Intrauterine Device (IUD) Systems

Abstract

An intrauterine device (IUD) system is disclosed. The IUD system includes multiple elements, each element having a length of 10 mm or less. Each element includes a magnetic core and an exterior coating on the magnetic core, the magnetic core being sized to assemble the multiple elements into a structure that withstands expulsion from a subject's uterus. A method of providing controlled contraception or treating or preventing a uterine disease, disorder, or condition in a subject is also disclosed. The method includes delivering the multiple elements to a uterus of a subject. A method of facilitating controlled contraception or treating or preventing a uterine disease, disorder, or condition in a subject is also disclosed. The method includes providing the multiple elements. A kit including the multiple elements and a delivery device is also disclosed.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 63 / 436,341, entitled "INTRAUTERINE DEVICE (IUD) SYSTEM," having a filing date of December 30, 2022, and U.S. Provisional Patent Application No. 63 / 541,557, entitled "INTRAUTERINE DEVICE (IUD) SYSTEM," having a filing date of September 29, 2023, each of which is incorporated herein by reference in its entirety for all purposes.

[0002] Aspects and embodiments disclosed herein are directed to intrauterine device (IUD) systems and methods that provide contraception and / or treatment or prevention of uterine diseases, disorders, or conditions. In particular, aspects and embodiments disclosed herein are directed to IUD systems having multiple magnetic IUD elements. Summary of the Invention

[0003] According to one aspect, an intrauterine device (IUD) system is provided. The IUD system can include multiple elements. Each element can have a length of 10 mm or less. Each element can include a magnetic core and a coating exterior to the magnetic core. The magnetic core can be sized to assemble the multiple elements into a structure that will withstand expulsion from a subject's uterus.

[0004] In some embodiments, the IUD system includes at least three elements.

[0005] In some embodiments, the IUD system includes three elements, each of which can have a magnetic core sized to assemble the elements into a triad structure.

[0006] In some embodiments, each element comprises a shell external to the magnetic core.

[0007] In some embodiments, the IUD system includes three elements, each having a shell sized to assemble the elements into a triad structure.

[0008] In some embodiments, the shell has an average thickness of between 0.10 mm and 1.50 mm.

[0009] In some embodiments, the coating is a contraceptive coating, and the contraceptive coating is embedded in the shell.

[0010] In some embodiments, the magnetic core is an axially magnetic core.

[0011] In some embodiments, the magnetic core is sized to disassemble the multiple elements into an axial or generally aligned configuration that allows for retrieval from the uterus of a subject by a magnetic retrieval device.

[0012] In some embodiments, each element consists of a magnetic core and a coating.

[0013] In some embodiments, each element has a round cross-sectional area with a diameter between 2.0 mm and 6.0 mm.

[0014] In some embodiments, each element is sized to pass through the subject's cervix.

[0015] In some embodiments, each element is sized to fit within a catheter with an OD of 4.0 mm to 5.0 mm.

[0016] In some embodiments, each element has a length between 2.0 mm and 10 mm.

[0017] In some embodiments, the magnetic core has rounded or beveled edges.

[0018] In some embodiments, the coating is a contraceptive coating, and the contraceptive comprises a cytotoxic drug.

[0019] In some embodiments, the cytotoxic drug coating comprises copper.

[0020] In some embodiments, the contraceptive coating is 175 mm 2 ~380mm 2 has a copper surface area of ​​.

[0021] In some embodiments, the coating is a contraceptive coating, and the contraceptive comprises a hormone.

[0022] In some embodiments, the coating is substantially free of hormonal agents.

[0023] In some embodiments, the coating is substantially free of nickel and / or nitinol.

[0024] In some embodiments, the magnetic core includes a south pole and a north pole opposite the south pole.

[0025] In some embodiments, the magnetic core forms at least 50% of the volume of each element.

[0026] In some embodiments, each of the plurality of elements is structurally independent from each other.

[0027] According to another aspect, there is provided a method of providing controlled contraception or treating or preventing a uterine disease, disorder, or condition in a subject. The method can include delivering a plurality of elements to a uterus of the subject, each element having a length of 10 mm or less and comprising a magnetic core and a coating exterior to the magnetic core, the magnetic core sized to assemble the plurality of elements into a structure that withstands expulsion from the uterus of the subject.

[0028] In some embodiments, the method can include delivering each element individually.

[0029] In some embodiments, the method can include delivering each element sequentially and / or simultaneously.

[0030] According to another aspect, a kit is provided that includes an intrauterine device (IUD) system including multiple elements, each element having a length of 10 mm or less and comprising a magnetic core and a coating exterior to the magnetic core; a delivery device dimensioned to enable placement of the multiple elements within a uterus of a subject; and instructions for delivering the multiple elements to the uterus of the subject using the delivery device.

[0031] In some embodiments, the kit may further comprise a retrieval device dimensioned to allow for the retrieval of multiple elements from the uterus of a subject.

[0032] According to another aspect, a method for facilitating controlled contraception or treating or preventing a uterine disease, disorder, or condition in a subject is provided. The method can include providing a plurality of elements, each element having a length of 10 mm or less and comprising a magnetic core and a coating exterior to the magnetic core, the magnetic core being sized to assemble the plurality of elements into a structure that withstands expulsion from the subject's uterus. The method can include providing instructions for delivering the plurality of elements to the subject's uterus.

[0033] The present disclosure contemplates all combinations of any one or more of the above aspects and / or embodiments, as well as combinations with any one or more of the embodiments described in the detailed description and examples.

[0034] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the USPTO upon request and payment of the necessary fee.

[0035] The accompanying drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component shown in various figures is represented by a like numeral. For purposes of clarity, not every component is labeled in every figure. [Brief explanation of the drawings]

[0036] [Figure 1A] FIG. 1 is a schematic diagram of a uterine implant element according to one embodiment. [Figure 1B] FIG. 1 is a schematic diagram of three uterine implant elements arranged in a triad configuration, including cross-sectional and partial cross-sectional views of the uterine implant elements, according to one embodiment. [Figure 1C] FIG. 1C is a cross-sectional view of three uterine implant elements arranged in a triad configuration, illustrating the relationship of shell thicknesses, according to one embodiment. [Figure 1D] FIG. 10 is a cross-sectional view of a uterine implant element showing angled features, according to one embodiment. [Figure 1E] FIG. 1C is a cross-sectional view of three uterine implant elements arranged in a triad configuration, showing an angled coupling relationship, according to one embodiment. [Figure 2A] 1A-1C are cross-sectional views of various uterine implant elements, according to certain embodiments. [Figure 2B] 1A-1C are cross-sectional views of various uterine implant elements, according to certain embodiments. [Figure 2C] 1A-1C are cross-sectional views of various uterine implant elements, according to certain embodiments. [Figure 3A] FIG. 10 is a schematic diagram illustrating the magnetic forces of three uterine implant elements arranged in a triad configuration, each element including a cylindrical magnetic core, according to one embodiment. [Figure 3B] FIG. 10 is a schematic diagram illustrating the magnetic forces of three uterine implant elements arranged in a triad configuration, each element including a cylindrical magnetic core with beveled edges, according to one embodiment. [Figure 3C] FIG. 1 is a schematic diagram illustrating the overall profile of three uterine implant elements arranged in a triad configuration, according to one embodiment. [Figure 3D]FIG. 3D is a schematic diagram illustrating the overall profile of three uterine implant elements arranged in a triad configuration, having a smaller overall profile than the uterine implant element of FIG. 3C, according to one embodiment. [Figure 4] FIG. 1 is a cross-sectional view of a uterine implant element according to one embodiment. [Figure 5] 1 is a table comparing magnetic forces for several magnetic core geometries and assembly configurations, according to certain embodiments. [Figure 6] FIG. 1 is a schematic diagram of a uterine implant element according to one embodiment. [Figure 7] FIG. 1 is a cross-sectional view of a uterine implant element according to one embodiment. [Figure 8] FIG. 10 is a cross-sectional view of a uterine implant element illustrating the magnetic flux pattern of axial charging, according to one embodiment. [Figure 9] 1 is a schematic diagram of an IUD system according to one embodiment. [Figure 10] FIG. 1 is a partial cross-sectional view of an IUD system showing magnetic flux patterns, according to one embodiment. [Figure 11] FIG. 1 is a schematic diagram of a uterine implant element according to one embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0037] Contraception can be provided by a variety of methods. One of the safest and most effective methods is the placement of an intrauterine device (IUD) in a subject's uterus to prevent pregnancy as a result of sexual intercourse. IUDs generally provide contraception for the duration that they remain in the uterus. This contraceptive effect can be easily reversed by removing the IUD from the uterus.

