Head assembly with controlled therapeutic agent release

Abstract

A leadless biostimulator, such as a leadless pacemaker, is described that includes a header assembly with a monolithic controlled release device (MCRD) for elution of a therapeutic agent. The MCRD is in fluid communication with a space between an insulator and an electrode of the header assembly for elution of the therapeutic agent into the space upon implantation of the leadless biostimulator. The therapeutic agent can be eluted through the space around the electrode to provide a controlled elution of the therapeutic agent to the surrounding environment. The electrode can extend longitudinally through the insulator lumen to a distal tip that provides a stable surface area and controlled impedance for pacing of target tissue. Other embodiments are also described and claimed.

Description

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 182,687, filed April 30, 2021, which is incorporated herein by reference in its entirety to provide for continuity of disclosure. Technical Field

[0002] This invention relates to biostimulators with a head assembly. More specifically, this disclosure relates to leadless biostimulators with a head assembly, the leadless biostimulator including electrodes, and the invention relates to a method of manufacturing such a head assembly. Background Technology

[0003] When the heart's natural pacemaker and / or conduction system are unable to provide synchronized atrial and ventricular contractions at a rate and interval sufficient to ensure the patient's health, cardiac pacing by an artificial pacemaker electrically stimulates the heart. This bradycardia pacing has provided symptom relief and even life support for thousands of patients. Cardiac pacing can also provide electrical overdrive stimulation to suppress or convert tachyarrhythmias, further relieving symptoms and preventing or terminating arrhythmias that could lead to sudden cardiac death.

[0004] Cardiac pacing in currently available or conventional pacemakers is typically performed by a pulse generator implanted subcutaneously or submuscularly in or near the patient's chest region. The pulse generator is usually connected to the proximal end of one or more implanted leads via a feedthrough assembly that creates an isolated electrical pathway into the sealed housing for delivering pulses / sensors to the target tissue. The feedthrough assembly can be used for low- or high-voltage applications. The distal end of the implanted leads is typically 50 to 70 cm long and contains one or more electrodes for positioning near the inner or outer wall of the ventricle. The leads have one or more insulated electrical conductors for connecting the pulse generator to the electrodes in the heart. Thus, the pulse generator can deliver pacing pulses to the target tissue from within the sealed housing via the feedthrough assembly, leads, and electrodes.

[0005] Conventional pacemakers have several drawbacks, including the risk of lead or feedthrough component breakage, complex connections between the lead and feedthrough components, and the risk of infection and morbidity due to separate lead and pulse generator components. Many of the problems associated with conventional pacemakers have been addressed by developing self-contained and self-continuous biostimulators, or so-called leadless biostimulators. Leadless biostimulators can be attached to tissues in dynamic environments, such as within the chambers of a beating heart, to deliver pacing pulses directly to the tissue without the use of leads. Summary of the Invention

[0006] Existing leadless biostimulators feature a hermetically sealed package containing internal components for generating and receiving electrical pulses via electrodes of the head assembly. The electrodes may include a sealed cup containing a therapeutic agent. The cup can be capped, and when the leadless biostimulator is implanted, the therapeutic agent can be eluted toward the target tissue through an opening in the cap. The capped cup provides a relatively large surface area, which may lead to inconsistent contact with the target tissue, thus providing inconsistent impedance and electrical pulse control. Furthermore, the small opening in the cap can restrict fluid delivery into the cup or become blocked, thereby limiting the elution of the therapeutic agent-containing fluid from the cup. Therefore, a head assembly with greater control over electrode impedance and therapeutic agent release is needed.

[0007] A leadless biostimulator is described, comprising a head assembly for controlled delivery of a therapeutic agent around an electrode to a target tissue. A method of manufacturing the head assembly is also described. In one embodiment, the head assembly includes a flange having a flange channel extending along a longitudinal axis. An insulator may be disposed within the flange channel and may include an insulating cavity. The head assembly may include an electrode extending longitudinally through the insulating cavity. A space may be formed between the insulator and the electrode. In one embodiment, a monolithic controlled release device (MCRD) is disposed within the insulating cavity such that when the leadless biostimulator is implanted into the bloodstream, the therapeutic agent is eluted from the MCRD into the space. The head assembly may include a helical fixation element to secure the biostimulator to the target tissue site. Thus, upon implantation, the therapeutic agent can be delivered to the target tissue site.

[0008] The MCRD may have a ring-shaped body. For example, the ring-shaped body may be tubular and may be disposed within an insulating cavity such that the central lumen of the tubular body is aligned with the longitudinal axis of the flange. Therefore, the electrode pin of the electrode can extend longitudinally through the central lumen. The electrode tip is mounted at the distal end of the electrode pin. Alternatively, an electrode helix can be mounted at the distal end of the electrode pin. The electrode tip and / or electrode helix may be disposed within a helical mounting channel of a helical mounting element supporting the helical fixation element. Furthermore, the electrode tip and / or electrode helix can deliver pacing pulses from the electrode to the target tissue. Thus, the therapeutic agent can be eluted from the MCRD and delivered between the helical mounting element and the distal end of the electrode pin to the target tissue at the pacing site.

[0009] The foregoing overview does not constitute an exhaustive list of all aspects of the invention. The invention is intended to encompass all systems and methods that can be implemented from all suitable combinations of the aspects summarized above, as well as those disclosed in the detailed description below and specifically pointed out in the claims filed with this application. Such combinations have particular advantages not specifically listed in the foregoing overview. Attached Figure Description

[0010] The novel features of the invention are set forth in detail in the following claims. A better understanding of the features and advantages of the invention will be obtained by referring to the following detailed description and accompanying drawings, which illustrate illustrative embodiments in which the principles of the invention are utilized.

