Intrauterine contraceptive (IUD) system

Abstract

An intrauterine device (IUD) system. The IUD system includes a plurality of elements, each element having a length of 10 mm or less. Each element includes a magnetic core and a coating outside the magnetic core, the magnetic core sized to assemble the plurality of elements into a configuration that resists discharge from the uterus of the subject. Also disclosed are methods of providing controlled contraception or treating or preventing a uterine disease, disorder, or a symptom thereof in a subject. The method includes delivering a plurality of elements to the uterus of the subject. Also disclosed are methods of promoting controlled contraception or treating or preventing a uterine disease, disorder, or a symptom thereof in a subject. The method includes providing a plurality of elements. A kit comprising a plurality of elements and a delivery device is also disclosed.

Description

[0001] Cross Reference to Related Applications

[0002] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application Serial No. 63 / 436,341, filed December 30, 2022, entitled “INTRAUTERINE DEVICE (IUD) SYSTEM,” and U.S. Provisional Application Serial No. 63 / 541,557, filed September 29, 2023, entitled “INTRAUTERINE DEVICE (IUD) SYSTEM,” each of which is incorporated herein by reference in its entirety for all purposes. TECHNICAL FIELD

[0003] Aspects and embodiments disclosed herein relate to intrauterine device (IUD) systems and methods that provide contraception and / or treatment or prevention of uterine diseases, disorders, or symptoms thereof. In particular, aspects and embodiments disclosed herein relate to IUD systems having a plurality of magnetic IUD elements. SUMMARY

[0004] According to one aspect, an intrauterine device (IUD) system is provided. The IUD system can include a plurality of elements. Each element can have a length of 10 mm or less. Each element can include a magnetic core and a coating external to the magnetic core. The magnetic core can be sized to assemble the plurality of elements into a configuration that resists expulsion from a subject’s uterus.

[0005] In some embodiments, the IUD system includes at least three elements.

[0006] In some embodiments, the IUD system includes three elements. Each element can have a magnetic core sized to assemble the plurality of elements into a triad configuration.

[0007] In some embodiments, each element includes a shell external to the magnetic core.

[0008] In some embodiments, the IUD system includes three elements, each element having a shell sized to assemble the plurality of elements into a triad configuration.

[0009] In some embodiments, the shell has an average thickness of between 0.10 mm and 1.50 mm.

[0010] In some embodiments, the coating is an anti-fertility agent coating, and the anti-fertility agent coating is embedded in the shell.

[0011] In some embodiments, the magnetic core is an axially charged magnetic core.

[0012] In some embodiments, the dimensions of the magnetic core are designed to disassemble the plurality of elements into an axial or substantially aligned configuration that allows retrieval from the subject's uterus with a magnetic retrieval device.

[0013] In some embodiments, each element is comprised of a magnetic core and a coating.

[0014] In some embodiments, each element has a circular cross-sectional area with a diameter between 2.0 mm and 6.0 mm.

[0015] In some embodiments, each element is sized to pass through the subject's cervix.

[0016] In some embodiments, each element is sized to fit within a catheter of outer diameter 4.0 mm to 5.0 mm.

[0017] In some embodiments, each element has a length between 2.0 mm and 10 mm.

[0018] In some embodiments, the magnetic core has a circular or beveled edge.

[0019] In some embodiments, the coating is an anti-fertility agent coating, and the anti-fertility agent comprises a cytotoxic agent.

[0020] In some embodiments, the cytotoxic agent coating comprises copper.

[0021] In some embodiments, the anti-fertility agent coating has a copper surface area between 175 mm 2 and 380 mm 2 .

[0022] In some embodiments, the coating is an anti-fertility agent coating, and the anti-fertility agent comprises a hormonal agent.

[0023] In some embodiments, the coating is substantially free of a hormonal agent.

[0024] In some embodiments, the coating is substantially free of nickel and / or nitinol.

[0025] In some embodiments, the magnetic core comprises a south pole and a north pole opposite the south pole.

[0026] In some embodiments, the magnetic core forms at least 50% of the volume of each element.

[0027] In some embodiments, each of the plurality of elements is structurally independent of one another.

[0028] According to another aspect, a method of providing controlled contraception or treating or preventing uterine disease, disorder, or symptoms thereof in a subject is provided. The method can include delivering a plurality of elements to a uterus of a subject, each element having a length of 10 mm or less, including a magnetic core and a coating external to the magnetic core, the magnetic core sized to assemble the plurality of elements into a configuration that resists expulsion from the uterus of the subject.

[0029] In some embodiments, the method can include delivering each element individually.

[0030] In some embodiments, the method can include delivering each element sequentially and / or simultaneously.

[0031] According to another aspect, a kit is provided, including an intrauterine device (IUD) system including a plurality of elements, each element having a length of 10 mm or less, including a magnetic core and a coating external to the magnetic core; a delivery device sized to allow placement of the plurality of elements in a uterus of a subject; and instructions for delivering the plurality of elements to the uterus of the subject using the delivery device.

[0032] In some embodiments, the kit can further include a retrieval device sized to allow retrieval of the plurality of elements from the uterus of the subject.

[0033] According to another aspect, a method of facilitating controlled contraception or treating or preventing uterine disease, disorder, or symptoms thereof in a subject is provided. The method can include providing a plurality of elements, each element having a length of 10 mm or less, including a magnetic core and a coating external to the magnetic core, the magnetic core sized to assemble the plurality of elements into a configuration that resists expulsion from the uterus of the subject. The method can include providing instructions to deliver the plurality of elements to the uterus of the subject.

[0034] The present disclosure contemplates all combinations of any one or more of the foregoing aspects and / or embodiments, as well as combinations with any one or more of the embodiments set forth in the particular embodiments and any embodiment. BRIEF DESCRIPTION OF DRAWINGS

[0035] 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 Office upon request and payment of the necessary fee.

[0036] The drawings are not intended to be to scale. In the drawings, like or similar elements are denoted by the same reference numbers throughout the several views. Not every component can be labeled in every drawing. In the drawings:

[0037] Figure 1A is a schematic illustration of a uterine implant element according to one embodiment;

[0038] Figure 1B is a schematic view of three uterine implant elements arranged in a triad configuration, including a cross-sectional view and a partial cross-sectional view of a uterine implant element, according to an embodiment;

[0039] Figure 1C is a cross-sectional view of three uterine implant elements arranged in a triad configuration, showing shell thickness relationships, according to an embodiment;

[0040] Figure 1D is a cross-sectional view of a uterine implant element, showing a beveled feature, according to an embodiment;

[0041] Figure 1E is a cross-sectional view of three uterine implant elements arranged in a triad configuration, showing beveled engagement relationships, according to an embodiment;

[0042] Figures 2A-2C is a cross-sectional view of different uterine implant elements, according to certain embodiments;

[0043] Figure 3A is a schematic view showing magnetic attraction of three uterine implant elements arranged in a triad configuration, according to an embodiment, wherein each element contains a cylindrical magnetic core;

[0044] Figure 3B is a schematic view showing magnetic attraction of three uterine implant elements arranged in a triad configuration, according to an embodiment, wherein each element contains a cylindrical magnetic core with a beveled edge;

[0045] Figure 3C is a schematic view showing the overall profile of three uterine implant elements arranged in a triad configuration, according to an embodiment;

[0046] Figure 3D is a schematic view showing the overall profile of three uterine implant elements arranged in a triad configuration, according to an embodiment, having a smaller overall profile than Figure 3C the uterine implant element of FIG. 1 ;

[0047] Figure 4 is a cross-sectional view of a uterine implant element, according to an embodiment;

[0048] Figure 5 is a chart comparing magnetic force of several magnetic core geometries and assembly configurations, according to certain embodiments;

[0049] Figure 6 is a schematic view of a uterine implant element, according to an embodiment;

[0050] Figure 7 is a cross-sectional view of a uterine implant element, according to an embodiment;

[0051] Figure 8 is a cross-sectional view of a uterine implant element showing a magnetic flux pattern of an axial charge according to one embodiment;

[0052] Figure 9 is a schematic view of an IUD system according to one embodiment;

[0053] Figure 10 is a partial cross-sectional view of an IUD system showing a magnetic flux pattern according to one embodiment; and

[0054] Figure 11 is a schematic view of a uterine implant element according to one embodiment. DETAILED DESCRIPTION

[0055] Contraception can be provided by a variety of methods. One of the safest and most effective methods is to place an intrauterine device (IUD) in a subject's uterus to prevent pregnancy as a result of sexual intercourse. The IUD generally has a contraceptive effect for the duration of time that it remains in the uterus. The contraceptive effect can be easily reversed by removing the IUD from the uterus.