[0038] Currently available IUDs are devices housed in a plastic, T-shaped frame that release spermicide or hormones to provide contraception. While these conventional IUDs can be highly effective, the T-shaped frame design causes significant pain during insertion, uterine perforation, and uterine expulsion, and the external retrieval strings can cause vaginitis. Therefore, there is a need for improved IUDs that provide easier and less painful insertion.

[0039] Embodiments described herein provide intrauterine device (IUD) systems, e.g., frameless IUD systems, that include one or more uterine implantation elements, that provide high efficacy, are easily implantable, easily retrievable, exhibit high retention rates, and do not affect future fertility. In certain embodiments, the IUD systems do not include external retrieval cords.

[0040] Selected Definitions As used herein, "contraceptive" refers to a drug, compound, or biological agent that has a contraceptive effect on a subject. The contraceptive can be the active agent of the composition. In some embodiments, the contraceptive can be a hormonal agent. In some embodiments, the contraceptive can be a cytotoxic agent, which may be referred to as a "spermicide." As used herein, contraceptives may also be referred to as "contraceptive agents."

[0041] As used herein, "hormonal agent" refers to a contraceptive agent that includes a hormone or signaling molecule. The hormonal agent can be a naturally occurring hormone, such as progesterone. The hormonal agent can be a synthetic hormone, such as a progestogen, such as a progestin.

[0042] As used herein, a "cytotoxic" drug refers to a non-hormonal contraceptive that targets sperm cells and / or egg cells. Cytotoxic drugs are also sometimes referred to as spermicides or spermicides. In certain exemplary embodiments, the cytotoxic drug can be copper.

[0043] As used herein, "contraception" means preventing pregnancy as a result of sexual intercourse. Contraception can include barrier methods, inhibiting ovulation in a woman, inactivating or killing sperm, reducing or inhibiting sperm motility, altering cervical mucus, and / or inhibiting implantation of a fertilized egg in the uterus.

[0044] As used herein, "inert" means not toxic or harmful to surrounding tissue. Inert materials can be biocompatible.

[0045] As used herein, a "subject" can include animals, mammals, humans, and non-human animals. The term "subject" is intended to include humans and non-human animals, such as mammals, large animals, livestock animals, companion animals, and primates. In certain embodiments, the subject is a mammalian subject, and in certain embodiments, the subject is a human subject. While human applications are clearly anticipated, veterinary applications, such as for non-human animals, are also contemplated herein. The term "non-human animal" in the present disclosure includes all mammals, such as non-human primates, livestock, laboratory / research, and agriculturally useful animals, such as horses, sheep, goats, dogs, cats, cats, cows, pigs, rodents, wild carnivores, such as wolves, bears, cheetahs, tigers, leopards, and lions, ungulates, such as wild hogs and boars, or ruminants / pseudoruminants, such as camels, deer, antelopes, and buffalo, or large mammals, such as elephants. The subject can be biologically capable of producing offspring. The subject can have a uterus or uterine cavity. The subject can be female. The subject can be of childbearing age.

[0046] As used herein, "retention rate" refers to the percentage of IUD systems that remain in a subject's uterus after a selected period of time has elapsed from the date of insertion, excluding voluntary removal, which can be 24 hours, 48 ​​hours, 72 hours, 7 days, 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months, 48 ​​months, 60 months, 72 months, 84 months, 96 months, 108 months, 120 months, 132 months, 144 months, or more.

[0047] As used herein, treating a disease or disorder refers to reducing the severity or frequency of at least one symptom of the disease or disorder compared to a similar but untreated patient. Treatment can also refer to halting, slowing, or preventing the progression of the disease or disorder compared to a similar but untreated patient. Treatment can include addressing the underlying cause of the disease and / or one or more symptoms.

[0048] Intrauterine Device (IUD) Systems The present disclosure provides an intrauterine device (IUD) system. The system can have one or more uterine implantation components, also referred to herein as intrauterine device components, "IUD components," or "components." The components can be devices inserted into a subject's uterus to provide contraception, inhibit, limit, or reduce menstrual side effects such as discomfort, pain, excessive bleeding, cramps, or inflammation, and / or treat or prevent uterine diseases, disorders, and symptoms such as abnormal uterine bleeding, irregular menstrual cycles, irregular vaginal discharge, endometriosis, adenomyosis, uterine fibroids, uterine polyps or cysts, polycystic ovary syndrome (PCOS), pelvic inflammatory disease, endometrial hyperplasia, uterine cancer, urinary problems, genital tuberculosis, uterine prolapse, bacterial, parasitic, or viral sexually transmitted infections, discomfort, pain, cramps, or inflammation.

[0049] Exemplary elements are shown in Figures 1A-1B. Figure 1A shows a lateral side view of one uterine implant element 10. Figure 1B shows a lateral side view of several uterine implant elements 10 assembled into a single structure, with one element shown in cross section and another shown in partial cross section. These elements can include a magnetic core 11. The magnetic core can be axially magnetic, with opposing north (N) and south (S) poles at each end.

[0050] Element 10 can include one or more layers on the exterior of magnetic core 11. Element 10 can include a shell 12 on the exterior of magnetic core 11. In other embodiments, element 10 can be substantially free of a shell 12. In one particular embodiment, element 10 can include a coating on the exterior of shell 12. In other embodiments, element 10 can be substantially free of a coating on the exterior of shell 12. One or more layers of element 10 can be selected based on function or manufacturing.

[0051] The contraceptive or therapeutic effect of these elements can be provided by implantation of the elements into the uterus. The contraceptive or therapeutic effect can be provided by the geometry and physical characteristics of these elements and / or the arrangement or configuration of the elements when placed in the uterus of a subject. In certain embodiments, the elements can be sized to provide contraception. For example, in certain veterinary applications, such as in mares, contraception can be provided by the suppression of estrus provided by the presence and / or geometry of the elements. In certain embodiments, the elements can be sized to provide treatment or prevention of a uterine disease, disorder, or condition. A therapeutic effect can also be provided in addition to, or instead of, a contraceptive effect.

[0052] In some embodiments, the contraceptive effect of the element can be provided by a contraceptive. In one particular embodiment, the contraceptive can be provided in a coating on the exterior of magnetic core 11. In certain embodiments, shell 12 can be formed from or can include a contraceptive. For example, the contraceptive can be homogeneously or heterogeneously embedded in shell 12. In other embodiments, the contraceptive coating can be disposed on the exterior of shell 12. Thus, the contraceptive coating can form the outermost layer of element 10, such as a wrapper, wire, sheath, or other structure on the exterior surface of element 10.

[0053] A coating, e.g., a contraceptive coating or other coating, need not cover the entire surface of element 10; for example, the coating can cover at least 25%, 25% to 50%, 50% to 75%, or 75% to 100% of the exterior surface of element 10. In yet other embodiments, the contraceptive coating can form an interior layer of element 10 (e.g., between core 11 and shell 12 layers) and can be released through shell 12. Exemplary contraceptives include hormonal agents and cytotoxic agents.

[0054] The elements can be sized to be ergonomic (conforming to uterine tissue, optionally maximizing effectiveness, efficiency, safety, and comfort when inserted into a subject's uterus). In some embodiments, the elements can be ergonomic by adapting to the shape and environment of the uterus. The core and / or shell of the elements can be ergonomically sized to provide desired characteristics of the element. The elements, e.g., core and / or shell, can have smooth edges, oval edges, or rounded edges. The elements, e.g., core and / or shell, can be sized to prevent, limit, or reduce distortion or perforation of the endometrium. The elements, e.g., core and / or shell, can be sized to reduce the likelihood of insertion-related side effects, such as discomfort, pain, bleeding (e.g., excessive bleeding), abdominal pain, or irritation. In some embodiments, the elements are ovoid (e.g., having a rounded, slightly elongated outline or shape like an egg, an oval, or an elliptical configuration).

[0055] Each element 10 can have a length of about 1 mm to about 100 mm, e.g., about 1 mm to 50 mm, 1 mm to 30 mm, 1 mm to 20 mm, 1 mm to 10 mm, or 5 mm to 10 mm. In exemplary embodiments, for example, for use in humans, the elements can have a length of less than 10 mm.

[0056] Each element 10 can have a width of about 1 mm to about 30 mm, e.g., about 1 mm to 15 mm, 1 mm to 10 mm, or 2 mm to 6 mm. In exemplary embodiments, for example, when used in a human, the elements can have a width that allows them to pass through a human cervix for placement within the uterine cavity. Exemplary elements can have a width of 3 mm to 4.5 mm. In some embodiments, the elements can have a width that allows them to pass through a catheter for implantation into the uterine cavity. Exemplary elements can have a width of less than 4.5 mm, e.g., 3 mm to 4.4 mm, 3 mm to 4.2 mm, or 3 mm to 4.0 mm.

