Segmented Glucan Dialysate for Ultrafiltration and Hyperglycemia Control
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Solution Overview
Problem
Current peritoneal dialysis solutions using high molecular weight saccharide polymers like Icodextrin suffer from slow ultrafiltration rates and high carbohydrate absorption, leading to prolonged dialysis sessions and increased risk of hyperglycemia, especially in diabetic patients, due to their low osmotic pressure and rapid absorption by the body.
Innovation Solution
A composition comprising maltose, glycerol, amino acids, or oligopeptides, along with glucan molecules of specific molecular weights, is developed to enhance osmotic pressure and ultrafiltration efficiency, allowing for shorter dialysis dwells and reduced carbohydrate absorption, while maintaining osmotic activity at lower carbohydrate concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-generated harmful factors
If high molecular weight saccharide polymers (e.g., Icodextrin) are used as osmotic agents, then carbohydrate absorption is reduced and dialysis can be performed without glucose, but ultrafiltration rate becomes slow and dialysis session duration increases
Solution Approach 1:
The patent segments the molecular weight distribution of saccharide polymers into multiple fractions (DP 3-10, DP 11-20, DP 21-50, DP 51-100) rather than using a single high molecular weight polymer. This segmentation creates a bimodal distribution that combines faster ultrafiltration from lower DP fractions with reduced carbohydrate absorption from higher DP fractions, resolving the contradiction between these two parameters.
Solution Approach 2:
The patent changes the parameter of molecular weight distribution from a single high molecular weight peak to a bimodal distribution with specific weight percentages in different DP ranges. This parameter change optimizes both ultrafiltration rate (enhanced by lower DP fractions) and carbohydrate absorption (reduced by higher DP fractions), simultaneously improving both contradictory parameters.
2Object-generated harmful factors
If high molecular weight saccharide polymers are used, then glucose-free dialysis is achieved, but dialysis session duration becomes prolonged
Solution Approach 1:
The segmented molecular weight distribution enables the solution to achieve effective ultrafiltration faster than single high-DP polymers, reducing the time required for adequate fluid removal while maintaining glucose-free status. The lower DP fractions provide faster initial ultrafiltration, shortening dialysis session duration while higher DP fractions prevent carbohydrate absorption.
Solution Approach 2:
The patent creates a composite saccharide polymer composition combining multiple DP fractions in specific proportions (DP 3-10: 10-40%, DP 11-20: 20-50%, DP 21-50: 20-40%, DP 51-100: 5-20%). This composite structure synergistically combines the fast ultrafiltration properties of lower DP fractions with the low carbohydrate absorption properties of higher DP fractions, achieving both reduced hyperglycemia risk and acceptable dialysis duration.
3Productivity
If low molecular weight saccharide polymers are used, then ultrafiltration rate increases, but carbohydrate absorption increases and hyperglycemia risk increases
Solution Approach 1:
Rather than using a single low molecular weight polymer, the patent segments the low DP range (DP 3-10) and combines it with higher DP fractions. The lower DP fraction (10-40% of total) provides enhanced ultrafiltration rate, while the higher DP fractions (DP 11-100 comprising 55-90% of total) limit carbohydrate absorption and hyperglycemia risk, resolving the contradiction between these parameters.
Solution Approach 2:
The composite composition combines saccharide polymers across a broad DP range (3-100) with specific weight percentages for each fraction. This composite approach allows the lower DP fractions to contribute to faster ultrafiltration while higher DP fractions control carbohydrate absorption, achieving both high productivity and low hyperglycemia risk simultaneously.
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 higher osmolality and net ultrafiltration volumes at lower carbohydrate concentrations, enabling shorter dialysis sessions and reduced carbohydrate absorption, potentially allowing for saccharide-polymer based PD to be used as a monotherapy, thereby reducing hyperglycemia risks in diabetic patients.
Implementation Method 1
Common PDFs use glucose as osmotic agent at concentrations between 1 and 5%, to achieve transfer of fluid and toxic agent out of the blood into the dialysate
Implementation Method 2
At the same time as some osmotic material gets lost by resorption through the body, intraperitoneal amylases cut the polymer into smaller saccharides, thereby increasing the osmotic pressure of the remaining intraperitoneal maltodextrins
Implementation Method 3
exchanging fluids and dissolved substances (electrolytes, urea, glucose, and other small molecules) between blood and the dialysate
Data Source
AI summary
Carbohydrate compositions for dialysis and methods of making and using them are provided.