Delivery devices for delivering therapeutic drugs

Abstract

In one example, a method for delivering a therapeutic agent to at least one of a patient's palatine canal or pterygopalatine fossa is described. The method includes inserting a delivery device into the patient's nasal cavity. The delivery device includes an elongated shaft having a proximal end and a distal end, a handpiece coupled to the proximal end of the elongated shaft, and a piercing element disposed at the distal end of the elongated shaft. The method also includes advancing the distal end of the elongated shaft to a position adjacent a palatine bone inside the nasal cavity, actuating the piercing element to form a passage in the palatine bone between the patient's nasal cavity and the palatine canal, and delivering the therapeutic agent into the palatine canal.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 684,917, filed on June 14, 2018, the content of which is hereby incorporated by reference in its entirety.

[0002] This application is related to U.S. Patent Application No. 15 / 693,216, filed on August 31, 2017; U.S. Patent Application No. 15 / 786,306, filed on October 17, 2017; U.S. Patent Application No. 15 / 682,804, filed on August 22, 2017; U.S. Patent Application No. 15 / 431,740, filed on February 13, 2017; U.S. Patent Application No. 15 / 624,632, filed on June 15, 2017; U.S. Provisional Patent Application No. 62 / 861,591, filed on June 14, 2019, the individual contents of which are hereby incorporated by reference in their entirety.

[0003] The present invention relates to systems, devices, and methods for delivering therapeutic agents into the bone cavity. More specifically, the present invention relates to delivering therapeutic agents into the patient's palatine canal. The therapeutic agent may be an anesthetic and may be used in the treatment of rhinitis.

Background Art

[0004] Figures 1A and 1B show the anatomical structure of the nasal cavity 100. In particular, Figure 1A shows a sagittal plan view of the lateral wall of the nasal cavity 100, including several bony structures within the region. More specifically, Figure 1A shows the nasal bone 102A, the frontal process of the maxilla 102B, the lacrimal bone 102C, the superior nasal concha 102D, the middle nasal concha 102E, the coronoid process of the ethmoid bone 102F, the sphenopalatine foramen 102G, the posterior fontanelle 102H, the greater and lesser palatine nerves 102I, the medial pterygoid plate of the sphenoid bone 102J, the vertical plate of the palatine bone 102K, the inferior nasal concha 102L, the greater palatine nerve 102M, the lesser alar cartilage 102N, the greater alar cartilage 102O, and the lateral process of the septal cartilage 102P. Figure 1B shows a similar figure, where a small section of bone has been removed to show the palatine canal and pterygopalatine fossa. Figure 1B shows several nasal nerves. In particular, Figure 1B shows the greater and lesser palatine nerves 102I, the pterygopalatine ganglion 102Q, and the palatine canal 102R. Figure 1C shows an inferior view of the oral palate showing the foramen palatine, which is the opening of the palatine canal in the hard palate, and notable nerves and blood vessels flow from the canal along the palate. For example, Figure 1C shows the incisive fossa 102S, greater palatine nerve 102I, greater palatine foramen 102T, lesser palatine foramen 102U, lesser palatine nerve 102I, uvula 102V, lesser palatine artery 102W, and greater palatine artery 102X.

[0005] As shown in Figure 1A, the sphenopalatine foramen 102G is a small opening near the upper surface of the palatine bone 102K, through which the sphenopalatine artery and posterior nasal nerve cross into the nasal cavity 100. The sphenopalatine foramen 102G and palatine foramina 102T, 102U provide access points to the pterygopalatine fossa and palatine canal 102R, where the roots of the sphenopalatine ganglion, maxillary nerve, and sphenopalatine artery are located. Although challenging, accessing and delivering therapeutic agents to the fossa and / or palatine canal 102R can allow physicians to have better control of pain and bleeding during surgical procedures in awake patients. Examples, though not limited to, are surgical procedures within the nasal cavity 100. Surgical procedures within the nasal cavity 100 in awake patients are becoming increasingly common, and the success of these procedures depends in part on how well the patient can tolerate the procedure and how well the physician can visualize the procedure being performed.

[0006] Currently, many physicians achieve local pain control and bleeding control during these procedures by applying anesthetics and / or vasoconstrictors topically to the mucosa within the nasal cavity, or by injecting these drugs directly into the mucosa. In some cases, physicians will attempt to inject submucosa near the sphenopalatine foramen, creating a large bleb and allowing the drug to migrate into the foramen for absorption by the trunk of the posterior nasal nerve and / or sphenopalatine artery. While both of these options have proven effective in controlling pain and bleeding close to the site of direct application, they have limitations in achieving reliable, adequate, and widespread control due to the wide expanse of blood vessels and nerves present within the nasal cavity. [Overview of the project]

[0007] In one example, a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa is described. The method involves inserting a delivery device into the patient's nasal cavity. The delivery device includes an elongated shaft having a proximal and distal end, a handpiece coupled to the proximal end of the elongated shaft, and a perforating element disposed at the distal end of the elongated shaft. The method also includes advancing the distal end of the elongated shaft to a position close to the palatine bone inside the nasal cavity, activating the perforating element to form a passage in the palatine bone between the patient's nasal cavity and palatine canal, and delivering the therapeutic drug into the palatine canal.

[0008] Another example describes a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa. The method involves inserting a device into the patient's mouth. The device includes an elongated shaft having a proximal and distal end, an access port coupled to the proximal end of the elongated shaft, and a therapeutic drug delivery member disposed on the distal portion of the elongated shaft. The therapeutic drug delivery member includes a delivery conduit. The method also includes advancing the distal end of the elongated shaft of the device to a position close to the greater palatine foramen of the patient's mouth. The method further includes using the delivery conduit to deliver the therapeutic drug into at least one of the palatine canal or pterygopalatine fossa using the therapeutic drug delivery member.

[0009] Another example describes a method for delivering a drug into at least one of a patient's palatine canal or pterygopalatine fossa. The method involves inserting a mouthpiece into the patient's mouth. The mouthpiece is U-shaped. The mouthpiece includes a well configured to receive the patient's teeth. The mouthpiece includes an introduction needle. The method also includes positioning the mouthpiece so that the teeth are received in the well and the introduction needle is inserted into the patient's greater palatine foramen. The method further includes delivering the drug through the introduction needle into the patient's greater palatine foramen, into the palatine canal.

[0010] The features, functions, and advantages discussed can be achieved independently in various examples, or combined in other examples, and further details can be understood by referring to the following description and diagrams.

[0011] Novel features that are considered characteristic of the illustrative examples are described in the attached claims. However, the illustrative examples, as well as preferred modes of use, further purposes and descriptions thereof, will be best understood by referring to the following detailed description of the illustrative examples of this disclosure, when interpreted in conjunction with the attached drawings. [Brief explanation of the drawing]

[0012] [Figure 1A] This is a diagram showing the anatomical structures of the nasal cavity and oral cavity. [Figure 1B] This is a diagram showing the anatomical structures of the nasal cavity and oral cavity. [Figure 1C] This is a diagram showing the anatomical structures of the nasal cavity and oral cavity. [Figure 2] This is a simplified block diagram of a delivery device, as an example. [Figure 3] This figure shows an example of a delivery device. [Figure 4] This figure shows a delivery device related to another example. [Figure 5] This figure shows a delivery device related to another example. [Figure 6A]A diagram showing a delivery device according to another example. [Figure 6B] A diagram showing the distal end of the delivery device shown in FIG. 6A with a spring in a compressed state according to an example. [Figure 6C] A diagram showing the distal end of the delivery device shown in FIG. 6A with a spring in a released state according to an example. [Figure 7A] A diagram showing a delivery device with an expandable member in a crushed state according to another example. [Figure 7B] A diagram showing the distal end of the delivery device shown in FIG. 7A with an expandable member in an expanded state according to an example. [Figure 8] A diagram showing a delivery device according to another example. [Figure 9] A diagram showing a delivery device according to another example. [Figure 10A] A diagram showing a cap in a first state according to another example. [Figure 10B] A diagram showing a cap in a second state according to another example. [Figure 11] A diagram showing a nose tool and a plug according to an example. [Figure 12] A diagram showing a delivery device according to another example. [Figure 13A] A diagram showing a delivery device according to another example. [Figure 13B] A diagram showing the distal end of the delivery device shown in FIG. 13A according to an example. [Figure 14A] A diagram showing a delivery device according to another example. [Figure 14B] A diagram showing the delivery device shown in FIG. 14A with a protrusion extending through an opening in a tissue or bone structure according to an example. [Figure 15] A diagram showing a delivery device according to another example. [Figure 16] A diagram showing a delivery device according to another example. [Figure 17] A flowchart diagram for a method of delivering a therapeutic agent according to another example. [Figure 18A]A diagram showing a delivery device in a first state according to an example. [Figure 18B] A diagram showing the delivery device of FIG. 18A in a second state according to an example. [Figure 18C] A side view of the delivery device shown in FIG. 18A according to an example. [Figure 18D] A side view of the delivery device shown in FIG. 18A according to an example. [Figure 19] A diagram showing a delivery device in a first state according to another example. [Figure 20] A diagram showing the delivery device of FIG. 19 in a second state according to an example. [Figure 21] A diagram showing the delivery device of FIG. 18A in the oral cavity according to an example. [Figure 22] A bottom view of the delivery device of FIG. 18A disposed in the oral cavity of a subject according to an example. [Figure 23] A diagram showing a method for delivering a therapeutic agent to at least one of the palatine canal or the pterygopalatine fossa of a patient according to an example. [Figure 24] A diagram showing a method for delivering a therapeutic agent to at least one of the palatine canal or the pterygopalatine fossa of a patient that can be used with the method of FIG. 23 according to an example. [Figure 25] A diagram showing a method for delivering a therapeutic agent to at least one of the palatine canal or the pterygopalatine fossa of a patient that can be used with the method of FIG. 24 according to an example. [Figure 26] A diagram showing a method for delivering a therapeutic agent to at least one of the palatine canal or the pterygopalatine fossa of a patient that can be used with the method of FIG. 24 according to an example. [Figure 27] A diagram showing a method for delivering a therapeutic agent to at least one of the palatine canal or the pterygopalatine fossa of a patient that can be used with the method of FIG. 23 according to an example. [Figure 28] A diagram showing a method for delivering a therapeutic agent to at least one of the palatine canal or the pterygopalatine fossa of a patient that can be used with the method of FIG. 27 according to an example. [Figure 29]This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 27, which illustrates one example. [Figure 30] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 27, which illustrates one example. [Figure 31] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 23, which illustrates one example. [Figure 32] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 23, which illustrates one example. [Figure 33] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 23, which illustrates one example. [Figure 34] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 23, which illustrates one example. [Figure 35] This figure shows a method for delivering a therapeutic drug to at least one of the palatine canal or pterygopalatine fossa of a patient in another example. [Figure 36] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 35, which illustrates one example. [Figure 37] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 36, which illustrates one example. [Figure 38] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 35, which illustrates one example. [Figure 39] This figure shows a method for delivering a therapeutic drug to at least one of a patient's palatine canal or pterygopalatine fossa, which can be used in conjunction with the method shown in Figure 35, which illustrates one example. [Figure 40]This figure shows a method for delivering a therapeutic drug to at least one of the palatine canal or pterygopalatine fossa of a patient in another example. [Figure 41] This figure shows a method for delivering a therapeutic drug to the canal of the skull of a patient, including nerves, in one example. [Modes for carrying out the invention]

[0013] The examples disclosed are described more fully below with reference to the accompanying drawings, some of which, though not all, will be shown. Certainly, several different examples could be described, but should not be construed as limiting us to those described herein. Rather, these examples are described in a manner that fully conveys the scope of this disclosure to those skilled in the art, ensuring that this disclosure is thorough and complete.

[0014] This technology relates to a system, device, and method for delivering therapeutic drugs into the palatine canal. In the example, drug delivery is achieved by penetrating the thin palatine bone 102K and creating a passage from the nasal cavity directly into the palatine canal, through which the drug can be delivered. While the described example discloses a system and method for accessing the palatine canal via the deployment of activity into the palatine bone 102K, the technology can also be applied to other anatomical regions.

