制药工程专业英语详细Unit1.3.6详细翻译教学提纲

合集下载

制药工程专业英语课文翻译

Unit 1 Production of DrugsAbout 5000 antibiotics have already been isolated from microorganisms，but of these only somewhat fewer than 100 are in therapeutic use. It must be remembered，however，that many derivatives have been modified by partial synthesis for therapeutic use;some 50，000 agents have been semisynthetically obtained from户lactams alone in the last decade. Fermentations are carried out in stainless steel fermentors with volumes up to 400 m3. To avoid contamination of the microorganisms with phages etc. the whole process has to be performed under sterile conditions. Since the more important fermentations occur exclusively under aerobic conditions a good supply of oxygen or air(sterile)is needed. Carbon dioxide sources include carbohydrates，e. g. molasses，saccharides，and glucose. Additionally the microorganisms must be supplied in the growth medium with nitrogen-containing compounds such as ammonium sulfate，ammonia，or urea，as well as with inorganic phosphates. Furthermore，constant optimal pH and temperature are required. In the case of penicillin G，the fermentation is finished after 200 hours，and the cell mass is separated by filtration. The desired active agents are isolated from the filtrate by absorption or extraction processes. The cell mass，if not the desired product，can be further used as an animal feedstuff owing to its high protein content.关于5000抗生素已经分离出的微生物，但其中只有不到100有些治疗使用。

制药工程专外

制药工程专业英语Unit 1production of drugs P1单词Compound 化合物intermediate 中间产物alkaloids 生物碱enzymes酶peptide 肽hormones 荷尔蒙modification 修饰chloramphenicol 氯霉素metabolites 代谢物substitute 替代品derivative衍生物active 活性absorption 吸收extraction 提取Recombinant 重组insulin 编码neuroactive 神经活性start materials 起始原料recrystallization 重结晶methanol 甲醇Ethanol 乙醇isopropanol 异丙醇butanol 丁醇benzene 苯翻译Known examples are the enzymatic cleavage of racemates of N-acetyl-D, L-amino acids to give L-amino acids, the production of 6-aminopenicillanic acid from benzylpenicillin by means of penicillinamidase and the aspartase-catalysed stereospecific addition of ammonia to fumaric acid in order to produce L-aspartic acid.著名的例子是对N -乙酰- D，L -氨基酸消旋给予L -氨基酸酶裂解，从青霉素生产8 -氨基青霉烷酸的青霉素酰胺酶手段和天冬氨酸酶，催化氨立体除了富马酸为了酸生产L -天门冬氨酸。

Reading material 1 p7Antagonist 抑制剂receptor 受体clinical investigation 临床研究antibacterial抗菌的inhibition 抑制mercurial 水银dominate 占主导Unit 3 chemotherapy: an introduction P29单词chemotherapy化学治疗superstition 迷信pathogenic 致病的翻译The activity of the arsenical drugs is explained as due to a blocking of essential thiol groups.For example, lipoic acid dehydrogenase contains two cysteine molecules, while are kept near each other by folding of the molecule. As a result, an arsenical can react with these thiol groups and inactivate the molecule, as show in equation.对含砷药物活性被解释为由于阻塞必不可少的巯基。

制药工程专业英语翻译吴达俊-11页word资料

完全（合成纤维）合成材料，Ⅱ。

天然产物，和Ⅲ。

产品从（半合成产品）的部分合成。

本书的重点是团体的最重要的化合物Ⅰ和Ⅲ一所以药物合成。

这并不意味着，但是，天然产品或其他代理人并不太重要。

它们可以作为有价值的领导结构，他们常常为原料，或作为重要的合成中间体产品的需要。

制药工程专业英语课文翻译

Unit 1 Production of Drugs
Depending on their production or origin pharmaceutical agents can be split into three groups:
I .Totally synthetic materials (synthetics)，
不顾来自某些微生物，大肠杆菌粘膜生产的葡聚糖克明串珠mesenteroides，2和3级是毒品有关的准备工作。葡聚糖本身5万〜10万分子量，是用作血浆代用品。其中主要来自谷氨酸棒杆菌代谢产物和黄色短杆菌突变体的L -氨基酸特别有趣。从这些味精约35万吨L -谷氨酸（食品添加剂）生物体和L -赖氨酸（用于植物蛋白补充）约70,000吨的生产。此外重要的初级代谢产物的普瑞纳核苷酸，有机酸，乳酸，柠檬酸和维生素，例如维生素B，从丙酸shermanii 2。
vitamins A, E，and K)
2.2 Animal organs一enzymes;peptide hormones;cholic acid from gall; insulin) from the
pancreas;sera and vaccines
1. cell material (single cell protein)，
2. enzymes，
3. primary degradation products (primary metabolites)，
4. secondary degradation products (secondary metabolites).
其中几个重要的治疗作用最初是从天然产品天然来源获得更有效的今天，我。大肠杆菌更经济的准备..由全合成。这样的例子包括L-氨基酸，氯霉素，咖啡因，多巴胺，肾上腺素，左旋多巴，肽类激素，前列腺素，D -青霉胺，长春胺，以及几乎所有的维生素。

