Generation of therapeutic microfoam

• US 7,357,336 B2
• Filed: 07/01/2005
• Issued: 04/15/2008
• Est. Priority Date: 05/26/1999
• Status: Expired due to Term

• Current Assignee: BTG International Limited (Boston Scientific Corporation)
• Original Assignee: BTG International Limited (Boston Scientific Corporation)
• Inventors: Shilton-Brown, Sheila Bronwen, Harman, Anthony David, Wright, David Dakin Iorwerth, Osman, Tariq, Boorman, Timothy David
• Primary Examiner(s): DOERRLER, WILLIAM CHARLES
• Application Number:
  US11/171,293
• Publication Number:
  US 20050266033A1
• Time in Patent Office: 1,019 Days
• Field of Search: 239/337, 424/400, 424/423, 424/600, 514/945, 604/140
• US Class Current: 239/337
• CPC Class Codes: A61K 31/08 acyclic, e.g. paraformaldehyde
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: B05B 11/02 Membranes or pistons acting on the contents inside the container, e.g. follower pistons
• CPC Class Codes: B05B 7/0037 including sieves, porous members or the like
• CPC Class Codes: B65D 83/14 for delivery of liquid or semi-liquid contents by internal gaseous pressure, i.e. aerosol containers comprising propellant for a product delivered by a propellant
• CPC Class Codes: B65D 83/20 operated by manual action, e.g. button-type actuator or actuator caps actuators formed as a rigid elongate spout B65D83/306
• CPC Class Codes: B65D 83/48 Lift valves, e.g. operated by push action B65D83/50 takes precedence
• CPC Class Codes: B65D 83/60 Contents and propellant separated
• CPC Class Codes: B65D 83/62 by membrane, bag, or the like containers in which the content is delivered by the contracting forces inherent in the bag B65D83/0061

Abstract

Improved therapeutic sclerosing microfoams and methods and devices for making them are provided that have advantage in producing a consistent profile injectable foam with minimal input by the physician yet using high volume percentages of blood dispersible gases, thus avoiding use of potentially hazardous amounts of nitrogen.

Claims

1. A method for producing a microfoam suitable for use in sclerotherapy of blood vessels, comprising:

passing a mixture of at least one physiologically acceptable blood dispersible gas including oxygen, carbon dioxide or a mixture thereof and at least one aqueous sclerosant liquid through one or more passages thereby producing the microfoam,

wherein a ratio of gas to liquid is such that the microfoam that is produced has a half-life of at least 2 minutes and a density ranging from 0.07 g/ml to 0.19 g/ml.

2. The method of claim 1, where the at least one physiologically acceptable blood dispersible gas comprises a mixture of 10 to 40% vol/vol carbon dioxide, 60-90% oxygen, and other physiological gases, the other physiological gases including under 30% vol/vol of nitrogen.

3. The method of claim 1, where the at least one physiologically acceptable blood dispersible gas comprises a mixture of 70% to 80% vol/vol oxygen, 20-30% carbon dioxide, the remainder being other physiological gases including nitrogen.

4. The method of claim 1, wherein the microfoam has a half-life of at least 2.5 minutes.

5. The method of claim 4, wherein the microfoam has a half-life of at least 3 minutes.

6. The method of claim 5, wherein the microfoam has a half-life of at least 4 minutes.

7. The method of claim 1, wherein the microfoam has a density ranging from 0.09 g/mL to 0.16 g/mL.

8. The method of claim 1, wherein the microfoam comprises at least 50% by number of the gas bubbles of 25 μ

m diameter and above are of no more than 200 μ

m diameter and at least 95% of these gas bubbles are no more than 280 μ

m diameter.

9. The method of claim 1, wherein the microfoam comprises at least 50% by number of the gas bubbles of 25 μ

m diameter and above are of no more than 150 μ

m diameter and at least 95% of these gas bubbles are no more than 250 μ

m diameter.

10. The method of claim 1, wherein the mixture of at least one physiologically acceptable blood dispersible gas and at least one aqueous sclerosant liquid is in the form of an aerosol, dispersion of bubbles in liquid or macrofoam.

