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HK1235699B - Nanoemulsions having reversible continuous and dispersed phases - Google Patents

Nanoemulsions having reversible continuous and dispersed phases

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Publication number
HK1235699B
HK1235699B HK17109610.2A HK17109610A HK1235699B HK 1235699 B HK1235699 B HK 1235699B HK 17109610 A HK17109610 A HK 17109610A HK 1235699 B HK1235699 B HK 1235699B
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nanoemulsion
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HK1235699A1 (en
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巫建嶔
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长春纳米生技公司
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Description

具有可逆的连续及分散相的纳米乳液Nanoemulsions with reversible continuous and dispersed phases

背景技术Background Art

存在两种类型的纳米乳液,即,水包油(o/w)纳米乳液及油包水(w/o)纳米乳液。o/w纳米乳液具有连续水相及分散油相,而w/o纳米乳液具有连续油相及分散水相。There are two types of nanoemulsions, namely, oil-in-water (o/w) nanoemulsions and water-in-oil (w/o) nanoemulsions. O/w nanoemulsions have a continuous water phase and a dispersed oil phase, while w/o nanoemulsions have a continuous oil phase and a dispersed water phase.

这两种类型的纳米乳液通过具有不同亲水性亲脂性平衡(HLB)值的乳化剂得以稳定。o/w纳米乳液通过HLB值为8至28的乳化剂得以稳定,且w/o分散液通过HLB值为3至6的乳化剂得以稳定。因此,其无法轻易地进行相互转化。These two types of nanoemulsions are stabilized by emulsifiers with different hydrophilic-lipophilic balance (HLB) values. O/w nanoemulsions are stabilized by emulsifiers with HLB values of 8 to 28, and w/o dispersions are stabilized by emulsifiers with HLB values of 3 to 6. Therefore, they cannot be easily converted into each other.

缺乏可易转化性可能会存在问题。当o/w纳米乳液的含水量降低时,其会发生崩解。同样,当w/o纳米乳液的含油量降低时,其会发生崩解。Lack of easy convertibility can be problematic. When the water content of an o/w nanoemulsion decreases, it can disintegrate. Similarly, when the oil content of a w/o nanoemulsion decreases, it can disintegrate.

因此,需要研发一种纳米乳液,其连续相及分散相可经该纳米乳液中所包含的同一乳化剂容易进行相互转化。Therefore, it is necessary to develop a nanoemulsion whose continuous phase and dispersed phase can be easily converted into each other via the same emulsifier contained in the nanoemulsion.

发明内容Summary of the Invention

本文公开了一种含有可逆的连续及分散相的纳米乳液。Disclosed herein is a nanoemulsion containing reversible continuous and dispersed phases.

本发明的纳米乳液包括水相及油相,水相与油相的重量比为1∶40至100∶1。在纳米乳液中,水相以纳米级小液滴形式(作为纳米尺寸的液滴,nanosized droplet)分散于油相中或油相以纳米级小液滴形式分散于水相中。占纳米乳液的2.5重量%以上的水相含有水或水溶液及水溶性有机纳米结构稳定剂。按水相的重量计,水或水溶液的含量小于75%,且按水相的重量计,水溶性有机纳米结构稳定剂的含量小于99%。油相含有油或油溶液、有机凝胶增稠剂及HLB值大于8.0的亲水性表面活性剂。按油相的重量计,油或油溶液的含量小于80%,按油相的重量计,有机凝胶增稠剂的含量小于60%,且按油相的重量计,亲水性表面活性剂的含量小于60%。此纳米乳液可用作化妆品、食品或医药组合物中的活性成分的载体。The nanoemulsion of the present invention comprises an aqueous phase and an oil phase, with the weight ratio of the aqueous phase to the oil phase being 1:40 to 100:1. In the nanoemulsion, the aqueous phase is dispersed in the oil phase in the form of nanosized droplets, or the oil phase is dispersed in the aqueous phase in the form of nanosized droplets. The aqueous phase, which accounts for at least 2.5% by weight of the nanoemulsion, contains water or an aqueous solution and a water-soluble organic nanostructure stabilizer. The water or aqueous solution comprises less than 75% by weight of the aqueous phase, and the water-soluble organic nanostructure stabilizer comprises less than 99% by weight of the aqueous phase. The oil phase comprises oil or an oil solution, an organogel thickener, and a hydrophilic surfactant having an HLB value greater than 8.0. The oil or oil solution comprises less than 80% by weight of the oil phase, the organogel thickener comprises less than 60% by weight of the oil phase, and the hydrophilic surfactant comprises less than 60% by weight of the oil phase. This nanoemulsion can be used as a carrier of active ingredients in cosmetic, food or pharmaceutical compositions.

用于制备上述纳米乳液的方法也在本发明的范围内。该方法包括以下步骤:(1)将水或水溶液与水溶性有机纳米结构稳定剂混合以形成水相,其中按水相的重量计,水或水溶液的含量小于75%,且按水相的重量计,水溶性有机纳米结构稳定剂的含量小于99%;(2)将油或油溶液、有机增稠剂及亲水性亲脂性平衡值大于8.0的亲水性表面活性剂混合以形成油相,其中按油相的重量计,油或油溶液的含量小于80%,按油相的重量计,有机凝胶增稠剂的含量小于60%,且按油相的重量计,亲水性表面活性剂的含量小于60%;及(3)将水相与油相混合以形成纳米乳液,水相与油相的重量比为1∶40至100∶1,其中水或水溶液占纳米乳液的74重量%以下。在适合温度,例如,5℃至95℃下,进行混合步骤中的每一个。The present invention also provides a method for preparing the nanoemulsion. The method comprises the following steps: (1) mixing water or an aqueous solution with a water-soluble organic nanostructure stabilizer to form an aqueous phase, wherein the water or aqueous solution comprises less than 75% by weight of the aqueous phase and the water-soluble organic nanostructure stabilizer comprises less than 99% by weight of the aqueous phase; (2) mixing an oil or an oil solution, an organic thickener, and a hydrophilic surfactant having a hydrophilic-lipophilic balance greater than 8.0 to form an oil phase, wherein the oil or oil solution comprises less than 80% by weight of the oil phase, the organic gel thickener comprises less than 60% by weight of the oil phase, and the hydrophilic surfactant comprises less than 60% by weight of the oil phase; and (3) mixing the aqueous phase with the oil phase to form a nanoemulsion, wherein the weight ratio of the aqueous phase to the oil phase is from 1:40 to 100:1, wherein the water or aqueous solution comprises less than 74% by weight of the nanoemulsion. Each of the mixing steps is performed at a suitable temperature, for example, from 5°C to 95°C.

在由此制得的纳米乳液中,水相以纳米级小液滴形式分散于油相中或油相以纳米级小液滴形式分散于水相中。换言之,纳米乳液中的连续及分散相为可逆的。In the nanoemulsion thus prepared, the aqueous phase is dispersed in the oil phase in the form of nanoscale droplets, or the oil phase is dispersed in the aqueous phase in the form of nanoscale droplets. In other words, the continuous and dispersed phases in the nanoemulsion are reversible.

一个或多个实施例的细节阐述于以下描述中。实施例的其他特征、目的及优点将由说明书与权利要求书变得显而易见。The details of one or more embodiments are set forth in the description below. Other features, objects, and advantages of the embodiments will become apparent from the description and claims.

具体实施方式DETAILED DESCRIPTION

本发明至少部分基于一项意外发现,即含有HLB值大于8的亲水性表面活性剂的纳米乳液可具有以纳米级小液滴形式分散于油相中的水相或以纳米级小液滴形式分散于水相中的油相。换言之,纳米乳液具有可逆的连续及分散相。The present invention is based, at least in part, on the unexpected discovery that nanoemulsions containing hydrophilic surfactants having an HLB value greater than 8 can have an aqueous phase dispersed in an oil phase as nanosized droplets, or an oil phase dispersed in an aqueous phase as nanosized droplets. In other words, the nanoemulsions have reversible continuous and dispersed phases.

此纳米乳液可带有油溶性活性成分及水溶性活性成分,其为优于现有纳米乳液的优点。该优点在制备化妆品、食品、家用化学品、农业用产品、印刷产品、染色产品、兽医用产品、诊断产品、疫苗及医药产品方面尤其至关重要,如以下两个实例所说明。This nanoemulsion can carry both oil-soluble and water-soluble active ingredients, which is an advantage over existing nanoemulsions. This advantage is particularly important in the preparation of cosmetics, foods, household chemicals, agricultural products, printing products, dyeing products, veterinary products, diagnostic products, vaccines, and pharmaceutical products, as illustrated in the following two examples.

o/w分散液优选用于化妆品中,因为相较于w/o分散液,其较不具有粘性及油脂性且具有期望的持水能力。然而,当将化妆品涂覆至皮肤或暴露于空气时,化妆品中的纳米乳液会经由蒸发而损失水。水损失会导致现有o/w纳米乳液崩解,而本发明的o/w纳米乳液则不会。取而代之,后一纳米乳液会缓慢转化成w/o纳米乳液,其中其水相以纳米级小液滴形式均匀地分散于其油相中。O/W dispersions are preferred for use in cosmetics because they are less viscous and greasy than W/O dispersions and have a desirable water-holding capacity. However, when the cosmetic is applied to the skin or exposed to air, the nanoemulsion in the cosmetic loses water through evaporation. This water loss causes existing O/W nanoemulsions to disintegrate, but the O/W nanoemulsions of the present invention do not. Instead, the latter nanoemulsion slowly transforms into a W/O nanoemulsion, in which the aqueous phase is uniformly dispersed in the oil phase as nanoscale droplets.

不同地,对于油溶性药物,优选使用w/o分散液,归因于其负载量高。然而,当w/o纳米乳液开始与体液接触时,由于体液为含水的,其含水量必然会有所增加。因此,现有w/o纳米乳液会发生崩解。而本发明的w/o纳米乳液会缓慢转化成o/w纳米乳液,其中其油相以纳米级小液滴形式均匀地分散于其水相中。值得注意的是,转化不仅会维持纳米乳液的完整性且也会提供其中的药物的持续释放。Differently, for oil-soluble drugs, w/o dispersions are preferred due to their high loading capacity. However, when a w/o nanoemulsion comes into contact with body fluids, since the body fluids are aqueous, their water content inevitably increases. Consequently, existing w/o nanoemulsions disintegrate. The w/o nanoemulsions of the present invention, on the other hand, slowly transform into o/w nanoemulsions, in which the oil phase is uniformly dispersed in the aqueous phase as nanoscale droplets. Notably, this transformation not only maintains the integrity of the nanoemulsion but also provides for sustained release of the drug therein.

如上文所指出,本发明的纳米乳液包括水相及油相。在纳米乳液中,水相可以纳米级小液滴形式分散于油相中。或者,油相可以纳米级小液滴形式分散于水相中。As noted above, the nanoemulsions of the present invention comprise an aqueous phase and an oily phase. In the nanoemulsion, the aqueous phase can be dispersed in the oily phase in the form of nanoscale droplets. Alternatively, the oily phase can be dispersed in the aqueous phase in the form of nanoscale droplets.

