Cyclized Peptide Inhalation for Intrapulmonary Inflammation
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Solution Overview
Problem
Current treatments for sepsis and intrapulmonary inflammation, such as those induced by systemic bacteremia and lipopolysaccharide infusion, are inadequate in effectively reducing inflammatory cytokines and enzymes in the lungs, leading to organ dysfunction and septic shock.
Innovation Solution
A cyclized compound with a specific amino acid sequence, such as Cyclo(4-aminobutanoic acid-GQRETPEGAEAKPWYD), is administered via inhalation to attenuate intrapulmonary inflammation by reducing the expression of inflammatory cytokines like TNF-α and COX-2, forming amide bonds between terminal amino acids to stabilize the peptide and enhance its anti-inflammatory effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments (intravenous fluids, antibiotics, corticosteroids) are used for sepsis, then systemic infection is addressed, but intrapulmonary inflammation and cytokine expression are not effectively reduced
Solution Approach 1:
The patent introduces a peptide compound as an intermediary substance that mediates between the systemic infection and the pulmonary inflammation. The peptide acts as a signaling molecule that specifically targets and reduces intrapulmonary inflammatory responses without interfering with conventional systemic treatments, thereby filling the therapeutic gap between antibiotics and corticosteroids.
Solution Approach 2:
The invention changes the parameter of treatment delivery by using inhalation administration instead of intravenous injection. This parameter change allows the peptide to directly reach the pulmonary target site, increasing local concentration and effectiveness while reducing systemic side effects and treatment complexity.
2Object-affected harmful factors
If corticosteroids are used to reduce inflammation, then inflammatory response is suppressed, but side effects and treatment controversy increase
Solution Approach 1:
The peptide treatment exhibits local quality by specifically targeting intrapulmonary inflammation while sparing other body systems from corticosteroid side effects. The inhalation route ensures high local concentration in the lungs with minimal systemic absorption, providing site-specific anti-inflammatory action that improves safety while maintaining efficacy.
Solution Approach 2:
The peptide compound acts as a short-lived, rapidly metabolized substance that provides acute anti-inflammatory effect without the cumulative side effects of corticosteroids. This disposable-like approach to treatment allows repeated administration without building up harmful systemic effects, resolving the reliability controversy surrounding steroid use.
3Quantity of substance
If LPS is used to induce sepsis model, then systemic inflammatory response is achieved, but intrapulmonary inflammation remains uncontrolled
Solution Approach 1:
The patent converts the harmful LPS-induced pulmonary inflammation into a beneficial therapeutic target. By using the same LPS challenge model to induce the problem, then applying peptide inhalation to specifically resolve the resulting intrapulmonary inflammation, the invention transforms the harmful effect into an opportunity for targeted therapy that protects lung tissue while allowing controlled study of the inflammatory response.
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 compound significantly reduces intrapulmonary expression of inflammatory markers and enzymes, providing a novel approach to mitigate lung injury and sepsis-induced inflammation, as demonstrated in a porcine model of LPS-induced sepsis, with stable and effective biological activity even without stabilizers.
Implementation Method 1
forming amide bonds between terminal amino acids to stabilize the peptide and enhance its anti-inflammatory effects
Data Source
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Figure 3a~3b
AI summary
A cyclized compound of the amino acid sequence of formula X1 -GQRETPEGAEAKPWY-X2 wherein X1 comprises an amino acid (sequence) with 1 to 4, in particular 1 to 3 members, comprising natural or unnatural amino acids, in particular selected from the amino acid (sequence) C, KSP, K, ornithin, 4-amino butanoic acid, β-alanine, and X2 comprises one amino acid, selected from natural amino acids, in particular selected from the group C, D, G and E, and wherein X comprises the N-terminal amino acid at ist first left position and X2 comprises the C-terminal amino acid at its last right position, optionally in the form of a salt for use in the treatment of inflammation, a pharmaceutical composition for treating inflammation comprising such compound and a method of treating inflammation comprising administering an effective amount of such compound to a mammal in need thereof.