ELECTRICAL AND HYDRAULIC GENERATOR (EH) OF FAST PULSE SHOCK WAVES AND METHOD

专利摘要:
abstract "rapid pulse shock wave electrohydraulic generator (eh) and methods for medical and cosmetic treatments" the present invention relates to devices and methods for the electrohydraulic generation of shock waves at a rate between 10 Hz and 5 MHz, and / or that allow a user to view a region of a patient comprising target cells during the application of shock waves generated to the region. and the invention also relates to methods of applying electro-hydraulic shock waves generated to target tissues (for example, to reduce the appearance of tattoos, treatment or reduction of certain conditions and / or diseases).
公开号:BR112015021939A2
申请号:R112015021939
申请日:2014-03-07
公开日:2020-02-27
发明作者:C Capelli Christopher；Crowley Robert
申请人:Univ Texas；Soliton Inc；
IPC主号:

专利说明:

ELECTRO-HYDRAULIC GENERATOR SYSTEM (EH) FOR QUICK PULSE SHOCK WAVES AND METHOD
CROSS REFERENCE TO RELATED APPLICATION [001] This application claims priority for US Patent Application No. 13 / 798,710, filed on March 13, 2013 and for US Provisional Patent Application No. 61 / 775,232, filed on March 8 2013. The contents of the orders mentioned above are incorporated into this specification by reference.
FIELD OF TECHNIQUE [002] The present invention relates generally to therapeutic uses for shock waves. More particularly, but not by way of limitation, the present invention relates to an apparatus for generating therapeutic shock waves or shock waves (shock waves with therapeutic uses).
BACKGROUND OF THE INVENTION [003] Acoustic shock waves have been used for certain therapies for several years. The "shock wave" is generally used to refer to an acoustic phenomenon (for example, resulting from an explosion or lightning) that creates a sudden and intense change in pressure. These intense pressure changes can produce strong waves of energy that can travel through elastic media such as air, water, human soft tissue, or certain solid substances such as bones, and / or can induce an inelastic response in such media. rubber bands. Methods for creating shock waves for therapeutic uses include: (1) electrohydraulic, or spark gap (EH); (2) electromagnetic, or EMSE; and (3) piezoelectric. Each is based on its own unique physical principles.
A. Shock wave generation devices and systems [004] U.S. Patent Application No. 13 / 574,228 (a national phase application of PCT / US2011 / 021692, which is published as WO 2011/091020), by one of
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2/73 present inventors, describes a device for producing shock waves at a high pulse rate using a transducer. This device includes an acoustic wave generator configured to emit acoustic waves with at least a frequency between 1 MHz and 1000 MHz; a shock wave housing coupled to the acoustic wave generator; and a shock wave means arranged in the shock wave housing; where the device is configured so that if the acoustic wave generator emits acoustic waves, then at least part of the acoustic waves will travel through the shock wave medium and form shock waves. This device can be triggered to form shock waves configured to cause particles within a patient to rupture one or more of the patient's cells, and the shock waves can be directed at a patient's cells so that the waves shock cells cause the particles to rupture one or more of the cells. This acoustic-transducer device can produce highly energized shock waves at high frequencies or pulse rates.
[005] Other systems for producing shock waves may include an electro-hydraulic wave generator (EH). EH systems can generally deliver energy levels similar to those of other methods, but they can be configured to deliver that energy over a wider area, and thus deliver a greater amount of shock wave energy to the target tissue over time. a shorter period of time. EH systems generally incorporate an electrode (ie, a spark plug) to initiate a shock wave. In EH systems, high energy shock waves are generated when electricity is applied to an electrode immersed in treated water contained in an enclosure. When the electric charge is triggered, a small amount of water is vaporized at the tip of the electrode and the rapid, almost instantaneous, expansion of the vaporized water creates a shock wave that spreads out through the liquid water. In some
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3/73 modalities, the water is contained in an ellipsoid casing. In these modalities, the shock wave can bounce off the sides of the ellipsoid shell and converge at a focal point that coincides with the location of the area to be treated.
[006] For example, U.S. Patent No. 7,189,209 (the '209 Patent) describes a method for treating pathological conditions associated with bone and musculoskeletal environments and soft tissues through the application of acoustic shock waves. The '209 patent describes that shock waves induce localized trauma and cell apoptosis, including microfractures, as well as inducing osteoblastic responses such as cell recruitment, stimulating the formation of molecular bone, cartilage, tendon, fascia and soft tissue morphogenesis and factors of growth, and to induce vascular neoangiogenesis. The ‘209 patent claims several specific implementations of its method. For example, the '209 patent claims a method for treating a diabetic foot ulcer or bed sores, which comprises: locating a suspicious site or site of the diabetic foot ulcer or bed sores in a human patient; generate acoustic shock waves; focus on acoustic shock waves throughout the localized site; and applying more than 500 to approximately 2500 acoustic shock waves per treatment to the localized site to induce microlesion and increased vascularity thereby inducing or accelerating healing. The '209 patent describes a frequency range of approximately 0.5-4 Hz, and the application of approximately 300 to 2500 or approximately 500 to 8,000 acoustic shock waves per treatment site, which can result in a treatment duration for each treatment site and / or a “total time per treatment” for all sites which is inconveniently large. For example, the '209 patent describes the total times per treatment for different examples in the range of 20 minutes to 3 hours.
[007] U.S. Patent No. 5,529,572 (the '572 Patent) includes another example of using electro-hydraulic generated shock waves to produce the effect
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4/73 therapeutic in tissues. The '572 patent describes a method for increasing bone density and strength (to treat osteoporosis), which comprises subjecting said bone to substantially flat collimated compression shock waves having substantially constant intensity as a function of distance from a source of shock wave, and where said collimated shock waves are applied to the bone in an intensity of 50 to 500 atmospheres. The '572 patent describes the application of unfocused shock waves to produce dynamic repetitive loading of bone to increase mean bone density, and thus reinforce bone against fracture. As described in the '572 patent, “the unfocused shock waves are preferably applied over a relatively large surface of the bone to be treated, for example, to cover an area of 10 to 150 cm ² . The intensity of the shock waves can be 50 to 500 atmospheres. Each shock wave has a duration of a few microseconds, as in a conventional lithotripter, and is preferably applied at a frequency of 1-10 shock waves per second for a period of 5 to 30 minutes, in each treatment. The number of treatments depends on the patient in particular ”.
[008] US Patent Application No. 10 / 415,293 (Application '293), which is also published as US 2004/0006288, describes another embodiment of the use of shock waves generated by EH to provide a therapeutic effect on tissues. The '293 application describes a device, system and method for generating therapeutic acoustic shock waves to at least partially separate a deposit from a vascular structure. Order '293 describes that the device can produce shock waves at a pulse rate of approximately 50 to approximately 500 pulses per minute (i.e., 0.83 to 8.33 Hz) with a number of pulses per treatment site ( in terms of per length of the vascular unit being treated) from approximately 100 to approximately 5,000 per 1 cm ² .
B. Shock wave rate
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5/73 [009] The prior art literature has indicated that faster pulse rates using EH systems to deliver shock waves can lead to tissue damage. For example, in one study (Delius, Jordan, et al. 1988) [2], the effect of shock waves on normal canine kidneys was examined in groups of dogs whose kidneys were exposed to 3000 shock waves. The groups differed only in the shock wave administration rate, which was 100 Hz and 1 Hz, respectively. The autopsy was performed 24 to 30 hours later. Macroscopically and histologically significantly more bleeding occurred in the renal parenchyma if shock waves were administered at a rate of 100 Hz (vs 1 Hz). The results showed that damage to the kidney is dependent on the rate of shock wave administration.
[010] In another study (Madbouly & et al., 2005) [7], the slow shock wave lithotripsy (SWL) rate was associated with a significantly higher success rate on fewer total shock waves compared with the rapid shock wave lithotripsy rate. In this paper, the authors discussed how human studies have shown a decrease in the incidence of SWL-induced kidney injury or need for anesthesia when slower rates of SWL testing were used.
[011] In yet another study (Gillitzer & others, 2009) [5], decreasing the delivery rate by 60 to 30 shock waves per minute also provides a drastic protective effect on the integrity of the actual vasculature in a porcine model. These results support potential strategies for reduced pulse rate frequency to improve safety and efficacy in shock wave extracorporeal lithotripsy.
C. Fabric as a viscoelastic material [012] One reason for the pulse sensitivity rate found in the prior art may be due in part to the tissue's relaxation time. the cells
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6/73 have both elastic and viscous characteristics, and thus are viscoelastic materials. Unlike most conventional materials, cells are highly non-linear with their modulus of elasticity depending on the degree of applied or internal stress. (Kasza, 2007) [6]. One study (Fernandez (2006) [3] suggests that fibroblast cells can be modeled as a gel having a network of cross-linked actin that shows a transition from a linear regime to stiffening deformation by power principle.
[013] The authors of another document (Freund, Colonius, and Evan, 2007) [4] assumed that the cumulative shear of many shocks is harmful, and that the mechanism may depend on whether there is enough time between shocks for the tissue to relax to the undeformed state. His viscous fluid model suggested that any deformation recovery that will occur is almost complete for the first 0.15 seconds after the shock. As a result, your model of the mechanism for cell damage would be independent of the shock rate for shock rates slower than ~ 6 Hz. However, the actual viscoelasticity of the interstitial material, with a relaxation time of approximately 1 second, it would be expected to introduce its sensitivity to the shock delivery rate. Assuming that the interstitial material has a relaxation time of ~ 1 second, the authors would expect to significantly decrease the damage for delivery rates below ~ 1 Hz. On the other hand, the damage should increase for faster delivery rates. Implications of your model are that delaying delivery rates and expanding focal areas should decrease the injury.
SUMMARY OF THE INVENTION [014] Soft tissues can transition from elastic to viscous behavior to pulse rates (PRs) between 1 Hz and 10 Hz. As a result, the potential damage to tissue from shock waves in PRs between 1 Hz and 10 Hz is unpredictable when typical lithotripsy energy levels are used. Perhaps
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7/73 as a result, the prior art describes slower PRs and longer total times per treatment (TTPT). For example, currently known EH shockwave systems generally deliver PRs of less than 10 Hz and require large total times per treatment (TTPT) (for example, TTPT periods of minutes or even hours for a single treatment site). When, as may be typical, a treatment requires repositioning a device at multiple treatment sites, TTPT becomes large and potentially impractical for many patients and treatment needs.
[015] Although long treatment times may be acceptable for extracorporeal shock wave lithotripsy, the use of shock waves to provide non-lithotripsy therapeutic effects on tissue in the medical environment is less than ideal, if not impractical. For example, the cost of treatment often increases with the time required to administer a treatment (for example, due to labor, facilities, and other resource costs allocated to administering the treatment). Furthermore, in addition to the costs, at some point, the duration of providing treatment to the patient becomes unbearable for the patient receiving the treatment and the health care team providing the treatment.
[016] This description includes device types and methods for the electro-hydraulic generation of therapeutic shock waves. The present EH shock wave systems and methods are configured to deliver shock waves to tissues to provide a predictable therapeutic effect on the tissue, such as delivering shock waves at a higher frequency (for example, greater than ~ 10 Hz) to reduce TTPT on known systems.
[017] The present electrohydraulic apparatus (EH) modalities can be configured to generate high frequency shock waves in a controlled manner (for example, using an electro-hydraulic sparking generator and
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8/73 a capacitive / inductive coil generation system). The present generation of pulses (for example, electro-hydraulic sparking circuits) may comprise one or more EH tips and, with the present capacitive / inductive coil generation systems, can produce a 10 Hz sparking pulse rate at 5 MHz. Shock waves can be configured to impose sufficient mechanical stress on target tissue cells to disrupt target cells, and can be delivered to certain patient cell structures for use in medical and / or aesthetic therapeutic applications.
[018] The present high pulse rate (PR) shock wave therapies can be used to provide a predictable therapeutic effect on tissue, having a practical total time per treatment (TTPT) at the treatment site. The present high PR shock wave therapies can be used to provide a predictable therapeutic effect on the tissue, if the viscoelastic nature of the tissue is considered. Specifically, shockwave therapy using a PR greater than 10 Hz and even greater than 100 Hz can be used to provide a predictable therapeutic effect on the tissue because in these PRs the tissue is, for the most part, predictably viscous in nature and, it generally does not vary between elastic and viscous states. Since the fabric behaves like a viscous material in PRs large enough, the PR and energy level can be adjusted to explain the viscous properties of the fabric. When the viscous nature of the tissue is explained using higher PRs, the lower energy levels can be used to achieve therapeutic effects. An advantage of using higher PRs in combination with lower energy levels is the reduction in cavitation formation, which further improves the predictability of the present shock wave therapies. The modalities of the present EH apparatus and methods can provide targeted disruption of specific cells without harmful side effects such as cavitation or thermal degradation of non-target cells
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9/73 neighbors.
[019] Some modalities of the present devices (to generate therapeutic shock waves) include: a housing defining a chamber and a shock wave output; a liquid disposed in the chamber; a plurality of electrodes configured to be arranged in the chamber to define one or more spark openings; and a pulse generation system configured to apply voltage pulses to the plurality of electrodes at a rate between 10 Hz and 5 MHz; where the pulse generation system is configured to apply voltage pulses to the plurality of electrodes so that portions of the liquid are vaporized to propagate the shock waves through the liquid and the shock wave output.
[020] Some modalities of the present devices (to generate therapeutic shock waves) include: a housing defining a chamber and a shock wave output, the chamber configured to be filled with a liquid; and a plurality of electrodes arranged in the chamber to define a plurality of spark openings; where the plurality of electrodes is configured to receive voltage pulses from a pulse generation system at a rate between 10 Hz and 5 MHz so that portions of the liquid are vaporized to propagate shock waves through the liquid and the output of shock wave.
[021] Some modalities of the present devices (to generate therapeutic shock waves) include: a housing defining a chamber and a shock wave output, the chamber configured to be filled with a liquid; and a plurality of electrodes configured to be arranged in the chamber to define one or more spark openings; where the plurality of electrodes is configured to receive voltage pulses from a pulse generation system, so that portions of the liquid are vaporized to propagate the shock waves through the liquid and the shock wave output; and where the housing comprises a translucent or transparent window that is configured to allow
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10/73 for a user to view a patient region comprising target cells.
[022] In some modalities of the present devices, the various electrodes are not visible to a user viewing a region through the window and the shock wave output. Some modalities still include: an optical protection arranged between the window and the plurality of electrodes. In some embodiments, the various electrodes are moved from an optical path that extends through the window and the shock wave output. Some modalities also include: an acoustic mirror configured to reflect shock waves from the plurality of electrodes for the shock wave output. In some embodiments, the acoustic mirror comprises glass. In some embodiments, the one or more sparking apertures comprise a plurality of sparking apertures. In some modalities, the various electrodes are configured to be removably coupled to the pulse generation system. In some modalities, the accommodation is replaceable.
[023] Some modalities of the present devices also include: a sparking module which comprises: a side wall configured to removably couple the sparking module to the housing; where the various electrodes are attached to the side wall so that the various electrodes are placed in the chamber if the spark module is attached to the housing. In some embodiments, the side wall comprises a polymer. In some embodiments, the side wall of the sparking module is configured to cooperate with the housing to define the chamber. In some embodiments, the side wall defines a sparking chamber within which the plurality of electrodes are arranged, the sparking chamber is configured to be filled with liquid, and at least part of the side wall is configured to transmit shock waves. from a liquid in the sparking chamber to a liquid in the housing chamber. In some embodiments, the wall
