TECHNICAL FIELD

The present disclosure relates generally to long-acting reversible contraception systems, and more specifically to intrauterine systems. Furthermore, the present disclosure relates to kits comprising an intrauterine system and an inserter.

BACKGROUND

An intrauterine system (IUS) or an intrauterine device (IUD) is a commonly-used safe and low maintenance long-acting reversible contraception system. In the following, the abbreviation IUS is used, and covers both IUS's and IUD's. The proper functioning of the IUS depends on an accurate placement of the IUS in the uterus. The IUS is usually positioned into the uterus using an inserter. A conventional IUS requires an insertion tube of that is inserted through the cervix into the uterus during insertion. Accordingly, the conventional IUS requires an insertion tube of the inserter to have a proportionately large cross-section in order to accommodate such IUS. As a consequence, the cross-sectional diameter of what needs to pass through the cervix is the diameter of the capsule and twice the wall thickness of the insertion tube.

Furthermore, during insertion of a conventional IUS with its inserter, there exists a risk of uterus penetration during insertion. Indeed, if an unexperienced physician performs the insertion procedure or the dimensions of the uterus have been wrongly determined in the sounding step, the inserter may penetrate the uterine wall or even perforate it. It is assumed that the pain and discomfort caused by insertion procedure is caused by stretching of the cervix channel. Therefore, there exists a need to overcome the aforementioned drawbacks associated with the conventional IUS and its insertion process.

SUMMARY

The present disclosure seeks to provide an intrauterine system (IUS). The present disclosure also seeks to provide a kit comprising an IUS and an inserter. The present disclosure thus seeks to provide a solution to the existing problem of pain and discomfort experienced by a subject during the placement of the IUS, while at the same time providing an IUS that is suitable for use for as long periods as the conventional IUS's. It is also one object of the current invention to diminish the diameter of the parts which have to pass the cervix channel during the IUS insertion process.

It is a further object of the invention to provide a new IUS and its inserter which reduces the risk of uterus penetration during insertion.

An aim of the present disclosure is to provide a solution that overcomes at least partially the problems encountered in prior art, and to provide an effective IUS that is highly flexible to enhance patient acceptability, and provides a relatively more comfortable experience during the insertion of the IUS through the cervical canal and its final placement into the uterus, as compared to existing systems.

In one aspect, an embodiment of the present disclosure provides an intrauterine system comprising

- a frame having a first end, a second end, a length Lf defined as the distance between the first end and the second end;

- at least one sleeve having a first end, a second end, a length Ls defined as the distance between the first end and the second end, and arranged to movably surround a part of the frame; and - at least one capsule comprising a pharmaceutically active agent, having a first end, a second end, a length Lc defined as the distance between the first end and the second end, and arranged to surround the sleeve; wherein

- the length Ls is 5-50 % of the length Lf; and

- the length Lc is 5-50 % of the length Lf.

In another aspect, an embodiment of the present disclosure provides a kit comprising an intrauterine system and an inserter, wherein the inserter comprises

- a handle having a proximal end, a distal end and an opening;

- an inner tube having a proximal end and a distal end, its proximal end being connected to the distal end of the handle and its distal end being configured to cooperate with the intrauterine system;

- a measurement tube having a proximal end and a distal end, its proximal end being movably connected to the distal end of the handle, the measurement tube being movably arranged to surround the inner tube;

- a flange movably arranged around the measurement tube;

- a tip cover arranged to surround the distal end of the measurement tube;

- a plunger movably arranged inside the inner tube, having a proximal end and a distal end, and its distal end being configured to cooperate with the intrauterine system; and

- means for moving the plunger, arranged in the opening of the handle.

Embodiments of the present disclosure substantially eliminate or at least partially address the aforementioned problems in the prior art, and enable the disclosed IUS to be efficiently and conveniently insertable into the uterine cavity The disclosed IUS is also suitable for insertion without the need for any part of the inserter that has a larger cross-sectional diameter than the capsule to pass through the cervix, thus decreasing the diameter of what actually passes through cervix. The IUS is thus designed to be inserted using a different type of inserter, when compared to conventional IUS's.

Indeed, due to the special design of the IUS disclosed in this application, there is no need that the capsule which contains the active drug to be covered by an insertion tube during the insertion procedure. This results in a reduced cross-sectional diameter of the object which has to pass the cervix channel, which minimizes discomfort and pain during its insertion through the cervix, when compared to conventional IUS's. Additional aspects, advantages, features and objects of the present disclosure would be made apparent from the drawings and the detailed description of the illustrative embodiments construed in conjunction with the appended claims that follow.

It will be appreciated that features of the present disclosure are susceptible to being combined in various combinations without departing from the scope of the present disclosure as defined by the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the appended drawings. For the purpose of illustrating the present disclosure, exemplary constructions of the disclosure are shown in the drawings. However, the present disclosure is not limited to specific methods and instrumentalities disclosed herein. Moreover, those skilled in the art will understand that the drawings are not to scale. Wherever possible, like elements have been indicated by identical numbers.

Embodiments of the present disclosure will now be described, by way of example only, with reference to the following diagrams wherein: FIG. 1 is a schematic view of an intrauterine system (IUS), in accordance with an embodiment of the present disclosure;

FIG. 2 is a schematic view of the IUS of FIG. 1 in a loaded configuration, in accordance with an embodiment of the present disclosure; FIG. 3 is a cross-sectional view of the IUS of FIG. 1, in accordance with an embodiment of the present disclosure;

FIG. 4 is a schematic representation of an arrangement of a capsule on a sleeve with a trumpet-shaped enlargement, in accordance with an embodiment of the present disclosure; FIG. 5 is a schematic view of an IUS, in accordance with another embodiment of the present disclosure;

FIG. 6 is a cross-sectional view of the IUS of FIG. 5, in accordance with an embodiment of the present disclosure;

FIG. 7 is a cross-sectional view of an IUS, in accordance with yet another embodiment of the present disclosure;

FIG. 8 is a cross-sectional view of an IUS, in accordance with still another embodiment of the present disclosure;

FIG. 9 is a schematic view of an IUS, in accordance with yet another embodiment of the present disclosure; FIG. 10 is a schematic view of an IUS, in accordance with another embodiment of the present disclosure; and

FIGs. 11A and 11B collectively, illustrate various operational stages related to assembling of a sleeve and a capsule on a frame of an IUS, in accordance with various embodiments of the present disclosure. FIGs. 12A and 12B are perspective views of an inserter in an assembled and unassembled states, respectively, in accordance with an embodiment of the present disclosure; FIG. 12C illustrates an arrangement of a sledge, a plunger, and an inner tube of an inserter, in accordance with an embodiment of the present disclosure;

FIG. 12D illustrates an arrangement of a sledge within a handle of an inserter, in accordance with an embodiment of the present disclosure;

FIGs. 13A-13D illustrate different views of an exemplary implementation of a slider, in accordance with an embodiment of the present disclosure;

FIG. 14 is a perspective view of an exemplary inner tube, in accordance with an embodiment of the present disclosure; FIGs. 15A-15J illustrate different views of an inserter depicting various operational stages to position an IUS into a uterus, in accordance with various embodiments of the present disclosure;

FIG. 16A is a perspective view of an inserter, in accordance with another embodiment of the present disclosure; and FIG. 16B and 16C illustrate a schematic top view of an inserter with an IUS in a preloaded state and an insertion state, respectively, in accordance with an embodiment of the present disclosure.

In the accompanying drawings, a non-underlined number relates to an item identified by a line linking the non-underlined number to the item. When a number is non-underlined and accompanied by an associated arrow, the non-underlined number is used to identify a general item at which the arrow is pointing.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description illustrates embodiments of the present disclosure and ways in which they can be implemented. Although some modes of carrying out the present disclosure have been disclosed, those skilled in the art would recognize that other embodiments for carrying out or practicing the present disclosure are also possible. In one aspect, an embodiment of the present disclosure provides an intrauterine system comprising

- a frame having a first end, a second end, a length Lf defined as the distance between the first end and the second end;

- at least one sleeve having a first end, a second end, a length Ls defined as the distance between the first end and the second end, and arranged to movably surround a part of the frame; and

- at least one capsule comprising a pharmaceutically active agent, having a first end, a second end, a length Lc defined as the distance between the first end and the second end, and arranged to surround the sleeve; wherein

- the length Ls is 5-50 % of the length Lf; and

- the length Lc is 5-50 % of the length Lf.

In another aspect, an embodiment of the present disclosure provides a kit comprising an intrauterine system and an inserter, wherein the inserter comprises

- a handle having a proximal end, a distal end and an opening;

- an inner tube having a proximal end and a distal end, its proximal end being connected to the distal end of the handle and its distal end being configured to cooperate with the intrauterine system;

- a measurement tube having a proximal end and a distal end, its proximal end being movably connected to the distal end of the handle, the measurement tube being movably arranged to surround the inner tube;

- a flange movably arranged around the measurement tube;

- a tip cover arranged to surround the distal end of the measurement tube;

- a plunger movably arranged inside the inner tube, having a proximal end and a distal end, and its distal end being configured to cooperate with the intrauterine system; and

- means for moving the plunger, arranged in the opening of the handle. The present disclosure provides the aforementioned intrauterine system (IUS) and the aforementioned kit comprising the IUS and the inserter, which enables efficient and convenient insertion of the IUS into the uterus. The IUS straightens when loaded in the inserter and regains its original shape upon insertion into the uterine cavity (i.e. when in a deployed state). Moreover, the disclosed IUS attains a smooth shape, such as a S-shape, a C-shape, a P-shape, a 7-shape or a hook-shape, in the deployed state. By smooth in this connection is meant a shape that does not have any sharp edges. Such smooth shape of the IUS not only ensures a proper fit of the IUS within the uterus but also reduces the risk of potential perforation of the uterus lining. Furthermore, for the insertion of the present IUS, the inserter can be such that no part of the inserter having a cross-sectional diameter larger than the IUS's largest diameter is entered into the cervical canal (and in consequence into the uterus). The present IUS is thus possible to insert with an inserter were the insertion tube does neither cover the capsule comprising the pharmaceutically active agent, nor were the insertion tube needs to pass the cervix channel.

