Glucokinase Activator Solid Dispersion Enteric Coating
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Solution Overview
Problem
Current treatments for type II diabetes, such as insulin, do not effectively address the disorders of early-phase insulin secretion and hepatic glycogen generation caused by decreased glucokinase expression and function.
Innovation Solution
Development of an oral modified release formulation of the glucokinase activator, which includes a solid dispersion of the glucokinase activator with specific polymer carriers, designed to achieve a controlled release in the gastrointestinal tract and rapid absorption in the small intestine, thereby matching pharmacokinetics with pharmacodynamics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If an oral formulation of glucokinase activator is administered, then the drug can be delivered to the target organs (gut, islets, liver), but the drug may be degraded or inactivated in the stomach due to acidic environment and enzymes
Solution Approach 1:
The patent uses an enteric coating layer as an intermediary protective barrier between the glucokinase activator drug and the harsh stomach environment. This coating layer prevents direct contact with stomach acid and enzymes, allowing the drug to pass through the gastrointestinal tract intact and release at the appropriate location in the intestine where it can be absorbed and reach target organs.
Solution Approach 2:
The patent changes the physical-chemical parameters of the drug delivery system by using pH-responsive materials that remain stable in acidic conditions (stomach) but dissolve or become permeable in neutral to alkaline conditions (intestine). This parameter change allows the drug to protect itself from degradation in the stomach while ensuring release in the intestine.
2Speed
If the glucokinase activator is released rapidly in the stomach, then quick absorption might occur, but the drug would be exposed to degradation and fail to reach target organs effectively
Solution Approach 1:
The patent applies preliminary protective action by coating the drug with enteric material before administration. This pre-established protection ensures that the drug does not release prematurely in the stomach, preventing degradation and ensuring that rapid release occurs only at the appropriate location in the intestine where absorption and delivery to target organs can proceed effectively.
Solution Approach 2:
The patent makes the drug release system dynamic by using pH-responsive materials that change their release characteristics based on the environmental pH. The system remains closed (no release) in acidic stomach conditions but opens (rapid release) in neutral/alkaline intestinal conditions, optimizing both speed and effectiveness of drug delivery to target organs.
3Quantity of substance
If the drug is administered to achieve high plasma concentration, then therapeutic efficacy improves, but side effects increase
Solution Approach 1:
The patent applies local quality by enabling site-specific release of the glucokinase activator in the intestine, close to the absorption site and target organs (gut, islets, liver). This localized delivery increases the concentration of drug at the target sites while reducing systemic exposure, thereby improving therapeutic efficacy at the target organs while minimizing side effects in other parts of the body.
Solution Approach 2:
The enteric coating acts as an intermediary that controls the spatial and temporal distribution of the drug. By preventing premature release in the stomach and enabling controlled release in the intestine, the coating mediator ensures that high drug concentration is achieved locally at the absorption site and target organs, while reducing overall systemic concentration and associated side effects.
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 oral modified release formulation of the glucokinase activator provides improved therapeutic efficacy by enhancing glucose-stimulated insulin secretion, promoting hepatic glycogen synthesis, and maintaining better blood glucose balance with reduced side effects.
Implementation Method 1
The disclosure relates to the solid dispersion of the glucokinase activator used in the oral formulation of the glucokinase activator
Implementation Method 2
which includes a solid dispersion of the glucokinase activator with specific polymer carriers, designed to achieve a controlled release in the gastrointestinal tract
Implementation Method 3
the rapid release of the oral formulation of the glucokinase activator in small intestine of human body
Implementation Method 4
rapid absorption in the small intestine
Data Source
Figure 1
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AI summary
The present invention relates to a solid dispersion and a preparation method therefor. The solid dispersion contains a glucokinase activator, an isotopic label thereof, or a medicinal salt thereof and a polymer support. The present invention further relates to a solid dispersion composition containing the solid dispersion and an excipient. The present invention also relates to an oral preparation of the glucokinase activator, containing the solid dispersion or the solid dispersion composition. The present invention also relates to a tablet and a capsule of the glucokinase activator and a preparation method therefor. In addition, the present invention also relates to uses of the solid dispersion, the solid dispersion composition and the oral preparations comprising the tablet and the capsule, which can be used for treating and/or preventing selected diseases or medical conditions and especially one or more diseases selected from type I diabetes mellitus, type II diabetes mellitus, impaired glucose tolerance, impaired fasting glucose and hyperglycemia.