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11/73 side of the sparking module comprises at least one of pins, grooves or threads, and the housing comprises at least one of the corresponding grooves, pins or threads for releasably coupling the sparking module to the housing. In some embodiments, the housing includes a first liquid connector configured to communicate fluidly with the camera when the spark module is coupled to the housing, and the side wall of the spark module includes a second liquid connector configured to communicate fluidly with the chamber when the spark module is attached to the housing. In some embodiments of the present devices, the housing also comprises two liquid connectors. Some modalities still include: a liquid reservoir; and a pump configured to circulate the liquid from the reservoir to the housing chamber via the two liquid connectors.
[024] In some modalities of the present devices, the pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate between 20 Hz and 200 Hz. In some modalities, the pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate between 50 Hz and 200 Hz. In some embodiments, the pulse generation system comprises: a first capacitive / inductive coil circuit comprising: an induction coil configured to be discharged to apply at least some of the tension pulses; a switch; and a capacitor; where the capacitor and the switch are coupled in parallel between the induction coil and a current source. In some embodiments, the pulse generation system comprises: a second capacitive / inductive coil circuit similar to the first capacitive / inductive coil circuit; and a timing unit configured to coordinate the discharge of the induction coils from each of the first and the second capacitive / inductive coil circuit.
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12/73 [025] Some modalities of the present apparatuses include: a sparking module which comprises: a side wall configured to releasably couple the sparking module to a probe; a plurality of electrodes arranged on a first side of the side wall and defining one or more spark openings; and a plurality of electrical connectors in electrical communication with the plurality of electrodes and configured to releasably connect the releasable electrodes to a pulse generation system, to generate sparks through one or more spark openings. In some embodiments, the side wall comprises a polymer. In some embodiments, the side wall includes a liquid connector configured to communicate liquid through the side wall. In some embodiments, the side wall defines a sparking chamber within which the plurality of electrodes is arranged, the sparking chamber is configured to be filled with a liquid, and at least part of the side wall is configured to transmit shock waves from a liquid in the sparking chamber to a liquid in the housing chamber. In some embodiments, the sparking module further comprises one or more liquid connectors in fluid communication with the sparking chamber such that the sparking chamber can be filled with liquid. In some embodiments, the one or more liquid connectors comprise two liquid connectors through which the liquid can be distributed through the sparking chamber. In some embodiments, the side wall is configured to releasably couple the spark module to a probe having a chamber so that the electrodes are disposed within the probe chamber. In some embodiments, the side wall and the probe cooperate to define the chamber. In some embodiments, the sparking module further comprises one or more liquid connectors in fluid communication with the probe chamber so that the probe chamber can
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13/73 be filled with liquid through one or more liquid connectors. In some embodiments, the one or more liquid connectors comprise two liquid connectors through which a liquid can be circulated through the probe chamber via the two liquid connectors. In some embodiments, the spark module includes a first liquid connector configured to communicate fluidly with the camera when the spark module is coupled to the probe and the probe includes a second liquid connector configured to communicate fluidly with the camera when the Spark module is coupled to the probe.
[026] In some embodiments of the present apparatus comprising a sparking module, the one or more sparking apertures comprise a plurality of sparking apertures. In some embodiments, the plurality of electrodes comprises three or four electrodes defining two spark openings. In some embodiments, the three or four electrodes comprise a first peripheral electrode, a second peripheral electrode separated from the first electrode, and one or two central electrodes configured to move back and forth between the peripheral electrodes. In some embodiments, the sparking module also comprises: an elongated element coupled to one or two central electrodes and configured to move the one or two central electrodes back and forth between the peripheral electrodes. In some embodiments, the one or two central electrodes comprise two central electrodes in electrical communication with each other and arranged on opposite sides of the elongated element. In some embodiments, the elongated element is configured to self-adjust the spark gap between the peripheral electrodes and one or two central electrodes within an expected operating frequency range. In some modalities, the expected operating frequency range is between 10 Hz and 5 MHz.
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14/73 modalities, the elongated element is articulated coupled to the side wall and inclined to an initial position by one or more spring arms. In some embodiments, the elongated member and one or more spring arms are configured to determine a pulse rate of the sparking module within an expected range of operating frequencies. In some modalities, the expected operating frequency range is between 10 Hz and 5 MHz. In some modalities, the device is configured to discharge electrical pulses between the electrodes while the electrodes are submerged in liquid, such that the movement of the elongated element automatically and alternately adjusts the spark gap between one or two central electrodes and each of the peripheral electrodes. In some embodiments, the elongated member comprises a resilient bundle that has a base that is fixedly attached to the side wall. In some embodiments, the resilient beam is configured to determine a pulse rate of the sparking module under expected operating conditions. In some embodiments, the device is configured to discharge electrical pulses between the electrodes while the electrodes are submerged in a liquid, such that the movement of the resilient beam automatically and alternately adjusts the spark gap between one or two central electrodes and each of the peripheral electrodes.
[027] In some embodiments of the present apparatus comprising a sparking module, the side wall of the sparking module comprises at least one of pins, grooves or threads, and is configured to be coupled to a probe comprising at least one of grooves, corresponding pins or threads to releasably couple the sparking module to the housing. Some modalities also include: a probe configured to be coupled to the sparking module so that the various electrodes are arranged in a chamber that is filled with a liquid, and so that the
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15/73 shock waves from the electrodes will travel through a shock wave output from the device. In some embodiments, the chamber is filled with liquid. In some embodiments, the probe does not define an additional chamber, so the sparking chamber is the only chamber through which the shock waves from the electrodes will propagate. In some embodiments, the probe defines a second chamber within which the sparking chamber is arranged, if the sparking module is coupled to the probe. In some embodiments, the probe includes a plurality of electrical connectors configured to be coupled to the plurality of electrical connectors of the spark module. In some embodiments, the probe includes one or more liquid connectors configured to be coupled to one or more liquid connectors on the spark module. In some embodiments, the probe includes two liquid connectors configured to be coupled to the two liquid connectors on the spark module. In some embodiments, the spark module is configured to be coupled to the probe so that the electrical and liquid connectors of the spark module are simultaneously connected to the respective electrical and liquid connectors of the probe as the spark module is coupled to the probe. . In some embodiments, the probe includes one or more liquid connectors configured to be coupled to one or more liquid connectors of the spark module. In some embodiments, the probe includes a combined connection having two or more electrical conductors and two lumens for liquid communication, the combined connection configured to be coupled to a current or combined cable that has two or more electrical conductors and two lumens to communicate liquid. In some embodiments, the combined connection is configured to be removably attached to the combined chain or cable.
[028] In some embodiments of the present apparatus comprising a
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16/73 sparking module and a probe, the probe includes a housing with a transparent or translucent window that is configured to allow a user to view a patient's region comprising target cells. In some modalities, if the spark module is coupled to the probe, the plurality of electrodes is not visible to a user viewing a region through the window and the shock wave output. Some modalities still include: an optical protection arranged between the window and the plurality of electrodes. In some embodiments, optical protection includes a light-sensitive material that darkens or increases in opacity in the presence of bright light. In some embodiments, the various electrodes are displaced from an optical path extending through the window and the shock wave output. Some modalities also include: an acoustic mirror configured to reflect the shock waves from the plurality of electrodes for the shock wave output. In some embodiments, the acoustic mirror comprises glass.
[029] Some modalities of the present apparatus comprise: a probe configured to be coupled to a sparking module having a plurality of electrodes defining one or more sparking openings so that the plurality of electrodes is arranged in a chamber that is filled with a liquid. In some embodiments, the chamber is filled with liquid. In some embodiments, the probe is configured to cooperate with the spark module to define the chamber. In some embodiments, the probe includes a first liquid connector configured to communicate fluidly with the camera when the spark module is attached to the probe, and is configured to be attached to a spark module that includes a second liquid connector which is configured to communicate fluidly with the camera when the spark module is attached to the probe.
[030] In some embodiments, the sparking module includes a wall
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17/73 lateral defining a sparking chamber within which the plurality of electrodes is arranged, and the probe does not define an additional chamber, so the sparking chamber is the only chamber through which shock waves from the electrodes will propagate . In some embodiments, the sparking module includes a side wall defining a sparking chamber within which the plurality of electrodes is disposed, when the probe defines a second chamber within which the sparking chamber is disposed if the sparking module is coupled the catheter. In some embodiments, the probe includes a plurality of electrical connectors configured to be coupled to a plurality of electrical connectors of the spark module that are in electrical communication with the plurality of electrodes. In some embodiments, the probe includes one or more liquid connectors configured to be coupled to one or more liquid connectors of the spark module. In some embodiments, the probe includes two liquid connectors configured to be coupled to the two liquid connectors on the spark module. In some embodiments, the sparking module is configured to be coupled to the probe so that the electrical and liquid connectors of the sparking module are simultaneously connected to the respective electrical and liquid connectors of the probe as the sparking module is coupled to the probe.
[031] In some embodiments of the present apparatus comprising a probe, the probe includes a combined connection having two or more electrical conductors and two lumens for the communication of liquid, the combined connection configured to be coupled to a combined chain or cable that has two or more electrical conductors and two lumens to communicate liquid. In some embodiments, the combined connection is configured to be removably attached to the combined chain or cable. In some embodiments, the probe includes a housing with a transparent or translucent window that is configured to
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18/73 allow a user to view a patient's region comprising target cells. In some modalities, if the spark module is coupled to the probe, the plurality of electrodes is not visible to a user viewing a region through the window and the shock wave output. Some modalities still include: an optical protection arranged between the window and the plurality of electrodes. In some embodiments, the various electrodes are displaced from an optical path extending through the window and the shock wave output. Some modalities also include: an acoustic mirror configured to reflect the shock waves from the plurality of electrodes for the shock wave output. In some embodiments, the acoustic mirror comprises glass.
[032] Some modalities of the present apparatus comprising a probe still comprise: a pulse generation system configured to store and release an electrical charge repeatedly, the pulse generation system configured to be coupled to the electrical connectors of the sparking module to release the electrical charge through the electrodes of the sparking module. In some embodiments, the pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate between 20 Hz and 200 Hz. In some embodiments, the pulse generation system is configured to apply voltage pulses to the plurality electrodes at a rate between 50 Hz and 200 Hz. In some embodiments, the pulse generation system includes a single charge / discharge circuit. In some embodiments, the pulse generation system includes a plurality of charge / discharge circuits and a timing unit to coordinate the charge and discharge of a plurality of charge / discharge circuits. In some embodiments, each of the charge / discharge circuits includes a capacitive / inductive coil circuit. In some embodiments, each capacitive / inductive coil circuit comprises: an induction coil configured to be discharged to apply at least some of the pulses of
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19/73 tension; a switch; and a capacitor; where the capacitor and switch are coupled in parallel between the induction coil and the timing unit. Some modalities still include: a liquid reservoir; and a pump configured to circulate the liquid from the reservoir to the housing chamber.
[033] Some modalities of the present apparatus include: a pulse generation system including a plurality of charge / discharge circuits and a timing unit configured to coordinate the charge and discharge of the plurality of charge / discharge circuits at a rate between 10 where the pulse generation system is configured to be coupled to a plurality of electrodes of a sparking module to discharge the charge / discharge circuits through the electrodes. Some modalities also include: configuring each of the charging / discharging circuits includes a capacitive / inductive coil circuit. Each capacitive / inductive coil circuit comprises: an induction coil configured to be discharged to apply at least some of the voltage pulses; a switch; and a capacitor; where the capacitor and the switch are coupled in parallel between the induction coil and the timing unit. The pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate between 20 Hz and 200 Hz. The pulse generation system is configured to apply voltage pulses to the plurality of electrodes at a rate between 50 Hz. and 200 Hz. Some modalities still include: a liquid reservoir; and a pump configured to circulate the liquid from the reservoir to the housing chamber.
[034] Some modalities of the present methods include: positioning the shock wave output of one of the present devices adjacent to a region of a patient that comprises the target cells; and activate a pulse generation system to propagate shock waves through the fluid with the target cells. In
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In some embodiments, at least part of the plurality of shock waves is delivered to a part of a patient's epidermis layer that includes a tattoo. In some embodiments, an instrument housing and / or probe includes a transparent or translucent window that is configured to allow the user to view a patient's region comprising target cells; and the method also comprises: viewing the region through the window while positioning the device. In some embodiments, the apparatus includes a sparking module (which comprises: a side wall configured to releasably couple the sparking module to the housing; where the plurality of electrodes are coupled to the side wall so that the various electrodes are arranged in the chamber if the sparking module is coupled to the housing), and the method further comprises: coupling the sparking module to the housing before activating the pulse generation system.
[035] Some modalities of the present methods include: to generate electro-hydraulically a plurality of shock waves in a frequency between 10; delivering at least a part of the plurality of shock waves to at least one cell structure comprising at least one region of heterogeneity; and disrupting at least one cell structure with the continued delivery of the plurality of shock waves. In some embodiments, at least one region of heterogeneity comprises an effective density greater than an effective density of at least one cell structure. Some modalities even include the step of varying the frequency of the acoustic waves. In some embodiments, at least part of the plurality of shock waves is delivered to a patient's epidermis layer. In some embodiments, part of the epidermis layer receiving the shock waves includes cells that contain particles of tattoo pigment. Some modalities also include: identifying at least one target cell structure to be disrupted before
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21/73 deliver at least a part of shock waves to at least one target cell structure.
[036] Some modalities of the present methods include: delivering a plurality of shock waves generated in an electrohydraulic manner to at least one cell structure comprising at least one region of heterogeneity until at least one cell structure breaks. In some embodiments, at least part of the plurality of shock waves is delivered to a part of a patient's epidermis layer, which includes cells that contain particles of tattoo pigment. In some embodiments, shock waves are delivered to at least one cell structure for no more than 30 minutes in a 24-hour period. In some embodiments, shock waves are delivered to at least one cell structure for no more than 20 minutes in a 24-hour period. In some embodiments, between 200 and 5000 shock waves are delivered between 30 seconds and 20 minutes to each of a plurality of positions of a shock wave output. Some modalities even include: tensing a part of a patient's skin while delivering shock waves. In some embodiments, tension is performed by pressing a convex outlet element against the patient's skin. Some modalities also include: delivering laser light to at least one cell structure; and / or delivering a chemical or biological agent to at least one cell structure.