A further advantage of an IUS according to the current invention is that the risk of uterus penetration during the insertion procedure is minimized as there is no insertion tube which could penetrate the uterus muscle if inserted too deep. Also, the IUS as such cannot penetrate the uterine wall as it starts to immediately form the final shape after passage of the cervix channel. Moreover, the aforementioned sleeve and the capsule of the IUS imparts sufficient stiffness to the IUS during the insertion process and further helps the IUS to attain a desired continuous smooth shape in its deployed state. Furthermore, the disclosed IUS (comprising a capsule) has a small cross-sectional area (without the need to be covered by any part of the inserter) that enables comfortable insertion of the IUS in the cervical region and the uterus, thereby minimising unnecessary pain and discomfort during the IUS insertion process. Additionally, the aforementioned inserter of the kit enables an increase in an overall rate of successful insertion of the IUS without causing any or only minimal discomfort to the subject.

The IUS comprises a frame. The frame of the IUS has a first end and a second end. The frame has a length Lf defined as the distance between the first end and the second end of the frame. Throughout the present disclosure, the term "first end " refers to the end that is closer to the uterus of a subject during the insertion of the IUS (also called distal end), and the term "second end" refers to the end opposite to the first end, i.e. the end that is closer to the user, such as a health care professional, during the insertion of the IUS by use of the aforementioned inserter (also called proximal end). The frame has a flexible tubular structure designed to adapt to the anatomical structure of the cervix region as well as the uterine cavity. The flexible structure enables the frame to bend easily into a shape and to withstand strain and stress associated with that shape. The frame deforms easily when pressure is applied to the frame (for example the IUS is withdrawn inside the inserter), and can regain its original shape once the pressure is released. For example, the frame may be stretched to almost a straight-line (i.e. a straightened configuration) during insertion of the IUS using the aforementioned inserter, and attains a desired shape (i.e. a prespecified configuration) when placed within the uterine cavity (i.e. expulsed from the inserter). Such flexibility of the frame thus enhances user comfort not only during insertion of the IUS into the cervical canal and the uterus, but also during removal of the IUS when required. The frame may be of a hollow structure, or it may be non hollow.

Typically, the material of the frame is such that the IUS can be momentarily straightened for insertion, and it still recovers its original shape after insertion. Indeed, most typically the IUS is not arranged inside the inserter until shortly before insertion, i.e. by the medical practitioner.

Optionally, the length Lf of the frame ranges from 50-110 mm in the straightened configuration (i.e. when loaded in the inserter). The length Lf may be typically from 50, 60, 70, 80, 90 or 100 mm up to 60, 70, 80, 90, 100 or 110 mm. The frame of the IUS once deployed in a desired position in the uterine cavity may attain a prespecified configuration (length x width) in a range of 25 x 20 mm to 31 x 28, preferably 27 x 23 mm to 31 x 25 mm. In the deployed state, the length is typically from 25, 27, or 29 mm up to 27, 29, or 31 mm. Similarly, in the deployed state, the breadth is typically from 20, 22, 24, 26 up to 22, 24, 26, or 28 mm. In an example, the configuration of a frame of an S-shaped IUS in the deployed state may be 29.5 x 23.8 mm (length x width).

Optionally, the frame has a shape selected from an S-shape, a P-shape, a C-shape, a 7-shape or a hook-shape. The frame regains its original shape as discussed above in the deployed state. Additionally, optionally, the frame may have a spiral-shape or an inverted P-shape in the deployed state. Optionally, the frame has a T-shape, i.e. a cylindrical contraceptive body with two arms in the deployed state. In such embodiment, the two arms may be made from a very thin material (or metal) so that the two arms may be accommodated inside the aforementioned capsule during loading of the IUS in the inserter.

Optionally, a cross-section of the frame is selected from circular and oval. The frame has a smooth cross-section and may have for example circular, oval, or elliptical cross-section to prevent any injuries in the uterine cavity. The optimal shape and cross-section of the frame provides a suitable resilience to the IUS while in use. For example, the resilience of the frame prevents expulsion or displacement of the IUS inside the uterine cavity during uterine contractions, as the flexible frame balances out the stress caused by the uterine contractions. Moreover, the resilience (or elasticity) of the frame depends on the material of the frame.

Optionally, the frame is manufactured from a material selected from polyethylene, polypropylene, polyether ether ketone, and thermoplastic polyurethane. Typically, the frame is made of an elastic material. The fabrication material of the frame may be an inert biocompatible material. Optionally, the frame is manufactured from a material that exhibits a shape memory effect, such as shape memory plastic. In an example, the frame is made of a shape memory material capable of having a first shape and a second shape, and capable of being changed from the first shape to the second shape, and from the second shape to the first shape after having been in the second shape for a (short) period of time. Examples of the shape memory plastic include, but are not limited to thermoplastic and thermosetting polymers, such as polyurethanes, polyurethane prepolymers, block copolymers (such as block copolymers of polyethylene terephthalate and polyethyleneoxide, block copolymers of polystyrene and poly(l, 4-butadiene), block copolymers of poly(2-methyl- 2-oxazoline) and polytetrahydrofuran), and amorphous polynorbornene. Furthermore, the frame may be made of fibre reinforced plastics or polymers, such as plastics reinforced with glass fibres.

Optionally, a rounded end part is arranged at the first end of the frame and the rounded end part has a larger diameter than the frame. The first end of the frame is smooth and curved (e.g. a semi-circular or rounded tip) to facilitate smooth and frictionless movement of the IUS into and out of the cervical canal and uterus, and avoid any risk of perforation of the fundus of the uterus. In other words, the rounded tip ensures safety of the fundus region of the uterus. The rounded end part may also function during the use of the IUS, to prevent the capsule from slipping off the frame, as well as to prevent the capsule from slipping off the frame during removal of the IUS.

According to an embodiment, the frame further comprises a means for engagement at its second end. The means for engagement enables the aforementioned plunger of the inserter to cooperate with the frame of the IUS. Examples of the means for engagement include, but are not limited to a knob, a recess, a notch, an indentation, and a combination thereof. Moreover, removal threads may be preferably coupled to the means of attachment (i.e. near the second end of the frame) by way of a knot or other method known in the art. It will be appreciated that the term "removal threads" as used herein refers to one or more threads (namely strings) attached to the IUS at one end and used for removing the IUS at the end of the wearing period (which is about 3-10 years, preferably 5-7 years). The removal threads are not only used for retaining the IUS in connection with the inserter during insertion, for removal and/or replacement of the IUS at a later time during the wearing period, but also to detect whether the IUS is in a correct position within the uterine cavity once the IUS is deployed in the uterus.

Optionally, the frame may comprise at least one diagnostic means for locating the IUS in the uterine cavity without a physical intervention. In an example, the at least one diagnostic means may be an X-ray opaque agent, such as barium sulphate, for example, up to 20 wt-% (weight percentage) of the polymeric/elastomeric material of the frame. In another example, the at least one diagnostic means may be a ferromagnetic agent or an agent detectable by ultrasound or fluoroscopic imaging of the IUS in the deployed state. Optionally, the at least one diagnostic means is provided as an inert metal, either coated on at least a part of the frame of the IUS, or provided as a partial embed in the IUS.

The IUS comprises at least one sleeve having a first end, a second end, a length Ls defined as the distance between the first end and the second end, and arranged to movably surround a part of the frame. The at least one sleeve is an elongated hollow tubular member or part surrounding a part of the frame. The at least one sleeve functions as a supporting means to reinforce the IUS and impart a suitable stiffness to it to enable the frame to attain a desired shape (i.e. a prespecified configuration). The length Ls is substantially smaller than the length Lf, and covers only a part of the frame. However, a cross-sectional area (or an inner diameter) of the at least one sleeve is larger than the cross-sectional area (i.e. the outer diameter) of the frame. The length Ls is 5-50 % of the length Lf. Optionally, the length Ls is 15- 30 % of the length Lf. The length Ls is typically from 5, 10, 15, 20, 25, 30, 35, 40 or 45 % up to 10, 15, 20, 25, 30, 35, 40, 45 or 50 % of the length Lf. For example, the length Ls may be from 2.5 to 55 mm, and preferably 7.5 to 33 mm. Optionally, the at least one sleeve is manufactured from polyether ether ketone, high density polyethylene, ultra-high molecular weight polyethylene, polypropylene, polymethyl methacrylate, polyacrylate, nickel-titanium alloy, copper, silver, and titanium. Mixtures of these materials may also be used. The at least one sleeve is typically made of an inert biocompatible material that has sufficient strength to withstand physiological and mechanical stress conditions that may prevail inside the uterus. Examples of the inert biocompatible material include, but are not limited to ceramics (such as alumina (AI2O3), zirconia (Zr02), bioglass

(such as Na20CaOP203-SiO), hydroxyapatite, tricalcium phosphate and the like), metals and alloys thereof (such as titanium, nitinol (an alloy of nickel and titanium) and the like), polymers (such as polyvinylchloride, polystyrene, polytetrafluoroethylene, polyurethanes, polyamides, polyether sulfone, polyetherimide, epoxy resins and the like), polymer composites and reinforced rubbers (such as fibre-reinforced rubber, silicone rubber and the like). It is furthermore advantageous if the sleeve is made of a material which has only marginal friction to ensure that the sleeve can easily move on the frame.

