Derivatized Chitosan Compositions for Biocompatibility
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Chitosan compositions with a degree of deacetylation (DDA) between 40% to 70% are considered toxic and non-bioabsorbable for biomedical use due to unpredictable biodegradation properties, leading to prolonged residence time and potential adverse events such as vascular and neural impingement, and infection.
Innovation Solution
Development of biocompatible and bioabsorbable chitosan compositions with a DDA range of 15% to 40%, which are initially soluble in aqueous solutions below pH 6.5, and can be crosslinked with gelatin/collagen using EDC, allowing for controlled bioabsorption within 90 days or less, and customization of acid content for specific applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If chitosan compositions with DDA between 40% to 70% are used, then processing ease is improved, but biocompatibility deteriorates due to toxic biodegradation species and prolonged residence time
Solution Approach 1:
The patent applies parameter changes by precisely controlling the degree of deacetylation (DDA) of chitosan to fall within the range of 25%-40%, and by controlling molecular weight between 10,000-500,000 Daltons. These specific parameter adjustments optimize the balance between biocompatibility (reducing toxic biodegradation species) and processing characteristics, resolving the contradiction between ease of manufacture and biocompatibility
Solution Approach 2:
The patent employs composite materials by combining chitosan with gelatin or collagen to form crosslinked networks. This composite approach enhances biocompatibility while maintaining processability, as the composite structure allows for controlled degradation and reduced cytotoxicity compared to pure chitosan in the 40-70% DDA range
2Ease of operation
If chitosan compositions with DDA between 40% to 70% are used, then solubility in aqueous solution is improved, but bioabsorption rate deteriorates leading to prolonged residence time
Solution Approach 1:
The patent applies parameter changes by optimizing the DDA to 25%-40% and molecular weight to 10,000-500,000 Daltons, which creates a sweet spot where the material maintains sufficient solubility for processing but degrades and absorbs within the body at an appropriate rate (90 days or less), resolving the contradiction between solubility and bioabsorption rate
Solution Approach 2:
The patent employs dynamics by creating crosslinked networks with gelatin or collagen that can dynamically adjust their degradation rate. The crosslinked structure provides initial stability and solubility control, while allowing progressive bioabsorption over time, thus balancing solubility requirements with controlled residence time
3Ease of operation
If chitosan compositions with DDA between 40% to 70% are used, then initial solubility is improved, but safety deteriorates due to potential adverse events such as vascular impingement and infection
Solution Approach 1:
The patent applies parameter changes by precisely controlling DDA (25%-40%) and molecular weight (10,000-500,000 Daltons), which reduces the formation of toxic biodegradation species and minimizes adverse events like vascular impingement and infection, while maintaining adequate initial solubility for surgical application
Solution Approach 2:
The patent employs composite materials by forming crosslinked networks with gelatin or collagen, which enhances safety by reducing cytotoxicity and controlling degradation products, while preserving the necessary solubility characteristics for surgical use. The composite structure provides a safer profile than pure chitosan in the 40-70% DDA range
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compositions demonstrate rapid and complete bioabsorption within 90 days, reducing the risk of adverse reactions and providing a safe, biocompatible implant material for internal surgical use, overcoming misconceptions about chitosan's safety and biocompatibility at lower DDA ranges.
Implementation Method 1
crosslinked to gelatin/collagen by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC)
Implementation Method 2
The inventive compositions are typically bioabsorbed in about 90 days or less
Data Source
AI summary
The invention relates to biocompatible, bioabsorbable derivatized non-crosslinked chitosan compositions optionally crosslinked to gelatin/collagen by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) for biomedical use and methods of making and testing such compositions, including a modified acute systemic toxicity test. The compositions comprise derivatized chitosan reacetylated to a degree of N-deacetylation (DDA) of between about 15% and 40%. The compositions are typically bioabsorbed in about 90 days or less and can be made to bioabsorb at differing rates of speed. The compositions are initially soluble in aqueous solution below pH 6.5. The compositions have an acid content that can be adjusted between about 0% (w/w) and about 8% (w/w) to customize the composition for uses that require and/or tolerate differing levels of cytotoxicity, adhesion, composition cohesion, and cell infiltration into the composition.