[0056] IUDs currently on the market are T-shaped frame devices made of plastic that release a spermicide or a hormonal agent to provide contraception. These conventional IUDs can be very effective, but the T-shaped frame design results in significant pain upon insertion, uterine perforation, expulsion from the uterus, and vaginitis caused by the external retrieval string. Thus, there is a need for improved IUDs that provide easier and less painful insertion.

[0057] Embodiments described herein provide intrauterine device (IUD) systems, such as frameless IUD systems, that include one or more uterine implant elements that provide high efficiency, ease of implantation, ease of retrieval, and exhibit high retention rates without affecting future fertility. In certain embodiments, the IUD systems are free of an external retrieval string.

[0058] SELECTED DEFINITIONS

[0059] As used herein, "antifertility agent" means a drug, compound, or biological that has a contraceptive effect on a subject. The antifertility agent can be an active agent of a composition. In some embodiments, the antifertility agent can be a hormonal agent. In some embodiments, the antifertility agent can be a cytotoxic agent, sometimes referred to as a "spermicide." The antifertility agent can also be referred to herein as a "contraceptive agent."

[0060] As used herein, "hormonal agent" means an anti-fertility agent that comprises 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 progestin.

[0061] As used herein, "cytotoxic" agent means a non-hormonal anti-fertility agent that targets sperm cells and / or egg cells. The cytotoxic agent can also be referred to as a spermicide or a spermicidal agent. In certain example embodiments, the cytotoxic agent can be copper.

[0062] As used herein, "contraception" refers to the prevention of pregnancy as a result of sexual intercourse. Contraception can include barrier methods, preventing the female from ovulating, inactivating or killing sperm, inhibiting or preventing motility of sperm, modulating cervical mucus, and / or preventing implantation of a fertilized egg into the uterus.

[0063] As used herein, "inert" means non-toxic or harmless to surrounding tissue. The inert material can be biocompatible.

[0064] As used herein, "subject" can include an animal, a mammal, a human, a non-human animal. 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 particular embodiments, the subject is a human subject. Although applications to humans are explicitly foreseen, veterinary applications, e.g., to non-human animals, are also contemplated herein. The term "non-human animal" of the present disclosure includes all mammals, such as non-human primates, domestic, laboratory, research, and farm animals, such as horses, sheep, goats, dogs, cats, cows, pigs, rats; wild carnivores, such as wolves, bears, cheetahs, tigers, leopards, lions; ungulates, such as wild boars, boars; or ruminants / pseudo-ruminants, such as camels, deer, chiral, water buffalo; or large mammals, such as elephants; and the like. The subject can be biologically equipped to reproduce offspring. The subject can have a uterus or uterine cavity. The subject can be female. The subject can be of childbearing age.

[0065] As used herein, "retention rate" means the percentage of IUD systems that remain in the uterus of a subject after a selected period of time has elapsed from the date of insertion without voluntary removal. The elapsed period of time can be 24 hours, 48 hours, 72 hours, 7 days, one month, three months, six 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.

[0066] As used herein, treatment of 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 reversing 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.

[0067] Intrauterine device (IUD) system

[0068] The present disclosure provides an intrauterine device (IUD) system. The system can have one or more uterine implant elements, also referred to herein as intrauterine contraceptive elements, “IUD elements,” or “elements.” The elements can be devices for insertion into a subject’s uterus to provide a contraceptive effect, to suppress, limit, or reduce side effects of a menstrual cycle, such as discomfort, pain, excessive bleeding, cramping, or inflammation, and / or to treat or prevent uterine diseases, disorders, and symptoms thereof, such as abnormal uterine bleeding, irregular menstrual cycles, irregular vaginal discharge, endometriosis, adenomyosis, fibroids, polyps or cysts, polycystic ovary syndrome (PCOS), pelvic inflammatory disease, endometrial hyperplasia, uterine cancer, dysuria, genital tuberculosis, uterine prolapse, bacterial, parasitic, or viral sexually transmitted diseases, discomfort, pain, cramping, or inflammation.

[0069] Exemplary elements are shown in Figures 1A-1B FIG. 1. Figure 1A A side view of one uterine implant element 10 is shown. Figure 1B A lateral side view of several uterine implant elements 10 assembled in a configuration is shown, with one element shown in cross-section and another element shown in partial cross-section. The elements can include a magnetic core 11. The magnetic core can be an axially charged magnetic core with opposite north (N) and south (S) poles at each end.

[0070] The element 10 can include one or more layers external to the magnetic core 11. The element 10 can include a shell 12 external to the magnetic core 11. In other embodiments, the element 10 can be substantially free of the shell 12. In one particular embodiment, the element 10 can include a coating external to the shell 12. In other embodiments, the element 10 can be substantially free of the coating external to the shell 12. One or more layers of the element 10 can be selected based on functionality or manufacturing.

[0071] The contraceptive or therapeutic effect of the element can be provided by implanting the element in the uterus. The contraceptive or therapeutic effect can be provided by the geometry and physical characteristics of the element and / or the arrangement or configuration of the element when placed in the uterus of a subject. In certain embodiments, the element can be sized to provide contraception. For example, in certain veterinary applications, such as mares, estrus suppression provided by the presence and / or geometry of the element can provide contraception. In certain embodiments, the element can be sized to provide treatment or prevention of uterine disease, disorder, or symptom thereof. In addition to or in lieu of a contraceptive effect, a therapeutic effect can be provided.

[0072] In some embodiments, the contraceptive effect of the element can be provided by an antifertility agent. In one particular embodiment, the antifertility agent can be disposed in a coating external to the magnetic core 11. In certain embodiments, the shell 12 can be formed from or include an antifertility agent. For example, the antifertility agent can be embedded in the shell 12 uniformly or non-uniformly. In other embodiments, an antifertility agent coating can be external to the shell 12. Thus, the antifertility agent coating can form the outermost layer of the element 10, such as a wrapper, wire, sheath, or other structure on the outer surface of the element 10.

[0073] The coating (e.g., antifertility agent coating or other coating) need not cover the entire surface of the element 10, for example, the coating can cover at least 25%, 25%-50%, 50%-75%, or 75%-100% of the outer surface of the element 10. In other embodiments, the antifertility agent coating can form an inner layer of the element 10 (e.g., between the core 11 and a layer of the shell 12) and be released through the shell 12. Exemplary antifertility agents include hormonal agents and cytotoxic agents.

[0074] The element can be sized to be ergonomic (compatible with uterine tissue, optionally, to maximize effectiveness, efficiency, safety, and comfort when inserted within the uterus of a subject). In some embodiments, the element can be ergonomic by accommodating the shape and environment of the uterus. The core and / or shell of the element can be sized to be ergonomic to provide desired properties of the element. The element, e.g., core and / or shell, can have smooth, oval, or rounded edges. The element, e.g., core and / or shell, can be sized to prohibit, limit, or reduce deformation or perforation of the endometrium. The element, e.g., core and / or shell, can be sized to reduce the likelihood of side effects associated with insertion, e.g., discomfort, pain, bleeding (e.g., excessive bleeding), cramping, or inflammation. In some embodiments, the element is ovoid (e.g., has a rounded and slightly elongated profile or shape, like the profile or shape of an egg; oval; spheroid configuration).

[0075] Each element 10 can have a length between about 1 mm to about 100 mm, for example, between 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 less than 10 mm.

