US20140271782A1 - Method for preparing nanolipids with encapsulated alcohol - Google Patents
Method for preparing nanolipids with encapsulated alcohol Download PDFInfo
- Publication number
- US20140271782A1 US20140271782A1 US13/840,810 US201313840810A US2014271782A1 US 20140271782 A1 US20140271782 A1 US 20140271782A1 US 201313840810 A US201313840810 A US 201313840810A US 2014271782 A1 US2014271782 A1 US 2014271782A1
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- United States
- Prior art keywords
- ethanol
- solvent
- nanolipidic
- particles
- precursor solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 272
- 238000000034 method Methods 0.000 title claims abstract description 50
- 239000002245 particle Substances 0.000 claims abstract description 92
- 239000000203 mixture Substances 0.000 claims abstract description 42
- 239000000126 substance Substances 0.000 claims abstract description 28
- 235000013361 beverage Nutrition 0.000 claims abstract description 26
- 235000013305 food Nutrition 0.000 claims abstract description 21
- 239000004615 ingredient Substances 0.000 claims abstract description 16
- 235000021185 dessert Nutrition 0.000 claims abstract description 9
- 239000002243 precursor Substances 0.000 claims description 84
- 239000000243 solution Substances 0.000 claims description 70
- 239000002904 solvent Substances 0.000 claims description 56
- 238000010790 dilution Methods 0.000 claims description 24
- 239000012895 dilution Substances 0.000 claims description 24
- 235000013611 frozen food Nutrition 0.000 claims description 24
- 239000003125 aqueous solvent Substances 0.000 claims description 16
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims description 10
- 230000000712 assembly Effects 0.000 claims description 10
- 238000000429 assembly Methods 0.000 claims description 10
- 150000003905 phosphatidylinositols Chemical class 0.000 claims description 10
- 238000007865 diluting Methods 0.000 claims description 9
- 150000003904 phospholipids Chemical class 0.000 claims description 7
- 235000013522 vodka Nutrition 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 6
- 238000013207 serial dilution Methods 0.000 claims description 5
- 235000020094 liqueur Nutrition 0.000 claims description 4
- 229960004756 ethanol Drugs 0.000 claims 78
- 235000019441 ethanol Nutrition 0.000 claims 75
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims 6
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims 6
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 229940127557 pharmaceutical product Drugs 0.000 claims 3
- 235000011850 desserts Nutrition 0.000 abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 18
- 239000003981 vehicle Substances 0.000 description 14
- 230000008014 freezing Effects 0.000 description 12
- 238000007710 freezing Methods 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 11
- 238000005538 encapsulation Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 9
- 235000003363 Cornus mas Nutrition 0.000 description 6
- 240000006766 Cornus mas Species 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 230000003381 solubilizing effect Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 244000099147 Ananas comosus Species 0.000 description 2
- 235000007119 Ananas comosus Nutrition 0.000 description 2
- 235000011034 Rubus glaucus Nutrition 0.000 description 2
- 244000235659 Rubus idaeus Species 0.000 description 2
- 235000009122 Rubus idaeus Nutrition 0.000 description 2
- 235000013334 alcoholic beverage Nutrition 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 235000019219 chocolate Nutrition 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000002356 laser light scattering Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000002324 mouth wash Substances 0.000 description 2
- 229940051866 mouthwash Drugs 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 235000019477 peppermint oil Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 240000004307 Citrus medica Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 244000293323 Cosmos caudatus Species 0.000 description 1
- 235000005956 Cosmos caudatus Nutrition 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 244000290333 Vanilla fragrans Species 0.000 description 1
- 235000009499 Vanilla fragrans Nutrition 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 230000018984 mastication Effects 0.000 description 1
- 238000010077 mastication Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000003880 negative regulation of appetite Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12G—WINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
- C12G3/00—Preparation of other alcoholic beverages
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G9/00—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor
- A23G9/32—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor characterised by the composition containing organic or inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G9/00—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor
- A23G9/44—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor characterised by shape, structure or physical form
- A23G9/48—Composite products, e.g. layered, laminated, coated, filled
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G9/00—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor
- A23G9/44—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor characterised by shape, structure or physical form
- A23G9/48—Composite products, e.g. layered, laminated, coated, filled
- A23G9/485—Composite products, e.g. layered, laminated, coated, filled hollow products, e.g. with inedible or edible filling, fixed or movable within the cavity
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
- A23P10/30—Encapsulation of particles, e.g. foodstuff additives
- A23P10/35—Encapsulation of particles, e.g. foodstuff additives with oils, lipids, monoglycerides or diglycerides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5192—Processes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12G—WINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
- C12G3/00—Preparation of other alcoholic beverages
- C12G3/04—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12G—WINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
- C12G3/00—Preparation of other alcoholic beverages
- C12G3/04—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs
- C12G3/05—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs with health-improving ingredients, e.g. flavonoids, flavones, polyphenols or polysaccharides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- This invention relates to the field of encapsulation of ethanol in nanolipidic particles.
- Frozen foods are very popular with consumers.
- Frozen desserts such as ice creams and sorbets are consumer favorites, and are frequently flavored with liqueurs such as Grand Marnier® and Kahlua®.
- Frozen beverages such as margaritas and pi ⁇ a coladas, are also popular. Attempts to provide such frozen desserts and beverages with an ethanol content comparable to the non-frozen counterparts has been met with limited success due to the substantially lower freezing point of ethanol as compared to water-based products.
- the freezing point of pure water is 0° C. (32° F.).
- the freezing point of pure ethanol is ⁇ 114° C. ( ⁇ 173.2° F.).
- the freezing point of ethanol containing products will fall into the range between these two limits, with the freezing point of an alcohol-containing food product depending upon the percentage of alcohol (ethanol) in the final product.
- Practical and physical limitations prevent the use of commercial freezing mechanisms capable of maintaining high-ethanol content foods at temperatures low enough to stay frozen.
- Most freezing apparatuses have a functional range for freezing a food product, and consumer safety will also dictate a temperature range wherein frozen foods may be safely ingested. Freezing food products with alcohol ranging up to 15% in the final concentration requires freezing at temperatures substantially below the freezing point of water.
- SDMC Solvent Dilution Microcarrier
- U.S. Pat. No. 5,269,979 An amphipathic carrier structure denoted as a Solvent Dilution Microcarrier (“SDMC”) was disclosed in U.S. Pat. No. 5,269,979.
