BALLOON CATHETERS

Description

[0001] The invention relates to a balloon catheter having a longitudinally extending shaft which has at least a first and a second section, wherein the first section is arranged distal to the second section and is more flexible than the second section.

[0002] The use of balloon catheters is now standard in everyday clinical practice. Their use in intravascular interventions usually involves the dilation of narrowed blood vessels, either with the balloon catheter itself or in combination with other medical devices such as balloon-expandable stents. In percutaneous transluminal angioplasty, a balloon catheter is guided to the site of the stenosis via a guidewire and a guiding catheter and expanded by the introduction of a fluid under pressure (approximately 4 to 12 bar). Deposits present in the area of the stenosis are pushed into the vessel wall. In addition, a stent (vascular endoprosthesis) can be inserted to keep the blood vessel permanently open.To prevent the recurrence of stenosis due to vasoconstrictive overgrowth of the enlarged site, drug-coated balloon catheters can also be used. These release an active ingredient such as paclitaxel at the site of the vascular constriction upon expansion. After treatment and subsequent collapse of the balloon, the balloon catheter is withdrawn from the vascular system and removed. 1 bar corresponds to 100,000 Pa.

[0003] The femoral artery in the groin is often chosen as the access site for balloon catheters. The femoral artery runs relatively superficially, at least in part, and is therefore easily accessible to the treating physician, both for coronary procedures and for other areas of the vascular system, such as the brain or extremities. Furthermore, relatively large-lumen catheters with large outer diameters can be inserted through the femoral artery (femoral artery).

[0004] One problem with inserting balloon catheters is the conflicting objectives of, on the one hand, designing the balloon catheter to be pushable over relatively long distances, while, on the other, having a sufficiently thin and flexible balloon catheter available so that it can also be inserted into narrow-lumen blood vessels. It is also important to design the balloon catheter to be as kink-resistant as possible, so that the physician's proximal advancement of the balloon catheter is transferred to the distal tip of the balloon catheter without jeopardizing the balloon catheter's advancement due to kinking between the access site and the target position.

[0005] In terms of good pushability and resistance to kinking, a relatively stiff balloon catheter would generally be advantageous, while for insertion into narrow-lumen, highly tortuous blood vessels, the greatest possible flexibility is desirable. To accommodate these contradictory properties, balloon catheters are often designed to be relatively stiff in the proximal region and relatively flexible in the distal region. For example, a proximal section may be made of a metal such as stainless steel, while more distal sections may be made of a plastic material, often polyamide.

[0006] In this context, balloon catheters are also known that have a distal section made of a particularly flexible material, a middle section made of a material of medium flexibility, and a proximal section made of a comparatively less flexible material. In principle, this meets the criterion of increasing flexibility from proximal to distal; however, the transitions between the individual sections represent potential weak points where repositioning or repositioning is possible.

[0007] Kinking of the balloon catheter can occur during distal advancement. Document DE-A-102013021998 discloses a balloon catheter according to the preamble of claim 1.

[0008] The task therefore arises to provide a balloon catheter that overcomes this problem and, in particular, does not have any points where there is an increased risk of kinking.

[0009] This object is achieved according to the invention by a balloon catheter with a shaft extending in the longitudinal direction, which has at least a first and a second section, wherein the first section is arranged distally of the second section and is more flexible than the second section, wherein the shaft has a first and a second tubular tube and a balloon is arranged at the distal end of the first tube, which balloon is expandable by pressurizing with a fluid passed through the first tube, and the second tube serves to receive a guide wire, ends distally of the balloon and has an opening at the distal end, wherein both the first and the second tube run along the first and second section and both the first and the second tube are more flexible in the first section than in the second section, wherein a transition section is arranged between the first and the second section, in which the first tube has the same material properties as in the first section and the second tube has the same material properties as in the second section or the first tube has the same material properties as in the second section and the second tube has the same material properties as in the first section.

[0010] The invention is therefore based on the idea of creating a transition section between the first and second sections, which, on the one hand, has an overall flexibility that lies between that of the first and second sections. This is achieved by the material properties of the first tube in the transition section being different from those of the second tube. Furthermore, material is used for either the first or the second tube whose properties correspond to those of the first or second section. In other words, the material properties overlap.While both the first and second tubes are more flexible in the first section than in the second, the transition between the first, more flexible section and the second, less flexible section does not occur at a single location, but rather at two locations: the distal and proximal ends of the transition section. This significantly reduces the risk of kinking at the transition from the first to the second section.