[0057] Each element can have a mass of 0.1 g to 100 g, e.g., 0.1 g to 1.0 g, 0.1 g to 0.5 g, 0.4 g to 0.6 g, 0.6 g to 0.8 g, 0.5 g to 1.0 g, 0.5 g to 50 g, 0.5 g to 10 g, 0.5 g to 5 g, or 1 g to 2 g. In exemplary embodiments, each element can have a mass of about 0.5 g, 0.4 g to 0.6 g, or 0.6 g to 0.8 g. Combined, the three elements can have a mass of about 1.2 g, 1.5 g, 1.8 g, 2.1 g, or 2.4 g. In particular, exemplary elements with polymeric shells can have a mass of about 0.1 g to 0.3 g. Combined, the three elements with polymeric shells can have a mass of about 0.6 g to 0.8 g.

[0058] These elements can be sized to fit within a target subject, for example, to pass through the target subject's cervix and into the target subject's uterine cavity. As disclosed herein, the uterine cavity can refer to the space inside the uterus, located within the opposing anterior and posterior moist, mucous endometrium and uterine muscle. In certain embodiments, the elements 10 can be sized to fit within a primate. For primates (e.g., humans), the length of the elements can be from about 1 mm to about 10 mm, e.g., from about 7 mm to about 8.5 mm, and the width (or diameter) can be from about 2 mm to about 6 mm, e.g., from about 3 mm to about 3.5 mm, from about 3.5 mm to about 4 mm, or from about 4 mm to about 5 mm.

[0059] The magnetic core 11 of element 10 can be formed from or can include a magnetic material. Exemplary magnetic materials include iron (or ores, alloys, or other materials) whose constituent atoms are arranged such that the material exhibits magnetic properties, such as attracting other iron-containing objects or self-aligning in an external magnetic field. For example, core 11 can be formed from or can include a magnetized material (called ferromagnetic or ferrimagnetic). Exemplary magnetic materials include iron, nickel, cobalt, or alloys thereof. The core can include alloys of rare earth metals (e.g., neodymium, which has a strong magnetic force) and naturally occurring minerals such as lodestone. In some embodiments, these elements may be substantially free of nickel.

[0060] The element 10 can include an optional shell 12 on the exterior of the magnetic core 11. The shell 12 can be formed from an inert material. The shell 12 can protect the magnetic core 11 from structural damage such as spalling, cracking, chipping, corrosion, or any other structural damage. For example, neodymium cores can tend to be hard and brittle. Multiple neodymium cores can shatter if impacted together. The shell can protect the neodymium cores to prevent spalling.

[0061] The shell 12 can have an average thickness of 0.1 mm to 1.5 mm, e.g., 0.1 mm to 0.15 mm, 0.15 mm to 0.25 mm, 0.25 mm to 0.5 mm, 0.1 mm to 0.5 mm, or 0.5 mm to 1.5 mm. In certain exemplary embodiments, the shell has an average thickness of at least 0.13 mm, e.g., 0.1 mm to 0.5 mm, e.g., about 0.25 mm.

[0062] Shell thickness can vary based on the geometry of the core or element. In some embodiments, shell 12 can have a variable thickness. For example, shell 12 can have a body thickness, an edge thickness, and / or an end thickness, each of which can be independently selected. The body portion of the shell can refer to the shell covering the lateral surface of the magnetic core, or side 12a shown in FIG. 1A. The edge portion of the shell can refer to the shell covering the edge of the magnetic core, or side 12b shown in FIG. 1A. The end surface of the shell can refer to the shell covering the end of the magnetic core, or side 12c shown in FIG. 1A. The thickness of shell 12 can be defined as the dimension of the outer surface of sides 12a, 12b, and 12c shown in FIG. 1A relative to the associated core surface of sides 11a, 11b, and 11c, respectively, shown in FIG. 1B.

[0063] The shell thickness can be selected to allow multiple elements to magnetically assemble into a selected configuration, for example, by introducing space between the magnetic core and the ends, edges, and periphery of the elements. In some embodiments, the thickness of the edge side 12b can be less than the thickness of the body side 12a. The ratio of the thickness of the shell edge side 12b to the thickness of the body side 12a can be 1:1 to 1:5, for example, 1:1 to 1:2, 1:2 to 1:3, 1:3 to 1:4, or 1:4 to 1:5. In some embodiments, the thickness of the end face 12c can be greater than the thickness of the body side 12a. The ratio of the thickness of the shell end face 12c to the thickness of the body side 12a can be 10:1 to 1:1, for example, 10:1 to 8:1, 8:1 to 6:1, 6:1 to 4:1, 4:1 to 2:1, or 2:1 to 1:1. In some embodiments, the thickness of the edge side 12b can be selected to provide a desired overall profile of the uterine implant element when introduced into the uterine cavity. For example, the diameter of the triad structure can be selected by controlling the thickness of the edge side 12b of the element 10.

[0064] The thickness of the shell edge side surface 12b (thickness B) can be 0.05 mm to 0.5 mm, for example, 0.05 mm to 0.1 mm, 0.1 mm to 0.15 mm, 0.15 mm to 0.2 mm, 0.2 mm to 0.25 mm, 0.25 mm to 0.3 mm, 0.3 mm to 0.35 mm, 0.35 mm to 0.4 mm, or 0.4 mm to 0.5 mm. The thickness of the shell main body side surface 12a (thickness A) can be 0.1 mm to 1.5 mm, for example, 0.1 mm to 0.15 mm, 0.15 mm to 0.25 mm, 0.25 mm to 0.5 mm, or 0.5 mm to 1.5 mm. The thickness (thickness C) of the shell end surface 12c can be 0.25 mm to 1.5 mm, e.g., 0.25 mm to 0.5 mm, 0.5 mm to 1.0 mm, or 1.0 mm to 1.5 mm. In some embodiments, the shell end can be hemispherical. In such embodiments, the thickness of the end surface 12c can refer to the thickness of the shell at the center of the hemisphere. In other embodiments, the shell end can be truncated. In such embodiments, the thickness of the end surface 12c can refer to the thickness of the shell at the center of the truncated surface.

[0065] FIG. 8 is a cross-sectional view of an element showing a diagrammatic representation of the magnetic flux pattern, illustrating a magnetic inner core 11. As shown in the exemplary embodiment of FIG. 8, the magnetic flux is oriented symmetrically around the center of the core 11, which is typical for an axially magnetic object. The magnetic flux of an axially magnetic object flows outward from one end, called the north pole of the magnet, toward the other end, called the south pole of the magnet, and then through the core in a continuous cycle. The magnetic flux generally flows through the axial end faces of the magnetic material, including the periphery. The magnetic flux also generally flows uninterruptedly through inert materials. Thus, as shown in the exemplary embodiment of FIG. 8, the magnetic flux flows through the inert shells 12 at both ends of the axially magnetic magnetic core 11.

[0066] The elements disclosed herein can have a core with a north pole at one end and a south pole at the other end. Typically, north (N) and south (S) poles of a magnetic object are attracted to each other. Typically, a north pole repels a north pole. Similarly, a south pole repels a south pole. Increasing the distance between the north and south ends of two opposing magnets typically reduces the magnetic force, generally in an exponential relationship with increasing distance. Conversely, bringing the north and south ends of two opposing magnetic objects closer together (reducing the distance) typically increases the magnetic force, generally in an exponential relationship with decreasing distance. Thus, these elements can be designed (e.g., have cores and / or shells dimensioned) to have a selected magnetic force between them when positioned closely together, thereby allowing a given number of elements to be urged into a desired configuration by their magnetic forces relative to each other.

[0067] Referring to FIG. 1C , an element can have a core and shell dimensioned to self-assemble the three elements into a triad structure when brought into close proximity. As shown in FIG. 1C , exemplary element 10 has a smallest shell thickness (thickness B) on side 12b, a middle thickness (thickness A) on side 12a, and a largest thickness (thickness C, referring to the shell and void thickness) on side 12c. Edge side 12b and end side 12c generally refer to the sides of both halves of element 10, although it should be understood that the thickness of each side can be independently selected. In some embodiments, as shown in FIG. 1C , the dimensions between the outer surfaces of sides 12a, 12b, and 12c and the associated core surfaces of sides 11a, 11b, and 11c, respectively, can include void and shell thicknesses, as shown, for example, for thickness C in FIG. 1C . Thus, in some embodiments, the element can include a void, inert filler, or gap between magnetic core 11 and shell 12 to accommodate a mating intersection between the physical portion of shell 12 and the enclosed inner core 11. The shell and voids, inert fillers, and / or interstices can form an overall thickness (providing the dimension between the outer surface of the shell and the associated core surface) of 0.05 mm to 1.50 mm, e.g., 0.05 mm to 0.1 mm, 0.1 mm to 0.25 mm, 0.25 mm to 0.5 mm, 0.5 mm to 1.0 mm, or 1.0 mm to 1.5 mm.

