Claims for Patent: 10,576,034

Summary for Patent: 10,576,034

Title:	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.
Inventor(s):	Edelson; Jonathan (Scarsdale, NY), Nicolosi; Robert (Nashua, NY)
Assignee:	University of Massachusetts Lowell (Lowell, MA)
Application Number:	15/288,311
Patent Claims:	1. A method of inhibiting release of acetylcholine at a neuromuscular junction in a subject, the method comprising transdermally administering a composition to the skin of the subject, wherein the composition comprises a nanoemulsion characterized in that a majority of its particles have diameters between approximately 10 and approximately 300 nanometers, and wherein said nanoemulsion comprises at least one botulinum toxin, thereby inhibiting the release of acetylcholine at the neuromuscular junction in the subject. 2. The method of claim 1, wherein the nanoemulsion comprises an amount of the at least one botulinum toxin such that the at least one botulinum toxin delivered into the skin partially or completely alleviates, ameliorates, relieves, inhibits, delays onset of, reduces severity of, or reduces incidence of one or more symptoms of a disease, disorder, or condition in the subject. 3. A method of treating a disease, disorder, or condition involving release of acetylcholine at a neuromuscular junction in a subject, the method comprising transdermally administering a composition to the skin of the subject, wherein the composition comprises a nanoemulsion characterized in that a majority of its particles have diameters between approximately 10 and approximately 300 nanometers, and wherein said nanoemulsion comprises at least one botulinum toxin, thereby treating the disease, disorder, or condition involving release of acetylcholine at a neuromuscular junction in the subject. 4. The method of claim 2 or claim 3, wherein the disease, disorder, or condition involves muscular spasm and/or muscular contracture. 5. The method of claim 4, wherein the disease, disorder, or condition is wrinkles, facial lines, neck lines, facial palsy, blepharospasm, facial contracture, dystonia, hemifacial spasm, tremors, spasticity, a condition involving a retroorbital muscle, an opthalmic condition, prostate hyperplasia, hyperhidrosis, constipation, limb spasticity following stroke, or migraines. 6. The method of claim 1, wherein the nanoemulsion is characterized in that its particles have an average particle size of about 10 to about 200 nanometers. 7. The method of claim 1, wherein the nanoemulsion is characterized in that fewer than 40% of its particles have a diameter in excess of 250 nanometers. 8. The method of claim 1, wherein the nanoemulsion comprises oily particles dispersed within an aqueous medium. 9. The method of claim 8, wherein the aqueous 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. 10. The method of claim 1, wherein the nanoemulsion further comprises a surfactant and an oil. 11. The method of claim 10, wherein the oil and surfactant are present in a ratio between 0.5:1 and 2.0:1. 12. The method of claim 10, wherein the percent of oil ranges from 1% to 30% of the nanoemulsion. 13. The method of claim 10, 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 glycocholate; sorbitan monolaurate; polysorbate 20; polysorbate 60; polysorbate 65; polysorbate 80; polysorbate 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-mono stearate; phospholipids; synthetic and/or natural detergents having high surfactant properties; deoxycholates; cyclodextrins; chaotropic salts; ion pairing agents; and combinations thereof. 14. The method of claim 1, wherein the at least one botulinum toxin can penetrate human skin without use of an abrasive or disrupting agent. 15. The method of claim 14, wherein the abrasive or disrupting agent is selected from the group consisting of: chemical permeation enhancers, mechanical permeation enhancers, electrical permeation enhancers and magnetic permeation enhancers. 16. The method of claim 1, 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. 17. The method of claim 16, wherein the botulinum toxin is type A botulinum toxin. 18. The method of claim 1, wherein the botulinum toxin is a botulinum toxin complex. 19. The method of claim 18, wherein the botulinum toxin complex comprises a non-toxin hemagglutinin protein and a non-toxic non-hemagglutinin protein. 20. The method of claim 1, wherein the at least one botulinum toxin is incorporated within an albumin matrix. 21. The method of claim 20, wherein the albumin is human albumin. 22. The method of claim 1, wherein the at least one botulinum toxin is a purified botulinum toxin protein or fragment thereof that retains at least one biological activity. 23. The method of claim 1, wherein the at least one botulinum toxin is isolated, or substantially isolated, from other proteins. 24. The method of claim 1, wherein the at least one botulinum toxin is isolated, or substantially isolated, from non-toxin proteins. 25. The method of claim 1, wherein the at least one botulinum toxin is isolated from Clostridium botulinum. 26. The method of claim 1, wherein the at least one botulinum toxin is chemically synthesized or produced recombinantly. 27. The method of claim 1, wherein the at least one botulinum toxin is: i) encapsulated within the particles; ii) adsorbed on the surface of the particles; and/or iii) associated with the particle interface. 28. The method of claim 1, wherein the nanoemulsion can penetrate the top layer of skin. 29. The method of claim 28, wherein the top layer of the skin is the surface of the stratum corneum, dermal pores, or dermal glands. 30. The method of claim 1, wherein the composition is administered to the skin at a dosage of 1-20,000 units. 31. The method of claim 1, wherein the composition is formulated as a lotion, an ointment, a gel, a cream, a patch, a spray, an oil, a powder, an emollient, a foam, or a combination thereof.

Details for Patent 10,576,034

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	October 21, 1942		2036-10-07
Takeda Pharmaceuticals U.s.a., Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	March 03, 1954		2036-10-07
Central Laboratory Of The Netherlands Red Cross Blood Transfusion Service	N/A	albumin (human)	Injection	101993	September 07, 1979		2036-10-07
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	July 23, 1976		2036-10-07