- SDMC Solvent Dilution Microcarrier
- the '979 patent described making a plurality of SDMC vehicles by solubilizing an amphipathic material and a passenger molecule in a first quantity of a non-aqueous solvent. Following this, a first quantity of water was added, forming a turbid suspension. In a subsequent step, a second quantity of non-aqueous solvent was added to form an optically clear solution.
- the final step of a preferred embodiment was to organize the optically clear solution into SDMC vehicles by mixing with air or a second quantity of water.
- SDMCs and the shelf-stable precursor solution provided for making vehicles suitable for delivering active ingredients in a variety of applications, a need remained for improved vehicles for delivery of passenger molecules.
- the shelf-stable precursor solution such as described in the '703 patent can be used as a starting material in a novel method which results in vehicles of a smaller size than previously reported.
- the starting material is manipulated by dilution with a non-aqueous solvent, either before or after loading with a passenger molecule, to provide one or more defined populations of nanolipidic particles (“NLPs”) which range in size from about 1 nanometer to about 20 nanometers.
- NLPs nanolipidic particles
- NLP assemblies are formed from the NLPs which range in size from about 30 nanometers to about 200 nanometers.
- NLPs can be used in a method for making carrier vehicle preparations which are mixed smaller and larger carrier vehicles, or having a larger mean size of about 200-300 nanometers, but improved encapsulation of passenger molecules.
- a method for preparing ethanol-containing food products, frozen desserts and beverages is disclosed using alcohol encapsulated in nanolipid particles and assemblies.
- the method comprises nanolipidic vehicles in which ethanol-containing substances are encapsulated, said ethanol-containing nanolipidic vehicles are combined with dessert or beverage ingredients which can subsequently consumed or incorporated into food products, such as frozen foods, desserts or beverages. These food items can remain in a frozen state during consumption by an individual without losing the characteristics of the alcohol encapsulated in nanolipid particles and assemblies.
- the method of the claimed invention provides for the encapsulation of various ethanol-containing substances in lipid-based vesicles, said vesicles being preferably soy-based, which may be added to ingredients appropriate for consumption in a food product, such as a dessert or beverage, and the combination may then be frozen by established means available in food service to produce an ethanol-containing food product or frozen food product capable of maintaining a frozen state at consumer-safe temperatures for a period of time sufficient for consumption of said product. Additional stabilizing materials do not need be added to the food product to achieve this result.
- NLPs Nanolipidic Particles
- Nanolipidic particles are prepared according to the techniques set forth in United States Patent Application Publication No. 2010/0239686 A1, published Sep. 23, 2010, and United States Patent Application Publication. No. 2012/00195940 A1, published Aug. 2, 2012, which are both herein incorporated by reference. NLPs are prepared from a Shelf-Stable Precursor Stock, prepared according to U.S. Pat. No. 5,879,703 which is also incorporated by reference as if fully set forth herein.
- NLPs are made from a precursor solution as described in U.S. Pat. No. 5,879,703.
- a precursor solution may be made by solubilizing an amphipathic material in a first quantity of a non-aqueous solvent appropriate to solubilize the amphipathic material to form a first mixture.
- the amphipathic material preferably comprises phospholipids (PL).
- Preferred phospholipids comprise one or more of the following phosphatides: phospatidylcholine (PC), phospatidylethanolamine (PE), phosphatidic acid (PA) and phosphatidylinositol (PI).
- PC, PE, PA and PI are combined.
- a preferred ratio of PLs useful in the invention is PC:PE:PA:PI of 6.5:2.5:0.7:0.3 in ethanol.
- one gram of PL is solubilized in 5.0-7.5 mL of ethanol solvent.
- a quantity of water is added to form a turbid suspension.
- the amount of water to add is approximately 9 kg of water to 31 kg of dissolved amphipathic material, but the amount of water can be varied to result in the desired turbid suspension.
- a second quantity of non-aqueous solvent, such as ethanol, is added until the turbid suspension is monophasic and has optical clarity at room temperature. This resulting product is a precursor solution which is shelf-stable over time.
- precursor solution made according to the process disclosed therein was shelf stable at least up to two years, and perhaps longer, as long as it remains in a monophasic condition. It has been recently determined that precursor solutions made by this method are stable for at least eight years, independent of manufacturing, location, season, year and lot.
- a precursor solution such as disclosed in '703 can be used as a starting material to make nanolipidic particles (NLPs) and NLP assemblies.
- the precursor solution was disclosed as being useful for making SDMCs (Solvent Dilution Microcarriers) at a later point in time and, perhaps, a remote location.
- SDMCs have a diameter of from about 230 to about 412 nm.
- NLPs have a mean diameter of from about 1 nm to about 20 nm and NLP assemblies have a mean diameter from about 30 nm to about 200 nm.
- NLP assembly populations may be made for various applications. Preferred populations range from about 40-60 nm; about 60-80 nm; about 80-110 nm; about 110-140 nm; and about 150-200 nm. NLP assembly populations are generally 20-30% smaller in diameter than SDMCs for the same passenger molecule.
- ECVs A slightly larger population or mixed population of carrier vehicles is referred to herein as ECVs or encapsulating carrier vehicles.
- ECVs are described as having a mean diameter from about 200 nm to 300 nm.
- the precursor solution as previously described in the '703 patent is diluted with a suitable solvent or mixed solvent system which is compatible with the solvent system used in the precursor solution. This dilution is performed either before or after addition of the passenger molecule as will be further described in detail below.
- the solvent is selected for biocompatibility if the end use of the carriers will require that characteristic.
- the solvent or mixed solvent system used for dilution must be miscible with the solvents in the precursor solution and should be effective to disperse rather than dissolve the carriers.
- the solvent used for dilution is ethanol, since it possesses the desired qualities.
- Ethanol is the solvent of choice for any end use wherein the particles are for ingestion.
- the dilution is preferably conducted in a sequential or serial manner. For example, a first dilution of 1:10 provides a population of carriers, and further serial dilution to about 1:0.5 provides a series of populations of carriers.
- the size of the carriers in each dilution can be determined by laser light scattering. Mixed populations of NLPs and larger vesicles may be created at lower dilutions with the non-aqueous solvent.
- An appropriate instrument for this purpose is the Zetasizer 1000 manufactured by Malvern Instruments, (Worcestershire United Kingdom). Diameters of particles reported herein were determining using the Multimodal Analysis Mode of the Zetasizer 1000 to determine particle size by peak intensities. Other techniques may be used to analyze particle size, which results can be correlated to the numerical values obtained with the light scattering technique described herein.
- Addition of the desired passenger molecule occurs prior to dilution with the solvent if the passenger molecule is lipophilic or amphipathic. Addition occurs after dilution if the passenger molecule is water soluble.
