巴西专利BR102016024625A2 NANOEMULSION, AND METHOD FOR PREPARING A NANOEMULSION

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nanoemulsion, and method for preparing a nanoemulsion The present invention is a nanoemulsion having reversible continuous and dispersed phases. nanoemulsion includes an aqueous phase and an oil phase, a weight ratio of the aqueous phase to the oil phase being 1:40 - 100: 1. In nanoemulsion, the aqueous phase is dispersed as nanodimension droplets in the oil phase or the oil phase is dispersed as nanodimension droplets in the aqueous phase. the aqueous phase contains water or an aqueous solution and a water soluble organic nanostructure stabilizer. the oil phase contains an oil or oily solution, an organic gel thickener, and a hydrophilic surfactant having an hlb value greater than 8.0. Also disclosed is a method for preparing the nanoemulsion described above.
公开号:BR102016024625A2
申请号:R102016024625-3
申请日:2016-10-21
公开日:2018-03-27
发明作者:Wu Chien-Chin
申请人:LG Bionano, LLC；
IPC主号:

专利说明:

(54) Title: NANOEMULSION, AND METHOD FOR PREPARING A NANOEMULSION (51) Int. Cl .: A61K 9/107; A61K 9/113 (52) CPC: A61K 9/107, A61K 9/113 (30) Unionist Priority: 10/23/2015 US 14 / 921,572 (73) Holder (s): LG BIONANO, LLC (72) Inventor ( es): CHIEN-CHIN WU (74) Attorney (s): DAVID DO NASCIMENTO ADVOGADOS ASSOCIADOS (57) Abstract: NANOEMULSION, AND METHOD FOR PREPARING A NANOEMULSION The present invention is a nanoemulsion with reversible continuous and dispersed phases. The nanoemulsion includes an aqueous phase and an oil phase, a weight ratio of the aqueous phase to the oil phase being 1:40 - 100: 1. In the nanoemulsion, the aqueous phase is dispersed as nanodimensioned droplets in the oil phase or the oil phase is dispersed as nanodimensioned droplets in the aqueous phase. The aqueous phase contains water or an aqueous solution and a water-soluble organic nanostructure stabilizer. The oily phase contains an oil or an oily solution, an organic gel thickener, and a hydrophilic surfactant having an HLB value greater than 8.0. Also disclosed is a method for preparing the nanoemulsion described above.
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NANOEMULSION, AND METHOD FOR PREPARING A
NANOEMULSION
BACKGROUND OF THE INVENTION [001] There are two types of nanoemulsions, that is, oil in water (w / o) nanoemulsion and a water in oil (w / o) nanoemulsion. An o / w nanoemulsion has a continuous water phase and a dispersed oil phase while a w / o nanoemulsion has a continuous oil phase and a dispersed water phase.
are of
One [002] These two types of nanoemulsions stabilized by emulsifiers that have different hydrophilic-lipophilic balance (HLB) values.
an o / w nanoemulsion is stabilized by an emulsifier having an HLB value of 8-28 and an w / o emulsion is stabilized by an emulsifier having an HLB value of 3-6. As a result, they cannot be easily interconverted.
[003] The absence of easy convertibility can be problematic. A nanoemulsion collapses when its water content decreases. Likewise, a w / o nanoemulsion collapses when its oil content decreases.
[004] Thus, there is a need to develop a nanoemulsion in which its continuous phase and the dispersed phase can be readily converted from one to the other with the same emulsifier contained therein.
SUMMARY OF THE INVENTION [005] A nanoemulsion containing continuous and dispersible reversible phases is disclosed here.
[006] The nanoemulsion of this invention includes an aqueous phase and an oil phase, a weight ratio of the phase
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2/38 aqueous for the oil phase being 1:40 -100: 1. In the nanoemulsion, the aqueous phase is dispersed as nanodimensioned droplets in the oil phase or the oil phase is dispersed as nanodimensioned droplets in the aqueous phase. The aqueous phase, which constitutes 2.5% by weight or more of the nanoemulsion, contains water or an aqueous solution and a stabilizer of the water-soluble organic nanostructure. The water or aqueous solution has a content of less than 75% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 99% by weight of the aqueous phase. The oily phase contains an oil or an oily solution, an organic gel thickener, and a hydrophilic surfactant having an HLB value greater than 8.0. The oil or oily solution has a content of less than 80% by weight of the oil phase, the organic gel thickener has a content of less than 60% by weight of the oil phase, and the hydrophilic surfactant has a content of less than 60% by weight of the oil phase. oily phase. This nanoemulsion can be used as a carrier for an active ingredient in a cosmetic, food or pharmaceutical composition.
[007] Also within the scope of the present invention is a method for preparing the nanoemulsion described above. The method includes the following steps: (1) mixing the water or aqueous solution and the soluble organic nanostructure stabilizer to form an aqueous phase, in which the water or aqueous solution has a content of less than 75% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 99% by weight of the aqueous phase; (2) mixture of an oil or aqueous solution, an organic thickener, and a hydrophilic surfactant having a hydrophilic-lipophilic equilibrium value greater than 8.0 for
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3/38 form an oily phase, in which the oil or oily solution has a content of less than 80% by weight of the oily phase, the organic gel thickener has a content of less than 60% by weight of the oily phase, and the surfactant hydrophilic has less than 60% by weight of the oil phase; and (3) mixing the aqueous phase and the oil phase, a weight ratio of the aqueous phase to the oil phase being 1: 40-100: 1, to form a nanoemulsion, in which water or aqueous solution constitutes 74% by weight or less of the nanoemulsion. Each mixing step is carried out at an appropriate temperature, for example, 5-95 ° C.
[008] In the nanoemulsion thus prepared, the aqueous phase is dispersed as nanodimensioned droplets in the oil phase or the oil phase is dispersed as nanodimensioned droplets in the aqueous phase. In other words, the continuous and dispersed phases in the nanoemulsion are reversible.
[009] The details of one or more achievements are set out in the description below. Other aspects, objectives and advantages of the achievements will be apparent from the specification and the claims.
DETAILED DESCRIPTION [010] The present invention is based, at least in part, on an unexpected discovery that a nanoemulsion, containing a hydrophilic surfactant having an HLB value greater than 8, may have or the aqueous phase dispersed as nanodimensioned droplets in the oil phase or the oil phase dispersed as nano-sized droplets in the aqueous phase. In other words, the nanoemulsion has reversible continuous and dispersed phases.
[011] This nanoemulsion can contain both oil-soluble active ingredients and active ingredients
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4/38 cosmetic, household, agricultural, water-soluble preparation, an advantage over conventional nanoemulsions. The advantage is especially important in food, chemicals, printing, inks, veterinary, diagnostic, vaccine and pharmaceutical products, as demonstrated by the following two examples.
[012] An o / w emulsion is preferably used in a cosmetic product, since it is less sticky and oily than an w / o emulsion and has the desirable ability to retain water. However, when a cosmetic product is applied to the skin or exposed to air, the nanoemulsion in the cosmetic product loses water through evaporation. The loss of water causes the collapse of a conventional o / a nanoemulsion, but not in the o / a nanoemulsion of this invention. Instead, the last nanoemulsion slowly converts to a w / o nanoemulsion in which its aqueous phase is dispersed evenly as nanodimensioned droplets in its oil phase.
