JP2004049772A - Artificial heart valve and production method therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a production method for an artificial heart valve, an artificial heart valve body reinforcement, or a bicupid or tricupid valve reinforcement, and the simple manufacturing process of the artificial heart valve. <P>SOLUTION: A process for forming a film layer (5) comprises a biodegradation absorptive resin around a pattern for a Valsalva sinus molding mold (4) having two or three swelling sections (4a) in a center part and a core metal interposed chamber (7) in the center part, wherein an outer cylinder body (6) consisting of another biodegradation absorptive resin is put on the outside of the film layer (5). Then, the production method for the artificial heart valve body reinforcement is provided which includes a process in which a metal mold for molding (2) having two or three recess parts (1)corresponding to the swelling sections (4a) is mounted so that the swelling sections (4a) of the pattern for the Valsalva sinus molding mold corresponds to the recess parts (1) of the above metal mold for molding and a process in which heating treating is conducted at a temperature which melts the resin composing the film layer (5), but does not melt a resin composing the outer cylinder body (6). <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a prosthetic heart valve, a method for manufacturing a prosthetic heart valve body reinforcing material or a bicuspid or tricuspid valve reinforcing material, and a prosthetic heart valve.
[0002]
[Prior art and its problems]
As an artificial heart valve, for example, the one described in JP-A-2001-238900 is known. This publication describes a method of obtaining a tricuspid valve by compounding the outer side of an artificial heart valve body (outer cylinder) by a suture prevention layer.
[0003]
However, this method has a disadvantage that blood leaks slightly.
[0004]
The present invention relates to a simplified method for manufacturing an improved artificial heart valve.
[0005]
[Means for Solving the Problems]
The present invention relates to the following inventions.
Item 1. A film made of biodegradable and absorbable resin around a Valsalva sinus mold (4) having two or three bulges (4a) in the center and a core insertion chamber (7) in the center. Forming a layer (5);
After covering an outer cylinder (6) made of a biodegradable and absorbable resin on the outside of the film layer (5), a mold for molding having two or three concave portions (1) corresponding to the bulging portion (4a). Mounting the mold (2) such that the bulging portion (4a) of the mold for forming Valsalva cavity corresponds to the concave portion (1) of the molding mold;
A method for producing a reinforcing material for an artificial heart valve body, comprising a step of performing a heat treatment at a temperature at which the resin constituting the film layer (5) melts but the resin constituting the outer cylinder (6) does not melt.
Item 2. The tip of the inner tubular body (15) made of a biodegradable and absorbable resin is inserted into the leaflet mold insertion portion (13a) of the leaflet molding die (13), and the hole ( With the leaflet mold (16) pulled out from the inner tube body (15), the leaflet portion (16a) of the leaflet mold is aligned with the hole (11) of the leaflet molding die from the inside of the inner cylinder (15). Mounting process,
A method for producing a two- or three-cuspid valve reinforcing material (18), comprising a step of heat-treating a state in which a leaflet mold (16) and an inner cylinder (15) are mounted in a leaflet molding die (13).
Item 3. Item 2: A two- or three-cuspid valve reinforcing material (18) obtained by the method of Item 2 is mounted inside the artificial heart valve body reinforcing material (19) obtained by the method of Item 1, and these are integrated. Process,
A step of immersing the integrated body of the artificial heart valve body reinforcing material (19) and the bi- or tricuspid valve reinforcing material (18) in a biodegradable absorbent resin solution to form a foam layer (20) covering these reinforcing materials A method for manufacturing an artificial heart valve, comprising:
Item 4. An artificial heart valve body reinforcing material (19) made of a biodegradable absorbent resin and a bi- or tricuspid valve reinforcing material (18) made of a biodegradable absorbent resin are provided inside a foam layer (20). A prosthetic heart valve having a bi- or tricuspid valve wherein the heart valve body reinforcement (19) has an outer cylinder (6) and a film layer (5a) surrounding the outer cylinder (6).
[0006]
The prosthetic heart valve of the present invention will be described below by taking as an example a prosthetic heart valve body reinforcing member having a tricuspid valve reinforcing material and three Valsalva sinuses. Prosthetic heart valves provided can likewise be manufactured and used.
[0007]
BEST MODE FOR CARRYING OUT THE INVENTION
Manufacture of the prosthetic heart valve body reinforcement In the following, the manufacture of the prosthetic heart valve body reinforcement having three sinus valsalva is described, but also for the prosthesis heart valve body having two sinus valsalva, It can be similarly manufactured using a Valsalva sinus mold having two bulges.
[0008]
In the present invention, the artificial heart valve body reinforcing material (19) is preferably manufactured by, for example, the following method.
