HK1194278B - Apparatus for generating therapeutic shockwaves - Google Patents

Description

Device for generating therapeutic shock waves

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Serial No. 61/508,343, filed on July 15, 2011, and U.S. Utility Application Serial No. 13/547,995, filed on July 12, 2012, the disclosures of which are incorporated herein by reference in their entireties.

Technical Field

Embodiments of the present invention generally relate to therapeutic uses of shock waves. More particularly, but not by way of limitation, embodiments of the present invention relate to devices for generating therapeutic shock waves (shock waves having therapeutic uses) and their applications.

Background Art

Shock waves have been used in certain medical and cosmetic procedures. For example, they have been used in extracorporeal lithotripsy, where pulses are used to create a shock wave front to break up kidney stones. The source of shock waves in lithotripsy is typically generated by the release of electrical energy between test electrodes.

Shock waves in medical treatments can come from other sources. For example, U.S. Patent No. 6,325,769 to Peter J. Klopotek describes applying a focused ultrasound beam to an area of human skin to generate shock waves to treat wrinkles. The problem with shock wave generation as described by Klopotek is that it is unpredictable.

As described by Klopotek, due to the nonlinear nature of skin tissue, shock waves are generated as they travel through the skin. The formation of shock waves depends on the frequency and amplitude of the acoustic wave. Furthermore, the formation of shock waves depends on the medium in which the waves travel. Depending on the frequency, amplitude, and medium, the distance from the transducer head at which shock waves are generated is relatively large and can vary significantly depending on the type of tissue. Available methods are not yet prepared to generate consistent, high-frequency shock waves suitable for treatment.

Summary of the Invention

Certain embodiments of the devices described in this disclosure are capable of generating high frequency shock waves from sound waves.

Certain embodiments of the methods described in this disclosure deliver generated high frequency shock waves to the patient's tissue to selectively disrupt cellular structures having specific characteristics, such as cellular structures containing particles.

Certain embodiments of the devices described in this disclosure have particular application in removing tattoos or other skin markings and offer certain advantages over current tattoo removal techniques.

Advantages provided by certain embodiments of the devices and methods described in this disclosure include the ability to remove or eliminate tattoos or other skin markings with minimal pain to the patient and with minimal damage or disruption to surrounding tissue.

According to certain aspects, the present disclosure includes methods and apparatus for directing shock waves to cells of a patient (eg, a mammal).

Some embodiments of the method include directing a shock wave toward cells of the patient; wherein the shock wave is configured to cause the particles to disrupt one or more cells.

Some embodiments of the present method include providing a device (e.g., comprising an acoustic wave generator configured to emit acoustic waves having at least one frequency between 1 MHz and 1000 MHz; a shock wave housing coupled to the acoustic wave generator; and a shock wave medium disposed in the shock wave housing; wherein the device is configured such that if the acoustic wave generator emits an acoustic wave, at least a portion of the acoustic wave will travel through the shock wave medium); actuating the device to form a shock wave, the shock wave configured to cause particles within a patient to damage one or more cells of the patient; and directing the shock wave to the cells of the patient such that the shock wave causes the particles to damage the one or more cells.

In some embodiments, the shockwave medium is integral with the shockwave housing. In some embodiments, the shockwave housing defines a chamber, and wherein the shockwave medium is disposed within the chamber. In some embodiments, the shockwave medium is configured to exhibit nonlinear properties in the presence of acoustic waves emitted from the acoustic wave generator. In some embodiments, the shockwave medium comprises one or more of: bubbles, solid particles, or a combination of bubbles and solid particles.

In some embodiments, the shockwave housing defines a chamber having an input end coupled to the acoustic wave generator and an output end extending from the acoustic wave generator, and wherein the shockwave housing includes an end cap covering the output end of the chamber. In some embodiments, the end cap is configured such that a shockwave emitted from the end cap is attenuated by less than 20%. In some embodiments, the shockwave housing is configured such that if an acoustic wave is incident on the shockwave housing from within the shockwave chamber, the shockwave housing reflects at least a portion of the incident acoustic wave back into the shockwave chamber. In some embodiments, the distance from the acoustic wave generator to the outlet end of the chamber is greater than or equal to:

Wherein, ω = nonlinear parameter of the shock wave medium; ω = frequency of the acoustic wave; ρ ₀ = density of the shock wave medium; λ = wavelength of the acoustic wave; C ₀ = velocity of sound in the shock wave medium; P ₀ = pressure amplitude in the shock wave medium; and M _ω = acoustic Mach number = P ₀ ÷ (C ₀ ² ρ ₀ ). In some embodiments, the acoustic wave generator comprises an ultrasonic head.

In some embodiments, a device includes a controller coupled to an acoustic wave generator and configured to actuate the acoustic wave generator to emit acoustic waves. In some embodiments, the controller is configured to adjust the acoustic wave generator to change at least one of the amplitude and frequency of the acoustic waves emitted from the acoustic wave generator. In some embodiments, the controller is configured to actuate the acoustic wave generator to continuously emit acoustic waves for a period of time. In some embodiments, the controller is configured to actuate the acoustic wave generator to emit acoustic waves in an intermittent on-off sequence.

In some embodiments, the acoustic wave generator is a first acoustic wave generator, and the apparatus includes: a second acoustic wave generator configured to emit acoustic waves having at least one frequency between 1 MHz and 1000 MHz; wherein the shockwave housing is also coupled to the second acoustic wave generator; wherein the apparatus is configured such that if the second acoustic wave generator emits an acoustic wave, at least a portion of the acoustic wave will travel through the shockwave medium and form a shockwave; and wherein the controller is also coupled to the second acoustic wave generator and configured to actuate the second acoustic wave generator to emit the acoustic wave. In some embodiments, the controller is configured to actuate the first and second acoustic wave generators such that the acoustic wave emitted from the second acoustic wave generator is out of phase with the wave emitted from the first acoustic wave generator.

In some embodiments, the device is configured to fit within a box having a length of 3 feet, a width of 2 feet, and a height of 2 feet. In some embodiments, the device is configured to fit within a box having a length of 2 feet, a width of 1 foot, and a height of 1 foot.

In some embodiments, the particles may comprise non-natural particles. In some embodiments, the particles comprise tattoo pigment. In some embodiments, at least a portion of the tattoo pigment is disposed between the patient's skin cells. In some embodiments, at least a portion of the tattoo pigment is disposed within the patient's skin cells. In some embodiments, the particles comprise an element with an atomic number less than 82. In some embodiments, the particles may comprise gold. In some embodiments, the particles may comprise one or more materials selected from the group consisting of titanium dioxide, iron oxide, carbon, and gold. In some embodiments, the particles comprise pigment particles comprising one or more materials selected from the group consisting of titanium, aluminum, silica, copper, chromium, iron, carbon, and oxygen. In some embodiments, the particles have an average diameter less than 1000 nm. In some embodiments, the particles have an average diameter less than 500 nm. In some embodiments, the particles have an average diameter less than 100 nm. In some embodiments, the particles comprise one or more materials selected from the group consisting of silk, silk fibroin, carbon nanotubes, liposomes, and gold nanoshells.

In some embodiments, the particles comprise natural particles. In some embodiments, the particles comprise crystallized microparticles. In some embodiments, the crystallized microparticles are disposed within the patient's musculoskeletal system. In some embodiments, the particles comprise one or more materials selected from the group consisting of urate crystals, calcium-containing crystals, and/or hydroxyapatite crystals. In some embodiments, the particles comprise dirt or debris disposed within pores of the patient's skin. In some embodiments, the particles comprise keratin disposed within the patient's skin. In some embodiments, the one or more shock waves are configured to have substantially no lasting effect on cells in the absence of the particles.

In some embodiments, the method includes directing particles to or near the location of the cells prior to directing the shock waves to the cells. In some embodiments, directing the particles includes injecting a fluid suspension containing the particles into the patient. In some embodiments, the fluid suspension includes saline. In some embodiments, the fluid suspension includes hyaluronic acid.

In some embodiments, the method includes directing a chemical or biological agent to or near the location of the cells. In some embodiments, directing the chemical or biological agent is performed by delivering the chemical or biological agent through the skin. In some embodiments, directing the chemical or biological agent is performed by delivering the chemical or biological agent systemically. In some embodiments, directing the chemical or biological agent is performed by injecting the chemical or biological agent into the patient. In some embodiments, the chemical or biological agent includes one or more of a chelating agent and ethylenediaminetetraacetic acid (EDTA). In some embodiments, the chemical or biological agent includes one or more of an immunomodulator and imiquimod. In some embodiments, directing the chemical or biological agent is performed before delivering one or more shock waves. In some embodiments, directing the chemical or biological agent is performed after delivering one or more shock waves. In some embodiments, directing the chemical or biological agent is performed simultaneously with delivering one or more shock waves.

