# US 11,298,318 B2 · One-step method for production of ultra-small lipid structures > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,298,318 B2 - Document ID: US11298318B2 - Status: Granted - Kind: B2 - Application number: 15/565,833 - Filed: 2016-04-13 - Published: 2018-04-26 - Granted: 2022-04-12 - Earliest claimed: 2015-04-13 - Assignees: Fountain Technologies International, LLC - Applicants: Fountain Technologies International, LLC - Inventors: Michael Fountain - Web page: https://patentgrep.com/patent/US11298318B2 ## CPC - A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)} - A23G 1/36: characterised by the fats used (containing dairy products A23G1/46) - A23J 7/00: Phosphatide compositions for foodstuffs, e.g. lecithin - A23L 2/52: Adding ingredients (adding preservatives A23B70/10) - A23L 27/84: {Flavour masking or reducing agents} - A23L 29/03: {Organic compounds} - A23L 33/10: using additives (addition of substantially indigestible substances A23L33/21) - A23L 33/115: Fatty acids or derivatives thereof; Fats or oils - A23L 33/15: Vitamins - A23L 33/16: Inorganic salts, minerals or trace elements - A61K 8/14: Liposomes; Vesicles - A61K 8/34: Alcohols - A61K 8/498: {having 6-membered rings or their condensed derivatives, e.g. coumarin} - A61K 8/553: {Phospholipids, e.g. lecithin} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 9/1277: Preparation processes; Proliposomes - A61K 31/353: 3,4-Dihydrobenzopyrans, e.g. chroman, catechin - A61K 31/714: Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12 - A61K 33/00: Medicinal preparations containing inorganic active ingredients - A61K 33/06: Aluminium, calcium or magnesium; Compounds thereof {, e.g. clay} - A61K 33/14: Alkali metal chlorides; Alkaline earth metal chlorides - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - A61Q 11/00: Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses - B01J 13/04: by physical processes, e.g. drying, spraying - A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs - A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)} - A61K 2800/262: Transparent; Translucent - A61K 2800/413: Nanosized, i.e. having sizes below 100 nm - 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) - A23G: COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF - A23J: PROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS - A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B) - A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS - B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS - A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION ## Abstract Ultra-small Lipid Structures (USLS) with an average mean particle diameter of less than 100 nm are made using a single step process by diluting a hydro-organic solution containing lipids and passenger compounds. These particles are capable of sequestering the passenger molecules and self-assemble in a single process step into USLS. The USLS have applications in, for example, agricultural, cosmetics, pharmaceutical and food and beverage industries. ## Claims ### Claim 1 A method for preparing at least one ultra-small lipid structure (USLS) comprising the step of diluting a solution, in a single dilution process step, with water at a dilution ratio of about 1:5 to about 1:200, wherein the solution comprises: (a) a hydro-organic solvent mixture containing about 0.1% to about 20% (v/v) water and about 80% to about 99.9% (v/v) of one or more water-miscible organic solvents; (b) about 50 mg/ml to about 250 mg/ml of one or more lipid compounds, wherein prior to diluting the solution, none of the one or more lipid compounds in the solution have a closed lipid structure; and (c) one or more passenger compounds, wherein the at least one ultra-small lipid structure has a closed lipid structure comprising at least one of the one or more passenger compounds sequestered therein as formed during the single dilution process step, and wherein the term “ultra-small lipid structures (USLS)” refers to lipid vesicles having a bilayer or non-bilayer lipid surrounding structure and an aqueous or semi-aqueous core, and having an average diameter of 100 nm or less as measured using a dynamic light scattering (DLS) analyzer, wherein the USLS product obtained contains a population of from 1% to 2% particles having diameter of from 1 nm to 5 nm as measured using a dynamic light scattering (DLS) analyzer. ### Claim 2 (depends on 1) The method of claim 1, wherein the solution further comprises one or more sugars. ### Claim 3 (depends on 1) The method of claim 1, further comprising dehydrating the at least one ultra-small lipid structure. ### Claim 4 (depends on 3) The method of claim 3, further comprising rehydrating the at least one ultra-small lipid structure. ### Claim 5 (depends on 1) The method of claim 1, wherein the hydro-organic solvent mixture contains about 10% (v/v) water. ### Claim 6 (depends on 1) The method of claim 1, wherein at least one of the one or more water-miscible organic solvents is selected from the group consisting of ethanol, propanol, butanol, isopropanol, chloroform, methanol, methylene chloride, and propyl glycol. ### Claim 7 (depends on 6) The method