Aqueous TPGS Resiniferatoxin Injection for Prolonged Knee Pain Relief
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing pharmaceutical dosage forms of Resiniferatoxin for treating knee joint pain, particularly osteoarthritic knee joint pain, are not satisfactory in terms of tissue distribution and efficacy, and there is a need for improved dosage forms that provide enhanced distribution and prolonged pain relief.
Innovation Solution
A pharmaceutical dosage form comprising Resiniferatoxin at ultra-low doses (50 to 900 ng, preferably less than 500 ng) with an aqueous ethanol solution, D-α-tocopherol polyethylene glycol succinate (TPGS) as a surfactant, and optionally a buffer and inorganic salts, which improves distribution and provides prolonged analgesia when administered intraarticularly.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional μg-scale doses of Resiniferatoxin are administered, then pain relief is achieved, but tissue distribution is insufficient and duration of action is limited
Solution Approach 1:
The patent applies parameter changes by transitioning from conventional μg-scale doses to ultra-low ng-scale doses (50-900 ng) of Resiniferatoxin. This dramatic reduction in dosage parameter, combined with optimized formulation parameters (aqueous ethanol solution with 0.5-5% ethanol, TPGS surfactant at 0.1-1% concentration), achieves prolonged analgesia of several months while improving tissue distribution within the knee joint.
Solution Approach 2:
The patent employs composite materials by formulating Resiniferatoxin with an aqueous ethanol solution containing TPGS (D-α-tocopherol polyethylene glycol succinate) surfactant. This composite formulation enhances the solubility, stability, and tissue distribution of Resiniferatoxin, enabling ultra-low doses to achieve prolonged and improved therapeutic effects compared to conventional formulations.
2Reliability
If higher doses of Resiniferatoxin are used, then analgesic effect is strengthened, but tolerability and safety deteriorate
Solution Approach 1:
The patent applies partial action by using ultra-low doses of Resiniferatoxin (50-900 ng) that are sufficient to achieve the desired analgesic effect without causing excessive pharmacological activity. This partial dosing strategy improves safety and tolerability by avoiding the adverse effects associated with conventional μg-scale doses, while still providing prolonged pain relief of several months.
3Ease of manufacture
If conventional formulations are used, then administration is simple, but tissue distribution and efficacy are insufficient
Solution Approach 1:
The patent introduces TPGS surfactant as an intermediary substance that facilitates the distribution of Resiniferatoxin within the knee joint tissue. The TPGS surfactant acts as a mediator between the drug and tissue, enhancing penetration and distribution without complicating the formulation or administration process. The ethanol in the aqueous solution also serves as an intermediary to improve solubility and tissue penetration.
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 ultra-low dose Resiniferatoxin formulation achieves prolonged pain relief of several months with improved tissue distribution within the knee joint, offering better tolerability and safety compared to conventional μg-scale doses.
Implementation Method 1
Resiniferatoxin is a potent and selective agonist of the transient receptor potential vanilloid 1 (TRPV1) being developed for treatment of pain related to knee osteoarthritis. Resiniferatoxin-mediated activation of TRPV1-expressing neurons is followed by reversible defunctionalization of the peripheral terminals of C- and A-delta nerve fibers that can lead to prolonged analgesia.
Data Source
AI summary
The invention relates to a pharmaceutical dosage form for injection, preferably intraarticular injection into a knee, comprising or essentially consisting of (i) Resiniferatoxin; preferably at a dose within the range of from 50 to 900 ng, preferably less than 500 ng; (ii) water; (iii) an organic solvent; preferably ethanol; (iv) a surfactant; preferably D-α-tocopherol polyethylene glycol succinate (TPGS); (v) optionally, a buffer; and (vi) optionally, one or more inorganic salts; wherein the weight content of the water is greater than the weight content of the organic solvent. The invention further relates to a liquid pharmaceutical dosage form comprising Resiniferatoxin at a dose within the range of from 50 to 900 ng, preferably less than 500 ng for use in the treatment of knee joint pain, preferably osteoarthritic knee joint pain, by intraarticular administration, preferably intraarticular injection. The invention further relates to administration regimens for the treatment of knee joint pain, preferably osteoarthritic knee joint pain, by intraarticular administration, preferably intraarticular injection of liquid pharmaceutical dosage forms comprising Resiniferatoxin at a dose within the range of from 50 to 900 ng, preferably less than 500 ng.