Compositions of a polyorthoester and an aprotic solvent
Inventors
Ottoboni, Thomas B. • Girotti, Lee Ann Lynn
Assignees
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Publication Number
US-10398686-B2
Publication Date
2019-09-03
Expiration Date
Abstract
Delivery systems and compositions comprised of a biodegradable polyorthoester polymer, an aprotic solvent, and a drug are described. The solvent is selected to modulate release of drug from the composition, where, in some embodiments, the solvent is rapidly released after administration and provides a corresponding rapid rate of drug release. Alternatively, in other embodiments, the solvent is slowly released from the composition after its administration, and provides a correspondingly slow rate of drug release.
Core Innovation
The invention is a biodegradable drug delivery system that includes a polyorthoester and dimethyl sulfoxide in which the polyorthoester is miscible to form a single phase, and bupivacaine dispersed or solubilized in the single phase. The polyorthoester is a polyorthoester of Formula III with defined structural and compositional parameters, including A as R1 or R3, R* as C1-4 alkyl, and n ranging from 5 to 1000.
The description further constrains the structural subunits, including p and q values, x as an integer of 0-10, R5 as H or methyl, and a fraction of A units of formula R1 between 0 and 25 mole percent. The delivery system uses solvent selection and solvent miscibility to form a miscible, single-phase composition, with release behavior driven by solvent release/interaction and later polymer erosion.
The system is described with physical constraints including viscosity below about 10,000 cP at 37°C. The described release behavior ranges from about 1 day to about 8 weeks, and the system is illustrated with therapeutically active agents including granisetron and local anesthetics such as ropivacaine and bupivacaine.
Claims Coverage
The independent claim coverage centers on a DMSO-miscible polyorthoester single-phase delivery system containing bupivacaine. The independent claim includes two inventive features driven by the single-phase miscibility requirement and the Formula III-defined polyorthoester structural and compositional constraints.
Single-phase DMSO-miscible polyorthoester formulation
A delivery system comprising a polyorthoester; dimethyl sulfoxide in which the polyorthoester is miscible to form a single phase; and bupivacaine dispersed or solubilized in the single phase.
Formula III-defined polyorthoester parameters
The polyorthoester is a polyorthoester of Formula III, where A is R1 or R3, R* is C1-4 alkyl, n ranges from 5 to 1000, p and q are integers that vary from between about 1 to 20, x is an integer of 0-10, R5 is H or methyl, and the fraction of A units that are of formula R1 is between 0 and 25 mole percent.
The claim coverage is anchored on the combination of DMSO miscibility to form a single phase with a Formula III polyorthoester having specified structural and compositional constraints, together with bupivacaine dispersed or solubilized in that single phase.
Stated Advantages
Biodegradable drug delivery system.
Higher mole percentages of α-hydroxy acid containing subunits are described as increasing bioerodibility.
Documented Applications
A delivery system for bupivacaine.
The system is illustrated using therapeutically active agents including granisetron and local anesthetics such as ropivacaine and bupivacaine.
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