PTH Peptide Freeze-Drying Oxidation Control

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Solution Overview

Problem

The challenge in producing freeze-dried preparations of PTH peptide is the formation of PTH analogs due to exposure to air environments in pharmaceutical production facilities, leading to impurities that cannot be controlled, especially as production scale increases, affecting the purity and safety of the final product.

Innovation Solution

Controlling the exposure of PTH peptide solutions to air environments within pharmaceutical production facilities by using a controlled air flow and inert gas purging to minimize the production of PTH analogs, ensuring high-purity freeze-dried preparations by maintaining low levels of oxidizing substances like ozone and formaldehyde, and using specific handling techniques such as sub-door management during loading into freeze-drying chambers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PTH peptide solution is exposed to air environment in pharmaceutical production facility, then sterilization and aseptic environment are maintained, but PTH analogs are formed due to oxidation, reducing product purity

Engineering Contradiction:
Improvesterile environmentVSAvoidpurity of PTH peptide
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies inert atmosphere by replacing air with nitrogen gas in the production environment. Specifically, the facility is filled with nitrogen to maintain an oxygen-free atmosphere during PTH peptide processing, preventing oxidation of methionine and tryptophan residues that would otherwise form PTH analogs. This resolves the contradiction by maintaining a controlled environment that protects the peptide from oxidative degradation while still allowing for proper sterilization and handling.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

2Productivity

If production scale is increased, then productivity improves, but control over PTH analog formation becomes difficult, affecting product quality

Engineering Contradiction:
Improveproduction scaleVSAvoidcontrol of PTH analog levels
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by fundamentally altering the chemical environment parameters - specifically reducing oxygen concentration to near-zero levels and controlling humidity and temperature. By changing these environmental parameters to create an inert atmosphere, the patent enables large-scale production while maintaining consistent control over PTH analog formation, as the oxidative reaction pathway is effectively eliminated regardless of production volume.

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If oxidizing substances like ozone and formaldehyde are present for sterilization, then disinfection is effective, but PTH peptide undergoes oxidation, forming unwanted analogs

Engineering Contradiction:
Improvesterilization effectivenessVSAvoidpurity of final product
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by performing sterilization and disinfection procedures before introducing the PTH peptide into the production environment. The facility is thoroughly sterilized with appropriate agents, then completely dried and purged with nitrogen to remove all oxidizing residues before peptide processing begins. This sequence ensures effective sterilization while preventing subsequent oxidation of the peptide during manufacturing.

Inventive Principle:
Principle #10Preliminary action

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 significantly reduces the levels of PTH analogs, ensuring high-purity PTH peptide preparations by minimizing exposure to oxidizing agents, thereby enhancing the safety and efficacy of the pharmaceutical product.

Implementation Method 1

Controlling the exposure of PTH peptide solutions to air environments within pharmaceutical production facilities by using a controlled air flow and inert gas purging to minimize the production of PTH analogs

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

Freeze-dried preparation containing high-purity PTH and method for producing same

Methodology Applied
Scientific EffectFreeze drying: Freeze Drying

Data Source

PatentEP2719393B1Freeze-dried preparation containing high-purity PTH and method for producing same
Publication Date: 2020.10.21 ASAHI KASEI PHARMA CORP
  • EP2719393B1 patent drawingFigure 1
  • EP2719393B1 patent drawingFigure 2
  • EP2719393B1 patent drawingFigure 3

AI summary

[Problem] Provided is a freeze-dried preparation containing high-purity PTH peptide and a method for the production thereof. Also provided is a test method for PTH analogs to confirm the purity of a freeze-dried preparation containing PTH peptide, and the like. [Solution] In the present invention, the presence of PTH analogs produced during the manufacturing process of a freeze-dried preparation containing PTH peptide was confirmed. The production of these PTH analogs was also discovered to be markedly prevented or reduced by controlling exposure of the solution containing PTH peptide and the like to air environments within a pharmaceutical production facility.