[0011] In the transition section, the material properties of the first and second tubes overlap. Either the material properties of the first tube in the transition section correspond to those in the first section, while the second tube has the material properties of the second section, or vice versa. This ensures that the material properties of one of the two tubes do not change at the distal and proximal ends of the transition section. This creates a material consistency that makes kinking significantly less likely. At both the distal and proximal ends of the transition section, only the properties of one of the two tubes change, not the properties of the other tube.

[0012] Like conventional balloon catheters, the balloon catheter according to the invention has at least two tubes, namely a first tube that serves to supply fluid for the purpose of expanding the balloon, and a second tube that is intended to accommodate a guidewire. Accordingly, the balloon is arranged at the distal end of the first tube. When the balloon of the balloon catheter has reached its target position, the fluid is introduced into the balloon through the first tube in order to expand it and, for example, press deposits on the vessels into the vessel wall or expand a stent. The fluid is then withdrawn through the first tube, whereupon the balloon deflates so that the balloon catheter can then be withdrawn as a whole in a proximal direction from the vascular system.The term "tube" is used in this context to mean a tube or hose that extends at least partially through the balloon catheter in the longitudinal direction and has a lumen running through the interior of the tube. The tube can be in the shape of a hollow cylinder with a circular or elliptical cross-section, but this is not absolutely necessary. Almost any other shape is conceivable when viewed in cross-section. A circular or elliptical cross-section, however, has the advantage that one tube can be easily guided through the other, with the second tube usually being placed through the first.

[0013] The second tube accommodates the guidewire. Unlike the first tube, this one is not closed distally, but ends distal to the balloon and has an opening at the distal end. The procedure is usually as follows: first, the guidewire is brought to the target position, then the balloon catheter is advanced over the guidewire to the target position, with the guidewire sliding through the second tube.

[0014] In connection with the second tube, two different systems are essentially known: over-the-wire (OTW) and rapid exchange (Rx) balloon catheters. The balloon catheter according to the invention can be available as either an OTW or an Rx balloon catheter. While in an OTW catheter the lumen for the guidewire extends over the entire length of the catheter from proximal to distal, the Rx catheter has a separate feed opening for the guidewire (Rx port), at which the guidewire exits the catheter well distal to the proximal end of the catheter. Accordingly, in the case of an OTW balloon catheter, the tubes or the lumens extending through the tubes for fluid supply and the guidewire run parallel or concentric to one another from the proximal end of the catheter to the balloon, whereas in an Rx catheter this is only the case between the Rx port and the balloon.The section between the Rx port and the proximal end, however, has only one tube for fluid supply.

[0015] In order to adjust the material properties in the first and second sections and in the transition section in the desired manner, in particular in the first section the first and second tubes can be made of a first material and in the second section the first and second tubes can be made of a second material, wherein the first material is more flexible than the second material and in the transition section the first tube is made of a different material than the second tube. For one of the two tubes the material is thus kept constant between the first section and the transition section, and for the other tube between the transition section and the second section. In this way the described overlapping transition between the material properties of the first and second tubes is brought about.

[0016] The first, particularly flexible or soft material is thermoplastic elastomers, such as polyether block amides (PEBA). This is a thermoplastic elastomer obtained by polycondensation of a carboxylic acid polyamide with a polyether with terminal OH groups. PEBA is marketed in particular under the name PEBAX® by Arkema. A flexible material in this context is understood to be one that adapts particularly well to external conditions and can also follow the fine branches of the vascular system. Soft and flexible are used synonymously in this application.

[0017] Alternatively, other polyamides can also be used as the first material for the balloon, for example those sold under the name Grilamid ®< by EMS-GRIVORY. The use of polyamide 12 (PA 12, Grilamid ®< L), a polyamide obtainable by the polycondensation of laurolactam, is particularly preferred. Other usable polyamides are polyamide 10.10 (PA 10.10, Grilamid ®< 1S), a polyamide obtainable by the polycondensation of decanediamine and sebacic acid, polyamide 6.10 (PA 6.10, Grilamid ®< 2S), a polyamide obtainable by the polycondensation of hexamethylenediamine and sebacic acid, or polyamide 6.12 (PA 6.12, Grilamid ®< 2D), a polyamide obtainable by the polycondensation of hexamethylenediamine and dodecanedioic acid.