- the NLP loaded populations form upon dilution with the solvent.
- NLP assembly populations or ECVs are formed by dilution of the NLP loaded population into water.
- the precursor solution is mixed with a passenger molecule dissolved in water.
- NLP assembly populations or ECVs are formed upon dilution with the non-aqueous solvent. If a serial dilution technique is used, distinct populations are formed.
- ranges for the finished NLP assembly population can be established for each NLP population used to form the final NLP assembly population. The more non-aqueous solvent that is used to dilute the NLPs, the smaller the NLP assembly populations.
- NLP loaded populations may be mixed and matched to provide a multifunctional NLP assembly product.
- the different NLP loaded populations within the NLP assembly could provide a preparation which allows one active ingredient to be preferentially absorbed over the other, thus allowing a control of the rates of release of different ingredients in a single preparation.
- a single NLP population could be loaded with more than one passenger molecule to provide the multifunctionality.
- an optically clear solution containing NLPs loaded with passenger molecules can be made by selecting conditions where the NLPs are less than about 150 nm in size. It is many times important that a product appear optically clear or it will fail to gain consumer acceptance.
- loaded NLPs in an optically clear solution have application in the beverage industry and the pharmaceutical industry for liquid products.
- a mouthwash can be prepared that contains NLPs which encapsulates an ingredient for time-release in the mouth. A consumer prefers to purchase an optically clear mouthwash rather than a cloudy one.
- passenger molecules suitable for use in forming a NLP loaded population are numerous.
- passenger molecules can be selected which exhibit lipid solubility or are amphipathic. These molecules have solubility profiles ideally suited for loading into NLPS.
- water soluble molecules may be incorporated into NLPs by solubilization into the aqueous solution used to form the finished NLP product. Using these two approaches virtually any molecule may be incorporated as a passenger molecule into NLP products of defined sizes.
- An innovative use of both approaches may be used to incorporate both lipid and water soluble compounds into a NLP assembly product by first incorporating lipid soluble compounds into NLPs prior to dilution with ethanol and second incorporating water soluble molecule(s) into the water solution used to form the finished NLP product of defined size.
- NLPs may also be used in the food and beverage industry.
- NLPs incorporating caffeine may be used in dietary supplements for appetite suppression. Encapsulation in NLPs has been found to be effective to mask the taste of the passenger molecule if it is desired that tasting of such be bypassed upon ingestion.
- NLPs which will be tasted, rather than masked. Flavorings such as peppermint oil and other oils are appropriately incorporated into NLPs.
- the encapsulation of oil-containing substances may lead to increased shelf life in that the encapsulated substance is protected from oxidation.
- the encapsulation of substances would permit additional options for manufacturers and consumers.
- a manufacturer of a beverage could prepare and bottle one base flavor. The consumer would then have the option of adding NLP packets to the beverage to meet the taste preferences of the consumer or to enrich it with vitamins.
- a consumer that prefers a strong peppermint flavoring in a chocolate drink could add NLPs containing peppermint oil to his or her beverage.
- Substances that are meant to be tasted can also be loosely associated with the exterior of the NLP by providing such substances in the aqueous phase of the procedure. For example, an NLP containing a vitamin that preferably should not be tasted can have a pleasant taste on the outside thereof.
- a natural carbohydrate or sugar can be linked to the NLP by merely providing it in the aqueous solution. This will stick to the inside of the mouth for a period of time, and normal mouth chemistry and mastication will release the contents of the NLPs to provide the desired effect.
- the NLPs can also be subjected to agitation and shear such as in a blender or heavy industrial equipment at a manufacturing site to provide flavorings to foods and beverages.
- the passenger molecule should first be dissolved in water.
- the incorporation step, or loading of the passenger molecule into the NLP, is accomplished when the NLP product is formed by adding the dissolved passenger molecule to the precursor solution.
- the nanolipidic particles with encapsulated ethanol of the invention have a softer “mouth feel” than a preparation containing free ethanol.
- the encapsulation process leads to the ethanol being sequestered inside the nanolipid such that the ethanol does not immediately contact the mucosa in the mouth.
- Other passengers molecules which may in the preparation, such as vitamins and pharmaceutical substances, are similarly sequestered within the nanolipidic particles.
- NLPs encapsulating ethanol-containing substances were prepared as follows:
- Solvent-diluted precursor stock was prepared by adding 1 part shelf-stable precursor stock to 0.3 part ethanol to form a solvent-diluted precursor.
- An ethanol-containing substance is dissolved in an aqueous solvent to form an aqueous-ethanol monophase.
- the size of the loaded NLPs may be determined by using the Malvern 1000 Zetasizer Laser Light Scattering Instrument set to analyze populations using multimodal analysis mode.
- the size of the finished preparation was determined to be 20 nm-150 nm.
- Nanolipid particle sizes useful for the preparation of the invention can be increased or decreased by adjusting the ratio of ethanol to Solvent Dilution Microcarrier (SDMC) used in preparation of the precursor stock solution.
- SDMC Solvent Dilution Microcarrier
- Particle sizes can range from approximately 60 nm using 20 parts ethanol: 1 part SDMC up to 170 nm using 0.3 part ethanol: 1 part SDMC.
- Sizes of NLP and NLP assembly populations useful for the method of the invention are 20 nm to 300 nm, preferably 20 nm to 170 nm.
- One or more additional dilutions of the precursor solution may be made with ethanol solvent in order to provide a desired size of NLPs and number of NLPs per unit volume.
- ethanol solvent that is used to dilute the NLPs, the smaller the resulting NLP assembly populations will be.
- nanolipid particles having ethanol encapsulated at a concentration of 5.0%-8.0% is added to base ingredients for gelato. This gelato mixture is then frozen by a commercially acceptable process to produce a frozen gelato for consumption.
- Frozen alcohol-containing gelatos which have been prepared by the claimed method of the invention include the following:
- nanolipidic particles having ethanol encapsulated at a concentration of 5.0% are added to base ingredients for a sorbet or frozen beverage.
- This sorbet or frozen beverage mixture is then frozen by a commercially acceptable process to produce a frozen sorbet, pops, or beverage for consumption. Ice pops and other frozen products of a similar nature can be prepared by the same method.
- Frozen alcohol-containing sorbets, pops, and beverages can be been prepared by the claimed method of the invention include the following:
- Sorbet or Beverage Flavor % Alcohol by volume Pi ⁇ a Colada 5.0% Mojito 5.0% Strawberry Margarita 5.0% Apple Martini 5.0%
- nanolipid particles having ethanol encapsulated at a concentration of up to 15.0% is added to base ingredients for a syrup or topping for a frozen dessert.
