Amphiphilic triblock copolymers B-A-B, wherein A is a linear poly(ethylene glycol) block, having a number average molecular weight (Mn) of between 900 and 3000 Daltons, determined with size exclusion chromatography; wherein B are hydrophobic blocks with at least two cyclic monomers selected from the
Amphiphilic triblock copolymers B-A-B, wherein A is a linear poly(ethylene glycol) block, having a number average molecular weight (Mn) of between 900 and 3000 Daltons, determined with size exclusion chromatography; wherein B are hydrophobic blocks with at least two cyclic monomers selected from the group consisting of glycolide, lactide, 1,3-dioxan-2-one, 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, each B-block having a number average molecular weight (Mn) of between 400 and 2000 Daltons, determined with size exclusion chromatography; and wherein 25% to 100% of the polymer hydroxyl end-groups are covalently modified with at least one derivative of a C2-C20 fatty acid. The invention also relates to compositions with such polymers and the use thereof.
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1. A pharmaceutical composition, comprising: an amphiphilic triblock copolymer B-A-B, a medically accepted solvent and an therapeutically active agent, wherein A is a linear poly(ethylene glycol) block having a number average molecular weight (Mn) of between 500 and 3000 Daltons, determined with siz
1. A pharmaceutical composition, comprising: an amphiphilic triblock copolymer B-A-B, a medically accepted solvent and an therapeutically active agent, wherein A is a linear poly(ethylene glycol) block having a number average molecular weight (Mn) of between 500 and 3000 Daltons, determined with size exclusion chromatography; wherein B are hydrophobic blocks comprising at least two cyclic monomers of glycolide, lactide, ε-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclo-tetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one, 2,5-diketomorpholine, pivalolactone, ε-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one, β-propiolactone, γ-butyrolactone, δ-valerolactone, ε-decalactone, 3-methyl-1,4-dioxane-2,5-dione, 1,4-dioxane-2,5-dione, 2,5-diketo-morpholine, α,α-diethylpropiolactone, γ-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 6,6-dimethyl-dioxepan-2-one, 6,8-dioxabicycloctane-7-one, or 5,5-dimethyl-1,3-dioxan-2-one, each B-block having a number average molecular weight (Mn) of between 400 and 3000 Daltons, determined with size exclusion chromatography; and wherein 25% to 100% of the polymer hydroxyl end-groups are covalently modified with at least one acid chloride, anhydride or isocyanate derivative of a C2-C20 fatty acid, and wherein the B-blocks comprise monomer combinations comprising a) between 50 and 100 mol % 5,5-dimethyl-1,3-dioxan-2-one (also called 5,5-dimethyl trimethylene carbonate), b) glycolide and at least one monomer that is 1,3-dioxan-2-one, 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, or 1,5-dioxepan-2-one, c) lactide and at least one monomer that is 1,3-dioxan-2-one, 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, or 1,5-dioxepan-2-one, or d) 1,3-dioxan-2-one and at least one monomer that is 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, or 1,5-dioxepan-2-one. 2. The pharmaceutical composition according to claim 1, wherein a block ratio, which is defined as a ratio between a sum of the number average molecular weight of the B-blocks and the number average molecular weight of the A-block, ranges between 0.5 and 3. 3. The pharmaceutical composition according to claim 2, wherein the number average molecular weight (Mn) of the linear poly(ethylene glycol) block ranges between 900 and 3000 Daltons; wherein the number average molecular weight (Mn) of each B-block ranges between 400 and 2000 Daltons; wherein the fatty acids derivatives used to modify the polymer hydroxyl end-groups are derivatives of caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, myristoleic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linoleic acid, gamma-linoleic acid, stearidonic acid, rumenic acid, beta-calendic acid, eleostearic acid, puninic acid, parinaric acid, pinolenic acid, arachidic acid, eicosenoic acid, eicosadienoic acid, eicosatrienoic acid, dihomo-gamma-linolenic acid, mead acid, eicosatetraenoic acid, arachidonic acid, or eicosapentaenoic acid; and wherein at least 90% of the polymer hydroxyl end-groups are covalently modified with the at least one acid chloride, anhydride or isocyanate derivative of a C2-C20 fatty acid. 4. A pharmaceutical composition according to claim 3, wherein one of the cyclic monomers of the B-blocks is glycolide, lactide, ε-caprolactone