水相包括水溶性有机纳米结构稳定剂。术语“水溶性有机纳米结构稳定剂”在本文中是指可使纳米乳液的各向同性结构稳定,由此产生热力学上稳定的透明或半透明纳米乳液的任何水溶性有机成分。其可为水溶性维生素、水溶性肽、水溶性寡肽、多元醇、水溶性糖、水溶性寡糖、二糖、单糖、氢化碳水化合物、氨基酸、氨基糖或其组合。特定实例包括脲、甲基磺酰基甲烷、羟乙基脲、葡糖胺、甘露糖醇、山梨糖醇、木糖醇、乳糖、果糖、右旋糖、核糖、海藻糖、棉子糖、麦芽糖醇、异麦芽糖、乳糖醇、赤藻糖醇、肌醇、牛磺酸、甘油、丙二醇、二丙二醇、丁二醇、己二醇、聚乙二醇、乙氧基二甘醇、肉毒碱、精氨酸、吡咯烷酮甲酸钠及水解胶原蛋白。The aqueous phase includes a water-soluble organic nanostructure stabilizer. The term "water-soluble organic nanostructure stabilizer" refers to any water-soluble organic component that can stabilize the isotropic structure of the nanoemulsion, thereby producing a thermodynamically stable transparent or translucent nanoemulsion. It can be a water-soluble vitamin, a water-soluble peptide, a water-soluble oligopeptide, a polyol, a water-soluble sugar, a water-soluble oligosaccharide, a disaccharide, a monosaccharide, a hydrogenated carbohydrate, an amino acid, an amino sugar, or a combination thereof. Specific examples include urea, methylsulfonylmethane, hydroxyethyl urea, glucosamine, mannitol, sorbitol, xylitol, lactose, fructose, dextrose, ribose, trehalose, raffinose, maltitol, isomaltose, lactitol, erythritol, inositol, taurine, glycerol, propylene glycol, dipropylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, ethoxydiglycol, carnitine, arginine, sodium pyrrolidone formate, and hydrolyzed collagen.

油相含有油或油溶液。可使用植物油、有机硅油、合成油、矿物油、动物油、精油或其组合来形成油相。特定实例包括椰子油、棕榈油、葡萄籽油、橄榄油、柚子油、亚麻籽油、鳄梨油、月见草油(evening primrose oil)、熏衣草油、迷迭香油、茶树油、桉树油、马脂、鱼油、羊毛脂油、角鲨烯(squalene)、环甲硅油(cyclomethicone)、环戊硅氧烷、苯基三甲基聚硅氧烷、辛酸/癸酸三甘油酯、肉豆蔻酸异丙酯、异硬脂酸异硬脂基酯、油酸癸酯、异壬酸乙基己酯、异十六烷、辛基十二醇、石蜡油、聚癸烯、聚异丁烯、薄荷醇或其组合。应注意,油溶液含有一种或多种作为用于溶解一种或多种油溶性溶质的溶剂的油。The oil phase contains oil or oil solution. Vegetable oil, silicone oil, synthetic oil, mineral oil, animal oil, essential oil or its combination can be used to form the oil phase. Specific examples include coconut oil, palm oil, grape seed oil, olive oil, grapefruit oil, linseed oil, avocado oil, evening primrose oil (evening primrose oil), lavender oil, rosemary oil, tea tree oil, eucalyptus oil, horse fat, fish oil, lanolin oil, squalene (squalene), cyclomethicone (cyclomethicone), cyclopentasiloxane, phenyl trimethicone, caprylic acid/capric triglyceride, isopropyl myristate, isostearyl isostearate, decyl oleate, ethylhexyl isononanoate, isohexadecane, octyldodecanol, paraffin oil, polydecene, polyisobutene, menthol or its combination. It should be noted that the oil solution contains one or more oils as the solvent for dissolving one or more oil-soluble solutes.

也如上文所指出,油相包括HLB值大于8.0的亲水性表面活性剂。优选地,亲水性表面活性剂的HLB值大于10,且更优选地,HLB值大于13。亲水性表面活性剂的实例包括聚氧乙烯脱水山梨糖醇脂肪酸酯(Tween 20、Tween 21、Tween 60、Tween 61、Tween 65、Tween 80、Tween 81、Tween 85)、聚氧乙烯山梨糖醇脂肪酸酯、聚氧乙烯酸酯脂肪酸酯(Myri 45、Myri52、Myri 53、Myri 59)、聚氧乙烯酸脂肪酸酯(Myri 45、Myri 52、Myri 53、Myri 59)、聚氧伸乙基醇酯(Brij 30、Brij 35、Brij 56、Brij 58、Brij 76、Brij 78、Brij 96、Brij 97、Brij 98、Brij 99)、壬基苯酚烷氧基化物(WitconolTM基于壬基苯酚的非离子表面活性剂)、烷基烷氧基化物(EthylanTM家族非离子表面活性剂)、Pluronic F-127、PEG二甲硅油、聚氧乙烯(40)脂肪酸酯、聚氧乙烯(20)糖脂肪酸酯、PEG-15甘油脂肪酸酯、PEG-35氢化蓖麻油、PEG-40氢化蓖麻油、聚甘油脂肪酸酯、脂肪胺衍生物或其组合。As also noted above, the oil phase includes a hydrophilic surfactant having an HLB value greater than 8.0. Preferably, the hydrophilic surfactant has an HLB value greater than 10, and more preferably, an HLB value greater than 13. Examples of the 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 sorbitan fatty acid esters, polyoxyethylene acid ester fatty acid esters (Myri 45, Myri 52, Myri 53, Myri 59), polyoxyethylene acid fatty acid esters (Myri 45, Myri 52, Myri 53, Myri 59), polyoxyethylene alcohol esters (Brij 30, Brij 35, Brij 56, Brij 58, Brij 76, Brij 78, Brij 96, Brij 97, Brij 98, Brij 99), nonylphenol alkoxylates (Witconol TM non-ionic surfactants based on nonylphenol), alkyl alkoxylates (Ethylan family of non-ionic surfactants), Pluronic F-127, PEG dimethicone, polyoxyethylene (40) fatty acid esters, polyoxyethylene (20) sugar fatty acid esters, PEG-15 glyceryl fatty acid esters, PEG-35 hydrogenated castor oil, PEG-40 hydrogenated castor oil, polyglyceryl fatty acid esters, fatty amine derivatives, or combinations thereof.

此外,油相含有有机凝胶增稠剂。术语“有机凝胶增稠剂”在本文中是指提高粘度且引起纳米乳液结构性形成的任何物质。有机凝胶增稠剂可为饱和脂肪酸、脂肪酸醇、熔点大于45℃的脂肪酸衍生物或其组合。有机凝胶增稠剂的实例包括硬脂酸、月桂酸、甘油单硬脂酸酯、PEG 6000 Diesterate、单甘油酯、二甘油酯、糖脂肪酸酯、丙二醇脂肪酸酯、二醇脂肪酸酯、脂肪酸己基癸酯、脂肪酸醇、硬脂酸十六烷酯、抗坏血酸脂肪酸酯、甘油脂肪酸酯、脂肪酸己基癸酯或其组合。In addition, the oil phase contains an organogel thickener. The term "organogel thickener" herein refers to any substance that increases viscosity and causes the structured formation of the nanoemulsion. The organogel thickener can be a saturated fatty acid, a fatty acid alcohol, a fatty acid derivative having a melting point greater than 45°C, or a combination thereof. Examples of organogel thickeners include stearic acid, lauric acid, glyceryl monostearate, PEG 6000 Diesterate, monoglycerides, diglycerides, sugar fatty acid esters, propylene glycol fatty acid esters, glycol fatty acid esters, fatty acid hexyldecyl esters, fatty acid alcohols, cetyl stearate, ascorbic acid fatty acid esters, glyceryl fatty acid esters, fatty acid hexyldecyl esters, or a combination thereof.

在一个实施例中,按水相的重量计,本发明的纳米乳液的水或水溶液的含量小于60%,且按水相的重量计,水溶性有机纳米结构稳定剂的含量小于70%;按油相的重量计,油或油溶液的含量为30%至70%,按油相的重量计,有机凝胶增稠剂的含量小于45%,且按油相的重量计,亲水性表面活性剂的含量小于45%;且水或水溶液占纳米乳液的38重量%以下,且水相与油相的重量比为1∶3至4∶1。优选地,按水相的重量计,水或水溶液的含量小于45%,且按水相的重量计,水溶性有机纳米结构稳定剂的含量小于50%;按油相的重量计,油或油溶液的含量小于45%至65%,按油相的重量计,有机凝胶增稠剂的含量小于25%,且按油相的重量计,亲水性表面活性剂的含量小于35%;且水或水溶液占纳米乳液的30重量%以下,且水相与油相的重量比为1∶2至3∶1。In one embodiment, the nanoemulsion of the present invention has a water or aqueous solution content of less than 60% by weight of the aqueous phase, and a water-soluble organic nanostructure stabilizer content of less than 70% by weight of the aqueous phase; the oil or oil solution content is 30% to 70% by weight of the oil phase, the organogel thickener content is less than 45% by weight of the oil phase, and the hydrophilic surfactant content is less than 45% by weight of the oil phase; the water or aqueous solution accounts for less than 38% by weight of the nanoemulsion, and the weight ratio of the aqueous phase to the oil phase is 1:3 to 4:1. Preferably, the content of water or aqueous solution is less than 45% by weight of the aqueous phase, and the content of water-soluble organic nanostructure stabilizer is less than 50% by weight of the aqueous phase; the content of oil or oil solution is less than 45% to 65% by weight of the oil phase, the content of organic gel thickener is less than 25% by weight of the oil phase, and the content of hydrophilic surfactant is less than 35% by weight of the oil phase; and the water or aqueous solution accounts for less than 30% by weight of the nanoemulsion, and the weight ratio of the aqueous phase to the oil phase is 1:2 to 3:1.

本发明的纳米乳液为透明或半透明的,其在3至11的pH下呈固态凝胶形式或液态形式。此外,其展现纳米特征,即,廷得尔光折射效应(Tyndall light refractioneffect)。参见Gold and Silver Nanoparticles,Center for Nanoscale Chemical-Electrical-Mechanical Manufacturing Systems,University of Illinois,http://Nano-cemms.illinois.edu/media/content/teaching_mats/online/gold_and_silver_nanoparticles/docs/presentation.pdf。The nanoemulsions of the present invention are transparent or translucent and are in solid gel form or liquid form at a pH of 3 to 11. In addition, they exhibit nano features, namely, the Tyndall light refraction effect. See Gold and Silver Nanoparticles, Center for Nanoscale Chemical-Electrical-Mechanical Manufacturing Systems, University of Illinois, http://Nano-cemms.illinois.edu/media/content/teaching_mats/online/gold_and_silver_nanoparticles/docs/presentation.pdf.

水或水溶液占纳米乳液的38重量%以下的本发明的纳米乳液具有自身防腐能力,且因此不需要在其中包括抗微生物防腐剂。防腐剂通常会引发安全性问题,因为其可能会造成介于轻度头痛至最严重疾病,例如癌症范围内的健康危害。The nanoemulsions of the present invention, wherein water or an aqueous solution comprises less than 38% by weight of the nanoemulsion, are self-preservative and therefore do not require the inclusion of an antimicrobial preservative. Preservatives generally raise safety concerns because they can cause health hazards ranging from mild headaches to the most serious diseases, such as cancer.