[0068] In one exemplary embodiment, as shown in FIG. 1C , three elements 10, each with an axially magnetic core 11, are brought close to one another. Opposing poles (N / S) attract and self-align the elements. By designing the end faces 12c to have the greatest thickness and the edge sides 12b to have the smallest thickness, the elements 10 generally favor self-assembly by joining the edges 12b of two elements 10 (“bevel-to-bevel”). Thus, by selecting a shell thickness, the elements 10 can be designed to favor self-assembly into a selected structure, such as a triad structure. The shell thickness can also be selected or designed to favor self-assembly of the elements 10 into a generally linear structure, for example, when confined within a catheter for insertion and / or retrieval.

[0069] The shell can be formed from or include an inert material. In particular, the shell can be formed from a high coercivity material, e.g., a material that prevents degradation, e.g., upon contact with tissue. The shell can be a polymeric material. The shell can be a non-toxic, physiologically acceptable material, such as Teflon, silicone, polyethylene, polypropylene, polyetheretherketone (PEEK), or ethylene vinyl acetate (EVA) elastomer. Other shell materials, such as any shell material available to those skilled in the art suitable for use in the uterus, can also be used for the elements disclosed herein.

[0070] In some embodiments, element 10 can include adhesive layer 15, as shown in Figures 2A-2C. Adhesive layer 15 can be positioned between magnetic core 11 and shell 12. Shell 12 can prevent oxidation corrosion of magnetic core 11. Adhesive layer 15 can be provided to improve the surface properties of core 11. Adhesive layer 15 can have a nominal thickness of, for example, about 0.1 mm or less, between 0.1 mm and 0.01 mm, or less than 0.01 mm.

[0071] In the exemplary embodiment of FIG. 2A, an internal magnetic core 11 can be contained within an oval shell 12. A coating 13, such as a contraceptive coating or other coating, can be disposed on the exterior of the shell 12. In the exemplary embodiment shown in FIG. 2B, an internal magnetic core 11 can be contained within an oval shell 12. The contraceptive, if present, can be part of the shell 12 layer. In the exemplary embodiment of FIG. 2C, the magnetic core 11 can be generally oval. The magnetic core 11 can be contained within a thin shell 12. Similar to the embodiment of FIG. 2B, the element 10 of FIG. 2C can also include a contraceptive as part of the shell 12.

[0072] In some embodiments, the uterine implant element may be free of contraceptives. In some embodiments, the uterine implant element may be free of hormonal contraceptives. The element may be free of cytotoxic contraceptives.

[0073] In some embodiments, the element can include a coating, for example, a contraceptive coating. The coating can be outer layer 13 of element 10 (FIG. 2A). The coating can be embedded in shell 12, for example, as shown in FIGS. 2B-2C. In some embodiments, the contraceptive can be released from shell 12. In such embodiments, the shell can be formed from an absorbent material and can have, for example, a microstructure, to provide a time-controlled release of the contraceptive.

[0074] Coating 13, e.g., a contraceptive coating or other coating, can be applied by, for example, electrostatic spraying, electroplating, electroless plating, ion deposition, or other methods. Coating 13 can be positioned on the exterior of magnetic core 11, e.g., on the outer surface of core 11, the outer surface of adhesive 15, or the outer surface of shell 12. Contraceptive coating 13, or the contraceptive embedded within and leaching from shell 12, can be a sustained-release and / or extended-release drug. Contraceptive coating 13 and / or shell 12 can be designed to provide a predetermined release profile of the contraceptive. For example, coating 13 and / or shell 12 can be designed to provide therapeutic release of the contraceptive over a period of 12, 18, 24, 30, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 months, or longer. The contraceptive can be a hormonal agent, a cytotoxic agent, or a combination thereof.

[0075] The contraceptive may be a substantially non-releasing drug. In other embodiments, the contraceptive may be a sustained release drug. Each element is 400 mm 2 For example, 300 mm 2 Below, 200mm 2 Below, 150mm 2 Below, 100mm 2 Below, 75mm 2 or less, or 50 mm 2 The following contraceptives may be used: IUD systems (e.g., made up of two or more elements) that are 500 mm 2 For example, 400 mm 2 Below, 300mm 2 Below, 200mm 2 Below, 150mm 2 Below, 100mm 2 or less, or 75mm 2 The following contraceptives may be used: IUD systems (e.g., made up of two or more elements) that are 400 mm 2 ~500mm 2 , 300mm 2 ~400mm 2 , 200mm2 ~300mm 2 , or 100mm 2 ~200mm 2 In certain exemplary embodiments, for example, for use in human subjects, the total active surface area of ​​the contraceptive may be typically 150 mm 2 ~400mm 2 , for example 175mm 2 ~380mm 2 The range can be:

[0076] In some embodiments, the element is permeable to a slow release of the contraceptive. Upon insertion into the uterus, the element can release a therapeutically effective amount of the contraceptive. A therapeutically effective amount can be a contraceptive and / or fertility suppressing amount. A therapeutically effective amount can be an amount effective to provide treatment or prevention of a uterine disease, disorder, or condition. The element can include a therapeutically effective amount of the contraceptive, for example, embedded in the shell or as a separate layer.

[0077] The contraceptive can be a hormonal agent. Exemplary contraceptives include progesterone or progestogens, such as progestins. The therapeutic amount of the contraceptive in each component can be 1 mg to 60 mg, for example, 1 mg to 3 mg, 3 mg to 5 mg, 5 mg to 7 mg, 7 mg to 10 mg, 10 mg to 20 mg, 20 mg to 30 mg, 30 mg to 40 mg, 40 mg to 50 mg, or 50 mg to 60 mg.

[0078] In some embodiments, the elements are substantially free of hormonal agents, for example, in some embodiments, the elements are substantially free of progesterone or progestogens, such as progestins.

[0079] The contraceptive agent can be a cytotoxic agent. One exemplary cytotoxic agent is copper. One exemplary cytotoxic agent is nonoxynol 9 (N-9).

[0080] Element 10 can include protrusions 14 (shown in FIG. 1A ), such as rings or ridges, on the exterior surface of element 10 that include a cytotoxic drug. Element 10 can include a cytotoxic drug embedded in shell 12 substantially flush with the surface. Element 10 or shell 12 can include cytotoxic drug microparticles. At least a portion or the entire exterior surface of element 10 or shell 12 can be a cytotoxic drug, or at least a portion or the entire exterior surface can include a cytotoxic drug.

[0081] In some embodiments, element 10 can have a smooth or substantially smooth exterior surface (FIG. 11). The smooth or substantially smooth exterior surface can be the exterior surface of a contraceptive, e.g., the surface of copper. In other embodiments, element 10 can have one or more surface modifications 14, as shown in FIG. 1A. As discussed above, one exemplary surface modification is protrusions. Another exemplary surface modification is indentations. Additionally, or alternatively, element 10 can have a textured surface. Surface modifications 14 can be or include, for example, shallow grooves, undulations, indentations, protrusions, articulations, textures, rings, ridges, or any other three-dimensional features.

[0082] In certain exemplary embodiments, the protrusions or indentations can be elongated. The surface modification can have a width of about 0.1 mm to 0.5 mm, such as about 0.2 mm to 0.4 mm, or about 0.3 mm. The surface modification 14 can be longitudinal (spanning at least a portion of the length of the body of the element), transverse (spanning at least a portion of the width of the body of the element), or a combination thereof.

[0083] The surface modification can include or be formed from a contraceptive. The surface modification can be provided to increase the surface area of ​​the contraceptive, for example to increase the dosage of the contraceptive.

[0084] In one exemplary embodiment, element 10 can have a smooth copper exterior surface (FIG. 11). Shell 12, e.g., a copper shell, that can contain the contraceptive can be formed by laser welding multiple shell portions together. In the exemplary embodiment of FIG. 11, shell 12 is formed by laser welding a top shell portion to a bottom shell portion. Thus, element 10 can include laser weld lines 17. Weld lines 17 can be vertical, horizontal, or any other orientation. In some embodiments, element 10 can include two or more weld lines 17. Weld lines 17 can have a thickness selected to be minimal (resulting in a negligible reduction in the surface area of ​​shell 12).

[0085] In some embodiments, only one element 10 is inserted into the subject's uterus. In other embodiments, two or more elements 10 are inserted into the subject's uterus to form an IUD system. For example, in some embodiments, at least two, three, four, five, six, seven, eight, nine, ten, or more elements 10 can be inserted into the subject's uterus to form an IUD system. When two or more elements 10 are inserted, each element 10 can be smaller (compared to using only one), because the multiple elements 10 self-assemble or self-arrange by magnetic force into a larger IUD system inside (intrauterine). The north pole of the magnetic core 11 of one element 10 attracts the opposite south pole of the magnetic core 11 of another element 10, allowing multiple elements 10 to assemble together into a larger structure that can withstand expulsion from the uterus. For example, multiple elements 10 can be fitted and adjacent to form a stable, bonded trilobal, circular, or coiled structure. These elements can generally self-assemble or self-arrange into a lower-energy structure.

