Method of microencapsulation of hyperbaric gas

• US 5,086,620 A
• Filed: 02/14/1991
• Issued: 02/11/1992
• Est. Priority Date: 02/14/1991
• Status: Expired due to Term

• Current Assignee: Wayne State University
• Original Assignee: Wayne State University
• Inventors: Spears, James R.
• Primary Examiner(s): Capossela, Ronald C.
• Application Number:
  US07/655,078
• Time in Patent Office: 362 Days
• Field of Search: 62/51.1, 62/78
• US Class Current: 62/51.1
• CPC Class Codes: A23L 2/54 Mixing with gases
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61M 1/1678 intracorporal peritoneal dialysis A61M1/28
• CPC Class Codes: A61M 1/32 Oxygenators without membranes
• CPC Class Codes: A61M 2202/0007 introduced into the body
• CPC Class Codes: A61M 2202/0476 Oxygenated solutions
• CPC Class Codes: A61M 25/09 Guide wires
• CPC Class Codes: B01F 23/2319 Methods of introducing gases into liquid media
• CPC Class Codes: B01J 13/04 by physical processes, e.g. drying, spraying
• CPC Class Codes: C01B 13/00 Oxygen; Ozone; Oxides or hydroxides in general
• CPC Class Codes: C01B 13/02 Preparation of oxygen by liquefying F25J
• CPC Class Codes: D21C 9/147 with oxygen or its allotropic modifications D21C9/16 takes precedence

Abstract

Method of encapsulating a hyperbaric gas for the treatment of diseases in humans with encapsulated gaseous precursors, such as microbubbles of oxygen. The method includes the step of immersing a receptacle containing an encapsulating material into a reaction vessel. An ultrasonic probe is then inserted into the reaction vessel. When the vessel is sealed, a source of hyperbaric gas is communicated therewith, and the vessel is then immersed within a cooling fluid so that the hyperbaric gas condenses. Thermal energy is then applied to the receptacle and ultrasound energy is delivered to the ultrasonic probe. When the probe vibrates, hyperbaric gas is distributed within the heated encapsulating material. After the cooling fluid chills the mixture of hyperbaric gas in the encapsulating material, the hyperbaric gas is entrapped therewithin. The encapsulated oxygen precursor can be used to treat atherosclerosis, infections and neoplasms, as well as to provide systemic oxygenation of tissues.

Claims

1. A method of encapsulating a hyperbaric gas, comprising the steps of:

supporting within a reaction vessel a receptacle containing an encapsulating material;

inserting an ultrasonic probe into the reaction vessel so that a portion of the ultrasonic probe is juxtaposed to the encapsulating material;

sealing the reaction vessel so that the receptacle and the ultrasonic probe are entrapped therewithin;

communicating a source of the hyperbaric gas with the reaction vessel so that a space between the encapsulating material and the ultrasonic probe is permeated thereby;

immersing the reaction vessel at least partially within a cooling fluid so that the hyperbaric gas condenses within the reaction vessel upon exposure to a cold environment created by the cooling fluid;

applying thermal energy to the receptacle so that the encapsulating material is heated thereby;

delivering ultrasound energy to the ultrasonic probe so that the probe is vibrated, thereby distributing hyperbaric gas within the heated encapsulating material; and

allowing the cooling fluid to chill the mixture of hyperbaric gas and the encapsulating material so that the hyperbaric gas is entrapped within the encapsulating material, thereby forming a hyperbaric gas-enriched encapsulating material.

2. The method of claim 1, further including the step of communicating a source of inert gas under a high pressure with the reaction vessel so that a super high pressure environment surrounds the ultrasonic probe, the encapsulating material, and the hyperbaric gas.

3. The method of claim 2, wherein the inert gas comprises a gas selected from the group consisting of argon, helium, and mixtures thereof.

4. The method of claim 1, wherein the encapsulating material is selected from a group consisting of water, ice, an inorganic salt, a carbohydrate, a phosphate glass, urea, hydroquinone, and mixtures thereof.

5. The method of claim 1, wherein the encapsulating material is ice which is enriched with deuterium oxide.

6. The method of claim 1, wherein the encapsulating material is an ice selected from a group consisting of cubic Type I ice, hexagonal Type I ice, Type II ice, Type V ice, Type VI ice, Type IX ice, vitreous ice, and mixtures thereof.

7. The method of claim 1, wherein the hyperbaric gas is oxygen.

8. The method of claim 1, wherein the step of applying thermal energy is provided by an electrical heating source.

9. The method of claim 1, wherein the step of applying thermal energy is provided by a source of laser energy.

10. The method of claim 1, wherein the step of applying thermal energy is provided by electrical energy.

11. The method of claim 1, wherein the receptacle comprises a Group VII metal.

12. The method of claim 1, wherein the ultrasonic probe comprises a Group IV metal.

13. The method of claim 1, wherein the cooling fluid comprises liquid nitrogen.

14. The method of claim 1, wherein the hyperbaric gas is dissolved within the encapsulating material.

15. The method of claim 1, wherein the hyperbaric gas entrapped within the encapsulating material exists about 100 microns.

