유제화에 의한 경구용 항암제인 테가푸르의 장관 임파수송

이용복,남권호,장우익,오인준,고익배,Lee, Yong-Bok,Nam, Kweon-Ho,Chang, Woo-Ik,Oh, In-Joon,Koh, Ik-Bae 한국약제학회 1995 Journal of Pharmaceutical Investigation Vol.25 No.1

W/O and O/W emulsions of tegafur (50 mg/5 ml/kg) were orally administered to rats to compare with their mesenteric lymphatic delivery effects. And also in order to demonstrate the lymph targeting associated to the oral route, it was deemed necessary to investigate the fate of solution after oral administration as a control. Lymph and plasma samples were periodically taken from each subject of mesenteric lymphatic duct cannulated rats. Then, lymph and plasma levels of tegafur and its active metabolite, 5-FU, were simultaneously observed. Also pharmacokinetic parameters were compared with each others. On the other hand, most previous studies of lymphatic transport have not addressed the question of whether an increase in mesenteric or thoracic lymph transport by the manipulation of a suspected variable was due to a selective delivery to the intestinal lymphatics or an overall increase availability. Therefore, based on a physiologically based pharmacokinetic model which represents the characteristics of lymphatic systems, we are also going to determine the contributions of mesenteric lymph transport versus thoracic lymph transport of tegafur reported in reference(13). In comparison with tegafur solution, AUC and mean residence time of plasma tegafur were significantly increased in W/O emulsion but significantly decreased in O/W emulsion. Lymph flow rates were similar in both solution and W/O emulsion but half in O/W emulsion. AUC of tegafur in mesenteric lymph and in plasma for W/O emulsion were 3.7 times and 2.9 times more than those for O/W emulsion, respectively. And AUC of 5-FU in thoracic lymph for W/O emulsion was 3.7 times more than that for O/W emulsion. These results suggested that lymphatic delivery or tegafur by W/O emulsion was more effective than that by on emulsion due to its differences or formation ability of chylomicrons.

센텔라 아시아티카 정량추출물을 함유한 Water in Oil in Water (W₁/O/W₂) 에멀젼 제조에 관한 연구

서동환 ( Dong Hoan Seo ),이홍선 ( Hong Seon Lee ),윤종혁 ( Jong Hyuk Yoon ),김연준 ( Youn Joon Kim ),변상요 ( Sang Yo Byun ) 대한화장품학회 2015 대한화장품학회지 Vol.41 No.4

센텔라 아시아티카 정량추출물(TECA)은 병풀에서 얻은 난용성 추출물로 상처치유 및 항주름 물질로 알려져 있다. 본 연구에서는 TECA를 함유한 water in oil in water (W₁/O/W₂) 에멀젼 제조에 필요한 최적의 실험 조건을 찾기 위해 연구를 진행하였다. TECA의 용해도는 UV 흡광도계를 이용하였으며, 디프로필렌 글라이콜(40.0 g), 에탄올(20.0 g) 및 정제수(10.0 g)의 조성에서 2.55 g의 TECA가 용해되는 것을 확인하였다. 에멀젼(W₁/O, W₁/O/W₂)의 안정도에 영향을 미치는 요인에 대하여 조사하였다. W1/O 에멀젼의 제조하기 위한 최적의 수상 조건은 디프로필렌글라이콜 : 에탄올 : 정제수 : TECA가 40.0 : 20.0 : 10.0 : 2.5%(w/w), 유상 조건은 스쿠알란 : 세틸피이지/피피지-10/1디메치콘 : 세테아릴알코올이 22.5 : 4.0 : 1.0%(w/w)임을 확인하였다. W1/O/W2 멀티에멀젼을 제조하기 위한 최적의 조건은 정제수 : W₁/O 에멀젼 : 폴리소르베이트 80 : 카보머 : 트리에탄올아민의 비율이 55.8 : 40.0 : 4.0 : 0.1 : 0.1% (w/w)임을 확인하였다. Titrated extract of Centella asiatica (TECA), which is poorly soluble in water is well known for wound healing and anti wrinkle agent. This study was conducted to find the optimum condition for the preparation of water in oil in water (W₁/O/W₂) emulsion containing TECA. Solubility of TECA were measured by UV spectrophotometer. 2.55 g of TECA was dissolved in solution composed of dipropylene glycol (40.0 g), ethanol (20.0 g), and water (10.0 g). Factors affecting stability of the emulsions (W₁/O, W₁/O/W₂) was investigated. The optimum conditions for the preparation of W₁/O emulsion was composed of dipropylene glycol : ethanol : water : TECA in a weight ratio of 40.0 : 20.0 : 10.0 : 2.5 for water phase and squalane : cetyl PEG/PPG-10/1 dimethicone : cetearyl alcohol in a weight ratio of 22.5 : 4.0 : 2.5 for oil phase. The optimum conditions for the preparation of W₁/O/W₂ multiple emulsion was composed of water : W₁/O emulsion : polysorbate 80 : carbomer : triethanolamine in a weight ratio of 55.8 : 40.0 : 4.0 : 0.1 : 0.1.