[0015] In this example, access to the palatine canal is achieved through the application of a fluid stream, applied under high pressure to the mucosal wall within the nasal cavity in the area where the palatine bone 102K covers the palatine canal. The high-pressure fluid jet perforates a small hole through the mucosa and bone, providing a pathway for access to the palatine canal and the nerves located inside it. In this example, the fluid used in the perforation process is also a therapeutic agent intended for delivery to the palatine canal. In this example, a non-toxic fluid such as water or saline is used to perforate the passage to the palatine canal, and the therapeutic agent is subsequently delivered through this passage. In this example, access to the palatine canal and pterygopalatine fossa for applying anesthetics or other therapeutic agents to the nerves and / or blood vessels inside the canal is performed without penetrating the bone. For example, transmucosal injection or natural openings such as holes (e.g., sphenopalatine foramen or greater palatine foramen) can be used to access the palatine canal for therapeutic agent delivery.

[0016] In the case of the methods and apparatus described within the scope of this application, physicians are enabled to more reliably control pain and bleeding by delivering therapeutic drugs into anatomical regions from which the nasal nerves and associated blood vessels originate. The delivery of drugs into the pterygopalatine fossa and through the palatine canal, and the associated potential benefits, have been disclosed in the past (i.e., Douglas and Wormald: Pterygopalatine Fossa Infiltration, Laryngoscope 116, July 2006). However, this technique has not been widely adopted due to the complexity of accessing these regions and potential safety challenges. Current access methods can cause damage to the sphenopalatine and palatine arteries and carry the risk of unintentionally injecting therapeutic drugs into the bloodstream. The present invention disclosed within the scope of this application describes methods and features for reducing these risks and simplifying the delivery process.

[0017] Figure 2 shows a simplified block diagram of an example drug delivery device 220 (hereinafter referred to as the "delivery device" for simplicity). As shown in Figure 2, the delivery device 220 includes an elongated shaft 222 extending between the proximal portion 224 and the distal portion 226 of the delivery device 220. The elongated shaft 122 can be configured to be at least partially inserted into the patient's nasal cavity. For example, the elongated shaft 122 can have a diameter between approximately 1 millimeter (mm) and approximately 4 mm. Additionally, for example, the elongated shaft 122 can be made from stainless steel and / or a semi-rigid polymer (e.g., nylon or Pebax).

[0018] Although the elongated shaft 222 is shown separated in Figure 2 from the proximal portion 224 and the distal portion 226, the proximal portion 224 and / or distal portion 226 of the delivery device 220 may include the respective portions of the elongated shaft 222. More generally, the proximal portion 224 may include one or more components of the delivery device 220 that are located relatively far from the target tissue to be treated with the therapeutic agent while applying the therapeutic agent to the target tissue, and the distal portion 226 may include one or more components of the delivery device 220 that are located relatively close to the target tissue while applying the therapeutic agent to the target tissue. As used herein, the term “target tissue” means the tissue to be treated with the therapeutic agent during a medical procedure.

[0019] The proximal portion 224 may include a handpiece 228, one or more user control devices 230 (e.g., one or more triggers, one or more knobs, one or more triggers, one or more buttons, one or more switches, one or more levers, and / or one or more dials), a therapeutic agent source 232, and / or other features. The distal portion 226 may include a therapeutic agent delivery member 234, and / or a perforating element 236.

[0020] Within the scope of the examples, the handpiece 228 can be configured to facilitate grasping and maneuvering the delivery device 220. For example, the handpiece 228 may have a shape and / or size that facilitates the user maneuvering the elongated shaft 222 and distal portion 226 using only one hand. In one example, the handpiece 228 may have a shape and / or size that facilitates the user holding the handpiece 228 in a pistol grip style (for example, the handpiece 228 may have an axis that crosses the axis of the elongated shaft 222). In another example, the handpiece 228 may, additionally or alternatively, have a shape and / or size that facilitates the user holding the handpiece 228 in a writing instrument grip style (for example, the handpiece 228 may have an axis that is substantially parallel to the axis of the elongated shaft 222). Additionally or alternatively, the handpiece 228 may (i) have a shape and / or size larger than the shape and / or size of the elongated shaft 122 to facilitate gripping and maneuvering the delivery device 220, and / or (ii) allow the user to operate the user control device 230 while gripping and maneuvering the delivery device 220 with only one hand.

[0021] The therapeutic agent source 232 can store the therapeutic agent 238. For example, the therapeutic agent 238 may include formulations of lidocaine, marcaine, tetracaine, bupivacaine, cocaine, another anesthetic, antibiotic, neurotoxin, and / or other therapeutic agents used during medical procedures. The therapeutic agent 238 may also be a gel, foam, mist, powder, and / or a bioabsorbable solid.

[0022] As shown in Figure 2, the elongated shaft 122 may include one or more lumens 240 that connect the therapeutic source 232 in the proximal portion 224 to the therapeutic delivery member 234 in the distal portion 226. The therapeutic delivery member 234 may be configured to deliver the therapeutic drug 238 to target tissue. For example, the therapeutic delivery member 234 may include (i) an exit port in the lumen 240 and / or in the elongated shaft 122 of the distal portion 226, and (ii) an exit port configured to allow the therapeutic drug 238 to exit the lumen 240 into the target tissue.

[0023] Within the scope of the example, the user control device 230 can control the flow of therapeutic agent 238 from the therapeutic agent source 232 to the therapeutic agent delivery member 234. For example, the user control device 230 may include one or more knobs, one or more triggers, one or more buttons, one or more switches, one or more levers, and / or one or more dials that can be operated to start, stop, increase, and / or decrease the flow of therapeutic agent 238 from the therapeutic agent source 232 to the therapeutic agent delivery member 234. Also within the scope of the example, the user control device 230 may be located on the handpiece 228 and / or in a location separate from the handpiece 228.

[0024] In some examples, the therapeutic source 232 can be distinguished from the handpiece 228. For example, the therapeutic source 232 may include a syringe containing the therapeutic drug 238. The syringe can be coupled to the infusion port of the handpiece 228, and the plunger of the syringe can be operated to supply the therapeutic drug 238 from the therapeutic source 232 (e.g., via the lumen 240) to the therapeutic drug delivery member 234, and from the therapeutic drug delivery member 234 to the target tissue. Thus, in this implementation, the therapeutic source 232 can provide the fluid pressure to deliver the therapeutic drug 238 through the lumen 240, out of the therapeutic drug delivery member 234, and to the target tissue.

[0025] In other examples, the therapeutic source 232 may be integrated with the handpiece 228 and / or operated by a user control device 230. For example, in one implementation, the therapeutic source 232 may be a disposable or reusable reservoir housed in the handpiece 228. The therapeutic source 232 may include one or more valves and / or one or more pumps to facilitate the supply of therapeutic agent 238 from the therapeutic source 232 to the therapeutic agent delivery member 234. The valves and / or pumps may be operable by the user control device 230 to start, stop, increase, and / or decrease the flow of therapeutic agent 238 from the therapeutic source 232 to the therapeutic agent delivery member 234.

[0026] In some implementations, locating the therapeutic agent source 232 within the handpiece 228 can beneficially provide a relatively compact size for the delivery device 220 by reducing or eliminating, for example, relatively long external connections (e.g., tubes and / or cables) between the handpiece 228 and the therapeutic agent source 232. However, in some implementations, locating the therapeutic agent source 232 in a separate housing from the handpiece 228 can beneficially allow the therapeutic agent source 232 to store a relatively large amount of therapeutic agent 238, among other things, without compromising the handling capabilities of the handpiece 228.

[0027] Within the scope of the example, the delivery device 220 can provide delivery of a therapeutic drug 238 to the patient's palatine canal and / or pterygopalatine fossa. The perforating element 236 is configured to form a passage in the palatine bone 102K between the patient's nasal cavity and palatine canal. In one example, the perforating element 236 may include a needle that can pierce and penetrate the palatine bone 102K. The perforating element 236 may also include a needle actuator that can apply force to the needle to cause it to penetrate the palatine bone 102K.

[0028] In another example, the perforating element 236 can apply a relatively high-pressure stream of perforating fluid 242 to the palatine bone 102K to form a passage in the palatine bone 102K. In this example, the perforating element 236 can be coupled (e.g., via the lumen 240) to a perforating fluid source 244 containing the perforating fluid 242 of the proximal portion 224. As an example, the perforating fluid 242 may include water, saline solution, and / or a therapeutic agent 238. Thus, in an implementation in which the perforating fluid 242 includes a therapeutic agent 238, the perforating fluid source 244 may be the same as the therapeutic agent source 232.

[0029] As described above, the delivery device 220 may include a therapeutic drug delivery member 234 and / or a perforating element 236. In some implementations, the delivery device 220 may be configured to deliver the therapeutic drug to the palatine canal and / or pterygopalatine fossa by forming a passage through the palatine bone 102K. In such implementations, the delivery device 220 may include a therapeutic drug source 232, a therapeutic drug delivery member 234, and a perforating element 236.

[0030] However, in other implementations, the delivery device 220 can be implemented as two separate devices. For example, the delivery device 220 may include a first device for forming a passage in the palatine bone 102K and a second device that can be inserted into the passage and then deliver the therapeutic agent to the palatine canal and / or pterygopalatine fossa. Thus, the first device may include a first handpiece, a first elongated shaft, a perforating fluid source 244, and a perforating element 236. The second device, however, may include a second handpiece, a second elongated shaft, a therapeutic agent source 232, and a therapeutic agent delivery member 234.

[0031] As shown in Figure 2, the delivery device 220 may also include one or more stabilizer functions 246 and / or one or more sensors 248. For example, in some examples, the delivery device 220 may include stabilizer functions 246 to help keep the delivery device 220 in a relatively fixed position while forming a passage in the palatine bone 102K and / or while delivering the therapeutic agent 238 to the target tissue. As will be described in more detail below, the stabilizer functions 246 may include a suction device that can apply suction to tissue in the nasal cavity and / or an expandable member (e.g., a balloon) that can expand the involved tissue adjacent to the target tissue.

[0032] The sensor 248 can facilitate positioning the delivery device 220 so that its distal portion 226 contacts a specific type of tissue and / or anatomical structure within the nasal cavity (e.g., the nasal wall). For example, the sensor 248 can be positioned on the distal portion 226 of the delivery device 220. As an example, the sensor 248 may include a pressure sensor or load cell, a temperature-sensitive element, an impedance monitoring element, a distance measuring sensor such as an ultrasound-based or IR-based sensor, and / or other suitable sensor types.

[0033] In some implementations, the perforating element 236 can be additionally or alternatively disabled unless the sensor 248 indicates that the distal portion 226 is in close proximity to a tissue surface. For example, if the sensor 248 does not indicate that the distal portion 226 is in close proximity to a tissue surface, the controller can prevent the perforating element 236 from being activated and / or deployed by disabling the user control device 230 associated with the perforating element 236 (for example, by locking out a spring mechanism that can be used to deploy the perforating element 236, or by preventing the opening of a valve that controls the lumen 240 through which high-pressure fluid can pass and advance). The controller can be implemented using hardware, software, and / or firmware. For example, the controller may include one or more processors and a non-temporary computer-readable medium (e.g., volatile and / or non-volatile memory) that stores machine language instructions or other executable instructions. When the instructions are executed by one or more processors, they can cause the controller to perform various operations of the delivery device 220 described herein.

[0034] In this configuration, the delivery device 220 can be used to perform a medical procedure on target tissue within the nasal cavity. For example, during operation, the delivery device 220 can be inserted into the nasal cavity to position its distal portion 226 adjacent to the palatine bone 102K. After the distal portion 226 is positioned against the palatine bone 102K, the user control device 230 can be operated to cause the perforating element 236 to form a passage within the palatine bone 102K. For example, the user control device 230 can cause the needle to extend and / or move toward the palatine bone 102K to penetrate it. Additionally or alternatively, for example, the user control device 230 can cause a perforating fluid source 244 to supply perforating fluid 242 to the perforating element 236 (e.g., via the lumen 240), and the perforating element 236 can apply the perforating fluid 242 to form a passage through the palatine bone 102K.

[0035] After the formation of a passage within the palatine bone 102K, the delivery device 220 can deliver the therapeutic agent 238 from the therapeutic agent source 232 to the therapeutic agent delivery member 234 (e.g., via the lumen 240). The therapeutic agent delivery member 234 can then deliver the therapeutic agent 238 through the passage to the palatine canal and / or pterygopalatine fossa. In some implementations, the distal portion 226 can extend through the passage in the palatine bone 102K so that the therapeutic agent delivery member 234 is positioned within the palatine canal while delivering the therapeutic agent 238. In other implementations, the therapeutic agent delivery member 234 can deliver the therapeutic agent 238 into the passage, and the therapeutic agent 238 can flow into the palatine canal through the passage in the palatine bone 102K.

