WO2007039159A1

WO2007039159A1 - Orthotopic artificial bladder prosthesis and production method thereof

Info

Publication number: WO2007039159A1
Application number: PCT/EP2006/009273
Authority: WO
Inventors: Antonio Sambusseti
Original assignee: Antonio Sambusseti
Priority date: 2005-10-03
Filing date: 2006-09-25
Publication date: 2007-04-12
Also published as: ITMI20051853A1

Abstract

An orthotopic artificial bladder prosthesis (1) is described, comprising an enclosure or bag or balloon formed by a multi-layered membrane (2) of soft silicone, with a thickness of about 600 microns so as to be compressible, deflatable and collapsible.

Description

ORTHOTOPIC ARTIFICIAL BLADDER PROSTHESIS AND PRODUCTION METHOD THEREOF

DESCRIPTION

The present invention refers to an orthotopic artificial bladder prosthesis and a production method thereof.

As is known, when a patient's bladder is affected by severe incurable disease which compromises proper function, the patient's very life is put at risk. The possibility of bladder replacement with an artifical bladder prosthesis is therefore particularly desirable.

The medical journal European Urology Eur Ur 1939, 35: 257-266 contains a description of the numerous attempts that have been made in the course of time to create artificial bladder prostheses to replace the human bladder. These atttempts of the prior art were based on the possibility of creating rigid or semirigid prostheses and obtaining filling and emptying thereof by means of a series of mechanical members such as valves, tubes and reservoirs. These mechanical members proved to be complex, unreliable and difficult or impossible to make.

For this reason research was directed towards other solutions.

A first solution is based on the possibility of removing the original natural bladder and replacing it with an orthotopic ileal bladder of bowel turned inside out. That is to say, during the surgical session the original bladder affected by total malignancy is removed and replaced with a new bladder obtained by cutting and fashioning the patient's bowel wall in situ, taking care to wash and clean it carefully to eliminate any source of infection, due above all to the intestinal mucus.

This system, however, presents some drawbacks. In fact residues of intestinal mucus cannot be completely removed from the new bladder during surgical session, resulting in possible infections.

Another drawback is due to the fact that bladder prostheses obtained with the bowel wall are excessively small, having a volume of about 200 - 300 cm³. Furthermore these artificial bladder prostheses obtained with the bowel wall have a short average life. They are indeed unable to go beyond a life of 10 years, because of tearing of the intestinal wall which wears out in a period of less than 2-3 years.

A second solution consists in removing the original natural bladder without replacing it. In this case, the patient's ureters are connected to two respective catheters (stents) which, passing through the lumbar wall, are iserted into two bags situated on the patients sides. These bags must be worn for life by the patient and replaced periodically to avoid infections. The bags are emptied by the patient himself whenever necessary, several times in the course of the day, by means of a special tap connected to a valve.

Object of the present invention is to overcome the drawbacks of the prior art, providing an orthotopic artifical bladder which is able to replace the natural bladder and which allows a considerable improvement in the patient's quality of life.

Another object of the present invention is to provide such an orthotopic artificial bladdes prosthesis that is reliable and long-lasting.

Yet another object of the present invention is to provide such an orthotopic artificial bladder prosthesis that is simple to produce.

These objects are achieved in accordance with the characteristics listed in appended independent claims 1 and 13.

Advantageous embodiments of the invention are apparent from the dependent claims.

The orthotopic artificial bladder prosthesis according to the invention comprises an enclosure or bag or balloon made from a multi-layered membrane of soft silicone, with a thickness of about 600 micro so as to be compressible, deflatable and collapsible.

In this manner hydraulic functioning of the prosthesis is ensured by the pressure difference between the air inside and outside the prosthesis, avoiding the complex valve- type hydraulic mechanisms of the prior art.

Further characteristics of the invention will be made clearer by the detailed description that follows, referring to a purely exemplifying and therefore non limiting embodiment thereof, illustrated in the appended drawings, in which:

Figure 1 is a perspective view of the orthotopic artificial bladder prosthesis according to the invention, connnected to the ureters and to the urethra; and Figure 2 is an enlarged cross sectional view of a portion of the prosthesis, in which the section is taken along the sectional plane II-II of Figure 1.

