Pharmaceutical composition comprising cyclic somatostatin analogues

1 . A pharmaceutical composition for parenteral administration comprising a somatostatin analogue comprising the amino acid sequence of formula I

-(D/L)Trp-LYs-X 1 -X 2 -  I

wherein X 1 is a radical of formula (a) or (b)

wherein R 1 is optionally substituted phenyl,

R 2 is -Z 1 -CH 2 —R 1 , —CH 2 —CO—O—CH 2 R 1 ,

wherein Z 1 is O or S, and

X 2 is an α-amino acid having an aromatic residue on the C α side chain, or an amino acid unit selected from Dab, Dpr, Dpm, His,(Bzl)HyPro, thienyl-Ala, cyclohexyl-Ala and t-butyl-Ala, the residue Lys of said sequence corresponding to the residue Lys 9 of the native somatostatin-14

in free form, salt form, or protected form and tartaric acid.

2 . A composition according to claim 1 wherein the somatostatin analogue is a compound of formula II

wherein the configuration at C-2 is (R) or (S) or a mixture thereof, and

wherein R is NR 1 R 2 —C 2-6 alkylene or guanidine-C 2-6 alkylene, and each of R 1 and R 2 independently is H or C 1-4 alkyl,

in free form, salt form or protected form.

3 . A composition according to claim 1 wherein the compound of the somatostatin analogue is in aspartate di-salt form.

4 . A composition according to claim 1 wherein the composition is adjusted to a pH of about 4 to about 4.5.

5 . A composition for parenteral administration buffered at a pH of about 4 to about 4.5 and comprising as active ingredient cyclo[{4-(NH 2 —C 2 H 4 —NH—CO—O—)Pro}-Phg-DTrp-Lys-Tyr(4-Bzl)-Phe] or a pharmaceutically acceptable salt thereof.

6 . A composition according to claim 5 wherein the composition is buffered by an acetate/acetic acid, lactate/lactic acid, or Glycin/HCl buffer.

7 . Use of a pharmaceutical composition according to claim 1 for the preparation of a medicament for acromegaly or cancer.

8 . Use according to claim 6 for the preparation of a medicament for Cushing's Disease.

9 . A method of treating acromegaly or cancer in a subject in need thereof which comprises administering a pharmaceutical composition according to claim 1 to the subject.

10 . A compound of formula III

wherein R is NR 1 R 2 —C 2-6 alkylene or guanidine-C 2-6 alkylene, and

each of R 1 and R 2 independently is H or C 1-4 alkyl,

in free form, in salt form or complex form, or in protected form, e.g. cyclo[{4-(NH 2 —C 2 H 4 —NH—CO—O—)Pro}-DPhg-DTrp-Lys-Tyr(4-Bzl)-Phe].