The IUS further comprises at least one capsule comprising a pharmaceutically active agent. The at least one capsule has a first end, a second end, and a length Lc defined as the distance between the first end and the second end. The at least one capsule is arranged to surround the sleeve. Specifically, the at least one capsule is a drug container comprising the pharmaceutically active agent. The at least one capsule arranged on the sleeve also provides stiffness to the IUS. The length Lc is 5-50 % of the length Lf. Optionally, the length Lc is 15- 30 % of the length Lf. The length Lc is typically from 5, 10, 15, 20, 25, 30, 35, 40 or 45 % up to 10, 15, 20, 25, 30, 35, 40, 45 or 50 % of the length Lf. Optionally, a cross-section of the capsule is selected from circular and oval. For example, the capsule may have a circular, an oval or a polygonal shape as long as the shape is suitable to be inserted into the cervical canal and into the uterus. Optionally, the outer diameter of the capsule is in a range of 2-3.5 mm, and preferably about 2.9 mm. The outer diameter of the capsule is typically from 2, 2.1, 2.3, 2.5, 2.7, 2.9, 3.1, or 3.3 mm up to 2.1, 2.3, 2.5, 2.7, 2.9, 3.1, 3.3 or 3.5 mm. Optionally, the length Ls is essentially identical to the length Lc. Specifically, the length Ls of the at least one sleeve, the length Lc of the at least one capsule, and the arrangement of the sleeve and the capsule on the frame affects the shape of the IUS as well as the rate of release of the pharmaceutically active agent into the uterine cavity. In an embodiment, the length Ls is smaller than the length Lc. In another embodiment, the length Ls is greater than the length Lc. In an example, the IUS has higher stiffness if the length Ls is more than the length Lc. In another example, the rate of release of the pharmaceutically active agent is affected if the length Ls is shorter than length Lc. The rate of release of the pharmaceutically active agent may be controlled (e.g. increased) by introducing a plurality of holes in the at least one sleeve, allowing the biological fluids in the uterine cavity to come in contact with the pharmaceutically active agent at the interior of the capsule.

In an embodiment, the at least one capsule is selected from a matrix system and a core-membrane system. In an example, the matrix system may be a polymer matrix, such as a siloxane-based elastomer, with the pharmaceutically active agent dispersed or dissolved therein. In another example, in the core-membrane system, the at least one capsule may comprise a pharmaceutically active agent core, and a membrane encasing the pharmaceutically active agent core. The core may be a hollow tube-like structure assembled on the frame (surrounding the sleeve) to deliver the pharmaceutically active agent at a controlled rate in the uterus. The membrane may be a permeable layer, made up of an inert material, that prevents direct contact between the pharmaceutically active agent and the biological fluids in the uterus. Furthermore, the membrane layer may adjust the release rate of the pharmaceutically active agent by acting as a diffusion layer surrounding the pharmaceutically active agent core. In an embodiment, the membrane may surround the first end and the second end of the at least one capsule, resulting in a closed capsule. In another embodiment, the first end and the second end of the at least one capsule or at least one of the ends is open, i.e. not surrounded by the membrane. In an embodiment, the membrane (when present) is more permeable to the pharmaceutically active agent as compared to the pharmaceutically active agent core.

Optionally, the at least one capsule is manufactured from poly(dimethyl silicone), siloxane based elastomer, a thermoplastic polyurethane, a thermoplastic polyurethane elastomer, ethyl vinyl acetate, a polyolefin- based elastomer, a silicone containing thermoplastic, polyurethane, polylactic acid, and polycaprolactone. Combinations and mixtures of these materials may also be used. More optionally, the at least one capsule is manufactured from a biocompatible polymer matrix. Examples of the biocompatible polymer matrix include, but are not limited to copolymers of dimethylsiloxanes and methylvinylsiloxanes, polyethylene, polypropylene, polybutadiene, polyisoprene, acrylic acid polymers, ethylene/propylene copolymers, ethylene/ethyl acrylate copolymers, poly(methacrylate), polymethyl methacrylate, styrene-butadiene- styrene block copolymers, styrene-isobutylene-styrene copolymers, poly(hydroxyethylmethacrylate), polyethers, polyacrylonitriles, polyethylene glycols, polymethylpentene, polyhydroxy alkanoates, polyorthoesters, hydrophilic polymers (such as hydrophilic hydrogels), cross-linked polyvinyl alcohol, polytetrafluoroethylene, polyvinyl chloride, polyvinyl acetate, neoprene rubber, and butyl rubber.

Optionally, the pharmaceutically active agent is selected from progesterone and its derivatives, oestrogen, progestin, levonorgestrel, cyproterone acetate, desogestrel, etonogestrel, lynestrenol, medroxyprogesterone acetate, norethisterone, norethisterone acetate, norgestimate, drospirenone, gestodene, 19-nor-17-hydroxyprogesterone esters, 17a-ethinyltestosterone and derivatives thereof, 17a-ethinyl-19- nortestosterone and derivatives thereof, ethynodiol diacetate, dydrogesterone, norethynodrel, allylestrenol, medrogestone, norgestrienone, ethisterone and dl-norgestrel; and androgenic steroids, such as danazol and gestrinone; naproxen, ibuprofen, mefenamic acid, flurbiprofen, indomethacin, diclofenac, piroxicam, meloxicam, ketoprofen, gonadotropin-releasing hormone agonists, progesterone receptor antagonists such as mifepristone (IIb-4-dimethylaminophenyl- 17 -hydroxy-17a-propinyl-4, 9-estradiene-3-one); ulipristale acetate, (11 ,17 )-17-Hydroxy-ll-[4-(methylsulphonyl) phenyl] -17- (pentafluoroethyl)-estra-4,9-dien-3-one, 17a-acetoxy-11 -[4-(/V,/V- d imethylamino) phenyl] -21 -methoxy-19-norpreg na-4,9-diene-3, 20- dione, 17a-acetoxy-11 -(4-/V,/V-dimethylaminophenyl)-19-norpregna- 4,9-diene-3,20-dione, 11 -(4-acetylphenyl)-17 -hydroxy-17a- (l,l,2,2,2-pentafluoroethyl)-4,9-estradiene-3-one, asoprisnil (benzal dehyde-4-[(11 ,17 )-17-methoxy-17-(methoxymethyl)-3-oxoestra-

4,9-dien-ll-yl)]-l -oxime).

Mixtures of these agents may also be used. In an example, the pharmaceutically active agent may be a hormone, a drug or a drug analogue, an active pharmaceutical ingredient, or a health-promoting substance having contraceptive properties. Such pharmaceutically active agent functions by either thickening cervical mucus, changing the endometrium making it unsuitable for egg implant, stopping ovulation, or acting as COX1/COX2 inhibitors. In an example, the pharmaceutically active agent may provide and/or enhance protection against various microbial infections, such as a bacterial infection, a fungal infection, and/or a sexually transmitted infection. As hormones, for example levonorgestrel can be used, and as COX inhibitor, indomethacin may be used. The pharmaceutically active agent may also be efficient in treating or preventing a medical condition, such as endometriosis.

It will be appreciated that the pharmaceutically active agent is administered in a suitable amount, such as in a maximum feasible amount suitable to a subject. Moreover, the amount of the pharmaceutically active agent varies depending on the particular pharmaceutically active agent to be administered, intended use, action time, release rate and therapy period as well as the age and medical condition of the subject. Furthermore, the pharmaceutically active agent typically has a pH level that is suitable for the uterus. Thus, the IUS functions not only as a long-acting reversible contraceptive method but may be used for a variety of other applications, such as treating a medical condition, swelling, pain in the uterus depending on the pharmaceutically active agent supplied via the IUS.

Optionally, the IUS comprises at least two capsules. In an example, the at least two capsules are placed at a predefined distance from each other on the frame. One of the at least two capsules may be arranged to surround the sleeve, while the other capsule may be directly arranged to surround the frame, i.e. without the sleeve. Optionally, the capsule without the sleeve is arranged at the first end of the frame, and the movement of the capsule may be restricted. Preferably, the at least two capsules are not in contact with each other once the IUS is inserted into the uterine cavity, as well as after insertion. In an example, the IUS may comprise two sleeves. In such example, each of the at least two capsules may surround a corresponding sleeve of the two sleeves. Optionally, at least a part of the at least one capsule is void of pharmaceutically active agent. In an example, the at least one capsule may comprise the pharmaceutically active agent distributed in certain part of the capsule, for example 20-40 % of the length Lc, and the rest of the at least one capsule may not include the pharmaceutically active agent. In another example, 70-95 % of the length Lc of the at least one capsule comprises the pharmaceutically active agent, and the remaining 5-30 % of the length LC may be void of the pharmaceutically active agent. In yet another example, the at least one capsule is completely void of the pharmaceutically active agent, thereby functioning only as a structural unit to provide a desired shape to the IUS when inserted into the uterus. In this case, the pharmaceutically active agent may be provided in the frame. In still another example, if two capsules are present, a first capsule may comprise a pharmaceutically active agent and a second capsule arranged at the first end of the frame may not comprise a pharmaceutically active agent. In such a case, the second capsule functions only as a structural unit to provide a desired shape to the IUS when inserted into the uterus.

