Insulin Formulation Stability via Zinc Complex Buffering

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Solution Overview

Problem

Existing insulin formulations face challenges in maintaining chemical and physical stability, particularly due to pH sensitivity and degradation at extreme pH levels, which affects their shelf life and efficacy.

Innovation Solution

A pharmaceutical formulation comprising at least one insulin analogue or derivative, zinc (Zn(II)), sodium chloride, and optionally protamine, with a pH range of 6.0 to 9.0, is developed without additional buffering agents, enhancing chemical and physical stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If additional buffering agents are added to maintain pH stability, then pH control is improved, but formulation complexity and risk of interactions increase

Engineering Contradiction:

ImprovepH stabilityVSAvoidformulation complexity

Core Design Contradiction:

Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent removes additional buffering agents from the formulation, relying instead on the inherent buffering capacity of zinc ion complexes with insulin and the physiological buffering systems in the body. This extraction of unnecessary components simplifies the formulation while maintaining pH stability through the zinc-insulin complex equilibrium.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The formulation uses the zinc-insulin complex itself to provide buffering capacity, eliminating the need for separate buffering agents. The zinc ion complexes with insulin to form a stable complex that naturally resists pH changes, allowing the formulation to self-regulate pH without external buffering systems.

Inventive Principle:

Principle #25Self-service

2Adaptability or versatility

If the pH range is extended to 6.0-9.0, then formulation versatility is improved, but chemical stability deteriorates at extreme pH levels

Engineering Contradiction:

ImprovepH range adaptabilityVSAvoidchemical stability

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent optimizes the zinc-to-insulin ratio and zinc salt selection to create a formulation that maintains stability across a broad pH range of 6.0-9.0. By adjusting these parameters, the zinc-insulin complex maintains its structural integrity and buffering capacity throughout the extended pH range, preventing degradation that would normally occur at extreme pH levels.

Inventive Principle:

Principle #35Parameter changes

3Device complexity

If buffering agents are omitted to simplify formulation, then formulation simplicity is improved, but pH control capability worsens

Engineering Contradiction:

Improveformulation simplicityVSAvoidpH control

Core Design Contradiction:

Device complexityVSStability of the object's composition

Solution Approach 1:

The formulation achieves pH control without external buffering agents by utilizing the inherent buffering capacity of the zinc-insulin complex. The equilibrium between free zinc ions, insulin, and zinc-insulin complexes provides natural pH resistance, allowing the simplified formulation to maintain pH stability through its own chemical structure rather than added components.

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS20250121034A1Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives

Publication Date: 2025.04.17 SANOFI SA(FR)

AI summary

Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives are disclosed.