Therapeutic foam

• US 7,731,986 B2
• Filed: 11/17/2004
• Issued: 06/08/2010
• Est. Priority Date: 11/17/2003
• Status: Active Grant

• Current Assignee: Boston Scientific Medical Device Limited (Boston Scientific Corporation)
• Original Assignee: BTG International Limited (Boston Scientific Corporation)
• Inventors: Harman, Anthony David, Van Liew, Hugh, Kadar, Adil, Wright, David Dakin Iorwerth, Robinson, Nikki, Hodges, Garry, Moggridge, Geoffrey D.
• Primary Examiner(s): Richter; Johann R
• Assistant Examiner(s): Soroush; Ali
• Application Number:
  US10/522,527
• Publication Number:
  US 20070104651A1
• Time in Patent Office: 2,029 Days
• Field of Search: 424/423
• US Class Current: 424/423
• CPC Class Codes: A61B 17/00008 Vein tendon strippers tube strippers A61M1/83
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61B 17/12022 Occluding by internal devices, e.g. balloons or releasable wires plugging an opening in the wall of an organ A61B17/0057; occluders for the cervical canal A61F6/146; vas deferens occluders A61F6/20
• CPC Class Codes: A61B 17/12109 in a blood vessel
• CPC Class Codes: A61B 17/12186 liquid materials adapted to be injected
• CPC Class Codes: A61B 2017/00495 for two-component glue
• CPC Class Codes: A61K 31/08 acyclic, e.g. paraformaldehyde
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• 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 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61K 9/124 characterised by the propellant
• CPC Class Codes: A61M 16/00 Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes stimulating the respiratory movement by mechanical, pneumatic or electrical means, iron lungs combined with gas breathing means A61H31/00
• CPC Class Codes: A61M 2202/00 Special media to be introduced, removed or treated applying radioactive material A61N5/1028
• CPC Class Codes: A61M 2210/086 Legs
• CPC Class Codes: A61M 2210/12 Blood circulatory system
• CPC Class Codes: A61M 5/178 Syringes
• CPC Class Codes: A61M 5/19 : having more than one chamber , e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly surgical glue applicators A61B17/00491
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: B01F 23/235 : for making foam
• CPC Class Codes: B01F 25/4512 : with reciprocating pistons
• CPC Class Codes: B01F 25/4523 : the components being pressed through sieves, screens or meshes which obstruct the whole diameter of the tube
• CPC Class Codes: B01F 33/50112 : of the syringe or cartridge type
• CPC Class Codes: B65B 3/003 : Filling medical containers such as ampoules, vials, syringes or the like
• CPC Class Codes: B65B 31/00 : Packaging articles or materials under special atmospheric or gaseous conditions; Adding propellants to aerosol containers

Abstract

A therapeutic foam for the treatment of, inter alia, varicose veins comprises a sclerosing solution foamed with a physiological gas such as carbon dioxide, oxygen or a mixture thereof. The foam has a nitrogen content of less than 0.8%. It may be generated using a pressurised canister system incorporating a fine mesh of micron dimensions through which the gas and sclerosing liquid are passed to make the foam. Alternatively, the foam may be generated by passing gas and solution between two syringes through a fine mesh. Techniques are described for minimising the amount of nitrogen in a canister or syringe based product. A technique for generating and delivering foam simultaneously using a syringe based device is also disclosed.

Claims

1. A foam comprising a liquid phase and a gas phase wherein

the liquid phase comprises at least one sclerosing agent and

the gas phase consists essentially of gaseous nitrogen present in an amount ranging from 0.01% to 0.8% by volume and a physiologically acceptable gas mixture comprising 10 to 90% vol/vol carbon dioxide with the remaining gas oxygen.

2. The foam of claim 1, wherein the gaseous nitrogen is present in an amount ranging from 0.01% to 0.7%.

3. The foam of claim 1, wherein the gaseous nitrogen is present in an amount ranging from 0.01% to 0.6%.

4. The foam of claim 1, wherein the foam has a density less than 0.25 g/cm and half life of greater than 100 secs.

5. The foam of claim 1, wherein the half life is at least 120 seconds.

6. The foam of claim 1, wherein the half life is at least 150 seconds.

7. The foam of claim 1, wherein the half life is at least 180 seconds.

8. The foam of claim 1, wherein the density ranges from 0.07 to 0.22 g/ml.

9. The foam of claim 1, wherein the density ranges from 0.07 to 0.19 g/ml.

10. The foam of claim 1, wherein the density ranges from 0.07 to 0.16 g/ml.

11. The foam of claim 1, wherein the density ranges from 0.08 to 0.14 g/ml.

12. The foam of claim 1, wherein the at least one sclerosing agent is chosen from polidocanol, glycerol and sodium tetradecyl sulphate.

