Rhein Conjugates for Oral Bioavailability and pH Stability
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Solution Overview
Problem
Rhein analogues have low water solubility and bioavailability, leading to ineffective oral administration due to their insolubility and strong base salts causing high pH values that are physiologically unacceptable, and poor stability when attempting to adjust pH levels.
Innovation Solution
Formation of conjugates between rhein or rhein analogues and nitrogen-containing organic bases or basic amino acids, which increase water solubility and bioavailability, and create stable, neutral pH solutions suitable for human physiology.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rhein analogues are used as medicinal compounds, then therapeutic effects are achieved, but water solubility is poor leading to ineffective oral administration
Solution Approach 1:
The patent introduces nitrogen-containing organic bases or basic amino acids as intermediary substances that form conjugates with rhein analogues. These conjugates act as mediators that bridge the hydrophobic rhein molecule and the aqueous physiological environment, enabling effective oral administration while maintaining therapeutic activity.
Solution Approach 2:
The patent changes the chemical parameters of rhein analogues by forming conjugates with nitrogen-containing compounds. This chemical modification alters the solubility parameters and molecular properties of rhein, transforming it from a poorly soluble compound into a water-soluble conjugate suitable for oral administration.
2Ease of manufacture
If strong base salts are used to increase water solubility, then solubility improves, but pH value becomes too high causing physiological unacceptable effects
Solution Approach 1:
The patent carefully controls the pH parameter by selecting nitrogen-containing organic bases or basic amino acids with appropriate basicity. The conjugates formed have neutral or slightly acidic pH values suitable for human physiology, avoiding the harmful high pH effects of strong base salts while maintaining adequate water solubility.
Solution Approach 2:
The patent uses nitrogen-containing organic bases or basic amino acids as temporary conjugating agents that facilitate solubility improvement. These conjugates are metabolized or excreted after serving their solubility-enhancing function, similar to how temporary mediators are used in chemical processes.
3Stability of the object's composition
If pH value is adjusted to improve stability, then stability improves, but the conjugates still cause irritation or instability in physiological conditions
Solution Approach 1:
The nitrogen-containing organic bases or basic amino acids serve as intermediary substances that stabilize rhein analogues in physiological conditions. The conjugates formed act as protective intermediaries that prevent direct interaction between rhein and physiological irritants, maintaining stability without causing irritation.
Solution Approach 2:
The patent converts the potentially harmful basicity of rhein analogues into a beneficial property by forming conjugates with nitrogen-containing compounds. The conjugation process transforms the harmful high pH and irritation potential into neutral or slightly acidic conjugates that are stable and non-irritating in physiological conditions.
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 conjugates enhance the bioavailability and stability of rhein analogues, allowing for effective oral administration and treatment of diabetic nephrosis, gastrointestinal issues, and arthritic conditions without causing irritation or instability.
Implementation Method 1
Formation of conjugates between rhein or rhein analogues and nitrogen-containing organic bases or basic amino acids
Implementation Method 2
increase water solubility and bioavailability
Implementation Method 3
create stable, neutral pH solutions suitable for human physiology
Data Source
AI summary
The conjugates of present invention are formed by the combination of rhein or their analogues with the organic bases or amino acids in molecular force between them. The methods for preparing the conjugates and their uses for manufacturing medicines in the treatment of diabetic nephrosis, recovery of gastrointestinal function and prevention of intestinal adhesion, as well as treatment of osteoarthritis, rheumatic arthritis and rheumatoid arthritis are also described. Rhein or their analogues as the left part of general formula (I) is selected from (1) the compounds of rhein or their analogues, in which one or two substituents of R2˜R3 and R6˜R7 are COOH at least two substituents of R1˜8 are —H; or (2) the rhein-containing extract derived from plants. In general formula (I), M represents nitrogen-containing organic bases or basic amino acids.