Infusion Preparation pH Control to Inhibit Insoluble Matter

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Solution Overview

Problem

Intravenous nutrient infusion preparations develop unwanted insoluble matter when stored for long periods due to the formation of free fatty acids, which is not effectively addressed by existing technologies.

Innovation Solution

Incorporating amino acids with buffer action, divalent organic acids, and trivalent organic acids in the first-chamber infusion at concentrations of 0.15 to 0.5 g/L, and maintaining a pH of 6.53 or less after mixing, inhibits the formation of free fatty acids and subsequent insoluble matter.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If the infusion preparation is stored for long periods, then the usable period is extended, but unwanted insoluble matter is generated due to free fatty acid formation

Engineering Contradiction:
Improveusable periodVSAvoidunwanted insoluble matter
Core Design Contradiction:
Duration of action of stationary objectVSObject-generated harmful factors

Solution Approach 1:

Amino acids with buffer action and organic acids are added to the first-chamber infusion in advance before storage, establishing a chemical environment that prevents free fatty acid formation during long-term storage, thereby preventing insoluble matter generation before it occurs

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The pH of the first-chamber infusion is controlled within a specific range (5.0-6.5) through the addition of buffer substances, changing the chemical parameters to a state where free fatty acid formation is suppressed, thus extending the usable period without generating harmful insoluble matter

Inventive Principle:
Principle #35Parameter changes

2Reliability

If amino acids with buffer action and organic acids are added to the first-chamber infusion, then free fatty acid formation is inhibited, but the device complexity increases

Engineering Contradiction:
Improvestability during storageVSAvoidcomposition complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Amino acids with buffer action serve multiple functions: they act as buffer substances to control pH, prevent free fatty acid formation, and provide nutritional value, thereby improving stability without significantly increasing composition complexity

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

By controlling the pH parameter within a specific range (5.0-6.5) through the addition of buffer substances, the chemical stability is improved to prevent free fatty acid formation, achieving higher reliability through parameter optimization rather than complex compositional changes

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 extends the usable period of the infusion preparation by preventing the generation of unwanted insoluble matter during long-term storage, ensuring stability and safety for clinical use.

Implementation Method 1

a first-chamber infusion comprising a fat emulsion and further comprising at least one member selected from the group consisting of amino acids that have a buffer action, divalent organic acids, and trivalent organic acids

Methodology Applied
Scientific EffectBuffer action:

Implementation Method 2

a mixture of the first- and second-chamber infusions has a pH of 6.53 or less as measured 48 hours after the partition is communicably opened

Methodology Applied
Scientific EffectpH control:

Data Source

PatentUS11890372B2Transfusion preparation
Publication Date: 2024.02.06 OTSUKA PHARMACEUTICAL FACTORY INC

AI summary

The present invention provides an infusion preparation that is inhibited from generation of unwanted insoluble matter after mixing of two liquids of the infusion preparation in long-term storage. More specifically, the present invention provides an infusion preparation comprising two chambers separated by a communicably openable partition, a first chamber containing a first-chamber infusion comprising a fat emulsion and further comprising at least one member selected from the group consisting of amino acids that have a buffer action, divalent organic acids, and trivalent organic acids, a second chamber containing a second-chamber infusion comprising an amino acid and at least calcium as an electrolyte, wherein a total concentration of the amino acids that have a buffer action, divalent organic acids, and trivalent organic acids in the first-chamber infusion is 0.15 to 0.5 g/L, and a mixture of the first- and second-chamber infusions has a pH of 6.53 or less as measured 48 hours after the partition is communicably opened.