WO2013190489A1

WO2013190489A1 - Device for transdermal and/or intradermal transport

Info

Publication number: WO2013190489A1
Application number: PCT/IB2013/055038
Authority: WO
Inventors: Bruno Massimo CETRONI; Massimo Teodoro SARTORI
Original assignee: Cetroni Bruno Massimo; Sartori Massimo Teodoro
Priority date: 2012-06-19
Filing date: 2013-06-19
Publication date: 2013-12-27
Also published as: EP2861298A1

Abstract

A device for transdermal and/or intradermal transport that can be connected to two electrodes, wherein one of the electrodes is configured for containing an active principle to be administered via transdermal and/or intradermal route. The device comprises a wave generator configured for generating a driving signal to be sent to the electrodes. In one embodiment, the driving signal comprises a plurality of packets grouped in trains of packets (Tr) and in groups of trains (TG), wherein each packet consists of a unidirectional signal that results from the combination of a modulating signal and a carrier signal, wherein each train of packets (Tr) consists of a series of packets, and wherein each group of trains (TG) comprises a series of trains of packets (Tr). In addition, the wave generator can be configured for reversing the polarity of the trains of packets (Tr) after a given time interval.

Description

"Device for transdermal and/or intradermal transport"

* * * *

TEXT OF THE DESCRIPTION

Field of the invention

The present invention relates to a device for transdermal and/or intradermal transport.

The present invention has been developed in particular for direct intradermal transport together with a direct intradermal and transdermal transport of active principles.

Description of the known art

Hydroelectrophoresis (developed and implemented since 1989) represents an evolution of classic iontophoresis therapy.

Hydroelectrophoresis has been presented to the medical field with a better passage of ions and with a passage also of small molecules through the skin, by means of new bipolar waves, which improved the transdermal transmission as compared to classic iontophoresis by virtue of acquisition of these modified bipolar currents.

Figure 1 shows an example of a device for transdermal transport designated as a whole by 1.

In the example considered, the device 1 comprises a wave generator 10, connected to which are two electrodes 20 and 30 via respective cables 12 and 14.

In particular, in the example considered, the electrode 30 is made of a conductive material and can have any shape, even though a flexible metal lamina is preferable. In fact, said flexible metal lamina can be applied adapting itself to the anatomical shape of the area of the body of the patient on which this electrode is to be applied.

In the embodiment considered, the electrode 20 is a handpiece made so as to contain an active principle that is to be administered via transdermal route. For instance, the active principle can be contained in a liquid or frozen solution, in a gel, etc. In general, the term "active principle" may include a drug, a product for treatment of skin blemishes, for example cellulitis or the like, or in general ions and/or molecules .

For instance, the Italian patent application No. FI99A000141 describes a wave generator that generates a particular waveform useful for hydroelectrophoresis.

Instead, the Italian patent applications No.

FI98A000137 and FI99A000055 describe possible embodiments of the handpiece 20.

The particular waveform used, together with the gel formulation, enables a deep penetration of the drug to a depth of 11 cm approximately in the tissue. This depth is greater than the one normally obtainable with other electrophoretic methods (just a few millimetres) . Moreover, high local concentrations of the drug used can be reached.

Object and summary of the invention

However, the inventors have noted that hydroelectrophoresis presents a deficit of phoretic transmission in so far as there is a massive electrolysis of the solute for low force of electromagnetic field.

Moreover, the therapies have very long times with a loss of almost 70% of the solute understood as mixture of the active principles.

Finally, the inventors have found that the flow of current is inadequate for many complex therapies, such as for example the therapies of pain, obesity, cellulitis of third and fourth degree, etc. It seems that this is due to the low force of the electromagnetic field and the loss of conductivity due, for example, to the cable, to the connector, and principally to the small lamellar surface of

ion of the handpiece.

In fact, it seems that there is a high resistance of the horny layer to the passage of current with extremely low conductance of current in the dermis. The reason for this is that, with the long times for closing of the circuit, transport is slow, and the continuous passage of inert gel from the roller causes soaking of the horny tissue, which in turn, owing to increase in the Joule effect, causes an increase in the concentration of the ceramides present at the level of the superficial horny layer that, in effect, constitute another barrier to the transport of molecules in addition to the natural one of the non-irrigated epidermal tissue. Hence, once the currents have overcome this natural and induced obstacle, they finally reach in an insufficient manner the dermis, which is a tissue rich in water that enables a better conductance, but by now with a transport that is inadequate in terms of force of currents for reaching the underlying tissues; in brief, there is only percolation towards the deep tissues. The object of the present invention is to overcome one or more of the disadvantages outlined above.

According to the present invention, the above object is achieved by a device having the characteristics recalled in the ensuing claims. The claims form an integral part of the teaching provided in relation to the invention.

In various embodiments, the device for transdermal transport can be connected to two electrodes, where an electrode is configured for containing an active principle to be administered via transdermal and/or intradermal route. The device further comprises a wave generator, which generates a driving signal for the electrodes .

In various embodiments, the driving signal comprises a plurality of packets grouped in trains of packets and in groups of trains. In particular, each packet consists of a unidirectional signal that results from the combination of a modulating signal, for example with a frequency of between 0.1 and 5 Hz, and a carrier signal, for example with a frequency of between 200 and 2000 Hz. Moreover, each train of packets consists of a series of packets and each group of trains comprises a series of trains of packets. In particular, in various embodiments, the trains of packets comprise packets that have the same polarity and the same duration, but at least one first packet has a carrier signal with a first frequency and at least one second packet has a carrier signal with a second frequency.

In various embodiments, the wave generator reverses the polarity of the trains of packets after a given time interval. For instance, in various embodiments, the wave generator reverses the polarity of each train of packets with respect to the polarity of the previous train of packets.

In various embodiments, the device moreover comprises an acoustic generator, such as for example a piezoelectric speaker, which is driven by the driving signal itself.

In various embodiments, the device moreover comprises a light source comprising at least one laser diode or one power LED, where said light source is driven via the driving signal itself.

Brief description of the drawings

The present invention will now be described in detail with reference to the attached drawings, which are provided purely by way of non-limiting example and in which:

- Figure 1 shows a generic device for transdermal transport ;

- Figures 2 to 9 show details of a signal useful for transdermal transport according to the present description;

- Figures 10 and 11 show a device that improves the result of transdermal transport; and

- Figures 12a to 12c show different views of a handpiece for a device for transdermal transport.

