JPS6318508B2 - - Google Patents

Description

Claim 1: A tubular support member (1) of an inert, at least partially non-absorbable material without adverse tissue reaction, and a tubular support member (1) supported by and substantially concentric with the tubular support member (1). at least one inner wall member 2 of absorbable material without adverse tissue reaction forming an inner wall structure, the inner wall member 2 being such that blood cells such as red blood cells and platelets pass through the free inner surface of the inner wall member 2 and at least the substance thereof. porosity sufficient to allow penetration into the intramural portion of the tubular support member 1, thereby forming a layer of thrombogenic material on the inside of the tubular support member 1 from which the vascular endothelial-coated muscle layer forms. An artificial blood vessel characterized by serving as a support for.

2. The inner wall member 2 has a portion spaced apart from the tubular support member 1 by a constant distance, thereby defining a gap 4 between the inner wall member and the tubular support member 1, during which blood cells can enter the tubular support member 1. The artificial blood vessel according to claim 1, wherein the artificial blood vessel can be penetrated.

3. Artificial blood vessel according to claim 1 or 2, characterized in that the inner wall member 2 consists of one or more layers of porous absorbent material.

4. Claim 1, characterized in that the inner wall member 2 consists of one or more nets of absorbent material.
The artificial blood vessel according to item 1, 2 or 3.

5. The artificial blood vessel according to any one of claims 1 to 4, wherein the tubular support member 1 is microporous or porous.

6. The artificial material according to any one of claims 1 to 5, wherein the absorbent material is polyglycolic acid, a copolymer of glycolic acid and lactic acid, or a lactide polymer or copolymer. Blood vessels.

7. The artificial blood vessel according to any one of claims 1 to 6, characterized in that the material of the tubular support member 1 is selected from polyethylene terephthalate, polytetrafluoroethylene, polyethylene, and polypropylene.

8. The artificial blood vessel according to any one of claims 5 to 7, wherein the tubular support member 1 is woven or knitted.

9 Between the inner wall member 2 and the tubular support member 1〓4
9. The artificial blood vessel according to any one of claims 2 to 8, wherein the diameter of the artificial blood vessel is in the range of about 10 μm to 5 mm.

Description The present invention relates to a new type of vascular graft for permanent or long-term implantation, which has distinctly improved properties compared to previously used prostheses.

Various prostheses for pathologically altered and functionally important arteries and veins have been used in surgical procedures. For this purpose, homogeneous materials (such as superficial veins from the lower limbs), non-homogeneous biological materials (such as chemically or physically treated blood vessels from other humans or animals) or synthetic materials (preparation method (such as Dacron and Teflon® tubing) with various configurations depending on the material used. It has been found that synthetic materials give acceptable results as prostheses for the aorta and large branch arteries. It has been found that the body's own veins provide by far the best results as prostheses for limb arteries or arteries of comparable size. However, in many cases patients do not have adequate venous material;
Attempts have therefore been made to use dissimilar materials or completely synthetic materials. However, such arterial remodeling gives poor results. Among other factors, factors contributing to the undesirable outcome are the lack of development of the special internal covering that characterizes blood vessels, namely the intimal layer. The normal intimal layer consists of a cell layer whose function is, on the one hand, to prevent the formation of intravascular thrombi (antithrombotic effect) and, on the other hand, to prevent the exchange of metabolic products between blood and smooth muscle cells in the vessel wall. It is to offer something in exchange. On the inner surface of the artificial blood vessels used so far, vascular endothelium does not develop, but is covered by a fibrin layer and sometimes connective tissue. Although the resulting surface does appear to be smooth, it lacks effective antithrombogenic properties. There is therefore a risk of thrombus formation, which can completely occlude the inserted prosthesis, with serious ischemic consequences for the patient. Essentially a similar situation occurs when a pathologically altered vein is replaced.

Previous attempts to achieve internal endothelial cell coverage in synthetic vascular grafts have been unsuccessful. This problem has now been solved by the present invention.

Such an endothelial cell coating is achieved by implantation of a vascular graft consisting entirely or partially of non-absorbable synthetic material and whose interior is essentially covered by an inner wall structure of absorbable material. It was found that it can be obtained. That is, according to the present invention,
forming a tubular support member of an inert, at least partially non-absorbable material without adverse tissue reaction and an inner wall structure supported by and substantially concentric with the tubular support member; at least one inner wall member of an absorbable material without adverse tissue reaction, the inner wall member being configured to prevent blood cells, such as red blood cells and platelets, from permeating through the free inner surface of the inner wall member into at least a substantial intramural portion thereof. characterized in that it is sufficiently porous to permit, thereby serving as a support for the formation of a layer of thrombogenic material produced by the vascular endothelial-coated muscle layer on the inside of the tubular support member; Artificial blood vessels are provided.