Optionally, the first capsule and the second capsule may be identical or different in structure, and may contain same or different pharmaceutically active agent. For example, the first capsule may include a first pharmaceutically active agent, such as progestin, and the second capsule may include a second pharmaceutically active agent, such as diclofenac. In another example, a third capsule (namely, a capsule without any active ingredient) may be placed between the at least two capsules. Furthermore, the release of the pharmaceutically active agents from the at least two capsules may be carried out simultaneously or one after another depending upon a rate of release of the pharmaceutically active agents to be achieved and their respective interactions with the biological fluid in the uterus. Optionally, the second end of the at least one sleeve comprises an enlargement. The enlargement functions as a retention or locking means to retain the at least one capsule and to prevent it from sliding off the frame during the insertion process and during use of the IUS. The enlargement may further enable to suitably engage with the aforementioned inner tube of the inserter during loading of the IUS in the inner tube of the inserter and during insertion. The enlargement may for example resemble a trumpet or a trumpet-shaped protrusion extending from the second end of the at least one sleeve. The term " trumpet " as used herein refers to a bell-like protrusion from the second end of the at least one sleeve. It will be appreciated that since the at least one sleeve is typically made of a same material throughout its length, the enlargement at the second end is also flexible to support and facilitate the assembly and movement of the at least one capsule around the sleeve and the frame during the IUS insertion process. According to an embodiment, various operational stages related to a possible assembly of the least one sleeve and the at least one capsule on the frame of the IUS is described below. Firstly, a frame is obtained by an injection moulding process or by extrusion. In the injection moulding process, the sleeve is obtained in an open configuration, and it has two longitudinal parts (e.g. resembling two halves of a hollow tube when split along the length of the hollow tube). The sleeve is longitudinally arranged along a part of the frame and is bent along the part of the frame such that the two longitudinal parts of the sleeve are joined with each other to obtain a sleeve-frame assembly. The joining may be performed, for example, by laser welding, or by other methods known in the art. In the extrusion process, the sleeve is formed by extruding a tube, and forming the optional above-mentioned enlargement (such as a trumpet-shape) by post-production. Thereafter, the sleeve is cut along its longitudinal direction and positioned on the frame. The sleeve may be welded or glued together, but this is not mandatory.

One capsule is then arranged to surround the sleeve-frame assembly that forms a capsule-sleeve-frame assembly. Optionally, at least one sleeve and at least one capsule are arranged close to the second end of the frame. However, in cases where there are more than one sleeve and capsule, the sleeves and the corresponding capsules may be arranged anywhere on the frame, i.e. between the first end of the frame and the second end the frame, depending on the desired shape of the IUS to be achieved.

The present disclosure also provides a kit comprising an intrauterine system and an inserter. The IUS of the kit is as described above. According to an embodiment, the IUS is pre-installed (or preloaded) with the inserter in a sterile sales package, but most typically the IUS itself is still outside the inserter, only the removal threads are within the inserter. The removal threads may for example be used for retracting the frame of the IUS inside the inserter (while the capsule mounted on the sleeve stays outside the inserter). Indeed, the frame is retracted or withdrawn inside the inserter, while the capsule moves to the end of the frame (its first end). Thus, the largest diameter passing through the cervix is the diameter of the capsule. The various embodiments and variants described above for the IUS apply mutatis mutandis to the IUS of the kit. The distal end of the inner tube is configured to cooperate with the intrauterine system, i.e. the cross-sectional shape and diameter of the frame matches the inner shape and diameter of the insertion tube. Furthermore, for example, the second end of the frame of the intrauterine system may be arranged to cooperate with the distal end of the plunger.

The present disclosure thus provides kit for efficiently and conveniently performing the IUS insertion into the uterus. The inserter enables insertion of the IUS in a stable position in the uterus. The inserter is easy- to-use and enables direct entry of the IUS into the cervical canal instead of insertion of any part of the inserter into the cervical canal. Therefore, the cross-sectional diameter which has to pass the cervix channel is solely determined by the diameter of the capsule with the active drug. No increase in size as caused by the wall thickness of an insertion tube of a conventional inserter occurs. This specific design reduces the pain associated with the IUS placement into the uterus. Moreover, a small cross-sectional area of the IUS makes the insertion of the IUS into the uterus almost painless or at least less painful than with conventional IUS's and inserters. The use of the kit therefore may enable an increase in an overall rate of successful insertion of the IUS without causing any or only minimal discomfort to the subject.

Indeed, the present inserter comprises a measurement tube having a proximal end and a distal end, its proximal end being movably connected to the distal end of the handle, the measurement tube being movably arranged to surround the inner tube; provided the measurement tube is arranged to remain outside the cervix channel during insertion. The present inserter also comprises a tip cover arranged to surround the distal end of the measurement tube; provided the tip cover is arranged to remain outside the cervix channel during insertion. A further advantage of an inserter of the current invention is that when properly used, the risk of uterus penetration is minimized, as the inserter does not comprise an insertion tube that reaches the uterine cavity.

In the present description, a proximal end is the end that is closest to the user (the medical practitioner) during insertion of the IUS, and a distal end is the opposite end, furthest away from the user.

The inserter comprises a handle having a proximal end, a distal end, and an opening. The handle is preferably designed for easy handling of the inserter with a single hand. Moreover, the handle is preferably designed to be devoid of any handedness preferences. Alternatively stated, the inserter works equally when held using the handle either with a right hand or a left hand.

According to an embodiment, the handle is fabricated from a polymeric material (e.g. medical-grade plastics material) and is employable for a single use for hygienic purpose. The handle may have various shapes and sizes. The handle is typically a hollow elongated structure, for example, tubular, cylindrical, elliptical, oval, cuboidal, or the like. The handle acts a housing and a support structure for various components of the inserter. Moreover, the handle may be designed to conform to a palm of a medical practitioner.

According to an embodiment, the aforementioned opening of the handle is a longitudinal opening having a longitudinal axis that is essentially the same as the longitudinal axis of the inserter. The opening is present between the proximal end and the distal end of the handle. It will be appreciated that the size and shape of the opening of the handle may vary. For example, the shape of the opening may be a rounded rectangle, a square, circular, elliptical, oval, cuboidal, or the like. The inserter further comprises an inner tube having a proximal end and a distal end. The proximal end of the inner tube is connected to the distal end of the handle and the distal end of the inner tube is configured to cooperate with the intrauterine system. The inner tube is a hollow tube. Optionally, the inner tube has a circular cross-section. It will be appreciated that the cross-sectional shape of the inner tube may vary. For example, the inner tube may have an oval or a polygonal shape as long as the shape essentially corresponds to the circumference of the IUS when loaded in the inner tube of the inserter. In an embodiment, the inner tube may not be a closed tube and may have a C-shape, i.e. have a longitudinal slit (i.e. a C-slit) along a portion of its length from the proximal end to the distal end. The inner tube has a diameter that is approximately similar to that of the largest outer diameter of the IUS. Optionally, the inner tube has a diameter of 2-3.5 mm, preferably 2.5- 2.9 mm.

Optionally, the distal end of the inner tube comprises at least one protrusion on its inner surface. In an example, the inner tube may include three protrusions, arranged equidistantly from one another. In an embodiment, the protrusion is in the form of a ring. For example, the protrusion may be directed inwards from an inner surface (i.e. inner circumference) of the distal end of the inner tube. The protrusion may be extended in a direction that is perpendicular to the direction of the length of the inner tube to form a ring-like structure on the inner surface of the inner tube. In another embodiment, the protrusion may be a hook. In an example, the wall thickness of the inner tube at the point(s) of the protrusion(s) may be diminished so that the distal end of the inner tube is slightly more flexible to cooperate with the IUS. According to an embodiment, the inner tube is malleable and accommodates the IUS when the IUS is loaded in the inserter. Optionally, the distal end of the inner tube is configured to cooperate with the aforementioned sleeve of the intrauterine system. Optionally, the second end of the sleeve of the IUS comprises at least one indentation arranged to cooperate with the at least one protrusion on the inner surface of the distal end of the inner tube. In an example, the at least one indentation may be a trumpet-shaped part. During loading of the IUS in the inserter, the trumpet-shaped part is pulled over the protrusion of the inner tube towards the handle. The trumpet-shaped part is pulled when the means for moving the plunger is moved towards the proximal end of the handle in the opening to load the IUS inside the inserter. Such protrusion further facilitates retention of the trumpet- shaped part of the IUS in a suitable position until the plunger pushes the IUS completely out of the inner tube and into the uterus during the IUS insertion process.

According to an embodiment, the proximal end of the inner tube is attached to the distal end of the handle. An attachment means is used to attach the proximal end of the inner tube to the distal end of the handle. For example, the attachment means may be a screw and nut-based attachment mechanism, a push member-slot based attachment mechanism, or other attachment mechanisms known in the art. The inner tube is attached to the distal end of the handle in such a way that the inner tube remains immobile in relation to the handle.

