Lyn Kinase Activator and TRPM8 Agonist for Adipocyte Beiging

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Solution Overview

Problem

Current drugs for modulating Lyn kinase and managing elevated glucose levels lack general utility in regulating lipid, lipoprotein, and insulin levels, and there is a need for safer, efficacious treatments for obesity, diabetes, and other glucose metabolism-related diseases.

Innovation Solution

Compositions comprising a Lyn kinase activator and a TRPM8 agonist, such as specific chemical formulas, are administered to reduce blood glucose levels, induce beiging of adipocytes, and treat various metabolic disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current drugs for modulating Lyn kinase are used, then glucose levels may be managed, but they lack general utility in regulating lipid, lipoprotein, and insulin levels

Engineering Contradiction:
Improveutility in regulating multiple metabolic parametersVSAvoidefficacy in glucose level management
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent combines a Lyn kinase activator with a TRPM8 agonist to create a composition that simultaneously addresses multiple metabolic parameters including glucose, lipid, lipoprotein, and insulin levels. This multi-functional approach resolves the contradiction by making the treatment versatile across different metabolic disorders while maintaining reliable efficacy through the synergistic action of both agents.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Reliability

If existing treatments for obesity and diabetes are used, then some metabolic parameters may be improved, but safer and more efficacious treatments are still needed

Engineering Contradiction:
ImproveefficacyVSAvoidsafety
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs a composite treatment approach by combining a Lyn kinase activator and a TRPM8 agonist in a single composition. This composite strategy enhances efficacy through synergistic mechanisms while potentially reducing safety concerns by allowing each component to be used at lower, safer doses compared to monotherapies. The combined approach addresses both efficacy and safety requirements for treating obesity and diabetes.

Inventive Principle:
Principle #40Composite materials

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 combination effectively reduces blood glucose levels, induces beiging of adipocytes, and treats metabolic syndrome, obesity, diabetes, and related conditions by enhancing insulin sensitivity and glucose utilization.

Implementation Method 1

inducing the beiging of adipocytes

Methodology Applied
Scientific EffectBeiging of adipocytes:

Implementation Method 2

A hallmark of both brown and beige adipocytes is the expression of thermogenic genes

Methodology Applied
Scientific EffectThermogenic gene expression:

Implementation Method 3

human white adipocytes express the cold-sensing receptor TRPM8 which activation by menthol and icilin induced a rise in [Ca2+]; and UCP1 expression

Methodology Applied
Scientific EffectTRPM8 activation:

Implementation Method 4

activation by menthol and icilin induced a rise in [Ca2+]

Methodology Applied
Scientific EffectCalcium signaling:

Implementation Method 5

increased mitochondrial membrane potential, glucose uptake and heat production

Methodology Applied
Scientific EffectGlucose uptake:

Implementation Method 6

enhancing insulin sensitivity and glucose utilization

Methodology Applied
Scientific EffectInsulin sensitivity enhancement:

Implementation Method 7

increased mitochondrial membrane potential, glucose uptake and heat production

Methodology Applied
Scientific EffectMitochondrial membrane potential increase:

Implementation Method 8

brown adipocytes, which arise from muscle precursors, are full of mitochondria to burn fat to create non-shivering thermogenic energy

Methodology Applied
Scientific EffectNon-shivering thermogenesis:

Data Source

PatentEP3609500B1Treatment of adipocytes
Publication Date: 2024.11.13 MELIOR DISCOVERY INC
  • EP3609500B1 patent drawingFigure 1
  • EP3609500B1 patent drawingFigure 2
  • EP3609500B1 patent drawingFigure 3

AI summary

The present disclosure provides compositions comprising a lyn kinase activator and TRPM8 agonist, and to methods of: reducing blood glucose levels, weight gain, or fat depot levels; treating metabolic syndrome, Syndrome X, obesity, prediabetes, type II diabetes, type I diabetes; treating hypercholesterolemia, hypertension, coronary heart disease, diabetic neuropathy, lipodystrophy, diabetic retinopathy, erectile dysfunction, kidney disease, dyslipidemia, dyslipoproteinemia, a peroxisome proliferator activated receptor-associated disorder, septicemia, a thrombotic disorder, or pancreatitis; inducing the beiging of adipocytes; and preventing pancreatic beta cell degeneration.