DEVICE FOR INTRACELLULAR TRANSPORT IN RESONANCE

Abstract

The invention pertains to a device for resonance intracellular transport wherein said device can be connected to two electrodes, wherein a first of said electrodes is configured to contain an active principle to be administered by an intracellular route, the device comprising a wave generator configured to generate a driving signal to be sent to said electrodes, wherein said driving signal comprises a plurality of packets grouped in trains of packets and in groups of trains, wherein each packet consists of a unidirectional signal resulting from the combination of a modulating signal and a carrier signal, wherein each train of packets consists of a series of packets, wherein each group of trains comprises a series of trains of packets, and said wave generator is configured to reverse the polarity of said trains of packets, characterised in that the device is configured to generate a driving signal having a first depth frequency of the carrier signal correlated to the depth of an organ or of a tissue to be treated and at least a second depth frequency correlated to the thickness of the said organ or tissue, and to generate resonance frequencies expressed by the repetition frequency of the packets, by the repetition frequency of the trains of packets and by the repetition frequency of the groups of trains.

Claims

1. A device (1) for resonance intracellular transport wherein said device can be connected to two electrodes (20, 30), wherein a first of said electrodes (20) is configured to contain an active principle to be administered by an intracellular route, the device comprising a wave generator (10) configured to generate a driving signal to be sent to said electrodes (20, 30), wherein said driving signal includes a plurality of packets (P) grouped into trains of packets (Tr) and into groups of trains (TG), wherein each packet (P) consists of a unidirectional signal resulting 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), in which each group of trains (TG) comprises a series of trains of packets (Tr), and said wave generator (10) is configured to at least reverse the polarity of said trains of packets (Tr); the device is configured to generate said at least one carrier signal (102) having a first depth frequency of the carrier signal correlated to the depth of an organ or of a tissue to be treated, characterised in that said device (1) is configured to generate at least a further driving signal generated by said wave generator (10) to drive a solenoid and at least a further signal to drive an ultrasound generator and is configured to generate at least further modulating signals (104) to build waveforms comprising packets (P) and trains of packets (Tr) and groups of trains of packets (Tg) and groups of groups of trains, to achieve at the same time the emission of the full spectrum of resonance frequencies in the area to be treated, these frequencies being univocally defined by the device, to act exclusively on that area to be treated, said areas to be treated being reached through water channel transport.

2. The device according to claim 1, wherein at least one modulating signal (104) groups and modulates that pulse into at least four packets (P) having the same pulse frequency.

3. The device according to the preceding claims, wherein at least one modulating signal (104) groups and modulates those packets (P) into trains of packets (Tr) which may have equal or different pulse frequencies within a group of trains.

4. The device according to the preceding claims, wherein at least one modulating signal (104) groups and modulates the trains (Tr) into groups of trains (Tg), and the modulating signal (104) modulates and groups the groups of trains into groups of groups of trains and reverses the polarity of the packets with respect to the polarity of the packets in the previous group of trains.

5. The device according to the preceding claims, wherein each group of trains (TG) comprises a plurality of trains of packets (Tr) followed by a pause (Ttg_off), wherein the length of the pause depends on the organ or on the tissue to be treated.

6. The device according to claim 1, wherein the device is configured to generate packets (P) which, within the same train of packets (Tr), have the same carrier signal frequency.

7. The device according to claim 1, wherein said first electrode (20) is connected to a handpiece (200) that comprises an ultrasound acoustic generator (210), wherein said ultrasound acoustic generator (210) is driven by means of said driving signal.

8. The device according to claim 6, wherein the ultrasound acoustic generator (210) operates at a frequency of between 20 and 40 kHz inclusive.

9. The device according to claim 1, wherein said first electrode (20) comprises a magnetic transducer, wherein said magnetic transducer is driven by means of said driving signal.

10. The device according to claims 6 and 8, wherein said magnetic transducer comprises a solenoid (280) having a ring shape and being built into said handpiece (200).

11. The device according to claim 6, wherein the handpiece (200) comprises an electrification chamber (205) entirely made of a metal material to contain an active principle to be administered.

12. The device according to claim 10, wherein the active principle contained in the electrification chamber (205) of the handpiece (200) is dissolved in agarose-based gel.

13. The device according to claim 6, wherein the handpiece (200) comprises a roller (220) having an external surface provided with knurling suitable to create microchannels in the stratum corneum of the epidermis.

14. The device according to claim 12, wherein the handpiece (200) comprises a dispenser (250) provided with a plane surface from which said roller (220) protrudes, wherein said plane surface of the dispenser (250) has an area no smaller than 5 cm2.

15. The device according to claim 1, characterized in that of comprising means for calculating intermediate frequencies between the first frequency of the carrier signal, correlated to the depth of an organ to be treated, and the second frequency, correlated to the thickness of said organ, in order to apply said intermediate frequencies in the resonance intracellular transport treatment.