[037] Any modality of any of the present systems, devices, and methods can consist or consists essentially of - instead of understanding / including / containing / having - any of the described steps, elements, and / or characteristics. Thus, in any of the claims, the term "consisting of" or "consisting essentially of" can be replaced by any of the link verbs described above, in order to change the scope of a given claim from what would be of another form using the link verb.
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22/73 [038] Details associated with the modalities described above and others are presented below.
DESCRIPTION OF THE DRAWINGS [039] The following drawings illustrate by way of example and not by way of limitation. For the sake of brevity and clarity, each feature of a given structure is not always marked on each figure on which that structure is displayed. Identical reference numbers do not necessarily indicate an identical structure. Preferably, the same reference number can be used to indicate a similar characteristic with similar functionality, as can non-identical reference numbers. Figures are drawn to scale (unless noted to the contrary), meaning that the sizes of the elements represented are accurate in relation to each other for at least the modality represented in the figures.
[040] Figure 1 represents a block diagram of a first modality of the present electro-hydraulic (EH) shock wave generation systems.
[041] Figure 2 represents a cross-sectional side view of a portable probe for some modalities of the present shock wave generation EH systems.
[042] Figure 2A represents a cross-sectional side view of a first embodiment of a removable sparking head usable with modalities of the present portable probes, as in Figure 2.
[043] Figure 2B represents a side sectional view of a second modality of a removable sparking head usable with the modalities of the present portable probes, as in Figure 2.
[044] Figure 2C represents a side sectional view of a third modality of a removable sparking head usable with the modalities of the present hand probes, as in Figure 2.
[045] Figures 3A-3B represent a time diagram of an example of the
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23/73 timed application of energy cycles or voltage pulses in the system in Figure 1 and / or the portable probe in Figure 2.
[046] Figure 4 represents a waveform that can be emitted by the system of Figure 1 and / or the portable probe of Figure 2 to the target tissue.
[047] Figure 5 represents a schematic diagram of a modality of a pulse generation system with multiple openings for use in or with some modalities of the present systems.
[048] Figure 6 represents a block diagram of a modality of an acoustic ablation system powered by radio frequency (RF).
[049] Figures 7A-7B represent perspective and cross-sectional views of a first prototype sparking chamber housing.
[050] Figure 8 represents a cross-sectional view of a second prototype type of sparking chamber housing.
[051] Figure 9 represents a schematic diagram of an electrical circuit for a prototype pulse generation system.
[052] Figure 10 represents a conceptual flowchart of a modality of the present methods.
[053] Figure 11 represents an exploded perspective view of an additional prototype modality of the present probes having a sparking head or module.
[054] Figures 12A and 12B represent parts of the probe assembly of Figure
11.
[055] Figures 13A and 13B illustrate perspective and cross-sectional views, respectively, of the probe in Figure 11.
[056] Figure 13C represents an enlarged cross-sectional view of a sparking opening of the probe in Figure 11.
[057] Figure 14 represents a schematic diagram of a second
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24/73 modality of an electrical circuit of a prototype pulse generation system.
DETAILED DESCRIPTION [058] The term “coupled” is defined as connected, although not necessarily directly, and not necessarily mechanically; two items that are “coupled” can be unitary to each other. The terms "one" and "one" are defined as one or more unless this description explicitly requires otherwise. The term "substantially" is defined as largely, but not necessarily completely, what is specified (and includes what is specified, for example, substantially 90 degrees includes 90 degrees and substantially parallel includes parallel), as understood by the skilled person . In any modality presented, the terms "substantially", and "approximately" can be replaced by "within [a percentage] of" what is specified, where the percentage includes 0.1, 1.5, and 10 percent.
[059] The terms "understand" (and any form of understanding such as "understands" and "understanding"), "have" (and any form of have such as "has" and "having"), "include" (and any form of including such as "includes" and "including") and "containing" (and any form of containing such as "contains" and "contain") are open link verbs. As a result, a system or device that “comprises”, “has”, “includes” or “contains” one or more elements has one or more of these elements, but is not limited to having only those elements. Likewise, a method that “understands”, “has”, “includes” or “contains” one or more steps has these one or more steps, but is not limited to having only one or more steps.
[060] Furthermore, a structure (for example, a device component) that is configured in a certain way is configured in at least one way, but it can also be configured in ways other than that specifically described.
[061] Certain modalities of the present systems and devices are configured
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25/73 to generate high frequency shock waves in a consistent and predictable manner. In some embodiments, shock waves generated by HE can be used in medical and / or aesthetic therapeutic applications (for example, when directed and / or delivered to a patient's target tissue). Examples of medical and / or aesthetic therapeutic applications in which the present systems can be used are described in: (1) U.S. Patent Application No. 13 / 574,228, published as US 2013/0046207; and (2) U.S. Patent Application No. 13 / 547,995, published as US 2013/0018287; both of which are incorporated here in their entirety. The shock waves generated by EH by the present systems can be configured to impose sufficient mechanical stress to disrupt the target tissue cells (for example, due to membrane degradation damage).
[062] When the target cells (target tissue cells) are exposed to the generated high PR shock waves, the cells experience steep gradients of mechanical stress due to the spatial heterogeneity parameters of the cells, such as the density and modulus of elasticity of shear of the different components of the cell. For example, dense and inelastic components within a cell experience greater mechanical stress when subjected to shock waves, compared to lighter components. In particular, the acceleration of higher density particles or components within the cell structure exposed to impact is typically very large. At the same time, the impact on lower density biological structures constituting the cell structure when exposed to such a large pressure gradient is significantly reduced, because the elasticity of lower density biological structures allows them to act generally as a material of low compatibility. The difference in mechanical stress results in the movement of dense and / or inelastic components within the cell.
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26/73 [063] When the cell is exposed to repeated shock waves at a certain frequency and energy level, the dense and / or inelastic components are repeatedly moved until they break the cell, thus breaking the cell. In particular, the incompatibility of cell structure properties and the ability of cells to experience deformation when exposed to frontal impact leads to cell destruction, as described. A possible theory to explain the phenomenon of disruption of the cellular structure can be found in (Burov, VA, 2002) [1], which is incorporated here by reference in its entirety.
[064] As discussed by Burov [1], while a cell can oscillate as an integrated unit when impacted by this pressure, sharp gradients of mechanical stress can be generated within the cell as a result of spatial heterogeneity parameters (ie density and shear elastic modulus). This concept can be illustrated by modeling the biological structure as two spheres connected with masses rm and m2 and the density (po) of the liquid oscillating around the spheres with the speed po (t) differ insignificantly from the densities of the spheres (by pi and p2 respectively). If only resistance to potential flow is taken into account, the force applied to the connection is calculated as shown in Equation (1):
⁽¹⁾ [065] Further discussions of Equation (1) and its variables are additionally provided in [1], For example, if the sphere radius (R) is approximately 10 μιτι and the difference between the sphere densities is 0 , 1 g, and results in a tensile strength, F / (KR ² ) m of 10 ⁹ dyne / cm ² . This is sufficient to break a cell membrane. The modalities of the present devices generate shock waves in a controlled manner that can be used to cause damage to certain cells, which have medical and / or aesthetic therapeutic applications which are discussed later.
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27/73 [066] Another possible theory to explain the cell rupture phenomenon is the shear stress of accumulation of the densest material in the cell structure. In heterogeneous media, such as cells with particles (for example, pigment particles), shock waves cause cell membranes to fail by a progressive (ie, accumulated) shear mechanism. On the other hand, in homogeneous media, compression by shock waves causes minimal damage, if any, to the membranes. Focusing and microscopic defocusing of the shock wave as it passes through heterogeneous media can result in a strengthening or weakening of the shock wave locally, which results in an increase in local shear. The relative shear movement of the cell membrane occurs on the scale of the heterogeneities of the cell structure. It is believed that when the shock waves reach a region of heterogeneities (for example, cells containing particles), the movement of the particles that is out of phase with the incoming waves generates a transfer of cell-breaking energy (for example, voltage shear). Out-of-phase movement (for example, shear stress) causes microscopic damage to the cell membrane that can progressively grow to failure of the cell membrane with successive additional accumulation of shear stress.
[067] The progressive shear mechanism of repeated exposure to shock waves can be considered dynamic fatigue of cell membranes. The damage caused by dynamic fatigue is dependent on three factors: (1) strain or applied stress, (2) the rate at which the stress is applied, and (3) cumulative number of strain cycles. These three factors can be manipulated to cause a cell with heterogeneities to experience catastrophic failure of the cell membrane, compared to a relatively larger number of homogeneities in a particular applied strain, strain rate, and strain cycles.
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28/73 [068] Factor manipulation can be done by providing EH shock waves of certain properties, such as the number of shock waves, the amount of time between each shock wave, and the strength of the applied shock waves. As discussed above, if there is too much time between the shock waves for the tissue to relax until its undeformed state, the cells will become more resistant to failure. As such, in the preferred mode for an EH system, shock waves at a PR greater than 5 Hz and preferably greater than 100 Hz and more preferably greater than 1 MHz are delivered to the target cell structures to achieve dynamic tissue fatigue. and do not allow time for the fabric to relax.
[069] At sufficiently high PR, fabrics behave like a viscous material. As a result, the energy level and PR can be adjusted to take into account the viscous properties of the fabric.
[070] A third possible theory is that EH shock waves cause a combination of effects of direct movement of particles contained in the cell structure and dynamic fatigue that disrupt cells. While cells containing particles are an apparent example of cell structures exhibiting heterogeneities, their description is not intended to limit the scope of the present description. Instead, the modalities described herein can be used to disrupt or damage other cell structures that exhibit heterogeneities, such as cell structures that have different regions of effective density. The parameters of the shock waves generated according to the described aspects can be adjusted based, at least, in the regions of different effective densities (that is, heterogeneities) to cause cellular damage, as described here. Heterogeneities can be regions within a single cell, a region of different types of cells, or a combination of both. In certain embodiments, a region of heterogeneity within a cell includes a region having an effective density greater than the effective density of the cell. In one example
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29/73 specific, the effective density of a fibroblast cell is approximately 1.09 g / cm ³ , a region of heterogeneity in the cell would be particles contained within the cell that have an effective density greater than 1.09 g / cm ² , such as graphite with a density of 2.25 g / cm ³ . In certain embodiments, a region of cellular heterogeneity between cells includes a region with different types of cells, where each type of cell has a different effective density, such as fibroblast cells and fat cells or hair follicles. The present invention provides further examples of cell structures containing the heterogeneities below.
[071] With reference now to the drawings, and more particularly to Figure 1, a block diagram of a modality of the present devices or systems for the electro-hydraulic generation of shock waves is shown and designated by reference number 10 controlled. In some embodiments, such as the one shown, system 10 includes a portable probe (for example, with a first housing, as in Figure 2) and a separate controller or pulse generation system (for example, in or with a second housing attached to the portable probe via a flexible cable or similar). In other embodiments, the present systems include a single portable device arranged in a single housing.
[072] In the embodiment shown, the apparatus 10 comprises: a housing 14 that defines a chamber 18 and a shock wave output 20; a liquid (54) disposed in the chamber 18; a plurality of electrodes (for example, in the sparking head or module 22) configured to be arranged in the chamber to define one or more sparking openings; and a pulse generation system 26 configured to apply voltage pulses to the electrodes at a rate between 10 Hz and 5 MHz. In this mode, the capacitive / inductive coil system 26 is configured to apply voltage pulses to the electrodes so that portions of the liquid are
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30/73 vaporized to propagate shock waves through the liquid and the shock wave outlet.
[073] In the mode shown, the pulse generation system 26 is configured to be used with an alternating current power source (for example, an outlet). For example, in this embodiment, the pulse generation system 26 comprises a socket 30 configured to be inserted into a 110V wall socket. In the modality shown, the pulse generation system 26 comprises a capacitive / inductive coil system, the example of which is described below with reference to Figure 6. In another embodiment, the pulse generation system 26 can comprise any structure or components configured for apply high voltages to the electrodes periodically to generate electrical sparks of sufficient power to vaporize the liquid in the respective spark openings, as described in this description.
[074] In the modality shown, the pulse generation system 26 is (for example, removably) coupled to the electrodes on the head or sparking module 22 via a high voltage cable 34, which can, for example, include two or more electrical conductors and / or be strongly protected with rubber or another type of electrically insulating material to avoid shock. In some embodiments, the high voltage cable 34 is a chain or combined cable that also includes one or more (for example, two) lumens of liquid, through which the chamber 18 can be filled with liquid and / or through which the liquid can be distributed through chamber 18 (for example, via the combined connection 36). In the embodiment shown, apparatus 10 comprises a portable probe or handpiece 38 and cable 34 is removably attached to probe 38 via a high voltage connector 42, which is attached to the head or sparking module 22 via two or more electrical conductors 44. In the embodiment shown, probe 38 comprises a head 46 and a handle 50, and probe 38 may comprise a polymer or other material
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31/73 electrically insulating to allow an operator to grasp handle 50 to position probe 38 during operation. For example, handle 50 may be molded with plastic and / or may be coated with an electrically insulating material, such as rubber.
[075] In the embodiment shown, a liquid 54 (for example, a dielectric liquid such as distilled water) is disposed in (for example, and substantially fills) chamber 18. In this embodiment, the sparking head 22 is positioned in chamber 18 and surrounded by the liquid so that the electrodes can receive voltage pulses from the pulse generation system 26 (for example, at a rate between 10 Hz and 5 MHz) so that portions of the liquid are vaporized to propagate the shock waves through the liquid and the shock wave outlet 20. In the embodiment shown, probe 38 includes an acoustic delay chamber 58 between chamber 18 and outlet 20. In this embodiment, the acoustic delay chamber is substantially filled with liquid 62 ( for example, of the same type as liquid 54) and has a length 66 that is sufficient to allow shock waves to form and / or go to outlet 20. In some embodiments, length 66 may then be re 2 mm (millimeters) and 25 millimeters (mm). In the embodiment shown, chamber 18 and acoustic delay chamber 58 are separated by a layer of somnolent material (acoustically permeable or transmissive) that allows sound waves and / or shock waves to travel from chamber 18 to the acoustic delay chamber 58. In other embodiments, liquid 62 may be different from liquid 54 (for example, liquid 62 may comprise bubbles, water, oil, mineral oil, and / or the like). Certain characteristics, such as bubbles, can introduce and / or improve a non-linearity in the acoustic behavior of the liquid 54 to increase the formation of shock waves. In other embodiments, the chamber 18 and the acoustic delay chamber 54 may be unitary (i.e., they may comprise a single chamber). In other modalities, the chamber
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32/73 acoustic delay 54 can be replaced with a solid element (for example, a solid cylinder of elastomeric material such as polyurethane). In the embodiment shown, probe 38 further includes an output member 70 removably coupled to the housing at a distal end of the acoustic delay chamber, as shown. Element 70 is configured to contact tissue 74, and can be removed and either sterilized or replaced between patients. Element 70 comprises a polymer or other material (e.g., low density polyethylene or silicone rubber) that is acoustically permeable to allow shock waves to leave the acoustic delay chamber 58 via outlet 20. Fabric 74 can, for example, being human skin tissue to be treated with the apparatus 10, and may, for example, include a tattoo, a scar, a subdermal lesion, or a basal cell abnormality. In some embodiments, an acoustic coupling gel (not shown) can be disposed between the element 70 and the fabric 74 to lubricate and provide additional acoustic transmission to the fabric 74.