The prosthesis according to the invention, indicated as a whole with reference numeral 1 , consists of an enclosure or bag or balloon made from a multi-layered membrane 2 (Figure 2) of soft silicone, with a thickness of about 600 microns so as to be compressible, deflatable and collapsible. The silicone used can consist, for example, of copolymers of dimethyl and netavinyl siloxane, reinforced with silicon. A medical silicone is preferably used, such as for example that known by the code number MED 4735™ and marketed by Nusil Technology.

The multi-layered membrane 2 is preferably obtained starting from the silicone raw material, by means of a manufacturing procedure known as dipping. By means of machinery known as dipping equipment, a balloon or bag is created starting from a single layer of silicone and overlapping other layers on top of each layer until the desired thickness of about 600 microns is reached. The membrane of the prosthesis 1 preferably consists of 20 layers of silicone, each having a thickness of about 30 microns.

This multi-layer dipping method consists in forming a first layer, evaporating it with cyclohexane for 10 minutes, overlapping the second layer, evaporating it, again with cyclohexane, for 10 minutes, and so on up to the last layer. At this point the layered silicone membrane 2 is in a semiliquid state; then, it is placed in an oven for vulcanization, at a temperature of about 150⁰C for a time ranging from 30 min to 1 h, according to the size of the prosthesis 1 that is to be produced. After the vulcanization cycle, the multi-layered silicone membrane 2 is in its optimal consistency of softness and elasticity, and no longer in the semi-liquid state.

The last, outermost layer 3 of the silicone membrane is advantageously texturised so as to obtain a rough surface which serves to reduce the risk of adhesion of the fibrotic capsule to the prosthesis 1. The texturising process involves only the last layer 3. Once the last layer of silicone 3 has been applied by dipping, it is evaporated with cyclohexane for 10 minutes and is sprinkled with normal cooking salt (NaCl) before vulcanization. The silicone membrane with the salted final layer 3 is then placed in the oven for vulcanization.

This procedure of salting of the last layer 3 and vulcanization is repeated twice. The final device is dipped into water and brushed to eliminate the salt from the last layer 3.

As shown in Figure 1, the prosthesis 1 is provided with three holes 5, 5' and 6 having a larger diameter than the diameter of the ureters 20,20' and the urethra 21. The two holes 5, 5' disposed in the top part of the prosthesis are suitable to receive the ureters 20, 20'; whilst the hole 6 disposed in the bottom part of the prosthesis is larger in diameter and is suitable to receive the urethra 21.

These holes 5, 5' and 6 are made with a special surgical instrument consisting of a handpiece or punch, with a tip with a square section 3 cm long and a final diameter between 8 and 14 charrrier (Ch), to comply with the possible dimensions of the ureters 20, 20' and the urethra 21.

The holes 5, 5' and 6 are closed by respective portions of membrane 7, 7' and 8 similar to the multi-layered membrane 2 which forms the bag of the prosthesis 1. The portions of membrane 7, T and 8 can be without the texturized layer. The portions of membrane 7, T and 8 are applied to the inner surface of the prosthesis 1 from the inside, by means of melting of the silicones into a single layer with the bag membrane 2, and subsequent vulcanization in an oven.

The inner surface of the prosthesis 1 is coated with a microfilm 4 of highly biocompatible biomaterial, such as for example pyrolytic turbostratic carbon, with a thickness of about 0,2 - 0,3 microns.

Experimental laboratory and bench tests with a scanning electron microscope have been performed on samples of silicone strips coated with said biomaterial. These samples were dipped into human urine for one week and subjected to torsion, bending and folding stress for cyles of 10,000 times. Microscope scanning did not provide any sign of deterioration due to the corrosive effect of the urine.

The inner coating 4 of biomaterial is carried out by making a large hole on the bottom of the prosthesis 1 , during construction, which then serves to turn the prosthesis inside out like a glove and carry out the coating with the layer of pyrolytic carbon 4 on the inner surface. The hole for turning the prosthesis inside out can be the same hole 6 as for the urethra. Once coating has been carried out, the prosthesis 1 , again through the same hole, is turned like a glove again, and is placed in position ready for use.