16. The working method consists of using the device (1) and handpiece according to the previous claims, wherein said method consists of at least the stages of: dissolving of substances to be transported in an aqueous gel, specifically, agarose gel; dispensing of the gel using the handpiece; transformation by a magnetic field generated by said solenoid to make the water clusters forming the agarose gel coherent with the currents delivered for electrophoresis and with the resonance frequencies of a tissue to be treated; gel deposition by gravity in the electromagnetic chamber; ionisation of the gel in said chamber; uptake of the gel by the roller, which turns and deposits it in the dermis; generation of mechanical action (by means of an ultrasound transducer present on the handpiece and driven by the device) to break the lipid bond in the corneocytes, thus preparing and promoting the creation of microchannels (micro tunneling) produced by the knurling and microneedles (size micron) present on the dispenser roller; transport (through resonance modulated currents by means of pulses/packets/trains/groups of trains/groups of groups of trains, according to said layout) of the compound molecules present in the agarose gel saturated with active principles linked molecularly as explained previously.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0062] Further characteristics and advantages shall become evident by reading the following description provided by way of a non-limiting example, with the help of the figures shown in the tables annexed hereto, wherein:

[0063] FIG. 1 shows a generic device for resonance transport;

[0064] FIG. 1a shows a block diagram of a preferred embodiment of the device for resonance transport;

[0065] FIGS. 2 to 9a show details of a signal useful for resonance intracellular transport according to this description;

[0066] FIG. 10 shows a handpiece for a device for resonance intracellular transport according to an aspect of the invention.

DETAILED DESCRIPTION OF SOME WAYS TO CARRY OUT THIS INVENTION

[0067] The following description illustrates various specific details aimed at allowing in-depth understanding of the embodiments. The embodiments may be carried out 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 shown or described in detail, in order to prevent making various aspects of the embodiments unclear.

[0068] Reference to an embodiment within the context of this description means that a particular configuration, structure or characteristic described in relation to the embodiment is included in at least one embodiment.

[0069] Therefore, phrases such as in an embodiment, which may be present in different places in this description, do not necessarily refer to the same embodiment. Furthermore, particular conformations, structures or characteristics may be appropriately combined in one or more embodiments.

[0070] The references used herein are for convenience purposes only and do not therefore define the scope of protection or the scale of the embodiments.

[0071] To facilitate a better understanding of the invention, some information shall be provided here, which is however known by technicians operating in the field, on the structure of the stratum corneum of the epidermis, which is made up of both the cellular component (i.e. corneocytes), and the space existing between them, which is rich in lipids with very important functions. The majority of these are: ceramides (which connect together corneocytes), cholesterol and free fatty acids that bind to both the corneocytes in the outermost layers and to those deeper down.

[0072] The stratum corneum can be informally compared to a brick wall, in which the stones represent the corneocytes and the mortar, the lipid-rich space between the cells.

[0073] Corneocytes are large flat cells which become bigger with age, as the epidermis is renewed more slowly and they remain longer in the area nearer the surface. During their migration to the outer layers, they take on keratin, bit by bit, and become corneocytes, forming the stratum corneum. Differentiation concludes with desquamation to make way for new cells.

[0074] The entire stratum corneum can be seen as the skin's external barrier: just one corneocyte protects between 1 and 20 basal cells under its area.

[0075] The outermost layers also contain large quantities of lipids produced by the sebaceous glands (triglycerides, wax esters and squalene).

[0076] To improve the connection between the cells and prevent them from sliding on top of each other, the corneocytes are secured to each other by protuberances called desmosomes.

[0077] The water content of the corneocytes is essential and is affected by ambient temperature and humidity level. The cells tend to become dehydrated if the surrounding air is very dry; if it has high moisture content, they can absorb a lot of water. In any case, the water cannot penetrate the stratum corneum in high quantities, due to the presence of the lipids between the cells. The integrity of the barrier is crucial for the skin's selective permeability. Some conditions such as psoriasis and atopic dermatitis destroy said barrier.

[0078] In general, even though a combination of all three mechanisms produces the best result, the mechanisms described above may also be used individually.

[0079] As mentioned previously, the invented device uses the following signal generated by a wave generator 10 and applied by means of connection cables 12 and 14 to two electrodes 20 and 30, wherein one of the two electrodes is designed to contain a carrier containing the active principle, all of which is better described below with reference to FIG. 10.

[0080] FIG. 1a shows an example, in schematic form, of a particularly preferred embodiment of the device for resonance cellular transport innovatively described by this invention. In particular, said device comprises at least one wave generator 10 or signals already present in the known art, but in this embodiment, it has been innovatively created to produce waves of various forms, including sine, triangle, square waves, etc. with frequency of 0 to 2200 Hz and variable currents and voltages, and built to generate a number of carrier signals at the same time, each carrier signal further characterised in that it modulates and groups the signals, or pulses P, into packets, the packets into wave-trains Tr, the wave trains into groups of trains Tg, the groups of trains into further groups of trains, and also made to be able to reverse the polarity of one or more signals, by means of specific device programming. Furthermore, the device comprises a feeder 2 and signal amplifier 2a, designed to amplify the signal generated by generator 10 comprising also a condenser discharge system in order to prevent electric shock during the change in polarity of the signal; there is also a battery pack and corresponding charger 3a and 3b, and also an output stage 4 to drive a solenoid on the handpiece and relative amplification (the signal is picked up by the generator 10 and then amplified and regulated according to the solenoid that will be connected); an audible warning device 30 is also included, which is actuated by a square wave generated by the generator 10 when there is a change in polarity of the signal.