[013] In contrast, for an oil-soluble drug, a w / o emulsion is preferably used due to its high loading capacity. However, since body fluids are aqueous, when a w / o nanoemulsion comes into contact with body fluids, its water content inevitably increases. As a result, the conventional w / o nanoemulsion collapses. In addition, the w / o nanoemulsion of this invention slowly converts to an w / o nanoemulsion in which its oil phase is uniformly dispersed as nanodimensioned droplets in the aqueous phase. Notably, the conversion not only maintains the integrity of a nanoemulsion, but also provides a sustained release of the drug in it.
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5/38 [014] As indicated above, the nanoemulsion of this invention includes an aqueous phase and an oil phase. In the nanoemulsion, the aqueous phase can be dispersed as nano-sized droplets in the oil phase. Alternatively, the aqueous phase can be dispersed as nanodimensioned droplets in the aqueous phase.
[015] The aqueous phase includes a water-soluble organic nanostructure stabilizer. The term water-soluble organic nanostructure stabilizer ”here refers to any water-soluble organic ingredient that can stabilize the isotropic structure of a nanoemulsion, thus resulting in a thermodynamically stable or translucent nanoemulsion. It can be a water-soluble vitamin, a water-soluble peptide, a water-soluble oligopeptide, a polyol, a water-soluble saccharide, a water-soluble oligosaccharide, a disaccharide, a monosaccharide, a hydrogenated carbohydrate, an amino acid, an amino sugar, or a combination of these. Specific examples include urea, methylsulfonylmethane, hydroxyethyl, urea, glucosamine, mannitol, sorbitol, xylitol, lactose, fructose, dextrose, ribose, trehalose, raffinose, maltilol, isomalt, lactitol, erythritol, inositol, taurine, glyceryl, glycol, glyceryl, glycol, glycine, glycol, glycine, glycol, glycol, glycine, glycol, glycol, glycol , hexylene glycol, polyethylene glycol, ethoxydiglycol, carnitine, arginine, sodium pyrolidine carboxylic acid and hydrolyzed collagen.
[016] The oily phase contains an oil or an oily solution. A vegetable oil, a silicone oil, a synthetic oil, a mineral oil, an animal oil, an essential oil, or a combination of these can be used to
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6/38 horse, cyclomethicone oils, lanolin, squalene, phenyl trimethicone, form the oily phase. Specific examples include coconut oil, palm oil, grape seed oil, olive oil, grapefruit seed oil, flax seed oil, avocado oil, evening primrose oil, lavender oil, rosemary oil, essential oil tea tree oil, eucalyptus oil, fish fat, cyclopentassiloxane oil, caprylic / capric triglyceride, isopropyl myristate, isostearyl isostearate, decyl oleate, ethylhexyl, isoexadecane, octyldodecanol, paraffin oil, polydecene, polydexene, polyolene a combination of these. Note that the oily solution contains one or more oils as solvents to dissolve one or more oil-soluble solutes.
[017] As also noted above, the oil phase includes a hydrophilic surfactant having an HLB value greater than 8.0. Preferably the HLB value of the hydrophilic surfactant is greater than 10 and, more preferably, the HLB value is greater than 13. Examples of hydrophilic surfactant include polyoxyethylene sorbitan fatty acid esters (Tween 20, Tween 21, Tween 60, Tween 61, Tween 65, Tween 80, Tween 81, Tween 85), polyoxyethylene sorbitol fatty acid ester, polyoxyethylene acid esters fatty acid esters (Myri 45, Myri 52, Myri 53, Myri 59), fatty acid esters polyoxyethylene (Myri 45, Myri 52, Myri 53, Myri 59), polyoxyethylene alcohol ester (Brij 30, Brij 35, Brij 56, Brij 58, Brij 76, Brij 78, Brij 96, Brij 97, Brij 98, Brij 99) , nonylphenol alkoxylates (nonionic surfactants based on nonylphenol Witconol ™), alkyl alkoxylates (nonionic surfactants of the Ethylan ™ family), Pluronic F-127, PEG dimethicone, acid ester
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7/38 polyoxyethylene fatty acid (40), polyoxyethylene saccharide fatty acid ester (20), glyceryl fatty acid ester PEG15, hydrogenated castor oil PEG-35, hydrogenated castor oil PEG-40, polyglycerol fatty acid ester , derivatives of fatty amines or a combination thereof.
[018] In addition, the oil phase contains an organic gel thickener. The term organic gel thickener ”here refers to any substance that increases viscosity and causes the structural formation of a nanoemulsion. The organic gel thickener can be saturated fatty acid, fatty acid alcohol, a fatty acid derivative having a melting point above 45 ° C, or a combination of these. Examples of organic gel thickeners include stearic acid, lauric acid, glycerol monostearate, PEG 6000 diesterate, monoglyceride, diglyceride, saccharide fatty acid ester, propylene glycol fatty acid ester, glycol fatty acid ester, decylhexyl fatty acid ester , fatty acid alcohol, cetylesterate, ascorbyl fatty esters, glyceryl fatty esters, hexildecyl fatty esters or a combination of these.
[019] In one embodiment, the water or aqueous solution of the nanoemulsion of this invention has a content of less than 60% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 70% by weight of the aqueous phase; the oil or oily solution has a content of 30-70% by weight of the oil phase, the organic gel thickener has a content of less than 45% by weight of the oil phase, and the hydrophilic surfactant has a content of less than 45% by weight the oily phase; and the water or aqueous solution constitutes 38% by weight or less of the nanoemulsion and a weight ratio of the aqueous phase to the
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8/38 1: 3-4: 1 oily phase. Preferably, the water or aqueous solution has a content of less than 45% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 50% by weight of the aqueous phase; the oil or oily solution has a content of 45-65% by weight of the oil phase, the organic gel thickener has a content of less than 25% by weight of the oil phase, and the hydrophilic surfactant has a content of less than 35% by weight the oily phase; and the water or aqueous solution constitutes 30% by weight or less of the nanoemulsion and a weight ratio of the aqueous phase to the oil phase of 1: 23: 1.
[020] The nanoemulsion of this invention is transparent or translucent in the form of a solid gel or liquid form at a pH of 3-11. Additionally, it exhibits a nano characteristic, that is, the Tyndall effect of light refraction. See Gold and Silver Nanoparticles, Center for Nanoscale Chemical-Electrical-Mechanical Manufacturing Systems, University of Illinois, http: // Nanocemms.illinois.edu/media/content/teaching_mats/online/gold_an d_silver_nanoparticles / docs / presentation.pdf.
[021] The nanoemulsion of this invention whose water or aqueous solution constitutes 38% by weight or less of the nanoemulsion has a capacity for self-preservation and, therefore, there is no need to include an antimicrobial preservative in it. A preservative usually raises safety concerns, as it can present health damage ranging from a mild headache to more serious illnesses, for example, cancer.
[022] When used in cosmetic, food and pharmaceutical compositions, this nanoemulsion may contain
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9/38 various active ingredients, for example, terbinafine, diclofenac, lorazepam, propofol, metronidazole, indomethacin, clotrimazole, ketoconazole, erythromycin, clibazole, kinetin, bifonazole, miconazole, tonalftate, clobetasol, econazoline, bezincine, bezoline, lovazoline dinitrate, nitroglycerin, farmotidine, bisabodol, lutein ester, melatonin, water-soluble vitamins, lycopene, resveratrol, ginsenosisides, butyl vanylyl ester, curcumin, and CoQ10. A nanoemulsion including a drug can be administered via several routes, for example, oral, topical, vaginal, rectal, sublingual, pulmonary and parenteral. If desired, certain sweeteners, flavors, coloring agents or fragrances can also be added.
