Prophylaxis of stenoses in the ureter

Abstract

The invention relates to an active ingredient for use in a method for the prophylaxis of stenoses in the ureter, wherein the active ingredient is a cell proliferation inhibitor and / or an inhibitor for inflammatory and / or fibrosis cascades. In particular in the case of urinary calculi treatments, there is a considerable risk of developing a ureteric stricture. The prophylactic use of the active compounds according to the invention is an effective strategy for preventing ureteric strictures, in particular in high-risk cases.

Description

[0001] RBBN0098

[0002] December 9, 2025

[0003] XD / KQ

[0004] Ureteral stenosis norophylaxis

[0005] The invention relates to a method for the prophylaxis of stenoses, in particular for the prevention of stenoses in the ureter.

[0006] Urinary stones are a very common condition, especially in Western countries. They form due to an oversaturation of stone-forming substances in the urine, leading to crystallization and subsequent stone formation. Depending on their location in the body, they are also called kidney stones, ureteral stones, or bladder stones.

[0007] The kidney stones that form, especially larger ones, can become lodged in the urinary tract. This can lead to urinary tract obstruction and / or serious infections. Therefore, medical treatment is necessary in such cases.

[0008] There are various treatment options for kidney stones, such as ureteroscopy, shock wave lithotripsy, electrohydraulic lithotripsy, or percutaneous nephrolithotomy. Of the different treatment methods, ureteroscopy is the preferred technique, especially in the form of laser lithotripsy.

[0009] Laser lithotripsy uses lasers to treat kidney stones, as it often achieves better results for patients than other methods. The laser fragments the kidney stones. The stones or their fragments are then physically captured or flushed out with urine, similar to traditional ureteroscopy. A significant complication risk of laser lithotripsy is the formation of ureteral strictures. The incidence of these is up to 10%, depending on factors such as the severity of the injury and the type of kidney stone. Kidney stones lodged at the renal end of the ureter or in a renal calyx may require intensive laser treatment, which can also damage the surrounding tissue. In particular, high temperatures can occur, sometimes reaching 60°C or higher in the tissue.The mucosa and submucosa are particularly susceptible to damage. Risk factors include urinary stones with a diameter greater than 1 cm and edema or inflammation of the ureteral wall at the time of lithotripsy. The composition of the urinary stone also plays a role; for example, particularly hard stones made of calcium oxalate monohydrate or cystine stones require higher laser energies to induce fragmentation, which in turn is associated with increased side effects.

[0010] Strictures are ureteral fibroses that can lead to stenosis of the ureteral lumen. They typically develop within weeks to months after surgery and may remain asymptomatic until they cause significant narrowing of the ureter, which can result in obstruction, hydronephrosis, or impaired kidney function, potentially leading to kidney death. In some cases, this damage is irreversible, necessitating nephrectomy (removal of the kidney) and requiring dialysis.

[0011] Currently, to ensure urine drainage immediately following kidney stone treatment, a ureteral stent or a renal catheter is used. The ureteral stent, also called a double-J catheter, is a thin tube that runs through the entire ureter, from the renal pelvis to the bladder. With a renal catheter, instead of flowing through the ureter, the urine is transported from the renal pelvis to the outside via a tube through the flank.

[0012] Both methods involve mechanical solutions for urine drainage, which are associated with significant limitations and discomfort for patients. Furthermore, removal or replacement requires at least one additional procedure. Moreover, the underlying cause of the strictures that frequently occur subsequently is not addressed by these current methods.

[0013] A study by L. Tang et al., UROLOGY 78 (6), 2011 suggests that routine placement of a ureteral stent after uncomplicated ureteroscopy offers no significant advantages but negatively impacts patient comfort, procedure duration, and treatment costs. There was no statistically significant difference in the incidence of ureteral stricture between patients with and without a ureteral stent.

[0014] Currently, there is no effective strategy to prevent ureteral strictures before they occur, especially in high-risk cases such as injuries caused by laser lithotripsy. Therefore, there is a need for a measure that effectively prevents the development of ureteral stenosis, for example, through stricture formation.

[0015] This task is solved by an active ingredient for use in a procedure for the prophylaxis of stenosis in the ureter, wherein the active ingredient is a cell proliferation inhibitor and / or an inhibitor of inflammatory and / or fibrosis cascades.