[0081] The device also comprises an ultrasound transducer driving stage 6 which will act as a function generator for a signal of between 20 kHz and 40 kHz inclusive, preferably 22.5 Kz and performs a non-linear frequency sweep from 22.5 to 40 kz.

[0082] Furthermore, in an innovative manner, a circuit 8 is present, dedicated to reading the currents and voltages emitted: said circuit makes it possible to control the actual emission of the currents and enables the system to self-regulate its voltage and/or current depending on the changes in impedance in the human body. Impedance is generated by the body positioned between the two electrodes (one electrode is positioned in the handpiecethe spray headand the other is the second electrode); the measurement is carried out by a dedicated feedback circuit in the device. Once the intensity has been set according to the patient's level of tolerance, the device shall keep said intensity (under current or voltage) constant, despite the changing impedance of the part. Circuit 8 sends the reading to stage 1 of the device and the latter automatically regulates the intensities in current or voltage.

[0083] This ensures uniform transport of molecules in the whole area to be treated and prevents any electric shocks in case of significant changes in impedance.

[0084] Lastly, the device comprises a wireless transmitter 31, for example WiFi and a 3G/4G connection module, GPRS UMTS, etc. able to connect the device itself to one or more networks to allow it to connect remotely to one or more data exchange terminals (e.g. for device recognition, gel consumption, etc.).

[0085] The signal driver typically has a current output, for example with maximum intensity of approximately 15-100 mA. However, the driver could also have a voltage output.

[0086] In various embodiments, the signal comprises a carrier signal with frequency of between 200 and 2000 Hz modulated in amplitude by means of a modulating signal with a frequency of between 0.1 and 5 Hz, preferably between 0.5 and 2 Hz.

[0087] For example, FIGS. 2a to 2f show examples of carrier signals 102, composed, in order, of: a rectified sinusoidal waveform, a positive sinusoidal waveform, a triangular waveform, a positive square waveform, a sawtooth wave 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 amplitude value.

[0088] For example, in one embodiment, the carrier signal is a positive sine wave whose amplitude as a function of time t has the following equation:

f(t)=sin 2.Math.f.sub.p.Math.t)+1(1)

where f.sub.p is the frequency of the carrier signal.

[0089] The modulating signal can also have different waveforms. For instance, FIGS. 3a to 3d show examples of modulating signals 104 composed, in order, of: a sawtooth waveform, a triangular waveform, a rectified sinusoidal waveform and a trapezoidal waveform. Therefore, in general, the modulating signal 104 also has a waveform oscillating periodically between zero and a maximum amplitude value.

[0090] For example, in one embodiment, the modulating signal 104 is a rectified sinusoidal wave, whose amplitude as a function of time t is given by:

f(t)=|sin(2.Math.f.sub.m.Math.t)|(2)

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

[0091] Therefore, according to this description, a packet is created with a duration T.sub.pac corresponding to the duration of a period T.sub.m of the modulating signal:

T.sub.pac=T.sub.m(3)

[0092] For instance, in various embodiments, the period of the modulating signal T.sub.m is between 0.3 and 0.8 s, preferably between 0.4 and 0.6 s, preferably 0.5 s. For example, for a modulating signal with a rectified sinusoidal waveform, the period of the modulating signal T.sub.m would correspond to 1/(2f.sub.m), i.e. only to the period of a half-wave. For instance, if the period of the modulating signal T.sub.m is equal to 0.5 s, then the rectified sine wave of the modulating signal 104 would have a frequency of 1 Hz.

[0093] For example, for the carrier signal according to equation (1) and the modulating signal according to equation (2), the packet would have the following waveform:

f(t)=|sin(2.Math.f.sub.m.Math.t)|.Math.(sin 2.Math.f.sub.p.Math.t)+1)(4)

[0094] For instance, FIG. 4 shows a possible embodiment of a signal comprising a sequence of two packets P.

[0095] In various embodiments, the polarity of these packets, which by definition are unidirectional, is periodically reversed. For example, in various embodiments, said polarity reversal is carried out after a time Ti.sub.inv which corresponds to the time of a group of trains, or a time that corresponds to a multiple of the time of a group of trains: for example, approximately 2 minutes

T.sub.inv=i.Math.T.sub.pac=i.Math.T.sub.m(5)

where i is an integer greater than zero.

[0096] In particular, in various embodiments, groups of packets are formed, comprising a number of packets with a first polarity followed by the same number of packets i with reversed polarity, i.e. the duration T.sub.gr of a group of packets is:

T.sub.gr=2.Math.T.sub.inv=2.Math.i.Math.T.sub.m(6)

[0097] In various embodiments, the frequency f.sub.p of the carrier signal remains constant for a group of packets.

[0098] For example, FIG. 5 shows a possible embodiment of a group of packets PG, comprising a packet with positive polarity P+ followed by a packet with negative polarity P.