- Alcohol-containing syrups and toppings for frozen desserts which have been prepared by the claimed method of the invention include the following:
- NLPs (1:10 Precursor to Ethanol, volume/volume) were prepared and diluted 1:10 (NLP volume/volume) in commercially available alcoholic beverage products and stored for one week at Room Temperature. After one week the mixtures were vortexed, diluted 1:10 (volume/volume) in distilled water, and the size of the NLPs were analyzed using a Zetasizer 1000 (Malvern Instruments). The results of the stability study were as follows:
- Citron ® Vodka 1:10 NLP 150 nm Malibu ® Coconut Rum 1:10 NLP 130 nm Beefeater ® Gin 1:10 NLP 150 nm Stability of NLPs in 100 Proof (50% volume/volume in Distilled Water) Ethanol Mixtures
- NLPs (1:10 and 1:20 Precursor to Ethanol, volume/volume) were prepared and diluted 1:10 in 100 proof mixtures of ethanol and water (50% ethanol, volume/volume). The samples were placed in a commercial freezer for 14 days, removed, allowed to thaw and warm to Room Temperature. Both samples were homogenous and optically clear, without any precipitation. The samples were vortexed and the size of the NLPs were determined using a Zetasizer 1000 (Malvern Instruments). The results of the analyses were:
- NLPs (1:5, 1:10 and 1:20 Precursor to Ethanol volume/volume) were prepared and added 1:10 (volume/volume) into solutions of 25 Proof Ethanol in Distilled Water (12.5% Ethanol in Distilled Water, volume/volume). All mixtures were optically clear.
- the initial size of the NLPs and subsequent size analyses conducted on days 7, 14 and 21 were performed using a Zetasizer 1000 (Malvern Instruments). After the initial size determinations the samples were placed into a commercial freezer for intervals of 7 days. On days 7, 14 and 21 the samples were removed from the freezer allowed to thaw and warm to Room Temperature.
- the NLPs and NLP assembly populations can also be used to formulate a delivery vehicle for pharmaceuticals, such as analgesics, as an admixed passenger with the NLPs with encapsulated ethanol.
- the admixed passenger loaded NLPs can then be mixed with ingredients suitable for making a frozen food product.
- the loaded NLP-frozen food ingredient mixture can be frozen in a form such as an ice pop to provide a delivery vehicle for the encapsulated ingredients.
- a delivery device would be in the treatment of sore throats in individuals.
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Abstract
Description
- Not Applicable
- Not applicable.
- This invention relates to the field of encapsulation of ethanol in nanolipidic particles.
- Frozen foods, particularly frozen desserts and frozen beverages, are very popular with consumers. Frozen desserts, such as ice creams and sorbets are consumer favorites, and are frequently flavored with liqueurs such as Grand Marnier® and Kahlua®. Frozen beverages, such as margaritas and piña coladas, are also popular. Attempts to provide such frozen desserts and beverages with an ethanol content comparable to the non-frozen counterparts has been met with limited success due to the substantially lower freezing point of ethanol as compared to water-based products.
- The freezing point of pure water is 0° C. (32° F.). The freezing point of pure ethanol is −114° C. (−173.2° F.). The freezing point of ethanol containing products will fall into the range between these two limits, with the freezing point of an alcohol-containing food product depending upon the percentage of alcohol (ethanol) in the final product. Practical and physical limitations prevent the use of commercial freezing mechanisms capable of maintaining high-ethanol content foods at temperatures low enough to stay frozen. Most freezing apparatuses have a functional range for freezing a food product, and consumer safety will also dictate a temperature range wherein frozen foods may be safely ingested. Freezing food products with alcohol ranging up to 15% in the final concentration requires freezing at temperatures substantially below the freezing point of water.
- This decreased freezing point has long been understood to a limiting factor in the ability to make products containing ethanol which can remain frozen long enough for an individual to reasonably consume the product while it remains in the frozen state. Various means have been employed to overcome this obstacle, most of which have involved the addition of stabilizing materials, such as gels or agar, to the food product. Even then, there has been limited success.
- Incorporating passenger molecules, such as pharmaceutical active ingredients, in lipid vesicles such as liposomes has been reported in the prior art. An amphipathic carrier structure denoted as a Solvent Dilution Microcarrier (“SDMC”) was disclosed in U.S. Pat. No. 5,269,979. In general, the '979 patent described making a plurality of SDMC vehicles by solubilizing an amphipathic material and a passenger molecule in a first quantity of a non-aqueous solvent. Following this, a first quantity of water was added, forming a turbid suspension. In a subsequent step, a second quantity of non-aqueous solvent was added to form an optically clear solution. The final step of a preferred embodiment was to organize the optically clear solution into SDMC vehicles by mixing with air or a second quantity of water.
- In U.S. Pat. No. 5,879,703, a method for preparing a shelf-stable precursor solution useful for remote encapsulation of active ingredients was described. In '703, the precursor solution was made by solubilizing an amphipathic material in a non-aqueous solvent. A quantity of water was added to the first mixture to form a precursor solution characterized by optical clarity and being monophasic at room temperature. The precursor solution could be stored for an extended period of time—and the desired active ingredient added at a later time, perhaps at a remote location, to form a loaded precursor solution. SDMCs could be formed, in preferred embodiments, from the loaded precursor solution by diluting with water or mixing with air. SDMCs ranged from about 230 to about 412 nanometers in size.
- Although SDMCs and the shelf-stable precursor solution provided for making vehicles suitable for delivering active ingredients in a variety of applications, a need remained for improved vehicles for delivery of passenger molecules.
- It has now been found that the shelf-stable precursor solution such as described in the '703 patent can be used as a starting material in a novel method which results in vehicles of a smaller size than previously reported. The starting material is manipulated by dilution with a non-aqueous solvent, either before or after loading with a passenger molecule, to provide one or more defined populations of nanolipidic particles (“NLPs”) which range in size from about 1 nanometer to about 20 nanometers.
- NLP assemblies are formed from the NLPs which range in size from about 30 nanometers to about 200 nanometers. In addition, it has been found that NLPs can be used in a method for making carrier vehicle preparations which are mixed smaller and larger carrier vehicles, or having a larger mean size of about 200-300 nanometers, but improved encapsulation of passenger molecules.
- A means has now been found by which ethanol can be effectively, efficiently and economically encapsulated in a nanolipid particle for possible consumer consumption, such as encapsulation of ethanol maintained at percentages not previously possible for consumer ingestion.
