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Batch and Continuous Crystallization of Form II Paracetamol through the Assistance of Additives

為了解決oil tank bund的問題，作者葉冠麟 這樣論述：

Table of Contents摘要 iAbstract iii誌謝 vTable of Contents viiList of Tables xiiList of Figures xivList of Schemes xxvChapter 1 Introduction 11.1 Pharmaceutical Industry 11.2 Crystallization Process 51.2.1 Fundamental

s of Crystallization 51.2.2 Batch and Continuous Crystallization 111.3 Solid Dosage Forms of API 131.3.1 Polymorphism 141.3.2 Co-crystal 161.4 Paracetamol and Its Polymorphs 181.4.1 Brief Introduction of Paracetamol 181.4.2 Polymorphs of PCA 191.5 Prep

aration of Metastable Form of PCA 211.5.1 Evaporation and Cooling Crystallization without Seeding or Additive 231.5.2 Evaporation and Cooling Crystallization with Seeding 251.5.3 Contact Line Crystallization 261.5.4 Ultrasound-Assisted Crystallization 271.5.5 Heterogene

ous Crystallization 281.5.6 Reaction Coupling 311.5.7 Multicomponent Crystallization 321.5.8 Summary 351.6 Polymorph Assembly by the Presence of Co-former 36Chapter 2 Experimental Procedures 422.1 Chemicals and Solvents 422.2 Experimental Procedures 432.2

.1 Additive Screening for PCA Polymorphs 432.2.2 Effects of the Additive Amounts on the Polymorphic Formation of PCA 442.2.3 Effects of Using ADI, FUM, MLC, SUC and OXADH as Seeds on the Polymorphic Formation of PCA 462.2.4 Solubility Measurements of Form I PCA in Aqueous Soluti

ons of OXA and FUM 472.2.5 Effects of Degrees of Supersaturation on the Cooling Recrystallization of PCA with OXA and FUM 482.2.6 Preparation of PCA Crystals by Cooling Recrystallization in the Aqueous Solutions at pH 1 and 2 482.2.7 Removal of FUM from the Produced Form II

PCA-FUM Mixed Crystals 492.2.8 Cooling Recrystallization of PCA in the Presence of Additives in a 500 mL-sized Stirred Tank 502.2.9 Cooling Recrystallization of PCA in the Presence of FUM in a Tubular Crystallizer 522.2.10 Preparation of PCA-MAL Co-crystals by Cooling Recrysta

llization 552.2.11 Establishment of the Ternary Phase Diagram of PCA-MAL-Water 552.3 Analytical Methods and Instruments 562.3.1 Optical Microscopy (OM) 562.3.2 Fourier Transform Infrared Microscopy (FTIR) 572.3.3 Powder X-ray Diffraction (PXRD) 572.3.4 Thermogravi

metric Analysis (TGA) 582.3.5 Differential Scanning Calorimetry (DSC) 582.3.6 Low-Temperature Differential Scanning Calorimetry (LT-DSC) 592.3.7 Nuclear Magnetic Resonance Spectroscopy (NMR) 592.3.8 High Performance Liquid Chromatography (HPLC) 602.3.9 Photoluminescence

Spectroscopy (PL) 61Chapter 3 Selective Polymorphic Formation of PCA by Additive Addition 623.1 Additive Screening for PCA Polymorphs 623.2 Effects of the Additive Amounts on the Polymorphic Crystallization of PCA 793.3 Effects of Using ADI, FUM, MLC, SUC and OXADH crystals

as Seeds to Induce Form II PCA 883.4 Freezing Point Measurement of the PCA-Additive Aqueous Solutions 933.5 Solubility Diagrams of the PCA-FUM and PCA-OXA Aqueous Solutions 953.6 Effects of Degrees of Supersaturation on the Recrystallization of PCA with FUM and OXA 1063.7 Re

moval of FUM Crystals from the Mixture of Form II PCA and FUM by Solvent Rinsing 113Chapter 4 Preparation of Polymorphic PCA in a Batch and a Continuous Crystallizer 1184.1 Recrystallization of PCA with FUM or OXA in a Stirred Tank 1184.2 Recrystallization of PCA with FUM or OXA in

a Tubular Crystallizer 127Chapter 5 1:1 Co-crystal of PCA-MAL 1365.1 Isomerization of MAL 1365.2 Preparation and Characterization of PCA-MAL Co-crystal 138Chapter 6 Conclusions and Future Works 1476.1 Conclusions 1476.2 Future Works 149Appendices 151A.

