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Pharmaceutica 2016 會議：策略性聚乙二醇化：生物藥物的半衰期延長 - Kang Choon Lee - 成均館大學

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生物製劑的巨大能力受到體內半衰期短的阻礙，其在非常基本的水平上實現的能力低於體外觀察到的活性。聚乙二醇化可以是一個階段性的進步，可以延長半衰期，同時保護勝肽和小蛋白藥物的天然活性。這些短效支持藥物需要存取劑量配置文件，這可能會降低中間的相關性，特別是在令人厭煩的情況下。沿著這些思路，半衰期延長的發展正在進入內部，以開發改進的或新的生物藥物。聚乙二醇化是一種常用技術，可提高鎮靜劑的溶解度和可靠性、延長血程時間、降低免疫原性和減少給藥重複。與亞核變化同樣相似，動態位點受到影響，可以從根本上降低治療專家的生物活性，特別是當對小亞核重量分子（如勝肽和小蛋白質）進行改變時。高核量 PEG 的空間阻礙可能會引發顆粒自然和藥理活性的激烈變化。核重越高，生物活性越低。因此，人們經常認識到，必須在 PEG 核堆和治療分子的開發之間取得平衡，才能達到令人滿意的處方適用性。這裡介紹的必不可少的聚乙二醇化技術為普通聚乙二醇化的勝肽和蛋白質提供了多種焦點。關鍵聚乙二醇化顯示聚乙二醇化對生物活性的權衡並不重要。具體來說，這個假設的亮點照亮了作為模型勝肽的 GLP-1 類似物的固體調節勝肽的關鍵聚乙二醇化。關鍵的聚乙二醇化可以是階段性開發，以延長半衰期，同時保護勝肽和小蛋白藥物的正常開發。

Regardless, natural meds are routinely hampered by their unmistakably short half-lives, which suggests that once coordinated, they can be cleared from the body shockingly quick. Due to this short half-life, patients with steady conditions, for instance, diabetes, hemophilia and neutropenia are every now and again required to coordinate higher estimations even more reliably, inciting likelihood of diminished consistence, more noteworthy costs and progressively genuine risks of responses. Prescriptions with a promising therapeutic worth are routinely confined by this factor. Along these lines, the pharmaceutical and biotech parts are giving growing thought to half-life enlargement methods, with different investigation associations and academic papers observing the creating design in making advancements that widen and improve the circulatory half-presence of peptides and proteins. An impressive part of the biotherapeutics insisted or a work in progress experience the evil impacts of a short half-life requiring progressive applications in order to keep up a therapeutic obsession over a comprehensive time span. The utilization of half-life growth procedures allows the period of reliable therapeutics with improved pharmacokinetic and pharmacodynamic properties. An impressive part of the biotherapeutics being embraced or being taken a shot at experience the evil impacts of a short serum half-life. Half-life growth has been seen as an approach to manage empower usage of biotherapeutics and encourage a patient's load by extending the time between applications. Half-life development procedures fundamentally target growing the size and, as such, hydrodynamic volume of the biotherapeutic, for instance by conjugation of polymers, blend of recombinant polymer mimetics, introduction of glycosylation regions, and mix to plasma proteins.

A segment of the half-life development strategies, for instance, blend to a Fc region or mix or definitive to serum egg whites similarly realize reusing by the neonatal Fc receptor, which can also extend the half-life.Several half-life increase frameworks consider a tweaking of half-life, for instance by changing the association or length of included invention or recombinant polymers. A plentitude of half-life growth systems is open and different techniques are starting at now utilized in supported biotherapeutics, with a great deal progressively half-life extended biotherapeutics being in preclinical and clinical new development. A noteworthy number of the biotherapeutics insisted or a work in progress experience the evil impacts of a short half-life requiring constant applications in order to keep up a healing concentration over a comprehensive time period. The utilization of half-life growth procedures allows the time of trustworthy therapeutics with improved pharmacokinetic and pharmacodynamic properties. Regions made sure about: This review gives an outline of the unmistakable half-life expansion strategies made over the earlier years and their application to deliver bleeding edge biotherapeutics. It bases on srategies successfully used in attested drugs and prescriptions that are in clinical new development. These frameworks consolidate those anticipated growing the hydrodynamic scope of the biotherapeutic and procedures which further complete reusing by the neonatal Fc receptor (FcRn). Ace end: Half-life extension systems have become a fundamental bit of progress for some biotherapeutics. A different course of action of these procedures is available for the altering of half-life and adaption to the arranged treatment system and sickness. Starting at now, half-life extension is controlled by techniques utilizing egg whites authority or blend, mix to an immunoglobulin Fcγ locale and PEGylation. Regardless, a collection of elective procedures, for instance, blend of versatile polypeptide chains as PEG mimetic substitute, have shown up at front line stages and offer further alternatives for half-life enlargement.

用聚乙二醇（PEG）或「聚乙二醇化」覆蓋奈米粒子的外部是一種常用的方法，用於提高處方的獲利能力和向目標細胞和組織的質量移動。從實現聚乙二醇化蛋白質以改善中心流時間和降低免疫原性開始，聚乙二醇塗層對一般意義上管理的奈米顆粒微妙性的預先確定的影響已經並將繼續受到廣泛的研究。奈米顆粒上的PEG 塗層可保護表面免受分類、調理作用和吞噬作用的影響，從而延長關鍵的散射時間。影響PEG 亞型等因素。一個不太常被談論的話題，我們當時描述了奈米顆粒上的 PEG 塗層如何用於克服與不同組織方式（從胃腸道到視覺）相關的有效藥物和質量傳輸的不同有機障礙。最後，我們描述了兩種聚乙二醇化奈米顆粒技術和描述聚乙二醇表面厚度的策略，聚乙二醇表面厚度是聚乙二醇表面覆蓋足以改善藥物和品質傳輸的關鍵因素。

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Kang Choon Lee 博士是韓國成均館大學藥學院 Haengdan 傑出教授。 35 年來，Lee 博士的藥物標靶實驗室一直專注於勝肽和蛋白質藥物的免疫標靶和生物共軛。李博士是國際公認的位點特異性勝肽/蛋白質聚乙二醇化領域的領先專家之一，並首次證明了新型位點特異性聚乙二醇化藥物（如 GLP-1 和 TRAIL）的治療潛力。他在同行評審期刊上發表了 150 多篇論文，並在許多國際會議上擔任特邀發言人。 Lee 博士是 20 多項與勝肽/蛋白質藥物的特定生物共軛和聚乙二醇化相關的專利的發明人。李博士於2003年榮獲美國藥學科學家協會（AAPS）院士。為了將其實驗室開發的位點特異性工程勝肽/蛋白質藥物進行臨床轉化和商業化，他創立了韓國 D&D PharmaTech，同時也是美國 Theraly Pharmaceuticals 的共同創辦人並擔任董事會成員。