The present invention relates to a drainage tube for urine used in combination with at least one absorbable tubular patch for the replacement of a natural segment of urethra in the tissue reconstruction of natural segments of urethra following surgical removal.

More particularly the present invention relates to the use of said drainage tube for avoiding urine leaking from the pre-sphincter section of urethra during the tissue reconstruction of natural segments which have been removed. The urethra may require surgical "repair" when affected by some disorders such as for example stenosis, tumours, necrosis, injury, iatrogenic lesions and the like, or by congenital malformations.

This surgical repair consists in the removal of a damaged section of urethra and in its replacement with flaps of autologous tissue taken from the patient so as to reconstruct naturally the tissue part removed.

These flaps generally come from the intestine, from the buccal mucosa and also from the peritoneal tissue.

Autologous tissues, while ensuring the nonexistence of rejection by the patient, do not however have the same elastic features typical of the urethra nor its impermeability to urine in that they are not tissues with urothelial cells. In order to overcome these disadvantages the Applicant has proposed the use, as permanent implant in place of a removed segment of urethra, of an elastic and flexible tubular device, made with a textured PGA fabric, as provided for example in the application MI2013A00080, or made with a supported tubular patch, as provided for example in the application MI2013A001716.

However said permanent implant has some disadvantages. In the first place, since urine represents a favourable terrain for the growth of most micro-organisms, the leaks of urine which take place near the removed zone exiting from the pre- sphincter urethral duct can spread the infection to other surrounding tissues. Moreover these leaks cannot be held back since the surrounding tissues do not contain urothelial cells impermeable to urine.

WO02/04039 A2 describes a system for the reconstruction of the urethra formed by a porous external patch and by an internal tube in silicone distanced from said patch where a third component is provided, in the form of a flexible tube placed between the external patch and the internal drainage tube, in order to apply autologous cells cultivated in vitro which migrate towards the outer surface of the patch, populating it.

WO2011/082295 A2 describes a coated graft which is housed in the patient permanently in that it constitutes the tube for bypassing occluded arteries, where the external coating of the graft in silicone has communication channels which traverse the thickness of the graft.

FR2759575 Al describes an artificial endoprosthesis for bladder where a urine discharge sphincter is provided formed by a single small tube made up of two layers, one different from the other.

WO2010/078949 Al describes an artificial endoprosthesis where the natural urethra is connected to the endoprosthesis by suturing the end of the urethra to said endoprosthesis without providing for the replacement of any segment of urethra with artificial tubular devices.

ΓΓΜΙ20121555 A describes an artificial endoprosthesis where the natural urethra is connected to the endoprosthesis by forcedly inserting it inside a hollow truncated cone element placed in the lower portion of said endoprosthesis, without providing for the replacement of any segment of urethra with artificial tubular devices.

The object of the present invention is that of overcoming, at least in part, the disadvantages of the prior art by providing an implant for the replacement and reconstruction of at least one segment of urethra which has been removed, which is improved with respect to the occurance of post-surgical bacterial infections and which avoids the leakage of said urine towards the surrounding tissues. A further object is that of providing such an implant which is easy and simple to make, and also economical. Yet another object is that of providing such an implant which has moreover substantially the same elastic and urine impermeability properties typical of the natural urethra and which allows the dimensions of the natural lumen of the urethra to be maintained constant even under the weight of the regrowing tissue segment. These and other objects are achieved by the implant for the tissue reconstruction of natural segments of urethra following surgical removal comprising a drainage tube for urine in accordance with the invention having the features listed in the annexed independent claim 1. Advantageous embodiments of the invention are disclosed by the dependent claims.

One object of the present invention relates to a flexible and biocompatible drainage tube, with homogeneous and continuous surface, made in silicone coated with pyrolytic turbostratic carbon, for the use in association with a tubular patch for urethra, of the type not coated externally, made in resorbable or non-resorbable material and in the form of a polymeric membrane or fibres fabric, wherein said patch is intended to replace at least one natural segment of urethra removed previously.

Said drainage tube, which has a slightly smaller outer diameter compared to the inner diameter of the urethra, is placed partly along the entire pre-sphincter section of urethra and partly inside the bladder (natural or artificial) and attached to said urethra with absorbable suture stitches.

This drainage tube has an inner diameter that varies from 12-14 French (Fr) or Charrier (Ch) up to a max of 24 Fr (or Ch) and a length that varies from 5 to 20 cm.

Said drainage tube for urine in silicone with carbon coating also acts as inner support for an absorbable device (patch) for tissue reconstruction of urethral segment.