当用于化妆品、食品及医药组合物中时,此纳米乳液可带有各种活性成分,例如,特比萘芬(terbinafine)、双氯芬酸二乙胺、辣椒碱(capsaicin)、安定(diazepam)、劳拉西泮(lorazepam)、异丙酚、甲硝哒唑、吲哚美辛(indomethacine)、克霉唑、酮康唑、红霉素、甘宝素、活动素、联苯苄唑、咪康唑、托萘酯、氯倍他索、益康唑、胺苯甲酸乙酯、苯妥英(phenytoin)、洛伐他汀(lovastatin)、异山梨醇二硝酸酯、硝化甘油、法莫替丁(farmotidine)、没药醇、叶黄素酯、抑黑素、油溶性维生素、西红柿红素、白藜芦醇(resveratrol)、人参皂苷(ginsenoiside)、香草基丁基醚、姜黄素及CoQ10。可经由各种途径,例如,口服、局部、阴道、经直肠、舌下、肺部及非经肠来投与包括药物的纳米乳液。如果需要,也可添加某些甜味剂、调味剂、着色剂或芳香剂。When used in cosmetic, food, and pharmaceutical compositions, the nanoemulsion can carry various active ingredients, for example, terbinafine, diclofenac diethylamide, capsaicin, diazepam, lorazepam, propofol, metronidazole, indomethacin, clotrimazole, ketoconazole, erythromycin, climbazole, actin, bifonazole, miconazole, tolnaftate, clobetasol, econazole, ethyl benzoate, phenytoin, lovastatin, isosorbide dinitrate, nitroglycerin, famotidine, bisabolol, lutein esters, melanin, oil-soluble vitamins, lycopene, resveratrol, ginsenosides, vanillyl butyl ether, curcumin, and CoQ10. Nanoemulsions comprising drugs can be administered via various routes, for example, orally, topically, vaginally, rectally, sublingually, pulmonaryly and parenterally. If desired, certain sweeteners, flavorings, colorings or aromas may also be added.

用于制备上述纳米乳液的本发明的方法包括首先分别形成水相及油相,且随后将两种相混合。可通过持续搅拌(手动或以其他方式)、高速及高剪切混合(例如,使用胶体研磨机)、高压混合(例如,使用微流化剂)或音波处理混合来混合水或水溶液及水溶性有机纳米结构稳定剂以形成水相。油或油溶液、有机增稠剂及亲水性表面活性剂也可由此混合而形成油相。所得水相及油相可随后以类似方式混合而形成纳米乳液。值得注意的是,如果需要,可在高温,例如45℃至85℃下进行全部混合步骤。重要的是,由此获得的油相及水相可用于制备o/w纳米乳液或w/o纳米乳液,其表明连续及分散相为可逆的。The present method for preparing the aforementioned nanoemulsions involves first forming an aqueous phase and an oil phase separately, and then mixing the two phases. The aqueous phase can be formed by mixing water or an aqueous solution and a water-soluble organic nanostructure stabilizer by continuous stirring (manually or otherwise), high-speed and high-shear mixing (e.g., using a colloid mill), high-pressure mixing (e.g., using a microfluidizer), or sonication. Oil or an oil solution, an organic thickener, and a hydrophilic surfactant can also be mixed in this manner to form an oil phase. The resulting aqueous and oil phases can then be mixed in a similar manner to form a nanoemulsion. Notably, all mixing steps can be performed at elevated temperatures, e.g., 45°C to 85°C, if desired. Importantly, the oil and aqueous phases thus obtained can be used to prepare o/w nanoemulsions or w/o nanoemulsions, demonstrating that the continuous and dispersed phases are reversible.

在不进一步详细描述的情况下,据信以上描述已充分实现本发明。因此,以下实施例应理解为仅为说明性的且无论如何不以任何方式限制本发明的其余部分。本文中所引用的出版物以全文引用的方式并入本文中。Without further detailed description, it is believed that the above description has fully realized the present invention. Therefore, the following examples should be understood to be merely illustrative and not to limit the remainder of the present invention in any way. The publications cited herein are incorporated herein by reference in their entirety.

实施例1:纳米乳液类型的测定Example 1: Determination of nanoemulsion type

将60ml水置放于100-ml烧杯中。将待测试的纳米乳液逐滴添加至水中。如果分散于水中的纳米乳液产生透明或半透明溶液,则所测试的纳米乳液为o/w纳米乳液。然而,如果纳米乳液在水中形成油状小液滴,则所测试的纳米乳液为w/o纳米乳液。实施例2:椰子油纳米乳液的制备Place 60 ml of water in a 100-ml beaker. Add the nanoemulsion to be tested dropwise to the water. If the nanoemulsion dispersed in water produces a transparent or translucent solution, the nanoemulsion tested is an o/w nanoemulsion. However, if the nanoemulsion forms oily droplets in water, the nanoemulsion tested is a w/o nanoemulsion. Example 2: Preparation of Coconut Oil Nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合210克纯化水、90克脲、60克木糖醇、60克海藻糖及30克甲基磺酰基甲烷的组合以形成水相。A combination of 210 grams of purified water, 90 grams of urea, 60 grams of xylitol, 60 grams of trehalose, and 30 grams of methylsulfonylmethane was mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合80克椰子油、20克石蜡油、50克环甲硅油(DC-345)、20克蜂蜡、10克单硬脂酸甘油酯、16克硬脂酸、14克脱水山梨糖醇单硬脂酸酯、36克聚乙二醇脱水山梨糖醇单硬脂酸酯及42克PEG-40氢化蓖麻油的组合以形成油相。A combination of 80 grams of coconut oil, 20 grams of paraffin oil, 50 grams of cyclomethicone (DC-345), 20 grams of beeswax, 10 grams of glyceryl monostearate, 16 grams of stearic acid, 14 grams of sorbitan monostearate, 36 grams of polyethylene glycol sorbitan monostearate, and 42 grams of PEG-40 hydrogenated castor oil were mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

在65℃至75℃下通过在200-ml烧杯中持续手动搅拌来混合下表1中所示的重量比的上文所制备的油相及水相的组合持续低于0.5小时以形成w/o或o/w纳米乳液。The combination of the above prepared oil phase and water phase in the weight ratio shown in Table 1 below was mixed by constant manual stirring in a 200-ml beaker at 65-75°C for less than 0.5 hours to form a w/o or o/w nanoemulsion.

表1Table 1

IDID 11 22 33 44 油相(g)Oil phase (g) 120120 9090 4040 2525 水相(g)Aqueous phase (g) 3030 6060 6060 7575 纳米乳液(g)Nanoemulsion (g) 150150 150150 100100 100100 类型type w/ow/o w/ow/o o/wo/w o/wo/w 物理外观Physical appearance 半透明translucent 透明transparent 透明transparent 透明transparent

全部纳米乳液在室温下稳定至少3个月且展现廷得尔(Tyndall)光折射效应。All nanoemulsions were stable at room temperature for at least 3 months and exhibited Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例3:棕榈油纳米乳液的制备Example 3: Preparation of palm oil nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

遵照实施例2中所述的程序制备由30克水相及120克油相组成的150克w/o纳米乳液,不同的处在于使用棕榈油代替椰子油。由此制备的纳米乳液为半透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。150 g of a w/o nanoemulsion consisting of 30 g of an aqueous phase and 120 g of an oily phase was prepared following the procedure described in Example 2, except that palm oil was used instead of coconut oil. The nanoemulsion thus prepared was translucent and stable at room temperature for at least 3 months. It exhibited the Tyndall light refraction effect.

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液,不同的处在于使用棕榈油代替椰子油。由此制备的纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。150 g of a w/o nanoemulsion consisting of 60 g of an aqueous phase and 90 g of an oil phase was prepared following the procedure described in Example 2, except that palm oil was used instead of coconut oil. The nanoemulsion thus prepared was transparent and stable at room temperature for at least 3 months. It exhibited the Tyndall refraction effect.

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克o/w纳米乳液,不同之处在于使用棕榈油代替椰子油。由此制备的纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。150 g of an o/w nanoemulsion consisting of 60 g of an aqueous phase and 90 g of an oil phase was prepared following the procedure described in Example 2, except that palm oil was used instead of coconut oil. The nanoemulsion thus prepared was transparent and stable at room temperature for at least 3 months. It exhibited the Tyndall light refraction effect.

遵照实施例2中所述的程序制备由75克水相及25克油相组成的100克o/w纳米乳液,不同之处在于使用棕榈油代替椰子油。由此制备的纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。100 g of an o/w nanoemulsion consisting of 75 g of an aqueous phase and 25 g of an oily phase was prepared following the procedure described in Example 2, except that palm oil was used instead of coconut oil. The nanoemulsion thus prepared was transparent and stable at room temperature for at least 3 months. It exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

此实施例中所制备的全部纳米乳液均通过遵照USP 35<51>,抗微生物有效性测试(Antimicrobial Effectiveness Testing),第52页中所述的程序进行的抗微生物测试。All nanoemulsions prepared in this example were tested for antimicrobial effectiveness following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52.

实施例4:马脂纳米乳液的制备Example 4: Preparation of horse fat nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液,不同之处在于使用马脂代替椰子油。150 g of w/o nanoemulsion consisting of 60 g of aqueous phase and 90 g of oil phase was prepared following the procedure described in Example 2 except that horse fat was used instead of coconut oil.

遵照实施例2中所述的程序制备由60克水相及40克油相组成的100克o/w纳米乳液,不同之处在于使用马脂代替椰子油。100 g of o/w nanoemulsion consisting of 60 g of aqueous phase and 40 g of oil phase was prepared following the procedure described in Example 2 except that horse fat was used instead of coconut oil.

由此制备的纳米乳液为透明的且在室温下稳定至少3个月。其均展现廷得尔光折射效应。The nanoemulsions prepared in this way were transparent and stable at room temperature for at least 3 months. They all exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的两种纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35<51>, Antimicrobial Effectiveness Testing, page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.

实施例5:马脂纳米乳液的制备Example 5: Preparation of horse fat nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在烧杯中持续手动搅拌来混合150克纯化水、150克脲及40克甘露糖醇的组合以形成水相。A combination of 150 grams of purified water, 150 grams of urea, and 40 grams of mannitol were mixed by constant manual stirring in a beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

遵照实施例2中所述的程序制备油相,不同之处在于使用马脂代替椰子油。The oil phase was prepared following the procedure described in Example 2 except that horse fat was used instead of coconut oil.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of w/o nanoemulsion consisting of 60 g of aqueous phase and 90 g of oil phase was prepared.

遵照实施例2中所述的程序制备由60克水相及40克油相组成的100克o/w纳米乳液。Following the procedure described in Example 2, 100 g of an o/w nanoemulsion consisting of 60 g of an aqueous phase and 40 g of an oily phase was prepared.

由此制备的纳米乳液为透明的且在室温下稳定至少3个月。其均展现廷得尔光折射效应。The nanoemulsions prepared in this way were transparent and stable at room temperature for at least 3 months. They all exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的两种纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35<51>, Antimicrobial Effectiveness Testing, page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.

