Synthetic peptides for use as inhibitors of neurotransmitter secretion and as inducers of cellular relaxation

Abstract

The present invention describes material and methods related to synthetic peptides which block the secretion of neurotransmitters and induce muscle relaxation, and use of said peptides as inhibitors of neurotransmitter secretion and muscle contraction, and as inducers of muscle relaxation.

What is claimed: 
     
         1 . A composition comprising one or more peptides wherein the peptide or peptides consists essentially of an amino acid sequence set out in SEQ ID NO: 1-23. 
     
     
         2 . The composition of  claim 1  wherein the peptides comprise L-enantiomers of the desired amino acids. 
     
     
         3 . The composition of  claim 1  wherein the peptides comprise D-enantiomers of the desired amino acids. 
     
     
         4 . The composition of  claim 1  wherein the peptides comprise a mixture of L or D enantiomers of the desired amino acids. 
     
     
         5 . The composition of any one of  claims 1 - 5  wherein the one or more peptides is a retro-inverso isomer of a peptide set out in SEQ ID NO: 1-23. 
     
     
         6 . The composition of any one of  claims 1 - 6  wherein the one or more peptides is a fusion protein. 
     
     
         7 . The composition of any one of  claims 1 - 6  wherein the one or more peptides are fused to a protein translocation domain. 
     
     
         8 . The composition of  claim 7  wherein the protein translocation domain is taken from the HIV TAT protein. 
     
     
         9 . The composition of  claim 7  wherein the protein translocation domain is an arginine-rich sequence. 
     
     
         10 . The composition of  claim 7  wherein the protein translocation domain is a guanidino-rich sequence. 
     
     
         11 . The composition of any one of  claims 1 - 6  wherein the peptide is fused to a nucleic acid. 
     
     
         12 . The composition of any one of  claims 1 - 6  wherein the peptide is fused to the lipolytic peptide GKH. 
     
     
         13 . The composition of any one of  claims 1 - 6  which is an oil in water emulsion. 
     
     
         14 . The composition of any one of  claims 1 - 6  which is a water in oil immersion. 
     
     
         15 . The composition of any one of  claims 1 - 6  which is formulated for topical use. 
     
     
         16 . The composition of any one of  claims 1 - 6  wherein the total concentration of the one or more peptides is from 0.00001% to 10% (w/w) of the total weight of the composition. 
     
     
         17 . The composition of  claim 16  wherein the total concentration of the one or more peptides is about 0.001 to 1% (w/w). 
     
     
         18 . The composition of any one of  claims 1 - 6  further comprising one or more neurotransmitter inhibitors selected from the group consisting of curare, a-bungarotoxin, gallamine, Pirenzepine AF-DX 116 pF-HHSiD, ipratroprium, scopolamine and atropine. 
     
     
         19 . The composition of any one of  claims 1 - 6  further comprising at least one active agent selected from the group consisting of moisturizers, de-and pro-pigmenting agents, desquamating agents, UV absorbing agents, sunscreen actives, viscosity modifying agents, abrasive agents, pH adjustors, anti-glycation agents, anti-oxidative agents, NO-synthase inhibitors agents, agents stimulating the synthesis of dermal and/or epidermal macromolecules, agents preventing the degradation of dermal and/or epidermal macromolecules, agents stimulating the synthesis of collagen, agents preventing the degradation of collagen, agents stimulating fibroblasts and/or keratinocyte proliferation or for stimulating keratinocyte differentiation, muscle relaxants, dermo relaxants, rejuvenating agents, anti-pollution agents and free-radical scavengers, agents acting on capillary circulation, agents acting on the metabolism of cells, anti-inflammatory agents, anti-perspiring agents, anti-microbial and anti-fungal agents, with adjuvant hydrophilic and lipophilic gel, active, preserving, solvents, fragrances, fillers, pigments, odor absorbers. 
     
     
         20 . A method for improving tissue turgor comprising the step of contacting a cell with an effective amount of the composition of any one of  claims 1 - 6 . 
     
     
         21 . A method for inhibiting muscle contractions comprising the step of contacting a cell with an effective amount of the composition of any one of  claims 1 - 6 . 
     
     
         22 . A method for inhibiting neuretransmitter release comprising contacting a cell secreting neurotransmitters with an effective amount of a composition of any one of  claims 1 - 6 . 
     
     
         23 . The method of  claim 22  wherein the composition comprises a peptide consisting of poly-arginine set out in any one of SEQ ID NOs: 11-22. 
     
     
         24 . The method of  claim 23  wherein the poly-arginine consists of D-amino acids. 
     
     
         25 . The method of  claim 21  or  22  wherein the contacting is performed by a route selected from the group consisting of transdermally, topically, intradermally, and subdermally. 
     
     
         26 . A method for enhancing wound healing comprising the step of administering to a subject in need of wound healing an effective amount of a composition of any one of  claims 1 - 6 . 
     
     
         27 . A method for enhancing muscle repair comprising the step of administering to a subject in need of wound healing an effective amount of a composition of any one of  claims 1 - 6 . 
     
     
         28 . A method for blocking the fibrotic process in a wound comprising the step of administering to a subject in need of wound healing an effective amount of a composition of any one of  claims 1 - 6 . 
     
     
         29 . A method for treating disorders selected from the group consisting of hyperhydrosis, focal dystonia, nondystonic disorders, inflammation, and pain, comprising the step of administering to a subject in need an effective amount of a composition of any one of  claims 1 - 6 . 
     
     
         30 . A purified and isolated polynucleotide encoding the polypeptides set out in any one of  claims 1 - 6 . 
     
     
         31 . A vector comprising the polynucleotide of  claim 30 . 
     
     
         32 . A method for transforming a host cell comprising the step of introducing a vector according to  claim 31  into said host cell. 
     
     
         33 . A host cell transformed by the method of  claim 32 . 
     
     
         34 . A method for improving the appearance of the skin, the method comprising applying topically a cosmetic comprising a composition of any one of  claims 1 - 6  and a cosmetically acceptable vehicle. 
     
     
         35 . The method according to  claim 34 , wherein said skin is aged, photoaged, dry, lined or wrinkled skin. 
     
     
         36 . The method according to  claim 35 , wherein said composition further comprises one or more of estradiol; progesterone; pregnanalone; coenzyme Q10; methylsolanomethane (MSM); copper peptide (copper extract); plankton extract (phytosome); glycolic acid; kojic acid; ascorbyl palmitate; all trans retinol; azaleic acid; salicylic acid; broparoestrol; estrone; adrostenedione; and androstanediols. 
     
     
         37 . The method according to  claim 34 , wherein said composition further comprises a sunblock. 
     
     
         38 . The method according to  claim 34 , wherein said cosmetically acceptable vehicle is an oil in water, or water in oil, emulsion. 
     
     
         39 . The method of  claim 34 , wherein said composition is selected from the group consisting of an emulsion, lotion, spray, aerosol, powder, ointment, cream and foam.