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 nanoemulsion comprising a population of particles, wherein more than 50% of particles have diameters between approximately 10 and approximately 300 nanometers, wherein the nanoemulsion comprises oily particles dispersed within an aqueous dispersion medium, and wherein said nanoemulsion comprises at least one botulinum toxin, a surfactant and an oil. 
     
     
         27 . The nanoemulsion 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, Normosol-M, Isolyte E, and combinations thereof. 
     
     
         28 . The nanoemulsion of  claim 26 , wherein the surfactant is selected from the group consisting of phosphoglycerides; phosphatidylcholines; dipalmitoyl phosphatidylcholine (DPPC); dioleylphosphatidyl 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 (Span 85) glycocholate; sorbitan monolaurate (Span 20); polysorbate 20 (Tween-20); polysorbate 60 (Tween-60); polysorbate 65 (Tween-65); polysorbate 80 (Tween-80); polysorbate 85 (Tween-85); polyoxyethylene monostearate; surfactin; a poloxomer; 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 sterate; isopropyl myristate; tyloxapol; poly(ethylene 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 nanoemulsion of  claim 26 , wherein the oil and surfactant are present in a ratio ranging from 0.5-2.0. 
     
     
         30 . The nanoemulsion of  claim 26 , wherein the percent of oil in the nanoemulsion ranges from 1%-30%. 
     
     
         31 . The nanoemulsion of  claim 26 , wherein the botulinum toxin is selected from the group comprising type A, type B, type C1, type C2, type D, type F, and type G. 
     
     
         32 . The nanoemulsion of  claim 26 , wherein the botulinum toxin is a botulinum toxin complex. 
     
     
         33 . The nanoemulsion of  claim 26 , wherein the botulinum toxin is incorporated within an albumin matrix. 
     
     
         34 . The nanoemulsion of  claim 33 , wherein the albumin is human albumin. 
     
     
         35 . The nanoemulsion of  claim 26 , wherein the 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 nanoemulsion of  claim 26 , wherein the botulinum toxin is chemically synthesized or wherein the botulinum toxin is produced recombinantly. 
     
     
         37 . The nanoemulsion of  claim 26 , wherein the botulinum toxin is encapsulated within the particles or wherein the botulinum toxin is adsorbed on the surface of the particles or wherein the botulinum toxin is associated with the particle interface. 
     
     
         38 . The nanoemulsion of  claim 26 , wherein the nanoemulsion can penetrate the top layer of skin without the use of skin permeation enhancers or abrasives. 
     
     
         39 . The nanoemulsion of  claim 38 , wherein the top layer of the skin is the surface of the stratum corneum or wherein the top layer of the skin includes dermal pores or wherein the top layer of the skin includes dermal glands. 
     
     
         40 . A pharmaceutical composition comprising the nanoemulsion of  claim 26 . 
     
     
         41 . The composition of  claim 40 , wherein the composition is formulated as a cream, a lotion, an ointment, a spray, a powder, an emollient and combinations thereof. 
     
     
         42 . A method of treating conditions or disorders associated with the skin of a subject, comprising transdermally administering a composition comprising the nanoemulsion of  claim 26  to the skin of the subject such that the conditions or disorders are treated. 
     
     
         43 . The method of  claim 42 , wherein the condition and disorder associated with the skin includes facial palsy, blepharospasm, facial contracture, hemifacial spasm and hyperhidrosis. 
     
     
         44 . A cosmetic method of treating wrinkles, facial lines, and/or neck lines, comprising the steps of:
 (a) providing a subject exhibiting symptoms of wrinkles, facial lines and/or neck lines; and   (b) administering a composition comprising the nanoemulsion of  claim 26  to the skin of the subject such that the symptoms are reduced.   
     
     
         45 . A cosmetic method of delaying the onset of wrinkles, facial lines, and/or neck lines, comprising the steps of:
 (a) providing a subject not exhibiting symptoms of wrinkles, facial lines and/or neck lines; and   (b) administering a composition comprising the nanoemulsion of  claim 26  to the skin of the subject such that the onset of symptoms is delayed.