Methods and compositions for treating conditions related to lack of blood supply, shock and neuronal injuries
Inventors
Assignees
Publication Number
US-9622968-B2
Publication Date
2017-04-18
Expiration Date
2028-12-16
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Abstract
A pharmaceutical composition comprising an amphiphilic emulsifier, a polar liquid carrier and, optionally, a lipid component. The amphiphilic emulsifier form free-moving, optionally lipid-carrying, micelles (LMs) in the polar liquid carrier. The pharmaceutical composition is free of hemoglobin and fluorocarbon and can be used for treating conditions related to lack of blood supply and to raise the blood pressure and correct hypovolemia.
Core Innovation
The invention relates to a pharmaceutical composition comprising an amphiphilic emulsifier, a polar liquid carrier, and optionally a lipid component, where the emulsifier forms free-moving, optionally lipid-carrying micelles with a lipophilic core in the polar carrier. The composition is free of hemoglobin and fluorocarbon and is designed for use as a blood volume expander and for treating conditions related to lack of blood supply, such as shock and neuronal injuries.
Existing therapies for shock, such as infusion of crystalloids and colloids like HETASTARCH™, or use of vasoconstrictors, have limited efficacy and may cause complications such as enhanced bleeding, renal failure, mortality, and decreased tissue perfusion. Current fluids fail to address the complex pathophysiology of shock, notably the generation of toxic mediators and insufficient oxygen/nutrient delivery, creating a need for a therapeutic volume expander that can bring oxygen and nutrients to tissues and reduce inflammatory responses.
The present invention provides a blood volume expander composed of an amphiphilic emulsifier and a polar liquid carrier, where the amphiphilic emulsifier forms micelles that can optionally carry lipids such as soybean oil or oils rich in omega 3 fatty acids. This composition can carry and deliver lipophilic gases such as oxygen, nitric oxide, xenon, or argon to tissues, reverse hypotension in hemorrhagic shock, and absorb or modulate mediators of inflammation and tissue injury. The composition can be tailored for specific therapeutic needs by selecting types and concentrations of emulsifier, lipid, buffering agents (such as histidine or histidine-containing peptides), and additional optional components, and is suitable for rapid and large volume infusion without the limitations of current blood substitutes.
Claims Coverage
There are two independent claims in this patent, each directed to a blood volume expander with specified inventive features.
Blood volume expander containing amphiphilic emulsifier, polar liquid carrier, and histidine or histidine-containing peptide as buffering agent
A blood volume expander comprising: - An amphiphilic emulsifier; - A polar liquid carrier; - A buffering agent of histidine or a histidine-containing peptide at a final concentration of 0.1 mM to 30 mM; - The amphiphilic emulsifier forms free-moving micelles having a lipophilic core in the polar liquid carrier; - The blood volume expander is free of hemoglobin and fluorocarbon.
Blood volume expander containing amphiphilic emulsifier, polar liquid carrier, and histidine or histidine-containing peptide forming micelles or liposomes
A blood volume expander comprising: - An amphiphilic emulsifier; - A polar liquid carrier; - A buffering agent of histidine or a histidine-containing peptide at a final concentration of 0.1 mM to 30 mM; - The amphiphilic emulsifier forms free-moving micelles or liposomes in the polar liquid carrier; - The blood volume expander is free of hemoglobin and fluorocarbon.
The claims are directed to blood volume expanders that use amphiphilic emulsifiers to create micelles or liposomes in a polar carrier, incorporating histidine or histidine-containing peptides as buffering agents, and expressly exclude hemoglobin and fluorocarbon from the compositions.
Stated Advantages
The pharmaceutical composition can carry and deliver oxygen or other hydrophobic gases to body tissue in the absence of hemoglobin or modified hemoglobin.
The composition is able to reverse hypotension characteristic of hemorrhagic shock and maintain blood pressure more effectively than standard resuscitation fluids.
The micelles in the composition are capable of exerting an osmotic force and absorbing mediators of tissue injury, such as prostaglandins, nitric oxide, leukotrienes, and thromboxane.
The composition is free of hemoglobin, perfluorocarbon, and derivatives thereof, reducing risks associated with these components.
The composition may minimize reactive oxygen species and provide anti-inflammatory effects due to additives like albumin and specific oils rich in omega 3 fatty acids.
Documented Applications
Treatment of conditions related to lack of blood supply, including hypovolemia caused by bleeding, dehydration, vomiting, severe burns, systemic inflammatory response syndrome (SIRS), and drug effects.
Raising blood pressure in subjects with hypovolemia and for use as a blood volume expander.
Carrying and delivering lipophilic gases (such as oxygen, nitric oxide, xenon, argon, hydrogen sulfide, and carbon monoxide) for therapeutic modulation of tissue oxygenation and vascular tone.
Treatment of seizure or neuronal injuries using xenon- or argon-carrying pharmaceutical compositions.
Absorbing endogenously produced nitric oxide to treat hypotension of septic shock.
Relieving vasoconstriction and hypertension by delivering nitric oxide in conditions such as Raynaud's disease, Prinzmetal's angina, cerebral vasospasm, atherosclerosis, and sickle cell crisis.
Preservation of organs from mammalian donors by perfusing the pharmaceutical composition into chilled or room-temperature organs.
Use as a diagnostic tool by absorbing lipophilic disease-related moieties during circulation for post-analysis.
Replacement for extracorporeal membrane oxygenation (ECMO) by delivering oxygen to tissues when lungs are damaged.
Exchange transfusion and whole circulation perfusion to wash out harmful materials such as infectious agents, cancerous agents, and toxins.
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