WO1990005628A1

WO1990005628A1 - Composite structure

Info

Publication number: WO1990005628A1
Application number: PCT/GB1989/001393
Authority: WO
Inventors: David Charlesworth; Christopher John Underwood; Kerm Sin Chian
Original assignee: Newtec V.P. Limited
Priority date: 1988-11-22
Filing date: 1989-11-22
Publication date: 1990-05-31
Also published as: AU4633789A; JPH04503332A; GB8827222D0; EP0445184A1; DK95691A; AU636861B2; DK95691D0

Abstract

There is disclosed a method for making a composite structure comprising coagulation casting a coating onto a film.

Description

-1-

COMPOSITE STRUCTURE

This invention relates to composite structures and methods for making them.

In GB-2,130,521 B there is described the production of a synthetic arterial prosthesis comprising a cellular polyurethane tube preformed by coagulation casting on to a former. A water soluble coating having a smooth surface is separately applied to another former and a polyurethane film is solvent cast on to the coating. The preformed tube is subsequently shrunk on to the film and the former is removed by dissolving the coating in water.

The resultant materials are said to be compliant to pulsatile flow, the inner film being smooth to within a tolerance of 10 microns for minimising frictional energy losses at the wall of the tube and inhibiting pooling of procoagulents and the adhesion of platelets, which would ultimately give rise to thrombosis. The purpose of the water soluble coating was to produce such a smooth inner surface.

It is now found that it is not absolutely essential to use such a coating for this purpose. The shrinking and bonding of the tube on to the film was, in GB-2 130 521 B, effected by heat - the assembly was subjected to a temperature of 100°C for an hour. The bonded assembly was then suspended in a circulating bath of water typically at 80°C for half an hour to dissolve the polyvinyi-alcohol release agent.

In Patent Application 8804695 (Publication No. GB-A-2,204,873) are described methods and apparatus for making the polymer material without the film by coagulation casting at lower temperatures than are used in the method of GB-2,130,521 B which were found to degrade the polymer so that its usefulness as a vascular prosthesis was compromised.

Vascular prostheses made according to the methods disclosed in GB-A-2,204,873 have now been implanted successfully. These prostheses were made without the heat-shrinking step on to a film.

However, a need is now perceived for a solid lining to a vascular prosthesis not solely for the purposes stated in GB-2,130,521 B, namely to minimise frictional energy losses at the wall of the tube and to inhibit pooling of procoagulants, but simply to form a self-sealing layer which will automatically close up after needle penetration. Thus a self-sealing -3-

vessel can be implanted at a site within the cardio vascular system where repeated penetration is required e.g. in dialysis procedures, and in the infusion of, for example, antibiotics and che otherapeutic agents.

The present invention provides a composite structure capable of being used for such purpose and having all of the advantages of GB-A-2,204,873 in regard to polymer integrity which permits prolonged viability.

The invention comprises a method for making a composite structure comprising coagulation casting a coating on to a film.

The invention may be of broader application than in the production of a vascular prosthesis as discussed in GB-2,130,521 B and GB-A,2,204,873, and accordingly it is not restricted to the production of tubular product or the use of bio-compatible materials or any particular materials save as it will be required to form film and to coagulation cast a coating thereorito.

The film and coating may be of the same material, therefor, or of different materials so long as they are compatible. -4-

For use as prostheses, clearly, the materials should be bio-compatible and may comprise a bio-compatible grade of polyurethane, but for other purposes either one may be of polyurethane or such other material as may be suitable for such purposes.

The film may be coated on to a release layer on a support surface and the release layer may comprise a polyvinyl alcohol film as disclosed in GB-2,130,521 B, which is later dissolved away. The film should not, of course, dissolve in the polymer solvent and a polyvinyl alcohol which is atleast 85% hydroxylated will normally be suitable.

The film, especially for prosthesis use, may have a thickness of the order of 50 microns. It may be formed as a tube on a mandrel, which may then be used in a coagulation casting process to make a composite tube having an inner wall of solid material and an outer wall of microporous material. The temperature throughout can be maintained so low as not substantially to adversely affect the material of the film and/or coating.

