Bioabsorbable urethral stents

Abstract

The present invention relates to a medical device that can be used to prevent blockage of a body lumen, such as the urethra. Advantageously, the stent can be inserted after a surgical procedure to reduce stricture, and since the stent is bioabsorbable, a second operation to remove the stent after it has performed its function can be avoided. The stent comprises a polymeric material prepared by copolymerization of ε-caprolactone, ε-decalactone, δ-valerolactone, ethylene brassylate or δ-hexalactone with lactide.

Description

[Technical field]

[0001] The present invention relates to a medical device that can be used to prevent blockage of a body lumen, such as the urethra. Advantageously, a stent can be inserted after a surgical procedure to reduce stricture, and because the stent is bioabsorbable, a second surgery to remove the stent after it has performed its function can be avoided. [Background technology]

[0002] Urethral stricture is an abnormal narrowing of the urethra that can block the flow of urine. It is caused by the formation of fibrous scar tissue along the canal, called ischemic spongiofibrosis, and is usually caused by an attack on the urethra or its mucosa, from a traumatic rupture, infection, congenital, previous surgery (catheter, catheterization, etc.), swelling, after another disease, or from a growing tumor near the urethra.

[0003] Urethral strictures have a prevalence of approximately 0.6% of the adult male population (229-627 patients per 100,000 men), with iatrogenic (disturbances caused by medical procedures of other types of surgery) being the main cause (etiology) of the condition, as well as trauma. This prevalence is increasing due to the aging population, as the average patient is 50-60 years old. Its treatment requires surgery, which can be performed by: Urethral incision → Used for small (<3cm) longitudinal strictures, especially in younger patients. This is done using a urethrotomy (endoscope) incorporating a knife that cuts the affected tissue. After surgery, the guide tube should be left in place for 1-4 weeks, which promotes urinary tract healing. It is then removed. Urethroplasty - This is the gold standard technique, but is complicated since it requires an open perineal incision to locate and remove the stricture. It is used for large strictures and requires urethral reconstruction by re-epithelialization of the urethra from healthy mucosa (obtained from other parts of the body, e.g. the mouth) joined with sutures. A non-biodegradable guide catheter must then be placed for the same period of time.

[0004] Foley catheters are used as guide tubes for this type of intervention. They are flexible latex tubes that are introduced into the bladder, and a balloon is inflated with sterile water for its precise placement, which helps to support the urethra and facilitate the passage of urine while re-epithelialization occurs. Currently, the tubes are usually coated with anti-fibrotic and anti-bacterial drugs by hand to prevent poor healing or to reduce the risk of infection.

[0005] On the other hand, non-bioabsorbable intraurethral stents such as Urolume (metal) are available on the market, but several analytical papers have reported problems with fibrosis, infection, and surgical complications, making their use discouraged in many cases. The same thing happens with others such as Memokath or Allium URS. On the other hand, Cook Medical, an American company, has a group of urethral stents designed for hypospadias, which are expelled during urination once the sutures are absorbed. Other companies such as SRS Medical are developing stents to replace the Foley catheter, but none of them are bioabsorbable.

[0006] EP 0 943 299 discloses stents based on bioabsorbable aliphatic polyesters, possibly even combinations of such polyesters. However, no specific combinations are disclosed. Furthermore, no examples of actual bioabsorption are given.

[0007] Thus, there remains a need for tubular structures suitable for insertion into a body lumen, such as the urethra, that have appropriate mechanical properties (flexibility / rigidity, elasticity, etc.) and that are bioabsorbable on a time scale compatible with the healing time of, for example, a urethral stricture that is surgically removed. Summary of the Invention

[0008] In a first aspect, the present invention relates to a tubular structure suitable for insertion into a body lumen such as the urethra, the structure comprising a polymeric material prepared by copolymerization of ε-caprolactone, ε-decalactone, δ-valerolactone, ethylene brassylate or δ-hexalactone with lactide. In a further aspect, the present invention relates to a polymeric material prepared by copolymerization of ε-caprolactone, ε-decalactone, δ-valerolactone, ethylene brassylate or δ-hexalactone with lactide for use in preventing obstruction of a body lumen such as the urethra. [Brief description of the drawings]

[0009] [Figure 1A-1B] 1A-1B show a perspective view (1A) and a longitudinal view (1B) of a tubular structure without any protrusions. [Figure 2A-2C] 2A-2C are diagrams of an exemplary tubular structure according to the present disclosure. [Figure 3A-3B] 3A-3B show a perspective view (3A) and a side view (3B) of an exemplary tubular structure according to the present disclosure. [Figure 4A-4B] 4A-4B show a perspective view (4A) and a side view (4B) of an exemplary tubular structure according to the present disclosure. [Figure 5A-5B] 5A-5B show a perspective view (5A) and a side view (5B) of an exemplary tubular structure according to the present disclosure. [Figure 6A-6B] 6A-6B are perspective (6A) and side (6B) views of an exemplary tubular structure according to the present disclosure. [Figure 7A-7B]7A-7B show a perspective view (7A) and a side view (7B) of an exemplary tubular structure according to the present disclosure. [Figure 8A-8B] 8A-8B show a perspective view (8A) and a side view (8B) of an exemplary tubular structure according to the present disclosure. [Figure 9A-9B] 9A-9B show a perspective view (9A) and a side view (9B) of an exemplary tubular structure according to the present disclosure. [Figure 10A-10B] 10A-10B show a perspective view (10A) and a side view (10B) of an exemplary tubular structure according to the present disclosure. [Figure 11A-11B] 11A-11B show a perspective view (11A) and a side view (11B) of an exemplary tubular structure according to the present disclosure. [Figure 12] 1A-1C show schematic examples of multiple protrusions according to the present disclosure. [Figure 13A-13B] 13A-13B are diagrams illustrating schematic examples of multiple protrusions according to the present disclosure. [Figure 14A-14B] 14A-14B are diagrams illustrating schematic examples of multiple protrusions according to the present disclosure. [Figure 15A-15B] 15A-15B show a perspective view (15A) and a side view (15B) of an exemplary tubular structure according to the present disclosure. [Figure 16A-16B] 16A-16B are diagrams illustrating schematic examples of multiple protrusions according to the present disclosure. [Figure 17A-17B] 17A-17B are diagrams illustrating schematic examples of multiple protrusions according to the present disclosure. [Figure 18] FIG. 18 is a perspective view of a tubular structure having one or more apertures. [Figure 19] FIG. 19 illustrates the geometry of the tubular structures tested according to the present disclosure. [Figure 20] FIG. 20 shows the results of testing the stress-strain curves of polymers. [Figure 21] FIG. 21 shows the results of testing the stress-strain curves of polymers. [Figures 22A-22C]22A-22C show the components of the designed test urethra. [Diagram 23] FIG. 23 shows the completed designed test urethra. [Figure 24] FIG. 24 shows the tensile strength results for the tested geometries of FIG. [Diagram 25] Figure 25 shows images of the bladders after removal and the results of histopathological analysis of control vs. treated after 10 and 30 days. Images at 10x and 40x. [Figure 26] FIG. 26 shows images of the copolymer membrane inserted into a rat bladder at 0, 10, 20, and 30 days. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The present invention is based on biodegradable materials prepared from naturally occurring monomers, which are provided from natural or synthetic sources. More specifically, the present invention is based on the copolymerization of two monomers. The copolymers defined herein can be used to form tubular structures, such as tubular stents, useful for insertion into body lumens, such as the urethra. Once inserted, the tubular structures avoid obstruction of the body lumen in a manner known in the art, for example for stents. Due to the specific properties of the copolymers, the tubular structures are absorbed or excreted by the body at a rate that allows them to perform their function for the desired time, avoiding the need for subsequent removal by surgery.