[0011] Figure 1 This is a perspective view of a leadless biostimulator according to one embodiment.

[0012] Figure 2 A perspective view of a head assembly with controlled release of a therapeutic agent according to one embodiment.

[0013] Figure 3 This is a cross-sectional view of a head assembly having a monolithic controlled release device (MCRD) between an insulator and an electrode, according to one embodiment.

[0014] Figure 4 This is a cross-sectional view of a head assembly having an MCRD within an insulating cavity of a ceramic spiral mount, according to one embodiment.

[0015] Figure 5 A perspective view of a head assembly with controlled release of a therapeutic agent according to one embodiment.

[0016] Figure 6 This is a cross-sectional view of a head assembly having an MCRD within an electrode spiral, according to one embodiment.

[0017] Figure 7 This is a flowchart of a method for manufacturing a leadless biostimulator according to one embodiment. Detailed Implementation

[0018] Embodiments of the present invention include leadless biostimulators, such as leadless cardiac pacemakers, having a head assembly including a monolithic controlled-release device (MCRD) for eluting therapeutic agents around electrodes. Leadless biostimulators can be used for pacing cardiac tissue, such as the ventricles or atria of the heart. However, leadless biostimulators can be used for other applications, such as deep brain stimulation. Therefore, referring to a leadless biostimulator as a cardiac pacemaker is not limiting.

[0019] Various embodiments are described with reference to the accompanying drawings. However, some embodiments may be implemented without one or more of these specific details, or in combination with other known methods and constructions. Numerous specific details, such as specific constructions, dimensions, and processes, are set forth in the following description to provide a thorough understanding of the embodiments. In other instances, well-known processes and manufacturing techniques are not described in particular detail to avoid unnecessarily obscuring the description. Throughout the specification, references to “an embodiment,” “embodiment,” etc., mean that a particular feature, structure, construction, or characteristic described is included in at least one embodiment. Therefore, phrases “an embodiment,” “embodiment,” etc., appearing in different places throughout the specification do not necessarily refer to the same embodiment. Furthermore, in one or more embodiments, a particular feature, structure, construction, or characteristic may be combined in any suitable manner.

[0020] Relative terms used in this specification may indicate relative positions or orientations. For example, "distal" may refer to a first direction along the longitudinal axis of the leadless biostimulator. Similarly, "proximal" may refer to a second direction opposite to the first direction. However, these terms are provided to establish a relative frame of reference and not to limit the use or orientation of the leadless biostimulator to the specific constructions described in the various embodiments below.

[0021] In one aspect, a leadless biostimulator includes a head assembly having an electrode extending longitudinally through an insulating cavity of an insulator. A therapeutic agent-containing MCRD can be located within the insulating cavity. For example, the MCRD can be held within the insulating cavity by the distal end of the electrode or via a press-fit between the MCRD and an electrode helix. Thus, when the leadless biostimulator is implanted into the bloodstream, the held MCRD can elute the therapeutic agent toward the target tissue into the insulating cavity. For example, the therapeutic agent can be eluted through the space between the insulator and the electrode, and eluted around the electrode into the surrounding environment through channels of the helical mount. The channels of the helical mount can have a sufficient cross-sectional area, such as an annular cross-sectional area, to allow exchange of blood and therapeutic agent between the MCRD and the surrounding environment. Thus, the head assembly described below can provide controlled release of the therapeutic agent.

[0022] In one aspect, the electrode of the head assembly includes an electrode pin for delivering pacing pulses distally toward target tissue. Furthermore, the electrode may have a distal end comprising a small distal surface area capable of securely engaging the target tissue. For example, the distal end may be a cap mounted on the distal end of the electrode pin, or an electrode screw that can be screwed into the target tissue. Thus, the electrode can provide consistent and stable surface area contact between the electrode and the target tissue. Therefore, the head assembly described below can provide controlled impedance and pacing.

[0023] refer to Figure 1 A perspective view of a leadless biostimulator is shown according to one embodiment. The biostimulator 100 may be a leadless biostimulator, such as a leadless pacemaker for delivering pacing pulses to the atria or ventricles of the heart. The biostimulator 100 may include a housing 102 having electrodes. For example, the biostimulator 100 includes each of a distal electrode 104 and a proximal electrode 106 disposed on or integrated into the housing 102. The distal electrode 104 and the proximal electrode 106 can be used to sense and pace the heart. Electrodes 104, 106 may be integrated into or attached to the housing 102, for example, at a distance of less than a few centimeters from the housing.

[0024] In one embodiment, housing 102 includes an energy source (not shown) for powering pacing electrodes 104, 106. For example, the energy source can generate a potential difference between the cathode (e.g., distal electrode 104) and anode (e.g., proximal electrode 106) of the device. The energy source can be, for example, a battery, such as a lithium-carbon fluoride (CFx) battery, or a hybrid battery, such as a combined CFx and silver vanadium oxide (SVO / CFx) hybrid chemical battery. Similarly, the energy source can be a supercapacitor. In one embodiment, the energy source can be an energy harvesting device, such as a piezoelectric device that converts mechanical strain into current or voltage. The energy source can also be an ultrasound transmitter that uses ultrasound technology to transfer energy from a subcutaneous ultrasound pulse generator to a receiver electrode implanted on the endocardial wall.

[0025] The housing 102 may have a longitudinal axis 108, which may be an axis of symmetry, along which several other biostimulator components are arranged. For example, a head assembly 110 may be mounted along the longitudinal axis 108 at the distal end of the housing 102. The head assembly 110 may include an electrical feed assembly comprising a flange 112, a screw mount 114, and a screw fastening element 116 mounted on the screw mount 114. The assembly components of the head assembly 110, further described below, may provide a distal region of the biostimulator 100, which is attached to the target tissue, for example, through engagement with the fastening element 116. When the leadless biostimulator 100 is implanted into the surrounding environment 117 (e.g., blood in the atrium or ventricle), the distal region may deliver pacing pulses to the target tissue, for example, via a distal electrode 104 held against the target tissue.