In some embodiments, the method includes identifying target cells in a patient to be disrupted; wherein identifying the target cells is performed prior to directing the shockwaves. In some embodiments, the target cells include tattoos. In some embodiments, the target cells include skeletal muscle cells containing crystallized microparticles. In some embodiments, the target cells include one or more skin conditions selected from the group consisting of blackheads, cysts, pustules, papules, and whiteheads. In some embodiments, the target cells include hair follicles and contain keratin. In some embodiments, the target cells include dental follicles and contain enamel. In some embodiments, the target cells include cancer cells.

In some embodiments, the method includes directing a beam from a Q-switched laser toward the cell. In some embodiments, directing the one or more shock waves and directing the beam are performed in an alternating sequence.

In some embodiments, directing the one or more shock waves includes focusing the one or more shock waves to a specific region of tissue comprising cells. In some embodiments, the region of tissue is at a depth beneath the patient's skin.

Some embodiments of the present apparatus for generating therapeutic shock waves include: an acoustic wave generator configured to emit acoustic waves having at least one frequency between about 1 MHz and about 1000 MHz; a shockwave housing coupled to the acoustic wave generator; and a shockwave medium disposed within the shockwave housing, wherein the shockwave housing is configured to be removably coupled to the acoustic wave generator such that the acoustic wave generator can be actuated to emit acoustic waves that travel through the shockwave medium and form one or more shockwaves. In some embodiments, the shockwave housing includes an input configured to be coupled to the acoustic wave generator and an output extending from the input. In some embodiments, the shockwave housing includes the shockwave medium within the shockwave housing. In some embodiments, the shockwave medium is integral with the shockwave housing.

Some embodiments of the present method include providing an embodiment of the present device; and actuating the device to generate a shock wave configured to cause particles within a patient to disrupt one or more cells of the patient. Some embodiments include directing the shock wave toward cells of the patient such that the shock wave disrupts the particles in the one or more cells. Some embodiments include coupling the shock wave housing to an acoustic wave actuator prior to actuating the device.

Any embodiment of any of the present systems and/or methods may consist of or consist essentially of the described steps, elements, and/or features—rather than comprising/including/containing/having the described steps, elements, and/or features. Thus, in any claim, the terms "consisting of" or "consisting essentially of" may be replaced by the above-mentioned open-ended linking verbs in order to alter the scope of a given claim from that defined using the open-ended linking verb.

According to another aspect, a method is provided, comprising the steps of providing a plurality of acoustic waves having at least one frequency of at least 1 MHz; propagating at least a portion of the acoustic waves through a shock wave medium to generate a plurality of shock waves, wherein the shock wave medium is configured to exhibit nonlinear characteristics in the presence of the propagated acoustic waves; and delivering at least a portion of the plurality of shock waves to at least one cellular structure including at least one region having heterogeneity; and disrupting the at least one cellular structure using the sequentially delivered plurality of shock waves, wherein the at least one region having heterogeneity includes an effective density greater than an effective density of the at least one cellular structure.

According to yet another aspect, an apparatus is provided that includes: an acoustic wave generator configured to emit acoustic waves having at least one frequency between about 1 MHz and about 1000 MHz; a shock wave medium coupled to the acoustic wave generator; and wherein the apparatus is configured to propagate at least a portion of the emitted acoustic waves through the shock wave medium to form a shock wave; and wherein the formed shock wave is configured to disrupt at least one cellular structure including at least one region having heterogeneity. In one embodiment, the shock wave medium has a Goldberg number greater than or equal to 1, wherein the Goldberg number is determined by dividing a length of the shock wave medium by an absorption length of the shock wave medium, wherein the absorption length is defined by at least the inverse of an attenuation coefficient of the shock wave medium. In another embodiment, the at least one region having heterogeneity comprises an effective density greater than an effective density of the at least one cellular structure.

Other advantages and features will be apparent from reading the following detailed description in conjunction with the accompanying drawings. The foregoing has outlined the technical advantages and features of embodiments of the present invention quite broadly so that the following detailed description may be better understood. Additional features and advantages of embodiments of the present invention will be described below, which constitute the subject matter of the claims of the present disclosure. It should be understood by those skilled in the art that the concepts and specific embodiments disclosed herein may be easily used as a basis for modifying or designing other structures to implement the same purposes disclosed herein. It should also be appreciated by those skilled in the art that such equivalent constructions do not depart from the spirit and scope of the embodiments of the present invention as set forth in the appended claims. The novel features that are considered to be features of the present invention, both in terms of their organization and method of operation, as well as further purposes and advantages, will be better understood by the following description when considered in conjunction with the accompanying drawings. However, it should be clearly understood that each figure is for illustration and description purposes only and is not intended to be a definition of limitations of the embodiments described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

The following figures illustrate by way of example and not limitation. For the sake of brevity and clarity, not every feature of a given structure is labeled in every figure in which that structure appears. Identical reference numerals do not necessarily indicate identical structures. Rather, identical reference numerals may be used to indicate similar features or features having similar functions, as may non-identical reference numerals.

FIG1 shows one embodiment of the present device for generating therapeutic shock waves.

FIG2 shows a second embodiment of the present device comprising two complementary parts removably coupled to each other shown in disassembled and assembled configurations.

FIG3 shows a conceptual flow chart of one of the methods.

It should be understood that the drawings are not necessarily drawn to scale and that the disclosed embodiments are sometimes shown schematically and in fragmentary views. In some cases, details that are not necessary for understanding the disclosed methods and apparatus or that obscure other details may be omitted. Of course, it should be understood that the present disclosure is not limited to the specific embodiments described herein.

DETAILED DESCRIPTION

The term "coupled" is defined as connected, although not necessarily directly, and not necessarily mechanically; two items that are "coupled" can be integral with one another. The terms "a" and "an" are defined as one or more, unless expressly stated otherwise in this disclosure. The terms "substantially," "approximately," and "about" are defined as referring to a large portion, but not necessarily all, of the specified matter, as understood by one of ordinary skill in the art.

The terms "comprises," "has," "includes," and "contains" are open-ended linking verbs. Thus, a method that "comprises," "has," "includes," and "contains" one or more steps possesses those one or more steps, but is not limited to possessing only those one or more steps. For example, in a method that includes directing shock waves to cells of a patient, the method includes the specified step, but is not limited to possessing only that step. Similarly, an apparatus that "comprises," "has," "includes," and "contains" one or more elements possesses those one or more elements, but is not limited to possessing only those elements. For example, in an apparatus that includes an acoustic wave generator and a shock wave housing coupled to the acoustic wave generator, the apparatus includes the specified elements, but is not limited to possessing only those elements. For example, such an apparatus may also include a shock wave medium disposed in the shock wave housing. Further, a device or structure that is configured in a particular manner is configured in at least that manner, but it may also be configured in other manners that are different from the manner specifically described.

Referring now to the drawings, and more particularly to FIG. 1 , illustrated therein and designated by reference numeral 10 is one embodiment of the present apparatus for generating shock waves in a controlled manner. Certain embodiments of the apparatus disclosed herein generate high-frequency shock waves in a predictable and consistent manner. In one embodiment, the generated shock waves comprise shock waves that can be used in medical and/or cosmetic treatment applications. Preferably, the generated high-frequency shock waves are delivered to a patient's tissue. The shock waves can be configured to exert sufficient mechanical stress on target cells in the tissue to rupture the target cells. In one embodiment, the rupture of the target cells occurs at least through degradation and destruction of the cell membrane. When the target cells are exposed to the generated high-frequency shock waves, they experience a steep gradient of mechanical stress due to spatially heterogeneous parameters of the cells, such as the density and/or shear modulus of different components of the cells. For example, dense and/or inelastic components within the cells experience greater mechanical stress when subjected to the shock waves than lighter components. In particular, the acceleration of higher-density particles or components within the cellular structure exposed to the shock front is typically very large. At the same time, when exposed to such a large gradient of pressure, the impact on the low-density biological structures that make up the cell structure is significantly reduced because the elasticity of lower-density biological structures generally allows them to act as low-compliance materials. The difference in mechanical stress leads to the movement of dense and/or inelastic components within the cell. When the cell is exposed to repeated shock waves of a specific frequency and energy level, the dense and/or inelastic components repeatedly move until they break through the cell, thereby causing the cell to rupture. In particular, the described cell destruction is caused by a mismatch between the characteristics of the cell structure and the cell's ability to withstand deformation when exposed to the shock front. Without intending to be bound by theory, a possible theory for explaining the rupture phenomenon of cell structure can be found in Burov, V.A., Nonlinear ultrasound: breakdown of microscopic biological structures and nonthermal impact on malignant tumor. Doklady Biochemistry and Biophysics, Vol. 383, pp. 101-104 (2002) (hereinafter referred to as "Burov"), the entire contents of which are incorporated herein by reference.

