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Title:
METHOD FOR ENHANCED DELIVERY OF MEMBRANE ACTIVE AGENTS
Document Type and Number:
WIPO Patent Application WO/2021/138714
Kind Code:
A1
Abstract:
A method and apparatus for enhanced delivery of therapeutically active, cosmetic or skin care agents onto membrane surfaces by use of a combination of magneto-wetting and electro-wetting on ultrasonically generated diamagnetic droplets, including enhanced delivery of substances (such as pharmaceuticals, nutraceuticals, biopharmaceuticals, cosmeceuticals, biologically active substances, detergents, cleaners, bleaches, dyes, fragrances, conditioners or polishes) to dermal or mucosal surfaces.

Inventors:
MCILDOWIE MATTHEW (AU)
EDWARDS JEFFREY (AU)
Application Number:
PCT/AU2021/050005
Publication Date:
July 15, 2021
Filing Date:
January 06, 2021
Export Citation:
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Assignee:
INTERNATIONAL SCIENT PTY LTD (AU)
International Classes:
A61M37/00; A61M11/00; A61M35/00; A61Q5/00; A61Q7/00; A61Q19/00
Domestic Patent References:
WO2020190331A1
WO2005049135A12005-06-02
WO2018169924A12018-09-20
Foreign References:
US5518179A1996-05-21
Other References:
ANONYMOUS: "STM8S003F3 STM8S003K3 Value line, 16 MHz STM8S 8-bit MCU, 8 Kbyte Flash, 128 byte data EEPROM, 10-bit ADC, 3 timers, UART, SPI, I2C", 19 November 2016 (2016-11-19), pages 1 - 103, XP055839928, Retrieved from the Internet [retrieved on 20210303]
BORMASHENKO EDWARD: "Moses effect: Physics and applications.", ADVANCES IN COLLOID AND INTERFACE SCIENCE, vol. 269, 1 January 2019 (2019-01-01), NL, pages 1 - 6, XP085705647, ISSN: 0001-8686, DOI: 10.1016/j.cis.2019.04.003
SUNG KWON CHO, HYEJIN MOON, CHANG-JIN KIM: "Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits. Journal of Microelectromechanical systems.", JOURNAL OF MICROELECTROMECHANICAL SYSTEMS, vol. 12, no. 1, 1 February 2003 (2003-02-01), pages 70 - 80, XP055294030, ISSN: 1057-7157, DOI: 10.1109/JMEMS.2002.807467
Attorney, Agent or Firm:
WRAYS PTY LTD (AU)
Download PDF:
Claims:
CLAIMS

1 . A method for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the method comprising the steps of: i) generating a stream of droplets comprising the active agent in a liquid composition; ii) moving the droplet through a magnetic field; and iii) moving the droplets of (ii) onto the surface wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplets such that the contact angle between the droplets and the surface is reduced and the contact area of the droplets to the surface is increased.

2. The method of claim 1 wherein the diameter of the droplets is between 1 pm and 500pm, preferably between 10pm and 250pm.

3. The method of claim 1 or claim 2 wherein the stream of droplets is generated by an ultrasonic atomiser.

4. The method of any one of claims 1 to 3 wherein the magnetic field is a time varying electromagnetic field comprising a variable electromagnetic waveform signal, wherein the electromagnetic waveform signal produces a magnetic flux density of between about 1 mT and about 50mT, about 1.5 mT and about 48mT, about 2mT and about 46mT, about 2.5mT and about 44mT, about 3mT and about 42mT, about 3.5mT and about 40mT, about 4mT and about 38mT, about 4.2mT and about 36mT, about 4.4mT and about 34mT, about 4.6mT and about 32mT, about 4.8mT and about 31 mT, or about 5mT and about 30mT, preferably of between about 5mT and about 30mT.

5. The method of any one of claims 1 to 4 wherein the magnetic field is a time varying electromagnetic field comprising a variable electromagnetic waveform signal, wherein the electromagnetic waveform signal comprises a waveform pattern (W1) and a waveform pattern (W2), and the electromagnetic waveform signal has a Wave Factor of between about 0.05 to about 5.0, about 0.06 to about 4.5, about 0.07 to about 4.0, about 0.08 to about 3.5, about 0.09 to about 3.0 or about 0.1 to about 2.9, preferably about 0.1 to about 2.7, wherein the Wave Factor is derived from the equation;

Wave Factor = (W1 factor) + (W2 factor); wherein

W1 factor is between about 0.01 to about 3.0, about 0.02 to about 2.9, about 0.03 to about 2.8, about 0.04 to about 2.7, about 0.05 to about 2.6, about 0.06 to about 2.5, about 0.07 to about 2.4, about 0.08 to about 2.3, about 0.09 to about 2.2, about 0.09 to about 2.1 , or about 0.1 to about 2.0, preferably about 0.1 to about 1 .9; and

W2 factor is between about 0.0 to about 2.0, about 0.01 to about 1.5, about 0.02 to about 1.4, about 0.03 to about 1.3, about 0.04 to about 1.2, about 0.05 to about 1.1 , or about 0.05 to about 1.0, preferably between about 0.05 to about 0.9.

6. The method of claim 5 wherein the waveform pattern W1 has: a) a duty cycle of between between about 1% to about 50%, about 1.1% to about 45%, about 1 .2% to about 40%, about 1 .3% to about 35%, about 1.4% to about 30%, about 1.5% to about 25%, about 1.6% to about 20%, about 1.7% to about 15%, about 1.8% to about 14%, about 1.9% to about 13%, about 2% to about 12%, about 2.1% to about 11.9%, about 2.2% to about 11.88%, or about 2.25% to about 11.88%, preferably a duty cycle of between about 1% to about 20%; and/or b) a duration of between about 1 ms to about 5000 ms, about 10 ms to about 4500 ms, about 20 ms to about 4000 ms, about 30 ms to about 3500 ms, about 40 ms to about 3000 ms, about 50 ms to about 2500 ms, about 60 ms to about 2000 ms, about 70 ms to about 1500 ms, about 80 ms to about 1000 ms, about 90 ms to about 900 ms, about 100 ms to about 850 ms, about 150 ms to about 800 ms, about 200 ms to about 750 ms, about 250 ms to about 650 ms, about 300 ms to about 640 ms, about 350 ms to about 630 ms, about 400 ms to about 620 ms, about 450 ms to about 615 ms, about 500 ms to about 612 ms, about 530 ms to about 609 ms, or about 534 ms to about 606 ms, preferably a duration of between about 100 ms to about 1000 ms; and/or c) wherein the number of pulses in W1 is between about 1 to about 5000, about 2 to about 4500, about 3 to about 4000, about 4 to about 3500, about 5 to about 3000, about 6 to about 2500, about 7 to about 2000, about 8 to about 1500, about 9 to about 1000, about 10 to about 500, about 12 to about 450, about 14 to about 400, about 16 to about 350, about 18 to about 300, about 20 to about 250, about 22 to about 200, about 24 to about 180, about 26 to about 160, about 28 to about 140, or about 30 to about 120, preferably between about 5 to about 500; and/or d) a magnetic flux density of between about 1 mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT.

7. The method of claim 5 or claim 6, wherein the waveform pattern W2 has: a) a duty cycle of between about 1% to about 50%, about 1.01% to about 45%, about 1 .02% to about 40%, about 1 .03% to about 35%, about 1.04% to about 30%, about 1.05% to about 25%, about 1.06% to about 20%, about 1.07% to about 15%, about 1.08% to about 14%, about 1.09% to about 13%, about 1.09% to about 12%, about 1.1% to about 11%, about 1.2% to about 10%, 1.22% to about 9%, 1.24% to about 8%, 1.26% to about 7%, 1.28% to about 6.5%, 1 .3% to about 6%, 1 .32% to about 5.8%, 1.33% to about 5.7%, 1.34% to about 5.6%, 1 .35% to about 5.58%, 1.36% to about 5.57%, 1.365% to about 5.56%, or about 1.37% to about 5.55%, preferably a duty cycle of between about 1% to about 20%; and/or b) a duration of between about 1 ms to about 5000 ms, about 100 ms to about 4500 ms, about 200 ms to about 4000 ms, about 300 ms to about 3500 ms, about 400 ms to about 3000 ms, about 500 ms to about 2900 ms, about 600 ms to about 2850 ms, about 700 ms to about 2800 ms, about 800 ms to about 2750 ms, about 900 ms to about 2700 ms, about 1000 ms to about 2650 ms, about 1100 ms to about 2600 ms, about 1200 ms to about 2550 ms, about 1300 ms to about 2500 ms, about 1400 ms to about 2450 ms, about 1500 ms to about 2400 ms, about 1600 ms to about 2350 ms, about 1700 ms to about 2300 ms, about 1800 ms to about 2250 ms, about 1900 ms to about 2200 ms, about 1950 ms to about 2150 ms, about 2000 ms to about 2100 ms, or about 2102 ms to about 2074 ms, preferably a duration of between about 100 ms to about 5000 ms; and/or c) wherein the number of pulses in W2 is between about 1 to about 5000, about 2 to about 4500, about 4 to about 4000, about 6 to about 3500, about 8 to about 3000, about 10 to about 2500, about 15 to about 2000, about 20 to about 1500, about 25 to about 1000, about 30 to about 500, about 35 to about 450, about 40 to about 400, about 45 to about 350, about 50 to about 300, about 55 to about 295, about 60 to about 292, about 65 to about 290, about 70 to about 289, or about 72 to about 288, preferably between about 5 to about 500; and/or d) a magnetic flux density of between about 1 mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT.

8. An apparatus for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, in accordance with the method of any one of claims 1 to 7, the apparatus comprising: a) a means to generate a stream of droplets comprising the active agent in a liquid composition; and b) a means to generate a magnetic field; wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplets such that the contact angle between the droplets and the surface is reduced and the contact area of the droplets to the surface is increased.

9. The apparatus of claim 8 wherein the stream of droplets is generated by an ultrasonic atomiser.

10. The apparatus of claim 9 wherein the ultrasonic atomiser comprises a piezo element.

11 . The apparatus of claim 9 or claim 10 wherein the ultrasonic atomiser is a piezo element with a plurality of holes that allow liquids to be atomised therethrough, comprising a circuit for generating the voltage to drive the atomiser, wherein the circuit is connected to a port from a microprocessor for controlling the atomiser, and wherein the piezo element is operably attached to a liquid supply vessel.

12. The apparatus of any one of claims 8 to 11 wherein the magnetic field is generated by one or more coil inductors for producing an electromagnetic waveform signal.