[0026] The housing 102 may include an electronics compartment 118 (shown in hidden lines). More specifically, the electronics compartment 118 may be a cavity laterally surrounded by a housing wall (e.g., a cylindrical wall) extending around a longitudinal axis 108. The housing wall may comprise a conductive, biocompatible, inert, and anodic-safe material, such as titanium, 316L stainless steel, or other similar materials, to laterally enclose the electronics compartment 118. More specifically, the electronics compartment 118 may be enclosed between the energy source of the biostimulator 100 (within the proximal portion of the housing 102) and the head assembly 110 (at the distal portion of the biostimulator 100). The energy source container may proximally enclose the electronics compartment 118, and the head assembly 110 may distally enclose the electronics compartment 118. The head assembly 110, the housing wall, and the energy source container may enclose the volume of the electronics compartment 118.

[0027] In one embodiment, the electronics compartment 118 includes an electronics assembly 120 (shown in hidden lines). The electronics assembly 120 may be mounted within the electronics compartment 118. For example, the electronics assembly 120 may include, but is not limited to, a flexible circuit or printed circuit board with an electrical connector that connects to an electrical pin of a power source and a head assembly 110. As described below, the head assembly 110 may include electrodes that connect to the electrical connectors (e.g., receptacle connectors) of the electronics assembly 120 within the electronics compartment 118 to transmit pacing and sensing signals to and from target tissue. The electronics assembly 120 has one or more electronic components mounted on a substrate. For example, the electronics assembly 120 may include one or more processors, capacitors, etc., interconnected via traces, vias, or other electrical connectors. The electronic components may be configured to perform sensing and pacing of the target tissue.

[0028] Biostimulator components, such as an energy source container, an electronics compartment 118 containing electronics assembly 120, and a head assembly 110, may be arranged along a longitudinal axis 108. Thus, each component may extend along the longitudinal axis 108 and have a corresponding axial position relative to another component along the longitudinal axis 108. For example, the energy source container may be offset from the electronics compartment 118 in a proximal direction 122, and the head assembly 110 may be offset from the electronics compartment 118 in a distal direction 124.

[0029] refer to Figure 2According to one embodiment, a perspective view of a head assembly with controlled therapeutic agent release is shown. The head assembly 110 can perform several functions. First, the head assembly 110 secures the leadless biostimulator 100 to target tissue via a helical fixation element 116 mounted on a helical mount 114. The fixation element can be screwed into the target tissue to hold the leadless biostimulator 100 in place, with the distal electrode 104 in contact with the target tissue. Second, the head assembly 110 provides electrical feedthrough from the electronics compartment 118 to the surrounding environment 117 to allow sensing and pacing of the target tissue. More specifically, the electrical feedthrough assembly of the head assembly 110 can transmit electrical pulses to the target tissue via the distal electrode 104. Third, the head assembly 110 contains a therapeutic agent between the helical mount 114 and the flange 112, which can be eluted outwards to the target tissue when the leadless biostimulator 100 is implanted into the surrounding environment 117. More specifically, fluids from the surrounding environment 117, such as blood, can flow inward through the gap 202 between the distal electrode 104 and the helical mount 114 into the axially contained space between the helical mount 114 and the flange 112, and then the agent-loaded fluid can flow outward through the gap 202 toward the target tissue.

[0030] refer to Figure 3 According to one embodiment, a cross-sectional view of a head assembly having a monolithic controlled release device (MCRD) between an insulator and an electrode is shown. In some embodiments, each component of the head assembly 110 may be formed symmetrically about the longitudinal axis 108. For example, Figure 3 The cross-section of the flange 112 shown can be swept around the longitudinal axis 108, so that the outer surface has such Figure 2 The outline shown is shown. In other embodiments, the outline of the components of the head assembly 110 may be non-cylindrical. For example, a cross-section of the flange 112 taken about a transverse plane extending orthogonally to the longitudinal axis 108 may show the outer surface of the flange 112 as square, pentagonal, elliptical, or any other suitable shape. Therefore, the specific shapes shown in the figures are provided as examples only and are not necessarily limitations.

[0031] Flange 112 can be installed on housing 102. Figure 1 For example, the proximal flange end 302, such as a lip, can be mounted at the distal end of the housing wall surrounding the electronics compartment 118. The flange 112 can be hermetically sealed to the housing 102, such as by welding or any other similar hermetically sealed connection. For example, a sealing weld can be formed circumferentially around the joint between the proximal flange end 302 and the distal end of the housing wall.

[0032] In one embodiment, flange 112 includes a shoulder 304. Flange 112 may have a flange wall extending distally from a proximal flange end 302 to the shoulder 304. Shoulder 304 may be a transition region between a flange wall extending substantially longitudinally from the proximal flange end 302 and a flange wall extending substantially laterally. In one embodiment, shoulder 304 has a substantially laterally extending distal shoulder surface, thus the distal shoulder surface may extend laterally to the longitudinal axis 108. Therefore, the distal shoulder surface may face distally in the direction 124. The distal shoulder surface extends radially inward toward flange connector 306. Flange connector 306 may extend distally from the distal shoulder surface and may receive a threaded mount 114. For example, flange connector 306 may have an external thread that engages with the internal thread of the threaded mount 114.

