마이크로유체 원리를 이용한 지질 나노-담체의 제조기술: 표면수식에 의한 막유동성 및 안정성제어 연구

학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2015. 8. 장판식.Lipid nano-vesicles (liposomes and niosomes) have been extensively used to increase bioavailability of nutraceuticals or pharmaceuticals. In this study, novel microfluidic assembly method was used for the lipid nano-vesicle production, because of its easy control of size distribution and food-grade solvent usage. For building block lipids of liposomes and niosomes, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and sorbitan mono-palmitate, Span 40 (SMP) were selected, respectively. Cholesterol was incorporated into the lipid bilayer to control mechanical firmness and membrane permeability. As a result, liposomes with 20%(mol) cholesterol and niosomes with 50%(mol) cholesterol showed monodisperse 100 nm size distribution from dynamic light scattering (DLS) analysis. Meanwhile, zeta potentials of the liposomes were near -5 mV, whereas those of the niosomes were below -30 mV. Therefore, the liposomes were fabricated with various ionic surfactants to enhance their colloidal stability. Accordingly, liposomes incorporated with 20%(mol) palmitic acid (PAL), 4%(mol) dicetyl phosphate (DCP), and 4%(mol) hexadecylamine (HDA) showed the greatest stability in their DLS, transmission electron microscopy (TEM), and zeta potential results. In addition, food-grade biodegradable polymers (chitosan and pectin) were coated onto the lipid nano-vesicles to endow additional physicochemical stability. Anionic pectin was coated onto cationic HDA liposomes, and 0.003%(w/v) pectin coating showed the best colloidal stability with -21.5 mV zeta potential. Meanwhile, cationic chitosan was coated onto anionic niosomes, DCP, and PAL liposomes, and those with 0.020%(w/v), 0.030%(w/v), and 0.080%(w/v) chitosan were shown to overpass the minimum zeta potential criterion (20.0 mV), respectively. Branched chain amino acids (BCAAs) were selected as model food materials for encapsulation efficiency measurement. For BCAA purification, gel permeation chromatography was conducted, and 3.0-5.5 mL fraction volume was collected. Finally, the encapsulation efficiencies of niosomes, DCP, and PAL liposomes were 42.2%, 31.2%, and 26.4%, respectively. On the basis of these results, in-depth researches on in vitro digestion model of BCAA encapsulated lipid nano-vesicles could be conducted in the near future.Abstract ················································································ ? Contents ·············································································· ??? List of tables ········································································· V? List of figures ······································································· V?? 1. Introduction ····································································· 1 2. Materials and Methods ························································ 4 2.1. Materials ··································································· 4 2.1.1. Lipid nano-vesicle production ·································· 4 2.1.2. Ninhydrin analysis ················································ 4 2.2. Microfluidic device ······················································· 5 2.3. Lipid nano-vesicle production ·········································· 7 2.4. Biopolymer coating ······················································· 8 2.5. Dynamic light scattering (DLS) ········································· 8 2.6. Zeta potential measurement ············································· 9 2.7. Transmission electron microscopy (TEM) ···························· 9 2.8. Encapsulation efficiency ················································ 10 2.8.1. Purification of BCAA encapsulated lipid nano-vesicles ··· 10 2.8.2. Ninhydrin analysis ·············································· 11 2.8.3. Encapsulation efficiency ······································· 12 3. Results and Discussion ·························································· 13 3.1. Flow rate adjustment of microfluidic device ························· 13 3.2. Lipid nano-vesicle production ········································· 17 3.2.1. Building block lipid selection ·································· 17 3.2.2. Cholesterol incorporation into lipid bilayer ·················· 18 3.3. Surface modifications of lipid nano-vesicles ························· 24 3.3.1. Ionic surfactant incorporation into liposomes ··············· 27 3.3.2. Biodegradable polymer coating ······························· 31 3.4. Encapsulation efficiency of lipid nano-vesicles ····················· 36 3.4.1. Purification of lipid nano-vesicles through GPC ············ 37 3.4.2. Encapsulation efficiency of lipid nano-vesicles ············· 43 4. References ········································································ 46 국문초록 ··········································································· 54Maste

A study on patent risk valuation model for defensive intellectual property management

학위논문(석사) - 한국과학기술원 : 지식재산대학원프로그램, 2015.2 ,[iv, 51p :]지식재산 비즈니스 산업은 지식재산에 기반을 둔 새로운 비즈니스로 특허를 활용하여 경제, 산업적 가치를 창출하고자 하는 활동을 말한다. 좀 더 구체적으로 말하면, 이러한 산업을 통해 지식재산을 이용하여 창출 가능한 가치의 지속적 증가, 지식재산 비즈니스 모델의 세분화 및 다양화를 통해 지식재산의 활용성에 대한 새로운 부가가치를 창출하고자 하는 것이다. 특허로 인한 미래의 수익화보다는 자신이 보유하고 있는 지식재산을 이용하여 경쟁자로부터 자신의 경제활동 영위 사업을 보호하는 것을 목적으로 한다면, 이는 방어적 단계의 지식재산 경영에 가깝다. 이러한 관점에서의 특허매입은 미래에 발생할 수 있는 특허소송과 분쟁을 사전에 예방하고자 하는 리스크 관리가 중점이다. 기업에서 인식하게 되는 매입의 필요성과 특허의 가치는 자사 제품과의 특허침해 여부에 따라 달라진다. 특허의 가치를 산출하기 위한 방법으로는 시장접근법, 비용접근법, 수익접근법 등이 있으나 이러한 가치평가 방법에서는 침해 여부를 반영할 수 없다는 한계가 있다. 이에 따라 본 연구에서는 침해 여부를 직접 반영한 가치 평가 모델로서 미래에 발생 가능한 특허 소송 리스크는 자사 제품과의 침해여부에 따라 달라진다는 점과 대상 특허 매입으로 소송 리스크를 헤지할 수 있는 점에서 침해 여부에 따른 특허를 소송 리스크 헤지 상품으로 가정하여 현재 시점에서의 특허 가치를 평가하였다. 그리고 실제적인 특허 매입에서 침해 여부를 반영한 리스크 가치 정보뿐만 아니라 침해 여부를 반영하지 않은 일반적인 가치평가법으로 산출된 가치 정보를 매입 검토 단계에서 활용할 수 있는 방안으로서의 매입 의사결정 모델을 제시하였다.한국과학기술원 :지식재산대학원프로그램