13. The apparatus of claim 12 wherein the one or more coil inductors are configured to provide electromagnetic pulse fields corresponding to a predetermined electromagnetic waveform signal, through which the atomised droplets of liquid travel, and wherein the one or more coil inductors are driven by an energisation signal from a bipolar transistor which is controlled via a microprocessor port.

14. A liquid composition, comprising one or more agents, when delivered to a membrane surface via the method of any one of claims 1 to 7, and/or via the apparatus of any one of claims 8 to 13.

15. A kit, comprising the apparatus of any one of claims 8 to 13, and instructions for use.

Description:
Method for Enhanced Delivery of Membrane Active Agents TECHNICAL FIELD

[0001] The present invention relates to a method and apparatus for enhanced delivery of therapeutically active, cosmetic or skin care agents onto membrane surfaces by use of a combination of magneto-wetting and electro-wetting on ultrasonically generated diamagnetic droplets, including enhanced delivery of substances (such as pharmaceuticals, nutraceuticals, biopharmaceuticals, cosmeceuticals, biologically active substances, detergents, cleaners, bleaches, dyes, fragrances, conditioners or polishes) to dermal or mucosal surfaces.

BACKGROUND ART

[0002] The delivery of therapeutic, cosmetic or skin care agents onto membranes, such as the skin, including mucosal or dermal surfaces, must occur in sufficient amounts and/or at sufficient concentrations to allow the therapeutic, cosmetic or skin care agents to achieve their purpose. Techniques and devices have been developed to assist in the transmission of active compositions or compounds through membranes. For example, International Patent Application PCT/AU2010/000782, filed by International Scientific Pty Ltd and entitled “An Apparatus and Method of Treatment Utilizing a Varying Electromagnetic Energisation Profile” (which is incorporated herein by reference) describes an apparatus which is designed to improve the delivery of desirable substances across a membrane by utilising a varying electromagnetic energisation profile.

[0003] However, many surfaces, including membrane surfaces, are hydrophobic and it is difficult to get penetration of many active agents, particularly hydrophilic agents, into hydrophobic and super hydrophobic surfaces. The contact angle of aqueous droplets on hydrophobic and super hydrophobic surfaces is very high resulting in a very small diffusion area.

[0004] Traditional electro-wetting techniques for decreasing the contact angle and contact surface area of droplets require a voltage potential to be generated between the droplet and the surface. This is achieved by inserting a very fine conducting wire into each droplet and providing a ground potential to the surface. This requirement greatly limits utility and convenience as it is complex and difficult to implement.

[0005] It is an object of the present invention to at least partially address one or more of the above illustrated problems in the art, or at least to provide an alternative to existing commercial products. It is against this background that embodiments of the present invention have been developed. [0006] The previous discussion of the background art is intended to facilitate an understanding of the present invention only. The discussion is not an acknowledgement or admission that any of the material referred to is or was part of the common general knowledge as at the priority date of the application.

SUMMARY OF INVENTION

[0007] The present invention employs a time varying magnetic field to induce both Magneto wetting and Electro-wetting properties to a droplet in flight, without the need for any direct electrode contact with the droplet, greatly enhancing efficacy, efficiency, utility and convenience, whilst reducing complexity and overcoming the difficulties of implementation associated with prior art Magneto-wetting and Electro-wetting processes.

[0008] The present invention provides a method for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the method comprising the steps of: i) generating a droplet comprising the active agent in a liquid composition; ii) moving the droplet through a magnetic field; and iii) moving the droplet of (ii) onto the surface wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplet such that the contact angle between the droplet and the surface is reduced and the contact area of the droplet to the surface is increased.

[0009] The present invention further provides a method for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the method comprising the steps of: i) generating a stream of droplets comprising the active agent in a liquid composition; ii) moving the droplets through a magnetic field; and iii) moving the droplets of (ii) onto the surface wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplets such that the contact angle between the droplets and the surface is reduced and the contact area of the droplets to the surface is increased.

[0010] The present invention further provides an apparatus for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the apparatus comprising: a) a means to generate a droplet comprising the active agent in a liquid composition; and b) a means to generate a magnetic field; wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplet such that the contact angle between the droplet and the surface is reduced and the contact area of the droplet to the surface is increased.

[0011] The present invention further provides an apparatus for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the apparatus comprising: a) a means to generate a stream of droplets comprising the active agent in a liquid composition; and b) a means to generate a magnetic field; wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplets such that the contact angle between the droplets and the surface is reduced and the contact area of the droplets to the surface is increased.

[0012] Preferably the droplet has a diameter between 10pm and 250pm.

[0013] Preferably the stream of droplets is generated by means of an ultrasonic atomiser or ultrasonic droplet generator.

[0014] Preferably the magnetic field is an electromagnetic field comprising a mnemonic describing the variance with time of the electromagnetic waveform.

[0015] Preferably the magnetic field also induces an electrical charge on the droplet.

[0016] In some embodiments of the method and apparatus of the invention, the magnetic field is a time varying electromagnetic field comprising a variable electromagnetic waveform signal, wherein the electromagnetic waveform signal produces a magnetic flux density of between about 1 mT and about 50mT, about 1.5 mT and about 48mT, about 2mT and about 46mT, about 2.5mT and about 44mT, about 3mT and about 42mT, about 3.5mT and about 40mT, about 4mT and about 38mT, about 4.2mT and about 36mT, about 4.4mT and about 34mT, about 4.6mT and about 32mT, about 4.8mT and about 31 mT, or about 5mT and about 30mT, preferably of between about 5mT and about 30mT.

[0017] In some embodiments of the method and apparatus of the invention, the magnetic field is a time varying electromagnetic field comprising a variable electromagnetic waveform signal, wherein the electromagnetic waveform signal produces a magnetic flux density of between 1mT and 50mT, 1.5 mT and 48mT, 2mT and 46mT, 2.5mT and 44mT, 3mT and 42mT, 3.5mT and 40mT, 4mT and 38mT, 4.2mT and 36mT, 4.4mT and 34mT, 4.6mT and 32mT, 4.8mT and 31 mT, or 5mT and 30mT, preferably of between 5mT and 30mT.

[0018] In some embodiments of the method and apparatus of the invention, the magnetic field is a time varying electromagnetic field comprising a variable electromagnetic waveform signal, wherein the electromagnetic waveform signal comprises a waveform pattern (W1) and a waveform pattern (W2), and the electromagnetic waveform signal has a Wave Factor of between about 0.05 to about 5.0, about 0.06 to about 4.5, about 0.07 to about 4.0, about 0.08 to about 3.5, about 0.09 to about 3.0 or about 0.1 to about 2.9, preferably about 0.1 to about 2.7, wherein the Wave Factor is derived from the equation;

Wave Factor = (W1 factor) + (W2 factor); wherein

W1 factor is between about 0.01 to about 3.0, about 0.02 to about 2.9, about 0.03 to about 2.8, about 0.04 to about 2.7, about 0.05 to about 2.6, about 0.06 to about 2.5, about 0.07 to about 2.4, about 0.08 to about 2.3, about 0.09 to about 2.2, about 0.09 to about 2.1 , or about 0.1 to about 2.0, preferably about 0.1 to about 1 .9; and

W2 factor is between about 0.0 to about 2.0, about 0.01 to about 1 .5, about 0.02 to about 1.4, about 0.03 to about 1.3, about 0.04 to about 1.2, about 0.05 to about 1.1 , or about 0.05 to about 1.0, preferably between about 0.05 to about 0.9.

[0019] In some embodiments of the method and apparatus of the invention, the magnetic field is a time varying electromagnetic field comprising a variable electromagnetic waveform signal, wherein the electromagnetic waveform signal comprises a waveform pattern (W1) and a waveform pattern (W2), and the electromagnetic waveform signal has a Wave Factor of between 0.05 to 5.0, 0.06 to 4.5, 0.07 to 4.0, 0.08 to 3.5, 0.09 to 3.0 or 0.1 to 2.9, preferably 0.1 to 2.7, wherein the Wave Factor is derived from the equation;

Wave Factor = (W1 factor) + (W2 factor); wherein

W1 factor is between 0.01 to 3.0, 0.02 to 2.9, 0.03 to 2.8, 0.04 to 2.7, 0.05 to 2.6, 0.06 to 2.5, 0.07 to 2.4, 0.08 to 2.3, 0.09 to 2.2, 0.09 to 2.1 , or 0.1 to 2.0, preferably 0.1 to 1.9; and

W2 factor is between 0.0 to 2.0, 0.01 to 1.5, 0.02 to 1 .4, 0.03 to 1 .3, 0.04 to 1 .2, 0.05 to 1 .1 , or 0.05 to 1 .0, preferably between 0.05 to 0.9.

[0020] In some embodiments of the method and apparatus of the invention, the waveform pattern W1 has: a) a duty cycle of between between about 1% to about 50%, about 1.1% to about 45%, about 1 .2% to about 40%, about 1 .3% to about 35%, about 1.4% to about 30%, about 1.5% to about 25%, about 1.6% to about 20%, about 1.7% to about 15%, about 1.8% to about 14%, about 1.9% to about 13%, about 2% to about 12%, about 2.1% to about 11.9%, about 2.2% to about 11.88%, or about 2.25% to about 11.88%, preferably a duty cycle of between about 1% to about 20%; and/or b) a duration of between about 1 ms to about 5000 ms, about 10 ms to about 4500 ms, about 20 ms to about 4000 ms, about 30 ms to about 3500 ms, about 40 ms to about 3000 ms, about 50 ms to about 2500 ms, about 60 ms to about 2000 ms, about 70 ms to about 1500 ms, about 80 ms to about 1000 ms, about 90 ms to about 900 ms, about 100 ms to about 850 ms, about 150 ms to about 800 ms, about 200 ms to about 750 ms, about 250 ms to about 650 ms, about 300 ms to about 640 ms, about 350 ms to about 630 ms, about 400 ms to about 620 ms, about 450 ms to about 615 ms, about 500 ms to about 612 ms, about 530 ms to about 609 ms, or about 534 ms to about 606 ms, preferably a duration of between about 100 ms to about 1000 ms; and/or c) wherein the number of pulses in W1 is between about 1 to about 5000, about 2 to about 4500, about 3 to about 4000, about 4 to about 3500, about 5 to about 3000, about 6 to about 2500, about 7 to about 2000, about 8 to about 1500, about 9 to about 1000, about 10 to about 500, about 12 to about 450, about 14 to about 400, about 16 to about 350, about 18 to about 300, about 20 to about 250, about 22 to about 200, about 24 to about 180, about 26 to about 160, about 28 to about 140, or about 30 to about 120, preferably between about 5 to about 500; and/or d) a magnetic flux density of between about 1 mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT.