[0033] In one embodiment, flange 112 includes a flange channel 308 extending along a longitudinal axis 108 from a proximal flange end 302 to a distal flange end. More specifically, flange channel 308 may be a through-hole extending entirely through flange 112 in the longitudinal direction. Shoulder 304 of flange 112 may extend around and circumferentially surround the proximal region of flange channel 308. Similarly, flange connector 306 may extend around and circumferentially surround the distal region of flange channel 308. Thus, shoulder 304 and flange connector 306 may define flange channel 308. When flange 112 is mounted on housing 102, the proximal region of flange channel 308 may define the distal region of electronics compartment 118 containing electronics assembly 120.

[0034] The head assembly 110 may include an insulator 310 in a flange passage 308. In one embodiment, the insulator 310 includes an insulator wall 312 extending around an insulator cavity 314. The insulator wall 312 may extend longitudinally from a proximal end of the insulator 310 to a distal end of the insulator 310. For example, the insulator wall 312 may be a cylindrical annular wall having a radially outward-facing outer insulator surface and a radially inward-facing inner insulator surface 316 that partially defines the insulator cavity 314. The insulator 310 may also include an insulator base 318 that extends laterally between the distal and proximal ends of the insulator 310. The insulator base 318 may be a transverse wall extending across the interior of the insulator 310, orthogonal to the longitudinal axis 108. The insulator base 318 may have a distally-facing upper wall surface that partially defines the insulator cavity 314 of the insulator 310. Therefore, the insulator 310 can be installed within the flange channel 308 to insulate the insulator cavity 314 from the metal flange connector 306 and to provide a containment for the therapeutic agent, as described below.

[0035] In one embodiment, the head assembly 110 includes an electrode 104 mounted within an insulator 310 and a flange 112. More specifically, the electrode 104 extends longitudinally through the insulator cavity 314 along a longitudinal axis 108. The electrode 104 may include several components. For example, the electrode 104 may include an electrode pin 320 extending along the longitudinal axis 108 from the electronics compartment 118 through the insulator cavity 314 to a distal end 322. The distal end 322 may be positioned distally from the insulator 310. In one embodiment, the electrode 104 includes an electrode tip 324 located at the distal end 322. The electrode tip 324 may be a cap mounted on and engaged with the distal end 322. For example, the electrode tip 324 may include an electrode cap having a countersunk or through-hole to receive and weld to the tissue-facing distal end of the electrode pin 320. Alternatively, the electrode tip 324 may be a portion of an electrode formed to have a different dimension than the electrode pin 320. For example, the external dimensions of the electrode tip 324 may be larger than the external dimensions of the electrode pin 320. Therefore, the electrode tip 324 may have a proximal surface facing the insulating cavity 314 to restrict the elution of therapeutic agents from the distal side of the insulating cavity 314.

[0036] Electrode tip 324 can serve as an active tissue contact electrode to sense and deliver electrical pulses to target tissue. In one embodiment, the size of the distal surface region of electrode tip 324 is designed to provide a predetermined impedance parameter. Electrode 104, such as a pin and cap, can be formed of platinum-iridium or another biocompatible conductor. Based on the electrical properties of the electrode material, the size of the distal surface region can be designed to provide a predetermined impedance in the contact area between the target tissue and the electrode. Generally, the smaller the distal surface region, the greater the impedance. Assuming that electrode tip 324 can be formed to be very small, and because the tip will reliably engage the target tissue on the surface region, the impedance of the electrode can be controllable and appropriately high for reliable pacing. It should be understood that the electrical feedthrough assembly can be a filtered or unfiltered assembly, as known in the art. More specifically, the electrical feedthrough assembly can include an integrated EMI filter capacitor that is electrically connected to electrode 104 (filtered feedthrough assembly) or not electrically connected to electrode 104 (unfiltered feedthrough assembly).

[0037] In one embodiment, flange 112, insulator 310, and electrode 104 are joined together. For example, a joint 326 may be formed between flange 112, insulator 310, and electrode 104 to fasten the components together and provide a seal between a flange passage region near insulator 310 (e.g., an electronics compartment) and a flange passage region away from insulator 310. In one embodiment, joint 326 is a brazed joint, such as a gold brazed joint, that radially surrounds a portion of the components to fill gaps between the components and form a sealing joint. Electrode 104 may pass through joint 326 and through a hole in insulator base 318 to transmit electrical signals between target tissue and the internal circuitry of leadless biostimulator 100.

[0038] In one embodiment, head assembly 110 includes MCRD 330. MCRD 330 may be a reagent-containing filler located within insulating cavity 314. For example, MCRD 330 may include a therapeutic agent loaded into a matrix or solid composition. In at least one embodiment, the therapeutic agent may include a corticosteroid, such as dexamethasone sodium phosphate, dexamethasone acetate, etc. When the therapeutic agent is sustained and released into the target tissue at a controlled dose, the therapeutic agent may reduce inflammation associated with device implantation.

[0039] The MCRD 330 can be placed or located within the insulator cavity 314, radially inward from the insulator wall 312 and away from the insulator base 318. The elution of the therapeutic agent from the MCRD 330 can be controlled by the geometry of the MCRD 330 and the entry and exit of fluids (e.g., blood) from the surrounding environment 117 into and out of the insulator cavity 314. Therefore, the head assembly 110 can be configured to allow fluid transport between the MCRD 330 and the surrounding environment 117 through the insulator cavity 314. Thus, a specific dose of therapeutic agent can flow from the MCRD 330 through the insulator cavity 314 and the helical mount 114 to or exude into the target tissue at the implantation site of the biostimulator 100 within the patient.

