HGF Protein Formulation Stabilization for CNS Delivery
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Solution Overview
Problem
Current HGF protein preparations for treating central nervous system diseases are not stable enough for intrathecal or intracerebroventricular administration, as they tend to form polymers and are not fully confirmed safe for direct delivery to the central nervous system.
Innovation Solution
Incorporating lactose, glycine, sodium chloride, a pH buffering agent, and a surfactant, such as polysorbate, into the HGF protein solution to prevent polymer formation and enhance stability, allowing for safe and effective administration through intrathecal or intracerebroventricular routes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If HGF protein is administered via intravenous, subcutaneous or intramuscular injection, then the protein can be delivered to peripheral tissues, but the protein cannot transfer to central nervous system tissues across the blood-brain barrier
Solution Approach 1:
The invention divides the administration approach into two separate routes: conventional peripheral injection (intravenous, subcutaneous, intramuscular) for general delivery, and direct CNS administration (intrathecal, intracerebroventricular, or injection into spinal/cerebral parenchyma) for targeted delivery to central nervous system tissues. This segmentation allows the HGF protein to bypass the blood-brain barrier limitation by directly entering the CNS space through the spinal canal or ventricular system.
2Duration of action of stationary object
If HGF aqueous solution is stored, then the protein can be maintained in liquid form, but the solution gradually becomes turbid and gelatinized due to aggregation of HGF protein molecules
Solution Approach 1:
The invention introduces a stabilizer substance as an intermediary component in the HGF aqueous solution. This stabilizer acts as a mediator that prevents direct aggregation between HGF protein molecules, thereby maintaining solution clarity and preventing gelatinization during storage. The stabilizer interferes with the aggregation process, allowing the solution to remain stable and clear over time.
3Duration of action of stationary object
If HGF aqueous solution is stored, then the protein can be maintained in liquid form, but the solution is prone to formation of HGF protein-based polymers, resulting in reduction in biological activity
Solution Approach 1:
The stabilizer substance serves as an intermediary that prevents polymer formation between HGF protein molecules during storage. By interfering with the polymerization process, the stabilizer maintains the biological activity of HGF over extended storage periods, ensuring that the protein does not aggregate into inactive polymer forms.
Solution Approach 2:
The invention modifies the chemical parameters of the HGF aqueous solution by adding a stabilizer substance, which changes the solution's physicochemical properties. This parameter change (addition of stabilizer) prevents polymer formation and maintains HGF biological activity during storage, thereby extending the effective storage duration while preserving functionality.
4Stability of the object's composition
If HGF preparation contains stabilizers such as albumin, human serum, gelatin, sorbitol, mannitol and xylitol, then the protein stability is improved, but the preparation is not fully confirmed safe for direct delivery to the central nervous system
Solution Approach 1:
The invention extracts and removes potentially harmful components from the HGF preparation formulation. By taking out substances that may be unsafe for direct CNS delivery, the preparation achieves both stability and safety for intrathecal, intracerebroventricular, or parenchymal administration to the central nervous system.
Data Source
AI summary
The present invention provides a hepatocyte growth factor (HGF) preparation in the form of an injection or the like that is highly safe for central nerves and highly stable and can be used for intrathecal or intracerebroventricular administration or for administration into the spinal or cerebral parenchyma for the treatment of central nervous system diseases. The HGF preparation of the present invention contains an HGF protein as an active ingredient and lactose, glycine, sodium chloride, a pH buffering agent and a surfactant as additional ingredients.