Creatine Amides for Neuroprotection via Solubility Tuning
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Solution Overview
Problem
Current Creatine derivatives face issues with stability and bioavailability, leading to high dosages required for effectiveness, which can cause adverse effects and limit their applications due to poor solubility and absorption.
Innovation Solution
Synthesis of Creatine amides through interaction with guanidinylating agents and sarcosine amides in polar organic solvents, resulting in compounds with enhanced solubility and stability, and demonstrated neuroprotective activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high dosages of Creatine derivatives are administered to achieve effectiveness, then therapeutic effect is improved, but adverse effects increase and tolerance decreases
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of Creatine derivatives through amide bond formation with various acids (fatty acids, aromatic acids, amino acids). This structural modification changes the physicochemical parameters including solubility, stability, and bioavailability, allowing effective doses to be reduced while maintaining therapeutic effect and decreasing adverse effects
2Stability of the object's composition
If high dosages of Creatine derivatives are administered to overcome poor solubility, then solubility issue is addressed, but adverse effects and treatment cost increase
Solution Approach 1:
The patent changes the solubility parameter by introducing amide groups with varying hydrophobic/hydrophilic characteristics. Different acid moieties (hydrophilic carboxylic acids, amphiphilic fatty acids, lipophilic aromatic acids) are used to tune solubility properties, allowing effective concentrations to be achieved without requiring high dosages that cause adverse effects
3Stability of the object's composition
If high dosages of Creatine derivatives are administered to overcome poor absorption, then absorption issue is addressed, but adverse effects and nitrogen exchange disturbance increase
Solution Approach 1:
The patent modifies absorption parameters through structural changes - creating amide derivatives with optimized molecular properties. The amide bond formation and selection of specific acid moieties improve membrane permeability and gastrointestinal absorption, allowing lower effective doses that do not disturb nitrogen exchange
4Ease of operation
If Creatine compositions are stored at room temperature for convenience, then ease of storage is improved, but degradation occurs within one week
Solution Approach 1:
The patent changes the stability parameter by forming amide bonds which are chemically more stable than the original Creatine structure. The amide derivatives exhibit enhanced resistance to hydrolysis and degradation, maintaining compositional stability at room temperature for extended periods without requiring refrigeration
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 synthesized Creatine amides exhibit improved stability and bioavailability, allowing for lower doses and broader biological actions, including significant neuroprotective effects, as shown in animal models of ischemic brain damage.
Implementation Method 1
Synthesis of Creatine amides through interaction with guanidinylating agents and sarcosine amides in polar organic solvents
Data Source
AI summary
The invention relates to pharmaceutical chemistry notably to new biologically active substances (BAS) and their properties. In particular, the invention relates to Creatine derivatives having a general formula: NH═C(NH2)—N(CH3)—CH2—CO—NH—R*X, wherein R—amino acid residue of aliphatic, aromatic or heteroaromatic L-amino acid or its derivative representing a salts of amino acid, amino acid esters, amino acid amides or peptides; X—lower organic or mineral acid or water. New substances are prepared by interaction of aforesaid amides of sarcosine having a general formula of HN(CH3)—CH2—CO—NH—R*X, wherein: R is amino acid residue or substituted amino acid residue; X is low-molecular-weight organic acid or mineral acid or water, with a guanidinylating agents with the in organic solvents at temperature not exceeding 50° C. New chemical compounds can be used as a remedy possessing a neuroprotective activity.