With such a configuration, the absorbent inner wall member, which has a porous structure through which blood cells such as red blood cells and platelets can enter or permeate, can serve as or define a growth zone for new tissue. This allows the formation of a relatively thick or uniform layer of thrombogenic material that serves as a support tissue for growth of the vascular endothelial muscle layer.

Therefore, after transplantation using the artificial blood vessel of the present invention, a muscular layer covering the vascular endothelium is formed inside the artificial blood vessel, and the inner wall member is absorbed and disappears, leaving the non-absorbable tubular support member. The inside is covered with living tissue that has a normal blood vessel structure, and this vascular endothelial layer prevents the formation of blood clots. Preferably, the absorbent material is arranged such that a generally continuous space is formed within the absorbent material and/or between the absorbent material and the at least partially non-absorbable material. This can be achieved, for example, by placing portions of the absorbent material at a certain distance, preferably a large distance, from the non-absorbent material.

Absorbent layers or coatings can be designed in a variety of ways and applied in a variety of ways. Thus, the absorbable material may be, for example, an inner tubular member, which is inserted and secured to an outer tubular prosthesis element of non-absorbable material. The inner tube may have a coarse or fine mesh structure, or may have a porous wall or a wall with holes. The absorbent structure may, for example, also consist of a thin wire structure protruding from or fixed to the outer tube member, or it may be another corresponding porous structure of absorbent material, such as a spongy layer. . It will be appreciated that attachment of the absorbable coating to the non-absorbable member may occur before the prosthesis material is formed into the tube. Similarly, non-absorbable surfaces can be coated with absorbable materials, if necessary by providing the absorbent material with interstices or growth zones and the necessary blood cell permeable structure. More detailed examples of absorbent structure arrangements are provided below.

In order to increase the thickness of the fibrin layer to be retained by the absorbable material in the post-implantation cutting phase, two or possibly more absorbable layers at least partially separated from each other are applied. Alternatively, relatively thick layers with sufficient porosity or perforation can be used. The absorbable mesh, tube, etc. can be secured to the non-absorbable prosthetic sleeve in a variety of ways, such as with absorbable suture systems or adhesives.

At least the inside of the outer non-absorbable member should be microporous, porous, or provided with pores to promote reattachment of tissue. All tubular prosthetic components can be used, from coarse mesh to microporous tubes. A suitable and fully functioning vascular graft according to the invention may, for example, be coated on the inside with one or more networks of absorbable material.
It can also consist of a conventional vascular graft itself.

The aforementioned gaps between the non-absorbable and absorbable materials of the vascular graft may be of large or small proportions, but the total area of these gaps is preferably as large as the inner surface of the outer non-absorbable material layer. The absorbent material should be of such a size that the area or point where the absorbent material comes into contact with the non-absorbent material in order to adhere to the non-absorbent material is as small as possible. The distance between the material surfaces of these gaps or growth zones should be at least about 10 μ to allow blood cell penetration, but should not exceed about 5-10 mm even for large prostheses. is appropriate. Preferably, said distance is approximately
It is 0.5 to 3 mm.

The absorbable material should be non-toxic without adverse tissue reactions and absorbed at a rate that allows adequate tissue regeneration and does not cause fibrous scar tissue.
Many such materials are known in the art and described in the literature. Examples include polyglycolic acid (PGA), copolymers of glycolic acid and lactic acid, and various lactide polymers. Polyglycolic acid can be considered a polymerization product of glycolic acid, which is essentially hydroxyacetic acid, and is represented in simple form by the formula below.

Preferably, n has a molecular weight of about 10,000 to about 500,000
The number is within the range of . Such polyhydroxyacetic esters are described, for example, in U.S. Pat.
Described in No. 3463158. Copolymers of glycolic acid and lactic acid are described, for example, in US Pat. No. 3,982,543, which copolymers contain from 15 to 85 mol% glycolic acid, the remainder lactic acid and possibly small amounts of other monomers. are doing. Homopolymers and copolymers of lactic acid are described, for example, in US Pat. No. 3,636,956. Each of the above US patents is incorporated herein by reference.

These polycratide compositions contain up to about 15% by weight of repeating units of the general formula:

where R is lower alkylene, preferably methylene or ethylene, m is 0 or 1,
R′ is hydrogen or lower alkyl; R″ is hydrogen or alkyl of up to about 22 carbon atoms when m is 0;
When m is 1, it is hydrogen or lower alkyl,
It may be the same as or different from R'.

