Crystalline teriparatide
A crystallization and cube technology, applied in the field of teriparatide, can solve problems such as instability
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Embodiment 1
[0057] Recombinant human rhPTH(1-34) (SEQ ID NO: 2) was prepared from previously purified and lyophilized material. The lyophilized protein was dissolved in water at a concentration of 5 mg / ml to 20 mg / ml. Protein was mixed with storage solution (20% isopropanol, 0.2M sodium citrate, 0.1M tris(hydroxymethyl)aminomethane in HCl buffer, pH=8.0) at a ratio of 1:1 on a silicon-coated glass coverslip. ratio mix. Slides were inverted and sealed over wells containing 1 mL of storage solution. Tetragonal flaky crystals appeared within 48-96 hours, with a size of 0.1mm×0.1mm×0.05mm. Mass spectroscopy confirmed the product. figure 1 Photographs of crystal growth are given.
[0058] X-ray crystallography of the tetrahedral platelets showed a P422 spacer and the following unit cell constants: a=b=91.071 Å, c=37.665 Å, α=β=γ=90°.
Embodiment 2
[0060] The same experiment was repeated as in Example 1 and mixed with a stock solution of 10% isopropanol, 10% polyethylene glycol, 0.1 M glycine buffer, pH=8.5.
Embodiment 3
[0062] Batch crystallization: rhPTH (SEQ ID NO: 1) with a concentration of 10 mg / ml and 50% isopropanol, 100 mM tris (hydroxymethyl) aminomethane, pH = 7.5, 0.2 M sodium citrate stock solution at a ratio of 1:1 ratios were mixed in test tubes. Crystals appeared within 48-96 hours, with a size of 0.1 mm x 0.1 mm x 0.05 mm.
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