This tube is made by extrusion, moulding or thermoforming of a silicone polymer suitable for medical use which is subsequently coated completely with a microfilm of pyrolytic turbostratic carbon, generally with thickness equal to approximately 0.2-0.3 microns on both inner and outer surfaces.

The silicone used for said drainage tube can consist, for example, of copolymers of dimethyl- and methavynil-siloxane reinforced with silicon. A medical silicone is preferably used, such as for example the one known by the code MED 4735™ and marketed by the company Nusil Technology. This silicone shows properties, such as tensile strength and elongation, particularly suitable for the application in the construction of a flexible tubular device.

The application of said layer of pyrolytic turbostratic carbon takes place according to the prior art for the obtaining of ultra-thin films in the order of the microns indicated above, for example using a PVD (physical vapour deposition) method. Said coating in pyrolytic turbostratic carbon is found to be neutral when in contact with biological molecules, for example the cells of growing new tissues.

Moreover the surfaces of the present drainage tube coated with pyrolytic turbostratic carbon are resistant to urine and remain free from incrustation and smooth over time.

Said drainage tube is flexible and not expandable radially with such a radial rigidity as to be able to support both a tubular patch and the autologous tissue growing on said patch, thus also acting as scaffold. In practice said drainage tube is capable of withstanding the radial stresses of the new tissue growing on the tubular patch so as to avoid reductions, both substantial and minimal, of the lumen of the tissue segment regrowing.

After having removed the necrotic section of the urethra, said drainage tube is inserted through the opening created and placed along the entire pre-sphincter urethra section and partly in the bladder. Subsequently said tube is fixed in position by means of sutures at the entry of the urethra in the bladder.

After which said drainage tube is coupled to a tubular patch as defined above, which can optionally be constructed during the operation with the winding of a planar patch around the tube and the tubular construction in situ of the patch for urethra in a similar manner to what takes place in the prior art already described by the Applicant.

Once inserted one inside the other, the tubular patch and the drainage tube are completely in contact one with the other without leaving any free space between them.

In practice the combined use of the present drainage tube with the features defined above with the tubular patch results in an implant for the replacement of one or more removed urethral segments which is improved since it allows not only the complete drainage of the urine from the bladder without side leaks but also the support of the urethral tissue growing on said patch thanks to the properties of radial rigidity provided by the drainage tube.

Moreover said implant is found to be extremely reliable in that the aforesaid drainage tube in coated silicone is extremely resistant to urine and incrustations are not deposited on its surfaces.

Moreover since said drainage tube does not withdraw outwards bacterial migrations and the consequent risk of infections are avoided. "Patch" here is intended to denote soft substrates, in a flat sheet or plate or tubular shape, used in medicine to repair soft tissues, provided with a greater flexibility and elasticity with respect to the scaffolds and to the substrates known as "mesh", "mesh tape" or reinforcement nets. However the present patch is of the type not coated externally since it is implanted in the patient without any coating, in particular without any coating of cultured cells, both internally and externally.

Said patch is preferably constructed in tubular form during the operating session starting from a planar patch, in the form of a polymeric membrane or sheet or in the form of fibres fabric, which is wound externally around the drainage tube, without leaving space between the two, stitched longitudinally and then attached to the ends of the resected section of urethra as will be explained here below. It is also to be understood that a patch can also be used in a single tubular piece, already ready for use, made by means of moulding or extrusion of an appropriate polymeric material, without thereby departing from the scope of the present invention.

The thickness of the patch can vary from 0.1 microns to 80 microns, preferably around 20-30 microns.

Said patch is made with a biocompatible material which can be resorbable or non- resorbable, preferably PGA so as not to determine any type of alteration in the tissues with which it comes into contact. PGA is a resorbable thermoplastic polymer characterised by a high degree of crystallinity, around 45-55% in the case of the homopolymer. Despite the fact this material degrades thanks to processes of random hydrolysis, and also thanks to some classes of enzymes, such as those belonging to the family of the esterases, it is particularly suitable for not deteriorating in contact with urine for a period of at least two months, not showing any swelling (increase in volume and dimensions) during this period.

PGA also has a time of degradation which ranges from 4-6 months even arriving at 12 months, yet starts to lose its mechanical strength already after 4 weeks and it is completely lost at the fifth month. This is compatible with the cell growth of the tissues of the urethra.

In the case wherein the patch is in PGA, it is preferably in the form of PGA fabric, optionally textured. The PGA fabric is made using an ultra-lightweight multifilament or monofilament yarn deriving from PGA fibres.

The PGA fabric of the patch used in the present invention can be made by weaving in various ways said PGA monofilament or multifilament, creating a knit fabric, a woven fabric or a nonwoven fabric.

