Liquid triblock copolymer
A bioresorbable triblock copolymer according to Formula 1 R-B-A-B-R (1) wherein A is a hydrophilic polymer, B a hydrophobic polymer and R are end-groups, wherein R is H or a C1-C30 organic moiety and wherein the copolymer is fluid in a temperature range of 0° C. to 37° C. A pharmaceutical composition including the triblock copolymer and at least one therapeutically active agent. The copolymer and pharmaceutical composition can be used for forming a depot in a human or animal body or as medical device.
1. A bioresorbable triblock copolymer according to Formula 1
R-B-A-B-R (1)
wherein A is a hydrophilic polymer, B a hydrophobic polymer and R are end-groups, wherein R is a C1-C30 organic moiety, wherein A is polyethyleneglycol (PEG) having a molecular weight between 180 and 700 g/mol, wherein a number average molecular weight (Mn) of the triblock copolymer is within the range of 700-2500 g/moL, and wherein the copolymer is fluid in a temperature range of 0° C. to 37° C.
2. The copolymer according to claim 1 , wherein the copolymer has a viscosity determined at 20° C. having a value below 30 Pa·s, as determined by shear rheology.
3. The copolymer according to claim 1 , wherein the copolymer has a Tg (midpoint) below −20° C.
4. The copolymer according to claim 1 , wherein the copolymer has a Tm (midpoint) below 20° C.
5. The copolymer according to claim 1 , wherein each B block is a combination of ε-caprolactone with anyone of lactide, glycolide, δ-valerolactone, p-dioxanone or trimethylenecarbonate; or a combination of δ-valerolactone with anyone of lactide, glycolide, p-dioxanone or trimethylenecarbonate; or a combination of p-dioxanone with lactide, glycolide or trimethylenecarbonate; or a combination of trimethylenecarbonate with lactide or glycolide.
6. The copolymer according to claim 1 , wherein R is chosen from fatty acid residues, ether residue or urethane residue.
7. The copolymer according to claim 1 , wherein R is chosen from an acetyl group, a propionyl group, a hexanoyl group, a nonanoyl group, a dodecanoyl group, pentadecanoyl group, a stearoyl group or a benzoyl group, and wherein R is linear, branched or cyclic and R can be optionally substituted with heteroatoms.
8. The copolymer according to claim 1 , wherein the copolymer has a viscosity determined at 20° C. having a value below 20 Pa·s as determined by shear rheology, wherein the copolymer has a Tg (midpoint) below −30° C., wherein the copolymer has a Tm (midpoint) below 10° C., and wherein the copolymer has a number average molecular weight (Mn) between 600 and 3,000 g/mol.
9. The copolymer according to claim 8 , wherein the copolymer has a viscosity determined at 20° C. having a value below 10 Pa·s as determined by shear rheology, wherein the copolymer has a Tg (midpoint) below −40° C., wherein the copolymer has a Tm (midpoint) below 0° C., and wherein the copolymer has a number average molecular weight (Mn) between 700 and 2500 g/mol.
10. The copolymer according to claim 9 , wherein each B block is a combination of ε-caprolactone with anyone of lactide, glycolide, δ-valerolactone, p-dioxanone or trimethylenecarbonate; or a combination of δ-valerolactone with anyone of lactide, glycolide, p-dioxanone or trimethylenecarbonate; or a combination of p-dioxanone with lactide, glycolide or trimethylenecarbonate; or a combination of trimethylenecarbonate with lactide or glycolide, and wherein R is chosen from fatty acid residues, ether residue or urethane residue.
11. A process for preparing a pharmaceutical composition, comprising the steps of providing the triblock copolymer according to claim 1 , providing at least one therapeutically active agent and mixing the copolymer with the therapeutically active agent.
12. A pharmaceutical composition comprising one or more triblock copolymers according to claim 1 , and at least one therapeutically active agent.
13. The pharmaceutical composition according to claim 12 , wherein the composition comprises at least 50 wt % of the triblock copolymers, relative to the total weight of the pharmaceutical composition.
14. The pharmaceutical composition according to claim 12 , wherein the composition has a dynamic viscosity below or equal to 30 Pa·s at 20° C., as determined by shear rheology.
15. The pharmaceutical composition according to claim 14 , wherein the composition has a dynamic viscosity below 20 Pa·s as determined by shear rheology.
16. The pharmaceutical composition according to claim 14 , wherein the composition has a dynamic viscosity below 5 Pa·s as determined by shear rheology.
17. A pharmaceutical composition comprising one or more triblock copolymers according to claim 9 , and at least one therapeutically active agent.