Amphiphilic oligomers

Abstract

A therapeutic formulation comprising a microemulsion of a therapeutic agent in free and/or conjugatively coupled form, wherein the microemulsion comprises a water-in-oil (w/o) microemulsion including a lipophilic phase and a hydrophilic phase, and has a hydrophilic and lipophilic balance (HLB) value between 3 and 7, wherein the therapeutic agent may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, papain, Ara-A (Arabinofuranosyladenine), Acylguanosine, Nordeoxyguanosine, Azidothymidine, Didesoxyadenosine, Dideoxycytidine, Dideoxyinosine Floxuridine, 6-Mercaptopurine, Doxorubicin, Daunorubicin, or I-darubicin, Erythromycin, Vancomycin, oleandomycin, Ampicillin; Quinidine and Heparin. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. The microemulsion compositions of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications.

What is claimed is:  
     
         1 . An oligomer having a formula:  
       A-(CH 2 ) m -(OC 2 H 4 ) n —XR  
       wherein 
 A is —C(O)ONH 2 , —C(O)OH, or —NH—C(O)OH;  
 m is 2 to 15;  
 n is 5 to 120;  
 X is —O—, —S—, —C(O)O—, or —C(O)NH—; and  
 R is an alkyl.  
 
     
     
         2 . The oligomer of  claim 1 , wherein A is —C(O)ONH 2 .  
     
     
         3 . The oligomer of  claim 1 , wherein A is —C(O)OH.  
     
     
         4 . The oligomer of  claim 1 , wherein A is —NH—C(O)OH.  
     
     
         5 . The oligomer of  claim 1 , wherein A is —C(O)O—.  
     
     
         6 . The oligomer of  claim 1 , wherein A is —NH—C(O)—.  
     
     
         7 . The oligomer of  claim 1 , wherein X is O.  
     
     
         8 . The oligomer of  claim 1 , wherein R is methyl.  
     
     
         9 . A method of modifying the pharmaceutical characteristics of a drug comprising conjugating the drug to an oligomer of  claim 1 .  
     
     
         10 . A salt of an oligomer of  claim 1 .  
     
     
         11 . An activated form of the oligomer of  claim 1 .  
     
     
         12 . An N-hydroxy-succinimide ester of the oligomer of  claim 1 .  
     
     
         13 . A branched oligomer comprising the oligomer of  claim 1 .  
     
     
         14 . A protein covalently coupled to the oligomer of  claim 1 .  
     
     
         15 . An oligomer having a formula:  
       A-(OC 2 H 4 ) n —XR  
       wherein 
 A is —C(O)ONH 2 , —C(O)OH, or —NH—C(O)OH;  
 n is 5 to 120;  
 X is —O—, —S—, —C(O)O—, or —C(O)NH—; and  
 R is an alkyl.  
 
     
     
         16 . The oligomer of  claim 15 , wherein A is —C(O)ONH 2 .  
     
     
         17 . The oligomer of  claim 15 , wherein A is —C(O)OH.  
     
     
         18 . The oligomer of  claim 15 , wherein A is —NH—C(O)OH.  
     
     
         19 . The oligomer of  claim 15 , wherein X is O.  
     
     
         20 . The oligomer of  claim 15 , wherein R is methyl.  
     
     
         21 . A method of modifying the pharmaceutical characteristics of a drug comprising conjugating the drug to an oligomer of  claim 15 ,  
     
     
         22 . A salt of an oligomer of  claim 15 .  
     
     
         23 . An activated form of the oligomer of  claim 15 .  
     
     
         24 . An N-hydroxy-succinimide ester of the oligomer of  claim 15 .  
     
     
         25 . A branched oligomer comprising the oligomer of  claim 15 .  
     
     
         26 . A protein or peptide covalently coupled to the oligomer of  claim 15 .  
     
     
         27 . Methyl(ethyleneglycol) 7 -O-hexanoic acid.  
     
     
         28 . An N-hydroxy-succinimide ester of the methyl(ethyleneglycol) 7 -O-hexanoic acid of  claim 27 .  
     
     
         29 . A protein or peptide covalently coupled to the methyl(ethyleneglycol) 7 -O-hexanoic acid of  claim 27.