[0016] Cell proliferation inhibitors are drugs that can inhibit the growth or multiplication of cells. These are primarily drugs with cytostatic or antiproliferative effects, which are intended to prevent stenosis. Cytostatic drugs, for example, can be used as cell proliferation inhibitors. Cytostatic drugs, which include both natural and synthetic substances, inhibit cell growth and cell division. In addition to classic cytostatic drugs that directly target the inhibition of cell growth, other substances with indirect effects can also be used. These include immunosuppressants. These can be used to suppress the body's foreign body reaction, which leads to tissue regeneration.In particular, cell proliferation inhibitors such as those capable of reducing the activation of fibroblasts and / or the formation of extracellular matrix (ECM) can be used. Fibroblasts are specific cells of connective tissue. They play an essential role in inflammation and wound healing. If the ureteral tissue is injured during laser lithotripsy, there is an increased formation of new fibroblasts, which can ultimately lead to narrowing of the ureter. Therefore, according to the invention, active substances that suppress the activation of fibroblasts, namely the conversion of fibroblasts into myofibroblasts, can be used. Furthermore, the reduction of fibroblast activation prevents the development of fibrosis, which is a pathological proliferation of connective tissue.

[0017] The formation of myofibroblasts also leads to the formation and deposition of new extracellular matrix on the inner wall of the ureter. Therefore, an active ingredient that reduces the formation of extracellular matrix is ​​beneficial.

[0018] Another group of active substances that can be used according to the invention are those that can interrupt or inhibit inflammatory cascades. In this context, the reduction of the secretion of pro-inflammatory cytokines plays a particularly important role.

[0019] In particular, the active ingredient may be selected from: paclitaxel, sirolimus, tacrolimus, everolimus, biolimus A9, zotarolimus, pimecrolimus, tretinoin, glucocorticoids, steroid hormones, and cell proliferation-modifying substances. Mixtures of these active ingredients may also be used. Furthermore, derivatives of the aforementioned active ingredients may also be used, whereby derivatives include, in particular, salts, esters, amides, and hydrates. Examples of paclitaxel derivatives are other taxanes such as larotaxel, ortataxol, or tesetaxol. Examples of steroid hormones that may be used are methylprednisolone, dexamethasone, or estradiol. Paclitaxel, sirolimus, or tacrolimus, or their respective derivatives, are preferred. The use of paclitaxel is particularly preferred. However, the applications are not limited to the active ingredients mentioned above but include all active ingredients that possess the corresponding properties.

[0020] A stenosis is usually caused by excessive cell proliferation in the affected section of the blood vessel. In this condition, cells of the ureter grow into the vessel lumen, obstructing the flow of urine. By using cell proliferation inhibitors, the underlying cause of the stenosis can be directly addressed, making this approach particularly promising for effectively preventing ureteral stenosis.

[0021] The risk of developing a ureteral stricture is up to seven times higher (34%) with impacted stones, as these stones can frequently cause significant inflammation, ischemia, and / or tissue damage before and during treatment. The treatment itself can cause additional tissue damage, which can lead to the formation of strictures during the healing process. Since there is a particular risk of developing ureteral stenosis following urinary stone treatment, an active ingredient according to the invention is preferably used for prophylaxis after such treatment. The unique aspect of the invention is that the treatment is preventive, aiming to prevent the development of a stenosis in the first place. Until now, ureteral stenoses have always been treated only after the stenosis has developed, with significantly lower success rates and greater effort.

[0022] A particularly preferred active ingredient is one used for prophylaxis following laser lithotripsy. In the case of laser lithotripsy, these injuries can occur due to mechanical or thermal damage during the laser treatment. The risk of ureteral injury is increased by the use of high-energy lasers and / or their duration of application. However, the active ingredient according to the invention can also be used in conjunction with other methods of urinary stone removal, for example, following ureteroscopy for mechanical stone removal, shock wave lithotripsy, or percutaneous nephrolithotomy. The timing of the application of the active ingredient according to the invention for the prophylaxis of ureteral stenosis is of great importance. It must be chosen so that the release of the active ingredient coincides with the time of the biological processes that lead to fibrosis.Application within the first seven days after the procedure is therefore preferred, since after more than seven days the fibrotic process has progressed to such an extent that a purely pharmacological solution for the complete prevention and regression of the already developing stricture can pose considerable difficulties. Application within the first 48 hours after the procedure is particularly preferred.