[023] The method of this invention for preparing the nanoemulsion described above includes first forming an aqueous phase and an oil phase separately, and then mixing the two phases. Water or aqueous solution and a water-soluble organic nanostructure stabilizer can be mixed by constant stirring (manually or otherwise), mixing at high speed or high shear (for example, using a colloid crusher), mixing at high pressure (for example, using a micro fluidizer) or sonication mixture to form the aqueous phase. An oil or an aqueous solution, an organic thickener, and a hydrophilic surfactant can also be mixed to form the oil phase. The resulting aqueous phase and the oil phase can then be mixed in a similar way to form a nanoemulsion. It is worth noting that all mixing steps can be carried out at an elevated temperature, for example, 45-85 ° C, if necessary. Still great
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Importantly, the oil phase and the aqueous phase thus obtained can be used to prepare either an o / nanoemulsion or an a / o nanoemulsion, indicating that the continuous and dispersed phases are reversible.
[024] Without further elaboration, it is believed that the above description has adequately enabled the present invention. Therefore, the following examples should be constructed for illustrative purposes only, and not to limit the rest of the disclosure in any way. The publication cited here is incorporated herein as a reference in its entirety.
EXAMPLE 1: DETERMINATION OF THE TYPE OF NANOEMULSION [025] 60 ml of water were placed in a 100 ml beaker. A nanoemulsion to be tested was added in drops to the water. If the nanoemulsion dispersed in the water creating a clear or translucent solution, the tested nanoemulsion was an o / a nanoemulsion. However, if the nanoemulsion formed oil-like droplets in the water, the nanoemulsion tested was a w / o nanoemulsion.
EXAMPLE 2: PREPARATION OF OIL NANOEMULSIONS
COCO [026] Nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [027] A combination of 210 g of purified water, 90 g of urea, 60 g of xylitol, 60 g of Trealose and 30 g of methyl sulphonyl methane were mixed with constant manual stirring in a beaker of 500 ml at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE OIL PHASE OF NANOEMULSIONS
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11/38 [028] A combination of 80 g of coconut oil, 20 g of paraffin oil, 50 g of cyclomethicone, 20 of beeswax, 10 g of glyceryl monostearate, 16 g of stearic acid, 14 g of sorbitan monostearate, 36 g of polyethylene glycol sorbitan monostearate and 42 g of hydrogenated castor oil PEG-40 were mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [029] A combination of the oil phase and aqueous phase prepared above in a weight ratio shown in Table 1 was mixed by means of constant manual stirring in a 200 ml beaker at 65-75 ° C for less than 0, 5 hours to form a w / o or w / o nanoemulsion.
TABLE 1
ID 1 2 3 4 Oily phase(g) 120 90 40 25 Aqueous phase (g) 30 60 60 75 Nanoemulsion(g) 150 150 100 100 Type to to o / a o / a Appearancephysics Translucent clear clear clear
[030] All nanoemulsions were stable at room temperature for at least 3 months and exhibited a Tyndall effect of light refraction.
[031] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[032] An antimicrobial test was conducted following the procedure described in USP 35 <51>,
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12/38
Antimicrobial Effectiveness Testing, on page 52, and all the nanoemulsions prepared in this example have passed the antimicrobial test.
EXAMPLE 3: PREPARATION OF OIL NANOEMULSIONS
PALMA [033] Nanoemulsions were prepared following the procedure described below.
[034] 150 g of a w / o nanoemulsion composed of g of the aqueous phase and 120 g of the oil phase was prepared following the procedure described in Example 2 except that palm oil was used instead of coconut oil. The nanoemulsion in this way was translucent and stable at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[035] 150 g of a w / o nanoemulsion composed of g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2 except that palm oil was used instead of coconut oil. The nanoemulsion in this way was clear and stable at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[036] 150 g of an o / w nanoemulsion composed of g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2 except that palm oil was used instead of coconut oil. The nanoemulsion in this way was clear and stable at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[037] 100 g of an o / a nanoemulsion composed of g of the aqueous phase and 25 g of the oil phase was prepared
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13/38 following the procedure described in Example 2 except that palm oil was used instead of coconut oil. The nanoemulsion in this way was clear and stable at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[038] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[039] All nanoemulsions prepared in this example passed the antimicrobial test, which was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52.
EXAMPLE 4: PREPARATION OF FAT NANOEMULSIONS
DE HORSE [040] Nanoemulsions were prepared following the procedure described below.
[041] 150 g of a w / o nanoemulsion composed of 60 g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2 except that horse fat was used instead of coconut oil.
[042] 100 g of an o / a nanoemulsion composed of 60 g of the aqueous phase and 40 g of the oil phase was prepared following the procedure described in Example 2 except that horse fat was used instead of coconut oil.
[043] The nanoemulsions prepared in this way were clear and stable at room temperature for at least 3 months. Both exhibited the Tyndall effect of refraction of light.
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14/38 [044] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[045] An antimicrobial test was conducted following the procedure described in USP 35 <51>,
Antimicrobial Effectiveness Testing, on page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 5: Preparation of horse fat nanoemulsions [046] Nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [047] A combination of 150 g of purified water, 150 g of urea, 40 g of mannitol was mixed with constant manual stirring in a beaker at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE OIL PHASE OF NANOEMULSIONS [048] The oil phase was prepared following the procedure described in Example 2 except that horse fat was used instead of coconut oil.
PREPARATION OF NANOEMULSIONS [049] 150 g of a w / o nanoemulsion composed of g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2.
[050] 100 g of an o / w nanoemulsion composed of g of the aqueous phase and 40 g of the oil phase was prepared following the procedure described in Example 2.
[051] Nanoemulsions prepared in this way were clear and stable at room temperature for at least
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15/38 months. Both exhibited the Tyndall effect of refraction of light.
[052] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[053] An antimicrobial test was conducted following the procedure described in USP 35 <51>,
Antimicrobial Effectiveness Testing, on page 52, and the two nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 6: PREPARATION OF PALM / SQUALENO OIL NANOEMULSIONS CONTAINING ONLY A HYDROPHYLIC SURFACTANT [054] The nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [055] A combination of 180 g of purified water, 100 g of urea, 20 g of butylene glycol was mixed with constant manual stirring in a 500 ml beaker at 65-75 ° C to form the aqueous phase .
PREPARATION OF THE NANOEMULSION OIL PHASE [056] A combination of 100 g of palm oil, g of squalene, 25 of cyclomethicone (DC-345), 10 g of beeswax, 20 g of stearic acid, 16 g of monostearate sorbitan, and 60 g of hydrogenated castor oil PEG-40 was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [057] A combination of the oil phase and aqueous phase prepared above in a weight ratio shown in Table 2 was mixed by means of constant manual agitation
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16/38 in a 500 ml beaker at 65-75 ° C for up to 0.5 hour to form a nanoemulsion also listed in Table 2.
TABLE 2
ID 1 2 3 4 Oily phase (g) 105 90 60 30 Aqueous phase (g) 15 60 90 120 Total weight (g) 120 150 150 150 Type to to o / a o / a Physical appearances Translucent clear clear clear
[058] All of the above nanoemulsions were stable at room temperature for at least 3 months and exhibited a Tyndall effect of light refraction.
