ULTRASONIC AEROSOLIZATION PLATFORM FOR THE APPLICATION OF THERAPEUTIC SUBSTANCES TO BODY CAVITIES

Abstract

The present invention relates to an ultrasonic aerosolization platform that has a single access port (10) provided with a trocar (11) inserted into the surgical cavity through a single incision and provided with at least one internal channel (101) in which is positioned an ultrasonic aerosolizer (20) provided with a head (21) that houses a power piezoelectric transducer (214) and a resonating rod (22) that extends orthogonally from the head (21), provided with an internal channel (221) in communication with the internal channel (212) of the head (21) and a free end (222) with an atomization nozzle (30) with orifices (31); a high-frequency ultrasound generator (40) that provides an electrical signal to the power piezoelectric transducer (214), which converts said electrical signal into mechanical oscillations transmitted to the resonating rod (22) in the form of mechanical standing waves; and a processing unit (50) provided with an interface (60) for adjusting the excitation frequency of the transducer (214), adjusting the flow of the therapeutic substance, and adjusting the operating and actuation time of the electrode (not shown) arranged in the resonating rod (22).

Claims

1. ULTRASONIC AEROSOLIZATION PLATFORM FOR THE APPLICATION OF THERAPEUTIC SUBSTANCES TO BODY CAVITIES that has a single access port (10) provided with a trocar (11) inserted into the surgical cavity by means of a single incision and provided with at least one internal channel (101) that extends between the proximal and distal ends, wherein in said proximal end a quick connector is arranged for the coupling of a seal having at least one orifice for positioning the instruments in the internal channel (101), a valve having a first route for inflation of carbon dioxide (CO2) in the proximal end of the trocar (11) and, optionally, a second route for the carbon dioxide exhaust, characterized in that it has: a) an ultrasonic aerosolizer (20) positioned on the internal channel (101) of the single access port (10) provided with a head (21) that houses a power piezoelectric transducer (214), a valve (211) which connects with the internal channel (212) arranged on the head (21) and connectors (213) for coupling the power cable of the high-frequency ultrasound generator (40); and a resonating rod (22) which projects orthogonally from the head (21) provided with an internal channel (221) in communication with the internal channel (212) of the head (21) and free end (222) having an atomizing nozzle (30) with orifices (31); b) a high-frequency ultrasound generator (40) that provides an electrical signal to the power piezoelectric transducer (214) that converts said electrical signal into mechanical oscillations transmitted to the resonating rod (22) in the form of mechanical standing waves; c) a processing unit (50) provided with a computer program and a database with a set of instructions, said processing unit (50) provided with an interface (60) for adjusting the excitation frequency of the transducer (214), adjusting the flow of the therapeutic substance by means of the activation of the peristaltic pump (not shown) installed in the feeding line of the therapeutic substance to the aerosolizer (20), adjusting the operation and actuation time of the electrode (not shown) arranged in the resonating rod (22).

2. ULTRASONIC AEROSOLIZATION PLATFORM FOR THE APPLICATION OF THERAPEUTIC SUBSTANCES TO BODY CAVITIES, according to claim 1, characterized in that the nozzle (30) is fixed or interchangeable at the free end (222) of the resonating rod (22).

3. ULTRASONIC AEROSOLIZATION PLATFORM FOR THE APPLICATION OF THERAPEUTIC SUBSTANCES TO BODY CAVITIES, according to claim 1, characterized in that the electrode (not shown) issues an electron current that collides with the aerosolized therapeutic substance in the internal channel (221) of the resonating rod (22).

4. ULTRASONIC AEROSOLIZATION PLATFORM FOR THE APPLICATION OF THERAPEUTIC SUBSTANCES TO BODY CAVITIES, according to claim 1, characterized in that it has a temperature sensor (not shown) installed on the resonating rod (22) or on the access port (10) which sends data to the processing unit (50).

5. ULTRASONIC AEROSOLIZATION PLATFORM FOR THE APPLICATION OF THERAPEUTIC SUBSTANCES TO BODY CAVITIES, according to claim 1, characterized in that it has a pressure sensor (not shown) arranged in the trocar (11) of the access port (10) which sends data to the processing unit (50).

Description

BRIEF DESCRIPTION OF THE FIGURES

[0023] FIG. 1 presents a representation of the ultrasonic aerosolization platform for the application of therapeutic substances to body cavities.

[0024] FIG. 2 presents a schematic diagram of the ultrasonic aerosolization platform for the application of therapeutic substances to body cavities.

[0025] FIG. 3 presents a cross-sectional view showing the single access port positioned in the body cavity.

[0026] FIG. 4A presents a perspective view showing the intracavitary single access port with the ultrasonic aerosolizer coupled and FIG. 4B presents a cross-sectional view.

[0027] FIGS. 5A and 5B present details of the nozzle coupled to the ultrasonic aerosolizer.

[0028] FIG. 6A presents a representation of the ultrasonic aerosolizer and FIG. 6B presents details of the piezoelectric transducer arranged on the head of the aerosolizer.