[0021] In some embodiments of the method and apparatus of the invention, the waveform pattern W1 has: a) a duty cycle of between between 1% to 50%, 1.1% to 45%, 1 .2% to 40%, 1 .3% to 35%, 1 .4% to 30%, 1.5% to 25%, 1.6% to 20%, 1 .7% to 15%, 1.8% to 14%, 1.9% to 13%, 2% to 12%, 2.1% to 11.9%, 2.2% to 11.88%, or 2.25% to 11.88%, preferably a duty cycle of between 1% to 20%; and/or b) a duration of between 1 ms to 5000 ms, 10 ms to 4500 ms, 20 ms to 4000 ms, 30 ms to 3500 ms, 40 ms to 3000 ms, 50 ms to 2500 ms, 60 ms to 2000 ms, 70 ms to 1500 ms, 80 ms to 1000 ms, 90 ms to 900 ms, 100 ms to 850 ms, 150 ms to 800 ms, 200 ms to 750 ms, 250 ms to 650 ms, 300 ms to 640 ms, 350 ms to 630 ms, 400 ms to 620 ms, 450 ms to 615 ms, 500 ms to 612 ms, 530 ms to 609 ms, or 534 ms to 606 ms, preferably a duration of between 100 ms to 1000 ms; and/or c) wherein the number of pulses in W1 is between 1 to 5000, 2 to 4500, 3 to 4000, 4 to 3500, 5 to 3000, 6 to 2500, 7 to 2000, 8 to 1500, 9 to 1000, 10 to 500, 12 to 450, 14 to 400, 16 to 350, 18 to 300, 20 to 250, 22 to 200, 24 to 180, 26 to 160, 28 to 140, or 30 to 120, preferably between 5 to 500; and/or d) a magnetic flux density of between 1mT and 50mT, 2mT and 45mT, 3mT and 40mT, or 4mT and 35mT, preferably of between 5mT and 30mT. [0022] In some embodiments of the method and apparatus of the invention, the waveform pattern W2 has: a) a duty cycle of between about 1% to about 50%, about 1.01% to about 45%, about 1 .02% to about 40%, about 1 .03% to about 35%, about 1.04% to about 30%, about 1 .05% to about 25%, about 1.06% to about 20%, about 1 .07% to about 15%, about 1 .08% to about 14%, about 1.09% to about 13%, about 1.09% to about 12%, about 1.1% to about 11%, about 1.2% to about 10%, 1.22% to about 9%, 1.24% to about 8%, 1.26% to about 7%, 1.28% to about 6.5%, 1 .3% to about 6%, 1 .32% to about 5.8%, 1.33% to about 5.7%, 1.34% to about 5.6%, 1 .35% to about 5.58%, 1.36% to about 5.57%, 1.365% to about 5.56%, or about 1.37% to about 5.55%, preferably a duty cycle of between about 1% to about 20%; and/or b) a duration of between about 1 ms to about 5000 ms, about 100 ms to about 4500 ms, about 200 ms to about 4000 ms, about 300 ms to about 3500 ms, about 400 ms to about 3000 ms, about 500 ms to about 2900 ms, about 600 ms to about 2850 ms, about 700 ms to about 2800 ms, about 800 ms to about 2750 ms, about 900 ms to about 2700 ms, about 1000 ms to about 2650 ms, about 1100 ms to about 2600 ms, about 1200 ms to about 2550 ms, about 1300 ms to about 2500 ms, about 1400 ms to about 2450 ms, about 1500 ms to about 2400 ms, about 1600 ms to about 2350 ms, about 1700 ms to about 2300 ms, about 1800 ms to about 2250 ms, about 1900 ms to about 2200 ms, about 1950 ms to about 2150 ms, about 2000 ms to about 2100 ms, or about 2102 ms to about 2074 ms, preferably a duration of between about 100 ms to about 5000 ms; and/or c) wherein the number of pulses in W2 is between about 1 to about 5000, about 2 to about 4500, about 4 to about 4000, about 6 to about 3500, about 8 to about 3000, about 10 to about 2500, about 15 to about 2000, about 20 to about 1500, about 25 to about 1000, about 30 to about 500, about 35 to about 450, about 40 to about 400, about 45 to about 350, about 50 to about 300, about 55 to about 295, about 60 to about 292, about 65 to about 290, about 70 to about 289, or about 72 to about 288, preferably between about 5 to about 500; and/or d) a magnetic flux density of between about 1 mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT.

[0023] In some embodiments of the method and apparatus of the invention, the waveform pattern W2 has: a) a duty cycle of between 1% to 50%, 1 .01 % to 45%, 1.02% to 40%, 1 .03% to 35%, 1.04% to 30%, 1.05% to 25%, 1.06% to 20%, 1.07% to 15%, 1.08% to 14%, 1.09% to 13%, 1.09% to 12%, 1.1% to 11%, 1.2% to 10%, 1.22% to 9%, 1.24% to 8%, 1.26% to 7%, 1.28% to 6.5%, 1 .3% to 6%, 1 .32% to 5.8%, 1.33% to 5.7%, 1 .34% to 5.6%, 1 .35% to 5.58%, 1 .36% to 5.57%, 1 .365% to 5.56%, or 1 .37% to 5.55%, preferably a duty cycle of between 1% to 20%; and/or b) a duration of between 1 ms to 5000 ms, 100 ms to 4500 ms, 200 ms to 4000 ms, 300 ms to 3500 ms, 400 ms to 3000 ms, 500 ms to 2900 ms, 600 ms to 2850 ms, 700 ms to 2800 ms, 800 ms to 2750 ms, 900 ms to 2700 ms, 1000 ms to 2650 ms, 1100 ms to 2600 ms, 1200 ms to 2550 ms, 1300 ms to 2500 ms, 1400 ms to 2450 ms, 1500 ms to 2400 ms, 1600 ms to 2350 ms, 1700 ms to 2300 ms, 1800 ms to 2250 ms, 1900 ms to 2200 ms, 1950 ms to 2150 ms, 2000 ms to 2100 ms, or 2102 ms to 2074 ms, preferably a duration of between 100 ms to 5000 ms; and/or c) wherein the number of pulses in W2 is between 1 to 5000, 2 to 4500, 4 to 4000, 6 to 3500, 8 to 3000, 10 to 2500, 15 to 2000, 20 to 1500, 25 to 1000, 30 to 500, 35 to 450, 40 to 400, 45 to 350, 50 to 300, 55 to 295, 60 to 292, 65 to 290, 70 to 289, or 72 to 288, preferably between 5 to 500; and/or d) a magnetic flux density of between 1 mT and 50mT, 2mT and 45mT, 3mT and 40mT, or 4mT and 35mT, preferably of between 5mT and 30mT.

[0024] In some embodiments of the method and apparatus of the invention, the stream of droplets is generated by an ultrasonic atomiser wherein the ultrasonic atomiser comprises a piezo element.

[0025] In some embodiments of the method and apparatus of the invention, the stream of droplets is generated by an ultrasonic atomiser wherein the ultrasonic atomiser is a piezo element with a plurality of holes that allow liquids to be atomised therethrough, comprising a circuit for generating the voltage to drive the atomiser, wherein the circuit is connected to a port from a microprocessor for controlling the atomiser, and wherein the piezo element is operably attached to a liquid supply vessel.

[0026] In some embodiments of the method and apparatus of the invention, the magnetic field is generated by one or more coil inductors for producing an electromagnetic waveform signal.

[0027] In some embodiments of the method and apparatus of the invention, the magnetic field is generated by one or more coil inductors wherein the one or more coil inductors are configured to provide electromagnetic pulse fields corresponding to a predetermined electromagnetic waveform signal, through which the atomised droplets of liquid travel, and wherein the one or more coil inductors are driven by an energisation signal from a bipolar transistor which is controlled via a microprocessor port.

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Further features of the present invention are more fully described in the following description of several non-limiting embodiments thereof. This description is included solely for the purposes of exemplifying the present invention. It should not be understood as a restriction on the broad summary, disclosure or description of the invention as set out above. The description will be made with reference to the accompanying drawings in which:

Figure 1 is a generalised diagram of a mnemonic describing the variance with time of the variable electromagnetic waveform signal which imposes a magnetic field onto an ultrasonically generated droplet of a diamagnetic liquid composition.

Figure 2 is a Functional Block Diagram of an STM Engine Microprocessor Implementation for driving the device and method of the invention.

Figure 3 is a Circuit Schematic of an Implementation for the device and method of the invention using an STM8S003F3P6 Integrated Circuit microprocessor, for delivery of the variable electromagnetic waveform signal to an ultrasonically generated droplet stream of a diamagnetic liquid composition.

Figure 4 is a Circuit Schematic of a coil inductor driver for producing an electromagnetic waveform signal in accordance with the present invention.

Figure 5 is a Circuit Schematic of a piezoelectric atomiser driver for generating a stream of droplets comprising a solution of a substance to be delivered to a target surface in accordance with the present invention.

Figure 6 is a diagram of an implementation of the present invention, wherein target surface A to be treated with a solution of a substance to be delivered, is subjected to droplet stream B of atomised liquid droplets comprising the substance to be delivered, wherein droplet stream B is subjected to in-flight treatment of an electromagnetic waveform signal C of a pre-determined Wave Factor Parameter generated by one or more induction coils D, wherein droplet stream B, is generated by atomizer E, and wherein atomizer E is operably connected to liquid supply vessel F, for supplying the solution of a substance to be delivered to the target surface A.

Figure 7 is a plot of absorption of inositol into skin samples with varying Wave Factor Parameter in accordance with the present invention.

DESCRIPTION OF INVENTION

[0029] The present invention provides a method for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the method comprising the steps of: i) generating a droplet comprising the active agent in a liquid composition; ii) moving the droplet through a magnetic field; and iii) moving the droplet of (ii) onto the surface wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplet such that the contact angle between the droplet and the surface is reduced and the contact area of the droplet to the surface is increased.

[0030] The present invention further provides a method for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the method comprising the steps of: i) generating a stream of droplets comprising the active agent in a liquid composition; ii) moving the droplets through a magnetic field; and iii) moving the droplets of (ii) onto the surface wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplets such that the contact angle between the droplets and the surface is reduced and the contact area of the droplets to the surface is increased.

[0031] The present invention further provides an apparatus for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the apparatus comprising: a) a means to generate a droplet comprising the active agent in a liquid composition; and b) a means to generate a magnetic field; wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplet such that the contact angle between the droplet and the surface is reduced and the contact area of the droplet to the surface is increased.

[0032] The present invention further provides an apparatus for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the apparatus comprising: a) a means to generate a stream of droplets comprising the active agent in a liquid composition; and b) a means to generate a magnetic field; wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplets such that the contact angle between the droplets and the surface is reduced and the contact area of the droplets to the surface is increased.

