TW202034892A - Water-in-oil type cosmetic composition comprising nano liposome - Google Patents
Water-in-oil type cosmetic composition comprising nano liposome Download PDFInfo
- Publication number
- TW202034892A TW202034892A TW108139384A TW108139384A TW202034892A TW 202034892 A TW202034892 A TW 202034892A TW 108139384 A TW108139384 A TW 108139384A TW 108139384 A TW108139384 A TW 108139384A TW 202034892 A TW202034892 A TW 202034892A
- Authority
- TW
- Taiwan
- Prior art keywords
- weight
- oil
- type composition
- water type
- less
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
- A61K8/062—Oil-in-water emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/30—Characterized by the absence of a particular group of ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/413—Nanosized, i.e. having sizes below 100 nm
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
Description
相關申請之交互參照Cross-reference of related applications
本申請主張2018年10月31日提交的韓國專利申請案第10-2018-0132097號及2019年10月24日提交的韓國專利申請案第10-2019-0133095號之優先權,且該申請案之全部內容及自其引起之所有權益在此被以引用的方式全部併入。This application claims the priority of Korean Patent Application No. 10-2018-0132097 filed on October 31, 2018 and Korean Patent Application No. 10-2019-0133095 filed on October 24, 2019, and the application All the contents and all rights and interests arising therefrom are incorporated herein by reference.
本揭露內容係關於一種包含奈米脂質體之油水型組成物及其製備方法。The present disclosure relates to an oil-water composition containing nanoliposomes and a preparation method thereof.
在化妝品工業中被稱作皺紋改良成分的諸如丁香油素(oleanolic acid)之活性成分係難溶性之成分,其幾乎不溶於水且亦具有穩定性及滴定度不穩定性問題(即使施加至調配物),因此存在關於包括大於預定量的成分之限制。詳言之,該等成分可不施加至具有大的水含量之溶液化之調配物,且在保證調配物中之穩定性方面具有大的困難。Active ingredients such as oleanolic acid, which are called wrinkle improving ingredients in the cosmetics industry, are poorly soluble ingredients, which are almost insoluble in water and also have stability and titer instability problems (even when applied to formulations)物), so there is a restriction on including more than a predetermined amount of ingredients. In detail, these ingredients may not be applied to a solubilized formulation with a large water content, and there are great difficulties in ensuring the stability of the formulation.
此外,類似於生物細胞膜之脂質體係兩親性的,且具有與親水性及親脂性兩種物質之親合性,且因此此技術已廣泛地用於藥物配送之領域中,作為生物友好載體。此技術近來已在化妝品工業中之各種調配物中研究,作為用於使難溶性之有效物質穩定及促進皮膚吸收之介質。為了製造用於塗覆至皮膚之調配物(諸如,化妝品),有必要理解脂質體之特性(諸如,用於高效皮膚滲透及吸收之粒度控制),及使用於形成脂質體之條件最佳化。In addition, the lipid system similar to biological cell membranes is amphipathic and has affinity for both hydrophilic and lipophilic substances. Therefore, this technology has been widely used in the field of drug delivery as a bio-friendly carrier. This technology has recently been studied in various formulations in the cosmetics industry as a medium for stabilizing poorly soluble effective substances and promoting skin absorption. In order to make formulations for application to the skin (such as cosmetics), it is necessary to understand the characteristics of liposomes (such as particle size control for efficient skin penetration and absorption), and to optimize the conditions for liposome formation .
相關技術中用於奈米乳液及脂質體生長之高壓乳化技術係特殊設備,其需要高能量且具有的經濟問題在於,製造成本通常比相關技術中之乳化方法之製造成本高得多,該製程亦難用於規模生產,且製造時間長。此外,藉由將為皮膚友好成分之卵磷脂溶解於有機溶劑中生產脂質體且溶劑經揮發之生產方法具有的問題在於,該產品不穩定,且其規模生產對於實際工業中之一般應用係困難的。The high-pressure emulsification technology used for the growth of nanoemulsions and liposomes in the related technology is a special equipment, which requires high energy and has economic problems in that the manufacturing cost is usually much higher than that of the emulsification method in the related technology. It is also difficult to use in mass production, and the manufacturing time is long. In addition, the production method of producing liposomes by dissolving lecithin, which is a skin-friendly ingredient, in an organic solvent and the solvent is volatilized has the problem that the product is unstable and its mass production is difficult for general applications in actual industry of.
[技術問題][technical problem]
本揭露內容之一目標為實現一種穩定奈米脂質體調配物,其包括乙醇可溶但水難溶之活性成分,諸如,丁香油素。 [問題之解決方案]One of the objectives of the present disclosure is to achieve a stable nanoliposome formulation, which includes active ingredients that are soluble in ethanol but insoluble in water, such as syringae oil. [Solution to the problem]
在一個態樣中,在本說明書中揭露之技術可提供一種包括奈米脂質體之油水型組成物,其中該奈米脂質體包括一囊泡,其包括氫化卵磷脂、膽固醇及辛酸/癸酸三酸甘油酯;及該囊泡中含有之一活性成分。In one aspect, the technology disclosed in this specification can provide an oil-and-water composition including nanoliposomes, wherein the nanoliposomes include a vesicle including hydrogenated lecithin, cholesterol, and caprylic/capric acid Triglyceride; and the vesicle contains an active ingredient.
在一個實施例中,該活性成分可為乙醇可溶且水難溶之活性成分。In one embodiment, the active ingredient may be an active ingredient that is soluble in ethanol and hardly soluble in water.
在一個實施例中,該奈米脂質體之一大小可為50 nm至300 nm。In one embodiment, one of the nano-liposomes may be 50 nm to 300 nm in size.
在一個實施例中,在粒度分佈中的該奈米脂質體之一PDI值可為0.03至0.2。In one embodiment, the PDI value of one of the nanoliposomes in the particle size distribution may be 0.03 to 0.2.
