Semi-solid delivery systems
The invention provides semi-solid systems for delivering biologically active materials that include a polymer comprising 1) one or more units of formula Ia, IIa, or IIIa: (formula Ia, IIa, IIIa) and 2) one or more units comprising polycaprolactone; wherein R and R a have any of the values defined in the application.
1. A polymer comprising 1) one or more units of formula Ia:
and 2) one or more units of formula:
or formula:
wherein:
each R is independently (C 1 -C 10 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, aryl(C 1 -C 10 )alkyl, (C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-O—(C 3 -C 8 )cycloalkyl-O—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl-(C 3 -C 8 )cycloalkyl-(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, or (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl; and
each R a is independently hydrogen, (C 1 -C 10 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, aryl(C 1 -C 10 )alkyl, or (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl.
2. The polymer of claim 1 which comprises one or more units of formula Ib:
wherein each A independently comprises one or more units of formula:
3. The polymer of claim 2 which consists of repeating units of formula Ib.
4. The polymer of claim 2 which comprises one or more units of formula:
wherein R x is cyclohexyl or —CH 2 CH 2 —.
5. The polymer of claim 2 wherein each R is independently (C 1 -C 10 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, aryl(C 1 -C 10 )alkyl, or (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl; and each A is independently a homopolymer or copolymer comprising one or more units of formula V or formula IV.
6. The polymer of claim 1 which comprises one or more units of formula Ic:
wherein each A independently comprises one or more units of formula:
and each D is a unit comprising polyethylene oxide.
7. The polymer of claim 6 which consists of repeating units of formula Ic.
8. The polymer of claim 1 wherein R is (C 2 -C 10 )alkyl.
9. The polymer of claim 1 wherein R is ethyl, propyl, butyl, pentyl, or hexyl.
10. The polymer of claim 1 wherein R is (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl.
11. The polymer of claim 1 wherein R is:
12. The polymer of claim 1 wherein R is:
13. The polymer of claim 1 that comprises one or more units that comprise polyethylene oxide.
14. A polymer comprising 1) one or more units of formula Ia:
and 2) one or more units of the following formula:
wherein:
each R a is independently hydrogen, (C 1 -C 10 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, aryl(C 1 -C 10 )alkyl, or (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl;
R 1 is (C 1 -C 10 )alkyl, or (C 1 -C 10 )alkenyl containing 1 to 3 double bonds;
R 2 is hydrogen, (C 1 -C 10 )alkyl, or (C 1 -C 10 )alkenyl containing 1 to 3 double bonds, wherein the position at which R 2 is connected to R 1 can be at the α,β,γ,δ,ε,ζ carbon of R 1 ;
m is an integer from 1-20; and
n is an integer from 1-20.
15. A pharmaceutical composition comprising a polymer of claim 1 and a biologically active agent.
16. The composition of claim 15 wherein the biologically active agent is a small molecular drug, large molecular drug, protein, antibody, peptide, polysaccharide, or nucleic acid.
17. A polymer comprising 1) one or more units of formula Ia:
and 2) one or more units of the following formula:
wherein:
each R is independently (C 1 -C 10 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, aryl(C 1 -C 10 )alkyl, (C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-O—(C 3 -C 8 )cycloalkyl-O—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl—(C 3 -C 8 )cycloalkyl-(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, or (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl;
each R a is independently hydrogen, (C 1 -C 10 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl(C 3 -C 8 )cycloalkyl(C 1 -C 6 )alkyl, aryl(C 1 -C 10 )alkyl, or (C 1 -C 10 )alkyl-O—(C 1 -C 10 )alkyl;
n is an integer from 1-10; and
m is an integer from 1-10.