Gastro-resistant Enzyme Dosage Form for Intestinal Delivery

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Solution Overview

Problem

Current oral administration of therapeutic enzymes for intestinal diseases faces challenges due to gastric and intestinal degradation, making it difficult to deliver enzymes effectively to the intestinal tract without loss of activity.

Innovation Solution

A gastro-resistant solid dosage form combining a cationic polymer like chitosan with an anionic polymer such as carboxymethylstarch, along with histaminase and catalase enzymes, is developed to protect enzymes from gastric acidity and ensure intestinal delivery, using a ratio of 9:1 to 1:9 for the enzymes and polymers, respectively.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If oral administration of therapeutic enzymes is used for intestinal diseases, then the therapeutic effect can be achieved, but the enzymes are degraded by gastric and intestinal enzymes, resulting in loss of activity

Engineering Contradiction:
Improveenzyme activityVSAvoidgastric and intestinal degradation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by pre-coating the enzyme with protective polymers (chitosan and carboxymethylstarch) before administration. This protective layer is established in advance to prevent degradation by gastric and intestinal enzymes, ensuring the enzyme remains active when it reaches the intestinal tract.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses polymer coatings (chitosan and carboxymethylstarch) as intermediary substances that protect the enzyme from direct contact with degrading enzymes in the gastrointestinal tract. These intermediaries form a protective barrier that allows the enzyme to survive passage through the stomach and intestines.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If polymer coatings are used to protect enzymes from degradation, then enzyme stability is improved, but the complexity of the formulation increases

Engineering Contradiction:
Improveenzyme stabilityVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent employs composite materials by combining chitosan (a cationic polymer) with carboxymethylstarch (an anionic polymer) to create a protective coating system. This composite approach provides enhanced stability through electrostatic interactions between the oppositely charged polymers, while the use of natural, biocompatible materials keeps the formulation relatively simple.

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 formulation provides effective protection against gastric degradation and controlled release of enzymes in the intestinal tract, enhancing the therapeutic potential for treating intestinal diseases by reducing histamine levels and oxidative stress.

Implementation Method 1

A gastro-resistant solid dosage form combining a cationic polymer like chitosan with an anionic polymer such as carboxymethylstarch

Methodology Applied
Scientific EffectElectrostatic interaction:

Implementation Method 2

The diamine oxidase (EC 1.4.3.6), also called histaminase, catalyses oxidative deamination of histamine and other biogenic amines

Methodology Applied
Scientific EffectEnzymatic degradation: Enzyme

Implementation Method 3

Catalase (EC 1.11.1.6) is an anti-oxidant enzyme that specifically catalyzes the decomposition of H2O2

Methodology Applied
Scientific EffectEnzymatic decomposition: Enzyme

Data Source

PatentEP2694098B1Oral enzyme compositions for intestinal delivery
Publication Date: 2018.09.26 HISTAPHARM
  • EP2694098B1 patent drawingFigure 1(a)~1(b)
  • EP2694098B1 patent drawingFigure 2
  • EP2694098B1 patent drawingFigure 3(a)~3(b)

AI summary

The present disclosure describes compositions for intestinal delivery of enzyme formulations and method of treating health problems with these formulations. More specifically, the enzyme formulations include at least one histaminase and various methods of treatment of physical conditions, such as inflammation, allergy, histamine intolerance, and intestinal cancer.