Materials and methods for treatment of inflammation

Abstract

The subject invention pertains to peptides and salts thereof that are useful as anti-inflammatory agents and to compositions containing such peptides and salts as active ingredients. Specifically exemplified herein are endomorphin-1 peptide (EM-1), analogs and salts thereof, and uses for modulation of calcitonin gene-related peptide (CGRP) production and/or substance P (SP) and for treatment of inflammation, particularly neurogenic inflammation.

1 . A method for treating a subject to reduce inflammation and/or to modulate an immune response, wherein said method comprises administering, to a subject in need of such treatment, an effective amount of an isolated peptide or salt thereof, wherein the peptide has a general formula:
   Tyr-X 1 —X 2 —X 3 ,
   wherein X 1  is Pro, D-Lys or D-Orn;   X 2  is Trp, Phe or N-alkyl-Phe, wherein alkyl contains 1 to about 6 carbon atoms; and   X 3  is Phe, Phe-NH 2 , D-Phe. D-Phe-NH 2  or p-Y-Phe, wherein Y is NO 2 , F, Cl or Br.   
     
     
         2 . The method, according to  claim 1 , wherein the subject is a human. 
     
     
         3 . The method, according to  claim 1 , wherein the peptide is selected from SEQ ID NOs: 1-26. 
     
     
         4 . The method, according to  claim 3 , wherein the peptide is SEQ ID NO: 13. 
     
     
         5 . The method, according to  claim 1 , wherein the salt is selected from the group consisting of acetate salt, aspartate (L) salt, citrate salt, fumarate salt, hippurate salt, hydrochloride salt, lactate salt, malate (L) salt, mucate salt, phosphate salt, sulfate salt, hemi-sulfate salt, tartrate (L) salt, gluconate (D) salt, maleate salt, and succinate salt. 
     
     
         6 . The method, according to  claim 1 , wherein the salt is selected from the group consisting of maleate salt, hydrochloride salt, lactate salt, aspartate salt, acetate salt, and trifluoro acetate salt. 
     
     
         7 . The method, according to  claim 1 , used to reduce inflammation. 
     
     
         8 . The method, according to  claim 7 , used to reduce neurogenic inflammation. 
     
     
         9 . The method, according to  claim 1 , used to reduce calcitonin gene-related peptide (CGRP) production. 
     
     
         10 . The method, according to  claim 1 , used to treat an inflammatory condition selected from the group consisting of osteoarthritis, dermatitis, inflammatory bowel disease, post-operative pain and inflammation, general blunt trauma, bone injury, soft tissue infection, shingles, asthma, fibromyalgia, eczema, rosacea, migraine, psoriasis, intestinal inflammation, rheumatoid arthritis, neurogenic swelling, edema, bruises, burn, sunburn, meningitis, septic shock, and allergy. 
     
     
         11 . The method, according to  claim 1 , used to treat an inflammatory skin condition selected from the group consisting of psoriasis, allergic contact dermatitis, eczema, urticaria, lichen planus, and dermatitis herpetiformis. 
     
     
         12 . The method, according to  claim 1 , comprising administering an anti-inflammatory agent selected from the group consisting of a steroidal compound, hydrocortisone, a non-steroidal anti-inflammatory compound, acetylsalicylic acid (aspirin), ibuprofen, acetaminophen, indomethacin, and any combination thereof, wherein the anti-inflammatory agent is administered before, during, or after the administration of said peptide or salt thereof. 
     
     
         13 . The method, according to  claim 1 , used to reduce substance P (SP) production. 
     
     
         14 . A method for treating a subject having a condition associated with overproduction of calcitonin gene-related peptide, wherein said method comprises administering, to the subject in need of such treatment, an effective amount of an isolated peptide or salt thereof, wherein the peptide has a general formula:
   Tyr-X 1 —X 2 —X 3 ,
   wherein X 1  is Pro, D-Lys or D-Orn;   X 2  is Trp, Phe or N-alkyl-Phe, wherein alkyl contains 1 to about 6 carbon atoms; and   X 3  is Phe, Phe-NH 2 , D-Phe, D-Phe-NH 2  or p-Y-Phe, wherein Y is NO 2 , F, Cl or Br.   
     
     
         15 . The method, according to  claim 14 , wherein the subject is a human. 
     
     
         16 . The method, according to  claim 14 , wherein the peptide is selected from SEQ ID NOs: 1-26. 
     
     
         17 . The method, according to  claim 16 , wherein the peptide is selected from SEQ ID NO: 13. 
     
     
         18 . The method, according to  claim 14 , wherein the salt is selected from the group consisting of acetate salt, aspartate (L) salt, citrate salt, fumarate salt, hippurate salt, hydrochloride salt, lactate salt, malate (L) salt, mucate salt, phosphate salt, sulfate salt, hemi-sulfate salt, tartrate (L) salt, gluconate (D) salt, maleate salt, and succinate salt. 
     
     
         19 . The method, according to  claim 14 , wherein the salt is selected from the group consisting of maleate salt, hydrochloride salt, lactate salt, aspartate salt, acetate salt, and trifluoro acetate salt. 
     
     
         20 . The method, according to  claim 14 , used to treat an inflammatory condition selected from the group consisting of osteoarthritis, dermatitis, inflammatory bowel disease, post-operative pain and inflammation, general blunt trauma, bone injury, soft tissue infection, shingles, asthma, fibromyalgia, eczema, rosacea, migraine, psoriasis, intestinal inflammation, rheumatoid arthritis, neurogenic swelling, edema, bruises, burn, sunburn, meningitis, septic shock, and allergy. 
     
     
         21 . The method, according to  claim 14 , used to treat an inflammatory skin condition selected from the group consisting of psoriasis, allergic contact dermatitis, eczema, urticaria, lichen planus, and dermatitis herpetiformis. 
     
     
         22 . The method, according to  claim 14 , comprising administering an anti-inflammatory agent selected from the group consisting of a steroidal compound, hydrocortisone, a non-steroidal anti-inflammatory compound, acetylsalicylic acid (aspirin), ibuprofen, acetaminophen, indomethacin, and any combination thereof, wherein the anti-inflammatory agent is administered before, during, or after the administration of said peptide or salt thereof. 
     
     
         23 . A composition comprising an isolated peptide or salt thereof, wherein the peptide has a general formula:
   Tyr-X 1 —X 2 —X 3 ,
   wherein X 1  is Pro, D-Lys or D-Orn;   X 2  is Trp, Phe or N-alkyl-Phe, wherein alkyl contains 1 to about 6 carbon atoms; and   X 3  is Phe, Phe-NH 2 , D-Phe, D-Phe-NH 2  or p-Y-Phe, wherein Y is NO 2 , F, Cl or Br and an anti-inflammatory agent.   
     
     
         24 . The composition, according to  claim 23 , wherein the anti-inflammatory agent is selected from the group consisting of a steroidal compound, hydrocortisone, a non-steroidal anti-inflammatory compound, acetylsalicylic acid (aspirin), ibuprofen, acetaminophen, and indomethacin.