JPS645904B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a medical sheet-like prosthetic material, particularly to a medical sheet-like prosthetic material for use in the cardiac vasculature.

Research into surgically repairing and restoring diseased or damaged blood vessels, cardiac tissues, etc. using artificial materials began in the 1950s, and has made great progress, particularly in the last 20 years, in parallel with advances in plastic materials.

Among these, the most practical materials in terms of dimensions, formation, ease of handling, storage stability, etc. are woven or made from threads of polyester (product name: Dacron, etc.) and polytetrafluoroethylene (product name: Teflon). It is a cloth-like or tubular medical prosthetic material made by knitting and weaving. Although these prosthetic materials are currently widely used in a variety of cardiovascular surgical procedures in a variety of shapes, structures, and sizes, they suffer from the following drawbacks.

In cardiac and large vessel surgery under extracorporeal circulation using a heart-lung machine, in addition to the use of heparin, the blood coagulation mechanism is not normal due to a deficiency of platelets and other coagulation factors, resulting in significantly prolonged bleeding and coagulation time. Therefore, hemostasis after completion of extracorporeal circulation is an important issue. Since conventional prosthetic materials are woven or knitted cloth or tubes, a large amount of blood leaks through the weaves or stitches, and therefore the weave or stitches are artificially sealed with blood clots. Requires pre-cropping. Furthermore, even with such pretreatment, bleeding may occur after prolonged extracorporeal circulation, and it takes a long time to stop the bleeding. Furthermore, because conventional prosthetic materials have a rough inner surface, strong blood flow can cause hemolysis, and their low antithrombotic properties can lead to thrombus formation on the inner surface, which can lead to embolism. .

Recently, tubes made from expanded porous polytetrafluoroethylene (hereinafter abbreviated as PTFE), which is obtained by stretching a molded product under specific conditions, have been developed as artificial blood vessels, without relying on weaving or knitting. It is attracting attention. The first applied research on this material as an artificial blood vessel was presented by Matsumoto et al. at the 9th Japanese Society for Artificial Organs held in Sapporo in October 1971, and was titled “Porous.
Application of Polytetrafluoroethylene to Artificial Blood Vessels”
Published on March 15, 1972, in "Artificial Organs" Volume 1, No. 1. Also, in foreign countries,
Soyer et al., Surgery Vol. 72 (1972), p. 864 “A.
"New Venous Prostheses" was the first research report written in English. Since these studies, numerous research reports have been published up to now, but to summarize them, tubes made from expanded porous PTFE have This means that it has a wide range of applications among artificial blood vessel materials, and has a high patency rate after surgery.

Additionally, several inventions and ideas regarding artificial blood vessels and prosthetic materials made of expanded porous PTFE materials are known. Listing them in chronological order, the
No. 9074 (Unexamined Japanese Patent Publication No. 49-22792), Publication No. 52-39838
(Utility Model Publication No. 49-82593), Utility Model Publication No. 52-39839 (Utility Model Application No. 49-82594), Special Publication No. 53-8362 (Japanese Utility Model Publication No. 50-102673), Japanese Patent Publication No. 53-39719 ( Tokukai 1975
-135894), JP-A-51-5897, JP-A-51-
No. 48597, JP-A No. 53-90698, etc. Among these, those related to two-layer prosthetic materials are disclosed in Japanese Patent Publication No. 52-9074, Japanese Patent Application Publication No. 5897-1973, and Japanese Patent Application Publication No. 51-51-
No. 48597 and Japanese Patent Application Laid-Open No. 53-90698.

First of all, Special Publication No. 52-9074 was developed for expanded porous PTFE.
This artificial blood vessel has expanded porous PTFE tape wrapped around the outer circumference of the tube in a helical manner to improve pressure resistance and suture retention than an expanded porous PTFE tube alone. Artificial blood vessels with this structure are already widely used in the United States, Europe, and other countries, and as already mentioned, many medical papers have reported good results such as high patency rate, good preservation, and ease of handling. .

