Integration-Promoting Peptide Formulation for Solubility and Stability
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Solution Overview
Problem
Peptides derived from HIV-1 integrase, such as those with the sequence TAVQMAVFIHNFKRK, are inherently unstable due to chemical and physical degradation, and have low solubility in physiological conditions, making them unsuitable for stable pharmaceutical compositions.
Innovation Solution
Development of stable pharmaceutical compositions comprising the peptide as a hydrochloride salt, combined with poloxamer 188 and lactose, formulated to maintain stability and bioavailability for parenteral administration, including intravenous and subcutaneous routes, and potentially lyophilized for solid forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptides are formulated in physiological conditions, then they maintain biological activity, but they exhibit low solubility and instability
Solution Approach 1:
The patent applies parameter changes by adjusting the pH to 4.0-7.5 and using specific excipients (poloxamer 188 at 0.3-15 wt%, lactose at 1-20 wt%) to transform the peptide from an insoluble state to a soluble and stable pharmaceutical composition suitable for parenteral administration
Solution Approach 2:
The patent uses poloxamer 188 and lactose as intermediary substances that mediate between the hydrophobic peptide and the aqueous environment, enhancing solubility and stability without compromising the peptide's biological activity
2Quantity of substance
If peptide concentration is increased for therapeutic efficacy, then therapeutic effect improves, but aggregation and precipitation increase
Solution Approach 1:
Poloxamer 188 acts as a surfactant intermediary that prevents peptide aggregation and precipitation at high concentrations (0.1-30 mg/ml), enabling therapeutic doses to be achieved while maintaining physical stability
Solution Approach 2:
The patent creates a composite pharmaceutical system combining the peptide with poloxamer 188 and lactose, where the excipients work synergistically to maintain stability at high peptide concentrations required for therapeutic efficacy
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 compositions ensure the peptides remain stable and soluble, maintaining therapeutic efficacy by preventing degradation and ensuring effective delivery for treating HIV-1 and cancer by promoting cell death in targeted cells.
Implementation Method 1
from about 0.3 wt % to about 15 wt % of a poloxamer having the structure of Formula I
Implementation Method 2
the peptide or a salt thereof... the salt of the peptide is a hydrochloride salt
Data Source
AI summary
The present invention provides pharmaceutical compositions of an integration-promoting peptide and hydroxyl halide salts of said peptide. The pharmaceutical compositions of the present invention are stable and maintain the peptide soluble upon administration. Methods of treating viral infection and cancer with the peptide salts and compositions thereof are also provided.