Process of manufacturing a heart valve made of a polymeric material and the heart valve thereby obtained

Abstract

A process for the manufacture of a heart valve of polymer material which provides for the deposition of a polymer solution comprising a copolymer which is preferably a copolymer of poly(carbonato-urethane) fluoridate (F-PCU) and intracatenary polydimethylsiloxane (PDMS), a PDMS with a functional group outside the chain and a solvent onto a mould using a spray technique associated with phase inversion.

Claims

1. A process for manufacturing a heart valve made of a polymer material, comprising: a) providing a mould shaped so as to replicate a profile to be conferred upon a valve; b) inserting an annular support onto the mould, so that the mould and support assembly forms a former; c) providing an apparatus for depositing a polymer material onto the former, which comprises a pair of spray guns arranged transversely with respect to a longitudinal axis of the former; d) rotating the former about the longitudinal axis; e) feeding one spray gun separately with a polymer solution comprising: (i) a copolymer containing an intrachain silicone [polydimethylsiloxane (PDMS)] and a polymer selected from the group consisting of a fluorinated poly (carbonate-urethane) (F-PCU), a polycarbonate urethane (PCU), a polyether urethane (PEtU), a polyurethane urea (PUR), a polycaprolactone (PCL); (ii) an extrachain functionalized PDMS, terminating in two diacetoxy silyl groups, which is able to cross-link itself thereby forming a semi-interpenetrating polymer network(semi-IPN) with the copolymer (i); and (iii) a solvent; and the other spray gun with a non-solvent for the polymer solution, said non-solvent being selected from the group comprising water, alcohols and mixtures thereof, so as to generate two jets that intersect along a direction substantially transverse to said longitudinal axis; f) keeping the jets focused on one or more sections of a lateral surface of the former until desired parameters of polymer thickness and distribution on the lateral surface of the former are satisfied; g) directing the jets to impact against a front surface of the former; h) keeping the jets focused frontally against the former, until the desired parameters of polymer thickness and distribution over the entire front surface of the former are satisfied; i) eliminating residual solvent traces; j) inserting the former into an outer mould comprising outer mould modules; k) radially compressing the former within the modules, continuing to exercise the compression force during subsequent process operations; l) heating the outer mould containing the former until cross-linking of the polymer material deposited on the former is complete; m) removing excess material from a resulting polymeric valve; n) opening the mould, removing the radial compression force of the outer mould against the former, and extracting the former from the outer mould; and o) removing the polymeric valve, including a support ring, from the mould.

2. The process according to claim 1, wherein the copolymer (i) contains a fluorinated poly (carbonate-urethane) (F-PCU) and an intrachain silicone [polydimethylsiloxane(PDMS)], and the copolymer is present in the polymer solution at a concentration ranging from 1% to 3% w/v per volume of the solution.

3. The process according to claim 2, wherein the intrachain silicone (PDMS) is present as about 20% (w/w) of the total weight of the co-polymer.

4. The process according to claim 1, wherein the solvent is selected from the group comprising tetrahydrofuran, dioxane, dimethylacetamide and mixtures thereof.

5. The process according to claim 4, wherein the solvent is a 1:1 mixture (v/v) of tetrahydrofuran and dioxane or tetrahydrofuran and dimethylacetamide.

6. The process according to claim 1, wherein the extrachain functionalized PDMS terminating in two diacetoxy silyl groups is present in the polymer solution at a concentration varying between 30% and 60% (w/w) of the total weight of polymer material.

7. The process according to claim 1, wherein the non-solvent is selected from the group comprising water, ethyl alcohol, propyl alcohol, benzyl alcohol and mixtures thereof.

8. The process according to claim 7, wherein the non-solvent contains pullulan and/or gelatin in solution.

9. The process according to claim 1, wherein during operations (f) and/or (g) and/or (h) the jets are made to converge or diverge with respect to directions imposed on the jets in previous operation/operations, to adjust a polymer density in the area in which the aforesaid jets intersect.

10. The process according to claim 1, wherein operation (f) is carried out by moving the spray guns laterally along a direction parallel to the longitudinal axis.

11. The process according to claim 1, wherein operation (g) is carried out while keeping the jets oriented as in operation (f), and rotating the former so that the longitudinal axis is arranged parallel to said direction of the jets.

