Composition, preparation, and use of chitosan shards for biomedical applications
Inventors
Kirsch, Wolff M. • Hudson, Samuel M. • Crofton, Andrew
Assignees
North Carolina State University • Loma Linda University
Publication Number
US-9259357-B2
Publication Date
2016-02-16
Expiration Date
2034-04-16
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Abstract
A thin chitosan-based material can be used for biomedical applications. The chitosan has been treated in a nitrogen field by applying energy to ionize nitrogen in and around the chitosan material. A single or multiple such treatments may be employed. For example, the chitosan material may be irradiated under nitrogen using γ-irradiation, treated under a nitrogen plasma, or both. A thin chitosan material can be readily treated by surface modifying treatments such as irradiating under nitrogen using γ-irradiation, treating under a nitrogen plasma, or both.
Core Innovation
The invention provides a method for creating a thin chitosan-based material for biomedical applications, particularly hemostatic and drug delivery devices. The method involves plasticizing chitosan flakes using an aqueous organic acid, physically compressing and consolidating these flakes under vacuum into a block, and then shredding or slitting the block into ultra-thin, excelsior-like chitosan fibrids or shards. These chitosan structures are then subjected to γ-irradiation under a nitrogen plasma to achieve surface modification and depyrogenation.
A key problem being addressed is the presence of pyrogens, especially endotoxins, in commodity- and medical-grade chitosan, which restrict its use in internal and implantable medical applications due to potential septic responses. Existing manufacturing processes leave harmful levels of endotoxins in the chitosan, and traditional depyrogenation methods often damage the polymer, reducing its efficacy or structural integrity for medical use.
By employing a combination of physical processing (compression and fragmentation), followed by nitrogen plasma and γ-irradiation treatment, the method effectively reduces endotoxin levels without degrading the molecular weight or hemostatic properties of chitosan. The result is an ultra-thin chitosan material with increased surface area, which enables improved depyrogenation and suitability for use as hemostats or drug delivery devices in both external and internal biomedical settings.
Claims Coverage
The patent contains one independent claim describing a method with multiple inventive features.
Producing excelsior-like chitosan fibrids via compression and shredding
Chitosan flakes are plasticized with an aqueous organic acid. These flakes are then physically compressed and consolidated under vacuum to form a chitosan block. The block is subsequently shredded or slit into excelsior-like chitosan fibrids characterized by a thickness of 1 μm to 250 μm, a width of 0.35 mm to 0.65 mm, and a length at least two times the width.
Depyrogenation by γ-irradiation under nitrogen plasma
The excelsior-like chitosan fibrids are subjected to γ-irradiation while under a nitrogen plasma. This step is explicitly defined to achieve depyrogenation and modify the chitosan material surface to inactivate endotoxins.
The independent claim focuses on an integrated method involving compression-based shaping of chitosan, formation of thin fibrids, and a combined nitrogen plasma and γ-irradiation treatment to produce depyrogenated excelsior-like chitosan materials suitable for biomedical use.
Stated Advantages
Provides a chitosan-based hemostatic material with reduced levels of pyrogens and endotoxins, enabling safe contact with mammalian tissue.
Achieves purification and depyrogenation of chitosan without significant degradation of molecular weight or hemostatic efficacy.
Increases material surface area, improving the efficiency of depyrogenation and enabling production of strong, flexible, and durable materials suitable for internal and external biomedical applications.
Allows formation of chitosan in various forms (e.g., shards, fibrids, films, fleeces) adaptable for different medical and surgical needs.
Documented Applications
Hemostatic devices (e.g., pads, sheets, puffs, fleeces, sponges, or non-woven fabrics) for controlling bleeding during surgical procedures, traumatic injuries, laparoscopic procedures, and neurosurgeries.
Drug delivery devices comprising a network of the ultra-thin chitosan material for therapeutic agent delivery.
Use in internal or implantable applications where depyrogenated chitosan is required, potentially including endoscopic or laparoscopic deployment.
Topical chitosan applications for wound healing and antibacterial action.
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