[0036] Therefore, in the configuration shown in Figure 2, the delivery device 220 can form a passage in the palatine bone 102K to apply the therapeutic agent 238 to the palatine canal and / or pterygopalatine fossa to treat the target tissue. As described above, accessing and delivering the therapeutic agent 238 to the palatine canal and / or pterygopalatine fossa can allow physicians to have better control of pain and bleeding during surgical procedures on awake patients.

[0037] Figures 3A–315 show several distal portions that can be implemented in relation to the delivery device 200 shown in Figure 2, according to an example of the present disclosure. In particular, Figures 3A–315 show various implementation examples of the elongated shaft 222, the drug delivery member 234, and / or the perforating element 236 shown in Figure 2. The examples shown in Figures 3A–315 will now be described.

[0038] Figure 3 shows an example of a delivery device 320. As shown in Figure 3, the delivery device 320 includes an elongated shaft 322 extending from a handpiece 328. The elongated shaft 322 may be flexible. This can help to navigate the elongated shaft 322 through the patient's nasal cavity to a position close to the palatine bone 102K.

[0039] In the proximal portion 324 of the delivery device 320, the handpiece 328 includes an inlet port 350 configured to be coupled to at least one outlet nozzle, for example, a pressurized fluid canister, a pressurized gas canister, or an external air compressor. The inlet port 350 is coupled to one or more output ports 352 in the distal portion 326 of the delivery device 320. More specifically, the delivery device 320 includes a handpiece 328 and a lumen 340 extending from the inlet port 350 to the output port 352 through an elongated shaft 322. In this example, the output port 352 provides the perforating element 236 and the therapeutic drug delivery member 234 described above with respect to Figure 2.

[0040] As shown in Figure 3, the user-controlled device 330 is a trigger and provides a release mechanism configured to cause the perforating fluid 342 (e.g., water, saline solution, and / or therapeutic agent) to be propelled through the lumen 340 in the elongated shaft 322 and exit through the output port 352 located near the distal end 354 of the elongated shaft 322. When pressed down, the user-controlled device 330 activates a pressure gradient provided through the inlet port 350 to cause the perforating fluid 342 to be driven out of the output port 352 as a fluid stream with relatively high pressure. When the user-controlled device 330 is released, the perforating fluid 342 can be stopped from being output from the output port 352.

[0041] Generally, when the user-controlled device 330 is pressed down (i.e., activated), the fluid stream of the perforating fluid 342 is suitable for forming a passage 358 into the patient's relatively thin bone structure 356 (e.g., about 0.1 mm to about 3 mm). For example, the output port 352 can output the perforating fluid 342 into the fluid stream, and the diameter, pressure, and / or velocity are suitable for perforating a small hole in the palatine bone 102K, creating a passage 358 through the palatine bone 102K to a location on the opposite side of the palatine bone 102K. As one example, the fluid stream of the perforating fluid 342 can have a diameter of about 0.1 mm and a pressure between about 200 pounds / square inch (PSI) and about 5000 PSI. In some examples, the pressure, velocity, and / or diameter of the fluid stream of the perforating fluid 342 can perforate the bone structure 356 for a period of less than about 60 seconds.

[0042] In some examples, access to the palatine canal is achieved by applying a perforating fluid 342 to the mucosal wall within the nasal cavity in the region where the palatine bone 102K covers the palatine canal. After a hole is created in the bone structure 356 and a passage is established, a therapeutic agent (e.g., therapeutic agent 238) can be delivered through the passage to the region of interest at a relatively low pressure. In some examples, a lower pressure for the therapeutic agent is provided by using a separate pressure source for the therapeutic agent (e.g., applying the therapeutic agent by operating a syringe and applying the perforating fluid 342 with the help of a pressurized canister). In other examples, different pressures for the delivery of the perforating fluid 342 and the delivery of the therapeutic agent can be achieved by using multiple lumens 340 of different shapes, lengths, and / or diameters.

[0043] As described above, within the scope of the example, the piercing fluid 342 may be the same as the therapeutic agent, or it may be different from the therapeutic agent. In implementations where the piercing fluid 342 is the same as the therapeutic agent, the delivery device 320 can adjust the pressure of the fluid stream at the output port 352 to switch from the piercing operating mode to the therapeutic agent delivery operating mode. In implementations where the piercing fluid 342 is different from the therapeutic agent, the lumen 240 can be disconnected from the piercing fluid source 244 and connected to the therapeutic agent source 232 to switch from the piercing operating mode to the therapeutic agent delivery operating mode. In other implementations where the piercing fluid 342 is different from the therapeutic agent, more than one lumen 240 may be available.

[0044] Referring here to Figure 4, the delivery device 420 is shown according to another example. As shown in Figure 4, the delivery device 420 is substantially similar to or identical to the delivery device 320 shown in Figure 4, except that the delivery device 420 includes a first lumen 440A for delivering the perforating fluid 442 and a second lumen 440B for delivering the therapeutic agent (i.e., the delivery device 420 includes separate fluid jet channels and substance delivery channels). Thus, the delivery device 420 may include a handpiece 428, an elongated shaft 440, an inlet port 450 in the proximal portion 424, one or more output ports 452 in the distal portion 426 (for example, adjacent to the distal end 454 of the elongated shaft 422), and / or a user control device 430 as described above.

[0045] In Figure 4, the first lumen 440A connects the inlet port 450 to the output port 452, thus providing a conduit for supplying the perforating fluid 442 to the output port 452 in response to user operation of the user control device 430. As described above, the output port 452 can output the perforating fluid 442 as a fluid stream capable of forming a passage 458 within a bone structure 456 (e.g., palatine bone 102K).

[0046] The second lumen 440B connects the therapeutic agent source 432 to the output port 452, thus providing a conduit for supplying the therapeutic agent to the output port 452. In Figure 4, the delivery device 420 includes a substance input port 460 on the handpiece 428. The substance input port 460 can connect the second lumen 440B to the therapeutic agent source 432. As an example, the substance input port 460 may be a Luer-type connector configured to interface with a medical syringe. In this configuration, when the plunger 430' of the therapeutic agent source 432 is pressed down, the therapeutic agent source 432 can supply the therapeutic agent to the output port 452 via the second lumen 440B (i.e., the user control device 230 in Figure 2 may include a user control device 430 in the form of a trigger and plunger 430').

[0047] Therefore, as described above, the output port 452 can provide the perforation element 236 and the drug delivery member 234 shown in Figure 2. In some implementations, the output port 452 may include a plurality of output ports 452, including a first output port 452 coupled to a first lumen 440A and a second output port 452 coupled to a second lumen 440B. In other implementations, each output port 452 may be coupled to both the first lumen 440A and the second lumen 440B. For example, in one example, the delivery device 420 may include a valve coupled to a user control device 430. The valve may be configured such that (i) the valve couples the output port 452 to the first lumen 440A when the user control device 430 is activated (e.g., pressed down), and (ii) the valve couples the output port 452 to the second lumen 440B when the user control device 430 is not activated (e.g., in a dormant state).

[0048] Within the scope of this example, the method for operating the delivery device 420 is to follow these steps: (1) position the delivery device 420 so that its distal portion 426 is proximal to the tissue or bone region where it is desired to drill a small hole to gain access to the opposite side of this tissue or bone region; (2) push down the user control device 430 to extrude a high-pressure fluid jet from the output port 452 (i.e., the drilling element 236) to create a small hole in the bone or tissue region; and (3) release the user control device 430. (4) the therapeutic agent can be applied via the output port 452 (i.e., the therapeutic agent delivery member 234) through the passage 458 or in approximate vicinity of the passage 458 at a relatively low output pressure (for example, by deploying the plunger of a syringe connected to the substance input port 460).

[0049] In Figures 3-4, the perforating elements 236 of the delivery devices 320, 420 are configured to deliver fluid streams of perforating fluid 242, 342, 442 to form passages 358, 458 into a bone structure (e.g., palatine bone 102K). However, as described above, the perforating elements 236 may additionally or alternatively include one or more needles for forming passages in other examples.

[0050] Therefore, within the scope of the example, the palatine canal can be directly accessed by using one or more needles to penetrate the palatine bone 102K. In some implementations, the needle can be dynamically and selectively deployed only when the needle is positioned in place, eliminating the discomfort associated with accidental interaction between the sharp edge of the needle and the nasal cavity tissue. After deployment, the needle can penetrate the palatine bone 102K and, in some cases, further penetrate the surrounding tissue to establish a passage to the palatine canal.

[0051] In some implementations, the therapeutic agent 238 can be delivered through the lumen of the needle while maintaining the needle in a fixed position through the palatine bone 102K. In other implementations, the needle can be retracted and otherwise removed, leaving a passage through which the therapeutic agent 238 can be delivered. In such implementations, a second device (e.g., a cannula or similar delivery container) can be deployed as part of the needle removal process to maintain the openness of the passage created through the palatine bone 102K.

[0052] Referring here to Figures 5A-5C, a delivery device 520 that can utilize a needle to puncture the palatine bone 102K to access the palatine canal is shown according to another example. As shown in Figure 5A, the delivery device 520 may include a handpiece 528, an elongated shaft 522, a lumen 540 within the elongated shaft 522, a substance input port 560 coupled to a first end of the lumen 540, and a therapeutic source 532 that can be coupled to the substance input port 560 as described above.

[0053] Additionally, as shown in Figures 5A–5C, the distal portion 526 of the delivery device 520 may include a compartment 562 and a needle 564. In Figures 5A–5C, the compartment 562 and needle 564 are located close to the distal end 554 of the elongated shaft 522. However, the compartment 562 and needle 564 may be located elsewhere in other examples.

[0054] As described above, the needle 564 can puncture bone structures such as the palatine bone 102K to form a passage through the bone structure. Thus, the needle 564 in Figures 5A-5C can provide the perforation element 236 shown in Figure 2. In the example, the needle 564 can be made of a lightweight material (e.g., titanium) with relatively high tensile strength. Also, in the example, the needle 564 can have a length of about 0.5 mm to about 5 mm.

[0055] As also described above, the piercing element 236 may also include a needle actuator that can apply force to the needle 564 to cause the needle 564 to penetrate a bone structure (e.g., the palatine bone 102K). In Figures 5B–5C, the needle actuator is an expandable member 566 (e.g., a balloon) coupled to the needle 564. For example, the expandable member 566 may be a relatively thin compliance structure made of a tear-resistant material (e.g., latex, nitrile, and / or neoprene). In one example, the expandable member 566 may be made from a material with a thickness less than about 1 mm. In another example, the expandable member 566 may be made from a material with a thickness less than about 0.25 mm. More generally, the expandable member 566 may be configured for high-pressure, high-speed rapid inflation without being subjected to material breakage, tearing, or detachment from the elongated shaft 522 of the delivery device 520.

[0056] Figure 5B shows the expandable member 566 in a contracted state, and Figure 5C shows the expandable member 566 in an expanded state. As shown in Figure 5B, when the expandable member 566 is in a contracted state, the expandable member 566 and the needle 564 can be retracted into compartment 562. This can be beneficially provided with a relatively small profile (e.g., size and shape) for the distal portion 526 of the delivery device 520, so that insertion of the delivery device 520 into the nasal cavity may be non-traumatic.

[0057] In this example, a user control device 530 (e.g., a button) on the handpiece 528 can be activated to transition the expandable member 566 from a contracted state to an expanded state. For example, pressing down the trigger of the user control device 360 ​​can cause rapid expansion of the expandable member 566, which forces the needle 564 to pass through the palatine bone 102K, oriented nearly perpendicular to the elongated shaft 522 at its distal portion 526, so that at least the tip of the needle 564 is in the area of ​​the palatine canal 568.

[0058] After the needle 564 perforates the palatine bone 102K 556 and creates a passage into the palatine canal 568, the delivery device 520 can deliver the therapeutic agent to the palatine canal 568. In one example, the needle 564 may include a lumen 540 to which the therapeutic agent is connected to a therapeutic agent source 532, so that the therapeutic agent can be delivered through the output port 552 of the needle 564. In another example, a second device can be used to deliver the therapeutic agent through the passage in the palatine bone 102K formed by the needle 564.

[0059] Referring here to Figures 6A-6C, a delivery device 620 including a needle 664 for forming a passage into the palatine bone 102K is shown according to another example. As shown in Figures 6A-6C, the delivery device 620 includes, as described above, a handpiece 628, an inlet port 650 of the handpiece 628 at the proximal portion 624 of the delivery device 620, an elongated shaft 622 extending from the handpiece 628, a lumen 640 within the handpiece 628 and the elongated shaft 622, a user control device 630, a compartment 662 within the elongated shaft 622 at the distal portion 626 of the delivery device 620, and a needle 664 within the compartment 662.