The inserter further comprises a measurement tube having a proximal end and a distal end. The proximal end of the measurement tube is movably connected to the distal end of the handle. The measurement tube is movably arranged to surround the inner tube. The measurement tube is a hollow tube-like structure. Specifically, the cross-section of the measurement tube is larger than the cross-section of the inner tube.

Optionally, the measurement tube has a circular or oval cross-section. The cross-sectional shape of the measurement tube is complementary to the cross-sectional shape of the inner tube. For example, if the inner tube has an oval or elliptical shape, the measurement tube also has a similar shape surrounding the inner tube. In an embodiment, the inner tube and the measurement tube have a C-shape, i.e. they do not have a complete circular cross-section and rather have a longitudinal slit along their whole length or along part of their length, such as along about 90 % of their length. Moreover, the measurement tube and the inner tube are typically arranged concentrically. In case both the measurement tube and the inner tube have a slit, the measurement tube may house the inner tube with both slits, the slit of the measurement tube and the slit of the inner tube facing in different directions, i.e. not facing each other. Optionally, the measurement tube is fabricated from a medical grade polymeric material, such as polyethylene, polypropylene, silicone, and the like, or metal. Optionally, the measurement tube may be made of polyether ether ketone, thermoplastic polyurethane, thermoplastic polyurethane elastomer, glass fibre, and the like. The inserter further comprises a tip cover arranged to surround the distal end of the measurement tube. The tip cover is arranged to prevent the measurement tube from entering into the cervical canal of the subject. According to an embodiment, the tip cover is movably arranged on the distal end of the measurement tube. Optionally, the tip cover is fixedly attached on the distal end of the measurement tube. The cross-section of the tip cover is larger than the measurement tube. During the insertion of the IUS, when the inserter is pushed towards the subject, the tip cover slides backwards (i.e. towards the handle), and locks itself on the outer surface of the measurement tube. The inserter further comprises a flange movably arranged around the measurement tube. In an embodiment, the length of the measurement tube includes a marking scale thereon to allow setting the position of the flange by a user. In the beginning of the IUS insertion procedure, the flange is manually moved to a specified position on the measurement tube with the help of markings of the marking scale on outer surface of the measurement tube. The specified position refers to the length of the uterine cavity plus the length of the cervical canal measured previously during uterine sounding (in some cases, the specified position may refer to the length of the uterus). Once set on the measurement tube of the inserter, a firm grip of the flange is established with respect to the measurement tube, thereby preventing an unwanted movement of the flange from its initial set position when the inserter is used in the IUS insertion process.

Optionally, the flange comprises a gripping surface on two diametrically opposing sides at an outer portion of the flange. In an example, the gripping surface has a waved structure to enable a firm grip of fingers of a single hand and for pressing an outer part of the flange towards an inner part of the flange for adjusting the flange at a correct position by sliding it over the measuring tube. According to another embodiment, the flange comprises a snap lock at its side, and closing the snap lock will ensure the flange is firmly held in place on the measurement tube.

Optionally, the flange has a length Lr. The length Lr is 2-10 %, preferably 4-8 % of the length L of the measurement tube of the inserter. In an example, Lr may be from 2, 4, 6, 8 up to 4, 6, 8, or 10 % of L. Optionally, the flange is made of a polymeric material, such as low-density polyethylene, high-density polyethylene, polypropylene, thermoplastic polyurethane, thermoplastic polyurethane elastomer, polyether ether ketone and/or a combination thereof. The flange may have various shapes, for example, a rounded rectangular shape, oval, elliptical, round, or the like.

The inserter further comprises a plunger movably arranged inside the inner tube. The plunger has a proximal end and a distal end. The distal end of the plunger is configured to cooperate with the intrauterine system. The plunger is a thin rod-like structure. The distal end of the plunger has for example a slit in a longitudinal direction to engage with the aforementioned second end of the frame of the IUS. Specifically, the slit at the distal end of the plunger accommodates a means of engagement provided at the second end of the frame of the IUS. Moreover, a portion of the plunger at the distal end may be non-tubular and have a curved part that includes the slit. Optionally, the plunger is made of a medical grade polymeric material, such as polyethylene, polypropylene, silicone, and the like, or metal. Optionally, the plunger and the inner tube are made of a flexible material to prevent perforation of the uterus. The inserter further comprises a means for moving the plunger, arranged in the opening of the handle. In accordance with an embodiment, the means for moving the plunger comprise a sledge movably arranged inside the handle. The means for moving the plunger further comprise a slider movably arranged in the opening of the handle in connection with the sledge, wherein the proximal end of the plunger is connected to the sledge. In an example, the handle has a first cover portion (e.g. an upper side) and a second cover portion (e.g. a bottom side). The slider is arranged in the opening provided in the first cover portion. The movement of the slider towards the proximal end of the handle loads the IUS into the inner tube of the inserter using removal threads.

It will be appreciated that the term "removal threads" as used herein refers to one or more threads (namely strings) attached to the IUS at one end and used for removing the IUS at the end of a wearing period (which is about 5-7 years). The removal threads are not only used for removal and/or replacement of the IUS at a later time during the wearing period, but also to detect whether the IUS is in a correct position within the uterine cavity once the IUS in deployed in the uterus. In an example, the IUS may be preloaded in the inserter in a sales package. In the preloaded state of the IUS, removal threads remain coupled to the aforementioned second end of the frame. Thus, the movement of the slider towards the proximal end of the handle pulls back the removal threads that facilitates loading of the IUS into the inner tube of the inserter. Moreover, the movement of the slider towards the distal end of the handle further pushes the plunger in the inner tube towards the subject. The plunger in turn pushes the aforementioned second end of the frame and thus a certain portion of the frame is released from the inserter into the uterine cavity.

In accordance with an embodiment, the handle comprises at least one first rack arranged inside the handle on a longitudinal side of the opening. The sledge comprises at least one second rack, the at least one second rack being arranged parallel to the at least one first rack. The slider further comprises at least one first pinion arranged to cooperate with the at least one first rack. The slider further comprises at least one second pinion arranged to cooperate with the at least one second rack, wherein the at least one first pinion is arranged to cooperate with the at least one second pinion to translate a movement of the slider.

In accordance with an embodiment, the inserter further comprises a third rack arranged inside the handle on a longitudinal side of the opening, opposite the first rack. The sledge comprises a fourth rack arranged parallel to the second rack. The slider comprises a third pinion arranged to cooperate with the third rack. The slider further comprises a fourth pinion arranged to cooperate with the fourth rack, wherein the third pinion is arranged to cooperate with the fourth pinion to translate movement of the slider. The term "rack" refers to a toothed bar or a toothed rod that is typically a linear gear bar. The term "pinion" refers to a circular gear that engages teeth on the rack, and the rotational motion applied to the pinion causes a movable rack (e.g. the second rack and the fourth rack of the sledge) to move relative to the pinion, translating the rotational motion of the pinion into a linear motion. In other words, when the pinion turns, a movable rack moves in a straight line. Use of the rack and pinion allows a larger movement of the various parts, without having to make the handle unnecessarily long. Moreover, the rack and pinion arrangement of the handle engages the removal threads of the IUS during the loading process by pulling the removal threads towards the proximal end of the handle.

In accordance with an embodiment, the means for moving the plunger comprises at least one rack arranged inside the handle, the rack having a proximal end and a distal end. The means for moving the plunger further comprises a pinion arranged in the opening of the handle and arranged to cooperate with the at least one rack, wherein the proximal end of the plunger is connected to the distal end of the rack. In such embodiment, the means for moving the plunger operates in a roller-like mechanism, and the pinion may resemble a roller that may be arranged in the opening of the handle. In an example, the rack may be a movable rack. The IUS is loaded within the inner tube of the inserter when the rack is moved to a first position (i.e. the rack is near the proximal end of the handle) by rolling the pinion forward (i.e. towards the distal end of the handle). During the insertion of the IUS, the frame of the IUS is partially released out from the inserter when the rack is moved to a second position (i.e. near the distal end of the handle) from the first position by rolling the pinion backwards (i.e. towards the proximal end of the handle). The movement of the rack from the first position to the second position pushes the proximal end of the plunger connected to the rack towards the distal end of the handle, thereby further releasing a part of the frame into the uterine cavity.

The inserter preferably comprises means for releasing the removal threads once the IUS is in the uterus. The means for releasing may be a simple knob, which when turned releases the threads. According to another embodiment, the inserter further comprises means for cutting the removal threads. The handle comprises a thread cutting button. In an example, the thread cutting button may be provided on the second cover portion (i.e. bottom side) of the handle. The handle may further include the means for cutting the removal threads (e.g. at least one cutter blade). In an example, when the thread cutting button is pushed, the at least one cutter blade inside the handle cuts the removal threads. After the IUS is suitably positioned in the uterine cavity, the removal threads are released by pushing the thread cutting button, which further pushes the at least one cutter blade to cut the removal threads within the handle.

According to an embodiment, the IUS insertion process into the uterus (namely, operational stages of the aforementioned inserter when used) is described by taking an example of a P-shaped IUS (i.e. the IUS having a P-shaped frame), and is as follows.

