (a) identifying a subject in need of a reduction in skin inflammation; and   (b) topically administering to said subject the topical composition of  claim 21 .   
     
     
         26 . The method of  claim 25 , wherein said serine protease inhibitor, cathelicidin inhibitor, kallikrein inhibitor, matrix metalloproteinase I inhibitor or any combination thereof comprises one or more of a peptide, a peptide incorporating a non-natural amino acid, an antibody, a peptidomimetic, a polymer, an amino acid, or an amino acid analog. 
     
     
         27 . The method of  claim 25 , wherein said subject in need of a reduction in skin inflammation has Rosacea, atopic dermatitis, acne, or Netherton syndrome, or any combination thereof. 
     
     
         28 . The method of  claim 25 , wherein said serine protease inhibitor, cathelicidin inhibitor, kallikrein inhibitor, matrix metalloproteinase I inhibitor or any combination thereof comprises: Cystatin, aprotinin, 4-(2-aminoethyl)-benzenesulfonylfluoride, aminocaproic acid, MMP-Specific Inhibitor I, BPTI (bovine pancreatic trypsin inhibitor, aprotinin) and variants thereof, kunitz-type protease inhibitor, amyloid beta protein precursor, TFPI (Tissue Factor Pathway Inhibitor), collagen alpha 3, collagen alpha 3 (VI) chain precursor, HKIB9 (Human Kunitz-type Inhibitor type 9), ITI-KD1 (Inter-Trypsin Inhibitor, Kunitz Domain 1), ITI-KD2 (Inter-Trypsin Inhibitor, Kunitz Domain 2), chelonianin, Beta-1-Bungarotoxin B chain, snake venom protease inhibitors, gamma amino butyric acid (GABA), hydroxyproline (Hyp), aminoadipic acid (Aad), o-aminobutyric acid (Aab or Abu), selenocysteine (SeCys2), tert-butylglycine (Bug or tert-BuGly), N-carbamyl amino acids, amino acid methyl esters, amino-propionic acid (or β-alanine, 13-Ala), adamentylglycine (Adg), N-ethylasparagine (Et-Asn), allo-hydroxylysine (aHyl), allo-isoleucine (alle), phenylglycine (Phg), pyridylalanine (Pal), thienylalanine (Thi), α-Δ-aminobutyric acid (Kbu), α-β-diaminopropionic acid (Kpr), 1- or 2-naptithylalanine (1 Nal or 2Nal), orthofluorophenylalanine (Phe(o-F)), N-methylglycine (MeGly), N-methyl-isoleucine (Melle), N-methyl-valine (MeVal), 2-amino-heptanoic acid (Ahe), 2- or 3-amino-isobutyric acid (Aib), 2-amino-pimellic acid (Dbu), 2-2′-diaminopimellic acid (Dpm), 2,3-diaminopropionic acid (Dpr), N-ethylglycine (EtGly), phenylglycine (Ph-Gly), cyclohexylalanine (Cha), cyclohexylglycine (Chg), or 4-amino phenylalanine (Phe(4-NH 2 ) or Aph) or any combination thereof. 
     
     
         29 . The method of  claim 25 , wherein said topical composition further comprises a sugar, polysaccharide, sugar alcohol or an oil. 
     
     
         30 . The method of  claim 29 , wherein said sugar, polysaccharide, sugar alcohol, or oil comprises one or more of lactose, 1,2-propylene glycol, a polygycol, a fatty alcohol, dextrose, glucose, glycogen, a glycolipid, glycerin, tocopheryl glucoside, inositol, lactitol, maltitol, maltose, mannitol, mannose, methoxy polyethylene glycol, polyglyceryl sorbitol, sorbitol, sucrose, vegetable oil, ethyl oleate, jojoba oil, avocado oil, sunflower seed oil, lanosterol, linoleic acid, linolenic acid, a phytosterol, a placental lipid,  vitis vinifera  seed oil, a sphingolipid, stearamidopropylbetaine, stearyl palmitate, tocopherol, tocopheryl acetate, tocopheryl linoleate, mineral oil, petrolatum, acetylated lanolin, apricot kernel oil, butoxyethyl stearate, ethylhexyl myristate, glyceryl isostearates, glyceryl oleate, hexyldecyl stearate, hexyl isostearate, hydrogenated palm glycerides, hydrogenated soy glycerides, hydrogenated tallow glycerides, isostearyl neopentanoate, isostearyl palmitate, isotridecyl isononanoate, laureth-2 acetate, lauryl polyglyceryl-6 cetearyl glycol ether, methyl gluceth-20 benzoate, mineral oil, myreth-3 palmitate, octyldecanol, octyldodecanol,  odontella aurita  oil, 2-oleamido-1,3 octadecanediol, polyethylene glycol castor oil, palm oil, coconut oil, beeswax, corn oil, sodium caproyl lactylate, sodium caprylate, sodium cocoate, sodium isostearate, sodium tocopheryl phosphate, steareths, ceramides, ceteareth-7, cetyl alcohol, glyceryl isostearate, propylene glycol, silicon oil, or trideceths or any combination thereof. 
     