[0009]
First, as shown in FIG. 1, liquid silicone rubber (room temperature hardening type or hardening at 100 ° C. or lower) is applied to a molding die (2) capable of being divided into three parts having a concave portion (1) corresponding to the Valsalva sinus in the center. Low-temperature curing type, one-pack type or two-pack type). At this time, it is preferable to use a liquid silicone rubber which has been defoamed in advance.
[0010]
Next, after further defoaming by vacuum defoaming, the core metal (3) is inserted and defoaming operation is further performed. In this state, the mold is allowed to stand at room temperature for about 6 to 24 hours, and is further subjected to heat treatment at about 60 to 100 ° C. for about 6 to 24 hours to produce a Valsalva sinus mold (4) made of silicon rubber.
[0011]
The valsalva cavity forming mold (4) is taken out of the mold (2), and the core metal (3) is withdrawn from the valsalva cavity forming mold (4). It is possible to obtain a Valsalva sinus mold (4) having (7) and having a bulging portion (4a) corresponding to the Valsalva sinus.
[0012]
A film layer (5) made of a biodegradable and absorbable polymer is formed on the outside of the obtained Valsalva sinus mold (4). The film layer can be obtained by immersing the mold for forming valsalva sinus in a biodegradable and absorbable polymer solution of about 3 to 5% by weight and drying with cold air for about 4 to 5 minutes. Can be repeated until a film having a thickness of Alternatively, a biodegradable and absorbable polymer film tube having a thickness of 0.1 to 0.3 mm is placed over a mold for forming Valsalva sinus, or a film having a thickness of 0.1 to 0.3 mm and a predetermined width. The film layer may be formed by winding a biodegradable and absorbable polymer tape having the following. The film layer (5) is melted in a subsequent heating step and is entangled with the outer cylinder (6), and functions as a reinforcing material (19) for the heart valve body integrally with the outer cylinder. That is, the outer cylinder (6) made of a biodegradable and absorbable resin is put on the outside of the film layer (5). FIG. 3B. The hatched portion indicates a melted film layer (5a). When cells are seeded on the heart valve, by seeding the cells inside the film inside the artificial heart valve body, the cells can take in nutrients from blood after transplantation and blood leakage is prevented. It is not necessary to seed the cells on the outside of the film, but the cells can be seeded on the outside as well as on the inside.
[0013]
Next, the mold for forming a valsalva sinus (4) covered with the outer cylinder (6) is used as a mold (2) for molding (the same or different from that used for the mold for forming a valsalva sinus). After inserting the core metal (3) into the core metal insertion chamber (7), heat it to the set temperature of 120 ° C., maintain it for about 5 minutes, cool it, take it out of the mold (2) and cool it Then, an artificial heart valve body reinforcing material (19) (having no foam) having the sinus of Valsalva (19a) is obtained. In this heating step, the heating time can be shortened by heating the mold in advance.
Manufacture of a bicuspid valve In the following, the manufacture of a tricuspid valve will be described, but a bicuspid valve can be manufactured in a similar manner.
[0014]
In the present invention, the tricuspid valve reinforcing member (18) to be mounted inside the artificial heart valve body reinforcing member (19) is preferably manufactured by, for example, the following method.
[0015]
First, as shown in FIG. 2B, the degassed liquid silicone rubber is poured into a container (12) having a hole (11) at the tip corresponding to the tricuspid valve, and vacuum degassing is performed. The mold (16) is inserted, degassed in a vacuum, cured at room temperature for 6 to 24 hours, and then cured at a temperature of 60 to 100 ° C. for 6 to 24 hours. 13) is obtained. The mold (13) may be formed of a material other than silicone rubber.
[0016]
Next, as shown in FIG. 2C, a biodegradable and absorbable inner cylindrical body (15) constituting a tricuspid valve is externally fitted to the guide pipe (14), and further, a leaflet is attached to the guide pipe (14). The mold (16) is fitted inside. In this state, the guide pipe (14) is pulled out while holding the A end (15a) of the inner cylinder (15), and the inner cylinder (15) is fitted to the leaflet mold (16) (FIG. 2A). Like the outer cylinder (6), the inner cylinder (15) may have any shape such as a nonwoven fabric, a woven fabric, a knit, a mesh, or a cylinder, but is preferably a mesh knit. .
[0017]
The inner cylindrical body (15) is inserted into the leaflet molding die (13) from the side opposite to the end A (15a), and its tip is pulled out from the holes (11) at the tips corresponding to the three leaflets. Insert the mold (16) so that the leaflets fit.
[0018]
In this state, the material is heated to a set temperature of 120 ° C., maintained for about 5 minutes, cooled, and taken out of the mold to obtain a tricuspid valve reinforcing material (18).