[0023] The acute phase lasts the first 48 hours after a procedure, such as kidney stone treatment. During this phase, tissue injury triggers the release of cytokines, leading to an inflammatory response and subsequent recruitment of immune cells. This, in turn, creates the conditions for subsequent stricture formation through fibroblast activation. Administering the drug during the acute phase blocks the initial steps of the fibrotic cascade, thereby reducing the likelihood of stricture formation. Administering the drug within the acute phase maximizes its ability to prevent fibrosis because it targets the triggers of the fibrotic cascade before they progress. These triggers are primarily the NF-κB and mTOR pathways. NF-κB is a specific transcription factor that plays a crucial role in the development of inflammation.mTOR is a protein to which the immunosuppressant sirolimus (rapamycin) indirectly binds and which plays a role in various signaling pathways. The drug can reduce the secretion of pro-inflammatory cytokines such as TGF-β, IL-6, and TNF-α, and downregulate the formation of extracellular matrix (ECM).

[0024] An application of the active ingredient according to the invention between the third and seventh day, during the subacute phase, can be chosen, for example, if immediate administration is not possible. In this phase, the active ingredient can suppress the existing inflammatory reaction and reduce fibroblast activity, thereby also decreasing the probability of developing ureteral stenosis.

[0025] Local application of the active ingredient at the target site is particularly preferred. The target site here refers to the portion of the ureter where a stenosis is most likely to develop. This is especially relevant to the site of kidney stone treatment. Specifically, it refers to the distal portion of the ureter, as kidney stones frequently become lodged there. The distal part of the ureter is the section closest to the kidney. It extends from the renal pelvis to the area above the sacroiliac joint. Targeted local application is desirable due to the significant impact of the active ingredients on the surrounding tissue and to minimize side effects.

[0026] The active ingredient can be administered in either solid or liquid form at the target site. Carriers can be used for the targeted application of solids. Carriers are materials onto which a functional layer has been applied or incorporated; that is, they are coated with or contain the active ingredient. Liquid administration can be achieved by introducing the active ingredient into the body within a carrier or by inserting a delivery route, such as a tube-like device like a catheter. When using a delivery route, the active ingredient can be transported to the target site through the route after it has been positioned there. Release at the target site can be achieved, for example, by injection.

[0027] Balloon catheters are known to be used in medicine in a wide variety of areas, for example, to treat stenoses. A defining characteristic of balloon catheters is the presence of an inflatable balloon, which is typically inflated with a liquid medium inside the patient's body. This allows the balloon to dilate specific sections of the body, such as narrowed blood vessels. Furthermore, in addition to the primarily mechanical treatment method, it is possible to coat the balloon catheter with active substances that are also delivered at the target site and can support the treatment.

[0028] For the prophylaxis of stenoses according to the invention, dilation, as is necessary in the case of existing stenoses, is not required. However, contrary to the conventional use of balloon catheters for dilating vascular constrictions, it is possible to use a coated balloon catheter in the application of the active ingredient according to the invention in order to apply it specifically in the ureter.

[0029] With this type of balloon catheter, hereinafter referred to simply as a balloon catheter, the active ingredient can be located on the outside of the balloon. The drug is transferred from the balloon to or into the inner wall of the blood vessel during balloon dilation.

[0030] The balloon catheter comprises a catheter shaft with at least one lumen and an inflation lumen, as well as at least one inflatable balloon, the inflation lumen being fluid-permeable to the balloon. Optionally, the balloon catheter includes a catheter shaft with at least two lumens, comprising an inflation lumen and an additional lumen, which may serve, for example, as a drainage lumen for draining urine or other fluids, as a guidewire lumen for receiving a guidewire, or as an application lumen for administering a fluid, such as a drug or lubricant. This is typically an over-the-wire (OTW) balloon catheter.

[0031] The balloon catheter may further comprise a flexible distal shaft located distal to the balloon and a distal tip. In embodiments with at least two lumens, the distal end of the additional lumen opens into a distal opening in the distal tip. If the additional lumen is intended, for example, as a drainage lumen, urine can be drained from its proximal end. This allows urine to flow through the ureter even during the procedure and prevents backflow. Whether the additional lumen is used as a drainage lumen or as an application lumen, a laterally outward orientation of the distal opening of this lumen in the distal tip is preferred. If the additional lumen is intended as a guidewire lumen, a centrally located distal opening in the distal tip is preferred.

