| 摘要 |
Compounds having a prolonged adrenocorticotropic hormonal activity consist of a sparingly soluble complex of a pharmaceutically suitable salt, hydroxide or oxide of a metal retarding the resorption of protein hormones and a peptide, having adrenal cortex stimulating activity, consisting of the amino-acid sequence of at least the first 19 and not more than the first 31 amine acid residues from the N-terminal end of an ACTH molecule as obtained from mammals. Suitable metals are Zu; Cu; Ni; Co; and Fe; and they are used in quantities of 1 to 20 mgs. of metal per 100 U.S.P. units of peptide. Preferred salts are phosphate, chloride, acetate and sulphate. Particular peptides mentioned are synthetic 19, 20, and 24 amino-acid residue peptides and 26 and 31 residue peptides prepared by enzymic degradation of a natural mammalian ACTH molecule. The term "peptide" includes functional derivatives thereof, such as amides, hydrazides, esters, and acid or alkali addition salts. Also, the invention relates to injectable compositions of the complexes suspended in an aqueous injectable vehicle; such compositions have a pH of 6.0 to 8.0, and preferably also contain a preservative, such as a phenol benzyl alcohol, or a p-hydroxy benzoic acid ester; a solute such as sodium chloride to make the solution isotonic with body fluids; a buffer, and a phosphorus oxy-acid, or its salt, or a derivative of such an acid (e.g. nucleoside phosphate; phosphoserine; or creatine phosphate), which substances have stabilizing properties. The complex may either be used in suspension, if a sparingly soluble metal salt is employed, or may, if a soluble salt is used, be in the form of a solution. The complexes are prepared by mixing aqueous solutions or suspensions of the salt, oxide or hydroxide, and the hormone. The injectible preparation may also take the form of an aqueous solution of salt and protein outside the stated pH range of 6.0 to 8.0 (e.g. pH 4.0) which, on injection, forms the sparingly soluble complex at the pH of the tissue fluids.
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