Multi-arm polyethylene glycol derivatives, conjugates and gels of pharmaceuticals and the same

Abstract

A multi-arm polyethylene glycol (I) having different kinds of reactive groups and the uses thereof are disclosed, which is formed by polymerizing ethylene oxide with oligo-pentaerythritol as an initiator, wherein, PEG is same or different and is —(CH2CH2O)m—, the average value of m is an integer of 2-250; l is an integer of 1 or more. The method for producing the multi-arm polyethylene glycol having different kinds of reactive groups, the multi-arm polyethylene glycol active derivatives comprising linking groups X attached to PEG and terminal reactive groups F attached to X, the gels formed by the multi-arm polyethylene glycol active derivatives, the drug conjugates formed by the multi-arm polyethylene glycol active derivatives and drug molecules, and the uses thereof in preparing drugs are also disclosed.

1 . A multi-arm poly(ethylene glycol) derivative selected from the group consisting of:
 a multi-arm poly(ethylene glycol)amino-single-acetic acid of formula V:   
       
         
           
           
               
               
           
         
         a multi-arm poly(ethylene glycol)amino-multi-acetic acid of formula VA: 
       
       
         
           
           
               
               
           
         
         a multi-arm poly(ethylene glycol)maleimide-single-N-hydroxysuccinimidyl ester of formula VI: 
       
       
         
           
           
               
               
           
         
         a multi-arm poly(ethylene glycol)maleimide-multi-N-hydroxysuccinimidyl ester of formula VIA: 
       
       
         
           
           
               
               
           
         
         a multi-arm poly(ethylene glycol)acrylate-single-N-hydroxysuccinimidyl ester of formula VII: 
       
       
         
           
           
               
               
           
         
       
       and
 a multi-arm poly(ethylene glycol)acrylate-multi-N-hydroxysuccinimidyl ester of formula VIIA: 
 
       
         
           
           
               
               
           
         
         wherein l is 1, 2 or 3. 
       
     
     
         2 . The multi-arm poly(ethylene glycol) derivative of  claim 1 , wherein said multi-arm poly(ethylene glycol) has a molecular weight of 400-80,000 daltons. 
     
     
         3 . The multi-arm poly(ethylene glycol) derivative of  claim 2 , wherein said multi-arm poly(ethylene glycol) has a molecular weight of 1,000-20,000 daltons. 
     
     
         4 . A conjugate formed from the active derivative of the multi-arm poly(ethylene glycol) of  claim 3  and a pharmaceutical molecule. 
     
     
         5 . A conjugate formed from the active derivative of the multi-arm poly(ethylene glycol) of  claim 1  and a pharmaceutical molecule. 
     
     
         6 . The conjugate of  claim 5 , wherein said pharmaceutical molecule is selected from the group consisting of proteins, enzymes, saccharides, organic acids, flavonoids, quinones, terpenoids, benzene phenols, steroidal, glycosides, alkaloids, and combinations thereof. 
     
     
         7 . The conjugate of  claim 6 , wherein said organic acids are amino acids. 
     
     
         8 . The conjugate of  claim 6 , wherein said glycosides are nucleosides. 
     
     
         9 . The conjugate of  claim 6 , wherein said pharmaceutical molecule is Irrinitecan. 
     
     
         10 . A gel, comprising an active derivative of the multi-arm poly(ethylene glycol) according to  claim 1 .