     
         31 . A topical composition comprising one or more topically acceptable excipients and aminocaproic acid. 
     
     
         32 . The topical composition of  claim 31 , further comprising a sugar, polysaccharide, sugar alcohol or an oil. 
     
     
         33 . The topical composition of  claim 32 , wherein said sugar, polysaccharide, sugar alcohol, or oil comprises one or more of lactose, 1,2-propylene glycol, a polygycol, a fatty alcohol, dextrose, glucose, glycogen, a glycolipid, glycerin, tocopheryl glucoside, inositol, lactitol, maltitol, maltose, mannitol, mannose, methoxy polyethylene glycol, polyglyceryl sorbitol, sorbitol, sucrose, vegetable oil, ethyl oleate, jojoba oil, avocado oil, sunflower seed oil, lanosterol, linoleic acid, linolenic acid, a phytosterol, a placental lipid,  vitis vinifera  seed oil, a sphingolipid, stearamidopropylbetaine, stearyl palmitate, tocopherol, tocopheryl acetate, tocopheryl linoleate, mineral oil, petrolatum, acetylated lanolin, apricot kernel oil, butoxyethyl stearate, ethylhexyl myristate, glyceryl isostearates, glyceryl oleate, hexyldecyl stearate, hexyl isostearate, hydrogenated palm glycerides, hydrogenated soy glycerides, hydrogenated tallow glycerides, isostearyl neopentanoate, isostearyl palmitate, isotridecyl isononanoate, laureth-2 acetate, lauryl polyglyceryl-6 cetearyl glycol ether, methyl gluceth-20 benzoate, mineral oil, myreth-3 palmitate, octyldecanol, octyldodecanol,  odontella aurita  oil, 2-oleamido-1,3 octadecanediol, polyethylene glycol castor oil, palm oil, coconut oil, beeswax, corn oil, sodium caproyl lactylate, sodium caprylate, sodium cocoate, sodium isostearate, sodium tocopheryl phosphate, steareths, ceramides, ceteareth-7, cetyl alcohol, glyceryl isostearate, propylene glycol, silicon oil, or trideceths or any combination thereof. 
     
     
         34 . A method of reducing skin inflammation of a subject comprising:
 (a) identifying a subject in need of a reduction in skin inflammation; and   (b) topically administering to said subject in need of a reduction in skin inflammation the topical composition of  claim 32 .   
     
     
         35 . The method of  claim 34 , wherein said topical composition further comprises a sugar, polysaccharide, sugar alcohol or an oil. 
     
     
         36 . The method of  claim 35 , wherein said sugar, polysaccharide, sugar alcohol, or oil comprises one or more of lactose, 1,2-propylene glycol, a polygycol, a fatty alcohol, dextrose, glucose, glycogen, a glycolipid, glycerin, tocopheryl glucoside, inositol, lactitol, maltitol, maltose, mannitol, mannose, methoxy polyethylene glycol, polyglyceryl sorbitol, sorbitol, sucrose, vegetable oil, ethyl oleate, jojoba oil, avocado oil, sunflower seed oil, lanosterol, linoleic acid, linolenic acid, a phytosterol, a placental lipid,  vitis vinifera  seed oil, a sphingolipid, stearamidopropylbetaine, stearyl palmitate, tocopherol, tocopheryl acetate, tocopheryl linoleate, mineral oil, petrolatum, acetylated lanolin, apricot kernel oil, butoxyethyl stearate, ethylhexyl myristate, glyceryl isostearates, glyceryl oleate, hexyldecyl stearate, hexyl isostearate, hydrogenated palm glycerides, hydrogenated soy glycerides, hydrogenated tallow glycerides, isostearyl neopentanoate, isostearyl palmitate, isotridecyl isononanoate, laureth-2 acetate, lauryl polyglyceryl-6 cetearyl glycol ether, methyl gluceth-20 benzoate, mineral oil, myreth-3 palmitate, octyldecanol, octyldodecanol,  odontella aurita  oil, 2-oleamido-1,3 octadecanediol, polyethylene glycol castor oil, palm oil, coconut oil, beeswax, corn oil, sodium caproyl lactylate, sodium caprylate, sodium cocoate, sodium isostearate, sodium tocopheryl phosphate, steareths, ceramides, ceteareth-7, cetyl alcohol, glyceryl isostearate, propylene glycol, silicon oil, or trideceths or any combination thereof. 
     
     
         37 . The topical composition of  claim 31 , wherein said topical composition is formulated in petrolatum, sorbitol, or propylene glycol. 
     
     
         38 . The method of  claim 34 , wherein said topical composition is formulated in petrolatum, sorbitol, or propylene glycol.