[0032] The inflation lumen extends from the proximal end of the balloon catheter to the inflatable balloon. The optional additional lumen extends from the proximal end of the balloon catheter to the tip of the distal shaft. Optionally, the distal shaft includes a thickened section located proximally at its tip.

[0033] The part of the balloon catheter comprising the catheter shaft and the balloon is also referred to as the proximal catheter section. The part of the balloon catheter comprising the distal shaft with an optional thickened section and a distal tip is also referred to as the distal catheter section.

[0034] The term "proximal" refers to the area along the catheter that points towards the user, and "distal" refers to the area that points away from the user. The catheter tip is positioned distally. A forward movement thus indicates a distal movement, and a backward movement indicates a proximal movement. The position of the balloon and other spatial relationships are illustrated in the figures.

[0035] As mentioned above, local application is of great importance here. This means not only that the active ingredient is transferred to the vessel wall at the target site, but also that the active ingredient does not detach during transport to the target site. Therefore, in a preferred embodiment, the coated balloon catheter additionally includes a protective sheath that serves to protect the balloon's coating.

[0036] The protective sheath is a covering, which is tubular at least in the area of ​​the balloon, and the tubular section is at least as long as the balloon. The balloon catheter is accordingly positioned at least partially, specifically at least with the balloon, within the distal tubular section of the protective sheath. The protective sheath is designed to be retractable or slid along the balloon catheter, particularly in the proximal direction. By varying the positioning of the protective sheath relative to the balloon, the entire balloon of the catheter can initially be covered, then, after partial retraction, a proximal portion of the balloon, and finally, after further retraction, the balloon can no longer be covered by the protective sheath.

[0037] To simplify positioning of the protective sheath, both relative to the balloon and during the advancement of the balloon catheter according to the invention through the ureter, a low-friction material is advantageous. Polytetrafluoroethylene (PTFE) or expanded polytetrafluoroethylene (ePTFE) are particularly preferred. Optionally, a handle can be provided at the proximal end of the protective sheath for easy grasping and retraction. The overall length of the protective sheath is preferably 60 to 80 cm.

[0038] Equipping at least some sections of the balloon or balloon catheter with radiopaque markers enables visualization in imaging procedures. The markers are preferably located on the catheter shaft to identify the specific structure located in that area, such as a balloon. It is particularly advantageous to include at least one such marker in the balloon area. This allows the treating physician to determine, even on X-ray images, when the balloon segment is located within the, preferably distal, region of the patient's ureter. For this purpose, two markers can be provided, marking the beginning and end of the coating. Additional markers can be provided to further refine the positioning of the balloon catheter.

[0039] The balloon is designed to be inflated and can be reversibly transformed from a compressed, deflated state to an expanded, inflated state. Conversely, the balloon can be returned from the inflated state to the compressed, contracted state through deflation.

[0040] According to the invention, the balloon serves to apply an active ingredient to the vessel wall, particularly in the distal region of the ureter, where the greatest risk of ureteral stenosis exists. Accordingly, the balloon is preferably semi-compliant or non-compliant in order to adhere better to the vessel wall when inflated and to promote a uniform release of the active ingredient into the tissue. Preferably, the balloon is manufactured from a polyamide such as Pebax, nylon (polyhexamethylene adipamide); a block copolymer of polyamides, polyethers, and polyesters; polyesters, polyurethanes, and / or polyolefins. Particularly robust materials such as Pebax or silicone are especially preferred. This material selection is advantageous because it allows for the production of tear-resistant balloons that can be inflated to an increased pressure of 2 to 20 bar, preferably 4 to 14 bar, and particularly 6 to 12 bar. A standard pressure of approximately...8 bar preferred.

[0041] In an advantageous embodiment, the balloon has a substantially tubular shape, as is known and customary for endovascular balloon catheters. The length of the balloon depends on the dimensions of the injured tissue. In a preferred embodiment, the balloon covers at least the area of ​​the injured tissue. Particularly preferred is an area encompassing the area of ​​the injured tissue and at least 1 cm both distal and proximal to it. The length of the balloon is generally between 2 and 10 cm, preferably 2 to 8 cm. The diameter of the balloon is typically 5 to 10 mm, preferably 6 to 7 mm. All combinations of the aforementioned diameters and lengths are conceivable.

[0042] In a further advantageous embodiment, the balloon catheter comprises a balloon with a constricted central segment and expanded proximal and distal ends. The described structure allows for the formation of a limited area in which the therapeutic agent is retained due to the expanded ends in the central segment, thus enabling controlled flushing of the agent at the target site.

