Thermochemical ablation of bodily tissue

Cross-reference of related applications This application is filed on February 27, 2007 and claims priority under US Patent Application No. 60 / 891,793, whose invention is entitled "Thermochemical Ablation of Body Tissue". The full disclosure of this prior application is incorporated herein by reference.

Technical field This document relates to delivering a chemical reagent to a target body tissue, eg, delivering a chemical reagent to the target body tissue to provide thermochemical ablation therapy.

background Numerous ablation procedures have been used to treat tumors or other tissues in the patient's body. In some cases, ablation therapy can be used to treat tumors that do not respond to chemotherapy or other techniques. For example, primary liver cancer or hepatocellular carcinoma (HCC) is a highly malignant neoplasm that may not respond well to intravenous chemotherapy.

The choice of HCC treatment is usually the severity of the underlying liver disease, the size and number of lesions, the location of the lesions, the ability to detect lesions on MRI, non-contrast CT or contrast CT, or ultrasound, and in-hospital. Depends on the expertise of. Traditionally, doctors have used RF ablation or microwave ablation, which destroys tumor tissue with heat, a combination of warming and co-administration of drug-containing liposomes, cryoablation to freeze the tumor, and hepatic arteries to remove the tumor. Drug infusion, aseptic arterial embolization, combination of chemotherapy and arterial embolization, selective internal radioembolization using radiolabeled iodide or radioactive microspheres as embolizers , External beam radiation therapy, or direct injection of a single agent (eg, ethanol, acetic acid, hydrochloric acid, thermophysiological saline, or sodium hydroxide).

One of the low cost and minimally invasive methods is percutaneous injection of ethanol or acetic acid. Although this method is generally not used with costly RF or microwave ablation systems, traditional single drug injections have been problematic. Injection of a single drug, such as acetic acid, may increase the acid load in patients, which can cause toxicity problems and cause renal failure. Injection of a single drug, such as ethanol, can also cause toxicity problems. The dose for each session is usually limited to control acid loading or other toxicity issues from injection of a single chemical. In general, lower doses of a drug may limit the ability of a physician to treat a tumor, except for small tumors.

Overview Some thermochemical ablation techniques can remove solid tumors such as liver cancer, lung cancer, kidney cancer, breast cancer, prostate cancer, sarcoma, and metastatic disease with minimal invasiveness. These ablation methods may also induce a chemical reaction to generate heat for ablation energy (eg, using chemical reaction energy rather than electrical energy, magnetic energy, or direct chemical toxicity). Such a chemical reaction may be induced by mixing at least one acid reagent and at least one base reagent. This can neutralize the acid load on the patient during the procedure. In some cases, it partially neutralizes the acid or base load while generating thermal energy, thereby providing a limited and safe level of remaining acid or base load to the heated solution. , The concentration of the base reagent or the concentration of the acid reagent can be selected. Thus, using the techniques described herein, physicians can inject at least two thermochemical ablation reagents at the same time without mixing them until they reach the distal portion of the delivery cannula. ..

In some embodiments, the thermochemical ablation system may comprise a transdermal liquid delivery cannula with a first lumen and a second lumen extending from the proximal part to the distal part. The distal portion may have at least a first side opening in fluid communication with the first lumen and a second side opening in fluid communication with at least the second lumen. The system also features a first reservoir containing the first thermochemical ablation reagent so that the first thermochemical ablation reagent is passed through the first lumen and distal to the transdermal liquid delivery cannula. It's okay. Some of the first thermochemical ablation reagents can be delivered through the first side mouth. This system further adds a second reservoir containing the second thermochemical ablation reagent so that the second thermochemical ablation reagent is passed through the second lumen and distal to the transdermal liquid delivery cannula. You may prepare. A portion of the second thermochemical ablation reagent is part of the second so that the first thermochemical ablation reagent and the second thermochemical ablation reagent are simultaneously dispersed and mixed in the distal direction in the radial direction. It can be delivered from the side mouth.

A particular aspect of the device for excising body tissue may include a multi-lumen thermochemical ablation cannula that simultaneously injects at least two thermochemical ablation reagents into the target tissue near the distal part of the cannula. The distal cannula may be provided with multiple liquid ports that supply at least two thermochemical ablation reagents, thereby mixing at least two thermochemical ablation reagents near the distal cannula. .. When at least two thermochemical ablation reagents are fed through multiple liquid mouths, the thermochemical ablation reagents can mix with each other to produce an exothermic chemical reaction sufficient to excise the tissue.

In some embodiments, the method for thermochemical ablation of the target tissue may include delivering a first thermochemical ablation reagent through a first lumen of a percutaneous needle. The method may also include delivering the second thermochemical ablation reagent through the second lumen of the percutaneous needle. In this method, the first thermochemical ablation reagent and the second thermochemical ablation reagent are simultaneously injected into the target tissue, and the first thermochemical ablation reagent and the second thermochemical ablation reagent are injected into the needle. Further may include a step of radially dispersing and mixing at the distal portion of the.

