Medical devices, kits, methods, and anti-inflammatory substances

Abstract

The present invention relates to a medical device (10) configured to be at least partially placed within a patient's body via the patient's vagina for treating dysmenorrhea and / or endometriosis. The medical device (10) includes at least one carrier (12), at least one release element (14) at least partially attached to the carrier (12) and made of at least one biodegradable material, and at least one anti-inflammatory substance (16) embedded in the release element (14) such that the anti-inflammatory substance (16) is releasable within the patient's body when the medical device (10) is placed within the patient's body. The present invention also relates to kits, methods, and anti-inflammatory substances.

Description

[Technical Field]

[0001] There are several known diseases associated with the female reproductive system, many of which can cause discomfort, particularly severe discomfort, in at least some cases. For example, dysmenorrhea and endometriosis are known disorders of the female reproductive system that can range from mild to severe cases.

[0002] Dysmenorrhea, also known as perimenstrual pain or menstrual cramps, is a condition estimated by the World Health Organization (WHO) to affect up to 81% of women during their reproductive years. From a clinical perspective, dysmenorrhea can be classified as primary dysmenorrhea and secondary dysmenorrhea. Primary dysmenorrhea, the most common form of dysmenorrhea, has no obvious underlying anatomical cause. Instead, primary dysmenorrhea appears to be based on interacting genetic, epigenetic, and environmental factors. Secondary dysmenorrhea, on the other hand, is caused by an identifiable underlying disease, of which endometriosis is the most common. Therefore, endometriosis can exacerbate dysmenorrhea and worsen symptoms in affected women.

[0003] The detailed mechanisms of dysmenorrhea are not yet fully understood (see Ferries-Rowe et al. (2020): Primary Dysmenorrhea: Diagnosis and Therapy). However, it is clear that abnormal prostaglandin synthesis and prostaglandin signaling are central to this disorder. In affected women, hormonal changes, namely the normal decline in progesterone just before menstruation, trigger increased production of inflammatory mediators, such as prostaglandins. Prostaglandins can cause constriction of small uterine blood vessels, leading to tissue ischemia and discomfort, such as pain. In addition, prostaglandins are directly involved in pain signaling. Although several external factors, such as reproductive history, nutrition, and physical activity, can affect uterine prostaglandin signaling and, therefore, pain development, the occurrence of primary dysmenorrhea is most likely determined by congenital and genetic factors.

[0004] Endometriosis is the most common cause of secondary dysmenorrhea, affecting approximately 6-10% of all women. Endometriosis is characterized by the presence of endometrium (the lining of the uterine cavity) in areas of the affected woman's body other than the uterine cavity. Most importantly, however, endometriosis is characterized by increased chronic cyclical inflammation of the uterus and other pelvic tissues. This inflammation is even more pronounced than in primary dysmenorrhea. Chronically recurrent inflammatory episodes during each menstrual cycle can lead to progressive tissue destruction and fibrosis.

[0005] The severity of dysmenorrhea, whether primary or secondary, can range from mild pelvic discomfort to disabling pain, occurring in up to 29% of all women. In a recent large-scale survey of 42,879 women, 85% of participants reported abdominal pain during their menstrual periods (see Schoep et al., The impact of menstrual symptoms on everyday life: a survey among 42,879 women, Am J Obstet Gynecol, 220(6):569, doi: 10.1016 / j.ajog.2019.02.048). It has been estimated that in the United States, 10–30% of all working or school-aged women with dysmenorrhea lose 1–2 work / school days per month due to dysmenorrhea, which equates to approximately 600 million lost work hours per year and results in a financial loss of approximately US$2 billion per year (see Ferries-Rowe et al., Primary Dysmenorrhea: Diagnosis and Therapy, Obstet Gynecol, 136(5):1047–1058, doi: 10.1097 / AOG.0000000000004096). Thus, the burden caused by dysmenorrhea is substantial, both to individual women and to the economy. Furthermore, there is currently no cure for dysmenorrhea. Therefore, improving care for affected women should be a major public health priority.

[0006] Although treatments for dysmenorrhea and / or endometriosis are available, the treatments known from the prior art have several drawbacks. In particular, the effectiveness of the treatments known from the prior art may be insufficient to alleviate the discomfort caused by dysmenorrhea and / or endometriosis. The consequences of inappropriate treatment can be serious, as they can lead to chronic pain. In addition, some known treatments are prescribed and / or used regularly on an "as-needed" basis, i.e., when dysmenorrhea symptoms are acute or imminent. This forces subjects to frequently actively seek treatment or at least actively take one or more measures when dysmenorrhea symptoms are acute or imminent, making treatment more cumbersome for affected women. This may also limit the effectiveness of the treatment. In addition, some known treatments may cause one or more side effects, particularly one or more relatively serious side effects. Prior art for managing dysmenorrhea includes hormonal treatments, which significantly interfere with many organ systems and often cause unacceptable adverse effects. Another mainstay of conventional management of dysmenorrhea is the systemic administration of anti-inflammatory drugs (e.g., orally ingested tablets). Systemic administration of these drugs also frequently causes adverse effects in non-reproductive organs, such as the gastrointestinal tract and / or kidneys. During systemic administration of drugs, these organs are exposed to high concentrations of the active anti-inflammatory drug, but only a small portion of the active drug has an effect on the target organs in the reproductive tract.

[0007] These shortcomings have not been addressed, or at least not adequately addressed, in the prior art.

[0008] U.S. Pat. No. 10,064,815 discloses the treatment of various progesterone-related disorders by vaginal administration of pullulan capsules and a fill formulation containing one or more antiprogestins dispersed in a mixture of isopropyl palmitate or isopropyl myristate and polyethylene glycol.