[0060] In Figures 6A–6C, the needle actuator is a spring 666 that can force the needle 664 from the retracted position shown in Figure 6B to the extended position shown in Figure 6C. For example, in Figure 6B, the spring 666 is in an initial compressed state with the needle 664 inside the lumen 640 and compartment 662 so that the needle 664 is not exposed. This can be beneficially provided with a relatively small profile (e.g., size and shape) for the distal portion 626 of the delivery device 620, so that insertion of the delivery device 620 into the nasal cavity may be non-traumatic.

[0061] When the distal end 654 of the elongated shaft 622 is positioned adjacent to the tissue and / or bone region to be penetrated, the operator activates a user control device 630 on the handpiece 628 to release the spring 666 from its initial compressed state, pushing the needle 664 out of the lumen 640 to penetrate thin bone such as the palatine bone 102K. In one example, the user control device 630 may be a button that can be pressed down by the operator to cause the spring 666 to push the needle 664 out of the lumen 640 and compartment 662. Within the scope of the example, the spring 666 may be made of stainless steel, brass, or other suitable material. The spring 666 may have a spring constant such that the spring 666 can apply a force to the needle 664 that is suitable for forcing the needle 664 through the bone structure (e.g., the palatine bone 102K).

[0062] In the example, the delivery device 620 may also include one or more contact sensors 670 located near the location of the needle 664 to facilitate the placement of the delivery device 620 so that the distal end 654 contacts the nasal wall. For example, the contact sensors 670 may include one or more pressure sensors, load cells, temperature-sensitive elements, impedance monitoring elements, and / or distance sensors (e.g., ultrasonic-based distance sensors or IR-based distance sensors). In some implementations, the user control device 630 may be disabled unless the contact sensor 408 indicates proximity to a tissue surface. This can help reduce (or prevent) the operator from prematurely activating the user control device 630 and extending the needle 664 into an unintended tissue area.

[0063] In one implementation, the controller can be coupled to a user control device 630 and a contact sensor 670. When the user control device 630 is activated, it can provide a signal to the controller. Similarly, when the contact sensor 670 detects a certain proximity to a tissue surface, it can provide a signal to the controller. The controller can be configured such that (i) when the controller receives signals from both the user control device 630 and the contact sensor 670, the controller releases the spring 666, and (ii) when the controller receives only one of the signals from the user control device 630 and the contact sensor 670, or receives no signals at all, the controller does not release the spring 666. In one example, the controller can send a signal to a motor to move a latch, thereby releasing the spring 666.

[0064] After the needle 664 has formed a passage through the bone structure, the delivery device 620 can deliver the therapeutic agent to the region of interest (e.g., the palatine duct) via the inflow port 650, the lumen 640, and the output port, as described above. Within the scope of examples, the delivery device 620 may also include a mechanism for retracting the needle 664 after the passage has formed and / or after the therapeutic agent has been delivered through the passage. For example, the delivery device 620 may include a mechanical dial that, when engaged and rotated, can retract a spring 666 back into the elongated shaft 622. Retracting the needle 664 can facilitate the removal of the delivery device 620 from the nasal cavity without causing unwanted collateral tissue damage during removal.

[0065] Within the scope of the examples, needles 564, 664 may include bioabsorbable materials (e.g., bioabsorbable materials) such as sugar-based compounds and / or synthetic polymers (e.g., polyglycolic acid (PGA) or polylactic acid (PLA)). The bioabsorbable material of needles 564, 664 may be absorbed over a relatively short period of time or decompose relatively slowly (e.g., over a year or more). For example, in some implementations, needles 564, 664 may be completely reabsorbed within a few weeks, while in other implementations, needles 564, 664 may be completely reabsorbed within a few hours (e.g., less than a day). In examples where needles 564, 664 are made from bioabsorbable materials, needles 564, 664 may initially have tensile strength comparable to stainless steel or similar materials used for puncturing rigid tissue.

[0066] In some cases, the degradation of needles 564, 664 made from bioabsorbable materials can be accelerated to limit the time the passage exists penetrating tissue and / or bone structure. This can be achieved, for example, by exposing the needles 564, 664 to a substance, temperature, or other environmental element that causes the needles 564, 664 to rapidly dissolve. For example, the needles 564, 664 can have greater mechanical integrity when they are dry and located within the elongated shafts 522, 622 before deployment (i.e., compared to after the needles 564, 664 have been deployed to puncture bone structure). In some cases, the delivery of therapeutic drugs via the needles 564, 664 can initiate and / or accelerate the degradation of the needles 564, 664, allowing the passage through bone structure to close.

[0067] As described above, in some examples, the delivery devices 220, 320, 420, 520, and 620 may include a stabilization function 246 to help hold the delivery devices 220, 320, 420, 520, and 620 in a relatively fixed position while forming a passage in the palatine bone 102K and / or while delivering the therapeutic agent 238 to the target tissue. The stabilization function 246 can thus help reduce the possibility that the fluid stream of the perforating fluid 242, 342, and 442 and / or the contact force of the needle 564, 664 on the palatine bone 102K may cause the delivery devices 220, 320, 420, 520, and 620 to be pushed away from the palatine bone 102K after initial contact with the hard bone surface (i.e., without penetrating the palatine bone 102K).

[0068] In one example, the stabilization function 246 may include one or more suction ports in the distal portions 226, 326, 426, 526, 626 of the delivery devices 220, 320, 420, 520, 620 (e.g., near the distal ends 354, 454, 554, 654 of the elongated shafts 222, 322, 422, 522, 622, which are adjacent to the output ports 352, 452 and / or needles 564, 664). The suction ports may be coupled to a negative pressure source (e.g., a vacuum source) in the proximal portion 224 via at least one of the lumens 240. The negative pressure source may be operable by a user control device 230 to apply suction to the suction ports via the lumens 240. During operation, the suction ports may engage with tissue adjacent to the site where a passage is to be formed. When the negative pressure source is activated (for example, by opening a valve), the negative pressure can pull the suction port and adjacent tissue into close contact and maintain this contact with a force proportional to the strength of the applied vacuum. Thus, the negative pressure source and vacuum port can provide a force to hold and stabilize the distal portions 226, 326, 426, 526, 626 of the delivery devices 220, 320, 420, 520, 620 that are close to the palatine bone 102K, in order to facilitate the fluid stream of the perforating fluid 242, 342, 442 and / or the needles 564, 664 penetrating the palatine bone 102K.

[0069] In another example, the stabilization function 246 may additionally or alternatively include a balloon. Figures 7A–7B show a delivery device 720 that includes an expandable member 772 (e.g., a balloon) as the stabilization function 246. As shown in Figures 7A–7B, the delivery device 720 includes an elongated shaft 722 having a distal end 754. The delivery device 720 also includes a perforating element 736 on a first side of the elongated shaft 722 and a balloon on a second side of the elongated shaft 722. The second side may be on the opposite side of the first side. The perforating element 736 may be configured to form a passage through a fluid stream and / or needles 564, 664 of the perforating fluid 242, as described above.

[0070] In Figure 7A, the distal end 754 of the elongated shaft 722 is positioned such that the perforating element 736 is adjacent to the lateral wall of the nasal cavity 700 in the region where the palatine bone 702K covers the palatine canal 702R. After the delivery device 720 is positioned adjacent to the lateral wall of the nasal cavity as shown in Figure 7A, at least one of the user control devices 230 shown in Figure 2 can be activated to inflate the expandable member 772. As shown in Figure 7B, once the expandable member 772 is inflated, it can establish contact with the inner wall 774 of the nasal cavity 700 or other nearby structure. Within the scope of the example, the expandable member 772 can be inflated to a pressure such that it is rigid and resists compression, thereby applying a stabilizing force to the opposing tissue and holding the delivery device 720 in place as the perforating element 736 forms a passage in the palatine bone 702K. After a passage in the palatine bone 702K is formed, the expandable member 772 can be retracted to facilitate the removal of the delivery device 720 from the nasal cavity.

[0071] In some implementations, the advantageous (or optimal) location for creating a pathway for access to a region may not be the same as the location where the therapeutic agent is desired to be delivered. For example, access to a region such as the palatine canal 102R (shown in Figure 1B) is most easily achieved in the area where the palatine bone 102K is thinnest, and where tool access is least restricted by the irregular shape of the nasal cavity 100 and / or the balance between these elements and other elements. This optimal access area may not directly coincide with the location of nerves within the palatine canal 102R or the pterygopalatine ganglion. Depending on the orientation of the anatomical structure (e.g., nasal cavity procedure) and / or the position / angle of the subject's head, gravity can cause the therapeutic agent to move naturally away from the introduction site towards the desired region. In other scenarios, gravity can cause the therapeutic agent to move naturally away from the introduction site and also away from the desired region. In examples, the delivery rate, as well as the density, thickness, and surface adhesion of the therapeutic agent, can be configured to limit the effect of gravity that causes the therapeutic agent to move away from the target treatment site.

[0072] As described above, delivery devices 220, 320, 420, 520, 620, and 720 can deliver the therapeutic agent 238 to target tissue via a passage formed in a bone structure (e.g., the palatine bone 102K). Figure 8 shows a delivery device 820 for applying the therapeutic agent 838 to target tissue 876, relating to one example. As shown in Figure 8, the delivery device 820 includes a delivery conduit 834 extending into the palatine canal 802R through a passage 858 in the palatine bone 802K. Within the scope of the example, the delivery conduit 834 may be the distal end of the elongated shaft of the delivery device 820 and / or a needle (e.g., needles 564, 664 in Figures 5A–6C).

[0073] In Figure 8, the target tissue 876 includes multiple nerves 878 and ganglion 802Q. Within the scope of the example, the therapeutic agent 838 can be applied directly to the nerves 878, and / or the therapeutic agent 838 can be applied directly to ganglion 802Q. As shown in Figure 8, the delivery conduit 834 may include one or more output ports 852 that can discharge the therapeutic agent 838 along one or more directions that are lateral (e.g., nearly perpendicular) to the longitudinal axis of the delivery conduit 834. This can facilitate the therapeutic agent 838 reaching anatomical targets that are off-axis with respect to the orientation of the passage 858 and / or the delivery conduit 834.

[0074] Within the scope of the example, the delivery device 820 may include a delivery conduit 834 and a perforating element, or the delivery device 820 may be a second device that includes only the delivery conduit 834 and omits the perforating element.

[0075] Figure 9 shows a delivery device 920 for applying a therapeutic agent 938 to a target tissue 976, relating to another example. As shown in Figure 9, the delivery device 920 includes a delivery conduit 934 extending into the palatine canal 902R through a passage 958 in the palatine bone 902K. Within the scope of the example, the delivery conduit 934 may be the distal end of the elongated shaft of the delivery device 920 and / or a needle (e.g., needles 564, 664 in Figures 5A–6C).

[0076] As shown in Figure 9, the delivery conduit 934 includes an output port 952 on the first side and a balloon 972 on the second side which may face the first side. In this example, the delivery conduit 934 is inserted into the passage 958 with the balloon 972 in an initial deflated state, and the delivery conduit 934 has a slender profile that can traverse a relatively small passage 958 (e.g., less than about 1 mm in diameter). Once positioned in the palatal tube 902R through the passage 958, the balloon 972 can be inflated using an inflation mechanism (e.g., a pump / valve system adjacent to the handpiece of the delivery device 920).

[0077] For example, the balloon 972 can be made of a compliant material (e.g., latex) that can contact the tissue wall and effectively seal a portion of the palatine canal 902R. Thus, when the therapeutic agent 938 is discharged from the output port 952, the balloon 972 may cause the therapeutic agent 938 to accumulate and remain in the space restricted by the balloon 972. This area where the therapeutic agent 938 accumulates may include the ganglion 902Q. After the delivery of the therapeutic agent 938 is complete, the balloon 972 can be deflated (e.g., by releasing a valve on the handpiece), and the delivery conduit 934 can be removed from the passage 958.

[0078] In some examples, the delivery conduit 934 can remove excess therapeutic agent 938 that has accumulated in the tissue area before the balloon 972 deflates. For example, after the delivery of therapeutic agent 938 is complete, a negative pressure gradient can be applied to the delivery conduit 934 to force any excess therapeutic agent 938 accumulated in the treatment area to be drawn back into the delivery conduit 934 and removed from the treatment area. In an alternative example, the delivery device 920 may include a separate fluid-transporting lumen configured to be coupled to a negative / pressure vacuum source.

