Purification method for prolyl-leucylglycinamide

DETAILED DESCRIPTION OF THE INVENTION The tripeptide L-prolyl-L-leucylglycinamide, hereinafter referred to as MIH for melanocite inhibiting hormone, has recently been shown to be a useful drug for combating depression and the symptoms of Parkinsonism when administered to warm-blooded animals afflicted with such symptoms.
Recently issued, U.
S.
Pat.
Nos.
3,708,593 and 3,795,738 show the specific benefits of this material upon oral administration to warm-blooded animals.
However, unfortunately, medicinally pure material is rather difficult to obtain.
Chemically, there is no difficulty in preparing this tripeptide and to obtain it in relatively pure crystalline form by crystallizing it from water.
While material obtained in this fashion is usually satisfactory for investigation of the effects of the drug, it is necessary to obtain a truly pure form of the material for pursuit of the drug in the medical treatment of humans.
While material known to date may analyze properly from the carbon, hydrogen and nitrogen content of the assigned structure of the hemihydrate of MIH, thin-layer chromatography shows that the material recrystallized several times from water still contains impurities, often exceeding 2% by weight.
A major proportion of these impurities is N-carbonbenzoxy-MIH, which has solubility characteristics so similar to MIH that recrystallization by previous methods will not remove it.
It is thus an object of the present invention to prepare MIH that shows essentially only a single spot upon thin-layer chromatography.
It is a particular object of this invention to purify MIH to a chemically and physically substantially pure form.
These and other objects are accomplished upon crystallizing MIH by dissolving one part by weight thereof in at least three parts by weight of methanol and adding at least the fourfold volume of ether thereto.
Crystals of highest purity of the hemihydrate of MIH are obtained in this manner.
They show only a single spot on thin-layer chromatography from the customary solvents or solvent mixtures