实施例6:仅含有一种亲水性表面活性剂的棕榈油/角鲨烯纳米乳液的制备Example 6: Preparation of Palm Oil/Squalene Nanoemulsion Containing Only One Hydrophilic Surfactant

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

通过在置放于65℃至75℃下的500-ml烧杯中持续手动搅拌来混合180克纯化水、100克脲、20克丁二醇的组合以形成水相。纳米乳液的油相的制备A combination of 180 grams of purified water, 100 grams of urea, and 20 grams of butanediol was mixed by constant manual stirring in a 500-ml beaker placed at 65° C. to 75° C. to form an aqueous phase. Preparation of the oil phase of the nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合100克棕榈油、20克角鲨烯、25克环甲硅油(DC-345)、10克蜂蜡、20克硬脂酸、16克脱水山梨糖醇单硬脂酸酯及60克PEG-40氢化蓖麻油的组合以形成油相。A combination of 100 grams of palm oil, 20 grams of squalene, 25 grams of cyclomethicone (DC-345), 10 grams of beeswax, 20 grams of stearic acid, 16 grams of sorbitan monostearate, and 60 grams of PEG-40 hydrogenated castor oil was mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合下表2中所示的重量比的上文所制备的油相及水相的组合至多0.5小时以形成也列于表2中的纳米乳液。The combination of the above prepared oil phase and water phase in the weight ratio shown in Table 2 below was mixed at 65-75°C by constant manual stirring in a 500-ml beaker for up to 0.5 hour to form the nanoemulsion also listed in Table 2.

表2Table 2

IDID 11 22 33 44 油相(g)Oil phase (g) 105105 9090 6060 3030 水相(g)Aqueous phase (g) 1515 6060 9090 120120 总重量(g)Total weight (g) 120120 150150 150150 150150 类型type w/ow/o w/ow/o o/wo/w o/wo/w 物理外观Physical appearance 半透明translucent 透明transparent 透明transparent 透明transparent

全部以上纳米乳液在室温下稳定至少3个月且展现廷得尔光折射效应。All of the above nanoemulsions were stable at room temperature for at least 3 months and exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例7:基于椰子油的医药纳米乳液的制备Example 7: Preparation of Coconut Oil-Based Pharmaceutical Nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

遵照实施例2中所述的程序制备由29.5克水相、溶解有0.5克油溶性医药活性成分的20克油相组成的50克o/w纳米乳液。油溶性医药活性成分为特比萘芬、双氯芬酸二乙胺、二乙胺、甲硝哒唑、吲哚美辛、克霉唑或红霉素。Following the procedure described in Example 2, 50 g of an o/w nanoemulsion was prepared consisting of 29.5 g of an aqueous phase and 20 g of an oil phase in which 0.5 g of an oil-soluble pharmaceutically active ingredient was dissolved. The oil-soluble pharmaceutically active ingredient was terbinafine, diclofenac diethylamine, diethylamine, metronidazole, indomethacin, clotrimazole, or erythromycin.

由此制备的六种纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。The six nanoemulsions thus prepared were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例8:基于棕榈油的医药纳米乳液的制备Example 8: Preparation of Palm Oil-Based Pharmaceutical Nanoemulsion

遵照实施例7中所述的程序制备纳米乳液,不同的处在于使用棕榈油代替椰子油,且油溶性医药活性成分为特比萘芬、双氯芬酸二乙胺、甲康唑(metroconazole)、活动素、联苯苄唑及咪康唑。Nanoemulsions were prepared following the procedure described in Example 7, except that palm oil was used instead of coconut oil, and the oil-soluble pharmaceutical active ingredients were terbinafine, diclofenac diethylamide, metroconazole, actin, bifonazole, and miconazole.

由此制备的六种纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。The six nanoemulsions thus prepared were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例9:含有甘宝素的精油纳米乳液的制备Example 9: Preparation of essential oil nanoemulsion containing climbazole

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合150克纯化水、150克脲及40克丙二醇的组合以形成水相。A combination of 150 grams of purified water, 150 grams of urea, and 40 grams of propylene glycol were mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合40克茶树油、20克桉树油、30克薄荷醇、50克石蜡油、50克环甲硅油(DC-345)、20克蜂蜡、10克单硬脂酸甘油酯、16克硬脂酸、14克脱水山梨糖醇单硬脂酸酯、36克聚乙二醇脱水山梨糖醇单硬脂酸酯及42克PEG-40氢化蓖麻油的组合以形成油相。A combination of 40 grams of tea tree oil, 20 grams of eucalyptus oil, 30 grams of menthol, 50 grams of paraffin oil, 50 grams of cyclomethicone (DC-345), 20 grams of beeswax, 10 grams of glyceryl monostearate, 16 grams of stearic acid, 14 grams of sorbitan monostearate, 36 grams of polyethylene glycol sorbitan monostearate, and 42 grams of PEG-40 hydrogenated castor oil were mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of w/o nanoemulsion consisting of 60 g of aqueous phase and 90 g of oil phase was prepared.

遵照实施例2中所述的程序制备由90克水相及60克油相组成的150克o/w纳米乳液。Following the procedure described in Example 2, 150 g of an o/w nanoemulsion consisting of 90 g of an aqueous phase and 60 g of an oily phase was prepared.

遵照实施例2中所述的程序制备由溶解有1克甘宝素的59克水相及40克油相组成的100克o/w纳米乳液。Following the procedure described in Example 2, 100 g of an o/w nanoemulsion consisting of 59 g of an aqueous phase and 40 g of an oil phase in which 1 g of climbazole was dissolved was prepared.

全部以上纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。All the above nanoemulsions were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例10:具有与实施例9中的水相不同的水相的精油纳米乳液的制备Example 10: Preparation of an essential oil nanoemulsion having an aqueous phase different from that in Example 9

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合210克纯化水、90克脲、60克木糖醇、60克海藻糖及30克甲基磺酰基甲烷的组合以形成水相。A combination of 210 grams of purified water, 90 grams of urea, 60 grams of xylitol, 60 grams of trehalose, and 30 grams of methylsulfonylmethane was mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合40克茶树油、20克桉树油、30克薄荷醇、50克石蜡油、50克环甲硅油(DC-345)、20克蜂蜡、10克单硬脂酸甘油酯、16克硬脂酸、14克脱水山梨糖醇单硬脂酸酯、36克聚乙二醇脱水山梨糖醇单硬脂酸酯及42克PEG-40氢化蓖麻油的组合以形成油相。A combination of 40 grams of tea tree oil, 20 grams of eucalyptus oil, 30 grams of menthol, 50 grams of paraffin oil, 50 grams of cyclomethicone (DC-345), 20 grams of beeswax, 10 grams of glyceryl monostearate, 16 grams of stearic acid, 14 grams of sorbitan monostearate, 36 grams of polyethylene glycol sorbitan monostearate, and 42 grams of PEG-40 hydrogenated castor oil were mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of w/o nanoemulsion consisting of 60 g of aqueous phase and 90 g of oil phase was prepared.

遵照实施例2中所述的程序制备由90克水相及60克油相组成的150克o/w纳米乳液。Following the procedure described in Example 2, 150 g of an o/w nanoemulsion consisting of 90 g of an aqueous phase and 60 g of an oily phase was prepared.

两种纳米乳液为透明的且在室温下稳定至少3个月。其均展现廷得尔光折射效应。The two nanoemulsions were transparent and stable at room temperature for at least 3 months. They both exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的两种纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35<51>, Antimicrobial Effectiveness Testing, page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.

实施例11:含有托萘酯或酮康唑的精油纳米乳液的制备Example 11: Preparation of essential oil nanoemulsion containing tolnaftate or ketoconazole

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合150克纯化水、150克脲及40克丙二醇的组合以形成水相。A combination of 150 grams of purified water, 150 grams of urea, and 40 grams of propylene glycol were mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合50克茶树油、20克桉树油、15克薄荷醇、15克水杨酸甲酯、50克环甲硅油(DC-345)、10克蜂蜡、10克月桂酸、6克硬脂酸、14克脱水山梨糖醇单硬脂酸酯、40克聚氧乙烯二醇(40)硬脂酸酯及40克PEG-40氢化蓖麻油的组合以形成油相。A combination of 50 grams of tea tree oil, 20 grams of eucalyptus oil, 15 grams of menthol, 15 grams of methyl salicylate, 50 grams of cyclomethicone (DC-345), 10 grams of beeswax, 10 grams of lauric acid, 6 grams of stearic acid, 14 grams of sorbitan monostearate, 40 grams of polyoxyethylene glycol (40) stearate, and 40 grams of PEG-40 hydrogenated castor oil were mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of w/o nanoemulsion consisting of 60 g of aqueous phase and 90 g of oil phase was prepared.

遵照实施例2中所述的程序制备由90克水相及60克油相组成的150克o/w纳米乳液。Following the procedure described in Example 2, 150 g of an o/w nanoemulsion consisting of 90 g of an aqueous phase and 60 g of an oily phase was prepared.

遵照实施例2中所述的程序制备由60克水相及溶解有1.8克托萘酯的88.2克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of a w/o nanoemulsion consisting of 60 g of an aqueous phase and 88.2 g of an oil phase in which 1.8 g of tolnaphthate was dissolved was prepared.

遵照实施例2中所述的程序制备由60克水相及溶解有1.8克酮康唑的88.2克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of a w/o nanoemulsion consisting of 60 g of an aqueous phase and 88.2 g of an oil phase in which 1.8 g of ketoconazole was dissolved was prepared.

全部以上纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。All the above nanoemulsions were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例12:芳香剂/精油纳米乳液的制备Example 12: Preparation of fragrance/essential oil nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合150克纯化水、150克脲及40克丙二醇的组合以形成水相。A combination of 150 grams of purified water, 150 grams of urea, and 40 grams of propylene glycol were mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合80克柠檬桉树油、40克香茅油、24克熏衣草油、22克桉树油、15克迷迭香油、15克樟脑、15克薄荷醇、6克百里香、10克蜂蜡、10克月桂酸、6克硬脂酸、14克脱水山梨糖醇单硬脂酸酯、40克聚氧乙烯二醇(40)硬脂酸酯及40克PEG-40氢化蓖麻油的组合以形成油相。A combination of 80 grams of lemon eucalyptus oil, 40 grams of citronella oil, 24 grams of lavender oil, 22 grams of eucalyptus oil, 15 grams of rosemary oil, 15 grams of camphor, 15 grams of menthol, 6 grams of thyme, 10 grams of beeswax, 10 grams of lauric acid, 6 grams of stearic acid, 14 grams of sorbitan monostearate, 40 grams of polyoxyethylene glycol (40) stearate, and 40 grams of PEG-40 hydrogenated castor oil were mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of w/o nanoemulsion consisting of 60 g of aqueous phase and 90 g of oil phase was prepared.

遵照实施例2中所述的程序制备由60克水相及40克油相组成的100克o/w纳米乳液。Following the procedure described in Example 2, 100 g of an o/w nanoemulsion consisting of 60 g of an aqueous phase and 40 g of an oily phase was prepared.

两种纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。Both nanoemulsions were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的两种纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35<51>, Antimicrobial Effectiveness Testing, page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.

