Pharmaceutical composition

Abstract

The present invention relates to pharmaceutical compositions having improved stability.

1 - 37 . (canceled) 
     
     
         38 . A liquid composition, comprising:
 a pharmaceutically active compound selected from:
 a compound having the formula (I): 
   
       
         
           
           
               
               
           
         
         
           wherein: n is selected from 0, 1 and 2; p is selected from 0, 1, 2, 3, 4, 5 and 6; R 1  is selected from aryl optionally substituted with at least one OH, F, Cl, Br, alkyl or O-alkyl substituent; R 2  is selected from R 4 , H, alkyl, cycloalkyl, aryl and 5- and 6-membered heteroaromatic ring systems; R 3  is selected from H and a covalent bond to R 2 , when R 2  is R 4 , to form a ring structure; R 4  is C 1-6  alkylene moiety substituted with at least one O-alkyl, S-alkyl or OH substituent; W and X are each independently selected from CH 2  and S, but may not both be CH 2 ; alkyl is selected from C 1-6  straight and C 4-8  branched chain alkyl and optionally has at least one hydroxyl substituent; aryl is selected from phenyl and mono- or poly-substituted phenyl; with the proviso that when R 2  is H, p is 1, R 3  is H, n is 1 and W and X are both S, R 1  is not 4-hydroxyphenyl, or a solvate or pharmaceutically acceptable salt thereof; and 
         
         a compound having structure of formula (II): 
       
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof;
 and an anti-oxidant; 
 wherein the pH of the composition is from 5.0 to 6.0. 
 
     
     
         39 . The composition of  claim 38 , wherein the pH of the composition is from 5.1 to 6. 
     
     
         40 . The composition of  claim 38 , wherein the pH of the composition is from 5.2 to 5.65. 
     
     
         41 . The composition of  claim 38 , wherein the pH of the composition is from 5.26 to 5.8. 
     
     
         42 . The composition of  claim 38 , further comprising a buffering agent. 
     
     
         43 . The composition of  claim 38 , wherein the anti-oxidant is methionine, EDTA, or a combination of methionine and EDTA. 
     
     
         44 . The composition of  claim 38 , further comprising an isotonicity agent. 
     
     
         45 . The composition of  claim 38 , wherein the pharmaceutically active compound is the compound of formula (II): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         46 . The composition of  claim 45 , wherein the pH of the composition is from 5.0 to 5.9. 
     
     
         47 . The composition of  claim 45 , wherein the pH of the composition is from 5.1 to 5.9. 
     
     
         48 . The composition of  claim 45 , wherein the pH of the composition is from 5.2 to 5.8. 
     
     
         49 . The composition of  claim 45 , further comprising a buffer. 
     
     
         50 . The composition of  claim 49 , wherein the buffer is a citrate/phosphate buffer. 
     
     
         51 . The composition of  claim 45 , wherein the concentration of the compound of formula (II) in the liquid composition is from 0.01 to 4 mg/mL. 
     
     
         52 . The composition of  claim 45 , wherein the concentration of the compound of formula (II) in the liquid composition is from 0.05 to 2 mg/mL. 
     
     
         53 . The composition of  claim 45 , wherein the concentration of the compound of formula (II) in the liquid composition is from 0.1 to 1.4 mg/mL. 
     
     
         54 . The composition of  claim 45 , wherein the concentration of the compound of formula (II) in the liquid composition is from 0.2 to 0.7 mg/mL. 
     
     
         55 . The composition of  claim 45 , further comprising an anti-oxidant. 
     
     
         56 . The composition of  claim 45 , further comprising an isotonicity agent. 
     
     
         57 . The composition of  claim 56 , wherein the isotonicity agent is NaCl. 
     
     
         58 . A method of treatment of compromised lactation conditions, labour induction impairment, uterine atony conditions, excessive bleeding, inflammation, pain, abdominal pain, back pain, male and female sexual dysfunction, irritable bowel syndrome (IBS), constipation, gastrointestinal obstruction, autism, stress, anxiety, depression, anxiety disorder, surgical blood loss, post-partum haemorrhage, wound healing, infection, mastitis, placenta delivery impairment, or osteoporosis, or a method for the diagnosis of cancer and placental insufficiency, comprising administration to a patient in need thereof the composition of  claim 38 . 
     
     
         59 . The method of  claim 58 , wherein the method is for the treatment of uterine atony conditions or excessive bleeding. 
     
     
         60 . The method of  claim 59 , wherein the method is for the treatment of uterine atony conditions following vaginal delivery of the infant or delivery of the infant by Caesarean section, or in a patient who is at risk of developing post-partum haemorrhage. 
     
     
         61 . The method of  claim 59 , wherein the method is for the treatment of excessive bleeding following vaginal delivery. 
     
     
         62 . A kit, comprising:
 a liquid pharmaceutical composition of  claim 38 ; and   a container for the composition.   
     
     
         63 . The kit of  claim 62 , wherein the pharmaceutically active compound is the compound of formula (II).