Methods and compositions for treating conditions related to lack of blood supply, shock, and neuronal injuries
Inventors
Assignees
Publication Number
US-9387162-B2
Publication Date
2016-07-12
Expiration Date
2028-12-16
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Abstract
A pharmaceutical composition comprising a lipid component; an amphiphilic emulsifier; and a polar liquid carrier. The lipid component and the amphiphilic emulsifier form free-moving 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.
Core Innovation
The invention provides a pharmaceutical composition comprising a lipid component, an amphiphilic emulsifier, and a polar liquid carrier, where the lipid component and emulsifier form free-moving lipid-carrying micelles (LMs) or liposomes in the carrier. The composition is characterized by being free of hemoglobin and perfluorocarbon, and can be loaded with an effective amount of oxygen for enhancement of aerobic metabolism. The micelles or liposomes can vary in diameter, including nano-size ranges, and the pharmaceutical composition can incorporate various additives such as amino acids, glycerol, albumin, and bioactive agents.
The invention addresses the problem of inadequate circulation and lack of effective resuscitation fluids for treating shock, conditions related to lack of blood supply, and neuronal injuries. Current treatments rely on crystalloids or colloids, both of which have significant limitations and complications such as rapid diffusion out of the bloodstream, enhanced bleeding (Hetastarch), or decreased tissue perfusion (vasoconstrictors). There is a need for a low-cost therapeutic volume expander that can deliver oxygen and nutrients to tissues and modulate the inflammatory response.
The pharmaceutical composition of this invention enables the delivery of oxygen and other hydrophobic gases to tissues through the micelles' lipid core, providing enhanced oxygen-carrying capacity compared to aqueous solutions. It also absorbs and releases important vascular mediators, exerts osmotic force, and can include additional agents such as anti-inflammatory compounds, antioxidants, coagulation factors, and organ-protective gases like xenon or nitric oxide. Methods of treatment are provided, such as raising blood pressure in shock patients via infusion of the composition, alone or in sequence with formulations containing different lipid sources tailored for specific phases of treatment.
Claims Coverage
There is one independent claim in this patent, covering a pharmaceutical composition with specific structural and functional features.
Pharmaceutical composition with lipid-carrying micelles or liposomes free of hemoglobin and fluorocarbon and with effective oxygen content
A pharmaceutical composition comprises: - A lipid component; - An amphiphilic emulsifier; - A polar liquid carrier; Where: - The lipid component and the amphiphilic emulsifier form free-moving lipid-carrying micelles (LMs) or liposomes in the polar liquid carrier. - The pharmaceutical composition is free of hemoglobin and fluorocarbon. - The pharmaceutical composition further comprises an effective amount of oxygen for enhancement of aerobic metabolism. These inventive features define the composition's structure (micelles/liposomes), the absence of hemoglobin and fluorocarbon, and a functional capacity for oxygen delivery.
The claim protects the novel pharmaceutical composition defined by its lipid micelle or liposome structure, the exclusion of hemoglobin and fluorocarbon, and its capacity to deliver an effective amount of oxygen for enhancing aerobic metabolism.
Stated Advantages
The pharmaceutical composition can effectively carry and deliver oxygen to tissues in the absence of hemoglobin, supporting aerobic metabolism during shock or blood loss.
The invention avoids complications associated with current resuscitation fluids, such as enhanced bleeding and decreased tissue perfusion.
The composition can absorb and modulate inflammatory mediators, offering potential reduction in inflammatory responses.
Lipid micelles or liposomes provide sustained intravascular retention and can be tailored for different distribution (intravascular or interstitial) by controlling particle size.
Addition of specific lipid sources, like soybean or chia bean oil, enables targeted procoagulant or anti-inflammatory effects depending on treatment phase.
Documented Applications
Treatment of shock, including hemorrhagic, cardiogenic, neurogenic, adrenal insufficiency, and septic shock.
Raising blood pressure in patients with severe blood loss by intravenous, intra-arterial, or intracardiac infusion of the pharmaceutical composition.
Oxygenating patients whose lungs are severely damaged and unable to absorb oxygen, potentially replacing extracorporeal membrane oxygenation (ECMO).
Absorption of toxic chemical molecules/biomolecules produced as a result of trauma or shock, such as leukotrienes and prostaglandins.
Exchange transfusion and circulating perfusion to wash out blood containing infectious agents, cancerous agents, or toxic agents.
Treatment of seizure or neuronal injury by administering a xenon- or argon-carrying pharmaceutical composition.
Treatment of vasoconstriction and/or hypertension by delivering nitric oxide-carrying pharmaceutical composition.
Preservation of organs for transplantation through perfusion with the pharmaceutical composition.
Use as a diagnostic tool by absorbing lipophilic moieties in the bloodstream for disease detection.
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