13. The foam of claim 1, wherein the at least one sclerosing agent is polidocanol.

14. The foam of claim 13, wherein the polidocanol is present in a concentration ranging from 0.5 to 4% vol/vol in the liquid phase.

25. A method for angiologic treatment comprising injecting the foam as described in claim 1 into vessels to be treated.

26. The method of claim 25 comprising having a patient breathe oxygen or an oxygen enriched atmosphere for a predetermined period prior to injecting the foam.

27. The method for phlebologic treatment comprising injecting the foam as described in claim 1 into vessels to be treated.

28. The method of claim 27 comprising having a patient breathe oxygen or an oxygen enriched atmosphere for a predetermined period prior to injecting the foam.

29. The method of claim 28, wherein substantially the entire greater saphenous vein of one leg of a human patient is treated by a single injection of foam.

30. The method of claim 29, wherein the single injection uses an amount ranging from 10 ml to 50 ml.

31. The method of claim 30, wherein the single injection uses an amount ranging from 10 ml to 40 ml.

32. The method of claim 31, wherein the single injection uses an amount ranging from 15 ml to 30 ml.

33. The foam of claim 1, wherein 50% or more by number of gas bubbles of 25 μ

m diameter and over present in the foam are of no more than 200 μ

m diameter and at least 95% by number of gas bubbles of 25 μ

m diameter and over are of no more than 280 μ

m diameter.

34. The foam of claim 33, wherein at least 50% by number of gas bubbles of 25 μ

m diameter and over present in the foam are of no more than 150 μ

m diameter and at least 95% by number of gas bubbles of 25 μ

m diameter and over are of no more than 250 μ

m diameter.

35. The foam of claim 1 wherein none of the gas bubbles of the foam is of greater than 500 μ

m diameter.

15. A canister, the contents of which consist of a liquid component and a gas component, maintained at above atmospheric pressure, wherein:

the liquid phase comprises at least one sclerosing agent and

the gas phase consists essentially of gaseous nitrogen present in an amount ranging from 0.01% to 0.8% by volume and a physiologically acceptable gas mixture comprising 10 to 90% vol/vol carbon dioxide with the remaining gas oxygen.

16. The canister of claim 15, further comprising a foam generating element with at least one aperture formed therein, the at least one aperture having maximum dimensions ranging from 0.1 to 200 micron.

17. The canister of claim 16, wherein the at least one aperture has maximum dimensions ranging from 1 to 50 micron.

18. The canister of claim 17, wherein the at least one aperture has maximum dimensions ranging from 2 to 30 micron.

19. The canister of claim 18, wherein the at least one aperture has maximum dimensions ranging from 3 to 10 micron.

20. The canister of claim 19, wherein the at least one aperture has maximum dimensions of about 5 micron.

21. The canister of claim 17, wherein the at least one aperture has a maximum dimension of 3 to 10 micron, and wherein the physiologically acceptable gas mixture is from 1 to 40% carbon dioxide and the remaining gas is oxygen.

22. The canister of claim 17, wherein the physiologically acceptable gas mixture is from 10 and 30% carbon dioxide gas and the remaining gas is oxygen.

23. A method of making a canister of claim 15 comprising:

(a) flushing the canister with a gas mixture essentially comprising the other physiological acceptable gas;

(b) introducing the at least one sclerosing agent sclerosing agent into the canister either before or after step (a);

(c) pressurizing the canister to a first predetermined pressure above atmospheric pressure from a source of the other physiological acceptable gas whose level of nitrogen contamination is between 0.0001% and 0.5%;

(d) partially exhausting the contents of the canister, followed by re-pressurizing the canister from the same or a different source of the other physiologically acceptable gas whose level of nitrogen contamination is between 0.0001% and 0.5%.

24. The method of claim 23, wherein the pressure in the canister is maintained at or above the surrounding atmospheric pressure.