在一個實施例中,該活性成分可為選自由丁香油素、積雪草、維他命E、維他命C、蝦青素、神經醯胺、3,4,5-三甲氧基肉桂酸百里酚酯或其立體異構物、鹽、水合物或溶劑化物組成之群組的一或多者。In one embodiment, the active ingredient may be selected from the group consisting of eugenol, Centella asiatica, vitamin E, vitamin C, astaxanthin, ceramide, 3,4,5-trimethoxycinnamate thymol or One or more of the group consisting of its stereoisomers, salts, hydrates or solvates.
在一個實施例中,該氫化卵磷脂之一含量可為關於該奈米脂質體之總重量的0.1重量%至5重量%。In one embodiment, the content of one of the hydrogenated lecithins may be 0.1% to 5% by weight with respect to the total weight of the nanoliposomes.
在一個實施例中,該膽固醇之一含量可為關於該奈米脂質體之該總重量的0.01重量%至3重量%。In an embodiment, the content of one of the cholesterol may be 0.01% to 3% by weight with respect to the total weight of the nanoliposome.
在一個實施例中,該辛酸/癸酸三酸甘油酯之一含量可為關於該奈米脂質體之總重量的0.1重量%至10重量%。In an embodiment, the content of one of the caprylic/capric triglycerides may be 0.1% to 10% by weight with respect to the total weight of the nanoliposomes.
在一個實施例中,該氫化卵磷脂、該膽固醇及該辛酸/癸酸三酸甘油酯之一重量比可為1至5:0.1至3:5至15。In one embodiment, a weight ratio of the hydrogenated lecithin, the cholesterol, and the caprylic/capric triglyceride may be 1 to 5:0.1 to 3:5 to 15.
在一個實施例中,該活性成分之一含量可為關於該奈米脂質體之該總重量的0.01重量%至5重量%。In one embodiment, the content of one of the active ingredients may be 0.01% to 5% by weight of the total weight of the nanoliposome.
在一個實施例中,該活性成分與該囊泡之一重量比可為1:18至38。In one embodiment, the weight ratio of the active ingredient to the vesicle may be 1:18 to 38.
在一個實施例中,該奈米脂質體可進一步包括選自由該囊泡中之二丁基羥基甲苯、季戊四醇四(雙-t-丁基羥基氫化肉桂酸)酯及生育酚組成之群組的一或多者。In one embodiment, the nanoliposome may further include a vesicle selected from the group consisting of dibutylhydroxytoluene, pentaerythritol tetrakis (bis-t-butylhydroxyhydrocinnamic acid) and tocopherol. One or more.
在一個實施例中,選自由二丁基羥基甲苯、季戊四醇四(雙-t-丁基羥基氫化肉桂酸)酯及生育酚組成之群組的該一或多者之一含量可為關於該脂質體之該總重量的0.01重量%至2重量%。In one embodiment, the content of one or more selected from the group consisting of dibutylhydroxytoluene, pentaerythritol tetrakis (bis-t-butylhydroxyhydrocinnamic acid) and tocopherol may be related to the lipid 0.01% to 2% by weight of the total weight of the body.
在另一態樣中,在本說明書中描述之技術提供一種製備根據以上實施例中之任一者的油水型組成物之方法,包括:溶解膽固醇、辛酸/癸酸三酸甘油酯及氫化卵磷脂以製備一第一相之一步驟;在乙醇中溶解一水難溶之活性成分以製備一第二相之一步驟;乳化該第一相與該第二相以製備一混合溶液之一步驟;及將該混合溶液分散於蒸餾水中以製備一分散液。In another aspect, the technology described in this specification provides a method for preparing an oil-water type composition according to any of the above embodiments, including: dissolving cholesterol, caprylic/capric triglyceride, and hydrogenated egg A step of preparing a first phase with phospholipids; a step of preparing a second phase by dissolving a poorly water-soluble active ingredient in ethanol; a step of emulsifying the first phase and the second phase to prepare a mixed solution; And disperse the mixed solution in distilled water to prepare a dispersion.
在一個實施例中,製備該第一相之該步驟可為進一步溶解選自由二丁基羥基甲苯、季戊四醇四(雙-t-丁基羥基氫化肉桂酸)酯及生育酚組成之群組的一或多者之一步驟。 [發明之有利效果]In one embodiment, the step of preparing the first phase may be to further dissolve one selected from the group consisting of dibutylhydroxytoluene, pentaerythritol tetrakis (bis-t-butylhydroxyhydrocinnamic acid) ester and tocopherol. Or one of more steps. [Advantageous Effects of Invention]
根據本說明書中揭露之技術,為水難溶之組分中之一者的諸如丁香油素之一活性成分包括於一脂質囊泡中以形成一穩定奈米脂質體調配物。此外,根據本揭露內容,有可能獲得包括在大小上均勻且穩定的諸如丁香油素之一活性成分之奈米脂質體。According to the technology disclosed in this specification, an active ingredient such as syringeol, which is one of the poorly water-soluble components, is included in a lipid vesicle to form a stable nanoliposome formulation. In addition, according to the present disclosure, it is possible to obtain nanoliposomes including an active ingredient such as syringe oil that is uniform and stable in size.
此外,為自然友好成分之兩親性氫化卵磷脂可用作一溶液化之調配物中的一乳化劑以擴張至一無增稠劑脂質體水型調配物。本揭露內容之油水型組成物不使用增稠劑使調配物穩定。In addition, the amphiphilic hydrogenated lecithin, which is a nature-friendly ingredient, can be used as an emulsifier in a solubilized formulation to expand to a thickener-free liposome aqueous formulation. The oil-water type composition of the present disclosure does not use a thickener to stabilize the formulation.
