Dry Powder Antibiotic Compositions for Multidrug-Resistant Infections

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Solution Overview

Problem

Current therapeutic options for multidrug-resistant bacterial infections, particularly respiratory infections caused by Gram-negative bacteria, are limited due to rising resistance rates, necessitating novel antibiotic compositions that can effectively target these pathogens while minimizing resistance emergence.

Innovation Solution

A dry powder composition comprising a polymyxin antibiotic combined with at least one other antibiotic from various classes, such as aminoglycosides, ansamycins, or carbapenems, formulated for inhalation to achieve high minimum inhibitory concentrations directly in the lungs, thereby enhancing treatment efficacy and reducing resistance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If combination regimens of multiple antibiotic classes are used, then efficacy against multidrug-resistant bacteria is improved and resistance emergence is prevented, but device complexity and formulation complexity increase

Engineering Contradiction:

Improvetreatment efficacyVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines multiple antibiotic classes (polymyxin with at least one other antibiotic from aminoglycoside, ansamycin, carbacephem, carbapenem, cephalosporin, glycopeptide, lincosamide, lipopeptide, macrolide, monobactam, nitrofuran, oxazolidonone, penicillin, polypeptide, quinolone, sulfonamide, tetracycline, chloramphenicol, phosphonic acid antibiotic or mycobacteria antibiotic groups) into a single dry powder composition that can be administered together, achieving synergistic effects while simplifying administration compared to separate formulations

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention creates a composite antibiotic formulation where polymyxin is combined with at least one other antibiotic from specified classes in specific weight ratios (polymyxin: 1-50 wt%, other antibiotic: 50-99 wt%), forming a unified dry powder composition that leverages the complementary mechanisms of action of different antibiotic classes to treat multidrug-resistant bacteria

Inventive Principle:

Principle #40Composite materials

2Reliability

If inhaled delivery of combination compounds is used to achieve high minimum inhibitory concentrations in lungs, then direct lung targeting and eradication effectiveness are improved, but manufacturing precision and formulation requirements increase

Engineering Contradiction:

Improvedirect lung targeting effectivenessVSAvoidformulation precision

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent delivers the dry powder composition directly to the lungs via inhalation, achieving high local concentrations of antibiotics at the site of infection (minimum inhibitory concentrations in lungs) while minimizing systemic exposure, thereby maximizing therapeutic effectiveness at the target site with reduced off-target effects

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention optimizes the aerodynamic properties of the dry powder formulation (particle size distribution, flow characteristics, dispersibility) to ensure efficient lung deposition, and carefully controls the weight ratios of antibiotics (polymyxin: 1-50 wt%, other antibiotic: 50-99 wt%) to achieve synergistic concentrations at the site of infection

Inventive Principle:

Principle #35Parameter changes

3Reliability

If higher doses of individual antibiotics are used to overcome resistance, then treatment effectiveness is improved, but side effects and treatment costs increase

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the problem of bacterial resistance into a benefit by using combination therapy where polymyxin (a last-line antibiotic with high toxicity) is combined with at least one other antibiotic class, allowing lower doses of each individual antibiotic to achieve synergistic killing effects, thereby reducing the side effects and toxicity associated with high-dose monotherapy while maintaining treatment effectiveness

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

By merging polymyxin with at least one other antibiotic from specified classes in optimized weight ratios (polymyxin: 1-50 wt%, other antibiotic: 50-99 wt%), the formulation achieves enhanced bactericidal activity at lower individual drug concentrations, reducing the harmful side effects and treatment costs associated with higher doses of single antibiotics

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS11883460B2Antibiotic compositions for treating bacterial infections

Publication Date: 2024.01.30 NAT UNIV HOSPITAL (SINGAPORE) PTE LTD

AI summary

The present disclosure provides dry powder antibiotic compositions that are effective in the treatment of bacterial infections and associated conditions. Moreover, the present disclosure provides dry powder antibiotic compositions for the treatment of bacterial infections, by multi-drug resistant bacteria, resulting in the subsequent reduction in the prevalent rates of drug resistance.