Detailed description of embodiments

Illustrated in the ensuing description are various specific details aimed at an in-depth understanding of the embodiments. The embodiments may be obtained without one or more of the specific details, or with other methods, components, materials, etc. In other cases, known structures, materials, or operations are not illustrated or described in detail so that various aspects of the embodiments will not be obscured.

Reference to "an embodiment" or "one embodiment" in the framework of the present description is intended to indicate that a particular configuration, structure, or characteristic described in relation to the embodiment is comprised in at least one embodiment. Hence, phrases such as "in an embodiment" or "in one embodiment" that may be present in various points of the present description do not necessarily refer to one and the same embodiment. Moreover, the particular conformations, structures, or characteristics may be combined adequately in one or more embodiments.

The references provided herein are used only for convenience and hence do not define the sphere of protection or the scope of the embodiments.

The present description develops further the technology of hydroelectrophoresis to improve its efficiency. In fact, with the mechanisms described herein, there are altogether overcome the limits of classic transcutaneous passage obtained with hydroelectrophoresis or other similar apparatuses, i.e., of passage of percolation through the horny layer, this tissue constituting a thorough-going natural barrier having an extremely high electrical resistance to the passage of currents and loss of active principle both in terms of quantity and in terms of excessively long times of therapy since there is a low ionic conductivity and the molecules that are withheld for an excessively long time by the horny tissue are rendered inactive.

Instead, the solutions described herein enable a practically total electro-ionic conductivity of the dermis with low electrical resistance of the horny tissue with a direct passage to the reticular dermis, substantially by-passing the horny tissue, which leads to a direct dermal transport (DDT or TDD) of molecules and proteins, which permits a DDT direct intradermal therapy .

For this purpose, an orderly electrotherapeut ic flow of electromagnetic field with extremely high ionic conductivity and extremely low electrical transport resistance is used.

In particular, according to the present description, the above improvement may be obtained via the following mechanisms:

1) a new signal that enables a direct dermal molecular-protein transport by means of highly specific currents, referred to hereinafter also as DDT (direct dermal transport) "dermaphoresis";

2) an additional light signal created at a coherent frequency by photons produced by laser diodes, referred to hereinafter also as "chromophoresis " ;

3) an additional acoustic signal emitted at a frequency coherent with that of dermaphoresis, referred to hereinafter also as "phonophoresis " ; and

4) a new handpiece.

In fact, the inventors have noted that DDT dermaphoresis, i.e., the new signal, enables a homogeneous, constant, continuous, powerful, and massive transport. Instead, it seems that chromophoresis , i.e., the light radiation generated by laser diodes, exerts an additional thrust on the molecules that are already moving towards the horny tissue. Finally, it seems that phonophoresis, i.e., the additional acoustic signal, makes it possible to direct the molecular and protein transport flow towards the deep tissues.

In general, it is already known to get active principles to pass through the epidermis - i.e., the outermost layer of the three layers that make up human skin (epidermis, dermis, hypodermis) - via irradiation with a laser, and in particular with a diode laser. However, this treatment can be used only for surface treatment and not for treatment in depth as occurs with hydroelectrophoresis . However, the inventors have noted that the result obtained by the combination of hydroelectrophoresis, in particular the dermaphoresis described herein, with laser irradiation improves surprisingly the result of the passage of the active principle also through the other layers of the skin, i.e., also through the dermis and hypodermis.

Moreover, it seems that the acoustic frequency also produces an effect of stochastic resonance, which, added to the flow of photons, enables creation of a soliton. A possible explanation of this effect is that the force of transport of the solitons, namely produced by the combination of the light force with the acoustic force, creates a self-reinforcing wave without dispersion of energy in the propagation medium that enables the waves produced by dermaphoresis not to lose considerable energy during traversal from the horny layer to the cutaneous layers, and then to the deep tissue layers. Consequently, it seems that this force, from the biological standpoint, creates a constant opening of the desmosomal layer at the level of the lamellar tissue of the corneocytes, enabling not only an orderly and durable complete molecular passage, but also a continuous complete, massive, and powerful passage of molecules of small, medium, and large dimensions, and protein fractions proper, with complete ease, and in a shorter time of therapy.

Consequently, irrespective of the possible scientific explanations, the techniques described herein represent a total revolution in physical therapies since they result in a force of translation expressed as a self-reinforcing wave generated in a propagation medium (constituted by a modified phoretic gel with a medical action, potentially with a massive polytherapeut ic action) . Movement of the substances is consequently substantially intradermal and only in part transdermal with a direct passage of molecules of small, medium, and large dimensions and protein fractions to the tissues, which has never been obtained with previous apparatuses.

The person skilled in the art will appreciate that in transdermal transport the passage is beyond the dermis, i.e., a relative and insignificant passage, where the dermis is defined only as a collector for percolation of the active principle. Consequently, in the case where the passage is insufficient, also the therapy is insufficient. Instead, in intradermal therapy the dermis is no longer a mere passage, but becomes biological tissue active to passage; i.e., it becomes an important biological carrier of the active principle. For instance, in some cases the passage of the drug (or active principle) can have an additional thrust, for example of approximately 60%, and the reticular dermis, i.e., the first layer of the dermis, can behave as a metabolic laboratory of the drug; i.e., part of the active principle, for example approximately 40%, may remain in the reticular dermis as a continuous pharmacological reserve that releases the drug in depth in the hours and days following upon treatment. Consequently, with the apparatus described herein it is possible for the first time to carry out a proper targeted intradermal therapy without the use of needles; i.e., the intradermal therapy by dermaphoresis described herein reflects to a surprising extent a pharmacological therapy using a needle.

In general, even though the best result is obtained with the combination of all three mechanisms, the mechanisms previously described may also be used individually .

Finally, the new handpiece comprises an electrification chamber entirely made of a conductive material, which enables the following to be obtained:

- a uniformity of traversal of dermaphoresis current ;

- a time of electrical pre-charge of the gel; in particular, the flow of current is homogeneous and uniform within the metal cavity of the dispenser and propagates also within the flask, contained in which is the gel that progressively drops by gravity into the chamber; consequently, since the conductive gel is also the gel in the flask, it is traversed by currents;

- the gel in the electrification chamber has a higher potential, which generates a constant motion of molecules, also attracting the molecules possibly pre- charged in the flask; and

- the molecules and the proteins are traversed by a current that is constant in time and massive from the surface of the horny layer with a higher attraction and at a higher rate to the passive electrode.