制药工程专业英语课文翻译1 5 6 11 13 16单元译文

完全（合成纤维）合成材料，Ⅱ。

天然产物，和Ⅲ。

产品从（半合成产品）的部分合成。

本书的重点是团体的最重要的化合物Ⅰ和Ⅲ一所以药物合成。

这并不意味着，但是，天然产品或其他代理人并不太重要。

它们可以作为有价值的领导结构，他们常常为原料，或作为重要的合成中间体产品的需要。

制药工程专业英语第1、5、13、16

Unit 1 Production of DrugsDepending on their production or origin pharmaceutical agents can be split into three groups:I .Totally synthetic materials (synthetics)，Ⅱ.Natural products，andⅢ.Products from partial syntheses (semi-synthetic products).The emphasis of the present book is on the most important compounds of groups I and Ⅲ一thus Drug synthesis. This does not mean，however，that natural products or other agents are less important. They can serve as valuable lead structures，and they are frequently needed as starting materials or as intermediates for important synthetic products.Table 1 gives an overview of the different methods for obtaining pharmaceutical agents.Table 1 Possibilities for the preparation of drugsMethods Examples1. Total synthesis -over 75 % of all pharmaceutical agents (synthetics)2. Isolation from natural sources (natural products):2.1 Plants -alkaloids;enzymes;heart glycosides;polysaccharides;tocopherol;steroid precursors (diosgenin, sitosterin);citral (intermediate product forvitamins A, E，and K)2.2 Animal organs一enzymes;peptide hormones;cholic acid from gall; insulin) from thepancreas;sera and vaccines2. 3 Other sources一cholesterol from wool oils;L-amino acids from keratin and gelatinehydrolysates3. Fermentation一antibiotics;L-amino acids;dextran; targeted modifications on steroids，e.g. 11-hydroxylation; also insulin, interferon, antibodies, peptidehormones，enzymes，vaccines4. Partial synthetic modification of natural products (semisynthetic agents):一alkaloid compounds;semisynthetic /3-lactam antibiotics;steroids;human insulinSeveral therapeutically significant natural products which were originally obtained from natural sources are today more effectively -i. e. more economically -prepared.. by total synthesis. Such examples include L-amino acids，Chloramphenicol，Caffeine, Dopamine，Epinephrine，Levodopa, peptide hormones，Prostaglandins，D-Penicillamine，Vincamine，and practically all vitamins.Over the last few years fermentation - i. e. microbiological processes has become extremely important. Through modern technology and results from genetic selection leading to the creation of high performance mutants of microorganisms，fermentation has already become the method of choice for a wide range of substances. Both Eukaryonts (yeasts and moulds)and Prokaryonts(single bacterial cells，and actinomycetes)are used microorganisms. The following product types can be obtained:1. cell material (single cell protein)，2. enzymes，3. primary degradation products (primary metabolites)，4. secondary degradation products (secondary metabolites).Disregarding the production of dextran from the mucous membranes of certain microorganisms，e. g. Leuconostoc mesenteroides，classes 2 and 3 are the relevant ones for the preparation of drugs. Dextran itself，with a molecular weight of 50,000 ~ 100,000，is used as a blood plasma substitute. Among the primary metabolites the L-amino acids from mutants of Corynebacterium glutamicum and Brevibacterium flavum are especially interesting. From these organisms some 350，000 tones of monosodium L-glutamate (food additive)and some 70，000 tones of L-lysine(supplement for vegetable proteins)are produced. Further important primary metabolites are the purina nucleotides，organic acids，lactic acid，citric acid，and vitamins，for example vitamin B,2 from Propionibacterium shermanii.Among the secondary metabolites the antibiotics must be mentioned first. The following five groups represent a yearly worldwide value of US-$17 billion:penicillins ( Penicillium chrysogenum )，cephalosporins ( Cephalosporium acremonium )，tetracyclines ( Streptomyces aureofaciens )，erythromycins ( Streptomyces erythreus )，aminoglycosides (e. g. streptomycin from Streptomyces griseus).About 5000 antibiotics have already been isolated from microorganisms，but of these only somewhat fewer than 100 are in therapeutic use. It must be remembered，however，that many derivatives have been modified by partial synthesis for therapeutic use;some 50，000 agents have been semisynthetically obtained from户lactams alone in the last decade. Fermentations are carried out in stainless steel fermentors with volumes up to 400 m3. To avoid contamination of the microorganisms with phages etc. the whole process has to be performed under sterile conditions. Since the more important fermentations occur exclusively under aerobic conditions a good supply of oxygen or air(sterile)is needed. Carbon dioxide sources include carbohydrates，e. g. molasses，saccharides，and glucose. Additionally the microorganisms must be supplied in the growth medium with nitrogen-containing compounds such as ammonium sulfate，ammonia，or urea，as well as with inorganic phosphates. Furthermore，constant optimal pH and temperature are required. In the case of penicillin G，the fermentation is finished after 200 hours，and the cell mass is separated by filtration. The desired active agents are isolated from the filtrate by absorption or extraction processes. The cell mass，if not the desired product，can be further used as an animal feedstuff owing to its high protein content.By modern recombinant techniques microorganisms have been obtained which also allow production of peptides which were not encoded in the original genes. Modified E. coli bacteria make it thus possible to produce A- and B- chains of human insulin or proinsulin analogs. The disulfide bridges are formed selectively after isolation，and the final purification is effected by chromatographic procedures. In this way human insulin is obtained totally independently from any pancreatic material taken from animals.Other important peptides，hormones，and enzymes，such as human growth hormone (HGH)，neuroactive peptides，somatostatin，interferons，tissue plasminogen activator (TPA)，lymphokines，calcium regulators like calmodulin，protein vaccines，as well as monoclonal antibodies used as diagnostics，are synthesized in this way.The enzymes or enzymatic systems which are present in a single microorganism can be used for directed stereospecific and regiospecific chemical reactions. This principle is especially usefulin steroid chemistry. Here we may refer only to the microbiological 11-a- hydro xylation of progesterone to 11-a-hydroxyprogesterone，a key product used in the synthesis of cortisone. Isolated enzymes are important today not only because of the technical importance of the enzymatic saccharification of starch，and the isomerization of glucose to fructose，They are also significant in the countless test procedures used in diagnosing illness，and in enzymatic analysis which is used in the monitoring of therapy.A number of enzymes are themselves used as active ingredients. Thus preparations containing proteases (e. g. chymotrypsin，pepsin，and trypsin)，amylases and lipases，mostly in combination with synthetic antacids，promote digestion. Streptokinase and urokinase are important in thrombolytics，and asparaginase is used as a cytostatic agent in the treatment of leukemia.Finally mention must be made of the important use of enzymes as `biocatalysts’in chemical reactions where their stereospecificity and selectivity can be used. Known examples are the enzymatic cleavage