Implantation material comprising biocompatible polymer
Inventors
Lee, Young Woo • Cho, Wan Jin • Jang, Ji Yeon
Assignees
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Publication Number
US-8822551-B2
Publication Date
2014-09-02
Expiration Date
Abstract
Disclosed herein is a hyaluronic acid epoxide derivative film comprises a polymer containing a hydroxyl (—OH) terminal group. The film is prepared by allowing an epoxy crosslinker to react with a mixture of hyaluronic acid and a polymer containing a hydroxyl (—OH) terminal group and has improved physical strength, in vivo stability, flexibility, adhesiveness to biological tissue, and biocompatibility.
Core Innovation
The invention relates to a hyaluronic acid epoxide derivative film in which a polymer containing a hydroxyl (—OH) terminal group is physically bonded to a crosslinked hyaluronic acid structure. The film is comprised of 50–90 wt% hyaluronic acid and 10–50 wt% of the polymer containing the hydroxyl (—OH) terminal group. The physical bonding to the crosslinked hyaluronic acid structure prevents shrinkage during film solidification and mitigates loss of physical strength during purification.
The crosslinked hyaluronic acid structure is formed by reacting 100 parts by weight of hyaluronic acid, hyaluronic acid salt, or a mixture thereof, with 5–25 parts by weight of an epoxide crosslinker under basic conditions. The derivative film has a crosslinking density of 1–100 mole%. The epoxide crosslinkers include specific diglycidyl ether epoxides, such as polyethylene glycol diglycidyl ether and other listed diglycidyl ethers.
The document further describes improving physical strength by post-purification precipitation in an organic solvent. Examples of organic solvents described for precipitation include DMSO, DMF, THF, acetone, and ethanol/methanol. The resulting film composition and crosslinking density are described in connection with characterization and comparative performance, including residual hydroxyl-terminal polymer evidence and mechanical property comparisons.
Claims Coverage
The independent claim covers a hyaluronic acid epoxide derivative film with physically bonded hydroxyl-terminal polymers, fixed composition ranges for hyaluronic acid and the hydroxyl-terminal polymer, crosslinking via specified epoxide crosslinkers under basic conditions, and a defined crosslinking density range. Dependent claims further refine counterion selection, crosslinker identity, a preparation precipitation solvent selection, and specified biomedical uses and optional additional functional components.
Physically bonded hydroxyl-terminal polymer to crosslinked hyaluronic acid
A hyaluronic acid epoxide derivative film wherein a polymer containing a hydroxyl (—OH) terminal group is physically bonded to a crosslinked hyaluronic acid structure.
Specified hyaluronic acid and hydroxyl-terminal polymer composition
The hyaluronic acid epoxide derivative film is comprised of 50–90 wt% of hyaluronic acid and 10–50 wt% of the polymer containing the hydroxyl (—OH) terminal group.
Crosslinking using hyaluronic acid with epoxide crosslinker under basic conditions
The crosslinked hyaluronic acid structure is formed by reacting 100 parts by weight of hyaluronic acid, hyaluronic acid salt or a mixture thereof, and 5–25 parts by weight of an epoxide crosslinker under basic conditions.
Defined crosslinking density range
The derivative film has a crosslinking density of 1–100 mole %.
Selection of hydroxyl-terminal polymers
The polymer containing the hydroxyl (—OH) terminal group is one or more selected from the group consisting of polyethylene oxide, polyvinyl alcohol, polypropylene oxide, a polyethylene oxide–polypropylene oxide copolymer, a polyethylene oxide–polylactic acid copolymer, a polyethylene oxide–polylactic glycolic acid copolymer, a polyethylene oxide–polycaprolactone copolymer, polybutylene oxide, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene stearates.
Overall, the claim set focuses on a hyaluronic acid epoxide derivative film where a hydroxyl-terminal polymer is physically bonded to a crosslinked hyaluronic acid network, with defined composition, crosslinking formed under basic conditions using an epoxide crosslinker within defined weight ratios, and a crosslinking density of 1–100 mole%, further refined by specific polymer and crosslinker selections and preparation precipitation solvent options.
Stated Advantages
Improved physical strength.
Prevention of shrinkage during film solidification.
Mitigation of loss of physical strength during purification.
Improved physical strength after post-purification precipitation in an organic solvent.
Improved in vivo stability/residence time (histology described).
Anti-adhesion performance to biological tissue (rat model described).
Bone regeneration efficacy comparable to Bio-Gide (micro-CT/soft X-ray described).
Documented Applications
Use as an adhesion barrier.
Use as a guided bone regeneration membrane.
Tissue repair material.
Optionally as part of a material comprising an antibacterial and anti-inflammatory natural substance.
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