Dermaphoresis

As mentioned previously, in dermaphoresis a new signal is used. This signal is generated by a wave generator 10 and applied through connection cables 12 and 14 to two electrodes 20 and 30, where one of the two electrodes is designed to contain a carrier containing the active principle.

Typically, driving is in current, for example with a maximum intensity of approximately 15-100 mA.

However, driving could also be in voltage.

In various embodiments, the signal comprises a carrier signal with a frequency of between 200 and 2000 Hz modulated in amplitude via a modulating signal with a frequency of between 0.1 and 5 Hz, preferably between 0.5 and 2 Hz.

For instance, Figures 2a to 2f show examples of carrier signals 102, which in order are: a rectified sinusoidal waveform, a positive sinusoidal waveform, a triangular waveform, a positive square waveform, a sawtooth waveform, and a series of pulses spaced at intervals apart. However, in general, the carrier signal has a waveform oscillating periodically between zero and a maximum value of amplitude.

For instance, in one embodiment, the carrier signal is a positive sinusoidal wave where the amplitude as a function of time t is given by

f(t) = sin (2π ^■ f_p ^■ t) + 1 (1) where f_p is the frequency of the carrier signal. Also the modulating signal can have different waveforms. For instance, Figures 3a to 3d show examples of modulating signals 104, which in order are: a sawtooth waveform, a triangular waveform, a rectified sinusoidal waveform, and a trapezial waveform. Consequently, in general, also the modulating signal 104 has a waveform oscillating periodically between zero and a maximum value of amplitude.

For instance, in one embodiment, the modulating signal 104 is a rectified sinusoidal wave, where the amplitude as a function of time t is given by

f(t) = (sin [2π ^■ f_m ^■ t)\ (2)

where f_m is the frequency of the modulating signal. For instance, in various embodiments, the modulating signal has a frequency f,„ of between 0.1 and 5 Hz, preferably substantially equal to 0.5, 1, or 2 Hz.

Consequently, according to the present description a packet is created that has a duration T_pac corresponding to the duration of a period T_m of the modulating signal:

Tpac = Tm (\3)I For instance, in various embodiments, the period of the modulating signal T_m is between 0.3 and 0.8 s, preferably between 0.4 and 0.6 s, preferably 0.5 s. For instance, for a modulating signal with a rectified sinusoidal waveform, the period of the modulating signal T_m would correspond to l/(2f_m) i.e., only to the period of a half-wave. For instance, in the case where the period of the modulating signal T_m is 0.5 s, the rectified sinusoidal wave of the modulating signal 104 would have a frequency of 1 Hz.

For instance, for the carrier signal according to Eq. (1) and the modulating signal according to Eq. (2), the packet would have the following waveform:

f(t) = |sm(27T · f._B ^■ t)| · (sin(2r · f_p ^■ t) + l) (4)

For instance, Figure 4 shows a possible embodiment of a signal that comprises a sequence of two packets P.

In- various embodiments, the polarity of these packets, which by definition are unidirectional, is periodically reversed. For instance, in various embodiments, the above reversal of polarity is performed after a time Tj_nv that corresponds to the time of a packet T_pac (or a time that corresponds to a multiple of the time of a packet T_pac)

T_lnv = i ^■ T_pac = i ^■ T_m (5)

where i is an integer greater than zero.

In particular, in various embodiments, groups of packets are formed that comprise a number of packets i with a first polarity followed by the same number of packets i with a reversed polarity, i.e., the duration T_gr of a group of packets is

T_gr = · T_inv = 2 · i · T_m (6) In various embodiments, the frequency f_p of the carrier signal remains stable for a group of packets.

For instance, Figure 5 shows a possible embodiment of a group of packets PG, which comprises a packet with positive polarity P+ followed by a packet with negative polarity P- .

Consequently, in the embodiment considered, the polarity is reversed after each half-wave of the modulating signal 104, which means that the modulating signal 104 behaves as a normal, i.e., non-rectified, sinusoidal signal

f(t) = sin(2;r · f_m ^■ t) · (sin(2;r · f₀ ^■ t) + l) (7)

Moreover, the inventors have noted that the depth of the penetration of the active principle depends principally upon the frequency of the carrier signal. In particular, the penetration depth p may be approximated with the following equation:

(2000 Hz - f )

p = — cm ( 8 )

180

i.e., it is possible to determine the frequency of the carrier signal f_p on the basis of the penetration depth p required

( 180 · ^',

f_P = 2000 - I Hz (9)

V cm

For instance, Figure 6 illustrates a table with 23 typical depths, identified by the letters from A to Z, with the corresponding penetration depth p measured in centimetres and the respective frequency f_p of the carrier signal measured in hertz.

In particular, the inventors have noted that the efficiency of the treatment can be improved by creating a sequence of signals with different carrier frequencies f_p.

For instance, in various embodiments, a train of packets Tr is created, which comprises a sequence of a plurality of packets P, where the frequency f_p of the carrier signal of each packet P is decreased, thus stimulating a movement of the active principle in depth .

For instance, Figure 7 shows an embodiment of a train of packets Tr comprising four packets Pi, P₂, P3, and P₄.

In various embodiments, these trains of packets are repeated periodically.

Moreover, in various embodiments, the frequency f_m of the modulating signal remains constant for the entire train of packets. Consequently, in the embodiment considered, the duration of a train of packets T_tr is

T_tr = ⁴ · ^TP (10)

For instance, in the case where the packet has a duration T_pac of 0.5 s, the train would have a duration T_tr of 2 s.

Consequently, in the currently preferred embodiment, the wave generator 10 is configured for generating a signal that comprises trains of packets Tr, wherein each train of packets Tr, comprises a plurality of packets P. In particular, the packets P consist of a unidirectional signal that results from the combination of a modulating signal 104 and a carrier signal 102. Moreover, whereas the frequency f_p of the carrier signal remains stable for a packet P, the frequencies of the carrier signals f_p of the packets P within a train of packets Tr are different from one another.

As mentioned previously, in the currently preferred embodiment, the train of packets Tr comprises four packets P.

In various embodiments, these trains of packets Tr are used for forming groups of trains.

For instance, Figure 8 shows a possible embodiment of a group of trains TG.