Next, JP-A-51-5897 discloses an artificial blood vessel in which expanded porous PTFE is coated on the outer peripheral surface of a conventional woven or knitted artificial blood vessel, and the purpose is to use the woven or knitted artificial blood vessel. This allows the pre-clotting required during surgery to be omitted.
Therefore, although this purpose is achieved with this artificial blood vessel, the anti-NFH and antithrombotic properties of the inner surface of the blood vessel are the same as those of conventional artificial blood vessels, and the reactivity of the outer surface of the blood vessel to body tissue is unique to PTFE. It tends to be inferior due to its slipperiness.

Next, the artificial blood vessel disclosed in JP-A No. 53-90698 has a two-layer structure in which a continuous porous coating layer of a resin such as polyurethane, which is highly reactive to living tissues, is provided on the outer peripheral surface of a stretched porous PTFE tube. It is a thing,
The purpose is to improve the bond between the artificial blood vessel and the living body by using a resin that is highly reactive to living tissue, and to provide the effect of closing the puncture hole made by an injection needle when used as a shunt for hemodialysis patients.

Note that JP-A No. 51-48597 is considered to be substantially the same as the artificial blood vessel disclosed in JP-A No. 52-9074.

As mentioned above, expanded porous PTFE has already been used as a medical prosthetic material either alone or in combination with other materials, but almost all of the materials used to date have been tubular and relatively small blood vessels. It is used in prosthetics, and as a sheet or cloth prosthetic material for large blood vessels (inner diameter 10 mm or more) and heart patches, a membrane made of four layers of expanded porous PTFE sheets has been applied to various heart surgeries. "Thoracic Surgery" No.
Volume 31, No. 1 (January 1978), a separate issue entitled “New
"Clinical Application of Expanded Polytetrafluoroethylene"
It has only been announced by Sakamoto and Imai as follows.

By the way, sheet-like or cloth-like prosthetic materials (usually referred to as patches) for use in cardiac surgery are roughly classified into the following three types depending on the purpose.

The first is pericardial prosthetic materials. The material itself is flexible and tissue-reactive because it prevents adhesion between the myocardium and external tissue as a result of damage to the pericardium during the initial surgery, especially in cases of surgery that requires reoperation. No artificial membrane is required. However, pericardial prosthetic materials do not particularly require blood pressure resistance or suture needle/thread resistance, and Sakamoto, Imai, and others have already developed two or more stretched porous PTFE sheets as materials that are extremely suitable for this purpose. A brief article was published in the aforementioned ``Thoracic Surgery'' journal about prosthetic materials laminated to each other with their main stretching directions crossing each other.

The second is a patch material that repairs the defective part of the atrium. Currently, cloth or mesh made of woven or knitted PTFE threads is widely used as a prosthetic material for septal defects. This type of patch is subject to only a small blood pressure difference (5-10 mmHg) between the two atria, and blood flow through the patch is not a problem since both sides are in constant contact with blood. Since tissue is gradually formed on the cloth or stitches after surgery, the purpose is almost fully achieved with the current patch materials.

The third is a prosthetic material that is the object of the present invention, that is, a prosthetic material for areas where large blood pressure is applied due to myocardial defects or defects. This material has the following characteristics: A. The outer surface has appropriate tissue reactivity for fixing the prosthetic material, and the inner surface has no tissue reactivity. B. There is no adhesion of platelets that can cause blood clots to the inner surface of the prosthetic material. , C: Tissues can grow inward from the prosthetic material, D: Pre-cropping during surgery is not required, E: The material does not stretch due to blood pressure, F: Will not be torn by suture needles/threads, G: Moderate It is desirable that the material satisfies all requirements A to G at the same time, such as having the following flexibility. Here, moderate tissue reactivity in requirement A means the following.