在一個態樣中,在本說明書中揭露之技術可提供一種包括奈米脂質體之油水型組成物,其中該奈米脂質體包括一囊泡,其包括氫化卵磷脂、膽固醇及辛酸/癸酸三酸甘油酯;及該囊泡結構中含有之一活性成分。In one aspect, the technology disclosed in this specification can provide an oil-and-water composition including nanoliposomes, wherein the nanoliposomes include a vesicle including hydrogenated lecithin, cholesterol, and caprylic/capric acid Triglycerides; and the vesicle structure contains an active ingredient.
在一個實施例中,該活性成分可為一乙醇可溶且水難溶之活性成分。In one embodiment, the active ingredient may be an active ingredient soluble in ethanol and insoluble in water.
在一個實施例中,該奈米脂質體之大小可為50 nm至300 nm。較佳地,該奈米脂質體之大小可為100 nm至200 nm。在另一實施例中,該奈米脂質體之大小可為50 nm或更大、60 nm或更大、70 nm或更大、80 nm或更大、90 nm或更大、95 nm或更大、100 nm或更大、105 nm或更大、110 nm或更大、115 nm或更大、120 nm或更大、125 nm或更大、130 nm或更大、135 nm或更大、140 nm或更大或145 nm或更大,且可為300 nm或更小、280 nm或更小、260 nm或更小、240 nm或更小、220 nm或更小、210 nm或更小、200 nm或更小、195 nm或更小、190 nm或更小、185 nm或更小、180 nm或更小、175 nm或更小、170 nm或更小、165 nm或更小、160 nm或更小或155 nm或更小。In one embodiment, the size of the nanoliposomes may be 50 nm to 300 nm. Preferably, the size of the nanoliposome may be 100 nm to 200 nm. In another embodiment, the size of the nanoliposomes may be 50 nm or greater, 60 nm or greater, 70 nm or greater, 80 nm or greater, 90 nm or greater, 95 nm or greater. Large, 100 nm or larger, 105 nm or larger, 110 nm or larger, 115 nm or larger, 120 nm or larger, 125 nm or larger, 130 nm or larger, 135 nm or larger, 140 nm or larger or 145 nm or larger, and can be 300 nm or smaller, 280 nm or smaller, 260 nm or smaller, 240 nm or smaller, 220 nm or smaller, 210 nm or smaller , 200 nm or less, 195 nm or less, 190 nm or less, 185 nm or less, 180 nm or less, 175 nm or less, 170 nm or less, 165 nm or less, 160 nm or less or 155 nm or less.
在一個實施例中,在粒度分佈中的該奈米脂質體之一PDI值可為0.03至0.2。在另一實施例中,PDI值可為0.03或更大、0.04或更大、0.05或更大、0.06或更大、0.07或更大、0.08或更大、0.09或更大、0.1或更大或0.11或更大,且可為0.2或更小、0.19或更小、0.18或更小、0.17或更小、0.16或更小、0.15或更小、0.14或更小、0.13或更小或0.12或更小。In one embodiment, the PDI value of one of the nanoliposomes in the particle size distribution may be 0.03 to 0.2. In another embodiment, the PDI value may be 0.03 or greater, 0.04 or greater, 0.05 or greater, 0.06 or greater, 0.07 or greater, 0.08 or greater, 0.09 or greater, 0.1 or greater Or 0.11 or more, and can be 0.2 or less, 0.19 or less, 0.18 or less, 0.17 or less, 0.16 or less, 0.15 or less, 0.14 or less, 0.13 or less, or 0.12 Or smaller.
在一個實施例中,該活性成分可為通常在化妝品中使用之任何活性成分,且可為選自由丁香油素、積雪草、維他命E、維他命C、蝦青素、神經醯胺、3,4,5-三甲氧基肉桂酸百里酚酯或其立體異構物、鹽、水合物或溶劑化物組成之群組的一或多者,且本發明不限於此。前述3,4,5-三甲氧基肉桂酸百里酚酯可依據商標名MelasolvTM 市售。In one embodiment, the active ingredient can be any active ingredient commonly used in cosmetics, and can be selected from the group consisting of syringe oil, centella asiatica, vitamin E, vitamin C, astaxanthin, ceramide, 3,4 One or more of the group consisting of 5-trimethoxycinnamate thymol or its stereoisomers, salts, hydrates or solvates, and the present invention is not limited thereto. The aforementioned 3,4,5-trimethoxycinnamate thymol ester is commercially available under the trade name Melasolv ™ .
在本說明書中,表達「立體異構物」意謂光學異構物,且其實例包括基本上純鏡像異構物、基本上純非鏡像異構物或其混合物。In this specification, the expression "stereoisomers" means optical isomers, and examples thereof include substantially pure enantiomers, substantially pure diastereomers, or mixtures thereof.
在本說明書中,表達「基本上純」意謂舉例而言,在與鏡像異構物或非鏡像異構物一起使用之情況中,鏡像異構物或非鏡像異構物按約90%或更大、較佳地約95%或更大、更佳地約97%或更大、甚至更佳地約98%或更大、仍更佳地約99%或更大且仍再更佳得多的約99.5%或更大(w/w)存在於一具體化合物中。In this specification, the expression "substantially pure" means that, for example, in the case of use with the enantiomers or diastereomers, the enantiomers or diastereomers are approximately 90% or Larger, preferably about 95% or more, more preferably about 97% or more, even more preferably about 98% or more, still more preferably about 99% or more, and still better More about 99.5% or more (w/w) is present in a specific compound.
