An orthotopic artificial bladder endoprosthesis includes a first portion connectable to a urethra of a patient and a second portion connectable to the ureters of the patient; the first portion including a collapsible cover made of a multi-layered silicone membrane having an external surface and an internal surface both coated with pyrolytic turbostratic carbon; the second portion including a resorbable cap including a fabric of PGA fibers and a frame, coupled with the cap, made using PGA/PLA copolymer; the cover and the cap being connected together along their respective edges, to define an enclosure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a §371 National Stage Application of International Application No. PCT/IB2013/058599 filed on Sep. 17, 2013, claiming the priority of Italian Patent Application No. MI2012A001555 filed on Sep. 19, 2012.

NOTICE OF INVENTION UNDER JOINT DEVELOPMENT AGREEMENT

The disclosure of US published patent application nos. 2015-0045907 and 2015-0148912 and the claimed invention were made by or on behalf of Antonio Sambusseti and Gianni Cancarini who were the parties to a joint research agreement under 35 U.S.C. 103(c), and the agreement was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement.

The present invention relates to an orthotopic artificial bladder endoprosthesis.

The application of the present invention lies in the replacement of the bladder of a patient, if the latter is suffering from serious incurable diseases such as to compromise the correct operation thereof.

Known bladder endoprosthesis comprise a balloon casing made with a layered silicone membrane.

This balloon is sufficiently rigid as to keep its shape stably and flexible enough to be able to be compressed manually to ensure that it empties.

The casing has a connection element located in a lower part of the casing to connect with the patient's urethra. Similarly, two connection bodies are located at the top to enable connection with the ureters.

These connections are achieved by suturing or by simply interlocking.

Disadvantageously, known bladder endoprostheses have some drawbacks.

Firstly, the connection of the ureters by means of the connection bodies can in some cases cause problems of stenosis of the ureters.

Furthermore, this type of connection increases the possibility of infections.

In fact, after the replacement operation, a catheter is inserted into the patient's urethra. It is sometimes the case that an infection enters the endoprosthesis via the catheter, making antibiotic treatment necessary.

However, this treatment has reduced effectiveness in the area where the ureters connect with the endoprosthesis because the bacterial load can install itself stably on the artificial material that constitutes the endoprosthesis.

In this context, the technical task at the heart of the present invention is to propose an orthotopic artificial bladder endoprosthesis that overcomes the above-mentioned technical drawbacks of the known art.

In particular, the aim of the present invention is to provide an orthotopic artificial bladder endoprosthesis that enables a significant reduction in the possibility of post-operative infections.

Another aim of the present invention is to provide an orthotopic artificial bladder endoprosthesis that reduces the risk of stenosis of the patient's ureters.

The specified technical task and the specified aim are substantially achieved by an orthotopic artificial bladder endoprosthesis having the technical characteristics described in one or more of the accompanying claims.

With reference to the accompanying Figures,1indicates an orthotopic artificial bladder endoprosthesis as a whole.

The endoprosthesis1comprises a first portion2connectable to the urethra of a patient and a second portion3connectable to the patient's ureters.

The first2and the second portion3are different and distinct, but are firmly connected to define a casing inside which is an enclosure to contain the urine. The enclosure has a volume of substantially between 100 cm3and 900 cm3, preferably being 400 cm3.

In particular, the first portion2is of a permanent type, whereas the second portion3is of a resorbable type.

More particularly, the first portion2comprises a cover4made with a multi-layered silicone membrane.

The membrane of the cover4is between 500 μm and 700 μm thick, preferably the thickness of the membrane is substantially, 600 μm.

In a preferred embodiment, the membrane substantially comprises 20 layers, each approximately 30 μm thick.

In this way, the cover4is therefore sufficiently rigid to maintain its shape, but at the same time sufficiently flexible to be able to be pushed from the outside to promote the expulsion of the urine.

The membrane is produced by means of a process illustrated in Patent Application WO 2007/039159, which is attached hereto for reference.

By way of example, the silicone used may comprise copolymers of dimethyl- and metavinyl-siloxane reinforced with silicon.