[0099] Therefore, in the embodiment considered, the polarity is reversed after each half-wave of the modulating signal 104, which means that modulating signal 104 behaves like a normal sine signal, nota rectified one:

f(t)=sin2(.Math.f.sub.m.Math.t).Math.(sin2(.Math.f.sub.p.Math.t)+1)(7)

[0100] Moreover, the inventors observed that the penetration depth of the active principle depends mainly on the frequency of the carrier signal. Specifically, the penetration depth p can be approximated using the following equation:

[00001]$\begin{array}{cc}p=\frac{\left(2000.Math..Math.\mathrm{Hz}-f_p\right)}{180}.Math.\mathrm{cm}& \left(8\right)\end{array}$

i.e. the frequency f.sub.p of the carrier signal can be calculated according to the penetration depth p required:

[00002]$\begin{array}{cc}{f}_p=\left(2000-\frac{180.Math.p}{\mathrm{cm}}\right).Math.\mathrm{Hz}& \left(9\right)\end{array}$

[0101] For instance, FIG. 6 shows a table with 23 typical depths, identified using the letters from A to Z, with the corresponding penetration depth p measured in cm and the respective frequency f.sub.p of the carrier signal measured in Hz.

[0102] In particular, the inventors observed that treatment efficiency can be improved, by creating a sequence of signals with different carrier frequencies f.sub.p.

[0103] For example, in various embodiments, a train of packets T.sub.r is created, comprising a sequence of a plurality of packets P, wherein the frequency f.sub.p of the carrier signal of each packet P is reduced, thereby encouraging the active principle to move downwards in depth.

[0104] For instance, FIG. 7 shows an embodiment of a train of packets T.sub.r comprising four packets P.sub.1, P.sub.2, P.sub.3, and P.sub.4.

[0105] These trains of packets are periodically repeated in various embodiments.

[0106] Moreover, in various embodiments, the frequency f.sub.m of the modulating signal remains constant for the entire train of packets. Therefore, in the embodiment considered, the duration of a train of packets T.sub.tr is:

T.sub.tr=4.Math.T.sub.pac(10)

[0107] For example, if the packet has a duration T.sub.pac of 0.5 s, the train would have a duration T.sub.tr of 2 s.

[0108] Therefore, in the currently preferred embodiment, the wave generator 10 is configured to generate 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 resulting from the combination of a modulating signal 104 and a carrier signal 102. Moreover, while the frequency f.sub.p of the carrier signal remains constant for a packet P, the frequencies of the carrier signals f.sub.p of the packets P within a train of packets Tr are all the same as each other.

[0109] As mentioned previously, in the currently preferred embodiment, the train of packets Tr comprises four packets P.

[0110] In various embodiments, these trains of packets Tr are used to form groups of trains.

[0111] For instance, FIG. 8 shows a possible embodiment of a group of trains TG.

[0112] In particular, in the embodiment considered, each group of trains TR comprises a plurality of trains Tr followed by a pause T.sub.tg_off, preferably lasting between 0.1 and 5 s, in which the signal is constant, for example at zero. Therefore, the trains are transmitted for a duration:

T.sub.tg_on=k.Math.T.sub.tr(11)

where k is an integer greater than one, equal to the number of trains Tr in a group of trains TG, and the entire duration of a group of trains T.sub.tg is

T.sub.tg=T.sub.tg_on+T.sub.tg_off=k.Math.T.sub.tr+T.sub.tg_of(12)

[0113] For example, in the currently preferred embodiment, the group of trains

[0114] TG comprises four trains Tr.sub.1, Tr.sub.2, Tr.sub.3 and Tr.sub.4, i.e. k=4, and the length of the pause T.sub.tg_off is 1 s. Therefore, in the embodiment considered, the duration Tt.sub.tg_on of a group of trains TG would be 9 s.

[0115] In this case, too, it may be envisaged that the polarity of the trains Tr included within a group of trains TG is reversed at the end of a group of trains TG, or rather at the end of a set time, for example 2 mins, or 120 s. In fact, the inventors observed that reversal in the packets as shown in FIG. 5 only slightly improves the result, and that efficiency increases considerably only with polarity reversal in the trains and groups of trains. Therefore, in the currently preferred embodiment, the packets within a train Tr have the same polarity.

[0116] For example, FIG. 9 shows a particularly preferred embodiment showing details of pulses P11, P12, P13 and P14 contained in the train Tr1.sub.1. Pulses P21 . . . etc . . . contained in the train Tr1.sub.2 are also shown, as well as pulses P31 . . . etc . . . contained in the train Tr1.sub.3, and pulses P41 . . . etc . . . contained in the train Tr1.sub.4

[0117] Pulse trains Tr1.sub.1, Tr1.sub.2, Tr1.sub.3 and Tr1.sub.4 form a first group of trains TG.sub.1.

[0118] The subsequent groups of trains, not shown here, for example TG.sub.2, TG.sub.3 and TG.sub.4 can have the same polarity as the first group of trains TG.sub.1, or reversed polarity between subsequent groups of trains TG.sub.2, TG.sub.3 and TG.sub.4.

[0119] Therefore the polarity of the second group of trains TG.sub.2 is reversed, for instance, for the four subsequent trains of packets Tr2.sub.1, Tr2.sub.2, Tr2.sub.3, Tr2.sub.4 contained in said second group of trains TG.sub.2; (to simplify matters, said trains of packets are not shown here but can be clearly inferred from the description of the preceding figures).

[0120] According to a particularly preferred example, the polarity of the groups of trains is reversed every 120 s. Consequently, the first four trains of packets Tr1.sub.1, Tr1.sub.2, Tr1.sub.3 and Tr1.sub.4 have the same waveform and the second four trains of packets Tr2.sub.1, Tr2.sub.2, Tr2.sub.3, Tr2.sub.4 have the same waveform as the first group of packets, but with reversed polarity.