[0086] In some embodiments, a single element can form an IUD system. A single exemplary element 100 having the overall length of at least two, three, or more elements 10 (e.g., at least 3 mm to 30 mm, as described above) can be used to form an IUD system (FIG. 6). Element 100 can have a flexible or semi-flexible body. Element 100 can have a single magnetic core with a north pole and a south pole, as described above, or multiple magnetic cores arranged to position the north pole of one magnetic core and the south pole of a second magnetic core at opposite ends. The north pole attracts the south pole, causing element 100 to assemble into a structure, such as a circular or coiled structure, that resists expulsion from the uterus.

[0087] In certain embodiments, a single element IUD system can be designed to assemble (e.g., into a circular or coiled configuration) via a spring-loaded mechanism, as shown in Figure 6. The elements can be substantially non-magnetic or can include a single magnet at one end. The spring-loaded mechanism can be provided by a spring 19 extending between both ends of the element 100.

[0088] Thus, although the present disclosure may generally refer to multiple elements, it should be understood that a single element having a similarly dimensioned flexible body, e.g., a width and overall length similar to the multiple elements, may also be used.

[0089] Thus, the IUD system can include elements having a length of 30 mm or less, e.g., 3 mm to 30 mm, and including a magnetic core and a coating on the exterior of the magnetic core. The magnetic core can include at least one of a north pole and a south pole. In some embodiments, the magnetic core can include a north pole opposite the south pole. The magnetic core can be formed from a north pole magnetic core and a south pole magnetic core. The magnetic core can be sized to assemble the elements into a structure that will withstand expulsion from a subject's uterus.

[0090] One or more elements can be generally independent of one another. For example, one or more elements may not include any connecting thread or filament. However, in some embodiments, when two or more elements are utilized in an IUD system, these elements may be connected to one another by a filament (e.g., a monofilament or tail thread) or any other connecting material. In some embodiments, the connected or connected elements may still not include a tail thread. Thus, in some embodiments, a thread or other connecting material may be utilized only between adjacent elements.

[0091] FIG. 9 shows an exemplary IUD system having three elements 10 joined by two filaments 18a, 18b, with each filament 18a, 18b extending between two adjacent elements 10. The first and last elements are not joined by filaments. The exemplary elements 10 shown in FIG. 9 do not include a tail thread. The first and last elements can each include a magnetic core that enables the connected elements to assemble into a structure that withstands expulsion from the uterus. The magnetic core of the first element can be or include a north pole, and the magnetic core of the last element can be or include a south pole. The central element (or any element positioned between the first and last elements) can be non-magnetic. In other embodiments, the central element or any element positioned between the first and last elements can also include a magnetic core. Any combination of magnetic and non-magnetic elements can be used.

[0092] Figure 10 illustrates an exemplary IUD system, such as that shown in Figure 9, with a graphical representation of the magnetic flux pattern. The exemplary IUD system of Figure 10 includes two magnetic elements 10 at opposite ends of the system, with a non-magnetic element 21 positioned between the magnetic elements 10. The magnetic flux of each of the elements 10 in the system of Figure 10 is directed symmetrically around the center of each magnetic core 11, as shown for the single axially magnetic object of Figure 8. As shown in Figure 10, an IUD system having two magnetic elements 10 and one non-magnetic element 21 can self-assemble into a triad structure by magnetic forces.

[0093] The connecting threads or filaments can be flexible to allow the elements to assemble into an axial or generally aligned configuration. The connecting threads or filaments can have a length selected to allow the elements to assemble into a desired configuration, such as a triad configuration. The threads or filaments can be affixed to the exterior surface of the elements. In certain embodiments, the connecting threads or filaments can be integrally molded, e.g., injection molded, with the shell.

[0094] In some embodiments, the connector can extend from one element as a longer filament or tail thread for retrieval of the IUD system. The filament can generally be formed from or coated with an inert material. The filament material can be selected to provide the desired structural stability within the uterine cavity. Exemplary filament materials include nitinol, e.g., nitinol wire, nylon, e.g., nylon suture, polypropylene, polyethylene, or polyether, e.g., polyetheretherketone (PEEK), etc. In some embodiments, the element and / or IUD system can be substantially free of nitinol.

[0095] The magnetic core 11 can be sized to assemble multiple elements into a structure that will withstand expulsion from a subject's uterus. The structure can be the lowest energy structure for magnetic assembly. In certain exemplary embodiments, the structure is a triad or triangle structure.

[0096] Each element 10, having a magnetic core 11, can have at least one north and south pole, optionally both north and south poles at both ends. The magnetic core 11 can be an axially magnetic core (magnetic around the central axis of the magnetic core). Multiple elements 10 can be assembled by attracting the ends of alternating elements 10 with opposite magnetic charges or polarities. Additionally, multiple elements 10 can be assembled by repelling the ends of alternating elements 10 with similar magnetic charges or polarities. In one exemplary embodiment, the lower energy structure (in the case of three elements) is a triad structure (FIGS. 1B, 1C, 1E). In another embodiment, the lower energy structure (in the case of two or more elements) is a raft structure. In a raft structure, multiple elements 10 are aligned laterally in a parallel arrangement. This structure can be flexible and / or malleable, for example, to accommodate the natural movement of surrounding tissue.

[0097] The magnetic core 11 can be, for example, cylindrical, polygonal, such as rectangular (e.g., cubic), triangular, pentagonal, hexagonal, or polyhedral. Thus, the core can have a round, circular, oval, or polygonal cross-section, such as rectangular, square, triangular, pentagonal, hexagonal, or polyhedral. In certain exemplary embodiments, the magnetic core 11 can have a circular cross-section. A circular cross-section can be selected to achieve the greatest magnetic force per volume of the element 10, which can be beneficial when providing an element 10 that can pass through the smallest sized lumen of a cylindrical catheter (of an inserter or retriever). Thus, in certain embodiments, an element 10 with a circular cross-section can provide the greatest magnetic force while minimizing patient discomfort during insertion or retrieval.

[0098] In some embodiments, the core 11 may be oval or elliptical, for example having a rounded, elongated contour or shape like an oval egg.

[0099] The core can be formed from one or more magnetic bodies. In some embodiments, the core can be formed from a single magnetic body having a north pole and a south pole, optionally with the north pole at one end and the south pole at the other end (FIG. 7). In other embodiments, the core can comprise two or more magnetic bodies or can be formed from two or more magnetic bodies (FIG. 6), each with at least one north pole (11n) positioned at one end of the element and at least one south pole (11s) positioned at the other end of the element. The two or more magnetic bodies can be positioned such that the opposite magnetic poles 11n, 11s of each magnetic body come together, causing the element to self-assemble into a desired structure. In the exemplary embodiment of FIG. 7, the magnetic bodies are positioned at opposite ends of the central axis of the element 100, each with opposite magnetic poles 11n, 11s at the distal ends of the magnetic body, such that the magnetic poles 11n, 11s come together, causing the element 100 to self-assemble into a coiled or circular structure.

[0100] The magnetic core 11 can have generally blunt or rounded edges, for example, to form an elliptical structure. In certain embodiments, the magnetic core 11 can have beveled edges 11b to induce self-assembly into a triad structure of three devices. The beveled edges 11b can be formed by a beveled angle 11d, as shown in FIG. 4. The beveled edges 11b can additionally facilitate the inclusion of larger or maximum-sized magnetic cores 11 in the oval-shaped element 10, which can be used to provide greater magnetic force per element volume. Thus, the dimensions of the magnetic core, e.g., the length of the sides 11a, 11b, and 11c, as well as the cross-sectional shape and thickness of the shell, e.g., sides 12a, 12b, and 12c (FIGS. 1A-1B), can be selected or designed to induce self-assembly after placement and maintain sufficient magnetic force to withstand ejection. In certain embodiments, the dimensions of the shell, e.g., the thickness of sides 12a, 12b, 12c, can be selected to provide sufficient magnetic force to form a stable IUD system that conforms to the uterine cavity, thereby adapting to cyclical changes in response to the natural movement of uterine tissue.

[0101] The edge side 11b of the core 11 may be defined as the side joining the lateral side 11a of the core 11 to the distal end 11c of the core 11, as shown in the cross-sectional view of Figure 4. The width of the core 11 may be defined as the dimension extending from the lateral side 11a to the opposite lateral side (optionally, the diameter for magnetic cores having a circular cross-section). The length of the core 11 may be defined as the dimension extending from one distal end 11c to the opposite distal end.