[076] In the modality shown, probe 38 includes an acoustic mirror 78, which comprises a material (for example, glass) and is configured to reflect most of the sound waves and / or shock waves that are incident on the mirror acoustic. As shown, the acoustic mirror 58 can be tilted to reflect sound waves and / or shock waves (for example, originating in the spark head 22) towards exit 20 (via the acoustic delay chamber). In the embodiment shown, housing 14 may comprise a translucent or transparent window 82 that is configured to allow a user to view (through window 82, chamber 18, chamber 58, and element 70) a region of a patient (for example, example, tissue 74) comprising target cells (for example, during the application of shock waves or before the application of shock waves to position the outlet 20 in the target tissue). In the embodiment shown, window 82 comprises an acoustically reflective material (for example, glass) that
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33/73 is configured to reflect most of the sound waves and / or shock waves that are incident on the window. For example, window 82 may comprise transparent glass of sufficient thickness and strength to withstand the high-energy acoustic pulses produced in the sparking head 22 (for example, tempered glass approximately 2 mm thick and an optical transmission efficiency greater than 50%).
[077] In Figure 1, a human eye 86 indicates a user viewing the target tissue through window 82, but it should be understood that the target tissue can be “seen” through window 82 via a camera (for example, a static digital and / or video camera). By direct or indirect observation, the acoustic energy can be positioned, applied, and repositioned according to the target tissues, such as existing tattoos, and by indications of acoustic energy, such as a change in the color of the tissue. However, if the sparking head 22 is arranged where a user can view sparking head 22, the sparkle resulting from sparking head 22 may be too bright for a user to comfortably view, and in the mode shown, probe 38 is configured such that the various electrodes are not visible by a user viewing a region (for example, the target tissue), through window 82 and exit 20. For example, in the mode shown, probe 38 includes an optical shield 90 arranged between the sparking head 22 and the window 82. The guard 90, for example, can have a width and / or a length that is less than a width and / or the corresponding length of the window 82 so that guard 90 is large enough to substantially block light from the sparking head 22 from traveling directly into the user's eye, but does not interfere with the field of view through the window 82 ed exit 20 more than necessary to block the light. Shield 90 may, for example, comprise a thin sheet of metal, such as stainless steel, or other opaque material, or may comprise
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34/73 welding glass (for example, an LCD darkened by a photoelectric cell or other light-sensitive material) that is optically activated and darkened by the brightness of sparks in the spark openings. The acoustic effect of protecting the resulting sparks from a sparking opening head needs to be considered, in order to maintain the effect of a point source from sparking head 22 and a resulting desired flat wavefront. If the guard 90 comprises an acoustically reflective material, to prevent pulse widening, the distance between the guard and the spark openings between the electrodes in the spark head 22 can be selected to minimize (for example, at least destroy) interference between sound waves and / or shock waves reflected from the shield and sound waves and / or shock waves originating in the sparking head 22 (for example, so that the intersecting waves do not produce echoes or excess reverberation). With a speed of sound waves in a medium such as distilled water of approximately 1500 m / s, the distance between the spark head and the shield can be calculated to be at 1/2 and 3/4 wavelengths from the source .
[078] The spark head 22 (for example, the electrodes on the spark head 22) can have a limited service life that can be extended by limiting the duration of activation. In the mode shown, apparatus 10 includes a switch or trigger 94 coupled to the pulse generation system 26 via a switch wire or other connection 98 via connector 42, so that switch 94 can be actuated to apply voltage pulses to electrodes on the spark head 22.
[079] Figure 2 represents a cross-sectional side view of a second embodiment 38a of the present portable probes or handpiece for use with some modalities of the present shock wave generation and apparatus EH systems. Probe 38a is substantially similar in some respects to probe 38,
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35/73 and the differences are then described first here. For example, probe 38a is also configured so that the plurality of electrodes of the head or sparking module 22a are not visible to a user viewing a region (e.g., target tissue) through window 82a and outlet 20a. However, instead of including optical protection, probe 38a is configured so that the spark head 22a (and the spark head electrodes) is moved from an optical path that extends through window 82a and the exit 20a. In this embodiment, the acoustic mirror 78a is positioned between the sparking head 22a and the outlet 20a, as shown, to define a chamber boundary 18a and to direct the acoustic waves and / or shock waves from the sparking head 22a to exit 20a. In the embodiment shown, the window 82a may comprise a polymer or other acoustically permeable material or transmissive material because the acoustic mirror 78a is disposed between the window 82a and the chamber 18a and the sound waves and / or shock waves are not directly incident on the window 82a (that is, because sound waves and / or shock waves are mainly reflected by the acoustic mirror 78a).
[080] In the embodiment shown, the spark head 22a includes a plurality of electrodes 100 that define a plurality of spark openings. The use of multiple spark openings can be advantageous because it can double the number of pulses that can be delivered in a given period of time. For example, after a pulse vaporizes an amount of liquid in a spark gap, either the vapor needs to return to its liquid state or it must be displaced by a different part of the liquid that is still in a liquid state. In addition to the time required for the spark gap to be refilled with water before a subsequent pulse can vaporize additional liquid, the sparks also heat the electrodes. As such, for a given rate of spark, increase the number of
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36/73 spark openings reduce the rate at which each spark open must be triggered and thus prolong the life of the electrodes. Thus, ten spark openings potentially increase the possible pulse rate and / or electrode life by a factor of ten.
[081] As noted above, high pulse rates can generate large amounts of heat that can increase fatigue in the electrodes and / or increase the time required for the vapor to return to the liquid state after being vaporized. In some embodiments, this heat can be managed by the liquid that circulates around the spark head. For example, in the embodiment of Figure 2, probe 38 includes ducts 104 and 108 extending from chamber 18a to respective connectors 112 and 116, as shown. In this embodiment, connectors 112 and 116 can be coupled to a pump to circulate the liquid through the chamber 18a (for example, and through a heat exchanger). For example, in some embodiments, the pulse generation system 26 (Figure 1) may comprise a pump and heat exchanger in series and configured to be connected to connectors 112 and 116 via ducts or similar. In some embodiments, a filter may be included in probe 38a, in a spark generation system (e.g. 26), and / or between the probe and the spark generation system to filter the liquid that circulates through the chamber.
[082] Additionally, due to the limited life of electrodes 100 at high pulse rates, some modalities of the present probes may be disposable. Alternatively, some modalities are configured to allow a user to replace the electrodes. For example, in the embodiment of Figure 2, the sparking head 22a is configured to be removable from probe 38a. For example, the sparking head 22a can be removable via the handle 50a, or the handle 50a can be removably attached (for example, via threads or the like) to the head 46a so that, by removing the handle 50a from the head 46, the head
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37/73 of sparking 22a can be removed from the head 46a and replaced.
[083] As illustrated in Figure 2, the application of each shock wave to a target tissue includes a wavefront 118 propagating from outlet 20a and traveling outward through tissue 74. As shown, wavefront 74 is curved according to its expansion, since it moves outwards and partially according to the shape of the outer surface of the outlet element 70a which contacts the fabric 74. In other embodiments, such as that of Figure 1, the outer shape of the element contact can be flat or otherwise affect certain properties of the wavefront as it passes through outlet 20a and propagates through target tissue.
[084] Figure 2A represents an enlarged cross-sectional view of the first modality of the removable sparking head or module 22a. In the embodiment shown, the sparking head 22a comprises a side wall 120 that defines a sparking chamber 124, and a plurality of electrodes 100a, 100b, 100c arranged in the sparking chamber. In the embodiment shown, the sparking chamber 124 is filled with liquid 128 which may be similar to liquid 54 (Figure 1). At least part of the side wall 120 comprises an acoustically permeable or transmissive material (for example, a polymer such as polyethylene) configured to allow sound waves and / or shock waves generated at the electrodes to travel through the side wall 120 and through the chamber 18a. For example, in the embodiment shown, the sparking head 22a includes a cup-shaped element 132 that can be configured to be acoustically reflective and an acoustically permeable cap element 136. In this embodiment, the cap element 136 is dome-shaped for approach the curved shape of an expanding wavefront that originates at the electrodes and to compress the skin when applied with moderate pressure. The cap element 136 can be coupled to the cup-shaped element 132 with a ring in
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38/73
O or gasket 140 and a retaining ring 144. In the embodiment shown, cup-shaped element 132 has a cylindrical shape with a circular cross section (for example, with a diameter of 5.08 cm (2 inches) or less) . In this embodiment, the cup-shaped element includes bayonet-style pins 148, 152 configured to align with corresponding grooves in the head 46a of the probe 38a (Figure 2) to lock the position of the sparking head 22a in relation to the probe.
[085] In the embodiment shown, an electrode core 156 having conductors 160a, 160b, 160c and extending through opening 164, with the interface between opening 164 and electrode core 156 sealed with an insulating ring 168. In the embodiment shown, a central conductor 160a extends through the center of the core 156 and serves as a ground for the corresponding central electrode 100a. Peripheral conductors 160b, 160c are in communication with peripheral electrodes 100b, 100c to generate sparks through the spark gap between electrodes 100a and 100b, and between electrodes 100a and 100c. It should be understood that, while two spark openings are shown, any number of spark openings can be used, and can be limited only by the size and spacing of the spark openings. For example, other modalities include 3, 4, 5, 6, 7, 8, 9, 10, or even more spark openings.
[086] Figure 2B represents an enlarged side view of a second modality of a removable sparking head or module 22b. In the embodiment shown, the sparking head or module 22b comprises a side wall 120a that defines a sparking chamber 124a, and a plurality of electrodes 100d-1, 100d-2, 100, 10Of arranged in the sparking chamber. In the embodiment shown, the sparking chamber 124a is filled with liquid 128a which may be similar to liquid 128 and / or 54. At least
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39/73 a side wall part 120a comprises an acoustically permeable or transmissive material (for example, a polymer such as polyethylene) configured to allow sound waves and / or shock waves generated in the electrodes to travel through the side wall 120a and through of chamber 18a (Figure 2). For example, in the embodiment shown, the sparking head 22b includes a cup-shaped element 132a that can be configured to be acoustically reflective and an acoustically permeable cap element 136a. In this embodiment, the cap element 136a is dome-shaped to approach a curved shape of an expanding wavefront that originates at the electrodes and to compress the skin when applied with moderate pressure. The cap element 136a can be coupled to the cup-shaped element 132a with an O-ring or gasket (not shown, but similar to 140) and a retaining ring 144a. In the embodiment shown, the cup-shaped element 132a has a cylindrical shape with a circular cross section (for example, with a diameter of 5.08 cm (2 inches) or less. In some embodiments, a cup-shaped element also may include bayonet-style pins (not shown, but similar to 148, 152) configured to align with the corresponding grooves in the head 46a of the probe 38a to lock the position of the sparking head 22b with respect to the probe.
[087] In the embodiment shown, conductors 160d, 160e and 160f extending through a rear part (the outlet end element opposite 136a) of side wall 132a, as shown. In this embodiment, the central conductor 160b and the peripheral conductors 160a, 160c can be molded on the side wall 120a so that insulating rings and the like are not necessary to seal the interface between the side wall and the conductors. In the modality shown, a central conductor 160d serves as a ground for the corresponding central electrodes 100d1 and 100d-2, which are also in electrical communication with each other. The drivers
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40/73 peripherals 160e, 160f are in communication with peripheral electrodes 100e, 10Of to generate sparks through the spark gap between electrodes 100d1 and 100e, and between electrodes 100d-2 and 10Of. It should be understood that, as long as two spark openings are shown, any number of spark openings can be used, and can be limited only by the size and spacing of the spark openings. For example, other modalities include 3, 4, 5, 6, 7, 8, 9, 10, or even more spark openings.
[088] In the illustrated embodiment, the central electrodes 100d-1 and 100d-2 are carried by, and can be unitary with, an elongated member 172 which extends into chamber 124a towards the cap member 136a from the side wall 120a. In this embodiment, the element 172 is mounted on a hinge 176 (which is fixed in relation to the side wall 120a) to allow the distal end of the element (adjacent electrodes 100d-1, 100d-2 to articulate back and forth between the electrodes 100e and 10Of, as indicated by arrows 180. In the mode shown, the distal part of element 172 is tilted towards electrode 100e by spring arms 184. In this mode, spring arms 184 are configured to position electrode 100d- 1 at an initial sparking opening distance from electrode 100e, by applying an electrical potential (for example, through a pulse generation system, as described elsewhere in this description) through electrodes 100d-1 and 100e, a spark will form between these two electrodes to release an electrical pulse to vaporize the liquid between these two electrodes. The expansion of steam between these two electrodes triggers the element 172 and the electrode 100d-2 down towards the electrode 10Of. During the period of time that element 172 travels down, the pulse generation system recharges and applies an electrical potential between electrodes 100d-2 and 10Of, so that when the distance between electrodes 100d-2
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41/73 and 10Of becomes small enough, a spark will form between these two electrodes to release the electrical pulse to vaporize the liquid between these two electrodes. The steam expansion between electrodes 100d-2 and 10Of then drives element 172 and electrode 100d-1 upwards towards electrode 100e. During the period of time in which element 172 travels upward, the pulse generation system can recharge and apply an electrical potential between electrodes 100d-1 and 100e, so that when the distance between electrodes 100d-1 and 100e becomes small enough, a spark forms between these two electrodes to release the electrical pulse and vaporize the liquid between these two electrodes, causing the cycle to start over. Thus, element 172 oscillates between electrodes 100e and 10Of until the electrical potential is no longer applied to the electrodes.
[089] Exposure to high-rate, high-energy electrical pulses, especially in liquid, subjects the electrodes to rapid oxidation, erosion, and / or other deterioration that can vary the distance of the spark gap between the electrodes if the electrodes are held in fixed positions (for example, requiring electrodes to be replaced and / or adjusted). However, in the modality of Figure 2B, the rotation of the element 172 and the electrodes 100d-1, 100d-2 between the electrodes 100e and 10Of effectively adjust the spark gap for each spark. In particular, the distance between the electrodes at which current arcs between the electrodes is a function of the electrode material and the electrical potential. As such, since the surfaces closest (even if eroded) to adjacent electrodes (for example, 100d-1 and 100e) reach a spark gap distance for a given modality, a spark is generated between the electrodes. As such, element 172 is configured to self-adjust the respective spark openings between electrodes 100d-1 and 100e, and between electrodes 100d-2 and 10Of.
[090] Another example of an advantage of the present mobile electrodes, as in
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Figure 2B, is that several coils are not necessary, since the electrodes are positioned in such a way that only one pair of electrodes is within the arc distance at any given time, and that single coil or coil system is configured to recharge in less time than it takes for joint element 172 from one electrode to the next. For example, in the form of Figure 2B, an electrical potential can be applied simultaneously to electrodes 100e and 10Of with electrodes 100d-1 and 100d-2 serving as a common ground, with the electrical potential in such a way that a spark will form between electrodes 100d-1 and 100e when element 172 is articulated upwards in relation to the horizontal (in the orientation shown), and will only form between electrodes 100d-2 and 10Of when element 172 is articulated downwards in relation to horizontal. As such, as element 172 pivots up and down as described above, a single coil or coil system can be connected to both peripheral electrodes 100e, 10Of and discharged alternately through each of the peripheral electrodes. In such embodiments, the pulse rate can be adjusted by selecting the physical properties of element 172 and spring arms 184. For example, properties (for example, mass, stiffness, transverse shape and area, length, and / or element 172 and the properties (for example, spring constant, shape, length and / or the like) of spring arms 184 can be varied to adjust the resonance frequency of the system, and thus the pulse rate of the head. or sparking module 22b. Similarly, the viscosity of liquid 128a can be selected or adjusted (for example, increased to reduce the travel speed of the arm 172, or decreased to increase the travel speed of the arm 172).