[0009] U.S. Patent Application Publication No. 2014 / 030313 discloses a method for relieving menstrual pain and reducing menstrual blood flow in a woman, the method comprising intravaginally administering to the woman a first therapeutically effective amount of a nonsteroidal anti-inflammatory drug that relieves menstrual pain and a second therapeutically effective amount of an active agent that reduces menstrual blood flow.

[0010] WO 2019 / 119059 discloses a method for treating pain associated with dysmenorrhea in a subject, the method comprising administering to the subject an effective amount of an agent that reduces spinal cord glial activation, thereby treating pain and / or pain-related symptoms in the subject.

[0011] It is therefore an object of the present invention to provide an improved therapeutic means for treating dysmenorrhea and / or endometriosis, in particular a therapeutic means that addresses one or more of the above-identified shortcomings.

[0012] This object is achieved by a medical device according to a first aspect of the present disclosure, as defined by the features of claim 1. Preferred embodiments are defined by the features of the respective dependent claims.

[0013] The medical device may be configured to be placed at least partially within a patient's body via the patient's vagina to treat dysmenorrhea and / or endometriosis.

[0014] The medical device may include at least one carrier and at least one release element. The release element may be made of at least one biodegradable material, preferably at least one biodegradable biopolymer. The medical device may further include at least one anti-inflammatory substance. The anti-inflammatory substance may be embedded in and / or trapped in the release element. Alternatively, the anti-inflammatory substance may be incorporated into the medical device in various other ways. For example, the anti-inflammatory substance may be directly attached to the carrier, in which case the release element may be omitted as an intermediate structure connecting the carrier and the anti-inflammatory substance. Alternatively or additionally, the anti-inflammatory substance may be coated on the surface, preferably the outer surface, of the release element and / or the surface, preferably the outer surface, of the carrier.

[0015] The release element may be at least partially, preferably firmly, attached to the carrier so that the anti-inflammatory substance is releasable within the patient's body when the medical device is placed within the patient's body. Alternatively, or additionally, the release element and carrier may be configured so that the release element can be attached, preferably firmly, to the carrier so that the release element remains attached to the carrier after the medical device is placed within the patient's body, preferably within the patient's uterus. In other words, the release element and carrier may be configured to remain within the patient's body, preferably as a single, integral unit, after the medical device is placed within the patient's body and for the entire period during which the anti-inflammatory substance is released within the patient's body, i.e., during treatment. After treatment is completed, the carrier, and any residue of the release element if the anti-inflammatory substance has not been completely released from the release element, may be retrieved from the patient's body and replaced with another medical device, such as the medical devices described herein.

[0016] Anti-inflammatory substances can prevent or at least reduce the production of inflammatory substances such as prostaglandins and / or prevent or at least reduce pain signaling caused by inflammatory substances such as prostaglandins, which can reduce a patient's pain and / or discomfort caused by dysmenorrhea and / or endometriosis.

[0017] Providing a medical device that includes an anti-inflammatory substance and that is deployable within a patient's body via the patient's vagina, for example, within the patient's uterus, more particularly within the patient's uterine cavity, may allow the anti-inflammatory substance to be released and applied primarily locally to one or more female reproductive organs, particularly within the patient's uterus, and particularly to or at least near one or more areas within the patient's body that are affected by a disease.

[0018] Such localized release and application of anti-inflammatory agents may reduce the adverse systemic effects of the anti-inflammatory agent, for example, compared to oral ingestion and / or injection of the therapeutic agent, which may also increase the effectiveness and / or efficiency of the anti-inflammatory agent in providing relief from the symptoms of dysmenorrhea and / or endometriosis, for example, compared to oral ingestion and / or injection of the therapeutic agent.

[0019] Furthermore, sustained release of an anti-inflammatory substance may prevent or at least suppress the production of inflammatory mediators, such as prostaglandins, locally, i.e., at the site of discomfort and / or pain, thereby allowing, for example, a lower dose of the anti-inflammatory substance compared to oral ingestion and / or injection of the therapeutic substance when inflammatory mediators have already accumulated and are causing symptoms. This may reduce the adverse effects, or at least the risk thereof, caused by the anti-inflammatory substance. Furthermore, because known anti-inflammatory treatments prescribed and / or used on a regular basis, e.g., "as needed," are generally taken after pain and / or discomfort has already occurred, such treatments may be less effective than treatments provided by the medical devices described herein, at least based on the same extent or dosage.

[0020] Furthermore, the medical device can release an anti-inflammatory substance in the patient's body continuously or for at least a specific period while it is indwelling in the patient's body. Therefore, the patient does not need to re-administer the medical device for at least an extended period, for example, at least 6 or 12 months, preferably at least 24 months. Therefore, the medical device described herein may provide a more reliable, convenient, patient-friendly, and / or effective treatment for treating dysmenorrhea and / or endometriosis, especially compared to known treatments that are prescribed and / or used periodically, for example, "as needed." In particular, it has been found that pain management, especially pain management for dysmenorrhea and / or endometriosis, can be more effective and / or more efficient when taken prophylactically, i.e., before the onset of pain and / or discomfort, especially when using an anti-inflammatory substance.

[0021] Hormonal-based contraceptives, such as oral contraceptive pills or hormone-releasing intrauterine devices (IUDs), are commonly used to treat dysmenorrhea, but they can cause one or more side effects, sometimes serious. For example, the estrogen and progestins typically used can cause side effects, including but not limited to mood swings (including depression), weight gain, and thrombosis. Therefore, some of these treatments are contraindicated in many women who are overweight, smoke, have a history of thrombosis, or suffer from arterial hypertension, liver disease, or migraines. For this reason, providing a medical device containing an anti-inflammatory substance may reduce the side effects of treatment, or at least reduce the risk of side effects, compared to, for example, hormone-based contraceptives.