[0043] The distal shaft or distal tip is preferably made of silicone, and the catheter shaft is preferably made of polyamide. The length of the catheter shaft depends on the patient's anatomical dimensions and is, in particular, between 60 and 130 cm. Optionally, the distal tip has at least one opening through which the optional additional lumen, which may be a drainage lumen, guidewire lumen, or application lumen, opens to the outside.

[0044] In an advantageous embodiment, the diameter of the balloon catheter in the folded state is between 0.5 and 3 mm, preferably between 0.9 and 1.8 mm. In a further advantageous embodiment, comprising the coated balloon catheter with a protective sheath, the overall diameter is 1.5 to 5 mm, preferably 2 to 3 mm.

[0045] For treatment, the attending physician can advance the balloon catheter until the balloon is at its target location in the ureter. This is primarily located at the kidney end of the ureter, particularly in the area where the kidney stone treatment was performed.

[0046] After positioning the balloon in the ureter, and after removing or retracting any protective sheath, the balloon can be inflated. Once sufficient time has passed for the medication to be released, the balloon can be deflated and removed from the ureter. A double-J catheter can then be inserted to ensure urine drainage. This typically remains in the ureter for approximately 10 to 14 days.

[0047] If the optional radiopaque markers are attached to the catheter, the balloon's position can also be checked using X-ray imaging. Such prophylactic treatment should last no more than one hour. Application over a maximum of 15 minutes is preferred. Generally, 5 or 10 minutes is sufficient. These are the times it takes for the active ingredient to be transferred from the balloon of the balloon catheter or other delivery system to the ureter, for example, through balloon expansion. The effect lasts for considerably longer periods of several weeks, during which the active ingredient remains detectable in the ureter.

[0048] In contrast to previous treatment methods, the invention addresses the potential formation of a stenosis in advance. Additionally, no sterically demanding materials remain in the patient's body, thus avoiding side effects such as pain or bloating. Furthermore, no further intervention is necessary.

[0049] The balloon can be coated, at least partially, with one or more active substances, the active substance being defined as above, for example, paclitaxel, sirolimus, or tacrolimus. Paclitaxel is particularly preferred. The coating preferably has a concentration of 0.1 pg to 10 pg per mm². 2 outer surface of the carrier. Preferably between 0.5 and 6 pg per mm. 2 The chosen concentration depends on the active ingredient used. A concentration of 1.5 to 3.5 pg per mm² is particularly preferred. 2 with the active ingredient paclitaxel.

[0050] By inflating the coated balloon, the active ingredient, in particular paclitaxel, can be applied to the surrounding vessel wall. This allows the drug to be deposited on the wall during the procedure. Cellular uptake then occurs over a period of approximately 24 hours, which inhibits the proliferation of the corresponding cells and can thus prevent stenosis caused by stricture formation.

[0051] The coating can consist of the active ingredient itself or of several substances. Additionally, the balloon coating, consisting of one or more active ingredients, can contain excipients. Excipients are substances that are not active ingredients but can affect the properties of the coating and / or the efficacy of the active ingredient by influencing factors such as solubility or diffusion. Such excipients can significantly improve the adhesion of the active ingredient to the vessel wall. A slow, controlled release allows the active ingredient to remain effective for an extended period.

[0052] According to an advantageous embodiment of the invention, at least the portion of the balloon's surface coated with the active ingredient is additionally coated with at least one excipient before, after, or simultaneously with the coating with the active ingredient. According to a further advantageous embodiment, the at least one excipient is located in the same layer as the active ingredient.

[0053] When the active ingredient is embedded in such an excipient, it is referred to as a matrix. The properties of the matrix generally influence the rate of drug release. Swellable hydrophilic or non-swellable hydrophobic polymers are frequently used for this purpose. Biodegradable substances are preferred. In one advantageous embodiment, the substances can be broken down by the human body. In another advantageous embodiment, they are substances that can be excreted by the body. Polysaccharides are an example of biodegradable excipients. Dextrans, particularly natural dextrans, are preferred. The amount of dextran present in the coating on the balloon is typically up to 5 pg / mm². 2 , preferably at 0 to 1 pg / mm 2 Dextran and other polysaccharides, used as excipients, facilitate the transfer of the active ingredient to the tissue.