[0079] In some examples, the delivery devices 220, 320, 420, 520, 620, 720, 820, and 920 can operate the puncture element 236 based on information provided by the location guidance system (e.g., using a fluid stream of puncture fluid and / or a needle). For example, one or more images provided by an endoscope may allow visualization of the tissue surface and anatomical landmarks that can guide the procedure, but may not allow direct visualization of anatomical structures deeper than the surface tissue. For example, when attempting to access the palatine canal 102R via the palatine bone 102K, endoscopic guidance can be used to identify landmarks such as the nasal turbinate or sphenopalatine foramen 102G for use as guidance on where to puncture the palatine bone 102K, but increased reliability and reduced user error may be achieved through a mechanism that directly identifies the location of the palatine canal 102R.

[0080] Within the scope of the example, the delivery devices 220, 320, 420, 520, 620, 720, 820, and 920 may include ultrasonic, infrared, laser, impedance, or other types of sensors at the distal ends 354, 454, 554, 654, and 754 of the elongated shafts 222, 322, 422, 522, 622, and 722 adjacent to the perforating element 236. For example, an infrared sensor may be provided at the distal ends 354, 454, 554, 654, and 754 so that the infrared sensor can identify the presence of a cavity such as the palatine canal 102R. Identification can be automated, and the information can be communicated to the user via an optical, auditory, or mechanical device. For example, a colored indicator can be illuminated when the perforating element 236 is located in a tissue area adjacent to the palatine canal 102R.

[0081] Within the scope of the example, sensors may be included to assist in determining a desirable (e.g., optimal) penetration site. For example, laser, ultrasonic, or other types of sensors can be used to scan locally within a limited area to determine the area where the bone is thinnest. Thin areas of the bone wall can enable simple access points that can be penetrated with less force and / or with a higher success rate than thicker bone areas. In the example, an ultrasonic transducer operating at a transmit frequency of 10–15 MHz can be mounted on the distal ends 354, 454, 554, 654, 754 of elongated shafts 222, 322, 422, 522, 622, 722 adjacent to the location of the drilling element 236. In one implementation, the ultrasonic transducer can be configured to generate A-mode scan and port data to the electronics in the handpiece 228. Additionally, for example, delivery devices 220, 320, 420, 520, 620, 720, 820, and 920 may include non-temporary computer-readable media that store instructions to be provided at processor execution time to implement algorithms for evaluating the characteristics of A-mode scans that can be used to determine wall thickness (e.g., edge detection algorithms that can be used to determine the leading and trailing edges of strong reflectors such as bone structures, and / or signal loss evaluation algorithms that can determine how much power the ultrasonic signal has lost due to the presence of a highly attenuating bone medium).

[0082] In some implementations, a desirable outcome would be to close the passage in the bone structure (e.g., the palatine bone 102K) after delivery of the therapeutic agent 238 to the target tissue. For example, in some examples, delivery devices 220, 320, 420, 520, 620, 720, 820, and 920 can deliver the therapeutic agent 238 over a period that may be substantially shorter than the time it would take for the passage to close naturally. Within the scope of examples, the devices may be configured to close or otherwise fill any remaining space after the passage has been created.

[0083] In one example, a nasal tool can be configured to deliver a cap that can be positioned to interface with a passage through tissue or bone structure so that the cap seals the hole created. The cap may have a smooth upper part with a low profile and a mushroom shape with a soft edge so as not to irritate nasal tissue or restrict airflow within the nasal passage. The diameter of the upper part of the cap may be larger than the diameter of the hole in the tissue and / or bone structure so as to completely seal the hole. In some examples, the stem extending from the cap may have an outer diameter slightly smaller than the diameter of the passage so that frictional force holds the cap in place when the cap is inserted into the hole.

[0084] Figures 10A–10B show a cap 1080 that seals a passage 1058 through tissue and / or bone structure (e.g., palatine bone 1002K), relating to one example. More specifically, Figure 10A shows the cap 1080 in a retracted state, and Figure 10B shows the cap 1080 in an expanded state. As shown in Figures 10A–10B, the cap 1080 may include an upper portion 1082 and a stem 1084 extending from the upper portion 1082. The upper portion 1082 may have a diameter larger than the diameter of the passage 1058 so that the upper portion 1082 can completely cover the hole in the palatine bone 1002K. The stem 1084 may have an adjustable diameter. The adjustability of the stem 1084's diameter facilitates positioning the cap 1080 over the passage 1058 and can provide sufficient radially outward force to maintain the cap 1080 in a fixed position.

[0085] During operation, the nasal tool can be used to deliver the cap 1080 to the opening associated with the passage 1058, with or without guidance such as endoscopic visualization. Within the scope of examples, the delivery device 1020 may include an endoscopic visualization system, such as the system disclosed in U.S. Patent Application Publication No. 2018 / 0153375, the contents of which are incorporated herein by reference in their entirety. As shown in Figure 10A, the stem 1084 may have a relatively small diameter, smaller than the diameter of the passage 1058, to facilitate the easy placement of the cap 1080 within the passage 1058 when the cap 1080 is in a retracted state. After the stem 1084 is positioned within the passage 1058, the nasal tool can perform an action on the upper portion 1082 to cause the diameter of the stem 1084 to expand to the expanded state shown in Figure 10B. As shown in Figure 10B, in the extended state, the cap 1080 can have a diameter approximately equal to the diameter of the passage 1058, providing a frictional force and / or radially outward force that firmly holds the cap 1080 in place.

[0086] In one example, a surgical tool can twist and / or rotate the top 1082 to move a screw 1086 or other internal component deeper into the stem 1084, which causes the anchor 1088 to expand outward and increase the diameter of at least a portion of the stem 1084. In some examples, the cap 1080 can be made of a bioabsorbable material that decomposes slowly over time, allowing the passage to close naturally.

[0087] Figure 11 shows a nasal tool 1190 that includes an insertion sheath 1192 for compressing a plug 1194. The plug 1194 can be expandable. The insertion sheath 1192 can be translated from a first position where the insertion sheath 1192 covers the plug 1194 to a second position where the insertion sheath 1192 exposes the plug 1194. When the insertion sheath 1192 is in the first position, the insertion sheath 1192 and plug 1194 can have a diameter smaller than the diameter of the passage 1158 in a bone structure (e.g., palatine bone 1102K). This can facilitate the insertion of the insertion sheath 1192 and plug 1194 into the passage 1158.

[0088] After the introduction sheath 1192 and plug 1194 are inserted into the passage 1158, the introduction sheath 1192 can be retracted from a first position to a second position to expose the plug 1194. In response to the exposure of the plug 1194, the plug 1194 can expand from a first size to a second size to fill the passage 1158. In some implementations, after the plug 1194 has filled the passage 1158, the plug 1194 can be detached from the nose tool 1090 and left in place within the passage 1158.

[0089] In some examples, the plug 1194 may be made of a soft, non-irritating material such as foam. The plug 1194 may also be made of one or more bioabsorbable materials that will spontaneously degrade over time, allowing the passage 1158 to close spontaneously. The plug 1194 may be coated with therapeutic agents such as antibiotics or steroids, or other agents that may aid in wound healing, infection control, or other purposes, or may be fitted to elute them.

[0090] In the example, accessing the palatine canal 102R and pterygopalatine fossa to apply anesthetic or other therapeutic agents to the nerves and / or blood vessels inside the palatine canal 102R can be performed without bone penetration. For example, transmucosal injection, or a natural opening such as a foramen, e.g., the sphenopalatine foramen 102G (shown in Figure 1A) or the greater palatine foramen 102T, can be used to access the palatine canal 102R. In implementations where transmucosal injection is used, the injection can create a bleb from which fluid can migrate into the foramen or micropore. Within the scope of the example, delivery devices and methods used to access a natural orifice can be configured to prevent accidental injection of therapeutic agents into arteries, which could pose a serious risk to the subject.

[0091] Figure 12 shows a delivery device 1220 relating to another example. As shown in Figure 12, the delivery device 1220 includes an elongated shaft 1222 and an deployment port 1295 adjacent to the distal end 1254 of the elongated shaft 1222. The deployment port 1295 can provide an aperture through which a guidewire 1296 can pass and extend. For example, the guidewire 1296 can be actuated by at least one of the user control devices 230 shown in Figure 2 (e.g., a dial on or near the handpiece 228) to extend or retract the guidewire 1296 relative to the elongated shaft 1222.

[0092] In one example, the guidewire 1296 can be made thin (e.g., having a diameter of less than approximately 0.04 inches and / or less than approximately 0.02 inches) and can be constructed from a material (e.g., stainless steel) that (i) provides some degree of flexibility and (ii) also provides mechanical rigidity suitable for the guidewire 1296 to be manipulated and moved by a user (e.g., using a user control device 230 with the handpiece 228). In one implementation, the guidewire 1296 can be manufactured to have rounded ends representing a blunt surface. This can help mitigate (or prevent) the guidewire 1296 from piercing any tissue structure. Also in some examples, the guidewire 1296 can be coated with a material such as polymer or lacquer to further reduce the risk of tissue damage resulting from accidental contact.

[0093] Under endoscopic guidance or another suitable guidance mechanism, the deployment port 1295 can be positioned close to the butterfly cap opening 1202G, and the guidewire 1296 can be extended and manipulated (e.g., by adjusting a dial on the handpiece 228) so that the guidewire 1296 enters the butterfly cap opening 1202G. When the guidewire 1296 is in place, the delivery conduit 1297 (e.g., a tube) can be extended over the guidewire 1296 so that the delivery conduit 1297 enters the butterfly cap opening 1202G (e.g., by manipulating another user control device 230 on the handpiece 228, e.g., by pressing a button or moving a slider along the tract of the handpiece 228). The delivery conduit 1297 can be made from a relatively soft and relatively flexible material. For example, the delivery conduit 1297 may be made of silicone or another material having mechanical properties that reduce (or minimize) the risk of tissue damage due to accidental contact, and that also allow the therapeutic agent to be delivered through the lumen of the delivery conduit 1297 at a reasonable pressure (e.g., the pressure that can be generated by pressing the plunger of a standard medical syringe).

[0094] When the delivery conduit 1297 is located within the sphenopalatine foramen 1202G, the guidewire 1296 can be retracted, allowing the therapeutic agent to be delivered through the delivery conduit 1297 into the anatomical region distal to the sphenopalatine foramen 1202G. This allows for the advantage of using a soft, safe material to deliver the therapeutic agent to a sensitive area while enabling the mechanical agility and maneuverability of a more rigid material.

[0095] In Figure 12, the delivery device 1220 is described in the context of delivering a therapeutic drug through the sphenopalatine pore 1202G in one example. However, in other examples, the delivery device can enter the palatal canal 1302R through the large palatal pore 1302T, as shown in Figures 13A-13B.

[0096] Figure 13A shows a delivery device 1320 relating to another example. As shown in Figure 13A, the delivery device 1320 includes an elongated shaft 1322. In one implementation, the delivery device 1320 can enter the mouth of a subject and extend posteriorly toward the molars. The elongated shaft 1322 of the delivery device 1320 may include an angled distal end 1354 that is adapted to aim upward toward the soft or hard palate.

[0097] Figure 13B shows the distal end 1354 of the elongated shaft 1322. As shown in Figure 13B, the distal end 1354 can be circular with a sufficiently large diameter (e.g., about 0.5 inches) so that it can surround the large palatine foramen 1302T. Using manual palpation, endoscopic guidance, or other appropriate visualization and locating techniques, the operator can maneuver the delivery device 1320 so that the distal end 1354 is positioned to surround the large palatine foramen 1302T.

[0098] In some examples, the distal end 1354 can be subjected to relatively gentle suction via one or more suction ports 1346 connected to one or more lumens within an elongated shaft 1322 that interface with a negative pressure or vacuum source in the handpiece area as described above. In other examples, the delivery device 1320 may additionally or alternatively include other stabilization features, such as one or more deployable anchors to help maintain the position of the distal end 1354 over the large palatal opening 1302T.

[0099] While the distal end 1354 is positioned over the large palatine opening 1302T, the operator can operate a user-controlled device to cause the delivery conduit 1397 (e.g., a tube) to extend through the large palatine opening 1302T into the palatine canal 1302R. The delivery conduit 1397 can be relatively soft and flexible as described above. After extending the delivery conduit 1397 through the large palatine opening 1302T, the delivery device 1320 can deliver the therapeutic agent into the palatine canal 1302R via the lumen 1340 within the delivery conduit 1397. In this example, a tissue seal created by the suction port 1346 allows the delivery device 1320 to collect and drain any therapeutic agent that leaks out of the large palatine opening 1302T after delivery (e.g., due to gravity). After the delivery of the therapeutic agent, the delivery conduit 1397 can retract and release the suction (for example, by eliminating a source of vacuum or negative pressure, or by adjusting a valve to alter the airflow through the delivery device 1320).