实施例13:含有CoQ10的中长链油纳米乳液的制备Example 13: Preparation of Medium- and Long-Chain Oil Nanoemulsion Containing CoQ10

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合150克纯化水、100克甘油、80克木糖醇、20克甘露糖醇及30克甲基磺酰基甲烷的组合以形成水相。A combination of 150 grams of purified water, 100 grams of glycerin, 80 grams of xylitol, 20 grams of mannitol, and 30 grams of methylsulfonylmethane was mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合170克中长链三酸甘油酯油、16克硬脂酸、14克脱水山梨糖醇单硬脂酸酯、30克聚乙二醇脱水山梨糖醇单硬脂酸酯及30克PEG-40氢化蓖麻的组合以形成油相。A combination of 170 grams of medium-chain triglyceride oil, 16 grams of stearic acid, 14 grams of sorbitan monostearate, 30 grams of polyethylene glycol sorbitan monostearate, and 30 grams of PEG-40 hydrogenated castor were mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由50克水相及溶解有5克CoQ10的95克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of a w/o nanoemulsion consisting of 50 g of an aqueous phase and 95 g of an oil phase in which 5 g of CoQ10 was dissolved was prepared.

遵照实施例2中所述的程序制备由90克水相及溶解有3克CoQ10的57克油相组成的150克o/w纳米乳液。Following the procedure described in Example 2, 150 g of an o/w nanoemulsion consisting of 90 g of an aqueous phase and 57 g of an oil phase in which 3 g of CoQ10 was dissolved was prepared.

遵照实施例2中所述的程序制备由120克水相及溶解有3克CoQ10的30克油相组成的153克o/w纳米乳液。全部以上纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。Following the procedure described in Example 2, 153 g of an o/w nanoemulsion consisting of 120 g of an aqueous phase and 30 g of an oil phase in which 3 g of CoQ10 was dissolved was prepared. All of the above nanoemulsions were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例14:中长链三酸甘油酯纳米乳液的制备Example 14: Preparation of medium- and long-chain triglyceride nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合100克纯化水、100克甘油、50克木糖醇、50克海藻糖、30克赤藻糖醇及15克麦芽糊精的组合以形成水相。A combination of 100 grams of purified water, 100 grams of glycerol, 50 grams of xylitol, 50 grams of trehalose, 30 grams of erythritol, and 15 grams of maltodextrin were mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合170克中长链三酸甘油酯、16克硬脂酸、14克脱水山梨糖醇单硬脂酸酯、30克聚乙二醇脱水山梨糖醇单硬脂酸酯及30克PEG-40氢化蓖麻油的组合以形成油相。A combination of 170 grams of medium-chain triglycerides, 16 grams of stearic acid, 14 grams of sorbitan monostearate, 30 grams of polyethylene glycol sorbitan monostearate, and 30 grams of PEG-40 hydrogenated castor oil was mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由54克水相及溶解有6克叶黄素的120克油相组成的180克w/o纳米乳液。Following the procedure described in Example 2, 180 g of a w/o nanoemulsion consisting of 54 g of an aqueous phase and 120 g of an oil phase in which 6 g of lutein was dissolved was prepared.

遵照实施例2中所述的程序制备由174克水相及溶解有6克叶黄素的120克油相组成的300克o/w纳米乳液。Following the procedure described in Example 2, 300 g of an o/w nanoemulsion consisting of 174 g of an aqueous phase and 120 g of an oily phase in which 6 g of lutein was dissolved was prepared.

纳米乳液均为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。The nanoemulsions were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的两种纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35<51>, Antimicrobial Effectiveness Testing, page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.

实施例15:含有CoQ10的中长链三酸甘油酯油纳米乳液的制备Example 15: Preparation of CoQ10-containing medium-chain triglyceride oil nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合100克纯化水、100克甘油、50克木糖醇、50克海藻糖、35克赤藻糖醇及15克麦芽糊精的组合以形成水相。A combination of 100 grams of purified water, 100 grams of glycerol, 50 grams of xylitol, 50 grams of trehalose, 35 grams of erythritol, and 15 grams of maltodextrin were mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合50克中长链三酸甘油酯、50克鱼油、10克硬脂酸、8克脱水山梨糖醇单硬脂酸酯、20克聚乙二醇脱水山梨糖醇单硬脂酸酯及20克PEG-40氢化蓖麻油的组合以形成油相。A combination of 50 grams of medium-chain triglycerides, 50 grams of fish oil, 10 grams of stearic acid, 8 grams of sorbitan monostearate, 20 grams of polyethylene glycol sorbitan monostearate, and 20 grams of PEG-40 hydrogenated castor oil was mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由20克水相及溶解有5克CoQ10的100克油相组成的125克w/o纳米乳液。Following the procedure described in Example 2, 125 g of a w/o nanoemulsion consisting of 20 g of an aqueous phase and 100 g of an oil phase in which 5 g of CoQ10 was dissolved was prepared.

遵照实施例2中所述的程序制备由58克水相及溶解有2克CoQ10的40克油相组成的100克o/w纳米乳液。Following the procedure described in Example 2, 100 g of an o/w nanoemulsion consisting of 58 g of an aqueous phase and 40 g of an oil phase in which 2 g of CoQ10 was dissolved was prepared.

纳米乳液均为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。The nanoemulsions were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例16:含有异山梨醇二硝酸酯或法莫替丁的角鲨烯/辛酸癸酸三甘油酯纳米乳液的制备Example 16: Preparation of Squalene/Caprylic Capric Triglyceride Nanoemulsion Containing Isosorbide Dinitrate or Famotidine

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合150克纯化水、150克脲及40克丙二醇的组合以形成水相。A combination of 150 grams of purified water, 150 grams of urea, and 40 grams of propylene glycol were mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合80克角鲨烯、80克辛酸癸酸三甘油酯、16克硬脂酸、14克脱水山梨糖醇单硬脂酸酯、40克聚氧乙烯二醇(40)硬脂酸酯及40克PEG-40氢化蓖麻油的组合以形成油相。A combination of 80 grams of squalene, 80 grams of caprylic capric triglyceride, 16 grams of stearic acid, 14 grams of sorbitan monostearate, 40 grams of polyoxyethylene glycol (40) stearate, and 40 grams of PEG-40 hydrogenated castor oil was mixed by constant manual stirring in a 500-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of w/o nanoemulsion consisting of 60 g of aqueous phase and 90 g of oil phase was prepared.

遵照实施例2中所述的程序制备由90克水相及60克油组成的150克o/w纳米乳液。Following the procedure described in Example 2, 150 g of an o/w nanoemulsion consisting of 90 g of aqueous phase and 60 g of oil was prepared.

遵照实施例2中所述的程序制备由88.5克水相及溶解有1.5克异山梨醇二硝酸酯的60克油相组成的150克o/w纳米乳液。Following the procedure described in Example 2, 150 g of an o/w nanoemulsion consisting of 88.5 g of an aqueous phase and 60 g of an oily phase in which 1.5 g of isosorbide dinitrate was dissolved was prepared.

遵照实施例2中所述的程序制备由88.5克水相及溶解有1.5克法莫替丁的60克油相组成的150克o/w纳米乳液。Following the procedure described in Example 2, 150 g of an o/w nanoemulsion consisting of 88.5 g of an aqueous phase and 60 g of an oily phase in which 1.5 g of famotidine was dissolved was prepared.

全部以上纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。All the above nanoemulsions were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例17:含有姜黄素或睪固酮的合成油纳米乳液的制备Example 17: Preparation of synthetic oil nanoemulsions containing curcumin or testosterone

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合150克纯化水、150克脲及40克丙二醇的组合以形成水相。A combination of 150 grams of purified water, 150 grams of urea, and 40 grams of propylene glycol were mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在400-ml烧杯中持续手动搅拌来混合80克辛酸癸酸三甘油酯、40克油酸乙酯、40克脱水山梨糖醇油酸酯、8克蜂蜡、8克月桂酸、8克脱水山梨糖醇单硬脂酸酯及64克聚氧乙烯二醇(40)硬脂酸酯的组合以形成油相。A combination of 80 grams of caprylic capric triglyceride, 40 grams of ethyl oleate, 40 grams of sorbitan oleate, 8 grams of beeswax, 8 grams of lauric acid, 8 grams of sorbitan monostearate, and 64 grams of polyoxyethylene glycol (40) stearate was mixed by constant manual stirring in a 400-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由45克水相及90克油相组成的135克w/o纳米乳液。Following the procedure described in Example 2, 135 g of w/o nanoemulsion consisting of 45 g of aqueous phase and 90 g of oil phase was prepared.

遵照实施例2中所述的程序制备由45克水相及溶解有1.8克睪固酮的88.2克油相组成的135克w/o纳米乳液。Following the procedure described in Example 2, 135 g of a w/o nanoemulsion consisting of 45 g of an aqueous phase and 88.2 g of an oil phase in which 1.8 g of testosterone was dissolved was prepared.

遵照实施例2中所述的程序制备由45克水相及溶解有0.6克姜黄素的89.4克油相组成的135克w/o纳米乳液。135 g of w/o nanoemulsion consisting of 45 g of aqueous phase and 89.4 g of oil phase in which 0.6 g of curcumin was dissolved was prepared following the procedure described in Example 2.

全部以上纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。All the above nanoemulsions were transparent and stable at room temperature for at least 3 months. They exhibited the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的全部纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and all the nanoemulsions prepared in this example passed the antimicrobial test.

实施例18:含有CoQ10、维生素A、维生素E及维生素D的纳米乳液的制备Example 18: Preparation of Nanoemulsion Containing CoQ10, Vitamin A, Vitamin E, and Vitamin D

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合280克纯化水、240克甘油、48克脲及32克海藻糖的组合以形成600克水相。A combination of 280 grams of purified water, 240 grams of glycerol, 48 grams of urea, and 32 grams of trehalose were mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form a 600-gram aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在400-ml烧杯中持续手动搅拌来混合2.4克CoQ10、4.8克维生素A、1.2克维生素D 1.2、30克维生素E、85.6克石蜡油、140克环甲硅油(DC-345)、32克硬脂酸、24克脱水山梨糖醇硬脂酸酯及80克聚乙二醇脱水山梨糖醇单硬脂酸酯的组合以形成400克油相。A combination of 2.4 grams of CoQ10, 4.8 grams of vitamin A, 1.2 grams of vitamin D 1.2, 30 grams of vitamin E, 85.6 grams of paraffin oil, 140 grams of cyclomethicone (DC-345), 32 grams of stearic acid, 24 grams of sorbitan stearate, and 80 grams of polyethylene glycol sorbitan monostearate was mixed by constant manual stirring in a 400-ml beaker at 65° C. to 75° C. to form a 400-gram oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由600克水相及400克油相组成的1000克纳米乳液。Following the procedure described in Example 2, 1000 g of a nanoemulsion consisting of 600 g of aqueous phase and 400 g of oil phase was prepared.

以上纳米乳液为透明o/w纳米乳液且在室温下稳定至少3个月。其展现廷得尔光折射效应。The above nanoemulsion is a transparent o/w nanoemulsion and is stable at room temperature for at least 3 months. It exhibits the Tyndall light refraction effect.

遵照实施例1中所述的程序测定纳米乳液的类型。The type of nanoemulsion was determined following the procedure described in Example 1.

遵照USP 35<51>,抗微生物有效性测试(AntimicrobialEffectivenessTesting),第52页中所述的程序进行抗微生物测试,且纳米乳液通过此抗微生物测试。Antimicrobial testing was performed following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and the nanoemulsion passed this antimicrobial test.