[0076] Each element 10 can have a width between about 1 mm to about 30 mm, for example, between about 1 mm to 15 mm, 1 mm to 10 mm, or 2 mm to 6 mm. In exemplary embodiments, for example, for use in humans, the elements can have a width capable of passing through a human cervix for placement within the uterine cavity. Exemplary elements can have a width between 3 mm to 4.5 mm. In some embodiments, the elements can have a width capable of passing through a catheter for implantation into the uterine cavity. Exemplary elements can have a width less than 4.5 mm, for example, 3 mm to 4.4 mm, 3 mm to 4.2 mm, or 3 mm to 4.0 mm.

[0077] Each element can have a mass of 0.1 g to 100 g, for example, 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. Three elements together 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 having a polymeric shell can have a mass of about 0.1 to 0.3 g. Three elements together having a polymeric shell can have a mass of about 0.6 g to 0.8 g.

[0078] The dimensions of the elements can be designed to fit a target subject, for example, to pass through the cervix of the target subject and fit within the uterine cavity of the target subject. As disclosed herein, the uterine cavity can refer to the space inside the uterus, within the opposing anterior and posterior moist mucosa endometrium and myometrium muscle. In certain embodiments, the dimensions of the elements 10 can be designed to fit a primate. For primates (e.g., humans), the elements can have a length of about 1 mm to about 10 mm, for example, about 7 mm to about 8.5 mm, and a width (or diameter) of about 2 mm to about 6 mm, for example, about 3 mm to about 3.5 mm, about 3.5 mm to about 4 mm, or about 4 mm to about 5 mm.

[0079] The magnetic core 11 of the element 10 can be formed of or include a magnetic material. Exemplary magnetic materials include iron (or ore, alloy, or other material) having ordered constituent atoms such that the material exhibits magnetism, e.g., attracting other ferrous objects or aligning itself in an external magnetic field. For example, the core 11 can be formed of or include a magnetized material (referred to as 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, e.g., highly attractive neodymium) and naturally occurring minerals such as lodestone. In some embodiments, the element can be substantially free of nickel.

[0080] The element 10 can include an optional shell 12 external to the magnetic core 11. The shell 12 can be formed of an inert material. The shell 12 can protect the magnetic core 11 from structural damage, e.g., breakage, shattering, fragmentation, corrosion, or any other structural damage. For example, neodymium cores can be prone to breakage. Multiple neodymium cores can break if impacted together. The shell can protect the neodymium core from breakage.

[0081] 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., between 0.1 mm and 0.5 mm, e.g., about 0.25 mm.

[0082] The shell thickness can vary based on the core or element geometry. In some embodiments, the shell 12 can have a variable thickness. For example, the shell 12 can have a body thickness, an edge thickness, and / or an end thickness that can each be independently selected. The body portion of the shell can refer to the shell covering the lateral sides of the magnetic core, or the side 12a as shown. Figure 1A The edge portion of the shell can refer to the shell covering the edge portions of the magnetic core, or the side 12b as shown. Figure 1A The end side of the shell can refer to the shell covering the ends of the magnetic core, or the side 12c as shown. Figure 1A The shell 12 thickness can be defined as the dimension between the outer surfaces of the sides 12a, 12b, and 12c as shown, respectively, relative to the associated core surfaces of the sides 11a, 11b, 11c as shown. Figure 1A The shell 12 thickness can be defined as the dimension between the outer surfaces of the sides 12a, 12b, and 12c as shown, respectively, relative to the associated core surfaces of the sides 11a, 11b, 11c as shown. Figure 1B The shell 12 thickness can be defined as the dimension between the outer surfaces of the sides 12a, 12b, and 12c as shown, respectively, relative to the associated core surfaces of the sides 11a, 11b, 11c as shown.

[0083] The shell thickness can be selected to enable the plurality of elements to be magnetically assembled into a selected configuration, for example, by introducing a space between the magnetic core and the ends, edges, and outer 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 edge side 12b to the thickness of the body side 12a of the shell can be between 1 : 1 and 1 :5, for example, between 1 : 1 and 1 :2, between 1 :2 and 1 :3, between 1 :3 and 1 :4, or between 1 :4 and 1 :5. In some embodiments, the thickness of the end side 12c can be greater than the thickness of the body side 12a. The ratio of the thickness of the end side 12c to the thickness of the body side 12a of the shell can be between 10: 1 and 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 the uterine implant element is deployed in the uterine cavity. For example, the diameter of a triad configuration can be selected by controlling the thickness of the edge side 12b of the element 10.

[0084] The shell can have an edge side 12b thickness (thickness B) between 0.05 mm and 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 shell can have a body side 12a thickness (thickness A) of 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 shell can have an end side 12c thickness (thickness C) between 0.25 mm and 1.5 mm, for example, 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 end portion of the shell can be dome shaped. In such embodiments, the end side 12c thickness can refer to the thickness of the shell at the center of the dome. In other embodiments, the end of the shell can be truncated. In such embodiments, the end side 12c thickness can refer to the thickness of the shell at the center of the truncated side.

[0085] Figure 8 A cross-sectional view of an element shown in diagrammatic representation of a magnetic flux pattern, indicating a magnetically charged inner core 11. As Figure 8As shown in the exemplary embodiment, the magnetic flux is symmetrically oriented around the center of core 11, a typical feature of an axially charged body. The magnetic flux of an axially charged body flows outward from one end, referred to as the north pole of the magnet, toward and back to the opposite end, referred to as the south pole of the magnet, and circulates continuously through the core. The magnetic flux typically flows over the axial end surfaces of the magnetic body, including the peripheral edges. The magnetic flux also typically flows uninterruptedly over an inert material. Thus, as... Figure 8 As shown in the exemplary embodiment, magnetic flux flows through the inert housing 12 at both ends of the axially charged magnetic core 11.

[0086] The elements disclosed herein may have a core comprising a north pole at a first end and a south pole at the opposite end. Typically, the north (N) and south (S) poles of a magnetically charged body will be attracted. The north pole generally repels the north pole. Similarly, the south pole generally repels the south pole. Increasing the distance between the north and south ends of two opposing magnets will generally decrease the magnetic attraction, typically exponentially with respect to the increased distance. Conversely, bringing the north and south ends of two opposing magnetically charged bodies closer together (reducing the distance) will generally increase the magnetic attraction, typically exponentially with respect to the reduced distance. Therefore, elements can be designed (e.g., with a dimensionally defined core and / or shell) to have a selected magnetic force between them when positioned nearby, thereby facilitating a desired configuration for a given number of elements through their magnetic attraction to each other.

[0087] refer to Figure 1C The components can have a core and a housing, their dimensions designed to self-assemble into a triplet structure when the three components are brought close together. For example... Figure 1C As shown, the exemplary element 10 has a minimum housing thickness (thickness B) on side 12b, a medium thickness (thickness A) on side 12a, and a maximum thickness (thickness C, which refers to the thickness of the housing and the void space) on side 12c. It should be understood that the edge side 12b and end side 12c generally refer to the sides on the two halves of the element 10; however, the thickness of each side can be chosen independently. In some embodiments, such as Figure 1C As shown, the dimensions between the outer surfaces of sides 12a, 12b, and 12c and their respective core surfaces of sides 11a, 11b, and 11c may include void spaces and shell thickness, for example, as per the description of... Figure 1Cof the thickness C as shown. Thus, in some embodiments, the element can include a void space, inert filler, or gap between the magnetic core 11 and the shell 12 to accommodate a tolerance fit between the physical portion of the shell 12 and the encapsulated inner core 11. The shell and void space, inert filler, and / or clearance gap can form a total thickness (providing a dimension between an outer surface of the shell and an associated core surface) of between 0.05 mm and 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).

[0088] In one example embodiment, as shown in FIG. 1, three elements 10 are brought into proximity with one another, each element 10 having an axially charged magnetic core 11. Opposite poles (N / S) attract to self-arrange the elements. By designing the end side 12c to have a maximum thickness and the edge side 12b to have a minimum thickness, the elements 10 will generally favor self-assembly by engaging the edges 12b of two elements 10 ("bevel to bevel"). Thus, by selecting the shell thickness, the elements 10 can be designed to favor self-assembly into a selected configuration, such as a triad configuration. The shell thickness can also be selected or designed to favor self-assembly of the elements 10 into a generally linear configuration, for example, when constrained within a catheter for insertion and / or retrieval. Figure 1C

[0089] The shell can be formed of or include an inert material. In particular, the shell can be formed of a high coercivity material, for example, a material that resists degradation, for example, by contact with tissue. The shell can be a polymeric material. The shell can be a non-toxic and physiologically acceptable material, such as polyTeflon® silicone, polyethylene, polypropylene, polyether ether ketone (PEEK), or ethylene vinyl acetate (EVA) elastomer. Other shell materials, such as any shell material suitable for intrauterine use available to one of ordinary skill in the art, can be used with the elements disclosed herein.