[0011] Thus, in a first aspect, the present invention relates to a tubular structure suitable for insertion into a body lumen, such as the urethra, comprising a polymeric material prepared by copolymerization of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone with lactide. In a further aspect, the present invention relates to a polymeric material prepared by copolymerization of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone with lactide for use in preventing obstruction of a body lumen, such as the urethra.

[0012] Copolymer The tubular structures according to the present invention comprise polymeric materials prepared by copolymerization of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone with lactide. Lactide is a cyclic lactone ester resulting from esterification between two lactic acid molecules. There are several stereoisomeric forms of lactide, including L-lactide, D-lactide and meso-lactide. Furthermore, racemic lactide is a 50:50 mixture of L-lactide and D-lactide. Thus, in one embodiment, the lactide is selected from L-lactide, D-lactide, meso-lactide, racemic lactide, and mixtures thereof. In a further embodiment, the lactide is racemic lactide.

[0013] The monomer copolymerized with lactide is selected from the group consisting of ε-caprolactone, ε-decalactone, δ-valerolactone, ethylene brassylate, and δ-hexalactone. In one embodiment, the monomer copolymerized with lactide is selected from the group consisting of ε-caprolactone, δ-valerolactone, ethylene brassylate, and δ-hexalactone. In a further embodiment, the monomer copolymerized with lactide is selected from the group consisting of ε-caprolactone, δ-valerolactone, and ethylene brassylate. In an even further embodiment, the monomer copolymerized with lactide is selected from the group consisting of ε-caprolactone and δ-valerolactone. In an even further embodiment, the monomer copolymerized with lactide is ε-caprolactone.

[0014] Depending on the specific needs, for example with respect to the absorption time of the polymeric material by the body or specific mechanical properties, the molecular weight of the polymeric material may be adjusted. This can be achieved by adjusting the polymerization conditions such as time, temperature, catalyst and stirring speed, among others. The molecular weight can be indicated as number average molecular weight or weight average molecular weight. In one embodiment, the number average molecular weight of the polymeric material is in the range of 15 kDa to 300 kDa. In another embodiment, the number average molecular weight of the polymeric material is in the range of 35 kDa to 125 kDa. In yet another embodiment, the number average molecular weight of the polymeric material is in the range of 45 kDa to 75 kDa. In a further embodiment, the weight average molecular weight of the polymeric material is in the range of 30 kDa to 600 kDa. In an even further embodiment, the weight average molecular weight of the polymeric material is in the range of 70 kDa to 250 kDa. In an even further embodiment, the weight average molecular weight of the polymeric material is in the range of 90 kDa to 150 kDa.

[0015] The molecular weight (weight average and number average) of polymeric materials can be determined by gel permeation chromatography-size exclusion chromatography (GPC-SEC) using polystyrene standards (as specified in Fernandez, J. et al, Journal of the Mechanical Behavior of Biomedical materials, 64, 2016, 209-219), and the dispersity (=M w / M n ) can also be obtained.

[0016] The proportions of monomeric materials used in the polymerization may be adjusted as necessary to obtain optimal results. Typically, the amount of lactide exceeds the amount of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone. In one embodiment, the mole fraction of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone is in the range of 2 to 35 of the polymeric material, and the mole fraction of lactide is in the range of 98 to 65 of the polymeric material. In a further embodiment, the mole fraction of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone is in the range of 8 to 20 of the polymeric material, and the mole fraction of lactide is in the range of 92 to 80 of the polymeric material. In yet a further embodiment, the mole fraction of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone is in the range of 8 to 18 of the polymeric material, and the mole fraction of lactide is in the range of 92 to 82 of the polymeric material.

[0017] Preparation of polymer The procedure for obtaining copolymers (or terpolymers) with a predominantly random configuration based on stereoisomers of lactones derived from (S)-lactic acid and (R)-lactic acid involves a single synthetic step using bulk polymerization techniques. Monomers used: a) Main monomer: lactone (lactide) derived from (S)-lactic acid and (R)-lactic acid [ka] b) Minor monomers: other cyclic esters (lactones) [ka] For these polymers, they can be considered to be random copolymers if their degree of randomness (R) is 0.80≦R≦1.20. The reaction can be carried out in a single synthetic reaction step, regardless of the order of addition of the different monomers and catalysts.

[0018] The reaction is classified as an ROP (ring-opening polymerization) type reaction based on the release of energy from the lactone ring by a catalyst or initiator. These ROP catalysts or initiators can be: Metallic catalysts (or metalloids) having metals or metalloids as active centers: metal salts, organometallic compounds, regardless of the oxidation state of the active centers and their non-metallic counterparts. Metals and metalloids such as Sn, Y, Bi, Al, Cu, Zn, Sb, Fe, Ni, or Co are included. b. Organic catalysts: for example, nucleophilic nitrogenated bases (1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 4-dimethylaminopyridine (DMAP), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD)). Thiourea derivatives, sulfonamidophosphines, phosphazene bases and N-heterocyclic carbenes, acid catalysts (diphenyl phosphate (DPP), triflic acid (TfOH), methanesulfonic acid (MsOH), phosphoramidic acid).

[0019] The molar ratio of the sum of the main monomer and the secondary monomer to the catalyst / initiator is preferably maintained during the reaction between 100:1 and 10,000:1, depending on the temperature and the inherent reactivity of the secondary monomer. The final molar composition of the polymer synthesized in the present invention is preferably between 2% and 35% with respect to the secondary monomer, regardless of the composition of the initial feed mixture. The final molar composition of the polymer synthesized in the present invention is preferably between 65% and 98% with respect to the main monomer, regardless of the composition of the initial feed mixture.

[0020] The reaction time can be from 1 hour to 72 hours (3 days) depending on the intrinsic reactivity of the secondary monomer, the activity or nature of the catalyst, the concentration of the catalyst, and the reaction temperature. The reaction is carried out under argon (Ar) or nitrogen (N 2 However, there are some catalysts that do not lose their catalytic activity even in the presence of atmospheric oxygen (e.g., triphenylbismuth (BiPh 3) or (1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)). The method advantageously avoids the use of stannous octoate, a catalyst often used in polymerization reactions, thereby avoiding trace amounts of this potentially cytotoxic substance coming into contact with body tissue. Thus, in one embodiment, the polymeric material of the invention is prepared using a catalyst that is substantially free of stannous octoate. In a further embodiment, stannous octoate is not used in the preparation of the polymeric material. In yet a further embodiment, the tubular structure of the invention does not contain detectable amounts of stannous octoate.