When a cell oscillates as a whole unit when impacted by these pressure fronts, a steep gradient of mechanical stress is generated inside the cell due to spatially heterogeneous parameters (i.e., density and shear modulus). This concept can be illustrated by modeling the biological structure as two connected spheres with masses m ₁ and m ₂ , and the density of the liquid oscillating around the spheres at a velocity μ _o (t) (ρ ₀ ) is not significantly different from the density of the spheres (ρ ₁ and ρ ₂ , respectively). If only the resistance to potential flow is considered, the force applied to the connection is calculated as shown in equation (1):

Additional discussion of equation (1) and its variables is provided further in Burov. For example, if the sphere radius (R) is approximately 10 μm, and the difference between the sphere densities is 0.1ρ ₀ , and the resulting stress force, F/(πR ² )m of 10 ⁹ dyne/cm ² . This is sufficient to rupture the cell membrane. Embodiments of the present device generate shock waves in a controlled manner that can be used to cause targeted damage to specific cells, which has applications in medical and/or cosmetic treatments as discussed further below.

Another possible explanation for the phenomenon of cell rupture is the cumulative shear stress of denser materials within the cell structure. In heterogeneous media, such as cells containing particles (e.g., pigment granules), shock waves cause cell membrane failure through a progressive (i.e., cumulative) shear mechanism. In homogeneous media, on the other hand, the compression caused by the shock wave causes minimal, if any, damage to the cell membrane. Microscopic focusing and defocusing of the shock wave as it passes through the heterogeneous medium can cause localized strengthening or weakening of the shock wave, resulting in increased local shear. The occurrence of relative shear motion of the cell membrane is related to the degree of heterogeneity in the cell structure. It is believed that when a shock wave impacts a heterogeneous region (e.g., a cell containing particles), the particle motion, out of phase with the input wave, generates a transfer of cell-breaking energy (e.g., shear stress). This out-of-phase motion (e.g., shear stress) causes microscopic damage to the cell membrane, which progresses to membrane failure as additional shear stress continues to accumulate. The progressive shear mechanism of repeated exposure to shock waves can be considered dynamic fatigue of the cell membrane. Damage from dynamic fatigue depends on three factors: (1) the applied stress or strain, (2) the rate at which the strain is applied, and (3) the cumulative number of strain cycles. These three factors can be manipulated so that, at a specific applied strain, strain rate, and strain cycles, cells with heterogeneity experience catastrophic cell membrane failure compared to relatively more uniform cells. Manipulation of the factors can be accomplished by providing shock waves with certain characteristics, such as the number of shock waves, the amount of time between each shock wave, and the intensity of the shock waves applied. For example, if there is too much time between shock waves for the tissue to relax to its unstrained state, the cell will be less likely to fail. Therefore, in a preferred embodiment, high frequency shock waves (at least about 1,000,000 shock waves per second from acoustic waves having a frequency of about 1 MHz) are delivered to the target cellular structure to achieve dynamic fatigue of the tissue without allowing the tissue time to relax.

A third possible theory is that the shock wave induces a combined effect of direct motion of particles contained within the cellular structure and dynamic fatigue that disrupts the cells. While cells containing particles are an obvious example of cellular structures exhibiting heterogeneity, their description is not intended to limit the scope of this disclosure. Rather, the embodiments disclosed herein can be used to disrupt or damage other cellular structures exhibiting heterogeneity, such as cellular structures having regions of varying effective density. The parameters of the shock wave generated according to the disclosed aspects can be adjusted based at least on the regions of varying effective density (i.e., heterogeneity) to induce cellular damage as described herein. Heterogeneity can be regions within a single cell, regions of different cell types, or a combination of both. In certain embodiments, regions of heterogeneity within a cell include regions with an effective density greater than that of the cell. In one specific example, fibroblasts have an effective density of approximately 1.09 g/ ^cm³ , and the regions of heterogeneity within the cell are particles contained within the cell with an effective density greater than 1.09 g/ ^cm³ , such as graphite with a density of 2.25 g/ ^cm³ . In certain embodiments, areas of cellular heterogeneity between cells include areas having different types of cells, where each cell type has a different effective density, such as fibroblasts and adipocytes or hair follicles. The present disclosure provides further examples of cellular structures comprising heterogeneity below.

Referring to FIG. 1 , apparatus 10 includes an acoustic wave generator 14, a shockwave housing 18 coupled to acoustic wave generator 14, and a shockwave medium 22 disposed within shockwave housing 18. In a preferred embodiment, shockwave housing 18 defines a chamber 26. Shockwave housing 18 may comprise, for example, a polymer, plastic, silicone, metal, and/or any other suitable material. Chamber 26 includes an input end 30 coupled to acoustic wave generator 14, an output end 34, and a body 56 extending between input end 30 and output end 34. In one embodiment, shockwave housing 18 further includes an end cap 38 that covers output end 34 of chamber 26. Referring to FIG. 1 , chamber 26 has a circular cross-sectional shape. In other embodiments, chamber 26 has a rectangular, square, oval, triangular, octagonal, and/or any other suitable cross-sectional shape. In a preferred embodiment, apparatus 10 further includes shockwave medium 22 disposed within chamber 26 between input end 30 and output end 34.

In a preferred embodiment, acoustic wave generator 14 is configured to emit a series or plurality of acoustic waves 58 from output 50, at least a portion of which enter chamber 26 and travel through shockwave medium 22 toward output end 34. As the acoustic waves move through shockwave medium 22, the properties of shockwave medium 22 alter acoustic waves 58 to form shockwaves 60 at or near output end 34.

In a preferred embodiment, the acoustic wave generator 14 is configured to emit shock waves having at least one frequency between approximately 1 megahertz (MHz) and approximately 1000 MHz (e.g., 1 MHz, 2 MHz, etc.). Additionally or alternatively, the acoustic wave generator 14 is configured to emit at least one wavelength corresponding to at least one frequency between 1 MHz and 1000 MHz in the shock wave medium 22 or in a reference medium such as atmospheric air. In one embodiment, the acoustic wave generator 14 comprises an ultrasonic head (e.g., a commercially available ultrasonic head). In other embodiments, the acoustic wave generator 14 comprises ceramic and/or piezoelectric acoustic elements. In some embodiments, the acoustic wave generator 14 is configured to emit acoustic waves having a beam radiant power between approximately or substantially equal to 5 and approximately 1000 watts per square centimeter (W/ ^cm² ) (e.g., 5 to 50 W/ ^cm² , 5 to 100 W/ ^cm² , 100 to 500 W/ ^cm² , or 100 to 400 W/ ^cm² ).

The progressive nonlinear distortion of the waveform results in the formation of pressure shock fronts or shock waves. In order to form the shock wave 60 at or near the output end 34, the shock wave medium 22 preferably comprises a material that exhibits or is capable of causing the sound wave 58 generated or emitted from the sound wave generator 14 to experience nonlinearity as the sound wave 58 propagates through the material. The nonlinearity is preferably sufficient to convert a sinusoidal sound wave propagating therethrough into a sawtooth wave with one shock per cycle as shown in FIG1 . In particular, the progressive nonlinear distortion of the sinusoidal wavelength results in shock fronts having a frequency f that periodically follow one another. The duration of the front can be much shorter than the period 1/f, as shown in equation (2):

Where b is the effective viscosity; is the nonlinear factor; and ρ and c are the medium density and the speed of sound, respectively. Additional discussion of equation (2) and its variables is provided in Burov. Because of the relatively high frequency of the sound waves, shock waves are also generated at a high frequency, with one shock wave per cycle. For example, certain embodiments of the present disclosure can be configured to generate approximately 1,000,000 shock waves per second from sound waves of approximately 1 MHz. In other embodiments, the device 10 is configured to generate 100 or more shock waves per minute (e.g., 200, 300, 400, 500, 1000, 2000, 5000, or more shock waves per minute).

Some embodiments of the present method of generating therapeutic shock waves include actuating an acoustic wave generator (e.g., 14) to emit acoustic waves having at least one frequency between 1 MHz and 1000 MHz, such that at least a portion of the acoustic waves travels through a shock wave medium (e.g., 22) disposed in a shock wave housing (e.g., 18) to form one or more shock waves. For example, embodiments of the present method may include actuating an acoustic wave generator of any of the present devices.