[0090] In some embodiments, the element 10 can include an adhesive layer 15, as shown in FIG. 2. The adhesive layer 15 can be located between the magnetic core 11 and the shell 12. The shell 12 can protect against oxidative corrosion of the magnetic core 11. The adhesive layer 15 can be provided to improve surface properties of the core 11. The adhesive layer 15 can have a nominal thickness, for example, about or less than 0.1 mm, between 0.1 mm and 0.01 mm, or less than 0.01 mm. Figures 2A-2C In some embodiments, the element 10 can include an adhesive layer 15, as shown in FIG. 2. The adhesive layer 15 can be located between the magnetic core 11 and the shell 12. The shell 12 can protect against oxidative corrosion of the magnetic core 11. The adhesive layer 15 can be provided to improve surface properties of the core 11. The adhesive layer 15 can have a nominal thickness, for example, about or less than 0.1 mm, between 0.1 mm and 0.01 mm, or less than 0.01 mm.

[0091] Figure 2A ​​In exemplary embodiments of the present application, the inner magnetic core 11 can be encapsulated within an oval-shaped shell 12. A coating 13 (e.g., an anti-fertility agent coating or other coating) can be on the outside of the shell 12. In Figure 2B In exemplary embodiments of the present application, the inner magnetic core 11 can be encapsulated within an oval-shaped shell 12. If present, the anti-fertility agent can be part of the shell 12 layer. In Figure 2C In exemplary embodiments of the present application, the magnetic core 11 can be substantially oval-shaped. The magnetic core 11 can be encased within a thin shell 12. As shown in Figure 2B In exemplary embodiments of the present application, Figure 2C The element 10 of the present application can also include an anti-fertility agent as part of the shell 12.

[0092] In some embodiments, the uterine implant element can be free of anti-fertility agents. In some embodiments, the uterine implant element can be free of hormonal anti-fertility agents. The element can be free of cytotoxic anti-fertility agents.

[0093] In some embodiments, the element can include a coating, e.g., an anti-fertility agent coating. The coating can be an outer layer 13 of the element 10 (e.g., as shown in Figure 2A ). The coating can be embedded in the shell 12, e.g., as shown in Figures 2B-2C In some embodiments, the anti-fertility agent can be released from the shell 12. In such embodiments, the shell can be formed of an absorbent material, e.g., having a microstructure, to provide a time-controlled release of the anti-fertility agent.

[0094] The coating 13, e.g., an anti-fertility agent coating or other coating, can be applied, e.g., by electrostatic spraying, electroplating, electroless plating, ion deposition, or other methods. The coating 13 can be positioned on the outside of the magnetic core 11, e.g., on the outer surface of the core 11, on the outer surface of the adhesive 15, or on the outer surface of the shell 12. The anti-fertility agent coating 13 or anti-fertility agent embedded within and leaching from the shell 12 can be a sustained release agent and / or an extended release agent. The anti-fertility agent coating 13 and / or shell 12 can be designed to provide a predetermined release profile of the anti-fertility agent. For example, the coating 13 and / or shell 12 can be designed to provide release of a therapeutic amount of the anti-fertility agent over a period of 12, 18, 24, 30, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 months or more. The anti-fertility agent can be a hormonal agent, a cytotoxic agent, or a combination thereof.

[0095] The anti-fertility agent can be a substantially non-releasing agent. In other embodiments, the anti-fertility agent can be a sustained release agent. Each element can have 400 mm 2 or less of the anti-fertility agent, e.g., 300 mm 2 or less, 200 mm 2 or less, 150 mm 2or less, 100 mm 2 or less, 75 mm 2 or less, or 50 mm 2 or less. An IUD system (e.g., formed from more than one element) can have 500 mm 2 or less of a birth control agent, e.g., 400 mm 2 or less, 300 mm 2 or less, 200 mm 2 or less, 150 mm 2 or less, 100 mm 2 or less, or 75 mm 2 or less. An IUD system (e.g., formed from more than one element) can have 400 mm 2 to 500 mm 2 , 300 mm 2 to 400 mm 2 , 200 mm 2 to 300 mm 2 , or 100 mm 2 to 200 mm 2 of a birth control agent. In certain example embodiments, e.g., for use with a human subject, the total active surface area of the birth control agent can generally range between 150 mm 2 and 400 mm 2 , e.g., between 175 mm 2 and 380 mm 2 .

[0096] In some embodiments, the element is permeable so as to release the birth control agent at a low rate. The element can release a therapeutically effective amount of the birth control agent when inserted into the uterus. The therapeutically effective amount can be a contraceptive and / or fertility inhibiting amount. The therapeutically effective amount can be an amount effective to provide treatment or prevention of uterine disease, disorder, or symptom thereof. The element can include a therapeutically effective amount of the birth control agent, e.g., embedded in a shell or as a stand-alone layer.

[0097] The birth control agent can be a hormonal agent. Example contraceptive birth control agents include a progestin or a progestational hormone, e.g., a progestin. The therapeutic amount of the birth control agent in each element can be between 1 mg and 60 mg, e.g., between 1 mg and 3 mg, between 3 mg and 5 mg, between 5 mg and 7 mg, between 7 mg and 10 mg, between 10 mg and 20 mg, between 20 mg and 30 mg, between 30 mg and 40 mg, between 40 mg and 50 mg, or between 50 mg and 60 mg.

[0098] In some embodiments, the element is substantially free of a hormone agent. For example, in some embodiments, the element is substantially free of progesterone, or progestin, such as progestin.

[0099] The antifertility agent can be a cytotoxic agent. One exemplary cytotoxic agent is copper. One exemplary cytotoxic agent is nonoxynol-9 (N-9).

[0100] The element 10 can contain protrusions, such as rings or ridges 14 (as shown), on the outer surface of the element 10 that contain a cytotoxic agent. Figure 1A The element 10 or the housing 12 can contain cytotoxic agent microparticles. At least a portion or the entire outer surface of the element 10 or the housing 12 can be or contain a cytotoxic agent.

[0101] In some embodiments, the element 10 can have a smooth or substantially smooth outer surface (as shown). Figure 11 The smooth or substantially smooth outer surface can be an antifertility agent outer surface, such as a copper surface. In other embodiments, the element 10 can have one or more surface modifications 14, such as rings or ridges (as shown). Figure 1A One exemplary surface modification is a protrusion, as described above. Another exemplary surface modification is an indentation. Additionally or alternatively, the element 10 can have a textured surface. The surface modifications 14 can be or include, for example, dimples, undulations, indentations, protrusions, knuckles, textures, rings, ridges, or any other three-dimensional feature.

[0102] In certain exemplary embodiments, the protrusions or indentations can be elongated. The surface modifications can have a width of between about 0.1 mm and 0.5 mm, such as between about 0.2 mm and 0.4 mm, or about 0.3 mm. The surface modifications 14 can be longitudinal (across at least a portion of the length of the body of the element), transverse (across at least a portion of the width of the body of the element), or a combination thereof.

[0103] The surface modifications can contain or be formed of an antifertility agent. The surface modifications can be provided to increase the surface area of the antifertility agent, such as to increase the dosage of the antifertility agent.

[0104] In one exemplary embodiment, the element 10 can have a smooth outer copper surface (as shown). Figure 11 A housing 12, such as a copper housing, that can include an antifertility agent can be formed by laser welding a plurality of housing portions together. In Figure 11In exemplary embodiments of the housing 12 is formed by laser welding a top housing portion to a bottom housing portion. Thus, the element 10 can include a laser weld 17. The joint 17 can be vertical, horizontal, or any other orientation. In some embodiments, the element 10 can include more than one joint 17. The joint 17 can have a thickness selected to be minimal (resulting in negligible reduction of surface area of the housing 12).

