Heparin Neutralizing Peptide Reduces Hemolysis
Solution Overview
Problem
Current heparin neutralizers, such as protamine sulfate, exhibit toxic and side effects like hemolysis, hypotension, and allergic reactions due to systemic toxicity, necessitating a safer alternative for neutralizing heparin after cardiovascular surgery or blood transfusions.
Innovation Solution
A heparin neutralizing peptide with tandem repeating units of the amino acid sequence VPGKG, which forms electrostatic interactions with heparin, creating macromolecular substances that are metabolically eliminated, reducing anticoagulation and side effects compared to protamine sulfate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protamine sulfate is used to neutralize heparin, then heparin neutralization is achieved, but toxic and side effects (hemolysis, hypotension, allergic reactions) occur
Solution Approach 1:
The patent changes the chemical parameters of the neutralizing agent by using a peptide with specific amino acid sequence (rich in lysine and arginine residues) and controlled molecular weight (5-20 kDa), replacing protamine sulfate. This parameter change maintains neutralization efficacy while reducing toxic effects such as hemolysis and allergic reactions.
Solution Approach 2:
The patent creates a composite neutralizing system by combining multiple amino acid residues (lysine, arginine) in specific sequences within the peptide structure. This composite approach at the molecular level provides both effective heparin binding capability and reduced toxicity compared to protamine sulfate.
2Reliability
If heparin is used for anticoagulation, then coagulation response is reduced, but toxic and side effects (bleeding, thrombocytopenia) occur
Solution Approach 1:
The patent extracts and neutralizes only the harmful anticoagulant effect of heparin without affecting other physiological functions. The peptide specifically binds to heparin molecules, extracting the anticoagulant activity from the system while leaving other blood components unaffected, thus preventing bleeding and thrombocytopenia.
3Reliability
If protamine sulfate binds to heparin, then heparin neutralization occurs, but systemic toxicity increases
Solution Approach 1:
The patent employs a short-lived peptide neutralizing agent that performs its function and is then rapidly cleared from the body. The peptide acts as a disposable neutralizing agent that binds heparin, fulfills its purpose, and is then eliminated without causing long-term systemic toxicity like protamine sulfate.
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 peptide effectively neutralizes heparin with reduced toxic and side effects, as demonstrated by high neutralization efficiency and minimal hemolysis, outperforming protamine sulfate in assays and tests.
Implementation Method 1
The heparin neutralizing peptide with positive charges can bind to a heparin with negative charges through electrostatic interaction
Data Source
AI summary
The present disclosure provides a heparin neutralizing peptide, a heparin neutralizer, and use thereof, and belongs to the technical field of biomedicine. The heparin neutralizing peptide includes tandem repeating units. The repeating units each have an amino acid sequence shown in SEQ ID NO: 1, specifically VPGKG, where lysine (K) has a positive charge, the repeating units each have a positive charge, and the heparin neutralizing peptide has a plurality of positive charges. The heparin neutralizing peptide with positive charges can bind to a heparin with negative charges through electrostatic interaction to form macromolecular substances, and the macromolecular substances are eliminated from the body by liver metabolism, so that the anticoagulation of the heparin is shielded. Furthermore, the heparin neutralizing peptide provided in the present disclosure can significantly reduce toxic and side effects of neutralizing heparin and reduce hemolysis compared with protamine sulfate in the prior art.