PLGA Microspheres for Controlled PTH Release

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Solution Overview

Problem

Current methods for administering parathyroid hormone (PTH) suffer from low bioavailability and require frequent injections, causing discomfort for patients, and protein/peptide instability in the gastrointestinal tract hinders effective clinical usage.

Innovation Solution

Development of controlled release microspheres using poly(lactic-co-glycolic acid) (PLGA) to encapsulate PTH(1-34), stabilizing it for prolonged release and maintaining therapeutic concentration, achieved through a water-in-oil-in-water emulsion method with polyvinyl alcohol, providing a stable and biologically active delivery system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PTH is administered by subcutaneous injection, then bioavailability is improved, but patient discomfort increases due to frequent injections

Engineering Contradiction:

ImprovebioavailabilityVSAvoidpatient discomfort

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent segments the PTH delivery system by encapsulating PTH within PLGA microspheres, creating a controlled release system that delivers the hormone over an extended period (at least 18 days), thereby reducing the frequency of administrations and patient discomfort while maintaining therapeutic bioavailability

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies preliminary action by pre-encapsulating PTH in PLGA microspheres with controlled release properties before administration, allowing the hormone to be released gradually over time according to a predetermined profile, thus eliminating the need for frequent injections while ensuring sustained bioavailability

Inventive Principle:

Principle #10Preliminary action

2Ease of operation

If PTH is administered orally, then patient convenience is improved, but bioavailability deteriorates due to low absorption

Engineering Contradiction:

Improvepatient convenienceVSAvoidbioavailability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent uses PLGA microspheres as an intermediary carrier system that protects PTH from degradation in the gastrointestinal tract and facilitates its absorption, enabling oral administration to achieve therapeutic bioavailability while maintaining patient convenience

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If PTH is released quickly to achieve therapeutic effect, then treatment efficacy is improved, but duration of action deteriorates requiring frequent dosing

Engineering Contradiction:

Improvetreatment efficacyVSAvoidduration of action

Core Design Contradiction:

ProductivityVSDuration of action of moving object

Solution Approach 1:

The patent applies dynamics by designing a PLGA microsphere system with controlled release kinetics that dynamically adjust PTH release rates, initially providing high concentrations for rapid therapeutic effect followed by sustained lower concentrations to maintain treatment efficacy over at least 18 days, thereby balancing treatment efficacy with extended duration of action

Inventive Principle:

Principle #15Dynamics

4Stability of the object's composition

If protein/peptide is administered in aqueous formulation, then stability is improved, but bioavailability deteriorates due to degradation in gastrointestinal tract

Engineering Contradiction:

Improveprotein stabilityVSAvoidbioavailability

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent uses PLGA microspheres as an intermediary protective system that shields PTH from degradation in the gastrointestinal tract while maintaining its stability, enabling both stable protein preservation and improved bioavailability through controlled release

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

The PLGA microspheres achieve a stable release of PTH(1-34) for 18 days with effective therapeutic concentration, reducing patient discomfort and improving bioavailability, suitable for treating PTH-related disorders like osteoporosis and osteoarthritis.

Implementation Method 1

achieved through a water-in-oil-in-water emulsion method with polyvinyl alcohol

Methodology Applied

Scientific EffectEmulsion: Emulsion

Implementation Method 2

The PLGA microspheres achieve a stable release of PTH(1-34) for 18 days with effective therapeutic concentration

Methodology Applied

Scientific EffectDiffusion: Diffusion

Data Source

PatentUS8865220B2Method for controlled release of parathyroid hormone from encapsulated poly(lactic-glycolic)acid microspheres

Publication Date: 2014.10.21 KAOHSIUNG MEDICAL UNIVERSITY

AI summary

The present invention provides a method for producing a controlled release microsphere with mean average size greater than 50 μm, comprising preparing a water-in-oil (w/o) emulsion comprising an inner aqueous layer containing a pharmaceutically effective amount of a biologically active polypeptide with activity similar to parathyroid hormone, and an oil layer containing a polymer substance of poly(lactic-co-glycolic acid) (PLGA), then adding the w/o emulsion into aqueous polyvinyl alcohol (PVA) solution to form a water-in-oil-in-water (w/o/w) double emulsion and then desorbing the solvent in the oil layer. The present invention also provides a controlled release microsphere prepared by the method and use thereof.