Preferred are units derived from α-hydroxycarboxylic acids, especially glycolide or
DL-A comonomer unit derived from lactide. Examples of suitable comonomers include glycolide, β-propiolactone, tetramethyl glycolide, β-butyrolactone, γ-butyrolactone, pivalolactone, and α-hydroxybutyric acid, α-hydroxyisobutyric acid, α-hydroxyvaleric acid, α- Hydroxyisovaleric acid, α-hydroxycaproic acid, α-hydroxy-α-ethylbutyric acid, α-hydroxyisocaproic acid, α-hydroxy-β-methylvaleric acid, α-hydroxyheptanoic acid, α-hydroxyoctanoic acid, α -Hydroxydecanoic acid, α-hydroxymyristic acid, α-
It is an intermolecular cyclic ester of hydroxystearic acid and α-hydroxylignoceric acid. In the particular case of using glycolide as a comonomer, the polycratide composition can contain about 35 mole percent of glycolide-derived repeat units.

The manufacture of various surgical products such as suture wires, suture nets, etc. from the above-mentioned materials is likewise described in the literature. Commercially available suture materials include, for example, polyglactin 910 (registered trademark VICRYL, Ethicon, Sommerville, New Jersey, USA), a copolymer containing 90% glycolic acid and 10% lactic acid, and polyglycolic acid. The registered trademark name is DEXON (Davis & Geck, Pearl River, New York, USA). Naturally, other materials may be used as well, provided they have the desired properties according to the foregoing.

As material for the non-absorbable prosthetic component, essentially any conventional bioacceptable absorbable material commonly used for similar purposes may be used.
Examples of such materials include polyethylene terephthalates such as Dacron and terylene, polytetrafluoroethylene (eg, microporous foam), linear polyethylene, isotactic polypropylene, nylon, and the like. This non-absorbable prosthetic part, as mentioned above, can be manufactured in various woven forms (knitted, woven, even with velor inner and outer surfaces) or as a more or less porous tube. . Optionally, the non-absorbable material can be combined with an absorbent material, for example made of a wire or fiber of non-absorbable material coated with an absorbent material, interspersed with woven wires of absorbent material, It can also be coated on the inside with a layer of absorbent material or the like. of course,
Other materials with properties that allow implantation can be used as well.

Absorbable material-coated prostheses ensure that their in vivo absorption is at least 20 days, preferably 40 to
It has to be something that happens in 150 days.

The artificial blood vessel according to the present invention will be described in more detail below with reference to several embodiments with reference to the accompanying drawings, but the present invention is not limited thereto.

The vascular graft shown in FIG. 1 comprises a tubular support member 1 of porous, essentially non-absorbable material and an inner wall member 2 forming an inner covering structure of absorbable material.
Consisting of The inner wall member 2 is formed in the form of a mesh in the drawings and is provided with a number of sutures (not shown) of absorbable material.
It is attached to the tubular support member 1 by.
The inner wall member 2 is connected to the tubular support member 1 only at fixed points.
, and the portion of the mesh therebetween is maintained at a constant distance from the inner surface 1a of the tubular support member 1, as schematically shown in FIG. Blood cells can pass through the mesh-like inner wall member 2 after transplantation. Although the mesh size of the mesh-like inner wall member 2 is not critical per se, mesh sizes of up to about 5 x 5 mm can generally be used.

As mentioned above, it is also possible, for example, to replace the inner wall element 2 with a tubular element of a more or less porous (eg microporous) material. Of course, both the tubular support member 1 and the inner wall member 2 may consist of mesh, and it is also possible to use woven or knitted materials. Furthermore, inner wall member 2
has a porous tubular structure, whereas the tubular support member 1 can also be a tubular mesh. The fixing of the inner wall member 2 and the tubular support member 1 can also be carried out in other ways than those indicated above, for example by gluing with a suitable material. The distance between the tube surface 1a and the inner wall member 2 is suitably selected to be approximately 0.5 to 3 mm.

The thickness of the myocyte/vascular endothelial layer to be formed is
This can be varied, for example, by using several reticular inner wall members 2 separated by suitable gaps as described above. If the inner wall member 2 is a porous tube, it will be understood that the above-mentioned thickness can vary, but the resulting porosity should be sufficient for good permeation of blood cells. The thicknesses of the tubular support member 1 and the inner wall member 2 are such that the tubular support member 1 corresponds to the outer layer (adventitia) of connective tissue, and the inner wall member 2 corresponds to the muscle cells of the blood vessel or blood vessel portion to be replaced by the artificial blood vessel. and the vascular endothelial layer. Similarly, in the case of a mesh it is also possible to use several mutually separated layers of porous material.

2 to 7 schematically illustrate some variations in the design and application of the inner wall arrangement for the tubular support member 1. FIGS. Thus, in FIG. 2, the inner wall member 2 of absorbent material has a mesh-like (as in FIG. It is supported in a flexible structure, whereby a gap 4 is formed between the inner wall member 2 and the respective portions of the tubular support member 1. (Of course, the inner wall member 2 could also be a more rigid absorbent structure designed and secured as described above.) As previously mentioned,
The fixation means may be, for example, absorbable sutures or adhesives.

