Dolcanatide Rectal Formulations for Ulcerative Colitis Treatment

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Solution Overview

Problem

Current treatments for ulcerative colitis, an inflammatory bowel disease, are inadequate as they often rely on corticosteroids and immunomodulators that come with significant side effects and do not provide a cure, necessitating a more effective and side-effect-free therapeutic option.

Innovation Solution

Rectal administration of dolcanatide (SP-333), a guanylate cyclase C (GC-C) agonist, which is administered as an enema or suppository, to alleviate symptoms of ulcerative colitis by stimulating cGMP production and reducing inflammation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If corticosteroids and immunomodulators are used to treat ulcerative colitis, then inflammation is reduced and symptoms are relieved, but significant side effects occur and the disease is not cured

Engineering Contradiction:
Improvesymptom relief effectivenessVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs parameter changes by modifying the chemical structure of GC-C agonists through various substitutions and modifications to optimize therapeutic efficacy while minimizing side effects. Different agonist variants are created with specific amino acid changes to achieve the desired balance between effectiveness and safety profile

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses GC-C agonists as intermediary substances that mediate the treatment of ulcerative colitis by activating the guanylate cyclase C receptor pathway. These agonists serve as intermediaries between the administered drug and the therapeutic effect, triggering a cascade of biochemical events that reduce inflammation without the harmful side effects of traditional treatments

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If current ulcerative colitis treatments are used, then symptoms are managed, but no cure is achieved and continuous treatment is required

Engineering Contradiction:
Improvesymptom management effectivenessVSAvoidtreatment duration
Core Design Contradiction:
ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by using GC-C agonists to proactively address the underlying inflammatory mechanisms of ulcerative colitis before symptoms become severe. The treatment aims to prevent disease progression and achieve remission through early and sustained activation of protective physiological pathways

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements continuity of useful action through formulations designed for sustained release and continuous therapeutic effect. The rectal formulations and dosing regimens are optimized to maintain continuous presence of the agonist at the site of action, ensuring uninterrupted anti-inflammatory activity and preventing symptom recurrence

Inventive Principle:
Principle #20Continuity of useful action

3Reliability

If rectal formulations of dolcanatide are administered, then treatment effectiveness is improved with minimal side effects, but formulation complexity increases

Engineering Contradiction:
Improvetreatment safety and toleranceVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the treatment approach into distinct formulation types (enemas, suppositories, gels) that can be selected based on patient needs and disease severity. Each formulation type is optimized for specific delivery requirements while maintaining the core active ingredient, allowing modular selection without increasing overall system complexity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs disposable single-use rectal formulations that eliminate the need for complex storage and handling infrastructure. Each dose is provided in a pre-prepared, sterile, single-use container that is discarded after one use, simplifying the overall system while ensuring treatment safety and efficacy

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

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

Dolcanatide effectively reduces symptoms of ulcerative colitis with minimal side effects, as demonstrated by a double-blind study showing significant improvement in patients with mild to moderate ulcerative colitis, indicating its potential as a safe and well-tolerated treatment.

Implementation Method 1

dolcanatide (i.e., SP-333 or SEQ ID NO: 9)... a guanylate cyclase C (GC-C) agonist... by stimulating cGMP production

Methodology Applied
Scientific EffectGuanylate cyclase C activation: Enzyme

Data Source

PatentUS10653744B2Formulations and methods for treating ulcerative colitis
Publication Date: 2020.05.19 BAUSCH HEALTH IRELAND LTD

AI summary

This invention provides composition and methods to prevent, treat or alleviate a symptom of ulcerative colitis comprising administering to a patient dolcanatide.