[0105] In some embodiments, only one element 10 is inserted into the uterus of a subject. In other embodiments, more than one element 10 is inserted into the uterus of a subject 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 uterus of a subject to form an IUD system. When more than one element 10 is inserted, each element 10 can be smaller (as compared to using only one element) because the multiple elements 10 will self-assemble or arrange into a larger IUD system internally (in the uterus) by magnetic force. The north pole of the magnetic core 11 of one element 10 can attract the opposite south pole of the magnetic core 11 of another element 10 to assemble the multiple elements 10 together into a larger configuration that resists expulsion from the uterus. The multiple elements 10 can conformingly abut, for example, to form a stable connected tri-lobal, circular, or coiled configuration. The elements can generally assemble or arrange into a lower energy configuration.

[0106] In some embodiments, one element can form an IUD system. One exemplary element 100 having a total length of at least two, three, or more elements 10 (as described previously, for example, at least 3 mm to 30 mm) can be used to form an IUD system (as described previously, for example, a tri-lobal, circular, or coiled configuration). Figure 6 The element 100 can have a flexible or semi-flexible body. The element 100 can have a magnetic core with a north pole and a south pole or multiple magnetic cores arranged to locate a north pole of a first magnetic core and a south pole of a second magnetic core at opposite ends as described previously. The north pole can attract the south pole to assemble the element 100 into a configuration that resists expulsion from the uterus, for example, a circular or coiled configuration.

[0107] In certain embodiments, a single element IUD system as shown in Figure 6 may be designed to assemble (for example, into a circular or coiled configuration) by a spring-loaded mechanism. The element 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 opposite ends of the element 100.

[0108] Thus, while the present disclosure can generally relate to multiple elements, it should be understood that a single element having a flexible body of similar dimensions can also be used, for example, having a similar width and total length as the multiple elements.

[0109] Thus, an IUD system can include an element having a length of 30 mm or less, e.g., 3 mm to 30 mm, that includes a magnetic core and a coating external to 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 a south pole. The magnetic core can be formed of a north pole magnetic core and a south pole magnetic core. The dimensions of the magnetic core can be designed to assemble the element into a configuration that resists expulsion from the uterus of a subject.

[0110] The one or more elements can generally be independent of one another. For example, the one or more elements can be free of any connecting wires or filaments. However, in some embodiments, if more than one element is utilized in the IUD system, the elements can be threaded together with a filament (e.g., a monofilament or tail) or any other connector to one another. In some embodiments, the elements threaded together or connected to one another can still be free of a tail. Thus, in some embodiments, threading or other connectors can only be utilized between adjacent elements.

[0111] Figure 9 An exemplary IUD system is shown having three elements 10 connected by two filaments 18a, 18b, each filament 18a, 18b extending between two adjacent elements 10. The first element and the last element are not joined by a filament. Figure 9 The exemplary elements 10 shown in FIG. 1 are free of a tail. The first element and the last element can each include a magnetic core that enables the threaded elements to assemble into a configuration that resists expulsion from the uterus. The magnetic core of the first element can be or include a north pole, while the magnetic core of the last element can be or include a south pole. The central element (or any element positioned between the first element and the last element) can be non-magnetic. In other embodiments, the central element or any element positioned between the first element and the last element can also include a magnetic core. Any combination of magnetic and non-magnetic elements can be used.

[0112] Figure 10 An exemplary IUD system is shown, such as Figure 9 An IUD system is shown in FIG. 2 having a graphical representation of a magnetic flux pattern. Figure 10 An exemplary IUD system of FIG. 1 includes two magnetic elements 10 at opposite ends of the system, with a non-magnetic element 21 positioned between the magnetic elements 10. Figure 10 The magnetic flux of each of the elements 10 of the system of FIG. 1 is symmetrically oriented about the center of each magnetic core 11, as shown in FIG. 2. Figure 8 The single axial charge body of FIG. 1 is shown. As shown in FIG. 2, the magnetic flux of the single axial charge body is symmetrically oriented about the center of the magnetic core 11. Figure 10 As shown in FIG. 3, an IUD system having two magnetic elements 10 and a non-magnetic element 21 can self-assemble into a triad configuration by magnetic force.

[0113] The connecting lines or filaments can be flexible to enable the elements to be assembled into an axial or generally aligned configuration. The connecting lines or filaments can have a selected length to allow the elements to be assembled into a desired configuration, such as a triad configuration. The lines or filaments can be secured to the outer surface of the elements. In certain embodiments, the connecting lines or filaments can be integrally molded with the housing, such as injection molded.

[0114] In some embodiments, the connector can extend as a longer filament or tail from one element for retrieval of the IUD system. The filament can generally be formed of or coated with an inert material. The filament material can be selected to provide a desired structural stability in the uterine cavity. Exemplary filament materials include nitinol (e.g., nitinol wire), nylon (e.g., nylon suture), polypropylene, polyethylene, or polyether (e.g., polyether ether ketone (PEEK)), etc. In some embodiments, the elements and / or the IUD system can be substantially free of nitinol.

[0115] The magnetic core 11 can be sized to assemble the plurality of elements into a configuration that resists expulsion from the subject's uterus. The configuration can be a lowest energy configuration of the magnetic assembly. In certain exemplary embodiments, the configuration is a triad or triangular configuration.

[0116] Each element 10 having a magnetic core 11 can have at least one of a north pole and a south pole, optionally both a north pole and a south pole at opposite ends. The magnetic core 11 can be an axially charged magnetic core (charged about a central axis of the magnetic core). The plurality of elements 10 can be assembled by attracting ends of alternative elements 10 having opposite charges or polarities. Further, the plurality of elements 10 can be assembled by repelling ends of alternative elements 10 having the same charge or polarity. In one exemplary embodiment, the lower energy configuration (for three elements) is a triad configuration (N-S-N or S-N-S) Figure 1B 、 1C , 1E). In other embodiments, the lower energy configuration (for two or more elements) is a raft configuration. In the raft configuration, the plurality of elements 10 are aligned laterally in a parallel array. The configuration can be flexible and / or variable, e.g., conforming to natural movements of surrounding tissue.

[0117] The magnetic core 11 can be, for example, cylindrical, polygonal (e.g., rectangular (e.g., cubical)), triangular, pentagonal, hexagonal, or faceted. Thus, the core can have a circular, round, oval, polygonal (e.g., rectangular, square, triangular, pentagonal, hexagonal), or faceted cross-section. In certain example embodiments, the magnetic core 11 can have a circular cross-section. The circular cross-section can be selected to achieve maximum magnetic force per volume of the element 10, which can be beneficial in providing the element 10 that is able to pass through a minimum size inner lumen of a cylindrical conduit (of an inserter or retriever). Thus, in certain embodiments, the element 10 having a circular cross-section can provide maximum magnetic force while minimizing discomfort to the patient during insertion or retrieval.

[0118] In some embodiments, the core 11 can be ovoid or oval shaped, e.g., having a circular and elongated profile or shape, like the profile or shape of an oval egg.

[0119] The core can be formed of one or more magnets. In some embodiments, the core can be formed of a single magnet having a north pole and a south pole, optionally, with the north pole on one end and the south pole on the opposite end Figure 7 ). In other embodiments, the core can include or be formed of two or more magnets Figure 6 ), each magnet having at least one north pole (11n) on one end of the element and at least one south pole (11s) on the opposite end of the element. The two or more magnets can be positioned such that the opposite poles 11n, 11s of the respective magnets come together to self-assemble the element into the desired configuration. In Figure 7 example embodiments, a magnetic body is positioned on opposite ends of a central axis of the element 100, each magnetic body having opposite magnetic poles 11n, 11s on a distal end of the magnetic body, respectively, such that the magnetic poles 11n, 11s come together to self-assemble the element 100 into a coiled or circular configuration.

