Pfizer penicillin

Pen (Wyeth-Ayerst)-(penicillin V potassium) Pfizerpen G (Pfizer)-(penicillin G potassium) Sugracillin (Upjohn) Wycillin (Wyeth-Ayerst)-(procaine-benzylpenicillin)... 

The industrial production of penicillin by Pfizer in 1943 transformed the chemistry of natural products. Microbiology became its field and pharmaceutical research became its leading trend. The main driving force behind the research of the chemistry of natural products was and still remains to be human health care. Since the advent of antibiotics, many sources of natural chemicals, such as plants, fungi and bacteria, have been searched for antibacterials, anticancer products, immuno-suppressors and chemicals that affect the human psyche. This research was so successful that, even today, more than half of all pharmaceuticals are either natural products or derived from, or inspired by them. The market of antibiotics alone was ca. US 30 billion in 2005. The majority of antibiotics is produced by submerged fermentation of filamentous microorganisms such as soil prokaryotic actinomycetes and eukaryotic moulds, ascomycetes. 

There are five basic sources of pharmaceuticals. By dollar value of products, fermentation is probably the most important, whereas by tonnage, chemical synthesis is dominant. Fermentation is used for antibiotics such as penicillins and tetracyclines. Chemical synthesis provides drugs such as the psychotropics and antihistamines. Animal extracts provide hormones. Biological sources lead to vaccines and serums. Vegetable extracts provide steroids and alkaloids. The top ten pharmaceutical companies in order of revenues are the following Merck, Pfizer, Bristol-Myers Squibb, Johnson ... 

Up to 9 X10 ton/a is produced world-wide by a number of companies, snch as Beechams, Toyo Jozo, Pfizer, Gist-brocades (now DSM) etc. The majority is produced using penicillin G acylase, although some companies prefer to nse the V acylase. This large commercial potential was obviously a very big incentive to companies to develop this technology. 

Eventually, 100,000 units of penicillin were produced by a consortium of American drug companies (Merck, Squibb, and Pfizer) by the middle of 1944. A tremendous improvement in yield was made possible by the use of a new strain of mold, as well as the use of deep fermentation tanks similar to those used in the brewery industry. Interestingly, the new strain of mold discovered was serendipitously found on a decaying cantaloupe in a Peoria food market. 

The natural penicillins, primarily G and V, have a relatively narrow spectrum. They act mostly on gram-positive organisms. The fact that proper selection of precursors could lead to new variations in the penicillin side chain offered the first source of synthetic penicillins. Penicillin V, derived from a phenoxy-acetic acid precursor, attracted clinical use because of its greater acid tolerance, which made it more useful in oral administration. Also, the widespread use of penicillin eventually led to a clinical problem of penicillin-resistant staphylococci and streptococci. Resistance for the most part involved the penicillin-destroying enzyme, penicillinase, which attacked the beta-lactam structure of the 6-aminopenicillanic acid nucleus (6-APA). Semisynthetic penicillins such as ampicillin and carbenicillin have a broader spectrum. Some, such as methicillin, orafi-cillin, and oxacillin, are resistant to penicillinase. In 1984, Beecham introduced Augmentin, which was the first combination formulation of a penicillin (amoxicillin) and a penicillinase inhibitor (clavulanic acid). Worldwide production of semisynthetic penicillins is currently around 10,000 tons/year, the major producers are Smith Kline Beecham, DSM, Pfizer, and Toyo Jozo. 

Merck plunged into the most cutting-edge research of the time— vitamins, sulfas (a precursor of antibiotics), antibiotics, and steroids and other hormones. In its labs, the TB cure streptomycin was discovered and the powerful hormone cortisone was first synthesized. During World War II, the government asked Merck, Pfizer, Squibb, and Lederle Labs to workjointly to speed up production of penicillin. 

Cer-O-Cillin [Pfizer]. TM for an antibacterial substance that differs from penicillin G in that the benzyl group is replaced with an allylmercapto-methyl group. In concentrations up to 500,000 units per cc in sterile water for injection, sterile sodium chloride for injection, or sterile 5% dextrose. 

During World War II, Glaxo became Britain s primary producer of penicillin, much as Pfizer did in the United States. By 1944 Glaxo, using Pfizer s fermentation process, had built four factories that produced 7.5 billion units, or about 80 percent of total British output. After the war, it remained Britain s leader in penicillin. At the same time, the company continued to expand its vitamin lines. Its managers then exploited this learning to enter the field of hormones by developing Britain s first commercial cortisones and then a series of corticosteroids. 

For an overview of Pfizer s history, see Derdak, ed.. International Directory, vol. 9 (1994), pp. 402-405. Edmund T. Pratt, Jr., Pfizer, Bringing Science to Life (Princeton, NJ Newcomen Society/Princeton University Press, 1985), (pp. 7-11), is particularly useful for its review of the development of penicillin. 

Production of 6-amino penicillanic acid (6-APA) from penicillin G or V by the action of penicillin amidase from E. coli, Bacillus megaterium, or Bovista plumba (Toyo Jozo Inc., Asahi Chemical Industry Co., Ltd., Fujisawa Pharmaceutical Co., Gist-Brocades/DSM, Novo-Nordisk, Pfizer, and others). Annual world production of 6-APA 6000 tons, used for the manufacture of semisynthetic penicillins. 

Antibiotic treatment should be continued for at least 4 weeks (i. e., until at least three doses of vaccine have been received). Penicillin and especially streptomycin are rarely used anymore, and hospital pharmacies will have very limited supplies on hand, but Pfizer will still ship streptomycin overnight. Ciprofloxacin and doxycycline are prescribed far more often, but they are expensive, especially ciprofloxacin, which may limit supplies in any one locale. 

Florey and Heatley convinced the NRRL and several American pharmaceutical companies (including Merck, Squibb, and Pfizer), to develop the production of penicillin. Heatley remained for a period at the NRRL to work with Moyer and Coghill and then worked for a while at Merck. Thus began a momentous cooperative effort among university and industrial laboratories in the United States and academic institutions in England, which lasted throughout the war. 

Pfizer Inc. This is a more specialized company which concentrates on pharmaceuticals. Its specialities are fine chemicals and fermentation products, particularly penicillin and streptomycin antibiotics. 

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