[0040] In one embodiment, when the leadless biostimulator 100 is implanted in the bloodstream, the MCRD 330 is in fluid communication with the space 332 between the insulator 310 and the electrode 104 to elute a therapeutic agent into the space 332. The space 332 may be between the inner insulator surface 316 and the outer electrode surface 317 of the electrode 104. More specifically, the space 332 may be radially defined between the inner insulator surface 316 and the outer electrode surface 317. Furthermore, the space 332 may be longitudinally defined between the insulator base 318 and the distal end of the insulator 310. Thus, in one embodiment, the space 332 is an annular region of the insulating cavity 314 defined between the electrode 104 and the insulator 310.

[0041] In one embodiment, the MCRD 330 may be housed within a space 332. For example, the MCRD 330 may have an annular body 334 located between the electrode 104 and the insulator 310 within the insulator cavity 314, and thus may be located within the space 332. The annular body 334 may include a generally cylindrical outer and inner surface and extend between the proximal and distal ends 322 of the MCRD 330. The inner surface of the MCRD 330 may define a central lumen 336 extending longitudinally through the MCRD 330. In one embodiment, the central lumen 336 receives the electrode 104. For example, an electrode pin 320 may extend longitudinally through the central lumen 336 to the distal end 322, away from the distal end of the MCRD 330. Thus, the therapeutic agent eluted from the MCRD 330 is initially in the space 332 between the electrode pin 320 and the inner surface of the insulator 310. After elution, the therapeutic agent may be transported outward to the surrounding environment 117 via blood transfer.

[0042] The head assembly 110 may include a screw mount 114. The screw mount 114 may be formed of an insulating material, such as a ceramic material (e.g., alumina, ruby, glass, or another ceramic insulating material) and / or a non-ceramic material (e.g., polyetheretherketone (PEEK)). The screw mount 114 may be mounted on a flange 112. For example, the screw mount 114 may have a threaded inner surface to engage the external threads of the flange connector 306. The screw mount 114 may also include external thread features. More specifically, the screw mount 114 may include a mounting flange 340, which may be a helical shoulder extending around the outer surface of the screw mount 114. The mounting flange 340 may receive a screw retaining element 116. More specifically, the screw retaining element 116 may be mounted on the screw mount 114 by screwing the retaining element onto the helical shoulder until the distal end of the retaining element is properly positioned for engagement.

[0043] In one embodiment, the helical mount 114 includes a helical mount channel 342 through which therapeutic agents can be eluted when the leadless biostimulator 100 is implanted in the bloodstream. The helical mount channel 342 may be an aperture extending through the distal wall of the helical mount 114. This aperture may be centrally positioned, for example along a longitudinal axis 108, such that the helical mount channel 342 is concentric with the electrode pin 320 and / or the electrode tip 324. Furthermore, the helical mount channel 342 may have a larger aperture size than that of the electrode pin 320 and the electrode tip 324, such that an annular gap 202 is formed between the helical mount 114 and the electrode 104. More specifically, the annular gap 202 may be a gap formed around the electrode 104 and extends from the insulating cavity 314 to the surrounding environment 117 to provide an elution path for the transfer of therapeutic agents. Therefore, when the leadless biostimulator 100 is implanted, blood can enter the insulating cavity 314 through the annular gap 202 to dissolve the therapeutic agent and transfer the drug-loaded agent to the surrounding environment 117 through the space 332 and the spiral mounting channel 342. Advantageously, the annular gap 202 is less prone to clogging than a single orifice, thus facilitating the consistent and continuous elution of the therapeutic agent into the target tissue.

[0044] Flange 112 may be part of proximal electrode 106, and therefore, the electrical feedthrough assembly of head assembly 110 may also include proximal electrode 106. In this case, the electrodes (electrode tip 324 and flange 112) may be very close, separated by an electrode gap extending radially between flange connector 306 and electrode 104. If blood is allowed to fill the electrode gap between flange 112 and electrode 104, electrodes 104, 106 may be electrically short-circuited, and pacing pulses may not properly pace cardiac tissue. Therefore, a barrier may be included in biostimulator 100 to prevent blood from filling the electrode gap and / or blocking the electrical path between flange 112 and electrode 104. In one embodiment, the barrier includes gasket 350. Gasket 350 may be an annular seal pressed between insulator 310 and the distal end of flange connector 306 and the proximal inner surface of screw mount 114. The gasket 350 bridges the gap between the insulating spiral mount 114 and the insulator 310, so that blood entering the insulator cavity 314 to promote the release of the therapeutic agent will not come into contact with the flange 112.

[0045] In one embodiment, the MCRD 330 is partially held by the electrode 104. For example, the external dimensions of the electrode tip 324 may be larger than the dimensions of the central lumen 336 of the MCRD 330. Therefore, the MCRD 330 can be prevented from slipping from the electrode 104 into the surrounding environment 117. Furthermore, the internal dimensions of the screw mount channel 342 may be smaller than the dimensions of the central lumen 336 of the MCRD 330. Therefore, the MCRD 330 can be prevented from sliding out of the insulator cavity 314 by the screw mount 114.

[0046] Instead of or supplementing the aforementioned retaining features, the MCRD 330 can be partially retained against one or more of the insulator 310 or the electrode 104 via a press fit. More specifically, the outer surface of the MCRD 330 can press against the inner insulating surface 316 of the insulator 310, and / or the inner surface of the MCRD 330 can press against the outer electrode surface 317. Therefore, friction caused by the press fit between the MCRD 330 and one or more of the insulator 310 or the electrode 104 can retain the MCRD 330 within the insulating cavity 314. In one embodiment, at least one of the side surfaces of the MCRD 330 has a gap with the opposing surface of the insulator 310 or the electrode 104. For example, when the MCRD 330 is press-fitted against the insulator 310, the MCRD 330 can have a gap fit with the electrode 104. Figure 3 This gap maximizes the surface area of ​​the MCRD exposed to blood after implantation, thereby facilitating the elution of therapeutic agents into space 332.

