Process for preparing microparticles through phase inversion phenomena

Abstract

A process for preparing nanoparticles and microparticles is provided. The process involves forming a mixture of a polymer and a solvent, wherein the solvent is present in a continuous phase and introducing the mixture into an effective amount of a nonsolvent to cause the spontaneous formation of microparticles.

1 - 40 . (canceled) 
     
     
         41 . A microencapsulated product prepared by a method comprising:
 dissolving a polymer in an effective amount of a solvent,   dissolving or dispersing an agent in said effective amount of said solvent, wherein said polymer, said agent and said solvent form a mixture having a continuous phase and wherein the solvent is said continuous phase, and   introducing said mixture into an effective amount of a nonsolvent to cause the spontaneous formation of a microencapsulated product, wherein said solvent and said nonsolvent are miscible and the difference in solubility parameter of solvent/nonsolvent pairs or the solubility parameter of the nonsolvent/solvent pairs is less than 6.   
     
     
         42 . A microencapsulated product prepared by a method comprising:
 dissolving a polymer in an effective amount of a solvent,   dissolving or dispersing an agent in said effective amount of said solvent, wherein said polymer, said agent and said solvent form a mixture having a continuous phase and wherein the solvent is said continuous phase, and   introducing said mixture into an effective amount of a nonsolvent to cause the spontaneous formation of a microencapsulated product, wherein said step of introducing does not include emulsification, agitation, and/or stirring, wherein said solvent and said nonsolvent are a hydrophilic solvent/nonsolvent pair, wherein the nonsolvent and solvent are used in effective amounts, wherein the effective amount of nonsolvent is at least tenfold greater than the amount of solvent.   
     
     
         43 . The microencapsulated product of  claim 41 , wherein the agent is dispersed as solid microparticles in the solvent. 
     
     
         44 . The microencapsulated product of  claim 41 , wherein the agent is contained in microdroplets dispersed in the solvent. 
     
     
         45 . The microencapsulated product of  claim 41 , wherein the agent is a liquid. 
     
     
         46 . The microencapsulated product of  claim 41 , wherein the agent is selected from the group consisting of: adhesives, gases, pesticides, herbicides, fragrances, antifoulants, dies, salts, oils, inks, cosmetics, catalysts, detergents, curing agents, flavors, foods, fuels, metals, paints, photographic agents, biocides, pigments, plasticizers, propellants. 
     
     
         47 . The microencapsulated product of  claim 41 , wherein the agent is a bioactive agent. 
     
     
         48 . The microencapsulated product of  claim 47 , wherein the bioactive agent is selected from the group consisting of: adrenergic agent, adrenocortical steroid, adrenocortical suppressant, aldosterone antagonist, amino acid, anabolic, analeptic, analgesic, anesthetic, anorectic, anti-acne agent, anti-adrenergic, anti-allergic, anti-amebic, anti-anemic, anti-anginal, anti-arthritic, anti-asthmatic, anti-atherosclerotic, antibacterial, anticholinergic, anticoagulant, anticonvulsant, antidepressant, antidiabetic, antidiarrheal, antidiuretic, anti-emetic, anti-epileptic, antifibrinolytic, antifungal, antihemorrhagic, antihistamine, antihyperlipidemia, antihypertensive, antihypotensive, anti-infective, anti-inflammatory, antimicrobial, antimigraine, antimitotic, antimycotic, antinauseant, antineoplastic, antineutropenic, antiparasitic, antiproliferative, antipsychotic, antirheumatic, antiseborrheic, antisecretory, antispasmodic, antithrombotic, anti-ulcerative, antiviral, appetite suppressant, blood glucose regulator, bone resorption inhibitor, bronchodilator, cardiovascular agent, cholinergic, depressant, diagnostic aid, diuretic, dopaminergic agent, estrogen receptor agonist, fibrinolytic, fluorescent agent, free oxygen radical scavenger, gastrointestinal motility effector, glucocorticoid, hair growth stimulant, hemostatic, histamine H2 receptor antagonists, hormone, hypocholesterolemic, hypoglycemic, hypolipidemic, hypotensive, imaging agent, immunizing agent, immunomodulator, immunoregulator, immunostimulant, immunosuppressant, keratolytic, LHRH agonist, mood regulator, mucolytic, mydriatic, nasal decongestant, neuromuscular blocking agent, neuroprotective, NMDA antagonist; non-hormonal sterol derivative, plasminogen activator, platelet activating factor antagonist, platelet aggregation inhibitor, psychotropic, radioactive agent, scabicide, sclerosing agent, sedative, sedative-hypnotic, selective adenosine A1 antagonist, serotonin antagonist, serotonin inhibitor, serotonin receptor antagonist, steroid, thyroid hormone, thyroid inhibitor, thyromimetic, tranquilizer, amyotrophic lateral sclerosis agent, cerebral ischemia agent, Paget's disease agent, unstable angina agent, vasoconstrictor, vasodilator, wound healing agent, xanthine oxidase inhibitor. 
     
     
         49 . The microencapsulated product of  claim 41 , wherein the agent is insulin. 
     
     
         50 . The microencapsulated product of  claim 41 , wherein the agent is an immunological agent. 
     
     
         51 . The microencapsulated product of  claim 50 , wherein the immunological agent is an allergen or an antigen selected from the group consisting of whole inactivated organisms, peptides, proteins, glycoproteins, carbohydrates, or combinations thereof. 
     