[0121] Note that within a given train of packets P11, P12, P13 and P14, the carrier signal frequencies fp11, fp12, fp13 and fp14 are the same, as is the case for fp21, fp22 and so on.

[0122] In various embodiments, the groups of trains TG are repeated for a certain duration that corresponds to the duration of treatment. For example, for typical applications, treatment duration is between 10 and 40 minutes, preferably 20 minutes.

[0123] It should be noted that the resonance frequencies are due to the repetition frequency of the packets, to the repetition frequency of the trains Tr and to the repetition frequency of the groups of trains T.sub.i where, as specified previously, each group of trains TG.sub.i comprises a plurality of trains of packets transmitted for a duration T.sub.tg_on followed by a pause Tt.sub.tg_off.

[0124] The length of the pauses (T.sub.tg_off) between groups of trains is preferably between 0.1 and 5 s inclusive.

[0125] See Table 1 below, as an example, in which burst frequency is used to indicate the frequency of the carrier signal fp:

TABLE-US-00001 TABLE 1 packet train Pause groups Program burst frequency frequency frequency of trains Base Hz Hz Hz Seconds 1 Varies 2.89 0.4 0.5 according to depth 2 Varies 3.98 0.5 0.5 according to depth 3 Varies 6.71 0.9 0.5 according to depth 4 Varies 8.71 1.1 0.5 according to depth 5 Varies 10.73 1.4 0.5 according to depth 6 Varies 13.07 1.6 0.5 according to depth 7 Varies 15.87 2.1 0.5 according to depth 8 Varies 21.85 2.8 0.5 according to depth 9 Varies 16.03 2.8 0.5 according to depth

[0126] More specifically, the device described is configured to generate a driving signal having a first depth frequency of the carrier signal 102 correlated with the depth of an organ to be treated and at least a second depth frequency correlated with the thickness of said organ.

[0127] FIG. 9a, on the other hand, defines the pulses, packets, trains and trains of trains in terms of signal, so as to define the actions performed by the innovative device 1. Specifically, carrier signal 201 defines the pulses, the aforesaid modulating signal 104 is further modulated as appropriate: in particular, a signal 104 modulates and groups the pulses into packets P, a modulating signal 104 modulates and groups the packets P into trains Tr, which can have the same or different pulse frequencies within a group of trains Tg and the signal 104 modulates and groups the groups of trains into groups of groups of trains and can reverse the polarity. The modulating signal shall always be labelled 104 and shall accordingly take on the characteristics described. The captions 104, 104, 104 and 104 shall only be used to define the various packets of signals (and/or of trains, etc.) in schematic form, as described in the figure. Note that said signals are emitted at the same time to cover, as mentioned, the emission of the full spectrum of resonance frequencies of the area to be treated, those frequencies being univocally defined by the device in accordance with specific tables taken from scientific data, to act exclusively on said area to be treated.

[0128] The inventors observed that with this wave generatorin itself generic and programmablevarious treatment programs can be created.

[0129] For example, the user can select the most suitable treatment program based on the organ to be treated.

[0130] First of all, the depth of action is selected, by choosing from the depths of action from A to Z set out in the table described above with reference to FIG. 6.

[0131] In a second step, the thickness of the organ to be treated is selected, where the thickness that can be selected ranges from a minimum of 0.5 cm to a maximum of 3 centimetres.

[0132] FIRST EXAMPLE

[0133] Let us suppose we want to treat a muscle at a depth of 2 cm, for a thickness of 3 cm. Consequently, the initial depth corresponds to the train Tr1=G.

[0134] The final depth corresponds to the train Tr4=N. The choice of resonance frequency varies according to the type of tissue to be treated.

[0135] Furthermore, the software of the device is configured to complete the intermediate trains with the intermediate depths, i.e. (Tr2=J)+(Tr3=L).

[0136] The final train of packets will therefore be TG=(G+J+L+N).

[0137] The packets forming a train always have the same carrier frequency fp.

SECOND EXAMPLE

[0138] Let us suppose we want to treat a bone at a depth of 5 cm for a thickness of 1 cm. Consequently, the initial depth corresponds to the train N. The final depth corresponds to the train P.

[0139] The software controlling the device is configured to complete the intermediate trains with the intermediate depths, i.e. O.

[0140] However, given that there are 4 trains, in that case the software will always double the deepest frequency.

[0141] The final train will therefore be N+O+P+P.

[0142] Essentially, the pulses IM are grouped into at least four packets p11-p12-p13-p14 with the same pulse frequency (fp11-f.sub.p12-f.sub.p13-f.sub.p14) to form a train TR1 where the repetition frequency of the packets is correlated with the area to be treated and in this case corresponds to the highest and/or maximum frequency, which is between 2 Hz and 25.9 Hz inclusive (Table 1), while the second train TR2 has the same packet repetition frequency but the pulse frequency for all the packets of TR2 can be equal to tr1 or different and corresponding to the second depth frequency, and so on for T3 and TR4.