Nonlinear distortion of the acoustic waves 58 can be induced by diffraction of the ultrasonic waves from the walls of the shockwave shell 18. Additionally or alternatively, nonlinearity can result from heterogeneity induced by the ultrasonic waves traveling through the shockwave medium (or media) 22. Furthermore, nonlinearity can result from the inclusion of particles or bubbles (i.e., air bubbles, nanoparticles, etc.) in the medium. In some embodiments, the shockwave medium 22 comprises a fluid. In some embodiments, the shockwave medium 22 comprises a gel. In some embodiments, the shockwave medium 22 comprises a liquid. In some embodiments, the shockwave medium 22 is configured such that, in the presence of acoustic waves from the acoustic wave generator 14, the shockwave medium 22 exhibits nonlinear properties. In some embodiments, the shockwave medium 22 comprises one or more of the following: water, glycerin, poly(ethylene glycol) (PEG), propylene glycol, silicone oil, ethanol, or a combination of two or more thereof. In some embodiments, the shockwave medium 22 comprises one or more of the following: bubbles (e.g., air bubbles), solid particles, or a combination of bubbles and solid particles. For example, gas bubbles may be introduced into the medium 22 by adding a gas such as carbon dioxide, and/or in the form of stable bubbles as may be found in ultrasound contrast agents or as part of nanoparticles.

Additionally, there are two other factors that affect the conversion of an acoustic wave propagating through shockwave medium 22 into a shockwave: the shockwave formation length and the absorption length of shockwave medium 22. The length of the nonlinear distortion is a factor because the distortion is gradual and requires sufficient propagation for the conversion to occur.

In some embodiments, the length of shockwave medium 22, or the shockwave formation distance, is a function of the nonlinear parameters, the frequency of the sound waves generated by sound wave generator 14, the pressure amplitude, the density of shockwave medium 22, and the speed of sound in shockwave medium 22. For example, the distance between when the sound wave leaves sound wave generator 14 and enters shockwave medium 22 and when the sound wave exits shockwave medium 22 is preferably greater than or equal to the value given by equation (3):

Where: ω = the nonlinear parameter of the shockwave medium; ω = the frequency of the acoustic wave; ρ ₀ = the density of the shockwave medium; λ = the wavelength of the acoustic wave; C ₀ = the speed of sound in the shockwave medium; P ₀ = the pressure amplitude in the shockwave medium; and M _ω = the acoustic Mach number = P ₀ ÷ (C ₀ ² ρ ₀ ). Generally speaking, the higher the frequency of the acoustic wave and/or the higher the intensity of the acoustic wave, the shorter the minimum length of the shockwave medium 22 required to allow shockwaves to form when the wave energy exits the shockwave medium 22. Referring to FIG. 1 , in a preferred embodiment, the length of the shockwave medium 22 is indicated by reference numeral 46 and extends from the output 50 of the acoustic wave generator 14 to the output end 38 of the shockwave chamber 26.

In a preferred embodiment, the shockwave medium 22 has at least a minimum length to convert acoustic waves into shockwaves for acoustic waves emitted having an amplitude and frequency within a specific range (preferably, a desired operating range of at least 1 MHz). The minimum length is preferably determined by Equation 3 above. In some embodiments, the shockwave medium 22 has a length greater than the minimum length determined to ensure that shockwaves are generated within the shockwave medium 22 before energy exits the shockwave medium 22. In one embodiment, the housing 18 is configured to have substantially the same length as the shockwave medium 22 so that the generated shockwaves are rapidly transported from the output end 34 to the treatment surface. In other embodiments, the housing 18 may provide a gap between the end of the shockwave medium 22 and the output end 34. While the length of the shockwave medium 22 configured to generate shockwaves from acoustic waves of a specific amplitude and frequency is sufficient to convert acoustic waves of any amplitude and frequency above the design range into shockwaves.

In addition to the shockwave formation length (e.g., the length of shockwave medium 22), the absorption length of shockwave medium 22 is another factor, as absorption of acoustic energy prevents shockwave formation or can cause any formed shockwave to dissipate. Absorption is based at least on the attenuation coefficient of the material of shockwave medium 22. Attenuation, in turn, depends on the frequency of the acoustic wave, which, as described above, is preferably at least approximately 1 MHz. Absorption is the inverse of the attenuation coefficient (α) of shockwave medium 22, or 1/attenuation coefficient (α).

In a preferred embodiment, the material of shock wave medium 22 is selected based on the relationship between shock wave formation length and absorption. In one embodiment, this relationship is represented by the Goldberg (r) number shown in equation (4):

r=I _s /I _a (4)

Where: I _s = shock wave formation distance = described in equation (3) and I _a = absorption length = inverse of the attenuation coefficient = 1/α.

Further discussion of Goldberg numbers can be found in Brooks LA, Zander AC, Hansen CH, "Investigation into the feasibility of using a parametric array control source in an active noise control system," Proceedings of ACOUSTICS 2005, 9-11, the disclosure of which is incorporated herein by reference in its entirety. Preferably, the shock wave medium 22 comprises a material having a positive Goldberg number at a frequency of at least about 1 MHz and a pressure of at least about 1 MPa at the output 50 of the acoustic wave generator 14. More preferably, the shock wave medium 22 comprises a material or combination of materials having a Goldberg number of at least 1 or greater than 1. Furthermore, the shock wave medium 22 preferably comprises a solid polymer having a solid state. Examples of solid polymers having a Goldberg number greater than 1 at frequencies greater than 1 MHz and pressures greater than 1 MPa include, but are not limited to, squalene, Pebax (polyether block amide), water, gelatin, and polyurethane elastomers such as Pellethane 2363-80.

Thus, the present disclosure achieves controlled generation of shockwaves from acoustic waves by subjecting the acoustic waves to sufficient progressive distortion nonlinearity to transform the sine waves into shockwaves. This can be achieved by selecting the desired frequency and amplitude range, the absorption properties of the material, and the length of the material based on the aforementioned relationships. Because these factors influence each other, they can be adjusted to achieve the desired dimensions. For example, if the desired length of shockwave medium 22 is known, the frequency and amplitude of the emitted acoustic waves, as well as the material of shockwave medium 22, can be determined to achieve this desired length. Other factors can be configured accordingly to achieve the desired result of generating shockwaves from acoustic waves.

Referring to FIG. 1 , the acoustic wave generator 16 is coupled to the housing 18, the chamber 26, and the shock wave medium 22 to allow at least a portion of the emitted acoustic wave 58 to propagate through the shock wave medium 22 to form a shock wave 60. In some embodiments, the input end 30 of the chamber 26 has a transverse internal dimension (e.g., diameter 42) that is at least as large as a corresponding transverse external dimension of the acoustic wave generator 14 (e.g., at the output 50). For example, in the illustrated embodiment, the diameter 42 of the chamber 26 is at least as large as (e.g., slightly larger than) the outer diameter of a corresponding portion of the acoustic wave generator 14 (e.g., the output 50). In other embodiments, the diameter 42 may be larger (e.g., and/or a gasket or coupler may be used to couple the housing 18 to the output 50 of the acoustic wave generator). In the illustrated embodiment, the chamber 26 has a substantially constant cross-section between the input end 30 and the outlet end 34. In other embodiments, the chamber 26 has a varying cross-section between the input end 30 and the outlet end 34.

In some embodiments, shock wave medium 22 and shell 18 comprise the same material, such as a polymer, silicone, or any other suitable material (e.g., medium 22 may be integral with shell 18 and/or end cap 38). In other embodiments, shock wave medium 22 and shock wave shell 18 are integral (e.g., comprise the same block of material). For example, shock wave medium 22 may comprise a solid material, where a separate shell 18 is not necessary. In some embodiments, shock wave shell 18 and shock wave medium 22 comprise silicone. In other embodiments, shock wave medium 22 comprises one or more bubbles (e.g., air bubbles, etc.).

In some embodiments, shockwave shell 18 is configured such that a distance 46 from sonic generator 14 (e.g., input end 30 of chamber 26) to outlet end 38 of chamber 26 is between 100% and 1000% of at least one (e.g., smallest) internal transverse dimension (e.g., diameter 42) of chamber 26. In some embodiments, distance 46 from sonic generator 14 (e.g., input end 30 of chamber 26) to outlet end 34 of chamber 26 is between 300% and 900% (and/or between 400% and 800%) of at least one (e.g., smallest) internal transverse dimension (e.g., diameter 42) of the chamber.

Furthermore, in the illustrated embodiment, shockwave housing 18 is configured such that if an acoustic wave 58 is incident on shockwave housing 18 from and within chamber 26 , shockwave housing 18 reflects at least a portion of the incident acoustic wave back into shockwave chamber 26 .

