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-9414967-B2
Publication Date
2016-08-16
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 producing chitosan-based materials, specifically ultra-thin forms such as chitosan shards and narrow strips, that are treated for biomedical applications. The process entails plasticizing chitosan flakes with an aqueous organic acid, physically compressing and consolidating these flakes under vacuum into a block, and then shredding or slitting the block to produce chitosan shards or narrow strips of precise dimensions. A key part of the method is subjecting these ultra-thin chitosan materials to γ-irradiation under a nitrogen plasma, which can be combined with prior alcohol soaking.
The problem addressed by the invention is the persistent presence of pyrogens, particularly endotoxins, in chitosan materials produced by traditional methods, which makes them unsuitable for biomedical and especially implantable applications due to the risk of septic responses in mammals. Existing materials do not reliably achieve the low endotoxin limits required for safe medical implantation, with even medical-grade chitosan often exceeding FDA thresholds.
By treating chitosan with ionized nitrogen fields—through methods such as nitrogen plasma, γ-irradiation under nitrogen, or both—the invention achieves depyrogenation to levels suitable for internal and implantable medical devices. The ultra-thin geometry increases surface area, allowing more effective reduction or inactivation of endotoxins without compromising the functional or structural properties of chitosan, enabling applications in hemostatic devices and drug delivery devices.
Claims Coverage
There are two independent claims, each directed to a method of making a material. The main inventive features are summarized below.
Production of chitosan shards subjected to γ-irradiation under nitrogen plasma
A method that includes: - Plasticizing chitosan flakes with an aqueous organic acid - Physically compressing and consolidating the plasticized flakes under vacuum into a block - Shredding or slitting the block into chitosan shards with 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 - Subjecting the resulting chitosan shards to γ-irradiation under a nitrogen plasma
Production of narrow strips of chitosan material subjected to γ-irradiation under nitrogen plasma
A method that includes: - Plasticizing chitosan flakes with an aqueous organic acid - Physically compressing and consolidating the plasticized flakes under vacuum into a block - Shredding or slitting the block into narrow strips of chitosan material with a thickness of 1 μm to 250 μm, a width of 0.5 mm to 1.5 mm, and a length of 1 cm to 5 cm - Subjecting the narrow strips to γ-irradiation under a nitrogen plasma
The claims focus on specific processes for preparing chitosan-based ultra-thin materials (shards or narrow strips), describing exact dimensional parameters and the novel application of γ-irradiation under a nitrogen plasma to reduce pyrogen levels.
Stated Advantages
The invention enables the production of chitosan materials with reduced levels of pyrogens, especially endotoxins, suitable for use in internal or implantable medical devices.
Treatment with nitrogen plasma and/or γ-irradiation effectively inactivates endotoxins without significantly damaging the structural or functional properties of chitosan.
Ultra-thin chitosan materials have increased surface area, allowing more effective and efficient depyrogenation techniques.
The treated chitosan materials retain flexibility, durability, and mucoadhesion, making them suitable for biomedical uses such as hemostatic devices and drug delivery.
Documented Applications
Use in hemostatic devices, including forms such as networked chitosan shards, puffs, fleece, sponges, and sheets for internal and topical control of bleeding.
Application in drug delivery devices comprising a network of ultra-thin chitosan material.
Deployment through endoscopic ports for internal surgical use, including laparoscopic procedures.
Use in neurosurgery for controlling oozing brain wounds with a flexible sheet form.
Use in oncological surgery, particularly liver surgery, to control oozing with sheet or sponge forms.
Application in dermatological procedures for wound healing using sheet forms.
Closing punctures in a blood vessel with a puff form.
Application as a suture form, such as microsuture or macrosuture.
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