     
         52 . The microencapsulated product of  claim 41 , wherein the polymer is a bioadhesive polymer. 
     
     
         53 . The microencapsulated product of  claim 52 , wherein the bioadhesive polymer is a bioerodible hydrogel. 
     
     
         54 . The microencapsulated product of  claim 53 , wherein the bioerodible hydrogel is selected from the group consisting of: polyhyaluronic acids, casein, gelatin, glutin, polyanhydrides, polyacrylic acid, alginate, chitosan, poly(methyl methacrylates), poly(ethyl methacrylates), poly butylmethacrylate), poly(isobutylmethacrylate), poly(hexlmethacrylate), poly(isodecl methacrylate), poly(lauryl methacrylate), poly(phenyl methacrylate), poly (methyl acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate), and poly(octadecl acrylate). Most preferred is poly(fumaric-co-sebacic)acid. 
     
     
         55 . The microencapsulated product of  claim 41 , wherein the polymer is selected from the group consisting of: polyamides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terepthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polyglycolides, polysiloxanes, polyurethanes and copolymers thereof, alkyl cellulose, hydroxyalkyl celluloses, cellulose ethers, cellulose esters, nitro celluloses, polymers of acrylic and methacrylic esters, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxy-propyl methyl cellulose, hydroxybutyl methyl cellulose, cellulose acetate, cellulose propionate, cellulose acetate butyrate, cellulose acetate phthalate, carboxylethyl cellulose, cellulose triacetate, cellulose sulphate sodium salt, poly (methyl methacrylate), poly(ethylmethacrylate), poly(butylmethacrylate), poly(isobutylmethacrylate), poly(hexlmethacrylate), poly(isodecylmethacrylate), poly(lauryl methacrylate), poly (phenyl methacrylate), poly(methyl acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate), poly(octadecyl acrylate), polyethylene, polypropylene poly(ethylene glycol), poly(ethylene oxide), poly(ethylene terephthalate), poly(vinyl alcohols), poly(vinyl acetate, poly vinyl chloride polystyrene and polyvinylpryrrolidone. 
     
     
         56 . The microencapsulated product of  claim 41 , wherein the polymer is a bioerodible polymer. 
     
     
         57 . The microencapsulated product of  claim 41 , wherein the polymer is a nonbioerodible polymer. 
     
     
         58 . The microencapsulated product of  claim 41 , wherein the microencapsulated product consists of particles having an average particle size of between 10 nanometers and 10 microns. 
     
     
         59 . The microencapsulated product of  claim 41 , wherein the microencapsulated product consists of particles having an average particle size of between 100 nanometers and 5 microns. 
     
     
         60 . The microencapsulated product of  claim 41 , wherein the microencapsulated product consists of particles having an average particle size of between 100 nanometers and 1 micron. 
     
     
         61 . The microencapsulated product of  claim 41 , wherein the solvent:nonsolvent volume ratio is greater than 1:40. 
     
     
         62 . The microencapsulated product of  claim 41 , wherein the solvent:nonsolvent volume ratio is between 1:40 and 1:1,000,000. 
     
     
         63 . The microencapsulated product of  claim 41 , wherein the solvent:nonsolvent volume ratio is between 1:50 and 1:200. 
     
     
         64 . The microencapsulated product of  claim 41 , wherein the concentration of the polymer in the solvent is less than 20% weight per volume. 
     
     
         65 . The microencapsulated product of  claim 41 , wherein the concentration of the polymer in the solvent is less than 10% weight per volume. 
     
     
         66 . The microencapsulated product of  claim 41 , wherein the concentration of the polymer in the solvent is less than 5% weight per volume. 
     
     
         67 . The microencapsulated product of  claim 41 , wherein the mixture has a viscosity less than 6 centipoise. 
     
     
         68 . The microencapsulated product of  claim 41 , wherein the mixture has a viscosity less than 4 centipoise. 
     
     
         69 . The microencapsulated product of  claim 41 , wherein the mixture has a viscosity less than 3 centipoise. 
     
     
         70 . The microencapsulated product of  claim 41 , wherein the mixture has a viscosity less than 2 centipoise. 
     
     
         71 . The microencapsulated product of  claim 41 , wherein the solvent and nonsolvent are hydrophilic pairs. 
     
     
         72 . The microencapsulated product of  claim 41 , wherein the solvent is a halogenated aliphatic hydrocarbon or a mixture of a halogenated aliphatic hydrocarbon and another solvent. 
     
     
         73 . The microencapsulated product of  claim 41 , wherein the solvent is a halogenated aromatic hydrocarbon or a mixture of a halogenated aromatic hydrocarbon and another solvent. 
     
     
         74 . The microencapsulated product of  claim 41 , wherein the solvent is an ether or a mixture of an ether and another solvent. 
     
     
         75 . The microencapsulated product of  claim 41 , wherein the solvent is a cyclic ether or a mixture of a cyclic ether and another solvent. 
     
     
         76 . The microencapsulated product of  claim 41 , wherein the microencapsulated product is separated from the nonsolvent. 
     
     
         77 . The microencapsulated product of  claim 41 , wherein a combination of solvents are used. 
     
     
         78 . The microencapsulated product of  claim 41 , wherein the solvent is methylene chloride and the nonsolvent is ethanol. 
     
     
         79 . The microencapsulated product of  claim 41 , wherein the nonsolvent is a mixture of ethanol and water.