Insulin animal sources

Human forms are derived from recombinant or biosynthetic human insulin. Animal sources are derived from purified pork insulin. 

Insulin is available as purified extracts from beef and pork pancreas and is biologically similar to human insulin. However, these animal source insulins are used less frequently today than in years past. They are being replaced by synthetic insulins, including human insulin or insulin analogy. 

Human insulin is derived from a biosynthetic process using strains of Escherichia coli (recombinant DNA, rDNA). Human insulin appears to cause fewer allergic reactions than does insulin obtained from animal sources. Insulin analogy, insulin lispro, and insulin aspart are newer forms of human insulin made by using recombinant DNA technology and are structurally similar to human insulin. 

Insulin was originally (since the 1930s) obtained from porcine and bovine extracts. Bovine insulin differs from human insulin by three amino acids, and it can elicit an antibody response that reduces its effectiveness. Porcine insulin, however, differs in only one amino acid. An enzymatic process can yield insulin identical to the human form. Currently, insulin is produced via the rDNA process it was the first recombinant biopharmaceutical approved by the FDA in 1982. The recombinant insulin removes the reliance on animal sources of insulin and ensures that reliable and consistent insulin is manufactured under controlled manufacturing processes. A description of diabetes meUitus and insulin is presented in Exhibit 4.13. 

Biotechnology-derived products have led to renewed interest in establishing reference standards based on the same bulk of material. Thus a single formulation, assay, and reference standard may be the fact worldwide. This situation can become complex such as with insulin where both biotechnology-derived insulin and animal-source insulin are in the marketplace at the same time. 

Mixing of insuiins-The effects of mixing insulin aspart or lispro with insulins of animal source or insulin preparations produced by other manufacturers have not been studied (see Warnings). 

Generai This human insulin product differs from animal-source insulins because it is structurally identical to the insulin produced by the body s pancreas and because of its unique manufacturing process. 

Make any change of insulin cautiously and only under medical supervision. Changes in purity, strength, brand (manufacturer), type (eg, regular, NPH, lente), species (beef, pork, beef-pork, human), or method of manufacturer (rDNA vs animal-source insulin) may result in the need for a change in dosage. 

Some patients taking this product may require a change in dosage from that used with animal-source insulins. If an adjustment is needed, it may occur with the first dose or during the first several weeks or months. 

A wide range of pharmaceutical substances are derived from animal sources (Table 1.10). Many are protein-based and detailed description of products such as insulin and other polypeptide hormones, antibody preparations, vaccines, enzymes, etc., have been deferred to subsequent chapters. (Many of the therapeutic proteins are now also produced by recombinant DNA technology. Considerable overlap would have been generated had a product obtained by direct extraction from native sources been discussed here, with further discussion of a version of the same product produced by recombinant DNA technology at a later stage.) Non-proteinaceous pharmaceuticals originally derived from animal sources include steroid (sex) hormones, corticosteroids and prostaglandins. A limited discussion of these substances is presented below, as they will not be discussed in subsequent chapters. Most of these substances are now prepared synthetically. 

Historically, commercial insulin in the USA contained beef or pork insulin. Beef insulin differs by three amino acids from human insulin, whereas only a single amino acid distinguishes pork and human insulins (Figure 41-1). The beef hormone is slightly more antigenic than pork insulin in humans. Of the insulins manufactured from animal sources, only purified pork insulin is still available and it requires special ordering. 

The scientific and technological achievements of the last decades have allowed the discovery and production of new biological medicines, or substitution of those previously extracted from animal sources, like insulin and growth hormone. Most of those medicines are proteins obtained by animal cell cultivation, which differs from bacteria and yeast in that animal cells carry out post-translational modifications needed for biological activity and similar to the natural protein. Biopharmaceutical production in mammalian cells, including hormones, monoclonal antibodies (mAbs), vaccines, and other molecules with medical interest, involves high cost processes due to factors such as ... 

The words natural and organic are quite appealing to the consumer. Synthetic is often considered less desirable. Many believe that natural is better, safer, or not foreign to the body, but quite the opposite may exist. Native is identical to what is produced by or present in the body. Natural products refers to substances that are use to promote health or treat illness derived from plant, mineral, or animal sources. Organic refers to the level of pesticides or chemicals used in the growing process. For example, insulin from pork or beef sources is natural, but not native. Recombinant insulin is synthetic, but native. Thus, synthetic, as in synthetic insulin or estrogen, does not necessarily mean foreign or less desirable. 

Leaching or solid-liquid extraction are terms that describe the extraction of soluble constituents from a solid or semisolid by means of suitable solvents. The process, which is used whenever tea or coffee is made, is an important stage in the production of many fine chemicals found naturally in animal and vegetable tissue. Examples are found in the extraction of fixed oils from seeds, in the preparation of alkaloids, such as strychnine from Nux vomica beans or quinine from Cinchona bark and in the isolation of enzymes, such as rennin, and hormones, such as insulin, from animal sources. In the past, a wider importance attended the process because the products of simple extraction procedures, known as galenicals, formed the major part of the ingredients used to fulfill a doctor s prescription. 

The foregoing section indicates some reasons why peptide-based drugs are needed. If a peptide hormone is not produced in sufficient quantities or is defective in structure, then a replacement is required. Peptides, especially very small molecules, have a very short half life in the body. The reason for this is the ubiquitous occurrence of proteolytic enzymes that effect hydrolysis of peptides to the constituent amino acids. Although longer peptides, especially those with structural features such as disulphide bonds, survive longer in vivo, they are more likely to stimulate the body s immune system to produce antibodies and effect removal of the peptides. This is particularly likely to occur with molecules that differ structurally from the naturally occurring hormones. Thus, treatment of juvenile-onset diabetes mellitus with insulins from animal sources can occasionally stimulate the patient s immune system... 

With the rapid increase in the incidence of diabetes among the population, it is no longer possible to satisfy the pharmaceutical requirement (estimated to be 15-20 tonnes per year in 2005) from animal sources. Furthermore, the animal-extracted insulins are slightly different from human insulin, which might cause formation of insulin-binding antibodies and allergic reactions. Porcine insulin, which differs from human insulin only by a single amino acid in position B30, can be converted to human insulin in a transpeptidation reaction, in which an alanine is replaced with a threonine [1]. 

The most common and important form of insulin-induced immunologic complication is the formation of insulin antibodies, which results in resistance to the action of the drug or allergic reactions. Human insulins ate less antigenic than insulin from animal sources. Lipodystrophy, a change in fatty tissue at the site of injection, was relatively common in the past. Use of more purified, less antigenic forms of insulin has almost eliminated this complication. 

A major achievement in drug discovery and development was the discovery of insulin in 1921 from animal sources. Frederick G. Bunting and Charles H. Best, working in the laboratory of John J.R. McLeod at the University of Toronto, isolated the polypeptide hormone and began testing it in dogs. By 1922, researchers, with the... 

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