[0143] In general, the trains are grouped into groups of at least four trains, where the repetition frequency of the trains corresponds to the second resonance frequency, which is between 0.4 and 2.8 Hz inclusive. The repetition frequency of the groups of trains occurs with a variable pause which in this case lasts 0.5 seconds. Each group of trains therefore comprises a plurality of trains of packets followed by a pause, where the length of the pause is correlated to the precise area to be treated.

[0144] The length of the pauses between groups of trains is preferably between 0.1 and 5 s inclusive.

[0145] FIG. 10 shows a handpiece 200 for a device for resonance intracellular transport, according to an aspect of the invention, where said handpiece is provided with a cover 230 and a bottom part 240 as well as with a solenoid 280. Moreover, the first electrode 20 of the device comprises an ultrasound acoustic generator 210, wherein said acoustic generator 210 is driven by means said driving signal and supported by the handpiece 200 itself.

[0146] The ultrasounds can be generated by means of a piezoelectric transducer with the following characteristics: [0147] Oscillation frequency between 20 and 40 kHz, preferably 20-25 kHz. [0148] Power supply voltage 12-24 V [0149] Maximum current supply 400-200 mA [0150] Power 2.5-3.5 W/cm.sup.2

[0151] The first electrode 20 of the device may additionally comprise a magnetic transducer, wherein said magnetic transducer is driven by means of said driving signal.

[0152] By magnetic transducer, we mean a solenoid 280 placed inside the handpiece 200, with the following characteristics. [0153] Diameter of the cable 0.35 mm Self-sealing [0154] Solenoid diameter 8 cm [0155] Solenoid thickness 3 mm [0156] Coil 50 [0157] Resistance 25 Ohm

[0158] Said solenoid 280 is driven with the same frequencies emitted for resonance. [0159] Power supply voltage, for example 5 V [0160] Current supply, for example max. 100 mA

[0161] Solenoid 280 is ring-shaped and built into the handpiece 200, generating a magnetic field all around in a coherent way.

[0162] The handpiece 200 comprises an electrification chamber 205 entirely made of a metal material to contain an active principle to be administered.

[0163] The active principle contained in the electrification (or ionisation) chamber 205 of handpiece 200 is dissolved in agarose-based gel as well as potentially in another carrier, too.

[0164] In this design, a saccharine glycoside gel is used, unlike in the case of classic transdermal transport solutions, where the gel is required to be saline.

[0165] Said solution is crucial for transporting substances for cosmetic and pharmacological use, or in general chemical substances, taking advantage of the fact that the cells prefer feeding on sugar, so in the days following application, the treated cells continue feeding, thus obtaining a long-lasting result.

[0166] For non-ionisable or heavy substances, on the other hand, (such as chemo) a further agarose-based carrier is added to break down the barrier of the stratum corneum to allow those substances to be transported.

[0167] Furthermore, the handpiece 200 comprises a roller 220 provided with knurling or grooves suitable to create microchannels in the stratum corneum of the epidermis.

[0168] The microchannels enable the gel to come into direct contact with the dermis by passing through the stratum corneum, thus cancelling out any resistance.

[0169] The handpiece 200 also comprises a dispenser 250 provided with a plane surface from which the roller 220 protrudes.

[0170] The plane surface of the dispenser 250 has an area of at least 5 cm.sup.2.

[0171] An advantage of this vast plane surface is that it also makes it possible to act in the corner of the handpiece, thus increasing the area of effectiveness of the handpiece.

[0172] It should be noted that, thanks to the invention, part of the product is metabolised immediately thanks to the opening of the cell receptors as a result of the effect of resonance, while the other part of the product is left deposited in the mesenchyme as a nutritional reserve, for which reason the action will continue to be effective even up to 72 hours after.

[0173] Specifically, it is also possible to summarise the combined action of the device and handpiece as follows, by describing a working method: [0174] dissolving of substances to be transported in an aqueous gel, specifically, agarose gel; [0175] dispensing of the gel using the handpiece; [0176] transformation by a magnetic field produced by said solenoid to make the water clusters forming the agarose gel coherent with the currents delivered for electrophoresis and with the resonance frequencies of a tissue to be treated; [0177] gel deposition by gravity in the electromagnetic chamber; [0178] ionisation of the gel in said chamber; [0179] uptake of the gel by the roller, which turns and deposits it in the dermis; [0180] generation of mechanical action (by means of an ultrasound transducer present on the handpiece and driven by the device) to break the lipid bond of the corneocytes, thus preparing and promoting the creation of microchannels (micro tunneling) produced by the knurling and microneedles (size micron) present on the dispenser roller; [0181] transport (through resonance modulated currents by means of pulses/packets/trains/groups of trains/groups of groups of trains, according to said layout) of the compound molecules present in the agarose gel saturated with active principles linked molecularly as explained previously.

[0182] Thanks to these modulations, transport occurs via the water channel and not the ion channel. The method involves the sending of currents with multiple cellular resonance frequencies at the same time. We wish to emphasise that the known art does not provide for specific repetition and modulation frequencies and is also different in the composition of packets, where at least one of the packets within a train must have a different pulse frequency and the frequency of the packets and trains, just like their duration, is not related in a targeted way.

