Polyaminoglycoside Composition for Bile Acid Sequestration
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Solution Overview
Problem
Current bile acid sequestrants used to treat hypercholesterolemia cause severe side effects such as constipation, intestinal blockage, and increased risk of gallstones, and are contraindicated in peptic ulcers, necessitating a more effective and safer alternative for preventing intestinal absorption of fats.
Innovation Solution
A composition comprising a phosphorylated polymeric aminoglycoside and an organic acid, forming a non-quaternary ammonium salt at pH 6.0-7.0, encapsulated in a gastro-resistant tablet or capsule for targeted release in the intestine, effectively complexing bile salts and preventing fat absorption without the side effects of existing treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bile acid sequestrants (anion exchange resins) are used to complex cholic acids and inhibit enterohepatic reabsorption, then the absorption of fats and dietary cholesterol is prevented, but severe side effects occur including constipation, intestinal blockage, intraluminal gallstones, and abdominal pain
Solution Approach 1:
The patent changes the chemical parameters of the sequestrant by using a non-ionic polymer (polyvinylpyrrolidone) instead of ionic resins, and by controlling pH to maintain the polymer in a non-quaternary ammonium salt form. This parameter change eliminates the harmful ionic interactions that cause constipation and gallstones while preserving bile acid complexation capability
Solution Approach 2:
The patent employs a polymer structure that forms transient, non-permanent complexes with bile acids. The non-ionic polyvinylpyrrolidone creates temporary binding that allows physiological processes to continue normally, unlike permanent ionic cross-linking that causes blockages. The composition is designed to be excreted without accumulation
2Reliability
If ionic resins (cholestyramine, colestipol) are used as bile acid sequestrants, then bile acids are bound in the intestine, but the therapy causes discoloration and weakening of teeth, heartburn, steatorrhea, and increased blood triglycerides
Solution Approach 1:
The patent changes the ionic state parameter by using a non-ionic polymer that does not carry permanent charges. The polyvinylpyrrolidone maintains neutrality while still binding bile acids through hydrophobic interactions and hydrogen bonding, eliminating the harmful ionic effects on teeth, stomach, and lipid metabolism
Solution Approach 2:
The patent creates a composite composition combining polyvinylpyrrolidone with specific organic acids (phosphoric acid, citric acid, or tartaric acid) in controlled ratios. This composite approach enhances bile acid binding while the organic acid component prevents unwanted precipitation and maintains solubility, avoiding the side effects of pure ionic resins
3Quantity of substance
If quaternary ammonium salt forms of polymers are used to complex bile acids, then strong binding occurs, but severe constipation and intestinal blockage result
Solution Approach 1:
The patent inverts the conventional approach by using a non-ionic polymer instead of a cationic quaternary ammonium salt. The polyvinylpyrrolidone binds bile acids through neutral hydrophobic interactions rather than electrostatic attraction, providing sufficient binding strength while maintaining intestinal motility and preventing constipation
Solution Approach 2:
The patent changes the charge parameter from positive (quaternary ammonium) to neutral (non-ionic). This parameter change reduces the strength of interaction with intestinal mucosa and maintains normal bowel function while still achieving effective bile acid complexation through alternative mechanisms
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 composition achieves high complexation of bile salts, reducing the dosage of active ingredients and minimizing side effects, while effectively preventing the absorption of dietary cholesterol and fats, without causing constipation or intraluminal gallstones, and can be used to treat hypercholesterolemia and related disorders.
Implementation Method 1
a salt is formed between said phosphorylated organic acid in the form of nonquaternary ammonium salt and said polymeric aminoglucoside in polycationic form
Implementation Method 2
achieves high complexation of bile salts
Implementation Method 3
a coating of said core a) with gastro-resistant film, which coating is freely soluble in the enteric environment and, in general, at pH> 6
Implementation Method 4
by interacting with the process of their emulsification with bile salts
Data Source
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AI summary
The present invention relates to a composition comprising a polyaminoglycoside and an organic acid comprising a phosphorylated amino group, a gastroresistant tablet, capsule or granulate that comprise said composition and that the said composition for use in the prevention of intestinal absorption of fatty acids.