[059] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[060] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and all nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 7: PREPARATION OF PHARMACEUTICAL NANOEMULSIONS BASED ON COCONUT OIL [061] The nanoemulsions were prepared following the procedure described below.
[062] 50 g of an o / a nanoemulsion composed of
29.5 g of the aqueous phase and 20 g of the oil phase dissolving 0.5 g of an oil-soluble pharmaceutically active ingredient was prepared following the procedure described in Example 2. The oil-soluble pharmaceutically active ingredient is terbinafine, diclofenac diethylamine, dithylamine , metronidazole, clotrimazole indomethacin or erythromycin.
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17/38 [063] The six nanoemulsions prepared in this way were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[064] The type of each nanoemulsion prepared in this example was determined following the procedure described in Example 1.
[065] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and all nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 8: PREPARATION OF PHARMACEUTICAL PHARMACEUTICAL NANOEMULSIONS BASED ON PALM OIL [066] Nanoemulsions were prepared following the procedure described in Example 7 except that palm oil was used instead of coconut oil and the oil-soluble pharmaceutically active ingredient is terbinafine, diclofenac diethylamine, metroconazole, kinetin, bifonazole and miconazole.
[067] The six nanoemulsions prepared in this way were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[068] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[069] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and all
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18/38 nanoemulsions prepared in this example have passed the antimicrobial test.
EXAMPLE 9: PREPARATION OF ESSENTIAL OIL NANOEMULSIONS CONTAINING CLIMBAZOL [070] The nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [071] A combination of 150 g of purified water, 150 g of urea, 40 g of propylene glycol was mixed with constant manual stirring in a 500 ml beaker at 65-75 ° C to form the aqueous phase .
PREPARATION OF THE NANOEMULSION OIL PHASE [072] The combination of 40 g of tea tree essential oil, 20 g of eucalyptus oil, 30 of menthol, 50 g of paraffin oil, 50 g of cyclomethicone (DC-345), 20 beeswax, 10 g of glyceryl monostearate, 16 g of stearic acid, 14 g of sorbitan monostearate, 36 g of polyethylene glycol sorbitan monostearate and 42 g of hydrogenated castor oil PEG-40 was mixed in a 500 beaker ml by means of constant manual stirring at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [073] 150 g of a w / o nanoemulsion composed of g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2.
[074] 150 g of an o / w nanoemulsion composed of g of the aqueous phase and 60 g of the oil phase was prepared following the procedure described in Example 2.
[075] 100 g of an o / a nanoemulsion composed of g of the aqueous phase dissolving 10 g of climbazole and 40 g of
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19/38 oily phase was prepared following the procedure described in
Example 2.
[076] All of the above nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[077] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[078] An antimicrobial test was conducted following the procedure described in USP 35 <51>,
Antimicrobial Effectiveness Testing, on page 52, and all the nanoemulsions prepared in this example have passed the antimicrobial test.
EXAMPLE 10: PREPARATION OF ESSENTIAL OIL NANOEMULSIONS HAVING AN WATER PHASE DIFFERENT FROM THAT IN EXAMPLE [079] The nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [080] A combination of 210 g of purified water, 90 g of urea, 60 g of xylitol, 60 g of Trealose and 30 g of methyl sulfonyl methane was mixed by means of constant manual stirring in a beaker 500 ml at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [081] The combination of 40 g of tea tree essential oil, 20 g of eucalyptus oil, 30 of menthol, 50 g of paraffin oil, 50 g of cyclomethicone (DC-345), 20 beeswax, 10 g glyceryl monostearate, 16 g stearic acid, 14 g sorbitan monostearate, 36 g
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20/38 polyethylene glycol sorbitan monostearate and 42 g of hydrogenated castor oil PEG-40 was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [082] 150 g of a w / o nanoemulsion composed of 60 g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2.
[083] 150 g of an o / w nanoemulsion composed of 90 g of the aqueous phase and 60 g of the oil phase was prepared following the procedure described in Example 2.
[084] The two prepared nanoemulsions were clear and stable at room temperature for at least 3 months. Both exhibited the Tyndall effect of refraction of light.
[085] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[086] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 11: PREPARATION OF ESSENTIAL OIL NANOEMULSIONS CONTAINING TOLNAFTATE OR KETOCONAZOLE [087] Nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [088] A combination of 150 g of purified water, 150 g of urea, 40 g of propylene glycol was
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21/38 mixed with constant manual stirring in a 500 ml beaker at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [089] The combination of 50 g of tea tree essential oil, 20 g of eucalyptus oil, 15 of menthol, 15 g of methyl salicylate, 50 g of cyclomethicone (DC-345), 10 g of beeswax, 10 g lauric acid, 6 g stearic acid, 14 g sorbitan monostearate, 40 g polyoxyethylene glycol stearate (40) and 40 g hydrogenated castor oil PEG-40 was mixed using manual stirring constant in a 500 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [090] 150 g of a w / o nanoemulsion composed of 60 g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2.
[091] 150 g of an o / w nanoemulsion composed of 90 g of the aqueous phase and 60 g of the oil phase was prepared following the procedure described in Example 2.
[092] 150 g of a w / o nanoemulsion composed of 60 g of the aqueous phase and 88.2 g of the oil phase by dissolving 1.8 g of tolnaftate was prepared following the procedure described in Example 2.
[093] 150 g of a w / o nanoemulsion composed of 60 g of the aqueous phase and 88.2 g of the oil phase dissolving 1.8 g of ketoconazole was prepared following the procedure described in Example 2.
[094] All of the above nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
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22/38 [095] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[096] An antimicrobial test was conducted following the procedure described in USP 35 <51>,
Antimicrobial Effectiveness Testing, on page 52, and all the nanoemulsions prepared in this example have passed the antimicrobial test.
EXAMPLE 12: PREPARATION OF THE NANOEMULSIONS OF
FRAGRANCE / ESSENTIAL OIL [097] Nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [098] A combination of 150 g of purified water, 150 g of urea, 40 g of propylene glycol was mixed by constant stirring in a beaker at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [099] A combination of 80 g of lemon eucalyptus oil, 40 g of citronella oil, 24 g of lavender oil, 22 g of eucalyptus oil, 15 g of menthol, 15 g of rosemary oil, 15 g of camphor, 15 g of menthol, 5 g of thyme, 10 g of beeswax, 10 g of lauric acid, 6 g of stearic acid, 14 g of sorbitan monostearati, 40 g of stearate polyoxyethylene glycol (40) and 40 g of hydrogenated castor oil PEG-40 was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS
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23/38 [0100] 150 g of a w / o nanoemulsion composed of g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2.
[0101] 100 g of an o / w nanoemulsion composed of 60 g of the aqueous phase and 40 g of the oil phase was prepared following the procedure described in Example 2.
