Calcium Phosphate Gatekeeper for pH-Selective Nitric Oxide Release
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Solution Overview
Problem
Existing methods for delivering nitric oxide face challenges due to its gaseous form and the issue of diazeniumdiolate releasing nitric oxide when contacting water, leading to inefficient and unpredictable release.
Innovation Solution
Development of nitric oxide releasing particles incorporating a silane coupling agent with a secondary amine group and calcium phosphate, which form diazeniumdiolate functional groups that release nitric oxide selectively based on pH changes, using calcium phosphate as a gatekeeper system to control release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If diazeniumdiolate is used to release nitric oxide, then a large amount of nitric oxide can be produced, but nitric oxide is released prematurely when contacting water
Solution Approach 1:
The patent introduces calcium phosphate as an intermediary material that mediates between the diazeniumdiolate functional group and water. The calcium phosphate coating prevents direct contact between water and the diazeniumdiolate group, thereby preventing premature nitric oxide release while allowing controlled release under specific pH conditions (pH 5.0-7.4) when the coating dissolves
Solution Approach 2:
The patent utilizes pH parameter changes to control nitric oxide release. The calcium phosphate coating is designed to dissolve at specific pH ranges (5.0-7.4), which triggers the release of nitric oxide from the diazeniumdiolate functional group. This parameter-based control ensures that nitric oxide is released only under controlled conditions rather than upon contact with water
2Stability of the object's composition
If nitric oxide is delivered in gaseous form, then it can be synthesized and stored, but there is a large limitation in effectively delivering nitric oxide
Solution Approach 1:
The patent creates a composite material system consisting of silica core, calcium phosphate coating, and diazeniumdiolate functional groups. This composite structure allows the nitric oxide to be stored stably in the diazeniumdiolate form within the protective coating, and then delivered efficiently when the coating dissolves under controlled pH conditions
Solution Approach 2:
The calcium phosphate coating serves as an intermediary that enables both stable storage and efficient delivery. During storage, it protects the diazeniumdiolate group from premature decomposition. During delivery, its controlled dissolution at pH 5.0-7.4 releases the stored nitric oxide efficiently to the target site
3Productivity
If nitric oxide is released for anti-cancer and anti-bacterial effects, then high concentration is needed for short time, but uncontrolled release reduces therapeutic effectiveness
Solution Approach 1:
The patent uses pH parameter changes as a trigger for selective nitric oxide release. The calcium phosphate coating is designed to dissolve specifically at pH 5.0-7.4, which creates selective release conditions at the target site while maintaining stability elsewhere. This ensures high concentration release only when and where needed for therapeutic effect
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
Stable and controlled delivery of nitric oxide to a desired site, improving therapeutic effects by ensuring nitric oxide release only under specific pH conditions, minimizing loss and enhancing biocompatibility.
Implementation Method 1
a case in which both the external stimuli and biocompatible product are applied is significantly rare. The present applicant tried to introduce a novel system of inducing release of nitric oxide by a change in pH while blocking a contact with the outside by introducing calcium phosphate
Implementation Method 2
adding nitric oxide gas thereto to form a diazeniumdiolate functional group
Implementation Method 3
Diazeniumdiolate may be stably stored in a solid form, has high solubility in water, and is decomposed under the body temperature and pH conditions, and a release form thereof is variously changed depending on pH
Data Source
AI summary
Provided is a method of controlling release of nitric oxide, and more particularly, to a method of selectively releasing nitric oxide depending on a change in pH using calcium phosphate.The method of selectively releasing nitric oxide according to the present invention may stably deliver nitric oxide to a desired site, and induce release of nitric oxide by a change in pH, thereby making it possible to improve a therapeutic effect while preventing a loss of nitric oxide.