Fluoropolymer-based emulsions for the intravenous delivery of fluorinated volatile anesthetics

A method of administering a fluorinated anesthetic compound to a patient, said method comprising the steps of:

• providing a therapeutic formulation comprising:
• an aqueous solution;
• semi-fluorinated block copolymers having a hydrophilic block and a fluorophilic block, wherein said fluorophilic block is a perfluorinated linear alkyl chain having a length of 6 to 16 carbons, and wherein said hydrophilic block is a poly(ethylene glycol) block having a molecular weight selected over the range of 500 g mol−1 to 5,000 g mol−1;
• a fluorinated anesthetic compound selected from the group consisting of sevoflurane, isoflurane, desflurane, enflurane and methoxyflurane;
• and
• a stabilizing additive comprising a perhalogenated fluorocarbon selected from the group consisting of perfluorooctyl bromide and perfluorodecalin;
• emulsifying said therapeutic formulation, thereby making a therapeutic nanoemulsion comprising a continuous phase and a dispersed phase, wherein said continuous phase comprises said aqueous solution and said dispersed phase comprises said semi-fluorinated block copolymers, said fluorinated anesthetic compound and said stabilizing additive;
• delivering said therapeutic nanoemulsion to said patient;
• and
• wherein said fluorinated anesthetic compound is greater than or equal to 5% by volume of said therapeutic formulation, said perhalogenated fluorocarbon is 1% to 20% by volume of said therapeutic formulation;
• and said semi-fluorinated block copolymers have a concentration selected over the range of 1 mg ml−1 to 45 mg ml−1.

A method of making a therapeutic nanoemulsion containing a fluorinated anesthetic compound, said method comprising the steps of:

• providing a therapeutic formulation comprising:
• an aqueous solution;
• semi-fluorinated block copolymers having a hydrophilic block and a fluorophilic block, wherein said fluorophilic block is a perfluorinated linear alkyl chain having a length of 6 to 16 carbons, and wherein said hydrophilic block is a poly(ethylene glycol) block having a molecular weight selected over the range of 500 g mol−1 to 5,000 g mol−1;
• a fluorinated anesthetic compound selected from the group consisting of sevoflurane, isoflurane, desflurane, enflurane and methoxyflurane;
• and a perhalogenated fluorocarbon stabilizing additive selected from the group consisting of:
• perfluorooctyl bromide and perfluorodecalin;
• emulsifying said therapeutic formulation, thereby making said therapeutic nanoemulsion comprising a continuous phase and a dispersed phase, wherein said continuous phase comprises said aqueous solution and said dispersed phase comprises said semi-fluorinated block copolymers, said fluorinated anesthetic compound and said fluorocarbon stabilizing additive;
• and
• wherein said fluorinated anesthetic compound is greater than or equal to 5% by volume of said therapeutic formulation, said perhalogenated fluorocarbon is 1% to 20% by volume of said therapeutic formulation;
• and said semi-fluorinated block copolymers have a concentration selected over the range of 1 mg ml−1 to 45 mg ml−1.

A method of stabilizing a therapeutic emulsion containing a fluorinated anesthetic compound, said method comprising the steps of:

• providing a therapeutic formulation comprising:
• an aqueous solution;
• semi-fluorinated block copolymers having a hydrophilic block and a fluorophilic block;
• and the fluorinated anesthetic compound, wherein said fluorophilic block is a perfluorinated alkyl chain having a length of 6 to 16 carbons, and wherein said hydrophilic block is a poly(ethylene glycol) block having a molecular weight selected over the range of 500 g mol−1 to 5,000 g mol−1;
• adding a perhalogenated fluorocarbon stabilizing additive selected from the group consisting of perfluorooctyl bromide and perfluorodecalin to said therapeutic formulation;
• emulsifying said therapeutic formulation to generate a nanoemulsion comprising a continuous phase and a dispersed phase, wherein said continuous phase comprises said aqueous solution and said dispersed phase comprises said semi-fluorinated block copolymers, said fluorinated anesthetic compound and said stabilizing additive, thereby stabilizing said therapeutic emulsion;
• and
• wherein said fluorinated anesthetic compound is selected from the group consisting of sevoflurane, isoflurane, desflurane, enflurane and methoxyflurane and is greater than or equal to 5% by volume of said therapeutic formulation, said perhalogenated fluorocarbon is 1% to 20% by volume of said therapeutic formulation;
• and said semi-fluorinated block copolymers have a concentration selected over the range of 1 mg ml−1 to 45 mg ml−1.