[0102] Both prepared nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[0103] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[0104] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and the two nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 13: PREPARATION OF MEDIUM CHAIN OIL NANOEMULSIONS CONTAINING COQ10 [0105] The nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [0106] A combination of 150 g of purified water, 100 g of glycerin, 80 g of xylitol, 20 g of mannitol and 30 g of methyl sulfonyl methane was mixed by means of constant manual stirring in a beaker 500 ml at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE OIL PHASE OF NANOEMULSIONS [0107] A combination of 170 g of medium chain triglyceride oil, 16 g of stearic acid, 14 g
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24/38 sorbitan monostearate, 30 g of polyethylene glycol sorbitan monostearate and 30 g of hydrogenated castor oil PEG-40 was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the phase oily.
PREPARATION OF NANOEMULSIONS [0108] 150 g of a w / o nanoemulsion composed of 50 g of the aqueous phase and 95 g of the oil phase by dissolving 5 g of CoQ10 was prepared following the procedure described in Example 2.
[0109] 150 g of an o / w nanoemulsion composed of 90 g of the aqueous phase and 57 g of the oil phase by dissolving 3 g of CoQ10 was prepared following the procedure described in Example 2.
[0110] 153 g of an o / w nanoemulsion composed of 120 g of the aqueous phase and 30 g of the oil phase by dissolving 3 g of CoQ10 was prepared following the procedure described in Example 2.
[0111] All of the above nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[0112] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[0113] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and all nanoemulsions prepared in this example passed the antimicrobial test.
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EXAMPLE 14: PREPARATION OF AVERAGE CHAIN TRIGLYCERID NANOEMULSIONS [0114] Nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [0115] A combination of 100 g of purified water, 100 g of glycerin, 50 g of xylitol, 50 g of trehalose, 30 g of erythrol and 15 g of maltodextrin was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [0116] A combination of 170 g of medium chain triglyceride oil, 16 g of stearic acid, 14 g of sorbitan monostearate, 30 g of polyethylene glycol sorbitan monostearate and 30 g of hydrogenated castor oil PEG-40 were mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [0117] 180 g of a w / o nanoemulsion composed of 54 g of the aqueous phase and 120 g of the oil phase by dissolving 6 g of lutein was prepared following the procedure described in Example 2.
[0118] 300 g of an o / w nanoemulsion composed of 174 g of the aqueous phase and 120 g of the oil phase by dissolving 6 g of lutein was prepared following the procedure described in Example 2.
[0119] Both prepared nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
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26/38 [0120] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[0121] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 15: PREPARATION OF MEDIUM CHAIN TRIGLYCERIDE OIL NANOEMULSIONS CONTAINING COQ10 [0122] Nanoemulsions were prepared following the procedure described below.
PREPARING THE AQUEOUS PHASE OF NANOEMULSIONS [0123] A combination of 100 g of purified water, 100 g of glycerin, 50 g of xylitol, 50 g of trehalose, 35 g of erythrol and 15 g of maltodextrin was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [0124] A combination of 50 g of medium chain triglyceride oil, 50 g of fish oil, 10 g of stearic acid, 8 g of sorbitan monostearate, 20 g of polyethylene glycol sorbitan monostearate, and 20 g of hydrogenated castor oil PEG-40 was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [0125] 125 g of a w / o nanoemulsion composed of g of the aqueous phase and 100 g of the oil phase by dissolving 5 g of
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CoQ10 was prepared following the procedure described in
Example 2.
[0126] 100 g of an o / w nanoemulsion composed of 58 g of the aqueous phase and 40 g of the oil phase by dissolving 2 g of CoQ10 was prepared following the procedure described in Example 2.
[0127] Both prepared nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[0128] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[0129] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and all nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 16: PREPARATION OF SQUALENE TRIGLYCERID NANOEMULSIONS / KAPPIC CAPRICULES CONTAINING ISOSORBIDE DIN OR PHARMOTIDINE [0130] The nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [0131] A combination of 150 g of purified water, 150 g of urea, 40 g of propylene glycol was mixed by constant stirring in a beaker at 65-75 ° C to form the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [0132] A combination of 80 g squalene, 80 g caprylic capric triglyceride, 16 g stearic acid,
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28/38 g of sorbitan monostearate, 40 g of polyoxyethylene glycol stearate (40) and 40 g of hydrogenated castor oil PEG-40 was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form the oily phase.
PREPARATION OF NANOEMULSIONS [0133] 150 g of a w / o nanoemulsion composed of 60 g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2.
[0134] 150 g of an o / w nanoemulsion composed of 90 g of the aqueous phase and 60 g of the oil phase was prepared following the procedure described in Example 2.
[0135] 150 g of an o / a nanoemulsion composed of
88.5 g of the aqueous phase and 60 g of the oil phase dissolving 1.5 g of isosorbide dinitrate was prepared following the procedure described in Example 2.
[0136] 150 g of an o / a nanoemulsion composed of
88.5 g of the aqueous phase and 60 g of the oil phase dissolving 1.5 g of famotidine was prepared following the procedure described in Example 2.
[0137] All of the above nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[0138] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[0139] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and all
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29/38 nanoemulsions prepared in this example have passed the antimicrobial test.
EXAMPLE 17: PREPARATION OF SYNTHETIC OIL NANOEMULSIONS CONTAINING CURCUMIN OR TESTOSTERONE [0140] Nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [0141] A combination of 150 g of purified water, 150 g of urea, 40 g of propylene glycol was mixed with constant manual stirring in a 500 ml beaker at 65-75 ° C to form the aqueous phase .
PREPARING THE OIL PHASE OF A NANOEMULSION [0142] A combination of 80 g caprylic capric triglyceride, 40 g ethyl oleate, 40 g sorbitan oleate, 8 g beeswax, 8 g lauric acid, 8 g mono stearate sorbitan, and 64 g of polyoxyethylene glycol stearate (40) was mixed in a 400 ml beaker by means of constant manual stirring in a 400 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [0143] 135 g of a w / o nanoemulsion composed of g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2.
[0144] 135 g of a w / o nanoemulsion composed of g of the aqueous phase and 88.2 g of the oil phase by dissolving 1.8 g of testosterone was prepared following the procedure described in Example 2.
[0145] 135 g of a w / o nanoemulsion composed of g of the aqueous phase and 89.4 g of the oil phase dissolving 0.6 g
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30/38 curcumin was prepared following the procedure described in Example 2.
[0146] All of the above nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[0147] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[0148] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and all nanoemulsions prepared in this example passed the antimicrobial test.
EXAMPLE 18: PREPARATION OF A NANOEMULSION CONTAINING COQ10, VITAMIN A, VITAMIN E, AND VITAMIN D [0149] The nanoemulsion was prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSION [0150] A combination of 280 g of purified water, 240 g of glycerin, 48 g of urea, and 32 g of trehalose was mixed by means of constant manual stirring in a 500 ml beaker in 65- 75 ° C to form 600 g of the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [0151] A combination of 2.4 g CoQ10, 4.8 g vitamin A, 1.2 g vitamin D 1.2, 30 g vitamin E,
