Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
  • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
  • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
  • A61M5/16831—Monitoring, detecting, signalling or eliminating infusion flow anomalies
  • A61M5/16836—Monitoring, detecting, signalling or eliminating infusion flow anomalies by sensing tissue properties at the infusion site, e.g. for detecting infiltration
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
  • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
  • A61M5/142—Pressure infusion, e.g. using pumps
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/327—Applying electric currents by contact electrodes alternating or intermittent currents for enhancing the absorption properties of tissue, e.g. by electroporation

Definitions

• the present invention refers to equipment for applying drugs in living tissues performed simultaneously with the electroporation of tissues during an electrochemotherapy procedure, the equipment comprising a drug applicator and electroporation device. Furthermore, the present invention refers to a method of preparing the applicator device for use and to a method of calculating and adjusting an electric current for electroporation.
• the procedure in question occurs such that the drug is injected at the site to be treated intratumorally or applied by systemic venous pathway, using a hypodermic syringe, before, during or after electroporation.
• the electrical pulses required for electroporation are calibrated in a console, manually, and applied to all tissues, whether of different electrical resistances or not, thus receiving the same energy load.
• there is a reduction in the effectiveness of the drug requiring higher injection volumes, requiring a measurement of the tumor and calculation of its volume in order to calculate the volume of drug to be injected.
• document PI0312459-2 presents a device for injection of substances into tissues and for application by electroporation, that is, the procedure of introducing substances into cells during or after the application of an electric field.
• the device disclosed in document PI0312459-2 comprises means for applying an electrical voltage to a needle, allowing the needle to be used not only for drug injection, but also as an electrode during electroporation, the electric field being applied in the same area as the injected substance. In this sense, both the volume of injected substance and the size of the electric field can be reduced, while a satisfactory adjustment between the electric field and the substance is achieved.
• the device of document PI0312459-2 describes the possibility of injecting a drug during the application of an electric field, it is observed that the device in question is not able to make any distinction with respect to the intensity of the electrical pulses applied in each region of the treated area, and there may therefore be an overload on more conductive tissues, injuring them, or subdose in more resistive tumor tissues, to the extent that the treatment is not able to achieve the expected result.
• One of the objectives of the present invention is to provide effective equipment for injecting drugs simultaneously with electroporation that is capable of measuring the electrical impedance of living tissues, specifically at the application site of the drugs, promoting the calculation and adjustment of an electric current necessary for the application of electrical pulses, besides providing an ideal amount of drug homogeneously and limiting a treatment area, reducing the volume of injected drug while allowing maximum efficiency of the electrochemotherapy procedure.
• a further objective of the present invention is to obtain equipment for injection of drugs simultaneously with the electroporation that is formed, among other parts, by a portable applicator device equipped with an infusion pump system, inserted inside the applicator device, enabling the injection of the drug simultaneously to the application of the electrical pulses, which are produced and controlled by a pulse generation module associated with the infusion pump system provided in the applicator device.
• An additional objective of the present invention is to provide a method for calculating and adjusting an electric current necessary to achieve an ideal electrical voltage for electroporation of living tissue, whereby achieving an ideal electrical charge according to the electrical impedance of the tissue.
• an objective of the present invention is to provide a method of preparing the applicator device that ensures the correct assembly of all the components necessary for applying drugs simultaneously to electroporation and identifies the assembly and removal of disposable parts, with a view to ensuring total protection of both the technician in charge and the patient.
• the present invention is designed to apply drugs or other substances in specifically designated areas, by electroporation of cells either for medical or aesthetic or veterinary use aiming to reduce the risk of contamination of the hospital environment by chemotherapy drugs, since it reduces the volume of drug needed for treatment, reducing the chances of systemic adverse effects and allowing the electrochemotherapy procedure to be performed in a laboratory environment.
• the objectives of the present invention are achieved by equipment for applying drugs simultaneous to the electroporation formed by a first generator module, calibrator and electric pulse trigger and a second gauge module of electrical resistance of living tissues in real time and applicator of drugs and electrical pulses, the first module comprising: i) a generator of electrical pulses; ii) a voltage calibrator module; and iii) a triggering device, and the second module comprising an applicator device.
