Peptide slow-release formulations

Abstract

A composition for the delayed delivery of a peptide active agent comprising; i) a salt of said peptide active agent comprising at least one positively charged peptide ion and at least one negatively charged counter-ion ii) a sustained-release delivery vehicle, wherein the at least one negatively charged counter-ion is a halide ion, preferably a chloride or bromide ion.

1 - 37 . (canceled) 
     
     
         38 . A method for the treatment of a human or non-human mammalian subject in need thereof with a somatostatin analogue, comprising administering to the subject a pre-formulation comprising a low-viscosity mixture of:
 a) at least one diacyl glycerol;   b) at least one phosphatidyl choline (PC);   c) at least one oxygen containing organic solvent; and   d) at least one halide salt of at least one somatostatin analogue selected from lanreotide and vapreotide;   wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid.   
     
     
         39 . The method of  claim 38 , wherein component a) comprises glycerol dioleate (GDO). 
     
     
         40 . The method of  claim 38 , wherein component b) comprises soy PC. 
     
     
         41 . The method of  claim 38 , wherein component c) comprises ethanol. 
     
     
         42 . The method of  claim 38 , wherein the halide salt is a chloride or bromide ion. 
     
     
         43 . The method of  claim 38 , wherein the pre-formulation comprises:
 a) 40-70 wt % of the at least one diacyl glycerol;   b) 30-60 wt % of the at least one phosphatidyl choline (PC); and   c) 0.1-20 wt % of the at least one oxygen containing organic solvent.   
     
     
         44 . The method of  claim 38 , wherein components a) and b) are present in a ratio of a:b of 40:60 to 70:30. 
     
     
         45 . The method of  claim 38 , wherein the pre-formulation comprises:
 a) 40-70 wt % of glycerol dioleate (GDO);   b) 30-60 wt % of soy PC;   c) 0.1-20 wt % of ethanol; and   d) 0.1-10 wt % of the at least one halide salt of at least one somatostatin analogue selected from lanreotide and vapreotide;   wherein the halide salt is a chloride or bromide ion,   wherein components a) and b) are present in a ratio of a:b of 40:60 to 70:30.   
     
     
         46 . The method of  claim 45 , wherein the pre-formulation comprises:
 a) 43-60 wt % of glycerol dioleate (GDO);   b) 35-55 wt % of soy PC; and   c) 0.1-10 wt % of ethanol,   wherein components a) and b) are present in a ratio of a:b of 45:55 to 60:40.   
     
     
         47 . The method of  claim 46 , wherein the pre-formulation comprises:
 a) 45-55 wt % of glycerol dioleate (GDO);   b) 40-50 wt % of soy PC; and   c) 2-8 wt % of ethanol;   wherein components a) and b) are present in a ratio of a:b of 48:52 to 55:45.   
     
     
         48 . The method of  claim 38 , wherein the method of treatment is a method for the treatment of at least one condition selected from acromegaly, cancers, carcinomas, melanomas, tumours expressing at least one somatostatin receptor, somatostatin receptor-2-positive tumours, somatostatin receptor-5-positive tumours, prostate cancers, gastro-entero-pancreatic neuroendocrine tumours, carcinoid tumours, insulinomas, gastrinomas, vasoactive intestinal peptide—producing-tumours and glucagonomas, elevated growth hormone, elevated insulin-like growth factor I, varicial bleeding, chemotherapy induced gastro intestinal problems, lymphorrhea, diabetic retinopathy, thyroid eye disease, obesity, pancreatitis, and related conditions. 
     
     
         49 . The method of  claim 38 , comprising administration by i.m., s.c. or preferably deep s.c. injection. 
     
     
         50 . The method of  claim 38 , comprising administration by a pre-filled administration device. 
     
     
         51 . The method of  claim 38 , comprising a single administration every 20 to 180 days.