Generally, when body tissues come into contact with a foreign substance, various reactions such as proliferation of the body tissue, inflammation of the body tissue, and carcinogenesis of the body tissue are caused depending on the nature of the foreign substance. , means that the prosthetic material as a foreign substance acts to increase the proliferation of body tissues without causing unfavorable conditions such as inflammation or carcinogenesis of body tissues, and therefore, requirement C of the prosthetic material is satisfied. It allows tissue to grow inward. Until now, no material has been known that satisfies the above requirements A to G (note that consideration of the above DEF requirements is not required for the first prosthetic material, and for the second patch material, (There is little need to consider BDE requirements).

However, this third type of prosthetic material is clinically used for congenital heart diseases such as cardiac malformations with right ventricular outflow tract stenosis, tetralogy of Farot, right ventricular two-chamber disease, and ventricular septum. It can be applied to all diseases that require right ventricular outflow tract formation, such as defective pulmonary artery stenosis, pulmonary artery stenosis complicated by infundibulum stenosis, and complete transposition of the great vessels.
It can also be applied to functional left atrial enlargement when performing Mustard surgery for some cases of bilateral great vessel right ventricular origin, and a considerable number of them are needed.

From this point of view, the present inventor conducted various studies to create the third type of sheet-like prosthetic material, and as a result, completed the present invention, which is a prosthetic material that simultaneously satisfies all of the above requirements.

That is, the present invention is located on the side that comes into contact with body tissue,
It consists of a woven or knitted fabric that has appropriate reactivity with body tissues and an expanded porous polytetrafluoroethylene layer located on the side that comes into contact with blood flow, and the expanded porous polytetrafluoroethylene layer has a large number of layers. This is a medical sheet-like prosthetic material for cardiac and vascular surgery having a microstructure in which micronodules are interconnected by a large number of fibrils and continuous micropores are formed between the micronodules and the fibrils.

First, the woven or knitted fabric used in the present invention may be any woven or knitted fabric that has been commercially available as a medical material and has appropriate reactivity with body tissue. Possible, but polyester thread or oriented PTFE
A polyester cloth or a PTFE cloth woven or knitted from yarns is suitable. The polyester cloth made of polyester threads is preferably a plain-woven polyester cloth or a polyester tricot cloth, and a polyester tricot cloth with raised one side is particularly suitable. It is also made of stretched PTFE thread.
As the PTFE cloth, polytetrafluoroethylene tricot cloth is preferable.

Next, the expanded porous polytetrafluoroethylene (hereinafter referred to as EPTFE) layer is
Publication No. 18991, Special Publication No. 18991, Special Publication No. 18991, Special Publication No. 18991-
A fired or unfired stretched porous PTFE membrane or sheet produced by the method described in Japanese Patent No. 26547, etc., in which a large number of micronodules are bonded to each other by a large number of fibrils (fine fibers), It is a stretched porous PTFE membrane or sheet with a microstructure in which continuous micropores are formed between micronodules and fibrils.

The manufacturing method is briefly as follows.
A mixture of PTFE fine powder and liquid lubricant (mixing weight ratio of approximately 80:20) is preformed, and this preform is paste-extruded into a desired shape (in the case of the present invention, a sheet shape), and as needed. Calender rolling. The liquid lubricant is removed from this extruded product (crystallinity of about 95% or more) by appropriate means (mainly by volatilization), and then the liquid lubricant is removed in one or more directions per unit time at an elevated temperature below the melting point of PTFE. Stretch the material at a stretching rate of 10%/sec or higher, and if necessary, heat the stretched material to 327°C.
Heat and bake at a temperature above. The material obtained in this way has a matrix tensile strength of 514 kg/cm ² or more.
Porous with the above-mentioned microstructure with high strength
It is a PTEF sheet. The physical properties of this porous PTFE sheet are as described in detail in Japanese Patent Publication No. 18991/1983. Moreover, it can be varied over a wide range by changing processing conditions (stretching ratio per unit time, stretching ratio, temperature, firing conditions, etc.). Among the physical properties of this porous PTFE sheet, it is convenient to specify the fibril length, porosity, and wall thickness as properties related to its suitability as a medical sheet prosthetic material such as the present invention. A length of 0.1 to 1000 μm, a porosity of 50% or more, and a wall thickness of about 0.01 mm to 2 mm are suitable for the purpose of the present invention. Although it is possible to make a single-layer sheet to make a wide range of thicknesses as mentioned above, considering the directionality, strength, hemostasis, antithrombotic properties, etc. of the sheet, it is recommended to make it as a laminate. It's easier to get something that suits your purpose.
The points to keep in mind in this case are that to eliminate the directionality of the sheet, it is best to cross the stretching directions, and to improve antithrombotic and hemostatic properties, the surface to which the fabric is not attached should be stretched with small pores. It is a good idea to arrange the sheets.