85.6 g of paraffin oil, 140 g of cyclomethicone (DC-345), 32 g of stearic acid, 24 g of sorbitan monostearate, 80 g of polyethylene glycol sorbitan monostearate was
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31/38 mixed by means of constant manual stirring in a 400 ml beaker at 65-75 ° C to form 400 g of the oil phase.
PREPARATION OF THE NANOEMULSION [0152] 1000 g of a w / o nanoemulsion composed of
600 g of the aqueous phase and 400 g of the oil phase was prepared following the procedure described in Example 2.
[0153] The above nanoemulsion was a clear and stable o / a nanoemulsion at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[0154] The type of nanoemulsion was determined following the procedure described in Example 1.
[0155] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and the nanoemulsion passed the antimicrobial test.
EXAMPLE 19: PREPARATION OF A NANOEMULSION OF VITAMIN AND / GRAPE SEED OIL / COCONUT / MONEY OIL / OIL
DE PARAFINA / CYCLOMETICONA [0156] The nanoemulsion was prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSION [0157] A combination of 168 g of purified water, 115 g of urea, 77 g of glycerin, 20 g of propylene glycol, 20 g of sodium pyrrolidine carbobixalate, and 20 g of trehalose was mixed by constant manual stirring medium in a 500 ml beaker at 65-75 ° C to form 420 g of the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE
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32/38 [0158] A combination of 30 g of vitamin E, 30 g of grape seed oil, 40 g of coconut oil, 8 g of mink oil, 24 g of paraffin oil, 60 g of cyclomethicone ( DC-345), 16 g of beeswax, 8 g of glyceryl monostearate, 19 g of stearic acid, 17 g of sorbitan monostearate, 50 g of hydrogenated castor oil PEG-40 and 28 g of polyoxyethylene glycol stearate ( 40) was mixed by means of constant manual stirring in a 400 ml beaker at 65-75 ° C to form 330 g of the oil phase.
PREPARATION OF THE NANOEMULSION [0159] 750 g of a nanoemulsion composed of 420 g of the aqueous phase and 330 g of the oil phase was prepared following the procedure described in Example 2.
[0160] The above nanoemulsion was a clear and stable o / a nanoemulsion at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[0161] The type of nanoemulsion was determined following the procedure described in Example 1.
[0162] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and the nanoemulsion passed the antimicrobial test.
EXAMPLE 20: PREPARATION OF A NANOEMULSION OF VITAMIN AND / GRAPE SEED OIL / COCONUT / VISON OIL / PARAFFIN OIL / CYCLOMETICONE [0163] The nanoemulsion was prepared following the procedure described below.
PREPARATION OF THE WATER PHASE OF NANOEMULSION
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33/38 [0164] purified, 115
A combination of 16 8 g water urea, 77 g glycerin, 20 g propylene glycol, 20 g sodium pyrrolidine carbobixalate, and 20 g trehalose was mixed by constant stirring in a 500 ml beaker at 65-75 ° C to form 420 g of the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [0165] A combination of 30 g of vitamin E, 30 g of grape seed oil, 40 g of coconut oil, 8 g of mink oil, 24 g of paraffin oil, 60 g of cyclomethicone (DC-345), 16 g of beeswax, 8 g of glyceryl monostearate, 19 g of stearic acid, 17 g of sorbitan monostearate, 50 g of hydrogenated castor oil PEG-40 and 28 g of polyethylene glycol stearate (40) was mixed by means of constant manual stirring in a 400 ml beaker at 65-75 ° C to form 33 g of the oil phase.
PREPARATION OF THE NANOEMULSION [0166] 750 g of a nanoemulsion composed of 420 g of the aqueous phase and 330 g of the oil phase was prepared following the procedure described in Example 2.
[0167] The above nanoemulsion was a clear and stable o / a nanoemulsion at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[0168] The type of nanoemulsion was determined following the procedure described in Example 1.
[0169] An antimicrobial test was conducted following the procedure described in USP 35 <51>,
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Antimicrobial Effectiveness Testing, on page 52, and the nanoemulsion passed the antimicrobial test.
EXAMPLE 21: PREPARATION OF A NANOEMULSION OF VITAMIN AND / GRAPE SEED OIL / COCONUT / MONEY OIL / OIL
DE PARAFINA / CYCLOMETICONA [0170] The nanoemulsion was prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSION [0171] A combination of 16 8 g of purified water, 115 g of urea, 77 g of glycerin, 20 g of propylene glycol, 20 g of sodium pyrrolidine carbobixalate, and 20 g of trehalose was mixed by means of constant manual stirring in a 500 ml beaker at 65-75 ° C to form 420 g of the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [0172] A combination of 30 g of vitamin E, 30 g of grape seed oil, 40 g of coconut oil, 8 g of mink oil, 24 g of paraffin oil, 60 g of cyclomethicone (DC-345), 16 g of beeswax, 8 g of glyceryl monostearate, 19 g of stearic acid, 17 g of sorbitan monostearate, 50 g of hydrogenated castor oil PEG-40 and 28 g of polyoxyethylene glycol stearate was mixed by means of constant manual stirring in a 400 ml beaker at 65-75 ° C to form 330 g of the oil phase.
PREPARATION OF THE NANOEMULSION [0173] 750 g of a nanoemulsion composed of 420 g of the aqueous phase and 330 g of the oil phase was prepared following the procedure described in Example 2.
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35/38 [0174] The above nanoemulsion was a clear and stable o / a nanoemulsion at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[0175] The type of nanoemulsion was determined following the procedure described in Example 1.
[0176] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and the nanoemulsion passed the antimicrobial test.
EXAMPLE 22: PREPARATION OF A NANOEMULSION OF VITAMIN AND / GRAPE SEED OIL / COCONUT / MONEY OIL / OIL
DE PARAFINA / CYCLOMETICONA [0177] The nanoemulsion was prepared following the procedure described below.
PREPARATION OF AQUEOUS PHASE OF NANOEMULSION [0178] A combination of 150 g of purified water, 150 g of urea, 40 g of propylene glycol was mixed by constant stirring in a beaker at 65-75 ° C to form 340 g of the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [017 9] A combination of 30 g of vitamin E, 30 g of grape seed oil, 40 g of coconut oil, 8 g of mink oil, 24 g of paraffin oil , 60 g of cyclomethicone (DC-345), 16 g of beeswax, 8 g of glyceryl monostearate, 19 g of stearic acid, 17 g of sorbitan monostearate, 50 g of hydrogenated castor oil PEG-40 and 28 g of polyoxyethylene glycol stearate (40) was mixed by stirring
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36/38 manual constant in a 400 ml beaker at 65-75 ° C to form 330 g of the oil phase.
PREPARATION OF THE NANOEMULSION [0180] 750 g of a nanoemulsion composed of 420 g of the aqueous phase and 330 g of the oil phase was prepared following the procedure described in Example 2.
[0181] The above nanoemulsion was a clear and stable o / a nanoemulsion at room temperature for at least 3 months. The nanoemulsion exhibited the Tyndall effect of light refraction.
[0182] The type of nanoemulsion was determined following the procedure described in Example 1.
[0183] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and the nanoemulsion passed the antimicrobial test.
EXAMPLE 23: PREPARATION OF ESSENTIAL OIL NANOEMULSIONS CONTAINING ONLY A HYDROPHYLIC SURFACTANT [0184] The nanoemulsions were prepared following the procedure described below.
PREPARATION OF THE AQUEOUS PHASE OF NANOEMULSIONS [0185] A combination of 200 g of purified water, 100 g of glycerin, 50 g of glucosamine and 50 g of methyl sulfonyl methane was mixed by means of constant manual stirring in a 500 ml beaker in 65-75 ° C to form the aqueous phase.
PREPARATION OF THE NANOEMULSION OIL PHASE [0186] A combination of 30 g of vitamin E, 30 g of grape seed oil, 40 g of coconut oil, 8 g of mink oil, 24 g of paraffin oil, 60 g of
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37/38 cyclomethicone (DC-345), 16 g of beeswax, 8 g of glyceryl monostearate, 19 g of stearic acid, 17 g of sorbitan monostearate and 68 g of hydrogenated castor oil PEG-40 was mixed by constant manual stirring in a 400 ml beaker at 65-75 ° C to form the oil phase.