Advantageously, the silicone can be admixed with opacifiers such as barium sulphate, titanium dioxide or suchlike, so that the endoprosthesis1can be detected by means of radiological diagnostic techniques.

The cover4has an external surface4aand an internal surface4b.

Both on the external surface4aand on the internal surface4brespective layers of a highly biocompatible protective material are applied. By way of example, this material is pyrolytic turbostratic carbon of a thickness of between 0.2 μm and 0.3 μm thick.

The application of the carbon layer on the external surface4aof the cover4allows the risk of the forming fibrous capsule adhering to the first portion2to be avoided. The application of the carbon layer on the internal surface4bof the cover4allows the first portion2to be protected against the corrosion caused by the urine.

The first portion2also comprises a connection body5fixed to the cover4to enable the connection of the patient's urethra to the endoprosthesis1.

As illustrated, the connection body5has a funnel shape and is glued to the cover4at an opening6made in the membrane to allow the urine to exit.

In particular, the connection body5is glued to the cover4at one of its larger bases.

According to a preferred embodiment, the connection body has a height of 15 mm and the larger base of 24 mm. Furthermore, the diameter of the hole in the smaller base is approximately 6 mm and the thickness approximately 1 mm.

The connection body5is made of silicone internally reinforced with a net or mesh inserted in the thickness. This net or mesh is made preferably of Dacron® or Goretex®. The connection body5is made using known techniques such as, for example, moulding, dipping or suchlike.

The net allows the patient's urethra to be stitched to the connection body5in a simpler and more stable way. The second portion3comprises a resorbable cap7connected to the cover4. In particular, the cap7and the cover4are connected along their respective edges7a,4cso that the respective concavities are facing each other.

The cap7comprises a fabric8of a substantially flat circular shape and a frame9fixed to the fabric8. The frame9acts as a supporting structure for the fabric8, enabling it to assume a domed shape which is maintained as such also under the weight of the growth of the fibrous capsule.

The fabric8of the cap7is made using an ultra-light thread or monofilament deriving from preferably homopolymer PGA (polyglycolide or poylglycolic acid) fibres. PGA is a highly biocompatible and resorbable polymer and resistant to urine. Specifically, the resorption time of PGA is approximately one month.

Advantageously, the use of PGA fibre to make the fabric8allows musculo-fibrous tissue to form on the outside of the endoprosthesis1. Inside, during resorption, we see the formation of a layer of transition epithelium, which is also called urothelium. Advantageously, the layer of urothelium is impermeable, an essential fact to guarantee the correct operation of the prosthesis and the neobladder that is being formed.

The fabric8can be obtained by weaving the PGA thread in various ways, giving rise to a knitted fabric, a woven fabric or a non-woven fabric.

Preferably, the fabric8is a knitted fabric and, even more preferably, a warp knitted fabric.

In this case, the fabric8has a rougher surface capable of assuming a net configuration with sufficiently small links.

More particularly, its weft is such that its interstitial space is less than 200 μm, preferably around 160 μm, corresponding to an average area of the holes of approximately 0.02 mm2. This guarantees impermeability to urine, preventing leaks.

Furthermore, the fabric8is preferably textured so as to give it even greater surface roughness and greater rigidity and impermeability. The greater roughness of the fabric limits the risk of adhesion of the fibrous capsule.

Purely by way of example, the fabric8has a diameter substantially between 8 mm and 10 mm.

Again purely by way of example, the fabric8has a thickness substantially between 0.3 mm and 0.6 mm, more preferably between 0.4 mm and 0.53 mm, even more preferably being substantially 0.45 mm.

On the fabric8of the cap7there are two interlock areas13designed for the connection of the patient's ureters to the endoprosthesis1. When the endoprosthesis1is implanted, the surgeon makes a hole in the cap7at the interlock areas13to suit the diameter of the ureters.

Note that the position of the interlock areas13shown is given purely by way of example.

Specifically, during the operation to implant the endoprosthesis1, the uereters are connected to the second portion3by stitching them to the cap7in the interlock areas by means of a resorbable thread.