of claim 6, wherein the at least one of the one or more water-miscible organic solvents is ethanol. ### Claim 8 (depends on 1) The method of claim 1, wherein the comprises about 20 mg/ml lipid compound. ### Claim 9 (depends on 1) The method of claim 1, wherein at least one of the one or more lipid compounds is derived from a plant source. ### Claim 10 (depends on 1) The method of claim 1, wherein at least one of the one or more lipid compounds comprises a soy phospholipid. ### Claim 11 (depends on 1) The method of claim 1, wherein the one or more passenger compounds are hydrophilic, lipophilic, amphipathic or a combination of one or more of hydrophilic, lipophilic, or amphipathic compounds. ### Claim 12 (depends on 1) The method of claim 1, wherein the one or more passenger compounds comprise a medicament. ### Claim 13 (depends on 1) The method of claim 1, wherein the one or more passenger compounds comprise a nutritional substance. ### Claim 14 (depends on 1) The method of claim 1, wherein the one or more passenger compounds comprise a food component. ### Claim 15 (depends on 1) The method of claim 1, wherein the dilution ratio is about 1:10 to about 1:100. ### Claim 16 (depends on 1) The method of claim 1, wherein the method has a rate of sequestration of the passenger compounds of at least 80%. ### Claim 17 (depends on 1) The method of claim 1, wherein the solution is produced by mixing together each component of (a), (b), and (c) added in its entirety. ### Claim 18 (depends on 1) The method of claim 1, wherein the at least one ultra-small lipid structure has an average diameter of 100 nm or less. ### Claim 19 (depends on 1) The method of claim 1, wherein the at least one ultra-small lipid structure is taste-masking. ### Claim 20 (depends on 1) The method of claim 1, wherein the at least one ultra-small lipid structure is shelf stable. ### Claim 21 (depends on 1) The method of claim 1, further comprising including the at least one ultra-small lipid structure in a food product. ### Claim 22 (depends on 21) The method of claim 21, wherein the food product is chocolate. ### Claim 23 (depends on 1) The method of claim 1, further comprising including the-at least one ultra-small lipid structure in a medicinal product. ### Claim 24 (depends on 23) The method of claim 23, wherein the medicinal product alters absorption and biodistribution of the one or more passenger compound compared to products carrying the same passenger compounds, but lacking the at least one ultra-small lipid structure. ### Claim 25 (depends on 23) The method of claim 23, further comprising formulating the medicinal product for oral administration, transmucosal administration, or intranasal administration. ### Claim 26 (depends on 1) The method of claim 1, further comprising including the at least one ultra-small lipid structure in an oral care product. ### Claim 27 (depends on 26) The method of claim 26, further comprising formulating the oral care product as a liquid mouth rinse, a gel, a chewing gum, or a dissolvable strip. ### Claim 28 A method for preparing at least one ultra-small lipid structure (USLS) comprising the step of diluting a solution, during a single step dilution process, with water at a dilution ratio of about 1:5 to about 1:200, wherein the solution comprises: (a) a hydro-organic solvent mixture containing about 0.1% to about 20% (v/v) water and about 80% to about 99.9% (v/v) of one or more water-miscible organic solvents; (b) about 50 mg/ml to about 250 mg/ml of one or more lipid compounds, wherein prior to diluting the solution, none of the one or more lipid compounds in the solution have a closed lipid structure; and (c) one or more passenger compounds, wherein the at least one ultra-small lipid structure has a closed lipid structure comprising at least one of the one or more passenger compounds internally sequestered therein as formed during the single step dilution process, and wherein the term “ultra-small lipid structures (USLS)” refers to lipid vesicles having a bilayer or non-bilayer lipid surrounding structure and an aqueous or semi-aqueous core, and having an average diameter of 100 nm or less as measured using a dynamic light scattering (DLS) analyzer. ### Claim 29 (depends on 1) The method of claim 1, wherein the one or more lipid compounds are mixed phospholipids derived from plant sources containing linolenic acid and linoleic acid as the acyl chains of the phospholipids; wherein the one or more lipid compounds comprise soy phospholipids. ### Claim 30 (depends on 1) The method of claim 1, wherein the one or more passenger compounds are hydrophilic, lipophilic, amphipathic or a combination of one or more of hydrophilic, lipophilic, or amphipathic compounds; or wherein the passenger compounds comprise a medicament; or wherein the passenger compounds comprise a nutritional substance; or wherein the passenger compounds comprise a food component; or wherein the dilution ratio is about 1:10 to about 1:100; or wherein the method has a rate of sequestration of the passenger compounds of at least 80%; or wherein the solution is produced by mixing together each component of (a), (b), and (c) added in its entirety.