• a drug applicator and electroporation device formed by at least two parts, a first part that comprises triggering components and controllers and a second part that comprises actuator and applicator components, the first part corresponding to a sealed part of the applicator device, which consists of at least one controller component and at least one pump system, and the second part corresponding to the part in which a syringe containing the drug to be applied to the patient is inserted, the second part consisting of a first base portion and a second cap portion, the first base portion having support points and movement of the syringe, containing a first flange for fastening and moving a syringe plunger and a second flange for fastening a syringe body, the second flange being able to move linearly towards the first flange, the first flange and the second flange each having a position sensor, wherein at the end of the first base portion a support wedge is
• a method of preparing a drug applicator and electroporation device comprising the steps of: i) opening a second cap portion of the applicator device; ii) fitting a syringe, containing drug and equipped with an injection needle, in a first base portion of the applicator device; iii) fitting an electroporation applicator tip, provided with at least one electroporation needle, on the injection needle; iv) establishment of electrical contact between the electroporation applicator tip and electrical terminals provided at one end of the first base portion of the applicator device; v) closing the second cap portion of the applicator device.
• a method of calculating and adjusting an electric current for electroporation comprising the steps of: a) activation of a trigger device that activates an electric pulse generator; b) emission of at least one previously calibrated electrical pulse, by means of the electric pulse generator, up to at least one electroporation needle provided in a drug applicator and electroporation device inserted in a region of a living tissue; c) real-time gauging of electric current propagated by living tissue by means of the applicator device; d) real-time calculation of electrical resistance of living tissue by the generator of electrical pulses, specifically in the insertion region of the applicator device; e) real-time adjustment of the electric current provided by the electric pulse generator by means of a calibrator module.
• Figure 1 - a schematic representation of the equipment for applying drugs simultaneously with the electroporation of the present invention
• Figure 2 - a first perspective view of the applicator device of the present invention in a closed position
• Figure 3 - a second perspective view of the applicator device of the present invention in an open position
• Figure 4 - a third perspective view of the applicator device of the present invention showing its internal components and the fitting of a syringe in a first position of the syringe plunger;
• Figure 5 - a fourth perspective view of the applicator device of the present invention showing its internal components and the fitting of a syringe in a second position of the syringe plunger;
• Figure 6 - a front perspective view of the tip of the applicator device of the present invention showing the assembly of a syringe and an injection needle;
• Figure 7 - a top perspective view of the tip of the applicator device of the present invention showing the assembly of a syringe and an injection needle;
• Figure 8 - a front perspective view of the tip of the applicator device of the present invention showing the electrical terminals provided at the end of the first base portion of the applicator device.
• FIGs 1 to 8 illustrate an example of the execution of the object of the present invention.
• the equipment 1 for applying drugs simultaneously to the electroporation of the present invention is formed substantially by two electrically associated modules, being a first module 11 generator, calibrator and electric pulse trigger and a second gauge module 12 of electrical resistance of living tissues in real time and applicator of drugs and electrical pulses.
• the first module 11 comprises: i) an electrical pulse generator 111 ; (ii) a voltage calibrator module 112; and iii) a trigger device 113.
• the electrical pulse generator 11 1 provides high voltage pulses of at least 600 Volts per centimeter (V/cm), ranging from 600 V/cm to 1500 V/cm, that is, they range from 0.6 kilovolts per centimeter (kV/cm) to 1.5 kV/cm, in square, monopolar and bipolar waves, at pulses of 50 to 200 microseconds each.
• High voltage pulses are applied in sets of 4 pulses to 12 pulses, or in sets at 6 pulses at 10 pulses, or, more preferably, in sets of 8 pulses, with frequency ranging from 1 Hertz (Hz) to frequencies in the order of kHz (kHz), ranging from 3 kHz to 5 kHz.
• Hz Hertz
• kHz kHz
• the generator 111 comprises a set of built-in (not illustrated) batteries that act as an embedded, uninterrupted power source (nobreak), allowing the use of equipment 1 for a period of at least 30 minutes without power to the electricity grid. Additionally, the generator 111 comprises a capacitor bank (not illustrated) that are electrically charged, allowing electrical pulses not to suffer power decay during electrochemotherapy treatment procedure.
• the voltage calibrator module 112 performs the calibration of the electrical pulse generator 11 1 based on a measurement of electrical resistance of the living tissues of the site where the electrochemotherapy procedure will be performed. This measurement is performed by the second module 12. It is noteworthy here that the calibration performed by the calibrator module 112 occurs in real time, that is, concomitantly with the measurement of the electrical resistance of the living tissues. In other words, while generator 11 1 measures the electrical resistance of living tissues, the calibrator module 1 12 is activated by calibrating the voltage of the electrical pulse generator 111. Thus, generator 111 and calibrator module 112 operate simultaneously. It should be noted that generator 111 and calibrator module 1 12 are online, that is, they communicate directly with immediate transmission of data.
• the trigger device 113 triggers the calibrator module 112, as well as the second module 12, for calibration and measurement of the electrical resistance of living tissues.