[091] Another example of an advantage of the present mobile electrodes, as in Figure 2B, is that the properties (for example, shape, cross-sectional area, depth, and the like) of the electrodes can be configured to achieve
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43/73 a known or effective life for the sparking head (e.g., a 30-minute treatment) so that sparking head 22b is inoperative or of limited effectiveness after that designated life. Such a feature can be useful to ensure that the sparking head is discarded after a single treatment, such as, for example, to ensure that a new sterile sparking head is used for each patient or treated area to minimize the potential cross contamination between the patients or treated areas.
[092] Figure 2C represents an enlarged side view of a third modality of a removable sparking head or module 22c. The sparking head 22c is substantially similar to the sparking head 22b, except as indicated below, and similar reference numbers are therefore used to designate structures of the sparking head 22c that are similar to the corresponding structures of the sparking head 22b. The main difference from the spark head 22b is that the spark head 22c includes a beam 172a that does not have a hinge, so that the bending of the beam itself provides the movement of the electrodes 100d-1 and 100d-2 in the directions for up and down indicated by arrows 180, as described above for the sparking head 22b. In this embodiment, the resonant frequency of the sparking head 22c is especially dependent on the physical properties (e.g., mass, stiffness, shape of cross-section and area, length, and / or the like) of beam 172a. As described for spring arms 184 of sparking head 22b, beam 172a is configured to be tilted towards electrode 100e, as shown, so that electrode 100d-1 is initially positioned at an initial sparking gap from electrode 100e. The function of the sparking head 22c is similar to the function of the sparking head 22b, with the exception that the beam 172a itself bends and provides some resistance to movement so that the hinge 176 and
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44/73 the spring arms 184 are unnecessary.
[093] In the embodiment shown, the spark head 22b also includes connectors or liquid ports 188, 192 through which the liquid can circulate through the spark chamber 124b. In the embodiment shown, a proximal end 196 of the sparking head 22b serves as a combined connection with two liquid lumens (connectors or ports 188, 192) and two or more (for example, three, as shown) electrical conductors (connectors 160d, 160e, 160f). In such embodiments, the combined 196 proximal end connection can be coupled (directly or via a probe or handpiece) with a combined chain or cable having two lumens for liquid (corresponding to connectors or ports 188, 192), and two or more electrical conductors (for example, a first electrical conductor for connection to connector 160d and a second electrical conductor for connection to both peripheral connectors 160e, 160f). Such a combined chain or cable can couple the spark head (for example, and a probe or handpiece to which the spark head is attached) to a pulse generation system having a liquid reservoir and pump such that the pump can circulate the liquid between the reservoir and the spark chamber. In some embodiments, the cap element 136a is omitted so that the connectors or ports 188, 192 can allow the liquid to be circulated through a larger chamber (e.g. 18a) of a handpiece to which the sparking head is coupled. Likewise, a probe or handpiece to which the spark head 22a is configured to be attached can include electrical connectors and liquid connectors that correspond to the respective electrical connectors (160d, 160e, 160f) and connectors for liquid (188, 192 ) of the spark head so that the electrical connectors and the liquid connectors of the spark head are simultaneously connected to the respective electrical connectors and connectors for
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45/73 liquid from the probe or handpiece as the spark module is attached to the handpiece (for example, by pressing the spark head and probe together and / or twisting or rotating the spark head in relation to the probe).
[094] In the present modalities, a pulse rate from a few Hz to many KHz (for example, up to 5 MHz) can be used. Since the stressful event produced by a plurality of pulses, or shock waves, is generally cumulative with higher pulse rates, treatment time can be significantly reduced by using many moderately fed shock waves in rapid succession instead of a few. higher power shock waves spaced for long periods of rest. As mentioned above, at least some of the present modalities (for example, those with multiple spark openings) allow the electrohydraulic generation of shock waves at higher rates. For example, Figure 3A represents an extended time diagram to show only two sequences of voltage pulses applied to the electrodes of the present modalities, and Figure 3B represents a time diagram showing a greater number of voltage pulses applied to the electrodes of the present modalities. present modalities.
[095] In additional modalities that are similar to any of the sparking modules 22a, 22b, 22c, a part of the respective side wall (120, 120a, 120b) can be omitted so that the respective sparking chamber (124, 124a, 124b) is also omitted or left open so that a liquid in the larger chamber (e.g., 18 or 18a) of a corresponding handpiece can circulate freely between the electrodes. In such embodiments, the sparking chamber (for example, the side wall 120, 120a, 120b) can include liquid connectors or the liquid can circulate through liquid ports that are independent of the sparking chamber (for example, as shown in Figure 2).
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46/73 [096] The part of the pulse train or sequence 200 shown in Figure 3A includes timed pulse groups 204 and 208 with a delay period 212 in the middle. Bursts or groups (for example, 204, 208) can include at least one or two, or at most thousands, of pulses. In general, each group 204, 208 can include several voltage pulses that are applied to the electrodes to trigger an event (i.e., a spark through a spark gap). The length of the delay period 212 can be configured to allow the electrodes to cool through each spark opening and to allow the electronics to be recharged. As used for the modalities of this description, the pulse rate refers to the rate at which the voltage pulse groups (each having one or more pulses) are applied to the electrodes; which means that individual pulses within groups of pulses having two or more pulses are applied at a higher frequency, as illustrated in Figures 3A-3B. Each of these groups of pulses can be configured to generate a shock wave or a plurality of shock waves.
[097] A series of events (sparks) initiated by a plurality of bursts or groups 204 and 208 delivered with the present systems and devices can comprise a higher pulse rate (PR), which can reduce the treatment time in relation to the PRs that may need to be applied over many minutes. Tattoos, for example, can span large areas and therefore take more time to treat, unless rapid cell destruction is achieved (for example, with the highest PRs in this description). In contrast to prior art systems noted above, the present modalities can be configured to deliver shock waves at a relatively high PR 216 of 10 to 5000 or more pulses per second (for example, greater than any of, or among any two of: 10 Hz, 30 Hz, 50 Hz, 1000 Hz, 10000 Hz, 1000000 Hz, 500000 Hz, and / or 5000000 Hz.
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47/73 [098] Figure 4 represents a waveform that can be emitted by any of the probes 38 or 38a in a volume of tissue, and that is in a way that can be useful for the elimination of tattoos. Pulse 300 is typically of an impulse generated by the present EH spark heads in relatively high voltage pulses. For example, pulse 300 has a fast rise time, a short duration, and a descent period. The vertical axis units V _a are arbitrary as can be displayed on an oscilloscope. The actual amplitude of the acoustic pulse can be at least 50 pPa and at most several MPa in several of the present modalities, at least because the cumulative energy delivery can be effective, as discussed above. The individual 304 time periods can be 100 nanoseconds each, which corresponds to short pulse lengths referred to in the art as "shock wave" pulses, due to their sharpness and short rise and fall times. For example, a rise time of <30 nanoseconds is considered to be a shock wave for the purposes of this description, speed being particularly effective for producing large relative time-pressure gradients through small cellular structures in the tissue (for example , the dermis). Rapid compression and decompression of dermal structures containing tattoo "inks", which are actually particulate pigments, is believed to result in fatigue and destruction of pigment-containing cells over time and to be an underlying mechanism of present methods, as described above. For example, shaking the tissue with such shock waves proved effective when applied at high pulse rates within a relatively short period of time, and at sufficient energy levels to produce a pigmented cell until rupture, with resulting release of retained particles and the subsequent spread of pigment particles in the body, thus reducing the appearance of the tattoo. It is believed that it is necessary to have a short pulse waveform 300, which
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48/73 can be applied several times and preferably many hundreds of millions of times to an area to be treated to produce the fatigue necessary to remove the "ink" from the tattoo.
[099] Figure 5 represents a schematic diagram of a modality 400 of a pulse generation system, for use in or with some modalities of the present systems. In the embodiment shown, circuit 400 comprises a plurality of charge storage / discharge circuits, each with a coil of the magnetic or induction storage type 404a, 404b and 404c, (for example, similar to those used in automobile ignition systems ). As illustrated, each of the coils 404a, 404b, 404c can be grounded via a resistor 408a, 408b, 408c to limit the current allowed to flow through each coil, similar to certain aspects of automobile ignition systems. Resistors 408a, 408b, 408c can comprise dedicated resistors, or the length and properties of the coil itself can be selected to provide a desired level of resistance. The use of components of the type used in automobile ignition systems can reduce costs and improve safety in relation to custom components. In the embodiment shown, circuit 400 includes a spark head 22b which is similar to spark head 22a with the exceptions that spark head 22b includes three spark openings 412a, 412b, 412c, instead of two, and that each one of the three spark openings is defined by a pair of separate electrodes instead of a common electrode (for example, 100a) cooperating with several peripheral electrodes. It should be understood that the present circuits can be coupled to the peripheral electrodes 100b, 100c of the sparking head 22a to generate sparks through the sparking openings defined with the common electrode 22a, as shown in Figure 2A. In the mode shown, each circuit is configured to function in a similar way. For example, coil 404a is
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49/73 configured to collect and store a current for a short duration so that when the circuit is interrupted at switch 420a, the coil's magnetic field contracts and generates a so-called electromotive force, or EMF, which results in a rapid discharge of the capacitor 424a through the sparking opening 412a.
[0100] The RL or inductance-resistance time constant of coil 404a can be affected by factors such as the size and inductive reactance of the coil, the resistance of the coil windings, and other factors - usually corresponds to the time it takes to overcome the resistance of the coil wires and the time to build the coil's magnetic field, followed by a discharge that is controlled again by the time it takes for the magnetic field to contract and the energy to be released through and overcome the resistance of the circuit. This time constant RL generally determines the maximum charge-discharge cycle rate of the coil. If the charge-discharge cycle is too fast, the current available in the coil can be very low and the resulting sparking pulse weak. The use of multiple coils can overcome this limitation by firing multiple coils in rapid succession for each group of pulses (for example, 204, 208, as shown in Figure 3A). For example, two coils can double the practical charge-discharge rate, doubling the (combined) current and the resulting sparking pulse, and three (as shown) can effectively triple the effective charge-discharge rate. When using multiple spark openings, time can be very important for the proper generation of spark spikes and liquid vaporization and resulting shock waves. As such, a controller (for example, microcontroller, processor, FPGA, and / or the like) can be coupled to each of the control points 428a, 428b, 428c to control the opening time of switches 420a, 420b, 420c and a discharge resulting from capacitors 424a, 424B, 424c and the generation of shock waves.
[0101] Figure 6 represents a block diagram of a 500 modality of
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50/73 a system for generating acoustic shock waves powered by radio frequency (RF). In the embodiment shown, the system 500 comprises a non-linear medium 504 (for example, as in the acoustic delay chamber 58 or non-linear element described above) that provides an acoustic path from a transducer 508 to the target tissue 512 to produce practical acoustic or harmonic energy (for example, shock waves). In the modality shown, transducer 508 is powered and controlled through bandpass filter and tuner 516, RF power amplifier 520, and control switch 524. The system is configured such that switching 524 activates a pulse generator 528 to produce timed RF pulses trigger amplifier 520 in a predetermined manner. A typical drive waveform, for example, can comprise a sine wave burst (for example, several sine waves in rapid succession). For example, in some embodiments, a typical burst can have a burst length of 10 milliseconds and comprises sine waves having a period duration from 0.1 (frequency of 100 MHz) to more than 2 microseconds (frequency of 50 kHz).
[0102] The embodiments of the present methods comprise positioning a modality of the present apparatus (for example, 10, 38, 38a, 500) adjacent to a region of a patient comprising the target cells (for example, tissue 74); and activate the spark generation system (for example, capacitive / inductive coil) (for example, 26, 400) to propagate shock waves to the target cells. In some embodiments, the region is viewed through a window (for example, 82, 82a), while positioning the device and / or while shock waves are generated and delivered to the region. Some embodiments also include attaching a removable sparking head or module (for example, 22a, 22b) to a device housing before activating the pulse generation system.
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Experimental results [0103] Experiments were conducted on samples of tattooed skin obtained from deceased primates to observe the effects of shock waves generated by HE on the tattooed skin. Figures 7A-7B and 8 represent two different prototype sparking chamber housings. The embodiment of Figures 7A-7B illustrates a first embodiment 600 of a sparking chamber housing that was used in described experiments. Housing 600 is similar in some respects to the part of housing 14a that defines the head 46a of probe 38a. For example, housing 600 includes fittings 604, 608 that allow liquid to be circulated through the sparking chamber 612. In the embodiment shown, housing 600 includes electrode holders 616 and 620 through which electrodes 624 can be inserted to define a 628 spark gap (for example, 0.127 mm or 0.005 inches in the experiments described below). However, housing 600 has an internal elliptical surface in order to reflect the shock waves that initially move backwards from the sparking opening towards the wall. In doing so, it has the advantage of producing, for each shock wave generated at the spark gap, a first shock wave or primary shock wave that propagates from the spark gap to output 640, followed by a wave of secondary shock that first spreads to the elliptical inner wall and is then reflected back to exit 640.
[0104] In this embodiment, the supports 616 and 620 are not aligned with (rotated approximately 30 degrees around the chamber 612 in relation to) fittings 604, 608. In the modality shown, the housing 600 has a hemispherical shape and the electrodes 624 are positioned so that an angle 632 between a central axis 636 through the center of the shock wave output 640 and a perimeter 644 of the chamber 612 is approximately 57 degrees. Other modalities
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52/73 can be configured to limit this angular sweep and thus direct sound waves and / or shock waves through a smaller output. For example, Figure 8 represents a cross-sectional view of a second embodiment 600a of a sparking chamber housing. The housing 600a is similar to the housing 600, with the exception that the fittings 604a, 608A are rotated 90 degrees with respect to the supports 616a, 620a. The housing 600a also differs in that the chamber 612a includes a hemispherical proximal or rear part and a trunk-conical front or distal part. In this embodiment, electrodes 624a are positioned so that such an angle 632a between a central axis 636a through the center of the shock wave output 640a and a perimeter 644a of chamber 612a is approximately 19 degrees.
[0105] Figure 9 represents a schematic diagram of an electrical circuit for a prototype pulse generation system used with the spark chamber housing of Figures 7A-7B in the present experimental procedures. The scheme includes symbols known in the art, and is configured to obtain pulse generation functionality similar to that described above. The described circuit is capable of operating in the relaxation discharge mode with modalities of the present shock wave heads (for example, 46, 46a, etc.). As shown, the circuit comprises a 110V alternating current (AC) power supply, an on-off switch, a timer (“control block”), an elevator transformer that has a secondary voltage of 3 kV or 3000 V. The secondary AC voltage is rectified by a pair of high voltage rectifiers in the full wave configuration. These rectifiers carry a pair of oppositely polarized capacitors of 25 mF that are each protected by a pair of resistors (100 kQ and 25 kQ) in parallel, which together temporarily store the high voltage energy. When the impedance of the shock wave chamber is low and the voltage load is high, a discharge begins, aided by