[0102] The core 11 can have edge sides 11b at either or both ends. The edge sides 11b can extend around the core 11, for example, around the circumference of a cross-section of the core 11. In some embodiments, the edge sides 11b can be beveled. A beveled edge can be defined as an edge that forms an angle between the distal end 11c and the edge sides 11b. The bevel angle 11d can be defined as the angle formed between the center of the end 11c (optionally, the center of the circular cross-sectional area) and the edge sides 11b, as shown in FIG. 4. The bevel angle can be between about 5° and 50°, e.g., between about 5° and 15°, between 15° and 30°, between 20° and 40°, between 30° and 45°, or between 30° and 50°. In certain exemplary embodiments, the bevel angle can be about 30°.

[0103] In one exemplary embodiment, as shown in the diagram of Figure 1D, the 30° bevel angle forms an inclusive 60° circumferential angle that forms a conical surface around both ends of the circular cross-section magnetic core 11. When the magnetic core 11 is encased in the oval shell 12 to form the element 10, the tapered end surface 12c of the oval shell 12 generally follows the conical surface of the magnetic core 11.

[0104] In one exemplary embodiment, when a set of three elements 10 are assembled together, each including a core 11, with 30° bevel angles forming an inclusive 60° end angle (as shown in FIG. 1E), the conical surfaces of each magnetic core 11 are typically induced to self-assemble into a magnetically attracted triad or conformal triangular structure (FIG. 1E). The edge sides 11b of two adjacent cores 11 are typically separated by the sum of the thicknesses of the edge sides 12b (FIG. 1C). Thus, when the exemplary elements 10 of FIG. 1E are introduced into the uterine cavity, the three magnetic elements 10 are induced to form a magnetically coupled structure effective to resist expulsion from the uterine cavity.

[0105] In some embodiments, the core can be sized such that the ratio of the length of the lateral sides 11a to the length of the edge sides 11b is about 1:1 to 5:1, e.g., 1:1 to 2:1, 2:1 to 3:1, 3:1 to 4:1, or 4:1 to 5:1. The length of the lateral sides 11a of the core can be 0.5 mm to 10 mm, e.g., 0.5 mm to 1 mm, 1 mm to 3 mm, 1 mm to 5 mm, or 5 mm to 10 mm. The length of the edge sides 11b of the core can be 0.1 mm to 5 mm, e.g., 0.1 mm to 0.5 mm, 0.3 mm to 1.0 mm, 0.5 mm to 1.0 mm, 1.0 mm to 3 mm, or 3 mm to 5 mm. The core may be sized so that the length of the distal end 11c is between about 1 mm and 6 mm, for example between 1 mm and 2 mm, 1 mm and 3 mm, 2 mm and 4 mm, 3 mm and 5 mm, or 4 mm and 6 mm.

[0106] The magnetic core 11 can form at least 50% of the volume of the element 10. In some embodiments, the magnetic core can form at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of the volume of the element.

[0107] The magnetic core 11 can be sized to provide a selected magnetic attraction force between two elements, e.g., two elements of opposite polarity. The magnetic force can be effective to resist expulsion from the subject's uterus. The magnetic force can be effective to accommodate natural movement of uterine tissue. In some embodiments, the core 11 can be sized to provide a magnetic force of about 0.1-22 N, e.g., about 0.1-5 N, about 0.1-0.5 N, about 0.5-0.75 N, about 0.75-1.0 N, about 1.0-1.25 N, about 1.25-1.5 N, about 1.5-2.0 N, about 2.0-3.0 N, about 3.0-4.0 N, or about 4.0-5.0 N. Core dimensions that can be selected to provide a desired magnetic force include the length and width (or diameter) of the core, the cross-sectional geometry of the core, and the edge geometry of the core, e.g., length and / or bevel. Additionally, the material of the core can be selected to provide the desired magnetic force.

[0108] Additionally, the dimensions of shell 12 can also be selected to provide a desired magnetic force. For example, the thickness of the shell can be selected to control the distance between two adjacent magnetic cores in an IUD system, e.g., two cores of opposite polarity, or three or more magnetic cores. In some embodiments, shell 12 can have a thickness selected to position opposing magnetic cores 0.25 mm to 1.0 mm from each other, e.g., 0.25 mm to 0.5 mm or 0.5 mm to 1.0 mm. In certain exemplary embodiments, the thickness of the shell can be selected to position opposing magnetic cores less than 0.5 mm from each other.

[0109] Additionally, the dimensions of the magnetic core can be selected to provide a selected magnetic attraction between the elements and the retrieval magnet. The magnetic core can be sized to break down into multiple elements from a structure that resists ejection to a structure that allows retrieval. The structure that allows retrieval can be, for example, an axial structure or a generally aligned structure. The magnetic core can be sized to break down into a generally linearly connected structure, such as an axial structure or a linear train-like structure, when brought into proximity with a magnetic retrieval device.

[0110] In certain embodiments, one to four elements are used to form an IUD system. The size and number may depend on the species (human or non-human mammal). For example, when multiple elements are used, the size of each element can individually be about 2 mm to about 30 mm in length, e.g., about 2 mm to about 15 mm in length or about 2 mm to about 10 mm in length, and about 2 mm to about 15 mm in width, e.g., about 2 mm to about 10 mm in width or about 2 mm to about 6 mm in width or about 2 mm to about 4 mm in width. The size can be selected to allow placement of the element into the uterus during any phase of the menstrual cycle while still maintaining a high retention rate. The retention rate of the IUD system can be at least about 90%, at least about 95%, at least about 99%, or at least about 100% retention. The size can be selected to allow easier and less painful insertion of the element through the subject's cervix, e.g., into the subject's uterus.

[0111] In some embodiments, the health, pregnant / non-pregnant status, and / or dimensions of a subject's reproductive system can be determined prior to insertion of an IUD system. For example, a two-dimensional or three-dimensional ultrasound examination of the uterus can be performed to determine the health, pregnant / non-pregnant status, and / or dimensions and approve or deny the subject from using an IUD system. Generally, a minimum precaution is to ensure that the subject is not pregnant before installing an IUD system. In some embodiments, the health, pregnant / non-pregnant status, and / or dimensions of a subject's reproductive system can be determined to aid in the selection of the size and / or number of components to be used. The dimensions of a subject's reproductive system can include, for example, anatomical geometry, anatomical dimensions, and / or anatomical location (e.g., normal or abnormal location of the uterus).

[0112] These methods can include delivering multiple uterine implant elements to a subject using a delivery device (also referred to herein as an "inserter" or "introducer" or "applicator") sized to allow placement of the multiple elements within the subject's uterus. In one particular embodiment, the delivery device can be specially designed to accompany the IUD elements described herein. In some embodiments, the inserter can comprise a catheter sized to deliver the elements through the cervical canal and into the uterine cavity of the subject.

[0113] These methods may include inserting an inserter through the subject's cervical canal, placing an implantation element within the subject's uterine cavity, and then removing the inserter from the subject. The delivery device may be sized for use with a target subject. For example, the delivery device may be sized for use with a human subject. Self-insertion or assisted insertion, e.g., insertion performed by a trained physician and / or medical professional, may be performed. The catheter may be sized to deliver the element to the subject's uterine cavity without the use of a balloon, e.g., a dilatation balloon. Thus, in some embodiments, the inserter may not include any expandable or inflatable component, such as a balloon.

[0114] These methods can include delivering multiple elements individually. For example, an inserter can be sized to deliver multiple elements individually. In other embodiments, these methods can include delivering multiple elements sequentially or simultaneously. For example, an inserter can be sized to deliver multiple elements simultaneously, optionally in a sequential configuration (axial configuration or generally aligned configuration). In certain embodiments, the inserter can comprise a catheter sized to deliver multiple elements in a sequential, axial, or generally aligned configuration.

[0115] These methods can include retrieving a plurality of uterine implant elements from a subject using a retrieval device (also referred to herein as a "retriever") dimensioned to retrieve the plurality of elements from the uterus of the subject. In one particular embodiment, the retrieval device can be specially designed to accompany the IUD elements described herein.

[0116] These methods can include inserting a retriever through a subject's cervical canal to reach the subject's uterine cavity, collecting at least one element, and optionally multiple elements simultaneously, and removing the retriever with the elements from the subject. The retrieval device can be sized for use with a target subject. For example, the retrieval device can be sized for use with a human subject. Self-retrieval or assisted retrieval can be performed. The catheter can be sized to retrieve the elements from the subject's uterine cavity without the use of a balloon, e.g., a dilatation balloon. Thus, in some embodiments, the retriever may not include any expandable or inflatable component, such as a balloon.

[0117] The retriever can generally include a magnetic tip effective to attract the elements. When the magnetic tip is brought into proximity with the elements, the elements can be induced to disassemble into an axial or generally aligned configuration to enable retrieval from the subject's uterus by the retrieval device. The magnetic tip can be positioned on the distal end of a rod or elongated structure dimensioned to retrieve the elements from the subject's uterus. In one particular embodiment, the retriever can be similar in size and assembly to the inserter. For example, in some embodiments, the retriever can comprise a catheter having a magnetic tip dimensioned to retrieve the elements in a sequential, axial, or generally aligned configuration.

