FSH Aqueous Composition Stabilization

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Follicle-stimulating hormone (FSH) is unstable in aqueous solutions, leading to chemical and physical changes such as denaturation, aggregation, and precipitation, which reduces its physiological activity, and existing stabilization methods are not universally effective for all proteins or peptides.

Innovation Solution

An aqueous composition containing FSH stabilized with histidine and methionine, optionally combined with saccharides, surfactants, and buffering agents, which significantly reduces chemical and physical changes, enhancing the stability of FSH during storage and distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If FSH is prepared as an aqueous solution, then it can be used as a medicament for ovulation induction, but it undergoes chemical and physical changes such as denaturation, aggregation, and precipitation, reducing its stability and physiological activity

Engineering Contradiction:
Improveusability as medicamentVSAvoidstability of FSH
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent introduces contaminant proteins such as human serum albumin as intermediary stabilizing agents in the aqueous FSH solution. These intermediary proteins interact with FSH molecules, preventing direct harmful interactions between FSH molecules themselves, thereby reducing denaturation, aggregation, and precipitation while maintaining the aqueous solution form needed for medicament use

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent optimizes multiple parameters including pH (adjusted to specific ranges using buffering agents), ionic strength, temperature, and concentration of stabilizing agents to create optimal conditions where FSH remains stable in aqueous solution. By carefully controlling these parameters, the solution maintains both usability and enhanced stability

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If contaminant proteins such as human serum albumin are added as stabilizing agents, then stability of FSH is improved, but risk of virus contamination increases

Engineering Contradiction:
Improvestability of FSHVSAvoidvirus contamination risk
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent employs highly purified FSH preparations where contaminant proteins are used only in controlled, defined amounts that can be precisely characterized and controlled. These stabilizing proteins serve their protective function and are then discarded, avoiding long-term storage risks. The approach uses minimal necessary stabilizing agents under controlled conditions rather than relying on complex natural sources

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent carefully controls the concentration, purity, and characterization parameters of any contaminant proteins used as stabilizers. By precisely defining these parameters and using highly purified materials with known properties, the risk of virus contamination is minimized while maintaining the stabilizing function. The approach transforms an uncontrolled natural mixture into a controlled pharmaceutical preparation with defined parameters

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If recombinant FSH preparations are used to avoid virus contamination, then safety is improved, but stability in aqueous solution deteriorates due to lack of natural stabilizing proteins

Engineering Contradiction:
Improvevirus contamination riskVSAvoidstability of FSH
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent introduces exogenous stabilizing proteins or other stabilizing compounds as intermediary agents that compensate for the absence of natural stabilizing proteins in recombinant FSH preparations. These added stabilizers perform the protective function that would naturally be provided by contaminant proteins, enabling recombinant FSH to remain stable in aqueous solution without virus contamination risks

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite pharmaceutical preparation combining recombinant FSH with carefully selected stabilizing agents, buffering systems, and other excipients. This composite formulation integrates multiple components with complementary functions: the recombinant FSH provides the therapeutic activity while the added stabilizing components provide structural protection and solution stability, achieving both safety and stability

Inventive Principle:
Principle #40Composite materials

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 use of histidine and methionine as stabilizing agents in an aqueous composition effectively maintains the activity of FSH, reducing denaturation and aggregation, resulting in a stable pharmaceutical formulation suitable for long-term storage and distribution.

Implementation Method 1

it has been investigated to increase stability of protein preparations by adding a compound having an action of forming a hydrogen bond with a protein molecule

Methodology Applied
Scientific EffectHydrogen bonding:

Implementation Method 2

adding a compound having an action of forming a hydrogen bond with a protein molecule or enhancing hydration of a protein molecule

Methodology Applied
Scientific EffectHydration:

Data Source

PatentEP2366401B1Aqueous composition containing follicle-stimulating hormone
Publication Date: 2015.07.15 ASKA PHARMACEUTICAL CO LTD
  • EP2366401B1 patent drawingFigure 1
  • EP2366401B1 patent drawingFigure 2
  • EP2366401B1 patent drawingFigure 3

AI summary

A stable aqueous composition containing follicle-stimulating hormone, which comprises follicle-stimulating hormone and histidine as a stabilizing agent.