[0021] Medical Use The tubular structures of the present invention are suitable for use in preventing blockage of body lumens, including, but not limited to, the urethra, ureters, blood vessels, ducts of the digestive system, pharynx, esophagus, small intestine, large intestine, biliary system, bile duct, gall bladder duct, pancreatic duct, airway, pharynx, trachea and bronchioles, especially the urethra. Stenosis of a body lumen, such as the urethra, may be of congenital origin or may be caused by trauma, infection or may be a side effect of a surgical procedure. The stenosis is typically surgically removed and a tubular structure, such as a stent, may be used to keep the lumen open for the passage of physiological substances that are transported through the lumen under normal circumstances. Thus, in a further aspect, the present invention relates to a polymeric material prepared by copolymerization of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone with lactide for use in preventing blockage of a body lumen, such as the urethra. In one embodiment, the polymeric material is used to prevent blockage of a body lumen, such as the urethra, after surgical removal of a stricture. In a further embodiment, the invention relates to a polymeric material of the invention for use in preventing blockage of the urethra after surgical removal of a stricture. In a further embodiment, the period of use is about 2-90 days, such as about 5-45 days, such as about 6-35 days or about 7-30 days. Without being bound to a particular theory, the rigid continuous tubular structures of the invention may be beneficial in protecting areas of the urethra that were treated during a previous stricture surgery by allowing the urethra to epithelialize from its healthy edges. Furthermore, unlike mesh-like expandable tubular structures, such rigid continuous tubular structures may prevent the damaged area from contacting urine, reducing the risk of infection.

[0022] Stent Design One or more exemplary tubular structures are disclosed herein. The tubular structures can be, for example, one or more of a tube, a device, an implant, a surgical implant, a cylinder, a medical device, a tubular device, a stent, a spiral stent, and a tubular stent. The tubular stent can be formed from the materials described above. The tubular structures can be completely formed from the materials described above. The tubular structures can be rigid. The tubular structures can be flexible. The tubular structures can include both rigid and flexible portions.

[0023] The tubular structure includes a radially outer surface. The tubular structure includes a radially inner surface. The radially inner surface may be opposite the radially outer surface. The tubular structure may include a first end and a second end. The first end and the second end may be considered as the longitudinal ends of the tubular structure. As used herein, "surface" refers to the outer wall of the tubular structure. Thus, the tubular structure is defined by a radially inner surface (which is its innermost wall) and a radially outer surface (which is its outermost wall). In a preferred embodiment, the radially inner surface and the radially outer surface are continuous walls. As used herein, the term "continuous wall" or "continuous surface" refers to a wall or surface that does not exhibit discontinuities along its entire longitudinal dimension or along a substantial portion of its longitudinal dimension (e.g., at least 80%, preferably 90%, more preferably 95%).

[0024] The tubular structure can be hollow and cylindrical or generally cylindrical. This particular shape is not limiting and modifications to the tubular structure are used. The tubular structure can have a longitudinal centerline (e.g., longitudinal axis) extending through the tubular structure. The longitudinal centerline can extend from a first end to a second end of the tubular structure.

[0025] The tubular structure may have a longitudinal length. For example, the tubular structure may have a longitudinal length of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 mm. The tubular structure may have a longitudinal length of more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 mm. The tubular structure may have a longitudinal length of less than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 mm.

[0026] The tubular structure may have an outer diameter of 3, 4, 5, 6, 7, 8, 9 or 10 mm.The tubular structure may have an inner diameter of 3, 4, 5, 6, 7, 8, 9 or 10 mm.

[0027] The tubular structure may have a thickness (e.g., from the radially inner surface to the radially outer surface and / or between the radially inner surface and the radially outer surface) of 0.1, 0.2, 0.3, 0.333, 0.4, 0.5, 0.6, 0.7, or 0.8 mm. The tubular structure may have a thickness greater than 0.1, 0.2, 0.3, 0.333, 0.4, 0.5, 0.6, 0.7, or 0.8 mm. The tubular structure may have a thickness less than 0.1, 0.2, 0.3, 0.333, 0.4, 0.5, 0.6, 0.7, or 0.8 mm. The thickness of the tubular structure may vary. For example, the thickness of the tubular structure may vary along the longitudinal length of the tubular structure. The thickness of the tubular structure may not vary.

[0028] The tubular structure includes a lumen. The lumen may be defined (e.g., formed, bounded) by a radially inner surface of the tubular structure. A longitudinal centerline may extend through the lumen. The lumen may have a circular cross-section. The lumen may have an oval cross-section. The lumen may have a polygonal cross-section.

[0029] A lumen may extend through the tubular structure. The lumen may extend along a longitudinal axis of the tubular structure. Fluids, and other objects smaller than the lumen, may pass through the lumen from one end of the tubular structure to the opposite end of the tubular structure.

[0030] The lumen may have the same dimensions throughout the tubular structure. For example, the lumen may be generally cylindrical in shape. The lumen may vary in dimensions throughout the tubular structure. For example, the radially inner surface may move toward or away from the longitudinal centerline.

[0031] In one or more exemplary tubular structures, the tubular structure may include one or more protrusions. In one or more exemplary tubular structures, the tubular structure may include multiple protrusions. The multiple protrusions may be present on a radially outer surface of the tubular structure (e.g., may extend from the radially outer surface of the tubular structure). The multiple protrusions may be present on a radially inner surface of the tubular structure. The multiple protrusions may not be present on a radially inner surface of the tubular structure. The multiple protrusions may be integrally formed with the tubular structure. The multiple protrusions may be attached to the tubular structure, such as on the radially outer surface of the tubular structure. For example, the multiple protrusions may be mechanically or chemically attached to the tubular structure.

[0032] The plurality of protrusions may have a longitudinal length of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mm. This particular longitudinal length is not limiting. The plurality of protrusions may extend 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5 mm in a direction away from the radially outer surface.

[0033] In one or more exemplary tubular structures, the tubular structure may include a single protrusion. For example, a single protrusion may be formed from multiple interconnected protrusions, as described below. Thus, a connected protrusion as discussed herein may be understood as a single protrusion.

[0034] The protrusions can be configured to provide a radially outward force. For example, the protrusions can provide a frictional force on a surface radially outward from the tubular structure. For example, the protrusions can be configured to provide a frictional force on tissue in contact with the radially outward surface. This can advantageously help hold the tubular structure in place once implanted (e.g., prevent unwanted movement of the tubular structure).

[0035] In one or more exemplary tubular structures, the protrusions may be one or more of knobs, rings, helixes, spirals, extensions, bubbles, protrusions, humps, protuberances, bumps, nubs, and any irregular pattern of protrusions. The protrusions may be corrugated. The protrusions may create a corrugated structure on the radially outer surface of the tubular structure. The protrusions may be friction increasing protrusions. The protrusions may be extensions. The protrusions may be rings. The protrusions may be a textured surface.

[0036] The rings can be perpendicular to the lumen and / or longitudinal centerline. The rings can be parallel to the lumen and / or longitudinal centerline. The rings can be angled relative to the lumen and / or longitudinal centerline.

[0037] In one or more exemplary tubular structures, the plurality of protrusions may be a plurality of circumferential rings. Each of the plurality of circumferential rings may extend partially or completely around the circumference of the tubular structure. Adjacent rings of the plurality of circumferential rings may be connected. Adjacent rings of the plurality of circumferential rings may not be connected. For example, adjacent rings of the plurality of circumferential rings may be longitudinally spaced apart by 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or 10.0 mm, although the particular dimensions are not limiting.