삼중블록 고분자 계면활성제의 재유화 억제 기능을 이용한 지속내수성 O/W 에멀젼형 자외선 차단용 화장품 개발

이지현 ( Ji Hyun Lee ),홍성윤 ( Sung Yun Hong ),이진용 ( Jin Yong Lee ),안소연 ( So Youn An ),이효진 ( Hyo Jin Lee ),김성용 ( Sung Yong Kim ),이준배 ( Jun Bae Lee ),김진웅 ( Jin Woong Kim ),신경희 ( Kyounghee Shin ) 대한화장품학회 2019 대한화장품학회지 Vol.45 No.2

본 연구는 poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) 삼중블록 고분자 계면활성제를 이용하여 제조된 우수한 사용감과 선택적인 클렌징 효과를 갖는 수중유(O/W) 에멀젼 타입의 내수성 자외선 차단 제형에 관한 것이다. 수영, 등산 등 다양한 야외 레저 활동이 많아짐에 따라 내수성 자외선 차단제의 수요가 증가하고 있다. 내수성 자외선 차단제는 물이나 땀에 지워지지 않아야하기 때문에 대부분 유중수(W/O) 에멀젼 제형으로 만들어진다. 하지만, W/O 에멀젼 제형은 오일리한 사용감과 클렌징이 어렵다는 단점이 있다. 이에 비해 O/W 에멀젼 제형은 사용감이 우수하고, 클렌징도 용이하지만, 물과의 재유화가 쉽기 때문에 내수성 특성을 갖는 것이 매우 어렵다. 본 연구에서는 이러한 문제를 해결하기 위해 O/W 에멀젼 제형의 HLB 값(~ 10)을 가지면서도 상대적으로 높은 계면장력을 가짐으로써 재유화에 강한 삼중블록 고분자 계면활성제를 도입하였고, 이를 통해 O/W 에멀젼형 지속내수성 자외선 차단제를 개발하였다. 본 연구를 통해 개발된 자외선 차단제는 우수한 사용감과 지속내수성, 그리고 폼 클렌저와의 선택적인 클렌징 효과를 보여준다. 향후 사용감이 다양화된 새로운 O/W 에멀젼형 자외선 차단제 제품 개발에 도움이 될 것으로 기대된다. This study reports water-resistant oil-in-water (O/W) emulsion-based sunscreening formulations prepared using a poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock polymeric surfactant. As a result of a variety of outdoor recreational activities such as swimming and hiking, consumer needs for development of advanced water-resistant sunscreen formulations are increasing. Water-resistant sunscreens are mostly based on water-in-oil (W/O) emulsions, because they should not be wiped off by water or sweat. However, the W/O emulsion formulations have a disadvantage in that the feeling of use is oily and difficult to remove. On the other hand, the O/W emulsion formulations are excellent in achieving the better skin feel as well as the easier removal. However, it is difficult to provide the O/W emulsion formulations with the water-repelling performance, since re-emulsification likely occurs upon getting touch with water. To solve this problem, this study proposes a O/W emulsion-based sunscreen formulation, a triblock polymeric surfactant having relatively high interfacial tension HLB value (~ 10). This allows the sunscreen formulations to exhibit the improved water repellence function by preventing their re-emulsification. The sunscreen formation system prepared in this study would be useful for diversification of functional sunscreen products, taking advantages of its excellent emulsion stability, UV protection performance, long lasting water-resistant function and selective cleansing effect with only foam cleanser.