[0022] The ejection element and carrier may be attached to each other by any means suitable for providing the desired degree of attachment between the ejection element and the carrier. The ejection element and carrier may be attached to each other in a fixed manner, i.e., so that the ejection element and carrier are immovable relative to each other. In particular, the carrier and ejection element may be rigidly fused to each other, at least after the carrier and ejection element are assembled. Alternatively, the attachment between the ejection element and carrier may allow some movement between the ejection element and the carrier.

[0023] The emissive element and carrier may be permanently attached to one another, i.e., attached such that the emissive element cannot be removed from the carrier without compromising the structural integrity of the carrier and emissive element.

[0024] Alternatively, the release element and carrier may be removably attached to one another. For example, this may allow the carrier and release element to be assembled and disassembled, preferably multiple times. This may allow, for example, the release element and carrier to be provided as a kit that can be assembled, for example, by a user and / or medical professional. This may allow, for example, the carrier to be configured as a reusable part that can be reloaded with one or more replacement release elements, such as after the anti-inflammatory substance of the original release element has been fully consumed. Furthermore, this may allow a carrier to be more easily combined with multiple different release elements, and / or vice versa, to accommodate different patient anatomies, such as by providing multiple different release elements and / or multiple different carriers having different shapes, sizes, materials, etc. Furthermore, this may allow multiple release elements, each differing in one or more characteristics, such as the amount and / or weight of the anti-inflammatory substance, the type of anti-inflammatory substance, the release rate of the anti-inflammatory substance, etc., to be combined with one or more carriers.

[0025] The medical device may be configured to remain securely placed within a patient's body, preferably within the patient's uterus, and more particularly within the patient's uterine cavity, for extended periods of time, including during daily activities such as exercise. To securely retain the medical device within the patient's body, the medical device, e.g., the carrier and / or release element, may include one or more fixation mechanisms, e.g., one or more engagement arms, configured to engage at least a portion of the patient's anatomy within the patient's body to secure the medical device within the patient's body.

[0026] The carrier may be made from a material that is non-resorbable and / or non-absorbable and / or non-degradable by the patient's body. Preferably, the carrier is made from plastic, such as low density polyethylene (LDPE).

[0027] Preferably, at least one anti-inflammatory substance comprises at least one non-hormonal and / or non-steroidal anti-inflammatory substance, preferably celecoxib and / or diclofenac.However, many alternative anti-inflammatory substances can also be used.For example, alternative anti-inflammatory substances can comprise one or more of ibuprofen, ketoprofen, mefenamic acid, naproxen, piroxicam, and indomethacin.Alternative non-hormonal anti-inflammatory substances can comprise glyceryl trinitrate, which may require a lower concentration than other anti-inflammatory substances, particularly non-hormonal anti-inflammatory substances.

[0028] Preferably, the medical device is configured to be placed in at least a portion of a patient's uterus, more specifically, in the patient's uterine cavity. In other words, the medical device may be configured as an intrauterine device. This allows for more targeted and localized release and application of the anti-inflammatory substance, i.e., application within the patient's uterus, and can more precisely target the source of discomfort and / or pain caused by dysmenorrhea and / or endometriosis.

[0029] Preferably, the medical device does not contain hormonal substances, which may prevent side effects caused by hormonal substances, as discussed above, compared to hormone-based contraceptives, such as oral contraceptive pills or hormone-releasing intrauterine devices (IUDs).

[0030] Preferably, the medical device is configured to continuously release the anti-inflammatory substance within the patient's body at a rate greater than zero when the medical device is placed within the patient's body, which may allow the medical device to continuously release the anti-inflammatory substance within the patient's body while the medical device is placed within the patient's body, which may more effectively and / or efficiently relieve the patient's discomfort and / or pain, as described above.

[0031] Preferably, the release element is configured to interact with an environment within the patient's body to trigger release of the anti-inflammatory substance. Preferably, the release element is configured to subsequently release the anti-inflammatory substance continuously. For example, release of the anti-inflammatory substance may be activated by an aqueous and / or warm environment within the patient's body.

[0032] Preferably, the release element is configured to at least partially disintegrate within the patient's body when the release element is attached to the carrier and / or when the medical device is placed within the patient's body. The anti-inflammatory substance may be at least partially embedded in the release element such that the anti-inflammatory substance is released into the patient's body as the release element disintegrates when the medical device is placed within the patient's body. Alternatively, the release element may not disintegrate, or may not disintegrate at least to release the anti-inflammatory substance. Alternatively, the anti-inflammatory substance may be applied to a portion of the carrier and / or the release element, for example as at least one coating, and the anti-inflammatory substance may be released / excreted from the release element.

[0033] Preferably, the anti-inflammatory substance is dispersed within the release element, which is preferably firmly attached to the carrier.

[0034] Preferably, the release element is configured to at least partially degrade within the patient's body when the medical device is placed within the patient's body, preferably at a constant rate, thereby releasing the anti-inflammatory substance into the patient's body as the release element degrades.

[0035] Preferably, the release element containing the anti-inflammatory substance is configured as a solid component. The release element may be at least partially hollow. The release element may be configured as a tube configured to at least partially surround at least a portion of the carrier to which the release element is attached. The term "solid" refers to the aggregated state of the release element containing the anti-inflammatory substance. Providing the release element containing the anti-inflammatory substance in a solid aggregated state may facilitate the introduction of the medical device into a patient's body, for example, by providing a more rigid structure to the medical device. Furthermore, this may allow for more precise control of the release of the anti-inflammatory substance, for example, allowing for a reduction in the dose and / or release rate of the anti-inflammatory substance.

[0036] Preferably, the carrier includes at least one receiving portion configured to securely receive the release element. The receiving portion may be configured as an elongate member configured to be at least partially received within the release element, or vice versa. Preferably, the release element includes at least one lumen configured to at least partially receive the receiving portion of the carrier, or vice versa.