Abbreviations and Notations 151B. Thermal Scanning for PCA and Co-former 153C. Form Space Establishment 154D. Crystallographic Data 157E. Solubility Data 158References 161

有益微生物的真菌學和細菌學研究： 在農業和人類健康中的應用

為了解決oil tank bund的問題，作者范明新 這樣論述：

近來從研究發現微生物可以進行改造，以調節植物抵抗禦環境的防禦機制，並強烈增強植物的生長和健康。木腐蘑菇在木質纖維素培養基中可促進植物生長並有提高農業生產力的潛力，杏鮑菇是存在於自然界的白色腐生性的真菌菌株，研究發現其可持續的在30oC和pH 5的環境下將10 mM L-色氨酸（TRP）轉化為酪氨酸-3-乙酸（IAA），跟其它的杏鮑菇種相比，杏鮑菇更適合在更適合於亞熱帶和熱帶氣候生長。真菌在纖維素存在會使用IPA途徑合成IAA，但是環境中高濃度的外源IAA（10 µg / mL）可能會抑制真菌的生長，IAA在單子葉植物（大米）中，發現會增加側根的數量，而在雙子葉植物（番茄）中，根的長度會增長，

通過實驗證明了對線蟲有吸引力和毒性。杏鮑菇有較佳的草酸溶解在菌絲體的區域有氧化物修飾的基質（CaO和ZnO）。在體外試管雙重培養實驗中發現肺假單尖孢鐮刀菌和霍亂單胞菌有拮抗作用，這些新發現及影響可能為在農業中的應用帶來新的見解。相反，Marasmius palmivorus在台灣的福爾摩沙棕櫚（Arenga engleri）樹木上產生症狀，從而使棕櫚樹分枝桿菌在棕櫚種植園中的危害比以往預期的要大。近來研究發現人體腸道細菌中檢測到電子產生可能與人體健康密切相關，腸系膜十二指腸菌Leuconostoc mesenteroides可促使亞油酸發酵來當作電子抗氧化機制，連續6週攝入高脂飲食（HFD）會

誘導的ROS（活性氧）的產生，脂肪細胞3T3-L1分化過程中，脂質積累的增加與ROS的釋放同時發生，這些可能都與腸系膜十二指腸菌誘導的亞油酸發酵產生的電子有關，提供對脂肪形成過程中脂質積累和ROS產生以及高脂飲食誘導的ROS的抑製作用，此外Cyclophilin A蛋白在腸道中可抑制電子產生的產生，我們的研究結果表明，腸系膜十二指腸菌藉由亞油酸的發酵的通過電子產生抑制ROS和脂質的產生，而電子產生受Cyclophilin A蛋白調節。膜糖蛋白是嚴重急性呼吸系統綜合症冠狀病毒2（SARS-CoV-2）的最豐富蛋白質，但其在2019年冠狀病毒病（COVID-19）中的作用機制尚未完全。與綠色熒光蛋

白 (GFP)的小鼠相比，鼻內接種膜糖蛋白的小鼠在支氣管肺泡灌洗液（BALF）白細胞介素-6增加，白細胞介素-6是細胞因子風暴的標誌。膜糖蛋白誘導的高水平的白細胞介素-6在磷酸二酯酶4（PDE4B）敲除小鼠中顯著降低，證明了PDE4B在白細胞介素-6信號傳導中的重要作用。鼠李糖乳桿菌EH8菌株的菌絲體發酵產生了丁酸，它可以下調巨噬細胞中PDE4B的表達和IL-6的分泌。用菌絲體餵養小鼠可增加鼠李糖乳桿菌的相對豐度。鼠李糖乳桿菌和菌絲體補充兩週後，可大大降低膜糖蛋白誘導的PDE4B表達和IL-6分泌。鼠李糖乳桿菌和菌絲體對膜糖蛋白的益生菌活性在用游離脂肪酸受體2 (Ffar2) 拮抗劑GLPG-

0974處理的小鼠中被取消。 Ffar2在腸肺軸中的激活以下調PDE4B-IL-6信號傳導可能為開發包括益生菌在內的治療包括COVID-19中細胞因子風暴的治療方法提供靶點。