It is in any case preferable to use a knit fabric, in particular warp knit, in that provided with a rougher surface with respect to the other types mentioned above. Moreover it is also preferable that the fabric of the patch in PGA is textured. It has in fact been found that texturing, as well as making the fabric rougher on the surface, also confers a greater impermeability to urine with respect to a non-textured fabric. In fact it can be presumed that the texturing goes to cover further the micro holes which exist between the meshes of the fabric. Texturing of the fabric can be carried out in various ways: through the use of rough surface monofilament obtained according to the methods known in the art, or by heat setting treatment of the fabric to obtain raised parts in the fibres, adding greater volume to the filament. This latter method of texturing is preferred. It is also possible to make the patch (in planar or tubular form) with biocompatible polymers other than PGA, such as for example polylactic acid (PLA), polycaprolactone (PCL) or mixtures thereof.

Other polymers which can be used as patch and normally used in the medical field can be silicone, polysulfone, PE, PP, Dacron (PET), PTFE, PVC, polypropylene and polystyrene, Nylon (66 or 6), Kevlar and more generally synthetic polyamides, Mylar, PE, polyurethanes (Biomer, Pellethane, Corethane and Tecoflex) and polyureas, polyacrylates and others, preferably completely covered by a layer of pyrolytic turbostratic carbon, with a thickness generally around 0.2-0.3 microns, to improve biocompatibility.

An example of these alternative materials to PGA can be a flexible and elastic membrane in soft silicone, which is coated completely with pyrolytic turbostratic carbon with thickness of approximately 0.2-0.3 microns on both sides of the membrane. If the tubular patch is formed during the operation, the starting point is a planar patch which is then wound externally around the tube for drainage inserted between the two free ends of the urethra and stitched longitudinally with suture yarn (resorbable or non- resorbable according to the type of material of the patch) so as to form a tubular patch. In the case wherein the patch is in non-resorbable material it is clear that it must be subsequently removed a certain period of time after grafting.

The tubular patch in a single piece or the membrane of the planar patch from which the non-resorbable tubular device is to be obtained in situ can also incorporate in its thickness a reinforcement net in Dacron which can facilitate the suture of the patch to the urethra avoiding the tearing of said sutures, and/or provide a greater rigidity according to the need.

Further features of the invention will be made clearer by the following detailed description referred to one of its embodiments which is purely a non-limiting example, illustrated in the accompanying drawings, in which:

Fig. 1 is a perspective and partial view of the pre-sphincter urethra section from which a necrotic segment has been removed, intended to be replaced during the operation by the patch illustrated in a blown-up view;

Figure 2 is a partially sectioned overall view of a human urinary system including bladder and pre-sphincter urethra with the necrotic section removed;

Fig. 3 illustrates the planar patch of Fig. 1 wound around the tube for drainage of Fig. 2 to form during the operation the tubular device in the removed section of urethra.

Figure 2 illustrates the pre-sphincter section of a urethra, denoted by reference numeral 1, affected by necrosis with the necrotic portion removed.

It is to be understood that the following description also applies in the case wherein the urethra has been affected by pathologies other than necrosis such as stenosis, tumours, trauma, iatrogenic lesions and the like, or by congenital malformations.

The surgical removal of the necrotic zone generates two distinct and separate segments of urethra, denoted in Figures 1-2 with the reference numeral 2, 2', which will be placed again in connection one with the other through the insertion, in the missing section, of a non-coated tubular patch in place of the removed zone.

This tubular patch, denoted in Figure 3 by reference numeral 100, is normally made during the operation by the surgeon starting from a planar patch 3, illustrated in Figure 1.

After having performed the resection (removal) of the damaged urethra segment, a drainage tube 10 (Fig. 2) is inserted inside respective lumens 7, 7' (Fig. 2) at the free ends of the two detached segments 2, 2' of urethra.

Said tube for drainage 10 can be straight or slightly curved at the tip if it is necessary to facilitate its passage through the curving of the prostatic urethra.

Moreover said tube 10 can extend just slightly beyond the entrance 4 of the urethra into the bladder or extend as far as the centre of the bladder (Fig. 2) without thereby departing from the scope of the present invention.

After having inserted the tube for drainage 10 in the lumens 7, 7' of the free ends 2, 2' of the two urethra segments, the tube 10 is sutured along the perimeter of the entrance 4 of the urethra in the bladder 8, using sutures 9 made with yarn for sutures with diameter 1/2 in resorbable material, for example Vycril.