The invention also comprises a bio-compatible prosthesis comprising a film having a coating deposited by coagulation casting, and a vascular -5-

prosthesis comprising a coagulation cast tube having an inner lining of solid film made by the method of the invention. The coating may have a thickness of the order of 1 mm, and the tube may have a diameter of 4 mm.

Embodiments of composite structure and methods for making the same will now be described with reference to the accompanying drawings, in which :-

Figure 1 is a side elevation of an injection unit;

Figure 2 is a plan view of the injection unit illustrated in Figure 1;

Figure 3 is a plan view of an extrusion arrangement;

Figure 4 is an axial cross-section of an extrusion head of the arrangement illustrated in Figure 3;

Figure 5 is an end view of an inlet manifold of the extrusion head illustrated in Figure 3; Figure 6 is a side view of a die used in the extrusion head illustrated in Figure 3;

Figure 7 is an end view in the direction of arrow 7 on Figure 6;

Figure 8 is a diagrammatic illustration of a control system;

Figure 9 is a diagrammatic illustration of a dip-coating process for applying a film to a mandrel of the injection unit of Figures 1 to 8;

and Figure 10 is a cross-section of a vascular prosthesis produced by the invention.

Figures 1 to 8 of the drawings illustrate apparatus according to Patent Application No. 8804695 (Publication No. GB-A-2,204,873) for making a synthetic polymer tube which is suitable as a vascular or arterial prosthesis and which is used also in the present invention for making such a tube with a "lining" of solid material. The tube is made by coagulation. The polymer, a medical grade linear segmented poly(ether)urethane with a number average molecular weight in the range 20,000 to 80,000 grams per mole is dissolved in an aprotic organic solvent, for example, N,N-dimethylacetamide or N,N-dimethylformamide to a concentration of between 10 and 30 grams/decilitre at a temperature less than 30°C. A water soluble filler is then added, for example ground particles of sodium hydrogen carbonate with an average diameter of 60 microns, to a concentration between 10% and 60% by weight.

To the resulting suspension a surfactant, for example sodium dodecyl sulphate, may be added at a concentration of between 0.1 and 10% by weight.

The solution is loaded into a piston-in- cylinder syringe arrangement illustrated in Figures 1 and 2. The cylinder 11 is adapted to move axially and is attached to a yoke 12 slidable on guide rods 13 extending between end pieces 14 of a base 15. The yoke 12 has a nut 16 engaging a lead screw 17 which extends through a bearing in the right hand end piece 14, as seen in the drawings, and which is rotated by a motor _.(not shown) through a coupling 18. The piston 19 is on the other, left hand, end of the lead screw 17 and thus rotates with it. The cylinder 11 does not, of course, rotate since it is constrained by the guide rods 13.

An outlet port 21 is provided at the nozzle end 22 of the cylinder 11 remote from the yoke 12, as well as a closable air vent 23.

Microswitches 24, 25 are provided on the end pieces 14 which are actuated by the yoke 12 indicating it is at one or other end of its range of travel.

The full cylinder 11 starts from an extended position left of that illustrated in Figures 1 and 2 and moves to the right under the action of the lead screw 17 pumping the solution out of the nozzle»

The outlet port 21 is connected by medical grade thick walled silicone rubber tubing to the extrusion arrangement illustrated in Figure 3.

The extrusion arrangement comprises generally an extrusion head 31, illustrated in more detail in Figures 4 to 7, a mandrel drive unit 32 and a coagulation bath 33,

The mandrel drive unit .32 has a lead screw- 34 supported between end pieces 35, of which only one is shown, of a base 36 and rotated by an electric motor not shown in this Figure. There are guide rods 30 also extending between the end pieces 35. A yoke 37 has a nut 38 engaging the lead screw 34 and runs on the guide rods 36. The yoke 37 is driven from right, as seen in Figure 3, to left and pushes a mandrel 39 through a ptfe bearing 41 in the left hand end piece 35.

