Hemostatic Microspheres for Homogeneous Clot Formation

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Solution Overview

Problem

Current hemostatic compositions, particularly those involving thrombin, face challenges in achieving rapid and reliable onset of hemostasis, especially in the presence of heparin or other anticoagulants, and often result in non-homogeneous clot formation.

Innovation Solution

The development of cross-linked polymer microspheres, such as gelatin microspheres with optimized particle size and pore diameter, combined with high doses of thrombin, which are designed to slowly release thrombin and improve mixing with blood, thereby enhancing clot strength and reducing the effects of heparin inhibition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high doses of thrombin are used to overcome heparin inhibition, then hemostasis reliability is improved, but clot formation becomes non-homogeneous

Engineering Contradiction:

Improvehemostasis reliabilityVSAvoidclot homogeneity

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The thrombin is distributed within numerous microsphere particles rather than applied as a single concentrated dose. Each microsphere contains a portion of the total thrombin load, and the collective effect of thousands of microspheres provides homogeneous distribution throughout the blood, achieving both high reliability and homogeneity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The microsphere serves as an intermediary carrier that facilitates uniform distribution of thrombin throughout the blood. The microspheres act as a delivery vehicle that prevents localized concentration spikes while ensuring broad, homogeneous thrombin distribution, thereby forming homogeneous clots even at high doses.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Speed

If thrombin is released rapidly to achieve quick hemostasis, then speed of action is improved, but clot strength decreases

Engineering Contradiction:

Improvespeed of hemostasisVSAvoidclot strength

Core Design Contradiction:

SpeedVSStrength

Solution Approach 1:

The thrombin release occurs in a controlled, progressive manner rather than all at once. The microsphere matrix allows for sustained release over time, providing continuous thrombin activity that maintains rapid hemostasis while ensuring sufficient thrombin accumulation for strong clot formation.

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The microsphere formulation changes the release kinetics parameter of thrombin. By controlling the microsphere degradation and pore structure, the thrombin is released at an optimized rate that balances speed of action with clot strength, preventing both premature termination and excessive delay.

Inventive Principle:

Principle #35Parameter changes

3Stability of the object's composition

If the microsphere particle size is reduced to improve mixing with blood, then homogeneity is improved, but the release rate decreases

Engineering Contradiction:

Improvemixing homogeneityVSAvoidthrombin release rate

Core Design Contradiction:

Stability of the object's compositionVSSpeed

Solution Approach 1:

Different regions of the microsphere structure are optimized for different functions. The outer surface and pore structure are designed to facilitate rapid release and mixing, while the internal matrix maintains structural integrity. This local optimization allows small particles to achieve both excellent mixing and adequate release rates.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The microsphere employs a porous structure that enhances surface area and facilitates rapid thrombin release. The pores allow blood to penetrate and access thrombin quickly, maintaining high release rates even as particle size is reduced to improve mixing homogeneity.

Inventive Principle:

Principle #31Porous 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

This approach leads to a rapid, reliable, and homogeneous clot formation, even in the presence of heparin or clopidogrel bisulfate, with significantly reduced time to hemostasis and increased clot stability, as demonstrated in various bleeding models.

Implementation Method 1

designed to slowly release thrombin and improve mixing with blood

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 2

cross-linked polymer microspheres, such as gelatin microspheres

Methodology Applied

Scientific EffectDegradation: Decomposition (biological)

Implementation Method 3

combined with high doses of thrombin... enhancing clot strength and reducing the effects of heparin inhibition

Methodology Applied

Scientific EffectCatalysis: Catalysis

Implementation Method 4

rapid, reliable, and homogeneous clot formation

Methodology Applied

Scientific EffectCoagulation: Coagulation

Data Source

PatentUS11246938B2Hemostatic microspheres

Publication Date: 2022.02.15 BAXTER INT INC

AI summary

Provided herein are hemostatic compositions. In one embodiment, the hemostatic composition includes cross-linked polymer microspheres, such as cross-linked gelatin microspheres with pores. In another embodiment, the hemostatic composition comprises an additive such as a wetting agent, a suspending agent, or both. The hemostatic compositions may also include a hemostatic agent such as thrombin, and may include a high concentration of thrombin. The hemostatic compositions may also include plasma. Also provided herein are devices for dispersing said hemostatic compositions in a diluent, and delivering said dispersed hemostatic composition. The hemostatic compositions may also fabricated with a selected geometry as administration suggests.