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53/73 ionization switches, which are large sparking openings that conduct when the limit voltage is reached. A positive voltage and a negative voltage flow to each of the electrodes so that the potential between the electrodes can be up to approximately 6 kV or 6000 V. The resulting spark between the electrodes results in the vaporization of a portion of the liquid into a bubble of rapidly expanding gas, which generates a shock wave. During the spark, the capacitors discharge and become ready for recharging by the transformer and rectifiers. In the experiments described below, the discharge was approximately 30 Hz, regulated only by the natural charge and discharge rate and therefore the term "relaxation oscillation". In other embodiments, the discharge rate can be as high (for example, at most 100 Hz) as the configuration of multiple openings in Figure 5.
[0106] A total of 6 primate skin samples tattooed and excised were obtained, and the specimens were segregated, immobilized on a substrate, and placed in a water bath. A total of 4 tattooed specimens and 4 non-tattooed specimens were segregated, with each of the tattooed and un-tattooed specimens kept as controls. Shock chamber housing 600 was placed over each of the excised specimens and voltage pulses applied to the 624 electrodes at full energy for several durations. The shock waves were generated at a voltage of approximately 5-6 kV and approximately 10 mA, which resulted in a power level of approximately 50 W per pulse, and the shock waves were delivered at a rate of approximately 10 Hz. For the purposes of the experiments described, several exposure periods were used and the results observed after the cumulative exposure periods (for example, the cumulative total time of 10 to 20 minutes) as indicative of a longer exposure period and / or a exposure period at a higher pulse rate. The immediate results observed in the water bath showed a
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54/73 clot formation around the edge of the samples, which is believed to indicate residual blood flow from repeated shock waves. All specimens were placed in formalin for histopathological examination. A histopathologist reported an observed rupture of cell membranes and a dispersion of tattoo particles to macrophages containing tattoo pigment in the treated tissue. Changes in the adjacent tissue - such as thermal damage, rupture of basal cells or formation of vacuoles - were not observed. The specimen showing the most obvious rupture, which could easily be seen by an untrained eye, had the duration of exposure to the highest shock wave in the group. This strongly suggests a limit effect that could be further illustrated as power and / or time are increased.
[0107] Additional tests in vivo on monkeys and pigs, and in vitro tests on monkeys were subsequently performed using an additional modality 38b of the present probes (for example, portable) for use with some modalities of the present EH shock wave generation systems. and apparatus shown in Figures 11-13C. Probe 38b is similar in some respects to probes 38 and 38a, and the differences are therefore mainly described here. In this embodiment, the probe 38b comprises: a housing 14b defining a chamber 18b and a shock wave output 20b; a liquid (54) disposed in the chamber 18b; a plurality of electrodes (for example, on the head or sparking module 22d) configured to be arranged in the chamber to define one or more sparking openings; and is configured to be coupled to a pulse generation system 26 configured to apply voltage pulses to the electrodes at a rate between 10 Hz and 5 MHz.
[0108] In the modality shown, the sparking head 22d includes a side wall or body 120d and a plurality of electrodes 100g that define a
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55/73 spark opening. In this embodiment, probe 38b is configured to allow liquid to be circulated through chamber 18b via connectors or liquid ports 112b and 116b, one of which is coupled to the spark head 22d and the other of which is coupled to housing 14b, as shown. In this embodiment, housing 14b is configured to receive sparking head 22d, as shown, so that housing 14b and housing 120d cooperate to define chamber 18b (for example, so that sparking head 22d and housing 14b include complementary parabolic surfaces that cooperate to define the chamber). In this embodiment, the housing 14b and the sparking head 22d include acoustically reflective coatings 700, 704 that cover their respective surfaces that cooperate to define the chamber 18b. In this embodiment, the housing 120d of the sparking head 22d includes a channel 188b (for example, along a central longitudinal axis of the sparking head 22d) that extends between the liquid connector 112b and the chamber 18b and aligned with the opening of sparking between the electrodes 100 g such that the circulating water will flow in close proximity and / or through the sparking opening. In the embodiment shown, housing 14b includes a channel 192b that extends between connection 116b and chamber 18b. In this embodiment, housing 120d includes a groove 708 configured to receive a resilient gasket or O-ring 140a to seal the interface between the spark head 22d and housing 14b, and housing 14b includes a groove 712 configured to receive a resilient gasket or O-ring 140b to seal the interface between housing 14b and cover element 136b when cover element 136b is attached to housing 14b by ring 716 and retaining ring 144b.
[0109] In the modality shown, each of the 100 g electrodes includes a flat bar part 724 and a perpendicular cylindrical part 728 (for example, comprising tungsten for durability), in electrical communication (for example
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56/73 example, unitary with) the bar part 724 so that the cylindrical part 728 can extend through a corresponding opening 732 in the sparking head 22d to the chamber 18b, as shown. In some embodiments, a portion of the sides of the cylindrical portion 728 may be covered with a resilient and / or electrically insulating material (e.g., retractable coating) such as, for example, to seal the interface between portion 728 and the housing 120b. In this embodiment, the housing 120b also includes longitudinal grooves 732 configured to receive parts of bars 724 of electrodes 100g. In the embodiment shown, the housing 38g also includes adjusting screws 736 positioned in line with the cylindrical parts 732 of electrodes 100g when the sparking head 22d is arranged in the housing 38g, so that the adjustment screws 736 can be tightened to press the cylindrical parts 736 inward to adjust the spark gap between the cylindrical parts of electrodes 100g. In some embodiments, the sparking head 22d is permanently adhered to housing 38b; however, in other embodiments, the sparking head 22d may be removable from housing 38b such as, for example, to allow replacement of the electrodes 100g individually or as part of a new replacement sparking head or head 22d.
[0110] Figure 14 represents a schematic diagram of a second modality of an electrical circuit of a prototype pulse generation system. The circuit in Figure 14 is substantially similar to the circuit in Figure 9, with the main exception that the circuit in Figure 14 includes an array of fired spark openings instead of ionization switches, and includes certain components with different properties than the corresponding components in the circuit of Figure 9 (for example, 200 kQ resistors instead of 100 ΚΩ). In the circuit of Figure 14, block “1” corresponds to a main controller (for example, processor) and block “2” corresponds to a timer controller of
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57/73 voltage (eg oscillator), both of which can be combined into a single unit in some modes.
[0111] In additional in vitro tests on monkeys, probe 38b of Figures 11-13C was placed over the respective subjects' tattoos and was powered by the circuit in Figure 14. In tests on monkeys, voltage pulses were applied to 100g electrodes in varied frequencies (30-60 Hz) for durations ranging from one minute to ten minutes. At the highest power, shock waves were generated at a voltage of approximately 0.5 kV (between a maximum of approximately + 0.4 kV and a minimum of approximately - 0.1 kV) and a current of approximately 2300 A (between a maximum of approximately 1300 A and a minimum of approximately -1000 A), which resulted in a total power of approximately 500 kW per pulse and delivered energy of approximately 420 mJ per pulse, and the shock waves were delivered at a rate of approximately 30 Hz. As with previous in vitro tests, a histopathologist reported an observed disruption of cell membranes and a dispersion of tattoo particles to macrophages containing tattoo pigment in the treated tissue. Changes to the surrounding tissue - such as thermal damage, rupture of basal cells or formation of vacuoles - were not observed. The specimens showing the most obvious disruption were those with power and duration of exposure to the highest shock waves. These results suggested that the increase in power and the increase in the number of shocks (resulting in an overall increase in power delivered) caused an increase in the breakdown of pigments, which was consistent with previous in vitro tests.
[0112] In the in vivo tests, the probe 38b of Figures 11-13C was placed on the tattoos of the respective subjects and was fed by the circuit of Figure 14. In tests on monkeys, voltage pulses were applied to the electrodes at 100g at maximum power for a duration of two minutes and repeated once a week
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58/73 for six weeks. The shock waves were generated at a voltage of approximately 0.5 kV (between a maximum of approximately + 0.4 kV and a minimum of approximately - 0.1 kV) and a current of approximately 2300 A (between a maximum of approximately 1300 A and a minimum of approximately 1000 A), which resulted in a total power of approximately 500 kW per pulse and energy delivered of approximately 420 mJ per pulse, and the shock waves were delivered at a rate of approximately 30 Hz. In vivo tests on pigs were similar, except that shock waves were applied for the duration of four minutes in each application. One week after the sixth shock wave application, biopsies were performed from each tattoo. All specimens were placed in formalin for histopathological examination. A histopathologist reported an observed rupture of cell membranes and a dispersion of tattoo particles to macrophages containing tattoo pigment in the treated tissue, with a relatively greater dispersion for specimens that underwent 4-minute treatments than those that underwent treatments 2 minutes. Changes to the surrounding tissue - such as thermal damage, rupture of basal cells or formation of vacuoles - were not observed. These results were consistent with those observed for in vitro tests on monkeys. In general, these studies suggested that the increase in power and the increase in the number of shocks (resulting in a general increase in power delivered - for example, due to the increase in the duration of treatment).
Methods [0113] Examples of diseases and / or conditions involving particles agglomerated in cellular structures include cancer, crystalline microparticles in the musculoskeletal system, or removal of tattoos. These are exemplified, merely non-limiting conditions that can be treated or addressed by rupture or destruction of cells containing particle clusters. In some
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59/73 modalities, the destruction of cells containing particle agglomeration can be caused by degradation of the non-thermal cell membrane of specific cells secondary to non-linear processes following the propagation of high frequency shock waves, as discussed above.
[0114] Some general modalities of the present methods include: delivering a plurality of shock waves generated in an electro-hydraulic way (for example, via one or more of the present devices) to at least one cellular structure comprising at least one region of heterogeneity up to that at least one cell structure breaks down. In some embodiments, shock waves are delivered for no more than 30 minutes in a 24-hour period. In some embodiments, shock waves are delivered for no more than 20 minutes in a 24-hour period. In some embodiments, between 200 and 5000 shock waves are delivered between 30 seconds and 20 minutes in each of a plurality of positions of a shock wave output.
A. Tattoos [0115] Tattoos are essentially phagocyting cells, such as fibroblast cells, macrophages, and the like, which contain clusters of ink particles. As the ink particles captured are denser than the biological structures of the cells, tattoos or cells containing ink particles have a big difference in elasticity in their structure. When subjected to shock waves, cells containing ink particles are subjected to greater mechanical stress compared to other cells that do not contain dense particles. The shock waves can be configured to be delivered at an optimal frequency and amplitude to accelerate the ink particles sufficiently to disrupt the particular cells, while leaving fibroblast cells that do not have the particular elasticity difference intact. The details of tattoos and the biological process of removing released cells are discussed below.
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60/73 [0116] Tattoo inks and dyes have historically been derived from substances found in nature and generally include a heterogeneous suspension of pigment particles and other impurities. An example is Indian ink, which includes a suspension of carbon particles in a liquid such as water. Tattoos are usually produced by applying tattoo ink to the dermis, where the ink usually remains substantially permanently. This technique introduces the suspension of pigment through the skin by an alternating pressure-sucking action caused by the elasticity of the skin in combination with the up and down movement of a tattoo needle. Water and other carriers for the pigment introduced into the skin diffuse through the tissues and are absorbed. For the most part, 20% to 50% of the pigment is disseminated in the body. However, the remaining part of the insoluble pigment particles is deposited in the dermis where it is placed. In tattooed skin, pigment particles are usually phagocytized by cells resulting in pigment clusters in the cytoplasm of cells (that is, in membrane-bound structures known as secondary lysosomes). The resulting pigment clusters (“particle clusters”) can vary up to a few micrometers in diameter. Once the skin has healed, the pigment particles remain in the interstitial space of the skin tissue within the cells. Tattoo inks generally resist elimination due to cell immobility due to the relatively large amount of insoluble pigment particles in the cells. A tattoo may discolor over time, but it will usually remain for the life of the person tattooed.
[0117] Tattoo inks typically comprise aluminum (87% of pigments), oxygen (73% of pigments), titanium (67% of pigments), and carbon (67% of pigments). The relative contributions of elements to tattoo ink compositions were highly variable across different compounds. To
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61/73 minus one study determined the particle size for three commercial tattoo inks as shown in Table 1:
Table 1: Pigment particle size d and tattoo Color Average diameter Standard deviation Viper Red 341 nm 189 nm Agent Orange 228 nm 108 nm Hello yellow 287 nm 153 nm
Tattoo removal B.
[0118] In conventional tattooing (decorative, cosmetic, and reconstructive), since the pigment or dye was administered in the dermis to form a tattoo, the pigment or dye generally remains permanently in place, as discussed above.
[0119] Despite the general permanence of tattoos, individuals may wish to change or remove tattoos for a variety of reasons. For example, over time people may experience a change of heart (or mind), and may wish to remove or change the design of a decorative tattoo. As another example, an individual with a cosmetic tattoo, such as coloring eyeliner, eyebrows, lips, may wish to change the color or the tattooed area as the fashion changes. Unfortunately, there is currently no simple and successful way to remove tattoos. Currently, methods of removing traditional tattoos (for example, skin containing pigment) can include salabrasion, cryosurgery, surgical excision, and CO2 laser. These methods may require invasive procedures associated with potential complications, such as infections, and usually result in the formation of visible scarring. More recently, the use of Q-switched lasers has gained wide acceptance for tattoo removal. By restricting the pulse duration, ink particles generally reach very high temperatures resulting in the destruction of cells containing tattoo ink pigment with relatively minimal damage to adjacent normal skin. This significantly lessens the scar that often results after
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62/73 non-selective tattoo removal methods, such as dermabrasion or carbon dioxide laser treatment. The mechanisms of tattoo removal by Q-switch laser radiation may still be poorly understood. It is known that the Q-switch laser allows the more specific removal of tattoos by the mechanisms of selective photothermolysis and thermokinetic selectivity. Specifically, it is known that the pigment particles in cells are capable of absorbing laser light causing the heating of the particles resulting in the thermal destruction of the cells containing said particles. The destruction of these cells results in the release of particles that can then be removed from the tissue through normal absorption processes.
[0120] While the Q-switch laser may be better than some alternatives for tattoo removal, it is not perfect. Some tattoos are resistant to all laser therapies, despite the predicted high particle temperatures achieved through selective photothermolysis. The reasons cited for failure to erase some tattoos include the absorption spectrum of the pigment, the depth of pigment, and the structural properties of some inks. Adverse effects after laser tattoo treatment with the Qswitched ruby laser can include textural changes, scarring, and / or pigmentary changes. Transient hypopigmentation and textural changes have been reported in up to 50 and 12%, respectively, of patients treated with Q-switched alexandrite laser. Hyperpigmentation and textural changes are uncommon adverse effects of the Q-switched Nd: YAG laser, and the incidence of hypopigmentary changes is generally lower than with the ruby laser. The development of localized and generalized allergic reactions is also an impossible (if rare) complication of tattoo removal with Q-switched ruby and Nd: YAG lasers. Additionally, laser treatment can be painful, so the use of a local injection with lidocaine or topical anesthesia cream is typically used
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63/73 before laser treatment. Finally, laser removal usually requires several treatment sessions (for example, 5 to 20) and may require expensive equipment for maximum disposal. Typically, since many wavelengths are needed to treat colored tattoos, not only can a laser system be used alone to remove all available inks and ink combinations. Even with various treatments, laser therapy may only be able to remove 50 to 70% of the tattoo pigment, resulting in a residual stain.