[0037] Preferably, the receiving portion has a diameter of 2.4 mm or less, more preferably 2.2 mm or less, more preferably 2 mm or less, more preferably 1.8 mm or less, more preferably 1.6 mm or less, more preferably 1.4 mm or less, more preferably 1.2 mm or less, and more preferably 1 mm or less. This can limit the size of the carrier and, therefore, the size of the medical device, and can reduce the discomfort the medical device may cause to the patient. The diameter, i.e., width, of the receiving portion can be configured to be relatively small, for example, according to the values ​​specified above, because the release element can be configured to provide stability to the carrier in the receiving portion, for example, by surrounding and / or extending along a portion of the receiving portion. In fact, the release element may partially or entirely replace the receiving portion.

[0038] Preferably, the medical device includes at least one fixation mechanism configured to secure the medical device within at least a portion of the patient's uterus, more particularly within the patient's uterine cavity. The fixation mechanism may be configured in any manner suitable for engaging with and securing the medical device within at least a portion of the patient's uterus. The fixation mechanism may be provided by the carrier. Preferably, the carrier including the fixation mechanism may be integrally formed. Alternatively, the carrier may include multiple assembled parts. Alternatively, or additionally, the fixation mechanism may be provided by the release element and / or one or more further components of the medical device.

[0039] Preferably, the fixation mechanism includes at least one arm configured to engage a wall of the patient's uterus to fix the medical device within the patient's uterus. The arm may be provided by the carrier. For example, the arm may extend from at least one main portion of the carrier, such as the receptacle. Preferably, the receptacle and the arm may be integrally formed. Alternatively, the receptacle and the arm may be configured as separate components that are assembled. The arm may be flexible, e.g., bendable and / or extensible, preferably elastically deformable, e.g., to facilitate deployment of the medical device within the patient's body and / or to facilitate fixation of the medical device within the patient's body.

[0040] Preferably, the fixation mechanism includes at least two arms configured to engage substantially opposite sides of the patient's uterus to fix the medical device within the patient's uterus, which may further reduce the risk of the medical device becoming displaced and / or dislodged from its intended position within the patient's uterus. The arms may be flexible, e.g., bendable and / or extensible, preferably elastically deformable.

[0041] Preferably, the arm is attached to the receiver such that the arm and receiver are configured in a substantially Y- or T-shape, which may provide a shape that corresponds to, or at least matches, the general shape of a woman's uterine cavity to facilitate secure placement of the medical device within the patient's uterine cavity.

[0042] Preferably, the release element having the anti-inflammatory substance embedded therein is at least partially attached to at least one of the arms, preferably both arms, which may allow the area of ​​the release surface of the medical device from which the anti-inflammatory substance can be released to be adapted to desired needs, such as providing a more effective and / or efficient treatment by increasing the area of ​​the release surface of the medical device.

[0043] Preferably, the medical device is configured to release the anti-inflammatory substance into the patient's body, more preferably continuously, for at least 10 months, more preferably at least 11 months, more preferably at least 12 months, more preferably at least 13 months, more preferably at least 14 months, more preferably at least 15 months, more preferably at least 16 months, more preferably at least 17 months, more preferably at least 18 months, more preferably at least 19 months, more preferably at least 20 months, more preferably at least 21 months, more preferably at least 22 months, more preferably at least 23 months, or more preferably at least 24 months. The specified period of time may allow the patient to use a single medical device for an extended period of time, i.e., the specified period of time, without having to re-administer additional medical devices during each period. This may provide a more reliable, convenient, patient-friendly, and / or effective treatment for treating dysmenorrhea and / or endometriosis.

[0044] Preferably, the medical device is configured to release the anti-inflammatory substance, more preferably continuously, at a daily release rate of less than 3 mg per day, more preferably less than 2.8 mg per day, more preferably less than 2.6 mg per day, more preferably less than 2.4 mg per day, more preferably less than 2.2 mg per day, more preferably less than 2 mg per day, more preferably less than 1.8 mg per day, more preferably less than 1.6 mg per day, more preferably less than 1.4 mg per day, more preferably less than 1.2 mg per day, or more preferably less than 1 mg per day. Limiting the daily release rate according to the values ​​specified above may allow for more precise control of the release of the anti-inflammatory substance and / or reduce the patient's exposure to the anti-inflammatory substance per unit time, compared to known treatments that are prescribed and / or used regularly on an "as needed" basis, for example. This may reduce potential side effects and / or toxicity of the anti-inflammatory substance.

[0045] Preferably, the medical device is configured to release the anti-inflammatory agent at a daily release rate in the range of 0.2 mg to 1 mg per day, more preferably 0.4 mg to 1 mg per day, more preferably 0.6 mg to 1 mg per day, more preferably 0.8 mg to 1 mg per day.

[0046] Preferably, the medical device is configured to release the anti-inflammatory agent at a daily release rate with a day-to-day variation of no more than 0.3 mg per day, more preferably no more than 0.2 mg per day, more preferably no more than 0.1 mg per day, which may allow for more precise control of the release of the anti-inflammatory agent, reducing potential side effects of the anti-inflammatory agent, and / or increasing the effectiveness and / or efficiency of treatment with the medical device described herein.

[0047] Preferably, the medical device comprises at least 100 mg, more preferably at least 150 mg, more preferably at least 200 mg, more preferably at least 250 mg, more preferably at least 300 mg, more preferably at least 350 mg, more preferably at least 400 mg, more preferably at least 450 mg, more preferably at least 500 mg of anti-inflammatory substance. It may be desirable to strike a balance between the weight of the medical device, which may be desirable to be relatively low, and the longevity and / or effectiveness of the anti-inflammatory substance, for example, by selecting an appropriate / desired amount / weight of the anti-inflammatory substance. Thus, the weight of the anti-inflammatory substance may be selected accordingly, for example, according to the values ​​specified above.