- A method for preparing ethanol-containing food products, frozen desserts and beverages is disclosed using alcohol encapsulated in nanolipid particles and assemblies. The method comprises nanolipidic vehicles in which ethanol-containing substances are encapsulated, said ethanol-containing nanolipidic vehicles are combined with dessert or beverage ingredients which can subsequently consumed or incorporated into food products, such as frozen foods, desserts or beverages. These food items can remain in a frozen state during consumption by an individual without losing the characteristics of the alcohol encapsulated in nanolipid particles and assemblies.
- The method of the claimed invention provides for the encapsulation of various ethanol-containing substances in lipid-based vesicles, said vesicles being preferably soy-based, which may be added to ingredients appropriate for consumption in a food product, such as a dessert or beverage, and the combination may then be frozen by established means available in food service to produce an ethanol-containing food product or frozen food product capable of maintaining a frozen state at consumer-safe temperatures for a period of time sufficient for consumption of said product. Additional stabilizing materials do not need be added to the food product to achieve this result.
- Nanolipidic particles (NLPs) are prepared according to the techniques set forth in United States Patent Application Publication No. 2010/0239686 A1, published Sep. 23, 2010, and United States Patent Application Publication. No. 2012/00195940 A1, published Aug. 2, 2012, which are both herein incorporated by reference. NLPs are prepared from a Shelf-Stable Precursor Stock, prepared according to U.S. Pat. No. 5,879,703 which is also incorporated by reference as if fully set forth herein.
- NLPs are made from a precursor solution as described in U.S. Pat. No. 5,879,703. As stated in the '703 patent, a precursor solution may be made by solubilizing an amphipathic material in a first quantity of a non-aqueous solvent appropriate to solubilize the amphipathic material to form a first mixture. The amphipathic material preferably comprises phospholipids (PL). Preferred phospholipids comprise one or more of the following phosphatides: phospatidylcholine (PC), phospatidylethanolamine (PE), phosphatidic acid (PA) and phosphatidylinositol (PI). In a preferred embodiment, PC, PE, PA and PI are combined. A preferred ratio of PLs useful in the invention is PC:PE:PA:PI of 6.5:2.5:0.7:0.3 in ethanol. Preferably, one gram of PL is solubilized in 5.0-7.5 mL of ethanol solvent.
- After dissolution of the amphipathic material, a quantity of water is added to form a turbid suspension. The amount of water to add is approximately 9 kg of water to 31 kg of dissolved amphipathic material, but the amount of water can be varied to result in the desired turbid suspension. A second quantity of non-aqueous solvent, such as ethanol, is added until the turbid suspension is monophasic and has optical clarity at room temperature. This resulting product is a precursor solution which is shelf-stable over time.
- In the '703 patent, it was disclosed that a precursor solution made according to the process disclosed therein was shelf stable at least up to two years, and perhaps longer, as long as it remains in a monophasic condition. It has been recently determined that precursor solutions made by this method are stable for at least eight years, independent of manufacturing, location, season, year and lot.
- It has now been found that a precursor solution such as disclosed in '703 can be used as a starting material to make nanolipidic particles (NLPs) and NLP assemblies. In '703, the precursor solution was disclosed as being useful for making SDMCs (Solvent Dilution Microcarriers) at a later point in time and, perhaps, a remote location. SDMCs have a diameter of from about 230 to about 412 nm. In contrast, NLPs have a mean diameter of from about 1 nm to about 20 nm and NLP assemblies have a mean diameter from about 30 nm to about 200 nm.
- Various populations of NLP assemblies may be made for various applications. Preferred populations range from about 40-60 nm; about 60-80 nm; about 80-110 nm; about 110-140 nm; and about 150-200 nm. NLP assembly populations are generally 20-30% smaller in diameter than SDMCs for the same passenger molecule.
- A slightly larger population or mixed population of carrier vehicles is referred to herein as ECVs or encapsulating carrier vehicles. Although overlapping the mean diameter of SDMCs, the ECV is made using a different method employing NLPs and the result is a carrier vehicle population which has been found to exhibit a higher encapsulating efficiency. The ECVs are described as having a mean diameter from about 200 nm to 300 nm.
- To make carriers for passenger molecules, such as NLP populations, NLP assemblies, or ECVs according to the method disclosed in United States Patent Application Publications No. 2010/0239686 and 2012/0195940, the precursor solution as previously described in the '703 patent is diluted with a suitable solvent or mixed solvent system which is compatible with the solvent system used in the precursor solution. This dilution is performed either before or after addition of the passenger molecule as will be further described in detail below.
- The solvent is selected for biocompatibility if the end use of the carriers will require that characteristic. The solvent or mixed solvent system used for dilution must be miscible with the solvents in the precursor solution and should be effective to disperse rather than dissolve the carriers. Most preferably, the solvent used for dilution is ethanol, since it possesses the desired qualities. Ethanol is the solvent of choice for any end use wherein the particles are for ingestion. The dilution is preferably conducted in a sequential or serial manner. For example, a first dilution of 1:10 provides a population of carriers, and further serial dilution to about 1:0.5 provides a series of populations of carriers.
- The size of the carriers in each dilution can be determined by laser light scattering. Mixed populations of NLPs and larger vesicles may be created at lower dilutions with the non-aqueous solvent. An appropriate instrument for this purpose is the Zetasizer 1000 manufactured by Malvern Instruments, (Worcestershire United Kingdom). Diameters of particles reported herein were determining using the Multimodal Analysis Mode of the Zetasizer 1000 to determine particle size by peak intensities. Other techniques may be used to analyze particle size, which results can be correlated to the numerical values obtained with the light scattering technique described herein.
- Addition of the desired passenger molecule occurs prior to dilution with the solvent if the passenger molecule is lipophilic or amphipathic. Addition occurs after dilution if the passenger molecule is water soluble.
- Thus, in the case of a lipophilic or amphipathic passenger molecule, the NLP loaded populations form upon dilution with the solvent. NLP assembly populations or ECVs are formed by dilution of the NLP loaded population into water.
- In the case of a water soluble passenger molecule, the precursor solution is mixed with a passenger molecule dissolved in water. NLP assembly populations or ECVs are formed upon dilution with the non-aqueous solvent. If a serial dilution technique is used, distinct populations are formed.
- Based on curves observed from different classes of compounds, ranges for the finished NLP assembly population can be established for each NLP population used to form the final NLP assembly population. The more non-aqueous solvent that is used to dilute the NLPs, the smaller the NLP assembly populations.
