Phospholipid-steroid ocular formulation reduces intraocular pressure

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Solution Overview

Problem

Intravitreal corticosteroid injections for conditions like macular edema and uveitis are effective but associated with significant side effects such as infectious endophthalmitis, retinal detachment, and increased intraocular pressure due to repetitive administration, necessitating a reduction in side effects.

Innovation Solution

A pharmaceutical composition combining a lipid cake mixture of phospholipids and cholesterol with a steroid solution, where the total amount of phospholipids is less than 2.5 umol per 50 ul, reducing side effects compared to compositions with higher phospholipid amounts, and is administered for ocular delivery to treat ophthalmic diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If intravitreal corticosteroid injection is administered to treat macular edema and uveitis, then therapeutic efficacy is improved, but side effects such as increased intraocular pressure, corneal edema, and opacity occur

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical composition parameters of the injection formulation by incorporating phospholipids at controlled concentrations (0.1-10% w/v) alongside corticosteroids. This parameter modification reduces side effects like increased intraocular pressure and corneal damage while preserving therapeutic efficacy for treating macular edema and uveitis

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite pharmaceutical formulation combining corticosteroids with phospholipids (such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, or phosphatidic acid). This composite material approach allows the formulation to deliver therapeutic benefits while reducing harmful side effects through the synergistic interaction between the two components

Inventive Principle:
Principle #40Composite materials

2Duration of action of stationary object

If repetitive intravitreal injection is performed to maintain optimal corticosteroid concentration, then therapeutic effect is maintained, but complications such as infectious endophthalmitis, retinal detachment, and traumatic cataract increase

Engineering Contradiction:
Improveduration of therapeutic effectVSAvoidinjection-related complications
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent employs phospholipid-based formulations that dynamically interact with ocular tissues, providing sustained drug release and extended therapeutic duration. This reduces the frequency of repetitive injections needed, thereby lowering the risk of injection-related complications while maintaining effective corticosteroid levels

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

Phospholipids act as intermediary carriers that facilitate prolonged retention and controlled release of corticosteroids in the ocular environment. This intermediary mechanism extends the duration of therapeutic action, reducing the need for frequent re-injection and associated complications

Inventive Principle:
Principle #24Intermediary (Mediator)

3Stability of the object's composition

If high concentration of phospholipids is used in the composition, then stability and retention in vitreous humor are improved, but side effects are increased

Engineering Contradiction:
Improvecomposition stabilityVSAvoidside effects
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the phospholipid concentration parameter within a specific range (0.1-10% w/v, preferably 0.5-5% w/v) to achieve the desired balance. This parameter optimization ensures sufficient stability and retention in the vitreous humor while avoiding the side effects associated with excessively high phospholipid concentrations

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS10350294B2Pharmaceutical compositions to reduce complications of ocular steroid
Publication Date: 2019.07.16 TLC BIOPHARMACEUTICALS INC

AI summary

The present invention relates to pharmaceutical compositions comprising a combination of a lipid cake mixture comprising one or more phospholipids, with or without cholesterol, and a steroid solution comprising an ocular steroid, derivative thereof, a pharmaceutically acceptable salt thereof or a prodrug thereof, wherein the total amount of the phospholipid in the said composition is about 0.1 umol to less than about 2.5 umol per 50 ul of pharmaceutical composition and the side effects of the ocular steroid are reduced. The pharmaceutical composition is preferably administered by ocular route to treat ophthalmic diseases.