The whole processing cycle is performed in a controlled atmosphere, that is with controlled contamination, in a clean room. Once processing is completed, the prosthesis is placed in a double blister pack closed with a sheet of Tyvek to avoid contamination, and sent to an ETO (ethylene oxide) sterilization cycle.

At this point the prosthesis 1 is ready to be used in a surgical session. The surgeon makes three holes 9, 9' and 10 in the three portions of membrane 7, T and 8, respectively. To pierce the portions of membrane, the surgeon can use the same handpiece or punch used to pierce the membrane 2. In fact, since the tip of the handpiece is 3 cm long, there is no risk of it may pass through the wall of the prosthesis on the other side.

The tip of the punch is chosen according to the size of the urethra 21 or ureters 20, 20', and the holes 9, 9' and 10 are made of the Ch measurement that the surgeon considers appropriate according to the size of the ureters 20, 20' or the urethra 21 during the surgical session.

The ureters 20, 20' and urethra 21 are inserted into the respective holes 9, 9' and 10, which are elastic, that is, they tighten slightly around the tube of the ureter 20, 20' or the urethra 21. Then, the portions of membrane 7, 7' and 8 are fixed respectively to the ureters 20, 20' and to the urethra 21 itself by means of four suture stitches 11, 11 ' and 12 disposed in a square, around the tube of the ureter 20, 20' and the urethra 21 and passing through the membrane and through the tissue of the ureters and the urethra.

For example, for the suture stitches a curved cylindrical needle must be used and Monocryl Ethicon™ 4-0 e 5-0 thread can be used, produced by Johnson & Johnson and consisting of polyglecaprone, that is: a coplymer made by synthesis of glycolide (75%) and epsilon caprolactone (25%). This thread is not coated, is monofilament and is not braided. The manufacturer indicates this thread as the most suitable for sutures in general for soft tissue and vessels, amongst which are included the ureters and urethra.

There are, however, other threads which could conveniently be adapted to the cases in question and to the requirements of the prosthesis; it is left to the surgeon's discretion to choose the one most congenial to him.

The holes for passage of the suture stitches 11, 11 ' and 12 in the ureters 20, 20' and in the urethra 21 do not constitue a risk of leakage of liquid, in that in a few hours the tissue reforms. In order to avoid leakage of urine (liquid) the suture stitch holes in the portions of membrane 7, T and 8 are bonded and closed with one cc (one drop) of surgical glue, such as Glubran 2™ for example, normally available commercially.

The Monocryl™ thread used for the suture stitches is absorbed in about 90-120 days, but begins its downward curve of loss of tension on the 22nd day, ending and losing 75% of its tensile strength on the 28th day. From the 28th day tensile strength is no longer present in the thread, but by this date the ureters 20, 20' and the urethra 21 are kept fixed by the glue and above all by the formation of the fibrotic capsule which acts as a retaining element for the ureters and urethra. It should be noted that the fibrotic or polyproteic capsule forms in about 30 days.

A simulation has been done in which which tubes of soft silicone, though not as soft as the ureters and urethra, were used in place of the ureters 20 and 20' and the urethra 21. In the simulation a larger thread than the Monocryl 4-0 and 5-0 and a much larger needle, not curved like that of the Monocryl 4-0 5-0, were used.

The simulation was tested by inflating the artificial bladder prosthesis with water and no leakage occurred from the suture stitches. Considering the remarkable larger size of the thread used, the real holes in the surgical session should not have any urine leakage.

In order to carry out the surgery, since it is a microsurgery procedure, it is necessary to use a helmet with a fibre optic transmitted light source and connected to a transformer equipped with a cable for connection to the power socket. This fibre optic transmitted light source produces a cold white light, with a perfectly round, collimated beam, not dispersed, concentrated on the site at which the suture stitches are to be applied. In addition, glasses with a binocular prismatic assembly (lens) with 2X up to 6X magnification are applied to the helmet to enlarge the image of the surgical site in particular.

The prosthesis 1 has a capacity of between 500 and 900 cm³ and is collapsible. That is to say the filling and emptying mechanism of the prosthesis 1 works through the pressure differences between the air inside the prosthesis and the air outside the prosthesis.

