Microbubbles and methods for oxygen delivery

a technology of oxygen delivery and microbubbles, which is applied in the direction of drug compositions, biocides, extracellular fluid disorders, etc., can solve the problems of ischemic injury that may take place within minutes or seconds, severe organ injury and death, failure,

Inactive Publication Date: 2009-07-30
CHILDRENS MEDICAL CENT CORP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009]It is yet a further object of the invention to provide impr...

Problems solved by technology

In cases where a patient's lungs are unable to transfer adequate amounts of oxygen to circulating erythrocytes, severe hypoxia results and can quickly lead to severe organ injury and death.
Ischemic injury may take place within minutes or seconds of insufficient oxygen delivery.
In these conditions, low oxygen tension can result in end-organ dysfunction, failure, and mortality.
However, patients with lung injury, comprising a significant population of intensive care unit patients, have difficulty exchanging oxygen across a damaged alveolar unit.
This requires clinicians to increase ventilator pressures, often causing further ...

Method used

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  • Microbubbles and methods for oxygen delivery
  • Microbubbles and methods for oxygen delivery
  • Microbubbles and methods for oxygen delivery

Examples

Experimental program
Comparison scheme
Effect test

example 1

Formation of Concentrated Microbubble Suspensions

[0158]Concentrated microparticle suspensions were formed using the following four main steps: (1) generation of the precursor suspension, (2) sonication, (3) concentration and (4) size isolation.

[0159]1. Generation of precursor suspension. Microparticle suspensions using each of the lipids listed in Table 2 below were created. The base lipids were received in powder form (Avanti Polar Lipids, Alabaster, Ala.) and dissolved in sterile saline to create a stock solution. The same was done with PEGylated lipid. Base lipids were mixed with the PEGylated lipid in a 95-5 molar ratio. The final concentration of each precursor solution was 3 mg total lipid / mL. Lipid precursor solutions were stored at 4° C.

TABLE 2List of Base Lipids and PEGylated Lipids with TransitionTemperature (Tm) and Reduced Temperature (TR)TmTR atTR atMicrobubble Lipid ComponentsAbbreviation(° C.)25° C.37° C.Base Lipids1,2-Dilauroyl-sn-Glycero-3-C12−11.101.14Phosphocholin...

example 2

Efficiency and Rate of Gas Transfer to Desaturated Human Hemoglobin

[0170]The base lipids used in the preparation of the microbubbles were 1,2-Dilauroyl-sn-Glycero-3-Phosphocholine; 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine; 1,2-Dipentadecanoyl-sn-Glycero-3-Phosphocholine; 1,2-dipalmitoyl-sn-Glycero-3-Phosphocholine; 1-Miristoyl-2-Palmitoyl-sn-Glycero-3-Phosphocholine; 1,2-Dimyristoyl-sn-Glycero-3-[Phospho-rac-(1-glycerol)]; and 1,2-Dimyristoyl-3-Trimethylammonium-Propane. The PEGylated lipid used in the microbubbles was 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-[Methoxy(Polyethylene glycol)-5000]. All lipids were purchased from Avanti Polar Lipids, Alabaster, Ala.

[0171]Venous whole blood was withdrawn from healthy donors and stored in heparinized syringes. The mean PO2 of the venous blood was 52.1 mm Hg.

[0172]Formation of the Microbubble Suspensions

[0173]Each of the above listed lipids was dissolved in sterile phosphate-buffered saline via sonication at high power for 10 m...

example 3

Comparison of Microbubbles Encapsulating Oxygen and Unencapsulated Oxygen in Desaturated, Venous Whole Blood Tested In Vitro

[0177]The effect of oxygen-bearing microbubbles containing DPPC as the base lipid and PEG stearate as the emulsifying agent in a molar ration of 95:5 (base lipid: emulsifying agent), which were prepared according to the method of Example 1 without the concentration and size isolation steps, on a 2 mL sample of desaturated, venous whole blood from a healthy human volunteer was studied. In one test tube, 0.2 mL of the microbubbles were added to 2 mL of desaturated, venous whole blood. To a second test tube, 0.2 mL of pure oxygen gas (unencapsulated) was added to 2 mL of desaturated, venous whole blood.

[0178]The test tubes were inverted once, and co-oximetry and blood gas values measurements were taken using a Radiometer ABL800 X blood gas machine.

[0179]The test tube containing microbubbles had a pH of 7.31, PCO2 of 50 mmHg, PO2 of 248 mmHG, and the amount of oxyg...

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Abstract

Compositions containing a carrier and microbubles encapsulating one or more gases, preferably oxygen, and methods for making and using the compositions are described herein. The microbubbles contain a lipid envelope formed of at least one base lipid and at least one emulsifying agent. The compositions may be administered to a patient to quickly deliver large amounts of oxygen to the patient's blood supply or directly to a tissue in need of oxygen. The compositions may be administered via injection or as a continuous infusion. The compositions contain a concentrated microbubble suspension, where the suspension contains at least 40 mL oxygen/dL suspension. The microbubbles are preferably less than 20 microns in diameter, more preferably less than 15 microns in diameter. The microbubbles described herein may be administered to a patient in an effective amount to increase in oxygen concentration in the patient's blood, and/or one or more tissues or organs. The microbubbles may be administered alone or in combination with other treatments as an adjuctive therapy.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Ser. No. 61 / 073,334, filed Jun. 17, 2008; U.S. Ser. No. 61 / 026,984, filed Feb. 7, 2008; and U.S. Ser. No. 60 / 975,705, filed Sep. 27, 2007.[0002]The disclosures in the applications listed above are herein incorporated by reference.FIELD OF THE INVENTION[0003]This present invention relates to compositions and methods for gas perfusion of tissues, and especially delivery of an effective amount of oxygen to a patient to alleviate or prevent ischemic injury.BACKGROUND OF THE INVENTION[0004]Every human cell requires a constant supply of oxygen to maintain cellular structure and homeostasis. This supply is primarily provided by hemoglobin, which carries inspired oxygen from the pulmonary capillaries to the tissues. In cases where a patient's lungs are unable to transfer adequate amounts of oxygen to circulating erythrocytes, severe hypoxia results and can quickly lead to severe organ injury and death.[000...

Claims

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Application Information

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IPC IPC(8): A61K33/00A61P9/00A61K9/00
CPCA61K47/48869A61K47/6925A61P7/00A61P9/00A61P9/10
Inventor KHEIR, JOHNBORDEN, MARK ANDREWMCGOWAN, FRANCIS X.
Owner CHILDRENS MEDICAL CENT CORP
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