[0029] FIG. 7A presents a representation of the unidirectional nozzle, and FIG. 7B presents a representation of the multidirectional nozzle, wherein a is the outlet angle of the therapeutic mist.

[0030] FIG. 8 presents the graph of the relation of the particle size according to the frequency.

DETAILED DESCRIPTION OF THE INVENTION

[0031] In the context of the present specification, the following expressions are conceptualized:

[0032] “therapeutic substance” comprises an active agent in liquid form, pharmaceutically acceptable for being administered to human beings selected among antibodies, chemotherapy, nanoparticulates, anti-adhesive, heat activated agents, among others.

[0033] “therapeutic mist” comprises an aerodispersoid constituted by liquid particles formed by mechanical rupture of a liquid and may also be denominated in the context of the present invention as being an aerosolized therapeutic substance.

[0034] The ultrasonic aerosolization platform for the application of therapeutic substances to body cavities, object of the present patent application, comprises a single access port (10) that allows the introduction of an endoscopic instrument and the administration of the aerosolized therapeutic substance in intracavitary and/or intraperitoneal space and/or organs of human beings by means of an ultrasonic aerosolizer (20) interlinked to an electronic module that allows for modulating both the size of the droplet of the therapeutic mist as the temperature of the substance and the electrophysical characteristic of the particles, without the need for equipment for pressure injection or other equipment for changing the characteristics of the therapeutic particle.

[0035] The ultrasonic aerosolization platform for the application of therapeutic substances in body cavities, compared to the HINAT Technologies (Hyperthermic Intracavitary Nanoaerosol Therapy) and PIPAC-MIP is presented in Table 1 as follows.

TABLE-US-00001 TABLE 1 comparative of the parameters of the HINAT, PIPAC-MIP technologies and the platform object of the present invention. Platform object Parameter HINAT PIPA-MIP of the invention Number of components 2    2    1 Diameter of the 0.5  0.2  01-0.2 aerosolizer (mm) Particle size (μm) 0.7-20   0.7-110  13-43 Average particle 1   20   15 size (μm) Application speed of 210-500 1250-3000  1.8-450  the liquid (l/h) Pressure (Bar) 1.0-3.0 6.10-13.8 Not applicable Particle modularization no no yes Variable flow no no yes Heating of liquid no no yes Control of time of no no yes application (3-30 min.)

[0036] This single access port (10), described in document BR102012021227 and used in the multifunctional single port platform disclosed in document BR102018075741, basically comprises a trocar (11) inserted in the surgical cavity by means of a single incision, said trocar (11) having at least one internal channel (101) which extends between the distal and proximal ends, wherein in said proximal end a quick connector is provided for the coupling of a seal having at least one orifice for the positioning of the instrumentals in the internal channel (101) so that the active ends remain positioned in the body cavity (100). In the proximity of the proximal end of the trocar (11) a valve is foreseen with a first route for inflation of carbon dioxide (002) to form the pneumoperitoneum and, optionally, a second route for the carbon dioxide exhaust. Considering that the single access port has already been described in previous patents, the technical details related to said single access port (10) will be disregarded in this document, presenting solely the characteristics that are necessary for the sufficient description of the aerosolization platform invention, which is the object of the present invention.

[0037] In the internal channel (101) of the single access port (10) an ultrasonic aerosolizer (20) is positioned wherein the liquid therapeutic substance is decomposed into droplets, generating a therapeutic mist to be dissipated in body cavities (100) by means of a nozzle (30) positioned on the distal end of the internal channel (101) of the port (10) which is found in the body cavity.

[0038] The ultrasonic aerosolizer (20) basically comprises a structure having a head (21) from which a resonating rod (22) extends provided with an internal channel (221) which receives the liquid therapeutic substance by means of a valve (211) and, free end (222) wherein an atomization nozzle (30) is arranged provided with orifices (31) for forming the therapeutic mist in the body cavity (100).

[0039] The valve (211) has a quick connector or similar wherein a tube is coupled in order to allow the inlet of the liquid therapeutic substance.

[0040] In the head (21) connectors (213) are foreseen for coupling the high-frequency ultrasound generator (40) which provides energy to the aerosolizer (20).

[0041] The head (21) houses a power piezoelectric transducer (214) which electrical signal received from the high-frequency ultrasound generator (40) is converted into mechanical oscillations. As is known to a person skilled in the art, a piezoelectric transducer (214) is constituted by ceramics compressed by two metallic masses by means of a pre-tensioning screw which maintains said ceramics compressed. The ceramics are polarized longitudinally and the polarization directions are alternating for each ceramic in the assembly of the transducer and excited by two metallic electrodes, placed one on each one of the faces thereof. When an electrical signal is applied to this transducer (214) the field that is created causes corresponding deformations in the ceramic, making it vibrate strongly and thus generate sound waves in the corresponding frequency.