[0118] These methods can include retrieving multiple elements individually. For example, the retriever can be sized to retrieve multiple elements individually. In other embodiments, these methods can include retrieving multiple elements sequentially or simultaneously. For example, the retriever can be sized to retrieve multiple elements simultaneously, optionally in a sequential configuration (axial or aligned).

[0119] In certain embodiments, retrieval can also be performed by a filament or tail, for example, by a length of filament or thread connected to and / or interconnecting multiple elements (similar to removal of conventional contraceptive devices), optionally tying the device together, although in other embodiments, these elements do not include a tail thread and / or any filament or thread.

[0120] The IUD elements 10 disclosed herein can be inserted, e.g., delivered, into a subject's uterus, and / or retrieved from a subject's uterus with reduced pain. After insertion or retrieval of the IUD element 10, the subject can be asked to rate their pain score based on a numerical rating scale (NRS). The NRS is a verbal or written assessment of pain level on a scale of 0 to 10, with 0 representing no pain and 10 representing extreme pain. In some embodiments, the average or maximum NRS pain score for insertion, e.g., delivery, of the IUD element 10 can be less than 10, e.g., less than 9, less than 8, less than 7, less than 6, less than 5, less than 4, less than 3, less than 2, or less than 1. In some embodiments, the average or maximum NRS pain score for retrieval of the IUD element 10 can be less than 10, e.g., less than 9, less than 8, less than 7, less than 6, less than 5, less than 4, less than 3, less than 2, or less than 1.

[0121] In other embodiments, after insertion or withdrawal of the IUD element 10, the subject may be asked to rate a pain score based on a visual analog scale (VAS). A VAS is a graphic rating scale that may utilize a line or a series of graphic depictions, such as cartoon faces, for the subject to select to indicate a degree of pain level. In the case of a line depiction, a first end of the line may represent no pain, and the other end of the line may represent extreme pain. The subject may be asked to indicate the pain level by identifying a point on the line. In some embodiments, the average or maximum VAS pain score for insertion, e.g., delivery, of the IUD element 10 may be less than 100% of the line (e.g., less than the extreme end of the line), e.g., less than 80% of the line, less than 75% of the line, less than 60% of the line, less than 50% of the line, less than 40% of the line, less than 25% of the line, or less than 20% of the line. In some embodiments, the average or maximum VAS pain score for withdrawal of the IUD element 10 can be less than 100% of the line, e.g., less than 80% of the line, less than 75% of the line, less than 60% of the line, less than 50% of the line, less than 40% of the line, less than 25% of the line, or less than 20% of the line.

[0122] In the case of graphic depictions, five shapes can visually represent increasing pain levels from no pain to extreme pain. The subject can be asked to indicate their pain level by identifying a unique shape that describes the pain level. In some embodiments, the average or maximum VAS pain score for entry, e.g., delivery, of the IUD element 10 can be less than the shape used to identify extreme pain (e.g., less than the fifth shape), less than the fourth shape, less than the third shape, or less than the second shape. In some embodiments, the average or maximum VAS pain score for withdrawal of the IUD element 10 can be less than the fifth shape, less than the fourth shape, less than the third shape, or less than the second shape.

[0123] According to one aspect, the present disclosure includes methods of providing and / or facilitating managed contraception to a subject. These methods can include delivering multiple uterine implant elements to a uterus of a subject. The multiple elements can be delivered individually or simultaneously. Individual delivery can include, for example, delivery of a single element with a single actuation of a delivery device. Simultaneous delivery can include, for example, delivery of multiple elements with a single actuation of a delivery device.

[0124] According to one aspect, the present disclosure includes methods for treating or preventing a uterine disease, disorder, or condition in a subject, and / or methods for facilitating the treatment or prevention of a uterine disease, disorder, or condition. These methods can include delivering multiple uterine implant elements to a uterus of a subject. The multiple elements can be delivered individually or simultaneously. Individual delivery can include, for example, delivery of a single element with a single actuation of a delivery device. Simultaneous delivery can include, for example, delivery of multiple elements with a single actuation of a delivery device.

[0125] Detection Sensor These methods can include scanning the subject for detection of the IUD system after insertion or withdrawal. Detection of the element can be performed by ultrasound or using a detection sensor. Exemplary detection sensors include a magnetic field detector, a gaussmeter, or a metal detector.

[0126] The detection sensor can provide contactless detection. The detection sensor can indicate detection of the device by a visual and / or audible alarm and / or by transmitting a notification to a computer or mobile device. The detection sensor can be equipped to detect the device from a distance of 2 inches or more, e.g., at least 2 inches, 4 inches, 6 inches, 8 inches, or 10 inches to 1 foot.

[0127] [Example] The function and advantages of these and other embodiments can be better understood from the following examples, which are intended to be illustrative in nature and are not to be construed as limiting the scope of the invention.

[0128] [Example 1] Magnetic force depending on the geometry of the magnetic core Digital simulation studies were conducted to evaluate the relative effectiveness of alternative magnetic core geometries for assembly into various configurations. Magnetic forces are a function of magnetic material, core geometry, size, and assembly configuration. Three magnetic core geometries were tested, including a cylindrical core (1), a core containing beveled edges with a circular cross section (2), and a solid elliptical magnet element (no shell).

[0129] Each configuration was evaluated for magnetic force when assembled into a triad configuration, a laterally aligned configuration (magnets aligned side-to-side), and an axially aligned configuration (magnets aligned end-to-end). Note that configurations (1) and (2) were sized to fit within an oval shell sized similarly to (3), i.e., the largest size that could be delivered through a catheter lumen of a particular size. The data are shown in the table in Figure 5.

[0130] As shown in Figure 5, the oval magnet (3) had the greatest magnetic force in each of the three configurations, but had a stronger tendency to remain assembled in a serial configuration (when inserted into the subject's uterus). The cylindrical core (1) attempted to assemble into a triad configuration because the magnetic force of that configuration was stronger than the transverse or axially aligned configurations. The core (2) containing the beveled edge also attempted to assemble into a triad configuration, exhibiting a much stronger magnetic force holding the elements together, which is preferred. The cylindrical core (1) had the weakest magnetic force in each of the configurations.

[0131] Figures 3A and 3B show shaded plots prepared to visualize the relative attractive force of a cylindrical core (1) (Figure 3A) compared to a larger diameter core (2) with a circular cross section and beveled ends (Figure 3B). Both core geometries have the same length. Both core geometries have the same diameter at each end. Cylindrical core (1) has the weakest magnetic force in each configuration. Core (2), which includes beveled ends, exhibited significantly stronger attractive force (3.6x) than cylindrical core (1) in the triad configuration. The gradation of the shaded plots ranges from red (strongest) > yellow > green > cyan > blue (weakest) to indicate the relative range of attractive force magnitude. Shades of red (1.0) are almost absent in the view of cylindrical core (1) (Figure 3A).

[0132] 3C and 3D illustrate the overall geometry of three elements 10 arranged in a triad configuration. The exemplary elements 10 in FIGS. 3C and 3D have cylindrical magnetic cores 11 with beveled edges. The element 10 in FIG. 3C has a smaller edge thickness 12b (thickness B) than the element 10 in FIG. 3D. As shown in FIGS. 3C-3D, by reducing the edge thickness 12b from 0.36 mm (FIG. 3C) to 0.2 mm (FIG. 3D), the diameter of the overall triad configuration can be reduced from 10.63 mm (FIG. 3C) to 10.07 mm (FIG. 3D). Accordingly, the elements 10 with smaller edge thicknesses 12b self-arrange into a triad configuration with a smaller overall profile and stronger magnetic forces between the elements 10.

[0133] [Example 2] Prophetic Examples of Methods for Providing Contraception The frameless IUD system disclosed herein is used to provide contraception to a subject. In particular, three uterine implant elements comprising the IUD system are delivered to the subject's uterus by an attached handler (developed by 3Daughters, Inc., Fort Lauderdale, Florida) to provide contraception. The uterine implant elements have magnetic cores sized to assemble into a structure that adapts to the uterine environment and resists expulsion. In this embodiment, the uterine implant elements have magnetic cores sized to adopt a stable triad configuration within the subject's uterus.

[0134] The uterus transplant element is having dimensions of less than 10 mm, e.g., 2.0 mm to 10 mm in length and 2.0 mm to 6.0 mm in width, sized to fit within, e.g., a 4.0 mm or 4.4 mm OD catheter; The magnetic core of the uterine implant element has a rounded cross-sectional area and beveled edges; The contraceptive coating, which forms a shell that protects and encases the magnetic core, has a varying thickness.

