Biodegradable block copolymer drug delivery composition
Inventors
Roberge, Christophe • RECH, Anthony • CROS, Jean-Manuel • ABBASSI, Myriam • LÓPEZ-NORIEGA, Adolfo • PEBREL, Lea • Petit, Audrey • SERINDOUX, Juliette
Assignees
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Publication Number
US-11801217-B2
Publication Date
2023-10-31
Expiration Date
Abstract
The present invention provides a biodegradable drug delivery composition comprising: (i) a mixture of at least three different block copolymers, wherein each block copolymer is: (a) a biodegradable triblock copolymer having the formula: Av-Bw-Ax wherein A is a polyester and B is polyethylene glycol and v and x are the number of repeat units from 1 to 3,000 and w is the number of repeat units from 3 to 300 and v=x or v≠x; or (b) a biodegradable diblock copolymer having the formula: Cy-Az wherein A is a polyester and C is an end-capped polyethylene glycol and y and z are the number of repeat units with y=2 to 250 and z=1 to 3,000; and wherein the mixture comprises at least one (a) and at least one (b); and the weight ratio between (a) and (b) is 1:19 to 5:1; and (ii) at least one pharmaceutically active ingredient.
Core Innovation
The invention relates to an injectable biodegradable drug delivery composition comprising a mixture of at least three different block copolymers and at least one pharmaceutically active ingredient. The block copolymer mixture includes biodegradable triblock copolymers having the formula Av-Bw-Ax, where A is a polyester and B is polyethylene glycol, and biodegradable diblock copolymers having the formula Cy-Az, where A is a polyester and C is an end-capped polyethylene glycol. The triblock and diblock components are present with a weight ratio of the sum of the biodegradable triblock copolymers to the sum of the biodegradable diblock copolymers ranging from 1:19 to 5:1.
The composition is characterized by the ability to modulate the release kinetics of the pharmaceutically active ingredient from the biodegradable drug delivery composition. This modulation is carried out without adversely affecting injectability and/or viscosity before injection and/or depot robustness after injection, compared to a composition having a single biodegradable triblock of the copolymer of (a) and a single biodegradable diblock of the copolymer of (b). The core approach uses the mixture of multiple block copolymers, including both Av-Bw-Ax triblock copolymers and Cy-Az diblock copolymers.
The biodegradable polyester and PEG-based components are described with polymer identity options, including polymer A polyester identities such as PLA, PLGA, PCL, PGA, PEA, and PHA, and PEG/PEG end-cap types such as methoxy-PEG. The disclosed framework includes ranges for composition parameters, including block copolymer loading and pharmaceutically active ingredient loading ranges, and specifies that release kinetics profiles can be modulated in a way that reduces burst and provides flattened (pseudo-zero order) release behavior while maintaining physical performance. The document further describes characterization contexts focused on injectability and viscosity, and depot robustness after injection.
Claims Coverage
Independent claim clm-00001 defines a composition with a mixed set of biodegradable triblock (Av-Bw-Ax) and diblock (Cy-Az) copolymers together with at least one pharmaceutically active ingredient, and requires release-kinetics modulation without adverse effects on injectability and/or viscosity before injection and/or depot robustness after injection. The dependent claims listed refine the independent claim by specifying active-ingredient selection, quantitative composition ranges, and additional constraints, and include a method for modulating release kinetics by administering the composition.
Mixed biodegradable triblock/diblock block copolymer injectable composition
An injectable biodegradable drug delivery composition comprising a mixture of at least three different block copolymers, including biodegradable triblock copolymers having formula Av-Bw-Ax and biodegradable diblock copolymers having formula Cy-Az, wherein each polyester block is A and polyethylene glycol/PEG appears as B and/or end-capped C, and wherein the weight ratio of the sum of biodegradable triblock copolymers of (a) to the sum of biodegradable diblock copolymers of (b) is 1:19 to 5:1.
Release kinetics modulation without harming injectability/viscosity and depot robustness
The composition further comprises at least one pharmaceutically active ingredient, and the release kinetics of said at least one active ingredient from the composition can be modulated without adversely affecting injectability and/or viscosity before injection and/or depot robustness after injection, compared to a composition having a single biodegradable triblock of the copolymer of (a) and a single biodegradable diblock of the copolymer of (b).
Active ingredient loading range
The composition includes at least one pharmaceutically active ingredient in an amount of 0.05% to 60% (w/w %) of the total composition.
Block copolymer mixture loading range
The composition contains a mixture of at least three different block copolymers at 2% to 60% (w/w %) of the total composition.
Selected pharmaceutically active ingredients
The at least one pharmaceutically active ingredient is selected from risperidone, bupivacaine, ivermectin, octreotide, meloxicam, or combinations thereof.
Low polymer solubility constraint
The block copolymers have less than 5% solubility in an aqueous solution.
Administration-based release-kinetics modulation method
A method of modulating the kinetics of release of at least one active ingredient by administering the injectable biodegradable drug delivery composition to a subject, where release is modulated without adversely affecting injectability and/or viscosity before injection and/or depot robustness after injection.
Overall, the claim set covers an injectable biodegradable drug delivery composition using a mixed set of biodegradable polyester-PEG triblock and biodegradable polyester-PEG end-capped diblock copolymers at a defined triblock:diblock weight ratio, together with an active ingredient whose release kinetics can be modulated without adverse effects on injectability/viscosity pre-injection and depot robustness post-injection. Dependent claims further narrow the composition by specifying active-ingredient options, quantitative polymer and active-ingredient loading ranges, a polymer solubility constraint, and an administration-based method for release-kinetics modulation.
Stated Advantages
Release kinetics of the active ingredient can be modulated without adversely affecting injectability and/or viscosity before injection.
Release kinetics of the active ingredient can be modulated without adversely affecting depot robustness after injection.
Modulation of release kinetics is achieved compared to a composition having a single biodegradable triblock and a single biodegradable diblock.
Documented Applications
Injectable biodegradable drug delivery, where release kinetics of at least one active ingredient are modulated by administering the composition to a subject.
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