- Various NLP loaded populations may be mixed and matched to provide a multifunctional NLP assembly product. The different NLP loaded populations within the NLP assembly could provide a preparation which allows one active ingredient to be preferentially absorbed over the other, thus allowing a control of the rates of release of different ingredients in a single preparation. Alternatively, a single NLP population could be loaded with more than one passenger molecule to provide the multifunctionality.
- Another advantage to the NLP technology is that an optically clear solution containing NLPs loaded with passenger molecules can be made by selecting conditions where the NLPs are less than about 150 nm in size. It is many times important that a product appear optically clear or it will fail to gain consumer acceptance. For example, loaded NLPs in an optically clear solution have application in the beverage industry and the pharmaceutical industry for liquid products. As one example, a mouthwash can be prepared that contains NLPs which encapsulates an ingredient for time-release in the mouth. A consumer prefers to purchase an optically clear mouthwash rather than a cloudy one.
- The passenger molecules suitable for use in forming a NLP loaded population are numerous. In one embodiment, passenger molecules can be selected which exhibit lipid solubility or are amphipathic. These molecules have solubility profiles ideally suited for loading into NLPS. In another embodiment, water soluble molecules may be incorporated into NLPs by solubilization into the aqueous solution used to form the finished NLP product. Using these two approaches virtually any molecule may be incorporated as a passenger molecule into NLP products of defined sizes. An innovative use of both approaches may be used to incorporate both lipid and water soluble compounds into a NLP assembly product by first incorporating lipid soluble compounds into NLPs prior to dilution with ethanol and second incorporating water soluble molecule(s) into the water solution used to form the finished NLP product of defined size.
- NLPs may also be used in the food and beverage industry. For example, NLPs incorporating caffeine may be used in dietary supplements for appetite suppression. Encapsulation in NLPs has been found to be effective to mask the taste of the passenger molecule if it is desired that tasting of such be bypassed upon ingestion.
- Another application in the food and beverage industry is the incorporation of substances into NLPs which will be tasted, rather than masked. Flavorings such as peppermint oil and other oils are appropriately incorporated into NLPs. The encapsulation of oil-containing substances may lead to increased shelf life in that the encapsulated substance is protected from oxidation. In addition, the encapsulation of substances would permit additional options for manufacturers and consumers.
- As just one example, a manufacturer of a beverage could prepare and bottle one base flavor. The consumer would then have the option of adding NLP packets to the beverage to meet the taste preferences of the consumer or to enrich it with vitamins. A consumer that prefers a strong peppermint flavoring in a chocolate drink could add NLPs containing peppermint oil to his or her beverage. Substances that are meant to be tasted can also be loosely associated with the exterior of the NLP by providing such substances in the aqueous phase of the procedure. For example, an NLP containing a vitamin that preferably should not be tasted can have a pleasant taste on the outside thereof.
- If it is desired that the NLPs remain in the mouth so that their contents can be tasted, a natural carbohydrate or sugar can be linked to the NLP by merely providing it in the aqueous solution. This will stick to the inside of the mouth for a period of time, and normal mouth chemistry and mastication will release the contents of the NLPs to provide the desired effect. The NLPs can also be subjected to agitation and shear such as in a blender or heavy industrial equipment at a manufacturing site to provide flavorings to foods and beverages.
- If the desired passenger molecule is water soluble, the passenger molecule should first be dissolved in water. The incorporation step, or loading of the passenger molecule into the NLP, is accomplished when the NLP product is formed by adding the dissolved passenger molecule to the precursor solution.
- The nanolipidic particles with encapsulated ethanol of the invention have a softer “mouth feel” than a preparation containing free ethanol. The encapsulation process leads to the ethanol being sequestered inside the nanolipid such that the ethanol does not immediately contact the mucosa in the mouth. Other passengers molecules which may in the preparation, such as vitamins and pharmaceutical substances, are similarly sequestered within the nanolipidic particles.
- Sample Preparation of NLPs and NLP Assembly Populations with Encapsulated Ethanol-Containing Substances
- NLPs encapsulating ethanol-containing substances were prepared as follows:
- Solvent-diluted precursor stock was prepared by adding 1 part shelf-stable precursor stock to 0.3 part ethanol to form a solvent-diluted precursor.
- An ethanol-containing substance is dissolved in an aqueous solvent to form an aqueous-ethanol monophase.
- An aliquot of solvent-diluted precursor stock added to an aliquot of the aqueous-ethanol monophase. This solution is stirred at room temperature resulting in a loaded NLP population with the desired ethanol-containing substance encapsulated within the nanolipid particles to yield a liposomal concentrate comprising ethanol in the amount of about 0.1% to 15.0% by volume.
- The size of the loaded NLPs may be determined by using the Malvern 1000 Zetasizer Laser Light Scattering Instrument set to analyze populations using multimodal analysis mode. The size of the finished preparation was determined to be 20 nm-150 nm.
- Nanolipid particle sizes useful for the preparation of the invention can be increased or decreased by adjusting the ratio of ethanol to Solvent Dilution Microcarrier (SDMC) used in preparation of the precursor stock solution. Particle sizes can range from approximately 60 nm using 20 parts ethanol: 1 part SDMC up to 170 nm using 0.3 part ethanol: 1 part SDMC. Sizes of NLP and NLP assembly populations useful for the method of the invention are 20 nm to 300 nm, preferably 20 nm to 170 nm.
- One or more additional dilutions of the precursor solution may be made with ethanol solvent in order to provide a desired size of NLPs and number of NLPs per unit volume. The more ethanol solvent that is used to dilute the NLPs, the smaller the resulting NLP assembly populations will be.
- In one embodiment, nanolipid particles having ethanol encapsulated at a concentration of 5.0%-8.0%, is added to base ingredients for gelato. This gelato mixture is then frozen by a commercially acceptable process to produce a frozen gelato for consumption.
- Frozen alcohol-containing gelatos which have been prepared by the claimed method of the invention include the following:
-
Gelato Flavor % Alcohol by volume Raspberry Cream 8.0% Orange Cream (Grand Marnier ™) 8.0% Bourbon Vanilla 5.0% - In another embodiment, nanolipidic particles having ethanol encapsulated at a concentration of 5.0% are added to base ingredients for a sorbet or frozen beverage. This sorbet or frozen beverage mixture is then frozen by a commercially acceptable process to produce a frozen sorbet, pops, or beverage for consumption. Ice pops and other frozen products of a similar nature can be prepared by the same method.