Some or all of these embodiments may provide one or more of the following advantages: First, thermochemical ablation techniques minimize other tissues, including solid tumors (eg, liver cancer, lung cancer, kidney cancer, breast cancer, prostate cancer, sarcoma, etc.) or varicocele, dilated tortuous veins, etc. It can be resected with limited invasiveness. Such techniques can be useful, for example, in treating patients who are not candidates for surgery due to the nature of the tumor or other intervention factors. Second, thermochemical ablation techniques include heat as the primary source of ablation, or another source of ablation (eg, RF ablation, microwave ablation, denaturant source, eg hardener, surfactant, or urea, or It is possible to induce a chemical reaction that produces heat that enhances (other sources of ablation). Third, the chemical reaction can be induced by mixing at least one acid reagent with at least one base reagent, which reduces the acid or base load on the tissue. Or it disappears. Since the acid or base load is reduced or eliminated, a larger amount of reagent can be applied without causing toxicity problems. Moreover, in some embodiments, the salt by-products resulting from the mixing of the first thermochemical ablation reagent and the second thermochemical ablation reagent can be extremely osmotic, thereby adding thermal energy. After that, a local environment that is incompatible with cell survival in the treated tissue is created. Fourth, some of the systems and equipment described herein can be manufactured without the use of costly components such as RF ablation probes. Fifth, the thermochemical ablation techniques described herein can be used to treat large tumors with a small number of treatment sessions, which enhances patient convenience. Sixth, the thermochemical ablation process can be monitored in real time using a medical imaging system such as an ultrasound imaging device. Moreover, in some embodiments, the thermochemical ablation process is a delivery device. It can be monitored in an MRI environment without the need for special (high cost) MRI compatible alloys. Seventh, using the equipment described herein, physicians can use the thermochemical ablation reagents without mixing them until at least two thermochemical ablation reagents reach the distal portion of the delivery cannula. Reagents can be injected at the same time. Thus, some aspects of the delivery device can be used to supply ablation thermal energy to internal body tissue without the need for an insulating outer layer. If an insulating outer layer is required, the outer shape of the delivery device (and the delivery path through the tissue) can be large (long). Eighth, the delivery cannula has a large number of sides that radially disperse the reagent as it exits the cannula, thereby facilitating mixing (eg, turbulence) and more even distribution of ablation thermal energy. Can be equipped with a mouth. In addition, the first thermochemical ablation reagent and the second thermochemical ablation reagent are more uniform (compared to direct injection of acetic acid or ethanol) at the treatment site due to their ability to transfer heat to surrounding tissues. Can provide a cutting action to mold. Ninth, in some cases, a portion of the first reagent and a portion of the second reagent can be mixed with each other in the distal portion of the cannula before being fed to the target tissue. A portion of the supplied liquid is supplied to the target tissue by mixing at least a portion of the first thermochemical ablation reagent and at least a portion of the second thermochemical ablation reagent in the distal portion. It can be heated by a thermochemical reaction just before it is ablated. It can be used to supply energy to internal body tissues. If an insulating outer layer is required, the outer shape of the delivery device (and the delivery path through the tissue) can be large (long). Eighth, the delivery cannula has a large number of sides that radially disperse the reagent as it exits the cannula, thereby facilitating mixing (eg, turbulence) and more even distribution of ablation thermal energy. Can be equipped with a mouth. In addition, the first thermochemical ablation reagent and the second thermochemical ablation reagent are more uniform (compared to direct injection of acetic acid or ethanol) at the treatment site due to their ability to transfer heat to surrounding tissues. Can provide a cutting action to mold. Ninth, in some cases, a portion of the first reagent and a portion of the second reagent can be mixed with each other in the distal portion of the cannula before being fed to the target tissue. A portion of the supplied liquid is supplied to the target tissue by mixing at least a portion of the first thermochemical ablation reagent and at least a portion of the second thermochemical ablation reagent in the distal portion. It can be heated by a thermochemical reaction just before it is ablated. It can be used to supply energy to internal body tissues. If an insulating outer layer is required, the outer shape of the delivery device (and the delivery path through the tissue) can be large (long). Eighth, the delivery cannula has a large number of sides that radially disperse the reagent as it exits the cannula, thereby facilitating mixing (eg, turbulence) and more even distribution of ablation thermal energy. Can be equipped with a mouth. In addition, the first thermochemical ablation reagent and the second thermochemical ablation reagent are more uniform (compared to direct injection of acetic acid or ethanol) at the treatment site due to their ability to transfer heat to surrounding tissues. Can provide a cutting action to mold. Ninth, in some cases, a portion of the first reagent and a portion of the second reagent can be mixed with each other in the distal portion of the cannula before being fed to the target tissue. A portion of the supplied liquid is supplied to the target tissue by mixing at least a portion of the first thermochemical ablation reagent and at least a portion of the second thermochemical ablation reagent in the distal portion. It can be heated by a thermochemical reaction just before it is ablated.

Details of one or more aspects of the invention are set forth in the accompanying drawings and the following description. Other features, objectives, and advantages of the present invention will be apparent from the description and drawings as well as the claims.

Similar symbols in various drawings indicate similar elements.

<figref num="1">It is sectional drawing of the thermochemical ablation system by an aspect.</figref><figref num="2">FIG. 5 is a cross-sectional view of a portion of a delivery cannula of a thermochemical ablation system according to an embodiment.</figref><figref num="3">FIG. 5 is a cross-sectional view of a portion of another delivery cannula of a thermochemical ablation system according to one embodiment.</figref><figref num="4">FIG. 5 is a cross-sectional view of a portion of yet another delivery cannula of a thermochemical ablation system according to one embodiment.</figref><figref num="5">It is sectional drawing of another aspect of a thermochemical ablation system.</figref>

Detailed description of exemplary embodiments Thermochemical ablation systems can use minimally invasive techniques to remove solid tumors or other target tissue. These ablation techniques can induce heat-generating chemical reactions for ablation energy. Such a chemical reaction may be induced by mixing at least one acid reagent and at least one base reagent. This can neutralize or reduce the acid or base load on the patient during the procedure. As the acid or base load is reduced or eliminated, more reagents can be applied and higher levels of ablation energy can be obtained without increasing toxicity in the patient. In some embodiments, the thermochemical ablation system allows the doctor to inject at least two thermochemical ablation reagents at the same time without mixing them until they reach the target tissue. Can be done.

The thermochemical ablation techniques described herein can be used to treat solid tumors that often occur, including liver cancer, lung cancer, kidney cancer, breast cancer, prostate cancer, sarcoma, and the like. These techniques can be useful, for example, in treating patients who are not candidates for surgery due to the nature of the tumor or other intervention factors. For example, some patients with HCC or other types of liver cancer are not candidates for surgery. The thermochemical ablation systems described herein are relatively convenient for patients (eg, may have fewer treatment sessions) and are relatively cost effective for healthcare providers (eg). It does not necessarily require a high cost device such as an RF ablation probe) and may be effective in the treatment of such liver cancer.