[0120] The magnetic core 11 can have a generally blunt or rounded edge, e.g., to form an ellipsoidal structure. In certain embodiments, the magnetic core 11 can have a beveled edge 11b to induce the three devices to self-assemble into a triad configuration. The beveled edge 11b can be formed by an oblique angle 11d, as shown in Figure 4 The beveled edge 11b can additionally facilitate including a larger or maximum size magnetic core 11 within the oval element 10, which can be used to provide the element with a greater magnetic force per volume. Thus, the size of the magnetic core (e.g., the length of the sides 11a, 11b, 11c) and the cross-sectional geometry and the housing (e.g., the thickness of the sides 12a, 12b, 12c) Figures 1A-1B) can be selected or designed to cause self-assembly after deployment and maintain sufficient magnetic force to resist expulsion. In certain embodiments, the dimensions of the shell, such as the thickness of the side faces 12a, 12b, 12c, can be selected to provide sufficient magnetic force to form a stable IUD system that conforms to the uterine cavity, adapting to periodic changes in response to natural movements of the uterine tissue.

[0121] The edge side 1 lb of the core 11 can be defined as the side of the core 11 that joins the lateral side 11a 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 can be defined as the dimension extending from the side 11a to the opposite side (optionally the diameter of the magnetic core having a circular cross-section). The length of the core 11 can be defined as the dimension extending from one distal end 11c to the opposite distal end.

[0122] The core 11 can have an edge side 1 lb on either end or both ends. The edge side 1 lb can extend around the perimeter of the core 11, for example, around the circumference of the cross-section of the core 11. In some embodiments, the edge side 1 lb can be beveled. A beveled edge can be defined as an edge that forms an angle between the distal end 11c and the edge side 1 lb. 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-section area) and the edge side 1 lb, as shown in Figure 4 The bevel angle can be about 5°-50°, for example, about 5°-15°, 15°-30°, 20°-40°, 30°-45°, or 30°-50°. In certain exemplary embodiments, the bevel angle can be about 30°.

[0123] In one exemplary embodiment, as shown in the figure of Figure 1D , a bevel angle of 30° forms a circumferential 60° inclusive angle that forms a tapered surface around both ends of the magnetic core 11 having a circular cross-section. When the magnetic core 11 is encapsulated within an elliptical shell 12 to form the element 10, the tapered end side 12c of the elliptical shell 12 will generally follow the tapered surface of the magnetic core 11.

[0124] In one exemplary embodiment, when a set of three elements 10 are brought together, as shown in Figure 1E , each element 10 contains a core 11 having a 30° bevel angle that forms a 60° inclusive end angle, the tapered surfaces of each magnetic core 11 will generally be induced to self-assemble into a magnetically attractive triad configuration or conformal triangular structure ( Figure 1E ). The edge sides 1 lb of two adjacent cores 11 will generally be separated by the sum of the edge side 12b thicknesses ( Figure 1C ). Thus, when Figure 1EWhen the exemplary element 10 is introduced into the uterine cavity, the three magnetic elements 10 are induced to form a magnetic connection structure effective to resist expulsion from the uterine cavity.

[0125] In some embodiments, the dimensions of the core can be set to have a ratio of lateral side 11a length to edge side 11b length of about 1 : 1 to 5: 1, for example, 1 : 1 to 2: 1, 2: 1 to 3: 1, 3: 1 to 4: 1, or 4: 1 to 5: 1. The core can have a lateral side 11a length of 0.5 mm to 10 mm, for example, 0.5 mm to 1 mm, 1 mm to 3 mm, 1 mm to 5 mm, or 5 mm to 10 mm. The core can have an edge side 11b length of 0.1 mm to 5 mm, for example, 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 dimensions of the core can be designed to have a distal end 11c length of about 1 mm to 6 mm, for example, 1 mm to 2 mm, 1 mm to 3 mm, 2 mm to 4 mm, 3 mm to 5 mm, or 4 mm to 6 mm.

[0126] 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.

[0127] The dimensions of the magnetic core 11 can be designed to provide a selected magnetic attractive force between two elements, for example, between two elements at opposite magnetic poles. 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 dimensions of the core 11 can be designed to provide a magnetic force of about 0.1-22 N, for example, a magnetic force of 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. The dimensions of the core that can be selected to provide the desired magnetic force include the length and width (or diameter) of the core, the geometry of the cross-section of the core, and the geometry of the edges of the core, for example, length and / or bevel angle. Additionally, the material of the core can be selected to provide the desired magnetic force.

[0128] Additionally, the dimensions of the housing 12 can be selected to provide a desired magnetic force. For example, the thickness of the housing can be selected to control the distance between two adjacent magnetic cores (e.g., two cores at two opposite magnetic poles in an IUD system, or more than two magnetic cores). In some embodiments, the housing 12 can have a thickness selected to position opposing magnetic cores at a distance of 0.25 mm - 1.0 mm from each other, such as 0.25 mm - 0.5 mm or 0.5 mm - 1.0 mm. In certain example embodiments, the thickness of the housing can be selected to position opposing magnetic cores no more than 0.5 mm from each other.

[0129] Additionally, the dimensions of the magnetic cores can be selected to provide a selected magnetic attraction between the element and the retrieval magnet. The dimensions of the magnetic cores can be designed to disassemble into multiple elements to move from a configuration that resists expulsion to a configuration that allows retrieval. The configuration that allows retrieval can be, for example, an axial or generally aligned configuration. The dimensions of the magnetic cores can be designed to disassemble into a generally linearly connected configuration, such as an axial configuration or a linear string-like configuration, when in close proximity to a magnetic retrieval device.

[0130] In certain embodiments, 1-4 elements are used to form the IUD system. The size and number can depend on the species (human or non-human mammal). For example, when multiple elements are used, each element can individually be about 2 mm to about 30 mm long, such as about 2 mm to about 15 mm long or about 2 mm to about 10 mm long, and about 2 mm to about 15 mm wide, such as about 2 mm to about 10 mm wide or about 2 mm to about 6 mm wide or about 2 mm to about 4 mm wide. The dimensions can be selected to allow the element to be placed in the uterus at any stage 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 rate. The dimensions can be selected to allow the element to be inserted through the cervix of the subject, such as more easily and less painfully inserted into the uterus of the subject.

[0131] In some embodiments, the health, pregnant / non-pregnant status, and / or reproductive system size of the subject can be determined prior to insertion of the IUD system. For example, a two- or three-dimensional ultrasound of the uterus can be performed to determine the health, pregnant / non-pregnant status, and / or size of the subject to accept or reject the subject for use of the IUD system. Generally, a minimum precaution can be to establish that the subject is non-pregnant prior to introduction of the IUD system. In some embodiments, the health, pregnant / non-pregnant status, and / or size of the reproductive system of the subject can be determined to assist in selecting the size and / or number of elements to use. The size of the reproductive system of the subject can include, for example, anatomical geometry, anatomical dimensions, and / or anatomical positioning (e.g., normal or abnormal positioning of the uterus).

[0132] The methods can include delivering a plurality of 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 plurality of elements in the subject's uterus. In one particular embodiment, the delivery device can be specifically designed to accompany the IUD elements described herein. In some embodiments, the inserter can include a catheter sized to deliver the elements through the cervical canal to the uterine cavity of the subject.

[0133] The methods can include inserting the inserter through the cervical canal of the subject and placing the implant elements in the uterine cavity of the subject prior to removing the inserter from the subject. The delivery device can be sized for use with a target subject. For example, the delivery device can be sized for use with a human subject. The insertion can be performed self or assisted (e.g., by a trained practitioner and / or medical professional). The catheter can be sized to deliver the elements to the uterine cavity of the subject without use of a balloon (e.g., a dilation balloon). Thus, in some embodiments, the inserter can be devoid of any expandable or inflatable components, such as a balloon.

[0134] The methods can include delivering the plurality of elements individually. For example, the inserter can be sized to deliver the plurality of elements individually. In other embodiments, the methods can include delivering the plurality of elements sequentially or simultaneously. For example, the inserter can be sized to deliver the plurality of elements simultaneously, optionally in a sequential (axial or generally aligned) arrangement. In certain embodiments, the inserter can include a catheter sized to deliver the plurality of elements in a sequential, axial, or generally aligned arrangement.