[0038] The multiple circumferential rings may be perpendicular to the lumen and / or longitudinal centerline. The multiple circumferential rings may be parallel to the lumen and / or longitudinal centerline. The multiple circumferential rings may be angled relative to the lumen and / or longitudinal centerline.

[0039] In one or more exemplary tubular structures, each of the plurality of circumferential rings may be at the same angle relative to the lumen and / or longitudinal centerline. In one or more exemplary tubular structures, one or more of the plurality of circumferential rings may be at a different angle relative to the lumen and / or longitudinal centerline than another one of the plurality of circumferential rings. In one or more exemplary tubular structures, each of the plurality of circumferential rings may be randomly angled relative to the lumen and / or longitudinal centerline.

[0040] As mentioned above, a plurality of protrusions, e.g., a plurality of circumferential rings, extend radially away from the radially outer surface of the tubular structure.

[0041] In one or more exemplary tubular structures, each of the plurality of circumferential rings may be rounded. In one or more exemplary tubular structures, at least one of the plurality of circumferential rings may be rounded. In one or more exemplary tubular structures, each of the plurality of circumferential rings may include at least one rounded edge. In one or more exemplary tubular structures, at least one of the plurality of circumferential rings may include at least one rounded edge.

[0042] In one or more of the exemplary tubular structures, each of the plurality of circumferential rings may include at least one edge. In one or more of the exemplary tubular structures, at least one of the plurality of circumferential rings may include at least one edge. The at least one edge may be a non-rounded edge.

[0043] In one or more exemplary tubular structures, at least one of the plurality of circumferential rings may include at least one edge and at least one of the plurality of circumferential rings may be rounded. In one or more exemplary tubular structures, one or more of the plurality of circumferential rings may have rounded and non-rounded edges.

[0044] In one or more of the exemplary tubular structures, the circumferential rings may be angled toward a first end or a second end of the tubular structure, or the circumferential rings may be centrally located (e.g., not angled toward a particular end of the tubular structure).

[0045] The protrusions, e.g., the circumferential rings, may be one or more of a square shape, a rectangular shape, a triangular shape, a circle shape, an ellipse shape, a semicircle shape, a trapezoid shape, a curved shape, a quadrant shape, a polygon shape, and any irregular pattern. For example, the protrusions may be triangular, thereby having one edge (e.g., one free edge) that is not directly integrated with the tubular structure. If the protrusions are square, they may have two edges (e.g., two free edges) that are not directly integrated with the tubular structure. If the protrusions are circular or oval (or curved), they may have no free edges. In one or more exemplary tubular structures, the protrusions may have a radius of curvature of 0.1, 0.2, 0.3, 0.4, 0.5, 0.5, 0.7, 0.8, or 0.9 mm.

[0046] In one or more exemplary tubular structures, adjacent ones of the plurality of circumferential rings may not be connected. In one or more exemplary tubular structures, all of the plurality of circumferential rings may not be connected to one another. For example, each of the plurality of circumferential rings may be longitudinally spaced apart from adjacent ones of the plurality of circumferential rings. Gaps may exist between adjacent ones of the plurality of circumferential rings.

[0047] In one or more exemplary tubular structures, adjacent ones of the circumferential rings may be connected. In one or more exemplary tubular structures, all of the circumferential rings may be connected. For example, the circumferential rings may be connected together to form a helical shape along the radially outer surface of the tubular structure. In one or more exemplary tubular structures, the protrusions, e.g., the circumferential rings, may form a helix.

[0048] In one or more of the exemplary tubular structures, some adjacent rings of the plurality of circumferential rings may be connected and other adjacent rings of the plurality of circumferential rings may not be connected.

[0049] In one or more of the exemplary tubular structures, the protrusions, e.g., the circumferential rings, may extend to the longitudinal ends of the tubular structure, e.g., the circumferential rings may define the first end and / or the second end of the tubular structure.

[0050] Alternatively, the projections, e.g., the circumferential rings, may not extend to the longitudinal ends of the tubular structure. Thus, there may be a gap between the first end and / or the second end of the tubular structure and a first projection of the projections, e.g., the circumferential rings. For example, the circumferential rings may be longitudinally spaced apart from the longitudinal ends of the tubular structure.

[0051] For example, there may be a gap of 0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, or 4.0 mm from the first end to the nearest one of the plurality of protrusions.

[0052] In one or more exemplary tubular structures, the multiple protrusions, e.g., multiple circumferential rings, may extend to a first end of the tubular structure, but may not extend to a second end of the tubular structure.

[0053] In one or more of the exemplary tubular structures, the tubular structure may further include one or more apertures (e.g., lumens, gaps, perforations, openings, holes). The one or more apertures may extend from a radially outer surface of the tubular structure to a radially inner surface of the tubular structure. The particular shape and size of the one or more apertures are not limiting.

[0054] Advantageously, the one or more apertures allow fluid to reach the outside of the tubular structure from the lumen of the tubular structure. For example, the one or more apertures can drain pus from a possible infection in a wound or sore. Furthermore, the one or more apertures can further improve frictional adhesion to tissue.

[0055] The one or more apertures may extend through one or more of the plurality of protrusions, e.g., one or more of the plurality of circumferential rings. The one or more apertures may not penetrate any of the plurality of protrusions.

[0056] The one or more apertures may be equally spaced around the circumference of the tubular structure. The one or more apertures may not be equally spaced around the circumference of the tubular structure.

[0057] The one or more apertures may be equally spaced about the longitudinal length of the tubular structure. The one or more apertures may not be equally spaced about the longitudinal length of the tubular structure.

[0058] Detailed explanation of the figure 1A-1B show a perspective view (1A) and a longitudinal view (1B) of a tubular structure 50, also called a smooth tube, without any protrusions. This design may be easy to insert into a patient, but does not have any profile such as multiple protrusions, thereby presenting minimal frictional forces, and therefore a high risk of axial displacement.

[0059] 2A-2C illustrate an exemplary tubular structure 100 according to the present disclosure. FIG. 2A illustrates a perspective view, FIG. 2B illustrates a cross-section along a longitudinal length, and FIG. 2C illustrates a radial cross-section. The shaded area illustrates the thickness of the tubular structure 100. The outer ring illustrates the height, e.g., radial length, of the plurality of protrusions 200. The tubular structure 100 may have a first end 102, a second end 104, and a body 106 extending between the first end 102 and the second end 104. Additionally, the tubular structure 100 may include a radially outer surface 108 and a radially inner surface 110. The radially inner surface 110 of the body 106 may define (e.g., form) a lumen 112 passing through the longitudinal length of the tubular structure 100 along a longitudinal axis 114 (shown in FIG. 2B). The lumen 112 may extend from the first end 102 to the second end 104, thereby providing openings at the first end 102 and the second end 104 for fluid to pass therethrough.

[0060] As shown, the tubular structure 100 may include a number of protrusions 200. In this illustration, the number of protrusions 200 are a number of circumferential rings 202. As discussed in detail throughout, the number of protrusions 200 may come in a variety of variations. Advantageously, the number of protrusions 200 may provide a frictional force when the tubular structure 100 is implanted.