[0019]
Manufacture of artificial heart valve The bi- or tricuspid valve reinforcing material obtained above and the artificial heart valve body reinforcing material are integrated by suturing or the like. That is, after the leaflets are inserted and integrated into the heart valve body reinforcing material, the whole is immersed in a biodegradable and absorbable resin solution (1 to 10% by weight), and then freeze-dried to form a whole foam material layer ( 20) to obtain an artificial heart valve. Of course, one or both of the tricuspid valve reinforcing material and the prosthetic heart valve body reinforcing material may be covered with a foam material layer, then integrated by suturing or the like, and a foam material layer may be formed as necessary.
[0020]
The foam or the film layer is preferably a low-melting resin that is flexible and melts under the condition that the outer cylinder does not melt, and is preferably L-lactide / ε-caprolactone copolymer (P (LA / CL)). Is exemplified.
[0021]
Examples of bioabsorbable materials constituting the bicuspid or tricuspid valve reinforcing material and the artificial heart valve body reinforcing material (outer cylinder and inner cylinder) include polyglycolic acid, polylactide (D-, L-, and DL-) Caprolactone, glycolic acid-lactic acid (D-form, L-form, DL-form) copolymer, glycolic acid-caprolactone copolymer, lactic acid (D-form, L-form, DL-form) -caprolactone copolymer, poly (p-dioxanone) ), Synthetic bioabsorbable polymers such as lactic acid-trimethylene carbonate copolymer, and natural polymers such as collagen, modified collagen, gelatin, chitin and chitosan. A preferred material is poly-L-lactic acid (PLLA).
[0022]
The heart valve manufactured by the manufacturing method of the present invention is sterilized with ethylene oxide gas, and living cells (endothelial cells and fibroblasts, etc.) are seeded on the inside of the heart valve body and the leaflets, and the inner surface of the artificial heart valve, Valsalva sinus And after it is converted into endothelial cells so as to cover the leaflets, it can be used for heart valve transplantation. The inner surface of the artificial heart valve, the valsalva sinus and the leaflets may be almost covered with endothelial cells and fibroblasts, but are more preferably completely covered.
[0023]
The heart valve obtained according to the present invention can be used for transplantation not only to adult humans and animals, but also to infants and children.
[0024]
The pore size of the foam is preferably such that cells adhere appropriately and proliferate, and at the same time, do not leak blood when transplanted as a heart valve. The pore size is usually 1 mm or less, preferably 5 to 100 μm. The thickness of the heart valve after foaming is determined by the absorption period or ease of suturing, and is usually 5 mm or less, preferably 500 μm to 2 mm.
[0025]
The following method can be exemplified as a method for producing a foam.
(1) Freeze-drying method The artificial heart valve body reinforcing material and / or the bi- or tricuspid valve reinforcing material is immersed in a biodegradable and absorbable resin solution, frozen, and freeze-dried. Foams having various pore sizes can be obtained depending on the freezing temperature and the concentration of the polymer.
(2) Elution method After mixing with a biodegradable resin solution containing a water-soluble substance and drying, the water-soluble substance is washed away with water. A foam having a diameter corresponding to the particles of the water-soluble substance is obtained. In this example, sucrose can be suitably used as the water-soluble substance.
[0026]
The reinforcing material needs to have greater strength than the foam, and can be selected from fibrous, non-woven, film, woven, knitted and the like. It is preferably a knitted fabric (mesh).
【The invention's effect】
According to the present invention, an artificial heart valve can be easily manufactured.
[0028]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples.
Example 1
Manufacture of artificial heart valve body reinforcing material ( 19 ) As shown in FIG. 1, a mold capable of being divided into three parts having a concave portion (1) corresponding to three sinuses (19 a) in the center as shown in FIG. 1. Into 2), a two-part liquid silicone rubber of a room temperature curing type is poured and vacuum defoamed.
[0029]
Next, the core metal (3) is inserted, and a defoaming operation is further performed. In this state, the mold is allowed to stand at room temperature for 12 hours, and further heat-treated at 80 ° C. for 12 hours to produce a Valsalva sinus mold (4) made of silicone rubber.
[0030]
A P (LA / CL) (50:50, molar ratio) tape having a thickness of 0.2 mm and a width of 15 to 20 mm is wrapped around the outside of the mold for forming a Valsalva sinus (4) from which the core has been removed to form a film layer. . A cylindrical PLLA mesh is placed over the outside of the film layer.
[0031]
Next, this is mounted on a molding die (2) heated to 120 ° C., inserted into the core (3), heated at 120 ° C. for 5 minutes, heat-set, and taken out from the die (2) after cooling. At the time of heat setting, the P (LA / CL) (50:50, molar ratio) film is melted and entangled with the PLLA mesh, and migrates into the mesh (see FIG. 3B).
Manufacture of tricuspid valve reinforcing material (18) First, as shown in FIG. 2B, defoaming was performed in the same manner as described above in a container (12) having a hole (11) at the tip corresponding to the tricuspid valve. Pour liquid silicone rubber, vacuum degassing, insert valve leaf mold, vacuum degassing, cure at room temperature for 12 hours, then cure at 80 ° C for 12 hours, for valve leaflet molding for tricuspid valve molding Obtain mold (13).