Looking at FIG. 1, the thermochemical ablation system 100 can inject a thermochemical ablation reagent into the target tissue 50 to induce a chemical reaction, thereby excising the tissue 50. The system 100 includes a first liquid reservoir 110 and a second liquid reservoir 120 that communicate fluidly with the thermochemical ablation device 130. The first reservoir 110 may contain a first thermochemical ablation reagent 115 (eg, an acid reagent) and a second reservoir 120 may contain a second thermochemical ablation reagent 125 (eg, a base reagent). May include. Reservoir 110 and 120 also include actuators 112 and 122 that can be adjusted to bring force for supply to reagents 115 and 125, respectively. Thus, the first reservoir 110 and the second reservoir 120 can be actuated to deliver reagents 115 and 125 to the proximal 132 of the liquid delivery device 130, which in turn the proximal 132 is the reagent 115. And 125 are passed through the distal portion 134 of device 130. In this embodiment, the first actuator 112 and the second actuator 122 are coupled to each other by a coupler 119 so that the actuators 112 and 122 can be adjusted simultaneously. For example, the user can apply force to the coupler 119 to adjust actuators 112 and 122 simultaneously, whereby the first reagent 115 and the second reagent 125 are delivered simultaneously to device 130. In another example, the physician or other user may selectively activate a computer control mechanism that acts on the coupler 119 to exert a force for adjustment. Such a computer control mechanism can provide accurate doses of reagents 115 and 125 delivered to reservoirs 110 and 120. In other embodiments, the first reservoir 110 and the second reservoir 120 may not be connected to each other and the actuators 112 and 122 are separately adjusted to supply the reagents simultaneously or in a chosen order. You may.

In this embodiment, the thermochemical ablation apparatus 130 can simultaneously inject the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 into the target tissue 50 near the distal portion 134. Equipped with a cannula 140. In particular, the cannula 140 comprises a first lumen 142 in fluid communication with the first reservoir 110 that delivers the first thermochemical ablation reagent 115 to the distal portion 134. The cannula 140 also comprises a second lumen 144 that is in fluid communication with the second reservoir 120 that delivers the first thermochemical ablation reagent 125 to the distal portion 134. The distal portion 134 of the cannula 140 radially disperses the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125, thereby causing the reagents 115 and 125 in the region close to the distal portion 134. May be provided with a plurality of liquid ports 145a to 145a to b. It should be understood that in other embodiments, three or more reservoirs may be used to deliver the three or more thermochemical ablation reagents to the target tissue 50. In such cases, the thermochemical ablation apparatus may include a multi-lumen cannula with three or more lumens, each of which has fluid communication with the associated liquid reservoir.

Continuing with FIG. 1, this aspect of the liquid delivery device 130 comprises a cannula 140 in the form of a percutaneous needle. For example, the cannula 140 may include a generally rigid needle body 146 having an outer diameter of about 0.135 inches or less, about 0.120 inches to about 0.008 inches, and about 0.072 inches to about 0.028 inches. The needle body 146 may contain stainless steel or another generally rigid material suitable for percutaneous insertion into the patient's skin 40. In addition, the distal portion of the cannula 140 may be provided with a sharp tip that penetrates the skin 40 and facilitates reaching the target tissue 50. The cannula 140 may also include an internal tube 147 through which the needle body 146 passes. In this aspect, the inner tube 147 comprises a smaller second needle body, generally coaxial with the outer needle body 146, whereby the first lumen 142 is defined within the second lumen 144. .. It should be understood that in other embodiments, the first lumen 142 and the second lumen 144 may be configured to be arranged in parallel (see, eg, FIG. 3). In such cases, the first lumen 142 and the second lumen 144 are defined by two lumens formed by the outer needle body 146 (eg, without the use of a centrally located inner tube 147). You may.

In some embodiments, the liquid delivery device 130 may be packaged as part of a thermochemical ablation kit that can be used by a physician or other user without further assembling any component of the device 130. For example, the liquid delivery device 130 may be manufactured such that the outer needle body 146, the inner tube 147, and the valve device 135 are fully assembled and packaged in a kit. The cannula 140 may also be manufactured such that the first lumen 142 communicates fluidly with the side opening 145a and the second lumen 144 communicates fluidly with the side opening 145b (eg, with respect to FIGS. 2-4 below). I will explain in more detail). In these cases, the physician or other user can easily unpack the liquid delivery device 130 from the kit and then connect the first liquid line 136 of the liquid delivery device 130 to the first reservoir 110. The second liquid line 137 can be connected to the second reservoir 120. When the liquid lines are connected in this way, the first reservoir 110 can communicate with the first lumen 142 in fluid communication, and the second reservoir 120 can communicate with the second lumen 144 in fluid communication.

As shown in FIG. 1, the distal portion 134 of the liquid delivery device 130 passes through one or more side openings 145a-b through which the first reagent 115 and the second reagent 125 supplied to the target tissue 50 pass. You may prepare. The side openings 145a-b may be oriented such that the thermochemical ablation reagents 115 and 125 are radially dispersed from the distal 132. The radial dispersion of the thermochemical ablation reagents in this way can improve the mixing of reagents 115 and 125 as they exit the liquid delivery device 130 (eg, due to increased turbulence). Further, since it is dispersed in the radial direction from the side openings 145a to 145a, the heat generated by the mixing of the reagents 115 and 125 can be distributed more uniformly.

The first set of side openings 145a is with the first lumen 142 so that the first thermochemical ablation reagent 115 is drained from the side opening 145a when the coupler 119 (and the first actuator 112) is adjusted. Fluid communication may be performed. Similarly, the second set of side openings 145b is a second set so that the second thermochemical ablation reagent 125 is expelled from the side opening 145b when the coupler 119 (and the second actuator 112) is adjusted. Fluid communication with lumen 144 may be performed. Thus, the liquid delivery device 130 simultaneously injects the first reagent 115 and the second reagent 125 into the target tissue 50, during which the thermochemical ablation reagents 115 and 125 mix with each other to produce an exothermic chemical reaction. When the first reagent 115 and the second reagent 125 are injected at different ratios, different amounts of liquid are supplied when the actuators 112 and 122 are adjusted simultaneously (eg, with coupler 119). The first reservoir 110 may have different forms (eg, different cross-sectional areas). In some embodiments, the concentration of the base reagent and the concentration of the acid reagent can be selected to completely neutralize the acid and base loads on the target tissue 50 after the thermochemical ablation reaction. In other embodiments, the acid or base load is partially neutralized while generating thermal energy, thereby bringing a limited safe level of the remaining acid or base load to the heated solution. , The concentration of the base reagent and the concentration of the acid reagent can be selected.