[0061] The multiple circumferential rings 202 are aligned perpendicular to the longitudinal axis 114 and / or lumen 112. Thus, the multiple circumferential rings 202 may extend circumferentially around the body 106 of the tubular structure 100 on the radially outer surface 108. As shown, the multiple circumferential rings 202 (e.g., multiple protrusions 200) may be integrally formed with the body 106. Alternatively, the multiple circumferential rings 202 (e.g., multiple protrusions 200) may be attached to the body 106 of the tubular structure 106.

[0062] The plurality of circumferential rings 202 may be rounded (e.g., curved, spherical, oval) as shown. Thus, the plurality of circumferential rings 202 may not include edges. In the illustrated tubular structure 100, the circumferential rings 202 may appear semicircular in cross section.

[0063] Additionally, as shown, each of the plurality of circumferential rings 202 may be longitudinally spaced apart (e.g., separate, spaced apart, disconnected) from adjacent circumferential rings of the plurality of circumferential rings 202. Additionally, the plurality of circumferential rings 202 may be longitudinally spaced apart (e.g., separate, spaced apart, disconnected) from the first end 102 and the second end 104.

[0064] 3A-4B show a tubular structure 100 having a plurality of triangular protrusions 200A / 200B. Thus, the plurality of protrusions 200A / 200B can be formed from a first wall and a second wall with a corner between the first wall and the second wall.

[0065] Specifically, Figures 3A-3B show multiple protrusions 200A that are right-angled triangles. Advantageously, the right-angled triangles can facilitate insertion into the penis and minimize pain on the part of the patient. Additionally, multiple protrusions 200A can penetrate the mucous membrane and minimize axial movement during urination.

[0066] 4A-4B show multiple protrusions 200B that are equilateral triangles. Similar to FIGS. 3A-3B, multiple protrusions 200B can facilitate insertion into the penis. By being geometrically symmetrical, this design can also be inserted in both directions (e.g., in either direction).

[0067] 5A-5B show a tubular structure 100 having a plurality of protrusions 200C in a rectangular shape. Thus, the plurality of protrusions 200C can be formed from a first wall, a top wall, and a second wall with a first corner between the first wall and the top wall, and a second corner between the top wall and the second wall. The plurality of protrusions can vary in dimension (such as width and / or height) along the longitudinal length of the tubular structure. Advantageously, this design can provide a fairly high friction force on both sides, which can prevent the tube from moving both outwardly and inwardly. Furthermore, this design can be inserted in both directions.

[0068] 6A-8B show a tubular structure 100 having multiple curved and / or circular projections 200D / 200E / 200F.

[0069] 6A-6B show the multiple protrusions 200D with a semicircular shape. This design can be inserted in both directions. Moreover, the multiple protrusions 200D can provide enough friction to prevent the tubular structure 100 from moving. Moreover, the multiple protrusions 200D have a curved shape without any spikes that may cause pain to the patient, allowing for easy insertion into the urethra.

[0070] 7A-7B show multiple projections 200E having a quadrant shape. This design advantageously allows for simple insertion while providing strong friction to prevent migration due to the right angle walls. Furthermore, pain is minimized during insertion due to the curved shape allowing for easy migration. As mentioned above, the vertical walls allow for more friction to be created to prevent the tubular structure 100 from exiting through the urethra.

[0071] 8A-8B show multiple protrusions 200F having a curved shape. The multiple protrusions 200F can be configured to bond to the mucosa and create friction that prevents the tubular structure 100 from moving. Furthermore, it can be easily inserted into a patient from any direction without the use of sharp corners and / or points.

[0072] 9A to 12 show the tubular structure 100 having different combination shapes of multiple protrusions 200G / 200H / 200I / 200J.

[0073] 9A-9B show a plurality of protrusions 200G having a semicircular shape combined with a rectangular shape. This design can allow for easy insertion through the curved portion on one side of the tubular structure 100. Additionally, it can have excellent gripping power since it has vertical walls that create a large gripping force within the urethra. The rectangular portion of the plurality of protrusions 200G can vary in width and number of geometries.

[0074] 10A-10B show multiple protrusions 200H that have a right angle triangle shape combined with a rectangular shape. This design allows for easy insertion. Additionally, it has good grip because it has vertical walls that provide high friction to keep the tube from moving within the urethra. The rectangular portions can vary in width and number of geometries.

[0075] 11A-11B show multiple protrusions 200I with a quadrant, a rectangle, and another quadrant shape. The rectangle portion allows the semicircular geometry to be longer. It allows insertion from both sides, which is painless and easy to handle. It also creates the necessary friction, so that a stuck tutor tube is not allowed. The number of geometries and the width of the rectangle portion are variable.

[0076] FIG. 12 shows multiple protrusions 200J with triangular, rectangular and another triangular shape. The rectangular portion allows the lengthening of the triangular geometry. It allows insertion from both sides, which is painless and easy to handle. It also creates the necessary friction, so that no stuck tutor tube is allowed. The number of geometries and the width of the rectangular portion are variable.

[0077] 13A-17B show a tubular structure 100 having asymmetric protrusions 200K / 200L / 200M / 200N / 200O. In particular, the protrusions may all be connected and may rotate around the circumference of the tubular structure 100. Alternatively, there may be connections or gaps between adjacent protrusions of the plurality of protrusions. For example, they may spiral around the tubular structure 100, forming a helix / helical shape.

[0078] 13A-14B show a tubular structure 100 having helical protrusions 200K / 200L.

[0079] Advantageously, different geometries can be obtained depending on the shape of the protrusions and their pitch along the tubular structure 100. As shown in Figures 13A-13B, the protrusions 200K can have a right triangle shape, while Figures 14A-14B show the protrusions 200L that can have an equilateral triangle shape.

[0080] 15A-17B show a tubular structure 100 having double helical lobes 200M / 200N / 200O. In particular, one set of lobes are all connected and can rotate around the circumference of the tubular structure 100. A second set of lobes are connected and can rotate in the opposite direction. For example, both sets of lobes can spiral around the tubular structure 100 to form a helix / helical shape.

[0081] 15A-15B show a tubular structure 100 having two sets of multiple protrusions 200M that form a double helix shape on the radially outer surface 108 of the tubular structure 100. FIG.

[0082] Advantageously, different geometries can be obtained depending on the shape of the protrusions and their pitch along the tubular structure 100. As shown in Figures 16A-16B, the protrusions 200N can have a right triangle shape, while Figures 17A-14B show the protrusions 200O that can have an equilateral triangle shape.

[0083] 18 illustrates a tubular structure 100 having one or more apertures 300. The one or more apertures 300 may extend between the radially outer surface 108 and the radially inner surface 110. Although one or more apertures 300 are illustrated in a particular tubular structure 100, the one or more apertures 300 may be used in any and / or all of the variations described herein.

[0084] The use of terms such as "first", "second", "third" and "fourth", "primary", "secondary, secondary", "tertiary", etc. does not imply any particular order, but is included to identify individual elements. Additionally, the use of terms such as "first", "second", "third" and "fourth", "primary", "secondary, secondary", "tertiary", etc. does not indicate order or importance, but rather the terms "first", "second", "third" and "fourth", "primary", "secondary, secondary", "tertiary", etc. are used to distinguish one element from another. Note that the terms "first", "second", "third" and "fourth", "primary", "secondary, secondary", "tertiary", etc. are used here and elsewhere for labeling purposes only, and are not intended to represent any particular spatial or temporal order. Additionally, the labeling of a first element does not imply the presence of a second element, and vice versa.

