Benzodiazepine Composition Inducing Opiate Effect

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Solution Overview

Problem

Current pharmaceutical compositions do not induce an opiate-analogous effect, despite containing benzodiazepines or their derivatives, which are used for anxiety and sedation but lack the morphine-like effects.

Innovation Solution

A pharmaceutical composition combining lormetazepam and/or its derivatives with macrogol 15 hydroxystearate as a non-ionic solubilizer, administered in specific concentrations to induce Straub's phenomenon, an opiate-analogous effect characterized by an S-shaped dorsiflexion of the tail and perineum protrusion in mice.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If benzodiazepines or their derivatives are used in pharmaceutical compositions, then anxiety and sedation effects are achieved, but opiate-analogous effects are not induced

Engineering Contradiction:
Improvepharmacological effect spectrumVSAvoidopiate-analogous effect induction
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent combines lormetazepam (a benzodiazepine derivative) with macrogol 15 hydroxystearate (a non-ionic solubilizer) in specific concentrations to create a composition that produces both benzodiazepine effects and opiate-analogous Straub's phenomenon, thereby expanding the pharmacological effect spectrum

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite pharmaceutical composition where lormetazepam and macrogol 15 hydroxystearate work synergistically. The specific combination ratio and formulation create a new therapeutic agent with dual mechanisms of action, producing both anxiety-sedation effects and morphine-like Straub's phenomenon

Inventive Principle:
Principle #40Composite materials

2Adaptability or versatility

If lormetazepam is combined with macrogol 15 hydroxystearate in specific concentrations, then Straub's phenomenon is induced, but the composition complexity increases

Engineering Contradiction:
Improveopiate-analogous effect inductionVSAvoidpharmaceutical composition formulation
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent specifies precise concentration ranges for lormetazepam (0.1-10 mg/ml) and macrogol 15 hydroxystearate (1-50% w/v) to optimize the induction of Straub's phenomenon while maintaining formulation feasibility. These parameter specifications balance effect induction with manufacturing practicality

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

The composition effectively induces Straub's phenomenon, previously only observed with morphine or morphine analogues, demonstrating an opiate-analogous effect suitable for anesthesia, intensive care, pain therapy, and neurology/psychiatry applications.

Implementation Method 1

Lormetazepam has a very high affinity for specific binding sites in the central nervous system. These binding sites are in close functional connection with the receptors of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). After binding to the receptor, lormetazepam potentiates GABAergic inhibition of the activity of downstream neurons.

Methodology Applied
Scientific EffectReceptor binding: Absorption (physical)

Implementation Method 2

The non-ionic solubilizer is macrogol 15 hydroxystearate. Macrogol 15 hydroxystearate dissolves in water, ethanol and 2-propanol to form a clear solution.

Methodology Applied
Scientific EffectSolubilization: Solvation

Data Source

PatentEP2231117B1Benzodiazepine and/or pharmaceutical composition comprising benzodiazapine derivatives
Publication Date: 2015.10.14 DR FRANZ KOHLER CHEM GMBH

AI summary

The invention relates to a pharmaceutical composition characterized in that it comprises a benzodiazapine and/or benzodiazapine derivative, and a non-ionic solubilizer, and induces in said combination an analogous effect to an opiate, described as a Straub phenomenon.