12. The process according to claim 1, wherein between operation (f) and operation (g), or between operation (h) and operation (i), there is interposed the operation of coating the former with a reinforcing resilient mesh, said operation being followed respectively by repeating operation (f) or by repeating operations (f) to (h), until desired parameters of polymer thickness and distribution on the former are satisfied.

13. The process according to claim 1, wherein at operation (b) a support ring comprises a wavy crown formed by three rounded projections, mutually radiused at a bottom by arched sections, rounded projections having a height of between 13 mm and 3 mm measured from a top of the projection to a lower ring.

14. A polymeric heart valve, wherein it is obtainable by a process for manufacturing a heart valve made of a polymer material, and in that the polymeric heart valve has a single-piece polymer structure without discontinuities, wherein the process comprises: a) providing a mould shaped so as to replicate a profile to be conferred upon a valve; b) inserting an annular support onto the mould, so that the mould and support assembly forms a former; c) providing an apparatus for depositing a polymer material onto the former, which comprises a pair of spray guns arranged transversely with respect to a longitudinal axis of the former; d) rotating the former about the longitudinal axis; e) feeding one spray gun separately with a polymer solution comprising: (i) a copolymer containing an intrachain silicone [polydimethylsiloxane (PDMS)] and a polymer selected from the group consisting of a fluorinated poly (carbonate-urethane) (F-PCU), a polycarbonate urethane (PCU), a polyether urethane (PEtU), a polyurethane urea (PUR), a polycaprolactone (PCL); (ii) an extrachain functionalized PDMS, terminating in two diacetoxy silyl groups, which is able to cross-link itself thereby forming a semi-interpenetrating polymer network(semi-IPN) with the copolymer (i); and (iii) a solvent; and the other spray gun with a non-solvent for the polymer solution, said non-solvent being selected from the group comprising water, alcohols and mixtures thereof, so as to generate two jets that intersect along a direction substantially transverse to said longitudinal axis; f) keeping the jets focused on one or more sections of the lateral surface of the former until the desired parameters of polymer thickness and distribution on a lateral surface of the former are satisfied; g) directing the jets to impact against a front surface of the former; h) keeping the jets focused frontally against the former, until desired parameters of polymer thickness and distribution over the entire front surface of the former are satisfied; i) eliminating residual solvent traces; j) inserting the former into an outer mould comprising outer mould modules; k) radially compressing the former within the modules, continuing to exercise the compression force during subsequent process operations; l) heating the outer mould containing the former until cross-linking of the polymer material deposited on the former is complete; m) removing excess material from a resulting polymeric valve; n) opening the mould, removing the radial compression force of the outer mould against the former, and extracting the former from the outer mould; and o) removing the polymeric valve, including a support ring, from the mould.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The functional and structural characteristics of some preferred embodiments of a technique for the manufacture of polymeric heart valves according to the invention will now be described. Reference will be made to the appended drawings, in which:

(2) FIGS. 1A and 1B are diagrammatical perspective views of a polymeric heart valve obtained by an embodiment of the process according to the invention, in the open and closed configurations;

(3) FIGS. 2A and 2B are diagrammatical perspective views of a mould and support for the manufacture of the valve illustrated in FIGS. 1A and 1B;

(4) FIG. 3 shows a partial functional diagram of equipment for manufacturing the polymeric heart valve in the preceding figures according to an embodiment of the process according to the invention;

(5) FIGS. 4A, 4B and 4C are diagrammatical perspective views of details of the machine in FIG. 3 during particular stages in the process according to the invention;

(6) Figures from 5A to 5F are diagrammatical perspective views of some stages in the process according to one embodiment of the invention.

DETAILED DESCRIPTION

(7) Before explaining the plurality of embodiments of the invention in detail, it must be pointed out that in its application the invention is not limited to the construction details and configurations of components described in the description below or illustrated in the drawings. The invention is capable of adopting other embodiments and being implemented or carried out in practice in different ways. It should also be understood that the phraseology and terminology are of a descriptive nature and should not be understood as being limiting. The use of includes and comprises and their variations are to be understood as including the items listed below and their equivalents, as well as additional elements and their equivalents.

(8) Initially with reference to FIG. 1, a polymeric heart valve 9 comprises an annular support 10 and a plurality of flexible leaflets or leaflets 12, shaped so as to form a Y-shaped through passage 14. This passage 14 dilates and closes as the upper edges 12a of leaflets 12 move apart or together in such a way as to allow rather than inhibit the blood flow passing through valve 9.