A microswitch 42 is actuated by the yoke 37 indicating that it has reached the left hand extremity of its travel.

The mandrel 39 is thus forwarded through the extrusion head 31 and into the coagulation bath 33.

In the bath 33, which is supplied with circulating, temperature controlled water through inlet and outlet ports 43, 44, are further guide rods 45 extending along the bath. A yoke 47 is slidable on these guide rods 45 from right to left as seen in the drawing against a resistive force from springs 48 and clips 49 on the guide rods 45. The yoke 47 is pushed along the guide rods 45 by the advancing mandrel 39. The guide rods 45 revolve about the mandrel 39 being carried in a bearing 45a at the left hand end wall 46 and in the rotary extrusion head 31. Figure 4 illustrates the extrusion head 31 in more detail. It comprises a body made up from an outer plate 51 with a central ptfe locating port 52 connected to a central member 53 carried in a ptfe bearing 54 in a frame member 55 and a pulley member 56 supported in a ptfe bearing 57 in the end wall 46 of the coagulating bath 33. The bearing 57 is held in position in the end wall 46 seal arrangement 58 secured by screws 59.

The plate 51, central member 53 and pulley member 56 are held together by bolts 61, which also secure the guide rods 45, which thereby revolve about the mandrel 39 as noted above.

A die 62 shown to a larger scale in Figures 6 and 7 comprises a ptfe member which extends through the extrusion head 31 from the outer plate 51 into the coagulating bath 33 and comprises a channel 63 and a bore 64 through which the solution passes from a solution chamber 65 in the extrusion head to the die orifice 66. The ptfe locating port 52 and the die 62 have - precision bores of the same diameter as the mandrel 39 which are self-sealing against leakage when the mandrel is in place and which centralise the mandrel 39 in the die orifice 66. The solution chamber 65 is bounded by the outer plate 51, the central member 53 and a ptfe inlet manifold 67, illustrated further in Figure 5. The manifold 67 comprises an annular member having an injection port 68 which is connected to the syringe arrangement of Figures 1 and 2 by the medical grade thick walled silicone rubber tubing mentioned above. The manifold 67 is prevented from rotating with the rest of the extrusion head by a movement restrictor 69 engaging the frame member 55. The head 31 is rotated by a v-belt 70 engaging the pulley member 56 and driven from a motor driven shaft 71.

The manifold 67 houses a pressure transducer 72 which is used in the control of the process.

The mandrel 39 rotates with the extrusion head 31 because it is securely gripped along the length of the bore of the die 62 and the locating port 52 as well as by the yoke 47 in the coagulation bath 33.

The purpose of the rotation is to maintain concentricity of the solution extruded on to the mandrel 39 during coagulation. The reason for rotating the die 62 as well as the mandrel 39 is to eliminate shear forces on the solution as it is being cast on to the mandrel 39. Figure 8 shows a control arrangement in which a microprocessor based control unit 81 controls the motor 82 that drives the injection unit of Figures 1 and 2, the motor 83 that drives the mandrel drive unit 32 and the motor 84 that rotates the extrusion head 31. A four channel feed back system uses opto-electronic transducers 82a, 83a and 84a on the shafts of the motors 82, 83 and 84 as well as the pressure transducer 72. The motors are d.c. motors which are regulated by pulse width modulation of the supply voltage.

In operation, after the injection unit has been filled with air vented through vent 23, the control unit 82 is powered up and set to manual while the mandrel 39 is positioned in the locating port 52 of the extrusion head 31. The injection unit is then turned on and polymer solution allowed to flow slowly into the extrusion head 31 and purge the solution chamber and flow channels of air. The mandrel 39 is then moved in to seal the die orifice and the bath 33 is filled with circulating water, which is usually, but not necessarily, the coagulant maintained at 40°C. The control unit 81 is then turned to automatic. In rapid (3 second delay) sequence the injection unit -motor 82, then the mandrel drive unit motor 83 and finally the extrusion head rotation motor -13-

84 are gradually (over about 5 seconds) powered up to predetermined levels.

