Trehalose-Free Spray-Dried Thrombin for Rapid Reconstitution
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Solution Overview
Problem
Current hemostatic compositions for preventing excessive bleeding and promoting healing are time-consuming to reconstitute, often require additional additives like trehalose, and may not be tolerable to all patients, while existing hemostatic agents made of non-biodegradable materials can cause undesirable side effects.
Innovation Solution
A spray-dried powdered thrombin material is developed, containing 2.2% to 2.5% albumin without trehalose or mannitol, which can be reconstituted quickly and effectively, maintaining thrombin activity and stability, and can be administered with biologically compatible polymers like gelatin to form a hydrogel.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If aqueous carrier or hydrogel composition is used for hemostatic agents, then biocompatibility and release characteristics can be optimized, but reconstitution time becomes too long for emergency situations
Solution Approach 1:
The invention utilizes phase transition by providing hemostatic agents in a dry powder form that rapidly transitions to an aqueous hydrogel state upon contact with blood or moisture at the bleeding site. This eliminates the need for pre-reconstitution while maintaining the biocompatible hydrogel properties, thus resolving the contradiction between biocompatibility and reconstitution time.
2Productivity
If additional additives like trehalose are added to improve reconstitution times and stability, then product performance is enhanced, but patient tolerance problems arise due to ingredient complexity
Solution Approach 1:
The invention extracts and eliminates unnecessary additives like trehalose and mannitol from the hemostatic agent formulation. By using only essential components (thrombin, calcium chloride, and stabilizing proteins), the product achieves rapid reconstitution and stability without the complexity and potential intolerance issues associated with multiple additives.
Solution Approach 2:
The invention changes the formulation parameters by reducing the albumin content to a specific range (2.2%-2.5% by weight) and eliminating carbohydrates entirely. This parameter optimization allows the product to achieve both rapid reconstitution and stability without requiring additional stabilizing sugars, thus resolving the contradiction between reconstitution speed and composition complexity.
3Reliability
If non-biodegradable barrier materials are used to prevent bleeding, then hemostatic effect is achieved, but undesirable side effects occur due to material persistence in the body
Solution Approach 1:
The invention uses a composite formulation combining thrombin (active hemostatic agent), calcium chloride (coagulation factor), and stabilizing proteins (albumin). This composite material provides effective hemostasis while being fully biocompatible and biodegradable, eliminating the harmful persistence effects of non-biodegradable barrier materials while maintaining reliable hemostatic effect.
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 spray-dried thrombin composition achieves rapid reconstitution in under 60 seconds, maintains thrombin activity, and provides effective hemostasis without the need for additional stabilizing sugars, demonstrating stability and efficacy comparable to commercial formulations.
Implementation Method 1
The thrombin material is aseptically spray-dried and does not require the addition of trehalose or a similar carbohydrate
Implementation Method 2
can be administered with biologically compatible polymers like gelatin to form a hydrogel
Implementation Method 3
The spray-dried thrombin composition achieves rapid reconstitution in under 60 seconds, maintains thrombin activity, and provides effective hemostasis without the need for additional stabilizing sugars
Implementation Method 4
Preventing excessive bleeding and promoting healing is an important aspect of many medical procedures
Data Source
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AI summary
Spray-dried thrombin materials obtained from feedstock solutions comprising less than 5% by weight albumin and excluding trehalose or other excipients as well as methods of manufacturing the thrombin materials and methods of treating bleeding wounds are disclosed. The methods of use include applying reconstituted spray-dried thrombin topically to a bleeding site, optionally in conjunction with gelatin.