[0183] This method, associated with the direct use of the innovative device and handpiece, sends pulses with frequency correlated with depth (see table) (Fr=frequency; pr=depth formula Fr=(2000180)*Pr). [0184] The pulses are grouped into packets, with a minimum of 4 per train, with a repetition frequency correlated to the area to be treated (table 1 column 3) [0185] Each train is composed of 4 packets with the same pulse frequency and therefore the same depth of transfer. [0186] The trains are grouped into groups of trains, with a minimum of 4 per group of trains, and the trains repeat with a frequency correlated to the area to be treated (table 1 column 2)

[0187] Uniform transfer through the thickness is obtained thanks to the increased duration of the train with the same transfer depth frequency (pulse). [0188] transfer of the oppositely charged compound molecules by reversing the polarity of the currents by means of the signal generator.

[0189] We wish to emphasise that this method advantageously makes it possible to transfer 60 ml of agarose gel saturated in active principles with a weight of 75 g into the selected tissue in 15 minutes without dispersion in circulation and exclusively localised in the selected tissue. As noted, in the known art, 20 ml of saline gel not saturated with active principles is transferred in 1 hour and in the best case in 45 minutes, by the transdermal route, therefore making it also systemic, with dispersion in circulation.

[0190] To conclude, this invention demonstrates the use of resonance, which exploits cellular communication by means of electromagnetic waves, as informational energy that enters electromagnetic resonance with the tissues and cells, which, through the DNA and the membranes, are electromagnetic emitters. Being open systems, or rather conditioned by environmental and endogenous (mind-body) stimuli, living beings can easily depart from biological vibrational harmony. In such cases, it becomes necessary to provide tested frequencies for the individual systems, or rather frequencies used and tested for treatments as described above.

[0191] Of course, changes or improvements may be added to the invention as described herein, without going beyond the scope of the invention as claimed below for this reason.

BIBLIOGRAPHY FOR CELLULAR RESONANCE/ELECTROMAGNETIC FIELDS

[0192] 1. A. R. Liboff Cyclotron resonance in membrane transport in A. Chiabrera et al. (Eds.) Interactions between electromagnetic fields and cells, pp. 281-296, Plenum Press, 1985 [0193] 2. C. F. Blackman et al. A role for the magnetic field in the radiation-induced efflux of calcium ions from brain tissue in vitro, Bioelectromagnetics, 6, pp. 327-337, 1985 [0194] 3. Liboff A. R., Smith S. D., McLeod B. R., Experimental evidence for ion cyclotron resonance mediation of membrane transport in M. Blank, E.Findl (eds.) Mechanistic approaches to interactions of electromagnetic fields with living systems, New York and London: Plenum Press, pp. 109-132,1987 [0195] 4. Smith S. D., McLeod B. R., Liboff A. R., Cooksey K. E., Calcium cyclotron resonance and diatom mobility Bioelectromagnetics, 8, 1987 [0196] 5. Warnke, U. Some primal mechanisms concerning the effects of pulsatine magnetic fields in the extremely low frequency (ELF) range on human beings. Electromagnetic Bio-information ed. F. A. Popp, ed. Munchen: Urban e Schwarzenberg, 1990 [0197] 6. Grundler W., Kaiser F., Keilmann F., Walleczek J., Mechanisms of electromagnetic interaction with cellular systems Max Planck Institut, Stuttgart, 1991 [0198] 7. F. A. Popp, Recent advances in biophoton research and its applications, World Scientific, 1992. [0199] 8. Warnke U. Survey of some working mechanisms of pulsating electromagnetic fields (PEMF) Bioelectrochemistry and bioenergetics 27, 1992 [0200] 9. Blackman C. F., Blanchard J. P., Benane S. G., House D. E., Empirical test of an ion parametric resonance model for magnetic field interactions with PC-12 cells, Bioelectromagnetics 15:239-260, 1994 [0201] 10. Blanchard J. P., Blackman C. F., Clarification and application of an ion parametric resonance model for magnetic field interactions with biological systems, Bioelectromagnetics 15:217-238, 199 [0202] 11. G. Preparata QUED coherence in matter, World Scientific, 1995 [0203] 12. R. Arani, I. Bono, E. Del Giudice, G. Preparata in E. Sassaroli et al (Eds.) QED coherence and the thermodynamics of Water Intern. Journal of modern Physics B9, pp.1813-1841, 1995 [0204] 13. Jermann I., Berden M., Ruzic R. Biological influence of ultraweak supposedly EM radiation from organism mediated through water Electro- and magnetobiology, 15(3),229-44, 1996 [0205] 14. Blank M., Goodman R. Do electromagnetic fields interact directly with DNA? Bioelectromagnetics, 18:111 5, 1997 [0206] 15.Novikov, V. Karnaukov A. Mechanism of action of weak electromagnetic Field on ionic currents in aqueous solutions of amino acidsBioelectromagnetics, pp.18-25, 1997 [0207] 16. M. N. Zhadin et al. Combined action of static and alternating magnetic fields on ionic current in aqueous glutamic acid solution, Bioelectromagnetics, 19, pp. 41-45, 1998 [0208] 17.E. Del Giudice, Preparata in E. Sassaroli et al. Macroscopic Quantum Coherence, pp. 108-129 World Scientific, 1998 [0209] 18.E. Del Giudice, G. Preparata, M. Fleischmann QED coherence and electrolyte solutions Journal of Electroanalytical Chemistry, 2000 [0210] 19. M. Covelli ATTI XVI SNAMID National Conference, February 2003: Onde elettromagnetiche e informazione biofisica. Applicazioni della biorisonanza nelle malattie osteo artro degenerative (Sistema Vital Body System) [Electromagnetic waves and biophysical information. Applications of bioresonance in degenerative bone and joint diseases (Vital Body System)] [0211] 20.U. Greco, M. L. Roseghini, Department of Human Physiology and

