In 1982, Eli Lilly made history by launching the world's first successful product of modern biotechnology for human healthcare: recombinant human insulin for treatment of diabetes. In 1969, Lilly filed a patent on a novel crystallization method for pancreatic insulin [33]. This crystallization process has been used for over thirty years to manufacture insulin. This is the 8.2 process, so named because the maximum yield of crystalline insulin occurs at pH 8.2 (Table 5.4). In this process, insulin is dissolved in 0.5 M acetic acid to yield a solution at pH 3.6. Addition of 1 M NaOH brings the solution to pH 8.2 where crystallization occurs spontaneously in about 15 min, and is complete after the solution is stirred for about 18 h at 22°C. Yield is about 90%. In 1996, Lilly introduced fast-acting insulin called lispro, which also uses crystallization for large-scale production. However, the 8.2 process does not work for lispro [34]. Instead, a solution of 20 g/l lispro in 0.75 M acetic acid, 37.5 mM NaCl, 23 ¡xM phenol is adjusted to pH 9.0 using 10% NaOH and held at 5°C under gentle agitation for 24 h. Well-defined crystals are observed. Oddly, the crystallization does not work without phenol, which was originally added to prevent bacterial growth. Even if the phenol is added, after pH adjustment and before crystallization, an amorphous precipitate forms along with a few crystals. If other preservatives are used such as meta-cresol, resorcinol, and methyl paraben, then crystallization is successful, but each crystal has a unique and different crystal habit, none of which match that for phenol. The crystallization temperature was not critical as tested in the range of 4 to 26°C. However, an optimum pH of 9.0 was observed with no crystals forming at slightly higher (pH 10.0) and lower (pH 8.2) values. These two examples are classic illustrations of the successful implementation of protein crystallization at process-scale in the biopharmaceutical industry.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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