[0047] Optionally, the MCRD 330 may include a delayed-release coating. The delayed-release coating may be applied to the outer surface of the MCRD 330, for example, by spraying or dipping. The delayed-release coating may be an absorbable coating, such as a hydrophilic coating, which is absorbed within minutes to an hour upon contact with blood. Thus, when the biostimulator 100 is implanted, the outer surface may come into contact with blood, and the release of the therapeutic agent may be delayed as the coating dissolves. After the coating dissolves, the therapeutic agent can be eluted from the MCRD 330 and flow along the elution path through space 332 and spiral mounting channel 342 to the surrounding environment 117.

[0048] refer to Figure 4 According to one embodiment, a cross-sectional view of a head assembly having an MCRD within an insulating cavity of a ceramic spiral mount is shown. The head assembly 110 may include a spiral mount 114, which incorporates the above-referenced... Figure 3The insulator 310 and the screw mount 114 are described. More specifically, in one embodiment, the insulator 310 and the screw mount 114 are integrally formed of ceramic. The all-ceramic screw mount 114 can be connected to the flange 112 by attaching a flange connector 306 to the threaded or threadless connector of the screw mount 114. For example, the screw mount 114 can be screwed onto the flange connector 306 to secure the flange 112 to the screw mount 114. Similarly, a fixing element can be screwed onto the mounting flange 340.

[0049] In one embodiment, the spiral mount 114 may have a hole extending from the proximal end of the spiral mount 114 to the distal end of the spiral mount 114. As described above, the electrode 104 may be inserted into the hole and secured by a connector 326. More specifically, the connector 326 may be a brazed joint that secures and seals the electrode 104 to the spiral mount 114. Thus, the head assembly 110 may include a flange 112, a spiral mount 114 (which incorporates an insulator 310), and an electrode 104, which are securely fastened to each other and hermetically sealed to prevent blood from entering the electronics compartment 118 from the surrounding environment 117.

[0050] An insulating cavity 314 may be formed directly within the screw mount 114. More specifically, a countersunk hole may be formed at the distal end of the all-ceramic screw mount 114, such that the countersunk hole includes an inner insulator surface 316. When the electrode 104 is fixed relative to the screw mount 114, the inner insulator surface 316 faces the outer electrode surface 317, providing a space 332 between the insulator 310 and the electrode 104. The MCRD 330 may be loaded into the space 332, and thus, when the biostimulator 100 is implanted into the bloodstream, therapeutic agents can be eluted into the space 332.

[0051] Electrode 104 may include a through-post configuration. The through-post configuration includes an electrode end 324 having a through-hole for receiving an electrode pin 320. More specifically, when the electrode pin 320 is inserted into the through-hole of the electrode end 324, the distal end 322 of the electrode pin 320 may be exposed to the surrounding environment 117.

[0052] In one embodiment, the electrode pin 320 includes a stop 402 providing a positional reference for the electrode tip 324. The stop 402 may include a protrusion or shoulder extending radially from the longitudinal pin of the electrode 104. The external dimensions of the stop 402 may be larger than the internal dimensions of the electrode tip through-hole, so that when the electrode tip 324 is inserted onto the distal end 322 of the electrode pin 320, the electrode tip 324 can rest on the stop 402. The electrode tip 324 may then be welded or otherwise attached to the electrode pin 320 to form the electrode 104.

[0053] As described above, the MCRD 330 may be located within the insulating cavity 314 between the electrode 104 and the insulator 310. For example, the internal dimensions of the MCRD 330 extending around the central lumen 336 may be smaller than the external dimensions of the electrode tip 324. Therefore, the electrode tip 324 can hold the MCRD 330 within the space 332 of the insulating cavity 314. Also as described above, when the biostimulator 100 is implanted in the bloodstream, the MCRD 330 can elute the therapeutic agent into the surrounding environment 117 through the space 332 and the annular gap 202.

[0054] As described above, combining the insulator 310 and the screw mount 114 within the all-ceramic screw mount 114 reduces the overall height of the head assembly 110. As shown, by utilizing the all-ceramic screw mount 114, the height of the flange connector 306 and the height of the screw mount 114 can be reduced, thus shortening the head assembly 110. Advantageously, by shortening the head assembly 110, the device length can be converted into a length dedicated to extending the energy source. Therefore, compared to a biostimulator 100 with non-integrated screw mount 114 and insulator 310 components, the energy capacity and operational life can be extended.

[0055] refer to Figure 5 According to one embodiment, a perspective view of a head assembly with controlled therapeutic agent release is shown. As described above, the head assembly 110 may include an all-ceramic spiral mount 114. In one embodiment, the electrode 104 of the head assembly 110 includes an electrode spiral 502. The electrode spiral 502 may provide a distal portion of the electrode 104. More specifically, the electrode spiral 502 may be part of the electrode 104 that engages tissue during implantation. For example, the electrode spiral 502 may be coaxial with a spiral fixation element 116, and both the spiral fixation element 116 and the electrode spiral 502 may be screwed into the target tissue during implantation.

[0056] Similar to electrode tip 324 described above, electrode helix 502 provides controlled impedance for reliable pacing. With electrode helix 502, electrode 104 can safely and predictably engage with the target tissue because the electrode is anchored within the tissue. Anchored electrodes can provide consistent tissue contact under varying conditions, thus providing more predictable impedance between the electrode and the tissue. Therefore, helical electrodes can provide more consistent impedance and pacing.

[0057] refer to Figure 6 According to one embodiment, a cross-sectional view of a head assembly having an MCRD within an electrode spiral is shown. Figure 6 Several features of the illustrated embodiment are similar to those described above. Figure 3 and Figure 4 The characteristics described are therefore omitted for the sake of brevity.