[0085] It should be noted that the word "comprising" does not necessarily exclude the presence of other elements or steps than those listed.

[0086] It should be noted that the word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements.

[0087] It should further be noted that any reference signs do not limit the scope of the claims.

[0088] While features have been shown and described, it will be understood that they are not intended to limit the claimed disclosure, and various changes and modifications may be made by those skilled in the art without departing from the scope of the claimed disclosure. Accordingly, the specification and drawings are to be regarded in an illustrative rather than a restrictive sense. The claimed disclosure is intended to cover all alternatives, modifications and equivalents. EXAMPLES

[0089] Example 1. Preparation of copolymers of ε-caprolactone and racemic lactide Triphenylbismuth (BiPh) was used as a catalyst. 3 Synthesis of poly(D,L-lactide-co-ε-caprolactone) (P(DLLA-CL)) copolymer with a feed composition of 80:20 (% w / w) was carried out in bulk by one-pot, one-step ring-opening polymerization using DLLA-CL at a molar ratio of comonomer to catalyst of 1500:1. When the temperature of the bulk reached 130°C, triphenylbismuth was injected into the reactor. The reaction mixture was stirred at 130°C for 3 h.

[0090] The bulk reaction mass was then dissolved in dichloromethane and precipitated into excess cold methanol, and the resulting slurry was dried under reduced pressure in a vacuum oven at 85°C.

[0091] The resulting copolymer is 1It has a final molar composition of 85 / 15 D,L-lactide / ε-caprolactone as determined by H-NMR spectroscopy, and an M w and a polydispersity of 1.93. Table 1 summarizes the characterization data of the synthesized copolymers (polydispersity or M w / M n (D), the average length unit of lactide and caprolactone (l LA and l CL ), randomness character (R) and glass transition temperature (Tg).

[0092] [Table 1]

[0093] The final copolymer composition is enriched in D,L-lactide comonomer compared to the feed due to the difference in comonomer reactivity. Since D,L-lactide is a small ring lactone (6 member ring, higher ring strain), it is more reactive than ε-caprolactone (7 member ring lactone, lower ring strain), and this more reactive comonomer is consumed faster. Thermal characterization shows that the amorphous P(DLLA-CL) copolymer has a glass transition temperature (T) of 30.1 °C. g ) was shown.

[0094] The repeating unit of poly(D,L-lactide-co-ε-caprolactone) is as follows: [ka]

[0095] Table 2 lists the assignments of various protons and carbons in poly(DL-lactide-co-ε-caprolactone) (shown above) for the calculation of molar composition and microstructural parameters. 1 The molar composition of the P(DLLA-CL) copolymer was calculated by averaging the results obtained from H-NMR spectroscopy.

[0096] [Table 2]

[0097] The chemical shift (δ) varies depending on the adjacent comonomer. Groups with two comonomers may show different magnetic shielding due to their different arrangement in the polymer sequence. In the case of copolymer P(DLLA-ε-CL), three different arrangements are possible: a) LA-LA; [ka] and d) there is CL-CL. [ka]

[0098] 1 Composition calculation from the area of ​​H-NMR spectrum As an example of the calculation of copolymer composition based on chemical shifts and integrals, we used a copolymer of P(DLLA-ε-CL) fed at 80:20 by weight. 1 The H-NMR chemical shifts are shown in Table 3.

[0099] [Table 3]

[0100] There are two independent signals for each monomer: the A signal corresponds only to the protons of the LA monomer (containing two -CH- diastereotopic groups), and the BB and CC signals correspond only to the protons of the ε-CL monomer (containing -CH at the 6-position). 2 - and in second place -CH 2 -) protons. The remaining protons are included in the signal between 1.7 and 1.3 ppm.

[0101] Therefore, the A, BB and CC signals are used to calculate the proton contribution of each comonomer: A signal for LA and BB and CC signals for ε-CL, using Eq. 1.

number

[0102] Using the proton contribution (CPH), it is possible to calculate the final mole fraction in the polymer of each comonomer using the following formula:

number

[0103] Considering that the molecular weight of LA is 144.13 g / mol and that of ε-CL is 114.14 g / mol, the final composition based on the weight of the copolymer is calculated using the following formula:

number

[0104] Thus, synthesis of an 80:20 weight ratio feed of LA to ε-CL resulted in a final copolymer weight composition of 81.5:18.5.

[0105] Example 2. Preparation of copolymer of ethylene brassylate and racemic lactide Triphenylbismuth (BiPh) was used as a catalyst. 3 Synthesis of poly(D,L-lactide-co-ethylene brassylate) (P(DLLA-EB)) copolymer with a feed composition of 70:30 (% w / w) was carried out in bulk by one-pot, one-step ring-opening polymerization using 100:1 comonomer to catalyst molar ratio using 100:1 cyclohexanediaminetetraacetate (100:1). When the temperature of the bulk reached 140° C., triphenylbismuth was injected into the reactor. The reaction mixture was stirred at 140° C. for 72 h.

[0106] The bulk reaction mass was then dissolved in dichloromethane and precipitated into excess cold methanol, and the resulting slurry was dried under reduced pressure in a vacuum oven at 85°C.

[0107] The resulting copolymer is 1 It has a final molar composition of 95 / 5 D,L-lactide / ethylene brassylate as determined by H-NMR spectroscopy, and an M of 111.6 kDa. w and a polydispersity of 2.01. Table 4 summarizes the characterization data of the synthesized copolymers (polydispersity or M w / M n (D), the average length unit of lactide and ethylene brassylate (l LA and l CL ), the randomness index (R) and the glass transition temperature (Tg).

[0108] [Table 4]

[0109] The final copolymer composition is enriched in DL-lactide comonomer compared to the feed due to the difference in comonomer reactivity. Since DL-lactide is a small ring lactone (6 member ring, higher ring strain), it is more reactive than ethylene brassylate (17 member ring macrolactone, lower ring strain), and this more reactive comonomer is consumed faster. In terms of thermal properties, the amorphous P(DLLA-EB) copolymer exhibits a glass transition temperature (T) of 27.9 °C in the differential scanning calorimetry (DSC) curve. g ) was shown.

[0110] The repeating unit of poly(D,L-lactide-co-ethylene brassylate) is as follows: [ka]

[0111] Table 5 shows the assignment of various protons and carbons in the repeat unit of poly(DL-lactide-co-ethylene brassylate) for the calculation of molar composition and microstructural parameters. The molar composition of P(DLLA-EB) copolymer is: 1 H and 13 The values ​​were calculated by averaging the results obtained from C-NMR spectroscopy.

[0112] [Table 5]

[0113] Table 5 shows the P(DLLA-EB) copolymer 1 The chemical shifts of the H-NMR spectrum are shown. The analysis shows that the ester bonded [ka] Methylene (H 14 and H 15 ), and EB methylene (H 2 and H 12 ) with 5.05 ppm of LA methine (H 2 ) signals. 1 The H NMR signal did not indicate sequence activity, so the average sequence length and randomness index data in Table 1 13 The relative mole fractions of LA-EB dyads were estimated based on the C-NMR spectra.