In order to overlay and bond the two materials, the woven or knitted fabric and the EPTFE layer, to each other,
Adhesion is achieved by a network of adhesive interposed between the seed materials, or by an adhesive distributed in dots or powder.

Applicable adhesives used for this purpose include hot-melt net materials such as polyethylene net (trade name: Delnet), hot-melt resins such as polyester or nylon nonwovens, polyester or nylon powder, cross-linked polyester adhesives, synthetic rubber adhesives (urethane elastomers,
butyl rubber, etc.), emulsion adhesives (emulsion of vinyl acetate resin, acrylic resin, etc.)
Examples include.

In addition, the adhesive for bonding the above two types of materials is:
As mentioned above, it is preferable to distribute it in the form of a network, or in the form of powder or dots. The reason for this is to maintain the softness and flexibility of the sheet-like prosthetic material, and to maintain continuous porosity as a whole of the material to enable penetration of body tissue into the microstructure.

Furthermore, when bonding the above two types of materials, it is necessary to apply a temperature that melts the adhesive sandwiched in between or accelerates curing. This can be done by heating the roll, sheet or plate used for gluing, or by fixing the assembly of the three above on a metal drum without wrinkles and placing it in a constant temperature bath maintained at the above temperature. Let's do it. In addition, when the woven or knitted layer is made of PTFE resin, it is also possible to melt the adhesive resin at a temperature of 327° C. or higher and to simultaneously bake the PTFE.

The medical sheet-like prosthetic material of the present invention thus obtained can be further shaped to fit the curved surface of the affected area to be repaired. This can be accomplished by preparing a mold of the desired shape, sandwiching the assembly or laminate of the three materials therein, heating the mold, and cooling the mold. This heating is also used in the lamination process to melt the resin or adhesive, or
It can also be carried out as a firing process.

Furthermore, the medical sheet-like prosthetic material of the present invention is usually made of woven or knitted fabric and EPTFE as described above.
Although it has a two-layer structure, in some cases,
It is also possible to have a three-layer structure in which a woven or knitted fabric is sandwiched between two layers of EPTFE.

The medical sheet-like prosthetic material of the present invention thus obtained is applied with the woven or knitted fabric side in contact with body tissue and the EPTFE layer in contact with blood flow. By doing this, PTFE
Fabric materials that are more tissue-reactive than the conventional fabric are more firmly anchored to body tissue by connective tissue. This has been clinically proven through experience as a material for conventional artificial blood vessels. On the other hand, EPTFE itself is a good material that satisfies the above-mentioned conditions B, C, D, and G, but it has problems such as extensibility and tearing due to suture needles and threads, and its tissue reactivity is too low. However, in the present invention, fixation by body tissue was insufficient.
The above-mentioned weaknesses of EPTFE are compensated for by bonding the EPTFE layer with a woven or knitted fabric that is moderately reactive with body tissues on the side (outer surface) that contacts body tissues, and its excellent antithrombotic properties are Since the EPTFE surface can be used as a surface that comes into contact with blood flow, the medical sheet-like prosthetic material of the present invention is very unique in that it simultaneously satisfies all of the conditions A to G above.

