Preterm Birth Animal Model via Cervical Excision and LPS Injection

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Solution Overview

Problem

Current animal models for preterm birth are inadequate in accurately replicating the condition induced by cervical damage, leading to high mortality rates and limited effectiveness in studying the mechanisms and developing therapies for preterm birth.

Innovation Solution

A method involving cervical excision in non-human mammals followed by intrauterine or intraperitoneal injection of lipopolysaccharide to induce preterm birth, allowing for controlled and predictable timing of preterm birth, reducing mortality rates and improving model accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If lipopolysaccharide is injected between two gestational sacs near the cervix at day 15-17 of gestation to induce preterm birth, then preterm birth can be induced, but mortality increases excessively and preterm birth yield decreases

Engineering Contradiction:
Improvepreterm birth yieldVSAvoidmortality
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The cervix is excised before pregnancy occurs, creating a pre-conditioned state that makes the animal more susceptible to preterm birth induction. This preliminary action allows for lower doses of lipopolysaccharide to be used later, reducing mortality while maintaining preterm birth yield

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The injection timing is changed from day 15-17 of gestation to day 18-20, and the injection location is changed from between gestational sacs to intrauterine or intraperitoneal administration. These parameter changes optimize the induction process to reduce mortality while maintaining effectiveness

Inventive Principle:
Principle #35Parameter changes

2Reliability

If bacteria are injected into the uteri of pregnant rabbits through a hysteroscope to induce preterm birth, then preterm birth can be induced, but the procedure becomes complicated and costs increase

Engineering Contradiction:
Improvepreterm birth inductionVSAvoidprocedure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The complex hysteroscope injection procedure is replaced by simpler cervical excision followed by straightforward intrauterine or intraperitoneal injection. This extracts the unnecessary complexity while maintaining the preterm birth induction effect

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention uses simple, inexpensive materials such as scissors for cervical excision and standard injection needles, replacing the expensive and complex hysteroscope equipment. This significantly reduces procedural costs while achieving the same biological effect

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Reliability

If bacteria are injected into the uteri of pregnant rabbits through a hysteroscope to induce preterm birth, then preterm birth can be induced, but the time required for symptoms to be reproduced becomes very long

Engineering Contradiction:
Improvepreterm birth inductionVSAvoidtime for symptom reproduction
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

Cervical excision is performed before pregnancy, creating a pre-conditioned state that accelerates the response to subsequent lipopolysaccharide injection. This preliminary preparation significantly reduces the time required for preterm birth symptoms to appear

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Changing from bacterial injection to lipopolysaccharide injection, and optimizing the timing to day 18-20 of gestation, accelerates the induction process. The lipopolysaccharide acts more rapidly than bacteria, and the optimized timing ensures faster symptom reproduction

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3453255B1Method for producing a non-human animal model of preterm birth, and non-human animal model of preterm birth produced by same
Publication Date: 2023.06.21 KOREA UNIV RES & BUSINESS FOUND
  • EP3453255B1 patent drawingFigure 1a~1b
  • EP3453255B1 patent drawingFigure 2~3
  • EP3453255B1 patent drawingFigure 4a~4b

AI summary

The present invention relates to a method for producing an animal model of preterm birth and an animal model of preterm birth produced by the method. The animal model of the present invention can be effectively applied to investigate the causes and symptoms of preterm birth induced by cervical injury. The mortality rate of the animal model according to the present invention is low until preterm birth despite its induced preterm birth. In addition, the animal model of the present invention is produced in a higher yield than any other existing model. Furthermore, the preterm birth of the animal model according to the present invention is induced at a desired time point. Due to these advantages, the animal model of the present invention can be effectively applied to investigate the causes and mechanisms of preterm birth. The mortality rate of premature neonates born from the animal model of the present invention is considerably low and the premature neonates are immature. Therefore, the animal model of the present invention can be effectively applied to studies on complications of premature neonates.