Inactivating agents

Inhibitory agents Table 23.3 Inactivating agents Inactivating agents... 

Figure 3.9. Generalized overview of the industrial-scale manufacture of recombinant E2 classical swine fever-based vaccine, using insect cell culture production systems. Clean (uninfected) cells are initially cultured in 500-1000 litre bioreactors for several days, followed by viral addition. Upon product recovery, viral inactivating agents such as /i-propiolactone or 2-bromoethyl-iminebromide are added in order to destroy any free viral particles in the product stream. No chromatographic purification is generally undertaken as the product is substantially pure the cell culture media is protein-free and the recombinant product is the only protein exported in any quantity by the producer cells. Excipients added can include liquid paraffin and polysorbate 80 (required to generate an emulsion). Thiomersal may also be added as a preservative. The final product generally displays a shelf-life of 18 months when stored refrigerated...

Nevertheless, the inactivated vaccine approach suffers from several shortcomings. The process could inactivate not only the organism but also destroy the antigen conformation required to elicit protective immunity. Incomplete inactivation (e.g., virion aggregation resulting in poor exposure to the inactivating agent) could result in disease transmission or severe complica-... 

Patrick, M.H. Haynes, R.H. (1964). Dark recovery phenomena in yeast 1. Comparative effects with various inactivating agents. Radiation Res. 21, 144-163. 

Strauss E, Zhai H, Brand LA, McLafferty FW, Begley TP. Mechanistic studies on phosphopantothenoylcysteine decarboxylase trapping of an enethiolate intermediate with a mechanism-based 33. inactivating agent. Biochemistry 2004 43 15520-15533. 

One of the most useful techniques for checking the microbial quality of water is by membrane filtration, as this permits the concentration of a small number of organisms from a large volume of water. When chlorinated water supplies are tested it is necessary to add an inactivating agent such as... 

An appropriate inactivating (neutralizing) agent (Table 20.7) is incorporated into the culture media. The inactivating agent must be non-toxic to microorganisms, as must any product resulting... 

Although Table 20.7 lists only benzylpenicillin and ampicillin as being inactivated by p-lactamase (from B. cereus), other P-lactams may also be hydrolysed by P-lactamases. Other antibioticinactivating enzymes are also known (Chapter 13) and have been considered as possible inactivating agents, e.g. chloramphenicol acetyltransferase (inactivates chloramphenicol) and enzymes that modify aminoglycoside antibiotics. 

Prions are very difficult to inactivate. Agents that completely denature protein, such as bleach and strong alkali or acid (see the Dementias section later in the chapter) are effective, but ultraviolet light, routine formalin fixative, and standard disinfectants fail to eradicate prions. 

Saikosaponin d (50) from Bupleurum falcatum is not suitable to be applied as an antiviral agent because of its strong cytotoxic activity on host cells, but it is highly active in vitro as an inactivating agent on viruses with envelopes such as measles and herpes [151]. 

Each filling trial should consist of at least 3000 items (it is normal practice to exceed the minimum to account for breakages, etc.). The medium of choice is Soybean Casein Digest Broth VSP. Where necessary, for instance in antibiotic filling processes where, no matter how effective the cleaning, residues cannot be excluded, an inactivating agent (e.g., penicillinase) should be added to the medium at an appropriate concentration. 

Figure 7.6. The inactivation of P450 by chloramphenicol involves oxidation of the dichloromethyl group to an acyl chloride that reacts with an amino group of the protein. A potent inactivating agent related to chloramphenicol is (2-p-bromophenethyl)dichloroacetamide.

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