[0114] Table 5 shows the results of the synthesis of poly(DLLA-co-EB) copolymer with 81% D,L-lactide content. 13 Chemical shifts of the C NMR spectrum are also shown. The molar composition was determined by comparing the areas under the peaks of the LA and EB carbons (independent of the EB carbonyl). The average relative values ​​for lactide are the signals at 170 and 70 ppm (C 1 and C 2 For ethylene brassylate, the signals used were 174 and 25 ppm (C 1, C 3 and C 11 ) signal. In Table 2, the different dyads from the tested core-based copolymers were also assigned. The average dyad relative mole fraction (LA-EB) was determined from the estimation of the chain microstructure parameters. This variable is [ka] The sum of the average diad mole fractions at 172 and 70 ppm [ka] Obtained from a diploid [ka] By doubling the average value of [ka] The estimate was made by multiplying the value provided by the diploid by two.

[0115] The bismuth catalyst results in a random distribution of the comonomers, resulting in a random copolymer (R = 1). The microstructural parameters were calculated using Equations 1-3, and the average sequence length of LA, l LA is 4.56, and the average sequence length of the EB, l EB was 1.51, and the randomness value R was obtained as 0.88.

[0116]

number

[0117] where (A) and (B) are the molar fractions of comonomer A and comonomer B, and (AA), (AB) and (BB) are the average relative molar fractions of the diads AA, AB and BB, respectively. (a) J. Fernandez et.al. Polymer Degradation and Stability, 2017, 137, 23-34. b) J. Fernandez et al. Journal of the Mechanical Behavior of Biomedical Materials, 2012, 9, 100-112. c) E. Prestch, T. Clerc, J. Seibl, W. Simon, Tables of spectral data for structure determination of organic compounds, Chemical Laboratory Practice Book. Springer-Verlag, Berlin Heidelberg, 2013. GmbH.

[0118] Example 3. Geometry of tubular structures Several different tubular construct geometries were tested using shaped urethras. Figure 19 shows the different geometries that were tested. Specifically, additive manufacturing (Stratasys Objet260 Connex3™) was used to print the probe and the sculpted urethra. Essentially, this allowed the two primary materials to be mixed in different proportions to obtain a third material with desired mechanical properties. For the experimental design, a mixture of Agilus30 black and a rigid polymer known as Veroblue was used. From these two primary materials, 12 materials were produced, 6 of which have flexible behavior (FLXA) and 6 of which have rigid behavior (RGDA). 1) FLXA-CK-S40-DM 2) FLXA-CK-S50-DM 3) FLXA-CK-S60-DM 4) FLXA-CK-S70-DM 5) FLXA-CK-S85-DM 6) FLXA-CK-S95-DM 7) RGDA-CK-K10-DM 8) RGDA-CK-K20-DM 9) RGDA-CK-K30-DM 10) RGDA-CK-K40-DM 11) RGDA-CK-K50-DM 12)RGDA-CK-K60-DM

[0119] Probes were fabricated using various materials to test on a tensile test stand to obtain stress-strain curves for the specific materials. Geometry was not a factor in this testing as all probes had the same dimensions. As shown in Figure 20, material K50 can behave most similarly to the reference material (poly(DL-lactide-co-ε-caprolactone) (PLCL) copolymer).

[0120] Furthermore, mechanical property tests based on oral mucosa were carried out. In the study Dynamic mechanical properties of oral mucosa: comparison with polymeric soft denture liners. Journal of the Mechanical Behavior of Biomedical Materials, vol. 4 (n°3), pp. 269-274, ISSN 1751-6161, a comparison was made between polymers and oral mucosa. The Young's modulus was stated to be about 2.72 MPa.

[0121] Figure 21 shows the resulting stress-strain curves, and the results are summarized in Table 6. Probes were made from the following materials: FLXA-CK-S60-DM, FLXA-CK-S70-DM, FLXA-CK-S85-DM, and FLXA-CK-S95-DM, from which it was found that the material most similar to the known Young's modulus is material S85.

[0122] [Table 6]

[0123] Next, to test the geometry of the tubular construct, a designed test urethra was constructed, which was made up of three sections, as shown in Figures 22A-22C: an outer section (Figure 22A), an inner section (Figure 22B), and an auxiliary section (Figure 22C).

[0124] The outer part, shown in Figure 22A, simulates the cavernosal muscle surrounding the urethra and was made from the softest material available in the 3D printer, with a Young's modulus of 0.45 MPa. The inner part, shown in Figure 22B, simulates the urethra itself and was made from the previously cited material S85. An auxiliary part, shown in Figure 22C, was added to the assembly to allow for subsequent tensile testing. This auxiliary part allowed the designed test urethra to be attached to the jaws of the device and tensile tested.

[0125] The final structure of the designed test urethra is shown in FIG. 23. Each of the tubular structures made of material K50, described above with respect to FIG. 19, was inserted into the inner part without being threaded to the point where it could not be advanced any further by the air in the designed test urethra. The tubular structure was then pulled out of the test urethra to determine its "holding force", e.g., the frictional force that prevents the tubular structure from exiting the designed test urethra. The test was performed to the point where the tubular structure completely exited the simulated urethra, e.g., the hole in the designed test urethra. The test speed was 1 mm / min. The test results are shown in Table 7. As shown, the tubular structure with the highest "holding force" is design 5. The test values ​​are from a 2 to 1 scale test, but each tubular structure in the inserted state is 1 to 1 scale.

[0126] [Table 7]

[0127] Additionally, displacement tests were performed on the tubular structure shown in Figure 19 using material K50. A thermal test stand was developed to perform the displacement tests as the fluid passes through the tubular structure in a non-alternating manner, i.e. the fluid cycles and stops every "x" number of times so that the tests are as realistic as possible.

[0128] Each tubular structure was tested in two different ways. The first test was done with a continuous flow of water for 5 hours, and the second test was done discontinuously for 5 hours. For the discontinuous flow test, the flow remains active for 30 seconds and off for 5 seconds. Since there are no stops in real life situations, each tubular structure was tested for a full day, 10 hours continuously, without breaks, to ensure that the results are as reliable as possible. Table 8 shows the test results.

[0129] [Table 8]

[0130] As shown, none of the tubular structures underwent measurable displacement, and it can be concluded that either geometry with respect to displacement could have worked.

[0131] Example 4. Preparation of copolymers of ε-caprolactone and racemic lactide and in vivo testing Poly(DL-lactide-co-ε-caprolactone) (PLCL) copolymers were synthesized in bulk by one-pot, one-step ring-opening polymerization (ROP) of each lactone with a comonomer to catalyst molar ratio of 1500 to 1. The reaction was carried out in a 2 L reactor at 130°C for 1 hour. 500 grams of copolymer was synthesized with a lactide to ε-caprolactone feed composition of 75 to 25 (% w / w). No initiator was added to the reaction mixture and the catalyst (BiPh 3 ) was added.

[0132] The reaction product was dissolved in dichloromethane and precipitated in excess methanol to remove catalyst impurities and unreacted monomers. The copolymer was dried at room temperature overnight and heat treated (100°C under vacuum for 1 hour) to ensure complete removal of residual solvent. Finally, the product was weighed to obtain the yield of the synthesis process.