The heat generated from this chemical reaction may be sufficient to remove at least a portion of the target tissue 50 surrounding the distal portion 134 of the liquid delivery device 130. When the liquid delivery device 130 injects two reagents that chemically react with each other (rather than directly injecting one acidic reagent), the by-products of the chemical reaction are weakly acid (or base) loaded toxic. Can be accompanied by large fever. For example, in some embodiments, the liquid delivery device 130 injects both acid and base reagents to reduce the acid load while targeting tissue, whether due to damage spread or thermal damage. 50 can produce greater damage (eg, damage greater than that obtained by direct injection of acetic acid alone). Therefore, the thermochemical ablation techniques described herein have less complications due to acid (or base) load toxicity and can be used to treat larger tumors in one or two sessions.

Thermochemical ablation reagents 115 and 125 injected into the target tissue 50 may be selected to provide adequate energy deposition in the tissue and other features such as hyperosmolarity. In some embodiments, the first thermochemical ablation reagent 115 may comprise an acid. For example, the first thermochemical ablation reagent 115 includes acetic acid, peracetic acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitrate, nitrite, perchloric acid, phosphoric acid, oxalic acid, pyruvate, It may contain an acid selected from the group consisting of malonic acid, amino acids (eg, carboxylic acid derivatives) and the like. Also, in some embodiments, the second thermochemical ablation reagent 125 may contain a base. For example, the second thermochemical ablation reagent 125 is KOH, NaOH, NH.₄OH, Ca (OH)₂, LVDS₃, K₂CO₃, BuLi, NaOEt or NaSEt (eg, Na or K salts of alkoxides or thio analogs), NaH, KH, specific amines and the like may contain a base selected from the group.

As mentioned above, specific acids and specific bases can be selected to produce the desired exothermic and low toxicity by-products. For example, in some embodiments, the first thermochemical ablation reagent 115 may be acetic acid or hydrochloric acid, and the second thermochemical ablation reagent 125 may be NaOH, NaOEt, or NH.₄It may be OH. Therefore, the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 reach the distal portion 134, and the reagents 115 and 125 are mixed and chemically react with each other to generate ablation thermal energy. Liquid delivery device 130 keeps reagents 115 and 125 separate until 50 is injected simultaneously. In addition, the injection of base reagents in addition to acid reagents neutralizes or reduces the acid load on the patient during the procedure, thereby solving some of the problems associated with acid load toxicity. Can be done. By-products of the chemical reaction of the first reagent 115 and the second reagent 125 may further benefit the ablation process, for example due to the high osmotic pressure of the environment.

In other embodiments, it should be understood from the description herein that the thermochemical ablation reagents 115 and 125 may contain other reactive substances. For example, the first thermochemical ablation reagent 115 may contain an electrophile and the second ablation reagent 125 may contain a nucleophile. In some embodiments, the first thermochemical ablation reagent 115 may comprise an electrophile selected from the group consisting of acetic anhydride, acetyl chloride, acetyl bromide, other anhydrides, other acid halides, and the like. .. In these cases, the second thermochemical ablation reagent 125 may include a nucleophile selected from the group consisting of alkoxides, thio analogs, mercaptans (eg, sulfhydryl), some amines and the like. Other nucleophiles may include alcohols, sugar molecules, water, and endogenous nucleophiles. Further, in some embodiments, the second thermochemical ablation reagent 125 is a base (eg, NaOH, NaOH, NH) described above.₄It may contain a nucleophile selected from the group (OH, etc.). Thus, one exemplary embodiment of the liquid delivery device 130 can inject an electrophile (eg, acetyl chloride) and a nucleophile (eg, NaOH) that chemically react with each other. By-products of chemical reactions can result in significant exotherm while at least partially neutralizing acid (or base) loads. Such thermochemical ablation techniques described herein can be used to treat larger tumors with less complications due to acid or base loading toxicity and in relatively few sessions.

In other embodiments, it should be understood from the description herein that the thermochemical ablation reagents 115 and 125 may contain other reactive substances. For example, the first thermochemical ablation reagent 115 may contain a specific oxidizing agent, and the second ablation reagent 125 may contain a specific reducing agent. Finally, in some embodiments, the thermochemical ablation reagent is a useful imaging property or other analyzable property that allows the physician to assess the reagent distribution within the target tissue 50 and the reagent distribution throughout the body (eg, for example. It can be selected to have fluorescence, nuclear isotope, MR imaging features, etc.).

In some embodiments, one or both of the thermochemical ablation reagents 115 and 125 may be mixed with a denaturing agent that enhances the tissue ablation process. For example, prior to injection by delivery device 130, a denaturant such as hardener, surfactant, urea, or sodium perchlorate (or another substance in the Hofmeister series) is added to the first reservoir 110. Can be added to and mixed with the first reagent 115. The denaturant can act on the target tissue 50 to enhance the ablation caused by the thermochemical reaction between the first reagent 115 and the second reagent 125.

Further, in some embodiments, one or both of the thermochemical ablation reagents 115 and 125 may be supplemented with a drug to provide a pharmacological effect on the target tissue in addition to the thermochemical ablation effect. In one example, the chemotherapeutic drug can be added to the second reservoir 120 and mixed with the second reagent 125 prior to injection by the delivery device 130. This chemotherapeutic drug can be administered to the target tissue 50 via the delivery device 130 to provide a pharmacological effect as well as an ablation effect by a thermochemical reaction between the first reagent 115 and the second reagent 125. it can.