1 , end cap 38 is configured to seal outlet end 34 of chamber 26 to substantially prevent shockwave medium 22 from exiting chamber 26 while allowing shockwaves to exit output end 34 of shockwave chamber 26. In some embodiments, end cap 38 is configured to have low shockwave attenuation (e.g., such that shockwaves exiting end cap 38 are attenuated by less than 20%) and/or low shockwave reflection. In some embodiments, end cap 38 comprises at least one of the following: a polymer, a hydrogel, a film, a plastic, or silicone.

Referring to FIG. 1 , the device 10 further includes a controller 54 coupled to the sound wave generator 14 and configured to activate the sound wave generator 14 to emit sound waves. The controller 54 may include any suitable programmed hardware, such as a processor with memory, a programmable logic controller (PLC), a personal digital assistant (PDA), and/or the like. Although shown as a separate component, the controller 54 may be integrated into the sound wave generator 14 (e.g., using a common housing). In some embodiments, the controller 54 is configured to adjust the sound wave generator 14 to change at least one of the amplitude and frequency of the sound waves emitted from the sound wave generator 14. In some embodiments, the controller 54 is configured to activate the sound wave generator 14 to continuously emit sound waves for a period of time (e.g., when the sound wave generator is activated "on"). In some embodiments, the controller 54 is configured to activate the sound wave generator 14 to emit sound waves 58 in a periodic on-off sequence (e.g., a sequence with regular, periodic intervals). In some embodiments, the controller 54 is configured to actuate the acoustic wave generator 14 to emit acoustic waves 58 in an intermittent on-off sequence (e.g., a non-periodic sequence without regular, periodic intervals). Actuation of the acoustic wave generator 14 in an on-off sequence can, for example, reduce heat buildup in tissue. In some embodiments, the controller 54 is configured to actuate the acoustic wave generator 14 to emit acoustic waves 58 in an on-off sequence and to adjust the duration of the on-off and/or off periods of the on-off sequence based on or in response to measured and/or predicted temperature. For example, temperature can be measured using a thermometer (e.g., an infrared thermometer) coupled to the controller 54, and/or the controller 54 can be configured to predict tissue temperature based at least in part on the intensity and/or other characteristics of the acoustic waves 58 emitted from the acoustic wave generator 14 and/or the shock waves 60 generated or delivered to the tissue within the housing 18.

In some embodiments, acoustic wave generator 14 is a first acoustic wave generator, and apparatus 10 further includes a second acoustic wave generator (not shown) configured to emit acoustic waves having at least one frequency between 1 MHz and 1000 MHz; wherein shockwave housing 18 is also coupled to the second acoustic wave generator. In such embodiments, apparatus 10 is configured such that when the second acoustic wave generator emits acoustic waves, at least a portion of the acoustic waves will travel through shockwave medium or media 22 and form one or more shockwaves. Some of these embodiments further include a controller 54 coupled to the second acoustic wave generator and configured to actuate the second acoustic wave generator to emit the acoustic waves. In some embodiments, controller 54 is configured to actuate first acoustic wave generator 14 and second acoustic wave generator (not shown) such that the acoustic waves emitted from the second acoustic wave generator are out of phase with the waves emitted from the first acoustic wave generator 14.

In some embodiments, the device 10 is configured to fit within a box having a length of 3 feet, a width of 2 feet, and a height of 2 feet. In some embodiments, the device 10 is configured to fit within a box having a length of 3 feet, a width of 1 foot, and a height of 1 foot. In some embodiments, the device 10 is configured to fit within a box having a length of 2 feet, a width of 1 foot, and a height of 1 foot. In some embodiments, the device 10 is configured to fit within a box having a length of 1 foot, a width of 8 inches, and a height of 8 inches. For example, in some embodiments, the housing 18 has an internal length of less than 3 inches and an internal maximum transverse dimension (e.g., diameter) of less than 3 inches. In some embodiments, the internal length (between the output end 50 of the acoustic wave generator 14 and the inner surface of the output end 34 and/or the end cap 38) is greater than 3 megapascals (MPa) (e.g., 10 MPa or more) at the target cells.

In the embodiment of FIG. 2 , a second embodiment of the present device 10a is shown in both disassembled and assembled configurations. Device 10a is similar in many respects to device 10 and may include any features of device 10 not expressly excluded, so that the differences are primarily described herein. In the illustrated embodiment, the acoustic wave generator 14 and shockwave housing 18 of device 10a are configured to be removably coupled to one another, such that the acoustic wave generator can be actuated to emit acoustic waves that will travel through the shockwave medium and form one or more shockwaves (e.g., as described for device 10 ). In such an embodiment, the input 30 can be sealed independently of the acoustic wave generator 14 to prevent the medium 22 from escaping from the housing 18 when the acoustic wave generator 14 is not coupled to the housing 18. The acoustic wave generator 14 and/or housing 18 can be removably coupled together in any suitable manner (e.g., using threads, interlocking tabs, a press fit to allow the acoustic wave generator to be inserted into the housing's input 30, etc.). In some embodiments, the acoustic wave generator 14 and housing 18 are not physically connected to prevent separation. For example, in some embodiments, the housing 18 is placed adjacent to the patient with the output end 34 directed toward the target cells, and the acoustic wave generator 14 is coupled to the housing 18 (e.g., positioned in contact with the housing 18) without inserting the acoustic wave generator 14 into the housing 18 or otherwise physically interconnecting the two. In some embodiments, different housings 18 can have different characteristics (e.g., size, media 22, end caps 38, etc.) so that different housings 18 can be coupled to a single acoustic wave generator 18 to generate shock waves with different characteristics. In such embodiments, the housing 18 can be disposable and/or a single-use device that is discarded after each use.

While the high-frequency shock waves generated by certain embodiments of the present disclosure, and the controlled and predictable manner in which they are generated, have numerous applications, certain embodiments of the present disclosure and the shock waves generated are particularly useful in therapeutic applications. Specifically, in treating certain skin conditions in patients. As described above, high-frequency shock waves can lead to controlled and targeted disruption of cellular structures based on differences in elasticity of their components. The ability to provide targeted and controlled disruption or damage to certain cellular structures is particularly useful in treating diseases and/or conditions involving particles that aggregate within cells ("cell-particle aggregates"), which contribute to these differences in elasticity. In particular, certain embodiments of the present disclosure, such as device 10, can continuously and/or predictably generate shock waves at high frequencies to disrupt specific cells in a targeted manner without inducing cavitation in the patient's tissue and without generating high amounts of thermal energy (e.g., heat) in the patient's skin that could cause further unintended damage. The released particles can be removed from the surrounding tissue by the patient's normal absorption processes.

Examples of diseases and/or conditions involving particle accumulation in cellular structures include cancer, crystalline microparticles in the musculoskeletal system, or tattoo removal. These are merely non-limiting examples of conditions that can be treated or resolved by disrupting or destroying cells containing particle aggregates. In some embodiments, the destruction of cells containing particle aggregates can be achieved by non-thermal cell membrane degradation of specific cells that is secondary to the nonlinear processes associated with the propagation of high-frequency shock waves, as discussed above.

A tattoo is essentially a fibroblast containing aggregates of ink particles. Because the trapped ink particles are denser than the biological structure of fibroblasts, the tattoo or fibroblast containing ink particles exhibits significant differences in their structural elasticity. When subjected to shock waves, fibroblasts containing ink particles experience greater mechanical strain than other fibroblasts that do not contain dense particles. Shock waves can be configured to deliver at an optimal frequency and amplitude to sufficiently accelerate the ink particles to rupture specific fibroblasts while leaving intact fibroblasts without specific elastic differences. Details of the biological process of tattoo removal and release from fibroblasts are discussed further below.

A. Tattoo

Tattoo inks and dyes have historically been derived from substances found in nature and typically consist of a heterogeneous suspension of pigment particles and other impurities. An example is India ink, which consists of a suspension of carbon particles in a liquid such as water. Tattoos are typically created by applying tattoo ink into the dermis, where the ink typically remains essentially permanent. This technique introduces a pigment suspension through the skin using alternating pressure-suction action caused by the elasticity of the skin combined with the up-and-down motion of the tattoo needle. The water or other carrier used to introduce the pigment into the skin diffuses through the tissue and is absorbed. In most cases, insoluble pigment particles are deposited in the dermis where they are deposited. In tattooed skin, pigment particles and aggregates are often found in the cytoplasm of skin cells (e.g., dermal fibroblasts) (i.e., in membrane-bound structures called secondary lysosomes). This entry into dermal cells (e.g., macrophages, fibroblasts) may occur through active phagocytosis. The resulting pigment aggregates ("granule aggregates") can be up to several microns in diameter. Once the skin heals, most pigment particles remain in the interstitial spaces of the skin tissue. Tattoo inks are generally not easily removed due to their inertness and the relatively large size of the insoluble pigment particles. Tattoos can fade over time, but generally remain in place for the lifetime of the tattooed individual.