[0133] Proton nuclear magnetic resonance ( 1 The copolymers were characterized for their composition and microstructure by H-NMR, for their thermal properties by differential scanning calorimetry (DSC) and for their molecular weight distribution by gel permeation chromatography (GPC). The results are shown in Table 9.

[0134] [Table 9]

[0135] Membranes of 250 μm were prepared by pressurized melting at 150° C. in a P 200 E (Collin) hot press and quenching with additional water. From these membranes, circular samples of 5 mm diameter were obtained to test for in vivo compatibility and degradation.

[0136] In vivo testing In vivo studies were performed under general anesthesia and in aseptic conditions by implanting five samples per animal into the bladder of adult male Wistar rats (250-300 g). The skin and muscle were incised with scissors along the caudal midline to expose the bladder. After caudal cystostomy, the sample was fixed in the bladder with a non-biodegradable suture (8 / 0). For SHAM controls, a non-biodegradable suture was placed without the sample. The bladder was closed using a biodegradable continuous suture (8 / 0) and the skin and muscle were closed using a vicryl / silk suture (4 / 0). After 10, 20 or 30 days, the animals were subjected to a gross evaluation, blood and urine were collected, and the animals were sacrificed for histological analysis (performed on days 10 and 30).

[0137] Macroscopic evaluation revealed no signs of pain or distress in the animals. Urine cultures in CLED, MacConkey and blood agar were negative or insignificant in all samples. Blood tests summarized in Table 10 showed no changes in the parameters tested, despite an increase in creatine kinase values ​​that could be due to the time lapse between harvest and analysis. Despite refrigeration, some samples were partially hemolyzed, which may have altered the parameters.

[0138] [Table 10]

[0139] Histopathological examination of the implantation sites was performed by counting the amount of polymorphonuclear cells (acute response), lymphocytes, plasma cells and macrophages (long-term response), giant cells, tissue necrosis and fibrosis. Histological examination showed no necrosis or fibrosis in the analyzed tissues. Very few inflammatory cells were detected in the tissues after surgery and subsequent implantation. Furthermore, as can be seen from Table 11, the highest inflammation level (level 2 out of 4) was detected on day 10 and decreased on day 30 (level 1 out of 4). This indicates that the inflammation was most likely caused by the surgical process. Figure 25 shows images of the bladders after removal and the results of histopathological analysis of the treated versus control after 10 and 30 days.

[0140] Overall, the urological, hematological and histological analyses demonstrated that the implantation or degradation of the copolymer did not induce any inflammatory, fibrotic or necrotic processes.

[0141] [Table 11]

[0142] The evolution of the molecular weight of the copolymer samples at three time points (10 days, 20 days, and 30 days) was evaluated using an HPLC-GPC apparatus (Metrohm, Azura, Column Linear (2) Phenogel-Phenomenex). The GPC results of the in vivo degradation samples are shown in Table 12. Figure 26 shows a photograph of the excised specimen, in which the residues showed a paste-like morphology, had gathered, and had lost their original shape. Also, the molecular weight was reduced by almost a quarter (at the end of the test) from its initial molecular weight (note that the molecular weight was slightly lower than the synthesized polymer as a result of the pressure melting process carried out to prepare the samples for the in vivo test).

[0143] [Table 12]

Claims

1. 1. A rigid tubular structure suitable for insertion into a body lumen, such as the urethra, said structure comprising a polymeric material prepared by copolymerization of ε-caprolactone, ε-decalactone, δ-valerolactone, ethylene brassylate or δ-hexalactone with lactide; the tubular structure includes a radially outer surface and a radially inner surface opposite the radially outer surface; the tubular structure includes a lumen extending therethrough, the lumen being defined by the radially inner surface; the tubular structure includes a plurality of protrusions extending radially away from the radially outer surface; the tubular structure is not expandable; Rigid tubular structure.

2. A rigid tubular structure as described in claim 1, wherein the rigid tubular structure is continuous.

3. 2. The rigid tubular structure of claim 1, wherein the lactide is selected from L-lactide, D-lactide, racemic lactide, and mixtures thereof.

4. 10. The rigid tubular structure of claim 1, wherein the lactide is racemic lactide.

5. 2. The rigid tubular structure of claim 1, wherein the number average molecular weight of the polymeric material is in the range of 15 kDa to 300 kDa, such as in the range of 35 kDa to 125 kDa, for example in the range of 45 kDa to 75 kDa.

6. 2. The rigid tubular structure of claim 1, wherein the weight average molecular weight of the polymeric material is in the range of 15 kDa to 600 kDa, such as in the range of 70 kDa to 250 kDa, for example in the range of 90 kDa to 150 kDa.

7. 10. The rigid tubular structure of claim 1, wherein the mole fraction of ε-caprolactone, ε-decalactone, δ-valerolactone, ethylene brassylate, or δ-hexalactone is in the range of 2 to 35 of said polymeric material, and the mole fraction of lactide is in the range of 98 to 65 of said polymeric material.

8. 8. The rigid tubular structure of claim 7, wherein the mole fraction of ε-caprolactone, δ-valerolactone, ethylene brassylate or δ-hexalactone is in the range of 8 to 20, e.g., in the range of 8 to 18, of the polymeric material, and the mole fraction of lactide is in the range of 92 to 80, e.g., in the range of 92 to 82, of the polymeric material.

9. 2. The rigid tubular structure of claim 1, wherein the ε-caprolactone, ε-decalactone, δ-valerolactone, ethylene brassylate, or δ-hexalactone is ε-caprolactone.

10. 10. The rigid tubular structure of claim 1, wherein said tubular structure does not contain detectable amounts of stannous octoate.

11. The rigid tubular structure of claim 1 , wherein said plurality of protrusions are a plurality of circumferential rings.

12. 12. The rigid tubular structure of claim 11, wherein each of said plurality of circumferential rings is perpendicular to said lumen.

13. 12. The rigid tubular structure of claim 11, wherein each of said plurality of circumferential rings is rounded.

14. 12. The rigid tubular structure of claim 11, wherein each of said plurality of circumferential rings is longitudinally spaced from adjacent ones of said plurality of circumferential rings.

15. 12. The rigid tubular structure of claim 11, wherein said plurality of circumferential rings are longitudinally spaced from longitudinal ends of said tubular structure.

16. 10. The rigid tubular structure of claim 1, wherein said plurality of protrusions create a corrugated structure on said radially outer surface of said tubular structure.

17. 10. The rigid tubular structure of claim 1, wherein said tubular structure is cylindrical.

18. A polymeric material according to any one of claims 1 to 17 for use in the prevention of urethral obstruction after surgical removal of a stricture.

19. 20. The polymeric material for use according to claim 18, wherein said polymeric material protects scar tissue caused by said surgical removal of a stricture.

20. 20. The polymeric material for use according to claim 19, wherein the polymeric material prevents urine from coming into contact with scar tissue.

21. 19. The polymeric material for use according to claim 18, wherein the period of use is from about 2 to 90 days, such as from about 5 to 45 days, such as from about 6 to 35 days or from about 7 to 30 days.

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