Gel-Type Antibiotic Composition for Localized Osteo-Articular Infection Treatment

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Solution Overview

Problem

Current antibiotic delivery methods, such as oral or parenteral administration, are insufficiently effective for localized bacterial infections, particularly osteo-articular infections, due to suboptimal bioavailability and inability to maintain effective antibiotic concentrations at the infection site.

Innovation Solution

A pharmaceutical composition comprising a gelled aqueous phase with hydrophilic polymer gélifiers and lipid nanocapsules containing daptomycin, which allows for controlled and prolonged release of the antibiotic directly to the infection site, enhancing bioavailability and maintaining effective concentrations for at least 14 days.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If antibiotics are administered orally or parenterally, then the treatment can be systematically delivered to the patient, but the diffusion at the site of infection is insufficient and effective concentrations cannot be maintained

Engineering Contradiction:
Improveantibiotic concentration at infection siteVSAvoidlocalized delivery effectiveness
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The antibiotic is segmented into two delivery forms: free antibiotic molecules in the gelled aqueous phase for immediate availability, and antibiotic-loaded lipid nanocapsules for sustained release. This segmentation allows simultaneous achievement of high initial concentration and prolonged maintenance at the infection site.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The lipid nanocapsules are nested within the gelled aqueous phase matrix. The nanocapsules contain the antibiotic in their core, while the gel matrix provides structural support and controlled release environment. This nested structure enables the composition to achieve both localized targeting and extended duration of action.

Inventive Principle:
Principle #7Nested doll (Nesting)

2Quantity of substance

If lipid nanocapsules are used to transport antibiotics, then bioavailability is improved, but the antibiotic loading rate is limited to below 50 mg/ml and release profile cannot be modulated

Engineering Contradiction:
Improveantibiotic loading rateVSAvoidnanocapsule formulation complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The invention merges lipid nanocapsules with a gelled aqueous phase into a single composite formulation. The gel matrix serves multiple functions: it provides structural stability, enables high antibiotic loading (up to 250 mg/ml), and allows modulation of release kinetics through its gel properties, thereby overcoming the limitations of nanocapsules alone.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The formulation is a composite system combining lipid nanocapsules (for encapsulation and targeted delivery) with a gelled aqueous phase (for high loading capacity and controlled release). This composite approach leverages the advantages of both components while mitigating their individual limitations.

Inventive Principle:
Principle #40Composite materials

3Reliability

If high antibiotic concentrations are used to ensure efficacy, then treatment effectiveness is improved, but the duration of action is insufficient and repeated administrations are required

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidduration of antibiotic release
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The dual-phase system ensures continuous antibiotic availability: the gelled aqueous phase provides immediate high-concentration antibiotic action for rapid efficacy, while the lipid nanocapsules embedded within gradually release antibiotic over extended periods (up to 14 days or more), maintaining therapeutic levels without requiring repeated administrations.

Inventive Principle:
Principle #20Continuity of useful action

4Quantity of substance

If conventional nanocapsules are used for antibiotic delivery, then bioavailability is enhanced, but localized targeting of osteoarticular infections remains difficult

Engineering Contradiction:
Improvebioavailability of antibioticVSAvoidlocalized targeting capability
Core Design Contradiction:
Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The gel formulation is specifically designed for local application at the infection site (e.g., intra-articular injection, local wound application, or implant coating). The gel matrix provides localized retention of high antibiotic concentrations exactly where needed, while the nanocapsules ensure sustained release at the target site, achieving both high bioavailability and precise localized targeting.

Inventive Principle:
Principle #3Local quality

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 achieves effective localized delivery of antibiotics, significantly reducing bacterial loads in osteo-articular infections and maintaining high antibiotic concentrations beyond the initial treatment period, thereby improving treatment outcomes and reducing the need for repeated administrations.

Implementation Method 1

a gelled aqueous phase with at least one polymeric hydrophilic gelling agent

Methodology Applied
Scientific EffectGelation: Gel

Implementation Method 2

triblock copolymers consisting of poly(ethylene oxide) and poly(propylene oxide) having a lower critical solubility temperature (LCST) of between 15°C and 40°C

Methodology Applied
Scientific EffectLower critical solubility temperature transition: Phase Change

Implementation Method 3

said gelled aqueous phase further comprising at least one polyol; said polyol being sorbitol

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 4

said antibiotic(s) being released constantly over a period of at least 14 days

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP3908265B1Gel type pharmaceutical composition for treating/preventing an infection
Publication Date: 2025.04.23 REGHAL AMOKRANE
  • EP3908265B1 patent drawingFigure 1~2
  • EP3908265B1 patent drawingFigure 3~4
  • EP3908265B1 patent drawingFigure 5

AI summary

The present invention relates to a pharmaceutical composition stabilised in a gelled state at at least one temperature varying from 15°C to 40°C, comprising at least one aqueous phase gelled with at least one polymeric hydrophilic gelling agent, lipid nanocapsules comprising a liquid or semi-liquid lipid core at ambient temperature coated with a solid lipid coating at ambient temperature, said gelled aqueous phase and nanocapsules containing at least one antibiotic that is identical or different, the antibiotic in said aqueous phase being present therein in the solute state.