Dissolution of gas in a fluorocarbon liquid

• US 4,927,623 A
• Filed: 01/04/1988
• Issued: 05/22/1990
• Est. Priority Date: 01/14/1986
• Status: Expired due to Term

• Current Assignee: PFC Therapeutics, LLC
• Original Assignee: Alliance Pharmaceutical Corporation
• Inventors: Long, David M. Jr.
• Primary Examiner(s): WADDELL, FREDERICK
• Application Number:
  US07/140,543
• Time in Patent Office: 869 Days
• Field of Search: 424/5, 514/772, 514/832
• US Class Current: 424/9.52
• CPC Class Codes: A61K 31/02 Halogenated hydrocarbons
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender

Abstract

Biocompatible fluorocarbon emulsions having fluorocarbon in concentrations of from 75% weight per volume to 125% weight per volume have small, biocompatible particle size stability through heat sterilization with one emulsifying agent, including phospholipids, in concentrations of from 3% to 7% weight per volume. The single emulsifying agent can be hydrogenated lecithins and synthesized lecithins. Fluorocarbon emulsions having fluorocarbon in concentrations of from 40% weight per volume to 125% weight per volume have stability of partial pressure of oxygen and of partial pressure of carbon dioxide through heat sterilization and storage for extended periods of time after having been oxygenated with dissolved oxygen. A method of preparing biocompatible fluorocarbon emulsions includes preparing a mixture of an emulsifying agent, osmotic agent, buffering agent, aqueous phase and fluorocarbon, forcing the mixture under high pressure into a cavity, against a surface and around a lip to cause turbulence and possibly cavitation to form high fluorocarbon concentration emulsions that are stable through heat sterilization; and, even when oxygenated, maintain substantially stable partial pressures of oxygen and of carbon dioxide, and substantially stable pH. A method of oxygenating high fluorocarbon concentration emuslions includes placing a measured amount of the emulsion in a container and causing the emulsion to form a thin film around the inner surface of the container when the oxygen is injected. An alternative method of oxygenating the high fluorocarbon concentration emulsion includes a two container system where one container, permeable to the to be dissolved gas, is formed within the other, and the emulsion is injected in one container and the to be dissolved gas is injected into the other container.

Claims

1. A method of dissolving a gas in a fluorocarbon emulsion comprising:

a. providing a first flexible container that is permeable to gas, but not to liquids or solids, in contact with the interior of a second container, said first and said second containers having means for introducing and removing fluid;

b. providing a fluorocarbon emulsion in one of said containers;

c. inserting said gas to be dissolved into the other of said containers and allowing the gas to permeate said one container to provide an oxygenated fluorocarbon emulsion in said one container.

2. The method of claim 1, wherein said first container is substantially impermeable to said fluorocarbon emulsion.

3. The method of claim 1 wherein said gas is oxygen.

4. The method of claim 1 wherein said fluorocarbon emulsion is inserted in said first container.

5. The method of claim 1 wherein said second container is flexible, and is substantially collapsed upon said first container until said gas is inserted into said second container.

6. The method of claim 1 wherein the first flexible container is inserted into the second container, wherein said second container is compromised substantially of glass, said first and second containers defining a space between them, and wherein the fluorocarbon emulsion is inserted into said space in an amount less than the amount of space, and wherein said first flexible container is initially empty of content, comprising the further steps of:

a. sparging the space remaining after insertion of the fluorocarbon emulsion with a second gas substantially inert to the emulsion; and

b. inserting the first gas to be dissolved into said emulsion, into said first container to expand said first container and force second gas out of said second container, allowing said first gas to permeate said space to provide an oxygenated fluorocarbon emulsion in said space.

7. A method of dissolving a first gas in a fluorocarbon emulsion comprising:

a. inserting a first flexible container that is permeable to said first gas into a second container comprised of substantially rigid glass, said first and said second containers having selectively penetrable ports for holding fluid inside said container, said first and said second containers defing a space between them;

b. inserting fluorocarbon emulsion into said space within said second container in an amount less than space space;

c. sparging the space not occupied with said fluorocarbon emulsion with a second gas that is substantially inert to said fluorocarbon emulsion;

d. inserting said first gas to be dissolved into said first container to expand said first container, withdrawing the substantially inert second gas from said space through the port of said second container, and allowing the first gas to permeate said first container;

d. withdrawing oxygenated fluorocarbon emulsion from said second container through its port.

8. A method of dissolving a gas in a fluorocarbon emulsion, comprising;

a. providing a first container and a second container, said first container having a fluorocarbon emulsion therein, wherein said second container is adapted to hold a gas, and wherein said first container is in contact with the interior of said second container through a wall that is permeable to said gas but not to said fluorocarbon emulsion; and

b. inserting a gas in said second container and allowing the gas to permeate said first container to provide an oxygenated fluorocarbon emulsion in said first container.

9. The method of claim 8, wherein said first container is inside said second container.

10. The method of claim 8, wherein said second container is inside said first container.

11. The method of claim 8, wherein said gas is an oxygen containing gas.