Pyrogens nature

Another concern with regard to the use of E. coli is the presence on its surface of LPS molecules. The pyrogenic nature of LPS (Chapter 7) renders essential its removal from the product stream. Fortunately, several commonly employed downstream processing procedures achieve such a separation without any great difficulty. 

The General Tests and Assays. This section of the USP gives methods for tests that are general in nature and apply to a number of the substances. Procedures are iacluded for such tests as heavy metals, melting point, chloride, sulfate, sterility, bacterial endotoxins, and pyrogens. Also iacluded are descriptions of various analytical techniques, such as spectrophotometry, chromatography, and nmr, and descriptions of tests to be used on glass or plastic containers, mbber closures, etc. 

Ellern (Ref 4, pp26—7 65—6) reports that Paracelsus (1490-1541), physician and philosopher on the nature of man and the origin of sickness, seems to have been the fust to discover the element of fire in the residue of the pyrogenic... 

Water produced by reverse osmosis (RO) is forced by an osmohc pressure through a semi-permeable membrane which acts as a molecular filter. The difiusion of solubles dissolved in the water is impeded, and those with a molecular weight in excess of 250 do not difftise at all. The process, which is the reverse of the natural process of osmosis, thus removes microorganisms and their pyrogens. Post-RO contaminahon m occur if the plant after the membrane, the storage vessel or the distribuhon system is not kept Ifee Ifom microorganisms. 

The important attributes of liposomes as a drug carrier are (a) they are biologically inert and completely biodegradable (b) they pose no concerns of toxicity, antigenicity, or pyrogenicity, because phospholipids are natural components of all cell membranes (c) they can be prepared in various sizes, compositions, surface charges, and so forth, depending on the requirements of... 

Another issue of relevance is that certain biopharmaceuticals (e.g. cytokines such as 1L-1 and TNF Chapter 9) themselves induce a natural pyrogenic response. This rules out use of the rabbit-based assay for detection of exogenous pyrogens in such products. Such difficulties have led to the increased use of an in vitro assay the Limulus ameobocyte lysate (LAL) test. This is based upon endotoxin-stimulated coagulation of amoebocyte lysate obtained from horseshoe crabs. This test is now the most widely used assay for the detection of endotoxins in biopharmaceutical and other pharmaceutical preparations. 

While the simultaneous presence of benzofuran and benzothiophene is established in some fractions from coal pyrogenation and from the distillation of some petroleums, benzothiophene is entirely absent in heterocyclic compounds extracted from natural substances of vegetable origin. However, numerous benzofuran or hydrobenzofuran derivatives of biogenetic or metabolic origin have been isolated. 

Van Damme J, De Ley M, Opdenakker G, Billiau A, et al. 1985. Homogenous interferon-inducing 22 K factor is related to endogenous pyrogen and interleukin-1. Nature. 314 266-268. 

For commercial processes, formed supports are more useful. Compared with other supports, fumed oxide supports showed new catalytic effects [41]. Some intensively investigated applications for these supports are abstracted in the following. SiC>2 pellets have been successfully introduced in a new generation of precious metal supports in vinylacetate monomer production [42]. This resulted in better selcctivities and an up to 50% higher space-time yield compared with supports based on natural alumo-silicates. In alkene hydration fumed silica pellets serve as a support for phosphoric acid. In this case, an increased catalyst lifetime and a higher space-time yield were observed [43]. Pyrogenic TiC>2 powder can be used as a starting material for the manufacture of monolithic catalysts [44] for the selective reduction of NOv with ammonia. 

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