[0018] A polyamide such as nylon (polyhexamethylene adipamide) can be used as a second material with medium flexibility. In particular, a material with a Shore D hardness in the range of approximately 25–72 can be used for the first section. For the second section, however, materials with a Shore D hardness in the range of 80–85 are recommended. The precise properties of the polymers can be adjusted by adding additives.

[0019] The material from which the balloon itself is constructed can be the same as or different from the material of the first tube in the first section. For example, the balloon itself can be made of nylon (polyhexamethylene adipamide), which has proven to be a proven material for balloons, even if the first tube in the first section is made of a more flexible material such as a polyether block amide. Other materials that can be used for the balloon include polyurethane, polyolefin copolymers, polyethylene, or silicone.

[0020] A balloon in the sense of the invention is understood to be the element of a balloon catheter that can be expanded by the supply of a fluid, regardless of the shape of the expandable element or the material it is made of. The balloon typically has an elongated structure. The fluid can be gaseous or liquid. The fluid can be, for example, water mixed with a contrast agent or a saline solution mixed with a contrast agent. The nominal pressure for expanding the balloon can be, for example, 4 to 12 bar, preferably 6 to 8 bar. At this pressure, the balloon reaches its nominal diameter in the expanded state. The dimensions of the balloon can vary greatly depending on the area of application. The diameter in the expanded state can, for example, be between approximately 1 and approximately 50 mm, and the length between approximately 5 and approximately 300 mm. However, the dimensions can also deviate from these, for example when the balloon / balloon catheter is used in urology or veterinary medicine.

[0021] Typically, the deflated balloon of the balloon catheter is folded. Depending on the size of the balloon, a varying number of folds can be formed, which are then wound around the axis of the catheter in the same direction. This achieves a significant reduction in diameter.

[0022] Alternatively or in addition to varying the material itself, the material thicknesses of the first and second tubes can also differ in the transition section. For example, the same material can be used for the first and second sections, but with different thicknesses. In this case, both the first and second tubes in the first section are made from the material with a comparatively thin material thickness, while the first and second tubes in the second section are made from the same (or a different) material, but with a thicker material. In the transition section, an overlapping transition is again created in such a way that the material properties of one tube match those in the first section and the material properties of the other tube match those in the second section.This means that either the first tube has the same material thickness in the first section and in the transition section, while the second tube has the same material thickness in the transition section and in the second section, or the first tube has the same material thickness in the transition section and in the second section, while the second tube has the same material thickness in the first section and in the transition section. The material thicknesses of the first and second tubes do not necessarily have to match in a certain section; for example, the second tube can have a thinner material thickness in the first section than the first tube. It is important, however, that the transition in material thicknesses for the first and second tubes does not occur at a single point along the longitudinal axis of the balloon catheter, but rather offset from one another as described.

[0023] When creating a transition section by varying the material thicknesses, nylon (polyhexamethylene adipamide), for example, can be used as the material for the first and second tubes, whereby, unlike when varying the material itself, the different properties are brought about by choosing a higher or lower material thickness.

[0024] For the purposes of the invention, "proximal" refers to the direction toward the outside of the body, i.e., toward the treating physician. "distal" refers to the opposite direction, i.e., toward the blood vessel to be treated. "Radial" refers to the plane perpendicular to the longitudinal axis of the balloon catheter.

[0025] The first and second tubes can run parallel to each other in the areas where both tubes are present, but it is preferred that the second tube extends at least partially through the first tube. Accordingly, the first and second tubes extend concentrically. Normally, the second tube is positioned on the inside, meaning the guidewire is guided through the inner second tube of the balloon catheter, while the first tube radially surrounds the second tube.

[0026] Proximal to the second section, a further, proximal section is preferably arranged. This typically has less flexibility than the first or second section, but makes up a significant portion of the overall length of the balloon catheter. It is also possible to provide further sections between the second section and the proximal section. With regard to the proximal section, the focus is less on flexibility than on pushability and resistance to kinking. Accordingly, the proximal section can be made of a metal, in particular stainless steel, for example. However, it is also possible to provide a proximal section made of a polymer, whereby this polymer is typically stiffer than the polymers used for the first and second sections as well as the transition section.