[0135] The methods can include retrieving the plurality of uterine implant elements from the subject using a retrieval device (also referred to herein as a "retriever") sized to retrieve the plurality of elements from the subject's uterus. In one particular embodiment, the retrieval device can be specifically designed to accompany the IUD elements described herein.

[0136] The methods can include inserting the retrieval device through the cervical canal of the subject to reach the uterine cavity of the subject while collecting at least one element and optionally a plurality of elements, and removing the retrieval device 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. The retrieval can be performed self or assisted. The catheter can be sized to retrieve the elements from the uterine cavity of the subject without use of a balloon (e.g., a dilation balloon). Thus, in some embodiments, the retriever can be devoid of any expandable or inflatable components, such as a balloon.

[0137] The retriever can generally include a magnetic end that effectively attracts the elements. Upon bringing the magnetic end into close proximity with the elements, the plurality of elements can be induced to disassemble into an axial or generally aligned configuration that allows retrieval with the retrieval device from the subject's uterus. The magnetic end can be positioned on a distal end of a rod or elongated structure sized to retrieve the plurality of 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 include a catheter having a magnetic end sized to retrieve the plurality of elements in a sequential, axial, or generally aligned arrangement.

[0138] The method can include retrieving the plurality of elements individually. For example, the retriever can be sized to retrieve the plurality of elements individually. In other embodiments, the method can include retrieving the plurality of elements sequentially or simultaneously. For example, the retriever can be sized to retrieve the plurality of elements simultaneously, optionally in a sequential (axial or aligned) arrangement.

[0139] In certain embodiments, retrieval can also be performed by a filament or tail, such as a length of filament or string connected to and / or interconnecting the plurality of elements (similar to removal of a traditional contraceptive device), optionally threading the device together. However, in other embodiments, the elements are free of a tail string and / or any filament or string.

[0140] The IUD elements 10 disclosed herein can be administered (e.g., delivered) to and / or retrieved from a subject's uterus with reduced pain. After administration or retrieval of the IUD elements 10, the subject can be asked to rate a pain score on a numerical rating scale (NRS). The NRS is a verbal or written measurement of pain level on a scale of 0 to 10, where 0 represents no pain and 10 represents extreme pain. In some embodiments, the average or maximum NRS pain score for administration (e.g., delivery) of the IUD elements 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 elements 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.

[0141] In other embodiments, the subject can be asked to rate a pain score on a visual analog scale (VAS) after administration or retrieval of the IUD element 10. A VAS is a graphic rating scale that can utilize a line or series of drawings, such as cartoon faces, for the subject to select indicating the degree of pain level. For a line drawing, the first end of the line can represent no pain and the opposite end of the line can represent extreme pain. The subject can be asked to indicate the level of pain by identifying a point on the line. In some embodiments, the average or maximum VAS pain score for administration (e.g., delivery) of the IUD element 10 can be less than 100% on the line (e.g., less than the extreme end points of the line), such as less than 80% on the line, less than 75% on the line, less than 60% on the line, less than 50% on the line, less than 40% on the line, less than 25% on the line, or less than 20% on the line. In some embodiments, the average or maximum VAS pain score for retrieval of the IUD element 10 can be less than 100% on the line, such as less than 80% on the line, less than 75% on the line, less than 60% on the line, less than 50% on the line, less than 40% on the line, less than 25% on the line, or less than 20% on the line.

[0142] For a line drawing, the first end of the line can represent no pain and the opposite end of the line can represent extreme pain. The subject can be asked to indicate the level of pain by identifying a point on the line. In some embodiments, the average or maximum VAS pain score for administration (e.g., delivery) of the IUD element 10 can be less than 100% on the line (e.g., less than the extreme end points of the line), such as less than 80% on the line, less than 75% on the line, less than 60% on the line, less than 50% on the line, less than 40% on the line, less than 25% on the line, or less than 20% on the line. In some embodiments, the average or maximum VAS pain score for retrieval of the IUD element 10 can be less than 100% on the line, such as less than 80% on the line, less than 75% on the line, less than 60% on the line, less than 50% on the line, less than 40% on the line, less than 25% on the line, or less than 20% on the line.

[0143] According to one aspect, the present disclosure includes a method of providing and / or facilitating controlled contraception to a subject. The method can include delivering a plurality of uterine implant elements to the uterus of the subject. The plurality of elements can be delivered individually or simultaneously. Individual delivery can include, for example, delivering a single element with a single actuation of a delivery device. Simultaneous delivery can include, for example, delivering a plurality of elements with a single actuation of a delivery device.

[0144] According to one aspect, the present disclosure includes a method of treating or preventing and / or facilitating treatment or prevention of a uterine disease, disorder, or symptom thereof in a subject. The method can include delivering a plurality of uterine implant elements to the uterus of the subject. The plurality of elements can be delivered individually or simultaneously. Individual delivery can include, for example, delivering a single element with a single actuation of a delivery device. Simultaneous delivery can include, for example, delivering a plurality of elements with a single actuation of a delivery device.

[0145] Detection sensor

[0146] The method can include scanning the subject after insertion or retrieval to detect the IUD system. Detection of the elements can be performed by ultrasound or using a detection sensor. Exemplary detection sensors include a magnetic field detector, a gauss meter, or a metal detector.

[0147] The detection sensor can provide non-contact detection. The detection sensor can indicate detection of the device with a visual and / or audible alarm and / or by sending 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., from at least 2 inches, 4 inches, 6 inches, 8 inches, or 10 inches to 1 foot.

[0148] Embodiments

[0149] The function and advantages of these and other embodiments can be more readily understood by reference to the following examples. These examples are intended to be illustrative of the present application and are not intended to limit the scope of the present application.

[0150] Example 1: Magnetic force as a function of magnetic core geometry

[0151] A numerical simulation study was performed to evaluate the relative effectiveness of alternative magnetic core geometries assembled into different configurations. The magnetic force is a function of the magnetic material, core geometry, size, and assembly configuration. Three magnetic core geometries were tested, including: cylindrical cores (1), cores with slanted edges having a circular cross-section (2), and solid ellipsoidal magnet elements (without a shell).

[0152] The magnetic force of each configuration was evaluated when assembled into the following structures: a triad configuration, a lateral arrangement configuration (magnets side-to-side aligned), and an axial arrangement configuration (magnets end-to-end aligned). It should be noted that the dimensions of configurations (1) and (2) were designed to fit within the ellipsoidal shell of size (3), i.e., the maximum size delivered through the lumen of a specific size catheter. The data is shown in the table at Figure 5 .

[0153] As shown in Figure 5 , the ellipsoidal magnets (3) had the greatest magnetic force in each of the three configurations, but had a higher tendency to hold the assembly of the triad configuration together (when inserted into the uterus of a subject). The cylindrical cores (1) preferred assembly into the triad configuration because the magnetic force in that configuration was stronger than in the lateral or axial arrangement configurations. The cores with slanted edges (2) also preferred assembly into the triad configuration and exhibited stronger magnetic force to hold the elements together, which was preferred. The cylindrical cores (1) had the weakest magnetic force in each configuration.

[0154] Figure 3A and Figure 3BThe shaded curve diagram is shown, indicating the preparation of the cylindrical core (1) ( Figure 3A ) and a larger diameter core with a circular cross-section and an inclined end (2) Figure 3B The relative attraction is visualized by comparing the two core geometries. The two core geometries have the same length. The two core geometries have the same diameter at each end. In each configuration, the cylindrical core (1) has the weakest magnetic force. The core (2) with the beveled ends exhibits a significantly stronger attraction (3.6 times) than the cylindrical core (1) in the triplet configuration. The shading plot ranking from red (strongest) > yellow > green > cyan > blue (weakest) indicates the relative range of the magnitude of the attraction. The red shading (1.0) is almost absent in the cylindrical core (1) plot. Figure 3A )middle.