[0100] In the examples described above, the drug delivery member 234 can be implemented by a structure that is inserted into an opening formed by a natural opening or a perforating element 236 (e.g., delivery conduits 1297, 397 in Figures 12-13B). In some implementations, the structure of the drug delivery member 234 may have a fixed size and / or shape. However, in other implementations, the drug delivery member 234 may have a variable size and / or shape.

[0101] For example, the drug delivery member 234 may have a relatively small diameter that can be inserted through a small opening and navigated to a fixed position with a lower required level of positional accuracy, thereby reducing the time for placement and allowing operators with lower skill levels to achieve routine success. However, the relatively small diameter of the drug delivery member 234 may also limit the speed at which the drug 238 can be delivered through the drug delivery member, and / or may require relatively high pressure to push the drug 238 through the relatively small size drug delivery member 234. In some examples, it would be advantageous for the drug delivery member 234 to have a relatively large diameter during the period of stable position through which the substance can be delivered, while being inserted and removed from the area despite having a relatively small diameter.

[0102] In some examples, the drug delivery member 234 may include a tube (e.g., delivery conduits 1297, 1397) constructed from a collapsible woven material having a relatively large diameter (e.g., about 1 mm) in a relaxed state. When a mechanical force (e.g., tensile force) is applied to the tube, the woven fibers may shift in orientation and collapse into a structure with a smaller diameter (e.g., about 0.5 mm). In some examples, this process, using tension to collapse the woven fibers, may result in a tube with a slight increase in overall length.

[0103] In one example, a collapsible weave can be covered with an outer tube to reduce (or minimize) leakage from the tube due to gaps in the woven fibers. For example, a flexible rubber or polymer tube can enclose the woven components of the tube. In this example, an inner rubber tube along the inner surface of the woven fibers can be attached to or replace the outer cover.

[0104] Figure 14A shows a delivery device 1420 relating to another example. As shown in Figure 14A, the delivery device 1420 includes an elongated shaft 1422 and a grid of projections 1498 at the distal end 1454 of the elongated shaft 1422. The elongated shaft 1422 may include a lumen that is fluidly coupled to the projections 1498.

[0105] The projections 1498 can be fabricated from a relatively soft and flexible material. For example, the grid of projections 1498 can be fabricated from a soft material such as silicone, which allows each projection 1498 to completely collapse or invert in response to the application of mechanical force or pressure (e.g., pressure from projections 1498 being pressed against tissue or bone structure). Each projection 1498 within the grid can be constructed to have a hollow fluid delivery lumen that is in fluid communication with a larger grid structure and a lumen within the elongated shaft 1422.

[0106] In some cases, the grid of projections 1498 can be initially coated with a mild adhesive that allows projections 1498 to adhere to tissue containing moist soft tissue in a relatively short time (e.g., less than about 30 minutes and / or less than about 15 minutes). Using endoscopic guidance, direct visualization, or another appropriate site selection method, the grid of projections 1498 can be positioned in a common location in a natural orifice (e.g., the greater palatine foramen 102T or the sphenopalatine foramen 102G) and adhere to the tissue wall in this region. At least one of the projections 1498 can provide a conduit for delivering therapeutic agents across the opening of the orifice to a desired tissue area (e.g., within the palatine canal 102R). The remaining portions of projections 1498 that are not spatially aligned with the opening press against the tissue wall, crushing or inverting, thereby closing their internal lumens to prevent the outward flow of material from these crushed lumens. As an example, Figure 14B shows a delivery device 1420 positioned against a tissue wall 1456, with two of the projections 1498 extending through an opening 1457, while the remaining projections 1498 are pressed against the tissue wall 1456 in a compressed state.

[0107] While the delivery device 1420 is positioned relative to the tissue wall in this manner, the therapeutic source can deliver the therapeutic agent (e.g., using a syringe injection mechanism) through the elongated shaft 1422 to the grid of projections 1498 and out of projections 1498 that are spatially aligned with the orifice and consequently not crushed, resulting in the transfer of the substance into the region of interest through the orifice. One advantage of using a system such as the one described is that it reduces the precision required to directly position the delivery mechanism in areas such as the butterfly palatine orifice 102G and the large palatine orifice 102T, enabling simpler delivery techniques.

[0108] In some of the examples described above, the drug delivery member 234 may extend through an opening formed by a natural opening and / or a perforating element 236 in order to deliver the drug 238. However, as described above, in other examples, the drug delivery member 234 may not extend through an opening formed by a natural opening and / or a perforating element 236.

[0109] For example, Figure 15 shows a delivery device 1520 that can deliver a therapeutic agent without extending through an opening formed by a natural opening and / or a perforating element 236. As shown in Figure 15, the delivery device 1520 includes an elongated shaft 1522 made of a semi-rigid but malleable material (e.g., aluminum). The malleable material of the elongated shaft 1522 can be encapsulated by a layer of rubber or polymer material to give the elongated shaft 1522 a soft feel that reduces the risk of harmful irritation caused by accidental contact of the body with soft or hard tissue.

[0110] As described above with respect to Figure 2, the elongated shaft 1522 may include one or more lumens (e.g., lumen 240) that allow the therapeutic agent to travel along the elongated shaft 1522 from the handpiece to the distal end 1554 of the delivery device 1520. The distal end 1554 of the delivery device 1520 may include a delivery pod 1599 that is positioned in a region of interest (e.g., one of or near the large palatal opening 1502T) and configured to discharge the therapeutic agent through an output port 1552. Within the scope of the example, the output port 1552 may discharge the therapeutic agent as foam, mist, liquid, gas, a high-pressure liquid stream, or in any other form.

[0111] In some implementations, the delivery pod 1599 may optionally include other features intended to assist in the delivery of therapeutic drugs, such as one or more aspiration ports 1546 and / or one or more image-guided sensors 1503. For example, the image-guided sensor 1503 may be a laser, infrared, ultrasonic, or other optical or acoustic sensor. For example, the image-guided sensor 1503 may be an ultrasonic transducer operating in A-mode configuration at frequencies between approximately 5 megahertz (MHz) and approximately 15 MHz. In this example, the electronics for operating the image-guided sensor 1503 may be positioned within or near the handpiece, and the elongated shaft 1522 may include an internal conduit (not shown) for a wire connecting the image-guided sensor 1503 to appropriate operational electronics. In some examples, the delivery pod 1599 may also be configured to assist in the delivery of therapeutic drugs via electrophoresis or iontophoresis and thus include the electronics required to invent those technologies.

[0112] In some cases, the delivery device may include a mouthpiece to facilitate access to the palatine canal 102R or other anatomical areas via the mouth. Given the proximity of the palatine foramen to the second and third molars, as well as to the posterior tori of the hard palate, examples of using teeth as anatomical landmarks may be found to be helpful in some subjects.

[0113] Figure 16 shows a mouthpiece 1604 for delivering a therapeutic drug in one example. As shown, the mouthpiece 1604 is configured to enter the mouth and interface with the molars. The mouthpiece 1604 may have a U-shape in which a first portion 1604A and a second portion 1604B extend from a central portion 1604C.

[0114] The mouthpiece 1604 may include a rigid penetration mechanism 1636 in the first portion 1604A and the second portion 1604B (i.e., each side of the mouthpiece 1604). The rigid penetration mechanism 1636 may be a needle capable of piercing tissue (e.g., a machined, sharpened rigid plastic member). The rigid penetration mechanism 1636 can be positioned so that it is slightly medial behind the molars when the mouthpiece 1604 is placed in the mouth. When the mouthpiece 1604 is held in place by the teeth and / or palate, the operator may push the rigid penetration mechanism 1636 into the mucosa in or near the area of ​​the great palatine foramen 102T (with or without the use of additional tools) to form a passage directly or adjacent to the palatine canal 102R.

[0115] In one example, after positioning the mouthpiece 1604 in the mouth, the subject can bite down on the mouthpiece 1604 so that the rigid penetration mechanism 1636 penetrates the tissue at or near the location of the great palatine foramen 102T. After the rigid penetration mechanism 1636 forms a passage in or near the palatine canal 102R, the therapeutic agent can be delivered into the palatine canal 102R through the respective lumens of the rigid penetration mechanism 1636.

[0116] As shown in Figure 16, the mouthpiece 1604 may include a substance input port 1660 (e.g., a Luer fitting) that can be connected to a therapeutic source 1632 (e.g., a syringe). In this example, pressing the plunger against the therapeutic source 1632 injects the therapeutic agent into the mouthpiece 1604. The therapeutic agent then flows through the mouthpiece 1604 via one or more internal lumens, exits the rigid penetration mechanism 1636, and enters the palatal canal 102R.

[0117] In one implementation, the substance input port 1660 can accept therapeutic agents in liquid form. In another implementation, the substance input port 1660 can accept therapeutic agents in gaseous form (e.g., via connection to a pressurized source of gas or mist).

[0118] Referring to Figure 17, Method 1700 for using a mouthpiece 1604 to deliver a therapeutic agent is shown. As shown in Figure 17, Method 1700 includes the following steps: (1) Block 1702, applying a local or needle-injectable anesthetic, e.g., lidocaine gel or injection, to the tissue along the gingival line and / or to the area of ​​the mouth adjacent to the greater palatine foramen; (2) Block 1704, inserting the mouthpiece 1604 into the mouth of the subject; (3) Block 1706, performing an activity that brings the rigid penetrating mechanism 1636 of the mouthpiece 1604 to cross the greater palatine foramen 102T or otherwise penetrate the tissue in order to access the palatine canal 102R or an area of ​​tissue adjacent to the palatine canal 102R; and (4) Block 1708, delivering a therapeutic agent to the nerve of the palatine canal 102R via the rigid penetrating mechanism 1636 of the mouthpiece 1604. In one example, step (2) may also include the step of placing an anesthetic substance, such as a gel or foam, onto the mouthpiece 1604 before inserting it into the subject's mouth.

[0119] Figures 18A–18D show a delivery device in the form of a mouthpiece 1804 relating to another example. The mouthpiece 1804 can facilitate access to the palatine canal 102R, pterygopalatine fossa, and / or other anatomical areas through the mouth. Given the proximity of the palatine foramen 102T to the second and third molars, as well as the posterior tori of the hard palate, examples of using teeth as anatomical landmarks can be found to be useful for some subjects.

[0120] As shown in Figures 18A–18D, the mouthpiece 1804 may include an access port 1860, a local anesthetic well 1806, bilateral working lumens 1808, a Moller housing 1810, an anterior tooth housing 1812, a translatable introduction port 1814, and a needle introducer 1816. The mouthpiece 1804 can enter the mouth and interface with the bilateral molars and anterior teeth. The local anesthetic well 1806 is configured to hold a local anesthetic gel or one or more immersed cotton threads against the palate while inhibiting (or preventing) the anesthetic from migrating to the back of the throat.

[0121] On each side of the mouthpiece 1804, the Moller housing 1810 may have an adjustable size to facilitate a secure fit of the mouthpiece 1804 around the molars. Within the range of examples, the Moller housing 1810 may be adjustable in an anterior-posterior manner to accommodate anatomical differences and ensure that the exit ports of the bilateral working lumen 1808 align with the bilateral palatal foramina.

[0122] As shown in Figures 18C–18D, the bilateral working lumens 1808 run through each side of the mouthpiece 1804 and can terminate at the anterior access port 1860 of the mouthpiece 1804. The access port 1860 is positioned below the anterior teeth and can extend just beyond the teeth to provide unobstructed access to the bilateral working lumens 1808.

[0123] In some examples, the access port 1860 can be rotated 180 degrees relative to the mouthpiece 1804. Rotating the access port 1860 can change access to the bilateral working lumen 1808 (for example, by activating a valve within the access port 1860). In one example, the access port 1860 can have three states: (i) a first state in which the access port 1860 is connected to the bilateral working lumen 1808 on a first side of the mouthpiece 1804; (ii) a second state in which the access port 1860 is connected to the bilateral working lumen 1808 on a second side of the mouthpiece 1804; and (iii) a third state in which the access port 1860 is connected to the bilateral working lumen 1808 on both the first and second sides of the mouthpiece 1804. This can facilitate the selective delivery of therapeutic agents to tissues and / or nerves on one or both sides of the mouthpiece 1804.