[0212] Pharmacology Vittorio Espamer of The Sapienza University of Rome, I fenomeni di biorisonanza per un nuovo modello integrativo della diagnostica e terapia [Bioresonance phenomena for a new integrative diagnostics and treatment model] [0213] 21.A. Laffranchi, XVII SNAMID National Congress, 20-22 FEBRUARY 2004, Milan II recupero delle lesioni sub-acute e croniche conseguenti alla radioterapia nel malato oncologico: 11 anni di esperienza presso IIstituto Nazionale per lo Studio e la Cura dei Tumori di Milano [The recovery of sub-acute and chronic lesions resulting from radiotherapy in the cancer patient: 11 years of experience at the Milan-based National Institute for the Study and Treatment of Tumours] [0214] 22. Luc Montagnier, II DNA tra fisica e biologia onde elettromagnetiche dal DNA e acqua [DNA between physics and biology electromagnetic waves from DNA and water] Montagnier L., Aissa J., Ferris S., Montagnier J.-L., LavaHe C. Electromagnetic Signals Are Produced by Aqueous Nanostructures Derived from Bacterial DNA Sequences. Interdiscip Sci Comput Life Sci, 2009; 1:81-90. [0215] 23. Montagnier L., Aissa J., Lavallee C., Mbamy M., Varon J., Chenal H. Electromagnetic detection of HIV DNA in the blood of AIDS patients treated by antiretroviral therapy. Interdiscip Sci Comput Life Sci, 2009; 1: 245-253. [0216] 24. Del Giudice E., Tedeschi A. Water and the autocatalysis in living matter, 2009; Electromagnetic Biology and Medicine, 28, 46. [0217] 25. Nesterov. PHYSICAL BASICS OF INFORMATIONAL INTERACTION Dedicated to 85th anniversary of the Academician Svyatoslav Pavlovich Nesterov [0218] 26. Avramenko R .F., Nikolaeva V. I., Pushkin V. N. To the matter of informational interaction of isolated systems without power transfer. // Matters of psychohygiene, psychophysiology and labour sociology in coal industry and psychoenergetics Moscow, NTGO, 1980, pp. 341-357 [0219] 27. Akimov A. E. Quantum non-locality and torsion fields. (together with [0220] 28. Blinkov I. L. Structural-resonance (contact) and electromagnetic (contactless) simulation Theoretical and clinical aspects of bioresonance multiresonance therapy: theses of the 2n International Conference. Moscow [0221] 29. Gariaev P. P., Wave genetic code. Moscow, lzdatcenter, 1997. [0222] 30. Gariaev P. P., Genetic structures as source and receiver of holographic information. Together with I. V. Prangishvili, G. G. Tertinshny and others. //Sensors and systems, 2000. No. 2(11).p2-8. [0223] 31. Gotovsky Y. V., Mhitaryan K. N. Structural conception of disease and a role of external control loop in its treatment. // Theoretical and clinical aspects of bioresonance and multiresonance therapy: Theses of the 2.sup.nd International Conference. Moscow, Imedis, 1996. P. 79_94. [0224] 32. Davydov A. S. Solitons in bioenergetics. Kiev, Nauk, Dumka, 1986. Devyatkov N. D., Golant M. B., Betsky O. V. Millimeter waves and their role in processes of vital activity. Moscow, Radio and communication [0225] 33. Smith S. Electromagnetic bio-information and water. // Biophysical medi_cine bulletin, 1994. No 1. pp. 3-13. [0226] 34. Fralich G. Coherent excitations in biological systems. // Biophysics, 1977. Vol. 22. No. 4. P. 743_744Henzel [0227] 35. Cherkasov A. V. Magneto-optical influence on water-dependant structures of living organism. // Biophysical medicine bulletin, 1994. No.1. P. 49_52. [0228] 36. Chirkova E. N. Wave nature of regulation of genetic activity: living cell as photon computer. // Russian thought, 1992. No.2. P. 29_41. [0229] 37. Chuguevsky A. V., Fedorenko N. E. Electromagnetic solitons. Moscow, 1980, 80 pages. VINITI No.8280. [0230] 38. Bertalanffy L. Das biologische Weltbild. Bd I.Bem, 1949. [0231] 39. Frohlich H. Biological coherence and response to external stimuli. Berlin, Heiderberg, Sprinder, 1988 [0232] 40. Popp F. A. Electromagnetic Bio-information/Ed. FA. Popp et al. Urban and Schwarzenberg MunchenBaltimore, 1979. Smith C. W. Electromagnetic phenomena in living biomedical systems //Proc. 6_th. Am. Conf._1984._P. 176_180. Smith C. W., Choy R., Monroe J. A. Water, Friend or Foe?//Laboratory Practice. 1985. _Vol. 34._P. 29_34. [0233] 41. Lagendijk A., van Tiggelen B.A., Resonant Multiple Scattering of Light, Physics Reports, v.270, pp. 143-216, 1996.