In particular, in the embodiment considered, each group of trains TG comprises a plurality of trains Tr followed by a pause T_{tg 0}ff, preferably of between 0.1 and 5 s, where the signal is constant, for example zero. Consequently, the trains are transmitted for a duration

^Ttg_on = ^k · ^Ttr ⁽ID

where k is an integer greater than one, which corresponds to the number of trains Tr in a group of trains TG, and the entire duration of a group of trains Ttg is

^Ttg = ^Tt_g_on + T_tg__off = k ^■ T_tr + T __off (12)

For instance, in the currently preferred embodiment, the group of trains TG comprises four trains Tr_x, Tr₂, Tr₃ and Tr₄, i.e., k = 4 , and the duration of the pause T_{tg off} is I s. Consequently, in the embodiment considered, the duration T_tg of a group of trains^' TG would be 9 s .

Also in this case, it may be envisaged that the polarities of the trains Tr within a group of trains TG are reversed. In fact, the inventors have noted that a reversal at the level of the packets as illustrated in Figure 5 improves the result only slightly, but the efficiency increases considerably with reversal of the polarity only at the level of the trains. Consequently, in the currently preferred embodiment, the packets within a train Tr have one and the same polarity.

For instance, Figure 9 shows the currently preferred embodiment, where the polarity of the second train Tr₂ and of the fourth train Tr₄ are reversed with respect to that of the first and third trains Tri and Tr₃; i.e., the polarity is reversed every 2 s. Consequently, the first and third trains Tri and Tr₃ have the same waveform and the second and fourth trains Ί∑2 and Tr₄ have the same waveform.

In various embodiments, the above groups of trains TG are repeated for a certain duration that corresponds to the duration of the treatment. For instance, for typical applications, the duration of the treatment is between 10 and 40 min, preferably 20 min.

The inventors have noted that with the above wave generator - which is in itself a general-purpose and programmable wave generator - different treatment programs may be created.

For instance, in one embodiment, the wave generator 10 is able to generate at least one of the following types of treatment or programs, with the following names:

1. Stretch marks,

2. Cellulitis ONE,

3. Cellulitis TWO,

4. Muscle, 5. Pain ONE,

6. Pain TWO,

7. Pain THREE,

8. Pain FOUR,

9. Pain FIVE,

10. Face ONE , and

11. Face TWO.

In various embodiments, the wave generator 10 may also enable generation of all the above eleven programs. For this purpose, the generator 10 could comprise a user interface that enables selection of a specific program.

However, the wave generator 10 could be able to generate even just a single program, such as for example the program "Stretch marks", or a subset of programs, such as for example the programs "Cellulitis ONE" and "Cellulitis TWO" .

Moreover, the apparatus may also comprise a wired or wireless communication interface, which enables setting of the parameters of one or more programs or an exchangeable memory that comprises the parameters, such as for example the number, the frequencies of the carrier signals, and/or the frequencies of the modulating signals of the groups of packets GP within a train of packets Tr.

In what follows, the specific characteristic data for the programs mentioned above will be described.

For simplicity it is assumed that all the programs substantially feature the same general timings described previously; namely,

- a packet P is obtained via a unidirectional signal that results from the combination of a carrier signal and a modulating signal, preferably both being sinusoidal signals;

- the number of packets P within a train of packets Tr is four, where the packets P have the same polarity and the same duration (preferably 0.5 s), i.e., the frequencies f_m of the modulating signals 104 are substantially identical, whereas the frequencies f_p of the carrier signals 102 are at least in part different;

- the number of trains of packets Tr within a group of trains TG is four; i.e., the duration T_tr on of a group of trains TG is preferably 8 s, where only the polarity of the trains of packets Tr is reversed, preferably after each train Tr;

- the trains of packets Tr are followed by a pause Ttr oft; preferably of 1 s; and

- the duration of the treatment is, for example, approximately 20 min.

In particular, in the currently preferred embodiment, the programs mentioned above have the following series of carrier signals, which principally determines the depth of the treatment:

- in the program "Stretch marks" for treatment of stretch marks the four groups of packets PG have the following typical depths in order: D-E-F-G, i.e., the depths required are 0.5, 1, 1.5 and 2 cm, and the frequencies of the respective carrier signals are 1910, 1820, 1730, and 1640 Hz;

- in the program "Cellulitis ONE", for the treatment of a first structural morphological aspect of cellulitis, the four packets P have the following typical depths in order: H-J-I-L, i.e., the required depths are 2.5, 3, 3.5 and 4 cm, and the frequencies of the respective carrier signals are 1550, 1460, 1370, and 1280 Hz;

- in the program "Cellulitis TWO", for the treatment of a second structural morphological aspect of cellulitis, the four packets P have the following typical depths in order: L^—M^— —0 , i.e., the required depths are 4, 4.5, 5, and 5.5 cm, and the frequencies of the respective carrier signals are 1280, 1190, 1100, and 1010 Hz;

- in the program "Muscle", for the treatment of muscles, the four packets P have the following typical depths in order: L-M-N-O, i.e., the required depths are 4, 4.5, 5. and 5.5 cm, and the frequencies of the respective carrier signals are 1280, 1190, 1100. and 1010 Hz;

- in the program "Pain ONE" for the treatment of superficial pain, the four packets P have the following typical depths in order: F-G-H-J, i.e., the required depths are 1.5, 2, 2.5, and 3 cm, and the frequencies of the respective carrier signals are 1730, 1640, 1550, and 1460 Hz;

- in the program "Pain TWO" for the treatment of neuro-muscular and tendon traumas, the four packets P have the following typical depths in order: H-J-L-N, i.e., the required depths are 2.5, 3, 4, and 4.5 cm, and the frequencies of the respective carrier signals are 1550, 1460, 1280, and 1190 Hz;

- in the program "Pain THREE" for the treatment of osteoarticular contusive traumas the four packets P have the following typical depths in order: O-Q-R-S, i.e., the required depths are 5.5, 6.5, 7, and 7.5 cm, and the frequencies of the respective carrier signals are 1010, 830, 740, and 650 Hz;

- in the program "Pain FOUR" for the treatment of osteoarticular contusive traumas the four packets P have the following typical depths in order: Q-R-S-T, i.e., the required depths are 6.5, 7, 7.5, and 8 cm, and the frequencies of the respective carrier signals are 830, 740, 650, and 560 Hz;

- in the program "Pain FIVE" for the treatment of osteoarticular contusive traumas the four packets P have the following typical depths in order: T-V-W-Z, i.e., the required depths are 8, 9, 9.5, and 10 cm, and the frequencies of the respective carrier signals are 560, 380, 290, and 200 Hz;

- in the program "Face ONE" for surface treatment of the face the four packets P have the following typical depths in order: E-F-G-H, i.e., the required depths are 1, 1.5, 2, and 2.5 cm, and the frequencies of the respective carrier signals are 1820, 1730, 1640, and 1550 Hz; and

- in the program "Face TWO" for the treatment of the face in depth the four packets P have the following typical depths in order: G-I-M-O, i.e., the required depths are 2, 3.5, 4.5, and 5.5 cm, and the frequencies of the respective carrier signals are 1640, 1370, 11900, and 1010 Hz.