[0135] The elements are generally elliptical in shape because they are provided by a shell that is dimensioned to allow the three elements to self-assemble into a stable triad configuration upon loading and disassemble into an axially aligned configuration (aligned configuration) upon retrieval.

[0136] Conventional contraceptive devices, which include a T-shaped design of the frame (plastic (polyethylene)), can cause painful insertion, uterine perforation, expulsion from the uterus, and contain threads that are required for removal from the uterus.

[0137] The frameless IUD system disclosed herein includes multiple uterine implant elements that conform and adapt to the uterine environment, provide an easier insertion process (fewer steps, reducing or eliminating pain points), have smooth external dimensions, and are structurally independent from one another. Thus, the frameless IUD system disclosed herein provides contraception to the subject while reducing insertion pain, reducing (or eliminating) the risk of expulsion (adapting to the uterine environment), reducing (or eliminating) the risk of uterine perforation, and does not require strings for removal.

[0138] [Example 3] Prophetic Examples of Methods for Providing Treatment or Prevention of Uterine Diseases, Disorders, or Conditions The frameless IUD system disclosed herein is used to provide treatment or prevention for a uterine disease, disorder, or condition (such as abnormal uterine bleeding) in a subject. In particular, three uterine implant elements comprising the IUD system are delivered to the subject's uterus by an attached handler (developed by 3Daughters, Inc., Fort Lauderdale, Florida) to provide treatment or prevention. The uterine implant elements have magnetic cores sized to assemble into a structure that adapts to the uterine environment and resists expulsion. In this embodiment, the uterine implant elements have magnetic cores sized to adopt a stable triad configuration within the subject's uterus.

[0139] The uterus transplant element is having dimensions of less than 10 mm, e.g., 2.0 mm to 10 mm in length and 2.0 mm to 6.0 mm in width, sized to fit within, e.g., a 4.0 mm or 4.4 mm OD catheter; The magnetic core of the uterine implant element has a rounded cross-sectional area and beveled edges; The coating that forms a shell (optionally a shell of inert material or a shell of contraceptives) that protects and encases the magnetic core has a variety of thicknesses.

[0140] The elements are generally elliptical in shape because they are provided by a shell that is dimensioned to allow the three elements to self-assemble into a stable triad configuration upon loading and disassemble into an axially aligned (registered) configuration upon retrieval.

[0141] Conventional intrauterine devices, which include a T-shaped design of the frame (plastic (polyethylene)), can cause painful insertion, uterine perforation, expulsion from the uterus, and include sutures that are required for removal from the uterus.

[0142] The frameless IUD system disclosed herein includes multiple uterine implant elements that conform and adapt to the uterine environment, provide an easier insertion process (fewer steps, reducing or eliminating pain points), have smooth exterior dimensions, and are structurally independent from one another. Thus, the frameless IUD system disclosed herein reduces insertion pain, reduces (or eliminates) the risk of expulsion (adapts to the uterine environment), reduces (or reduces) the risk of uterine perforation, and does not require strings for removal, while providing targeted treatment or prevention of uterine diseases, abnormalities, or symptoms.

[0143] The terms and terminology used herein are for purposes of description and should not be considered limiting. As used herein, the term "plurality" refers to two or more items or components. The terms "comprising," "including," "carrying," "having," "containing," and "involving," regardless of written description or claims, are open-ended terms, i.e., meaning "including, but not limited to." Thus, the use of such terms is meant to encompass the items listed thereafter, and equivalents thereof, as well as additional items. The transitional phrases "consisting of" and "consisting essentially of" are closed or semi-closed transitional phrases, respectively, with respect to the claims. In the claims, the use of ordinal numbers such as "first," "second," "third," etc. to modify claim elements does not in itself imply any priority, precedence, or ordering among the claim elements, or the chronological order in which method actions are performed, but is merely used as a label to distinguish one claim element having a particular name from another element having the same name (but using an ordinal number).

[0144] Having thus described several aspects of at least one embodiment, it will be understood that various alterations, modifications, and improvements will readily occur to those skilled in the art. Any feature described in any embodiment can be included in, or substituted for, any feature of any other embodiment. Such alterations, modifications, and improvements are intended to be part of this disclosure and are intended to be within the scope of the invention. Accordingly, the foregoing description and drawings are by way of example only.

[0145] Those skilled in the art will understand that the parameters and configurations described herein are exemplary and that the actual parameters and / or configurations will depend on the specific application for which the disclosed methods and materials are used. Equivalents to the specific embodiments disclosed should be recognized or able to be determined by those skilled in the art using no more than routine experimentation.

Claims

1. 1. An intrauterine device (IUD) system comprising a plurality of elements, each element having a length of 10 mm or less, comprising a magnetic core and a coating exterior to the magnetic core, the magnetic core being sized to assemble the plurality of elements into a structure that will withstand expulsion from a subject's uterus.

2. 10. The IUD system of claim 1, wherein the IUD system comprises at least three elements.

3. 3. The IUD system of claim 2, wherein the IUD system includes three elements, each element having a magnetic core sized to assemble the elements into a triad structure.

4. 10. The IUD system of claim 1, wherein each element comprises a shell exterior to the magnetic core.

5. 5. The IUD system of claim 4, wherein the IUD system includes three elements, each element having a shell sized to assemble the elements into a triad structure.

6. 5. The IUD system of claim 4, wherein the shell has an average thickness of 0.10 mm to 1.50 mm.

7. 5. The IUD system of claim 4, wherein the coating is a contraceptive coating, and the contraceptive coating is embedded in the shell.

8. 10. The IUD system of claim 1, wherein the magnetic core is an axially magnetized magnetic core.

9. 10. The IUD system of claim 8, wherein the magnetic core is sized to disassemble the multiple elements into an axial or generally aligned configuration that allows for retrieval from a subject's uterus by a magnetic retrieval device.

10. 10. The IUD system of claim 1, wherein each element comprises the magnetic core and the coating.

11. 10. The IUD system of claim 1, wherein each element has a round cross-sectional area with a diameter of 2.0 mm to 6.0 mm.

12. 12. The IUD system of claim 11, wherein each element is sized to pass through the subject's cervix.

13. 13. The IUD system of claim 12, wherein each element is sized to fit within a catheter with an OD of 4.0 mm to 5.0 mm.

14. 10. The IUD system of claim 1, wherein each element has a length between 2.0 mm and 10 mm.

15. 10. The IUD system of claim 1, wherein the magnetic core has rounded or beveled edges.

16. 10. The IUD system of claim 1, wherein the coating is a contraceptive coating, and the contraceptive comprises a cytotoxic drug.

17. 17. The IUD system of claim 16, wherein the cytotoxic agent comprises copper.

18. The contraceptive coating is 175 mm 2 ~380mm 2 18. The IUD system of claim 17, having a copper surface area of

19. 10. The IUD system of claim 1, wherein the coating is a contraceptive coating, and the contraceptive comprises a hormone.

20. 10. The IUD system of claim 1, wherein the coating is substantially free of hormonal agents.

21. 10. The IUD system of claim 1, wherein the coating is substantially free of nickel and / or nitinol.

22. 10. The IUD system of claim 1, wherein the magnetic core includes a south pole and a north pole opposite the south pole.

23. 10. The IUD system of claim 1, wherein the magnetic core forms at least 50% of the volume of each element.

24. 10. The IUD system of claim 1, wherein each of the plurality of elements is structurally independent from each other.

25. 1. A method for providing controlled contraception or treating or preventing a uterine disease, disorder, or condition in a subject, comprising:

1. A method comprising delivering a plurality of elements to a uterus of a subject, each element having a length of 10 mm or less and comprising a magnetic core and an exterior coating on the magnetic core, the magnetic core being sized to assemble the plurality of elements into a structure that will withstand expulsion from the uterus of the subject.

26. 26. The method of claim 25, comprising delivering each element individually.

27. 26. The method of claim 25, comprising delivering the multiple elements sequentially and / or simultaneously.

28. 1. A method for facilitating controlled contraception or treating or preventing a uterine disease, disorder, or condition in a subject, comprising: providing a plurality of elements, each element having a length of 10 mm or less, comprising a magnetic core and an exterior coating of the magnetic core, the magnetic core being sized to assemble the plurality of elements into a structure that will withstand expulsion from the uterus of a subject; providing instructions for delivering the plurality of elements to the uterus of the subject; A method comprising:

29. an intrauterine device (IUD) system including a plurality of elements, each element having a length of 10 mm or less and comprising a magnetic core and a coating on the exterior of the magnetic core; a delivery device dimensioned to allow placement of the plurality of elements within the uterus of a subject; instructions for delivering the plurality of elements to the uterus of the subject using the delivery device; A kit comprising:

30. 30. The kit of claim 29, further comprising a retrieval device dimensioned to allow retrieval of the plurality of elements from the uterus of the subject.

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