[0058] Electrode pin 320 may extend longitudinally through insulator cavity 314. In one embodiment, electrode spiral 502 is mounted on electrode pin 320. For example, electrode spiral 502 may slide over and be mounted on distal end 322 of electrode pin 320. Electrode pin 320 may include stop 402, so electrode spiral 502 may rest on stop 402. Therefore, electrode spiral 502 may be welded to electrode pin 320 in a consistent manner. More specifically, stop 402 may provide a position reference to ensure proper positioning of electrode spiral 502 relative to a fixing element. Thus, electrode pin 320 and electrode spiral 502 may be combined to form electrode 104, which transmits electrical signals between electronic device compartment 118 and target tissue into which electrode spiral 502 is screwed.

[0059] In one embodiment, the MCRD 330 is cylindrical. More specifically, the MCRD 330 can be a cylindrical plug without a central channel and can be inserted into the internal cavity of the electrode spiral 502. Alternatively, the MCRD 330 can have the aforementioned annular or ring-shaped structure and can be loaded into the electrode spiral 502. The plug can be press-fitted into the electrode spiral 502. Therefore, the press-fit between the electrode spiral 502 and the MCRD 330 can retain the MCRD and prevent the MCRD from being dislodged from the insulating cavity 314.

[0060] It should be understood that although MCRD 330 is located radially inside electrode spiral 502 (rather than...) Figure 3-4 (Radially outward from the electrode pin 320 shown), the MCRD 330 can still elute the therapeutic agent along the elution path through the space 332 between the insulator 310 and the electrode 104. More specifically, when blood enters the insulator cavity 314, the therapeutic agent can dissolve and flow radially outward from the inner lumen of the spiral through the spiral coil into the space 332 between the outer electrode surface 317 of the spiral coil and the inner insulator surface 316 of the spiral mount 114. From the space 332, the therapeutic agent can travel outwardly and distally from the insulator cavity 314 into the surrounding environment 117 through the annular gap 202. Advantageously, elution through the space 332 allows for the controlled release of the therapeutic agent through the annular gap 202, which is larger and less prone to clogging than, for example, a single orifice in an electrode cup.

[0061] refer to Figure 7This diagram shows a flowchart of a method for manufacturing a leadless biostimulator according to one embodiment. As a preliminary operation, an insulator 310 may be loaded into a flange channel 308 such that the insulator cavity 314 and the flange channel 308 are concentric. The insulator 310 may have a thin metallic coating deposited on its outer surface to allow for brazing processes thereon, as described below. An electrode 104 may be loaded into the concentrically arranged flange channel 308 and insulator cavity 314. More specifically, an electrode pin 320 may be inserted into a hole in the insulator base 318 such that the electrode 104 extends longitudinally through the insulator cavity 314. The electrode pin 320 may be cut to a certain length (before or after loading the electrode into the assembly) such that the electrode pin 320 extends to predetermined lengths both away from and near the insulator base 318. The distal portion of the electrode pin 320 may have a length that aligns the distal end 322 of the pin with the threaded mounting channel 342. The proximal region of the electrode pin 320 may have a length extending to the proximal end of the pin, which will engage the electronic device assembly 120 in the electronic device compartment 318.

[0062] In operation 702, flange 112, insulator 310, and electrode 104 are connected together. The concentrically arranged components can be secured via joint 326. In one embodiment, during brazing, gold flows into the joint between the components. The molten gold can be cooled to braze the components together, thereby providing an hermetically sealed seal through which electrode 104 can transmit electrical signals.

[0063] In operation 704, the MCRD 330 is mounted within the insulating cavity 314. In one embodiment, the MCRD 330 may be mounted on the electrode 104, for example, by inserting the electrode pin 320 through the central channel of the annular MCRD 330. Alternatively, the MCRD 330 may be mounted within the electrode 104, for example, by sliding the MCRD 330 into the inner cavity of the electrode spiral 502.

[0064] After the MCRD 330 is inserted into the insulator cavity 314, the MCRD 330 can be held in place to a certain extent. For example, the MCRD 330 can be press-fitted with one or more of the insulator wall 312, electrode pin 320, or electrode spiral 502, depending on the head assembly configuration being manufactured. The MCRD 330 can be further held in place during operation 706. More specifically, the electrode tip 324 or electrode spiral 502 can be mounted on the distal end 322 of the electrode pin 320 to hold the MCRD 330 within the insulator cavity 314. In the case of the electrode tip 324, the electrode 104 may include a cap having an external dimension larger than the central lumen 336 of the MCRD 330, thus preventing the MCRD 330 from moving from the distal side of the electrode pin 320. In the case of the electrode spiral 502, the MCRD 330 can be press-fitted into the interior of the spiral. Electrode spiral 502 can be connected (e.g., welded) to the distal end 322 of electrode pin 320, thus preventing movement of MCRD 330 relative to the distal side of electrode pin 320. In either case, the electrode features can hold MCRD 330 within insulating cavity 314 and provide electrical conduction of pacing signals to target tissue.

[0065] The operations of this method can be performed in an alternative order. For example, for Figure 6 In the head assembly structure shown, the operation of mounting (and optionally welding) the electrode spiral 502 onto the electrode pin 320 during operation 706 can precede the operation of inserting the MCRD 330 into the electrode spiral 502 (and the insulating cavity 314) during operation 704. Therefore, it is understood that these operations can be rearranged, omitted, or modified as needed to manufacture the head assembly structure described above.

