Method and device for generating injectable foam

Abstract

The present invention relates to methods and devices for production of injectable foams, such as those used in the treatment of varicose veins and other venous disorders. The method requires the delivery or supply of foamable liquid sclerosing agent and a suitable gas or a gas mixture to a foam producing structure in which the liquid and gas are combined to produce foam, wherein the liquid is delivered independently of the delivery of gas. Devices for producing injectable foam comprise a foam producing structure in which liquid and gas are combined to produce foam, the structure comprising an inlet for liquid and gas and an outlet for foam; a liquid pathway in communication with the inlet; and a gas pathway in communication with the inlet, characterised in that the liquid pathway comprises a means for delivering liquid through the liquid pathway independently of gas delivery through the gas pathway. In preferred embodiments, the delivery of liquid and/or gas is controlled with volumetric pumps.

Claims

1. A method of producing injectable foam comprising: selecting a desired density value as a chosen parameter of the injectable foam; independently delivering a foamable liquid and a gas to a foam producing structure; passing the foamable liquid and the gas through at least one element defining at least one passage within the foam producing structure; independently controlling the flow rate of the foamable liquid and the gas using a control unit; wherein the control unit adjusts the relative amounts and flow rates of the foamable liquid and gas delivered to the foam producing structure; producing foam in the foam producing structure; passing the foam from the foam producing structure through a waste valve; opening the waste valve when inferior quality foam not having the chosen parameter is produced and diverting the inferior quality foam into a waste chamber; closing the waste valve when foam having the chosen parameter is being produced; and producing and dispensing the injectable foam having the chosen parameter.

2. The method according to claim 1 wherein the foamable liquid is delivered by a pump.

3. The method according to claim 2 wherein the pump is a volumetric pump.

4. The method according to claim 1 wherein the gas is delivered by a volumetric pump.

5. The method according to claim 1 wherein the gas is delivered under pressure.

6. The method according to claim 5 wherein the pressure is between 0.9 and 2.0 bar absolute.

7. The method according to claim 1 wherein the foamable liquid is delivered at a flow rate of between 7 ml/min and 10 ml/min.

8. The method according to claim 1 wherein the gas is delivered at a flow rate of between 24 ml/min and 36 ml/min.

9. The method according claim 7 wherein the volumetric ratio of foamable liquid to gas delivered to the foam producing structure is between 0.10 and 0.25.

10. The method according to claim 9 wherein the density of the injectable foam produced is between 0.09 g/ml and 0.16 g/ml.

11. The method according to claim 1, wherein selecting the desired density value includes selecting a desired density value in g/ml.

12. A method of producing injectable foam comprising: selecting a desired density value from a range of 0.09 g/ml to 0.16 m/ml for the injectable foam; independently delivering a foamable liquid and a gas to a foam producing structure; passing the foamable liquid and the gas through at least one element defining at least one passage within the foam producing structure; independently controlling the flow rate of the foamable liquid and the gas using a control unit; wherein the control unit adjusts the relative amounts and flow rates of the foamable liquid and gas delivered to the foam producing structure; producing foam in the foam producing structure; passing the foam from the foam producing structure through a waste valve; opening the waste valve when the foam being produced does not have the desired density value, and diverting the foam into a waste chamber; closing the waste valve when the foam being produced has the desired density value; and dispensing the injectable foam having the desired density value.

13. The method according to claim 12, wherein the foamable liquid is delivered by a pump.

14. The method according to claim 12 wherein the gas is delivered by a volumetric pump.

15. The method according to claim 12 wherein the gas is delivered under pressure.

16. The method according to claim 15 wherein the pressure is between 0.9 and 2.0 bar absolute.

17. The method according to claim 12 wherein the foamable liquid is delivered at a flow rate of between 7 ml/min and 10 ml/min.

18. The method according to claim 12 wherein the gas is delivered at a flow rate of between 24 ml/min and 36 ml/min.

19. The method according to claim 17 wherein the volumetric ratio of foamable liquid to gas delivered to the foam producing structure is between 0.10 and 0.25.