在本說明書中,表達「鹽」意謂根據本發明之一個態樣的鹽,其可接受於藥品、化妝品及食品中,且具有母體化合物之所要的活性。鹽之實例包括(1)酸添加鹽,其由諸如鹽酸、氫溴酸、硫酸、硝酸、磷酸之無機酸形成;或諸如乙酸、丙酸、己酸、環戊丙酸、乙醇酸、丙酮酸、乳酸、丙二酸、琥珀酸、蘋果酸、順丁烯二酸、反丁烯二酸、酒石酸、檸檬酸、苯甲酸、3-(4-羥苯甲醯基)苯甲酸、肉桂酸、苦杏仁酸、甲磺酸、乙磺酸、1,2-乙烷-二磺酸、2-羥基乙磺酸、苯磺酸、4-氯苯磺酸、2-萘磺酸、4-甲苯磺酸、樟腦磺酸、4-甲基雙環[2,2,2]-八-2-烯-1-羧酸、葡萄糖甲酸、3-苯丙酸、三甲基乙酸、四-丁基乙酸、月桂磺酸、葡萄糖酸、谷氨酸、羥萘甲酸、柳酸、硬脂酸及己二烯二酸之有機酸形成;或(2)當在母代化合物中存在之酸質子經取代時形成之鹽。此外,鹽可為藥學上可接受之鹽。In this specification, the expression "salt" means a salt according to one aspect of the present invention, which is acceptable in medicines, cosmetics and foods and has the desired activity of the parent compound. Examples of the salt include (1) acid addition salt, which is formed by inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid; or such as acetic acid, propionic acid, caproic acid, cyclopentapropionic acid, glycolic acid, pyruvic acid , Lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzyl)benzoic acid, cinnamic acid, Mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluene Sulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2,2,2]-octa-2-ene-1-carboxylic acid, gluconic acid, 3-phenylpropionic acid, trimethylacetic acid, tetra-butylacetic acid , Lauric sulfonic acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid and adiponic acid are formed by organic acids; or (2) when the acid protons present in the parent compound are replaced The salt of formation. In addition, the salt may be a pharmaceutically acceptable salt.
在本說明書中,表達「藥學上可接受」意謂藉由避免當按相關技術中之藥物劑量使用時之顯著毒性效果、列在藥典中或經辨識為另一一般藥典,能夠被或已被政府或同等管理機構批准在動物、更具體言之在人身上使用。In this specification, the expression "pharmaceutically acceptable" means that by avoiding significant toxic effects when used at the drug dosage in the relevant technology, listed in the pharmacopoeia or recognized as another general pharmacopoeia, it can be or has been The government or equivalent regulatory agency approves use on animals, more specifically on humans.
在本說明書中,表達「水合物」意謂水鍵結至之一化合物,且為包括不具有水與化合物之間的化學鍵結力之包括化合物之一廣泛概念。In this specification, the expression "hydrate" means that water is bonded to a compound, and is a broad concept that includes compounds that do not have the chemical bonding force between water and the compound.
在本說明書中,表達「溶劑化物」意謂形成於溶質之分子或離子與溶劑之分子或離子之間的較高階化合物。In this specification, the expression "solvate" means a higher-order compound formed between the molecules or ions of the solute and the molecules or ions of the solvent.
在一個實施例中,該氫化卵磷脂之含量可為關於該奈米脂質體之總重量的0.1重量%至5重量%。在另一實施例中,該氫化卵磷脂之含量可為關於該奈米脂質體之總重量的0.1重量%或更大、0.12重量%或更大、0.14重量%或更大、0.16重量%或更大、0.18重量%或更大、0.2重量%或更大、0.22重量%或更大、0.24重量%或更大、0.26重量%或更大、0.28重量%或更大或0.29重量%或更大,且可為5重量%或更小、4重量%或更小、3重量%或更小、2重量%或更小、1重量%或更小、0.8重量%或更小、0.6重量%或更小、0.55重量%或更小、0.5重量%或更小、0.48重量%或更小、0.46重量%或更小、0.44重量%或更小、0.42重量%或更小、0.4重量%或更小、0.38重量%或更小、0.36重量%或更小、0.34重量%或更小、0.32重量%或更小或0.31重量%或更小。較佳地,該氫化卵磷脂之含量可為關於該奈米脂質體之總重量的0.3重量%。In one embodiment, the content of the hydrogenated lecithin may be 0.1% to 5% by weight of the total weight of the nanoliposomes. In another embodiment, the content of the hydrogenated lecithin may be 0.1% by weight or more, 0.12% by weight or more, 0.14% by weight or more, 0.16% by weight or more with respect to the total weight of the nanoliposomes. Greater, 0.18% by weight or greater, 0.2% by weight or greater, 0.22% by weight or greater, 0.24% by weight or greater, 0.26% by weight or greater, 0.28% by weight or greater, or 0.29% by weight or greater Large, and may be 5 wt% or less, 4 wt% or less, 3 wt% or less, 2 wt% or less, 1 wt% or less, 0.8 wt% or less, 0.6 wt% Or less, 0.55 wt% or less, 0.5 wt% or less, 0.48 wt% or less, 0.46 wt% or less, 0.44 wt% or less, 0.42 wt% or less, 0.4 wt% or Less, 0.38% by weight or less, 0.36% by weight or less, 0.34% by weight or less, 0.32% by weight or less, or 0.31% by weight or less. Preferably, the content of the hydrogenated lecithin may be 0.3% by weight of the total weight of the nanoliposomes.
