Butylphthalide Intravenous Emulsion for Brain Targeting
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Solution Overview
Problem
Current butylphthalide preparations, primarily in soft capsule form, suffer from low bioavailability due to a first pass effect, making them unsuitable for cerebral ischemia patients with dysphagia or coma, who require rapid and effective brain-targeted treatment.
Innovation Solution
A butylphthalide intravenous emulsion is developed, comprising butylphthalide or derivatives combined with an oil phase, emulsifier, stabilizer, and osmoregulation agent, processed using ultrasonic or high-speed shearing methods, and homogenized to achieve a particle size of 10-2000 nm for quick systemic circulation and brain targeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If butylphthalide is administered via soft capsules, then the drug can be packaged and stored, but the bioavailability is low due to first pass effect and it cannot be used for patients with dysphagia or coma
Solution Approach 1:
The patent changes the physical state and delivery route of butylphthalide from oral capsule to intravenous emulsion. This parameter change eliminates first pass metabolism, dramatically improving bioavailability, and enables administration to patients who cannot swallow, directly resolving both aspects of the contradiction.
Solution Approach 2:
The patent introduces an emulsion system as an intermediary carrier for butylphthalide. The emulsion consists of oil phase, water phase, and emulsifier, creating a stable colloidal system that can be intravenously administered. This intermediary solution bypasses the limitations of both oral capsules and direct oil injection, resolving the contradiction between bioavailability and administerability.
2Quantity of substance
If butylphthalide is dissolved in oil phase to form emulsion, then the solubility is improved, but the particle size must be controlled for intravenous administration
Solution Approach 1:
The patent controls the particle size parameter of the emulsion within a specific range (50-2000 nm, preferably 100-500 nm) to ensure both adequate solubility of butylphthalide in the oil phase and safety for intravenous administration. This parameter control resolves the contradiction between maximizing drug loading and ensuring clinical safety.
Solution Approach 2:
The patent creates a heterogeneous emulsion system where the oil phase droplets containing butylphthalide are distributed within the aqueous phase. The local composition of each droplet maintains high drug concentration for solubility, while the overall particle size distribution ensures safety for intravenous use, resolving the contradiction through spatial differentiation.
3Speed
If butylphthalide is administered intravenously, then the action is quick and brain targeting is improved, but the emulsion formulation complexity increases
Solution Approach 1:
The patent uses emulsion technology as an intermediary system to achieve intravenous administration of lipophilic butylphthalide. The emulsion formulation with specific components (oil phase, water phase, emulsifier) provides a standardized platform that enables quick systemic circulation and brain targeting while managing the complexity through established pharmaceutical technology.
Solution Approach 2:
The patent creates a composite emulsion system combining hydrophobic oil phase containing butylphthalide with hydrophilic water phase and emulsifier. This composite structure enables the lipophilic drug to be administered intravenously, achieving quick action and brain targeting, while the systematic formulation approach manages the inherent complexity.
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 emulsion enhances bioavailability, reduces dosage, and improves brain targeting, minimizing toxic side effects, allowing for rapid action and effective treatment of cerebral ischemia.
Implementation Method 1
The step of preparing the primary emulsion is carried out by utilizing ultrasonic method or high-speed shearing method
Implementation Method 2
The step of preparing the primary emulsion is carried out by utilizing ultrasonic method or high-speed shearing method
Implementation Method 3
The step of homogenizing is carried out by utilizing a two-stage high pressure emulsifying and homogenizing method
Data Source
AI summary
The present invention discloses a butylphthalide intravenous emulsion for intravenous injection or infusion, containing butylphthalide or derivatives thereof as an active ingredient in an amount of 0.01˜50 wt % and an excipient in an amount of 50˜99.99 wt %, based on the total weight of the emulsion.