Prevention of rosacea inflammation
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. A method of treating rosacea comprising contacting a subject having rosacea with a composition comprising a mast cell stabilizer, a serine protease inhibitor, and an agent that inhibits a neuropeptide selected from the group consisting of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), neurokinin A (NKA), pituitary adenylate cyclase-activating peptide (PACAP), and any combination thereof, wherein the mast cell stabilizer is selected from the group consisting of lodoxamide, nedocromil, cromolyn, pemirolast, pharmaceutical salts thereof, and any combination thereof, wherein the serine protease inhibitor is selected from the group consisting of Cystatin, aprotinin, 4-(2-aminoethyl)-benzenesulfonylfluoride, aminocaproic acid, 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, and any combination thereof, and wherein the composition reduces the production of a peptide comprising amino acid 134 to amino acid 170 of SEQ ID NO:2 in the subject.
2. The method of claim 1 , wherein the composition reduces the production of one or more proteases selected from the group consisting of chymase, tryptase, MMP-1, and MMP-9 in the subject.
3. The method of claim 1 , wherein the serine protease inhibitor comprises Cystatin, aprotinin, 4-(2-aminoethyl)-benzenesulfonylfluoride, aminocaproic acid and any combination thereof.
4. The method of claim 1 , wherein the serine protease inhibitor inhibits kallikrein SCTE.
5. The method of claim 1 , further comprising contacting the subject with a vitamin D receptor inhibitor.
6. The method of claim 1 , wherein the contacting is by topical application.
7. The method of claim 5 , wherein the vitamin D receptor inhibitor comprises 6-fluoro-vitamin D3 (6-F-D3).
8. The method of claim 1 , wherein the composition is formulated for topical administration.
9. The method of claim 8 , wherein the composition comprises a sugar, polysaccharide, sugar alcohol or an oil.
10. The method of claim 9 , wherein the 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.
11. The method of claim 8 , wherein the composition is formulated in petrolatum, sorbitol, and/or propylene glycol.
12. The method of claim 1 , wherein the composition comprises a skin lightening agent, a sunscreen agent, a skin conditioning agent, a skin protectant, an emollient, a humectant, or any combination thereof.
13. The method of claim 1 , wherein the composition further comprises a matrix metalloproteinase inhibitor.