Liposomal Cytochrome C Nitric Oxide Complex Stability

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Solution Overview

Problem

Existing methods for obtaining pharmacologically active nitric oxide complexes are inefficient, particularly due to the use of multiple phases requiring special storage and the lack of biologically relevant liposomal cytochrome c hemocomplexes, which are not stable and have limited duration of action.

Innovation Solution

A method involving the treatment of liposomal cytochrome c emulsions with gaseous nitric oxide, followed by the addition of S-nitroso compounds, to form a stable liposomal cytochrome c and nitric oxide complex that maintains activity and liposome size stability during storage, using inert carrier gases and filtration through hydrophilic membranes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing methods for obtaining nitric oxide complexes are used, then the process can be performed with conventional reagents, but the efficiency is low and stability is poor

Engineering Contradiction:

Improvestability of nitric oxide complexVSAvoidefficiency of obtaining complex

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The invention uses liposomal cytochrome c as a composite material that combines the nitric oxide binding capability of heme proteins with the stabilizing properties of liposomal structures. This composite approach allows the complex to maintain both high stability during storage and efficient nitric oxide release when needed, resolving the contradiction between reliability and productivity.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The invention changes the physical and chemical parameters of the nitric oxide complex by incorporating it into liposomal cytochrome c structures. This transformation alters the stability profile and release characteristics of the complex, enabling it to remain stable during storage while maintaining high efficiency upon administration.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If multiple phases are used in the preparation process, then the complex can be formed, but special storage requirements and complexity increase

Engineering Contradiction:

Improveformation of complexVSAvoidstorage and handling complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention merges the nitric oxide complex formation with the liposomal cytochrome c structure into a single integrated system. This eliminates the need for separate phase-based preparation and storage systems, reducing complexity while maintaining the ability to form stable complexes.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The liposomal structure acts as a flexible shell that encapsulates the nitric oxide complex, providing a single-phase system that is easier to store and handle compared to multi-phase systems. The liposomal membrane maintains complex integrity without requiring specialized storage infrastructure.

Inventive Principle:

Principle #30Flexible shells and thin films

3Ease of manufacture

If conventional hemocomplexes are used, then the preparation is simpler, but biologically relevant stability and duration of action are limited

Engineering Contradiction:

Improvesimplicity of preparationVSAvoidduration of action of complex

Core Design Contradiction:

Ease of manufactureVSDuration of action of moving object

Solution Approach 1:

The invention employs a nested structure where nitric oxide is bound within the cytochrome c heme group, which is in turn encapsulated within the liposomal bilayer. This multi-level nesting protects the nitric oxide complex from degradation while maintaining biological relevance, extending duration of action without significantly complicating the manufacturing process.

Inventive Principle:

Principle #7Nested doll (Nesting)

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 resulting complex exhibits stable activity and prolonged efficacy, with enhanced vasodilatory effects and improved stability, maintaining effectiveness at different stages of storage and retaining liposome size up to 300 nm.

Implementation Method 1

Binding of NO to heme iron of the regulatory subunit of guanylate-cyclase causes a disruption in the bond between iron and nitrogen of a histidine imidazole group

Methodology Applied

Scientific EffectHeme iron binding: Chemical Bonding

Implementation Method 2

addition of an S-nitroso compound to the liposomal cytochrome c emulsion

Methodology Applied

Scientific EffectS-nitrosylation: Chemical Bonding

Implementation Method 3

cytochrome c, incorporated in liposomes

Methodology Applied

Scientific EffectLiposomal encapsulation: Emulsion

Data Source

PatentUS10772835B2Method of obtaining a pharmacologically active liposomal cytochrome c and nitric oxide complex

Publication Date: 2020.09.15 OLEKSANDR PYLYPENKO

AI summary

The invention relates to pharmaceutical industry and discloses a method of obtaining a new pharmacologically active liposomal agent containing substances that exhibit specific pharmacological activity on peripheral vessels and cavernous bodies of a mammal. More particularly, the invention relates to a method of obtaining a pharmacologically active liposomal cytochrome c containing nitric oxide. The new liposomal agent acts as a donor of the key biologically active substance—nitric oxide (NO).A method of obtaining a pharmacologically active liposomal cytochrome c and nitric oxide complex comprises the treatment of the liposomal cytochrome c emulsion with gaseous nitric oxide (NO) until liposomal cytochrome c is completely reconstituted and the addition of an S-nitroso compound to the liposomal cytochrome c emulsion.