The programs described above guarantee that the ■specific areas are treated only at a targeted depth. For instance, the program "Muscle" guarantees that the depth from 0 to 0.3 cm is not substantially traversed by currents. The person skilled in the art will appreciate that the programs in themselves define only a given depth, whilst the therapeutic effect is obtained by the active principle that must be appropriate for the type of treatment.

Listed below are all the programs currently tested and their characteristic data:

1. "SMI RED" for the treatment of red stretch marks: sequence F-H-H-J, with a treatment time of 20 min;

2. " SM2 WHITE" for the treatment of recent white stretch marks: sequence G-J-I-I, with a treatment time of 30 min;

3. "SM3 WHITE" for the treatment of wide white stretch marks: sequence I-I-J-L, with a treatment time of 30 min;

4. "TRICHOl" for the treatment of re-growth of hair: sequence L-M-M-N, with a treatment time of

30 min;

5. "TRICH02 " for the treatment of re-growth of hair: sequence M-N-N-O, with a treatment time of 30 min;

6. "TRICE 3" for the treatment of re-growth of hair: sequence N-N-N-0, with a treatment time of between 30 and 40 min;

7. "NAIL" for the treatment of nail pathological conditions: sequence L-O-O-N, with a treatment time of 20 min;

8. "TROPHISM OF MUCOSAE" or "VAGI A-PENIS " for rejuvenation of the mucosae: sequence L-M-M-N, with a treatment time of 20 min;

9. "FACE1" for the treatment of ultra-sensitive skins: sequence G-H-H-J, with a treatment time of 20 min;

10. " FACE2 " for the treatment of the skin of patients between 20 and 40 years old: sequence J-I-L-M, with a treatment time of 20 min;

11. " ACE3 " for the treatment of the skin of patients over 40 years old: sequence L-M-M-O, with a treatment time of 20 min;

12. "FACE4" for the treatment of the skrn with active acne: sequence L-I-I-L, with a treatment time of 20 min;

13. "FACE5" for the treatment of post-acne skin: sequence L-N-N-M, with a treatment time of 20 min;

14. "FACE6" for the treatment of large wrinkles: sequence -O-O-P, with a treatment time of 30 min;

15. "FACE 7" for the treatment of scars or burns: sequence N-M-N-O, with a treatment time of 30 min;

16. "FACE 8" for the treatment of blotches on the face: sequence H-J-L-L, with a treatment time of 20 min;

17. "BODYACNE" for the treatment of acne diffused over the body: sequence N-N-O-0, with a treatment time of 30 min;

18. "SCARS" for the treatment of scars on the body: sequence M-N-N-0, with a treatment time of 20 min;

19. "AFTER-EFFECTS OF BURNS" for the treatment of burns on the body: sequence O-P-P-0, with a treatment time of 30 min;

20. "KELOIDS" for the treatment of keloids: sequence P-P-Q-Q, with a treatment time of 30 min;

21. "BODY BLOTCHES" for the treatment of blotches on the body: sequence N-O-O-P, with a treatment time of

30 min;

22. "CAPILLARIES" for the treatment of the capillaries: sequence N-I-M-M, with a treatment time of 30 min;

23. "BREAST1 " for the treatment of moderate trophism: sequence M-M-O-0, with a treatment time of 20 min;

24. "BREAST2 " for the treatment of slight hypotrophism: sequence N-P-P-Q, with a treatment time of 30 min;

25. "BREAST3 " for the treatment of medium hypotrophism: sequence P-R-P-R, with a treatment time of 30 min;

26. "BREAST4 " for the treatment of severe hypotrophism: sequence Q-Q-R-R, with a treatment time of 30 min;

27. "CELL1" for the treatment of first-degree or second-degree cellulitis: sequence L-M-M-N, with a treatment time of 20 min;

28. "CELL2" for the treatment of second-degree or third-degree cellulitis: sequence M-O-P-P, with a treatment time of 30 min;

29. "CELL3" for the treatment of third-degree cellulitis: sequence 0-N-O-O, with a treatment time of 30 min;

30. "CELL4" for the treatment of fourth-degree cellulitis and beyond, and lymphoedema: sequence O-P-Q- Q, with a treatment time of 30 min;

31. "CELL5" for the treatment of fourth-degree cellulitis and beyond, and phleboedema Q-Q-P-Q, with a treatment time of 30 min;

32. "PAIN1" for the treatment of pain of fine joints: sequence H-G-J-J, with a treatment time of 20 min;

33. "PAIN 2" for the treatment of pain of the epicondyle: sequence J-L-L-M, with a treatment time of

20 min;

34. "PAIN 3" for the treatment of tendon pain: sequence M-N-M-0, with a treatment time of 20 min;

35. "PAIN 4" for the treatment of slight muscular pains: sequence N-N-O-P, with a treatment time of

20 min;

36. "PAIN 5" for the treatment of medium muscular pains: sequence 0-O-P-Q, with a treatment time of

20 rain;

37. "PAIN 6" for the treatment of deep muscular pains: sequence Q-R-S-S, with a treatment time of

30 min;

38. "PAIN 7" for the treatment of torn muscle: sequence R-S-T-T, with a treatment time of 30 min;

39. "PAIN 8" for the treatment of first-degree pains of the joints: sequence Q-Q-Q-S, with a treatment time of 20 mm;

40. "PAIN 9" for the treatment of second-degree pains of the joints: sequence R-R-S-S, with a treatment time of 30 min;

41. " PAI 10" for the treatment of third-degree pains of the joints: sequence T-T-U-U, with a treatment time of 30 min;

42. " PAIN 11" for the treatment of first-degree bone pain: sequence T-T-V-V, with a treatment time of 30 min;

43. "PAIN 12" for the treatment of second-degree bone pain: sequence U-V-W-W, with a treatment time of 30 min;

44. "PAIN 13" for the treatment of third-degree bone pain: sequence W-Z-Z-Z, with a treatment time of

