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US 6,524,606 B1Granted
Bioerodible polyorthoesters containing amine groups
AssigneeA.P. Pharma, Inc.
InventorsSteven Y. Ng, Jorge Heller
Life of this patent
Estimating the term…
Abstract
Bioerodible polyorthoesters useful as orthopedic implants or vehicles for the sustained delivery of pharmaceutical, cosmetic and agricultural agents contain amine functionalities and α-hydroxy acid-containing groups.
Claims32
A polyorthoester of formula I or formula II:
- where:
- R* is a C1-4 alkyl;
- R is a bond, —(CH2)a—, or —(CH2)b—O—(CH2)c—;
- where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5;
- n is an integer of at least 5;
- and
- A is a mixture of R1 and R4, and optionally R2 and or R3, where R1 is:
- where:
- p is an integer of 1 to 20;
- R5 is hydrogen or C1-4 alkyl;
- and
- R6 is:
- where:
- s is an integer of 0 to 30;
- t is an integer of 2 to 200;
- and
- R7is hydrogen or C1-4 alkyl;
- R2 is:
- R3 is:
- where:
- x is an integer of 0 to 30;
- y is an integer of 2 to 200;
- R8 is hydrogen or C1-4 alkyl;
- R9 and R10 are independently C1-12 alkylene;
- R11 is hydrogen or C1-6 alkyl and R12 is C1-6 alkyl;
- or R11 and R12 together are C3-10 alkylene;
- and
- R4 is the residual of a diol containing at least one amine functionality incorporated therein;
- in which at least 0.1 mol % of the A units are R1, and at least 0.1 mol % of the A units are R4.
26 more elements
A process of preparing a polyorthoester of formula I or formula II:
- where:
- R* is a C1-4 alkyl;
- R is a bond, —(CH2)a—, or —(CH2)b—O—(CH2)c—;
- where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5;
- n is an integer of at least 5;
- and
- A is a mixture of R1 and R4, and optionally R2 and/or R3, where R1 is:
- where:
- p is an integer of 1 to 20;
- R5 is hydrogen or C1-4 alkyl;
- and
- R6 is:
- where:
- s is an integer of 0 to 30;
- t is an integer of 2 to 200;
- and
- R7 is hydrogen or C1-4 alkyl;
- R2 is:
- R3 is:
- where:
- x is an integer of 0 to 30;
- y is an integer of 2 to 200;
- R8 is hydrogen or C1-4 alkyl;
- R9 and R10 are independently C1-12 alkylene;
- R11 is hydrogen or C1-6 alkyl and R12 is C1-6 alkyl;
- or R11 and R12 together are C3-10 alkylene;
- and
- R4 is the residual of a diol containing at least one amine functionality incorporated therein;
- in which at least 0.1 mol % of the A units are R1, and at least 0.1 mol % of the A units are R4, the process comprising reacting a diketene acetal of formula III or formula IV:
- where R is a bond, —(CH2)a—, or —(CH2)b—O—(CH2)c—;
- where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5;
- L is hydrogen or a C1-3 alkyl;
- with a diol of the formula HO—R1—OH and a diol of the formula HO—R4—OH, and optionally at least one diol of the formulae HO—R2—OH and HO—R3—OH.
30 more elements
A polyorthoester that is the product of a reaction between:
- (a) a diketene acetal of formula III or formula IV:
- where R is a bond, —(CH2)a—, or —(CH2)b—O—(CH2)c—;
- where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5;
- L is hydrogen or a C1-3 alkyl, and
- (b) a polyol or mixture of polyols in which at least 0.1 mole percent of the total polyol content is a diol of the formula HO—R1—OH, where
- R1 is:
- where:
- p is an integer of 1 to 20;
- R5 is hydrogen or C1-4 alkyl;
- and
- R6 is:
- where:
- s is an integer of 0 to 30;
- t is an integer of 2 to 200;
- and
- R7 is hydrogen or C1-4 alkyl;
- R11 is hydrogen or C1-6 alkyl and R12 is C1-6 alkyl;
- or R11 and R12 together are C3-10 alkylene;
- and at least 0.1 mole percent of the total polyol content is a diol of the formula HO—R4—OH, where R4 is the residual of a diol containing at least one amine functionality incorporated therein.
16 more elements
The polyorthoester of claim 18 where at least one of the polyols is a polyol having more than two hydroxy functional groups.
Dependencies are inferred from the claim text.