[0027] At the proximal end of the balloon catheter, adjacent to the shaft, there is usually a so-called catheter hub, i.e. a connector for the device for fluid supply and pressurization. The connection can be a conventional Luer or Luer-Lock connection, for example. It is particularly useful to provide two Luer-Lock connectors, typically female connectors, one of which connects the first lumen to a balloon dilator and another for inserting the guidewire into the balloon catheter. The connectors can be made of polycarbonate, for example. The guidewire running through the balloon catheter can be held at its proximal end by a torquer, which facilitates handling of the usually very thin guidewire.

[0028] To ensure the transition section fulfills its intended role as a safeguard against unwanted kinking of the balloon catheter, it should have a length of ≥ 3 cm, preferably 3 to 10 cm. A transition section length of 5 to 7 cm is particularly preferred. A transition section that is too short might not provide the desired anti-kinking protection, while a transition section that is too long might be unsuitable for insertion into narrow-lumen blood vessels.

[0029] A length of 3 to 20 cm, particularly 5 to 15 cm, has proven to be suitable for the first section, and 5 to 35 cm, particularly 20 to 30 cm, for the second section. In this context, the length of the first section is understood to be the length from the distal tip of the balloon catheter to the beginning of the transition section. The total length of the balloon catheter is often more than 1 m, allowing insertion in the groin region and the balloon catheter to be advanced to a wide variety of locations in the vascular system. Often, the proximal section alone has a length of ≥ 1 m.

[0030] A typical outer diameter of the first tube in the first section is 0.8 - 1.0 mm, in particular approximately 0.9 mm. The inner diameter is typically in the range of 0.7 - 0.8 mm. The outer diameter of the second tube can be, for example, 0.5 - 0.6 mm, and the inner diameter of the second tube 0.4 - 0.5 mm. This is particularly true if the second tube extends through the first tube. In the second section, the outer diameter of the first tube can be slightly larger than in the first section and can be, for example, 0.9 - 1.1 mm. The inner diameter of the first tube in the second section is usually 0.8 - 0.9 mm, while the second tube has dimensions that largely correspond to those in the first section.

[0031] To prevent a re-narrowing of the treated vessel segment following an initially successful angioplasty, balloons coated with a drug can be used. Restenosis is usually caused by cell proliferation in the corresponding vessel segment, i.e., blood vessel cells grow into the vessel lumen and, in turn, obstruct blood flow. To prevent this, balloon catheters coated with anti-proliferation drugs are increasingly being used. These drugs usually have a particular effect on the Smooth Muscle Cells (SMC) and are intended to prevent restenosis caused by excessive growth of these cells. The drug is located on the outside of the balloon and is transferred from the balloon to or into the inner vessel wall during balloon dilation.

[0032] The active ingredient used is in particular a pharmaceutical or drug, preferably a pharmaceutical that has an anti-proliferation effect and prevents vasoconstrictive overgrowth at the site dilated by the balloon. It can also be a hormone-like or regulatory agent that can influence organ-specific effects or regulatory functions in certain cells. In particular, the active ingredient can be selected from: tretinoin, orphan receptor agonists, elafin derivatives, corticosteroids, steroid hormones, paclitaxel, rapamycin, tacrolimus, hydrophobic proteins, and cell proliferation-altering substances. Mixtures of these active ingredients can also be used. Derivatives of the aforementioned active ingredients can also be used, whereby derivatives are understood to mean, in particular, salts, esters, and amides. Examples of steroid hormones that can be used include methylprednisolone, dexamethasone, or estradiol.The use of paclitaxel, rapamycin or tacrolimus or corresponding derivatives is particularly preferred.

[0033] In general, however, the term "active ingredient" should be understood broadly. This means that it can refer to any coating on the balloon of the balloon catheter intended to achieve a specific effect at the target site. When introduced into blood vessels, this effect can particularly consist of inhibiting cell proliferation. In other areas of medicine, however, the desired effect may be different, such as in the field of urology with urinary catheters, where the coating is intended specifically to inhibit bacterial colonization. Here, heparin, for example, can be used as the active ingredient.

[0034] The coating of the balloon surface with the active ingredient is typically achieved by bringing the balloon surface into contact with a solution of the active ingredient. This can be achieved in particular by immersing the balloon in the solution. The immersion usually lasts a maximum of 1 minute, typically 10 to 30 seconds. After immersion, the balloon should be withdrawn from the first solution at a speed of up to 10 mm / s. It is even more advantageous if the withdrawal takes place at a speed of less than 5 mm / s, preferably at a speed between 0.5 mm / s and 2 mm / s. The slow withdrawal ensures that the surface dries slowly.