Continuing with FIG. 1, certain aspects of the thermochemical ablation system 100 may include a medical imaging system that monitors the insertion of device 130 and the delivery of reagents 115 and 125 in real time. For example, the medical imaging system may include an ultrasound imaging system 190 that allows the physician or other user to see the distal portion 134 of the liquid delivery device 130 in the target tissue 50. .. In this aspect, the ultrasound imaging system 190 comprises an ultrasound probe device 192 that can be operated outside the patient's body or within the body cavity. The ultrasonic probe 192 may be connected to an ultrasonic display system 194 that reads a signal from the probe 192 and displays a target portion of the patient's body. For example, as shown in FIG. 1, when the distal portion 134 of the device 130 is inserted into the target tissue 50 for delivery of the thermochemical ablation reagents 115 and 125, the ultrasonic display system 194 is far from the device 130. The position 134 can be shown. In other embodiments, it should be understood that the imaging system may include other types of systems other than the ultrasonic imaging system 190. For example, the medical imaging system may include a CT imaging system or the like. Some or all of the delivery device 130 may include materials compatible with the imaging system of choice so that the delivery device 130 can be monitored during insertion. For example, the cannula 140 may include a metallic material that can be visualized using the ultrasound imaging system 190. In another example, the distal portion 134 of the delivery device 130 may comprise a magnetic resonance marker, or other property that allows visibility with a selected imaging system. Further, in some embodiments, the delivery device 130 is a depth marker (depth) that is directly visible to the physician or other user. Marker) may be provided. For example, the cannula 140 may include a number of depth markers on the outer surface of the needle body 146. The doctor or other user can see these depth markers while inserting the cannula 140 through the skin 40 to know the approximate depth of insertion.

As seen in FIG. 2, the distal portion 134 of the liquid delivery device 130 may include one or more side openings 145a-b in the cannula 140. As mentioned above, the side openings 145a-b disperse the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 in the radial direction, whereby the reagents are dispersed in the region near the distal portion 134. It can be used to mix 115 and 125. This radial dispersion of the thermochemical ablation reagents can improve the mixing of reagents 115 and 125 as they exit the cannula 140 (eg, due to increased turbulence). The first lumen 142 and the second lumen 144 keep the reagents 115 and 125 separate from each other until the reagents 115 and 125 reach the distal 134 and are fed through the side mouth, after which the reagents are targeted. An exothermic chemical reaction for excision of tissue can occur. In such a case, since it is dispersed in the radial direction from the side openings 145a to 145a, the heat generated by the mixing of the reagents 115 and 125 can be distributed more uniformly.

In some embodiments, the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 may be mixed at least partially in the distal portion 134 just prior to being fed from the side openings 145a-b. It should be understood (see, for example, Figure 3). Further, in another aspect, the number of the first side opening 145a and the number of the second side opening 145b may be different from the number shown in FIG. For example, the cannula 140 may include only one first side opening 145a and only one second side opening 145b. In another example, the cannula 140 may include a first side opening 145a of 3, 4, 5, 6, 7, 8, 9, 10, or more. The cannula 140 may also include a second side opening 145b of 3, 4, 5, 6, 7, 8, 9, 10, or more. Further, in some embodiments, the number of first side openings 145a may differ from the number of second side openings 145b. For example, the cannula 140 may include three first side openings 145a and four, five, or six second side openings 145b.

In this aspect illustrated in FIG. 2, the first lumen 142 is arranged coaxially with the second lumen 144. For example, the inner tube 147 defines at least a portion of the first lumen 142 within the inner tube 147 and at least a portion of the second lumen 144 between the inner tube 147 and the needle body 146. As such, it may be placed within the needle body 146 of the cannula 140. The inner tube 147 may generally contain rigid materials such as stainless steel, hard polymers and the like. Alternatively, the inner tube may contain a non-metallic material (eg, a biocompatible polymer) that is generally housed in a rigid needle body 146. In other embodiments, it should be understood that the first lumen 142 and the second lumen 144 may be arranged in the cannula 140 in a non-coaxial arrangement. For example, the first lumen 142 and the second lumen 144 may be arranged in a parallel configuration (see, eg, the embodiments described with respect to FIG. 3).

Continuing with FIG. 2, the first lumen 142 is the first set of side openings 145a so that the first thermochemical ablation agent 115 can be delivered out of the side opening 145a through the first lumen 142. And fluid communication. Also, the second lumen 144 is fluid communicated with the second set of side openings 145b so that the second thermochemical ablation agent 125 can be delivered out of the side opening 145b through the second lumen 144. There is. The walls that at least partially define the first and second lumens (eg, in this embodiment, the needle body 146 and the inner tube 147) allow reagents 115 and 125 to reach the distal 134 and the lateral opening. Reagents 115 and 125 are configured to remain separate from each other until supplied from 145a-b. When the thermochemical ablation reagents 115 and 125 are supplied from the side openings 145a to 145a and b, they mix with each other to cause an exothermic chemical reaction, whereby the target tissue can be excised using the chemical reaction energy.

In this aspect, the cannula 140 comprises a closed distal end 143. Therefore, the thermochemical ablation reagents 115 and 125 are supplied from the side openings 145a-b rather than from the end opening of the distal end 143. In some embodiments, one or more terminal ports may be formed at the distal ends, which are plugged so that the thermochemical ablation reagents 115 and 125 are supplied only from the side ports 145a-b. Or be sealed in another way. As mentioned above, the side openings 145a-b can be used to radially disperse the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125. This can improve the mixing of reagents 115 and 125 as they exit the cannula 140 (eg, due to increased turbulence) and allow the heat generated by the mixing of reagents 115 and 125 to be more evenly distributed. ..

Continuing with FIG. 2, certain embodiments of the liquid delivery device 130 may include one or more sensors located on the distal 134. For example, in this aspect, the distal 134 comprises at least one temperature sensor 148 located on or near the outer surface of the cannula 140. The temperature sensor 148 may include a thermocouple device, eg, a K-type thermocouple, where the thermocouple device is a lead wire incorporated into the body of the cannula 140 (eg, a wire embedded in a wall, an inner wall or It has an insulated electric trace formed on the outer wall, etc.). The lead may be returned from the temperature sensor 148 to the proximal portion 132 (FIG. 1) of the liquid delivery device 130 (not shown in FIGS. 1-2) so as to connect to the sensor computer system. The sensor computer system may be configured to indicate the temperature of tissue placed near the temperature sensor 148 based on the signal transmitted from the temperature sensor 148. Such temperature information can be used, for example, by a physician or other user to monitor the excision of target tissue during the procedure.

