Dobesilic Acid Ophthalmic Ointment for Posterior Segment Delivery

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Solution Overview

Problem

Current methods for treating posterior segment eye diseases face challenges due to ocular barriers, leading to low bioavailability and invasive treatment options with significant risks, particularly for highly polar or hydrophilic drugs like calcium dobesilate monohydrate, which are quickly oxidized and have limited absorption across the corneal epithelium.

Innovation Solution

Topical administration of dobesilic acid and its pharmaceutically acceptable salts, such as calcium dobesilate and etamsylate, directly onto the eye surface, allowing these compounds to bypass anterior segment barriers and achieve higher bioavailability in the posterior segment, where they can exert vasoprotective, antioxidant, and anti-inflammatory effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If intravitreal injection is used to treat posterior segment eye diseases, then drug bioavailability is maximized, but the risk of blinding complications and retinal detachment increases

Engineering Contradiction:
Improvedrug bioavailabilityVSAvoidrisk of blinding complications
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent uses the conjunctival sac as an intermediary reservoir to accumulate drug before it gradually permeates through the cornea and other ocular barriers. This mediates between the need for high drug concentration and the need to avoid invasive procedures, allowing sustained drug release directly into the eye without intravitreal injection

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies drug-containing ointment to the conjunctival sac before the drug needs to reach the posterior segment. This preliminary placement allows the drug to gradually permeate through ocular barriers over time, achieving therapeutic concentrations in the vitreous cavity without direct intravitreal injection

Inventive Principle:
Principle #10Preliminary action

2Ease of operation

If topical administration is used for anterior segment disease, then the treatment is non-invasive, but drug residence time is limited due to blinking and tear film turnover

Engineering Contradiction:
Improvenon-invasive treatmentVSAvoiddrug residence time
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The patent uses an ointment formulation that forms a semi-solid film on the ocular surface, which is more stable and longer-lasting than aqueous eye drops. This ointment film persists through blinking and tear turnover, maintaining drug availability for prolonged periods

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

The ointment is applied preliminarily to the conjunctival sac, creating a reservoir that slowly releases drug over time. This preliminary placement ensures continuous drug availability despite blinking and tear film turnover that would otherwise rapidly clear aqueous formulations

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If highly polar drugs like calcium dobesilate monohydrate are topically administered, then the treatment is non-invasive, but absorption across the corneal epithelium is limited due to oxidation and hydrophilicity

Engineering Contradiction:
Improvenon-invasive treatmentVSAvoiddrug absorption
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The patent changes the physical state of the drug from a highly soluble crystalline form to an ointment formulation with different release characteristics. This formulation modification allows the polar drug to be delivered through the ocular surface by altering how the drug is presented and released, overcoming the limitation of corneal permeation for highly polar substances

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The ointment base acts as an intermediary vehicle that facilitates the delivery of highly polar drugs like calcium dobesilate monohydrate through the corneal epithelium. The ointment formulation protects the drug from premature oxidation and provides a sustained release mechanism that overcomes the rapid clearance and poor absorption issues of topical polar drugs

Inventive Principle:
Principle #24Intermediary (Mediator)

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

This approach enables effective treatment of posterior segment eye diseases with higher bioavailability and reduced side effects compared to systemic or invasive intravitreal injections, as dobesilic acid salts remain active and effective in the posterior segment for an extended period, providing therapeutic benefits without the risks associated with invasive treatments.

Implementation Method 1

They topically administered, they pass through cornea, conjunctiva and sclera, but also overcome the barrier of iris and lens

Methodology Applied
Scientific EffectPermeation: Permeation

Implementation Method 2

CDO is the monohydrate of calcium salt of dobesilic acid... CDO is a compound that can be easily oxidized to calcium 3,6-dioxocyclohexa-1,4-diene-1-sulfonate and thus it is highly unstable

Methodology Applied
Scientific EffectOxidation: Oxidation

Data Source

PatentEP3720428B1Ophthalmic topical composition comprisng dobesilic acid for treating diseases of the posterior segment of the eye
Publication Date: 2023.01.11 LAB SALVAT SA
  • EP3720428B1 patent drawingFigure 1~2
  • EP3720428B1 patent drawingFigure 3
  • EP3720428B1 patent drawing

AI summary

The invention relates to a new therapeutic approach for treatment and/or prevention of a disease of the posterior segment of the eye, in particular for retinal and optic nerve pathologies. Dobesilic acid and/or a pharmaceutically acceptable salt,or an ester of any of the acid or the salt,are proposed for use topically administered onto eye surface. There are also disclosed new compositions comprising dobesilic acid and/or a pharmaceutically acceptable salt,or an ester of any of the acid or the salt, adapted for performing the treatment and/or prevention of diseases of the posterior segment of the eye.