of racemates of N-acetyl-D，L-amino acids to give L-amino acids，the production of 8-aminopenicillanic acid from benzylpenicillin by means of penicillinamidase and the aspartase-catalysed stereospecific addition of ammonia to fumaric acid in order to produce L-aspartic acid.In these applications the enzymes can be used in immobilized forms-somehow bound to carriers - and so used as heterogeneous catalysts. This is advantageous because they can then easily be separated from the reaction medium and recycled for further use.Another important process depending on the specific action of proteases is applied for the production of semisynthetic human insulin. This starts with pig insulin in which the alanine in the 30-position of the B-chain is replaced by a threonine tert-butyl ester by the selective action of trypsin. The insulin ester is separated，hydrolyzed to human insulin and finally purified by chromatographic procedures.Sources for enzymes include not only microorganisms but also vegetable and animal materials.In Table 1 it was already shown that over 75%of all pharmaceutical agents are obtained by total synthesis. Therefore knowledge of the synthetic routes is useful. Understanding also makes it possible to recognize contamination .of the agents by intermediates and by- products. For the reason of effective quality control the registration authorities in many countries demand as essentials for registration a thorough documentation on the production process. Knowledge of drug syntheses provides the R&D chemist with valuable stimulation as well.There are neither preferred structural classes for all pharmaceutically active compounds nor preferred reaction types. This implies that practically the whole field of organic and in part also organometallic chemistry is covered. Nevertheless，a larger number of starting materials and intermediates are more frequently used，and so it is useful to know the possibilities for their preparation from primary chemicals. For this reason it is appropriate somewhere in this book to illustrate a tree of especially important intermediates. These latter intermediates are the key compounds used in synthetic processes leading to an enormous number of agents. For the most part chemicals are involved which are produced in large amounts. In a similar way this is also true for the intermediates based on the industrial aromatic compounds toluene，phenol and chlorobenzene. Further key compounds may be shown in a table which can be useful in tracing cross-relationships in syntheses.fIn addition to the actual starting materials and intermediates solvents are required both as a reaction medium and ,for purification via recrystallization. Frequently used solvents are methanol，ethanol，isopropanol，butanol，acetone，ethyl acetate，benzene，toluene and xylene. To a lesser extent diethyl ether，tetrahydrofuran，glycol ethers，dimethylformamide (DMF) and dimethyl sulphoxide (DMSO) are used in special reactions.Reagents used in larger amounts are not only acids (hydrochloric acid，sulfuric acid，nitric acid，acetic acid) but also inorganic and organic bases (sodium hydroxide，potassium hydroxide，potassium carbonate，sodium bicarbonate，ammonia，triethylamine，pyridine). Further auxiliary chemicals include active charcoal and catalysts. All of these supplementary chemicals (like the intermediates) can be a source of impurities in the final product.In 1969 the WHO published a treatise on `Safeguarding Quality in Drugs'.Appendix 2 is concerned with the `Proper Practice for Reparation and Safeguarding Quality in Drugs' (WHO Technical Report No. 418，1969，Appendix 2;No. 567，1975，Appendix 1A). This has in the meantime become known as `Good Manufacturing Practices' or GMP rules，and these should now be obeyed in drug production. They form the basis for mutual recognition of quality certificates relating to the production of pharmaceuticals and for inspections of the production. facilities.For a long time the US drug authority，the Food and Drug Administration (FDA)，has issued regulations for the preparation of drugs analogous to the WHO rules，and it applies these strictly. Exports of drugs to the USA，like those of finished products，require regular inspection of the production facilities by the FDA. 5It may merely be noted here that such careful control applies not only to the products，but also to the raw materials (control of starting Materials)，and also to the intermediates. Clearly. the technical and hygienic equipment of the production and the storage areas have to fulfill set conditions.Since only a few compounds，such as acetylsalicylic acid，paracetamol and vitamins，are prepared in large amounts，most of the actual production takes place in multi-purpose (multi-product) facilities. .Special care has to be taken to avoid cross-contamination by other products what can be effected by good cleansing of used apparatus. A careful description and definition of all stored intermediates and products is needed.Selected -from H. J. Roth and A. Kleemann, Pharmaceutical Chemistry, Vol. 1，Drug Synthesis, Ellis Horwood Limited，England, 1988.6 Exercises1. Answer the following questions:(1)How many groups can pharmaceutical agents be split into depending on their production or origin?(2)Can you illustrate any significant examples of pharmaceutical agents obtained by total synthesis?(3) What is the difference between the synthetic drugs and traditional Chinese herbal medicine?2. Put the following into English:3. Put the following into Chinese:Polysaccharide peptide hormone vaccine heterogeneous catalyst contamination plasma steroid penicillin metabolite4. Fill in the blanks with the following verb words:derive term distinguish present composeNucleic acids are polyanionic molecules of high molecular weight. These polymers are _____ of a sequence of subunits or nucleotides so that the whole is usually _____ a polynucleotide. The nucleic acids are of two main varieties，ribonucleic(RNA)and deoxyribonucleic (DNA).DNA is found primarily in the chromatin of the cell nucleus，whereas 90%of RNA is _____ in the cell cytoplasm and 10 0 o in the nucleolus. The two classes of nucleic acids are _____ primary on the basis of the five-carbon atom sugar or pentose present. Two general kinds of bases are found in all nucleic acids. One type is a derivative of the parent compound purine. Principle examples are guanine and adenine. The second class of bases found in all nucleic acids is _____ from the parent compound pyrimidine.Unit 5 Drug Development (I)1. IntroductionDrug Development is a very complex process requiring a great deal of coordination and communication between a wide range of different functional groups. It is expensive，particularly in the later phases of clinical development，where studies involve hundreds of patients. It is currently estimated that the development of a new drug costs about$230 million(1987 dollars)and takes somewhere between 7 and 10 years from initiation of preclinical development to first marketing (excluding regulatory delays). Drug development is a high-risk business;although the rate is increasing，only about ONE out of every TEN new chemical entities studied in human beings for the first time will ever become a product. As a drug candidate progresses through development the risks of failure decrease as ‘hurdles’are overcome along the way. Typical reasons for failure include unacceptable toxicity，lack of efficacy，or inability to provide advantages over competitive products(Fig. 1).Attrition Rate of New Chemical Entities(NCE's) entering development. On averageonly about I in 400^1000 compoundssynthesized enters development.Reasons for termination of development of NCE's(excluding anti-infectives)1:Lack of efficacy2: Pharmacokinetics3: Animal toxicity4: Miscellaneous5: Adverse effects in man6: Commercial reasonsFig. 