30 min;

45. "MUSCLE Tl" for the treatment of muscular trophism: sequence L-M-M-M, with a treatment time of

20 min;

46. "MUSCLE T2" for the treatment of muscular trophism: sequence M-O-O-P, with a treatment time of 30 min;

47. "MUSCLE T3" for the treatment of muscular trophism: sequence O-P-Q-Q, with a treatment time of 30 min;

48. "MUSCLE T4" for the treatment of muscular trophism: sequence P-P-Q-Q, with a treatment time of

30 min;

49. "MUSCLE T5" for the treatment of muscular trophism: sequence R-S-S-T, with a treatment time of

40 min;

50. "FAT Dl" for the treatment of localized adiposity: sequence U-U-T-U, with a treatment time of 30 min;

51. " FAT D2" for the treatment of localized adiposity: sequence V-V-U-V, with a treatment time of 30 rain;

52. "FAT D3" for the treatment of localized adiposity: sequence W-W-V-W, with a treatment time of 40 min;

53. "FAT Ml" for the treatment of localized adiposity: sequence W-W-Z-Z, with a treatment time of 40 min;

54. "FAT M2" for the treatment of the diffused adiposity: sequence Z-Z-W-Z, with a treatment time of 40 min;

55. "FIBROSIS 1" for the treatment of superficial fibroses: sequence M-O-O-R, with a treatment time of

20 min;

56. "FIBROSIS 2" for the treatment of medium fibroses: sequence P-R-R-S, with a treatment time of

30 min;

57. "FIBROSIS 3" for the treatment of deep fibroses: sequence S-S-T-T, with a treatment time of

40 min;

58. "SKIN1" for the treatment of the skin of the hands: sequence I-L-L-L, with a treatment time of 20 min;

59. "SKIN 2" for the treatment of the skin of the body: sequence M-N-N-N, with a treatment time of 30 min;

60. "SKIN 3 M" for the treatment of the skin of the body: sequence N-O-O-P, with a treatment time of 40 min;

61. "ULCERS 1" for the treatment of sores: sequence M-L-N-N, with a treatment time of 20 min;

62. "ULCERS 2" for the treatment of diabetic ulcers: sequence O-P-P-P, with a treatment time of 20 min;

63. "ULCERS 3" for the treatment of vascular ulcers: sequence Q-Q-P-Q, with a treatment time of 20 min;

64. "POST-OP 1" for the post-operative treatment of the face: sequence G-G-H-H, with a treatment time of

20 min;

65. "POST-OP 2" for the post-operative treatment of the body: sequence M-N-N-0, with a treatment time of

30 min;

66. "POST-OP 3" for the post-operative treatment of the body: sequence Q-Q-S-S, with a treatment time of

40 min.

Consequently, the wave generator 10 may also enable generation of all the above programs or a subset thereof .

Phonophoresis and Chromophoresis

As mentioned previously, in chromophoresis an additional light signal is used, produced by laser diodes, whereas in phonophoresis an additional acoustic signal is used.

Figure 10 illustrates a device 40 designed for chromophoresis and/or phonophoresis.

In particular, Figure 10 shows the device 40 from beneath .

In one embodiment, the device 40 comprises at least one laser diode 44 for chromophoresis. For instance, in Figure 10 four laser diodes 44 are represented.

As mentioned previously, it seems that the photons generated by the above laser diodes 44 exert an additional thrust on the molecules that are already moving towards the horny tissue.

Consequently, in general, any laser diode or power LED, i.e., with an adequate power of emission, may be used, and chromophoresis may be used with any device for transdermal transport.

In the present description, by "LEDs" are meant p- n junction LEDs formed by a layer of semiconductor material. Typically, the electrons and the holes are injected in a recombination zone through two regions of the diode coated with impurities of different types, i.e., of an n . type for the electrons and a p type for the holes. When a direct voltage is applied for reducing the potential barrier of the junction, the electrons of the conduction band of the semiconductor recombine with the holes of the valence band, releasing energy in the form of photons. As is well known, the colour or frequency of the radiation emitted by a LED is defined by the distance in energy between the energy levels of electrons and holes and typically corresponds to the value of the forbidden band of the semiconductor in question.

Also a laser diode is made up of a p-n junction, and when an electron and a hole are present in one and the same region, they can recombine with spontaneous emission, emitting a photon with an energy equal to the difference between the states of the electron and of the hole involved. However, in appropriate conditions, the electron and the hole may coexist in one and the same area for a certain time before recombining. Then, a nearby photon with energy equal to the recombination energy may cause recombination with stimulated emission. This generates another photon of the , same frequency, which travels in one and the same direction, having the same polarization and phase as the first photon. Consequently, stimulated emission causes a gain in an optical wave in the injection region, and the gain increases as the number of electrons and holes injected through the junction increases.

Hence, whereas a LED emits light only by spontaneous emission, a laser diode principally generates coherent light by stimulated emission. Consequently, a laser diode has a quasi-monochromatic spectrum of radiation. Moreover, at low current the laser diode has a spontaneous emission like the LED and, above a given value of current referred to as "threshold current", the power increases more rapidly, and there is stimulated emission.

Consequently, a laser diode can be supplied like a classic LED, ensuring only that the current that traverses the laser diode is higher than its threshold current .

In various embodiments, the laser diode or diodes 44 has/have coupled thereto appropriate optical means, such as for example lenses, which broaden the beam of light over a more extensive area.

In particular, in various embodiments, chromophoresis is driven by the same signal, i.e., by the same frequencies, emitted for the specific treatment selected. Consequently, the signal sent to the electrodes 20 and 30 is also sent to the laser diodes 44. The person skilled in the art will appreciate that a rectifier may be required for driving the laser diodes 44, again with a positive driving signal .

In a currently preferred embodiment, the laser diodes 44 emit light of at least two different colours.

In fact, as described previously, the dermaphoresis signal is sufficiently complex, and certain times must be met for guaranteeing that the complete sequence of trains Tr is applied to a certain area. In this case, the laser diodes 44 may be driven in a synchronised, way to indicate the state of the treatment .

For instance, in one embodiment, the device 40 comprises at least one first group of laser diodes that emits light having a first colour, such as for example red, and at least one second group of laser diodes that emits light having a second colour, such as for example green. In this case, during a first time interval, for example for the duration of a train Tr, only the laser diodes of the first group are lit up, whereas, during a second time interval, for example for the duration of a subsequent train Tr with reversed polarity, only the laser diodes of the second group are lit up. In this way, the physician immediately obtains macroscopic information on advance of the treatment.