PREPARATION OF NANOEMULSIONS [0187] 150 g of a w / o nanoemulsion composed of 60 g of the aqueous phase and 90 g of the oil phase was prepared following the procedure described in Example 2.
[0188] 150 g of an o / w nanoemulsion composed of 90 g of the aqueous phase and 60 g of the oil phase was prepared following the procedure described in Example 2.
[0189] The above nanoemulsions were clear and stable at room temperature for at least 3 months. They exhibited the Tyndall effect of refraction of light.
[0190] The type of each nanoemulsion prepared in this example was described following the procedure described in Example 1.
[0191] An antimicrobial test was conducted following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, on page 52, and the two nanoemulsions prepared in this example passed the antimicrobial test.
OTHER ACHIEVEMENTS [0192] All features revealed in this specification can be combined in any combination. Each feature revealed in this specification can be replaced by an alternative feature serving a similar, equivalent or the same purpose.
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Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.
[0193] From the above description, a person skilled in the art can easily determine the essential characteristics of the present invention, and without departing from the spirit and scope of this invention, can make several changes and modifications of the invention to adapt it to different uses and conditions . Thus, other achievements are also within the scope of the following claims.
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权利要求:
Claims (2)
[1]
1. NANOEMULSION, characterized by understanding:
(A) an aqueous phase including:
(1) water or an aqueous solution, and (2) a water-soluble organic nanostructure stabilizer, in which the water or aqueous solution has less than 75% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer. has a content of less than 99% by weight of the aqueous phase, and (B) an oil phase including:
(1) an oil or an oily solution, (2) an organic gel thickener, and (3) a hydrophilic surfactant having a hydrophilic-lipophilic equilibrium value greater than 8.0, in which the oil or oily solution has a content less than 80% by weight of the oil phase, the organic gel thickener has a content less than 60% by weight of the oil phase, and the hydrophilic surfactant has a content less than 60% by weight of the oil phase, where water or aqueous solution constitutes 2.5% by weight or more of the nanoemulsion, a weight ratio of the aqueous phase to the oil phase of 1: 40-100: 1, and the aqueous phase is dispersed as nanodimensioned droplets in the oil phase or the oil phase it is dispersed as nanodimensioned droplets in the aqueous phase.
2. NANOEMULSION, according to claim 1, characterized in that the oil phase is dispersed as nanodimensioned droplets in the aqueous phase.
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3. NANOEMULSION, according to claim 1, characterized in that the aqueous phase is dispersed as nanodimensioned droplets in the oil phase.
4. NANOEMULSION, according to claim 2, characterized in that the hydrophilic-lipophilic equilibrium value is greater than 10.
5. NANOEMULSION, according to claim 4, characterized in that the hydrophilic-lipophilic equilibrium value is greater than 13.
6. NANOEMULSION, according to claim 3, characterized in that the hydrophilic-lipophilic equilibrium value is greater than 10.
7. NANOEMULSION, according to claim 6, characterized in that the hydrophilic-lipophilic equilibrium value is greater than 13.
8. NANOEMULSION, according to claim 4, characterized in that the water-soluble organic nanostructure stabilizer is a water-soluble vitamin, water-soluble peptide, a water-soluble oligopeptide, a polyol, a water-soluble saccharide, a soluble oligosaccharide in water, a disaccharide, a monosaccharide, a hydrogenated carbohydrate, an amino acid, amino sugar or a combination of these; the oil is a vegetable oil, a silicone oil, a synthetic oil, a mineral oil, an animal oil, an essential oil or a combination thereof; and the organic gel thickener is saturated fatty acid, fatty acid alcohol, a fatty acid derivative having a melting point above 45 ° C or a combination thereof.
9. NANOEMULSION, according to claim 4, characterized by the organic nanostructure stabilizer
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3/9 water soluble be urea, methylsulfonylmethane, hydroxyethyl, urea, glucosamine, mannitol, sorbitol, xylitol, lactose, fructose, dextrose, ribose, trehalose, raffinose, maltitol, isomalt, lactitol, erythritol, inositol, propylene glycol, taurine , dipropylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, ethoxydiglycol, carnitine, arginine, sodium pyrolidine carboxylic acid and hydrolyzed collagen, or a combination thereof; the oil is coconut oil, palm oil, grape seed oil, olive oil, avocado oil, evening primrose oil, tea tree essential oil, eucalyptus oil, lavender oil, rosemary oil, horse fat, fish, lanolin oil, squalene, cyclomethicone, cyclopentassiloxane, phenyl trimethicone, caprylic / capric triglyceride, isopropyl myristate, isostearyl isostearate, decyl oleate, ethylexyl isononate, isoexadecane, octyldodecene, polyethine, polyethine, paraffin oil, paraffin oil a combination of these; the organic gel thickener is stearic acid, lauric acid, glycerol monostearate, PEG 6000 diesterate, monoglyceride, diglyceride, saccharide fatty acid ester, propylene glycol fatty acid ester, glycol fatty acid ester, decylhexyl fatty acid ester, fatty acid alcohol, cetylesterate, ascorbyl fatty esters, glyceryl fatty esters, hexyldecyl fatty esters or a combination thereof; and the hydrophilic surfactant includes Tween 20, Tween 21, Tween 60, Tween 61, Tween 65, Tween 80, Tween 81, Tween 85, Myri 45, Myri 52, Myri 53, Myri 59, Myri 45, Myri 52, Myri 53, Myri 59, Brij 30, Brij 35, Brij 56, Brij 58, Brij 76, Brij 78, Brij 96, Brij 97, Brij 98, Brij 99, nonylphenol alkoxylates, alkyl alkoxylates, Pluronic F45 / 59
4/9
127, PEG dimethicone, polyoxyethylene fatty acid ester (40), polyoxyethylene saccharide fatty acid ester (20), glyceryl fatty acid ester PEG-15, hydrogenated castor oil PEG-35, hydrogenated castor oil PEG- 40, polyglycerol fatty acid ester, derivatives of fatty amines, or a combination thereof.
10. NANOEMULSION, according to claim 9, characterized in that the hydrophilic-lipophilic equilibrium value is greater than 13; the water or aqueous solution has a content of less than 60% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 50% by weight of the aqueous phase; the oil or oily solution has a content of 45-65% by weight of the oily phase, the organic gel thickener has a content of less than 25% by weight of the oily phase, and the hydrophilic surfactant has a content of less than 35% by weight the oily phase; the water or aqueous solution constitutes 30% by weight or less of the nanoemulsion and a weight ratio of the aqueous phase to the oil phase of 1: 2-3: 1; and the nanoemulsion has a pH of 3-11 and is transparent or translucent.
11. NANOEMULSION, according to claim 6, characterized in that the water-soluble organic nanostructure stabilizer is a water-soluble vitamin, water-soluble peptide, a water-soluble oligopeptide, a polyol, a water-soluble saccharide, a soluble oligosaccharide in water, a disaccharide, a monosaccharide, a hydrogenated carbohydrate, an amino acid, amino sugar, or a combination of these; the oil is a vegetable oil, a silicone oil, a synthetic oil, a mineral oil, an oil of animal origin, an essential oil, or a combination of these; and the organic gel thickener is saturated fatty acid, fatty acid alcohol,
46/59
5/9 a fatty acid derivative having a melting point above
45 ° C, or a combination of these.