[0121] Some modalities of the present methods include: directing the shock waves generated in an electro-hydraulic way (for example, from a modality of the present devices) to the cells of a patient; where the shock waves are configured to cause the particles to rupture one or more of the cells. Some modalities include: providing a modality of the present devices; activate the device for the first shock waves configured to cause the particles inside a patient to rupture one or more cells of the patient; and directing the shock waves to a patient's cells so that the shock waves cause the particles to rupture one or more of the cells (for example, such as by degradation of the cell wall or membrane). In some embodiments, one or more shock waves are configured to have substantially no lasting effect on cells in the absence of particles (for example, configured to cause substantially no permanent or lasting damage to cells that are not close enough to the particles to be damaged by particles in the presence of shock waves).
[0122] Some modalities of the present methods comprise focusing one or more shock waves on a specific region of tissue that comprises the cells. In some embodiments, the region of tissue in which one or more waves
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64/73 shock focus is a depth under the patient's skin. Shock waves can be focused by any of a variety of mechanisms. For example, a surface of the present apparatus that is configured to contact a patient during use (for example, of the outlet element 70a) can be shaped (for example, convex) to focus or formed (for example, convex) to disperse the shock waves, such as, for example, to narrow the area to which the shock waves are directed or to expand the area to which the shock waves are directed. Focusing on shock waves can result in higher pressures on target cells, such as, for example, pressures of 10 MPa, 15 to 25 MPa, or greater. In some embodiments, the convex outer shape is configured to stretch a part of the patient's skin as the outlet element is pressed against the skin.
[0123] Some modalities of the present methods further include: identifying target patient cells to be disrupted (for example, before directing one or more shock waves to the target cells). In various embodiments, the target cells can comprise any of a variety of target cells, such as, for example, target cells comprising a condition or disease involving clusters of cell particles. For example, target cells may comprise: a tattoo, musculoskeletal cells comprising crystalline microparticles, hair follicles that contain keratin protein, dental follicles that contain enamel, cancer cells, and / or the like. As another example, the target cells may comprise one or more skin diseases selected from the group consisting of: blackheads, cysts, pustules, papules and pimples.
[0124] In some embodiments, the particles may comprise unnatural particles. An example of unnatural particles includes tattoo pigment particles, as they are normally arranged in the human dermis to create a
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65/73 tattoo. In some embodiments, the pigments may comprise an element with an anatomical number less than 82. In some embodiments, the particles may comprise any or a combination of: gold, titanium dioxide, iron oxide, carbon, and / or gold. In some embodiments, the particles have an average diameter of less than 1000 nm, (for example, less than 500 nm and / or less than 100 nm).
[0125] Figure 10 illustrates an embodiment of a method 700 of using the apparatus 10 to direct shock waves to the target tissue. In the embodiment shown, method 700 comprises a step 704 in which target cells 708 of tissue from a patient 712 are identified for treatment. For example, tissue 712 may comprise skin tissue, and / or target cells 708 may comprise cells containing tattoo pigment within or near the skin tissue. In the embodiment shown, method 700 also comprises a step 716 in which a probe or handpiece 38 is disposed adjacent to tissue 712 and / or tissue 716, so that shock waves originating in probe 38 can be directed towards cells target 708. In the embodiment shown, method 700 also comprises a step 720 in which a pulse generation system 26 is coupled to probe 38. In the embodiment shown, method 700 also comprises a step 724 in which the pulse generation system 26 is activated to generate sparks through the electrodes within a probe 38 to generate shock waves at probe 38 for delivery to target 708 cells, as shown. In the embodiment shown, method 700 also comprises an optional step 728 in which the pulse generation system 26 is decoupled from probe 38, and probe 38 is removed or moved relative to tissue 712. In the embodiment shown, target cells 708 they are omitted from step 728, representing their destruction. Other embodiments of the present methods may comprise some or all of the steps illustrated in Figure 10.
C. Methods for removing marks on fabrics
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66/73 [0126] In some embodiments of the present methods of reducing tissue marks (for example, tattoos) caused by pigments in the dermis fabric involve the use of one of the present devices. In such methods, high frequency shock waves are transmitted to the skin of a patient, so that when the shock waves generated from the apparatus of the present description reach the dermal cells and vibrate or accelerate the intradermal particles, these particles they experience movement in relation to cell membranes which can lead to fatigue and cell breakdown, thus releasing pigment particles. The released particles can then be removed from the surrounding tissue through normal absorption processes from the patient's body. In some embodiments, one of the present devices may be arranged adjacent, and / or so that the shock waves from the device are directed to the site of the tissue that has the tattoo, other marks on the tissue, or other cellular structures containing agglomerates of particles. To cause particle change (for example, enough cell degradation to release particles for absorption), shock waves can be delivered to a specific area for a period of time long enough to disrupt the cells containing and / or adjacent to the pigment particles so that the pigment particles are released. In some embodiments, the present devices have an effective focus or area that can be relatively smaller than a tattoo, so that the device can be periodically and sequentially focused and directed to different areas of a tattoo to cause a reduction in the perceived pigments on the entire tattoo area. For example, the parameters of the apparatus modalities described here can be modified to achieve the desired number of shocks delivered to a particular site in a desired amount of time. For example, in one mode, shock waves are produced from acoustic waves with a frequency of at least 1 MHz.
Petition 870180062119, of 7/19/2018, p. 77/89
67/73 according to aspects of the present invention and exposed to a particular treatment site for the appropriate period of time to deliver at least approximately 100, 200, 300, 400, 500, or 1000 shock waves to the treatment site. Shock waves can be delivered all at once or through intervals (for example, bursts) of shock waves (such as, 5, 10, 15, 20, 25, 30, 40, 50, etc. shock at a time). The appropriate interval and time between the interval can be modified and / or determined to achieve the desired effect at the treatment site, for example, disruption of the segmented cellular structures. It is understood that if acoustic waves with a higher frequency are used, such as 2 MHz, 3 MHz, 4 MHz, or 5 MHz, the treatment time can be adjusted, probably a shorter exposure time, to reach the amount shock waves delivered to the treatment area.
[0127] As will be appreciated by those skilled in the art, in the modalities of the present methods for removing tattoos, the particles affected by the shock waves can comprise tattoo pigment (particles), just as they can, for example, be at least partially arranged between and / or within the patient's skin cells. Such pigment particles can, for example, include at least one or a combination of any of the following: titanium, aluminum, silica, copper, chromium, iron, carbon, or oxygen.
[0128] The use of high frequency shock waves to remove or reduce marks on the skin has many advantages over the use of lasers. For example, laser treatments for tattoo removal can be very painful. In contrast, high-frequency shock waves (for example, ultrasound shock waves) can be configured and / or applied so that tattoos or other marks on the skin can be removed or reduced with little or no pain for the patient , in particular, for example, where shock waves are directed or otherwise configured to degrade only cells
Petition 870180062119, of 7/19/2018, p. 78/89
68/73 containing tattoo pigments. As another example, laser light directed at the tissue has been shown to cause damage or destruction of surrounding tissues; where high frequency shock waves can be applied in such a way as to cause little damage or destruction to surrounding tissues (for example, because surrounding non-tattooed tissues generally lack tattoo pigment or other particles that can otherwise interact with cells neighbors to cause cell degradation). Finally, laser tattoo removal often requires multiple treatment sessions (for example, 5 to 20 sessions) for maximum tattoo removal, and / or, often requires the use of expensive equipment. Additionally, as many wavelengths of a laser light may be required to remove multicolored tattoos, several laser systems may be required to remove the variety of inks and / or combinations of inks available. As a result, the overall cost of laser tattoo removal can be prohibitively expensive. Even with various treatments, laser therapy can be limited to eliminating only 50 to 70% of the tattoo pigment, and can leave a residual "stain". In contrast, high frequency shock waves are not dependent on the color of the tattoo pigments so that the therapeutic application of high frequency shock waves does not require different devices for different pigment colors, and so the shock waves high frequency can be applied to a relatively large area (for example, the entire area of a tattoo), thereby reducing the number of treatment sessions required to achieve a level of tattoo removal or reduction that is acceptable to the patient ( for example, 30, 40, 50, 60, 70, 80, 90, 95 percent or more of a noticeable reduction in pigment on the patient's skin).
[0129] In some embodiments, the present methods include the application of high frequency shock waves (for example, with one or more of the present devices) and the application of laser light. For example, some modalities of
Petition 870180062119, of 7/19/2018, p. 79/89
69/73 present methods further comprise directing a beam of light from a Q-switched laser at target cells (eg, tattooed skin). In some modalities, directing one or more shock waves and directing the beam of light are performed in an alternating sequence.
[0130] In some embodiments, the present methods include delivering one or more chemical or biological agents (for example, configured to assist in the removal of tissue marks, such as tattoos) to a position at or near the target cells, before, after , and / or simultaneously with the directing of one or more shock waves to the target cells. For example, some modalities of the present methods further include applying a chemical or biological agent to the skin (for example, before, after and / or simultaneously with the direction of one or more shock waves and / or a beam of laser light on the skin ). Examples of chemical or biological agents include: chelating agents (for example, ethylene diaminetetraacetic acid (EDTA)); immune modulators (for example, Imiquimod [5]); their combinations; and / or other suitable chemical or biological agent. In various modalities, chemical or biological agents to be delivered transdermally and / or systemically (for example, injection) to target cells (for example, can be applied topically to tattooed skin).
[0131] Some modalities of the present tattoo removal methods include multiple shock wave applications to the tattooed skin tissue (for example, for a duration of at least 1 second (for example, 10 seconds or more), once a week for 6 weeks or more).
D. Method for Treating Additional Diseases and Conditions [0132] In addition to tattoo removal, the modalities of the present methods may include applying high frequency shock waves to treat a variety of diseases under conditions caused by and / or including symptoms in
Petition 870180062119, of 7/19/2018, p. 80/89
70/73 clusters of cellular particles and / or particles arranged in intracellular spaces and / or interstitial spaces. For example, such diseases and / or conditions can include: crystal deposition disease in the joints, ligament, tendon and muscles, and / or dermatological diseases involving clusters of particles including acne, age spots, etc. In addition, the modalities of the present methods may include the application of high frequency shock waves after delivery of nanoparticles to a region of the patient that includes the target cells. For example, in some embodiments, nanoparticles (for example, gold nanoparticles) are delivered to a patient's bloodstream intravenously and allowed to travel to a region of the patient that includes the target cells (for example, a cancerous tumor) , so that high frequency shock waves can be directed to the target region to make the nanoparticles interact with and disrupt the target cells.
[0133] Furthermore, the modalities of the present devices (for example, device 10) can be used to reduce wrinkles. For example, some modalities of the present methods of generating therapeutic shock waves include: providing any of the present devices (for example, the device 10); and activate the device to generate one or more shock waves. Some embodiments further include: arranging the apparatus (for example, the outlet end 34 of housing 18) adjacent to a patient's tissue so that at least one shock wave enters the tissue. In some embodiments, the tissue comprises skin tissue on the patient's face.
[0134] In embodiments of the present methods which include directing the particles (for example, microparticles and / or nanoparticles) to a position at or near the target cells (before directing the shock waves to the cells), the particles may comprise: silk, silk fiber, carbon nanotubes, liposomes and / or gold nanoinformations. For example, in some modalities, directing particles
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71/73 may comprise injecting the patient with a fluid suspension that includes the particles. Including the suspension may, for example, comprise saline and / or hyaluronic acid.
[0135] The deposition of crystals and other miscellaneous crystals in joint tissues and particular tissues can result in a number of disease states. For example, deposition of monosodium urate monohydrate (MSUM) in a joint can result in gout. As another example, dehydrated calcium pyrophosphate (CPPD) in joint tissues and fluids can result in a number of disease conditions, such as, for example, chondrocalcinosis (that is, the presence of calcium-containing crystals detected as radiodensities in the cartilage articular). As an additional example, the deposition of hydroxyapatite (HA) crystals can result in calcified tendinitis and perarthritis. In some embodiments of the present methods, the particles may comprise natural particles (for example, particles that occur naturally within the body), such as, for example, crystalline microparticles as may be in shape and / or become arranged in the musculoskeletal system of a patient. Other examples of natural particles that can be treated and / or applied in the present methods include: urate crystals, calcium-containing crystals, and / or hydroxyapatite crystals.
[0136] In modalities of the present methods for the treatment of acne or other skin conditions, the particles may comprise dirt and / or debris that are arranged in one or more pores of the patient's skin, and / or may comprise keratin protein disposed of. patient's skin. In modalities of the present methods of treating conditions (for example, pathological) associated with bone and musculoskeletal and soft tissue environments through the application of shock waves it can induce localized trauma and cell apoptosis (including microfractures), or it can induce osteoblastic responses such as cellular recruitment, stimulate the formation of molecular bone, cartilage, tendon, fascia and
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Ί2Π3 soft tissue morphogens and growth factors, and / or can induce vascular neoangiogenesis.
[0137] Some modalities of the present methods of treating tumors or other diseases include various applications of shock waves to the target tissue (for example, a tumor, an area of the skin with acne or other conditions, etc.), such as, for example , for a duration of at least (for example, 10 seconds or more), once a week for 6 weeks or more.
[0138] The above specification and examples provide a description of the structure and use of exemplified modalities. Although certain modalities have been described above, with a certain degree of particularity, or with reference to one or more individual modalities, those skilled in the art could make several changes to the described modalities without departing from the scope of this invention. As such, the various illustrative embodiments of the present devices are not intended to be limited to the particular forms described. Preferably, they include all modifications and alternatives that fall within the scope of the claims, and modalities other than that shown may include some or all of the characteristics of the represented modality. For example, components can be combined as a unitary structure. In addition, where appropriate, aspects of any of the examples described above can be combined with aspects of any of the other examples described to form additional examples having comparable or different properties and addressing the same or different problems. Similarly, it should be understood that the benefits and advantages described above can refer to one modality or can refer to several modalities.
[0139] The claims are not intended to include, and should not be interpreted to include, device limitations plus function or step plus function, unless such limitation is explicitly cited in a given
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73/73 claim using the phrase (s) “device to” or “step to”, respectively.
References [1] Burov, V. A., Nonlinear ultrasound: breakdown of microscopic biological structures and nonthermal impact on malignant tumor. Doklady Biochemistry and Biophysics Vol. 383, p. 101 to 104 (2002).
[2] Delius, M., Jordan, M., & et al. (1988). Biological effects of shock waves: Kidney Haemorrhage by shock waves in dogs-administration rate dependence. Ultrasound in Med. & Biol., 14 (8), 689 to 694.
[3] Fernandez, P. (15 May 2006). A master relation defines the nonlinear viscoelasticity of single fibroblasts. Biophysical journal, Vol. 90, Issue 10, 3796 to 3805.
[4] Freund, J. B., Colonius, T., & Evan, A. P. (2007). A cumulative shear mechanism for tissue damage initiation in shock-wave lithotripsy. Ultrasound in Med & Biol, 33 (9), 1495 to 1503.
[5] Gillitzer, R., & et al. (2009). Low-frequency extracorporeal shock wave lithotripsy improves renal pelvic stone disintegration in a pig model. BJU Int, 176, 1284 to 1288.
[6] Kasza, K. E. (2007). The cell as a material. Current Opinion in Cell Biology 2007, 19: 101 to 107.
[7] Madbouly, K., & et al. (2005). Slow versus fast shock wave lithotripsy rate for urolithiasis: a prospective randomized study. The Journal of urology, 173, 127 to 130.