1 Attrition rates and reasons for terminations2. Planning for developmentAssessment of whether a drug candidate is likely to provide competitive advantages highlights the need first to have in place a set of product `goals' or target product profile. Particular attention should be paid to the differentiation from competitors. This is becoming 55 more andmore critical with the increasing emphasis on limited formularies，healthcare costs，and pharmacoeconomics (discussed later in the chapter).A target profile will define the indication(s) that a drug candidate will be developed for，along with goals such as once a day dosing，faster onset of action，better side effect profile than a major competitor. The target profile can be refined and revised as a drug candidate moves through development and new data on the drug candidate or competitors become available. The logical next steps are to define the development strategy，for example，which indications to develop first，which countries to aim to market the drug in and then to define the core clinical studies necessary to achieve regulatory approval and commercial success.This chapter will describe the main activities required for successful development of a new drug. All these activities，many of which are interdependent，need to be carefully planned and co-ordinate. Speed to market with collection of high quality data is critical for success. The path of activities which determine the time it will take to get to registration is called，in project management terms，the critical path. It is vital to plan and prepare before studies begin and to monitor and manage problems so as to ensure that the critical path remains on schedule. With increased economic pressures and competitive intensity it is important for companies to explore ways to shorten this critical path. Running activities in parallel，or overlapping studies which would usually run sequentially，often involves an increase in risk but the dividends in time-saving can make such strategies worthwhile.The critical path for development of a new drug generally runs through the initial synthesis of compound，subacute toxicology studies，and then the clinical program. A chart showing the critical path activities for a typical drug candidate is shown in Fig. 2.Chemistry chemical Synthesis Route selection Pilot plant,scale up and stability testing Manufacturing plant productionToxicology Acute&subacute toxicology Long term and repro-toxicologyClinical Phase I Phase ll Phase lll Analysis data and report Phase lV Review Regulatory Submission and updating of clinical trial application prepare submit AuthorityMAA/NDARegulatory ApprovalPost marketing SurverillancePharmaceutics Preclinical,clinical and commercial formulationDevelopment and stability testing Prepare labellingDrug metabolismand pharmacokinetics Animal ADME* Healthy humans Human patients Activities likely to be on the critical path are shown in bold* Absorption , Distribution , Metabolism , ExcretionFig. 2 The major processes in new drug developmentThe following sections highlight the objectives and activities of drug development work.Activities within each technical discipline are described broadly in chronological order.At any one time，work in all these disciplines may be proceeding in parallel. The timing and outcome of much of the work has direct impact on work in other disciplines. The major phases of drug development are Preclinical ( studies required before the compound can be dosed in humans)，Phase I (clinical studies usually in healthy human volunteers ) Phase Ⅱ( initial efficacy and safety and dosefinding studies in patients)，and Phase Ⅲ(studies in several hundred patients). There then follows assembly of a marketing application dossier for subsequent review by country regulatory authorities.3. Chemical developmentRapid development of a drug candidate is dependent on the availability of sufficient quantity of the compound. The purity of compound needs to reach certain standards in order for it to be used in safety (toxicology)，pharmaceutical，and clinical studies. Initially，chemists will work on a small to medium scale to investigate production of the compound by several different methods so as to identify the optimum route for synthesizing the compound. ‘Optimum’ here may mean a combination of several factors，for example，most efficient，cheapest safe，or that producing minimal waste. Analysis of the final product as well as intermediates and impurities plays a key role in identifying the best method of synthesis. Development and validation of analytical methods are necessary to support process development and guarantee the purity of the drug substance.In some cases levels of impurities may be unacceptably high and either improved purification procedures will need to be developed or the synthetic process may require significant alterations. The main aim is to ensure that the composition of compound is understood and that ultimately the material that is prepared is as pure as possible.As a drug candidate progresses through development，larger and larger amounts of compound are required. The amount of material required for different tests will often depend on the actual potency and dosage form of the compound. A pilot plant can be regarded as a mini-manufacturing set-up. Before transferring to a pilot plant，extensive evaluation and testing of the chemical synthesis is undertaken to ensure that any changes and hazards are minimized. Procedures are optimized，particular attention being paid to developing environmentally acceptable ways of disposing of waste products. Commercial production of bulk drug substance for production of a drug，once approved and marketed，will likely take place on a larger scale or at a registered manufacturing plant.4. Formulation developmentThe dosage form of a drug is the form by which it is administered to the patient. There are a vast array of possible dosage forms ranging from transdermal patches to inhalers to intranasal medicines. The more common dosage forms include oral tablets or capsules，oral liquids，topical ointments or creams，and injectables. The dosage form or forms chosen for a particular drug candidate will be defined in the target profile.Sometimes a more simple dosage form，for example an oral solution，is chosen for early 57 clinical studies in human beings. This may save time and upfront costs at an early，high-risk stage of the drug development process. Later clinical studies would use the expected marketed dosage form.Whatever the dosage form，the combination of drug and other materials which constitute it must fulfil certain criteria. One of the most important is that of adequate stability. That means a predetermined potency level must remain after，for example，two or three years. The stability data generated on a dosage form will determine its shelf-life and recommended storage conditions. Early in development the shelf-life may be limited to several months. This will not be a problem provided it is sufficient to cover use of the drug over the duration of the clinical study or studies.5. PharmacologyBefore a drug candidate is given to man，its pharmacological effects on major systems are often investigated in a number of species. The body systems studied include cardiovascular，respiratory，and nervous systems;the effects on gross behavior can also be studied.Experiments are sometimes conducted to see whether the drug candidate interferes with the actions of other medicines which，because of their specific effects or because of their common use，are likely to be taken concurrently with the drug candidate. Any synergism or antagonism of drug effects should be investigated，and any necessary warning issued to clinical investigators.