实施例19:维生素E/葡萄籽油/椰子油/貂油/石蜡油/环甲硅油纳米乳液的制备Example 19: Preparation of Vitamin E/Grapeseed Oil/Coconut Oil/Mink Oil/Paraffin Oil/Cyclomethicone Nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合168克纯化水、115克脲、77克甘油、20克丙二醇、20克吡咯烷酮甲酸钠及20克海藻糖的组合以形成420克水相。A combination of 168 grams of purified water, 115 grams of urea, 77 grams of glycerol, 20 grams of propylene glycol, 20 grams of sodium pyrrolidone formate, and 20 grams of trehalose were mixed with constant manual stirring in a 500-ml beaker at 65-75°C to form 420 grams of an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在400-ml烧杯中持续手动搅拌来混合30克维生素E、30克葡萄籽油、40克椰子油、8克貂油、24克石蜡油、60克环甲硅油(DC-345)、16克蜂蜡、8克单硬脂酸甘油酯、19克硬脂酸、17克脱水山梨糖醇单硬脂酸酯、50克PEG-40氢化蓖麻油及28克聚氧乙烯二醇(40)硬脂酸酯的组合以形成330克油相。A combination of 30 grams of vitamin E, 30 grams of grapeseed oil, 40 grams of coconut oil, 8 grams of mink oil, 24 grams of paraffin oil, 60 grams of cyclomethicone (DC-345), 16 grams of beeswax, 8 grams of glyceryl monostearate, 19 grams of stearic acid, 17 grams of sorbitan monostearate, 50 grams of PEG-40 hydrogenated castor oil, and 28 grams of polyoxyethylene glycol (40) stearate were mixed by constant manual stirring in a 400-ml beaker at 65° C. to 75° C. to form 330 grams of an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由420克水相及330克油相组成的750克纳米乳液。Following the procedure described in Example 2, 750 g of a nanoemulsion consisting of 420 g of an aqueous phase and 330 g of an oil phase was prepared.

以上纳米乳液为透明o/w纳米乳液且在室温下稳定至少3个月。其展现廷得尔光折射效应。The above nanoemulsion is a transparent o/w nanoemulsion and is stable at room temperature for at least 3 months. It exhibits the Tyndall light refraction effect.

遵照实施例1中所述的程序测定纳米乳液的类型。The type of nanoemulsion was determined following the procedure described in Example 1.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且纳米乳液通过此抗微生物测试。Antimicrobial testing was performed following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and the nanoemulsion passed this antimicrobial test.

实施例20:维生素E/葡萄籽油/椰子油/貂油/石蜡油/环甲硅油纳米乳液的制备Example 20: Preparation of Vitamin E/Grapeseed Oil/Coconut Oil/Mink Oil/Paraffin Oil/Cyclomethicone Nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合168克纯化水、115克脲、77克甘油、20克丙二醇、20克吡咯烷酮甲酸钠及20克海藻糖的组合以形成420克水相。A combination of 168 grams of purified water, 115 grams of urea, 77 grams of glycerol, 20 grams of propylene glycol, 20 grams of sodium pyrrolidone formate, and 20 grams of trehalose were mixed with constant manual stirring in a 500-ml beaker at 65-75°C to form 420 grams of an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在400-ml烧杯中持续手动搅拌来混合30克维生素E、30克葡萄籽油、40克椰子油、8克貂油、24克石蜡油、60克环甲硅油(DC-345)、16克蜂蜡、8克单硬脂酸甘油酯、19克硬脂酸、17克脱水山梨糖醇单硬脂酸酯、50克PEG-40氢化蓖麻油及28克聚乙二醇脱水山梨糖醇单硬脂酸酯的组合以形成330克油相。A combination of 30 grams of vitamin E, 30 grams of grapeseed oil, 40 grams of coconut oil, 8 grams of mink oil, 24 grams of paraffin oil, 60 grams of cyclomethicone (DC-345), 16 grams of beeswax, 8 grams of glyceryl monostearate, 19 grams of stearic acid, 17 grams of sorbitan monostearate, 50 grams of PEG-40 hydrogenated castor oil, and 28 grams of polyethylene glycol sorbitan monostearate were mixed by constant manual stirring in a 400-ml beaker at 65° C. to 75° C. to form 330 grams of an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由420克水相及330克油相组成的750克纳米乳液。Following the procedure described in Example 2, 750 g of a nanoemulsion consisting of 420 g of an aqueous phase and 330 g of an oily phase was prepared.

以上纳米乳液为透明o/w纳米乳液且在室温下稳定至少3个月。其展现廷得尔光折射效应。The above nanoemulsion is a transparent o/w nanoemulsion and is stable at room temperature for at least 3 months. It exhibits the Tyndall light refraction effect.

遵照实施例1中所述的程序测定纳米乳液的类型。The type of nanoemulsion was determined following the procedure described in Example 1.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且纳米乳液通过此抗微生物测试。Antimicrobial testing was performed following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and the nanoemulsion passed this antimicrobial test.

实施例21:维生素E/葡萄籽油/椰子油/貂油/石蜡油/环甲硅油纳米乳液的制备Example 21: Preparation of Vitamin E/Grapeseed Oil/Coconut Oil/Mink Oil/Paraffin Oil/Cyclomethicone Nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合168克纯化水、115克脲、77克甘油、20克丙二醇、20克吡咯烷酮甲酸钠及20克海藻糖的组合以形成420克水相。A combination of 168 grams of purified water, 115 grams of urea, 77 grams of glycerol, 20 grams of propylene glycol, 20 grams of sodium pyrrolidone formate, and 20 grams of trehalose were mixed with constant manual stirring in a 500-ml beaker at 65-75°C to form 420 grams of an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在400-ml烧杯中持续手动搅拌来混合30克维生素E、30克葡萄籽油、40克椰子油、8克貂油、24克石蜡油、60克环甲硅油(DC-345)、16克蜂蜡、8克单硬脂酸甘油酯、19克硬脂酸、17克脱水山梨糖醇单硬脂酸酯、50克PEG-40氢化蓖麻油及28克聚氧乙烯脱水山梨糖醇单油酸酯的组合以形成330克油相。A combination of 30 grams of vitamin E, 30 grams of grapeseed oil, 40 grams of coconut oil, 8 grams of mink oil, 24 grams of paraffin oil, 60 grams of cyclomethicone (DC-345), 16 grams of beeswax, 8 grams of glyceryl monostearate, 19 grams of stearic acid, 17 grams of sorbitan monostearate, 50 grams of PEG-40 hydrogenated castor oil, and 28 grams of polyoxyethylene sorbitan monooleate were mixed by constant manual stirring in a 400-ml beaker at 65° C. to 75° C. to form 330 grams of an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由420克水相及330克油相组成的750克纳米乳液。Following the procedure described in Example 2, 750 g of a nanoemulsion consisting of 420 g of an aqueous phase and 330 g of an oily phase was prepared.

以上纳米乳液为透明o/w纳米乳液且在室温下稳定至少3个月。其展现廷得尔光折射效应。The above nanoemulsion is a transparent o/w nanoemulsion and is stable at room temperature for at least 3 months. It exhibits the Tyndall light refraction effect.

遵照实施例1中所述的程序测定纳米乳液的类型。The type of nanoemulsion was determined following the procedure described in Example 1.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且纳米乳液通过此抗微生物测试。Antimicrobial testing was performed following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and the nanoemulsion passed this antimicrobial test.

实施例22:维生素E/葡萄籽油/椰子油/貂油/石蜡油/环甲硅油纳米乳液的制备Example 22: Preparation of Vitamin E/Grapeseed Oil/Coconut Oil/Mink Oil/Paraffin Oil/Cyclomethicone Nanoemulsion

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在烧杯中持续手动搅拌来混合150克纯化水、150克脲及40克丙二醇的组合以形成340克水相。A combination of 150 grams of purified water, 150 grams of urea, and 40 grams of propylene glycol were mixed by constant manual stirring in a beaker at 65-75°C to form 340 grams of an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在400-ml烧杯中持续手动搅拌来混合30克维生素E、30克葡萄籽油、40克椰子油、8克貂油、24克石蜡油、60克环甲硅油(DC-345)、16克蜂蜡、8克单硬脂酸甘油酯、19克硬脂酸、17克脱水山梨糖醇单硬脂酸酯、50克PEG-40氢化蓖麻油及28克聚氧乙烯二醇(40)硬脂酸酯的组合以形成330克油相。A combination of 30 grams of vitamin E, 30 grams of grapeseed oil, 40 grams of coconut oil, 8 grams of mink oil, 24 grams of paraffin oil, 60 grams of cyclomethicone (DC-345), 16 grams of beeswax, 8 grams of glyceryl monostearate, 19 grams of stearic acid, 17 grams of sorbitan monostearate, 50 grams of PEG-40 hydrogenated castor oil, and 28 grams of polyoxyethylene glycol (40) stearate were mixed by constant manual stirring in a 400-ml beaker at 65° C. to 75° C. to form 330 grams of an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由420克水相及330克油相组成的750克纳米乳液。Following the procedure described in Example 2, 750 g of a nanoemulsion consisting of 420 g of an aqueous phase and 330 g of an oily phase was prepared.

以上纳米乳液为透明o/w纳米乳液且在室温下稳定至少3个月。其展现廷得尔光折射效应。The above nanoemulsion is a transparent o/w nanoemulsion and is stable at room temperature for at least 3 months. It exhibits the Tyndall light refraction effect.

遵照实施例1中所述的程序测定纳米乳液的类型。The type of nanoemulsion was determined following the procedure described in Example 1.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且纳米乳液通过此抗微生物测试。Antimicrobial testing was performed following the procedure described in USP 35 <51>, Antimicrobial Effectiveness Testing, page 52, and the nanoemulsion passed this antimicrobial test.

实施例23:仅含一种亲水性表面活性剂的精油纳米乳液的制备Example 23: Preparation of essential oil nanoemulsion containing only one hydrophilic surfactant

遵照如下所述的程序制备纳米乳液。The nanoemulsions were prepared following the procedure described below.

纳米乳液的水相的制备Preparation of the aqueous phase of nanoemulsion

在65℃至75℃下通过在500-ml烧杯中持续手动搅拌来混合200克纯化水、100克甘油、50克葡糖胺及50克甲基磺酰基甲烷的组合以形成水相。A combination of 200 grams of purified water, 100 grams of glycerin, 50 grams of glucosamine, and 50 grams of methylsulfonylmethane was mixed by constant manual stirring in a 500-ml beaker at 65-75°C to form an aqueous phase.

纳米乳液的油相的制备Preparation of the oil phase of nanoemulsion

在65℃至75℃下通过在400-ml烧杯中持续手动搅拌来混合30克维生素E、30克葡萄籽油、40克椰子油、8克貂油、24克石蜡油、60克环甲硅油(DC-345)、16克蜂蜡、8克单硬脂酸甘油酯、19克硬脂酸、17克脱水山梨糖醇单硬脂酸酯及68克PEG-40氢化蓖麻油的组合以形成油相。A combination of 30 grams of vitamin E, 30 grams of grapeseed oil, 40 grams of coconut oil, 8 grams of mink oil, 24 grams of paraffin oil, 60 grams of cyclomethicone (DC-345), 16 grams of beeswax, 8 grams of glyceryl monostearate, 19 grams of stearic acid, 17 grams of sorbitan monostearate, and 68 grams of PEG-40 hydrogenated castor oil were mixed by constant manual stirring in a 400-ml beaker at 65° C. to 75° C. to form an oil phase.

纳米乳液的制备Preparation of nanoemulsion

遵照实施例2中所述的程序制备由60克水相及90克油相组成的150克w/o纳米乳液。Following the procedure described in Example 2, 150 g of w/o nanoemulsion consisting of 60 g of aqueous phase and 90 g of oil phase was prepared.