In FIG. 3, a tubular absorbent inner wall member 2 having a smaller diameter than the inner diameter of the tubular support member 1 is shown.
are fixed to the tubular support member 1 by a connecting member 5 of non-absorbable material extending from the tubular support member 1, thereby forming a gap 4 between the two tubes. FIG. 4 shows a similar arrangement, but here an abutment member (protrusion or abutment element) 5 projects from the absorbent inner wall member 2. FIG.

In FIG. 5, the joining members 5 are fewer and therefore spaced apart by greater distances. The joining member 5 can be arranged and designed in any suitable way. They can therefore have small linear dimensions and can be distributed uniformly or non-uniformly along the material surface of the tubular support member 1 and the inner wall member 2 in any suitable specification. However, they can also have large dimensions and can, for example, be formed into partition walls or structures that run, for example, radially or circumferentially.

In FIG. 6, the inner wall member 2 is fixed to the tubular support member 1 by a more porous or rough joining element 6 of absorbable or partially absorbable material, for example a wire structure. Finally, in FIG. 7, the absorbent inner wall member 2 is applied to the tubular support member 1 without any suitable spacing as described above, but rather with a fine wire structure in the form of loops or skeins. Structures of a porous nature or of highly porous or spongy materials. The inner wall member 2 may also have a wire structure, for example in the form of a "claw or pin carpet" or the like with pins, or the wires protrude from a layer of absorbent material applied to a non-absorbent material.

As previously stated, the embodiments shown in FIGS. 1-7 are illustrative of various methods of incorporating absorbent materials, and other variations, such as various combinations of the above-described examples, are also within the scope of the present invention. Of course it is possible within the range.

In animal studies using the novel artificial blood vessel according to the present invention, it was observed that a vascular endothelial layer and a lower cell layer of smooth muscle tissue were generated inside the synthetic non-absorbable artificial blood vessel material. . A remodeling layer inside the synthetic material develops in a short time through the regeneration of the normal components of the vessel wall from the end of the animal's own duct, while at the same time the absorbable material disappears. The reshaped vascular endothelium exhibits characteristics of normal vascular endothelium. Thus, after the therapeutic procedure is completed, the implanted conduit segment consists of an outer portion of synthetic material that provides sufficient strength to the conduit and an inner portion of biological tissue having the normal conduit structure. Thus, the artificial blood vessel according to the present invention functions essentially like a normal blood vessel.

Hereinafter, the present invention will be further explained by an example of an animal test using the artificial blood vessel according to the present invention (corresponding to the modification shown in FIGS. 1 and 2). The present invention is in no way limited to the specific vascular graft design specifications used herein.

Example 1 A mesh of polyglactin 910 (registered trade name: VICRYL, Ethicon, Sommerville, New Jersey, USA) was mixed with foamed polytetrafluoroethylene (Impra Inc., Phoenix, Arizona, USA) having a length of 10 cm and an inner diameter of 13 mm. An artificial blood vessel was manufactured by applying it to the inside of a tube. The mesh is 140±20μ line thickness and 400×
It has a pore size of 400μ and was attached to a PTFE tube with polyglactin glue. The tube constructed in this way was then sutured to the swine's transthoracic aorta to reduce the resected portion.

The implanted tubes functioned very satisfactorily and the animals were sacrificed 6 weeks after surgery and the implants were subjected to microscopic examination. Microscopic examination showed that the polyglactin network was virtually completely absorbed. A considerable layer of smooth muscle cells grew at the location of the omentum, and this layer was lined with endothelial cells.

Example 2 The outer tube has the same length as in Example 1 and 10
Double velor woven Dacron® tubing (Meadox Medicals, Oakland, New Jersey, USA) with an inner diameter of An artificial blood vessel was manufactured in the same manner as in Example 1 using a polyglactin network. The mesh was attached to the outer tube using polyglactin glue. Then, the same test as in Example 1 was conducted using this device. The results 6 weeks after transplantation were completely equivalent to the results of Example 1.

Example 3 As an outer tube, the wire thickness is approximately 20μ, the mesh size is 600
A tube having the same structure as in Example 1 was manufactured by using a Dacron fabric tube of ×600μ and an inner tube made of the same type of polyglactin network as in Example 1. Next, using this device, the same test as in Example 1 was conducted on pigs. The results 6 weeks after transplantation were completely equivalent to those of Example 1.

The invention is, of course, not limited to the embodiments particularly shown above, but is capable of numerous modifications and variations within the scope of the appended claims. This is especially true in the design of absorbable and non-absorbable materials, jackets and outer tubes, sizing of various components, etc.