在一個實施例中,該膽固醇之含量可為關於該奈米脂質體之該總重量的0.01重量%至3重量%。在另一實施例中,該膽固醇之含量可為關於該奈米脂質體之總重量的0.01重量%或更大、0.02重量%或更大、0.03重量%或更大、0.04重量%或更大、0.05重量%或更大、0.06重量%或更大、0.07重量%或更大、0.08重量%或更大或0.09重量%或更大,且可為3重量%或更小、2重量%或更小、1.5重量%或更小、1重量%或更小、0.8重量%或更小、0.6重量%或更小、0.5重量%或更小、0.4重量%或更小、0.3重量%或更小或0.2重量%或更小。較佳地,該膽固醇之含量可為關於該奈米脂質體之總重量的0.1重量%。In an embodiment, the content of the cholesterol may be 0.01% to 3% by weight with respect to the total weight of the nanoliposome. In another embodiment, the cholesterol content may be 0.01% by weight or greater, 0.02% by weight or greater, 0.03% by weight or greater, 0.04% by weight or greater, relative to the total weight of the nanoliposomes. , 0.05% by weight or more, 0.06% by weight or more, 0.07% by weight or more, 0.08% by weight or more or 0.09% by weight or more, and can be 3% by weight or less, 2% by weight or Smaller, 1.5% by weight or less, 1% by weight or less, 0.8% by weight or less, 0.6% by weight or less, 0.5% by weight or less, 0.4% by weight or less, 0.3% by weight or less Or 0.2% by weight or less. Preferably, the content of the cholesterol may be 0.1% by weight with respect to the total weight of the liposomes.
在一個實施例中,該辛酸/癸酸三酸甘油酯之含量可為關於該奈米脂質體之總重量的0.1重量%至10重量%。在另一實施例中,該辛酸/癸酸三酸甘油酯之含量可為關於該奈米脂質體之總重量的0.1重量%或更大、0.2重量%或更大、0.3重量%或更大、0.4重量%或更大、0.5重量%或更大、0.6重量%或更大、0.7重量%或更大、0.8重量%或更大或0.9重量%或更大,且可為10重量%或更小、9重量%或更小、8重量%或更小、7重量%或更小、6重量%或更小、5重量%或更小、4重量%或更小、3重量%或更小、2.5重量%或更小、2重量%或更小、1.8重量%或更小、1.6重量%或更小、1.5重量%或更小、1.4重量%或更小、1.3重量%或更小、1.2重量%或更小或1.1重量%或更小。較佳地,該辛酸/癸酸三酸甘油酯之含量可為關於該奈米脂質體之總重量的1重量%。In an embodiment, the content of the caprylic/capric triglyceride may be 0.1% to 10% by weight with respect to the total weight of the nanoliposomes. In another embodiment, the content of caprylic/capric triglyceride may be 0.1% by weight or more, 0.2% by weight or more, or 0.3% by weight or more with respect to the total weight of the nanoliposomes. , 0.4% by weight or greater, 0.5% by weight or greater, 0.6% by weight or greater, 0.7% by weight or greater, 0.8% by weight or greater or 0.9% by weight or greater, and may be 10% by weight or Smaller, 9% by weight or less, 8% by weight or less, 7% by weight or less, 6% by weight or less, 5% by weight or less, 4% by weight or less, 3% by weight or less Small, 2.5% by weight or less, 2% by weight or less, 1.8% by weight or less, 1.6% by weight or less, 1.5% by weight or less, 1.4% by weight or less, 1.3% by weight or less , 1.2% by weight or less or 1.1% by weight or less. Preferably, the content of caprylic/capric triglyceride may be 1% by weight of the total weight of the nanoliposomes.
在一個實施例中,氫化卵磷脂、膽固醇及辛酸/癸酸三酸甘油酯之重量比可為1至5:0.1至3:5至15。在另一態樣中,重量比可為2至4:0.5至1.5:7至12。重量比較佳地為3:1:10。In an embodiment, the weight ratio of hydrogenated lecithin, cholesterol, and caprylic/capric triglyceride may be 1 to 5:0.1 to 3:5 to 15. In another aspect, the weight ratio may be 2 to 4:0.5 to 1.5: 7 to 12. The weight is preferably 3:1:10.
在一個實施例中,該活性成分之含量可為關於該奈米脂質體之該總重量的0.01重量%至5重量%。在另一實施例中,該活性成分之含量可為關於該奈米脂質體之總重量的0.01重量%或更大、0.02重量%或更大、0.03重量%或更大或0.04重量%或更大,且可為5重量%或更小、4重量%或更小、3重量%或更小、2重量%或更小、1重量%或更小、0.8重量%或更小、0.6重量%或更小、0.4重量%或更小、0.2重量%或更小、0.16重量%或更小、0.12重量%或更小、0.1重量%或更小、0.09重量%或更小、0.08重量%或更小、0.07重量%或更小或0.06重量%或更小。較佳地,該活性成分之含量可為關於該奈米脂質體之總重量的0.05重量%。In one embodiment, the content of the active ingredient may be 0.01% to 5% by weight of the total weight of the nanoliposome. In another embodiment, the content of the active ingredient may be 0.01% by weight or more, 0.02% by weight or more, 0.03% by weight or more, or 0.04% by weight or more with respect to the total weight of the nanoliposomes. Large, and may be 5 wt% or less, 4 wt% or less, 3 wt% or less, 2 wt% or less, 1 wt% or less, 0.8 wt% or less, 0.6 wt% Or less, 0.4% by weight or less, 0.2% by weight or less, 0.16% by weight or less, 0.12% by weight or less, 0.1% by weight or less, 0.09% by weight or less, 0.08% by weight or Smaller, 0.07 wt% or less, or 0.06 wt% or less. Preferably, the content of the active ingredient may be 0.05% by weight with respect to the total weight of the nanoliposomes.
在一個實施例中,該活性成分與該等囊泡之重量比可為1:18至38。在另一態樣中,重量比可為1:23至33、1:25至31或1:27至29。重量比較佳地為約1:28。In one embodiment, the weight ratio of the active ingredient to the vesicles may be 1:18 to 38. In another aspect, the weight ratio may be 1:23 to 33, 1:25 to 31, or 1:27 to 29. The weight is preferably about 1:28.