Polyglyceryl-10 Stearate를 이용한 W/O/W 다중 에멀젼의 제조에 관한 연구

유정민 ( Jung Min Yoo ),최세범 ( Se Bum Choi ),김경민 ( Kyung Min Kim ),김성호 ( Seong Ho Kim ),이청희 ( Chung Hee Lee ),이상길 ( Sang Gil Lee ),표형배 ( Hyeong Bae Pyo ) 대한화장품학회 2014 대한화장품학회지 Vol.40 No.3

다중 에멀젼은 다층 구조를 갖는 에멀젼으로 W/O/W형과 O/W/O형으로 구분된다. 화장품 분야에서 다중에멀젼은 불안정한 유효성분의 안정화를 위해 이용되지만, 제조의 어려움과 안정성 등의 문제로 잘 이용되지 않는다. 본 연구에서는 다중 에멀젼의 제조에 있어 2 단계(two-step) 유화법을 이용하여 W/O/W형 다중 에멀젼을 제조하였고, 다중 에멀젼의 형성에 영향을 주는 요소 중 유화제의 계열에 초점을 두어 유화 안정성 및 에멀젼 형성정도를 측정하였다. 결과를 통해 다중 에멀젼은 오일의 특성에 따라 polyglyceryl-10 stearate 유화제에 의해 다중 에멀젼의 형성이 달라지는 것을 확인하였고, 이를 통해 주 유화제로써 polyglyceryl-10 stearate 유화제의 적용이 다중 에멀젼 형성 및 안정화의 가능성이 있음을 제시하였다. Multiple emulsions, called multiphase emulsions, include water-in-oil-in-water (W/O/W) type and oil-in-water- in-oil (O/W/O) type emulsions. In cosmetic industry, they are used to stabilize active ingredients but the applicability of the multiple emulsions is limited because of low stability and difficulty of manufacturing. In this study, we investigated a two-step emulsification process for a W/O/W type emulsion. We also investigated the change of stability using different emulsifiers and oil polarity. The results suggested that polyglyceryl-10 stearate, as a main emulsifier, played an important role in the stability and the formation of the multiple emulsions.

Surfactant micelle이 W/O/W multiple emulsion의 산화에 미치는 영향

Woen-Seup Cha(차원섭),Young-Je Cho(조영제) 한국생명과학회 2010 생명과학회지 Vol.20 No.11

W/O/W multiple emulsion의 산화에 미치는 surfactant micelle의 영향을 규명하기 위하여 W/O/W multiple emulsion에서 continuous phase로 전이되는 ferric iron의 양과 hydroperoxide의 양을 측정한 결과, continuous phase로 전이된 ferric iron과 hydroperoxide의 양은 첨가한 과량의 surfactant micelle에 의해, 저장기간이 길어질수록 증가하였다. Ferric iron을 함유한 W/O/W multiple emulsion의 지방산화 정도는 hydroperoxide와 TBA값 및 headspace hexanal을 측정하여 살펴본 결과 과량의 surfactant에 의해 산화는 감소하였다. 이상의 결과로 첨가된 과량의 surfactant에 의해 W/O/W multiple emulsion에서 prooxidant로 작용하는 ferric iron의 위치가 변화되어 산화를 줄일 수 있을 것으로 판단하였다. The purpose of this research was to determine the effect of surfactant micelles on lipid oxidation in W/O/W multiple emulsions. The content of ferric irons and hydroperoxide in the continuous phase in W/O/W multiple emulsions was measured as a function of Brij micelle. The concentration of ferric iron and hydroperoxide in the continuous phase increased with increased storage time (1~6 days). Lipid oxidation rates, as determined by the formation of lipid hydroperoxides, TBARs and headspace hexanal, in the W/O/W multiple emulsions containing ferric iron decreased when 3% surfactant micelles were exceeded. These results indicate that excess surfactant micelles could alter the physical location and prooxidant activity of iron in W/O/W multiple emulsions.