Tattoo inks typically include aluminum (87% of the pigment), oxygen (73% of the pigment), titanium (67% of the pigment), and carbon (67% of the pigment). The relative contributions of these elements to the composition of tattoo inks vary greatly between different compounds. Additional information can be found in Timko, AL; Miller, CH; Johnson, FB; Ross, EV: "In Vitro Quantitative Chemical Analysis of Tattoo Pigments," Arch Dermatol, Vol. 137, February 2001, pp. 143-147, the disclosure of which is incorporated herein by reference in its entirety. Pigments can range in diameter from approximately 20 nm to approximately 900 nm. Transmission electron microscopy (TEM) images of the pigments reveal a variety of shapes (e.g., needles, platelets, cubes, strips, and numerous irregular shapes). In addition to primary particles, aggregates, including primary particles grown together on their surfaces and agglomerates (groups of single crystals bound together at their edges), were observed in the same TEM images. Full details of the TEM images can be found in Baumler, W; Eibler, ET; Hohenleutner, U; Sens, B; Sauer, J, and Landthaler, M; Q-switched laser and tattoo pigments: First results of the chemical and photophysical analysis of 41 compounds. Lasers in Surgery and Medicine 26: 13-21 (2000), which is incorporated herein by reference in its entirety.

At least one study has determined the particle sizes of three commercial tattoo inks shown in Table 1:

Table 1: Tattoo pigment particle size

color Average diameter Standard deviation Viper Red 341nm 189nm Potion Orange 228nm 108nm Light yellow 287nm 153nm

B. Tattoo Removal

In traditional tattooing (decorative, cosmetic, and reconstructive), once a pigment or dye has been applied to the dermis to form a tattoo, it typically remains permanently in place. This is often attributed to active phagocytosis of the particles into dermal cells (macrophages, fibroblasts), which prevents the particles from being absorbed and dispersed throughout the body. The resulting pigment aggregates ("particle aggregates") can be up to several micrometers in diameter.

Although tattoos are generally permanent, individuals may wish to change their tattoos for various reasons. For example, over time, a person's mood (or whims) may change, and they may wish to remove or alter the design of a decorative tattoo. By way of another example, individuals with cosmetic tattoos, such as eyeliner, eyebrow tattoos, or lip pigmentation, may wish to change the color or area of the tattoo as fashions change. Unfortunately, there is currently no simple and successful method for tattoo removal. One approach that has been disclosed (see U.S. Patent Application Publication No. US2003/0167964) utilizes tattoo inks that are removable on demand. Such inks may include microparticles constructed with specific electromagnetic absorption and/or structural properties that are activated by the application of specific energy (e.g., electromagnetic radiation from a laser or flashlight). In other embodiments, the pigment and/or pigment carrier may be susceptible to specific externally applied energy sources, such as heat or light (e.g., laser, infrared, or ultraviolet light). A problem with this type of approach is that it requires these new types of inks and has little or no effect on tattoos that utilize traditional pigments.

Currently, methods for removing traditional tattoos (e.g., pigmented skin) may include salt abrasion, cryoablation, surgical excision, and _CO2 lasers. These methods can require invasive procedures associated with potential complications (such as infection) and often result in significant scarring. More recently, the use of Q-switched lasers has gained widespread acceptance for tattoo removal. Additional information regarding the use of Q-switched lasers for tattoo removal can be found in Ross, EV; Naseef, G; Lin, C; Kelly, M; Michaud, N; Flotte, TJ; Raythen, J; Anderson, RR; Comparison of Responses of Tattoos to Picosecond and Nanosecond Q-Switched Neodymium:YAG Lasers. Arch Dermatol 134:167-171 (1998), the disclosure of which is incorporated herein by reference in its entirety. By limiting the pulse duration, the ink particles typically reach very high temperatures with relatively minimal damage to adjacent normal skin. This significantly reduces the scarring that often results after non-selective tattoo removal methods (such as dermabrasion or treatment with a CO2 laser). The mechanism of tattoo removal by Q-switched laser radiation remains poorly understood. It is believed that Q-switched lasers achieve more specific tattoo removal through the mechanisms of selective photothermolysis and thermodynamic selectivity. Further details can be found in Solis, RR; Dayna, DG; Colome-Grimmer MO; Snyder, M; Wagner RF: Experimental nonsurgical tattoo removal in a guinea pig model with topical imiquimod and tretinoin, Dermatol Surg 2002; 28: 83-877, the entire contents of which are incorporated herein by reference. Specifically, it is believed that the pigment particles are able to absorb the laser light that heats the particles, thereby causing thermal destruction of the cells containing the particles. The destruction of these cells leads to the release of the particles, which can then be removed from the tissue by normal absorption processes.

While Q-switched lasers may be superior to some alternative methods for tattoo removal, they are not perfect. Despite achieving the predicted high particle temperatures through selective photothermal treatment, some tattoos are resistant to all laser treatments. Reasons cited for the failure of some tattoo removals include the pigment's absorption spectrum, pigment depth, and the structural properties of some inks. Adverse effects of laser tattoo treatments with Q-switched ruby lasers can include textural changes, scarring, and/or pigmentary changes. Transient hypopigmentation and textural changes have been reported in up to 50% and 12% of patients treated with Q-switched alexandrite lasers, respectively. Pigmentation and textural changes are rare adverse effects of Q-switched Nd:YAG lasers, and the incidence of hypopigmentary changes is generally lower than with ruby lasers. The development of local and systemic allergic reactions is also an unlikely (if unusual) complication of tattoo removal with Q-switched ruby and Nd:YAG lasers. Furthermore, laser treatment can be painful, so topical lidocaine injections or topical anesthetic creams are often used prior to laser treatment. Additional information regarding the effects of laser treatments can be found in Kuperman-Beade, M; Levine, V J; Ashinoff, R; Laser removal of tattoos. Am J Clin Dermatol. 2001; 2(1): 21-5, the disclosure of which is incorporated herein by reference in its entirety.

Finally, laser removal typically requires multiple treatment sessions (e.g., 5 to 20) and may require expensive equipment to achieve maximum removal. Often, because multiple wavelengths are required to treat multi-colored tattoos, it's impossible to remove all available inks and ink combinations with a single laser system. Even with multiple treatments, laser treatments can only remove 50-70% of the tattoo's pigment, resulting in residual stains.

Some embodiments of the present methods include directing a shock wave (e.g., from an embodiment of the present device) toward cells of a patient; wherein the shock wave is configured to cause the particles to disrupt one or more cells. Some embodiments include providing an embodiment of the present device; actuating the device to generate a shock wave configured to cause particles within a patient to disrupt one or more cells of the patient; and directing the shock wave toward the cells of the patient such that the shock wave disrupts the one or more cells affected by the particles (e.g., by degradation of the cell wall or membrane). In some embodiments, the one or more shock waves are configured to have substantially no lasting effect on the cells in the absence of the particles (e.g., configured to cause substantially no permanent or lasting damage to cells that are not sufficiently close to the particles to be damaged by the particles in the presence of the shock wave).

Some embodiments of the present method include focusing one or more shock waves to a specific area of tissue containing cells. In some embodiments, the area of tissue to which the one or more shock waves are focused is a depth beneath the patient's skin. The shock waves can be focused by any of a variety of mechanisms. For example, where the sound wave generator includes an ultrasound head, the ultrasound head can be a parabolic ultrasound head so that the generated sound waves are focused in the target direction according to a parabolic shape. By way of another example, an embodiment of the present device includes multiple sound wave generators that can focus the shock waves by generating sound waves of different frequencies such that the sound waves and the resulting shock waves are focused and guided by the interaction of the frequencies (e.g., in a manner similar to a phased or array radar). The focused shock waves result in higher pressures at the target cells, such as 10 MPa, 15-25 MPa, or greater.

Some embodiments of the present method further include identifying target cells in the patient to be disrupted (e.g., prior to directing one or more shock waves to the target cells). In various embodiments, the target cells can include any type of target cells, including, for example, target cells for conditions or diseases involving aggregates of cellular particles. For example, the target cells can include: tattoos, skeletal muscle cells containing crystalline microparticles, hair follicles containing keratin, dental follicles containing enamel, cancer cells, and/or the like. By way of another example, the target cells can include one or more skin conditions selected from the group consisting of: blackheads, cysts, pustules, papules, and whiteheads.

In some embodiments, the particles may comprise non-natural particles. One example of non-natural particles includes tattoo pigment particles, such as those typically placed in the human dermis to create tattoos. In some embodiments, the pigment may comprise an element with an atomic number less than 82. In some embodiments, the particles may comprise any one or a combination of the following: gold, titanium dioxide, iron oxide, carbon, and/or gold. In some embodiments, the particles have an average diameter less than 1000 nm (e.g., less than 500 nm and/or less than 100 nm).