在一個實施例中,除了囊泡之外,該奈米脂質體亦可進一步包括選自由二丁基羥基甲苯、季戊四醇四(雙-t-丁基羥基氫化肉桂酸)酯及生育酚組成之群組的一或多者。較佳地,該奈米脂質體可進一步包括生育酚。In one embodiment, in addition to vesicles, the nanoliposomes may further include a group selected from the group consisting of dibutylhydroxytoluene, pentaerythritol tetrakis (bis-t-butylhydroxyhydrocinnamic acid) ester and tocopherol One or more of the group. Preferably, the nanoliposomes may further include tocopherol.
在一個實施例中,選自由二丁基羥基甲苯、季戊四醇四(雙-t-丁基羥基氫化肉桂酸)酯及生育酚組成之群組的該一或多者之含量可為關於脂質體之該總重量的0.01重量%至2重量%。在另一實施例中,選自由二丁基羥基甲苯、季戊四醇四(雙-t-丁基羥基氫化肉桂酸)酯及生育酚組成之群組的該一或多者之含量可為關於該脂質體之總重量的0.01重量%或更大、0.03重量%或更大、0.05重量%或更大、0.06重量%或更大、0.07重量%或更大、0.08重量%或更大或0.09重量%或更大,且可為2重量%或更小、1.5重量%或更小、1重量%或更小、0.7重量%或更小、0.5重量%或更小、0.4重量%或更小、0.3重量%或更小或0.2重量%或更小。較佳地,其含量可為約0.1重量%。In one embodiment, the content of the one or more selected from the group consisting of dibutylhydroxytoluene, pentaerythritol tetrakis (bis-t-butylhydroxyhydrocinnamic acid) and tocopherol may be related to liposomes 0.01% to 2% by weight of the total weight. In another embodiment, the content of the one or more selected from the group consisting of dibutylhydroxytoluene, pentaerythritol tetrakis(bis-t-butylhydroxyhydrocinnamic acid) and tocopherol may be related to the lipid 0.01% by weight or greater, 0.03% by weight or greater, 0.05% by weight or greater, 0.06% by weight or greater, 0.07% by weight or greater, 0.08% by weight or greater, or 0.09% by weight of the total weight of the body Or greater, and may be 2% by weight or less, 1.5% by weight or less, 1% by weight or less, 0.7% by weight or less, 0.5% by weight or less, 0.4% by weight or less, 0.3 % By weight or less or 0.2% by weight or less. Preferably, its content may be about 0.1% by weight.
在一個實施例中,油水型組成物可不包括增稠劑。本揭露內容之油水型組成物可不使用增稠劑(諸如,黃原膠)使調配物穩定。In one embodiment, the oil-water type composition may not include a thickener. The oil-water type composition of the present disclosure may not use a thickener (such as xanthan gum) to stabilize the formulation.
在另一態樣中,在本說明書中描述之技術提供一種製備根據以上實施例中之任一者的油水型組成物之方法,包括:溶解膽固醇、辛酸/癸酸三酸甘油酯及氫化卵磷脂以製備一第一相之一步驟;在乙醇中溶解一水難溶之活性成分以製備一第二相之一步驟;乳化該第一相與該第二相以製備一混合溶液之一步驟;及將該混合溶液分散於蒸餾水中以製備一分散液。In another aspect, the technology described in this specification provides a method for preparing an oil-water type composition according to any of the above embodiments, including: dissolving cholesterol, caprylic/capric triglyceride, and hydrogenated egg A step of preparing a first phase with phospholipids; a step of preparing a second phase by dissolving a poorly water-soluble active ingredient in ethanol; a step of emulsifying the first phase and the second phase to prepare a mixed solution; And disperse the mixed solution in distilled water to prepare a dispersion.
在一個實施例中,製備該第一相之該步驟可為進一步溶解選自由二丁基羥基甲苯、季戊四醇四(雙-t-丁基羥基氫化肉桂酸)酯及生育酚組成之群組的一或多者之一步驟。較佳地,製備該第一相之該步驟可為進一步溶解生育酚之一步驟。In one embodiment, the step of preparing the first phase may be to further dissolve one selected from the group consisting of dibutylhydroxytoluene, pentaerythritol tetrakis (bis-t-butylhydroxyhydrocinnamic acid) ester and tocopherol. Or one of more steps. Preferably, the step of preparing the first phase may be a step of further dissolving tocopherol.
下文,參考實例更詳細地描述本發明。此等實例僅用於說明本發明,且對熟習此項技術者顯而易見的是,本發明之範疇不應被解釋為限於此等實例。Hereinafter, the present invention will be described in more detail with reference to examples. These examples are only used to illustrate the present invention, and it is obvious to those skilled in the art that the scope of the present invention should not be construed as limited to these examples.
脂質體之製備
[表1]
表1之成分1至3經在70℃或更高下按agi混合器(agi mixer)之30 rpm分散及溶解以製備第一相。確認氫化卵磷脂是否完全在80℃或更高之一溫度下溶解。隨後,在丁香油素於50℃溶解於乙醇中後,成分6至8經在50℃或更高下按agi混合器之30 rpm進一步分散及溶解以製備第二相。接著,藉由均質混合將第一相與第二相乳化,且乳化以10,000 rpm、在70℃下繼續進行達10分鐘以製備混合溶液。將混合溶液緩慢地添加至處於50℃之蒸餾水,且按5,000 rpm之均勻速度分散達10分鐘或更多,以製備其中分散有包括丁香油素之脂質體的溶液。
通常用作潤膚劑、親脂性載劑、皮膚滲透增強劑及增溶劑之辛酸/癸酸三酸甘油酯包括親水性及親脂性兩種基團,且因此對包括乙醇可溶及水難溶之活性成分(諸如,丁香油素)的調配物之穩定性有影響。Caprylic/capric triglycerides, which are commonly used as emollients, lipophilic carriers, skin penetration enhancers, and solubilizers, include both hydrophilic and lipophilic groups, and are therefore suitable for alcohol-soluble and poorly water-soluble groups. The stability of the formulation of active ingredients (such as syringae oil) has an impact.