遵照实施例2中所述的程序制备由90克水相及60克油相组成的150克o/w纳米乳液。Following the procedure described in Example 2, 150 g of an o/w nanoemulsion consisting of 90 g of an aqueous phase and 60 g of an oily phase was prepared.

以上纳米乳液为透明的且在室温下稳定至少3个月。其展现廷得尔光折射效应。The above nanoemulsion is transparent and stable at room temperature for at least 3 months. It exhibits the Tyndall light refraction effect.

遵照实施例1中所述的程序来测定此实施例中所制备的各纳米乳液的类型。The procedure described in Example 1 was followed to determine the type of each nanoemulsion prepared in this example.

遵照USP 35<51>,抗微生物有效性测试(Antimicrobial EffectivenessTesting),第52页中所述的程序进行抗微生物测试,且此实施例中所制备的两种纳米乳液均通过此抗微生物测试。The antimicrobial test was performed according to the procedure described in USP 35<51>, Antimicrobial Effectiveness Testing, page 52, and both nanoemulsions prepared in this example passed the antimicrobial test.

其他实施例Other embodiments

本说明书中公开的所有特征可以任何组合形式组合。本说明书中公开的各特征可经用于相同、等效或类似目的的替代性特征置换。因此,除非另外明确说明,否则所公开的各特征仅为一系列等效或类似通用特征的一个实施例。All features disclosed in this specification may be combined in any combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Therefore, unless expressly stated otherwise, each feature disclosed is merely one example of a series of equivalent or similar general features.

根据以上描述,本领域技术人员可易于确定本发明的基本特征,且在不脱离本发明的精神及范围的情况下可对本发明作出各种改变及修改以使其适应各种用途及条件。因此,其他实施例也处于以下权利要求书的范围内。Based on the above description, those skilled in the art can easily ascertain the essential features of the present invention and, without departing from the spirit and scope of the present invention, can make various changes and modifications to the present invention to adapt it to various uses and conditions. Therefore, other embodiments are also within the scope of the following claims.

Claims (22)