- Frozen alcohol-containing sorbets, pops, and beverages can be been prepared by the claimed method of the invention include the following:
-
Sorbet or Beverage Flavor % Alcohol by volume Piña Colada 5.0% Mojito 5.0% Strawberry Margarita 5.0% Apple Martini 5.0% - In yet another embodiment, nanolipid particles having ethanol encapsulated at a concentration of up to 15.0% is added to base ingredients for a syrup or topping for a frozen dessert.
- Alcohol-containing syrups and toppings for frozen desserts which have been prepared by the claimed method of the invention include the following:
-
Syrup or Topping Flavor % Alcohol by volume Caffe (Kahlua ®) 15.0% Chocolate Mint 15.0% Caramel 15.0% Raspberry 15.0% Grand Marnier ® 15.0% Limoncello 15.0% - NLPs (1:10 Precursor to Ethanol, volume/volume) were prepared and diluted 1:10 (NLP volume/volume) in commercially available alcoholic beverage products and stored for one week at Room Temperature. After one week the mixtures were vortexed, diluted 1:10 (volume/volume) in distilled water, and the size of the NLPs were analyzed using a Zetasizer 1000 (Malvern Instruments). The results of the stability study were as follows:
-
Citron ® Vodka 1:10 NLP 150 nm Malibu ® Coconut Rum 1:10 NLP 130 nm Beefeater ® Gin 1:10 NLP 150 nm
Stability of NLPs in 100 Proof (50% volume/volume in Distilled Water) Ethanol Mixtures - NLPs (1:10 and 1:20 Precursor to Ethanol, volume/volume) were prepared and diluted 1:10 in 100 proof mixtures of ethanol and water (50% ethanol, volume/volume). The samples were placed in a commercial freezer for 14 days, removed, allowed to thaw and warm to Room Temperature. Both samples were homogenous and optically clear, without any precipitation. The samples were vortexed and the size of the NLPs were determined using a Zetasizer 1000 (Malvern Instruments). The results of the analyses were:
-
100 Proof Ethanol in Distilled Water Containing NLPs 1:10 NLP 163 nm 1:20 NLP 142 nm
Stability of NLPs after Repeated Freeze Thaw Stored in 25 Proof Ethanol in Distilled Water - NLPs (1:5, 1:10 and 1:20 Precursor to Ethanol volume/volume) were prepared and added 1:10 (volume/volume) into solutions of 25 Proof Ethanol in Distilled Water (12.5% Ethanol in Distilled Water, volume/volume). All mixtures were optically clear. The initial size of the NLPs and subsequent size analyses conducted on days 7, 14 and 21 were performed using a Zetasizer 1000 (Malvern Instruments). After the initial size determinations the samples were placed into a commercial freezer for intervals of 7 days. On days 7, 14 and 21 the samples were removed from the freezer allowed to thaw and warm to Room Temperature.
- They were vortexed and subjected to size analyses after which they were returned to the commercial freezer. At days 7, 14 and 21 all preparations after equilibrating to Room Temperature were optically clear and free of any precipitation. The results of the size analyses were:
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NLP Time 0 7 Days 14 Days 21 Days 1:5 156 nm 160 nm 167 nm 162 nm 1:10 77 nm 82 nm 92 nm 94 nm 1:20 105 nm 100 nm 106 nm 116 nm - The NLPs and NLP assembly populations can also be used to formulate a delivery vehicle for pharmaceuticals, such as analgesics, as an admixed passenger with the NLPs with encapsulated ethanol. The admixed passenger loaded NLPs can then be mixed with ingredients suitable for making a frozen food product. The loaded NLP-frozen food ingredient mixture can be frozen in a form such as an ice pop to provide a delivery vehicle for the encapsulated ingredients. One practical application of such a delivery device would be in the treatment of sore throats in individuals.
- The examples of ethanol encapsulation in NLPs and NLP assemblies presented herein, are representative examples only. The method of the invention is applicable to other types of ethanol containing substances and these examples are not meant to constitute the entire range of ethanol-containing substances that may be used in the method disclosed herein.
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US15/479,847 Expired - Fee Related US10266800B2 (en) | 2005-12-30 | 2017-04-05 | Method for preparing nanolipids with encapsulated alcohol |
US15/673,603 Expired - Fee Related US10246672B2 (en) | 2005-12-30 | 2017-08-10 | Nanolipids with encapsulated alcohol |
US15/673,588 Expired - Fee Related US10240115B2 (en) | 2005-12-30 | 2017-08-10 | Method for preparing nanolipids with encapsulated alcohol |
US16/256,661 Active US10774295B2 (en) | 2005-12-30 | 2019-01-24 | Nanolipids with encapsulated alcohol |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016168236A1 (en) * | 2015-04-13 | 2016-10-20 | Fountain Technologies International, Llc | One-step method for production of ultra-small lipid structures |
US20190031987A1 (en) * | 2013-10-31 | 2019-01-31 | Steven J. Hollenkamp | Mass produced, alcohol-containing spherical bead with improved shelf life and "pop" |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20140271782A1 (en) * | 2013-03-15 | 2014-09-18 | Dermazone Solutions, Inc. | Method for preparing nanolipids with encapsulated alcohol |
WO2008005045A2 (en) * | 2005-12-30 | 2008-01-10 | Dermazone Solutions, Inc. | Nanolipidic particles |
US10077419B2 (en) * | 2013-10-31 | 2018-09-18 | Steven J. Hollenkamp | Method for mass producing alcohol-containing spherical beads |
US20200078427A1 (en) | 2018-09-06 | 2020-03-12 | NuVessl, Inc. | Cannabis Sativa Derived Formulation for Transmucosal and Transdermal Delivery |
CN113166754A (en) | 2018-10-16 | 2021-07-23 | 蓝色等位基因有限责任公司 | Method for targeted insertion of DNA into genes |
US20200188298A1 (en) | 2018-12-14 | 2020-06-18 | NuVessl, Inc. | Method For Using Composition With Enhanced Passenger Molecule Loading |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5019414A (en) * | 1988-06-06 | 1991-05-28 | Valdes Mario A | Pipeable gelled food and ethyl alcohol beverages |