[0033] It has recently been reported that magnetic fields perturb the vapour liquid interface and are capable of deforming the surface of diamagnetic liquids such as water, in an effect known as the “Moses Effect” (Bormashenko, E., “Moses effect: physics and applications”, Advances in Colloid and Interface Science, 269, 2019, 1-6), that treatment of water with a magnetic field demonstrates a decrease of surface tension and an increase in viscosity over the treatment time (Cai, R., et al., “The effects of magnetic fields on water molecular hydrogen bonds”, Journal of Molecular Structure, 938, 2009, 15-19), and that magnetic fields change the physical properties of water including lowering specific heat and boiling point, and increasing the evaporation rate of water post treatment (Wang, Y., et al., “Effect of magnetic field on the physical properties of water”, Results in Physics, 8, 2018, 262-267).

[0034] Without wishing to be bound by theory, it is believed that the enhanced wetting of droplets observed when treated using the method or apparatus of the present invention is related to one or more of the effects observed in the abovementioned scientific journal publications, with the result that the time varying magnetic field exerted on and/or the induced electric field formed within the droplet, decreases the contact angle of the droplet upon contact with the target surface, providing enhanced wettability and therefore enhanced delivery of the droplet composition to the target surface, in accordance with the below diagram:

[0035] Wherein (a) represents a diamagnetic fluid droplet without treatment from a time varying magnetic field, resulting in a large contact angle with the surface (in this case greater than 90 degrees), and (b) represents a diamagnetic fluid droplet treated with a time varying magnetic field, resulting in a substantially reduced contact angle with the surface (in this case less than 90 degrees).

Droplet

[0036] Preferably the droplet has a diameter between 1 pm and 500pm. Most preferably, the droplet has a diameter between 10pm and 250pm.

[0037] Preferably the droplets have a magnetic susceptibility of less than zero. Diamagnetic materials are repelled by a magnetic field; an applied magnetic field creates an induced magnetic field in them in the opposite direction, causing a repulsive force. Diamagnetic materials, like water, or water-based materials, have a relative magnetic permeability that is less than or equal to 1 , and therefore a magnetic susceptibility less than or equal to 0.

[0038] The droplet comprises a liquid composition comprising the active agent. Preferably the liquid composition comprising the active agent is a water-based or aqueous composition.

Ultrasonic Atomiser

[0039] Preferably the droplet is generated by means of an ultrasonic atomiser or ultrasonic droplet generator.

[0040] Such ultrasonic atomisers are known in the art and are usually driven by an ultrasonic transducer such as a piezo-ceramic element.

[0041] Matsushita US Pat. No. 4,533,082 (1985) and US Pat. No. 4,605,167 (1986) disclose an atomizer using a perforated micro-hole vibrating membrane. The membrane has a curved portion (protuberance or dome) at its center to diverge the generated droplets. The membrane has micro-perforations of 30 to 100 microns (pm) in diameter. The vibrating element is an annular piezoelectric ceramic having an outside diameter of 5 to 15 mm and an inside diameter of 2 to 8 mm. The vibrating membrane with a thickness of 30 to 120 pm is glued on the annular ceramic. This piezoelectric ceramic is excited at frequencies between 30 and 200 kHz in its mode of radial deformation.

[0042] Bespack US Pat. No. 5,152,456 (1992) reproduces the principle proposed by Matsushita. However, the vibrating element (or vibrator) consists of an aluminum annular disk 22 mm in diameter. The piezoelectric ceramic is fixed on this aluminum disk. The operating mode of the piezoelectric ceramic corresponds to a radial deformation. The central opening of the aluminum disc is 4 mm. The nickel membrane has 1500 perforations (or holes) 3 pm in diameter.

[0043] Toda US Pat. No. 5,297,734 (1994) refers to a vibrating blade atomizer having a square geometry allowing flow rates up to 1 mL/Sec. The atomizer consists of a 50 pm thick nickel membrane bonded to a piezoelectric ceramic disc with an outer diameter of 24 mm, an internal diameter of 12 mm and a thickness of 6 mm. The diaphragm has tapered holes with an inside diameter of 100 pm and an outside diameter of 20 pm.

[0044] The Technology Transfer Partnership (1 "IP) patent US 5,261 ,601 (1993) discloses a Bespack patented generation of droplet generation device (or atomizer), whereas US Patent No. 5,518,179 (1996) discloses reference to a disk atomizer or the perforated membrane is in electroformed nickel The TTP atomizer does not require a liquid chamber behind the membrane and the liquid supply is carried out by capillarity (use of wick or porous material). Atomizer TTP emphasizes its bimorphic structure specifying the bending mode of the assembly composed of the piezoelectric ceramic and the micro-perforated membrane. The membrane has a rigidity comparable to that of the annular piezoelectric ceramic consists of a brass ring with an outside diameter of 20 mm and a thickness of 200 pm. The piezoelectric ceramic ring has an outer diameter of 20 mm, an internal diameter of 6 mm.

[0045] The Aerogen US Pat. No. 6,085,740 (2000) discloses a means for atomizing a liquid into fine droplets using a micro-grid. The membrane, provided with micro-holes 6 pm in diameter, is vibrated by a piezoelectric bimetallic operating at 45 kHz. The liquid is supplied by capillarity and the membrane is separable from the vibrator. US Patent 6,427,682 (2002) to Aerogen describes the making of a drug diffusion apparatus using a vibrating membrane. Its principle is very close to that of Matsushita. It consists of an aluminum part flexibly vibrated by means of an annular piezoelectric ceramic. The vibrating membrane provided with micro-holes is made by electroforming. A chamber containing the liquid is in contact with the membrane. In addition, Omron has developed an ultrasonic pump technology for atomizing a liquid through a micro- perforated membrane. This technology is described in US Pat. No. 6,901 ,926 (2005). In Omron technology, the micro-perforated membrane is not directly vibrated by the vibrating element. The droplets are formed by ejecting the liquid through the holes during dynamic pressure variation due to the ultrasonic pump.

[0046] These and other forms of ultrasonic atomisers, nebulisers or ultrasonic droplet generators, including that described in French Patent No. FR2908329A1 to Telemaq represent suitable means for implementing the present invention.

[0047] In one embodiment of the invention, the atomiser is a piezo element with a plurality of holes that allow liquids to be atomised therethrough, comprising a circuit for generating the voltage to drive the atomiser, wherein the circuit is connected to a port from a microprocessor for controlling the atomiser, and wherein the piezo element is operably attached to a liquid supply vessel.

Magnetic Field

[0048] Preferably the magnetic field is a time varying electromagnetic field comprising a variable electromagnetic waveform signal. Preferably the magnetic field is applied to the droplet after the droplet is formed (rather than applied to the bulk liquid composition comprising the active agent), and before the droplet comes in contact with the membrane surface. Preferably the variable electromagnetic waveform signal imposes a magnetic field onto an ultrasonically generated droplet of a liquid composition comprising an active agent according to an embodiment of the invention. Preferably, the droplet contains ions in solution.

[0049] Preferably the magnetic field produced by the time varying electromagnetic waveform signal also induces an electrical field on the droplet via standard induction processes, in accordance with the Maxwell-Faraday equation.

[0050] The apparatus for the generation of a magnetic field to enhance the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface of the invention may include one or more actuators (i.e., switches, buttons, sensors, or the like), which enable a user or practitioner to activate or deactivate the therapeutic, cosmetic or skin care active agent delivery device and/or one or more features of the therapeutic, cosmetic or skin care active agent delivery device (e.g., turn the therapeutic, cosmetic or skin care active agent delivery device on or off and/or select a pre-programmed electromagnetic waveform setting or software application).

[0051] When activated, the apparatus for the delivery of therapeutic, cosmetic or skin care active agents into or across a membrane surface can generate an electromagnetic waveform, for example, by sending an energisation signal to an electromagnetic waveform generating component such as a coil or the like. The energisation signal may be in the form of a direct current (DC) signal, an alternating current (AC) signal, and/or a modified AC or DC signal. The duration, amplitude, number of electrical pulses, and/or frequency of the energisation signal may be controlled by control circuitry in electronic communication with the electromagnetic waveform generating component.

[0052] The control circuitry may include a programmable microcontroller in electronic communication with a solid-state switching device, which can control current flow to the electromagnetic waveform generating device. The microcontroller, when present, may be programmed to change one or more characteristics of the electromagnetic waveform. In some instances, the electromagnetic waveform can be configured to enhance delivery of one or more other therapeutic, cosmetic or skin care active agents according to the surface to which the active is being delivered and the nature of the active agent.

[0053] In one embodiment, the means for producing an electromagnetic waveform signal includes a capacitively coupled plate or coil. The means for producing an electromagnetic waveform signal may further include a solid-state switching device which may be a transistor such as a bipolar transistor connected in series with the coil.

[0054] In one embodiment, the device of the invention comprises one or more coil inductors for producing an electromagnetic waveform signal, wherein the one or more coil inductors are configured to provide electromagnetic pulse fields corresponding to a predetermined electromagnetic waveform signal, through which the atomised droplets of liquid travel, and wherein the one or more coil inductors are driven by an energisation signal from a bipolar transistor which is controlled via a microprocessor port.

[0055] In some embodiments, the energisation signal is provided as a plurality of electrical signal pulses that generally define a rectangular pulse or square wave having a frequency of between about 0.1 Hz to about 2000 Hz, about 0.1 Hz to about 1900 Hz, about 0.1 Hz to about 1800 Hz, about 0.1 Hz to about 1700 Hz, about 0.1 Hz to about 1600 Hz, or about 0.1 Hz to about 1550 Hz, preferably a frequency of between about 0.1 Hz and about 1500 Hz. The rectangular pulse or square wave shape may be provided by cycling a DC power supply on and off and/or using a switch (e.g., a solid state switching device such as a transistor) to apply and remove voltage to the waveform generating device. The duration of each electrical pulse in the energisation signal is selected to provide a desired duty cycle for the resulting waveform. For example, in some embodiments, the electrical pulse duration may be between about 1 ps and about 100 ms, about 10 ps and about 50 ms, 5 about 0 ps and about 10 ms, or even between about 100 ps and about 1 ms. The amplitude, duration, and/or frequency properties of the energisation signal can be varied individually or in combination to provide the desired electromagnetic waveform. While this example describes the energisation signal in the form of a square wave, it is to be appreciated that other wave shapes may also be selected, as desired. For example, an AC or bipolar DC energisation signal could be used to provide pulses of sinusoidal configuration. It will also be appreciated by the skilled addressee that the exact shape of the wave may vary depending on the properties of the waveform generating device employed, such as inductor time constant or other physical limitations of the device.