A) Flange adjustment: the flange is manually moved at a specified position on the measurement tube with the help of markings of the marking scale on the outer surface of the measurement tube. The specified position refers to the length of the uterine cavity plus the length of the cervical canal measured previously during uterine sounding. In an example, the gripping surface provided on the two diametrically opposing sides of the flange may be used to press an outer part towards an inner part of the flange. The inserter is used in aseptic conditions with a pair of sterile gloves put on by a user (e.g. a health care professional). In another example, the flange has a snap lock which is open in the initial step (i.e. in the sales package) and which the user closes by pressing, when the flange is in its correct position.

B) Loading stage: typically, the IUS comprising the P-shaped frame is preloaded in the inserter and stored in a sales package in its final shape (i.e. P-shape). According to an embodiment, the IUS is preloaded on the inserter in such a manner that the aforementioned capsule of the IUS is arranged to be in contact with the distal end of the inner tube. In the preloaded state, the capsule is covered by the tip cover of the inserter, while the remaining part of the frame of the IUS is outside the inserter. The means for moving the plunger (e.g. a slider) is moved backwards (i.e. towards the proximal end of the handle in the opening) to load the IUS inside the inserter using the removal threads. The backwards movement of the means for moving the plunger pulls the removal threads towards the proximal end of the handle. In the loaded state, about 10 mm of the frame is left outside the inserter (i.e. outside the tip cover of the measurement tube). C. First IUS insertion stage: the measurement tube is passed through vagina towards the cervix. The inserter is positioned such that the tip cover reaches the cervix (i.e. external orifice) and a small part of the frame left outside the inserter enters into the cervical canal. The measurement tube itself is not passed into the cervical canal at any operational stages during the IUS insertion process, thereby decreasing discomfort during the IUS insertion process.

D. Second IUS insertion stage: the inserter is gently pushed towards the subject, which makes the tip cover move backwards (i.e. towards the handle), and part of the frame (for example about 30 mm) is released from the inserter in the cervical canal. When the tip cover moves backwards, the tip cover locks itself on the outer surface of the measurement tube. At this stage, the capsule is still in contact with the inner tube, and only a part of the frame of the IUS enters the cervical canal. The means for moving the plunger (e.g. a slider) is still near the proximal end of the handle in the opening. The inserter is gently pushed towards the subject until a resistance from the inserter, typically a physical pressure, is felt by the user.

E. Third IUS insertion stage: while maintaining a firm contact of the tip cover to the portio of the cervix, the means for moving the plunger (e.g. the slider) is moved forward towards the distal end of the handle in the opening, which moves the plunger of the inserter. The plunger pushes an end (i.e. the aforementioned second end) of the frame and thus more frame is released from the inserter into the uterine cavity.

F. Fourth IUS insertion stage: the inserter is pushed towards the patient until the flange abuts the handle. A part of the proximal end of the measurement tube enters inside the handle. In this state, the IUS moves into its fundal position and the whole IUS is positioned within the uterine cavity. Alternatively stated, the IUS is completely deployed into the uterine cavity and attains the desired shape (i.e. the P-shaped configuration in this example) in the uterine cavity. When the plunger reaches the distal end of the inner tube, the capsule of the IUS is also released from the inner tube of the inserter into the uterine cavity.

G. Removal threads releasing or cutting and removal of the inserter: the removal threads are released. In an embodiment, the removal threads are released by turning or pushing the thread releasing knob or by pushing the thread cutting button provided on the second cover portion (i.e. bottom side) of the handle. When the thread releasing or cutting button is actioned, the means of releasing or cutting the removal threads (i.e. a knob or a cutter blade) inside the handle releases or cuts the removal threads. In case the threads are cut, the inserter is positioned such that the removal threads are cut to leave about 2-3 cm visible outside the cervix (i.e. outside the external orifice and about 2-3 cm into vagina to be detectable by touch). The inserter is then pulled out from the subject denoting the completion of the IUS insertion process by the inserter.

It is to be understood that the IUS insertion process is described by taking the example of the P-shaped frame. Flowever, in case of S-shaped frame or hook shaped frame (that resemble almost a question mark without the period), the IUS insertion process is similar except for the loading stage. For example, in case of S-shaped frame, the IUS is preloaded such that the capsule is outside the inserter and the tip cover is in its pulled back state (i.e. a position closer to the handle). During the loading of the IUS in the inserter, the tip cover is pulled over the capsule of the IUS, i.e. to its distal (or extended) position, and the IUS insertion is performed similar to the P-shaped IUS. In an example, the pulling over of the tip cover may be performed manually or automatically. The present inserter is also suitable for other types of IUS's than what are described here.

DETAILED DESCRIPTION OF THE DRAWINGS

Referring to FIG. 1, there is shown a schematic view of an IUS 100, in accordance with an embodiment of the present disclosure. The IUS 100 comprises a frame 102, a sleeve 104, and a capsule 106. In this embodiment, the frame 102 is an S-shaped frame. The frame 102 has a first end 108 and a second end 110. Moreover, a rounded end part 114 is arranged at the first end 108 of the frame 102. The rounded end part 114 has a larger diameter than the rest of the frame 102. Furthermore, the second end 110 of the frame 102 includes a means for engagement 116 that facilitates a plunger of an inserter to cooperate with the IUS 100. Further, shown are removal threads 118 attached to an opening 120 in the means for engagement 116. The sleeve 104 has a first end (not visible here) and a second end 122. The sleeve 104 is arranged to movably surround a part of the frame 102. The second end 122 of the sleeve 104 comprises an enlargement 124 that has a trumpet-like shape. The capsule 106 has a first end 126 and a second end 128. The capsule 106 is arranged to surround the sleeve 104, and comprises a pharmaceutically active agent.

Now referring to FIG. 2, shown is a schematic view of the IUS 100 of FIG. 1 in a loaded configuration, in accordance with an embodiment of the present disclosure. As shown, the IUS 100 comprising the frame 102, the sleeve 104, and the capsule 106, is straightened and stretched when loaded in an inserter before insertion of the IUS 100 in a uterus. Further, shown is an outer diameter 202 of the IUS 100 (i.e. the largest diameter of the IUS 100) that essentially corresponds to the outer diameter of the capsule 106. In this embodiment, a length Lc of the capsule 106 is about 25 % of a length Lf of the frame 102.

Now referring to FIG. 3, shown is a cross-sectional view of the IUS 100 of FIG. 1, in accordance with an embodiment of the present disclosure. As shown, the sleeve 104 is arranged to movably surround a part of the frame 102, and the capsule 106 is arranged to surround the sleeve 104. Further, shown is a length Ls of the sleeve 104, a length 304 and a width 306 of the frame 102 when the frame 102 is in the S-shaped configuration in the deployed state in the uterus.

Now referring to FIG. 4, shown is a schematic representation of the capsule 106 arranged on the sleeve 104 with an enlarged view 402 of the enlargement 124 at the second end of the sleeve 104. The enlargement 124 has a trumpet-like shape and functions as a retention means to retain the capsule 106 at a suitable position on the frame 102 and to prevent it from sliding off the frame 102 during the IUS insertion process. Now referring to FIG. 5, shown is a schematic view of an IUS 500, in accordance with another embodiment of the present disclosure. The IUS 500 comprises a frame 502. In this embodiment, the frame 502 is a 7- shaped frame. As shown, the IUS 500 comprises two capsules 504 and 506. The capsule 504 is arranged on a sleeve 508 and the capsule 506 is arranged on another sleeve (not visible here). The two capsules 504 and 506 are separated by a predefined distance in the deployed state in the uterus. The frame 502 comprises a rounded end part 510 at a first end 512 of the frame 502 and a means for engagement 514 at a second end 516 of the frame 502. The means for engagement 514 comprises an opening 518. As shown, the frame 502 has one protrusion 520 each near a first end 522 and a second end 524 of the sleeve 508 at alternating sides of the frame 502. The frame 502 has only one protrusion 520 near a second end of the sleeve underneath the capsule 506. The rounded end part 510 of the frame 502 prevents the capsule 506 from sliding off of the frame 502 from the first end 512.

Now referring to FIG. 6, shown is a cross-sectional view of the IUS 500 of FIG. 5. With reference to FIG. 6, there is shown a sleeve 602 arranged on the frame 502. The sleeve 602 has a first end 604 and a second end 606. The sleeve 602 is surrounded by the capsule 506, and the sleeve 508 is surrounded by the capsule 504. Further, shown are removal threads 608 coupled to the opening 518 in the means for engagement 514.