[0048] Preferably, the medical device further includes an extraction device configured to allow the medical device to be extracted from the patient's body. The extraction device may be configured as one or more graspable elements that can be grasped by a human, such as a patient and / or a medical professional. The extraction device may allow for safe and secure retrieval of the medical device from the patient's body. For example, the extraction device may include one or more elongated elements, such as one or more strings, that extend toward or into the patient's cervix and / or vagina when the medical device is in operative use within the patient's body. The extraction device is preferably made from a material that is non-resorbable and / or non-absorbable and / or non-degradable by the patient's body.

[0049] Preferably, the medical device further comprises at least one hemostatic agent, preferably attached to the carrier, which may stop or at least reduce bleeding that may occur at or near the deployment site of the medical device within the patient's body due to, for example, potential interactions between the patient's body anatomy and the medical device and / or increased menstrual bleeding.

[0050] The object stated at the outset is also solved by a kit according to a second aspect of the present disclosure, as defined by the features of claim 13. The features, embodiments and advantages explained above with respect to the medical device according to the first aspect of the present disclosure apply analogously to the kit.

[0051] The kit may include at least one carrier configured to be at least partially placed within the patient's body via the patient's vagina, and at least one release element, which may be made from at least one biodegradable material.

[0052] The kit may further include at least one anti-inflammatory agent, which may be embedded in the release element.

[0053] The release element may be configured to be at least partially attachable to the carrier such that when the release element is attached to the carrier and the carrier containing the release element is placed in the patient's body, the anti-inflammatory substance is releasable within the patient's body.

[0054] The object stated at the beginning is also solved by a method for treating at least one disease of the female reproductive system of a patient, preferably dysmenorrhea and / or endometriosis, by means of a medical device, preferably by means of the medical device described above. The features, embodiments and advantages explained above with respect to the medical device according to the first aspect of the present disclosure apply equally to the method.

[0055] The method is configured to treat at least one disorder of the patient's female reproductive system, preferably dysmenorrhea and / or endometriosis, preferably with a medical device according to any of the embodiments described herein.

[0056] The method may include placing a medical device at least partially into the patient's body via the patient's vagina, the medical device including at least one carrier, at least one release element made from at least one biodegradable material, and at least one anti-inflammatory substance embedded in the release element. The release element may be preferably firmly attached to the carrier. The release element may remain attached to the carrier after the medical device is placed in the patient's body, preferably in the patient's uterus.

[0057] The method may further include releasing an anti-inflammatory substance within the patient's body when the medical device is placed within the patient's body.

[0058] The object stated at the outset is also solved by an anti-inflammatory substance according to a fourth aspect of the present disclosure, as defined by the features of claim 14. The features, embodiments and advantages explained above with respect to the medical device according to the first aspect of the present disclosure apply analogously to the anti-inflammatory substance.

[0059] The anti-inflammatory substance is preferably a nonsteroidal anti-inflammatory substance and / or a non-hormonal anti-inflammatory substance. The anti-inflammatory substance may be diclofenac and / or celecoxib. However, many alternative anti-inflammatory substances may also be used. For example, alternative anti-inflammatory substances may include one or more of ibuprofen, ketoprofen, mefenamic acid, naproxen, piroxicam, and indomethacin. Alternative (non-hormonal) anti-inflammatory substances may include other anti-inflammatory substances, particularly glyceryl trinitrate, which may require even lower concentrations than non-hormonal anti-inflammatory substances. Anti-inflammatory substances may be used to treat dysmenorrhea and / or endometriosis, preferably by a medical device according to any of the embodiments described herein.

[0060] The anti-inflammatory substance may be embedded in at least one release element made of at least one biodegradable material. The release element may be at least partially attached to at least one carrier. The carrier including the release element and the embedded anti-inflammatory substance may be at least partially placed within the patient's body via the patient's vagina. The anti-inflammatory substance may be released within the patient's body when the carrier including the release element is placed within the patient's body.

[0061] The following list of aspects provides preferred embodiments of the present disclosure: 1. 1. A medical device configured to be at least partially placed within a patient's body via the patient's vagina for treating dysmenorrhea and / or endometriosis, said medical device comprising: at least one carrier; at least one anti-inflammatory substance at least partially attached to the carrier such that the anti-inflammatory substance is releasable within the patient's body when the medical device is placed within the patient's body; 2. A medical device, comprising: 2. 10. The medical device of aspect 1, further comprising at least one release element at least partially attached to the carrier, wherein the anti-inflammatory substance is attached to, or preferably at least partially embedded in, the release element. 3. The medical device of aspect 2, wherein the release element is made at least partially, preferably completely, from at least one biodegradable material. 4. 10. The medical device of any of the previous embodiments, wherein the at least one anti-inflammatory agent comprises at least one non-hormonal and / or non-steroidal anti-inflammatory agent, preferably celecoxib and / or diclofenac. 5.