[0035] Before coating the balloon, it is advisable to clean the surface of the balloon. This can be done, for example, with an appropriate solvent, such as the one used to apply the active ingredient.

[0036] The solution may be saturated with respect to the active ingredient, but this is not absolutely necessary. Examples of solvents that can be used include methylene chloride, chloroform, alcohol, especially ethanol, methanol, or isopropanol, acetone, diethyl ether, liquid hydrocarbons such as pentane, hexane, heptane, cyclohexane, or octane, toluene, tetrahydrofuran (THF), or ethyl acetate. The use of solvent mixtures is also possible. The preferred solvent is a solution of the active ingredient in methylene chloride.

[0037] As an alternative to coating by immersion, this can also be done in other ways, e.g. by spraying.

[0038] The balloon catheters according to the invention can be used in blood vessels, particularly in the field of angioplasty. In this case, the target location of the balloon is a blood vessel, with blood vessels in various areas being considered, particularly coronary, intracranial, and peripheral. However, balloon catheters can also be used in other medical fields. One possible application is in urology, where balloon catheters are inserted into the urinary bladder as bladder catheters. The catheter is secured via the balloon. In this case, the balloon can be provided with a coating, for example, with heparin, that prevents bacterial colonization and encrustation.

[0039] In pulmonology, balloon catheters can be used to dilate or close a bronchus. Balloon catheters can also be used in gynecology. In orthopedics, balloon catheters can be used to treat vertebral fractures by realigning the vertebrae using balloon expansion (balloon kyphoplasty). The balloon catheter according to the invention can be used in all areas of medicine in which balloon catheters are used, with the balloon catheter being particularly important for insertion into narrow-lumen blood vessels.

[0040] Furthermore, the balloon catheter according to the invention can be used not only to eliminate stenoses and deliver local drugs, but also to place a stent (endoprosthesis) in the body lumen. Stents are tube-like support structures that are implanted in a body lumen, e.g., a blood vessel, to keep it permanently open. Such stents can be self-expanding or expanded with the help of a balloon. For this purpose, the stent is crimped onto the balloon and introduced into the body lumen using the balloon catheter. At the intended location, the balloon is then expanded by supplying a fluid, which also expands the stent and anchors it in the body lumen. At the same time, when using the balloon according to the invention, the drug is released into the wall of the body lumen. Finally, the balloon is retracted and removed from the body lumen, while the stent remains in the body lumen.

[0041] Radiopaque markers can be placed at various positions along the balloon catheter to aid visualization of the catheter in X-ray images. These markers can be made of platinum or a platinum alloy such as platinum-iridium.

[0042] The invention is explained in more detail by way of example with reference to the accompanying figures. They show: Fig. 1: A balloon catheter according to the invention in a side view; Fig. 2: the distal part of the shaft of the balloon catheter Fig. 1 in longitudinal section.

[0043] In Fig. 1 the balloon catheter 1 according to the invention is shown in side view, with right meaning proximal and left meaning distal in the representation chosen here. The balloon catheter 1 has a shaft 2 extending in the longitudinal direction, the outer diameter of which is larger in the proximal section 6, which is only shown in abbreviated form here, than further distally. The section of the shaft 2 in which the balloon 3 is arranged is marked with the letter A. A first lumen for the fluid supply and a second lumen for receiving the guide wire run through the shaft 2 (not shown here), with the two lumens each being formed by a tube.

[0044] Proximally, the proximal section 6 of the shaft 2 is connected to two catheter hubs in the form of Luer-Lock connections 4, 5, whereby the connection 4 serves to supply fluid into the first lumen by means of a balloon dilator and the connection 5 serves to introduce the guide wire into the second lumen.

[0045] In Fig. 2 only the distal part of the shaft 2 is shown. A first tube 10 is designed such that it can accommodate the second tube 11, ie the second tube 11 runs longitudinally through the first tube 10. The first tube 10 is connected at its distal end to the balloon 3, which can be expanded by supplying fluid through the first tube 10. The second tube 11, on the other hand, has an opening at the distal end and serves to accommodate the guide wire (not shown here).