此外,氫化卵磷脂在許多情況中通常經由在水部分中之高溫水合製程而用作界面活性劑,但在本揭露內容中用以形成囊泡。In addition, hydrogenated lecithin is usually used as a surfactant through a high-temperature hydration process in the water part in many cases, but is used to form vesicles in the present disclosure.
確認調配物之穩定性Confirm the stability of the formulation
如在表2及3中所示製備實例1至5及比較實例1至4以比較調配物之穩定性。在實例2至4中,將二丁基羥基甲苯、季戊四醇四(雙-t-丁基羥基氫化肉桂酸)酯或生育酚進一步添加至實例1之組成物,以便確認丁香油素之滴定度穩定性,且在實例5中,添加3,4,5-三甲氧基肉桂酸百里酚酯以便確認3,4,5-三甲氧基肉桂酸百里酚酯作為活性成分之滴定度穩定性。
[表2]
實例1至5及比較實例1至4之調配物穩定性分別係在室溫、冷凍條件、在45℃下之條件及循環條件下確認。循環條件係確認調配物之穩定性之結果,同時自-10℃至45℃執行循環達12小時。在五個溫度範圍中之每一者中按兩週之間隔(共八週)確認穩定性,且每一樣本經取出且允許在室溫下使溫度平衡達四小時,且接著視覺確認調配物之穩定性。結果展示於下表4中。
[表4]
調配物之穩定性在實例1、4及5中係良好的,且確認在實例2至4當中之實例4中,在較長時間週期內保證滴定度穩定性。假定添加為抗氧化成分之生育酚以保證丁香油素之功能滴定度。在比較實例4之情況中,不添加乙醇,且確認在製備後立即觀測到沉澱,因此不能夠量測初始粒度。能夠自比較實例2之結果確認取決於膽固醇之存在或不存在的調配物之穩定性。應理解,穩定性在45℃下且在存在膽固醇之情況下的循環條件中較佳。The stability of the formulation was good in Examples 1, 4, and 5, and it was confirmed that in Example 4 of Examples 2 to 4, the titer stability was ensured over a longer period of time. It is assumed that tocopherol is added as an antioxidant component to ensure the functional titer of eugenol. In the case of Comparative Example 4, no ethanol was added, and it was confirmed that precipitation was observed immediately after preparation, so the initial particle size could not be measured. It can be confirmed from the results of Comparative Example 2 that the stability of the formulation depends on the presence or absence of cholesterol. It should be understood that the stability is better in cycling conditions at 45°C and in the presence of cholesterol.
根據實例1製備的奈米脂質體之長期粒度改變展示於表6及第1圖中。自以下結果,確認實例1為穩定調配物,因為在室溫條件下,直至D+58天,粒度改變方顯著。此外,亦確認維持均勻粒度分佈,因為PDI值小。此外,實例1之cryoTEM影像圖示於第2圖中。能夠自第2圖確認奈米脂質體之囊泡結構。確認脂質體粒子之大小為100 nm至200 nm。The long-term particle size changes of nanoliposomes prepared according to Example 1 are shown in Table 6 and Figure 1. From the following results, it is confirmed that Example 1 is a stable formulation, because at room temperature, the particle size changes significantly until D+58 days. In addition, it was confirmed that a uniform particle size distribution was maintained because the PDI value was small. In addition, the cryoTEM image of Example 1 is shown in Figure 2. The vesicle structure of nanoliposomes can be confirmed from Figure 2. Confirm that the size of liposome particles is 100 nm to 200 nm.
量測奈米脂質體之長期粒度改變之方法如下。如在穩定性之確認中,在五個溫度範圍中,在一共八週內,按兩週之間隔確認粒度,且每一樣本經取出且允許在室溫下使溫度平衡達四小時,且接著使用Zetasizer (Nano-ZS,馬爾文儀器(Malvern Instruments),UK. 17)量測粒度。
[表5]
在嚴格條件下,根據實例1製備的奈米脂質體之大小及PDI值展示於下表6中。在嚴格之冷凍條件條件、冰凍、45℃及循環條件下,在D+32點,粒度改變不顯著,且PDI值仍然小,因此應理解,粒度並不改變且係均勻的。因此,確認奈米脂質體調配物經製備為穩定的。藉由視覺評估及表6之確認,不存在丁香油素之沉澱,且因此應理解,丁香油素在奈米脂質體中穩定。
[表6]
根據實例4製備的奈米脂質體之長期粒度改變展示於表7及第3圖中。確認在室溫條件下均勻地維持粒度,直至D+64。自在實例4中的室溫下之Z平均值之觀測,確認粒度係處於160 nm至170 nm之級別中,且在長時間週期上不存在粒度之改變。
[表7]
在嚴格條件下,根據實例4製備的奈米脂質體之大小及PDI值展示於表8及第4圖中。確認甚至在嚴格條件下,調配物係穩定的,無大小之改變。
[表8]
根據實例5製備的奈米脂質體之長期粒度改變展示於表9及第5圖中。確認在室溫條件下均勻地維持粒度,直至D+64。自在實例5中的室溫下之Z平均值之觀測,確認粒度係處於180 nm至200 nm之級別中,且在長時間週期上不存在粒度之改變。此外,實例5之cryoTEM影像圖示於第6圖中。能夠自第6圖確認奈米脂質體之囊泡結構。確認脂質體粒子之大小為150 nm至200 nm。
[表9]
在嚴格條件下,根據實例5製備的奈米脂質體之大小及PDI值展示於表10及第7圖中。確認甚至在嚴格條件下,調配物係穩定的,無大小之改變。
[表10]
藉由使用高效能液相層析法(high performance liquid chromatography;HPLC)確認在實例2至5中之每一者,甚至在2、4、8、16及24週後,活性成分(丁香油素、3,4,5-三甲氧基肉桂酸百里酚酯)是否維持滴定度。結果展示於下表11中。確認在實例2至5中的活性成分之滴定度經良好地維持。
[表11]
無no
第1圖為本揭露內容之實例1的長期粒度資料量測之曲線圖。Figure 1 is a graph of the long-term particle size data measurement of Example 1 of the disclosure.