[0023] 20. The medical device of any of the preceding embodiments, wherein the at least one anti-inflammatory agent comprises diclofenac and / or celecoxib. 6. Aspect 14. The medical device of any of the preceding aspects, wherein the medical device is configured to be placed in at least a portion of a uterus of a patient. 7. Aspect 14. The medical device of any of the preceding aspects, wherein the medical device is free of hormonal substances. 8. Aspect 14. The medical device of any of the preceding aspects, wherein the medical device is configured, when placed within a patient, to release the anti-inflammatory substance continuously within the patient at a rate greater than zero. 9. A medical device according to any of aspects 2-8, wherein the release element is configured to interact with an environment within the patient's body to trigger the release of the anti-inflammatory substance, and preferably the release element is configured to subsequently release the anti-inflammatory substance continuously. 10. A medical device according to any one of Aspects 2-9, wherein the release element is configured to at least partially disintegrate within a patient's body when the medical device is placed within the patient's body, and the anti-inflammatory substance is at least partially embedded within the release element such that the anti-inflammatory substance is released into the patient's body as the release element disintegrates when the medical device is placed within the patient's body. 11. Aspect 11. The medical device of any one of aspects 2 to 10, wherein the anti-inflammatory substance is dispersed within the release element. 12. A medical device according to any one of Aspects 2 to 11, wherein the release element is configured to at least partially degrade within the patient's body, preferably at a constant rate, when the medical device is placed within the patient's body, and to release the anti-inflammatory substance into the patient's body as the release element degrades. 13. 13. The medical device of any of aspects 2-12, wherein the release element containing the anti-inflammatory substance is configured as a solid component, and the release element is at least partially hollow, preferably the release element is configured as a tube configured to at least partially surround at least a portion of the carrier. 14. A medical device described in any of aspects 2 to 13, wherein the carrier includes at least one receiving portion configured to securely receive the release element, and preferably the receiving portion is configured as an elongated member configured to be at least partially received within the release element. 15. 15. The medical device of aspect 14, wherein the receiving portion has a diameter of 2.4 mm or less, preferably 2.2 mm or less, more preferably 2 mm or less, more preferably 1.8 mm or less, more preferably 1.6 mm or less, more preferably 1.4 mm or less, more preferably 1.2 mm or less, more preferably 1 mm or less. 16. Aspect 10. The medical device of any of the preceding aspects, wherein the medical device includes at least one fixation mechanism configured to secure the medical device to at least a portion of the patient's uterus. 17. A medical device as described in aspect 16, wherein the fixation mechanism includes at least one arm configured to engage a wall of the patient's uterus to secure the medical device within the patient's uterus. 18. A medical device described in aspect 16 or 17, wherein the fixation mechanism includes at least two arms configured to engage substantially opposite sides of the patient's uterus to secure the medical device within the patient's uterus. 19. Aspect 19. The medical device of aspect 18, wherein the arm is attached to the receiver such that the arm and the receiver are configured substantially in a Y-shape or a T-shape. 20. Aspect 14. The medical device of any of the preceding aspects, wherein the anti-inflammatory substance is at least partially attached to at least one of the arms, preferably both arms. twenty one. 10. The medical device of any of the preceding aspects, wherein the medical device is configured to release the anti-inflammatory agent, preferably continuously, in the patient's body for at least 10 months, more preferably at least 11 months, more preferably at least 12 months, more preferably at least 13 months, more preferably at least 14 months, more preferably at least 15 months, more preferably at least 16 months, more preferably at least 17 months, more preferably at least 18 months, more preferably at least 19 months, more preferably at least 20 months, more preferably at least 21 months, more preferably at least 22 months, more preferably at least 23 months, and more preferably at least 24 months. twenty two. 10. The medical device of any of the preceding aspects, wherein the medical device is configured to release the anti-inflammatory agent, preferably continuously, at a daily release rate of less than 3 mg per day, more preferably less than 2.8 mg per day, more preferably less than 2.6 mg per day, more preferably less than 2.4 mg per day, more preferably less than 2.2 mg per day, more preferably less than 2 mg per day, more preferably less than 1.8 mg per day, more preferably less than 1.6 mg per day, more preferably less than 1.4 mg per day, more preferably less than 1.2 mg per day, and more preferably less than 1 mg per day. twenty three. 10. The medical device of any of the preceding aspects, wherein the medical device is configured to release the anti-inflammatory agent at a daily release rate ranging from 0.2 mg to 1 mg per day, preferably from 0.4 mg to 1 mg per day, more preferably from 0.6 mg to 1 mg per day, and more preferably from 0.8 mg to 1 mg per day. twenty four.

[0023] A medical device according to any of the preceding aspects, wherein the medical device is configured to release the anti-inflammatory agent at a daily release rate having an interday variation of less than or equal to 0.3 mg per day, preferably less than or equal to 0.2 mg per day, and more preferably less than or equal to 0.1 mg per day. twenty five. 10. The medical device of any of the preceding aspects, wherein the medical device comprises at least 100 mg, preferably at least 150 mg, more preferably at least 200 mg, more preferably at least 250 mg, more preferably at least 300 mg, more preferably at least 350 mg, more preferably at least 400 mg, more preferably at least 450 mg, more preferably at least 500 mg of the anti-inflammatory agent. 26. Aspect 12. The medical device of any of the preceding aspects, further comprising an extraction apparatus configured to allow the medical device to be extracted from the patient's body. 27. 10. The medical device of any of the preceding aspects, further comprising at least one hemostatic agent, said hemostatic agent preferably attached to said carrier. 28. A kit comprising: at least one carrier configured to be at least partially placed within the patient's body via the patient's vagina; at least one anti-inflammatory agent; Including, The anti-inflammatory substance is configured to be at least partially attachable to the carrier such that when the anti-inflammatory substance is attached to the carrier and the carrier including the release element is placed in the patient's body, the anti-inflammatory substance is releasable within the patient's body. 29. 29. The kit of claim 28, further comprising at least one release element, wherein the anti-inflammatory substance is attached to or preferably at least partially embedded in the release element, and wherein the release element is configured to be at least partially attachable to the carrier such that the anti-inflammatory substance is releasable within the patient's body when the release element is attached to the carrier and the carrier is placed within the patient's body. 30. 30. The kit of embodiment 29, wherein the release element is made at least partially, and preferably completely, from at least one biodegradable material. 31. 28. A method for treating at least one disorder of the female reproductive system, preferably dysmenorrhea and / or endometriosis, in a patient, preferably using a medical device according to any of aspects 1 to 27, said method comprising: placing at least partially within the patient's body via the patient's vagina a medical device comprising at least one carrier and at least one anti-inflammatory substance at least partially attached to said carrier; releasing the anti-inflammatory substance within the patient's body when the medical device is placed within the patient's body; A method comprising: 32. 32. The method of embodiment 31, wherein the anti-inflammatory substance is attached to, or preferably at least partially embedded in, at least one release element, which release element is at least partially attached to the carrier. 33. 33. The method of embodiment 32, wherein the release element is at least partially, and preferably completely, made from at least one biodegradable material. 34. 28. An anti-inflammatory substance, preferably a nonsteroidal and / or non-hormonal anti-inflammatory substance, preferably diclofenac and / or celecoxib, for use in treating dysmenorrhea and / or endometriosis, preferably with a medical device according to any of aspects 1 to 27, wherein the anti-inflammatory substance is embedded in at least one release element made of at least one biodegradable material, the release element being at least partially attached to at least one carrier, the release element and the carrier comprising the embedded anti-inflammatory substance being at least partially placed within a patient's body via the patient's vagina, and the anti-inflammatory substance is released within the patient's body when the carrier comprising the release element is placed within the patient's body.