Specific examples of the usage and effects of the medical sheet-like prosthetic material of the present invention are as follows. For right ventricular outflow tract stenosis, a vertical incision was made from the main pulmonary artery to the right ventricular outflow tract, and the sheet-shaped prosthetic material manufactured in Example 1 was sterilized and cut to fit the size and shape of the surgical site, and EPTFE was applied to the inner surface. towards 3-0 or 5
Sewn with a continuous stitch of -0 grade monofilament nylon thread or other monofilament thread.

For the purpose of functional left atrium expansion for Mustard surgery, the right atrium was transversely incised to the left atrium near the right pulmonary vein inflow, and the sheet-shaped prosthetic material manufactured in Example 1, cut into an oval shape, was similarly sutured continuously. sew. This material has appropriate flexibility, so it adheres closely to the cardiac incision wound,
Bleeding from the suture line is slight and easy to stop, and because the inner surface has high antithrombotic properties, no embolism has occurred.

In patients with Fallot's tetralogy where the right ventricular outflow tract is severely hypoplastic, it is necessary to enlarge the vertical incision from the right ventricular outflow tract to the main pulmonary artery with a patch. Materials with antithrombotic properties are preferred. Therefore, the sheet-like prosthetic material produced in Example 1 was cut into a long oval shape of approximately 3 x 5 to 7 cm, and the outflow channel was enlarged by continuous stitching with 3-0 or 4-0 monofilament nylon thread. In this case, the present material, which had appropriate flexibility, was suitable because it was easy to mold to match the shape of the outflow tract, and there was little post-operative bleeding. In addition, long-term long-term results showed no complications such as thrombosis or embolism, and no pseudoaneurysm formation.

In addition, in the case of functional left atrial enlargement due to complete transposition of the great arteries, the sheet-like prosthetic material produced in Example 2 was gas sterilized, cut into an oval shape (major axis 5 cm, minor axis 4 cm), and 3-0 or 4 cm. -0 monofilament nylon thread by continuous suture. This material had appropriate strength and flexibility, was easy to suture, did not bleed from the patch surface, and conformed well to the cardiac surface.

As described above, good results have been achieved in all surgeries using the medical sheet-like prosthetic material of the present invention. During the postoperative period, there was no formation of pseudoventricular aneurysm in the right ventricular outflow tract, and no thrombi or embolism occurred, including those used for dilatation of the atrium. Of particular note is the reduction in intraoperative bleeding, which shortened the surgical time and stabilized hemodynamics.

Example 1 Polytetrafluoroethylene fine powder (trade name: Teflon 6J) was prepared according to the method of Japanese Patent Publication No. 48-44664.
and about 18% of its weight of naphtha, and the preform is processed by a ram extruder to
Extrude into a 0.7mm thick sheet. This sheet-like material is rolled to a thickness of about 0.03 mm using calender rolls, and the rolled sheet is heated to about 300°C to remove naphtha, and at the same time stretched about 5 times in the length direction to form an unfired stretched PTFE sheet. I got it. This unfired stretching
The physical properties of the PTFE sheet were as follows.

Wall thickness: 0.03mm Porosity: Approximately 80% Average pore size: 0.4μm Density: 0.4g/cc The above four unfired PTFE sheets (60 x 30cm, length x width) - The fibril orientation of these sheets is vertical and horizontal. Two types of each, two of each type, were stacked one after another on the curved surface of a metal cylinder (diameter 15 cm, length 30 cm) without wrinkles, and the opposing longitudinal ends were secured with stainless steel pieces and clamps. was used to fix it on a metal cylindrical surface. Next, the metal tube was placed in a constant temperature bath maintained at 370° C. for 30 minutes, then taken out and cooled in air to obtain a fired expanded PTFE four-layer laminate.

