دانلود ترجمه مقاله بررسی پروسه ایجاد داروی جدید

• فهرست مطالب:

چکیده
مقدمه
مرحله کشف دارو
مرحله ی غیر بالینی- پیش بالینی
اهداف کوتاه مدت و بلند مدت مطالعه ی پیش بالینی
محدودیت های آزمایش پیش بالینی
مرحله ی توسعه ی بالینی
رضایت آگاهانه
تصادفی سازی
طراحی کار آزمایی بالینی
مراحل کار آزمایی های بالینی
مرحله ۱ کار آزمایی های بالینی
مرحله ی ۲ کار آزمایی بالینی
مرحله ۳،کار آزمایی های بالینی
مرحله ۴ ،مطالعه ی نظارتی بعد از بازار یابی
چهار برآیند و پیامد احتمالی کار آزمایی بالینی
نتیجه گیری

• بخشی از ترجمه:

به طور خلاصه کشف داروی مدرن و فرایند توسعه ی دارویی جدید حاصل یک سری رویداد هایی است که می تواند به طور متوسط ۱۰ تا ۱۵ سال طول بکشد و هزینه ی تقریبی آن ۸۰۰ میلیون تا ۱ میلیارد دلار است. این رویداد ها شامل مراحل پیش از کشف برای شناسایی نیاز درمانی،مرحله کشف برای شناسایی هدف ،انتخاب هدف،یافتن و بهینه سازی هدف، مرحله توسعه ی پیش بالینی برای قبل از تست در انسان، تقاضای IND ، توسعه ی بالینی برای تست در انسان از جمله کار آزمایی های بالینی FDA تایید و پایش بازار جاری است.
این یک زمان فوق العاده برای انجام کشف دارو است.ما ثروت غیر قابل باوری از دانش داریم که طی چندین سال گذشته کشف شده است(توماس هاگ، Ph.D ،ناوارتیس)
برخی از ایده ها ممکن است برای مدت زمان طولانی در یک مقاله باقی بمانند اما سایرین راه خود را برای تبدیل شده به یک قرص،به یک شربت در داروخانه طی می کند.(دبرا لافراطلس، Ph.D،الی لیلی و شرکت)

• بخشی از مقاله انگلیسی:

Introduction Drugs have the possibility to provoke desirable and undesirable effects when they are administered to animals or humans. Prior to the approval for marketing, a new drug must be shown to be safe and effective. It has been reported that over the past 30 years in the USA, mortality rate mainly due to cardiovascular and stroke diseases have been reduced by more than 50%, in part by new antihypertensive, anti-hyperlipedimic, anti-coagulant and thrombolytic drugs [1]. It has been estimated that a single new compound to receive approval for marketing is one of the 5,000-10,000 of compounds that have been extensively tested and a net cost of more than $800 million-$1billion and overall time may be more than 10 years[2-3]. Academic institutions neither have the incentive nor massive funds for such a tedious job. Therefore, most of the new drug development researches are conducted by leading pharmaceutical companies as shown in Table 1[4] while the academic institutions mainly committed to basic research [5]. In general, drugs existing today are prepared and developed in bulk scale from synthetic sources. The stages through which a new drug is discovered, developed and regulated are generally same in most countries of the world with minor differences. These include drug discovery, preclinical and clinical development [6] as shown in simplified form in Figure 1 and a detail schematic diagram in Figure 3. Drug discovery stage During new drug development process, first of all a therapeutic need is identified and then a project is designed accordingly (pre-discovery study) [6-7] . After completion of human genome project in 2001, drug development has revolutionized the modern practice of pharmacotherapy. A multidisciplinary research areas are involved in the new drug development process including cellular biology, pharmaceutical organic chemistry, basic and clinical pharmacology, toxicology, pharmaceutical formulation, analytical research and regulatory sciences[8]. All these research areas work jointly to develop a new drug for marketing. These multidisciplinary research areas identify a therapeutic target (receptor, ion channel or enzyme), develop and optimize a potential drug candidate called lead compound. The following general approaches are used for the new drug discovery or development irrespective of the source [1, 5, 9-13] . i. New biochemical target selection or identification e.g. enzymes, ionic channels or receptors. Drug discovery phase starts by targeting a particular clinical disorder to be treated [6] . ii. Based on extensive knowledge of molecular mechanisms, drug structure and drug receptor, development of a new drug as a rational drug design [14] . iii. Modification of the chemical structure of known compound with the plan of synthesizing a more effective or a less perilous drug (SAR study). iv. Random screening of completely novel compounds for pharmacological activities. v. Biotechnology and the cloning techniques using genes (genomics) to produce large peptides and proteins (proteomics) of crucial importance. vi. Discovery of novel uses of drugs previously in use based either on discovery of mechanism of action or serendipity. First of all a chemical with potential therapeutic benefits (lead compound/potential drug candidate) must be identified through various research techniques. Several techniques have been employed to obtain compounds for drug discovery including synthetic organic chemistry, drug modeling, combinatorial chemistry and natural sources [15-18] . Currently drug molecular docking, combinatorial chemistry,bioisosterism [19] and other synthetic chemistry techniques are widely used by leading R & D pharmaceutical organizations [18, 20]. Molecular modeling is a technique where computers are used to operate virtual chemical structures and compute protein binding capacities. Computer-assisted drug design (CADD) molecular modeling [21-23], have been tested in quantitative structure activity relationship (QSAR) and computational chemistry to identify the shape of compounds [24-26]. In order to provide an insight as to the preferred conformation of a molecule, molecular mechanics and quantum mechanics calculations are conducted in conformational studies.