Description

(1) The invention will now be described further with reference to the accompanying drawings, in which:

(2) FIGS. 1A and 1B shows a schematic view of the key components necessary to produce foam according to the method of the invention;

(3) FIG. 2 shows a schematic view of a combination of components that may be used to produce foam according to the method of the invention;

(4) FIG. 3 shows a schematic view from the combination of components from FIG. 2 engaged with additional components that may be provided in a durable machine;

(5) FIG. 4 shows a graph of the Liquid flow rate:Gas flow rate ratio against foam density obtained using a device of the invention. The data used are presented in tabular form in Table 2;

(6) FIGS. 5A to 5D show graphs of Liquid flow rate against Gas flow rate for production of foam having densities of 0.11 g/ml, 0.12 g/ml, 0.13 g/ml and 0.14 g/ml respectively using a device of the invention. The data used are presented in tabular form in Table 2;

(7) FIG. 6 shows a section view of a device according the invention;

(8) FIG. 7 shows a section view of a device according to the invention incorporating the device of FIG. 6; and

EXAMPLES

(9) FIGS. 1A and 1B show schematic views of the key components of the invention in which a foam producing structure (4) is shown having an inlet for liquid and gas (5) and an outlet for foam (6). A liquid pathway (1) is in communication with an inlet (5), and a gas pathway (2) is in communication with a separate inlet (5). A pump (3) is provided within the liquid pathway (1).

(10) The device comprises a minimal combination of structural features necessary to produce foam according to the invention, and therefore it is particularly suitable for use as a disposable device in combination with a machine that drives the pump (3) and provides sources of liquid and gas.

(11) FIG. 2 shows a schematic view of a combination of components that may be used to produce foam in which a liquid pathway (10) and a gas pathway (20) are in communication with a foam producing structure (31) through separate inlets for liquid and gas (not identified in the drawing). In this example the foam producing structure (31) includes a mesh stack. The liquid pathway (10) and the gas pathway (20) each comprise silicone tubing.

(12) Gas is provided to the gas pathway (20) from an external pressurised gas source (not shown) through a gas connector (21) at a pressure that is controlled by an external gas pressure regulator (not shown) arranged inline between the pressurised gas source (not shown) and the gas connector (21).

(13) Gas passage through the gas pathway (20) is controlled by a gas valve (22) that may be open or closed. When the gas valve (22) is open during use of the device gas passes through a gas filter (23) to ensure that gas provided to the foam producing structure (31) is sterile. Sterile gas is delivered to the foam producing structure (31) through the gas pathway (20) by a gas pump (24). The gas pump (24) is a volumetric pump that propels 20 μl of gas with each pump stroke. Adjustments can be made to the rate or frequency of operation of the gas pump (24) so as to deliver a desired volume of gas to the foam producing structure (31).

(14) Pressure sensors (25) are provided in the gas pathway (20) to measure gas pressure on entry to the gas pump (24) and on entry to the foam producing structure (31). Gas pump (24) operation typically increases gas pressure before entry to the foam producing structure (31).

(15) Liquid is provided to the liquid pathway (10) from an external liquid source (not shown) through a liquid connector (11) at ambient pressure and propelled through the liquid pathway (10) by a liquid pump (12) that operates independently of the gas pathway (20) and the gas pump (24). The liquid pump (12) is a volumetric pump that propels 5 μl of gas with each pump stroke. Adjustments can be made to the rate or frequency of operation of the liquid pump (12) so as to deliver a desired volume of liquid to the foam producing structure (31). A back pressure valve (13) is located between the liquid pump (12) and foam producing structure (31) to prevent liquid reflux in the liquid pathway (10).

(16) Liquid and gas are independently delivered to the foam producing structure (31) where they mix and pass across a series of 4 mesh filters having a mean pore size of 5 μm with the filters being separated from each other by between 3.5 mm and 3.7 mm to produce foam. Foam produced in the foam producing structure (31) is delivered to the foam pathway (30) through the outlet. The foam is then passed through a foam conditioning structure (33) which comprises a further mesh stack of 4 filters, each having a mean pore size of 5 μm, and the filters being separated from each other within the stack by between 3.5 mm and 3.7 mm (Filtertek). Passage through the foam conditioning structure (33) yields steady state foam with increased stability compared to foam that is not passed through the foam conditioning structure (33).

(17) Optimal quality foam is separated from inferior quality foam produced on initial operation of the device by activating a waste valve (34) arranged within the foam pathway (30) to control communication between the foam pathway (30) and a waste chamber (35). Opening the waste valve (34) allows communication between the waste chamber (35) and the foam pathway (30) to allow a portion of foam to be diverted into and retained within the waste chamber (35). The waste valve (34) is closed once optimal quality foam is produced, and foam is provided through the foam pathway (30) to the foam port (36) for use by the user.