FIG3 illustrates one embodiment of a method 100 for directing shock waves to target tissue using device 10a. In the illustrated embodiment, method 100 includes step 104, in which target cells 108 of patient tissue 112 are identified for treatment. For example, tissue 112 may include skin tissue, and/or target cells 108 may include fat cells within or adjacent to the skin tissue. In the illustrated embodiment, method 100 also includes step 116, in which housing 18 is positioned adjacent to tissue 112 and/or tissue 116 so that the shock waves can be directed toward target cells 108. In the illustrated embodiment, method 100 also includes step 120, in which acoustic wave generator 14 is positioned adjacent to (and/or coupled to) housing 18. In the illustrated embodiment, method 100 also includes step 124, in which acoustic wave generator 14 is activated to generate acoustic waves (the acoustic wave generator and housing are acoustically coupled) to form shock waves within housing 18 for delivery to target cells 108, as shown. In the embodiment shown, method 100 further includes step 128, wherein acoustic wave generator 14 is decoupled from housing 18 and housing 18 is removed from or moved relative to tissue 112. In the embodiment shown, target cells 108 are omitted from step 128, indicating their destruction. Other embodiments of the method may include some or all of the steps shown in FIG3. Apparatus 10 may be implemented similarly to apparatus 10a, except that apparatus 10 may not be configured to be detachable and, therefore, may be configured as a single piece to direct shock waves to target cells.

Methods for removing tissue markers

Some embodiments of the present methods for reducing tissue markings caused by pigment in dermal tissue (e.g., tattoos) involve the use of one of the present devices. In such methods, high-frequency shock waves are delivered into the patient's skin. When the shock waves generated by the disclosed device reach dermal cells and vibrate or accelerate intradermal particles, these particles undergo motion relative to the cell membrane, which can lead to fatigue degradation and cell rupture, thereby releasing the pigment particles. The released particles can then be removed from the surrounding tissue through the patient's body's normal absorption processes. In some embodiments, one of the present devices can be positioned adjacent to and/or directed at a tissue site containing a tattoo, other tissue marking, or other cellular structure containing particle aggregates. To cause particle modification (e.g., cellular degradation sufficient to release the particles for absorption), the shock waves can be delivered to a specific area and for a duration sufficient to rupture cells containing and/or adjacent to the pigment particles, thereby releasing the pigment particles. In some embodiments, the present device has a focal or active area that can be smaller than the tattoo, allowing the device to be periodically and sequentially focused and directed at different areas of the tattoo to result in a perceived reduction in pigment across the entire tattoo area. For example, the parameters of embodiments of the devices disclosed herein can be modified to achieve a desired number of shock waves delivered to a specific site within a desired amount of time. For example, in one embodiment, shock waves are generated by acoustic waves having a frequency of at least 1 MHz according to aspects of the present invention and exposed to a specific treatment site for an appropriate period of time to deliver at least about 100, 200, 300, 400, 500, or 1000 shock waves to the treatment site. The shock waves can be delivered all at once or in intervals (e.g., bursts) of shock waves (e.g., 5, 10, 15, 20, 25, 30, 40, 50, etc., of shock waves at a time). Appropriate intervals and the time between intervals can be modified and/or determined to achieve a desired effect at the treatment site, such as disruption of target cellular structures. It should be understood that if acoustic waves having a higher frequency, such as 2 MHz, 3 MHz, 4 MHz, or 5 MHz, are used, the treatment time can be adjusted, such as with a shorter exposure time, to achieve the desired number of shock waves delivered to the treatment area.

As will be understood by one of ordinary skill in the art, in embodiments of the present method for tattoo removal, the particles affected by the shock waves include tattoo pigment (particles), which may, for example, be at least partially disposed between and/or within the patient's skin cells. Such pigment particles may, for example, include at least one or a combination of any of the following: titanium, aluminum, silicon dioxide, copper, chromium, iron, carbon, or oxygen.

Using high-frequency shockwaves to remove or reduce skin markings offers numerous advantages over using lasers. For example, laser treatments for tattoo removal can be very painful. In contrast, high-frequency shockwaves (e.g., ultrasonic shockwaves) can be configured and/or applied so that tattoos or other skin markings can be removed or reduced with minimal pain to the patient, particularly if the shockwaves are targeted or otherwise configured to degrade only the cells containing the tattoo pigment. By way of another example, laser light directed into tissue has been found to damage or destroy surrounding tissue; whereas high-frequency shockwaves can be applied with minimal damage or destruction to surrounding tissue (e.g., because non-tattooed surrounding tissue often lacks tattoo pigment or other particles that could otherwise interact with neighboring cells and cause cellular degradation). Finally, laser tattoo removal often requires multiple treatment sessions (e.g., 5-20 sessions) to achieve maximum tattoo reduction and/or often requires the use of expensive equipment. Furthermore, because multiple wavelengths of laser light are required to remove multi-colored tattoos, multiple laser systems may be required to remove the various available inks and/or combinations of available inks. As a result, the overall cost of laser tattoo removal can be very expensive. Even with multiple treatments, laser treatments are limited to removing only 50% to 70% of the tattoo pigment and can leave a residual "stain." In contrast, high-frequency shockwaves are not dependent on the color of the tattoo pigment, allowing therapeutic application of high-frequency shockwaves without the need for different devices for different pigment colors and allowing high-frequency shockwaves to be applied to a relatively large area (e.g., the entire area of the tattoo), thereby reducing the number of treatment sessions required to achieve a patient-acceptable level of tattoo removal or reduction (e.g., a 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or greater reduction in perceptible pigment in the patient's skin).

In some embodiments, the method includes applying high-frequency shock waves (e.g., using one or more of the present devices) and applying a laser. For example, some embodiments of the method further include directing a beam from a Q-switched laser to target cells (e.g., tattooed skin). In some embodiments, directing the one or more shock waves and directing the beam are performed in an alternating sequence.

In some embodiments, the method includes delivering one or more chemical or biological agents (e.g., configured to assist in removing a tissue marker such as a tattoo) to or near the location of the target cells before, after, and/or simultaneously with directing one or more shock waves to the target cells. For example, some embodiments of the method further include applying a chemical or biological agent to the skin (e.g., before, after, and/or simultaneously with directing one or more shock waves and/or laser beams to the skin). Examples of chemical or biological agents include: chelating agents (e.g., ethylenediaminetetraacetic acid (EDTA)); immunomodulators (e.g., imiquimod[5]); combinations thereof; and/or other suitable chemical or biological agents. In various embodiments, the chemical or biological agent is delivered to the target cells transdermally and/or systemically (e.g., by injection) (e.g., may be applied topically to the skin of a tattoo).

Some embodiments of the present method of tattoo removal include applying shock waves to the tattooed skin tissue multiple times (eg, for a duration of at least 1 second (eg, 10 seconds or more), once a week for 6 weeks or more).

Methods for managing additional diseases and conditions

In addition to tattoo removal, embodiments of the present method may include applying high-frequency shock waves to treat various conditions caused by and/or conditions involving cellular particle aggregates and/or particles disposed within intracellular and/or interstitial spaces. For example, such conditions and/or diseases may include: arthritis, ligament, tendon, and muscle disorders, and/or skin disorders involving particle aggregates, including acne, age spots, and the like. Furthermore, embodiments of the present method may include applying high-frequency shock waves after delivering nanoparticles to an area of the patient containing target cells. For example, in some embodiments, nanoparticles (e.g., gold nanoparticles) are delivered intravenously into the patient's bloodstream and allowed to travel to an area of the patient containing target cells (e.g., a cancerous tumor), so that high-frequency shock waves can be directed to the target area to cause the nanoparticles to interact with and rupture the target cells.

Furthermore, embodiments of the present device (e.g., device 10) can be used to reduce wrinkles. For example, some embodiments of the present method of generating therapeutic shock waves include: providing any present device (e.g., device 10); and actuating the device to generate one or more shock waves. Some embodiments further include: positioning the device (e.g., outlet end 34 of housing 18) adjacent to tissue of a patient such that at least one shock wave enters the tissue. In some embodiments, the tissue includes skin tissue on the patient's face.

In embodiments of the present method, particles (e.g., microparticles and/or nanoparticles) are directed to or near the location of target cells (before directing shock waves to the cells). The particles may include silk, silk fibroin, carbon nanotubes, liposomes, and/or gold nanoshells. For example, in some embodiments, directing the particles may include injecting a fluid suspension containing the particles into the patient. The suspension may include, for example, saline and/or hyaluronic acid.