Now referring to FIG. 7, shown is a cross-sectional view of an IUS 700 in accordance with still another embodiment of the present disclosure. The IUS 700 comprises a frame 702, two sleeves 704 and 706, and two capsules 708 and 710. In this embodiment, the frame 702 is a P-shaped frame (specifically an open-ended P-shaped frame). As shown, the capsules 708 and 710 are arranged on the sleeves 704 and 706, respectively. The capsules 708 and 710 are separated by a predefined distance in the deployed state in the uterus. The frame 702 comprises a rounded end part 712 at a first end 714 of the frame 702 and a means for engagement 716 at a second end 718 of the frame 702. The means for engagement 716 comprises an opening 720. As shown, the frame 702 has one protrusion 722 each near a first end 724 and a second end 726 of the sleeve 706. The rounded end part 712 of the frame 702 prevents the capsules 710 from sliding off the frame 702 and further facilitates comfortable insertion of the IUS 700 in the cervical canal and the uterus. Further, shown is a first end 728 and a second end 730 of the sleeve 704. Notably, the frame 702 is void of protrusions near the first end 728 and the second end 730 of the sleeve 704. Now referring to FIG. 8, shown is a cross-sectional view of an IUS 800, in accordance with yet another embodiment of the present disclosure. The IUS 800 comprises a frame 802, three sleeves 804, 806 and 808, and three capsules 810, 812 and 814. In this embodiment, the frame 802 is a P-shaped frame (specifically a close-ended P-shaped frame). As shown, the capsules 810, 812 and 814 are arranged on the sleeves 804, 806 and 808 respectively. The capsules 810, 812 and 814 are separated by a predefined distance when the frame 802 attains the P- shape in the deployed state in the uterus. The frame 802 comprises a rounded end part 816 at a first end 818 of the frame 802 and a means for engagement 820 at a second end 822 of the frame 802. The means for engagement 820 comprises an opening 824 for receiving removal threads 826. As shown, the frame 802 has one protrusion 828 each near a first end 830 of the sleeve 804, a second end 832 of the sleeve 806 and a first end 834 of the sleeve 808 on the same side of the frame 802. The protrusion 828 facilitates assembly of the sleeves 804, 806 and 808 on the frame 802 as well as controls their movement during insertion and use.

Now referring to FIG. 9, shown is a cross-sectional view of an IUS 900, in accordance with still another embodiment of the present disclosure. The IUS 900 comprises a frame 902, and two capsules 904 and 906. In this embodiment, the frame 902 is a hook-shaped frame. As shown, the capsules 904 and 906 are arranged directly on the frame 902 at different parts of the frame, i.e. parts 908 and 910 respectively. The capsules 904 and 906 are separated by a predefined distance when the frame 902 attains the hook-shape in the deployed state in the uterus. The frame 902 comprises an end part 912 at a first end 914 of the frame 902 and a means for engagement 916 at a second end 918 of the frame 902. The means for engagement 916 comprises an opening 920. As shown, the frame 902 has one protrusion 922 each near a first end 924 and a second end 926 of the capsule 904, and further near a first end 928 and a second end 930 of the capsule 906 at the same side of the frame 902.

FIG. 10 is a schematic view of an IUS 101, in accordance with an embodiment of the present disclosure. The IUS 101 comprises a frame 103, a sleeve (not shown), and a capsule 105. In this embodiment, the frame 103 is another form of S-shaped frame. The removal thread 107 attached to an opening 109.

Now referring to FIG. 11A and 11B, there is shown various operational stages 1002-1014 related to assembling of a sleeve 1016 and a capsule 1018 on a frame 1020, in accordance with an embodiment of the present disclosure. With reference to FIG. 11A, at operation 1002, the frame 1020 is obtained by an injection moulding process. At operation 1004, the sleeve 1016 is obtained in an open configuration also by an injection moulding process. In the open configuration, the sleeve 1016 has a first end 1022, a second end 1024, and two longitudinal parts 1026A and 1026B. At operation 1006, the two longitudinal parts 1026A and 1026B of the sleeve 1016 are longitudinally arranged along a part 1028 of the frame 1020.

With reference to FIG. 11B, at operation 1008, the longitudinal parts 1026A and 1026B of the sleeve 1016 are bent along the part 1028 of the frame 1020. At operation 1010, a capsule 1018 is obtained. As shown, the capsule 1018 is a hollow tube-like structure. At operation 1012, the longitudinal parts 1026A and 1026B of the sleeve 1016 are joined together by laser welding to obtain a sleeve-frame assembly 1030. At operation 1014, the capsule 1018 is arranged to surround the sleeve-frame assembly to form a capsule-sleeve-frame assembly 1032.

Referring to FIG. 12A, there is shown a perspective view of an inserter 1100 in an assembled state, in accordance with an embodiment of the present disclosure. The inserter 1100 comprises a handle 1102 having a proximal end 1104, a distal end 1106, and an opening 1108. The inserter 1100 further comprises a measurement tube 1110 having a proximal end 1112 and a distal end 1114. The proximal end 1112 of the measurement tube 1110 is movably connected to the distal end 1106 of the handle 1102. A tip cover 1116 is arranged to surround the distal end 1114 of the measurement tube 1110. The inserter 1100 further comprises a flange 1118 movably arranged around the measurement tube 1110. A means 1120 for moving a plunger (not shown here) is arranged in the opening 1108 of the handle 1102. Referring to FIG. 12B, there is shown a perspective view of the inserter 1100 of FIG. 12A in an unassembled state, in accordance with an embodiment of the present disclosure. The inserter 1100 further comprises an inner tube 1122 having a proximal end 1124 and a distal end 1126. The distal end 1126 of the inner tube 1122 is configured to cooperate with an IUS. The inserter 1100 further comprises a plunger 1128 having a proximal end 1130 and a distal end 1132. In an assembled state of the inserter 1100, the plunger 1128 is movably arranged inside the inner tube 1122, and the measurement tube 1110 is movably arranged to surround the inner tube 1122. The handle 1102 has a first cover portion 1134A and a second cover portion 1134B. The first cover portion 1134A includes the opening 1108.

The inserter 1100 further comprises a first rack 1136A arranged inside the handle 1102, and a sledge 1138 that comprises a second rack 1140A. The inserter 1100 further comprises a third rack 1136B that is arranged inside the handle 1102 opposite the first rack 1136A. The sledge 1138 comprises a fourth rack 1140B. Further, shown is a slider 1142. In the assembled state of the inserter 1100, the slider 1142 comprises a first pinion 1144 arranged to cooperate with the first rack 1136A, a second pinion 1146 arranged to cooperate with the second rack 1140A, a third pinion 1148 arranged to cooperate with the third rack 1136B, and a fourth pinion 1150 arranged to cooperate with the fourth rack 1140B. The FIG. further shows a front gear axis 1147. Further, shown are a first attachment means 1152 and a second attachment means 1154. The first attachment means 1152 is used to attach the inner tube 1122 to the handle 1102 and support the measurement tube 1110 such that the measurement tube 1110 is movable with respect to handle 1102. The second attachment means 1154 is used to attach the plunger 1128 to the sledge 1138.

Referring to FIG. 12C, there is shown an arrangement of the sledge 1138, the plunger 1128, and the inner tube 1122 of the inserter, in accordance with an embodiment of the present disclosure. The proximal end 1130 of the plunger 1128 is connected to the sledge 1138, and the plunger 1128 is movably arranged inside the inner tube 1122.

Referring to FIG. 12D, there is shown an arrangement of the sledge 1138 within a handle of an inserter, in accordance with an embodiment of the present disclosure. The sledge 1138 is movably arranged inside the second cover portion 1134B of the handle. Notably, the sledge 1138 is arranged between the first rack 1136A and the third rack 1136B of the second cover portion 1134B of the handle. The second rack 1140A of the sledge 1138 is arranged parallel to the first rack 1136A of the handle. The fourth rack 1140B of the sledge 1138 is arranged parallel to the third rack 1136B of the handle.

FIGs. 13A-13D are different views of an exemplary implementation of a slider 1200, in accordance with an embodiment of the present disclosure. With reference to FIG. 13A, there is shown a schematic top view of the slider 1200. In this embodiment, the slider 1200 is rectangular in shape with rounded corners. With reference to FIG. 13B, there is shown a schematic bottom view of the slider 1200. The slider 1200 comprises a first pinion 1202, a second pinion 1204, a third pinion 1206, and a fourth pinion 1208. The first pinion 1202 is connected to the third pinion 1206 by an axis. The second pinion 1204 is connected to the fourth pinion 1208 by an axis. The first pinion 1202 and the third pinion 1206 are arranged to cooperate with the second pinion 1204 and the fourth pinion 1208 respectively, to translate a linear movement of the slider. With reference to FIG. 13C, there is shown a perspective view of the slider 1200 with the first pinion 1202 that is connected to the third pinion 1206. With reference to FIG. 13D, there is shown a schematic side view of the slider 1200 that depicts an arrangement of the third pinion 1206 with respect to the fourth pinion 1208. Referring to FIG. 14, there is shown a perspective view of an exemplary inner tube 1300, in accordance with an embodiment of the present disclosure. The inner tube 1300 has a proximal end 1302, a distal end 1304, and a C-slit 1306 along almost 90 % of the length of the inner tube 1300. In this embodiment, the inner tube 1300 has three protrusions 1308 in an inner surface 1310A of the distal end 1304 of the inner tube 1300. An attachment means 1312 is attached on an outer surface 1310B of the proximal end 1302 of the inner tube 1300. The attachment means 1312 is used to attach the inner tube 1300 to the handle. FIGs. 15A-15J illustrates different views of an inserter 1400 depicting various operational stages to position an IUS 1402 into a uterus, in accordance with an embodiment of the present disclosure. With reference to FIG. 15A, there is shown an adjustment of a flange 1404 on a measurement tube 1406 of the inserter 1400, in accordance with an embodiment of the present disclosure. The flange 1404 is manually moved at a specified position on the measurement tube 1406 with the help of markings of a marking scale 1408 on the outer surface of the measurement tube 1406. The specified position refers to the length of the uterine cavity plus the length of the cervical canal measured previously during uterine sounding. FIGs 15B and 15C show details of the flange 1404. The flange is originally in an "open" position, where a snap lock 1410 is in an open state, and the flange can be easily moved. Once the flange is in its correct position (on the marking scale 1408), the snap lock 1410 is closed by pressing the flange, and thus the snap lock will be in a "closed" position.