(9) Annular support 10 (which can be seen in FIG. 2B), generally comprises a lower ring 10a on which there is mounted a wavy crown formed of three rounded projections 10b, joined together at the bottom by arched sections 10c. From tests made to prevent tearing of valve leaflets 12, rounded projections 10b must have a height of between 13 and 3 mm measured from the apex of projection 10b to the base of the crown (or lower ring 10a). If projections 10b are of shorter height the crown is more level, and as a consequence there is a smaller concentration of stresses loading the joining lines between the crown and leaflets.

(10) The overall architecture of the valve, which is in itself known, will not be further described.

(11) In order to manufacture the valve from the preselected polymer material, the characteristics and composition of which have been described previously, a mould 16 (which may be seen in FIG. 2A) provided with a shaft 18 and shaped in such a way that the polymer forms the profile of valve 9 when it becomes attached to outer surface 20 of mould 16 is prepared. Mould 16, which in the example illustrated has a shape which can be inscribed in a gently tapering cylinder or frustoconical shape has a lateral surface 20a which extends along a longitudinal axis A of the mould and a front surface 20b which is projected along axis A in the plane of confluence of the leaflets or the plane which contains the Y-shaped line where the flexible leaflets of valve 9 are joined at the top. Annular support 10, to which the base of leaflets 12 will adhere along their lower arch, is then made of one piece with mould 16.

(12) FIG. 3 shows the circuit diagram for a portion of a spray machine 22 for the manufacture of heart valve 9. In a first stage of the process of valve manufacture according to the invention the mould and the support are joined together in one piece, the assembly forming a former 24, and caused to rotate about longitudinal axis A, for example by attaching shaft 18 of the former to a rotating tailpiece 26 located on machine 22.

(13) A pair of sprays 28 is orientated in such a way as to direct two spray jets 30 generated by respective nozzles onto former 24 along a direction which is substantially transverse with respect to longitudinal axis A.

(14) In all this description and the claims the terms and expressions indicating positions and orientations, such as longitudinal, transverse, vertical, or horizontal relate to longitudinal axis A.

(15) Each spray 28 is fed separately through corresponding tanks 32 in such a way as to produce two independent jets 30 which intersect close to former 24, giving rise to the phenomenon known as phase inversion. Optionally the sprays can be orientated, including independently, in such a way as to cause jets 30 to converge or diverge, so as to concentrate or dilute the polymer in the intersection zone.

(16) One spray respectively will be fed with a polymer solution, while the other will generate a flow of non-solvent which by intersecting the jet of polymer solution will give rise to precipitation of the polymer on the former. Deposition of the polymer on former 24 will give rise to a three-dimensional filamentous structure of the non-woven type.

(17) Qualities of the filamentous structure such as porosity, thickness and other morphological characteristics can be adjusted by adjusting the strength of the jets by means of a central control unit 34, altering the orientation of the jets and/or their position with respect to the longitudinal axis of former 24. According to one embodiment of the invention sprays 28 are positioned on a powered carriage 36 which can move laterally along a direction parallel to longitudinal axis A of the former in such a way as to vary the point of incidence of the jets along the length of longitudinal axis A.

(18) In an embodiment which is not illustrated the sprays may be attached to the powered carriage by means of spherical connectors which make it possible to orientate the axis of the jets in such a way that they are also incident on the former in directions which are not perpendicular with respect to axis A.

(19) Preferably a suction head 38 is located on one side opposite the nozzles with respect to longitudinal axis A of the former in such a way as to remove substances which do not precipitate on the former. Head 38 may move longitudinally in synchrony with the similar movement of the nozzles.

(20) Conveniently, once processing with the jets orientated to generate deposition of the polymer on the former in a direction substantially transverse with respect to longitudinal axis A has been completed, or when the polymer deposited on lateral surface 20a of the mould has achieved the desired uniformity and thickness, the former is caused to rotate 90 towards the sprays so that the jets produced by the nozzles are incident on front surface 20b of the mould.

(21) According to an embodiment which is not illustrated it is possible to arrange machine 22 in such a way that instead of causing the former to rotate (for example by removing shaft 18 from rotating tailpiece 26 and securing it to a supporting plate 40, as may be seen in FIG. 4C), the sprays can be rotated through 90 in such a way as to locate the jets frontally with respect to the former, or have the effect that the jets intersect along a direction parallel to or coincident with longitudinal axis A. Similar positioning of the sprays may for example be achieved by causing the carriage to move along a curved guide track which intersects longitudinal axis A.