1.一种纳米乳液,其包含:1. A nanoemulsion comprising: (A)水相,其包括:(A) Aqueous phase, which includes: (1)水或水溶液,及(1) Water or aqueous solution, and (2)一种或多种水溶性有机纳米结构稳定剂,(2) One or more water-soluble organic nanostructure stabilizers, 其中按所述水相的重量计,所述水或水溶液的含量小于75%,并且按所述水相的重量计,所述一种或多种水溶性有机纳米结构稳定剂的含量小于99%,所述一种或多种水溶性有机纳米结构稳定剂选自脲、赤藻糖醇、海藻糖、麦芽糊精、木糖醇、甘露糖醇和葡糖胺,和The water or aqueous solution contains less than 75% by weight of the aqueous phase, and the one or more water-soluble organic nanostructure stabilizers contain less than 99% by weight of the aqueous phase. The one or more water-soluble organic nanostructure stabilizers are selected from urea, erythritol, trehalose, maltodextrin, xylitol, mannitol, and glucosamine. (B)油相,其包括:(B) Oil phase, which includes: (1)油或油溶液,(1) Oil or oil solution, (2)有机凝胶增稠剂,及(2) Organic gel thickeners, and (3)亲水性亲脂性平衡值大于8.0的亲水性表面活性剂,所述亲水性表面活性剂是PEG-40氢化蓖麻油、聚乙二醇脱水山梨糖醇单硬脂酸酯、聚氧乙烯二醇(40)硬脂酸酯、聚氧乙烯脱水山梨糖醇单油酸酯或其混合物,(3) A hydrophilic surfactant with a hydrophilicity-lipophilicity balance value greater than 8.0, wherein the hydrophilic surfactant is PEG-40 hydrogenated castor oil, polyethylene glycol dehydrated sorbitan monostearate, polyoxyethylene glycol (40) stearate, polyoxyethylene dehydrated sorbitan monooleate, or a mixture thereof. 其中按所述油相的重量计,所述油或油溶液的含量小于80%,按所述油相的重量计,所述有机凝胶增稠剂的含量小于60%,并且按所述油相的重量计,所述亲水性表面活性剂的含量小于60%,The oil or oil solution contains less than 80% by weight of the oil phase, the organic gel thickener contains less than 60% by weight of the oil phase, and the hydrophilic surfactant contains less than 60% by weight of the oil phase. 其中所述水或水溶液占所述纳米乳液的38重量%以下,所述水相与所述油相的重量比为1:40至100:1,所述水相以纳米级小液滴形式分散于所述油相中或所述油相以纳米级小液滴形式分散于所述水相中,而且所述纳米乳液在没有抗微生物防腐剂的情况下为自身防腐的并且具有可逆的连续及分散相。The water or aqueous solution comprises less than 38% by weight of the nanoemulsion, the weight ratio of the aqueous phase to the oil phase is 1:40 to 100:1, the aqueous phase is dispersed in the oil phase in the form of nano-sized droplets or the oil phase is dispersed in the aqueous phase in the form of nano-sized droplets, and the nanoemulsion is self-preservative in the absence of antimicrobial preservatives and has a reversible continuous and dispersed phase. 2.如权利要求1所述的纳米乳液,其中所述油相以纳米级小液滴形式分散于所述水相中。2. The nanoemulsion of claim 1, wherein the oil phase is dispersed in the aqueous phase in the form of nanoscale droplets. 3.如权利要求1所述的纳米乳液,其中所述水相以纳米级小液滴形式分散于所述油相中。3. The nanoemulsion of claim 1, wherein the aqueous phase is dispersed in the oil phase in the form of nanoscale droplets. 4.如权利要求2所述的纳米乳液,其中所述亲水性亲脂性平衡值大于10。4. The nanoemulsion of claim 2, wherein the hydrophilicity-lipophilicity balance value is greater than 10. 5.如权利要求4所述的纳米乳液,其中所述亲水性亲脂性平衡值大于13。5. The nanoemulsion of claim 4, wherein the hydrophilicity-lipophilicity balance value is greater than 13. 6.如权利要求3所述的纳米乳液,其中所述亲水性亲脂性平衡值大于10。6. The nanoemulsion of claim 3, wherein the hydrophilicity-lipophilicity balance value is greater than 10. 7.如权利要求6所述的纳米乳液,其中所述亲水性亲脂性平衡值大于13。7. The nanoemulsion of claim 6, wherein the hydrophilicity-lipophilicity balance value is greater than 13. 8.如权利要求4所述的纳米乳液,其中所述油为植物油、有机硅油、合成油、矿物油、动物油、精油或其组合;并且所述有机凝胶增稠剂为饱和脂肪酸、脂肪酸醇、熔点大于45℃的脂肪酸衍生物或其组合。8. The nanoemulsion of claim 4, wherein the oil is a vegetable oil, silicone oil, synthetic oil, mineral oil, animal oil, essential oil, or a combination thereof; and the organic gel thickener is a saturated fatty acid, fatty acid alcohol, fatty acid derivative with a melting point greater than 45°C, or a combination thereof. 9.如权利要求4所述的纳米乳液,其中所述油为椰子油、棕榈油、葡萄籽油、柚子油、橄榄油、鳄梨油、月见草油、茶树油、桉树油、熏衣草油、迷迭香油、马脂、鱼油、角鲨烯、羊毛脂油、环甲硅油、环戊硅氧烷、苯基三甲基聚硅氧烷、辛酸或癸酸三甘油酯、肉豆蔻酸异丙酯、异硬脂酸异硬脂基酯、油酸癸酯、异壬酸乙基己酯、异十六烷、辛基十二醇、石蜡油、聚异丁烯、聚癸烯、薄荷醇或其组合;并且所述有机凝胶增稠剂为硬脂酸、月桂酸、甘油单硬脂酸酯、PEG 6000二硬脂酸酯、单甘油酯、二甘油酯、糖脂肪酸酯、丙二醇脂肪酸酯、二醇脂肪酸酯、脂肪酸己基癸酯、脂肪酸醇、硬脂酸十六烷酯、抗坏血酸脂肪酸酯、甘油脂肪酸酯或其组合。9. The nanoemulsion of claim 4, wherein the oil is coconut oil, palm oil, grapeseed oil, grapefruit oil, olive oil, avocado oil, evening primrose oil, tea tree oil, eucalyptus oil, lavender oil, rosemary oil, horse fat, fish oil, squalene, lanolin oil, cyclomethicone, cyclopentasiloxane, phenyltrimethylpolysiloxane, caprylic or caprylic triglyceride, isopropyl myristate, isostearyl isostearate, decyl oleate, ethylhexyl isononanoate, isohexadecane, octyldodecyl alcohol, paraffin oil, polyisobutylene, polydecene, menthol, or a combination thereof; and the organic gel thickener is stearic acid, lauric acid, glyceryl monostearate, PEG 6000 distearate, monoglycerides, diglycerides, sugar fatty acid esters, propylene glycol fatty acid esters, glycol fatty acid esters, fatty acid hexyldecyl ester, fatty acid alcohol, hexadecyl stearate, ascorbic acid fatty acid ester, glyceryl fatty acid ester, or a combination thereof. 10.如权利要求9所述的纳米乳液,其中所述亲水性亲脂性平衡值大于13;按所述水相的重量计,所述水或水溶液的含量小于60%,并且按所述水相的重量计,所述水溶性有机纳米结构稳定剂的含量小于50%;按所述油相的重量计,所述油或油溶液的含量小于65%,按所述油相的重量计,所述有机凝胶增稠剂的含量小于25%,并且按所述油相的重量计,所述亲水性表面活性剂的含量小于35%;所述水或水溶液占所述纳米乳液的30重量%以下,并且所述水相与所述油相的重量比为1:2至3:1;并且所述纳米乳液的pH为3至11且为透明或半透明的。10. The nanoemulsion of claim 9, wherein the hydrophilicity-lipophilicity balance value is greater than 13; the content of water or aqueous solution is less than 60% by weight of the aqueous phase, and the content of water-soluble organic nanostructure stabilizer is less than 50% by weight of the aqueous phase; the content of oil or oil solution is less than 65% by weight of the oil phase, the content of organic gel thickener is less than 25% by weight of the oil phase, and the content of hydrophilic surfactant is less than 35% by weight of the oil phase; the water or aqueous solution accounts for less than 30% by weight of the nanoemulsion, and the weight ratio of the aqueous phase to the oil phase is 1:2 to 3:1; and the pH of the nanoemulsion is 3 to 11 and it is transparent or translucent. 11.如权利要求6所述的纳米乳液,其中所述油为植物油、有机硅油、合成油、矿物油、动物油、精油或其组合;并且所述有机凝胶增稠剂为饱和脂肪酸、脂肪酸醇、熔点大于45℃的脂肪酸衍生物或其组合。11. The nanoemulsion of claim 6, wherein the oil is a vegetable oil, silicone oil, synthetic oil, mineral oil, animal oil, essential oil, or a combination thereof; and the organic gel thickener is a saturated fatty acid, a fatty acid alcohol, a fatty acid derivative with a melting point greater than 45°C, or a combination thereof. 12.如权利要求6所述的纳米乳液,其中所述油为椰子油、棕榈油、葡萄籽油、柚子油、橄榄油、鳄梨油、月见草油、茶树油、桉树油、熏衣草油、迷迭香油、马脂、鱼油、角鲨烯、羊毛脂油、环甲硅油、环戊硅氧烷、苯基三甲基聚硅氧烷、辛酸或癸酸三甘油酯、肉豆蔻酸异丙酯、异硬脂酸异硬脂基酯、油酸癸酯、异壬酸乙基己酯、异十六烷、辛基十二醇、石蜡油、聚异丁烯、聚癸烯、薄荷醇或其组合;并且所述有机凝胶增稠剂为硬脂酸、月桂酸、甘油单硬脂酸酯、PEG 6000二硬脂酸酯、单甘油酯、二甘油酯、糖脂肪酸酯、丙二醇脂肪酸酯、二醇脂肪酸酯、脂肪酸己基癸酯、脂肪酸醇、硬脂酸十六烷酯、抗坏血酸脂肪酸酯、甘油脂肪酸酯或其组合。12. The nanoemulsion of claim 6, wherein the oil is coconut oil, palm oil, grapeseed oil, grapefruit oil, olive oil, avocado oil, evening primrose oil, tea tree oil, eucalyptus oil, lavender oil, rosemary oil, horse fat, fish oil, squalene, lanolin oil, cyclomethicone, cyclopentasiloxane, phenyltrimethylpolysiloxane, caprylic or caprylic triglyceride, isopropyl myristate, isostearyl isostearate, decyl oleate, ethylhexyl isononanoate, isohexadecane, octyldodecyl alcohol, paraffin oil, polyisobutylene, polydecene, menthol, or a combination thereof; and the organic gel thickener is stearic acid, lauric acid, glyceryl monostearate, PEG 6000 distearate, monoglycerides, diglycerides, sugar fatty acid esters, propylene glycol fatty acid esters, glycol fatty acid esters, fatty acid hexyldecyl ester, fatty acid alcohol, hexadecyl stearate, ascorbic acid fatty acid ester, glyceryl fatty acid ester, or a combination thereof. 13.如权利要求12所述的纳米乳液,其中所述亲水性亲脂性平衡值大于13;按所述水相的重量计,所述水或水溶液的含量小于60%,并且按所述水相的重量计,所述水溶性有机纳米结构稳定剂的含量小于50%;按所述油相的重量计,所述油或油溶液的含量小于65%,按所述油相的重量计,所述有机凝胶增稠剂的含量小于25%,并且按所述油相的重量计,所述亲水性表面活性剂的含量小于35%;所述水或水溶液占所述纳米乳液的30重量%以下,并且所述水相与所述油相的重量比为1:2至3:1;并且所述纳米乳液的pH为3至11且为透明或半透明的。13. The nanoemulsion of claim 12, wherein the hydrophilicity-lipophilicity balance value is greater than 13; the content of water or aqueous solution is less than 60% by weight of the aqueous phase, and the content of the water-soluble organic nanostructure stabilizer is less than 50% by weight of the aqueous phase; the content of oil or oil solution is less than 65% by weight of the oil phase, the content of the organic gel thickener is less than 25% by weight of the oil phase, and the content of the hydrophilic surfactant is less than 35% by weight of the oil phase; the water or aqueous solution accounts for less than 30% by weight of the nanoemulsion, and the weight ratio of the aqueous phase to the oil phase is 1:2 to 3:1; and the pH of the nanoemulsion is 3 to 11 and it is transparent or translucent. 14.如权利要求8所述的纳米乳液,其中按所述水相的重量计,所述水或水溶液的含量小于60%,并且按所述水相的重量计,所述水溶性有机纳米结构稳定剂的含量小于70%;按所述油相的重量计,所述油或油溶液的含量为30%至70%,按所述油相的重量计,所述有机凝胶增稠剂的含量小于45%,并且按所述油相的重量计,所述亲水性表面活性剂的含量小于45%;并且所述水相与所述油相的重量比为1:3至4:1。14. The nanoemulsion of claim 8, wherein the content of water or aqueous solution is less than 60% by weight of the aqueous phase, and the content of the water-soluble organic nanostructure stabilizer is less than 70% by weight of the aqueous phase; the content of oil or oil solution is 30% to 70% by weight of the oil phase, the content of the organic gel thickener is less than 45% by weight of the oil phase, and the content of the hydrophilic surfactant is less than 45% by weight of the oil phase; and the weight ratio of the aqueous phase to the oil phase is 1:3 to 4:1. 15.如权利要求14所述的纳米乳液,其中按所述水相的重量计,所述水或水溶液的含量小于45%,并且按所述水相的重量计,所述水溶性有机纳米结构稳定剂的含量小于50%;按所述油相的重量计,所述油或油溶液的含量为45%至65%,按所述油相的重量计,所述有机凝胶增稠剂的含量小于25%,并且按所述油相的重量计,所述亲水性表面活性剂的含量小于35%;并且所述水或水溶液占所述纳米乳液的30重量%以下,并且所述水相与所述油相的重量比为1:2至3:1。15. The nanoemulsion of claim 14, wherein the content of water or aqueous solution is less than 45% by weight of the aqueous phase, and the content of the water-soluble organic nanostructure stabilizer is less than 50% by weight of the aqueous phase; the content of oil or oil solution is 45% to 65% by weight of the oil phase, the content of the organic gel thickener is less than 25% by weight of the oil phase, and the content of the hydrophilic surfactant is less than 35% by weight of the oil phase; and the water or aqueous solution accounts for less than 30% by weight of the nanoemulsion, and the weight ratio of the aqueous phase to the oil phase is 1:2 to 3:1. 16.如权利要求11所述的纳米乳液,其中按所述水相的重量计,所述水或水溶液的含量小于60%,并且按所述水相的重量计,所述水溶性有机纳米结构稳定剂的含量小于70%;按所述油相的重量计,所述油或油溶液的含量为30%至70%,按所述油相的重量计,所述有机凝胶增稠剂的含量小于45%,并且按所述油相的重量计,所述亲水性表面活性剂的含量小于45%;并且所述水相与所述油相的重量比为1:3至4:1。16. The nanoemulsion of claim 11, wherein the content of water or aqueous solution is less than 60% by weight of the aqueous phase, and the content of the water-soluble organic nanostructure stabilizer is less than 70% by weight of the aqueous phase; the content of oil or oil solution is 30% to 70% by weight of the oil phase, the content of the organic gel thickener is less than 45% by weight of the oil phase, and the content of the hydrophilic surfactant is less than 45% by weight of the oil phase; and the weight ratio of the aqueous phase to the oil phase is 1:3 to 4:1. 17.如权利要求16所述的纳米乳液,其中按所述水相的重量计,所述水或水溶液的含量小于45%,并且按所述水相的重量计,所述水溶性有机纳米结构稳定剂的含量小于50%;按所述油相的重量计,所述油或油溶液的含量为45%至65%,按所述油相的重量计,所述有机凝胶增稠剂的含量小于25%,并且按所述油相的重量计,所述亲水性表面活性剂的含量小于35%;并且所述水或水溶液占所述纳米乳液的30重量%以下,并且所述水相与所述油相的重量比为1:2至3:1。17. The nanoemulsion of claim 16, wherein the content of water or aqueous solution is less than 45% by weight of the aqueous phase, and the content of the water-soluble organic nanostructure stabilizer is less than 50% by weight of the aqueous phase; the content of oil or oil solution is 45% to 65% by weight of the oil phase, the content of the organic gel thickener is less than 25% by weight of the oil phase, and the content of the hydrophilic surfactant is less than 35% by weight of the oil phase; and the water or aqueous solution accounts for less than 30% by weight of the nanoemulsion, and the weight ratio of the aqueous phase to the oil phase is 1:2 to 3:1. 18.如权利要求15所述的纳米乳液,其中所述纳米乳液的pH为3至11且为透明或半透明的。18. The nanoemulsion of claim 15, wherein the nanoemulsion has a pH of 3 to 11 and is transparent or translucent. 19.如权利要求17所述的纳米乳液,其中所述纳米乳液的pH为3至11且为透明或半透明的。19. The nanoemulsion of claim 17, wherein the nanoemulsion has a pH of 3 to 11 and is transparent or translucent. 20.如权利要求1所述的纳米乳液,其中所述纳米乳液的pH为3至11且为透明或半透明的。20. The nanoemulsion of claim 1, wherein the nanoemulsion has a pH of 3 to 11 and is transparent or translucent. 21.如权利要求1所述的纳米乳液,其中所述纳米乳液为化妆品、医药产品、食品、家用化学品、农业用产品、印刷产品、染色产品、兽医用产品或诊断产品。21. The nanoemulsion of claim 1, wherein the nanoemulsion is a cosmetic, pharmaceutical product, food, household chemical, agricultural product, printing product, dyeing product, veterinary product, or diagnostic product. 22.一种用于制备如权利要求1所述的纳米乳液的方法,所述方法包括:22. A method for preparing the nanoemulsion as described in claim 1, the method comprising: (1)将水或水溶液与水溶性有机纳米结构稳定剂混合以形成水相,其中按所述水相的重量计,所述水或水溶液的含量小于75%,并且按所述水相的重量计,所述水溶性有机纳米结构稳定剂的含量小于99%;(1) A mixture of water or an aqueous solution with a water-soluble organic nanostructure stabilizer is formed to form an aqueous phase, wherein the content of the water or aqueous solution is less than 75% by weight of the aqueous phase, and the content of the water-soluble organic nanostructure stabilizer is less than 99% by weight of the aqueous phase. (2)将油或油溶液、有机增稠剂及亲水性亲脂性平衡值大于8.0的亲水性表面活性剂混合以形成油相,其中按所述油相的重量计,所述油或油溶液的含量小于80%,按所述油相的重量计,所述有机凝胶增稠剂的含量小于60%,并且按所述油相的重量计,所述亲水性表面活性剂的含量小于60%;和(2) An oil or oil solution, an organic thickener, and a hydrophilic surfactant with a hydrophilic-lipophilic balance value greater than 8.0 are mixed to form an oil phase, wherein the content of the oil or oil solution is less than 80% by weight of the oil phase, the content of the organic gel thickener is less than 60% by weight of the oil phase, and the content of the hydrophilic surfactant is less than 60% by weight of the oil phase; and (3)将所述水相与所述油相混合以形成纳米乳液,所述水相与所述油相的重量比为1:40至100:1,其中所述水或水溶液占所述纳米乳液的38重量%以下;(3) The aqueous phase and the oil phase are mixed to form a nanoemulsion, wherein the weight ratio of the aqueous phase to the oil phase is 1:40 to 100:1, and wherein the water or aqueous solution accounts for less than 38% by weight of the nanoemulsion. 由此所述水相以纳米级小液滴形式分散于所述油相中或所述油相以纳米级小液滴形式分散于所述水相中,其中所述纳米乳液在没有抗微生物防腐剂的情况下为自身防腐的并且具有可逆的连续及分散相。Thus, the aqueous phase is dispersed in the oil phase in the form of nano-sized droplets, or the oil phase is dispersed in the aqueous phase in the form of nano-sized droplets, wherein the nanoemulsion is self-preservative in the absence of antimicrobial preservatives and has a reversible continuous and dispersed phase.
HK17109610.2A 2015-10-23 2017-09-21 Nanoemulsions having reversible continuous and dispersed phases HK1235699B (en)

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