(It may be judged necessary to investigate such effects further in clinical studies，and any potential or proven drug interactions are likely to be noted in the product labeling for the drug.)It may also be appropriate to identify a substance for possible use in the management of overdosage，particularly if the therapeutic margin of the drug candidate is small.6. Safety evaluationThe objective of animal toxicology testing，carried out prior to the administration of a drug to man，is to reject compounds of unacceptable toxicity and to identify potential target organs and timings for adverse effects of the drug. This means that in early human studies these organs and tissues can be monitored with particular attention. It is important to establish whether toxic effects are reversible or irreversible，whether they can be prevented and，if possible，the mechanism of the toxicological effects. It is also important to interrelate drug response to blood levels in humans and blood levels in various animal species.The toxicological studies required for the evaluation of a drug candidate in man will be relevant to its proposed clinical use in terms of route of administration and duration of treatment of the clinical studies. The size and frequency of the doses and the duration of the toxicology studies are major determinants of permissible tests in man. Countries，including UK，USA，Australia，and Nordic countries，have regulatory guidelines which relate the duration of treatment allowed in man to the length of toxicity studies required in two species. Points from the guidelines are referenced in the subsequent sections.58 Initially，the pharmacological effects of increasing doses of the test substances are established in acute toxicity studies in small numbers of animals，generally using two routes of administration (one being that used in man). Results provide a guide to the maximum tolerated doses in subsequent chronic. toxicity tests，aid selection of dose levels，and identify target organs.The main aim of the subsequent sub-acute toxicity tests is to determine whether or not the drug candidate is adequately tolerated after administration to animals for a prolonged period as a guide to possible adverse reactions in man. Two to four week (daily dosing) studies are required，using the same route of administration as in man，in two species (one non-rodent)prior to administration of the compound to man. Three dose levels are usually necessary:the low daily dose should be a low multiple of the expected therapeutic dose，and the highest dose should demonstrate some toxicity.A general guide for the evaluation of new chemical entities would be that toxicology studies of a minimum duration of 14 days are required to support single-dose exposure of a new drug candidate in normal volunteers in Phase 1. Toxicology studies of 30 days duration are required to support clinical studies of 7 to 10 days duration. Clinical studies of greater than 7 to 10 days up to 30 days duration require the support of at least 90 days toxicology studies. These requirementsillustrate the need to plan ahead in drug development. The duration and approximate timings for future clinical trials need to be considered well in advance in order to schedule and conduct the appropriate toxicology studies to support the clinical program and avoid any delays.Two types of safety test are used to detect the ability of the drug candidate to produce tumours in man. The first are short-term in vitro genotoxicity tests，for example bacterial tests. The second are long-term animal carcinogenicity studies which are conducted in mice and rats;their length of often 2 years covers a large part of the lifespan of the animal. Mice and rats are used because of their relatively short life span，small size，and ready availability. Also，knowledge，which has accumulated concerning spontaneous diseases and tumours②in particular strains of these species，helps greatly in the interpretation of‘results.Long-term toxicology and carcinogenicity studies are conducted in order to obtain approval to test and finally to market a product for chronic administration to man. These studies may need to start during the late preclinical/ early clinical phase in order to `support' the subsequent clinical program. Long-term toxicity studies will normally include toxicity studies of six and twelve months duration in two species (one non-rodent).Any toxicity previously detected may be investigated more closely，for example extra enzymes looked at in blood samples.Reproductive toxicology is that part of toxicology dealing with the effect of compounds on reproduction-fertility，foetal abnormalities，post-natal development. Prior to clinical studies in women of child-bearing age，regulatory authorities require teratology data from two species (normally rat and rabbit)as well as clinical data from male volunteers. No reproductive data are required prior to clinical studies in male subjects. The effects of 59 compounds on reproduction differ with the period of the reproductive cycle in which exposure takes place and studies are designed to look at these phases. Teratology`'' studies are designed to detect foetal abnormalities，fertility studies to investigate the compounds' effect on reproductive performance，And peri- and post-natal studies to study the development of pups.Selected from F. D. King，’Medicinal Chemistry Principles and Practice ’ the Royal Society of Chemistry Thomas , Graham House G. B. , 1994.Exercises1 .Answer the following questions:(1)Why do people consider the discovery of the novel drug is a long，expensive and tortuous process with no guarantee of success?(2) How many major processes are there in new drug development?(3) What has been achieved in the novel drug development in the past century?(4) Please list the disadvantages or barriers in Chinese novel drug development.2. Put the following into English:3. Put the following into Chinese:pharmacokinetics assessment optimum highlight regulatory approval preclinical pharmacology side effect excretion safety evaluation4. Fill the blanks with the following words:Pharmacodynamics toxicology pharmacognosyPharmacotherapeutics pharmacokinetics pharmacy____ is a descriptive science concerned with the physical characteristics of natural drugs，primarily those derived from plants and animals. ____ is the art and science of preparing，compounding，and dispensing medicines. ____ is the study of the way drugs are absorbed into。