[0054] Instead of an externally coated balloon catheter, a perforated balloon catheter can also be used for drug delivery. When using a perforated balloon catheter, the drug is administered in liquid form. The openings allow for precise and uniform delivery directly to the tissue. When using a perforated balloon catheter, a solution with a concentration of 0.5 to 5 mg mL is preferably used, for example, with paclitaxel. 1 The volume of fluid administered, regardless of the method of administration, is generally between 1 and 2 mL, depending on the anatomical dimensions of the ureter. However, the methods of administration are not limited to the examples mentioned, but include all procedures that can lead to the corresponding application of the active ingredient.

[0055] Instead of a balloon catheter, a stent coated with the drug can also be used as a delivery vehicle to apply it at the target site. Stents can be self-expanding, meaning that after being released from a catheter, they expand independently and conform to the inner wall of the ureter. The drug can then take effect through direct contact between the stent and the ureter. Self-expanding stents are often made of shape-memory materials such as nitinol, a nickel-titanium alloy. Drug-coated stents that are expanded using other methods, such as a balloon catheter, are also suitable.

[0056] In another variant, the active ingredient is administered into the ureter via a biodegradable matrix inserted into the ureter. This matrix contains the active ingredient and typically other excipients. The biodegradable matrix can also be administered using a simple catheter from which the active ingredient is released.

[0057] The invention also includes a method for the prophylaxis of ureteral stenosis by applying an active ingredient. This can involve, for example, the delivery of the active ingredient via a coated balloon or the administration of the active ingredient in liquid form, particularly via a perforated balloon. The following describes a method using a balloon catheter as an example. However, the described method is not limited exclusively to balloon catheters, but can also be applied analogously to other methods of administration. The method comprises the following steps: a) providing a balloon catheter according to the invention containing the active ingredient; b) inserting the balloon catheter into the ureter of a patient, after treatment for kidney stones;c) Advance the balloon catheter into the ureter and, if necessary, lubricate the catheter tip by introducing a suitable fluid through the drainage lumen; d) Position the balloon catheter by advancing it into the ureter to the point where the drug is to be administered; e) If necessary, determine the positioning using imaging techniques; f) If necessary, retract the protective sheath so that the balloon can be inflated; g) Inflate the balloon; h) Deflate the balloon; i) If necessary, repeat steps (g) and (h) once or several times until sufficient drug delivery is achieved; j) Remove the balloon catheter with the deflated balloon by completely withdrawing the balloon catheter from the ureter.

[0058] The invention is explained in more detail below with reference to the figures. It should be noted that the figures show a particularly preferred embodiment of the invention. However, the invention is not limited to the embodiment shown. In particular, the invention encompasses, insofar as it is technically feasible, any combination of the technical features listed in the claims or described as relevant to the invention in the description.

[0059] They show:

[0060] Fig. 1 shows a balloon catheter with an active ingredient according to the invention with a protective sheath in the deflated state;

[0061] Fig. 2 shows a balloon catheter with an active ingredient according to the invention with a partially retracted protective sheath in the deflated state;

[0062] Fig. 3 shows a balloon catheter with an active ingredient according to the invention with retracted protective sheath in the deflated state and

[0063] Fig. 4 shows a balloon catheter with an active ingredient according to the invention with the protective sheath retracted in the inflated state.

[0064] Figure 1 shows a preferred embodiment of a balloon catheter 1 with an active ingredient according to the invention. The balloon catheter 1 comprises a proximal region 2 and a distal region 3. The proximal region 2 comprises a catheter shaft 4 with at least one lumen (shown here in abbreviated form) with an inflation lumen and an optional further lumen (not shown) and a balloon 5 coated with the active ingredient according to the invention. The distal region 3 comprises a distal shaft 6 and a distal tip 7.

[0065] The inflation lumen and optional drainage lumen begin at the proximal end of the catheter shaft 4. Distally, the inflation lumen extends to the balloon 5 and is fluid-permeable to it for inflation and deflation. The drainage lumen terminates distally with one or more openings, possibly also lateral ones, in the region of the distal tip 7.

[0066] Additionally, a tubular protective sheath 8 is provided, preferably made of a low-friction material, and extends distally at least beyond the coated balloon 5. The protective sheath 8 serves in particular to protect the coating of the balloon 5.

[0067] The balloon catheter 1 is shown here in its deflated state and with the protective sheath 8 fully covering it, i.e., the sheath 8 extends to the distal end of the balloon catheter 1. The balloon catheter 1 is presented in this manner particularly before use, during storage, or during placement at or guidance to the target site.