When the urine enters the prosthesis 1 through the ureters 20, 20', negative pressure is created inside the prosthesis 1 with respect to the outside pressure. This negative pressure prevents the urine inside the prosthesis from flowing down through the urethra 21, avoiding problems of incontinence in the patient.

In order to empty the prosthesis 1 , the patient must exert pressure manually on the lower abdomen over the bladder, so as to press the prosthesis 1 to overcome the outside pressure. In this manner the urine contained in the prosthesis 1 exits through the urethra 21 and the prosthesis 1 is emptied of air and is ready to receive urine again.

In any case, even if the patient feels no urge, it is advisable to perform the prosthesis- emptying operation at least twice a day, to avoid complete filling of the prosthesis.

Numerous changes and modifications of detail within the reach of a person skilled in the art can be made to the present embodiment of the invention, without thereby departing from the scope of the invention as set forth in the appended claims.

Claims

1. An orthotopic artificial bladder prosthesis (1) characterized in that it comprises an enclosure or bag or balloon made from a multi-layered membrane (2) of soft silicone, with a thickness of about 600 microns so as to be compressible, deflatable and collapsible.

2. An orthotopic prosthesis (1) according to claim 1, characterized in that it has a capacity of between 500 and 900 cm³.

3. An orthotopic prosthesis (1) according to claim 1 or 2, characterized in that it is produced by means of layers of silicone overlapped with a dipping process and vulcanized.

4. An orthotopic prosthesis (1) according to any one of the preceding claims, characterized in that said membrane (2) comprises 20 overlapped layers of silicone, in which each layer has a thickness of about 30 microns.

5. An orthotopic prosthesis (1) according to any one of the preceding claims, characterized in that it comprises an outermost layer of texturized silicone (3) to reduce the risk of adhesion of the fibrotic capsule.

6. An orthotopic prosthesis (1) according to any of the preceding claims, characterized in that said silicone layers of the membrane (2) consist of copolymers of dimethyl and metavinyl siloxane, reinforced with silicon.

7. An orthotopic prosthesis (1) according to claim 6, characterized in that the silicone layers of the membrane (2) comprise a silicone for medical use, such as MED 4735™ by Nusil Technology.

8. An orthotopic prosthesis (1) according to any one of the preceding claims, characterized in that it comprises an inner coating (4) of highly biocompatible bio- material.

9. An orthotopic prosthesis (1) according to claim 8, characterized in that said inner coating (4) is made of turbostatic pyro lytic carbon.

10. An orthotopic prosthesis (1) according to claim 8 or 9, characterized in that said inner coating (4) is a microfilm with a thickness of about 0.2 - 0.3 microns.

11. An orthotopic prosthesis (1) according to any one of the preceding claims, characterized in that it comprises three holes (5, 5', 6) larger in diameter than the ureters (20, 20') and the urethra (21), said holes (5, 5', 6) being covered by three respective portions of silicone membrane (7, 7', 8) heat bonded to said membrane (2).

12. An orthotopic prosthesis according to claim 11, characterized in that said portions of membrane (7, T, 8) have the same structure and are of the same material as the membrane (2) and are possibly not provided with the outer texturized layer.

13. A manufacturing method for an orthotopic artificial bladder prosthesis (1) characterized in that it comprises the formation of an enclosure or bag or balloon by means of a multi-layered membrame (2) of soft silicone, with a thickness of about 600 microns so as to be compressible, deflatable and collapsible.

14. A method according to claim 13, characterized in that said multilayered membrane (2) of soft silicone is produced by means of a process of dipping and subsequent vulcanizaion.

15. A method according to claim 13 or 14, characterized in that said outermost layer (3) of said multi-layered membrane (2) undergoes a process of texturization.

16. A method according to any one of claims from 13 to 15, characterized in that the inner surface of said prosthesis (1) is coated with a coating (4) of biocompatible biomaterial.

17. A method according to any one of claims 13 to 16, characterized in that three holes (5, 5', 6), larger in diameter than the ureters (20, 20') and the urethra (21), are made in said prosthesis (1) and subsequently said holes (5, 5', 6) are covered by three respective portions of silicone membrane (7, 7', 8) heat bonded to said membrane (2) of the prosthesis.