Human Pancreatic Lipase Measurement Using pH-Adjusted Bile Acids

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Solution Overview

Problem

Current methods for measuring human pancreatic lipase activity using diglyceride substrates are influenced by non-pancreatic lipases like lipoprotein lipase or hepatic lipase, leading to reduced specificity and reproducibility.

Innovation Solution

Adjusting the pH to 7.4 or lower and using specific conjugated or non-conjugated bile acids, such as glycodeoxycholic acid or deoxycholic acid, in combination with colipase to maximize human pancreatic lipase activity while minimizing the influence of non-pancreatic lipases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If a diglyceride substrate is used to measure human pancreatic lipase activity, then the measurement can be performed with clear substrate solution, but the measurement is influenced by non-pancreatic lipases such as lipoprotein lipase or hepatic lipase, reducing specificity

Engineering Contradiction:
Improvesubstrate clarityVSAvoidspecificity to pancreatic lipase
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the pH parameter of the measurement system to 7.4 or lower, which selectively inhibits non-pancreatic lipases while maintaining pancreatic lipase activity. This parameter change resolves the contradiction by allowing clear substrate solution usage while improving specificity through pH-dependent enzyme selectivity.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If the pH is adjusted to 7.4 or lower to reduce non-pancreatic lipase influence, then specificity improves, but the measurement must be performed under more controlled acidic conditions

Engineering Contradiction:
Improvespecificity to pancreatic lipaseVSAvoidpH control requirement
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent establishes a specific pH range (7.4 or lower) as the optimal condition for measuring human pancreatic lipase activity with reduced non-pancreatic lipase interference. By defining this parameter threshold, the patent simplifies the control requirement while maintaining high specificity, rather than requiring complex dynamic pH control.

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If conventional triglyceride emulsion is used as substrate, then the measurement can be performed, but phase separation occurs during storage and reproducibility is reduced

Engineering Contradiction:
Improvesubstrate preparationVSAvoidreproducibility
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent changes the substrate from triglyceride emulsion to diglyceride, which has different physical properties that prevent phase separation during storage. This parameter change in substrate type maintains ease of preparation while significantly improving reliability and reproducibility of measurements.

Inventive Principle:
Principle #35Parameter changes

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

This approach enhances the specificity and reproducibility of human pancreatic lipase activity measurements by reducing the impact of non-pancreatic lipases, allowing for more accurate detection of pancreatic lipase activity in samples.

Implementation Method 1

a bile acid that makes a pH for giving a maximum value of the human pancreatic lipase activity to be lower than 7.7

Methodology Applied
Scientific EffectpH adjustment:

Implementation Method 2

the conformation of the human pancreatic lipase is changed if the colipase is additionally present, and the active center of the human pancreatic lipase can bound to a substrate

Methodology Applied
Scientific EffectConformational change:

Implementation Method 3

a triglyceride is conventionally used as the substrate. The triglyceride is used in the form of what is called an emulsion in which it is emulsified and dispersed in a buffer solution

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentUS10000791B2Measurement method for human pancreatic lipase activity
Publication Date: 2018.06.19 NAGASE DIAGNOSTICS CO LTD
  • US10000791B2 patent drawing
  • US10000791B2 patent drawing
  • US10000791B2 patent drawing

AI summary

A measurement method for human pancreatic lipase activity in a sample, includes bringing a bile acid that makes a pH for giving a maximum value of human pancreatic lipase activity to be lower than 7.7, a diglyceride and a colipase into contact with the sample at pH 7.4 or lower; and detecting a signal amount varying in accordance with the human pancreatic lipase activity in the sample, and the bile acid is a bile acid containing: one of or two or more of a-type bile acids selected from the group consisting of GDCA, GCDCA, TDCA, TCDCA and salts thereof; and/or a combination of one of or two or more of b-1-type bile acids selected from the group consisting of GCA, GUDCA, TCA, TUDCA and salts thereof, and one of or two or more of b-2-type bile acids selected from the group consisting of DCA, CDCA and salts thereof.