[0056] In some instances, the electromagnetic waveform includes two or more discrete waveform patterns, each comprising one or more energisation signal packets. Each energisation signal packet comprises active portions defined as “on time”, which correspond to the active portions of the electrical signal pulse used to generate the energisation signal packet (i.e., when voltage is applied to the electromagnetic waveform generating device), and inactive portions defined as “off time”, which correspond to the inactive portions of the electrical signal pulse (i.e., when voltage is removed from the electromagnetic waveform generating device). The discrete waveform patterns are configured to provide a suitable magnetic field to the droplets comprising the therapeutic, cosmetic or skin care active agent, and therefore decrease the contact angle and/or increase the contact surface area of the droplet, individually and/or cooperatively.

[0057] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises a discrete waveform pattern defined as “WT\ [0058] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises a discrete waveform pattern defined as “W2”.

[0059] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises a waveform pattern W1 , and a waveform pattern W2.

[0060] In one embodiment, the electromagnetic waveform signal of the invention produces a magnetic flux density of between about 1 mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT.

[0061] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises waveform pattern W1 , wherein the magnetic flux density of waveform pattern W1 produces a magnetic flux density of between about 1 mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT.

[0062] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises waveform pattern W2, wherein the magnetic flux density of waveform pattern W2 produces a magnetic flux density of between about 1 mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT.

[0063] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises a waveform pattern W1 , and a waveform pattern W2, wherein the magnetic flux density of waveform pattern W1 is greater than the magnetic flux density of waveform pattern W2.

[0064] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises a waveform pattern W1 , and a waveform pattern W2, wherein most of the magnetic flux density of the electromagnetic waveform signal resides in waveform pattern W1 .

[0065] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises a waveform pattern W1 , and a waveform pattern W2, wherein the magnetic flux density of waveform pattern W1 is of about the same magnitude as the magnetic flux density of waveform pattern W2.

[0066] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises a waveform pattern W1 , and a waveform pattern W2, wherein the magnetic flux density of waveform pattern W1 is less than the magnetic flux density of waveform pattern W2.

[0067] In some embodiments of the invention, the electromagnetic waveform signal of the invention comprises a waveform pattern W1 , and a waveform pattern W2, wherein most of the magnetic flux density of the electromagnetic waveform signal resides in waveform pattern W2.

[0068] In one embodiment, the apparatus includes a control means arranged to produce an energisation signal useable to control switching of the solid state switching device, the energisation signal including a repeating energisation signal packet, each energisation signal packet including a plurality of energisation signal pulses of generally rectangular or square wave configuration.

[0069] The control means may comprise a microcontroller which may be programmable by a user, patient, subject or practitioner. The microcontroller may be programmed such that user controlled or practitioner prescribed therapeutic, cosmetic or skin care active agent delivery is effected at one or more specific times, is increased for a specific period of time, and so on.

[0070] In one embodiment, the energisation of each electromagnetic pulse within the electromagnetic waveform signal is at a frequency of between 0.1 Hz and 2000 Hz, 0.1 Hz and 1900 Hz, 0.1 Hz and 1800 Hz, 0.1 Hz and 1700 Hz, 0.1 Hz and 1600 Hz, 0.1 Hz and 1550 Hz, more particularly between 0.1 Hz and 1500 Hz.

[0071] In one embodiment, the invention described herein provides a method for enhanced delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, comprising the steps of: i) generating a droplet comprising the active agent in a liquid composition; ii) moving the droplet through a magnetic field; and iii) moving the droplet of (ii) onto the surface, wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplet such that the contact angle between the droplet and the surface is reduced and the contact area of the droplet to the surface is increased; wherein the magnetic field is generated by an electromagnetic waveform signal; wherein the electromagnetic waveform signal comprises a waveform pattern (W1) and a waveform pattern (W2), and the electromagnetic waveform signal has a Wave Factor of between about 0.05 to about 5.0, about 0.06 to about 4.5, about 0.07 to about 4.0, about 0.08 to about 3.5, about 0.09 to about 3.0 or about 0.1 to about 2.9, preferably about 0.1 to about 2.7, wherein the Wave Factor is derived from the equation:

Wave Factor = (W1 factor) + (W2 factor); wherein W1 factor is between about 0.01 to about 3.0, about 0.02 to about 2.9, about 0.03 to about 2.8, about 0.04 to about 2.7, about 0.05 to about 2.6, about 0.06 to about 2.5, about 0.07 to about 2.4, about 0.08 to about 2.3, about 0.09 to about 2.2, about 0.09 to about 2.1 , or about 0.1 to about 2.0, preferably about 0.1 to about 1.9; and

W2 factor is between about 0.0 to about 2.0, about 0.01 to about 1.5, about 0.02 to about 1.4, about 0.03 to about 1 .3, about 0.04 to about 1 .2, about 0.05 to about 1 .1 , or about 0.05 to about 1 .0, preferably between about 0.05 to about 0.9.

[0072] Optionally, W2 factor is less than W1 factor.

[0073] In some embodiments of the method of the invention described herein, enhanced absorption by the membrane surface of the active agent in the droplet due to a decrease in the contact angle of the droplet leading to an increase in contact surface area between the droplet and the membrane surface is enhanced by at least 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 150%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, 550%, 600%, 650%, 700%, 750%, 800%, 850%, 900%, 950%, or 1000% relative to applying the therapeutic, cosmetic or skin care composition without applying the electromagnetic waveform signal to the droplet.

[0074] In some embodiments of the method of the invention described herein, the enhancement absorption of the active agent relative to absorption of the therapeutic, cosmetic or skin care agent without applying the electromagnetic waveform signal to the droplet is measured by tape stripping analysis.

[0075] In some embodiments of the method of the invention described herein, the enhancement of the absorption of the therapeutic, cosmetic or skin care active agent relative to absorption of the therapeutic, cosmetic or skin care composition without applying the electromagnetic waveform signal to the droplet is measured using a Courage + Khazaka MDD4 Skin analysis unit with hydration probe.

[0076] In some embodiments of the method of the invention described herein, the therapeutic, cosmetic or skin care active agent is present at an amount of about 0.01% to about 10%, about 0.02% to about 9%, about 0.03% to about 8%, about 0.04% to about 7%, about 0.05% to about 6.5%, about 0.06% to about 6.4%, about 0.07% to about 6.3%, about 0.08% to about 6.2%, about 0.09% to about 6.1%, about 0.1% to about 6%, about 0.11% to about 5.9%, about 0.12% to about 5.8%, about 0.13% to about 5.7%, about 0.14% to about 5.6%, about 0.15% to about 5.5%, about 0.16% to about 5.4%, about 0.17% to about 5.3%, about 0.18% to about 5.2%, about 0.19% to about 5.1%, or about 0.2% to about 5%, preferably at an amount of about 0.1% to about 5% by weight of the therapeutic, cosmetic or skin care liquid composition.

[0077] In some embodiments of the method and apparatus of the invention described herein, the electromagnetic waveform signal produces a magnetic flux density of between about 1 mT and about 50mT, about 1 .5 mT and about 48mT, about 2mT and about 46mT, about 2.5mT and about 44mT, about 3mT and about 42mT, about 3.5mT and about 40mT, about 4mT and about 38mT, about 4.2mT and about 36mT, about 4.4mT and about 34mT, about 4.6mT and about 32mT, about 4.8mT and about 31 mT, or about 5mT and about 30mT, preferably of between about 5mT and about 30mT.

[0078] In some embodiments of the method and apparatus of the invention described herein, the waveform pattern W1 has a duty cycle which may vary between about 1% to about 50%, about 1.1% to about 45%, about 1.2% to about 40%, about 1.3% to about 35%, about 1.4% to about 30%, about 1.5% to about 25%, about 1.6% to about 20%, about 1.7% to about 15%, about 1.8% to about 14%, about 1.9% to about 13%, about 2% to about 12%, about 2.1% to about 11.9%, about 2.2% to about 11 .88%, or about 2.25% to about 11.88%, preferably of between about 1 % to about 20%.

[0079] In some embodiments of the method and apparatus of the invention described herein, W1 has a duration which may vary between about 1 ms to about 5000 ms, about 10 ms to about 4500 ms, about 20 ms to about 4000 ms, about 30 ms to about 3500 ms, about 40 ms to about 3000 ms, about 50 ms to about 2500 ms, about 60 ms to about 2000 ms, about 70 ms to about 1500 ms, about 80 ms to about 1000 ms, about 90 ms to about 900 ms, about 100 ms to about

850 ms, about 150 ms to about 800 ms, about 200 ms to about 750 ms, about 250 ms to about

650 ms, about 300 ms to about 640 ms, about 350 ms to about 630 ms, about 400 ms to about

620 ms, about 450 ms to about 615 ms, about 500 ms to about 612 ms, about 530 ms to about

609 ms, or about 534 ms to about 606 ms, preferably of between about 100 ms to about 1000 ms.

[0080] In some embodiments of the method and apparatus of the invention described herein, the number of pulses in W1 may vary between about 1 to about 5000, about 2 to about 4500, about 3 to about 4000, about 4 to about 3500, about 5 to about 3000, about 6 to about 2500, about 7 to about 2000, about 8 to about 1500, about 9 to about 1000, about 10 to about 500, about 12 to about 450, about 14 to about 400, about 16 to about 350, about 18 to about 300, about 20 to about 250, about 22 to about 200, about 24 to about 180, about 26 to about 160, about 28 to about 140, or about 30 to about 120, preferably between about 5 to about 500. [0081] In some embodiments of the method and apparatus of the invention described herein, the waveform pattern W2 has a duty cycle which may vary between about 1% to about 50%, about 1.01% to about 45%, about 1.02% to about 40%, about 1.03% to about 35%, about 1 .04% to about 30%, about 1 .05% to about 25%, about 1.06% to about 20%, about 1.07% to about 15%, about 1.08% to about 14%, about 1.09% to about 13%, about 1.09% to about 12%, about 1.1% to about 11%, about 1.2% to about 10%, 1.22% to about 9%, 1.24% to about 8%, 1 .26% to about 7%, 1 .28% to about 6.5%, 1.3% to about 6%, 1.32% to about 5.8%, 1 .33% to about 5.7%, 1 .34% to about 5.6%, 1.35% to about 5.58%, 1.36% to about 5.57%, 1.365% to about 5.56%, or about 1.37% to about 5.55%, preferably of between about 1% to about 20%.

