制药工程专业外语1翻译156111316文档格式.docx

1、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和一所以药物合成。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。表1给出了获取药剂的不同方法的概述。Table 1 Possibilities for the preparation of drugsMethods Examples1. Total synthesis -over 75 % of all pharmaceutical agents （synthetics）2. Isolation from natural sources （nat

2、ural products）: 2.1 Plants -alkaloids;enzymes;heart glycosides;polysaccharides;tocopherol; steroid precursors （diosgenin, sitosterin）;citral （intermediate product for vitamins A, E，and K） 2.2 Animal organs一enzymes;peptide hormones;cholic acid from gall; insulin） from the pancreas;sera and vaccines 2

3、. 3 Other sources一cholesterol from wool oils;L-amino acids from keratin and gelatine hydrolysates3. Fermentation一antibiotics;L-amino acids;dextran; targeted modifications on steroids， e.g. 11-hydroxylation; also insulin, interferon, antibodies, peptide hormones，enzymes，vaccines4. Partial synthetic m

4、odification of natural products （semisynthetic agents）: 一alkaloid compounds;semisynthetic /3-lactam antibiotics;steroids;human insulin 表1对药物的可能性准备方法举例全合成，超过75的药剂（合成纤维）2。分离（天然产物）天然来源：2.1植物-生物碱;酶;心甙，多糖，维生素E;类固醇的前体（薯蓣皂素，sitosterin），柠檬醛（中间产品维生素A，E和K）2.2动物器官一酶;肽激素;胆酸从胆;胰岛素）从胰脏;血清和疫苗从角蛋白和明胶L -氨基酸;三一胆固醇从羊毛

5、油脂的其他来源水解3。一抗生素发酵;L -氨基酸，葡聚糖，对类固醇有针对性的修改，例如11 -羟基化;也胰岛素，干扰素，抗体，肽激素，酶，疫苗4。部分合成修改（半合成剂）天然产品：一生物碱化合物;半合成/ 3-内酰胺类抗生素;类固醇;人胰岛素Several therapeutically significant natural products which were originally obtained from natural sources are today more effectively -i. e. more economically -prepared. by total sy

6、nthesis. Such examples include L-amino acids，Chloramphenicol，Caffeine, Dopamine， Epinephrine，Levodopa, peptide hormones，Prostaglandins，D-Penicillamine，Vincamine， and practically all vitamins.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

7、乎所有的维生素。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

8、 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. se

9、condary degradation products （secondary metabolites）.在过去的几年里发酵-岛大肠杆菌微生物过程变得极其重要。通过现代技术和基因选择的结果导致了突变体的微生物创造高性能，发酵，已成为首选方法各种各样的物质。这两个Eukaryonts（酵母菌和霉菌）和Prokaryonts（单细胞细菌，放线菌和）用于微生物。下列产品类型可以得到：细胞的物质（单细胞蛋白），酶，主要降解产物（主要代谢物），二级降解产物（次生代谢物）。 Disregarding the production of dextran from the mucous membranes o

10、f 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

11、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

12、 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: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

13、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。其中次生代谢产物的抗生素必须首先提到。以下五组代表了美国每年170亿美元的全球价值： penicillins （ Penicillium chrysogenum ）， cephalosporins （ Cephalosporium acre

14、monium ）， tetracyclines （ Streptomyces aureofaciens ）， erythromycins （ Streptomyces erythreus ）， aminoglycosides （e. g. streptomycin from Streptomyces griseus）.青霉素（青霉）头孢菌素（头孢枝顶）四环素（金色链霉菌）erythromycins（链霉菌）氨基糖苷类（如链霉素从灰色链霉菌）。 About 5000 antibiotics have already been isolated from microorganisms，but of

15、 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

16、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

17、）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，constan

18、t 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，

19、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。必须记住，但是，许多衍生工具已被用于治疗使用部分合成修改;约50,000剂已被semisynthetically取得户内酰胺在过去十年孤独。发酵都是在不锈钢发酵罐出来的量高达400立方米。为了避免与噬菌体等微生物污染的全过程都必须在无菌条件下进行。由于更重要的发酵只发生在有氧条件下的氧气或空气好电源（无菌）是必要的。二氧化碳的来源包括碳水化合物，大肠杆菌克糖蜜，糖和葡萄糖

20、。另外必须提供的微生物在与含氮如硫酸铵，氨水或尿素化合物生长介质，以及与无机磷酸盐。此外，不断最适pH和温度是必需的。在青霉素G的情况下，发酵完成200小时后，细胞的质量是由过滤分离。所需的活性剂是隔离的滤液吸收或提取工艺。大规模的细胞，如果不理想的产品，可进一步用作动物，由于其蛋白质含量高的饲料。 By modern recombinant techniques microorganisms have been obtained which also allow production of peptides which were not encoded in the original gen

21、es. 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 ind

22、ependently 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 mon

23、oclonal antibodies used as diagnostics，are synthesized in this way. 利用现代微生物重组技术已获得这也让其中不是在原来的基因编码多肽的生产。改性大肠杆菌从而使可能产生A型和B -人胰岛素或胰岛素原类似物链。二硫键形成的选择性分离后，最终由色谱净化工序的影响。通过这种方式获得的人类胰岛素完全独立采取任何从动物胰腺材料。其他重要肽，激素和酶，如人类生长激素（hGH），神经活性肽，生长抑素，干扰素，组织型纤溶酶原激活物（tPA），淋巴因子，如钙调节钙调蛋白，蛋白疫苗，以及作为诊断用单克隆抗体是合成了这种方式。 The enzymes

24、or enzymatic systems which are present in a single microorganism can be used for directed stereospecific and regiospecific chemical reactions. This principle is especially useful in steroid chemistry. Here we may refer only to the microbiological 11-a- hydro xylation of progesterone to 11-a-hydroxyp

25、rogesterone，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

26、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，pr

27、omote digestion. Streptokinase and urokinase are important in thrombolytics，and asparaginase is used as a cytostatic agent in the treatment of leukemia.这些酶或微生物在一个单一的酶系统，目前可用于立体定向和regiospecific化学反应。这个原则是有用的，尤其是在化学类固醇。在这里，我们只能引用的微生物十一水电黄体酮xylation至11人羟，一个关键的产品在可的松合成。隔离酶是重要的，不仅因为淀粉的酶法糖化技术重要性的今天，和葡萄糖异构果

28、糖，他们也都在无数次试验在诊断疾病所用的程序显着，在酶的分析，在使用监测治疗。数量的酶本身作为活性成分。因此，含有蛋白酶制剂（如糜蛋白酶，胃蛋白酶和胰蛋白酶），淀粉酶和脂肪酶的合成主要是在与抗酸药相结合，促进消化。链激酶和尿激酶溶栓是重要的，是天冬酰胺酶在治疗白血病细胞生长剂。 Finally mention must be made of the important use of enzymes as biocatalystsin chemical reactions where their stereospecificity and selectivity can be used. Kno

29、wn 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.最后必须提到的，作为他们在那里biocatalystsin化学stereospecificity和选择性反应的酶可用于制造重要的用途。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