(22) According to a further embodiment of the invention (not illustrated), after a preliminary layer of polymer material has been deposited onto former 24 (that is interrupting the stage of depositing polymer onto lateral surface 20a of the former before the said polymer has achieved the desired final thickness), it is possible to cover this material with a thin reinforcing mesh, in the form of a caul, preferably made using threads of elastomer material as an interconnected warp, whose diameter may vary between 10 and 100 microns and the size of the mesh opening of which may vary between 0.2 and 2.0 mm. The elastomer threads may be made of different resilient materials, for example: urethane polyester (PEsU), urethane polyether (PEtU), urea polyurethane (PUR) or those based on urethane polycarbonate (PCU) and urethane polycarbonate (PCU)polydimethylsiloxane (PDMS) copolymers. Possibly, after deposition of the polymer onto lateral surface 20a of the former has been interrupted (before the said polymer has achieved the desired final thickness), a similar preliminary layer of material may also be deposited on front surface 20b of the former in order to then insert the reinforcing mesh.

(23) Once inserted the elastomer mesh matches the geometry of the former and becomes incorporated with the material previously deposited upon it. After this stage deposition of polymer on former 24 is continued until the thin mesh is completely incorporated in the thickness of the valve leaflets, and the desired thickness and uniformity of the material coating the former is achieved. The presence of the elastomer mesh within the valve leaflets is intended to increase their mechanical resistance to fatigue, preventing possible failure and tearing of the leaflets.

(24) Once this cycle of depositing polymer onto the former has been completed, any excess solvent is removed, for example by immersion in distilled water heated to approximately 60 C.

(25) The former is then housed in an outer mould 42, which may be seen in FIG. 5B. Preferably outer mould 42 comprises a body 44 on which Y-shaped grooves 46 are conveniently excavated, flowing towards a central point P in which the shaft of the former is inserted.

(26) A modular outer mould 48 comprises separate portions or modules 48a which can slide within grooves 46 in body 44 in such a way as to close onto the former, adhering thereto so as to impart the desired curvature on leaflets 12. In fact said modules 48a have an internal surface whose shape imparts the preselected profile of the leaflets onto the non-woven tissue deposited on the former. In the case illustrated here, because the leaflets of valve 9 are three in number, matrix 48 is subdivided into the same number of modules 48a.

(27) Mould modules 48a are then pressed radially against former 24 so as to impart the shape of the valve as designed onto the precipitated polymer; the pressure of the outer mould onto the former gives rise to a partial escape of polymer material through the gaps between the modules, due to compression of the material within the outer mould. This compressive action is maintained during the subsequent stages of the process until the mould is reopened.

(28) In order to do this, the mould, once the modules have been pressed against the former so as to form an assembly of cylindrical shape, is held in the closed position by means for example of a metal ring 50 in such a way that subsequent stages of the process do not allow the pressed polymer material to expand and the modules of the mould to move apart.

(29) The assembly of former, outer mould and metal containing ring is placed in water heated to approximately 60 C. or in a heated stove and subsequently in water heated to approximately 60 C. for the time required for complete cross-linking of the material and removal of the solvent. The force of the outer mould also favours compaction of the deposited polymer composite structure/reinforcing mesh of elastomer thread, where the stage of covering the former with the said reinforcing mesh is provided.

(30) Once the heat cycle has been completed and the polymer materials have become consolidated the aforesaid assembly is removed from the heated bath or stove and subsequent heated bath. The excess material leaving mould 48 through the compressive force exerted by the outer mould onto the former is removed by suitable means (for example a knife 52 as illustrated in FIG. 5E or laser cutting).

(31) Finally modules 48a of the outer mould are separated and the mould opened in this way allows the former to be extracted, after which mould 16 is separated from the heart valve finally formed by the deposition of polymer onto the outer part of annular support 10 (lower ring 10a surmounted by a wavy crown formed of three rounded projections 10b).

(32) The advantage accomplished is that of obtaining a heart valve of polymer material made in such a way that the polymer material is dosed in an optimal way, at the same time ensuring maximum flexibility and accuracy when defining the valve's structural parameters.

(33) Different aspects and embodiments of a technique for the manufacture of polymeric heart valves according to the invention have been described. It is intended that each embodiment should be capable of being combined with any other embodiment. The invention is also not limited to the embodiments described, but may be varied within the scope defined by the appended claims.