[0062] Preferred embodiments of the present invention will be further elucidated below with reference to the drawings, in which: The described embodiments are merely examples and are not intended to limit the present invention. [Brief explanation of the drawings]

[0063] [Figure 1] FIG. 1 shows a schematic diagram of a medical device according to one embodiment of the present disclosure. [Figure 2] FIG. 2 shows, in a schematic diagram, a medical device according to a further embodiment of the present disclosure.

[0064] 1 schematically illustrates a medical device 10 that may be configured to be at least partially placed within a patient's body via the patient's vagina to treat dysmenorrhea and / or endometriosis. Medical device 10 may include at least one carrier 12 and at least one release element 14, which may be made from at least one biodegradable material, preferably at least one biodegradable biopolymer. Medical device 10 may further include at least one anti-inflammatory substance 16 that may be at least partially embedded or entrapped in release element 14. Release element 14 may be at least partially attached to carrier 12 such that anti-inflammatory substance 16 is releasable within the patient's body when medical device 10 is placed within the patient's body.

[0065] The release element 14 may be configured to at least partially disintegrate or degrade within a patient's body when the medical device 10 is placed within the patient's body. The anti-inflammatory substance 16 may be released within the patient's body as the release element 14 disintegrates / degrades when the medical device 10 is placed within the patient's body.

[0066] Preferably, the release element 14 containing the anti-inflammatory substance 16 is configured in a solid aggregate state. The release element 14 may include at least one lumen (not shown) configured to receive at least a portion of the carrier 12 to secure the release element 14 to the carrier 12. Preferably, the release element 14 may be configured as a tube configured to at least partially surround at least a portion of the carrier 12.

[0067] The at least one anti-inflammatory substance 16 includes at least one non-hormonal and / or non-steroidal anti-inflammatory substance, preferably celecoxib and / or diclofenac. However, many alternative anti-inflammatory substances 16 can be used. For example, alternative anti-inflammatory substances can include one or more of ibuprofen, ketoprofen, mefenamic acid, naproxen, piroxicam, and indomethacin. Alternative non-hormonal anti-inflammatory substances can include glyceryl trinitrate, which may require even lower concentrations and / or release rates than other anti-inflammatory substances, particularly non-hormonal anti-inflammatory substances.

[0068] An advantage of the medical device 10 described herein is that the release of the therapeutic substance, i.e., the anti-inflammatory substance 16, may be relatively precisely controlled, e.g., allowing the dose and / or release rate of the anti-inflammatory substance to be reduced and / or kept relatively constant / continuous. For example, the release rate of the anti-inflammatory substance 16 may be controlled / adjusted by controlling / adjusting the rate of disintegration / degradation of the release element 14.

[0069] The medical device 10 may be configured to continuously release the anti-inflammatory substance 16 at a rate greater than zero within the patient's body when the medical device 10 is placed within the patient's body. The medical device 10 may be configured to preferably continuously release the anti-inflammatory substance 16 at a daily release rate of less than 3 mg per day, more preferably less than 2 mg per day, and more preferably less than 1 mg per day.

[0070] The medical device 10 may include at least one fixation mechanism 30 configured to secure the medical device 10 within the patient's body, preferably to at least a portion of the patient's uterus, and more specifically to the patient's uterine cavity. The fixation mechanism 30 may include at least one arm 32 configured to engage a wall of the patient's uterus to secure the medical device 10 within the patient's uterus. Alternatively, the fixation mechanism 30 may include multiple arms, e.g., at least two arms 32, as shown in Figures 1 and 2. The arms 32 may be configured to engage substantially opposite sides of the patient's uterus to secure the medical device 10 within the patient's uterus.

[0071] The carrier 12 may include at least one receptacle 34 configured to securely receive the release element 14. For example, the receptacle 34 may be configured as an elongated member configured to be at least partially received within the release element 14.

[0072] The arm 32 may be attached to the receiver 34 such that the arm 32 and receiver 34 are configured in a substantially Y- or T-shape.

[0073] The medical device 10 may further include an extraction device 36 configured to allow the medical device 10 to be extracted from the patient's body. The extraction device 36 may be configured as one or more graspable elements that can be grasped by a human, such as a patient and / or a medical professional. For example, the extraction device 36 may include one or more elongated elements, such as one or more strings, that extend toward or into the patient's cervix and / or vagina when the medical device 10 is in operative use within the patient's body, as shown in FIGS. 1 and 2 .