[0124] The mouthpiece 1804 may also include an introduction needle 1836 in the bilateral working lumen 1808 on each side of the mouthpiece 1804. In Figures 18A and 18C, the introduction needle 1836 is retracted into the bilateral working lumen 1808 on each side of the mouthpiece 1804. In Figures 18B and 18D, the introduction needle 1836 extends outward from the bilateral working lumen 1808 on each side of the mouthpiece 1804 (for example, extending only about 10 mm from the bilateral working lumen 1808).

[0125] In one example, the guide needle 1836 can operate between the retracted position shown in Figures 18A and 18C and the extended position shown in Figures 18B and 18D by translating the translatable guide port 1814 in the axial direction. In one implementation, the translatable guide port 1814 is configured to translate a distance 1819 in the axial direction from approximately 1 mm to approximately 20 mm (or, in another implementation, from approximately 5 mm to approximately 10 mm).

[0126] Within the scope of the example, the introduction needle 1836 can be made of rigid plastic or metal similar to those used to construct subcutaneous injection needles. The gauge of the introduction needle 1836 can range from 16 gauge to 31 gauge. The size of the introduction needle 1836 can be based on the type of therapeutic agent to be delivered. For example, in an implementation where the therapeutic agent is a fluid, the introduction needle 1836 may have a size between 25 gauge and 31 gauge. In another implementation where the therapeutic agent is not a fluid (e.g., a gas), the introduction needle 1836 may have a size between 16 gauge and 22 gauge.

[0127] During the procedure, the steps are to use the mouthpiece 1804 to (1) apply a local anesthetic into the anesthetic well 1806 (e.g., lidocaine or tetracaine gel or solution), (2) insert the mouthpiece 1804 into the subject's mouth to ensure that the Moller housing 1810 is properly positioned and the anterior tooth housing 1812 is fixed to the anterior teeth, (3) wait for a certain period of time (e.g., about 5-15 minutes) for the local anesthetic to numb the palate, and (4) rotate the access port 1860 to a selected state from the first, second, and third states. This can be done by (5) preparing a syringe of 1-5cc of anesthetic, with or without a decongestant; (6) attaching the syringe to the translatable introduction port 1814 and translating the translatable introduction port 1814 a distance of 1819 (for example, until the translatable introduction port 1814 contacts the access port 1860) to deploy the introduction needle 1836 into the palate; (7) aspirating the syringe to confirm that the injection is clear; and (8) injecting the therapeutic agent through the introduction needle 1836 into the apex of the mouth and into the palatine foramen 102T.

[0128] The method described above can achieve anesthesia of a significant portion of the posterior region of the nasal cavity as well as the palate by anesthetizing a relatively large proportion of the nasal and oral branches of the maxillary nerve. This method can also be used to help control intranasal bleeding during nasal surgical procedures as the primary blood supply to the nose passes through this duct and fossa. The paper “An Evaluation of Effect of Pterygopalatine fossa Injection with Local Anesthetic and Adrenalin in the Control of Nasal Bleeding during Endoscopic sinus surgery,” authored by Peter-John Wormald, MD, is incorporated by reference.

[0129] In some implementations, it would be desirable to reach the pterygopalatine fossa to deliver a more controlled amount of therapeutic agent and ensure that the agent reaches the target site in the fossa (e.g., the sphenopalatine ganglion). Accessing the fossa via the palatine foramen 102T can cause trauma to arteries, nerves, and tissues surrounding the canal. In the example described below, the risk of such trauma is reduced (or minimized) and a more reliable and safer method is provided for cannulating the fossa and delivering therapeutic agent.

[0130] Figures 19-22 show the mouthpiece 1804 of Figure 18 and a guidewire needle 1921 for cannula treatment in the pterygopalatine fossa in one example. The guidewire needle 1921 may include a guidewire inlet port 1923, a proximal section 1925, a distal section 1927, a distal tip 1929 having a delivery outlet port, and a central lumen that can extend from the guidewire inlet port 1923 to the delivery outlet port of the distal tip 1929. The proximal section 1925 may be made from a semi-rigid material, and the distal section 1927 may be made from a flexible material.

[0131] The distal tip 1929 of the guidewire needle 1921 can be inserted into the access port 1860 of the mouthpiece 1804. The guidewire needle 1921 and the access port 1860 may have respective sizes and / or shapes suitable for allowing the guidewire needle 1921 to translate through the access port 1860 with relatively easy and appropriate pushability.

[0132] The guidewire inlet port 1923 can be configured to connect to a syringe. In one example, the guidewire inlet port 1923 can be made from stainless steel and / or rigid to semi-rigid plastic (e.g., polycarbonate). As described above, the guidewire needle 1921 may include a proximal section 1925 and a distal section 1927. The proximal section 1925 can be sufficiently rigid to withstand and transmit torque and translational forces from the user to the distal end with minimal loss. In one example, the proximal section 1925 may include a stainless steel hypotube.

[0133] The distal section 1927 may be flexible, and at the same time still be translatable and rotatable via the force applied to the proximal section. In one example, the distal section 1927 may include a round or flat wire that is tightly wound clockwise and / or counterclockwise (i.e., the wire may come into contact with the central lumen and the central lumen may be sealed). The distal section 1927 of the guidewire needle 1921 may be terminated at a distal tip 1929. The distal tip 1929 may have a non-traumatic size and / or shape to help mitigate (or prevent) the risk of the guidewire needle 1921 puncturing the arterial wall or tearing tissue.

[0134] In some implementations, the distal tip 1929 may include a radiopaque marker and / or an illumination element that can emit light. The radiopaque marker and / or illumination element of the distal tip 1929 can help the user track the location of the distal tip 1929 of the guidewire needle 1921 as it passes through tissue and / or bone structures. In some implementations, when the distal tip 1929 includes an illumination element, the translation of the guidewire needle 1921 can be observed within the nasal canal or potentially through the sides of the face.

[0135] As described above, the guidewire needle 1921 may include a central lumen. The central lumen allows the therapeutic agent to pass through from the other end without leakage. The distal end of the central lumen has a delivery exit port through which the therapeutic agent exits the central lumen. In one example, the distal tip 1929 of the guidewire needle 1921 may extend from approximately 25 mm to approximately 50 mm from the bilateral working lumen 1808 (shown in Figure 22, extending into the Moller housing 1810).

[0136] The method for using the mouthpiece 1804 and guidewire needle 1921 is as follows: (1) applying a local anesthetic to the anesthetic well 1806 (e.g., lidocaine or tetracaine gel or solution); (2) inserting the mouthpiece 1804 into the subject's mouth to ensure that the Moller housing 1810 is properly positioned and the anterior tooth housing 1812 is fixed to the anterior teeth; (3) waiting for a certain period of time (e.g., about 5-15 minutes) for the local anesthetic to numb the palate; (4) rotating the access port 1860 to a selected state from the first, second, and third states; and (5) administering 1-5 cc of anesthetic with or without a decongestant. The procedure may include the steps of: (6) preparing a syringe; (7) deploying the introduction needle 1836 into the palate by translating the translatable introduction port 1814 a distance 1819 (for example, until the translatable introduction port 1814 contacts the access port 1860); (8) attaching the syringe to the guidewire needle 1921; (9) feeding the guidewire needle 1921 into the palatine canal through the introduction needle 1836, advancing the guidewire needle 1921 until its distal tip 1929 reaches the fossa; (10) aspirating the syringe to confirm that the injection is clear; and (11) injecting the therapeutic agent into the fossa through the guidewire needle 1921.

[0137] Within the scope of the examples, the mouthpiece 1804 can be configured to surround one or more teeth to assist in positioning and stability. In some examples, the mouthpiece 1804 can interface primarily with the hard palate or soft palate, interface only with the medial edges of one or more teeth, or not interface with teeth at all.

[0138] In some implementations, the mouthpiece 1804 can be manufactured in one or more pre-configured sizes and is not customized for a specific patient. In other implementations, the mouthpiece 1804 can be customized to fit a specific patient, for example, based on a mold taken from the patient's mouth, or based on CT / MR or other scans of the relevant patient's anatomical structure. The mouthpiece 1804 can be constructed from a flexible material such as silicone, or from multiple materials, for example, a plastic overmolded with an internal stainless steel backbone, to provide enhanced mechanical stability.

[0139] In some implementations, the mouthpiece 1804 may include one or more sensors to help position a hole, such as the large palatal hole 102T, in order to guide access for a substance or substance delivery mechanism into the palatal canal 102R. In one implementation, the sensors can guide the overall positioning of the mouthpiece 1804 itself. In some implementations, the sensors can allow for fine-tuning of the position of the mouthpiece 1804 or a portion of the mouthpiece 1804 to align more closely with the hole 102T.

[0140] In some examples, the sensor may include an imaging modality that allows the user to directly visualize the hole 102T (for example, the sensor may record video or photographs of nearby structures during placement, which are transmitted with or without the use of a video cable to a monitor viewed by the operator).

[0141] In some examples, the mouthpiece 1804 may include a lumen (e.g., a bilateral working lumen 1808) adapted to interface with a syringe or similar substance delivery mechanism at its proximal end, which terminates with a delivery tube at its distal end. This delivery tube at the distal end of the lumen may be configured to enter the orifice when properly positioned via camera guidance. Proximally adjacent to the delivery tube are one or more cameras adapted to visualize the structure in a manner that guides positioning. In the example, a light source may also be positioned close to the delivery tube for the purpose of illuminating the site structure in a manner suitable for visualization. In the example, the delivery tube, camera, and light source may be located on only one side (left or right) of the mouthpiece 1804. In alternative examples, these components are positioned on both sides.

[0142] In the example, the delivery tube, camera, and light source are mounted on attachments to the mouthpiece 1804 that are movable independently of the body of the mouthpiece 1804. For example, a small attachment can be attached to the body of the mouthpiece 1804 near its rear end via a ball joint or another mechanism that allows the attachment to move independently of the body of the mouthpiece 1804. In the example of how to use, the mouthpiece is positioned in the patient's mouth by an operator and secured in place by fitting it snugly around the upper teeth. The camera and / or light source can be activated, and the relative position of the attachments, including the delivery tube, can be adjusted using video or photographic feedback displayed on a screen located outside the patient's mouth. This adjustment can be performed until the delivery tube is inserted or otherwise positioned in the desired location with a hole. Once positioned, drug delivery can be initiated, for example, by pressing down the plunger of a syringe interfaced with the mouthpiece, or by adjusting the valve of the mouthpiece 1804, to allow the substance to flow through the lumen into the palatine canal via the delivery tube.

[0143] The example may utilize non-photographic sensors as an alternative or additional measure. For example, the example may employ visualization techniques including medical imaging techniques such as ultrasound, optical coherence tomography, or laser. In the example, an ultrasonic transducer or laser emitter is mounted near the rear of the mouthpiece to guide the insertion or placement of one or more delivery tubes. In the example, the ultrasonic transducer is adapted to operate in A mode to detect when the echo signal is amplitude reduced or time delayed (or both), indicating that the transducer is transmitting into the opening and is not emitting a signal that is strongly reflected at the interface of the hard or soft palate. In the example, a bonding balloon containing a gel or fluid is used to ensure proper acoustic coupling of the ultrasonic signal emitted from the transducer into the tissues inside the mouth. In various examples, the transducer array is configured to operate in B mode, and live ultrasonic images are displayed on a video screen, allowing the user to adapt to the position of the delivery tube in real time. In various examples, optical-based techniques can similarly be used to map the surface of the palate by utilizing the signal irregularities resulting from the presence of openings, as a means of identifying entry points into the palatine canal.

[0144] Within the scope of the examples, the devices, systems, and methods described herein can be additionally or alternatively configured to deliver a subject in or near a region of interest. For example, in some examples, the devices, systems, and methods can be configured to deliver a therapeutic agent 238 (e.g., a drug / pharmaceutical or anesthetic) in a solid form that can provide a long-term release over time. In one implementation, the therapeutic agent 238 can be mixed in a solid composed of absorbable sugars that dissolve over time when exposed to moisture in the environment of mucosal tissue. In another implementation, the drug can be manufactured in the form of a thin film or gelatinous substrate that similarly dissolves after exposure to the tissue of the region of interest. In some implementations, the mechanism of substrate degradation can be triggered by body heat and / or moisture. Within the scope of the examples, degradation of the solid or substrate triggers the release of the therapeutic agent 238, the release being gradual and proportional to the timescale of degradation. As described above, delivery devices 220, 320, 420, 520, 620, 720, 820, 920, 1020, 1120, 1220, 1320, 1420, 1520, 1620, and 1804 can deliver solid therapeutic agents to natural orifices and / or to passages formed using perforating elements 236 to deliver solid therapeutic agents to regions of interest.