In another example of the sensor, the distal portion 134 of the delivery device 130 may include at least one pH sensor 149 arranged and placed near the outer surface of the cannula 140. The temperature sensor 149 may include a pH probe device having electrical leads built into the body of the cannula 140 (eg, wires embedded in the wall, insulated electrical traces formed on the inner or outer wall, etc.). The lead may be returned from the pH sensor 149 to the proximal portion 132 (FIG. 1) of the liquid delivery device 130 (not shown in FIGS. 1-2) so as to connect to the sensor computer system. The sensor computer system may be configured to indicate the pH value of a material near the distal portion based on the signal transmitted from the pH sensor 149. Such pH information can be used, for example, by a physician or other user to monitor the acid load on tissues during delivery of thermochemical ablation reagents 115 and 125 during treatment.

Next, looking at FIG. 3, some embodiments of the liquid delivery device may include a multi-lumen cannula in which at least one lumen is not arranged in a coaxial configuration. In this aspect, another distal portion 134'of the liquid delivery device comprises a cannula 240 having at least two lumens 242 and 244 in a non-coaxial configuration. The first lumen 242 is arranged adjacent to the second lumen 244. For example, the first lumen 242 and the second lumen 244 may be at least partially defined by two adjacent lumens passing through the cannula 140. In such cases, the cannula 140 may include a generally rigid needle body 246 in which a first lumen 242 and a second lumen 244 are formed, thereby being separated by an intermediate wall portion 247.

Thus, a wall that at least partially defines the lumen (eg, in this embodiment, the needle body 246 and the intermediate wall portion 147) will allow reagents 115 and 125 to reach each other until reagents 115 and 125 reach the distal portion 134'. It is configured to keep it separate. The first reagent 115 and the second reagent 125 can then be mixed at least partially (via internal ports 248a and 248b) before being fed from the cannula 240. The first internal port 248a allows a portion of the first reagent 115 to pass through the first lumen 242 to the second lumen 244 and mix with a portion of the second reagent 125 at the distal portion 134'. To enable. Also, in the second internal port 248b, a portion of the second reagent 125 is mixed with a portion of the first reagent 115 at the distal portion 134'through the second lumen 244 to the first lumen 242. Allows you to. In some cases, a portion of the first reagent 115 and a portion of the second reagent 125 may be mixed with each other in the distal portion 134', the other portion of the first reagent 115 and the second Other portions of Reagent 125 may be mixed after being fed through the mouth of distal 134'. By mixing at least a portion of the first thermochemical ablation reagent 115 and at least a portion of the second thermochemical ablation reagent 125 at the distal portion 134'before being fed to the target tissue, the target tissue. A part of the supplied liquid can be heated by a thermochemical reaction immediately before being supplied to. In another embodiment, the cannula 240 is such that the first reagent 115 and the second reagent 125 do not mix in the distal 134'(eg, after being fed from the distal 134'). It should be understood that does not have to have internal ports 248a-b.

Similar to the above embodiment, the distal portion 134'can be used in the cannula 240 to radially disperse the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125. It may be provided with one or more side openings 245a-b. This radial dispersion of thermochemical ablation reagents 115 and 125 mixes at least a portion of reagents 115 and 125 in the region near the distal 134', thereby causing an exothermic chemical reaction for target tissue resection. Can be used to generate. In addition, the radial dispersion of the liquid from the side openings 245a-b can be used to more evenly distribute the thermal energy from the exothermic chemical reaction. As shown in FIG. 3, the first set of side openings 245a extends from the first lumen 242 and the second set of side openings 245b extends from the second lumen 244. The number of first side openings 245a and the number of second side openings 245b may differ from the numbers illustrated in FIG.

Continuing with FIG. 3, in this aspect, the cannula 240 comprises a distal end with end ports 243a and 243b. The first thermochemical ablation agent 115 (and the combined portion of the first reagent 115 and the second reagent 125 mixed through the internal port 248b) passes through the first lumen 242 and the first. The first terminal port 243a extends from the first lumen 242 so that it can be delivered out of the terminal port 243a. Also, the second thermochemical ablation agent 125 (and the portion of the combination of the first reagent 115 and the second reagent 125 mixed through the internal port 248a) passes through the second lumen 244 and is second. The second terminal port 243b extends from the second lumen 244 so that it can be delivered out of the terminal port 243b. Therefore, the thermochemical ablation reagents 115 and 125 can be supplied from the terminal ports 243a and 243b in addition to the side ports 245a and 245b. When the unmixed portion of the first reagent 115 is delivered through the first terminal port 243a and the unmixed portion of the second reagent 125 is delivered through the second terminal port 243b. The unmixed portions of reagents 115 and 125 can then be mixed in the distal region of the cannula 240 and react with each other. In these cases, the physician or other user delivers thermochemical ablation energy from the distal 134'to the radial lateral and anterior-distal region of the distal 134'. Cannula 240 can be operated as such. In some embodiments, it should be understood that the cannula 240 with the non-coaxial lumens 242 and 244 may have a closed distal end similar to that described with respect to FIG.

In certain embodiments, the distal portion 134'of the liquid delivery device may comprise one or more sensors located on the cannula 240. For example, the cannula 240 may incorporate a temperature sensor (eg, the sensor 148 described with respect to FIG. 2), a pH sensor (eg, the sensor 149 described with reference to FIG. 2), and the like. Such sensors can provide useful information to the physician or other user during the ablation procedure.

In another embodiment, the cannula 240 may be provided with terminal openings 243a-243b without any side openings 245a-b. In such an embodiment, the one or more terminal ports 243a may extend from the first lumen 242 and the one or more terminal ports 243b may extend from the second lumen 244. The first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 are delivered from the terminal ports 243a to b without the opportunity to pass through the side ports 245a to 245a to b. Such a configuration can be used, for example, to excise a specific and localized target tissue area generally distal to the tip of the cannula 240. In these aspects, it should be understood that the first lumen and the second lumen may be arranged in a coaxial configuration, a parallel configuration, or a different configuration.

