LMWH Stability via Buffering Agents
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Solution Overview
Problem
Low molecular weight heparins (LMWHs) with glycol split uronic acid residues are sensitive to degradation under stress conditions, such as increased temperature and altered pH, leading to reduced shelf-life and stability issues.
Innovation Solution
Formulating LMWH preparations with glycol split uronic acid residues in combination with buffering agents like citrate, phosphate, histidine, maleate, succinate, or acetate buffers, and antioxidants, while maintaining a pH between 4.0-9.0, to enhance stability and preserve chemical integrity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If LMWH preparations with glycol split uronic acid residues are stored under stress conditions (increased temperature and altered pH), then the shelf-life is reduced, but the stability and chemical integrity are compromised
Solution Approach 1:
The patent applies parameter changes by optimizing the pH range (4.0-9.0) and incorporating buffering agents to maintain stable chemical conditions. This resolves the contradiction by creating an environment where the LMWH preparation remains chemically intact over extended storage periods, thereby extending shelf-life without compromising stability.
Solution Approach 2:
Buffering agents and antioxidants are introduced as intermediary substances that mediate between the LMWH preparation and degrading environmental factors. These intermediaries neutralize pH fluctuations and prevent oxidation, protecting the chemical integrity of the preparation during storage and thus extending its shelf-life.
2Stability of the object's composition
If buffering agents and antioxidants are added to LMWH preparations, then stability and chemical integrity are improved, but the formulation complexity increases
Solution Approach 1:
The patent employs buffering agents that serve multiple functions: maintaining pH stability, preventing degradation, and ensuring solubility. This multi-functionality allows a single additive to address multiple stability concerns simultaneously, improving chemical integrity without proportionally increasing formulation complexity.
Solution Approach 2:
The formulation creates a composite system combining LMWH preparation with buffering agents and antioxidants. This composite approach integrates multiple functional components into a unified formulation that achieves enhanced stability while managing complexity through systematic design and optimization of component interactions.
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 formulation improves the stability of LMWH preparations under accelerating and standard storage conditions, extending shelf-life and maintaining structural integrity by minimizing degradation pathways.
Implementation Method 1
one or more buffering agents (e.g., one or more buffering agents described herein (e.g., a citrate buffer, a phosphate buffer, a histidine buffer, a maleate buffer, a succinate buffer, an acetate buffer, or any combination thereof))
Implementation Method 2
one or more antioxidant (e.g., alpha tocopherol, ascorbic acid, acorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, and/or sodium sulfite)
Data Source
AI summary
Described herein are pharmaceutical compositions comprising a LMWH preparation having at least one chain having a glycol split uronic acid residue (UG) in the preparation and uses thereof.