制药工程专业英语(第一部分)

Red-brown
红棕色
Reddish-brown 微红棕色
Gray-black
灰黑色
Straw yellow 稻草黄色
Vocabulary （词汇）
Crystalline a. 水晶般的;水晶制成的
Crystallin 晶状体球蛋白 crystalline rocks 水晶石 Crystal n. 结晶; 水晶 Crystallization n. 结晶化 Amorphous 无定形的 Allotropic a.同素异形的 Diamond 金刚石 Graphite 石墨
Family
（周期表的）族
Group
族\基\团
Metaloid
准金属
Alkali metal 碱金属
Alkaline
碱的
Alkaline earth metal 碱土金属
Property
性质\特性
Characteristic 特性 \特点
Vocabulary （词汇）
Molecule Molecular Molecular weight (M. W.) Intermolecular
Diatomic molecule 双原子分子 Structure 结构 Valent 价的 Covalent 共价的 Valence (原子)价 Bond 键, 结合, 相连接
Orbital
轨道
Energy
能级
Radius (pls:radii) 半径
Electron
电子
Electron cloud 电子云
Science)
Part 1: Inorganic Chemistry
Vocabulary （词汇）

制药工程专业英语课文翻译1 5 11 13 16单元原文加翻译

完全（合成纤维）合成材料，Ⅱ。

天然产物，和Ⅲ。

产品从（半合成产品）的部分合成。

本书的重点是团体的最重要的化合物Ⅰ和Ⅲ一所以药物合成。

这并不意味着，但是，天然产品或其他代理人并不太重要。

它们可以作为有价值的领导结构，他们常常为原料，或作为重要的合成中间体产品的需要。

1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。

Unit 1 Production of Drugs根据其生产或来源不同药物制剂可以分为三类：Ⅰ.人工合成材料（全合成材料）Ⅱ.天然产物，和Ⅲ.半合成天然产物（半合成药物）。

本书的重点是这些第一组和第三组化合物都是合成药物。

然而这并不意味着那些天然药物和其他药物就不重要。

他们可以作为很有价值的先导结构，并经常被用为重要合成药物的原料或中间体。

表1概述了获取药物制剂的不同方法。

Table 1 Possibilities for the preparation of drugs表1药物制备的可能性几种最初来自于天然原料有治疗意义天然产物如今用更有效也就是经济的全合成法制备。

这样的例子包括L-氨基酸，氯霉素，咖啡因，多巴胺，肾上腺素，左旋多巴，肽类激素，前列腺素，D -青霉胺，长春蔓胺，以及几乎所有的维生素。

在过去的几年里发酵（即微生物处理）变得极其重要。

通过现代技术和遗传选择的结果产生了高效能微生物突变株，发酵已成为广泛的底物（物质）都可以选择的一种方法。

真核微生物（酵母菌和霉菌）和原核微生物（单细胞细菌和放线菌）用于微生物。

可以得到以下产品类型：1.细胞原料（单细胞蛋白）2.酶3.主要降解产物（初级代谢物）4.次要降解产物（次级代谢物）。

除了某些微生物（如肠膜明串珠菌）的黏膜所合成葡萄糖以外第2类和第3类都是与药物的制备相关的物质。

分子量为5万到10万的葡萄糖可以作为血浆替代品。

在这些初级代谢物中谷氨酸棒状杆菌和黄色短杆菌的突变体产生的L -氨基酸是特别有意义的。

利用这些生物体大约可以生产35万吨味精（食物添加剂）和7万吨L -赖氨酸（用于植物蛋白补充）。

更重要的初级代谢产物有嘌呤。

核苷酸，有机酸，乳酸，柠檬酸和维生素，例如谢曼丙酸杆菌产生的维生素12其中首先要提到的次级代谢物是抗生素。

以下五类抗生素每年全球销售额170亿美元：青霉素（黄青霉）头孢菌素（假头状孢子头枝顶孢属）四环素（金色链霉菌）红霉素（红霉素链霉菌）氨基糖苷类抗生素（灰色链霉菌）微生物已经分离出大约5000种抗生素的，但其中只有不到100种应用于临床治疗。