Turbiscan^®을 이용한 Glyceryl Monooleate(GMO) 함유 W/O 유제의 안정성 평가

조경진,조원경,이전평,김민수,김정수,황성주,Cho, Kyung-Jin,Cho, Won-Kyung,Lee, Jeon-Pyung,Kim, Min-Soo,Kim, Jeong-Soo,Hwang, Sung-Joo 한국약제학회 2009 Journal of Pharmaceutical Investigation Vol.39 No.4

The main object of this study was to prepare of w/o emulsion including glyceryl monooleate(GMO) and to evaluate its stability by using the recently developed $Turbiscan^{(R)}LAB$. GMO is the polar oily surfactant with the low HLB value, and it forms the gel phase of cubic structures after dissolves in aqueous media. Phosphate buffer solution (PBS) of pH 7.4 was prepared as the water phase and Marcol 52(mineral oil) was used as the oil phase in this study. GMO was used as the surfactant of W/O emulsion. W/O emulsion using GMO alone as a surfactant was very unstable. But the emulsion using both GMO and poloxamer 407 was more stable. The stability of W/O emulsions was evaluated after centrifuging the emulsions. But it was difficult with naked eye because an opaque and concentrated system like W/O emulsion was very turbid. So $Turbiscan^{(R)}LAB$ was used to detect the destabilization phenomena in non-diluted emulsion. As a result, the W/O emulsion using the proper amounts of GMO and poloxamer 407 was more stable among them using GMO of various amounts. But it seems that the other element for the stability of W/O emulsion including GMO was required. Furthermore, the $Turbiscan^{(R)}LAB$ was a very efficient analyzer for evaluating the physical stability of emulsion.

화장품용 W(마이크로바이오젤)/O/W 멀티-에멀젼 제조

정원욱(Won-Wook Jeong),서상권(Sang Gwon Seo),이의정(Eui Jung Lee),오주영(Joo-young Oh),이경진(Kyung Jin Lee) 한국고분자학회 2024 폴리머 Vol.48 No.1

Microbiogels made from natural polymers are attractive for biomedical applications such as drug delivery and have various manufacturing methods. However, it has drawbacks such as unstable yield and cumbersome separation process. This study presents a simple method to form cosmetic W (microbiogel)/O emulsion that produces microbiogel directly during cosmetic W/O emulsion manufacturing process and then stably produce the W (microbiogel)/O/W multi-emulsion through a continuous room temperature process. We confirmed that a partitioned structure was formed in which other particles exist within the particles dispersed in the outer water phase from microscopic observation of the prepared W/O/W multi-emulsion and the particle size and viscoelasticity of W/O emulsion and W/O/W multi-emulsion increased as the ratio of inner water phase (microbiogel) increased. This manufacturing method can produce high-content microbiogels and is of significant value in research on W/O/W cosmetic formulations that can encapsulate various water-soluble and oil-soluble active ingredients within a partitioned structure.

현탁된 고형지질나노입자 내로 친수성 약물의 봉입률을 증대시키기 위한 w/o/w 에멀션 가온용융유화법의 평가

이병무,최성업,이재휘,최영욱 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.1

Recently increasing attention has been focused on solid lipid nanoparticles (SLN) as a parenteral drug carrier due to its numerous advantages that can come from both polymeric particle and fat emulsions, together with the possibility of controlled release and increasing drug stability. Lipophilic drugs such as paclitaxel. cyclosporin A, and all-trans retinoic acid have been successfully entrapped in SLN but the incorporation of hydrophilic drugs in SLN is very limited because of their very low affinity to the lipid. Therefore, as a new approach to improve the loading of hydrophilic drugs, a w/o/w emulsion technique has been developed. The primary objective of the current study was to improve the loading efficiency of a model hydrophilic drug, glycine (Log P = -3.44) into SLN. The proposed preparation process is as follows: A heated aqueous phase consisting of 0.1 ml of glycine solution in water (100 mg/ml), and poloxamer 188 (5 mg) were then added to a molten oil phase containing precirol (100 mg) and lecithin (5 mg). This mixture was dispersed by sonicator, leading to a w/o emulsion. A double emulsion (w/o/w) was formed after the addition of 2% poloxamer solution to the above dispersed system. After cooling the double emulsion, solid lipid nanosuspensions were successfully formed. The lipid nanoparticles had the mean particle size of 441.25 nm, and the average zeta potential of -20.98 mV. The drug loading efficiency was measured to be 8.54% and the drug loading amount was measured to be 0.92%. The w/o/w emulsion method showed an increased loading efficiency compared to conventional o/w emulsion method.

