Process for preparing biodegradable polymers of high molecular weight
Inventors
KOFTIS, V. THEOCHARIS • Neokosmidis, Efstratios • KARIDI, KONSTANTINA • VARVOGLI, ANASTASIA-AIKATERINI
Assignees
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Publication Number
US-11046810-B2
Publication Date
2021-06-29
Expiration Date
Abstract
A novel method for the preparation of biodegradable polymers is disclosed. The method produces polymers of high molecular weight and particularly allows for stirring throughout the polymerization reaction.
Core Innovation
The invention relates to the polymerization of lactide and glycolide using ring-opening polymerization under stirring in the presence of an organic solvent and a metal catalyst, optionally with a co-initiator. The polymerization is performed in a closed sealed reactor system that does not allow air or other gas exchange between an inner and an outer part of the reactor once it is sealed. This arrangement supports solvent-based polymerization with stirring and aims at improved thermal control and mixing.
The disclosed process emphasizes solvent solution polymerization in an organic solvent to enable stirring and improved heat transfer and thermal control. By performing the polymerization in a closed sealed reactor system while maintaining stirring, the invention addresses in homogeneity and hot spots that can arise in other polymerization setups. The process is used to obtain polymers with controlled copolymer composition and molecular weight, including higher molecular weight polymers in shorter times compared to certain prior approaches described in the document.
The invention further specifies catalyst and co-initiator options for the lactide/glycolide polymerization. Metal catalysts include Sn, Zn and Al, with tin catalysts including Sn(Oct)2 highlighted, and co-initiators include mono-, di- and polyalcohols such as methanol and other alcohols. The resulting polymer properties are characterized using methods including GPC for Mn, Mw and polydispersity index, and intrinsic viscosity, and the document also describes producing drug delivery systems, including surgical sutures and implants, using polymers produced by the disclosed method.
Claims Coverage
The independent claim covers a lactide/glycolide polymerization method defined by stirring, organic solvent, a metal catalyst, optional co-initiator, and a closed sealed reactor system that prevents air or other gas exchange after sealing. Dependent claims further specify catalyst and solvent classes, a solvent-to-monomer ratio constraint, a molecular weight minimum, and application to a drug delivery system with an active pharmaceutical ingredient.
Stirred solvent-based lactide/glycolide polymerization in a closed sealed reactor system
Perform polymerization of lactide and glycolide under stirring in the presence of an organic solvent and a metal catalyst, optionally a co-initiator, where the polymerization is performed in a closed sealed reactor system that does not allow air or other gas exchange between an inner and an outer part once sealed.
Metal catalyst selected from tin, zinc, or aluminum
Perform the method using a metal catalyst selected from tin, zinc, or aluminum.
Organic solvent selected from specified solvent classes
Perform the method using a solvent chosen from aliphatic and aromatic hydrocarbons, halogenated aliphatic and aromatic hydrocarbons, and aliphatic and aromatic ethers.
Solvent-to-monomer mass ratio of at least 1 mL per gram
Perform the method using a solvent-to-total-monomer mass ratio of at least 1 mL per gram.
Molecular weight minimum for the resulting polymer measured by GPC
Obtain a polymer whose molecular weight (Mw) is at least 5×10^4 Da, as measured by GPC.
Drug delivery system containing an active pharmaceutical ingredient
Produce a drug delivery system by producing a polymer that contains an active pharmaceutical ingredient, using the polymerization method defined in the stirred solvent-based closed sealed reactor method.
Across the independent claim and its refinements, the core claimed protection centers on stirred lactide/glycolide ring-opening polymerization in a closed sealed reactor system without air or other gas exchange, using an organic solvent and a metal catalyst with optional co-initiator. Dependent refinements focus on catalyst and solvent selection, a solvent-to-monomer ratio constraint, a molecular weight minimum measured by GPC, and application to producing a drug delivery system with an active pharmaceutical ingredient.
Stated Advantages
Improved heat transfer and thermal control and mixing by enabling solvent-based polymerization with stirring.
Avoids in homogeneity and hot spots associated with polymerization setups that do not support effective stirring.
Enables higher molecular weight polymers in shorter times compared to certain prior solvent versus bulk approaches described in the document.
Documented Applications
Surgical sutures produced using polymers produced by the disclosed lactide/glycolide polymerization method.
Implants produced using polymers produced by the disclosed lactide/glycolide polymerization method.
Drug delivery systems, including drug delivery systems made from polymers produced by the disclosed polymerization method, including polymers containing an active pharmaceutical ingredient.
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