然而我们要记住的是，为了适应临床治疗的需要，通过半合成的方法修饰获得许多衍生物，在过去十年里，单单从β-内酰胺类通过半合成的方法制备获得药物制剂就有大约50000种。

发酵可以在容量高达400立方米的不锈钢发酵罐中进行。

为了避免微生物被噬菌体污染，整个过程都必须在无菌条件下进行。

由于比较重要的发酵过程只仅仅在耗氧条件下进行，因此需要提供优良的氧气和无菌空气。

二氧化碳的来源包括碳水化合物例如蜜糖、糖类和葡萄糖。

另外微生物的培养基必须提供含氮化合物如硫酸铵，氨水和以及含氮的无机磷酸盐。

此外，还需要保持恒定的最佳的pH和温度。

以青霉素G为例，发酵过程需要200小时，通过过滤分离出细胞体。

通过吸收或萃取工艺，人所期望的活性制剂可以从滤液中分离。

如果细胞体不是我们所期望的产物，则可进一步用作动物饲料，因为它们含有较高含量的蛋白质。

利用现代基因重组技术可以获得微生物，可以允许在原始的基因中没有编码的多肽的生产。

改良的大肠杆菌可以生产人胰岛素A链和B 链或胰岛素原类似物。

人胰岛素A链和B 链分离后有选择性的形成二硫键，用色谱法进行纯化。

用这种方式获得的人类胰岛素可以完全不依赖任何从动物体内获得的胰腺材料。

其他重要肽类，激素和酶，如人类生长激素，神经活性肽，生长激素抑制素，干扰素，组织型纤溶酶原激活物还有淋巴因子，如钙调节子钙调蛋白，蛋白疫苗还有用于诊断的单克隆抗体用这种方式合成。

单细胞微生物体内的酶或多酶体系可以用来定向的立体专一性和区域专一性的化学反应。

在甾体化学中这个原理非常有用。

这里我们只仅仅举一个例子，通过黄体酮11-α羟基化作用可以生成11-α羟基黄体酮，这是生成可的松的重要中间体。

如今分离酶是非常重要的，这不仅是因为其在催化淀粉糖化和葡萄糖异构化生成果糖方面有重要价值，在用于疾病诊断的无数检验程序中，以及用于治疗监测的酶法分析中也有重要意义。

许多酶本身就可以作为活性成分。

因此，含有蛋白酶（如糜蛋白酶，胃蛋白酶和胰蛋白酶），淀粉酶和脂肪酶的这些制剂通常与合成的抗酸药联合使用促进消化。

链激酶和尿激酶是重要的溶栓剂，并且天冬酰胺酶可以作为细胞生长抑制剂用来治疗白血病。

最后必须要提到的是酶作为生物催化剂在化学反应中它的立体专一性和选择性有重要的用途。

众所周知的例子是酶催化的N -乙酰化氨基酸的外旋体的拆分用来生产L -氨基酸酶，利用青霉胺酶以苄青霉素为原料生产6-氨基青霉烷酸，天门冬氨酸酶催化氨的氨水对富马酸的立体专一性加成，用来生产L-氨基酸。

