制药工程专业英语课文

Unit 1 Production of Drugs Depending on their production or origin pharmaceutical agents can be split into three groups: I .Totally synthetic materials (synthetics)， Ⅱ.Natural products，and Ⅲ .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 drugs Methods                             Examples 1. 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 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 Other sources一cholesterol from wool oils;L-amino acids from keratin and gelatine hydrolysates 3. Fermentation一antibiotics;L-amino acids;dextran; targeted modifications on steroids， e.g. 11-hydroxylation; also insulin, interferon, antibodies, peptide hormones，enzymes，vaccines 4. Partial synthetic modification of natural products (semisynthetic agents): 一alkaloid compounds;semisynthetic /3-lactam antibiotics;steroids;human                                      insulin Several 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.