[0074] The anti-inflammatory substance 16 may be disposed on, and optionally attached to, one or more of the arms 32, as shown in Figure 2. For example, the release element 14 may extend across at least a portion of one or more of the arms 32. In this case, preferably, the medical device 10 may include multiple release elements 14, for example, at least one first release element 14 disposed on, and optionally attached to, one or more of the arms 32, and at least one second release element 14 disposed on, and optionally attached to the receiver 34.

Claims

1. 1. A medical device (10) for treating dysmenorrhea and / or endometriosis, configured to be placed in at least a portion of a patient's uterus via the patient's vagina, said medical device (10) comprising: At least one carrier (12); At least one emitting element (14) attached to said carrier (12); at least one anti-inflammatory substance (16) embedded in the release element (14) so ​​as to be releasable within the patient's body when the medical device (10) is placed in the patient's uterus, the at least one anti-inflammatory substance (16) comprising at least one non-steroidal anti-inflammatory substance; at least one fixation mechanism (30) configured to fix the medical device (10) to at least a portion of the patient's uterus; A medical device (10) comprising:

2. 10. The medical device (10) of claim 1, wherein the at least one anti-inflammatory substance (16) comprises at least one non-hormonal anti-inflammatory substance.

3. 3. The medical device (10) of claim 1 or 2, wherein the at least one anti-inflammatory substance (16) is celecoxib and / or diclofenac.

4. The medical device (10) of any one of claims 1 to 3, wherein the release element (14) is configured to at least partially disintegrate within a patient's body when the medical device (10) is placed within the patient's body, and the anti-inflammatory substance (16) is at least partially embedded within the release element (14) such that the anti-inflammatory substance (16) is released into the patient's body as the release element (14) disintegrates when the medical device (10) is placed within the patient's body.

5. The medical device (10) of any one of claims 1 to 4, wherein the release element (14) is configured to at least partially degrade within the patient's body, preferably at a constant rate, when the medical device (10) is placed within the patient's body, and to release the anti-inflammatory substance (16) into the patient's body as the release element (14) degrades.

6. The medical device (10) of any one of claims 1 to 5, wherein the release element (14) containing the anti-inflammatory substance (16) is configured as a solid component, the release element (14) being at least partially hollow, preferably the release element (14) being configured as a tube configured to at least partially surround at least a portion of the carrier (12).

7. 7. The medical device (10) of any one of claims 1 to 6, wherein the fixation mechanism (30) includes at least two arms (32) configured to engage substantially opposite sides of the patient's uterus to fixate the medical device (10) within the patient's uterus.

8. The medical device (10) of any one of claims 1 to 7, wherein the release element (14) containing the embedded anti-inflammatory substance (16) is at least partially attached to at least one of the arms, preferably both arms.

9. 9. The medical device (10) of any one of claims 1 to 8, wherein the medical device (10) is configured to release, preferably continuously, the anti-inflammatory substance (16) in a patient's body for at least 10 months, more preferably at least 11 months, more preferably at least 12 months, more preferably at least 13 months, more preferably at least 14 months, more preferably at least 15 months, more preferably at least 16 months, more preferably at least 17 months, more preferably at least 18 months, more preferably at least 19 months, more preferably at least 20 months, more preferably at least 21 months, more preferably at least 22 months, more preferably at least 23 months, more preferably at least 24 months.

10. 10. The medical device (10) of any one of claims 1 to 9, wherein the medical device (10) is configured to release, preferably continuously, the anti-inflammatory substance (16) at a daily release rate of less than 3 mg per day, more preferably less than 2.8 mg per day, more preferably less than 2.6 mg per day, more preferably less than 2.4 mg per day, more preferably less than 2.2 mg per day, more preferably less than 2 mg per day, more preferably less than 1.8 mg per day, more preferably less than 1.6 mg per day, more preferably less than 1.4 mg per day, more preferably less than 1.2 mg per day, more preferably less than 1 mg per day.

11. 11. The medical device (10) of any one of claims 1 to 10, wherein the medical device (10) is configured to release the anti-inflammatory substance (16) at a daily release rate having an interday variation of 0.3 mg or less, preferably 0.2 mg or less, more preferably 0.1 mg or less per day.

12. A kit comprising: at least one carrier (12) configured to be placed in at least a portion of the patient's uterus via the patient's vagina; At least one release element (14) made from at least one biodegradable material; at least one anti-inflammatory substance (16) embedded in said release element (14), said at least one anti-inflammatory substance (16) comprising at least one non-steroidal anti-inflammatory substance; Including, the carrier (12) and / or the release element (14) includes at least one fixation mechanism (30) configured to fix the carrier (12) and / or the release element (14) to at least a portion of the patient's uterus; The release element (14) is configured to be at least partially attachable to the carrier (12) such that when the release element (14) is attached to the carrier (12) and the carrier (12) containing the release element (14) is placed in the patient's uterus, the anti-inflammatory substance (16) is releasable within the patient's body.

13. 12. A non-steroidal anti-inflammatory substance for use in treating dysmenorrhea and / or endometriosis, preferably with a medical device (10) according to any one of claims 1 to 11, wherein the anti-inflammatory substance (16) is embedded in at least one release element (14) made of at least one biodegradable material, the release element (14) being at least partially attached to at least one carrier (12), the carrier (12) including the release element (14) and the embedded anti-inflammatory substance (16) being placed in at least a portion of the patient's uterus via the patient's vagina, the anti-inflammatory substance (16) being released within the patient's body when the carrier (12) including the release element (14) is placed in the patient's uterus, and the carrier (12) and / or the release element (14) include at least one fixation mechanism (30) configured to fix the carrier (12) and / or the release element (14) to at least a portion of the patient's uterus.

14. 14. The nonsteroidal anti-inflammatory substance of claim 13, wherein the substance is diclofenac and / or celecoxib.

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