[0042] The high-frequency sound waves generated in the transducer (214) are transmitted to the resonating rod (22) in the form of mechanical standing waves, creating a type of nodes and anti-nodes, having a “whiplash” effect which increases the vibration amplitude. In this manner, the therapeutic substance in liquid form which enters through the valve (211) of the head (21) and crosses through the internal channel (212) of said head (21), when entering the internal channel (221) of the resonating rod (22) in the direction of the extreme portion (222) decomposes into uniform droplets of micrometric size, forming a therapeutic mist to be released by the orifices (31) of the nozzle (30) to be dissipated in the body cavity (100) by means of cavitation.

[0043] The nozzle (30) arranged in the free end (222) of the resonating rod (22) can be fixed or interchangeable, allowing to adapt nozzles (30) of several shapes that allows modifying the shape, the outlet volume and/or the aerosolized particle size to be dissipated by the orifices (31), to direct the therapeutic mist generated in the direction of the base and the walls of the body cavity (100), as described by Dobre & Bolle (Dobre, M. and Bolle L. Practical design of ultrasonic spray devices: experimental testing of several atomizer geometries. Experimental Thermal and Fluid Science. Elsevier, 2002).

[0044] The high-frequency ultrasound generator (40) that provides energy to the power piezoelectric transducer (214), is interlinked to a processing unit (50) provided with a computer program and a database with a set of instructions, said processing unit (50) which identifies the natural frequency of the transducer (214) and stimulates it in the previously adjusted working frequency, to obtain the maximum energetic efficiency, allowing the modulation of the size of the particle of the therapeutic mist by means of the adjustment of the excitation frequency of the transducer (214) as will be described next.

[0045] By means of an interface (60), the operator adjusts the parameters of the processing unit (50) to control, for example, the flow of the therapeutic liquid substance in the ultrasonic aerosolizer (20) by means of intervention at the speed of the peristaltic pump (not shown) installed in the feeding line of the therapeutic substance to the aerosolizer (20), providing continuous and/or pulsed infusion, as well as adjusting the delivery/dissipation time of the aerosolized substance in the body cavity (100).

[0046] For the electric charging to the particles of therapeutic mist, there is foreseen an electrode (not shown) on the resonating rod (22) which issues an electron current which collides with the aerosolized therapeutical substance promoting the electric charging of the particles. A positively charged blanket is provided on the body surface of the patient which electrostatically attracts the particles to the surface of the body cavity in treatment, guaranteeing the adhesion and the depth, said electrode being fed by means of the supply of energy from the high-frequency ultrasound generator (40).

[0047] For the distance actuation of the high-frequency ultrasound generator (40), a remote control is foreseen.

[0048] The mechanical waves that propagate on the resonating rod (22) generate heat (caused by the interaction between the incident wave and the reflected wave) which can be used to provide the heating of the therapeutic substance which dislocates in the internal channel (221) of the resonating rod (22). Thus, the flow of the therapeutic substance can be adjusted on the peristaltic pump (not shown) of the ultrasound generator (40) flows in the order of 1.8 l/h to 450 l/h being obtained, obtaining a temperature between 25° C. to 50° C. Additionally, the temperature is intrinsically connected to the size of the particle [Avvaru, B. et all. Ultrasonic atomization: Effect of liquid phase properties. Ultrasonics 44 146-158. Elsevier, 2006].

[0049] The average particle size of the therapeutic mist is obtained by means of Equation 1, based on LANG (Lang, R. J., Ultrasonic atomization of liquids, J. Acoust. Soc. Am., Vol. 34, No. 1, 1962, pp. 6-8).

[00001]$\begin{array}{cc}{D}_g=0.34\times l{0}^6\times {\left(\frac{8\times \pi \times \gamma }{\rho \times f^2}\right)}^{1/3}& \mathrm{Equation}1\end{array}$

[0050] Where:

[0051] Dg=average diameter of the particle/drop (μ)

[0052] Y=surface tension of the liquid (N/m)

[0053] ρ=density of the liquid at 20° C. (kg/m3)

[0054] f=excitation ultrasound frequency (Hz)

[0055] According to the increase of the excitation frequency of the transducer (214), the size of the particle diminishes, in other words, the average particle size of the aerosolized mist is inversely proportional to the frequency. In the working frequency from 30 KHz to 100 KHz, the particle diameter can be at least 13 microns and at most 43 microns, as evidenced in FIG. 8.

[0056] Optionally, on the resonating rod (22) or on the port (10) at least one temperature sensor is arranged (not shown) which sends signals to the processing unit (50) to control the temperature in the body cavity (100), indicating, by means of an alarm, reaching a distinct temperature from the one previously parametrized.

[0057] Optionally, in the port (10) at least one pressure sensor is arranged (not shown) which sends signals to the processing unit (50) to control the pressure in the body cavity (100).

[0058] Optionally, the ultrasonic aerosolizer (20) is positioned in video-surgery sheaths having from 10 to 12 mm diameter, the use of the single access port (10) being dispensed with.

[0059] The processing unit (50) can be coupled to the ultrasound generator (40), providing a single structure.