• the trigger device 113 corresponds, preferably, but not necessarily, to a drive pedal, and can of course take other appropriate forms, such as a drive button, a drive lever, etc.
• the second module 12 is capable of gauging the electrical resistance of living tissues, the local application of drugs and the local application of electrical pulses.
• the second module 12 basically comprises an applicator device 121 that has internal and external components to perform all functions designed for the second module 12.
• the applicator device 121 has an oblong shape, similar to a pen or probe, which comprises two essential parts, a first part 122 comprising trigger and controller components and a second part 123 that comprises actuator and applicator components.
• the first part 122 corresponds to a sealed part of the applicator device 121 , that is, that cannot be accessed by the user, and essentially comprises a controller component 124 and a pump system 125, as illustrated in figures 4 and 5.
• the controller component 124 refers to an electronic circuit board that has customized software to control the pump system 125.
• the controller component 124 is driven by electrical energy from the electric pulse generator 1 11 , energy transmitted by means of electric cable 126 that makes the association between the electric pulse generator 11 1 and the applicator device 121 , as illustrated in Figure 1.
• the pump system 125 is formed by an infusion pump, driven by means of a set of gears and a stepper motor, responsible for the displacement of a syringe plunger 151 , housed inside the second part 123 of the applicator device 121.
• the second part 123 of the applicator device 121 refers to the part in which a syringe 15 containing the drug to be applied to the patient is inserted and the part in which an electroporation applicator tip is mounted, which is endowed with at least one electroporation needle (not illustrated).
• the second part 123 consists of a first base portion 127 and a second cap portion 128.
• the first base portion 127 comprises support and movement points of the syringe 15, such that it has a first flange 130 for fastening and moving a syringe plunger 151 and a second flange 131 for fastening a syringe body 152.
• the syringe 15 works by the movement of the syringe plunger 151 inside the syringe body 152 to push the drug contained in the syringe body 152 out of syringe 15 and into the patient's living tissues.
• the first flange 130 moves linearly toward the second flange 131 to push the syringe plunger 151 into the syringe body 152.
• the linear movement of the second flange 131 in relation to the first flange 130 is performed by means of a movement spindle 132 and kept stable by means of a stability guide 133, which physically associates the first and second flange 130, 131.
• the monitoring of linear movement between the second flange 131 in relation to the first flange 130 is carried out by means of at least one pair of sensors S1 , S2, with the first flange 130 containing a first sensor S1 and the second flange 131 containing a second S2 sensor, both sensors S1 , S2 provided in a lower region of the first and second flange 130, 131 , when the applicator device 121 is observed in a top perspective view.
• Syringe 15 refers to a hypodermic syringe, usual market, with capacity for five milliliters, single use, sterile and apyrogenic.
• an injection needle 154 is associated, threaded to the tip of the syringe 15.
• the injection needle 154 refers to a hypodermic needle, usual market, single use, 0.8 mm thick and 25 mm long. Of course, other injection needles can be used, with other thicknesses and lengths, according to each need.
• the use of the applicator device 121 is not limited in any way to the type of injection needle 154 used.
• the injection needle 154 is mounted to the tip of the syringe 15 still capped, to be subsequently uncapped for aspiration of the drug into the syringe 15.
• injection needle 154 is mounted on the tip of syringe 15 and the drug has been aspirated into the syringe body 152, syringe 15 is fitted to the first base portion 127 of the second part 123 of the applicator device 121 and then an electroporation applicator tip (not illustrated) is mounted on the injection needle 154.
• a support wedge 129 At the end of the first base portion 127 of the applicator device 121 is a support wedge 129, which provides the necessary support to keep the injection needle 154 positioned correctly throughout the application procedure of the drug.
• T1 , T2 electrical terminals are provided, which are set inside the support wedge 129 and are electrically associated with the controller component 124 and pump system 125 provided in the first part 122 of the applicator device 121.
• the first module 11 should be connected to an electrical power supply network, either at a voltage of 110 V or 220 V or automatic bivolt.
• a standard power button provided in the first module 11 .
• the electric pulse generator 111 runs, automatically, that is, without the activation of a second button, a test of its functions, according to desired parameters and that are factory programmed. Being apt, the generator 111 evaluates the need for recharging and, if necessary, performs a recharge of its batteries and, simultaneously, electrically charges its capacitor banks. That is, the recharging of the batteries occurs at the same time that the capacitor banks are charged.
• the test sequence of functions, recharging of batteries and charging of capacitor banks lasts, on average, a period of two minutes.
• a keyboard (not illustrated) provided in the first module 1 1.
• a customized keyboard is used, made of polycarbonate. It should be noted, however, that any other means for data input can be used, so the use of the equipment 1 of the present invention is not limited to the component by which data are input from the treatment of electrochemotherapy.
• the method of preparing the applicator device 121 comprising the steps of:
• step v) of closing the second cap portion 128 of applicator device [0049] After step v) of closing the second cap portion 128 of the applicator device 121 , the applicator device 121 is ready for use. Then, the electric cable 126, coming from the electric pulse generator 11 1 , is associated with the applicator device 121 , enabling the transmission of the electrical energy required to drive its controller component 124.
• the electrochemotherapy treatment procedure is initiated by inserting the applicator 121 into the patient's tissue and activating the triggering device 113.
• the electrical pulse generator 111 previously charged, emits a single electric pulse, pre-calibrated and with known parameters, to the electroporation application tip endowed with at least one electroporation needle (not illustrated), enabling the electrical pulse generator 111 to calculate the electrical impedance of the tissue, specifically at the application site of the at least one electroporation needle.
• the term electrical impedance of living tissue In the study of physics, the term electrical resistance refers to the characteristic of a material to oppose an electric current that is established between a potential difference.
• capacitance refers to the characteristic of a material to store electricity, which occurs, for example, in the cells of the organism.
• the calculated characteristic for living tissue refers to electrical impedance, which relates electrical resistance to capacitance.
• the calculated electrical resistance is 100 ohms. This calculation must necessarily be done at each point of application, because, as it is a living tissue, the electrical resistance varies significantly from one point to the other.
• the calibrator module 112 promotes an automatic adjustment so that the electric current is adequate to the electrical voltage parameter required for electroporation. For example, if the application of an electrical voltage of 1000 Volts is required, which is suitable for electroporation, and it is calculated, as described above, that the electrical resistance is 100 ohms, then the equipment 1 must be supplied with an electric current of 10 Amps. It should be noted that electrical resistance is a characteristic of living tissue at the application site and therefore cannot be controlled by the operator of the equipment 1.
• the stepper motor provided in the first part 22 of the applicator device 121 is activated, initiating the movement of the first flange 130, which, in turn, acts by pushing the syringe plunger 151 , resulting in the injection of the desired drug volume, calibrated at the origin.
• the volume of the drug is fixed for each application point, regardless of the electrical impedance of the living tissue that will receive it. This calibration of the drug volume is done in the factory, and it is up to the operator to adjust whether or not the drug will be applied at the site, considering that there is the option of intravenous application. However, when injected concomitantly, the volume is preset as factory standard.
• a sequence of electrical pulses is triggered, at a frequency ranging from 3 kHz to 5 kHz, for the at least one electroporation needle provided at the electroporation applicator tip.
• the applicator device 121 is removed from the patient's tissue and applied to a new treatment site. The entire sequence of procedures, from the insertion of the applicator device 121 , is repeated for each new treatment site.
• the trigger device 113 is triggered at each new application point. The time to be spent at each point of application should vary and cannot therefore be foreseen by the operator. Thus, for each new patient treatment site, the trigger device 113 is activated, initiating a new calibration cycle of the first module 11.
• the first module 11 can issue a report stating the identification of the clinic, patient and physician, as well as the date, start and end time of the treatment session, in addition to the total volume of drug used.
• the report can be generated in a digital file and made available for both printing and internet transmission.
• the information for each treatment session is stored in an internal memory device.
• the first module 11 is turned off, making the applicator device 121 devoid of electrical power, whereby enabling the safe handling of the applicator device 121.
• the second cap portion 128 is opened and syringe 15 is removed from the applicator device 121 , along with the injection needle 154 and the electroporation applicator tip, which are discarded after each treatment session. Said materials are collected in usual market cutting material collector devices.
• the method of preparing the equipment 1 of the present invention comprises the steps of:
• the equipment 1 of the present invention is highly effective, promoting the injection of drugs simultaneous to electroporation, such that it enables the application parameters of the electrical pulses of electroporation to be calculated and adjusted according to the electrical resistance of the tissue to which the treatment is applied, while providing an ideal amount of drug homogeneously, reducing the volume of injected drug and achieving maximum electroporation efficiency.
• the present invention presents portable equipment 1 , easy and safe to handle, and that is capable of reducing the volume of drug needed for treatment, reducing the chances of systemic adverse effects and enabling the electrochemotherapy procedure to be performed in a laboratory environment.

Landscapes

• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Biomedical Technology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Anesthesiology (AREA)
• Hematology (AREA)
• Heart & Thoracic Surgery (AREA)
• Vascular Medicine (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Radiology & Medical Imaging (AREA)
• Biophysics (AREA)
• Infusion, Injection, And Reservoir Apparatuses (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=72178309

Family Applications (1)

Country Status (2)

Citations (2)

• 2019
  • 2019-06-28 BR BR102019013577-8A patent/BR102019013577A2/pt unknown
• 2020
  • 2020-05-15 WO PCT/BR2020/050165 patent/WO2020257895A1/en active Application Filing

Patent Citations (2)

Also Published As

Similar Documents

Legal Events