[0032]
Next, as shown in FIG. 2C, a cylindrical PLLA mesh (15) constituting a tricuspid valve is fitted over the guide pipe (14), and the guide pipe (14) is further fitted with a leaflet mold (16). ). In this state, the guide pipe (14) is pulled out while holding the A end (15a) of the PLLA mesh (15), and the PLLA mesh (15) is externally fitted to the leaflet mold (16) (FIG. 2A). The side opposite to the A end of the PLLA mesh is pulled out from the holes (11) corresponding to the three leaflets at the tip of the leaflet molding die, and the leaflets (16a) of the leaflet mold (16) are bored ( 11) Insert so that they fit exactly.
[0033]
In this state, heat treatment is performed at 120 ° C. for 5 minutes, and after cooling, it is taken out of the mold to obtain a tricuspid valve reinforcing material (18).
[0034]
Manufacture of artificial heart valve The tricuspid valve reinforcing material (18) obtained above is inserted into an artificial heart valve main body reinforcing material (19) as shown in FIG. 3A, and after suturing with PLLA suture, The whole is immersed in a dioxane solution (5% by weight) of P (LA / CL) (50:50, molar ratio) and then freeze-dried to foam the entire outer cylinder (6) and the molten film layer (5a). Cover with a material layer (20) to obtain a prosthetic heart valve. The obtained artificial heart valve is shown in FIG.
[Brief description of the drawings]
FIG. 1 illustrates the production of a mold for Valsalva sinus formation.
FIG. 2 shows a method for manufacturing a tricuspid valve.
FIG. FIG. 3 is a schematic view showing insertion of a tricuspid valve reinforcing material into a prosthetic heart valve body, and FIG. FIG. 4 is a view showing that a film (5a) after melting exists around an outer cylinder (6) having a foam layer (20).
FIG. 4 shows an example of the prosthetic heart valve of the present invention having a foam layer.
[Explanation of symbols]
REFERENCE SIGNS LIST 1 concave portion 2 molding die 3 core metal 4 valsalva cavity molding die 4a bulging portion 5 film layer 5a film layer after melting 6 outer cylinder 7 core metal insertion chamber 11 hole 12 container 13 valve tip molding die 13a valve Pin tip insertion part 14 Guide pipe 15 Inner cylinder 15a A-end 16 Valve leaf mold 16a Valve leaf 18 Tricuspid valve reinforcing material 19 Artificial heart valve body 19a Valsalva sinus 20 Foam layer

Claims (4)

A film made of biodegradable and absorbable resin around a Valsalva sinus mold (4) having two or three bulges (4a) in the center and a core insertion chamber (7) in the center. Forming a layer (5);
After covering an outer cylinder (6) made of a biodegradable and absorbable resin on the outside of the film layer (5), a mold for molding having two or three concave portions (1) corresponding to the bulging portion (4a). Mounting the mold (2) such that the bulging portion (4a) of the mold for forming Valsalva cavity corresponds to the concave portion (1) of the molding mold;
A method for producing a reinforcing material for an artificial heart valve body, comprising a step of performing a heat treatment at a temperature at which the resin constituting the film layer (5) melts but the resin constituting the outer cylinder (6) does not melt. The tip of the inner tubular body (15) made of a biodegradable and absorbable resin is inserted into the leaflet mold insertion portion (13a) of the leaflet molding die (13), and the hole ( With the leaflet mold (16) pulled out from the inner tube body (15), the leaflet portion (16a) of the leaflet mold is aligned with the hole (11) of the leaflet molding die from the inside of the inner cylinder (15). Mounting process,
A method for producing a two- or three-cuspid valve reinforcing material (18), comprising a step of heat-treating a state in which a leaflet mold (16) and an inner cylinder (15) are mounted in a leaflet molding die (13). A bi- or tricuspid valve stiffener (18) obtained by the method of claim 2 is mounted inside a prosthetic heart valve body stiffener (19) obtained by the method of claim 1, and these are attached. Process of integrating,
A step of immersing the integrated body of the artificial heart valve body reinforcing material (19) and the bi- or tricuspid valve reinforcing material (18) in a biodegradable absorbent resin solution to form a foam layer (20) covering these reinforcing materials A method for manufacturing an artificial heart valve, comprising: An artificial heart valve body reinforcing material (19) made of a biodegradable and absorbable resin and a bi- or tricuspid valve reinforcing material (18) made of a biodegradable and absorptive resin are provided inside a foam layer (20). A prosthetic heart valve having a bi- or tricuspid valve in which a heart valve body reinforcement (19) has an outer cylinder (6) and a film layer (5a) surrounding the outer cylinder (6).

Images