The frame9comprises a plurality of arms10arranged in a star and defining a dome profile. More specifically, the arms10all have a curved shape and are fixed together at a joining portion11located at the top of the cap7. For example, the frame9comprises a plurality of spaced apart radially extending curved arms10arranged in a star configuration and defining a dome profile. The arms10are fixed together at a joining portion11of the frame9. The fabric8of the resorbable cap7is connected to the frame9so as to assume the dome profile of the frame. The fabric8is supported by the frame and extends between the respective arms10of the frame9.

The frame9is located outside the cap7with reference to the enclosure defined in combination with the cover4.

In particular, the frame9is fixed to the fabric8by means of resorbable sutures.

Generally, the thickness of the frame9, that is, the arms10and the joining portion11, is between 0.1 mm and 10 mm, preferably between 0.5 mm and 2 mm. In a preferred embodiment, the thickness is substantially 1 mm.

The frame9is obtained by injection of a copolymer of lactic acid and glycolic acid, indicated as PGA/PLA (poly(lactic-co-glycolic) acid) whose domed shape is imparted when hot by means of thermoforming.

Since lactic acid is a chiral molecule, different types of polymer, PDLA, PLLA, PDLLA exist, where D and L represent the two stereoisomers. PLLA has a crystallinity of 37%, a vitreous transition temperature of between 50° C. and 80° C. and a melting temperature of between 173° C. and 178°, whereas polymer deriving from the polymerisation of a racemic mixture, PDLLA, is amorphous.

The term poly(lactic) acid is here intended to identify all of the various above-mentioned types of PLA.

The PGA/PLA copolymer with which the frame9is made is formed by a quantity of PGA of between 20% and 30% and by a quantity of PLA of between, correspondingly, 70% and 80%.

Particularly preferred as a PGA/PLA (poly(lactic-co-glycolic) acid) is the copolymer poly(L-lactic-co-glycolic) (PLLA/PGA) in which the L-lactic acid has a molar percent of 82-88% in moles whereas glycolic acid has a molar percent of 18-12%. This copolymer is commercially known by the name of Resomer® LG855S.

The applicant has surprisingly found that the cap7made using the PGA fabric8as described above, particularly when textured, in combination with the PGA/PLA frame9, shows a good mechanical consistency and sufficient rigidity, even in the presence of urine, and so is capable of guaranteeing a correct deformation of the bladder during emptying and/or filling, showing at the same time a good resistance to leaks of urine.

Furthermore, the fabric8and the frame9have been proved to be neutral when in contact with growing neotissue. This involves a rapid population of the device by the cells of the surrounding growing tissue. At the same time, adhesion has been proved to be reduced due to the reduced interaction between the polymers that comprise the fabric8and the frame9and the biological molecules, thus guaranteeing a fusion with the patient's internal tissues.

The cover4comprises a strip12that protrudes from the edge4cof said cap4.

In particular, the strip12extends along the entire edge4cof the cover4.

The strip12is made of a biocompatible and preferably non-resorbable material.

The strip12is fixed to the cap7at the edge7a. In particular, the strip12is fixed along the entire edge7aof the cap7.

Preferably, the strip12is fixed to the cap7by means of stitching made using a resorbable thread. By way of example, this thread may be formed by PGA.

In the preferred embodiment, the strip12is formed by a fabric made of DACRON (i.e. polyethylene terephthalate) and/or GORETEX (i.e. expanded polytetrafluoroethylene). According to that illustrated (FIG. 3), the strip12is “embedded” in the membrane that constitutes the cover4. In other words, the strip12is comprised between two adjacent layers of silicone of the membrane. In particular, the strip12is positioned between two layers located near the external surface4aof the cover4.

The invention thus described achieves the proposed aims. In fact, since the ureters are connected to the resorbable portion, the ureters are gradually welded to the biological tissue of the neobladder forming on the cap.

The connection between the biological material of the ureters and the biological material of the neobladder allows the spread of post-operative infections to be reduced. In fact, the use of antibiotic drugs is effective when the bacterial load is nested on biological rather than artificial tissue. Consequently, the antibiotic drug can act effectively also at the connection between the endoprosthesis and the ureters, preventing the infection from rising.

Furthermore, the connection between ureters and resorbable portion enables a reduction in the risk of stenosis of the ureters.