[0082] In some embodiments of the method and apparatus of the invention described herein, W2 has a duration which may vary between about 1 ms to about 5000 ms, about 100 ms to about 4500 ms, about 200 ms to about 4000 ms, about 300 ms to about 3500 ms, about 400 ms to about 3000 ms, about 500 ms to about 2900 ms, about 600 ms to about 2850 ms, about 700 ms to about 2800 ms, about 800 ms to about 2750 ms, about 900 ms to about 2700 ms, about 1000 ms to about 2650 ms, about 1100 ms to about 2600 ms, about 1200 ms to about 2550 ms, about 1300 ms to about 2500 ms, about 1400 ms to about 2450 ms, about 1500 ms to about 2400 ms, about 1600 ms to about 2350 ms, about 1700 ms to about 2300 ms, about 1800 ms to about 2250 ms, about 1900 ms to about 2200 ms, about 1950 ms to about 2150 ms, about 2000 ms to about 2100 ms, or about 2102 ms to about 2074 ms, preferably between about 100 ms to about 5000 ms.

[0083] In some embodiments of the method and apparatus of the invention described herein, the number of pulses in W2 may vary between about 1 to about 5000, about 2 to about 4500, about 4 to about 4000, about 6 to about 3500, about 8 to about 3000, about 10 to about 2500, about 15 to about 2000, about 20 to about 1500, about 25 to about 1000, about 30 to about 500, about 35 to about 450, about 40 to about 400, about 45 to about 350, about 50 to about 300, about 55 to about 295, about 60 to about 292, about 65 to about 290, about 70 to about 289, or about 72 to about 288, preferably between about 5 to about 500.

[0084] In some embodiments of the method and apparatus of the invention described herein, the waveform pattern W1 has a duty cycle which may vary between about 1% to about 50%, about 1.1% to about 45%, about 1.2% to about 40%, about 1.3% to about 35%, about 1.4% to about 30%, about 1.5% to about 25%, about 1.6% to about 20%, about 1.7% to about 15%, about 1.8% to about 14%, about 1.9% to about 13%, about 2% to about 12%, about 2.1% to about 11 .9%, about 2.2% to about 11.88%, or about 2.25% to about 11.88%, preferably between about 1% to about 20%; and/or

W1 has a duration which may vary between about 1 ms to about 5000 ms, about 10 ms to about 4500 ms, about 20 ms to about 4000 ms, about 30 ms to about 3500 ms, about 40 ms to about 3000 ms, about 50 ms to about 2500 ms, about 60 ms to about 2000 ms, about 70 ms to about 1500 ms, about 80 ms to about 1000 ms, about 90 ms to about 900 ms, about 100 ms to about

850 ms, about 150 ms to about 800 ms, about 200 ms to about 750 ms, about 250 ms to about

650 ms, about 300 ms to about 640 ms, about 350 ms to about 630 ms, about 400 ms to about

620 ms, about 450 ms to about 615 ms, about 500 ms to about 612 ms, about 530 ms to about

609 ms, or about 534 ms to about 606 ms, preferably between about 100 ms to about 1000 ms; and/or the number of pulses in W1 may vary between about 1 to about 5000, about 2 to about 4500, about 3 to about 4000, about 4 to about 3500, about 5 to about 3000, about 6 to about 2500, about 7 to about 2000, about 8 to about 1500, about 9 to about 1000, about 10 to about 500, about 12 to about 450, about 14 to about 400, about 16 to about 350, about 18 to about 300, about 20 to about 250, about 22 to about 200, about 24 to about 180, about 26 to about 160, about 28 to about 140, or about 30 to about 120, preferably between about 5 to about 500; and/or

W1 produces a magnetic flux density of between about 1mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT; and/or the waveform pattern W2 has a duty cycle which may vary between about 1% to about 50%, about 1.01% to about 45%, about 1.02% to about 40%, about 1.03% to about 35%, about 1.04% to about 30%, about 1.05% to about 25%, about 1.06% to about 20%, about 1.07% to about 15%, about 1.08% to about 14%, about 1.09% to about 13%, about 1.09% to about 12%, about 1.1% to about 11%, about 1 .2% to about 10%, 1.22% to about 9%, 1.24% to about 8%, 1 .26% to about 7%, 1 .28% to about 6.5%, 1 .3% to about 6%, 1.32% to about 5.8%, 1 .33% to about 5.7%, 1 .34% to about 5.6%, 1.35% to about 5.58%, 1.36% to about 5.57%, 1 .365% to about 5.56%, or about 1.37% to about 5.55%, preferably between about 1% to about 20%; and/or

W2 has a duration which may vary between about 1 ms to about 5000 ms, about 100 ms to about 4500 ms, about 200 ms to about 4000 ms, about 300 ms to about 3500 ms, about 400 ms to about 3000 ms, about 500 ms to about 2900 ms, about 600 ms to about 2850 ms, about 700 ms to about 2800 ms, about 800 ms to about 2750 ms, about 900 ms to about 2700 ms, about 1000 ms to about 2650 ms, about 1100 ms to about 2600 ms, about 1200 ms to about 2550 ms, about 1300 ms to about 2500 ms, about 1400 ms to about 2450 ms, about 1500 ms to about 2400 ms, about 1600 ms to about 2350 ms, about 1700 ms to about 2300 ms, about 1800 ms to about 2250 ms, about 1900 ms to about 2200 ms, about 1950 ms to about 2150 ms, about 2000 ms to about 2100 ms, or about 2102 ms to about 2074 ms, preferably between about 100 ms to about 5000 ms; and/or the number of pulses in W2 may vary between about 1 to about 5000, about 2 to about 4500, about 4 to about 4000, about 6 to about 3500, about 8 to about 3000, about 10 to about 2500, about 15 to about 2000, about 20 to about 1500, about 25 to about 1000, about 30 to about 500, about 35 to about 450, about 40 to about 400, about 45 to about 350, about 50 to about

300, about 55 to about 295, about 60 to about 292, about 65 to about 290, about 70 to about

289, or about 72 to about 288, preferably between about 5 to about 500; and/or W2 produces a magnetic flux density of between about 1mT and about 50mT, about 2mT and about 45mT, about 3mT and about 40mT, or about 4mT and about 35mT, preferably of between about 5mT and about 30mT.

Contact Angle

[0085] The contact angle is the angle where a liquid interface meets a solid surface; it quantifies the wettability of a solid surface by a liquid. If the liquid molecules are strongly attracted to the solid molecules then the liquid drop will completely spread out on the solid surface, corresponding to a contact angle of 0°. If the contact angle between a liquid and a surface is <90°, the liquid will tend to wet the surface and spread over it. If the contact angle is >90°, the liquid will tend to stay on the surface as a bead. Generally, if the water contact angle is smaller than 90°, the solid surface is considered hydrophilic and if the water contact angle is larger than 90°, the solid surface is considered hydrophobic.

[0086] Without wishing to be bound by theory, the inventors believe that the method and apparatus of the present invention decreases the contact angle between the droplet comprising the active agent and the membrane surface. This increases the contact area for absorption or coverage and therefore the rate at which the active agent can cover and/or penetrate the surface.

[0087] The method and apparatus of the present invention does not affect or change the nature or properties of the membrane surface to which the active agent is being applied.

[0088] The method and apparatus of the present invention are capable of reducing the contact angle of a liquid droplet compared to the contact angle the droplet would have exhibited on the same surface, prior to in-flight treatment with the electromagnetic waveform signal produced by the apparatus of the invention, thereby increasing wettability of the droplet on the surface.

[0089] The method and apparatus of the present invention are capable of reducing the contact angle of a liquid droplet to less than 90° in a droplet that would otherwise exhibit a contact angle of 90° or more on the same surface, prior to in-flight treatment with the electromagnetic waveform signal produced by the apparatus of the invention, thereby increasing wettability of the droplet on the surface.

Surface [0090] The membrane surface to which the active agent is delivered by the present invention is preferably a skin surface or mucosal membrane (eg oral mucosa, pulmonary mucosa, nasal mucosa, buccal tissues of the mouth, or pulmonary tissues).

[0091] The term “membrane surface” includes the layers of the skin (epidermis, dermis), including the stratum corneum, granular cell layer, spinous cell layer, basal cell layer and other components of the integumentary system. It further encompasses mucosal membrane surfaces such as the oral mucosa, pulmonary mucosa, nasal mucosa and luminary mucosa.

Composition

[0092] The compositions of the present invention are liquid compositions comprising an active agent. Preferably the liquid composition comprising the active agent is a water-based or aqueous composition.

[0093] Preferably the liquid compositions and/or the active agents have a magnetic susceptibility of less than zero, and thus are diamagnetic.

[0094] The liquid composition may be diamagnetic, but the active agent may not be. In such an instance, the ultrasonically generated droplets of the liquid composition comprising the active agent will still be affected by the magnetic field, as well as affected by the electric field being concomitantly induced within the droplet, and a Moses Effect, or a perturbation in the vapour liquid interface or a decrease in the surface tension, or an increase in the viscosity, or a reduction in the specific heat or boiling point, or an increase in the evaporation rate will be exerted on the droplet, such that the contact angle of the droplet with the membrane surface will be reduced. This in turn increases the contact area between the droplet and the surface for absorption and therefore the rate at which the active agent can penetrate the surface, even though the active agent itself may not be affected by the magnetic field.

[0095] As used herein the term "therapeutic, cosmetic or skin care active agent" is directed to Active Pharmaceutical Active agents (APIs), nutraceuticals, cosmeceuticals or any other substance desired to be applied to the skin for the purpose of obtaining a beneficial therapeutic, cosmetic or skin care effect. For example, they may be ions, phytochemicals, enzymes, antioxidants, herbs, spices, natural or semi- natural or refined plant extracts, oils, essential oils, vitamins, nutrients, minerals, macromolecules, DNA fragments, genes, proteins, amino acid sequences or any other substances desired to be applied to the skin for the purpose of obtaining a beneficial therapeutic, cosmetic or skin care effect. More preferably, particularly in relation to cosmetic or skin care active agents, the substance is a product that is well tried and tested for mildness, efficacy, biodegradability, low toxicity, cleansing ability, emulsification, moisturisation, sun or UV screening effectiveness, toning, colouring or whitening effectiveness, skin appearance and feel, smell (fragrance) or lubrication.