Next, looking at FIG. 4, some embodiments of the liquid delivery device may include a cannula with adjustable side protrusions that supply the thermochemical ablation reagents 115 and 125. In this aspect, another distal portion 134'' of the liquid delivery device comprises a cannula 340 having at least two lumens 342 and 344 that can be adjusted relative to the outer needle body 346. For example, the first lumen 342 can be moved at least by a first tube 348 that can be moved from the proximal position to the distal position so that the first lateral protrusion 345a projects outward from the radial plane of the cannula 340. It may be partially specified. Similarly, the second lumen 344 can be moved from the proximal position to the distal position by the second tube 347 so that the second lateral protrusion 345b projects outward from the radial plane of the cannula 340. It may be specified at least partially. The first side protrusion 345a and the second side protrusion 345b may have a port for supplying the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 from the protrusion. Thus, the first flank 345a and the second flank 345b enter a wide area of the target tissue and are recessed to further distribute thermochemical ablation energy during delivery of reagents 115 and 125. It can be adjusted from a protruding position (see, eg, FIG. 4) from (eg, generally a position within the lumen of the outer needle body 346).

In this aspect, the outer needle body 346 generally contains a rigid material (eg, stainless steel, etc.), and the first tube 348 and the second tube 347 are shaped to exhibit superelastic features when in the patient's body. Contains memory alloys. For example, the first tube 348 and the second tube 347 protrude from a retracted position (eg, lateral protrusions 345a-b are generally confined in the lumen of the outer needle body 346). It may also include a nitinol material that provides superelastic flexibility during the transition to position (see, eg, FIG. 4). Therefore, the side protrusions 345a-b may have a curved shape or other configuration that allows the mouth of the side protrusions to face a particular region.

During use, the physician or other user can point the distal 134'' to the target tissue under the guidance of the medical imaging system 190 (FIG. 1). In such cases, the lateral protrusions 345a-b may be in recessed positions to facilitate insertion of the cannula 340 into the patient. When the distal 134'' reaches the target tissue, the doctor or other user may reposition the first tube 348 and the second tube 347 with respect to the outer needle body 346 as a trigger or other actuator (Figure). (Not shown in 4) can be moved. For example, the trigger device adjusts the first tube 348 and the second tube 347 to be distal, thereby causing the lateral protrusions 345a-b to protrude radially outward of the cannula 340. Can be pushed to. Therefore, the lateral processes 345a-b act as tines that penetrate a wide area of the target tissue. The physician or other user then asks the coupler 119 (FIG. 1) so that the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 are supplied through the mouth of the lateral protrusions 345a-b. ) Or other devices can be adjusted. The first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125, when released from the mouth, mix with each other in a heat-generating chemical reaction that excises the target tissue.

In some embodiments, it should be understood that the cannula 340 may have lumens 342 and 344 arranged in a coaxial configuration, a parallel configuration, or different configurations. In another embodiment, the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 are fed through the mouth of the side protrusions 345a-b (eg, as in the embodiment described with respect to FIG. 3). Immediately before being mixed, it may be mixed at least partially in the distal portion 134''. Also, in some embodiments, the cannula 340 may have a number of side openings that supply the first and second reagents directly from the cannula 340 (in addition to liquid delivery from the side projections 345a-b). Good. Further, in some embodiments, the cannula 340 may have a closed distal end similar to that described with respect to FIG. 2 or a terminal opening similar to that described with respect to FIG. In certain embodiments, the distal portion 134'' of the liquid delivery device may include one or more sensors located on the cannula 340. For example, the cannula 340 may incorporate a temperature sensor (eg, the sensor 148 described with respect to FIG. 2), a pH sensor (eg, the sensor 149 described with reference to FIG. 2), and the like. Such sensors can provide useful information to the physician or other user during the resection procedure.

Next, looking at FIG. 5, some embodiments of the thermochemical ablation system 400 may include a liquid delivery device 430 with at least a partially flexible cannula 440. For example, the cannula 440 may include a flexible catheter body 446 that can be delivered through a body passage 45 that includes veins, arteries, urethra, rectum, vagina, esophagus, and the like. Thus, a physician or other user may pass the distal portion 434 of the liquid delivery device 430 through the body passage 45 for excision or other treatment of the target tissue 50'(eg, tumor). , Can be directed towards obstruction of the vascular structure, eg varicocele or dilated tortuous vein, ureteral obstruction, etc.).

Similar to the above aspect, the thermochemical ablation system 400 includes a first liquid reservoir 410 and a second liquid reservoir 420 that are in fluid communication with the thermochemical ablation device 430. The first reservoir 410 contains a first thermochemical ablation reagent 115 and the second reservoir 420 contains a second thermochemical ablation reagent 125. Reservoir 410 and 420 include actuators 412 and 422, which can be adjusted to bring force for supply to reagents 115 and 125, respectively. The first actuator 412 and the second actuator 422 may be mechanically coupled to each other by a coupler 419 so that they can be adjusted simultaneously.

Similar to the above aspect, the cannula 340 of the liquid delivery device 430 has a first lumen 442 in fluid communication with the first reservoir 410 and a second lumen 444 in fluid communication with the second reservoir 420. Be prepared. Also, the distal portion 434 of the delivery device 430 supplies the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125, whereby the reagents 115 and 125 in the region close to the distal portion 434. A plurality of liquid ports 445a to 445a to b may also be provided.

Continuing with FIG. 5, this aspect of the liquid delivery device 430 comprises a cannula 440 in the form of a flexible catheter device. For example, the cannula 440 may include a generally flexible catheter body 446 made of a biocompatible polymer. The liquid delivery device 430 may include a steering mechanism (eg, steering wire, shape memory actuator, etc.) so that the distal end of the cannula 440 can travel through the body passage 45. The cannula 440 may also include an internal tube 447 formed inside the catheter body 446. Thus, the first lumen 442 is at least partially defined by the internal tube 447 and the second lumen 444 is at least partially defined between the catheter body 446 and the internal tube 447. Therefore, in this embodiment, the first lumen 442 and the second lumen 444 are arranged in a coaxial configuration. In other embodiments, the first lumen 442 and the second lumen 444 may be arranged in parallel or other configurations.