[0068] Figure 2 shows the balloon catheter 1 according to Figure 1 in its deflated state during use in a prophylactic application. The balloon 5 is completely deflated and partially exposed, as the protective sheath has been shifted so far proximally that half of the coated balloon 5 is exposed.

[0069] Figure 3 shows the balloon catheter 1 according to Figure 2, wherein after the placement of the balloon catheter 1 at the target location the protective sheath 8 was completely retracted in a proximal direction and fully released the balloon 5, allowing the balloon to be transferred unhindered from the deflated to the inflated state in the next step.

[0070] Figure 4 shows the balloon catheter 1 according to Figure 3, depicted in its inflated state. This state is reached after placement of the catheter 1 and complete retraction of the protective sheath, allowing the drug to be released from the balloon 5 onto the vessel wall of the ureter. The balloon remains inflated for as long as necessary for sufficient drug delivery. Reference numeral list

[0071] 1 balloon catheter

[0072] 2 proximal area of ​​the balloon catheter

[0073] 3 Distal area of ​​the balloon catheter 4 Proximal catheter shaft

[0074] 5 Balloon

[0075] 6 distal shaft

[0076] 7 distal tip

[0077] 8 Protective case

Claims

Patent claims 1. Active ingredient for use in a method for the prophylaxis of ureteral stenosis, wherein the active ingredient is a cell proliferation inhibitor and / or an inhibitor of inflammatory and / or fibrosis cascades.

2. Active ingredient for use according to claim 1, characterized in that the active ingredient reduces the activation of fibroblasts.

3. Active ingredient for use according to claim 1 or 2, characterized in that the active ingredient reduces the formation of extracellular matrix.

4. Active ingredient for use according to one of claims 1 to 3, characterized in that the active ingredient reduces the secretion of pro-inflammatory cytokines.

5. Active ingredient for use according to any one of claims 1 to 4, characterized in that the active ingredient is paclitaxel, sirolimus, tacrolimus, everolimus, biolimus A9, zotarolimus, pimecrolimus and / or their derivatives.

6. Active ingredient for use according to one of claims 1 to 5, characterized in that the active ingredient is used for the prophylaxis of stenoses in the ureter as a result of urinary stone treatment.

7. Active ingredient for use according to claim 6, characterized in that the urinary stone treatment is laser lithotripsy.

8. Active ingredient for use according to claim 6 or 7, characterized in that the prophylactic treatment is carried out within seven days after the urinary stone treatment.

9. Active ingredient for use according to claim 8, characterized in that the prophylactic treatment is carried out within 48 hours after the urinary stone treatment.

10. Active ingredient for use according to one of claims 6 to 9, characterized in that a local application takes place in the ureter in the area of ​​urinary stone treatment.

11. Active ingredient for use according to one of the preceding claims, characterized in that the application in the ureter is carried out by means of a carrier coated with the active ingredient.

12. Active ingredient for use according to claim 11, characterized in that the carrier is a balloon catheter (1 ).

13. Active ingredient for use according to claim 12, characterized in that the balloon (5) of the balloon catheter (1) is provided with a retractable protective cover (8).

14. Active ingredient for use according to claim 12 or 13, characterized in that the balloon (5) of the balloon catheter (1) has perforations.

15. Active ingredient for use according to claim 11, characterized in that the carrier is a stent.

16. Active ingredient for use according to any one of claims 11 to 15, characterized in that the active ingredient is present in an amount of 0.1 pg to 10 pg per mm² 2is applied to the outer surface of the carrier.

17. Active ingredient for use according to claim 16, characterized in that the active ingredient is present in an amount of 0.5 pg to 6 pg per mm² 2 is applied to the outer surface of the carrier.

18. Active ingredient for use according to any one of claims 1 to 10, characterized in that the application in the ureter is via a route inserted into the The biodegradable matrix is ​​introduced into the ureter.

19. Active ingredient for use according to any of the preceding claims, characterized in that the prophylactic treatment comprises a period of at most one hour, preferably at most 15 minutes.

20. Composition comprising an active ingredient according to any of the preceding claims and excipients for controlled release of the active ingredient.

21. Method for the prophylaxis of ureteral stenosis by application of an active substance, wherein the active substance is a cell proliferation inhibitor and / or an inhibitor of inflammatory and / or fibrosis cascades.

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