Bile Acid Derivative Salts for Stable FXR Agonist Formulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing bile acid derivatives have low melting points, poor solubility, and stability issues, making them difficult to formulate and store, and they lack effective FXR receptor agonist activity.
Innovation Solution
The development of bile acid derivative salts, specifically hydrochloride and mesylate salts, formed by reacting a compound of Formula (I) with hydrochloric or methanesulfonic acid, enhancing solubility, stability, and FXR receptor agonist activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bile acid derivative compounds are used to treat cholestasis and activate FXR receptor, then therapeutic efficacy is improved, but physical stability and solubility deteriorate due to low melting points and poor solubility
Solution Approach 1:
The patent applies parameter changes by converting the bile acid derivative from free base form to salt form (hydrochloride or mesylate), which fundamentally changes the physical and chemical parameters of the compound. This transformation increases melting point, improves solubility, and enhances stability while preserving the core therapeutic activity. The salt formation modifies the molecular structure parameters without altering the pharmacophore responsible for FXR receptor activation.
Solution Approach 2:
The patent creates composite materials by forming salts of bile acid derivatives with specific acids (hydrochloric acid or methanesulfonic acid). This results in a composite structure where the bile acid derivative cation is paired with an anion (chloride or mesylate), creating a new material with combined properties that overcome the limitations of the parent compound while maintaining therapeutic efficacy.
2Reliability
If bile acid derivative compounds are used for therapeutic purposes, then FXR receptor agonist activity is achieved, but ease of manufacture and formulation deteriorate due to low melting points and handling difficulties
Solution Approach 1:
The patent applies parameter changes by transforming the compound from low-melting-point free base to high-melting-point salt form. This parameter change in melting point (from below 100°C to above 150°C) and solubility characteristics makes the material much easier to handle, weigh, and formulate during manufacturing processes, while preserving the essential FXR agonist activity.
Solution Approach 2:
The patent uses salt formation as an intermediary step in the manufacturing process. The bile acid derivative is converted to a stable salt form that serves as an intermediate for further formulation development. This intermediary form facilitates easier processing, storage, and formulation while maintaining the ability to achieve the desired therapeutic effect through FXR activation.
3Reliability
If bile acid derivative compounds are stored and handled, then therapeutic effects are maintained, but storage stability deteriorates due to poor solubility and handling difficulties
Solution Approach 1:
The patent applies parameter changes by converting the compound to a salt form with fundamentally different storage characteristics. The hydrochloride and mesylate salts exhibit superior storage stability compared to the free base form, with higher melting points reducing risk of degradation during storage, and improved solubility preventing precipitation and crystallization issues that could compromise stability over time.
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 salts exhibit improved solubility, stability, and FXR receptor agonist activity, effectively treating cholestasis, reducing portal pressure, and improving liver function, suitable for manufacturing medicaments for chronic liver diseases and metabolic disorders.
Implementation Method 1
a salt of a bile acid derivative, produced by reacting a compound having structure of Formula (F-1) with an acid
Data Source
Figure 1~2
Figure 3~4
Figure 5~6
AI summary
The present invention provides a salt of a bile acid derivative, a crystal form thereof, a preparation method therefor and use thereof. The salt of a bile acid derivative, the crystal form thereof and a composition thereof provided by the present invention can improve cholestasis, reduce portal pressure, and improve liver function, and can be used for preparing medicaments for treating or alleviating chronic liver diseases, metabolic diseases, portal hypertension and related diseases.