[0145] Within the scope of the examples, the delivery devices and methods described above may include one or more components for performing cryotherapy procedures (e.g., cryoablation procedures). For example, delivery devices 220, 320, 420, 520, 620, 720, 820, 920, 1020, 1120, 1220, 1320, 1420, 1520, 1620, and 1804 may include a cryotherapy source for storing a cryotherapy agent (e.g., nitrous oxide, liquid carbon dioxide, and / or liquid chlorofluorocarbon) in a proximal portion, an applicator having a cryotherapy delivery function that can use the cryotherapy agent to apply thermal energy to a target tissue, and a lumen that connects the cryotherapy source to the cryotherapy delivery function.

[0146] In some examples, cryotherapy components can be integrated with the functions of delivery devices described above. This can beneficially enable the delivery device to deliver therapeutic drugs, heat projections and / or needles, and / or form pathways before, during, or after applying cryotherapy to target tissue. Additional details regarding devices that combine cryotherapy components with functions for delivering therapeutic drugs (e.g., anesthetics) are described in U.S. Provisional Patent Application No. 62 / 861,591, filed June 14, 2019, which is incorporated herein by reference in its entirety. In other examples, cryotherapy components can be implemented in a second device distinct from components for forming pathways, delivering therapeutic drugs, and / or generating the heat described above.

[0147] Referring here to Figure 23, a flowchart of Method 2300 for delivering a therapeutic agent to at least one of the patient's palatine canal or pterygopalatine fossa is shown according to an example. In block 2310, Method 2300 includes inserting a delivery device into the patient's nasal cavity. The delivery device includes an elongated shaft having a proximal end and a distal end, a handpiece coupled to the proximal end of the elongated shaft, and a perforating element disposed at the distal end of the elongated shaft. In block 2312, Method 2300 includes advancing the distal end of the elongated shaft to a position close to the palatine bone inside the nasal cavity. In block 2314, Method 2300 includes activating the perforating element to form a passage in the palatine bone between the patient's nasal cavity and the palatine canal. In block 2316, Method 2300 includes delivering the therapeutic agent into the palatine canal.

[0148] Figures 24–34 show additional embodiments of method 2300 relating to further examples. As shown in Figure 24, activating the perforating element in block 2314 may include discharging the perforating fluid in the fluid stream from the elongated shaft into the palatine bone in order to perforate a passage through the palatine bone in block 2318.

[0149] As shown in Figure 25, delivering the therapeutic agent in block 2316 may include discharging a fluid stream of the therapeutic agent from an elongated shaft through a passage in the palatine bone into the palatine canal in block 2320.

[0150] In one example, the delivery device may include a therapeutic drug delivery member in the distal portion of an elongated shaft. As shown in Figure 26, delivering the therapeutic drug in block 2316 may include discharging a fluid stream of the therapeutic drug from the therapeutic drug delivery member of the elongated shaft through a passage in the palatine bone into the palatine canal in block 2322.

[0151] In one example, the piercing element may include a needle. As shown in Figure 27, activating the piercing element in block 2314 may include protruding the needle laterally from the distal portion of the elongated shaft through the palatine bone in block 2324.

[0152] As shown in Figure 28, projecting the needle laterally from the distal portion of the elongated shaft through the palatine bone in block 2324 may include inflating the expandable member connected to the needle in block 2326.

[0153] As shown in Figure 29, extending the needle laterally away from the distal portion of the elongated shaft through the palatine bone in block 2324 may include releasing the compression spring connected to the needle in block 2328.

[0154] As shown in Figure 30, Method 2300 may include positioning the distal end of the elongated shaft so that the perforating element is adjacent to the palatine bone by inflating an expandable member coupled to the distal end of the elongated shaft in block 2330 to stabilize the needle while the needle penetrates the palatine bone, before activating the perforating element in block 2314.

[0155] In one example, the delivery device may further include a therapeutic drug delivery member having a delivery conduit disposed at the distal end of an elongated shaft. As shown in Figure 31, delivery of the therapeutic drug into the palatine canal in block 2316 may include (i) inserting the delivery conduit into the palatine canal through a passage in the palatine bone in block 2332, and (ii) directly discharging the therapeutic drug into the palatine canal through the delivery conduit in block 2334.

[0156] As shown in Figure 32, method 2300 may also include positioning the plug inside the passage after the therapeutic agent has been delivered to close the passage with block 2336.

[0157] In one example, the delivery device may further include a cryotherapy delivery function. As shown in Figure 33, method 2300 may further include positioning the cryotherapy delivery function in block 2338 in close proximity to a target nerve in the nasal cavity, and using the cryotherapy delivery function to cryoablate the target nerve in block 2340 to alleviate symptoms of rhinitis after delivery of the therapeutic agent into the palatine duct.

[0158] As shown in Figure 34, Method 2300 may further include inserting a second device into the patient's nasal cavity in block 2342. The second device may include a second shaft having a second proximal end and a second distal end, a second handpiece coupled to the second proximal end, and a therapeutic drug delivery member disposed at the second distal end. Method 2300 may also include advancing the second distal end of the second shaft through a passage into the palatine canal in block 2344, and delivering a therapeutic drug into the palatine canal using the therapeutic drug delivery member in block 2346.

[0159] Referring here to Figure 35, a flowchart of method 3500 for delivering a therapeutic drug to at least one of the patient's palatine canal or pterygopalatine fossa is shown according to another example. In block 3510, method 3500 includes inserting a device into the patient's mouth. The device includes an elongated shaft having a proximal end and a distal end, an access port coupled to the proximal end of the elongated shaft, and a therapeutic drug delivery member disposed on the distal portion of the elongated shaft. The therapeutic drug delivery member includes a delivery conduit. In block 3512, method 3500 includes advancing the distal end of the elongated shaft of the device to a position close to the greater palatine foramen of the patient's mouth. In block 3514, method 3500 includes using the delivery conduit to deliver the therapeutic drug into at least one of the palatine canal or pterygopalatine fossa using the therapeutic drug delivery member.

[0160] Figures 36-39 show additional embodiments of Method 3500 relating to further examples. As shown in Figure 36, Method 3500 may also include activating a drug delivery member in block 3516 to advance the delivery conduit through the large palatine orifice into the patient's palatine canal. As shown in Figure 37, drug delivery in block 3514 may include direct discharge of the drug through the delivery conduit into the palatine canal in block 3518.

[0161] In one example, the delivery device may include a suction port located at the distal end of an elongated shaft. As shown in Figure 38, method 3500 may include applying suction using the suction port in block 3520 to stabilize the distal end of the elongated shaft in close proximity to the orifice of the palate. As shown in Figure 39, delivering the therapeutic agent in block 3514 may include draining the therapeutic agent through the orifice of the palate in block 3522.

[0162] Referring here to Figure 40, a flowchart for method 4000 for delivering a drug into at least one of the patient's palatine canal or pterygopalatine fossa is shown according to another example. In block 4010, method 4000 includes inserting a mouthpiece into the patient's mouth. The mouthpiece is U-shaped. The mouthpiece includes a well configured to receive the patient's teeth. The mouthpiece includes an introduction needle. In block 4012, method 4000 includes positioning the mouthpiece so that the teeth are received in the well and the introduction needle is inserted into the patient's great palatine foramen. In block 4014, method 4000 includes delivering the drug into the patient's great palatine foramen, into the palatine canal, through the introduction needle.

[0163] Referring here to Figure 41, a flowchart for method 4100 for the delivery of a therapeutic agent to a canal in the patient's skull containing a nerve is shown according to one example. In block 4110, method 4100 includes inserting a device into the patient's nasal cavity. The device includes a shaft having a proximal end and a distal end, a handpiece coupled to the proximal end of the shaft, and a perforating element disposed at the distal end of the shaft. In block 4112, method 4100 includes advancing the distal end of the shaft to a position close to the bone inside the nasal cavity that at least partially defines a canal in the patient's skull containing a nerve. In block 4114, method 4100 includes activating the perforating element to create a passage in the bone between the nasal cavity and the canal. In block 4116, method 4100 includes delivering a therapeutic agent into the canal. In one example, the bone is the sphenoid bone and the canal is the pterygoid canal.

[0164] The terms “almost” or “substantially” are used with respect to quantities or measurements described herein to mean that the described characteristics, parameters, or values ​​do not need to be achieved exactly, but deviations or variations, including, for example, tolerances, measurement errors, measurement accuracy limits, and other factors known to those skilled in the art, may occur in an amount that does not interfere with the effect that the characteristic is intended to provide.

[0165] Descriptions of different advantageous arrangements are presented for illustrative and explanatory purposes and are not intended to be exhaustive or to be limited to the examples in the disclosed form. Many modifications and variations will be obvious to those skilled in the art. Furthermore, different advantageous examples may illustrate different advantages compared to other advantageous examples. One or more selected examples are described for the purpose of illustrating the principle of the example, its practical applications, and enabling those skilled in the art to understand the disclosure of various examples with various modifications suitable for the particular intended use.

Claims

1. A delivery device for delivering a therapeutic drug to at least one of the patient's palatine canal or pterygopalatine fossa, wherein the delivery device is A slender shaft having a proximal end and a distal end, A handpiece coupled to the proximal end of the elongated shaft, A lumen extends through the elongated shaft to the output port in the distal portion of the elongated shaft that is close to the distal end, A perforating element is disposed in the distal portion of the elongated shaft and configured to form a passage in the palatine bone, A therapeutic drug delivery member is disposed in the distal portion of the elongated shaft and configured to deliver the therapeutic drug to the passage formed by the perforating element via the output port, The handpiece includes one or more user-controlled devices, The delivery device is configured to form the passage with the perforating element, and to deliver the therapeutic agent to the passage formed by the perforating element with the therapeutic agent delivery member. The one or more user-controlled devices are operable to cause the perforating element to perform at least one operation selected from the group consisting of (i) and (ii) below, thereby causing the perforating element to form the passage in the palatine bone. (i) The piercing element includes a needle, and the needle is moved so as to protrude from the distal portion of the elongated shaft, (ii) The one or more user-controlled devices are operable to cause a perforating fluid source to supply a perforating fluid to the output port, and to discharge the fluid stream of the perforating fluid from the output port of the elongated shaft, Delivery device.

2. The perforating element is configured to discharge the fluid stream of the perforating fluid through the output port in order to form the passage. The lumen includes a first lumen extending from the inlet port on the handpiece to the output port, The delivery device according to claim 1, wherein the inflow port is configured to be coupled to the perforating fluid source.

3. The delivery device according to claim 2, wherein the inlet port is configured to be disconnected from the perforating fluid source and then connected to the therapeutic drug source in order to switch from a perforating operating mode to a therapeutic drug delivery operating mode.

4. The delivery device according to claim 2, wherein the lumen further comprises a second lumen configured to supply the therapeutic drug from a therapeutic drug source to the output port.

5. The delivery device according to claim 1, wherein the perforating element is operated by one or more user-controlled devices to cause the needle to protrude from the distal portion of the elongated shaft through the palatine bone.

6. The needle further comprises an expandable member coupled to the needle, The delivery device according to claim 5, wherein the expandable member is configured to expand to cause the needle to protrude from the distal portion of the elongated shaft through the palatine bone.

7. The needle is further fitted with a compression spring, The delivery device according to claim 5, wherein the compression spring is configured to be released to allow the needle to protrude from the distal portion of the elongated shaft through the palatine bone.

8. The device further comprises one or more stabilizer functions configured to hold the delivery device in a relatively fixed position while the perforating element forms the passage in the palatine bone and / or while the drug delivery member delivers the drug, The delivery device according to any one of claims 1 to 7, wherein the one or more stabilizer functional units are at least one functional unit selected from the group consisting of (i) an expandable member coupled to the distal end of the elongated shaft, and (ii) one or more suction ports.

9. One or more sensors configured to indicate whether the distal end of the elongated shaft is close to the tissue surface, A controller configured to prevent the perforating element from being activated by disabling the one or more user-controlled devices associated with the perforating element when one or more of the sensors do not indicate that the distal end is close to the tissue surface, and A delivery device according to any one of claims 1 to 8, further comprising the above.

10. The delivery device according to any one of claims 1 to 9, further comprising a cryotherapy delivery function configured to cryoablate target nerves in order to alleviate the symptoms of rhinitis after delivery of the therapeutic drug.

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