When the mandrel has been fully coated, the polymer solution is allowed to coagulate for one or two hours in the bath 33, rotation of the mandrel 39 and circulation of the temperature controlled coagulant being maintained throughout this period.

The coagulation bath 33 is then drained and the mandrel removed. The arterial prosthesis, now fully formed, is removed from the mandrel, rinsed in distilled water and placed in dilute hydrochloric acid for half an hour to remove any last traces of filler. The prosthesis is finally rinsed thoroughly in deionised water and stored prior to sterilisation.

The coagulation bath 33 is of the order of 1 metre in length, and the mandrel 39 will be of comparable length so as to be able to extend substantially through the bath.

As a mandrel is used a polished steel rod of circular cross-section which is 4 mm in diameter. The die 62 is such that the thickness of the solution extruded on to the mandrel is about 1.5mm. It will be appreciated that the mandrel could be a steel tube, or a carbon fibre tube or rod.

However, prior to coagulation casting, the mandrel 39 is first coated with a polyvinyl alcohol release film by dipping in a bath 91 (Figure 9) and then coated with a film of the same poly(ether) urethane as is used for the coagulation casting, by dipping in a bath 92. The dipped mandrel, after drying, is used directly in the coagulation casting operation.

A suitable thickness of film is deposited on the polyvinyl alcohol coated mandrel in about 2 minutes from a suitable concentration of solvent of the poly(ether)urethane. A thickness of 50 microns is suitable for the prosthesis herein contemplated, but other thicknesses can, of course, be produced by a shorter or longer dip time.

Figure 10 illustrates in cross section a vascular prosthesis made as above described. The prosthesis is about 4 mm in internal diameter and has a wall thickness of 1 mm, which has an inner "lining¹* of solid poly(ether)urethane of thickess about 50 microns, the remainder of the wall being of the microporous coagulation-cast poly(ether)urethane. The result is a length of. synthetic arterial prosthesis which is bio-compatible and which closely approximates natural artery in its mechanical properties as regards strength, elastic extensibility and compressibility and which has a self-sealing inner lining which will close up after penetration e.g. during dialysis.

The methods and apparatus described are of course not limited to the production of tubular prostheses - more complicated shapes could be produced by different forming techniques yet still utilise the principles of the invention. It is envisaged that a flat sheet of material could be produced, for example, by forming a poly(ether)urethane film on a release layer on a flat support and then coagulation casting the poly(ether)urethane on to the film. Such could have a variety of prosthetic uses and other uses which might involve the use of different materials.

Claims

-16-CLAIMS

1. A method for making a composite structure comprising coagulation casting a coating onto a film.

2. A method according to claim 1, in which the film and the coating are of the same material.

3. A method according to either of claims 1 or 2, *in which the film comprises polyurethane.

4. A method according to any one of claims 1 to

3, in which the coating comprises polyurethane.

5. A method according to any one of claims 1 to

4, in which the film is coated on to a relaese layer on a support surface.

6. A method according to claim 5, in which said release layer comprises a polyvinyl alcohol film.

7. A method according to any one of claims 1 to

6, in which the film has a thickness of the order of 50 microns.

8. A method according to any one of claims 1 to

7, in which the film is formed as a tube on a mandrel.

9. A method according to claim 8, in which the mandrel with the film is used in a coagulation casting process .to make a composite tube having an inner wall of said material and an outer wall of microporous material.

10. A method according to claim 9, carried out at such low temperatures as not substantially to degrade the material of the film and/or the coating.

11. A method according to any one of claims 1 to 10, used for making a bio-compatible prosthesis.

12. A biocompatible prosthesis comprisisng a film having a coating deposited by coagulation casting.

13. A vascular prosthesis comprising a coagulation cast tube having an inner lining of said film.

14. A prosthesis according to either of claims 12 or 13, of which the film has a thickness of the order of 50 microns.

15. A prosthesis according to any one of claims 12 to 14, of which the coating has a thickness of the order of 1mm.

16. A prosthesis according to any one of claims 12 to 15, comprising a tube having a diameter of 4mm.