Microspheres useful for therapeutic vascular embolization
Inventors
Reb, Philippe • Pierre, Marion • De Gioannis, Barbara • Krom, James
Assignees
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Publication Number
US-10022469-B2
Publication Date
2018-07-17
Expiration Date
Abstract
Provided herein, for example, are microspheres comprising a gelatin or gelatin substitute and a copolymer of a N-tris-hydroxymethyl methylacrylamide monomer unit, a diethylaminoethylacrylamide monomer unit and a N,N-methylene-bis-acrylamide monomer unit. Also provided are methods of producing microspheres comprising a gelatin or gelatin substitute and a copolymer of a N-tris-hydroxymethyl methylacrylamide monomer unit, a diethylaminoethylacrylamide monomer unit and a N,N-methylene-bis-acrylamide monomer unit. Further provided herein, for example, are compositions comprising the microspheres and methods of using the microspheres and compositions thereof.
Core Innovation
The invention discloses gelatin-containing polymer or copolymer microspheres and methods for their production using an aqueous monomer solution and a liquid organic phase. Disclosed monomers include trisacryl, DEAE acrylamide, and MBA, with optional gelatin crosslinking and ultrasonication. The feed configurations include feed equipment disposed in the organic phase, a feed system with spaced fingers extending from a cross-member, and feed ring equipment.
The methods utilize ultra-pure monomers associated with improved polymerization efficiency, product consistency, yield, and microsphere size uniformity. Ultrasonication is described to reduce sticking microspheres without causing observed breakage. Because the background section is omitted in the partial content, the underlying problem is not explicitly described in patent. The resulting microspheres are intended for vascular embolization and managing angiogenesis-dependent diseases.
Claims Coverage
The patent claims disclose three independent claims representing three inventive features for producing polymer or copolymer microspheres distinguished by feed-system configuration.
Feed equipment disposed in the liquid organic phase
Claim 1 covers producing polymer or copolymer microspheres by passing an aqueous solution comprising one or more monomers through feed equipment disposed in a liquid organic phase, thereby injecting it into the phase before or while stirring. [procedural detail omitted for safety]
Feed system with spaced fingers
Claim 15 covers producing polymer or copolymer microspheres using a feed system comprising a longitudinal axis and a plurality of spaced fingers extending outward from a cross-member connected to the longitudinal axis, injecting the aqueous monomer solution into the liquid organic phase before or while stirring. [procedural detail omitted for safety]
Feed ring equipment
Claim 18 covers producing polymer or copolymer microspheres by passing an aqueous solution comprising one or more monomers through feed ring equipment and into a liquid organic phase before or while stirring. [procedural detail omitted for safety]
The independent claims cover microsphere production using feed equipment disposed in the liquid organic phase, a feed system with spaced fingers, or feed ring equipment to introduce an aqueous monomer solution into a liquid organic phase.
Stated Advantages
Ultra-pure monomers are stated to improve polymerization efficiency, yield, product consistency, and microsphere size uniformity.
Ultrasonication is stated to reduce sticking microspheres, with no observed microsphere breakage reported.
Documented Applications
The gelatin-containing microspheres are proposed for vascular embolization.
The microspheres are proposed for management of angiogenesis-dependent diseases.
Embolization applications for tumor treatment, including liver and prostate cancers, arteriovenous malformations, uterine fibroids, and benign prostatic hyperplasia (BPH), as well as imaging agents and microsphere kits.
Production of microspheres comprising a polymer or copolymer with one or more monomer units.
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