Stable Aqueous CD-RAP Formulations with Charged Amino Acids
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current protein pharmaceutical formulations face challenges in maintaining stability, particularly for CD-RAP, which is prone to aggregation and degradation at high concentrations, leading to instability during storage and administration, resulting in reduced efficacy and increased side effects due to high volume injections.
Innovation Solution
A stable aqueous formulation comprising at least 5 mg/mL CD-RAP with a charged amino acid, such as histidine, arginine, or glutamic acid, which maintains solubility and inhibits aggregation, allowing for high concentration without significant loss of biological activity through repeated freeze-thaw cycles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If CD-RAP is formulated at high concentrations to reduce injection volume, then productivity and ease of operation are improved, but stability deteriorates due to aggregation and degradation
Solution Approach 1:
The patent applies parameter changes by systematically varying formulation components including charged amino acids (arginine, histidine, lysine) at different concentrations, pH levels (6.0-8.0), and ionic strengths to identify conditions that maintain CD-RAP stability at high concentrations up to 30 mg/mL, resolving the contradiction between concentration and stability
Solution Approach 2:
The patent uses charged amino acids as intermediary substances that mediate between CD-RAP molecules to prevent aggregation. These amino acids act as spacers or protective agents that maintain solubility and stability at high protein concentrations, enabling the formulation to achieve both high productivity and reliability
2Reliability
If lyophilization is used to improve protein stability and storage, then stability is improved, but ease of operation deteriorates due to reconstitution requirements
Solution Approach 1:
The patent inverts the conventional approach by formulating CD-RAP as a stable liquid solution rather than lyophilized powder. This inversion eliminates the need for reconstitution while maintaining stability through optimized formulation components, particularly charged amino acids and controlled pH, making the product easier to administer while preserving reliability
3Reliability
If frozen storage is used to maintain stability, then stability is improved, but loss of time increases due to thawing requirements before administration
Solution Approach 1:
The patent applies preliminary action by incorporating stability-enhancing formulation components during manufacturing that preemptively protect against degradation during storage and transport. The charged amino acids and optimized pH buffer system are pre-configured to maintain stability at room temperature, eliminating the need for frozen storage and associated thawing time delays
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 achieves long-term stability and reduced aggregation of CD-RAP, enabling lower volume injections with minimized side effects and maintaining therapeutic efficacy.
Implementation Method 1
a stable aqueous formulation comprising at least 5 mg/mL CD-RAP and a charged amino acid
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to stable aqueous formulations comprising at least 5 mg/mL CD-RAP and a charged amino acid, said amino acid preferably having a net charge at a pH between about 6 and 8. The ingredients of the formulation preferably provide stability over repeated freeze-thaw cycles. In a preferred aspect, the formulation is for use in therapy, preferably for use in the treatment of inflammatory disorders, preferably osteoarthritis. Furthermore, a kit comprising the formulation of the invention is provided.