16. The method of claim 1, wherein the hyperbaric gas is entrapped within the encapsulating material as a clathrate.

17. The method of claim 16, wherein the clathrate is a hydrate.

18. The method of claim 1, wherein the hyperbaric gas-enriched encapsulating material is removed from the reaction vessel and pulverized into a powder having granules with a mean diameter of less than about 100 microns.

19. The method of claim 1, wherein the step of delivering ultrasound energy comprises sonicating in juxtaposition with an immiscible liquid, thereby producing a suspension of granules of the encapsulating material within the immiscible liquid upon cooling.

20. The method of claim 19, wherein the immiscible liquid is subsequently removed from the granules of hyperbaric gas-enriched encapsulating material, thereby producing a free-flowing powder.

21. The method of claim 1, further comprising the step of providing a solvent, within which partial dissolution of the gas-enriched encapsulating material is arrested to produce small granules of the gas-enriched encapsulating material.

22. The method of claim 21, wherein the solvent is removed to produce a free-flowing powder of the hyperbaric gas-enriched encapsulating material.

23. The method of claim 1, further including the step of injecting hyperbaric gas-enriched encapsulating material intravenously in vivo, thereby promoting contact with body tissues and a release of oxygen.

24. The method of claim 1, wherein the encapsulating material is water enriched by deuterium oxide.

25. The method of claim 1, wherein the encapsulating material is water in the form of water of hydration within a non-aqueous compound.

26. The method of claim 25, wherein the non aqueous compound is selected from a group consisting of an inorganic salt, a carbohydrate, a protein, a phosphate glass, urea, hydroquinone, and mixtures thereof.

27. The method of claim 1, wherein the encapsulating material is water which includes approximately 5g % dextrose dissolved in the water.

28. The method of claim 1, wherein the encapsulating material is ice and includes the step of providing an aqueous carrier at about 0°

C. to about 37°

C. to facilitate transport of powdered ice.

29. The method of claim 1, wherein the encapsulating material is powdered ice which melts upon contact with blood, thereby releasing micro bubbles of oxygen which rapidly disappear as a result of the affinity of oxygen for hemoglobin and dissolution in plasma.

30. The method of claim 29, wherein injection of the powdered ice is facilitated by fluid transport with supercritical carbon dioxide.

31. The product of claim 1, wherein the hyperbaric gas-enriched encapsulating material includes micro bubbles having an average size of between about 0.01 microns and about 3.00 microns in diameter.

32. The product of claim 1, wherein particles of the hyperbaric gas-enriched encapsulating material are coated with a material having a slower rate of dissolution upon contact with water than that of the encapsulating material, thereby producing a controlled, slower-release preparation of hyperbaric gas.

33. A product prepared according to the method of claim 1, wherein the hyperbaric gas captured within the encapsulating material yields greater than about 20 cc'"'"'s of gas per gram of encapsulating material when liberated therefrom under atmospheric pressure.

34. A method of encapsulating hyperbaric gas comprising the steps of:

connecting a fiber optic to a receptacle formed of a Group VIII metal for delivery of thermal energy thereto;

adding an encapsulating material to the receptacle;

communicating a source of thermal energy to the fiber optic;

placing the receptacle at least partially within a reaction vessel so that the receptacle and the encapsulating material are supported therewithin;

inserting an ultrasonic probe so that the ultrasonic probe terminates in juxtaposition with the encapsulating material;

securing the reaction vessel so that the probe, the receptacle, and the fiber optic are sealingly engaged therewithin;

immersing the reaction vessel in a cooling fluid;

introducing a gas into the reaction vessel so that the density of the gas increases upon exposure to a cold environment generated by the cooling fluid;

activating the source of thermal energy in order to deliver such energy through the fiber optic to the encapsulating material;

delivering ultrasonic energy to the ultrasonic probe, thereby promoting a rapid distribution of hyperbaric oxygen throughout the encapsulating material during sonication; and

discontinuing the supply of thermal and ultrasonic energy and allowing the hyperbaric gas-enriched encapsulating material to cool, thereby entrapping the hyperbaric gas within the encapsulating material.

35. The method of claim 34, further comprising the step of communicating an inert gas into the reaction vessel so that the pressure therein rises to about 50,000 psi.

36. The method of claim 34, wherein the step of delivering ultrasonic energy comprises the step of delivering such energy at a frequency within a 20 hertz to 200 kilohertz range.

37. The method of claim 34, wherein the hyperbaric gas is selected from a group consisting of oxygen, oxygen radicals, singlet oxygen, or any combination of oxygen moieties.

38. The method of claim 34, further comprising the step of at least partially dissolving the hyperbaric gas-enriched encapsulating material in a solvent so that granules containing micro bubbles are produced;

and

arresting the dissolution step when granules of an appropriate size are reached.