US20020094344A1 (en) * | 1996-01-18 | 2002-07-18 | The University Of British Columbia | Method of loading preformed liposomes using ethanol |
US20070154539A1 (en) * | 2005-12-30 | 2007-07-05 | Fountain Michael W | Nanolipidic particles |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS494960B1 (en) | 1970-12-18 | 1974-02-04 | ||
DE3585967D1 (en) | 1984-03-08 | 1992-06-11 | Phares Pharma Holland | LIPOSOME FORMING COMPOSITION. |
US4880635B1 (en) * | 1984-08-08 | 1996-07-02 | Liposome Company | Dehydrated liposomes |
US4790999A (en) | 1986-10-31 | 1988-12-13 | Heublein, Inc. | Alcoholic soft ice |
US5009819A (en) | 1987-11-12 | 1991-04-23 | The Liposome Company, Inc. | Taste moderating composition |
US5269979A (en) | 1988-06-08 | 1993-12-14 | Fountain Pharmaceuticals, Inc. | Method for making solvent dilution microcarriers |
US5498420A (en) * | 1991-04-12 | 1996-03-12 | Merz & Co. Gmbh & Co. | Stable small particle liposome preparations, their production and use in topical cosmetic, and pharmaceutical compositions |
GB9208339D0 (en) | 1992-04-15 | 1992-06-03 | Unilever Plc | Treatment composition |
DK88692D0 (en) | 1992-07-06 | 1992-07-06 | Danochemo As | PROCEDURE FOR MANUFACTURING MICROCAPPLES |
US6096331A (en) | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
US5437274A (en) | 1993-02-25 | 1995-08-01 | Gholam A. Peyman | Method of visualizing submicron-size vesicles and particles in blood circulation |
ES2145132T3 (en) | 1993-02-26 | 2000-07-01 | Fountain Pharm Inc | VACCINE SUPPLY SYSTEM AND STABLE PRECURSORY SOLUTION IN STORAGE FOR REMOTE ENCAPSULATION OF ACTIVE INGREDIENTS. |
US20010041208A1 (en) | 1994-05-13 | 2001-11-15 | Ice Cream Bar, Inc. | Stabilization process for combining ethyl alcohol and ice cream |
US5540934A (en) | 1994-06-22 | 1996-07-30 | Touitou; Elka | Compositions for applying active substances to or through the skin |
US5965185A (en) | 1996-04-24 | 1999-10-12 | Cool Care, Ltd. | Transportable and size-adjustable apparatus with multiple air flow control units for ripening of fresh produce |
US5885921A (en) | 1996-10-25 | 1999-03-23 | Ligochem, Inc. | Hydrophobic silica adsorbents for lipids |
IN190388B (en) | 1997-10-01 | 2003-07-26 | Biomira Usa Inc | |
US7381423B2 (en) | 1998-05-11 | 2008-06-03 | Ciba Specialty Chemicals Corp. | Use of nanodispersions in cosmetic end formulations |
US6203778B1 (en) | 1998-12-08 | 2001-03-20 | The Regents Of The University Of California | Particulate radiopaque contrast agent for diagnostic imaging and microvascular characterization |
US6511693B2 (en) | 2000-02-15 | 2003-01-28 | Softpac Industries, Inc. | Frozen slushy in a squeezable pouch |
US20050142253A1 (en) | 2002-05-23 | 2005-06-30 | Arctic Island, Llc | Method of making an alcoholic popsicle-style frozen confection/beverage |
US20040253360A1 (en) | 2003-06-10 | 2004-12-16 | Squicciarini John B. | Hard frozen food containing alcohol |
US20100062134A1 (en) | 2004-02-26 | 2010-03-11 | David Hart Melvin | Alcohol based frozen dessert product |
US20070128317A1 (en) * | 2005-12-01 | 2007-06-07 | Jody Helfend | Frozen alcoholic cocktail |
US20140271782A1 (en) * | 2013-03-15 | 2014-09-18 | Dermazone Solutions, Inc. | Method for preparing nanolipids with encapsulated alcohol |
US20090155427A1 (en) * | 2007-12-12 | 2009-06-18 | Clabber Girl Corporation | Alginate crosslink coating of an edible alcohol |
WO2009075699A1 (en) | 2007-12-11 | 2009-06-18 | Aegs Ventures, Llc | Solid alcohol product and process |
US11298318B2 (en) | 2015-04-13 | 2022-04-12 | Fountain Technologies International, Llc | One-step method for production of ultra-small lipid structures |
-
2013
- 2013-03-15 US US13/840,810 patent/US20140271782A1/en not_active Abandoned
-
2015
- 2015-08-12 US US14/824,923 patent/US9635876B2/en active Active
-
2017
- 2017-04-05 US US15/479,847 patent/US10266800B2/en not_active Expired - Fee Related
- 2017-08-10 US US15/673,603 patent/US10246672B2/en not_active Expired - Fee Related
- 2017-08-10 US US15/673,588 patent/US10240115B2/en not_active Expired - Fee Related
-
2019
- 2019-01-24 US US16/256,661 patent/US10774295B2/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5019414A (en) * | 1988-06-06 | 1991-05-28 | Valdes Mario A | Pipeable gelled food and ethyl alcohol beverages |
US20020094344A1 (en) * | 1996-01-18 | 2002-07-18 | The University Of British Columbia | Method of loading preformed liposomes using ethanol |
US20070154539A1 (en) * | 2005-12-30 | 2007-07-05 | Fountain Michael W | Nanolipidic particles |
US8597678B2 (en) * | 2005-12-30 | 2013-12-03 | Dermazone Solutions, Inc. | Nanolipidic particles |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20190031987A1 (en) * | 2013-10-31 | 2019-01-31 | Steven J. Hollenkamp | Mass produced, alcohol-containing spherical bead with improved shelf life and "pop" |
WO2016168236A1 (en) * | 2015-04-13 | 2016-10-20 | Fountain Technologies International, Llc | One-step method for production of ultra-small lipid structures |
CN107530235A (en) * | 2015-04-13 | 2018-01-02 | 方丹科技国际股份有限公司 | For producing the one-step method of microminiature lipid conformation |
EP3283045A4 (en) * | 2015-04-13 | 2018-11-21 | Fountain Technologies International, LLC | One-step method for production of ultra-small lipid structures |
AU2016250068B2 (en) * | 2015-04-13 | 2021-04-29 | Fountain Technologies International, Llc | One-step method for production of Ultra-small Lipid Structures |
US11298318B2 (en) | 2015-04-13 | 2022-04-12 | Fountain Technologies International, Llc | One-step method for production of ultra-small lipid structures |
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US20170335261A1 (en) | 2017-11-23 |
US10246672B2 (en) | 2019-04-02 |
US10266800B2 (en) | 2019-04-23 |
US20150342226A1 (en) | 2015-12-03 |
US20170335260A1 (en) | 2017-11-23 |
US10774295B2 (en) | 2020-09-15 |
US9635876B2 (en) | 2017-05-02 |
US10240115B2 (en) | 2019-03-26 |
US20170204355A1 (en) | 2017-07-20 |
US20190153371A1 (en) | 2019-05-23 |
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