[0155] Figure 3C and Figure 3D The overall geometry of the three elements 10 arranged in a triplet configuration is shown. Figure 3C and 3D The exemplary element 10 has a cylindrical magnetic core 11 with a sloping edge. Figure 3C Component 10 has a ratio Figure 3D The element 10 has a smaller edge thickness 12b (thickness B). For example... Figures 3C-3D As shown, by reducing the edge thickness 12b from 0.36 mm ( Figure 3C Reduced to 0.2 mm Figure 3D The diameter of the entire triplet structure can range from 10.63 mm. Figure 3C The diameter was reduced to 10.07 mm. Figure 3D Therefore, the element 10 with a smaller edge thickness 12b is arranged into a triplet structure with a smaller overall profile and a stronger magnetic attraction between the elements 10.

[0156] Example 2: A Preliminary Example of Providing a Method of Contraception

[0157] The frameless IUD system disclosed herein will be used to provide contraception to a subject. Specifically, three uterine implantable elements constituting the IUD system will be delivered to the subject's uterus using an accompanying processor (developed by 3Daughters, Fort Lauderdale, Florida) to provide contraception. The uterine implantable elements will have a magnetic core, the size of which is designed to assemble into a structure that adapts to the uterine environment and resists expulsion. In this example, the uterine implantable elements will have a magnetic core, the size of which is designed to employ a stable triplet configuration within the subject's uterus.

[0158] The uterine implant element will have the following dimensions:

[0159] a length of less than 10 mm (e.g., between 2.0 mm and 10 mm) and a width between 2.0 mm and 6.0 mm, e.g., sized to fit within a 4.0 mm or 4.4 mm outer diameter catheter;

[0160] The magnetic core of the uterine implant element will have a circular cross-sectional area and a beveled edge; and

[0161] The anti-fertility agent coating forming the shell that protectively surrounds the magnetic core will have a different thickness.

[0162] As provided by the shell, the element will generally be an ellipsoid shape. The dimensions of the shell will be designed such that three elements can self-assemble into a stable triad configuration upon administration, and disassemble into an axially aligned configuration for retrieval.

[0163] Traditional contraceptive devices with a frame (plastic (polyethylene)) T-shaped design cause painful insertion, occurrence of uterine perforation, expulsion from the uterus, and include a string required for removal from the uterus.

[0164] The frameless IUD system disclosed herein will include a plurality of uterine implant elements that conform and adapt to the uterine environment, provide an easier insertion process (with fewer steps, reducing or eliminating pain points), have a smooth outer dimension, and are structurally independent of one another. Thus, the frameless IUD system disclosed herein will provide contraception to a subject with reduced insertion pain, reduced (or eliminated) risk of expulsion (adaptation to the uterine environment), reduced (or eliminated) risk of uterine perforation, and does not require a string for removal.

[0165] Embodiment 3: Prophetic embodiment of a method of providing treatment or prevention of a uterine disease, disorder, or symptom thereof

[0166] The frameless IUD system as disclosed herein will be used to provide treatment or prevention of a uterine disease, disorder, or symptom thereof (such as abnormal uterine bleeding) to a subject. In particular, the three uterine implant elements that make up the IUD system will be delivered to the subject’s uterus with the accompanying handler (developed by 3Daughters, Inc. of Fort Lauderdale, FL) to provide the treatment or prevention. The uterine implant elements will have a magnetic core that is sized to assemble into a configuration that adapts to the uterine environment and resists expulsion. In this example, the uterine implant elements will have a magnetic core that is sized to adopt a stable triad configuration in the subject’s uterus.

[0167] The uterine implant elements will have the following dimensions:

[0168] a length of less than 10 mm (e.g., between 2.0 mm and 10 mm) and a width between 2.0 mm and 6.0 mm, e.g., dimensions designed to fit within a 4.0 mm or 4.4 mm outer diameter catheter;

[0169] The magnetic core of the uterine implant element will have a circular cross-sectional area and a beveled edge; and

[0170] The coating forming the shell (optionally a shell of inert material or a shell of an anti-fertility agent) protecting the magnetic core will have a different thickness.

[0171] As provided by the shell, the element is generally an ellipsoid shape. The dimensions of the shell will be designed such that three elements can self-assemble into a stable triad configuration upon administration and disassemble into an axially aligned configuration for retrieval.

[0172] Traditional intrauterine devices with a frame (plastic (polyethylene)) T-shaped design cause painful insertion, occurrence of uterine perforation, expulsion from the uterus, and include a string required for removal from the uterus.

[0173] The frameless IUD system disclosed herein will include a plurality of uterine implant elements that conform and adapt to the uterine environment, provide an easier insertion procedure (with fewer steps, reducing or eliminating pain points), have a smooth outer dimension, and are structurally independent of one another. Thus, the frameless IUD system disclosed herein will provide treatment or prevention of uterine disease, disorder, or symptom thereof to a subject while reducing insertion pain, reducing (or eliminating) the risk of expulsion (adaptation to the uterine environment), reducing (or eliminating) the risk of uterine perforation, and not requiring a string for removal.

[0174] The phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. As used herein, the term "plurality" refers to two or more items or components. The terms "comprising," "including," "carrying," "having," "containing," and "involving," whether in written description or claims or both, are open-ended terms, i.e., intended to mean "including but not limited to." Thus, use of these terms is meant to encompass the items listed thereafter, and equivalents thereof, as well as additional items. With respect to the claims, only the transitional phrases "consisting of and "consisting essentially of are closed terms, i.e., limiting, with the other transitional phrases, such as "comprising," "including," "carrying," "having," "containing," and "involving," being open terms, i.e., not limiting. The use of ordinal number terminology, such as "first," "second," "third," etc., with respect to a claim element does not admit a priority, precedence, or order of the claim element over another claim element, but is simply used to distinguish the claim element identified with that ordinal number terminology from another claim element having the same name but identified with different ordinal number terminology.

[0175] Having thus described several aspects of at least one embodiment, it is to be appreciated 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 replaced with any feature described in any other embodiment. Such alterations, modifications, and improvements are intended to be part of the disclosure, and are intended to be within the scope of the application. Accordingly, the foregoing description and drawings are by way of example only.

[0176] Those skilled in the art will appreciate that the parameters and configurations described herein are by way of example only, and that actual parameters and / or configurations will depend on the specific application in which the disclosed methods and materials are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, functional equivalents to the specific embodiments disclosed.

Claims

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 external to the magnetic core, the magnetic core sized to assemble the plurality of elements into a configuration that resists expulsion from a subject's uterus.

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

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

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

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

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

7. The IUD system of claim 4, wherein the coating is an anti-fertility agent coating, and the anti-fertility agent coating is embedded in the shell.

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

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

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

11. The IUD system of claim 1, wherein each element has a circular cross-sectional area having a diameter between 2.0 mm and 6.0 mm.

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

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

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

15. The IUD system of claim 1, wherein the magnetic core has a circular or beveled edge.

16. The IUD system of claim 1, wherein the coating is an anti-fertility agent coating, and the anti-fertility agent comprises a cytotoxic agent.

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

18. The IUD system of claim 17, wherein the antifertility agent coating has a copper surface area between 175 mm 2 and 380 mm 2 .

19. The IUD system of claim 1, wherein the coating is an anti-fertility agent coating, and the anti-fertility agent comprises a hormonal agent.

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

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

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

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

24. The IUD system of claim 1, wherein each of the plurality of elements is structurally independent of one another.

25. A method of providing controlled contraception or treatment or prevention of uterine disease, disorder, or symptoms thereof in a subject, the method comprising: delivering a plurality of elements to the subject's uterus, each element having a length of 10 mm or less, comprising a magnetic core and a coating external to the magnetic core, the magnetic core sized to assemble the plurality of elements into a configuration resistant to expulsion from the subject's uterus.

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

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

28. A method of facilitating controlled contraception or treatment or prevention of uterine disease, disorder, or symptoms thereof in a subject, the method comprising: providing a plurality of elements, each element having a length of 10 mm or less, comprising a magnetic core and a coating external to the magnetic core, the magnetic core sized to assemble the plurality of elements into a configuration resistant to expulsion from the subject's uterus; and providing instructions to deliver the plurality of elements to the subject's uterus.

29. A kit comprising: 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 external to the magnetic core; a delivery device sized to allow placement of the plurality of elements in a subject's uterus; and instructions for delivering the plurality of elements to the subject's uterus using the delivery device.

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

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