or 1,3-dioxan-2-one. 5. A pharmaceutical composition, comprising: an amphiphilic triblock copolymer B-A-B, a medically accepted solvent and an therapeutically active agent, wherein A is a linear poly(ethylene glycol) block having a number average molecular weight (Mn) of between 500 and 3000 Daltons, determined with size exclusion chromatography; wherein B are hydrophobic blocks comprising at least two cyclic monomers of glycolide, lactide, ε-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclo-tetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one, 2,5-diketomorpholine, pivalolactone, ε-diethylpropionlactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one, β-propiolactone, γ-butyrolactone, δ-valerolactone, ε-decalactone, 3-methyl-1,4-dioxane-2,5-dione, 1,4-dioxane-2,5-dione, 2,5-diketo-morpholine, α,α-diethylpropiolactone, γ-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 6,6-dimethyl-dioxepan-2-one, 6,8-dioxabicycloctane-7-one or 5,5-dimethyl-1,3-dioxan-2-one, each B-block having a number average molecular weight (Mn) of between 400 and 3000 Daltons, determined with size exclusion chromatography; and wherein 25% to 100% of the polymer hydroxyl end-groups are covalently modified with at least one acid chloride, anhydride or isocyanate derivative of a C2-C20 fatty, acid and wherein the B-blocks comprise monomer combinations a) comprising ε-caprolactone and at least one monomer that is 1,3-dioxan-2-one, 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, or 1,5-dioxepan-2-one, b) consisting of between 50 and 100 mol % glycolide; and caprolactone as a second monomer, or c) having between 50 and 100 mol % trimethylene carbonate. 6. The pharmaceutical composition according to claim 5, wherein a block ratio, which is defined as a ratio between a sum of the number average molecular weight of the B-blocks and the number average molecular weight of the A-block, ranges between 0.5 and 3. 7. The pharmaceutical composition according to claim 6, wherein the number average molecular weight (Mn) of the linear poly(ethylene glycol) block ranges between 900 and 3000 Daltons and the number average molecular weight (Mn) of each B-block ranges between 400 and 2000 Daltons; wherein the fatty acids derivatives used to modify the polymer hydroxyl end-groups are derivatives of caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, myristoleic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linoleic acid, gamma-linoleic acid, stearidonic acid, rumenic acid, beta-calendic acid, eleostearic acid, puninic acid, parinaric acid, pinolenic acid, arachidic acid, eicosenoic acid, eicosadienoic acid, eicosatrienoic acid, dihomo-gamma-linolenic acid, mead acid, eicosatetraenoic acid, arachidonic acid or eicosapentaenoic acid; and wherein at least 90% of the polymer hydroxyl end-groups are covalently modified with the at least one acid chloride, anhydride or isocyanate derivative of a C2-C20 fatty acid. 8. The pharmaceutical composition according to claim 1, wherein the B-blocks comprise the monomer combinations comprising a) between 50 and 100 mol % 5,5-dimethyl-1,3-dioxan-2-one (also called 5,5-dimethyl trimethylene carbonate). 9. The pharmaceutical composition according to claim 1, wherein the B-blocks comprise the monomer combinations comprising the b) glycolide and at least one monomer that is 1,3-dioxan-2-one, 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, or 1,5-dioxepan-2-one. 10. The pharmaceutical composition according to claim 1, wherein the B-blocks comprise the monomer combinations comprising the c) lactide and at least one monomer that is 1,3-dioxan-2-one, 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, or 1,5-dioxepan-2-one. 11. The pharmaceutical composition according to claim 1, wherein the B-blocks comprise the monomer combinations comprising the d) 1,3-dioxan-2-one and at least one monomer that is 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, or 1,5-dioxepan-2-one. 12. The pharmaceutical composition according to claim 5, wherein the B-blocks comprise the monomer combinations a) comprising ε-caprolactone and at least one monomer that is 1,3-dioxan-2-one, 5,5-dimethyl-1,3-dioxan-2-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, or 1,5-dioxepan-2-one. 13. The pharmaceutical composition according to claim 5, wherein the B-blocks comprise the monomer combinations b) consisting of between 50 and 100 mol % glycolide; and caprolactone as a second monomer. 14. The pharmaceutical composition according to claim 5, wherein the B-blocks comprise the monomer combinations c) having between 50 and 100 mol % trimethylene carbonate.
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