With reference to FIG. 15D, there is shown a preloaded state 1412 (on the left) and a loaded state 1414 (on the right) of the IUS 1402, in accordance with an embodiment of the present disclosure. In the preloaded state 1412, a part of a frame 1416 of the IUS 1402 is outside the inserter 1400. In this embodiment, the frame 1416 is a P-shaped frame. Further, shown is a handle 1418, a means 1420 for moving the plunger, a tip cover 1422 of the measurement tube 1406, and the flange 1404 set at the specified position on the measurement tube 1406. The handle 1418 has a proximal end 1424, a distal end 1426, and an opening 1428. In the preloaded state 1412, the means 1420 for moving the plunger is positioned towards the distal end 1426 of the handle 1418.

In the loaded state 1414, the means 1420 for moving the plunger has been moved backwards (i.e. towards the proximal end 1424 of the handle 1418 in the opening 1428) to load the IUS 1402 inside the inserter using the removal threads 1430. The backwards movement of the means 1420 for moving the plunger pulls the removal threads 1430 towards the proximal end 1424 of the handle 1418. In the loaded state 1414, part (for example about 10 mm) of the frame 1416 is left outside the tip cover 1422 of the measurement tube 1406. The flange 1404 once set previously does not move during the insertion process of the IUS 1402.

With reference to FIG. 15E, there is shown a first insertion stage of the IUS 1402 using the inserter 1400, in accordance with an embodiment of the present disclosure. In this stage, the measurement tube 1406 is passed through vagina 1432 towards portio of the cervix. As shown, the inserter 1400 is positioned such that the tip cover 1422 reaches an external orifice 1434 and a small part of the frame 1416 that is left outside the inserter 1400 enters into a cervical canal 1436. With reference to FIG. 15F, there is shown a second insertion stage of the IUS 1402 using the inserter 1400, in accordance with an embodiment of the present disclosure. In this stage, the inserter 1400 is gently pushed towards the subject, which makes the tip cover 1422 move backwards (i.e. towards the handle 1418), and a part (for example about 30 mm) of the frame 1416 is released from the inserter 1400 into the cervical canal 1436. When the tip cover 1422 moves backwards, the tip cover 1422 locks itself on the outer surface of the measurement tube 1406. At this stage, the means 1420 for moving the plunger is still near the proximal end 1424 of the handle 1418 in the opening 1428. With reference to FIG. 15G, there is shown a third insertion stage of the IUS 1402 using the inserter 1400, in accordance with an embodiment of the present disclosure. In this stage, while maintaining a firm contact of the tip cover 1422 to the portio of the cervix, the means 1420 for moving the plunger is moved forward towards the distal end 1426 of the handle 1418 in the opening 1428, which moves the plunger within an inner tube 1438 of the inserter 1400. The plunger pushes an end (i.e. the second end) of the frame 1416 and thus more frame 1416 is released from the inner tube 1438 of the inserter 1400 into a uterine cavity 1440. With reference to FIG. 15H, there is shown a fourth insertion stage of the IUS 1402 using the inserter 1400, in accordance with an embodiment of the present disclosure. In this stage, the inserter 1400 is pushed towards the patient until the flange 1404 abuts the handle 1418 (i.e. a part of the proximal end of the measurement tube 1406 enters inside the distal end 1426 of the handle 1418). During this stage, the IUS 1402 moves into its fundal position and the whole IUS 1402 is completely deployed into the uterine cavity 1440 and attains the desired P-shape in the uterine cavity 1440. In this stage, the IUS 1402 that comprises a capsule 1442 is also released from the inner tube 1438 of the inserter 1400 in the uterine cavity 1440. Further, shown is a first end 1444 and a second end 1446 of the frame 1416 of the IUS 1402. In the FIG. 4H, there is further shown an enlarged view of a portion of the inserter and a portion of the IUS 1402 to depict the interaction of a plunger with a means 1450A of engagement at the second end 1446 of the frame 1416 of the IUS 1402. The plunger 1448 is movably arranged within the inner tube 1438.

With reference to FIG. 151, there is shown a cutting stage of the removal threads 1430 using the inserter 1400 after the IUS 1402 is deployed in the uterine cavity 1440, in accordance with an embodiment of the present disclosure. In this stage, the removal threads 1430 are released by pushing a thread cutting button 1452 provided on a second cover portion 1454 (i.e. bottom side) of the handle 1418. Further shown, is an enlarged view of an internal structure of the inserter 1400 to depict cutting mechanism of the removal threads 1430 using the thread cutting button 1452. When the thread cutting button 1452 is pushed, a means 1456 for cutting the removal threads inside the handle 1418 cuts the removal threads 1430.

With reference to FIG. 15J, there is shown removal of the inserter 1400 from a subject, in accordance with an embodiment of the present disclosure. After the removal threads 1430 are cut, the inserter 1400 is pulled out from the vagina 1432 denoting the completion of the IUS 1402 insertion process by the inserter 1400. In this case, about 2-3 cm of removal threads 1430 is visible outside the cervix (i.e. outside the external orifice 1434) and about 2-3 cm into vagina 1432. Further, shown is an enlarged cross-sectional view of the IUS 1402 in the deployed state in the uterine cavity. The IUS 1402 comprises a sleeve 1458 that is arranged to surround a part of the frame 1416. The sleeve 1458 has a first end 1460 and a second end 1462. The second end 1462 of the sleeve 1458 comprises an indentation 1464 (i.e., an enlargement). The IUS 1402 further comprises the capsule 1442 arranged to surround the sleeve 1458. The capsule 1442 has a first end 1466, a second end 1468, and comprises a pharmaceutically active agent. The arrangement and length of the sleeve 1458 and the capsule 1442 facilitates the frame 1416 to attain the P-shape. Moreover, a rounded end part 1470 is arranged at the first end 1444 of the frame 1416 and the rounded end part 1470 has a larger diameter than the frame 1416. Further, shown are the removal threads 1430 attached to the recess 1450B in the means 1450A for engagement at the second end 1446 of the frame 1416. Referring to FIG. 16A, there is shown a perspective view of an inserter 1500, in accordance with another embodiment of the present disclosure. The inserter 1500 comprises a handle 1502, a measurement tube 1504, and an inner tube 1506. The handle 1502 has a proximal end 1508, a distal end 1510, and an opening 1512. A means 1514 for moving the plunger is arranged in the opening 1512 of the handle 1502. In this embodiment, the means 1514 for moving the plunger operates in a roller-like mechanism. The measurement tube 1504 has a proximal end 1516 and a distal end 1518. The proximal end 1516 of the measurement tube 1504 is movably attached to the distal end 1510 of the handle 1502. A tip cover 1520 is arranged to surround the distal end 1518 of the measurement tube 1504. The measurement tube 1504 is movably arranged to surround the inner tube 1506. Further shown is an IUS 1522. A part of a frame 1524 and a capsule 1526 of the IUS 1522 is present outside the inserter 1500. In this embodiment, the frame 1522 is a S-shaped frame. In case of the S-shaped frame, the IUS 1522 is preloaded in the inserter 1500 such that the capsule 1526 is outside the inserter 1500 and the tip cover 1520 is in a pulled back state (i.e. pulled back towards the handle 1502). A distal end 1528 of the inner tube 1506 is configured to cooperate with the IUS 1522. A flange 1530 is movably arranged on the measurement tube 1504. FIGs. 16B and 16C illustrate a schematic top view of the inserter 1500 depicting an exemplary internal structure of handle 1502 with an IUS 1522 in a preloaded state and an insertion state, respectively, in accordance with an embodiment of the present disclosure. With reference to FIG. 16B, there is shown the inserter 1500 with the means 1514 for moving the plunger. The means 1514 for moving the plunger comprises a rack 1530 arranged inside the handle 1502. The rack 1530 has a proximal end 1532 and a distal end 1534. The means 1514 for moving the plunger further comprises a pinion 1536 arranged in the opening of the handle 1502. The pinion 1536 is arranged to cooperate with the rack 1530. A proximal end 1538 of a plunger 1540 of the inserter 1500 is connected to the distal end 1534 of the rack 1530. The rack 1530 is in a first position 1542 (i.e. when the rack 1530 is near the proximal end 1508 of the handle 1502). The IUS 1522 is loaded within the inner tube of the inserter 1500 when the rack 1530 is moved to the first position 1542 by rolling the pinion 1536. The tip cover 1520 is pushed forward

(i.e. pushed away from the handle 1502).

With reference to FIG. 16C, there is shown the inserter 1500 with the rack 1530 in a second position 1544 (i.e. when the rack 1530 is near the distal end 1510 of the handle 1502). In the insertion state, the IUS 1522 is partially released out from the inserter 1500 when the rack

1530 is moved to the second position 1544 by rolling the pinion 1536.

Modifications to embodiments of the present disclosure described in the foregoing are possible without departing from the scope of the present disclosure as defined by the accompanying claims. Expressions such as "including", "comprising", "incorporating", "have", "is" used to describe and claim the present disclosure are intended to be construed in a non exclusive manner, namely allowing for items, components or elements not explicitly described also to be present. Reference to the singular is also to be construed to relate to the plural.