In an embodiment, the device 40 comprises an acoustic-wave generator 42 for phonophoresis, such as for example a piezoelectric speaker.

In particular, in various embodiments, phonophoresis is driven by the same signal, i.e., by the same frequencies, emitted for the specific treatment selected. Consequently, the signal sent to the electrodes _.20 and 30 is also sent to the acoustic generator 42.

The inventors have noted that an improvement of the treatment is obtained also with other driving signals, used for example in known devices, for instance with the driving signal described in the Italian patent application No. FI99A000141 or in the European patent application No. EP- 1 185 334 Al, which are incorporated herein for reference.

Consequently, also phonophoresis may be used with any device for transdermal transport, using only for phonophoresis the driving signal sent also to the electrodes 20 and 30 of the device for transdermal transport .

However, as described previously, the combination of dermaphoresis , i.e., of the signal described previously, and phonophoresis, achieves results never seen previously. Consequently, in the currently preferred embodiment, dermaphoresis and phonophoresis are used in combination.

In general, the aforesaid device 40 may be integrated in the handpiece 20 of the treatment device or may be an additional device (potentially sold separately) that is rigidly coupled to the handpiece

20.

For instance, Figure 11 shows an embodiment, in which the device 40 is fixed laterally to the handpiece 20 and the light ray and/or the acoustic signal are emitted in the direction of the area to be treated. Dispenser

Figures 12a to 12c show a handpiece or dispenser 20 that can be used with the device for transdermal transport illustrated in Figure 1.

In particular, as mentioned previously, the electrification chamber of the above dispenser 20 is made entirely of a metal material, preferably steel.

Figure 12a shows a perspective view of the handpiece 20, without its outer casing.

In particular, in the embodiment considered, the handpiece 20 comprises an electrification chamber 210 with a hollow portion.

For instance, Figure 12b shows a possible embodiment of the electrification chamber 210.

In the embodiment considered, the electrification chamber 210 has a substantially tubular shape, preferably with a rectangular cross section, and comprises on its upper side a first opening 212 and on its underside a second opening 214.

In particular, the opening 212 may be used for introducing a gel or some other substance containing an active principle into the electrification chamber 210.

For instance, in the embodiment considered, the above opening 212 has a circular cross section and comprises a thread that enables direct screwing of a flask (not illustrated) containing the gel. In this case, the gel containing the active principle drops progressively by gravity through the opening 212 into the chamber 210.

Instead, the opening 214 is used as outlet for the electrified gel. For instance, in the embodiment considered, the opening 214 has a rectangular shape and is substantially closed via a roller 220, also this being made of a metal material, preferably steel. Consequently, in the embodiment considered, the electrified gel exits from the opening 214 only when the handpiece 20 is moved and the roller 220 is turned.

The electrification chamber 210 moreover comprises an electrical contact 216 for connection to the wave generator 10. For instance, in the embodiment considered, the contact is made via a blind hole 216 with internal thread. In this case, the cable 12 may be fixed directly to the electrification chamber 210 via a screw.

Consequently, in the embodiment considered, the entire dispenser 20 is made of a metal material that principally enables uniformity of ^'traversal of current.

In various embodiments, the handpiece 20 moreover comprises an outer casing that covers the electrification chamber 210, leaving only space for the opening 212 and the roller 220. In particular, this outer casing is made of an insulating material, such as for example plastic or a resin.

Of course, without, prejudice to the principle of the invention, the details of construction and the embodiments may vary widely with respect to what has been described and illustrated herein purely by way of example, without thereby departing from the scope of the present invention, as defined in the ensuing claims .

Claims

1. A device designed for transdermal and/or intradermal transport that can be connected to two electrodes (20, 30), wherein one of said electrodes (20) is configured for containing an active principle to be administered via transdermal and/or intradermal route, the device comprising a wave generator (10) configured for generating a driving signal to be sent to said electrodes (20, 30),

said device being characterized in that:

a) said driving signal comprises a plurality of packets (P) grouped in trains of packets (Tr) and in groups of trains (TG) , wherein each packet (P) consists of a unidirectional signal that results from the combination of a modulating signal (104) and a carrier signal (102), wherein each train of packets (Tr) consists of a series of packets (P), wherein each group of trains (TG) comprises a series of trains of packets (Tr ) , and

b) said wave generator (10) is configured for reversing the polarity of said trains of packets (Tr) after a given time interval.

2. The device according to Claim 1, wherein said carrier signal (102) has a frequency of between 200 and 2000 Hz and/or said modulating signal (104) has a frequency of between 0.1 and 5 Hz.

3. The device according to Claim 1 or Claim 2, wherein said carrier signal (102) and/or said modulating signal (104) has a waveform oscillating periodically between zero and a maximum value of amplitude .

4. The device according to Claim 3, wherein:

- said carrier signal (102) has a rectified sinusoidal waveform, a positive sinusoidal waveform, a triangular waveform, a positive square waveform, a sawtooth waveform or a series of pulses spaced at intervals apart; and/or

- said modulating signal (104) has a sawtooth waveform, a triangular waveform, a rectified sinusoidal waveform, or a trapezial waveform.

5. The device according to any one of the preceding claims, wherein said train of packets (Tr) comprises packets (P) that have one and the same polarity and/or one and the same duration.

6. The device according to any one of the preceding claims, wherein said train of packets (Tr) comprises at least one first packet (P) with a carrier signal (102) having a first frequency and at least one second packet (P) with a carrier signal (102) having a second frequency.

7. The device according to any one of the preceding claims, wherein said train of packets (Tr) comprises four packets (P) and/or said group of trains (TG) comprises four trains of packets (Tr) .

8. The device according to any one of the preceding claims, wherein said wave generator (10) is configured for reversing the polarity of each train of packets (Tr) with respect to the polarity of the previous train of packets (Tr) .

9. The device according to any one of the preceding claims, wherein each group of trains (TG) consists of a series of trains of packets (Tr) followed by a pause ( T_tg o_ff ) ·

10. The device according to any one of the preceding claims, comprising:

- an acoustic generator (42), wherein said acoustic generator (42) is driven via said driving signal; and/or

- a light source (44) comprising at least one laser diode or one power LED, wherein said light source (44) is driven via said driving signal.