[0046] The part of the shaft 2 shown here (without the proximal section 6 from Fig. 1) has a first section 7 and a second section 8, with the first section 7 being arranged distal to the second section 8. However, the first and second sections 7, 8 do not directly adjoin one another; instead, there is a transition section 9 between the first section 7 and the second section 8. In the transition section 9, the first tube 10, in the example chosen here, is made of the same material as in the first section 7, for example PEBAX ®< . The second tube 11, on the other hand, is made of the same material in the transition section 9 as in the second section 8, for example nylon. The transition from the stiffer to the more flexible material therefore occurs at different points for the first and second tubes 10, 11, in one case at the transition from the second section 8 to the transition section 9, in the other case at the transition from the transition section 9 to the first section 7.The properties of the other tube remain unchanged at the corresponding points, so the risk of kinking is significantly reduced. In the present example, the first tube 10 (including the balloon area) has a length of 15 cm at the distal end for the softer material and a length of 25 cm further proximally for the less soft material. The second tube 11, on the other hand, has a length of 10 cm at the distal end for the softer material and a length of 30 cm further proximally for the less soft material. Thus, the first section 7 has a length of 10 cm, the transition section 9 has a length of 5 cm, and the second section 8 has a length of 25 cm.

Claims

1. Balloon catheter comprising a shaft (2) extending in the longitudinal direction, which has at least a first and a second section (7, 8), with the first section (7) being arranged distal to the second section (8) and being more flexible than the second section (8), with the shaft (2) being provided with a first and a second hose-like tube (10, 11) and a balloon (3) being arranged at the distal end of the first tube (10), said balloon (3) being expandable by pressurization with a fluid led through said first tube (10), and said second tube (11) serving for accommodating a guidewire and terminating distally of said balloon (3) and being provided with an opening at said distal end, wherein both said first and second tubes (10, 11) extend along said first and second sections (7, 8), and both said first and second tubes (10, 11) are more flexible in said first section (7) than in said second section (8), characterized in that a transition section (9) is arranged between said first and second sections (7, 8), in which - the first tube (10) has the same material properties as in the first section (7) and the second tube (11) has the same material properties as in the second section (8) or - the first tube (10) has the same material properties as in the second section (8) and the second tube (11) has the same material properties as in the first section (7).

2. Balloon catheter according to claim 1, characterized in that in the first section (7) the first and the second tube (10, 11) are made of a first material and in the second section (8) the first and the second tube (10, 11) are made of a second material, with the first material being more flexible than the second material and in the transition section (9) the first tube (10) being made of another material than that of the second tube (11).

3. Balloon catheter according to claim 2, characterized in that the first material is a thermoplastic elastomer.

4. Balloon catheter according to claim 2 or 3, characterized in that the second material is a polyamide.

5. Balloon catheter according to any one of claims 1 to 4, characterized in that the material thicknesses of the first and second tubes (10, 11) differ in the transition section (9).

6. Balloon catheter according to any one of claims 1 to 5, characterized in that the second tube (11) extends at least partially through the first tube (10).

7. Balloon catheter according to any one of claims 1 to 6, characterized in that a proximal section (6) is arranged proximal to the second section (8).

8. Balloon catheter according to claim 7, characterized in that the shaft (2) in the proximal section (6) is at least partially made of metal.

9. Balloon catheter according to claim 8, characterized in that the shaft (2) in the proximal section (6) is at least partially made of stainless steel.

10. Balloon catheter according to any one of claims 1 to 9, characterized in that the transition section (9) has a length of ≥ 3 cm, preferably ranging between 3 and 10 cm.

11. Balloon catheter according to any one of claims 1 to 10, characterized in that the length of the first section (7) amounts to 3 to 20 cm, in particular ranges between 5 and 15 cm.

12. Balloon catheter according to any one of claims 1 to 11, characterized in that the length of the second section (8) amounts to 5 to 35 cm, in particular ranges between 20 and 30 cm.

13. Balloon catheter according to any one of claims 1 to 12, characterized in that the balloon (3) is coated with one or more active substances.

14. Balloon catheter according to claim 13, characterized in that the active agent used is selected from the following group: Tretinoin, orphan receptor agonists, elafin derivatives, corticosteroids, steroid hormones, paclitaxel, rapamycin, tacrolimus, hydrophobic proteins, heparin and / or hormone-like or cell proliferation-modifying substances.