[0096] As used herein a “therapeutic, cosmetic or skin care composition” is directed to a composition containing a therapeutic, cosmetic or skin care active agent, such compositions including but not being limited to nutraceuticals, cosmeceuticals, colouring agents including coloured cosmetics, foundations, primers, concealers, contouring agents, blemish balms, pigments, highlighting agents, bronzing agents, fillers, setting agents, fixing agents, boosting agents, staining agents, exfoliating agents, dermabrasives, whitening agents, tanning agents, plumping agents, anti-inflammatory agents, anti-aging agents, anti-wrinkle agents, moisturisers, emollients, rehydrating agents, skin nourish agents, humectants, sloughing agents, pore treatment agents, detergents, cleaners, cleansers, bleaches, dyes, perfumes, fragrances, conditioners or polishes, oils, creams, gels and serums; antiperspirants, deodorants, and agents that alter the skin’s topography; peptides; astringents; antioxidants; vitamins; nutrients; minerals; skin restorative agents.

[0097] Therapeutic, cosmetic or skin care compositions or active agents suitable for use in the invention may be in the form of liquids, solutions, suspensions, emulsions, solids, semi-solids, gels, foams, pastes, ointments, or triturates. They may also be mixed with a range of optional or additional active agents and those referred to herein as matrices or excipients including penetration enhancers, adhesives and solvents. Some non-limiting examples of non-active or additional and optional active agents include vitamins, minerals, peptides and peptide derivatives, sugar amines, oil control agents, flavonoid compounds, anti-oxidants and/or anti oxidant precursors, preservatives, phytosterols, protease inhibitors, tyrosinase inhibitors, anti inflammatory agents, moisturizing agents, emollients, humectants, exfoliating agents, skin lightening agents, sunscreens, sunless tanning agents, pigments, film formers, thickeners, pH adjusters, opacifying agents, colorings/colorants, particles, fragrances, essential oils, lubricants, anti-acne actives, anti-cellulite actives, chelating agents, anti-wrinkle actives, anti-atrophy actives, phytosterols and/or plant hormones, N-acyl amino acid compounds, antimicrobials, antifungals, and combinations of these. Some particularly suitable examples of optional active agents are vitamin B3 compounds such as niacinamide, vitamin C, vitamin E and its derivatives (e.g., tocopherol), pantothenic acid and its salts and derivatives (e.g., panthenol), undecylenoyl phenylalanine, caffeine, green tea extract, carob fruit extract, aloe, cucumber extract, palmitoyl pentapeptide-4, palmitoyl dipeptide-7, hexamidine, hexyldecanol, hyaluronic acid and its salts, olive oil extracts such as sodium PEG-7 olive oil carboxylate, tapioca powder, titanium dioxide, and combinations of these.

[0098] As used herein, “therapeutic composition” means a composition comprising at least one therapeutic active agent, such as, without limitation, a compound or combination of compounds that, when administered transdermally, intradermally or transappendageally, provides a therapeutic benefit or outcome. Therapeutic active agents include, without limitation, vitamins, minerals, nutrients, APIs, medicines, drugs, anti-oxidants, anti-inflammatory compounds and the like. Therapeutic active agents may be ions, phytochemicals, enzymes, antioxidants, herbs, spices, natural or semi- natural or refined plant extracts, oils, essential oils, vitamins, nutrients, minerals, macromolecules, organic molecules, salts, DNA fragments, genes, proteins, amino acid sequences or any other substances desired to be applied to the skin for the purpose of obtaining a therapeutic effect.

[0099] As used herein, “cosmetic composition” means a composition comprising at least one cosmetic active agent, such as, without limitation, a compound or combination of compounds that, when applied to skin, provides a preferred or favourable change in visual appearance, for example a preferred or favourable change in colour, hue, translucence, pearlescence, pigmentation, brightness, sheen etc. More preferably, the composition is a product that is well tried and tested for mildness, efficacy, biodegradability, low toxicity, cleansing ability, emulsification, moisturisation, sun or UV screening effectiveness, toning, colouring or whitening effectiveness, skin appearance and feel, smell (fragrance) or lubrication.

[00100] As used herein, “skin care composition” means a composition comprising at least one skin care active agent, such as, without limitation, a compound or combination of compounds that, when applied to skin, provides an acute and/or chronic benefit to skin or a type of cell commonly found therein. Skin care active agents may regulate and/or improve skin or its associated cells (e.g., improve skin elasticity; improve skin hydration; improve skin condition; and improve cell metabolism), for example by improving skin appearance and/or feel by providing a smoother, more even appearance and/or feel; increasing the thickness of one or more layers of the skin; improving the elasticity or resiliency of the skin; improving the firmness of the skin; and reducing the oily, shiny, and/or dull appearance of skin, improving the hydration status or moisturization of the skin, improving the appearance of fine lines and/or wrinkles, crevices, bumps, and large pores, improving skin exfoliation or desquamation, plumping the skin, improving skin barrier properties, improve skin tone, reducing the appearance of redness or skin blotches, and/or improving the brightness, radiancy, or translucency of skin, thickening of keratinous tissue (e.g., building the epidermis and/or dermis and/or sub-dermal layers of the skin, and where applicable the keratinous layers of the nail and hair shaft, to reduce skin, hair, or nail atrophy); increasing the convolution of the dermal-epidermal border (also known as the rete ridges); preventing loss of skin or hair elasticity, for example, due to loss, damage and/or inactivation of functional skin elastin, resulting in such conditions as elastosis, sagging, loss of skin or hair recoil from deformation; reduction in cellulite; change in coloration to the skin, hair, or nails, for example, under-eye circles, blotchiness (e.g., uneven red coloration due to, for example, rosacea), sallowness, discoloration caused by hyperpigmentation, etc.

[00101] The composition or formulation employed in the delivery process may include additives such as other buffers, diluents, carriers, adjuvants or excipients. Any pharmacologically acceptable buffer that is magnetically inert or neutral or which has a magnetic susceptibility that is either paramagnetic in nature or greater than that of the active agent(s) being delivered, may be used, e.g., tris or phosphate buffers. Other agents may be employed in the formulation for a variety of purposes. For example, buffering agents, preservatives, co solvents, surfactants, oils, humectants, emollients, chelating agents, stabilizers or antioxidants may be employed. Water soluble preservatives which may be employed include, but are not limited to, benzalkonium chloride, chlorobutanol, thimerosal, sodium bisulfate, phenylmercuric acetate, phenylmercuric nitrate, ethyl alcohol, methylparaben, polyvinyl alcohol, benzyl alcohol and phenylethyl alcohol. A surfactant may be Tween 80. Other vehicles that may be used include, but are not limited to, polyvinyl alcohol, povidone, hydroxypropyl methyl cellulose, poloxamers, carboxymethyl cellulose, hydroxyethyl cellulose, purified water, etc. Tonicity adjustors may be included, for example, sodium chloride, potassium chloride, mannitol, glycerin, etc. Antioxidants include, but are not limited to, sodium metabisulfite, sodium thiosulfate, acetylcysteine, butylated hydroxyanisole, butylated hydroxytoluene, etc.

[00102] The indications, effective doses, contra-indications, vendors etc, of the active agents in the formulations are available or are known to one skilled in the art.

[00103] The active agents may be present in individual amounts of from about 0.001 to about 5% by weight and preferably about 0.01% to about 2% by weight. However, it is contemplated that the active agents may be present in individual amounts greater than this, for example up to 100%.

[00104] Suitable water soluble buffering agents that may be employed include sodium carbonate, sodium borate, sodium phosphate, sodium acetate, sodium bicarbonate, etc., as approved by the US FDA for the desired route of administration. These agents may be present in amounts sufficient to maintain a pH of the system of between about 2 to about 9, preferably about 4 to about 8, more preferably 4.5, 5, 5.5, 6, 6.5, 7 or 7.5 (or any pH in between). As such the buffering agent may be as much as about 5% on a weight to weight basis of the total formulation. Electrolytes such as, but not limited to, sodium chloride and potassium chloride may also be included in the formulation where appropriate.

[00105] The compositions of the present invention can comprise, consist essentially of, or consist of, the essential components as well as optional active agents described herein. Kits

[00106] The present invention further provides kits comprising: i) an apparatus for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface, the apparatus comprising: a) a means to generate a droplet comprising the active agent in a liquid composition; and b) a means to generate a magnetic field; ii) instructions for use wherein the magnetic field exerts a Moses Effect and/or perturbs the vapour/liquid interface and/or decreases the surface tension and/or increases the viscosity and/or lowers the specific heat or boiling point and/or increases the evaporation rate and/or induces an electric field within the droplet such that the contact angle between the droplet and the surface is reduced and the contact area of the droplet to the surface is increased.

General

[00107] Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. The invention includes all such variation and modifications. The invention also includes all of the steps, features, formulations and compounds referred to or indicated in the specification, individually or collectively and any and all combinations or any two or more of the steps or features.

[00108] Each document, reference, patent application or patent cited in this text is expressly incorporated herein in their entirety by reference, which means that it should be read and considered by the reader as part of this text. That the document, reference, patent application or patent cited in this text is not repeated in this text is merely for reasons of conciseness.

[00109] Any manufacturer’s instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated herein by reference, and may be employed in the practice of the invention.

[00110] The present invention is not to be limited in scope by any of the specific embodiments described herein. These embodiments are intended for the purpose of exemplification only. Functionally equivalent products, formulations and methods are clearly within the scope of the invention as described herein.

[00111] The invention described herein may include one or more range of values (eg. Size, displacement and field strength etc). A range of values will be understood to include all values within the range, including the values defining the range, and values adjacent to the range which lead to the same or substantially the same outcome as the values immediately adjacent to that value which defines the boundary to the range. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. Hence “about 80 %” means “about 80 %” and also “80 %”. At the very least, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.

[00112] Throughout this specification, unless the context requires otherwise, the word “comprise” or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers. It is also noted that in this disclosure and particularly in the claims and/or paragraphs, terms such as “comprises”, “comprised”, “comprising” and the like can have the meaning attributed to it in U.S. Patent law; e g., they can mean “includes”, “included”, “including”, and the like; and that terms such as “consisting essentially of” and “consists essentially of have the meaning ascribed to them in U.S. Patent law, e.g., they allow for elements not explicitly recited, but exclude elements that are found in the prior art or that affect a basic or novel characteristic of the invention.

[00113] Other definitions for selected terms used herein may be found within the detailed description of the invention and apply throughout. Unless otherwise defined, all other scientific and technical terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the invention belongs. The term “active agent” may mean one active agent, or may encompass two or more active agents.

[00114] The following examples serve to more fully describe the manner of using the above- described invention, as well as to set forth the best modes contemplated for carrying out various aspects of the invention. It is understood that these methods in no way serve to limit the true scope of this invention, but rather are presented for illustrative purposes.

EXAMPLES

[00115] Further features of the present invention are more fully described in the following non-limiting Examples. This description is included solely for the purposes of exemplifying the present invention. It should not be understood as a restriction on the broad description of the invention as set out above.