(18) Pressure sensors (25) are provided in the foam pathway (30) to measure foam pressure on exit from the foam producing structure (31) and on exit from the foam conditioning structure (33). Foam pressure is reduced to ambient pressure on exit from the foam conditioning structure (33).

(19) FIG. 3 shows a schematic view of the combination of components from FIG. 2 in the form of a disposable (101) engaged with additional components likely provided in a durable machine (501). In this scheme a liquid pump motor (111) and a gas pump motor (211) are arranged to engage and drive the liquid pump (12) and the gas pump (24) respectively so as to deliver liquid and gas independently to the foam producing structure (31) where they are combined to produce foam as described in FIG. 1. The user defines the foam specification required and programmes the apparatus using a data input device (302), which is a 7″ touchscreen device arranged in electronic communication with a control unit (300).

(20) The control unit (300) is a programmable computer device arranged in electronic communication with a liquid pump motor controller (112) and a liquid pump motor (111) which mechanically engages the liquid pump (12). The user provides instruction to the control unit (300) through the data input device (302) instructing the liquid pump motor controller (112) to operate the liquid pump motor (111) at a defined speed. The liquid pump motor (111) then drives the liquid pump (12) at the defined speed so as to deliver liquid through the liquid pathway (10) to the foam producing structure (31) independently of the delivery of gas through the gas pathway (20).

(21) The control unit (300) is similarly and independently arranged in electronic communication with a gas pump motor controller (212) and a gas pump motor (211) which mechanically engages the gas pump (24). The user provides instruction to the control unit (300) through the data input device (302) instructing the gas pump motor controller (212) to operate the gas pump motor (211) at a defined speed. The gas pump motor (211) then drives the gas pump (24) at the defined speed so as to deliver gas through the gas pathway (20) to the foam producing structure (31) in the required amount.

(22) The device also includes a pressure sensor system (221) arranged in electronic communication with pressure sensors (25) located in the gas pathway (20) and in the foam pathway (30). The pressure sensor system (221) is in electronic communication with an analog measurement system (222) and provides pressure readings from the pressure sensors (25) to the analog measurement system (222). Pressure readings are standardised and provided to the control unit (300) where they are stored and can then be monitored by the user on the data input device (302).

(23) The apparatus further includes a data interface (301) that allows the user to download data and information form the control unit (300). In this example the data interface (301) is a USB connector.

(24) Table 1 describes the characteristics of foam produced under varied conditions using a device of the invention as shown in FIG. 3. The liquid used was a 1% (w/v) aqueous solution of polidocanol, and the gas used was a mixture of oxygen (65%) and carbon dioxide (35%).

(25) Table 2 describes production of foam having defined density using a device of the invention comprising the combination of components as shown in FIG. 3. The liquid used was a 1% (w/v) aqueous solution of polidocanol, and the gas used was a mixture of oxygen (65%) and carbon dioxide (35%). The data are presented in graphic form in FIGS. 4 and 5A to 5D. These data demonstrate that foam having desired properties can be produced using a method and a device of the inventions under various conditions that influence the density and production rate of foam.

(26) FIG. 6 shows a section view of a disposable component of the device according to the second aspect of the invention. An external source of gas (not shown) is arranged in communication with a gas connector (21) to provide gas to a gas pathway (20). Gas is delivered through the gas pathway (20) to a foam producing structure (31) by a gas pump (24). A source of liquid (9) in the form of a vial is arranged in communication with a liquid connector (11) in the form of a vial spike to provide liquid to a liquid pathway (10). Liquid is delivered through the liquid pathway (10) to the foam producing structure (31) by a liquid pump (12). Liquid and gas are combined in the foam producing structure (31) to produce foam, which then enters a foam pathway (30). Initial poor quality foam is diverted into a waste chamber (35) together with any gas to be purged from the device by activating a waste valve (34) to open communication between the foam pathway (30) and the waste chamber (35). The waste valve (34) is then closed and foam for use in sclerotherapy is delivered to a foam port (36).

(27) FIG. 7 shows a section view of a device according to the second aspect of the invention in which the disposable component of FIG. 6 (100) is engaged with a durable machine (500) to produce foam.

(28) Electrical power is supplied to the machine (500) through a mains input (401) to provide electricity to the power supply (400). A power switch (402) is used to engage (on) and disengage (off) electrical power to the device through the mains input (401). The power supply provides the appropriate electrical power supply to a control unit (300) to control operation of the device.