Next, a commercially available medical plain-woven polyester cloth (density: warp 75D, 38.5 threads/cm, weft 70D,
33.5 pcs/cm) was spread flat, and then polyethylene net (product name: Delnet) was layered on top of it, followed by the above-mentioned fired and stretched PTFE laminate so that there were no wrinkles. I put it on. By this ironing, the polyethylene net is melted and press-fitted into the weave of the polyester cloth and the micropores of the PTFE laminate that are in contact with both sides of the net, and solidified, thus forming a medical sheet in which the polyester cloth and the PTFE laminate are integrated. A prosthetic material was obtained.

The strength of this medical sheet prosthetic material was measured using an Instron tensile tester at a pulling speed of 200 mm/min, and the results are shown below.

Tensile strength (longitudinal direction) 12.6 Kg/cm Elongation rate at maximum tension of 52% Tensile strength (lateral direction) 8.6 Kg/cm Elongation rate at maximum tension of 48% Also resistant to tearing of the material by surgical sutures Resistance was measured with the same tensile testing machine as above. In that case, one tension clamp is attached with both ends of a 4-0 suture passed through the prosthetic material specimen, the other clamp is attached with the specimen intact, and the test is performed at a pulling speed of 200 mm/min. I got the result.

The suture thread breaks at 2.6 kg, and the needle hole spreads out to 4 mm. The suture thread breaks at 2.3 kg, and the needle hole spreads to 7 mm. : 20×20cm, weight: 1.85×10 ^-2 g/cm ² ),
Place the brushed side down on the surface of a stainless steel curved plate with a radius of curvature of 30 cm, and layer polyethylene net (product name: Delnet) of the same size on top of it.
Furthermore, a fired stretched PTFE laminate similar to that used in Example 1 was placed on top of this, and these four sides were fixed with pins to prevent the fabric from shrinking. Next, cover the laminate with aluminum foil, press it with stainless steel fabric, and place the curved plate in a constant temperature bath.
The mixture was heated at 150°C for 30 minutes and allowed to cool to room temperature to obtain the desired medical sheet prosthetic material.

The strength of this prosthetic material was measured in the same manner as in Example 1, and the results are shown below.

Tensile strength (longitudinal direction) 52% elongation at maximum tension of 13.2Kg/cm Tensile strength (transverse direction) 8.4Kg/cm Elongation 108% at maximum tension Tear test with suture Tear at 2.0Kg When tension is applied, the needle hole spreads 4.5 mm (vertical).When the suture thread breaks with a tension of 2.2 kg, the needle hole spreads 9 mm (horizontal).

Claims (1)

[Scope of Claims] 1. A woven or knitted fabric that is located on the side that comes into contact with body tissue and has appropriate reactivity with the body tissue, and an expanded porous polytetrafluoroethylene that is located on the side that comes into contact with the bloodstream. The stretched porous polytetrafluoroethylene layer has a large number of micro nodules interconnected by a large number of fibrils, and continuous micropores are formed between the micro nodules and the fibrils. Medical sheet prosthetic material for vascular surgery with a structure. 2. The medical sheet-shaped prosthetic material for cardiac and vascular surgery according to claim 1, wherein the expanded porous polytetrafluoroethylene layer is a single expanded porous polytetrafluoroethylene sheet. 3 Two stretched porous polytetrafluoroethylene layers
The medical sheet-shaped prosthetic material for cardiac and vascular surgery according to claim 1, which is a laminate of two or more stretched porous polytetrafluoroethylene sheets. 4. Claims 1 to 3, in which the woven or knitted fabric and the stretched porous polytetrafluoroethylene layer are bonded by a network adhesive, or an adhesive distributed in dots or powders. The sheet-shaped prosthetic material for medical use in cardiac and vascular surgery according to any one of paragraphs. 5. The medical sheet-shaped prosthetic material for cardiac and vascular surgery according to any one of claims 1 to 4, which is processed into a curved surface to match the shape of the surgical site.