Apparatus for the delivery of therapeutic, cosmetic or skin care active agents onto a membrane surface [00116] In a particular implementation of the invention, a stream of droplets of a diamagnetic fluid composition are treated with the electromagnetic waveform signal of the invention, en-route to the target surface. With reference to Figure 1 there is provided a variable electromagnetic waveform signal which imposes a magnetic field onto an ultrasonically generated droplet of a liquid composition comprising an active agent according to an embodiment of the invention. The waveform comprises a waveform pattern (W1) and a waveform pattern (W2).

[00117] Each waveform pattern of the electromagnetic waveform signal is defined by certain base parameters which are listed and defined below:

W1 % duty = Duty cycle of waveform 1

= Sum of “on time” for W1 pulses / W1 Duration * 100

• W1 Duration = Duration of waveform pattern 1 in milliseconds W2 % duty = Duty cycle of waveform 2

= Sum of “on time” for W2 pulses / W2 Duration * 100

• W2 Duration = Duration of waveform pattern 2 in milliseconds

[00118] From the above base parameters, the following further parameters are derived, which are then used to calculate the Wave Factor Parameter:

W1 pulse x duty = (number of pulses in W1 ) x (W1 % duty)

W2 pulse x duty = (number of pulses in W2) x (W2 % duty)

• W1 factor = (W1 pulse x duty) / W1 Duration

• W2 factor = (W2 pulse x duty) / W2 Duration

• Wave Factor = (W1 factor) + (W2 factor)

[00119] The calculated Wave Factor Parameter is then plotted against skin wetting or delivery enhancement data to define the relationship or correlation between the applied electromagnetic waveform signal and skin wetting or delivery enhancement of the specific therapeutic, cosmetic or skin care active agent composition being tested, as depicted for example in Figure 7 (delivery of inositol).

[00120] Utilising this data, an increase in the delivery or wetting or coverage of diamagnetic liquid compositions comprising specific therapeutic, cosmetic or skin care active agents may be determined. This relationship or correlation is unique for each liquid composition and may be obtained by following the general experimental principles described in this specification.

[00121] Enhanced delivery of an active agent via user controlled or practitioner prescribed electromagnetic waveform signals according to the present invention may be achieved according to one non-limiting embodiment, by a user, patient, subject or practitioner controlled device as depicted in functional block diagram form in Figure 2.

[00122] Referring to Figure 2, the device includes the following I/O ports:

• coil (output)

• beeper (output)

• vibration motor (output)

• red led (output)

• 3x green led (output)

• switch (input)

• programming.

[00123] The unit depicted in functional block diagram form in Figure 2 is powered by li- polymer battery that is charged via USB (mini USB plug).

[00124] A recharge circuit utilising a Microchip MCP73832T-2ATI/OT (RS 738-6626) ensures correct charging of the battery.

[00125] A surface mount side emitting LED is used to indicate battery charging status. The board may also have through hole-pads in parallel to allow a 3mm leaded LED to be fitted if required.

[00126] A side activated push button switch is used to start the device from halt/sleep mode. Since this unit may be used in various products/formats, it includes pads in parallel to the switch, to mount a top activated push button switch on the front of the board or on the back of the board.

[00127] Solder pads for battery, motor and coil are plated through hole. The pads for the battery are in the shape of a “+” and a to easily identify the pads. There is also another battery minus connection pad at the other end of the board, allowing for batteries that have leads that are at opposite ends or battery packs that have leads from only one end.

[00128] Four indicator LEDs are top emitting surface mount (3 green and 1 red). Optionally the pad that connects the LED to the port pin may also have a plated through hole pad to allow the use of flying leads if required.

[00129] Delivery of electromagnetic waveform signals according to the present invention may be achieved according to a further non-limiting embodiment, by a user, patient, subject or practitioner controlled device depicted in schematic circuit diagram form in Figure 3, which represents an Implementation for the device and a method of the invention using an STM8S003F3P6 Integrated Circuit.

[00130] In some embodiments, an electromagnetic waveform signal in accordance with the present invention may be suitably generated by one or more coil inductors attached to a port of a microprocessor such as the the STM8S003F3P6 Integrated Circuit implementation of the invention, for producing an electromagnetic waveform signal, wherein the one or more coil inductors are configured to provide electromagnetic pulse fields corresponding to a specific electromagnetic waveform signal, through which the atomised droplets of liquid travel, and wherein the one or more coil inductors are driven by an energisation signal from a bipolar transistor which is controlled via the microprocessor port. The schematic circuit diagram for such an embodiment of the invention is depicted in Figure 4.

[00131] In some embodiments, a stream of droplets comprising a solution of a substance to be delivered to a target surface may be suitably generated by an atomiser comprising a piezo element with a plurality of holes that allow liquids to be atomised therethrough, also attached to a port of a microprocessor such as the the STM8S003F3P6 Integrated Circuit implementation of the invention, wherein the piezo element is driven by a circuit for generating the voltage to drive the atomiser, wherein the circuit is connected to the microprocessor to enable control of the atomiser, and wherein the piezo element is operably attached to a liquid supply vessel for supplying the solution of the substance to be delivered to the target surface. The schematic circuit diagram for such an embodiment of the invention is depicted in Figure 5.

[00132] With reference to Figure 6, in one embodiment of an implementation of the present invention, the target surface A to be treated with a solution of a substance to be delivered to the target surface A, is subjected to a droplet stream B of atomised liquid droplets comprising the substance to be delivered to the target surface A, wherein the droplet stream B of atomised liquid droplets is subjected to in-flight treatment of an electromagnetic waveform signal C of a pre-determined Wave Factor Parameter in accordance with the present invention, wherein the electromagnetic waveform signal C of a pre-determined Wave Factor Parameter is generated by one or more induction coils D, wherein the droplet stream B of atomised liquid droplets comprising the substance to be delivered to the target surface A, is generated by an atomizer E comprising a piezo element with a plurality of holes that allow liquids to be atomised therethrough, and wherein the atomizer E is operably connected to a liquid supply vessel F, for supplying the solution of a substance to be delivered to the target surface A. In some embodiments, the liquid supply vessel F is refillable and/or detachable and/or replaceable. In some embodiments, the liquid supply vessel F is a detachable and/or replaceable single-use disposable pod. [00133] Utilising such an electromagnetic waveform generating device a spectrum or continuum of varying electromagnetic waveform signals may be applied to a stream of droplets of a test composition being applied to a test subject, in order to correlate the Wave Factor Parameter of the present invention to wetting or enhancement of delivery of particular therapeutic, cosmetic or skin care active agents to particular membrane surfaces or skin types.

[00134] Various test points along the spectrum or continuum of potential electromagnetic waveform signals capable of being produced using the electromagnetic waveform generating device of the invention were chosen for the purposes of providing a consistent test method for correlating the degree of delivery or wetting enhancement of different therapeutic, cosmetic or skin care active agents from different therapeutic, cosmetic or skin care compositions, as shown in Table 1 .

Table 1 - Test spectrum of applied electromagnetic waveform signals and corresponding calculated Wave Factor Parameters:

[00135] The skilled addressee will of course understand and appreciate that a test spectrum of applied electromagnetic waveform signals and corresponding calculated Wave Factor Parameters differing from the one described above in Table 1 may be employed and applied to testing a particular composition, programmed within the practical limitations of the implementation of the particular electromagnetic device being used.

[00136] Utilising the test spectrum of electromagnetic waveform signals represented by the above selected test points from the spectrum of calculated Wave Factor Parameters in Table 1 , a number of therapeutic, cosmetic or skin care compositions may be tested according to the standard test methods known in the art. The present invention thus provides a principle of general application that may be applied to enhancing wetting and delivery of any solution of interest to any hydrophobic or semi-hydrophobic surface. [00137] Tape stripping analysis may be performed using the procedure of Lademann et al (J. Lademann, U. Jacobi, C. Surber, H.-J. Weigmann, J. W. Fluhr. The tape stripping procedure— evaluation of some critical parameters. European Journal of Pharmaceutics and Biopharmaceutics 72 (2009) 317-323).

[00138] Utilising the test spectrum of electromagnetophoretic waveform signals represented by the above selected test points from the spectrum of calculated Wave Factor Parameters in Table 1 , a standard solution of inositol (2% w/v) in deionised water was applied to a 6.911 cm 2 disc of skin via the atomiser apparatus of the present invention, concomitantly subjecting the generated stream of droplets of solution to in-flight treatment with an electromagnetic waveform signal having a predetermined Wave Factor Parameter. Treatments were carried out for a period of 5 seconds. After treatment the skin samples were then analysed via the above referenced tape stripping analysis procedure for inositol content. The results of the tests are plotted in Figure 7, and summarised below in Table 2:

Table 2 - Test results: inositol absorption in skin

[00139] The above results demonstrate the ability of the present invention to enhance delivery and absorption of an aqueous solution of a compound of interest to hydrophobic membrane surfaces, and provide an effective dynamic range for the delivery of inositol that may be used to select for or pre-program a desired outcome via the device of the invention.

[00140] The results demonstrate that a variable degree of enhancement of delivery and absorption of an aqueous solution of a compound of interest to hydrophobic membrane surfaces is enabled by varying the wave factor delivered by the device of the invention.

[00141] The results demonstrate the ability to vary the absorption of an aqueous solution of a compound of interest to hydrophobic membrane surfaces by more than 350%, with a minimum of 0.2 pg inositol absorbed at Wave Factor 0.17 and a maximum of 0.72 pg inositol absorbed at Wave Factor 0.86. [00142] This is a surprising and advantageous effect of the invention as it enables delivery of an aqueous solution of a compound of interest to hydrophobic membrane surfaces at low concentration or intensity initially, in order to avoid undue irritation or inflammation, and after one or more treatments and/or a period of time in which the user or subject acclimatises and adjusts to the composition being used, the delivery of an aqueous solution of a compound of interest to hydrophobic membrane surfaces may be ramped up in terms of the concentration or intensity of treatment by varying the wave factor applied across the dynamic range available.

[00143] Other analyses may be performed using standard equipment in the art such as a Courage + Khazaka MDD4 Skin analysis unit with hydration probe, for example.

[00144] It will be understood that the above described examples are non-limiting and that the general methods for testing particular therapeutic, cosmetic or skin care compositions with an embodiment of the device of the invention to produce a correlation between Wave Factor Parameter and enhancement of delivery, absorption, coverage or wetting of a particular therapeutic, cosmetic or skin care ingredient selected represent a principle of general application that may be applied to any therapeutic, cosmetic or skin care ingredient or diamagnetic liquid composition, including a therapeutic, cosmetic or skin care composition containing multiple active ingredients.