[0066] In operation 708, the screw mount 114 is mounted on the flange 112. The screw mount 114 can be fastened to the flange connector 306, for example, through mating threads of the engaging parts. Alternatively, other fasteners can secure the screw mount 114 to the flange 112. When the screw mount 114 is attached to the flange 112, the screw mount channel 342 can be positioned to receive the electrode 104, such as the electrode tip 324, such that the gap 202 provides an elution path between the insulating cavity 314 within the head assembly 110 and the surrounding environment 117. The gap 202 can be dimensioned to allow for good fluid exchange between the interior and exterior of the head assembly 110.

[0067] In operation 710, the helical retaining element 116 is mounted on the helical mounting member 114. The helical retaining element 116 can be screwed onto the mounting member flange 340. Alternatively, the retaining element can be adhered to the mounting member flange 340 by thermal welding or adhesive welding. Thus, when the retaining element is screwed into the target tissue during device implantation, the retaining element can be secured to the helical mounting member 114 to keep the head assembly 110 against the target tissue.

[0068] In the foregoing specification, the invention has been described with reference to specific exemplary embodiments thereof. It will be apparent that various modifications may be made thereto without departing from the broader spirit and scope of the invention as set forth in the following claims. Therefore, the specification and drawings should be considered illustrative rather than restrictive.

Claims

1. A head assembly for a leadless biostimulator, comprising: Flange, including flange passages extending along the longitudinal axis; An insulator, located in the flange passage and including an insulator cavity; Electrodes, extending longitudinally through the insulator cavity; and A monolithic controlled release device is located within the insulator cavity, wherein the monolithic controlled release device is radially positioned within the space between the insulator and the electrode in the flange channel to elute therapeutic agents into the space upon implantation of the leadless biostimulator.

2. The head assembly according to claim 1, wherein, The space is located within the insulator cavity between the inner insulator surface of the insulator and the outer electrode surface of the electrode.

3. The head assembly according to claim 1, wherein, The monolithic controlled release device has an annular body including a central lumen, wherein the electrode extends longitudinally through the central lumen.

4. The head assembly according to claim 1, wherein, The electrode includes an electrode pin extending longitudinally through the insulating cavity and an electrode end mounted at the distal end of the electrode pin.

5. The head assembly according to claim 1, wherein, The electrode includes an electrode pin extending longitudinally through the insulator cavity and an electrode spiral mounted at the distal end of the electrode pin.

6. The head assembly according to claim 1, further comprising: A helical mount mounted on the flange, wherein the helical mount includes a helical mount channel in fluid communication with the space, such that when the leadless biostimulator is implanted, the therapeutic agent is eluted into the surrounding environment through the space and the helical mount channel; and A spiral fixing element installed on the spiral mounting component.

7. The head assembly according to claim 6, wherein, The spiral mounting channel includes an annular gap between the spiral mounting and the electrode.

8. The head assembly according to claim 6, wherein, The insulator and the spiral mounting are integrally formed of ceramic.

9. The head assembly according to claim 1, wherein, The single-piece controlled release device is press-fitted against one or more of the insulator or the electrodes.

10. A leadless biostimulator, comprising: The housing has electronic component compartments containing electronic component assemblies; A flange, mounted on the housing and including a flange passage extending along a longitudinal axis; An insulator, located in the flange passage and including an insulator cavity; Electrodes, extending longitudinally through the insulator cavity; and A single-piece controlled release device is located in the cavity of the insulator, wherein the single-piece controlled release device is radially located in the space between the insulator and the electrode in the flange channel to elute a therapeutic agent into the space during implantation of the leadless biostimulator.

11. The leadless biostimulator according to claim 10, wherein, The space is located within the insulator cavity between the inner insulator surface of the insulator and the outer electrode surface of the electrode.

12. The leadless biostimulator according to claim 10, wherein, The monolithic controlled release device has an annular body including a central lumen, wherein the electrode extends longitudinally through the central lumen.

13. The leadless biostimulator according to claim 10, wherein, The electrode includes an electrode pin extending longitudinally through the insulating cavity and an electrode end mounted at the distal end of the electrode pin.

14. The leadless biostimulator according to claim 10, wherein, The electrode includes an electrode pin extending longitudinally through the insulator cavity and an electrode spiral mounted at the distal end of the electrode pin.

15. The leadless biostimulator according to claim 10, further comprising: A helical mount mounted on the flange, wherein the helical mount includes a helical mount channel in fluid communication with the space, such that when the leadless biostimulator is implanted, the therapeutic agent is eluted into the surrounding environment through the space and the helical mount channel; and A spiral fixing element installed on the spiral mounting component.

16. The leadless biostimulator according to claim 15, wherein, The spiral mounting channel includes an annular gap between the spiral mounting and the electrode.

17. A method for manufacturing a leadless biostimulator, comprising: A flange, an insulator, and an electrode are connected such that the insulator and the electrode in the flange channel of the flange extend along a longitudinal axis through the flange channel of the flange and the insulator cavity of the insulator; and A monolithic controlled release device is installed within the insulator cavity, wherein the monolithic controlled release device is radially located within the space between the insulator and the electrode in the flange channel to elute therapeutic agents into the space during implantation of the leadless biostimulator.

18. The method according to claim 17, wherein, The monolithic controlled release device has an annular body including a central lumen, wherein the electrode extends longitudinally through the central lumen.

19. The method of claim 17, further comprising mounting an electrode tip or electrode spiral to the distal end of an electrode pin of the electrode.

20. The method of claim 17, further comprising: A helical mount is installed on the flange, wherein the helical mount includes a helical mount channel in fluid communication with the space, such that when the leadless biostimulator is implanted, the therapeutic agent is eluted into the surrounding environment through the space and the helical mount channel; and A spiral fixing element is installed on the spiral mounting component.

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