第2圖為藉由cryoTEM觀測的本揭露內容之實例1的奈米脂質體之一影像。Figure 2 is an image of the nanoliposomes of Example 1 of the present disclosure observed by cryoTEM.
第3圖為本揭露內容之實例4的長期粒度資料量測之曲線圖。Figure 3 is a graph of the long-term particle size data measurement of Example 4 of the disclosure.
第4圖為本揭露內容之實例4的在嚴格條件下之粒度資料量測之曲線圖。Figure 4 is a graph of the particle size data measurement under strict conditions in Example 4 of the disclosure.
第5圖為本揭露內容之實例5的長期粒度資料量測之曲線圖。Figure 5 is a graph of the long-term particle size data measurement of Example 5 of the disclosure.
第6圖為藉由cryoTEM觀測的本揭露內容之實例5的奈米脂質體之一影像。Figure 6 is an image of the nanoliposome of Example 5 of the present disclosure observed by cryoTEM.
第7圖為本揭露內容之實例5的在嚴格條件下之粒度資料量測之曲線圖。Figure 7 is a graph of the particle size data measurement under strict conditions of Example 5 of the disclosure.
國內寄存資訊(請依寄存機構、日期、號碼順序註記) 無 國外寄存資訊(請依寄存國家、機構、日期、號碼順序註記) 無Domestic deposit information (please note in the order of deposit institution, date and number) no Foreign hosting information (please note in the order of hosting country, institution, date and number) no
Claims (15)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2018-0132097 | 2018-10-31 | ||
KR20180132097 | 2018-10-31 | ||
KR1020190133095A KR20200049592A (en) | 2018-10-31 | 2019-10-24 | Water-in-oil type cosmetic composition comprising nano liposome |
KR10-2019-0133095 | 2019-10-24 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW202034892A true TW202034892A (en) | 2020-10-01 |
TWI826564B TWI826564B (en) | 2023-12-21 |
Family
ID=70677176
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW108139384A TWI826564B (en) | 2018-10-31 | 2019-10-31 | Oil-in-water type cosmetic composition comprising nano liposome and method of preparing the same |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR20200049592A (en) |
TW (1) | TWI826564B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102495676B1 (en) * | 2020-10-29 | 2023-02-07 | 코스맥스 주식회사 | Cosmetic composition of containing solubilized nanocomposition |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005265876A (en) | 2004-03-16 | 2005-09-29 | Renesas Technology Corp | Method for manufacturing semiconductor device |
KR101624888B1 (en) * | 2009-12-29 | 2016-05-30 | 코웨이 주식회사 | Vesicle Having Self-emulsifying Nano Liposome and Multilayer Liquid Crystal, a Preparation Method Therof and Its Use |
-
2019
- 2019-10-24 KR KR1020190133095A patent/KR20200049592A/en unknown
- 2019-10-31 TW TW108139384A patent/TWI826564B/en active
Also Published As
Publication number | Publication date |
---|---|
KR20200049592A (en) | 2020-05-08 |
TWI826564B (en) | 2023-12-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU738455B2 (en) | Gellable pharmaceutical compositions | |
US4363806A (en) | Pharmaceutical composition | |
US8541010B2 (en) | Cosmetic composition comprising double-shell nano-structure | |
JPS6295134A (en) | Production of liposome | |
KR20080026960A (en) | Synthesis of silica impregnated with nanosized liposome emulsion comprising coenzyme q10 and cosmetic compositions using it | |
EP1565191A1 (en) | Delivery composition and method | |
CN104490782A (en) | Temperature control foaming agent for external use, making method thereof and application thereof | |
WO2021192861A1 (en) | Ionic liquid, solvent, preparation, and transdermally absorbable agent | |
TWI826564B (en) | Oil-in-water type cosmetic composition comprising nano liposome and method of preparing the same | |
JPH0341025A (en) | Method for improving therapeutic effect of fat-soluble corticosteroid and composition for executing this method | |
CN114917133A (en) | Supramolecular solvent liposome and preparation method and application thereof | |
CN114848533A (en) | Preparation method of nano-liposome efficiently-coated composite ceramide | |
JP7094321B2 (en) | A composition containing at least one ceramide, at least one sphingoid base and triethyl citrate. | |
CA2089494C (en) | Vesicles in non-polar media | |
JP2022501314A (en) | Topical composition | |
JP2015227354A (en) | Oil-in-water emulsion of mometasone and propylene glycol | |
PT2204174E (en) | Metronidazole solubilisation process with niacinamide and two glycols, and the resulting solution | |
TWI719318B (en) | Preparation method of positively charged charged liposome and charged liposome | |
KR20200030191A (en) | Manufacturing method of cosmetic composition comprising superoxide dismutase capsule | |
KR20190109511A (en) | Topical composition | |
WO2020091416A1 (en) | Oil-in-water type cosmetic composition comprising nanoliposome | |
KR20150000371A (en) | Solubilizing composition of insoluble cosmetic compounds and the method for preparing the same | |
EP3362045B1 (en) | A process for preparing a composition comprising a high concentration of one or more avermectins | |
KR20170117771A (en) | Cosmetic composition containing phenoxyethanol | |
KR20200040369A (en) | Method for producing liposome of poorly soluble sphingolipid using hydrogenated lysophosphatidylcholine and sophorolipids |