Hansen Solubility Parameter를 통한 W/O형 자외선차단 제형의 유화 안정성에 관한 연구

김동희 ( Dong Hee Kim ),이진재 ( Jin Jae Lee ) 대한화장품학회 2021 대한화장품학회지 Vol.47 No.4

자외선차단 제형은 내수성이 중요하므로 수상이 유상에 분산되는 water-in-oil (W/O) 에멀젼으로 만드는 것이 바람직하다. 이 경우에는 오일 특유의 무겁고 끈적이는 사용감 때문에 이를 보완하는 방법으로 실리콘계 오일을 사용한다. 이러한 오일은 유기 자외선차단제와의 상용성이 낮아 에멀젼의 안정성에 문제가 되고 있다. 본 연구에서는 자외선차단 제형의 W/O 에멀젼에서 다양한 오일들 간의 상용성을 Hansen solubility parameter (HSP)를 이용하여 수치적으로 도출하였다. HSP는 물질의 분산, 극성 및 수소 결합을 나타내는 지표로 물질간의 상용성을 판단하는데 유용하다. 본 연구에서는 HSP가 다른 다양한 오일을 선정하여 W/O 에멀젼을 제조하고 제형의 시간에 따른 점도 변화 및 안정성을 조사하여 HSP 수치와의 상관관계 또는 일치성을 고찰하였다. HSP를 이용하면 상용성이 높은 오일 선택을 용이하게 할 수 있었다. 또한, W/O 에멀젼에서 유상의 상용성이 높으면 점도의 경시변화가 작았으며 freeze-thaw cycle (-15 ℃ ∼ 45 ℃) 조건에서 안정성이 향상된 것을 확인하였다. 향후 HSP를 통해 성분 구성을 최적화한다면 사용감이 우수하면서 안정성을 확보한 W/O형 자외선차단 제형 개발에 도움이 될 것이라 기대된다. The water resistance is important factor for sunscreen formulations. Generally a sunscreen cream was formulated by a water-in-oil (W/O) emulsion. In the W/O emulsion system, silicone oils a re added to improve the texture of formulations. Silicone oils have low compatibility with organic sunscreen agent, causing problems with the stability in emulsion. In this study, the compatibility between various oils in the W/O emulsion was derived numerically using Hansen solubility parameter (HSP) at first. HSP is represented a dispersion degree, a polarity, and a hydrgen bond in a composition. In this study, various emulsions were prepared according to the types of oils with different HSP values and then monitored by a viscosity and morphology according to the time and temperature. The HSP values of components and the experimental results have similar activities for the stability of emulsions. HSP made it easy to select oil with high compatibility. When the compatibility of the oil phase in the W/O emulsion was high, the viscosity change over time was small. The stability was improved under the freeze-thaw cycle (-15 ℃ ∼ 45 ℃). In the future, if the composition of the ingredients is optimized through HSP, it is expected that it will be helpful in the development of W/O type sunscreen formulations that are excellent in use and stability.

화장품용 W(마이크로바이오젤)/O/W 멀티-에멀젼 제조

정원욱,서상권,이의정,오주영,이경진 한국고분자학회 2024 폴리머 Vol.48 No.1

Microbiogels made from natural polymers are attractive for biomedical applications such as drug delivery and have various manufacturing methods. However, it has drawbacks such as unstable yield and cumbersome separation process. This study presents a simple method to form cosmetic W (microbiogel)/O emulsion that produces microbiogel directly during cosmetic W/O emulsion manufacturing process and then stably produce the W (microbiogel)/O/W multi-emulsion through a continuous room temperature process. We confirmed that a partitioned structure was formed in which other particles exist within the particles dispersed in the outer water phase from microscopic observation of the prepared W/O/W multi-emulsion and the particle size and viscoelasticity of W/O emulsion and W/O/W multi-emulsion increased as the ratio of inner water phase (microbiogel) increased. This manufacturing method can produce high-content microbiogels and is of significant value in research on W/O/W cosmetic formulations that can encapsulate various water-soluble and oil-soluble active ingredients within a partitioned structure.