Biodegradable block copolymeric compositions for drug delivery
View Patent ↗An improved drug delivery composition and method of use is disclosed. The composition comprises one or more biodegradable block copolymer drug carriers; and a reconstitution enhancing and enabling agent comprising polyethylene glycol (PEG), a PEG derivative or a mixture of PEG and a PEG derivative. The composition can be administered as is or after being be dissolved or rapidly reconstituted in an aqueous vehicle to afford a homogeneous solution or uniform colloidal systems.
1. A composition comprising:
1) one or more biodegradable block copolymer drug carriers comprising A-B, A-B-A or B-A-B block copolymers having a total weight average molecular weight of 2400 to 4999 Daltons, wherein the A block is a biodegradable polyester or poly(ortho ester) and the B block is polyethylene glycol(PEG), and the weight percentage of the A block is between 50.1% to 65% and the weight percentage of the B block is between 35% to 49.9%, wherein said block copolymer, when formed as an aqueous polymer solution, remains a free flowing liquid upon parenteral administration; and
2) a polyethylene glycol(PEG), a PEG derivative, or a mixtures of PEG and a PEG derivative, said PEG or PEG derivative having a molecular weight of 150 to 1100 Daltons; and wherein at least one of the biodegradable block copolymeric drug carriers is soluble in an aqueous solution and miscible with the PEG, PEG derivatives, or mixtures thereof, and wherein the weight ratio of the biodegradable block copolymeric drug carrier and the PEG, PEG derivative or mixtures thereof is within the range of 5:1 to 1:99 and said composition can be reconstituted in water or an aqueous solution to form a homogeneous solution or an uniform colloidal system within 0.01 minutes to 180 minutes.
2. The composition according to claim 1 wherein the PEG derivative is an ester derivatized PEG wherein the PEG is derivatized from D,L-lactide, D-lactide, L-lactide, D,L-lactic acid, D-lactic acid, L-lactic acid, glycolide, glycolic acid, ε-caprolactone, 1,4-dioxan-2-one, ε-hydroxy hexanoic acid, γ-butyrolactone, γ-hydroxy butyric acid, δ-valerolactone, δ-hydroxy valeric acid, hydroxybutyric acids, malic acid, or mixtures thereof.
3. The composition according to claim 1 wherein the PEG derivative is an ortho ester derivatized PEG.
4. The composition according to claim 1 wherein the PEG derivative is represented by R 1 —O—O—(CH 2 —CH 2 —O) n —CO—R 2 or R 1 —O—(CH 2 —CH 2 —O) n —R 2 wherein R 1 and R 2 are independently H or C 1 to C 10 alkyl and n is an integer between 3 and 20.
5. The composition according to claim 1 further comprising a drug.
6. The composition according to claim 1 wherein the weight ratio of the biodegradable block copolymeric drug carrier and the PEG, PEG derivative or mixtures thereof is within the range of 2:1 to 1:99.
7. The composition according to claim 1 wherein the weight ratio of the biodegradable block copolymeric drug carrier and the PEG, PEG derivative or mixtures thereof is within the range of 1:2 to 1:5.
8. A composition comprising:
1) one or more biodegradable block copolymer drug carriers comprising A-B, A-B-A or B-A-B block copolymers having a total weight average molecular weight of 2400 to 4999 Daltons, wherein the A block is a biodegradable polyester or poly(ortho ester) and the B block is polyethylene glycol(PEG), and the weight percentage of the A block is between 50.1 % to 65% and the weight percentage of the B block is between 35% to 49.9%, wherein said block copolymer, when formed as an aqueous polymer solution, remains a free flowing liquid upon parenteral administration; and
2) a polyethylene glycol(PEG), a PEG derivative, or a mixture of PEG and a PEG derivative, said PEG or PEG derivative having a molecular weight of 150 to 1100 Daltons; and wherein at least one of the biodegradable block copolymeric drug carriers is soluble in an aqueous solution and miscible with the PEG, PEG derivatives, or mixtures thereof, and wherein the weight ratio of the biodegradable block copolymeric drug carrier and the PEG, PEG derivative or mixtures thereof is within the range of 5:1 to 1:99 and said composition can be reconstituted in water or an aqueous solution to form a homogeneous solution or an uniform coloidal system within 0.01 minutes to 180 minutes,
3) water to form an aqueous solution of said composition.
9. The composition according to claim 8 wherein the PEG derivative is an ester derivatized PEG wherein the PEG is derivatized from D,L-lactide, D-lactide, L-lactide, D,L-lactic acid, D-lactic acid, L-lactic acid, glycolide, glycolic acid, ε-caprolactone, 1,4-dioxan-2-one, ε-hydroxy hexanoic acid, γ-butyrolactone, γ-hydroxy butyric acid, δ-valerolactone, δ-hydroxy valeric acid, hydroxybutyric acids, malic acid, and mixtures thereof.
10. The composition according to claim 8 wherein the PEG derivative is an ortho ester derivatized PEG.
11. The composition according to claim 8 wherein the PEG derivative is represented by R 1 —CO—O—(CH 2 —CH 2 —O) n CO—R 2 or R 1 —O—(CH 2 —CH 2 —O) n —R 2 -wherein R 1 and R 2 are independently H or C 1 to C 10 alkyl and n is an integer between 3 and 20.
12. The composition according to claim 8 wherein the weight ratio of the biodegradable block copolymeric drug carrier and the PEG, PEG derivative or mixtures thereof is within the range of 5:1 to 1:99.
13. The composition according to claim 8 wherein the weight ratio of the biodegradable block copolymeric drug carrier and the PEG, PEG derivative or mixtures thereof is within the range of 1:2 to 1:5.
14. The composition according to claim 8 further comprising a drug. carrier further comprises a biodegradable polyester or poly(ortho ester) oligomer having a weight average molecular weight of between 400 and 10,000 daltons.
15. A composition comprising:
1) one or more biodegradable block copolymer drug carriers comprising A-B, A-B-A or B-A-B block copolymers having a total weight average molecular weight of 2400 to 4999 Daltons, wherein the A block is a biodegradable polyester or poly(ortho ester) and the B block is polyethylene glycol(PEG), and the weight percentage of the A block is between 50.1% to 65% and the weight percentage of the B block is between 35% to 49.9%, wherein said block copolymer, when formed as an aqueous polymer solution, remains a free flowing liquid upon parenteral administration; and
2) a polyethylene glycol(PEG), a PEG derivative, or a mixture of PEG and a PEG derivative, said PEG or PEG derivative having a molecular weight of 150 to 1100 Daltons; and wherein at least one of the biodegradable block copolymeric drug carriers is soluble in an aqueous solution and miscible with the PEG, PEG derivatives, or mixtures thereof, and wherein the weight ratio of the biodegradable block copolymeric drug carrier and the PEG, PEG derivative or mixtures thereof is within the range of 1:2 to 1:5 and said composition can be reconstituted in water or an aqueous solution to form a homogeneous solution or an uniform colloidal system within 0.01 minutes to 180 minutes,
3) water to form an aqueous solution of said composition, and
4) a solubilized drug.
16. The composition according to claim 13 , wherein the solubilized drug is paclitaxel.