Thermosensitive Bio-adhesive Hydrogel for Ureteral Stone Clearance

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Solution Overview

Problem

Current methods for treating nephrolithiasis, such as flexible ureteroscopy and laser lithotripsy, fail to effectively remove small stone fragments and often result in thermal damage to the urothelium due to temperature spikes during the procedure, with no effective mechanism to mitigate these issues.

Innovation Solution

Administration of a thermosensitive bio-adhesive hydrogel comprising chitosan or tri-block copolymers before lithotripsy to protect the urothelium from thermal damage and encapsulate renal stones, allowing for enhanced stone clearance and prevention of regrowth by maintaining a temperature below 36°C and encapsulating fragments within the hydrogel for easier removal.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If laser lithotripsy is used to fragment renal calculi, then stone fragmentation is achieved, but temperature spikes occur causing thermal damage to the urothelium

Engineering Contradiction:
Improvestone fragmentationVSAvoidthermal damage to urothelium
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

A thermosensitive hydrogel is introduced as an intermediary substance between the laser energy and the urothelium. The hydrogel absorbs and dissipates thermal energy, preventing direct thermal damage to the urothelium while allowing laser fragmentation of stones. The gel acts as a thermal buffer that mediates the interaction between laser energy and tissue.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The thermosensitive hydrogel undergoes phase transition from liquid to gel state in response to temperature changes. This phase transition enables the gel to solidify around stone fragments at elevated temperatures, providing mechanical protection and thermal insulation to the urothelium during and after laser lithotripsy.

Inventive Principle:
Principle #36Phase transitions

2Productivity

If high-powered lasers are used for lithotripsy, then stone fragmentation efficiency is improved, but the risk of thermal damage to surrounding tissues increases

Engineering Contradiction:
Improvestone fragmentation efficiencyVSAvoidthermal damage to surrounding tissues
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The thermosensitive hydrogel serves as a protective intermediary that allows high-powered lasers to be used for efficient stone fragmentation while simultaneously protecting surrounding tissues from thermal damage. The gel absorbs excess thermal energy and dissipates it safely.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The hydrogel is administered before laser lithotripsy to establish a protective barrier around the stone and surrounding tissues. This beforehand cushioning prepares the tissue environment to withstand the thermal effects of high-powered lasers during the procedure.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Productivity

If stone baskets are used to remove fragments, then larger fragments can be extracted, but fragments smaller than 2 mm are not effectively removed

Engineering Contradiction:
Improvestone fragment removalVSAvoidremoval of small fragments
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The thermosensitive hydrogel acts as an intermediary carrier that envelops and transports stone fragments of all sizes, including those too small to be captured by stone baskets. The gel's粘附 properties enable it to bind and retrieve even sub-2mm fragments effectively.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Object-affected harmful factors

If ureteral access sheath is used to promote cooling irrigation, then thermal damage is mitigated, but the cost of the procedure increases and ureter splitting occurs in 20% of cases

Engineering Contradiction:
Improvethermal damage mitigationVSAvoidprocedure cost and ureter splitting risk
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The thermosensitive hydrogel serves as a direct protective intermediary applied to the urothelium, eliminating the need for ureteral access sheath. The gel provides thermal protection at the tissue level, avoiding the complications and costs associated with sheath insertion.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention extracts the thermal protection function from the ureteral access sheath system and transfers it directly to the urothelium via the thermosensitive hydrogel. This removes the unnecessary complexity and risks of sheath insertion while maintaining thermal protection.

Inventive Principle:
Principle #2Taking out (Extraction)

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 hydrogel achieves a stone clearance rate of at least 90% while protecting the urothelium from thermal damage and preventing renal backflow, reducing the risk of urosepsis and stone regrowth by effectively encapsulating and removing stone fragments and dust.

Implementation Method 1

thermosensitive bio-adhesive hydrogel... thermo-reversible hydrogel comprises chitosan or at least one tri block copolymer

Methodology Applied
Scientific EffectThermosensitive phase transition: Phase Change

Implementation Method 2

protecting the patient from potential harm from excessive temperatures... protects the subject from urothelium thermal damage... maintaining a temperature below 36°C

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Implementation Method 3

thermosensitive bio-adhesive hydrogel... administration of the thermosensitive bio-adhesive hydrogel protects the subject from urothelium thermal damage

Methodology Applied
Scientific EffectAdhesion: Adhesive

Data Source

PatentUS11576744B2Thermosensitive bio-adhesive hydrogel for removal of ureteral and renal stones
Publication Date: 2023.02.14 UROGEN PHARMA LTD

AI summary

Provided herein are methods for treating nephrolithiasis and protecting the urothelium and inner lining of the kidney from thermal damage during lithotripsy by use of a thermosensitive bio-adhesive hydrogel. The described method dramatically improved the efficiency and effectiveness of stone clearance compared to conventional techniques while providing protection to the urothelium from potentially damaging temperature spikes.