Deposition of crystals and other miscellaneous crystals in joints and specific tissues can lead to a number of disease states. For example, deposition of monosodium urate crystals (MSUM) in joints can lead to gout. As another example, calcium pyrophosphate dehydrate (CPPD) in joint tissues and body fluids can lead to a number of disease states, such as cartilage calcification (i.e., the presence of calcium-containing crystals detected as radiodensities in articular cartilage). By way of further example, deposition of hydroxyapatite (HA) crystals can lead to calcific tendinitis and perarthritis. In some embodiments of the present method, the particles may include natural particles (e.g., particles that occur naturally in the body), such as crystalline microparticles that can form and/or become set in the patient's musculoskeletal system. Other examples of natural particles that can be processed and/or distributed in the present method include: urate crystals, calcium-containing crystals, and/or hydroxyapatite crystals.

In embodiments of the present method for treating acne or other skin-based conditions, the particles may include dirt and/or debris disposed in one or more pores of the patient's skin and/or may include keratin removed from the patient's skin.

Some embodiments of the present methods of treating tumors or other diseases include applying shock waves to target tissue (e.g., a tumor, an area of skin with acne or other conditions) multiple times, such as, for a duration of at least (e.g., 10 seconds or more), once a week for 6 or more weeks.

The various exemplary embodiments of the devices, systems, and methods described herein are not intended to be limited to the specific forms disclosed. Rather, they encompass all modifications and alternatives falling within the scope of the claims. For example, the methods may include any combination and/or repetition of the steps and features described in the above embodiments (e.g., in combination with other steps or features).

The claims are not intended to include, and should not be interpreted as including, “means+function” or “step+function” limitations unless such limitations are expressly recited in a given claim using the phrase “means for” or “step for” respectively.

As disclosed, certain embodiments of the present invention offer advantages over other methods of using ultrasound in therapeutic applications. For example, U.S. Patent 5,618,275 discusses a method for promoting the penetration of a therapeutic agent through human skin by applying relatively low-frequency ultrasonic pressure waves in the range of approximately 15,000 to 25,000 Hz of sufficiently high intensity to induce cavitation in the skin. The low-frequency ultrasonic pressure waves act to increase the permeability of the skin, allowing the therapeutic agent to penetrate within a limited time period. In another example, U.S. Patent 6,487,447 discloses a device for applying ultrasonic radiation to a drug solution to be administered to a patient. The ultrasonic radiation has a frequency in the range of 15 kHz to 1 MHz and is applied at an intensity, time period, and distance from the skin area effective to generate cavitation bubbles. The cavitation bubbles collapse and transfer their energy to the skin area, resulting in the formation of pores in the skin area. U.S. Patent Publication No. US2008/009774 (by the present inventors) discloses a method for treating diseases caused by particles in tissue by utilizing ultrasonic radiation. The ultrasonic radiation has a frequency in the range of 15 kHz to 2 MHz and is applied at an intensity and for a period of time effective to generate cavitation bubbles, which effectively collapse and transfer their energy to the particles, thereby causing particle modification. As described above, the method of Klopotek's U.S. Patent No. 6,325,769 produces a negative pressure or vacuum effect after the pulse, which can induce tissue damage, tear tissue structures apart, heat the area, and thereby initiate the synthesis of new connective tissue. The disclosures of U.S. Patent Nos. 6,325,769 and 6,487,447 and U.S. Patent Application Publication Nos. US2008/009774 and US2003/0167964 are incorporated herein by reference in their entirety.

Unlike these methods, certain embodiments of the present disclosure achieve targeted disruption of heterogeneous cellular structures (e.g., cells containing particles) with minimal cavitation damage. Furthermore, the direct application of hypersonic energy by existing methods can lead to indiscriminate alteration and potential destruction of cells other than those containing particle aggregates. The shock waves generated by the present disclosure can be configured to disrupt target cells without exposing non-target cells to thermal damage. That is, disruption can be achieved with minimal indiscriminate heating of the surrounding area.

Although the embodiments of the present disclosure and advantages thereof have been described in detail, it will be understood that various changes, substitutions and modifications may be made without departing from the spirit and scope of the present disclosure as defined by the appended claims. In addition, the scope of this application is not intended to be limited to the specific embodiments of the processes, machines, manufactures, material compositions, means, methods and steps described in the specification. As will be readily understood by those skilled in the art based on the disclosure of the present invention, processes, machines, manufactures, material compositions, means, methods or steps currently existing or to be developed later that perform substantially the same functions as the corresponding embodiments described herein, or achieve substantially the same results, may be utilized according to the present invention. Therefore, the appended claims are intended to include such processes, machines, manufactures, material compositions, means, methods or steps within their scope.

Claims (17)

1. A method for generating a therapeutic shockwave, comprising: Multiple sinusoidal sound waves with at least one frequency between 1 MHz and 1000 MHz are provided by a sound wave generator; At least a portion of the sound wave is propagated through a shock wave medium disposed in and contained within a shock wave housing that is removably coupled to and contained in the sound wave generator, the shock wave medium being configured to exhibit nonlinear characteristics in the presence of the propagating sound wave to generate multiple shock waves. The plurality of shock waves are capable of rupturing at least one cell structure, including at least one region of heterogeneity, wherein the at least one region of heterogeneity has an effective density greater than the effective density of the at least one cell structure, thereby reducing tissue markers caused by pigments in the dermal tissue. 2. The method according to claim 1, further comprising the step of changing the frequency of the sound wave. 3. The method according to claim 1, further comprising the step of changing the amplitude of the sound wave. 4. The method according to claim 1, wherein the plurality of shock waves are generated in the shock wave medium. 5. The method of claim 1, further comprising the step of actuating a first acoustic wave generator to provide the plurality of acoustic waves. 6. The method of claim 5, further comprising the step of actuating a second acoustic wave generator to provide the plurality of acoustic waves. 7. An apparatus for generating therapeutic shock waves, comprising: A sound wave generator configured to emit a sinusoidal sound wave having at least one frequency between 1 MHz and 1000 MHz; A shock wave medium disposed within and contained in a shock wave housing that is removably coupled to and enclosed by the shock wave housing; and The device is configured to allow at least a portion of the emitted sound wave to propagate through the shock wave medium, thereby forming a shock wave emitted from the shock wave housing; and The shock wave is configured to rupture at least one cell structure comprising at least one region having heterogeneity, wherein the at least one region having heterogeneity has an effective density greater than the effective density of the at least one cell structure. 8. The apparatus of claim 7, wherein the apparatus further comprises a shock wave housing configured to contain the shock wave medium. 9. The apparatus according to claim 8, wherein the shock wave housing and the shock wave medium are integral. 10. The apparatus of claim 7, wherein the shock wave medium is configured to exhibit nonlinear characteristics in the presence of sound waves emitted from the sound wave generator. 11. The apparatus of claim 7, wherein the shock wave medium comprises one or more of the following: bubbles, solid particles, or a combination of bubbles and solid particles. 12. The apparatus of claim 8, wherein the shock wave housing defines a chamber having an input terminal coupled to the sound wave generator and an output terminal extending from the sound wave generator, and wherein the shock wave housing further includes an end cap coupled to the output terminal of the chamber. 13. The apparatus of claim 12, wherein the end cap is configured such that the attenuation of the shock wave emitted from the end cap is less than 20%. 14. The apparatus of claim 7, wherein the length of the shock wave medium through which the emitted sound wave propagates is greater than or equal to L, as determined by the following equation: Wherein, ∈ = nonlinear parameter of the shock wave medium; ω = frequency of the sound wave; ρ ₀ = density of the shock wave medium; λ = wavelength of the sound wave; c ₀ = velocity of the sound in the shock wave medium; P ₀ = pressure amplitude in the shock wave medium; and M _ω = acoustic Mach number = P ₀ ÷ (c ₀ ² ρ ₀ ). 15. The apparatus of claim 7, wherein the acoustic generator comprises an ultrasonic head. 16. The apparatus of claim 14, wherein the shock wave medium has a Goldberg number greater than or equal to 1, wherein the Goldberg number is determined by dividing the length of the shock wave medium by the absorption length of the shock wave medium. 17. A method for generating a therapeutic shockwave, comprising: Multiple shock waves are formed by propagating at least one sinusoidal sound wave with a frequency between 1 MHz and 1000 MHz provided by a sound wave generator through a shock wave medium disposed in and contained within a shock wave housing that is removably coupled to the sound wave generator, the shock wave medium being configured to exhibit nonlinear characteristics in the presence of the propagating sound waves. The shock wave is capable of rupturing at least one cell structure comprising at least one region of heterogeneity, the at least one region of heterogeneity having an effective density greater than the effective density of the at least one cell structure, thereby reducing tissue markers caused by pigments in the dermal tissue.