权利要求:
Claims (10)
[1]
1. System, CHARACTERIZED by the fact that it comprises a sparking module configured to be removably coupled to a probe, the sparking module comprising one or more walls defining a chamber associated with a shock wave output, the chamber configured for be filled with liquid, a first connector coupled to one or more walls and configured to be electrically coupled to the probe via the second probe connector, and a plurality of electrodes arranged in the chamber to define one or more spark openings, at least one electrode the plurality of electrodes electrically coupled to the probe connector, in which the spark module is removable from the probe as a single unit that includes one or more walls, the probe connector and the plurality of electrodes, and in which when the chamber is filled with a liquid and the sparking module is coupled to the pulse generation system through the probe, the plurality The electrode array is configured to receive voltage pulses from the pulse generation system through the first and second connectors so that portions of the liquid are vaporized to generate therapeutic shock waves that propagate through the liquid and the shock wave output.
[2]
2. System, according to claim 1, CHARACTERIZED by the fact that the sparking module additionally comprises a hinge electrically coupled to the first electrode, the hinge configured to allow a change in the physical position of the first electrode in relation to the second electrode.
[3]
3. System according to one of claims 1 to 2, CHARACTERIZED by the fact that the sparking module comprises
Petition 870180062119, of 7/19/2018, p. 85/89
2/4 additionally an acoustically permeable cover configured to be removably coupled to one or more walls, in which the plurality of electrodes is removably disposed in the chamber.
[4]
4. System according to one of claims 1 to 3, CHARACTERIZED by the fact that the sparking module additionally comprises a translucent or transparent window incorporated in the housing and positioned so that a portion of the chamber is intermediate to the translucent or transparent window and the shock wave output, in which the translucent or transparent window is configured to allow a user of the device to look through the translucent or transparent window into the housing chamber, to view, through the chamber and the shock waves exit, a a patient's region comprising target cells, and in which the plurality of electrodes is positioned inside the chamber, so that the plurality of electrodes is not visible to the user and visualizes the region through the translucent or transparent window.
[5]
System according to one of claims 1 to 4, CHARACTERIZED by the fact that it additionally comprises the probe coupled to the sparking module, the probe comprising: a handle portion, a high voltage connector positioned at the first end of the portion of handle and coupled to the pulse generation system, the second connector positioned on a second end of the handle opposite the first end, a plurality of electrical connectors coupled to the high voltage connector and the second connector,
Petition 870180062119, of 7/19/2018, p. 86/89
3/4 a manually operated switch for the handle portion and configured to be electrically coupled to the pulse generation system.
[6]
6. System according to one of claims 1 to 5, CHARACTERIZED by the fact that the sparking module additionally comprises one or more walls of the sparking module comprising at least one of pins, grooves or threads, and two liquid connections in communication fluid with the chamber, and the probe additionally comprising at least one of corresponding slots, pins and threads for releasably coupling the sparking module to the probe, and two conduits extending from the first end of the handle to the second end of the handle and coupled to the two liquid connections of the spark module, the two conduits are configured to allow the circulation of the liquid.
[7]
7. System, according to claim 6, CHARACTERIZED by the fact that it additionally comprises a liquid reservoir coupled to the spark module via one or more liquid connectors, and a pump configured to circulate at least a portion of the reservoir liquid to the chamber through one or more liquid connectors.
[8]
8. System according to one of claims 1 to 7, CHARACTERIZED by the fact that it additionally comprises the pulse generation system coupled to the probe, the pulse generation system comprising a first capacitive / inductive coil circuit comprising a induction configured to be
Petition 870180062119, of 7/19/2018, p. 87/89
4/4 discharged to apply at least some of the voltage pulses, a switch, and a capacitor, in which the capacitor and switch are coupled in parallel between the induction coil and a current source.
[9]
9. Method, CHARACTERIZED by the fact that it comprises the steps of positioning the sparking module, according to any one of claims 1 to 8, adjacent to a region of a patient comprising target cells, and to generate electro-hydraulically a first plurality of shock waves using the sparking module so that the first plurality of shock waves propagates through the liquid to the target cells.
[10]
10. Method according to claim 9, CHARACTERIZED by the fact that it additionally comprises, after activating the pulse generation system to propagate the plurality of shock waves through the fluid, changing a physical position of the first electrode in relation to the second electrode, after changing the physical position of the first electrode in relation to the second electrode, uncouple the sparking module from the probe, attach the second sparking module to the probe, and after attaching the second sparking module to the probe, generate electro-hydraulically a second plurality of shock waves using the second sparking module.

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法律状态:
2018-05-22| B11A| Dismissal acc. art.33 of ipl - examination not requested within 36 months of filing|

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2019-01-02| B04C| Request for examination: application reinstated [chapter 4.3 patent gazette]|

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2019-01-08| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2020-05-26| B25G| Requested change of headquarter approved|Owner name: SOLITON, INC (US) ; BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (US) |

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2020-06-16| B25G| Requested change of headquarter approved|Owner name: SOLITON, INC (US) ; BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (US) |

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2020-06-30| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2021-10-13| B350| Update of information on the portal [chapter 15.35 patent gazette]|

优先权:

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申请号 | 申请日 | 专利标题

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US201361775232P| true| 2013-03-08|2013-03-08|

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US13/798,710|US10835767B2|2013-03-08|2013-03-13|Rapid pulse electrohydraulicshockwave generator apparatus and methods for medical and cosmetic treatments|

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PCT/US2014/021746|WO2014138582A2|2013-03-08|2014-03-07|Rapid pulse electrohydraulicshockwave generator apparatus and methods for medical and cosmetic treatments|

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