12. NANOEMULSION, according to claim 4, characterized in that the water-soluble organic nanostructure stabilizer is urea, methylsulfonylmethane, hydroxyethyl, urea, glucosamine, mannitol, sorbitol, xylitol, lactose, fructose, dextrose, ribose, trehalose, raffinose, maltol , isomalt, lactitol, erythritol, inositol, taurine, glycerin, propylene glycol, dipropylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, ethoxydiglycol, carnitine, arginine, sodium pyrolidine carboxylic acid and a hydrolyzed combination; the oil is coconut oil, palm oil, grape seed oil, grapefruit seed oil, olive oil, avocado oil, evening primrose oil, tea tree essential oil, eucalyptus oil, lavender oil, rosemary oil, horse fat, fish oils, lanolin oil, squalene, cyclomethicone, cyclopentassiloxane, phenyl trimethicone, caprylic / capric triglyceride, isopropyl myristate, isostearyl isostearate, decyl oleate, ethylhexyl isononate, isoexadecane, paraxydodine polydecene, polyisobutene, menthol or a combination thereof; the organic gel thickener is stearic acid, lauric acid, glycerol monostearate, PEG 6000 diesterate, monoglyceride, diglyceride, saccharide fatty acid ester, propylene glycol fatty acid ester, glycol fatty acid ester, decylhexyl fatty acid ester, fatty acid alcohol, cetylesterate, ascorbyl fatty esters, glyceryl fatty esters, hexyldecyl fatty esters or a combination thereof; and the hydrophilic surfactant includes Tween 20, Tween 21, Tween 60, Tween 61,
47/59
6/9
Tween 65, Tween 80, Tween 81, Tween 85, Myri 45, Myri 52, Myri 53, Myri 59, Myri 45, Myri 52, Myri 53, Myri 59, Brij 30, Brij 35, Brij 56, Brij 58, Brij 76 , Brij 78, Brij 96, Brij 97, Brij 98, Brij 99, nonylphenol alkoxylates, alkyl alkoxylates, Pluronic F-127, PEG dimethicone, polyoxyethylene fatty acid ester (40), polyoxyethylene saccharide fatty acid ester (20 ), glycerol fatty acid ester PEG-15, hydrogenated castor oil PEG-35, hydrogenated castor oil PEG-40, polyglycerol fatty acid ester, derivatives of fatty amines, or a combination thereof.
13. NANOEMULSION, according to claim 12, characterized in that the hydrophilic-lipophilic equilibrium value is greater than 13; the water or aqueous solution has a content of less than 60% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 50% by weight of the aqueous phase; the oil or oily solution has a content of 45-65% by weight of the oily phase, the organic gel thickener has a content of less than 25% by weight of the oily phase, and the hydrophilic surfactant has a content of less than 35% by weight the oily phase; the water or aqueous solution constitutes 30% by weight or less of the nanoemulsion and a weight ratio of the aqueous phase to the oil phase of 1: 2-3: 1; and the nanoemulsion has a pH of 3-11 and is transparent or translucent.
14. NANOEMULSION, according to claim 8, characterized in that the water or aqueous solution of the nanoemulsion has a content of less than 60% by weight of the aqueous phase and the stabilizer of water-soluble organic nanostructure has a content of less than 70% in weight of the aqueous phase; the oil or oily solution has a content of 30-70% by weight of the oil phase,
48/59
7/9 the organic gel thickener has a content of less than 45% by weight of the oil phase, and the hydrophilic surfactant has a content of less than 45% by weight of the oil phase; and the water or aqueous solution constitutes 38% by weight or less of the nanoemulsion and a weight ratio of the aqueous phase to the oil phase of 1: 34: 1.
NANOEMULSION, according to claim 14, characterized in that the water or aqueous solution of the nanoemulsion has a content of less than 45% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 50% by weight of the aqueous phase; the oil or oily solution has a content of 45-65% by weight of the oil phase, the organic gel thickener has a content of less than 25% by weight of the oil phase, and the hydrophilic surfactant has a content of less than 35% by weight the oily phase; and the water or aqueous solution constitutes 30% by weight or less of the nanoemulsion and a weight ratio of the aqueous phase to the oil phase of 1: 23: 1.
16. NANOEMULSION, according to claim 11, characterized in that the water or aqueous solution of the nanoemulsion has a content of less than 60% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 70% in weight of the aqueous phase; the oil or oily solution has a content of 30-70% by weight of the oil phase, the organic gel thickener has a content of less than 45% by weight of the oil phase, and the hydrophilic surfactant has a content of less than 45% by weight the oily phase; and the water or aqueous solution constitutes 38% by weight or less of the nanoemulsion and a weight ratio of the aqueous phase to the oil phase of 1: 34: 1.
49/59
8/9
17. NANOEMULSION, according to claim 16, characterized in that the water or aqueous solution of the nanoemulsion has a content of less than 45% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer has a content of less than 50% by weight of the aqueous phase; the oil or oily solution has a content of 45-65% by weight of the oily phase, the organic gel thickener has a content of less than 25% by weight of the oily phase, and the hydrophilic surfactant has a content of less than 35% by weight the oily phase; and the water or aqueous solution constitutes 30% by weight or less of the nanoemulsion and a weight ratio of the aqueous phase to the oil phase of 1: 23: 1.
18. NANOEMULSION, according with the claim 15, characterized by the nanoemulsion having one pH of 3-11 and to be transparent or translucent. 19. NANOEMULSION, according with the claim 17, characterized by the nanoemulsion having one pH of 3-11 and to be
transparent or translucent.
20. NANOEMULSION, according to claim 1, characterized in that the nanoemulsion has a pH of 3-11 and is transparent or translucent.
21. NANOEMULSION, according to claim 1, characterized by the nanoemulsion being self-preserving.
22. NANOEMULSION, according to claim 1, characterized in that the nanoemulsion is a cosmetic product, a pharmaceutical product, a food product, a household chemical, an agricultural product, a printing product, a dye product, a veterinary product, or a diagnostic product.
50/59
9/9
23. METHOD FOR PREPARING A NANOEMULSION, the method being characterized by understanding:
(1) mixing the water or the aqueous solution and the soluble organic nanostructure stabilizer to form an aqueous phase, wherein the water or aqueous solution has a content of less than 75% by weight of the aqueous phase and the soluble organic nanostructure stabilizer in water has less than 99% by weight of the aqueous phase;
[2]
(2) mixture of an oil or aqueous solution, an organic thickener, and a hydrophilic surfactant having a hydrophilic-lipophilic equilibrium value greater than 8.0 to form an oily phase, in which the oil or oily solution has a content less than 80% by weight of the oil phase, the organic gel thickener has a content of less than 60% by weight of the oil phase, and the hydrophilic surfactant has a content of less than 60% by weight of the oil phase; and (3) mixing the aqueous phase and the oil phase, a weight ratio of the aqueous phase to the oil phase being 1: 40-100: 1, to form a nanoemulsion, in which water or aqueous solution constitutes 74% by weight or less of the nanoemulsion;
wherein the aqueous phase is dispersed as nano-sized droplets in the oil phase or the oil phase is dispersed as nano-sized droplets in the aqueous phase.
51/59
1/1

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US9872832B2|2018-01-23|

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EP3159012B1|2019-08-14|

DK3159012T3|2019-11-11|

CA2945444A1|2017-04-23|

TW201714605A|2017-05-01|

SG10201608533VA|2017-05-30|

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法律状态:
2018-03-27| B03A| Publication of a patent application or of a certificate of addition of invention [chapter 3.1 patent gazette]|

2020-01-28| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |

2020-08-04| B07E| Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]|

2020-08-18| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

优先权:

申请号 | 申请日 | 专利标题

US14/921,572|US9872832B2|2015-10-23|2015-10-23|Nanoemulsions having reversible continuous and dispersed phases|

US14/921,572|2015-10-23|

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