The distal portion 434 of the liquid delivery device 430 may include one or more side openings 445a-b through which the first reagent 115 and the second reagent 125 fed to the target tissue 50'pass. The side openings 445a-b may be oriented such that the thermochemical ablation reagents 115 and 125 are radially dispersed from the distal portion 432. This radial dispersion of the thermochemical ablation reagents can improve the mixing of reagents 115 and 125 as they exit the liquid delivery device 430 (eg, due to increased turbulence). Further, since it is dispersed in the radial direction from the side openings 445a to 445a, the heat generated by the mixing of the reagents 115 and 125 can be distributed more uniformly. In some embodiments, it should be understood that the cannula 440 may have a closed distal end similar to that described with respect to FIG. 2, or a terminal opening similar to that described with respect to FIG. is there. In another embodiment, the cannula 440 may have no side openings 445a-b and may include a terminal opening. In certain embodiments, the distal portion 434 of the liquid delivery device 430 may include one or more sensors located on the cannula 440. For example, the cannula 440 may incorporate a temperature sensor (eg, the sensor 148 described with respect to FIG. 2), a pH sensor (eg, the sensor 149 described with reference to FIG. 2), and the like. Such sensors can provide useful information to the physician or other user during the resection procedure.

As shown in FIG. 5, the first set of side openings 445a drains the first thermochemical ablation reagent 115 from side openings 445a when coupler 419 (and first actuator 412) is adjusted. As such, fluid communication with the first lumen 442 may be performed. Similarly, the second set of side openings 445b is such that the second thermochemical ablation reagent 125 is expelled from side opening 445b when coupler 419 (and second actuator 412) is adjusted. It may communicate with the lumen 444 of the fluid. Thus, the liquid delivery device 430 simultaneously injects the first reagent 115 and the second reagent 125 into the target tissue 50', during which the thermochemical ablation reagents 115 and 125 mix with each other to cause an exothermic chemical reaction. .. The heat generated from this chemical reaction may be sufficient to remove at least a portion of the target tissue 50'around the distal portion 434 of the liquid delivery device 430. As mentioned above, the liquid delivery device 430 injects two reagents that chemically react with each other (rather than injecting one acidic reagent directly), so that the by-products of the chemical reaction are weak acids (or bases). ) Load toxicity can be accompanied by large fever. In some embodiments, the first thermochemical ablation reagent 115 and the second thermochemical ablation reagent 125 are distal (eg, as described with respect to FIG. 3) just prior to being fed from the side openings 445a-b. It should be understood that in part 434 it may be mixed at least partially (via the internal mouth).

Continuing with FIG. 5, the liquid delivery device 430 may optionally include an expandable balloon device 441 located along the distal portion 434. The expandable balloon device 441 can be used to secure the distal end of the cannula 340 to the desired position by the body passage 45. Alternatively, the expandable balloon can be used to temporarily seal the body passage 45 while delivering the thermochemical ablation reagents 115 and 125 from the catheter body 446. For example, the balloon 441 may be filled with saline or another fluid to press against the wall of a vein or artery, thereby temporarily blocking blood flow through that portion of the vein or artery. Thermochemical ablation reagents 115 and 125 can be supplied as described above while expanding the balloon 441. This allows reagents 115 and 125 to mix with each other near the target tissue and without being swept away by normal blood flow. After the excision procedure is complete, the balloon may be folded to remove the liquid delivery device 430.

One aspect of the thermochemical ablation system 400 may include a medical imaging system that monitors the insertion of device 430 and the delivery of reagents 115 and 125 in real time. For example, the medical imaging system allows the physician or other user to see the distal portion 434 of the liquid delivery device 430 in the target tissue 50'(eg, FIG. 1). (See) may be provided. In another example, the medical imaging system may include a CT imaging system and the like. The delivery device 430 may include one or more types of material compatible with the imaging system of choice so that the delivery device 430 can be monitored during insertion. For example, the cannula 440 may include a metallic material that can be visualized using the ultrasound imaging system 190. In another example, the catheter body 446 of the cannula 440 may be inserted with a magnetic resonance marker that provides visibility using the imaging system of choice. Further, in some embodiments, the delivery device 430 may comprise a depth marker that can be directly viewed by a physician or other user. For example, the lateral catheter body 446 may include a number of depth markers. The doctor or other user can see these depth markers while inserting the cannula 140 through the skin 40 to know the approximate depth of insertion. Thus, a physician or other user may pass the distal portion 434 of the liquid delivery device 430 through the body passage 45 for excision or other treatment of the target tissue 50'(eg, tumor). , Can be directed towards obstruction of the vascular structure, eg varicocele or dilated tortuous vein, ureteral obstruction, etc.).

The thermochemical ablation systems described herein can be used in minimally invasive techniques to remove solid tumors or other target tissues. These ablation techniques may induce a chemical reaction that produces heat due to the ablation energy. Such chemical reactions may be induced by mixing at least one acid reagent and at least one base reagent, thereby neutralizing or reducing the acid load on the patient during the procedure. be able to. As mentioned above, other reagents can be used to induce the desired exothermic chemical reaction. The thermochemical ablation techniques described herein can be used to treat solid tumors that often occur, including liver cancer, lung cancer, kidney cancer, breast cancer, prostate cancer, sarcoma, and the like. In addition, the thermochemical ablation techniques described herein can be used to treat obstructions that occur in other target tissues, such as the body passages. Finally, the thermochemical ablation techniques described herein are not limited to use in human patients. For example, the thermochemical ablation system described herein can be used to treat other animal patients, including mammalian patients.

Although many aspects of the invention have been described, it will nevertheless be understood that various modifications are possible without departing from the spirit and scope of the invention. Therefore, other aspects are within the scope of the appended claims.