Antibodies to Bufalin Prevent Na/K ATPase Inhibition

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Solution Overview

Problem

Current treatments for conditions associated with decreased Na/K ATPase activity, such as hemorrhagic shock, septic shock, and cardiovascular diseases, are inadequate due to the inability to effectively manage bufadienolide-induced inhibition of Na/K ATPase, leading to cellular depolarization and fluid imbalance.

Innovation Solution

Administration of a therapeutically effective amount of molecules like polyclonal or monoclonal antibodies or antigen binding fragments that inhibit or stimulate the immune system to target bufadienolides, specifically bufalin, to restore or maintain Na/K ATPase activity, thereby counteracting the inhibitory effects on the enzyme.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional resuscitation methods (fluid infusion) are used to treat hemorrhagic shock, then blood volume is restored and oxygen delivery is improved, but the underlying cause (bufadienolide-induced Na/K ATPase inhibition) is not addressed, leading to continued cellular depolarization and fluid imbalance

Engineering Contradiction:
Improveresuscitation effectivenessVSAvoidsurvival rate
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent introduces antibodies as intermediary substances that specifically bind to bufadienolides, preventing them from inhibiting Na/K ATPase. This intermediary approach neutralizes the harmful substance without directly affecting the enzyme, allowing physiological processes to恢复正常 while addressing the root cause of shock

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the harmful effect of bufadienolides into a beneficial therapeutic opportunity by using the immune system to produce antibodies against them. The same substance that causes shock (bufadienolide) becomes the target of a therapeutic intervention (antibody therapy), transforming the harmful pathway into a治愈 mechanism

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

2Stability of the object's composition

If large volumes of fluid are infused to restore blood volume in hemorrhagic shock, then cardiovascular stability is improved, but cellular fluid imbalance and depolarization persist due to ongoing Na/K ATPase inhibition

Engineering Contradiction:
Improvecardiovascular stabilityVSAvoidcellular depolarization
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent transforms the harmful bufadienolide substance into a therapeutic target by inducing antibody production. The same substance causing cellular depolarization becomes the antigen that triggers a protective immune response, converting the harmful pathway into a治愈 mechanism that restores cellular function

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

Antibodies serve as intermediary molecules that specifically bind to bufadienolides in the circulation, preventing them from reaching and inhibiting Na/K ATPase at the cellular level. This intermediary approach protects cells from the harmful substance while allowing systemic fluid resuscitation to stabilize cardiovascular function

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 proposed solution effectively prolongs survival in hemorrhagic shock and alleviates symptoms in conditions characterized by decreased Na/K ATPase activity by preventing bufadienolide-induced inhibition, thereby maintaining cellular homeostasis and restoring vital functions.

Implementation Method 1

Administration of a therapeutically effective amount of molecules like polyclonal or monoclonal antibodies or antigen binding fragments that inhibit or stimulate the immune system to target bufadienolides, specifically bufalin

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentUS8062639B2Antibodies to bufalin prevent inhibition of Na/K ATPase and prolong survival in shock
Publication Date: 2011.11.22 SHOCK THERAPEUTICS BIOTECH INC
  • US8062639B2 patent drawing
  • US8062639B2 patent drawing
  • US8062639B2 patent drawing

AI summary

The present invention relates to compositions and methods of use thereof for treatment of clinical conditions manifested from and/or exacerbated by a decrease or an inhibition of Na/K ATPase activity. The invention relates to composition comprises monoclonal or polyclonal antibodies to bufalin and/or bufalin sulfate, or vaccination against bufalin and/or bufalin sulfate, which prevents or attenuates inhibition of Na/K ATPase activity thereby attenuating the adverse physiological effects of bufalin and/or bufalin sulfate inhibition. The invention also relates to methods of treating hemorrhagic, septic shock, cardiogenic shock, shock resulting from physical trauma, diabetes, mental depression, bipolar disorder and schizophrenia comprising administering a therapeutically effective amount of an bufalin monoclonal or polyclonal antibody.