11. The method of claim 1, wherein the ratio of gas to liquid used in the mixture is 1 gram sclerosant liquid to from 6.25 to 14.3 volumes of gas at standard temperature and pressure.

12. The method of claim 1, wherein the physiologically acceptable blood dispersible gas comprises a major proportion of carbon dioxide and/or oxygen.

13. The method of claim 12, wherein the physiologically acceptable blood dispersible gas comprises 99% carbon dioxide.

14. The method of claim 1, wherein the aqueous sclerosant liquid is a solution of polidocanol or sodium tetradecylsulfate (STS) in an aqueous carrier.

15. The method of claim 1, wherein a carrier comprises a saline solution.

16. The method of claim 1, wherein the gas is pressurized at 0.1 to 9 bar over atmospheric pressure.

17. The method of claim 1, wherein the gas is pressurized at 0.1 to 3 bar over atmospheric pressure.

18. The method of claim 1, wherein the aqueous solution contains a minor amount of alcohol.

19. The method of claim 1, wherein the mixture further comprises 1 to 10% vol/vol glycerol.

20. A method for producing a microfoam suitable for use in sclerotherapy of blood vessels, comprising:

passing a mixture of at least one physiologically acceptable blood dispersible gas including 60-90% vol/vol oxygen, 10-40% vol/vol carbon dioxide or a mixture thereof and at least one aqueous sclerosant liquid through one or more passages thereby producing the microfoam,

wherein a ratio of gas to liquid is such that the microfoam that is produced has a half-life of at least 2 minutes and a density ranging from 0.07 g/ml to 0.19 g/ml.

21. The method of claim 20, where the at least one physiologically acceptable blood dispersible gas comprises a mixture of 10 to 40% vol/vol carbon dioxide and other physiological gases, the other physiological gases comprising oxygen with under 30% vol/vol of nitrogen.

22. The method of claim 20, where the at least one physiologically acceptable blood dispersible gas comprises a mixture of 60% vol/vol or more oxygen, the remainder being carbon dioxide or carbon dioxide and nitrogen.

23. The method of claim 20, wherein the microfoam has a density ranging from 0.09 g/mL to 0.16 g/mL.

24. The method of claim 20, wherein the microfoam has a half-life of at least 2.5 minutes.

25. The method of claim 24, wherein the microfoam has a half-life of at least 3 minutes.

26. The method of claim 25, wherein the microfoam has a half-life of at least 4 minutes.

27. The method of claim 20, wherein the microfoam comprises at least 50% by number of the gas bubbles of 25 μ

m diameter and above are of no more than 200 μ

m diameter and at least 95% of these gas bubbles are no more than 280 μ

m diameter.

28. The method of claim 20, wherein the microfoam comprises at least 50% by number of the gas bubbles of 25 μ

m diameter and above are of no more than 150 μ

m diameter and at least 95% of these gas bubbles are no more than 250 μ

m diameter.

29. The method of claim 20, wherein the mixture of at least one physiologically acceptable blood dispersible gas and at least one aqueous sclerosant liquid is in the form of an aerosol, dispersion of bubbles in liquid or macrofoam.

30. The method of claim 20, wherein the ratio of gas to liquid used in the mixture is 1 gram sclerosant liquid to from 6.25 to 14.3 volumes of gas at standard temperature and pressure.

31. The method of claim 20, wherein the physiologically acceptable blood dispersible gas comprises a major proportion of carbon dioxide and/or oxygen.

32. The method of claim 20, wherein the aqueous sclerosant liquid is a solution of polidocanol or sodium tetradecylsulfate (STS) in an aqueous carrier.

33. The method of claim 20, wherein a carrier comprises a saline solution.

34. The method of claim 20, wherein the gas is pressurized at 0.1 to 9 bar over atmospheric pressure.

35. The method of claim 20, wherein the gas is pressurized at 0.1 to 3 bar over atmospheric pressure.

36. The method of claim 20, wherein the aqueous solution contains a minor amount of alcohol.

37. The method of claim 20, wherein the mixture further comprises 1 to 10% vol/vol glycerol.