Lipophilic Hydrophilic Statin Combination for LDL Reduction

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Solution Overview

Problem

Current statin therapies for cardiovascular and vascular diseases only achieve modest LDL cholesterol reductions with higher doses leading to increased side effects, and no combination of lipophilic and hydrophilic statins has been previously explored for enhanced cholesterol lowering.

Innovation Solution

A composition comprising a combination of one or more lipophilic statins (such as atorvastatin, simvastatin, and lovastatin) with one or more hydrophilic statins (such as pravastatin, fluvastatin, and rosuvastatin), along with optional adjuncts like ezetimibe and niacin, to synergistically lower LDL cholesterol levels, with dose titration and adjunct addition strategies to achieve therapeutic goals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If the dose of a single statin is increased to maximally reduce LDL cholesterol levels, then LDL cholesterol decreases by only 6-10%, but side effect rates easily double

Engineering Contradiction:
ImproveLDL cholesterol reductionVSAvoidside effect rates
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent combines two different statins (a lipophilic statin and a hydrophilic statin) into a single composition, allowing the therapeutic effects to be additive or synergistic while maintaining lower individual doses of each component, thereby reducing side effects while achieving greater LDL cholesterol reduction

Inventive Principle:
Principle #5Merging (Combining)

2Object-affected harmful factors

If a single statin is used at recommended starting doses, then side effects are minimized, but LDL cholesterol reduction is only 20-40%

Engineering Contradiction:
Improveside effect ratesVSAvoidLDL cholesterol reduction
Core Design Contradiction:
Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The patent combines two different statins (a lipophilic statin and a hydrophilic statin) into a single composition, allowing the therapeutic effects to be additive or synergistic while maintaining lower individual doses of each component, thereby reducing side effects while achieving greater LDL cholesterol reduction

Inventive Principle:
Principle #5Merging (Combining)

3Object-affected harmful factors

If combination therapy with lipophilic and hydrophilic statins is used at lower doses, then side effects are reduced, but achieving LDL levels below 70 mg/dL becomes more challenging

Engineering Contradiction:
Improveside effect ratesVSAvoidLDL cholesterol reduction magnitude
Core Design Contradiction:
Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The patent changes the parameter of statin combination by selecting specific lipophilic and hydrophilic statins with different pharmacokinetic properties, allowing for optimized dosing that achieves both safety and efficacy

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite therapeutic composition combining two不同类型的 statins, leveraging their complementary mechanisms and tissue distribution patterns to achieve enhanced LDL lowering at reduced doses

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 of lipophilic and hydrophilic statins demonstrates additive to synergistic LDL cholesterol lowering effects, significantly improving symptoms and health outcomes in high-risk patients, with reduced side effects and enhanced efficacy when used at lower doses, often achieving LDL levels below 70 mg/dL, thereby stabilizing or regressing plaques.

Implementation Method 1

Statins are medicines that lower blood cholesterol levels by inhibiting HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase), an enzyme that is involved in the biosynthesis of cholesterol

Methodology Applied
Scientific EffectHMG-CoA reductase inhibition: Enzyme

Data Source

PatentEP1984026B1Compositions treating cardiovascular, cerebrovascular and other vascular disease patients
Publication Date: 2013.05.01 BRYSON ISRAEL BEN DAVID

AI summary

Disclosed are compositions having one or more statins from two different groups, 1) one or more lipophilic statins and 2) one or more hydrophilic statins. The present invention is also directed towards methods of treating patients with cardiovascular diseases and other vascular diseases, including but not limited to Diabetes Mellitus type I and/or II (DM), coronary artery diseases (CAD), peripheral vascular diseases (PVD), cerebrovascular disease, post myocardial infarctions (post MI), post cerebrovascular accidents (post CVA), Hypertriglyceridemia, Hypercholesterolemia, and abdominal aortic aneurysms (AAA) using the composition of the present invention.