Botulinum nanoemulsions

Abstract

The embodiment described herein are related nanoemulsions comprising botulinum toxins. In one embodiment, the nanoemulsions are prepared by high pressure microfluidization and comprise a particle size distribution exclusively between 10 and 300 nm. The nanoemulsions contemplated by the present invention are useful for the cosmetic and medical treatment of muscular contracture states. For example, botulinum toxin may relax facial muscles such that skin wrinkles become smoother and less noticeable. Further, the present invention contemplates a cosmetic formulation that may be self-administered, for example, in the privacy of one's home and without medical supervision.

1 .- 25 . (canceled) 
     
     
         26 . A nanoparticle composition comprising a population of particles,
 wherein the nanoparticle composition is an oil-in-water or water-in-oil nanoemulsion in that oily particles are dispersed within an aqueous dispersion medium or aqueous particles are dispersed within an oily dispersion medium,   wherein a majority of the particles have diameters between approximately 10 and approximately 300 nanometers, and   wherein the nanoparticle composition comprises at least one botulinum toxin, a surfactant, an oil, and an aqueous medium.   
     
     
         27 . The nanoparticle composition of  claim 26 , wherein the aqueous dispersion medium is selected from the group consisting of water, saline solution, phosphate buffered saline, short chain alcohols, 5% dextrose, Ringer's solution, lactated Ringer's injection, lactated Ringer's plus 5% dextrose injection, acylated Ringer's injection, and combinations thereof. 
     
     
         28 . The nanoparticle composition of  claim 26 , wherein the surfactant is selected from the group consisting of phosphoglycerides; phosphatidylcholines; dipalmitoyl phosphatidylcholine (DPPC); dioleoylphosphatidyl ethanolamine (DOPE); dioleyloxypropyltriethylammonium (DOTMA); dioleoylphosphatidylcholine; cholesterol; cholesterol ester; diacylglycerol; diacylglycerolsuccinate; diphosphatidyl glycerol (DPPG); hexanedecanol; fatty alcohols such as polyethylene glycol (PEG); polyoxyethylene-9-lauryl ether; a surface active fatty acid, such as palmitic acid or oleic acid; fatty acids; fatty acid monoglycerides; fatty acid diglycerides; fatty acid amides; sorbitan trioleate glycocholate; sorbitan monolaurate; poly sorbate 20; polysorbate 60; polysorbate 65; polysorbate 80; polysorbate 85; polyoxyethylene monostearate; surfactin; a poloxamer; a sorbitan fatty acid ester such as sorbitan trioleate; lecithin; lysolecithin; phosphatidylserine; phosphatidylinositol, sphingomyelin; phosphatidylethanolamine (cephalin); cardiolipin; phosphatidic acid; cerebrosides; dicetylphosphate; dipalmitoylphosphatidylglycerol; stearylamine; dodecylamine; hexadecyl-amine; acetyl palmitate; glycerol ricinoleate; hexadecyl stearate; isopropyl myristate; tyloxapol; polyethylene glycol) 5000-phosphatidylethanolamine; poly(ethylene glycol) 400-monostearate; phospholipids; synthetic and/or natural detergents having high surfactant properties; deoxycholates; cyclodextrins; chaotropic salts; ion pairing agents; and combinations thereof. 
     
     
         29 . The nanoparticle composition of  claim 26 , wherein the oil and the surfactant are present in a ratio ranging from 0.5-2.0. 
     
     
         30 . The nanoparticle composition of  claim 26 , wherein the oil ranges from 1%-30% in the nanoparticle composition. 
     
     
         31 . The nanoparticle composition of  claim 26 , wherein the at least one botulinum toxin is selected from the group consisting of type A, type B, type C1, type C2, type D, type F, and type G. 
     
     
         32 . The nanoparticle composition of  claim 26 , wherein the at least one botulinum toxin is a botulinum toxin complex. 
     
     
         33 . The nanoparticle composition of  claim 26 , wherein the at least one botulinum toxin is incorporated within an albumin matrix. 
     
     
         34 . The nanoparticle composition of  claim 33 , wherein the albumin is human albumin. 
     
     
         35 . The nanoparticle composition of  claim 26 , wherein the at least one botulinum toxin is a purified botulinum toxin protein or fragment thereof or wherein the botulinum toxin is isolated, or substantially isolated, from other proteins or wherein the botulinum toxin is isolated, or substantially isolated, from non-toxin proteins or wherein the botulinum toxin is isolated from  Clostridium botulinum.    
     
     
         36 . The nanoparticle composition of  claim 26 , wherein the at least one botulinum toxin is chemically synthesized or wherein the botulinum toxin is produced recombinantly. 
     
     
         37 . The nanoparticle composition of  claim 26 , wherein the at least one botulinum toxin is encapsulated within the particles, adsorbed on the surface of the particles or associated with the particle interface. 
     
     
         38 . The nanoparticle composition of  claim 26 , wherein the nanoparticle composition can penetrate the top layer of skin without the use of skin permeation enhancers or abrasives. 
     
     
         39 . A pharmaceutical composition comprising the nanoparticle composition of  claim 26 . 
     
     
         40 . The composition of  claim 39 , wherein the composition is formulated as a cream, a lotion, an ointment, a spray, a powder, an emollient and combinations thereof. 
     
     
         41 . A method of treating conditions or disorders associated with the skin of a subject, comprising transdermally administering a composition comprising the nanoparticle composition of  claim 26  to the skin of the subject such that the conditions or disorders are treated. 
     
     
         42 . The method of  claim 41 , wherein the condition and disorder associated with the skin includes facial palsy, blepharospasm, facial contracture, hemifacial spasm and hyperhidrosis. 
     
     
         43 . A cosmetic method of treating one or more of wrinkles, facial lines, or neck lines, comprising the steps of:
 (a) providing a subject exhibiting symptoms of one or more of wrinkles, facial lines, or neck lines; and   (b) administering the nanoparticle composition of  claim 26  to the skin of the subject such that the symptoms are reduced.   
     
     
         44 . A cosmetic method of delaying the onset of one or more of wrinkles, facial lines, or neck lines, comprising the steps of:
 (a) providing a subject not exhibiting symptoms of one or more of wrinkles, facial lines, or neck lines; and   (b) administering the nanoparticle composition of  claim 26  to the skin of the subject such that the onset of symptoms is delayed.   
     
     
         45 . A method of manufacturing a nanoparticle composition, comprising:
 (a) providing a premix comprising at least one botulinum toxin, a surfactant, an oil, and an aqueous medium; and   (b) subjecting the premix to high shear force or high pressure homogenization for a period of time and under conditions which achieve a nanoparticle composition of  claim 26 .