| 摘要 |
Disclosed is a method of obtaining an acid addition salt, crystalline compound of the formula: H-MetO2-Glu-His-Phe-D-Lys-Phe-OH. The resulting crystalline hexapeptide salt has better intranasal absorption characteristics in comparison to amorphous hexapeptide. The method includes: a) dissolving relatively pure hexapeptide into an aqueous acidic solvent; b) concentrating the resulting solution under reduced pressure at an elevated temperature; c) measuring the pH of the concentrated solution, and if the pH is between 4.5 and 4.8, then d) maintaining the temperature of the concentrated solution between 6 and 20<o> C, if the measured pH of the concentrated solution is lower than 4.5, then adding water to the solution and repeating step b) until a pH of 4.5 to 4.8 is attained; and then e) removing the crystals from the concentrated solution by filtration at lower temperatures. Previously obtained "seed" crystals comprising the acid addition salt of the hexapeptide may be used to hasten the process. Once obtained, the crystalline compound may be used in the treatment or prevention of neuropathies or dementia. |
