# US 4,394,372 A · Process for making lipid membrane structures > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,394,372 A - Document ID: US4394372A - Status: Granted - Kind: A - Application number: 06/339,567 - Filed: 1982-01-15 - Granted: 1983-07-19 - Earliest claimed: 1980-12-22 - Assignees: The Procter & Gamble Company - Inventors: James L. Taylor - Web page: https://patentgrep.com/patent/US4394372A ## CPC - B01J 13/125: {by evaporation of the solvent (apparatus therefor B01J13/043)} - B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery - A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) - B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract A process for producing lipid membrane structures (vesicles or liposomes) is disclosed, wherein a solution of bilayer forming compounds in a narrowly-defined two component solvent system is dispersed in an aqueous solution and, subsequently, at least a portion of that solvent system is stripped off. This process permits the readily-reproducible production of lipid membrane structures under gentle processing conditions, ideal for use when they contain pharmaceutically-active materials. ## Claims ### Claim 1 A process for producing vesicles wherein a solution containing lipids, amphiphiles and other membrane materials, capable of forming vesicles, in a solvent system is dispersed in an aqueous solution and, subsequently, at least a portion of that solvent system is stripped off, characterized in that said solvent system comprises at least two organic components, S.sub.1 and S.sub.2, wherein: (a) S.sub.1 is highly soluble in the aqueous solution; (b) S.sub.2 is hydrophobic; (c) S.sub.2 is more volatile than the aqueous solution; (d) the membrane materials are not entirely soluble in S.sub.2 alone; (e) the mixture of S.sub.1 and S.sub.2 forms an interface with the aqueous solution; and (f) the membrane materials may be dissolved in a mixture of S.sub.1 and S.sub.2. ### Claim 2 (depends on 1) A process according to claim 1 wherein the partition coefficient of S.sub.1 in the aqueous solution is greater than about 0.1. ### Claim 3 (depends on 2) A process according to claim 2 wherein the partition coefficient of S.sub.1 in the aqueous solution is greater than about 0.5. ### Claim 4 (depends on 3) A process according to claim 3 wherein the aqueous solution has dissolved in it at least one material to be contained in the vesicles. ### Claim 5 (depends on 4) A process according to claim 4 wherein the dispersion of membrane solution in the aqueous solution undergoes gentle agitation or no agitation. ### Claim 6 (depends on 4) A process according to claim 4 wherein the membrane solution is injected into the aqueous solution. ### Claim 7 (depends on 6) A process according to claim 6 wherein the membrane solution is injected into the aqueous solution through one or more openings having a diameter of about 0.03 to about 200 microns. ### Claim 8 (depends on 7) A process according to claim 7 wherein the injection openings have a diameter of from about 0.03 to about 20 microns. ### Claim 9 (depends on 6) A process according to claim 6 wherein the solvent system comprises from about 5% to about 50% by weight of S.sub.1. ### Claim 10 (depends on 9) A process according to claim 9 wherein the solvent system comprises from about 50% to about 95% by weight of S.sub.2. ### Claim 11 (depends on 10) A process according to claim 10 wherein the partition coefficient of S.sub.1 in the aqueous solution is greater than about 10. ### Claim 12 (depends on 11) A process according to claim 11 wherein at least one pharmaceutically-active agent is dissolved in the aqueous solution. ### Claim 13 (depends on 12) A process according to claim 12 wherein the pharmaceutically-active agent is selected from the group consisting of insulin, interferon, or mixtures thereof. ### Claim 14 (depends on 7) A process according to claim 7 wherein the membrane material is selected from the group consisting of distearoyl lecithin, dipalmitoyl lecithin or mixtures thereof. ### Claim 15 (depends on 7) A process according to claim 7 wherein the membrane material is a long-chain di-alkyl dimethyl ammonium compound. ### Claim 16 (depends on 14) A process according to claim 14 wherein S.sub.1 is selected from the group consisting of methanol, ethanol, propanol, isopropanol, and mixtures thereof. ### Claim 17 (depends on 15) A process according to claim 15 wherein S.sub.2 is selected from the group consisting of hexane, cyclohexane, 2,2-dimethylbutane, pentane, isopentane, 1,1,2-trichlorotrifluoroethane, and mixtures thereof. ### Claim 18 (depends on 7) A process according to claim 7 wherein after the membrane solution is dispersed in the aqueous solution, the temperature of the dispersion is raised, in a controlled manner, so as to remove substantially all of S.sub.2.