在这些应用中，酶可以以固定化的形式应用（以某种形式与载体结合），这种应用形式叫做多相催化剂。

这是固定化酶的优势，因为固定化酶可以容易地从反应介质中分离出来，从而进一步回收再利用。

另一个依赖与蛋白酶的特异性的重要过程用来生产半合成人工胰岛素。

以猪胰岛素为原材料通过胰蛋白酶的选择作用将B链30位的丙氨酸替换成一个苏氨酸叔丁酯。

猪胰岛素酯经水解分离成人胰岛素并且最终通过色谱法技术纯化。

酶的来源不仅包括微生物，还有植物和动物材料。

由表1可见所有的药物中75％以上要通过全合成法得到。

因此，有关合成路线方面的知识是有用的。

理解合成路线可以使人们认清药物制剂被哪些中间体和副产物污染。

为了有效的控制药品质量，许多国家的注册机构要求提供关于生产过程的全部文件作为药物注册的必要文件。

药物合成方面的知识为药物研发的化学家带来了（有价值的）宝贵的启发。

对于所有药学活性化合物既没有首选的结构类型也没有首选的反应类型。

这意味着药物合成涉及几乎全部有机化学领域和部分有机金属化学的知识。

然而，大量的原料和中间体使用频率比较高，因此知道如何由基本的化学品合成这些物质是非常有用的。

基于这个原因，在本书中某处来阐述一些重要中间体的树型图是非常合适的。

后面提到的中间体是许多药物合成中都要用到的重要化合物。

本书涉及的这些化合物多半要大量生产的。

按类似的方式，本书提到的以甲苯，苯酚和氯苯等工业芳香族化合物为原料合成的中间体也是正确的。

更关键的化合物被归纳在一个表格内，在追踪合成中交叉关系时比较有用。

除了当前的起始原料和中间体溶剂不仅可以作为反应介质，也可以作为重结晶纯化。

常用的溶剂是甲醇，乙醇，异丙醇，丁醇，丙酮，醋酸乙酯，苯，甲苯和二甲苯。

其次在特殊反应中还有用乙醚，四氢呋喃，乙二醇醚，二甲基甲酰胺和二甲基亚砜作为溶剂。

大量使用的试剂不仅有酸（盐酸，硫酸，硝酸，醋酸），还有无机和有机碱（氢氧化钠，氢氧化钾，碳酸钾，碳酸氢钠，氨，三乙胺，吡啶）。

此外合成中还需要辅助的化学剂包括活性炭和催化剂。

所有这些辅助的化学（像中间体）都可以作为最终产品中杂质的来源。

1969年，世界卫生组织发布了一篇关于保障药品质量的论文。

附录二是有关于药品的制备和药品质量保障的一个恰当规范。

（WHO技术报告号418,1969，附录二，编号567,1975，附件1A）。

这现在已成为被我们熟知的GMP条约，按照这个规范化操作来进行。

这个标准它构成了药品生产品质证书互相认可的基础，也是药品生产企业进行生产设施检查的基础。

长期以来，美国药品权利机构，已经出版了与WHO规则相似的药品制备规则，而且严格照此执行。

像成品药出口到美国，FDA要对其生产企业进行定期检查。

这里要注意的是如此仔细的控制不仅适用于成品，也适用于原材料，还适用于中间体。

明显的对生产技术和卫生设备和仓储区，都要满足设定的标准。

由于只有少数的化合物，如乙酰水杨酸，对乙酰氨基酚和维生素，需要大量的制备。

因此我们必须要特别注意要避免其他产品的交叉污染，这个过程可以通过将使用过的设备进行彻底的清洁来实现。

需要详细的记录和描述所有储存的中间体和成品。

Chemotherapy : an Introduction (1)化疗被定义为使用化学物质消灭具有传染性的寄生虫或者生物体，而不损坏其动物宿主。

古文献中记载了早期的化学治疗药，但是其中大多数是和迷信和巫术有关的无效药品。

然而，其中一些化合物经过多年的反复实验被证明是具有治疗价值的。

在公元前3000年，中国皇帝神农在《本草经》中记载了许多治病的药物。

据记载，长山对突发性疟疾及其引起的发烧具有治疗价值。

早在那时就已经确认长山具有抗疟疾的活性。

其疗效也已经被现代研究者证实。

疾病的微生物理论在19世纪，建立了疾病的微生物理论。

A of L 证明了蚕类疾病是靠病原微生物传播的，并且提出了某些人类疾病也是通过这些微生物传播的。

D推断动物的炭疽病是由细菌引起的，这种说法后来被P证实。

在1865年，L证明苯酚具有杀菌的性能，医学界开始接受疾病的微生物理论，一个医学新时代开始了。

P E对化学治疗法发展的影响，最早出现在世纪之初。

由于他的发现，他被视为化学治疗之父。

他首先检查染料在血液中的分布规律，然后又检查了染料在动物活体中的分布情况。

之所以选择染料是因为他们在动物体内分布以后易于观察。

E发现特定的染料可以选择性的给与特定的器官和系统染色，而其他的染料给该组织染色的效果一般。

随着细菌学的发展，E将他的注意力转向了细菌染色。

他研制出给结核菌染色的抗酸性染色法，并且完成了许多前期的工作，这些工作引起了革兰氏染色剂的使用。

苯酚在1865年，L将P的微生物理论应用于外科手术。

他发现用苯酚清洗伤口和消毒可以防止可怕的腐败，这种方法在那时很常见。

这会该领域的进一步研究提供了动力。

随后发现了被烷基化和卤化的苯酚类化合物更具有抗菌活性。

在1932年，开始研究双酚类化合物，并在1941年取得了六氯酚的专利权。

染料与砷剂在1887年，R报到了某些细菌的菌株不能在含有某些染料的营养琼脂上生长。

1890年，S报道了苯胺染料是高活性的抗菌物质。

1891年，E发现了亚甲蓝可以给患有疟疾的生物体染色，但是当他试着给患有疟疾患者治疗时，仅有少数获得成功。

因为昏睡病是欧洲人在非洲发展的主要问题，E试图寻找对于治疗锥虫病的有效染色。

锥虫红和偶氮萘磺酸衍生物，被发现可以杀死锥虫种类，但是对于其他类型作用不大。

后来发现该系列的其它染料更具有实用价值，比如说锥虫蓝和阿弗里多紫。

微生物进化出了耐药菌株，也发现了对含砷药物产生了抵抗力。

但是对于一类药物的产生抵抗作用的寄生虫，对其他类型没有抵抗力。

E通过他的化学受体理论对此进行解释。

如果寄生虫的受体对一类药的亲和力减小，但他仍然可以和其它类的药物结合。

这个理论还指出受体可能存在其他不同的类型。

在1859年，B将苯胺和三氧化二碘供热，得到了被认为是酰替苯胺的化合物。

该反应可以用方程式(1)来表示。

1903年，E假定先前的结构是正确的，并且对这个化合物进行测试。

在1905年，T和B测试了这个化合物在体内抗锥虫的效果，发现它不但有活性，并且比亚甲酸钠的毒性低40倍。