(29) The control unit (300) is in electrical communication with a liquid pump motor controller (112) that controls a liquid pump motor (111). The pump motor (111) indirectly engages and drives a liquid pump to deliver liquid through the liquid pathway into the foam producing structure within the disposable component (100). The indirect engagement between the pump motor (111) and the pump is mediated by a drivetrain mechanism (200).

(30) An external source of gas (not shown) is arranged in communication with a gas connector (21) to provide gas to a gas pathway (20) that includes a gas valve (22) and a gas pressure regulator (28). Gas is delivered through the gas pathway (20) to the disposable component (100) as described in FIG. 6.

(31) The control unit (300) is independently in electrical communication with a gas pump motor controller (212) that controls a gas pump motor (211). The pump motor (211) indirectly engages and drives a gas pump to deliver gas through the gas pathway into the foam producing structure within the disposable component (100). The indirect engagement between the pump motor (211) and the pump is mediated by a drivetrain mechanism (200). The drivetrain mechanism (200) mediates engagement of the liquid pump independently from engagement of the gas pump thereby providing independent delivery of liquid and gas to the foam producing structure within the disposable device (100).

(32) The user defines the foam specification required and programmes the apparatus using a data input device (302) that is arranged in electronic communication with the control unit (300). User programming of the control unit (300) through the data input device (302) instructs the motor controllers (112, 212) to operate the pump motors (111, 211) at defined speeds and thereby deliver liquid and gas to the foam producing structure within the disposable component (100).

(33) TABLE-US-00001 TABLE 1 Gas pump Liquid speed.sup.# pump.sup..diamond-solid. Gas flow Liquid flow Pressure* Foam half- Foam Syringe fill (Hz) speed (Hz) rate (ml/h) rate (ml/hr) (bar) life (s) density time (s) 6 18 432 324 2.232 149 0.178 65 10 18 720 324 2.216 149 0.113 42 6 12 432 216 2.239 148 0.140 76 6 16 432 288 2.254 148 0.175 66 8 18 576 324 2.214 157 0.133 46 8 10 576 180 1.230 142 0.143 89 8 8 576 144 1.221 156 0.129 88 12 10 864 180 0.638 142 0.191 103 6 8 432 144 2.256 166 0.094 69 .sup.#20 μl volumetric pump .sup..diamond-solid.5 ml volumetric pump *pressure measured before entry of gas into the gas pump.

(34) TABLE-US-00002 TABLE 2 Density Gas flow rate * Liquid flow rate Liquid/Gas (g/ml) (ml/min) (ml/min) ratio 0.09 27.108 3.6 0.132802 0.09 27.126 3.6 0.132714 0.10 60.15 10.2 0.169576 0.11 45.03 6.6 0.146569 0.11 36.054 6 0.166417 0.11 45.03 6.6 0.146569 0.11 38.448 6 0.156055 0.11 38.376 6 0.156348 0.11 36.036 6 0.1665 0.11 72.252 10.8 0.149477 0.11 54.108 7.2 0.133067 0.11 72.216 10.8 0.149551 0.11 27.054 4.8 0.177423 0.11 36.054 7.08 0.196372 0.11 48 9.72 0.2025 0.11 27.108 4.8 0.177069 0.11 36.09 7.08 0.196176 0.12 36.108 7.08 0.196078 0.12 36 7.08 0.196667 0.12 36.054 7.08 0.196372 0.12 38.4 7.2 0.1875 0.12 38.52 7.2 0.186916 0.12 36.072 7.08 0.196274 0.12 38.496 7.2 0.187032 0.12 43.272 6.6 0.152524 0.12 60 10.2 0.17 0.13 54.072 7.2 0.133156 0.13 38.4 7.2 0.1875 0.13 45.18 8.4 0.185923 0.13 43.452 6.6 0.151892 0.13 45.06 8.4 0.186418 0.13 45.03 8.4 0.186542 0.13 45 8.4 0.186667 0.13 48.072 9.72 0.202197 0.13 48.024 9.72 0.202399 0.13 48 9.72 0.2025 0.13 48.048 9.72 0.202298 0.13 48.09 9.6 0.199626 0.13 48 9.72 0.2025 0.14 48.168 9.72 0.201794 0.14 48.144 9.72 0.201894 0.14 48.03 9.6 0.199875 0.14 43.272 8.4 0.194121 0.14 43.2 8.4 0.194444 0.14 36.108 8.4 0.232635 0.15 36.072 8.4 0.232868 0.16 71.964 14.76 0.205103 0.16 72.072 14.76 0.204795 * gas flow rate normalised for pressure