Subsequent to insertion of the tube for drainage 10, the patch in planar form 3 is wound around the portion of drainage tube 10 which is visible, then stitching longitudinally said patch 3 so as to create the tubular patch 100. The longitudinal stitching (not illustrated in the drawing) will be carried out with resorbable or non-resorbable suture yarn according to the type of material used for the patch. In a preferred embodiment said patch 3 and said suture yarn for patch are made in resorbable material.

Once the tubular patch 100 has formed around the tube for drainage 10 its ends are sutured to the free ends of the segments 2, 2' of urethra by means of head-to-head sutures 11 (i.e. the two terminal portions of the lumen of the ureter and of the tubular device are facing one to the other and sutured with continuity).

The tube for drainage 10 will be held in the pre- sphincter urethra section until total regrowth of the urethral new tissue on the patch, generally for a period of approximately 2 months. After which the drainage tube 10 may be removed without surgical intervention, through simple withdrawal thanks to the resorbability of the stitches used.

It should be noted that it is possible to use also an improved method of connection between the segments of urethra and the tubular patch according to what is described in the application MI2012A000646 and in the application USSN 13/481,135 incorporated here in full for reference.

Using the abovementioned procedure, after the removal of the section of urethra affected by a disorder a small longitudinal incision is made on the layer of muscle tissue which forms the external sheath 5 and 5' (Fig. 2) of the two segments 2, 2' of the urethra, leaving instead intact the respective underlying urothelial tissue 6 and 6' : in this way the detachment is obtained of a portion of external muscle tissue 5 from the underlying portion of urothelial tissue 6.

At this point the ends of the tubular patch 100 will be fitted over the corresponding free ends of the urothelial tubular tissues 6 and 6' and subsequently the flaps of the incision will be brought close together and sutured longitudinally with resorbable yarn so as to restore the external tubular sheath 5 and 5', then suturing as a sandwich the perimeter edge of the tubular patch 100 to both said tissues by means of sutures along the circumference.

In this way it is possible to obtain a homogeneous and uniform regrowth of the muscle tissue 5 and of the urothelial tissue 6 on the surfaces of the tubular patch 100.

It is also possible that the tubular patch 3 is supported with a specific tubular mesh support, of length substantially equal to that of the patch, as described in the patent application MI2013A001716 incorporated here in full for reference, and in this case the drainage tube 10 will be placed inside said tubular support around which said tubular patch 3 is placed. In this case too, once inserted one inside the other, the tubular patch, the tubular support and the drainage tube will be completely in contact one with the other without leaving any free space between the three elements (drainage tube, tubular support, tubular patch).

The polymer of the support is preferably resorbable, for example PGA/PLA (poly(lactic- co-glycolic) acid) the copolymer of lactic acid and glycolic acid where the acronym PLA here is intended to identify the poly(lactic) acid deriving from any type of molecule of lactic acid (chiral molecule): there are in fact different types of polymer indicated by specific acronyms such as PDLA, PLLA, PDLLA, where D and L represent the two stereoisomers of lactic acid, L-lactic acid and D-lactic acid. The PLLA (poly(L- lactic)acid) has a crystallinity of 37%, a glass transition temperature between 50 and 80°C and a melting temperature of 173-178°C, while the polymer deriving from the polymerisation of a racemic mixture of D and L isomers, the PDLLA, is amorphous.

It is to be understood that it is also possible to use a polymeric blend of the two single PLA polymers as defined above and PGA. Preferably the PLLA is used as PLA.

Generally the copolymer PLLA/PGA (or blend of PGA and PLLA) is formed by 30% of PGA and by 70% of PLLA; preferably as PLLA/PGA a poly(L-lactic-co-glycolic) (PLLA/PGA) copolymer is used in which the L-lactic acid is 82-88% in moles while the glycolic acid is 18-12% in moles.

This specific material makes it possible to obtain a support with mechanical properties of rigidity necessary for supporting the weight of the tubular patch on which the autologous tissue of the urethra is regrowing.

Said support can be obtained by means of moulding, for example injection moulding, and/or thermoforming of the PGA/PLA. Alternatively it is also possible to obtain a very thin tubular support by means of extrusion and subsequently incise the meshes with technologies of cutting for plastics, obtaining directly the geometry required, without the need for mechanical or thermal joints.

The diameter of the support for the tubular patch can be approximately 10 mm in the case of adults and approximately 6 mm in the case of paediatric applications, with a length of 7 mm.

The thickness of the support is generally comprised between 0.056 mm to 1.15 mm or in any case extremely reduced in order to offer the minimal resistance to the urinary flow. Without departing from the scope of the invention a person skilled in the art can bring to the present invention previously described all the changes and the improvements suggested by normal experience and/or by the natural development of the art.