11. The device according to any one of the preceding claims, comprising a handpiece (20) configured for containing an active principle to be administered via transdermal and/or intradermal route, wherein said handpiece (20) comprises an electrification chamber (210) entirely made of a metal material .

12. A device designed for transdermal and/or intradermal transport that can be connected to two electrodes (20, 30), wherein one of said electrodes (20) is configured for containing an active principle to be administered via transdermal and/or intradermal route, the device comprising a wave generator (10) configured for generating a driving signal to be sent to said electrodes (20, 30),

said device being characterized in that it comprises an acoustic generator (42), wherein said acoustic generator (42) is driven via said driving signal .

13. The device according to Claim 12, wherein said acoustic generator (42) is a piezoelectric speaker.

14. The de.vice according to Claim 12 or Claim 13, wherein said driving signal comprises a plurality of packets (P) grouped in trains of packets (Tr) and in groups of trains (TG) , wherein each packet (P) consists of a unidirectional signal that results from the combination of a modulating signal (104) and a carrier signal (102), wherein each train of packets (Tr) consists of a series of packets (P), wherein each group of trains (TG) comprises a series of trains of packets (Tr) .

15. The device according to Claim 14, wherein said carrier signal (102) has a frequency of between 200 and 2000 Hz and/or said modulating signal (104) has a frequency of between 0.1 and 5 Hz.

16. The device according to Claim 14 or Claim 15, wherein said carrier signal (102) and/or said modulating signal (104) have/has a waveform oscillating periodically between zero and a maximum value of amplitude, preferably:

- said carrier signal (102) has a rectified sinusoidal waveform, a positive sinusoidal waveform, a triangular waveform, a positive square waveform, a sawtooth waveform or a series of pulses spaced at intervals apart, and

17. The device according to any one of Claims 14 to 16, wherein said wave generator (10) is configured for reversing the polarity of said trains of packets (Tr) after a given time interval, preferably said wave generator (10) is configured for reversing the polarity of each train of packets (Tr) with respect to the polarity of the previous train of packets (Tr) .

18. The device according to any one of Claims 14 to 17, wherein said train of packets (Tr) comprises:

- four packets (P); and/or

- packets (P) that have the same polarity and/or the same duration; and/or

- at least one first packet (P) with a carrier signal (102) having a first frequency and at least one second packet (P) with a carrier signal (102) having a second frequency.

19. The device according to any one of Claims 14 to 18, wherein:

- each group of trains (TG) comprises four trains of packets (Tr) ; and/or

- each group of trains (TG) consists of a series of trains of packets (Tr) followed by a pause ( T_tg off) ■

20. The device according to any one of the preceding claims, comprising a light source (44) comprising at least one laser diode or one power LED, wherein said light source (44) is driven via said driving signal.

21. The device according to Claim 20, wherein said light source (44) and said acoustic generator (42) are configured for emitting in one and the same direction a respective light radiation and respective acoustic waves .

22. The device according to any one of the preceding Claims 12 to 21, comprising a handpiece (20) configured for containing an active principle to be administered via transdermal and/or intradermal route, wherein said handpiece (20) comprises an electrification chamber (210) entirely made of a metal material .

23. A device designed for transdermal and/or intradermal transport that can be connected to two electrodes (20, 30), wherein one of said electrodes (20) is configured for containing an active principle to be administered via transdermal and/or intradermal route, the device comprising a wave generator (10) configured for generating a driving signal to be sent to said electrodes (20, 30),

said device being characterized in that it comprises a light source (44) comprising at least one laser diode or one power LED, wherein said light source (44) is driven via said driving signal.

24. The device according to Claim 23, wherein said driving signal comprises a plurality of packets (P) grouped in trains of packets (Tr) and in groups of trains (TG) ,. wherein each packet (P) consists of a unidirectional signal that results from the combination of a modulating signal (104) and a carrier signal (102), wherein each train of packets (Tr) consists of a series of packets (P), wherein each group of trains (TG) comprises a series of trains of packets (Tr) .

25. The device according to Claim 24, wherein said carrier signal (102) has a frequency of between 200 and 2000 Hz and/or said modulating signal (104) has a frequency of between 0.1 and 5 Hz.

26. The device according to Claim 24 or Claim 25, wherein said carrier signal (102) and/or said modulating signal (104) have/has a waveform oscillating periodically between zero and a maximum value of amplitude, preferably:

- said carrier signal (102) has a rectified sinusoidal waveform, a positive sinusoidal waveform, a triangular waveform, a positive square waveform, a sawtooth waveform, or a series of pulses spaced at intervals apart; and

27. The device according to any one of Claims 24 to 26, wherein said wave generator (10) is configured for reversing the polarity of said trains of packets (Tr) after a given time interval, preferably said wave generator (10) is configured for reversing the polarity of each train of packets (Tr) with respect to the polarity of the previous train of packets (Tr) .

28. The device according to any one of Claims 24 to 27, wherein said light source (44) comprises a first group of laser diodes that emits light having a first colour, such as for example red, and at least one second group of laser diodes that emits light having a second colour, such as for example green, and wherein:

- when said train of packets (Tr) has a first polarity, for example when said train of packets (Tr) has a positive polarity, only the laser diodes of the first group are lit up; and

- when said train of packets (Tr) has a second polarity, for example when said train of packets (Tr) has a negative polarity, only the laser diodes of the second group are lit up.

29. The device according to any one of Claims 24 to 28, wherein said train of packets (Tr) comprises:

- four packets (P) ; and/or

- packets (P) that have one and the same polarity and/or one and the same duration; and/or

- at least one first packet (P) with a carrier signal (102) having a first frequency, and at least one second packet (P) with a carrier signal (102) having a second frequency.

30. The device according to any one of Claims 24 to 29, wherein:

- each group of trains (TG) comprises four trains of packets (Tr) ; and/or

- each group of trains (TG) consists of a series of trains of packets (Tr) followed by a pause ( T_{tg 0}ff)

31. The device according to any one of the preceding Claims 23 to 30, comprising an acoustic generator (42), wherein said acoustic generator (42) is driven via said driving signal.

32. The device according to Claim 31, wherein said light source (44) and said acoustic generator (42) are configured for emitting a respective light radiation and respective acoustic waves in one and the same direction .

33. The device according to any one of the preceding claims, comprising a handpiece (20) configured for containing an active principle to be administered via transdermal and/or intradermal route, wherein said handpiece (20) comprises an electrification chamber (210) entirely made of a metal material .